[Risk prediction and function evaluation by T-cell epitope model and expression model of HLA-DPB1 mismatching in unrelated-donor hematopoietic stem cell transplantations].

Objective: To evaluate the risk prediction and assessment function of HLA-DPB1 T-cell epitope (TCE) model and expression model in human leukocyte antigen (HLA)-matched unrelated hematopoietic stem cell transplantation (MUD-HSCT) with HLA-DPB1 mismatching. Methods: A total of 364 (182 pairs) potential MUD-HSCT donors and recipients confirmed by HLA high-resolution typing in Shaanxi Blood Center from 2016 to 2019 were analyzed retrospectively. Of the 182 recipients, there were 121 males and 61 females with an average age of (26.3±14.2) years. Of the 182 donors, there were 148 males and 34 females with an average age of (33.7±7.5) years. Polymerase chain reaction-sequence-based typing (PCR-SBT), next-generation sequencing (NGS) and polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSO) based on LABScan®3D platform were used for high-resolution typing of HLA-A, B, C, DRB1, DQB1, DPB1 gene, and PCR-SBT was used for single nucleotide polymorphism (SNP) typing. TCE model and expression model were used to predict and evaluate the HLA-DPB1 mismatch pattern and acute graft-versus-host-disease (aGVHD) risk. Results: A total of 26 HLA-DPB1 alleles and their 3'-UTR rs9277534 SNP genotypes were detected in this study population, and two new alleles HLA-DPB1*1052∶01 and HLA-DPB1*1119∶01 were found and officially named. The overall mismatch rate of HLA-DPB1 in MUD-HSCT donors and recipients was 90.66% (165/182). In TCE model, the HLA-DPB1 mismatch rates of permissible mismatch (PM) and non-permissible mismatch (non-PM) were 47.80% (87/182) and 42.86% (78/182), respectively. The non-PM in GvH direction was 13.73% (25/182), and which in HvG direction was 29.12% (53/182). A total of 73 pairs of donors and recipients in TCE model met the evaluation criteria of expression model. Among of TCE PM group, recipient DP5 mismatches accounted for 34.25% (25/73) were predicted as aGVHD high risk according to expression model. For the TCE non-PM group, both the recipient DP2 mismatches of 6.85% (5/73) and recipient DP5 mismatches of 10.86% (8/73) were predicted to be at high risk for aGVHD. Risk prediction by TCE model and expression model was 27.27% concordant and 16.97% unconcordant. Conclusions: TCE model and expression model are effective tools to predict aGVHD risk of MUD-HSCT. Comprehensive application of the two models is helpful to the hierarchical assessment of HSCT risk.

[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.

[Inhibitory effect of downregulating G protein-coupled receptor class C group 5 member A expression on lipopolysaccharide-induced inflammatory response in human gingival fibroblasts].

