[Explorations about the correlation between biological changes of meninges in periodontitis mice and cognitive impairment via single-cell RNA sequencing].

Objective: To clarify the potential correlation between biological changes of meninges in periodontitis mice and cognitive impairment by analyzing the biological changes of meninges in periodontitis mice using single-cell RNA sequencing. Methods: Thirty C57BL/6 mice were divided into two groups by using random number table method (15 mice in each group). Mice in the control group were locally administered 2% carboxyl methyl cellulose (CMC) without Porphyromonas gingivalis (Pg) on both buccal sides. A mixture of Pg W83 and 2% CMC was applied on both buccal sides in the experimental group mice three times a week, lasting for 16 weeks in total. The absorption of alveolar bone, locomotor activity and cognitive function, the activation of microglia and astrocytes in the cortex were observed and assessed. The mRNA expression levels of Occludin in meninges and brain were detected in two groups. Single-cell RNA sequencing data of meninges were processed by uniform manifold approximation and projection (UMAP). Differential genes expressions of endothelial cells were processed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. In addition, real-time fluorescence quantitative PCR (RT-qPCR) was used to verify the expressions of transcription activating factor 3 (Atf3) and apolpoprotein L domain-containing 1 (Apold 1). Results: Methylene blue staining found the distances of buccal and palatal cement-enamel junction-alveolar bone crest in experimental mice [(185.60±17.60), (206.90±13.37) µm] increased significantly compared with the control group [(135.33±9.57), (163.05±14.98) µm] (t=5.02, P=0.002; t=4.37, P=0.005). Open field experiment showed the total distance and average speed of mice in the experimental group [(971.88±164.57) cm, (3.25±0.55) cm/s] were not statistically significant compared with the control group [(914.24±278.81) cm, (3.05±0.93) cm/s] (t=0.65, P=0.525; t=0.65, P=0.520). The recognition index of the experimental group [(48.02±16.92) %] was lower than the control group [(66.27±17.90) %] (t=2.40, P=0.027) by novel object recognition tests. Compared with the control group [(63.56±11.88) %], the alternation of experimental group [(50.99±14.17) %] was significantly decreased in Y maze tests (t=2.33, P=0.030). Immunohistochemistry results showed microglia and astrocytes were activated in the cortex of experimental mice. Compared with the control group (1.02±0.25, 1.04±0.31), the relative mRNA expressions of Occludin decreased significantly in the meninges and brain of periodontitis mice, respectively (0.61±0.10, 0.64±0.20) (t=3.47, P=0.010; t=2.66, P=0.024). By single-cell RNA sequencing, meninges cells were divided into 11 types, such as endothelial cells, fibroblasts, immune cells and so on. Endothelial cells were the main cell types in meninges [the control group: 26.47% (1 589/6 004), the experimental group: 26.26% (807/3 073)]. Compared with the control group [5.56% (334/6 004)], the percentage of granulocytes increased in the periodontitis mice [11.65% (358/3 073)]. Using clustering analysis to further focus on endothelial cells, GO enrichment analysis revealed differential genes were mainly related to angiogenesis, cell adhesion, apoptosis and so on. KEGG enrichment analysis revealed that differential genes were related to signaling pathways of interleukin-17, relaxin and so on. The relative mRNA expressions of Atf3 and Apold1 in meninges of periodontitis mice (0.42±0.24, 0.54±0.27) were significantly lower than the control group (1.03±0.26, 1.02±0.23) (t=3.88, P=0.005; t=3.02, P=0.017). Conclusions: The mice chronically infected with Pg W83 occurred memory impairment, neuroinflammation and changes of barrier function. In the meninges of periodontitis mice, there were infiltration of immune cells and down-regulation expressions of Atf3 and Apold1 by single-cell RNA sequencing. Meningeal immunity and changes of barrier function may play an important role in the cognitive impairment caused by periodontitis.

[Comparison of the efficacy of different surgical strategies in the treatment of patients with initially resectable gastric cancer liver metastases].

Objective: To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM). Methods: This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging (M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results: (1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95%CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference (P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options (HR=1.98, 95%CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients' prognosis (HR=2.01, 95%CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors (HR=2.84, 95%CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver (HR=2.06, 95%CI 1.19 to 3.57, P=0.010). Conclusions: In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.

[Clinical effect of modified vertical rectus abdominis myocutaneous flap in repairing skin and soft tissue defects after abdominoperineal resection for rectal cancer].

