Interaction between handgrip strength and vitamin D deficiency on all-cause mortality in community-dwelling older adults: a prospective cohort study.

OBJECTIVE: Muscle strength decline and vitamin D deficiency are coexisting conditions associated with multiple adverse health outcomes. This prospective study aimed to investigate the multiplicative and additive interactions between handgrip strength (HS) and serum 25-hydroxyvitamin D [25(OH)D] on all-cause mortality in Chinese community-dwelling older adults. STUDY DESIGN: This is a population-based cohort study. METHODS: 2635 older adults (85.15 ± 12.01 years) were recruited from the Chinese Longitudinal Healthy Longevity Survey (2012-2018). Low HS was defined according to the Asian Working Group for Sarcopenia 2019 updated consensus (<28 kg for men and <18 kg for women). Serum 25(OH)D < 50 nmol/L were defined as vitamin D deficiency. Cox proportional hazard models were used to examine the association of HS and 25(OH)D with all-cause mortality. Socio-demographics, health status, and clinical characteristics were included as covariates. RESULTS: 1715 (65.09 %) and 1885 (71.54 %) participants had low HS and vitamin D deficiency, respectively. During a median follow-up of 3.52 years, 1107 older people died. After multivariable adjustment, both HS and 25(OH)D levels were inversely associated with all-cause mortality risk (Ps < 0.001). The hazard ratios (HRs) of low HS and vitamin D deficiency for all-cause mortality were 1.73 (95 % CI: 1.41-2.13) and 1.61 (95 % CI: 1.32-1.93), respectively. Although significant multiplicative interactions were not found, the association between low HS and all-cause mortality was attenuated in the higher 25(OH)D subgroup than in the lower 25(OH)D subgroup (stratified by 50 nmol/L). The multiple-adjusted HR of mortality for combined low HS and vitamin D deficiency was 2.18 (95 % CI: 1.73-2.56), which was higher than that for these two conditions alone. Significant additive interactions between low HS and vitamin D deficiency on mortality were observed (relative excess risk due to interaction: 0.71, 95 % CI: 0.37-1.05). CONCLUSIONS: Low HS and low 25(OH)D levels synergistically increased the risk of all-cause mortality. Our results added new insights to the priority of early detection for older adults with comorbid muscle strength decline and vitamin D deficiency.

[Comparison of 1-year outcomes between Roux-en-Y gastric bypass and sleeve gastrectomy with Roux-en-Y duodenojejunal bypass in the patients of obesity with type 2 diabetes mellitus].

Objective: To compare the 1-year effects of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy with Roux-en-Y duodenal bypass (SG+RYDJB) on weight loss, remission of diabetes, and postoperative complications in patients with obesity and type 2 diabetes. Methods: A single-center retrospective cohort study was conducted at the First Affiliated Hospital of Nanjing Medical University from January 2020 to December 2020. Sixty-four patients with type 2 diabetes and body mass index (BMI) of 27.5-40.0 kg/m2 were included in this study and divided into the RYGB group (n=34) and the SG+RYDJB group (n=30). In both procedures, the biliopancreatic branch was measured 100 cm distal to the Treitz ligament, and the food branch was measured 100 cm distal to the gastric or duodenojejunal anastomosis. Patients were followed up by telephone or WeChat, a free messaging and calling app at 1, 3, 6, and 12 months postoperatively to determine their weight loss and remission of diabetes. The primary outcomes were the weight loss and reduction in blood glucose concentrations at 1 year after surgery and postoperative complications. Other postoperative changes, including body weight, BMI, percentage of total weight loss (%TWL), percentage of excess weight loss (%EWL), glycated hemoglobin A1c (HbA1c), and fasting blood glucose at 1 year after surgery were also assessed. Results: There were no significant differences in baseline data between the two groups (all P>0.05). No conversion to open surgery or death occurred in either group. Operation time was longer in the SG+RYDJB than the RYGB group (137.8±22.1 minutes vs. 80.0±24.9 minutes, t=9.779, P<0.001) and the incidence of perioperative complications was higher in the SG+RYDJB than the RYGB group (20% [6/30] vs. 2.9% [1/34], χ2=4.761, P=0.029). However, the postoperative hospital stay was similar between the two groups [3.0 (3.0, 4.3) days vs. 3.0 (4.0, 6.0) days, U=641.500, P=0.071]. Perioperative complications comprised small gastric pouch anastomotic leakage in one patient in the RYGB group and leakage (three patients) and bleeding (two patients with gastrointestinal bleeding and one with trocar site bleeding) in the SG+RYDJB group. Long-term complications were as follows. The incidence of anemia was significantly higher in the RYGB than the SG+RYDJB group (26.5% [9/34] vs. 3.3% [1/30], χ2=6.472, P=0.011). However, there were no significant differences in incidences of postoperative reflux, dumping syndrome, alopecia, diarrhea, constipation or foul-smelling flatus between the two groups (all P>0.05). Compared with 1 year before surgery, the body weights and fasting plasma glucose concentrations of patients in the SG+RYDJB and RYGB group (72.4±10.6 kg vs. 98.5±14.2 kg, respectively; 68.2±10.0 kg vs. 91.9±14.8 kg, respectively), BMI (25.2±2.9 kg/m2 vs. 34.3±4.2 kg/m2, respectively; 24.3±2.4 kg/m2 vs. 32.7±3.7 kg/m2, respectively) (5.5±1.6 vs. 10.6±3.3, respectively; 5.8±2.1 vs. 9.0±3.4, respectively); HbA1c (5.7±0.8 vs. 9.7±1.2, respectively; 9.1±1.9 vs. 5.9±0.9, respectively) were significantly lower at 1 year after surgery (all P<0.05). However, the % TWL (26.5%±6.0% vs. 25.6%±4.4%, t=0.663, P=0.510) and % EWL (109.1%±38.2% vs. 109.4%±40.3%, t=-0.026, P=0.026), rate of complete remission of diabetes at 1 year (80.0% [24/30] vs. 82.4% [28/34], χ2=0.058, P=0.810] did not differ significantly between the two groups (all P>0.05). Conclusions: Although SG+RYDJB surgery compared with RYGB is more difficult to perform, it can achieve similar weight loss and remission of diabetes and is associated with a lower incidence of anemia because of the preservation of the pylorus.