Objective: To clarify the effect and the mechanism of G protein-coupled receptor class C group 5 member A (GPRC5A) on lipopolysaccharide (LPS)-induced inflammatory response in human gingival fibroblasts (GFs), thus to provide a foundation for delving into the role of G protein coupled receptor (GPCR) in periodontitis. Methods: Gingival tissue samples were collected from 3 individuals periodontally healthy (health group) and 3 patients with periodontitis (periodontitis group) in Shandong Stomatological Hospital from December 2022 to February 2023. The expressions of GPRC5A of the two groups were detected by immunohistochemistry staining. GFs used in this study were isolated from a portion of gingiva for the extraction of impacted teeth in School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University from December 2022 to February 2023. GFs were isolated with enzymic digestion and transfected with 30, 50 and 80 µmol/L small interfering RNA-GPRC5A (siGPRC5A) or small interfering RNA-negative control (siNC), regarded as the experimental group and the negative control one, respectively. The silencing efficiency of siGPRC5A was evaluated by real-time fluorescence quantitative PCR (RT-qPCR). Experiments were then conducted using these cells which were divided into four groups of negative control (NC), LPS, siGPRC5A+LPS and siGPRC5A. The mRNA and protein levels of GPRC5A in GFs under 1 mg/L LPS-induced GFs inflammatory state were evaluated by RT-qPCR and Western blotting analysis after GPRC5A knockdown. RT-qPCR was used to detect the gene expression levels of the inflammatory cytokines in GFs induced by LPS, namely, interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor (TNF)-α, prostaglandin endoperoxide synthase 2 (PTGS2) after GPRC5A knockdown. Western blotting analysis and immunofluorescence staining were used to further investigate the activation of nuclear factor-kappa B (NF-κB) signaling pathway. Results: Immunohistochemistry staining showed that the expression of GPRC5A in gingival tissues of periodontitis group (0.132±0.006) increased compared with that in periodontally healthy group (0.036±0.019) (t=8.24, P=0.001). Meanwhile, RT-qPCR results showed that the gene expression levels of GPRC5A at different time point (2, 6, 12, 24 h) in LPS-induced GFs (0.026±0.002, 0.042±0.005, 0.004±0.000, 0.016±0.000) were upregulated compared with those in the NC group (0.004±0.000, 0.004±0.000, 0.002±0.000, 0.007±0.000) (all P<0.001), respectively, and peaked at 6 h. The 50 µmol/L group displayed the most significant decrease in siGPRC5A expression (31.16±3.29) compared with that of the siNC group (100.00±4.88) (F=297.98, P<0.001). The results of RT-qPCR and Western blotting analysis showed that siGPRC5A (0.27±0.03, 0.71±0.00) suppressed the expressions of GPRC5A at both gene and protein levels, while LPS (1.30±0.10, 1.43±0.03) was able to promote the expressions of GPRC5A compared with those of the NC group (1.00±0.01, 1.00±0.00)(all P<0.001). The siGPRC5A+LPS group (0.39±0.03, 1.06±0.16) also inhibited the increase of GPRC5A at both gene and protein levels induced by LPS (1.30±0.10, 1.43±0.03) (F=208.38, P<0.001; F=42.04, P<0.001). RT-qPCR results showed that the expressions of IL-8, IL-1ß, IL-6, TNF-α, and PTGS2 at the gene level in LPS group were highly increased compared with those in the NC group (all P<0.001). siGPRC5A significantly suppressed LPS-induced expressions of these inflammatory cytokines in GFs (all P<0.001). Western blotting analysis showed that the levels of p65 and IκBα protein phosphorylation in the LPS group were highly increased compared with those in the NC group, and siGPRC5A could effectively suppressed LPS-induced protein phosphorylation (all P<0.01). Furthermore, immunofluorescence staining showed that NF-κB p65 in the control group was mainly concentrated in the cytoplasm, and partially translocated to the nucleus under the stimulation of LPS. siGPRC5A was able to inhibit LPS-induced intranuclear translocation of p65 to a certain extent. Conclusions: GPRC5A expression was upregulated in periodontitis, and GPRC5A knockdown inhibited LPS-induced inflammation. Moreover, GPRC5A played a role in inflammation regulation by interacting with NF-κB signaling pathway.

[The detecting value of virtual non-calcium technique of dual-energy CT for bone marrow edema around nontraumatic osteonecrosis of the femoral head].