Objective: To investigate the clinical effect of the modified vertical rectus abdominis myocutaneous flap in repairing the skin and soft tissue defect after abdominoperineal resection for rectal cancer. Methods: This study was a retrospective observational study. From June 2019 to July 2022, five male patients with low rectal cancer who were conformed to the inclusion criteria were admitted to the Department of Basic Surgery of Xiangya Hospital of Central South University, with ages ranging from 65 to 70 years and the sizes of the perianal skin ulcers ranging from 5 cm×4 cm to 11 cm×9 cm, and all of them underwent abdominoperineal resection. The secondary skin and soft tissue defects in the perineum with an area of 8 cm×6 cm-14 cm×12 cm (with the depth of pelvic floor dead space being 10-15 cm) were repaired intraoperatively with transplantation of modified vertical rectus abdominis myocutaneous flaps with the skin area being 9 cm×7 cm-16 cm×12 cm, the volume of the muscle being 18 cm×10 cm×5 cm-20 cm×12 cm×5 cm, and the vessel pedicle being 18-20 cm in length. During the operation, most of the anterior sheath of the rectus abdominis muscle was retained, the flap was transferred to the recipient area through the abdominal cavity, the remaining anterior sheaths of the rectus abdominis muscle on both sides of the donor area were repeatedly folded and sutured, the free edge of the transverse fascia of the abdomen was sutured with the anterior sheath of the rectus abdominis muscle, and the donor area skin was directly sutured. After the operation, the survival of the transplanted myocutaneous flap was observed. The occurrence of complications in the perineal recipient area was recorded within 2 weeks after the operation. The recovery of the perineal recipient area and the abdominal donor area was observed during follow-up, and the occurrence of complications in the donor area of the abdomen as well as the recurrence of tumors and metastasis were recorded. Results: All transplanted myocutaneous flaps in 5 patients survived after surgery. One patient had dehiscence of the incision in the perineal recipient area 2 days after surgery, which healed after 7 d with intermittent dressing changes and routine vacuum sealing drainage treatment. In the other 4 patients, no complications such as incisional rupture, incisional infection, or fat liquefaction occurred in the perineal recipient area within 2 weeks after surgery. Follow-up for 6-12 months after discharge showed that the skin of the perineal recipient area had good color, texture, and elasticity, and was not bloated in appearance; linear scars were left in the perineal recipient area and the abdominal donor area without obvious scar hyperplasia or hyperpigmentation; no complications such as incisional rupture, incisional infection, intestinal adhesion, intestinal obstruction, or weakening of the abdominal wall strength occurred in the abdominal donor area, and the abdominal appearance was good with no localized bulge or formation of abdominal hernia; there was no local recurrence of tumor or metastasis in any patient. Conclusions: The surgical approach of using the modified vertical rectus abdominis myocutaneous flap to repair the skin and soft tissue defects after abdominoperineal resection for rectal cancer is relatively simple in operation, can achieve good postoperative appearances of the donor and recipient areas with few complications, and is worthy of clinical promotion.

[Repair methods of complex facial defect wounds involving paranasal sinuses and their clinical effectiveness].

Objective: To explore the repair methods of complex facial defect wounds involving paranasal sinuses and their clinical effectiveness. Methods: A retrospective observational study was conducted. From January 2020 to May 2022, 5 patients admitted to the Department of Burns and Plastic Surgery of Xiangya Hospital of Central South University and 4 patients admitted to the Department of Burns and Plastic Surgery of Chenzhou First People's Hospital with complex facial defect wounds involving paranasal sinuses met the inclusion criteria, including 6 males and 3 females, aged 35-69 years, including 4 patients with titanium mesh exposure combined with paranasal sinuses injury and 5 patients with tumor involving paranasal sinuses. After an adequate assessment of the damage by a multiple discipline team, titanium mesh removal, paranasal sinus debridement, and paranasal sinus mucosa removal were performed in patients with exposed titanium mesh, and radical tumor resection was performed in patients with tumors, with postoperative skin and soft tissue defects areas of 5.0 cm×2.5 cm to 18.0 cm×7.0 cm, anterior paranasal sinus wall defects/absence areas of 3 cm×2 cm to 6 cm×4 cm, and sinus cavity depths of 1 to 4 cm. Depending on the perforator course of the descending branch of the lateral circumflex femoral artery, the anterolateral femoral chimeric flap or anterolateral femoral myocutaneous flap (with flap area of 9 cm×4 cm to 19 cm×8 cm, muscle size of 5 cm×3 cm×3 cm to 11 cm×6 cm×3 cm) was transplanted to repair the defect, and the donor site wound was sutured directly. The type of tissue flap transplanted, the blood vessel of the recipient area, and the vascular anastomosis way during the operation, the recovery of the donor and recipient areas and the occurrence of complications after operation were observed. The appearance and blood supply of the recipient area and the recurrence of ulcers and tumors were followed up. Results: The anterolateral femoral myocutaneous flap transplantation was performed in 6 patients, and the anterolateral femoral chimeric flap transplantation was performed in 3 patients. The blood vessels in recipient areas were facial arteries and veins in 3 cases and superficial temporal arteries and veins in 6 cases. The superficial temporal arteries and veins were bridged with blood vessels in tissue flaps by flow-through way in 2 patients, and end-to-end anastomosis of blood vessels in donor and recipient areas was performed in 7 patients. After operation, all the tissue flaps survived, and the facial defect wounds were well repaired without cerebrospinal fluid leakage or paranasal sinus secretion leakage, no intracranial infection occurred, and the wounds in donor areas were healed well. Follow-up of 6-35 months after operation showed that all the patients had good blood supply in the recipient area, and the shape was acceptable; 4 patients with exposed titanium mesh had no recurrence of ulceration, and 5 patients with tumor had no local tumor recurrence or metastasis. Conclusions: Based on an adequate assessment of the extent of paranasal sinuses involved in the facial wound and the nature of the defect, good clinical effects can be achieved by using the anterolateral femoral muscle flap or the anterolateral femoral chimeric flap transplantation to repair complex facial defect wounds with open paranasal sinuses.

Association of non-alcoholic fatty liver disease with total testosterone in non-overweight/obese men with type 2 diabetes mellitus.