Q-TWiST analysis of survival benefits with brigatinib versus crizotinib in patients with anaplastic lymphoma kinase-positive non-small cell lung cancer based on results of the ALTA-1L trial.

OBJECTIVES: The ALTA-1L phase 3 open-label trial demonstrated increased progression-free survival (PFS) with brigatinib versus crizotinib in patients with anaplastic lymphoma kinase-positive (ALK-positive) locally advanced or metastatic non-small cell lung cancer (NSCLC) previously untreated with ALK-targeted therapy. This post-hoc analysis of data from the ALTA-1L trial used the quality-adjusted (QA) time without symptoms of disease or toxicity (Q-TWiST) methodology to compare the QA survival benefit of brigatinib versus crizotinib in this patient population. PATIENTS AND METHODS: The Q-TWiST analysis was performed using final (January 29, 2021) individual patient-level blinded independent review committee (BIRC)- and investigator-assessed survival data for brigatinib (n = 137) and crizotinib (n = 138) in adult patients (N = 275) with ALK-positive locally advanced or metastatic NSCLC previously untreated with ALK-targeted therapy. Q-TWiST was compared between the two treatments. Subgroup analyses were performed in patients stratified by various clinicopathological characteristics, including presence or absence of brain metastases at baseline. RESULTS: Brigatinib was associated with significantly longer time without symptoms of disease or toxicity (P < 0.001) than crizotinib, with significantly greater Q-TWiST (mean [SE] months: BIRC-assessed, 28.2 [1.2] versus 25.1 [1.1], P = 0.045; investigator-assessed, 28.5 [1.2] versus 24.8 [1.1], P = 0.018). Relative gains in Q-TWiST with brigatinib compared to crizotinib were clinically meaningful (BIRC-assessed, 10.4%; investigator-assessed, 12.3%). Patients with brain metastases at baseline receiving brigatinib had significantly greater Q-TWiST (mean [SE] months: BIRC-assessed, 29.0 [1.9] versus 19.0 [1.9], P = 0.0001) than those receiving crizotinib. CONCLUSION: First-line brigatinib treatment was associated with significant and clinically meaningful gains in Q-TWiST compared to crizotinib in patients with ALK-positive locally advanced or metastatic NSCLC, supporting the results of the ALTA-1L trial and brigatinib as a safe and effective first-line treatment for ALK-positive NSCLC.

[Membrane anatomy-based splenic hilar lymph node dissection for gastric cancer].

There is a consensus that selectively perform splenic lymph node dissection is necessary for high-risk patients with proximal gastric cancer to achieve radical treatment. However, there are still some outstanding issues that need to be solved during the practice of splenic lymph node dissection. These include poorly defined boundaries, technical difficulties, and blurred boundaries in No. 10 and No. 11 lymph nodes, etc. Membrane anatomy has achieved successful applications in the field of gastric and colorectal surgery in recent years. The study of membrane anatomy in the splenic hilum region is controversial due to the special location of the splenic hilum, which involves multiple organs and affiliated mesentery undergoing complex rotation, folding, and fusion during embryonic development. In this manuscript, we summarize the following points based on existing research and personal experience regarding membrane anatomy. 1. There is a membrane anatomical structure that can be used for lymph node dissection in the splenic hilum region. 2. The membrane structure in the splenic hilum region can be divided into two layers: the superficial layer is composed of the dorsal mesogastrium, and the deep layer is composed of Gerota fascia, the tail of the pancreas, and the mesentery of the transverse colon (from head to tail). 3. There is a loose space between the two layers that can be used for separation during surgery. The resection of the dorsal mesogastrium belongs to D2 dissection. The No. 10 lymph node in the deeper layer belongs to the duodenal mesentery, and the resection of the No.10 lymph node exceeds D2 dissection. The complete excision of the gastric dorsal mesentery is consistent with the D2+CME surgical mode proposed by Gong Jianping's group.