PURPOSE: Non-alcoholic fatty liver disease (NAFLD) is considered as both a vital risk factor and a consequence of type 2 diabetes mellitus (T2DM). Low total testosterone (TT) is common in men with T2DM, contributing to increased risks of metabolic diseases. This study aimed to investigate the association between TT levels and the prevalence of NAFLD in men with T2DM. METHODS: In this cross-sectional study, 1005 men with T2DM were enrolled in National Metabolic Management Center (MMC) of First Affiliated Hospital of Wenzhou Medical University between January 2017 and August 2021. NAFLD was diagnosed using ultrasound as described by the Chinese Liver Disease Association. Overweight/obesity was defined as body mass index (BMI) ≥ 25 kg/m2 according to WHO BMI classifications. RESULTS: Individuals without NAFLD had higher serum TT levels than those with NAFLD. After adjustments for potential confounding factors, the top tertile was significantly associated with lower prevalence of NAFLD compared with the bottom tertile of TT level [odds ratio (OR) 0.303, 95% confidence interval (CI) 0.281-0.713; P < 0.001]. The association between TT with NAFLD in individuals with normal weight (OR 0.175, 95% CI 0.098-0.315; P < 0.001) was stronger than in individuals with overweight/obesity (OR 0.509, 95% CI 0.267-0.971; P = 0.040). There was a significant interaction of TT with overweight/obesity (P for interaction = 0.018 for NAFLD). CONCLUSION: Higher serum TT was significantly associated with a lower prevalence of NAFLD in men with T2DM. We found that the relationship of TT and NAFLD was stronger in individuals with non-overweight/obesity.

[Real-world data analysis of 3012 patients undergoing laparoscopic radical gastrectomy in a single center over the past 12 years].

Objective: To Summarize the safety, clinical outcome and technical evolution of laparoscopic gastric cancer surgery. Methods: A retrospective cohort study was carried out. Clinical data of 3012 patients who underwent laparoscopic radical gastrectomy for gastric cancer from January 2010 to March 2022 at Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University were retrospectively collected and analyzed. Case inclusion criteria were gastric malignancies confirmed by pathology, without distant metastasis by examination before operation and exploration during operation, patients undergoing laparoscopic radical gastrectomy, intact function of important organs and with complete data. Exclusion criteria were patients who underwent emergency gastric cancer resection due to gastric bleeding, perforation or obstruction, etc., tumor found to invade adjacent organs such as pancreas or transverse colon during the operation, conversion to open surgery during the operation, those who had other malignant tumors (except thyroid cancer) within 5 years, and those had severe cardiopulmonary, liver, or kidney insufficiency before surgery. Outcomes included: (1) baseline information of patients; (2) trend of the quantity of laparoscopic radical gastrectomy year by year; (3) evolution of the mode of digestive tract reconstruction; (4) periopertive outcome short-term complication was defined as complication occurring within 30 days after operation and classified accordiny to the clavien-Dindo criteria; and (5) 5-year overall survival. SPSS software was used for statistical analysis. Continuous variables that obeyed the normal distribution were expressed in the form of Mean±SD. Days of hospital stay that did not follow a normal distribution were expressed as median (Q1,Q3), and the Mann-Whiney U test was used for comparison. Discrete variables were expressed as cases (%), and chi-square test or rank sum test was used for comparison between groups. Linear regression analysis was used to analyze the relationship between the amount of surgery and the year of surgery. Kaplan-Meier method and log-rank test were used for survival analysis. Two-tailed P<0.05 was considered as statistically significant. Results: Among the 3012 cases, 2114 were male and 898 were female. The patients' average age at surgery was (61.1±10.7) years old. According to the number of cumulative cases, the patients were divided into three groups: early, intermediate and late, with 1004 patients in each group. The early group consisted of patients undergoing operation from January 2010 to October 2018, the intermediate group consisted of patients undergoing operation from October 2018 to January 2021, and the late group consisted of patients undergoing operation from January 2021 to March 2022. (1) General information: There were 691 (68.8%), 699 (69.6%) and 724 (72.1%) male patients in early, intermediate and late groups respectively; the average age increased from 56.6 years in 2010 to 62.8 years in March 2022. As for the tumor stage T1, T2, T3, T4, there were 49.0%, 14.4%, 23.9% and 12.6% in the early group; 47.5%, 12.9%, 26.9% and 12.6% in the intermediate group; 39.7%, 14.6%, 30.0%, and 15.6% in the late group, respectively. Patients with N0, N1, N2, N3a, N3b stage were 56.8%, 13.7%, 13.4%, 11.0%, and 5.0% in the early group; 55.7%, 12.9%, 12.8%, 11.6%, and 6.9% in the intermediate group; 51.0%, 16.1%, 12.8%, 12.5%, and 7.5% in the late group, respectively. (2) Year-by-year change in the number of gastric cancer operations: From 19 cases per year in 2010 to 786 per year in 2021, the annual number of gastric cancer operations was proportional to the year of operation (y=47.505x, R2=0.67). The proportion of patients with stage I disease showed a fluctuating downward trend over time, while the proportion of patients with stage III disease increased slightly, accounting for 34% until March 2022. (3) Evolution of digestive tract reconstruction methods: Except in 2010, the digestive tract reconstruction method of distal gastrectomy focused on Billroth-II+Braun anastomosis among patients undergoing laparoscopic gastric cancer surgery in other years, whose proportion had gradually increased from less than 20% in 2016 to about 70% after 2021; the gastrointestinal reconstruction methods after total gastrectomy had gradually increased in π anastomosis and overlap anastomosis since 2016, of which π anastomosis reached about 65% in 2019, and overlap anastomosis reached almost 30% in 2020; the anastomosis methods after proximal gastrectomy had been mainly double-channel anastomosis (54%) and esophagogastric anastomosis (30%) since 2016, and double-channel anastomosis accounted for up to 70% in 2019. (4) Operation time: The operation time of early, intermediate and late group was (193.3±49.8) min, (186.9±44.3) min and (206.7±51.4) min respectively. Intermediate group was significantly shorter than early group (t=3.005, P=0.003), while late group was significantly longer than early group (t=5.875, P<0.001) and intermediate group (t=9.180, P<0.001). (5) Postoperative hospital stay: The median length of hospital stay for gastric cancer patients in early, intermediate and late groups was 9 (8, 11) d, 8 (7, 10) d, and 8 (7.5, 10) d respectively. The postoperative hospital stay of intermediate group and late group was significantly shorter than that of early group (Z=-12.467, Z=-5.981, both P<0.001), but there was no significant difference between intermediate group and late group (Z=0.415,P=0.678). (6) Postoperative complication: The morbidity of short-term complication in early, intermediate and late group was 20.4% (205/1004), 16.2% (163/1004), and 16.2% (162/1004) respectively, and above morbidity of intermediate group and late group was significantly lower than that of early group (χ2=5.869, P=0.015; χ2=6.165, P=0.013), while there was no significant difference between intermediate group and late group (χ2=0.004,P=0.952). The morbidity of short-term complication of grade IIIor higher was 8.0% (80/1004), 7.6% (76/1004), and 4.9% (49/1004) in early, intermediate and late group respectively, and above morbidity of late group was significantly lower than that of early and intermediate group (χ2=7.965, P=0.005; χ2=6.219,P=0.013), while there was no significant difference between intermediate group and early group (χ2=0.111,P=0.739). (7) Survival analysis: The follow-up deadline for survival data was December 31, 2021, and the median follow-up time was 29.5 months. The overall 5-year survival rate of all the patients was 74.7%. The 5-year survival rates of stage I, II and III patients were 92.0%, 77.2%, and 40.3% respectively and 5-year survival rates of patients with stage IA, IB, IIA, IIB, IIIA, IIIB and IIIC were 93.2%, 87.8%, 81.1%, 72.7%, 46.2%, 37.1%, and 34.0% respectively. Conclusions: The number of laparoscopic gastric cancer operation in our center is increasing year by year. With the maturity of laparoscopic technology, the morbidity of complication in laparoscopic gastric cancer surgery is decreasing.

[Analysis of change in esophageal varices and clinical characteristics in hepatitis B virus-related cirrhosis after antiviral therapy].

Objective: To clarify the effect and related factors of antiviral therapy on the change of esophageal varices in patients with hepatitis B virus-related cirrhosis. Methods: Fifty-two cases with hepatitis B virus-related cirrhosis who underwent endoscopy before and after antiviral therapy were selected from prospective cohorts. Patients were divided into three groups: no, mild, and moderate-severe based on the degree of esophageal varices. The changes in the severity of esophageal varices in each group were compared after antiviral therapy. Clinical characteristics (platelet, liver and kidney function, liver stiffness, and virological response) of patients with different regressions were analyzed. Measurement data were analyzed by independent sample t-test, one-way ANOVA, Mann-Whitney U test and Kruskal-Wallis H test, and Chi-Square test was used for count data. Results: All patients received entecavir-based antiviral therapy. The median treatment time was 3.1 (2.5-4.4) years. The proportion of patients without esophageal varices increased from 30.8% to 51.9%, the proportion of mild esophageal varices decreased from 40.4% to 30.8%, and the proportion of patients with moderate-to-severe esophageal varices decreased from 28.8% to 17.3% (χ2=14.067, P=0.001). A total of 40.4% of patients had esophageal varices regression, and 13.5% had esophageal varices progression. The progression rate was significantly higher in patients with moderate-severe esophageal varices than patients with mild and no esophageal varices (χ2=28.126, P<0.001), and 60.0% of patients with moderate-severe esophageal varices still remained in moderate-severe state after antiviral treatment. Baseline platelet count and 5-year mean change rates were significantly lower in patients with progressive moderate-to-severe esophageal varices than in those without progression (+3.3% vs. +34.1%, Z=7.00, P=0.027). Conclusion: After effective antiviral treatment, 40.4% of patients with hepatitis B virus-related cirrhosis combined with esophageal varices has obtained esophageal varices regression, but those with moderate to severe esophageal varices still have a considerable risk of progression while receiving mono antiviral treatment only. Thrombocytopenia and without significant improving are the clinical signs of progression risk after receiving antiviral treatment.

[Gene expression signature analysis of peripheral blood mononuclear cells from patients with for high altitude pulmonary hypertension and value for potential drug selection].

Objective: To investigate the gene expression characteristics of peripheral blood mononuclear cells from patients with high altitude pulmonary hypertension (HAPH) in Naxi residents living in Lijiang, Yunnan, and to explore the underlying pathogenesis and value for potential drug selection. Methods: This is a case-control study. Six patients with HPAH (HPAH group) and 4 normal subjects (control group) were selected from the Naxi residents who originally lived in Lijiang, Yunnan Province. The general clinical data of the two groups were collected, and the related indexes of pulmonary artery pressure were collected. Peripheral blood mononuclear cells of the subjects were collected for RNA sequencing. The differences on gene expression, regulatory network of transcription factors and drug similarity between the two groups were compared. The results were compared with the public data of idiopathic pulmonary arterial hypertension (IPAH). Biological processes and signal pathways were analyzed and compared between HPAH and IPAH patients. Results: The age of 6 patients with HAPH was (68.1±8.3) years old, and there were 2 males (2/6). The age of 4 subjects in the control group was (62.3±10.9) years old, and there were 2 males (2/4). Tricuspid regurgitation velocity, tricuspid pressure gradient and pulmonary systolic pressure in HAPH group were significantly higher than those in control group (all P<0.05). The results of RNA sequencing showed that compared with the control group, 174 genes were significantly upregulated and 169 genes were downregulated in peripheral blood mononuclear cells of HAPH group. These differentially expressed genes were associated with 220 biological processes, 52 molecular functions and 23 cell components. A total of 21 biological processes and 2 signal pathways differed between HPAH and IPAH groups, most of which were related to inflammation and immune response. ZNF384, SP1 and STAT3 were selected as highly correlated transcription factors by transcription factor prediction analysis. Trichostatin A and vorinostat were screened out as potential drugs for the treatment of HAPH by drug similarity analysis. Conclusions: There are significant differences in gene expression in peripheral blood monocytes between HAPH patients and normal population, and inflammation and immune dysfunction are the main pathogenic factors. Trichostatin A and Vorinostat are potential drugs for the treatment of HAPH.