[Development of membrane anatomy theory in gastric cancer surgery].

In the past decade, the concept of membrane anatomy has been gradually applied in gastric cancer surgery. Based on this theory, D2 lymphadenectomy plus complete mesogastric excision (D2+CME) has been proposed, which has been demonstrated to significantly reduce intraoperative bleeding and intraperitoneal free cancer cells during surgery, decrease surgical complications, and improve survival. These results indicate that membrane anatomy is feasible and efficacious in gastric cancer surgery. In this review, we will describe the important contents of membrane anatomy, including "Metastasis V"(2013, 2015), proximal segmentation of dorsal mesogastrium (2015), D2+CME procedure (2016), "cancer leak"(2018), and surgical outcomes of D2+CME (2022).

[Impact of the depth of remission by induction chemotherapy on the prognosis of limited stage small cell lung cancer].

Objective: To evaluate the effect of depth of remission of induction chemotherapy on the overall prognosis of limited stage small cell lung cancer (L-SCLC). Methods: The study was a retrospective, L-SCLC patients who contained complete imaging data and underwent consecutive standardized treatments at the Department of Thoracic Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University between January 2013 and June 2021 were included. To delineate the volume of tumor before and after induction chemotherapy and to calculate the depth of remission caused by the induced chemotherapy. The time receiver operating characteristic (timeROC) method was used to determine the optimal predictors for prognosis, multi-factor analysis using Cox risk proportional model. Results: A total of 104 patients were included in this study. The median PFS and OS of this cohort were 13.7 months and 20.9 months, respectively. It was observed by timeROC analysis that residual tumor volume after induction chemotherapy had the optimal predictive value of PFS at 1 year (AUC=0.86, 95% CI: 0.78~0.94) and OS at 2 years (AUC=0.76, 95% CI: 0.65~0.87). Multivariate analysis showed residual tumor volume after induction chemotherapy was the independent prognostic factor to PFS (HR=1.006, 95% CI: 1.003~1.009, P<0.01) and OS (HR=1.009, 95% CI: 1.005~1.012, P<0.001). For those whose residual tumor volume remitted to less than 10 cm(3) after induction chemotherapy, the favorable long-term outcomes could be achieved, regardless of their initial tumor load. Conclusion: The depth of remission of induction chemotherapy could be a promising prognostic predictor to the L-SCLC and provide the individualized treatment guidance.

[The value of machine learning models based on biparametric MRI for diagnosis of prostate cancer and clinically significant prostate cancer].

Objective: To evaluate the value of machine learning (ML) models based on biparametric magnetic resonance imaging (bpMRI) for diagnosis of prostate cancer (PCa) and clinically significant prostate cancer (csPCa). Methods: A total of 1 368 patients, aged from 30 to 92 (69.4±8.2) years, from 3 tertiary medical centers in Jiangsu Province were retrospectively collected from May 2015 to December 2020, including 412 cases of csPCa, 242 cases of clinically insignificant prostate cancer (ciPCa) and 714 cases of benign prostate lesions. The data of center 1 and center 2 were randomly divided into training cohort and internal testing cohort at a ratio of 7∶3 by random number sampling without replacement using Python Random package, and the data of center 3 were used as the independent external testing cohort. The training cohort includs 243 cases of csPCa, 135 cases of ciPCa and 384 cases of benign lesions, the internal testing cohort includs 104 cases of csPCa, 58 cases of ciPCa and 165 cases of benign lesions, and the external testing cohort includs 65 cases of csPCa, 49 cases of ciPCa and 165 cases of benign lesions. The radiomics features were extracted on T2-weighted imaging, diffusion-weighted imaging and apparent diffusion coefficient map, and optimal radiomics features were selected by using Pearson correlation coefficient method and analysis of variance. The ML models were built using two ML algorithms, including support vector machine and random forest (RF) and were further tested in the internal testing cohort and external testing cohort. Finally, the PI-RADS scores evaluated by the radiologists were adjusted by the ML models which had superior diagnostic performance, namely adjusted PI-RADS. The receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of the ML models and PI-RADS. DeLong test was used to compare the areas under curve (AUC) of models with those of PI-RADS. Results: For PCa diagnosis, in internal testing cohort, the AUC of ML model using RF algorithm and PI-RADS were 0.869 (95%CI: 0.830-0.908) and 0.874 (95%CI: 0.836-0.913), respectively, and the difference between the model and PI-RADS did not reach to the statistical significance (P=0.793). In the external testing cohort, the AUC of model and PI-RADS were 0.845 (95%CI: 0.794-0.897) and 0.915 (95%CI: 0.880-0.951), respectively, and the difference was statistically significant (P=0.01). For csPCa diagnosis, the AUC of ML model using RF algorithm and PI-RADS were 0.874 (95%CI: 0.834-0.914) and 0.892 (95%CI: 0.857-0.927), respectively, in internal testing cohort, and the difference between the model and PI-RADS was not statistically significant (P=0.341). In the external testing cohort, the AUC of model and PI-RADS were 0.876 (95%CI: 0.831-0.920) and 0.884 (95%CI: 0.841-0.926), respectively, and the difference between the model and PI-RADS was not statistically significant (P=0.704). When PI-RADS assessment was adjusted with the assistance of ML models, the specificities increased from 63.0% to 80.0% in the internal testing cohort and from 92.7% to 93.3% in the external test group in diagnosing PCa. In diagnosing csPCa, the specificities increased from 52.5% to 72.6% in the internal testing cohort and from 75.2% to 79.9% in the external testing cohort. Conclusions: The ML models based on bpMRI showed comparable diagnostic performance to PI-RADS assessed by senior radiologists and achieved good generalization ability in both diagnosing PCa and csPCa. The specificities of the PI-RADS were improved by ML models.