[Comparison of clinicopathological features for indications of different types of antiviral therapy in chronic hepatitis B].

Objective: To compare and analyze the clinicopathological features and significance for indications of different types of antiviral therapy in chronic hepatitis B (CHB). Methods: Clinical data of 861 CHB cases who received liver biopsy, had hepatitis B virus (HBV) DNA-positive (> 30 IU/ml) and met the indications for antiviral therapy from January 2014 to December 2019 were included. Liver pathological changes and their correlation with clinical characteristics were compared and analyzed. According to different data, t-test, analysis of variance, nonparametric test, χ2 test, Ridit and logistic regression analysis were used for statistical analysis. Results: Most of the cases (72.24%) had remarkable pathological damage. The degree of liver fibrosis was higher in the normal than the abnormal group (P<0.001). 17.54% cases had hepatic steatosis. The vast majority of cases (97.33%) had positive hepatitis B surface antigen (HBsAg), while only 50.87% had positive hepatitis B core antigen (HBcAg). The positive correlation factors affecting the severity of liver histopathology were alkaline phosphatase level, while the negative correlation factors were positive HBcAg staining, albumin and platelet level. The degree of liver inflammation and fibrosis had statistically significant differences with different HBcAg staining levels (χ2=44.142 and 102.386, respectively; P<0.001), and the severity was more apparent in the negative group. Conclusion: There exist differences in clinicopathological features for indications of different types of antiviral therapy in patients with CHB. Liver function test range is inconsistent with degrees of hepatic histological severity. The positive and intensity of liver tissue HBcAg staining, and albumin and alanine aminotransferase levels have negative correlation with disease severity.

[Clinicopathological analysis in patients with chronic hepatitis B virus infection in immune tolerant phase].

Objective: To analyze the liver pathology, clinical characteristics and influence factors in patients with chronic hepatitis B virus (HBV) infection in immune tolerant phase (IT). Methods: The clinical data of 273 patients in IT phase who underwent liver biopsy from January 2015 to December 2019 were included in this study. The correlation between liver pathological changes and clinical features was analyzed. Results: There were 43 cases (15.75%) with liver histologic activity ≥ G2, 30 cases (10.99%) with liver fibrosis ≥ S2, and 55 cases (20.15%) with liver pathology ≥ G2 and/or ≥ S2. A total of 17.95% patients had liver steatosis. The majority (98.17%) of tissue samples were positive for HBsAg staining, while only 79.49% were positive for HBcAg. The characteristics of liver pathology were comparable in men from women patients. The differences of G and S were not statistically significant according to different HBsAg positivity, while those were statistically significant according to different HBcAg positivity. By univariate and multivariate analysis, the independent risk factors of pathological severity were HBcAg intensity, HBeAg level, and age. However, the differences of liver histologic activity and fibrosis were not statistically significant between those younger than 30 years old group from those older than 30 years old, neither between those younger or older than 40. Although the diagnostic value of liver inflammation and fibrosis 5 (LIF-5) was better than that of aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis 4 score (FIB-4), three diagnostic models for predicting the pathological severity were not strong enough (all area under the curves<0.8). Only the specificity of LIF-5 for predicting≥ G2, ≥ G2 and/or ≥ S2 was over 80%. Conclusions: Approximately 20% patients with chronic HBV infection in IT phase have progressive liver inflammation or fibrosis. The intensity of liver HBcAg and HBeAg level are negatively correlated with the severity of disease. The diagnostic models or most clinical indicators have low predictive effect for chronic HBV infections in IT phase.

[Repair methods and clinical effects of full-thickness burn wounds deep to tendon or even bone in fingers].