[Clinical efficacy and prognostic risk factors of salvage liver transplantation, rehepatectomy, and local ablation in the treatment of postoperative recurrence of hepatocellular carcinoma].

Objective: To investigate and analyze the clinical efficacy of salvage liver transplantation (SLT), rehepatectomy (RH), local ablation (LA), and prognostic risk factors in patients with postoperative recurrence of hepatocellular carcinoma. Methods: Clinical data of 145 patients with recurrent liver cancer in the 900th Hospital of the Joint Logistics Support Force of the People's Liberation Army from January 2005 to June 2018 were retrospectively collected. SLT group, RH group, and LA group included 25, 44, and 76 cases, respectively. Follow-up and statistics were recorded on the overall survival rate, relapse-free survival rate, and complications of the three groups of patients at 1, 2, and 3 years after surgery. Univariate and multivariate COX analyses were used to analyze the prognostic risk factors in patients with recurrent HCC. Results: The overall survival rates of 1, 2, and 3 years following surgery in the SLT, RH, and LA groups were 100.0%, 84.0%, 72.0%, 95.5%, 77.3%, 65.9%, 90.8%, 76.3%, and 63.2%, respectively, when the recurrence of liver cancer met the Milan criteria. The overall survival rate did not differ statistically between SLT and RH (P = 0.303) or between RH and LA (P = 0.152). There were statistically significant differences in recurrence-free survival between SLT and RH or RH and LA (P = 0.046). There was no statistically significant difference in the incidence of complications between SLT and RH or RH and LA (P > 0.017). Age > 65 years was an independent risk factor affecting the overall survival rate in patients with recurrent HCC. Age > 65 years and recurrence time < 24 months were independent risk factors affecting the recurrence-free survival rate in patients with recurrent HCC. Conclusion: SLT is the best treatment option when the recurrence of HCC meets Milan's criteria. RH and LA are the appropriate treatment plans for recurrent HCC when the liver source is limited.

Incidence of sacroiliac joint pain after lumbosacral spine fusion: A systematic review.

OBJECTIVES: To determine the incidence of sacroiliac joint (SIJ) pain after lumbosacral spinal fusion. BACKGROUND: Persistent low back pain is a potential source of disability and poor outcomes following lumbar spine fusion. The SIJ has been described as a potential source. However, there is a paucity of data concerning its importance. METHODS: This is a PROSPERO registered systematic review. A systematic search of the English literature was performed in Medline, Embase and Cochrane Library databases. MeSH terms such as Lumbar vertebrae, Sacrum, Spinal Fusion, Pain, Sacrum, Ligaments, Sacroiliac Joint were utilized for the search. Key words such as "sacroiliac dysfunction.mp." and "sacroiliac complex.mp." were utilized for the search. Two independent reviewers reviewed articles to determine eligibility for final review and analysis. The Newcastle-Ottawa Scale was used to appraise the quality of all nonrandomized observational studies. Inverse variance weighting with random effects was used to pool data. The GRADE approach, PRISMA workflow and checklists was performed. RESULTS: Twelve studies were included. All studies were observational and of moderate to low quality. The pooled incidence of sacroiliac joint pain was 15.8%. The pooled incidence of SIJ pain for patients without fusion extending to the sacrum was 15.8%. The pooled incidence of SIJ pain for patients with fusion extending to the sacrum was 32.9%. There was high heterogeneity. CONCLUSION: SIJ pain is a potential cause of persistent pain after lumbar spine surgery. The current literature of poor quality. Patients presenting with pain after lumbosacral spine fusion should be evaluated for SIJ related pain.

[Characteristics of plasma Epstein-Barr virus DNA in children with primary infection].