Objective: To explore the repair methods and clinical effects of full-thickness burn wounds deep to tendon or even bone in fingers. Methods: A retrospective non-randomized controlled trial was conducted on the 98 patients with full-thickness finger burns deep to tendon or even bone who met the inclusion criteria and were hospitalized in Xiangya Hospital of Central South University from January 2010 to December 2019. Among the 98 patients, there were 81 males and 17 females, aged from 1 to 72 years, with 160 fingers involved. The wound area of each of affected fingers ranged from 2.0 cm×1.5 cm to 12.0 cm×3.5 cm, and the maximum wound area after merging the affected fingers was 12.0 cm×10.0 cm. For adult hands with multiple full-thickness burn wounds deep to tendon or even bone in multiple fingers or children with full-thickness finger burns deep to tendon or even bone, pedicled abdominal flaps were selected. For adults with single or two fingers with full-thickness burns deep to tendon or even bone, the pedicled internal hand flaps and free tissue flaps were selected. The free tissue flap repair requires good vascular conditions in the recipient area with arteries and veins available for anastomosis. For thumb nail burns deep to tendon or even bone or partial absence of the thumb after burns, the thumbs were reconstructed with the first toenail flap or dorsal foot flap with the second toe. In this study, 45 pedicled abdominal flaps were used to repair the wounds in 91 fingers, 37 pedicled internal hand flaps were used to repair the wounds in 37 fingers, 26 free tissue flaps were used to repair the wounds in 28 fingers, 3 first toenail flaps were used to reconstruct 3 patients' thumb nails and to repair hand wounds, and 1 dorsal foot flap with the second toe was used to reconstruct 1 patient's thumb and to repair hand and wrist wounds. The tissue flap area was from 2.0 cm×1.5 cm to 20.0 cm×10.0 cm. The wound in the donor site was repaired by direct suture or full-thickness skin grafting from the medial upper arm of the affected limb or split-thickness skin grafting from the outer thigh. The postoperative survival of the tissue flap, postoperative complications, and appearance and function of the flap donor site were observed. For the patients who were followed up, their finger functions were evaluated at the last follow-up using the trial criteria for replantation function evaluation of the amputated finger issued by the Hand Surgery Society of the Chinese Medical Association, and the satisfaction of the patients was investigated using the Efficacy Satisfaction Scale. Data were statistically analyzed with Kruskal-Wallis H test and Nemenyi test. Results: Of the 112 tissue flaps, 104 tissue flaps survived completely and had good blood circulation; 1 pedicled thumb dorsal ulnar reverse island flap, 1 pedicled finger artery cutaneous branch reverse island flap, and 1 free grafted anterolateral thigh perforator flap were slightly necrotic at the end, which were repaired with outer thigh split-thickness skin graft after dressing change and granulation tissue growth; 2 free grafted tarsal external artery flaps and 1 pedicled thumb dorsal ulnar reverse island flap suffered from postoperative venous return obstruction, which survived after partial suture removal and heparin saline cleansing of the wound; 1 pedicled modified dorsal metacarpal artery retrograde island flap and 1 free grafted peroneal artery perforator flap were necrotic, which were repaired by a pedicled abdominal flap and a lateral upper arm flap free transplantation respectively in stage Ⅱ. After transplantation, the tissue flaps had good shape, soft texture, and good elasticity, without bloating. There was no functional disorder in the flap donor site, and only slight scar remained. A total of 117 fingers of the 72 patients received 3-24 months of outpatient or telephone follow-up. At the last follow-up, the excellent and good rates of function evaluation of fingers repaired with pedicled abdominal flap, pedicled internal hand flap, and free tissue flap were respectively 77.3% (51/66), 96.3% (26/27), and 95.8% (23/24). The function of fingers repaired with free tissue flap and pedicled internal hand flap was significantly better than that with pedicled abdominal flap (P<0.01). The satisfaction of patients with fingers repaired by free tissue flaps was significantly higher than that by pedicled abdominal flap (P<0.05). Conclusions: According to the specific situation of full-thickness burn wounds deep to tendon or even bone in fingers, the pedicled abdominal flap is used to repair the multiple full-thickness burn wounds deep to tendon or even bone in multiple fingers of adult or the full-thickness burn wounds deep to tendon or even bone in fingers of children, the pedicled internal hand flap or free tissue flap is used to repair the full-thickness burn wounds deep to tendon or even bone in single or two fingers of adult patients, and the first toenail flap or the dorsal foot flap with the second toe is used to reconstruct the thumbs with full-thickness burn deep to tendon or even bone, with high postoperative tissue flap survival rate and few complications. The functional recovery of the affected finger is better after repair with free tissue flap and pedicled internal hand flap, and the patients' satisfaction is the highest after free tissue flap repair.

[Establishment and test results of an artificial intelligence burn depth recognition model based on convolutional neural network].

Objective: To establish an artificial intelligence burn depth recognition model based on convolutional neural network, and to test its effectiveness. Methods: In this evaluation study on diagnostic test, 484 wound photos of 221 burn patients in Xiangya Hospital of Central South University (hereinafter referred to as the author's unit) from January 2010 to December 2019 taken within 48 hours after injury which met the inclusion criteria were collected and numbered randomly. The target wounds were delineated by image viewing software, and the burn depth was judged by 3 attending doctors with more than 5-year professional experience in Department of Burns and Plastic Surgery of the author's unit. After marking the superficial partial-thickness burn, deep partial-thickness burn, or full-thickness burn in different colors, the burn wounds were cut according to 224×224 pixels to obtain 5 637 complete wound images. The image data generator was used to expand images of each burn depth to 10 000 images, after which, images of each burn depth were divided into training set, verification set, and test set according to the ratio of 7.0∶1.5∶1.5. Under Keras 2.2.4 Python 2.8.0 version, the residual network ResNet-50 of convolutional neural network was used to establish the artificial intelligence burn depth recognition model. The training set was input for training, and the verification set was used to adjust and optimize the model. The judging accuracy rate of various burn depths by the established model was tested by the test set, and precision, recall, and F1_score were calculated. The test results were visualized to generate two-dimensional tSNE cloud chart through the dimensionality reduction tool tSNE, and the distribution of various burn depths was observed. According to the sensitivity and specificity of the model for the recognition of 3 kinds of burn depths, the corresponding receiver operator characteristics (ROC) curve was drawn, and the area under the ROC curve was calculated. Results: (1) After the testing of the test set, the precisions of the artificial intelligence burn depth recognition model for the recognition of superficial partial-thickness burn, deep partial-thickness burn, or full-thickness burn were 84% (1 095/1 301), 81% (1 215/1 499) and 82% (1 395/1 700) respectively, the recall were 73% (1 095/1 500), 81% (1 215/1 500) and 93% (1 395/1 500) respectively, and the F1_scores were 0.78, 0.81, and 0.87 respectively. (2) tSNE cloud chart showed that there was small overlapping among different burn depths in the test results for the test set of artificial intelligence burn depth recognition model, among which the overlapping between superficial partial-thickness burn and deep partial-thickness burn and that between deep partial-thickness burn and full-thickness burn were relatively more, while the overlapping between superficial partial-thickness burn and full-thickness burn was relatively less. (3) The area under the ROC curve for 3 kinds of burn depths recognized by the artificial intelligence burn depth recognition model was ≥0.94. Conclusions: The artificial intelligence burn depth recognition model established by ResNet-50 network can rather accurately identify the burn depth in the early wound photos of burn patients, especially superficial partial-thickness burn and full-thickness burn. It is expected to be used clinically to assist the diagnosis of burn depth and improve the diagnostic accuracy.