Objective: To explore the characteristics of plasma Epstein-Barr virus (EBV) DNA in primary infection in pediatric cases. Methods: The laboratory and clinical data of 571 children diagnosed with EBV primary infection in Children's Hospital of Fudan University during September 1st, 2017 to September 30th, 2018 were retrospectively analyzed. According to the results of plasma EBV DNA, they were divided into positive group and negative group. According to the EBV DNA, they were devided into high plasma virol load group and low plasma virol load group. The Chi-square test, Wilcoxon rank sum test were used to compare the differences between groups. Results: Among the 571 children with EBV primary infection, 334 were males and 237 were females. The age of first diagnosis was 3.8 (2.2, 5.7) years. There were 255 cases in positive group and 316 cases in negative group. The percentage of cases with fever,hepatomegaly and (or) splenomegaly, elevated transaminase in the positive group were higher than those in the negative group (235 cases (92.2%) vs. 255 cases (80.7%), χ2=15.22, P<0.001; 169 cases (66.3%) vs. 85 cases (26.9%), χ2=96.80, P<0.001; and 144 cases (56.5%) vs. 120 cases (38.0%), χ2=18.27, P<0.001; respectively).In the positive group, 70 cases were followed up for 46 (27, 106) days, 68 cases (97.1%) turned negative within 28 days, with the exception of 2 cases (2.9%) developed chronic active EBV infection by follow-up revision.There were 218 cases in high plasma viral DNA copies group and 37 cases in low copies group. More cases presented with elevated transaminases in the high plasma viral DNA copies group than those in the low group (75.7% (28/37) vs. 56.0%(116/207), χ2=5.00, P=0.025).Both the positive rate of EBV DNA in peripheral blood leukocytes (84.2% (266/316) vs. 44.7% (255/571), χ2=76.26, P<0.001) and the copies of EBV DNA (7.0×107 (1.3×107, 3.0×108) vs. 3.1×106 (1.6×106, 6.1×106) copies /L, Z=15.23, P<0.001) were higher than that of plasma. Conclusions: In immunocompetent pediatric cases diagnosed as EBV primary infection, cases with positive plasma EBV DNA were prone to have fever, hepatomegaly and (or) splenomegaly, and elevated transaminase than those with negative plasma viral DNA. The plasma EBV DNA usually turns negative within 28 days after initial diagnosis.Most cases with high viral load in plasma showed elevated aminotransferase.

[Outcomes of different types of pulmonary atresia in neonates treated by ductus arteriosus stenting].

Objective: To summarize the outcomes of different types of pulmonary atresia in neonates treated by ductus arteriosus stenting. Methods: This study was a retrospective cohort study. A total of 19 neonates who had pulmonary atresia treated by ductus arteriosus stenting in Xinhua Hospital, Shanghai Jiao Tong University School of Medicine from April 2014 to June 2021 were included. They were divided into the intact ventricular septum (PA-IVS) group and the ventricular septal defect (PA-VSD) group. Ductus arteriosus stents were implanted by different approaches. These children were followed up regularly at the 1, 3, 6, and 12 months after the surgery and annually since then to evaluate the outcome. Independent sample t-test was used for the statistical analysis. Results: There were 12 children in PA-IVS group and 7 in PA-VSD group. All of them were full term in fants. The gestational age of the PA-IVS group and the PA-VSD group was (38.8±1.1) and (37.7±1.8) weeks, the birth weights were (3.2±0.4) and (3.4±1.1) kg, and the age at operation was (10±9) and (12±7) days, respectively, without significant difference (all P>0.05). Among the 12 children with PA-IVS, 9 had stents successfully implanted through the femoral artery and 3 through the femoral vein. Of the 7 children with PA-VSD, 2 had the stents successfully implanted via the femoral artery and 2 failed, and the remaining 3 had stents successfully implanted via the left carotid artery. There was no postoperative thromboembolism, arteriovenous fistula, pseudoaneurysm or other vascular complications. Five children with PA-VSD who had successful operations were followed up at 6 months of age. They all had the operation for pulmonary atresia, repair of the ventricular septal defect, removal of arterial duct stents, and ligation of the arterial duct. All children survived without any stent displacement or stenosis and biventricular circulation was achieved during the follow-up. Conclusions: Ductus arteriosous stenting can be the first-stage treatment for children with PA-IVS and PA-VSD. In addition to the traditional femoral vein and femoral artery approach, the carotid artery can be used as a route for stent placement.

[Clinical features and prognostic analysis of transarterial chemoembolization combined with targeted immunotherapy in the treatment of patients with hepatitis B virus-related intermediate-and advanced-stage hepatocellular carcinoma with secondary cholestasis].

Objective: To study the clinical features and prognostic impact of transarterial chemoembolization (TACE), immune checkpoint inhibitors (ICIs), and tyrosine kinase inhibitors (TKIs) combination therapy regimens in the treatment of patients with hepatitis B virus-related intermediate-and advanced-stage hepatocellular carcinoma with secondary cholestasis. Methods: Patients with HBV-related intermediate-and advanced-stage hepatocellular carcinoma (HBV) who visited the Affiliated Hospital of Xuzhou Medical University between January 1, 2020, and December 31, 2022, were enrolled. TACE+TKIs +ICIs combination therapy was used to treat all patients. The occurrence and factors influencing cholestasis, as well as the impact on prognosis after combined therapy, were analyzed. The measurement data were compared using a t-test and a non-parametric rank sum test. The count data was compared using the χ(2) test. The survival rates were compared using a log-rank test between different groups. Results: A total of 106 cases with HBV-related intermediate-and advanced-stage hepatocellular carcinoma were enrolled. The probabilities of secondary cholestasis within 3 and 6 months, 1, 2, and 3 years after TACE+ICIs+TKIs combination therapy were 9.4%, 12.3%, 14.2%, 24.5%, and 24.5%, respectively. Patients with secondary cholestasis had persistent symptoms and rapid progression. During the treatment course, the median survival time was significantly longer in patients with hepatocellular carcinoma without secondary cholestasis than that of patients with cholestasis (26.9 months vs. 13.7 months, respectively, P < 0.05). Secondary cholestasis, baseline aspartate aminotransferase, and prothrombin activity levels were independent risk factors that affected the survival and prognosis of patients treated with combination therapy. There was no statistically significant difference in the occurrence of other adverse reactions between the two groups with secondary and non-secondary cholestasis during the treatment course (47.5% vs. 43.3%, χ(2)=0.058, P = 0.810). Conclusion: TACE+ICIs+TKIs therapy combination is relatively common in the treatment of patients with HBV-related intermediate-and advanced-stage hepatocellular carcinoma with secondary cholestasis. Moreover, accelerated disease progression is an independent risk factor affecting the survival and prognosis of patients.

[Analysis of early severe postoperative complications and risk factors in 4255 patients who underwent bariatric and metabolic surgery in a single cente].

Objective: To analyze the incidence of early severe complications following bariatric and metabolic surgery and the experience of their diagnosis, treatment, and risk factors. Methods: In this retrospective observational study, the clinical data of 4255 patients who underwent bariatric and metabolic surgery between May 2010 and May 2022 in the Department of Bariatric and Metabolic Surgery of the First Affiliated Hospital of Nanjing Medical University were retrospectively collected. Among these patients, 1125 were male and 3130 were female. The mean age and body mass index (BMI) of the patients at the time of operation were 31.3±4.5 years and 36.5±6.4 kg/m2, respectively. Regarding surgical type, 2397 patients underwent sleeve gastrectomy (SG), 489 underwent Roux-en-Y gastric bypass (RYGB), 1028 underwent sleeve gastrectomy plus jejunojejunal bypass (SG+JJB), and 341 underwent single anastomosis duodenal switch (SADS). The inclusion criteria were patients (1) with a Clavien-Dindo grade of ≥III; (2) who were undergoing SG, RYGB, SG-JJB, or SADS; and (3) who had complete clinical data. The exclusion criteria were patients (1) undergoing revisional surgery and (2) other operations during the bariatric and metabolic surgery. The Clavien-Dindo classification was used to analyze the incidence of early severe postoperative complications and their prognosis. Early severe postoperative complications were defined as Clavien-Dindo ≥ III complications within 30 days after surgery. Meanwhile, multivariate logistic regression model was used to identify risk factors of the complications. Results: Summary of early severe complications following bariatric and metabolic surgery: (1) of the 4255 patients, 22 (12 male and 10 female) exhibited early severe complications (0.52%). The mean age and BMI of these patients were 41.1±9.9 years and 36.9±8.2 kg/m2, respectively. Preoperatively, 7 patients had hypertension, 10 had type 2 diabetes mellitus, 1 had respiratory failure, and 1 had heart failure. The severe complications included 9 patients (0.21%) with grade IIIa, 11 (0.26%) with grade IIIb, 1 (0.02%) with grade IVa, and 1 (0.02%) with grade V complications. The incidences of severe postoperative complications in the different surgical procedures were 0.17% for SG (4/2397), 0.61% for RYGB (3/489), 0.58% for SG+JJB (6/1028), and 2.64% for SADS (9/341). The common severe complications were leakage (0.28%, 12 patients), bleeding (0.14%, 6 patients), and obstruction (0.05%, 2 patients). (2) Management of complications: Grade IIIa complications (including eight patients with leakage and one with severe inflammation) were treated with antibiotics, nasogastric and nutritional tube placements, and CT-guided drainage. For grade IIIa complications, five patients with bleeding were treated with reoperation, and all the patients recovered; four patients with leakage were treated with reoperation, wherein three were converted to RYGB and one patient underwent resuturing of the leakage site; two patients with obstruction were treated with adhesiolysis. The patient with grade IVa complication (including respiratory failure complicated with acid aspiration) was treated in the ICU. For the grade V complication, bleeding in a patient with SG+JJB was treated with reoperation, which confirmed the bleeding of short gastric vessels. Unfortunately, the patient died. (3) Risk factor analysis of early severe complications: univariate analysis detected that sex, age, type 2 diabetes mellitus, operation time, and surgical type were associated with postoperative complications (P<0.05). However, multivariate analysis indicated that an age of ≥31.3 years (odds ratio [OR] = 5.423, 95% confidence interval [CI]: 1.004-29.278, P=0.049) and surgical type (SADS: OR = 19.758, 95%CI: 5.803-67.282, P<0.001; RYGB: OR = 9.752, 95%CI: 2.456-38.723, P=0.001; SG+JJB: OR = 5.706, 95%CI: 1.966- 16.559, P=0.001) were independent risk factors of early severe complications following bariatric and metabolic surgery. Conclusion: Bariatric and metabolic surgery is safe. Its common postoperative complications include leakage, bleeding, and obstruction, which require early detection, diagnosis, and treatment to improve treatment outcomes. Age and surgical type are independent risk factors of early severe complications following bariatric and metabolic surgery.