[Clinical effectiveness of simultaneous reconstructions of multiple joint scar contracture deformity of limb].

Objective: To explore the clinical effects of simultaneous reconstruction of multiple joint scar contracture deformity of limb. Methods: From January 2010 to June 2018, 24 patients with multiple joint scar contracture deformity of the same limb were reconstructed in simultaneous operations in Xiangya Hospital of Central South University, including 16 males and 8 females, aged 3-42 years, with 15 patients having deformities in the upper limbs and 9 patients having deformities in the lower limbs. One operation was performed to repair contracture deformity of axillary fossa and elbow in 3 patients, cubital fossa and palmar of wrist in 4 patients, cubital fossa and hand in 5 patients, palmar of wrist, palm, and palmar of finger in 3 patients, groin and medial knee in 2 patients, popliteal fossa and posterior ankle in 1 patient, and anterior ankle and dorsum of foot in 6 patients. After the release of various joint scar contractures, the area of skin defect was 140 to 580 cm(2). Autologous full-thickness skin grafts were used in 7 patients, autologous medium-thickness skin grafts were used in 4 patients, autologous full-thickness skin grafts combined with local skin flaps were used in 9 patients, and allogeneic acellular dermal matrix and autologous thin skin grafts were used in 4 patients. Comprehensive measures for rehabilitation were taken and the survival of the skin graft was observed after operation. Six months to eight years after the operation, all the patients were followed up for the functions of the affected limbs, among which the functions of the upper limbs were evaluated according to the trial standard for the evaluation of the functions of the upper limbs of the Hand Surgery Society of the Chinese Medical Association. The joint mobility, walking, and squatting function of lower extremity were examined after operation. Recurrence of contractures in all the affected limbs and reoperation were recorded. Results: The grafts survived after operation in 22 patients. Two patients had necrosis in small full-thickness skin area, of which one was healed by skin grafting after debridement, and the other one was healed after dressing changes. The deformity of scar contracture at each repaired joint was completely or partially corrected. During a follow-up for 6 to 96 months, the upper limb functions of 15 patients were rated excellent in 12 patients and good in 3 patients. Among the 9 patients of lower limb scar contractures, except for one 3-year-old child who experienced recurrence of medial knee scar contracture and underwent surgical release and skin grafting 5 years later, the remaining 8 patients basically recovered normal joint functions with pretty good outcomes. Conclusions: For continuous scar contracture deformity of multiple joints of the same limb, simultaneous surgical release and skin grafting can reduce operation frequency and obtain better outcomes of surgical operation.

Expanding the phenotypic and genetic spectrum of Chinese patients with congenital absence of vas deferens bearing CFTR and ADGRG2 alleles.

BACKGROUND: Congenital absence of vas deferens (CAVD) is a major cause of obstructive azoospermia. Mutations in CFTR and ADGRG2 are responsible for this disease. However, until now the genetic spectrum of the CFTR and ADGRG2 genes in Chinese population and the reasons of the differences from Caucasian cohorts were not clear. OBJECTIVES: (i) To study the characteristic and functional consequences of CFTR and ADGRG2 mutations in Chinese CAVD patients. (ii) To describe the genetic spectrum of Chinese CAVD patients and explain the reasons of the differences from Caucasian cohorts and Chinese cystic fibrosis (CF) patients. MATERIALS AND METHODS: Patients were screened for mutations in CFTR by Sanger sequencing. Patients with only one or no mutations were further investigated by multiplex ligation-dependent probe amplification analysis and direct sequencing of ADGRG2 gene. Bioinformatic analysis and structural modeling of proteins were performed. RESULTS: A total of 28 mutations in CFTR were identified in 72 patients, of which five mutations were novel. Fifty-five patients (76.39%) had CFTR mutations but no indels, among which 80.00% CBAVD patients have at least one CFTR mutation and 66.67% CUAVD have at least one CFTR mutation. Two novel mutations (p.Lys818* and p.Arg1008Gln) in ADGRG2 were detected. These novel mutations were predicted to be damaging by bioinformatics and were absent or extremely low frequency among our controls and databases. The genetic spectrum of Chinese CAVD patients revealed that the most common mutations were c.1210-12T[5], p.Ile556Val and p.Gln1352His, the last two of which were predicted to reduce the domains' contacts and weaken adenosine triphosphate binding. DISCUSSION AND CONCLUSION: This study illustrates the significance of all exon sequencing in CFTR and ADGRG2. A picture of the genetic spectrum of Chinese CAVD patients and the most common mutations can be described, which are different from Caucasian cohorts and Chinese CF patients.

[Disparity of minnesota multiphasic personality inventory between positions and its relationship with job burnout in a general hospital].

Objective: To explore the difference of personality characteristics of physicians, nurses, medical skills and administrative personnel in a general hospital and its influence on job burnout. Methods: Employee entered the hospital before 2018 were enrolled in the current study and the position was classified as physicians, nurses, medical technician and administrative staff. Minnesota Multiphasic Personality Inventory (MMPI) was completed by the employee at the time of entering the hospital. Status of job burnout was assessed in 2018 using the Maslach Burnout Inventory-General Survey (MBI-GS) . Results: Physicians have a higher rate of paranoia than others (P<0.05) , and administrative staff and medical technician have a slightly higher score than the other two categories of people (P<0.05) , and administrators lie at a higher rate than others (P<0.05) . Further analysis found that personality traits did not have a significant association with job burnout at the time of entry. Conclusion: The administrative and medical staff is slightly more irritable, the administrative staff lying slightly higher score, the staff after the entry of job burnout is not affected by the personality characteristics of the onboarding.

[Reversal of cirrhotic decompensation: re-compensation].

Liver cirrhosis is the end stage of chronic liver disease and as the disease progresses to decompensated stage cirrhosis, the mortality rate of patients' increases significantly. The goal of controlling the etiology or treatment in decompensated stage cirrhosis is to improve the liver function of patients, stabilize the disease condition or reverse decompensation, reduce the recurrence of decompensated events and reduce the mortality rate. However, presently, there are few studies on the reversal of cirrhotic decompensation/ re-compensation. Moreover, the effect of prophylactic treatment on re-compensation, evaluation indicators and duration of re-compensation, structure of hepatic lobules and whether microvessels can be reconstructed are unclear, so require further research.

[Clinical application of negative pressure dressing in the full-thickness skin grafting].

Objective: To investigate the effect of different negative pressure of wound negative pressure dressing (NPD) on the survival of full-thickness skin grafts of patients. Methods: One hundred and eleven patients who need skin grafting, conforming to the inclusion criteria were hospitalized in our unit from August 2012 to March 2017, and their clinical data were retrospectively analyzed. Forty-seven patients hospitalized from August 2012 to October 2015 were assigned into traditional treatment group. Sixty-four patients hospitalized from November 2015 to March 2017 were divided into -9.975 kPa negative pressure treatment group (n=34) and -13.300 kPa negative pressure treatment group (n=30). Patients in traditional treatment group received conventional dressing after full-thickness skin grafting. Patients in -9.975 kPa and -13.300 kPa negative pressure treatment groups received -9.975 kPa and -13.300 kPa NPD based on traditional treatment after vacuum sealing, respectively. Dot necrosis area of skin grafts and erosion and escharosis of graft edges of patients in the three groups on post operation day 10 were observed. The percentage of dot necrosis area of skin grafts and occurrence rate of erosion and escharosis of skin graft edges were calculated, respectively. Data were processed with chi-square test, Fisher's exact test, and Kruskal-Wallis H test. Results: Percentages of dot necrosis area of skin grafts of patients in traditional treatment group and -9.975 kPa and -13.300 kPa negative pressure treatment groups were 17.81%, 3.20%, and 3.00%, respectively. Percentage of dot necrosis area of skin grafts of patients in traditional treatment group was significantly higher than that in -9.975 kPa and -13.300 kPa negative pressure treatment groups (Z=-5.770, -4.690, P<0.001). Percentages of dot necrosis area of skin grafts of patients in -9.975 kPa and-13.300 kPa groups were close (Z=-0.619, P>0.05). The occurrence rates of erosion and escharosis of skin graft edges of patients in traditional treatment group and -9.975 kPa and -13.300 kPa negative pressure treatment groups were 78.7% (37/47), 32.4 (11/34), and 36.7% (11/30), respectively. Erosion and escharosis of skin graft edges of patients in -9.975 kPa and -13.300 kPa negative pressure treatment groups were better than those in traditional treatment group (P<0.001). Erosion and escharosis of skin graft edges of patients in -9.975 kPa and -13.300 kPa negative pressure treatment groups were close (P>0.05). Conclusions: The use of -9.975 kPa and -13.300 kPa NPD in skin grafts after full-thickness skin grafting significantly diminishes the occurrence rates of dot necrosis area of skin grafts and erosion and escharosis of graft edges.

Effect of calcium pyrophosphate on microstructural evolution and in vitro biocompatibility of Ti-35Nb-7Zr composite by spark plasma sintering.

ß-type Ti-35Nb-7Zr alloy has attracted considerable attentions as a bone implant material. The alloy, however, has poor bioactivity, which difficult to form a strong osseointegration between the bone tissues. Combining Ti alloy with a bioactive and biodegradable ceramic has been of interest to researchers. But the large difference in physicochemical property of high-melting metal and ceramic elements would bring the manufacturing restriction. In this work, Ti-35Nb-7Zr-CPP composites were fabricated with mechanical alloy of Ti, Nb, Zr and Nano calcium pyrophosphate (CPP) powders mixture followed by spark plasma sintering (SPS) routes. The effect of CPP ceramic on microstructural evolution and in vitro biocompatibility were investigated. As the addition of CPP (10-30 wt%), ceramic elements spreading towards the matrix, the generated metal-ceramic bioactive phases CaTiO3 are observed well consolidated with ß-Ti matrix. With the CPP increasing, Ca and P atoms rapidly migrated to the ß-Ti matrix to form granulated Ti5P3, which leads to the increasing porosity (10%-18%) in the composites. The results demonstrated that the favorable cell viability (the cell proliferation rates were higher than 100%) and growth inside the pores of the composites arise from the rough micro-porous surface and the release of bioactive metal-ceramic phase ions into the biological environment. The enhanced bioactivity and microstructural evolution behaviors of the Ti-35Nb-7Zr-CPP composites may provide a strategy for designing and fabricating multifunctional implants.