[Research advances on the regulatory mechanism of sweat secretion ion channels of eccrine sweat glands].

Sweat glands are widely distributed in human skin, among which eccrine sweat glands play major roles in heat dissipation and sweat secretion. Sweat secretion is mainly regulated by nervous system and includes two processes of secretion of secretory coil and reabsorption of sweat duct, involving various ion channels and proteins such as calcium ion channel, potassium ion channel, sodium-potassium-chloride co-transporter 1, Best2 protein, aquaporin 5, cystic fibrosis transmembrane conductance regulator, and epithelial sodium ion channel. This paper reviews the nerve conduction system and various ion channels involved in sweat secretion of exocrine sweat glands in order to provide a theoretical basis for the study of regeneration, repair, and transformation of stem cells.

[An exploratory clinical study of the efficacy and safety of tumor-infiltrating lymphocytes in the treatment of metastatic osteosarcoma].

Objective: To explore the safety and efficacy of tumor-infiltrating lymphocytes (TILs) extracted from tumor tissue in patients with pulmonary metastasis of osteosarcoma, the TILs were amplified in vitro to reach clinical dosage and reinfused to the patients combined with high-dose interleukin 2 (IL-2). Methods: Twelve subjects with pathologically diagnosed osteosarcoma were enrolled from December 2019 to June 20, 2021 in Shanghai General Hospital. All subjects progressed with metastasis after standard chemotherapy and failed multiple lines of treatments. Fresh tumor tissue was obtained from the metastatic site and extracted and amplified by Good Manufacturing Practice (GMP) workshop to produce TILs to clinical treatment dosage (109-1011). High-dose IL-2 (100 000-200 000 U/kg) was administered immediately after autogenous TILs infusion to promote the activation, proliferation and antitumor cytolytic activity in vivo. Adverse events (AE) were graded according to Common Terminology Criteria for Adverse Events (CTCAE) standard and tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Results: One patient did not receive treatment due to failure in isolating TILs, total of 11 patients received a single re-infusion of autologous TILs. There were 10 males and 1 female with a median age of 19.9 years (12-33 years). Six of these patients received higher dose levels of 1.0×1010 TILs. The 11 patients were followed-up for 1 to 13 months and tolerated well. The most common adverse events reported were fever (10/11), constipation (3/11) and elevated gamma-glutamyl transferase (GGT) (3/11). The high incidence of fever was due to the IL-2 infusion. All patients experienced a transient drop in lymphocyte count and leukopenia leading to non-myeloid ablative lymphocyte clearance. The AE included grade 4 hematologic toxicity, including 8 cases of lymphocytopenia, 2 cases of neutropenia and 1 case of thrombocytopenia. No AE of neurotoxicity occurred. Of all the 11 patients, 9 patients got stable disease (SD) and 2 patients had progressive disease (PD). The disease control rate was 9/11. The median duration of SD was more than 4 months, and the maximum tumor volume decreased by close to 20%. Patient number 9 had sustained SD status for more than 6 months. Conclusions: TILs with in vitro expansion ability could be isolated from tumor tissues of advanced osteosarcoma patients. TILs amplified and reinfused in vitro have anti-osteosarcoma activity.

Survival analysis of 80 elderly patients with esophageal squamous cell carcinoma receiving definitive concurrent chemoradiotherapy with S-1.

PURPOSE: This single-center retrospective study aimed to observe survival and prognosis of elderly patients with esophageal cancer receiving radical radiotherapy combined with S1 chemotherapy, and to preliminarily explore whether hematologic indicators or inflammatory indicators before radiotherapy are prognostic factors. MATERIAL AND METHODS: We retrospectively collected data of 80 elderly patients with esophageal cancer who had received radical concurrent chemoradiotherapy from January 2015 to July 2018. The patients were older than 70 years. Radiation therapy was delivered with intensity-modulated irradiation therapy (IMRT) or volumetric modulated arc therapy (VMAT), while the chemotherapy regimen was S1 alone. Toxicities were evaluated in accordance with the criteria of the Radiation Therapy Oncology Group. Baseline hematologic basic nutritional indicators, such as hemoglobin (HGB), albumin (ALB), and prealbumin (PAB), along with inflammatory indicators, such as the ratio of neutrophils to lymphocytes (NLR), the ratio of platelets to lymphocytes (PLR), were collected to preliminarily analyze their relationship with progression and survival. RESULTS: The median follow-up time was 39 months (range 30-65 months). The median overall survival and progression-free survival times were 24 and 17 months, respectively. The 1-, 2-, and 3-year overall survival rates were 76.5%, 48.1%, and 31.3%, respectively. The 1-, 2-, and 3-year progression-free survival rates were 57.5%, 37.8%, and 29.4%, respectively. T stage, clinical staging, and lesion region were independent prognostic factors for OS. No significant associations with prognosis were observed either for baseline hematologic or for inflammatory indicators (all P>0.05). The rates of esophagitis (grade 2 and above) and hematologic toxicity were 60% and 45%, respectively. CONCLUSION: Oral S-1 combined with definitive concurrent radiotherapy for elderly patients with esophageal cancer has a significant survival benefit. The toxicities are well tolerated. It seems that prognosis does not correlate with baseline hematologic nutritional indicators and inflammatory indicators.

[miR-20a-5p inhibits proliferation of lung cancer A549 cells by down-regulating HOXB13].

OBJECTIVE: To investigate the molecular mechanism by which miR-20a-5p regulates HOXB13 gene expression and inhibits lung cancer cell proliferation. METHODS: The expression levels of HOXB13 mRNA and protein in lung cancer A549 cells transfected with HOXB13 overexpression plasmid or HOXB13 siRNA were detected with real-time fluorescence quantitative PCR (qRT-PCR) and Western blotting. CCK-8 and EdU assays were used to examine the effect of modulation of HOXB13 expression on cell proliferation. We screened possible binding miRNAs of HOXB13 by bioinformatics analysis. In A549 cells transfected with miR-20a-5p mimic or miR-20a-5p inhibitor, the expression level of miR-20a-5p was detected by qRT-PCR and the protein expression of HOXB13 was determined with Western blotting. CCK-8 and EdU assays were used to assess the effect of miR-20a-5p overexpression on the proliferation of A549 cells. miR-20a-5p mimic and HOXB13 overexpression plasmids were co-transfected into A549 cells, and the changes in cell proliferation were evaluated with CCK-8 and EdU assays. RESULTS: HOXB13 overexpression obviously promoted the proliferation of A549 cells (P < 0.05). miR-20a-5p was identified as the potential binding miRNA of HOXB13. Overexpression of miR-20a-5p in A549 cells significantly decreased the expression of HOXB13 protein (P < 0.05), while interference of miR-20a-5p obviously increased HOXB13 expression (P < 0.05). The results of cell proliferation experiment showed that miR-20a-5p and HOXB13 had opposite effects on cell proliferation, and the cells overexpressing both miR-20a-5p and HOXB13 showed a lower proliferation activity than the cells overexpressing HOXB13 but higher than the cells overexpressing miR-20a-5p alone (P < 0.05). CONCLUSION: miR-20a-5p inhibits proliferation of lung cancer cells by down-regulating the expression of HOXB13.

[Follow-up study of fetal cardiac birth defects after prenatal diagnosis and graded counseling].

Objective: To explore accurate prenatal diagnosis, full-coverage graded counseling and follow-up for the fetus with cardiac birth defects (CBD). Methods: CBD fetus diagnosed prenatal by echocardiography from January 2018 to December 2020 in Guangdong Provincial People's Hospital were enrolled. Fetal CBD was graded (Ⅰ-Ⅵ) according to prognosis and possible operation time after birth, and the classification criteria and common diseases included were proposed. After the prenatal grading counseling, the outcome of the fetus was followed-up. The induced labor rate, live birth rate, prenatal and postnatal ultrasound diagnosis coincidence rate and other indicators were calculated. The disease composition ratio, prognosis of fetus with different grades and the outcome of integrated treatment were analyzed. Results: The detection rate of fetal CBD was up to 16.2% (1 971/12 188), 30 cases of which were excluded. A total of 1 941 cases were included in this study, including 196 cases (10.1%) of gradeⅠ, 433 cases (22.3%) of gradeⅡ, 615 cases (31.7%) of grade Ⅲ, 261 cases (13.4%) of grade Ⅳ, 388 cases (20.0%) of gradeⅤ, 48 cases (2.5%) of grade Ⅵ. Grade Ⅱ and gradeⅢ (the operation time was within 1 year after birth) accounted for 54.0% (1 048/1 941). The distribution of some diseases in different grades had obvious proportion advantage, which was representative. Among 1 747 CBD fetus, 736 cases (induced labor rate 42.1%) chose to terminate pregnancy due to CBD. Of the 1 010 live births, 975 cases (96.5%) had the same prenatal and postnatal diagnosis, 3 cases were missed diagnosis and 32 cases were misdiagnosed. The diagnostic accuracy of live births with severe and complex congenital heart disease was 383 out of 389 (98.5%). A total of 258 cases have received surgery or intervention. The age at the time of surgery or intervention was different among grades（χ²=47.3，P<0.001）. With the improvement of prognosis from gradeⅠ to Ⅴ, the live birth rate increased and the induced labor rate decreased accordingly; the difference between grades was significant（χ²=623.6，P<0.001）. Conclusions: Prenatal diagnosis and graded counseling is important in the integrated model. Fetal CBD grading could refine post-natal treatment strategies, guide delivery decisions and become an evaluation standard.