Objective: To evaluate the value of virtual non-calcium (VNCa) technique of dual-energy CT (DECT) for detecting bone marrow edema (BME) around nontraumatic osteonecrosis of the femoral head (ONFH) using MRI as reference standard. Methods: Nontraumatic ONFH patients were prospectively studied in the Fourth Medical Center of Chinese PLA General Hospital from October 2022 to May 2023, and their MRI and DECT images were analyzed. The diagnostic efficiency of the subjective assessment of BME around ONFH by two radiologists in VNCa color-coded images were calculated using the MRI results as the reference standard. The BME ranges were compared between VNCa images and MRI. Traditional CT values and VNCa CT values were compared between normal bone marrow and BME. The receiver operator characteristic (ROC) curve was established based on the statistically different CT values, and the area under the curve (AUC) was calculated to find the threshold to distinguish normal bone marrow from BME and evaluate the diagnostic efficacy. Results: Thirty patients with ONFH were included, including 24 males and 6 females, aged (39±12) years. There were 18 bilateral hips and 12 unilateral hips, with a total of 48 hips, 34 hips of which showed BME on MRI. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of subjective detection of BME on VNCa color coded maps by two physicians were 97.1% (33/34) and 97.1% (33/34), 92.9% (13/14) and 71.4% (10/14), 97.1% (33/34) and 89.2% (33/37), 92.9% (13/14) and 90.9% (10/11), 95.8% (46/48) and 89.6% (43/48), respectively, with no statistical difference (all P>0.05).There was no statistical difference between VNCa color-coded images and MRI in the BME range (P=1.160). The traditional CT values measured by the two radiologists were in good agreement with VNCa CT values, with intraclass correlation coefficient (ICC) of 0.948 (95%CI: 0.908-0.971) and 0.982 (95%CI: 0.969-0.990), respectively. The traditional CT value of normal bone marrow was (400.7±82.8) HU, and that of BME was (443.7±65.7) HU, with no statistical difference (P=0.062). The VNCa CT value of normal bone marrow was (-103.1±27.8) HU, and that of BME was (-32.9±25.7) HU, with statistical difference (P<0.001). The AUC of distinguishing normal bone marrow from BME based on VNCa CT value was 0.958 (95%CI: 0.857-0.995). The best cut-off value was -74.5 HU, and when the VNCa CT value was higher than -74.5 HU, the sensitivity, specificity, PPV, NPV and accuracy of diagnosing BME were 97.1%, 92.9%, 97.1%, 92.9% and 95.8 %, respectively. Conclusion: The VNCa technique of DECT has high efficiency in detecting BME around ONFH, and can accurately demonstrate the range of BME.

[Quality control of perioperative management after radical surgery for locally advanced gastric cancer].

Gastric cancer is a common malignant tumor in China. Most gastric cancer patients are already in the locally advanced stage when they seek medical treatment. Radical surgery is the main treatment for gastric cancer. The quality control of postoperative perioperative management is of great significance in improving the surgical treatment effect and the quality of life of patients. This article systematically summarizes seven aspects, including diet and nutrition management, antimicrobial drug management, pain management, prophylactic anticoagulation management, airway management, postoperative complication management, and discharge and follow-up management, establishes clear quality standards, and achieves the goals of reducing postoperative complications, standardizing perioperative medication use, reducing hospitalization time and costs, thereby reducing patient burden and improving the economic and social benefits of medical institutions.

[Imaging classification and analysis of the diagnosis and treatment of infected pancreatic necrosis:a report of 126 cases].

Objective: To explore the clinical characteristics of various types of infected pancreatic necrosis(IPN) and the prognosis of different treatment methods in the imaging classification of IPN proposed. Methods: The clinical data of 126 patients with IPN admitted to the Department of Pancreatic and Biliary Surgery, the First Affiliated Hospital of Harbin Medical University from December 2018 to December 2021 were analyzed retrospectively. There were 70 males(55.6%) and 56 females(44.4%), with age(M(IQR)) of 44(17)years (range: 12 to 87 years). There were 67 cases(53.2%) of severe acute pancreatitis and 59 cases (46.8%) of moderately severe acute pancreatitis. All cases were based on the diagnostic criteria of IPN. All cases were divided into Type Ⅰ(central IPN)(n=21), Type Ⅱ(peripheral IPN)(n=23), Type Ⅲ(mixed IPN)(n=74) and Type Ⅳ(isolated IPN)(n=8) according to the different sites of infection and necrosis on CT.According to different treatment strategies,they were divided into Step-up group(n=109) and Step-jump group(n=17). The clinical indicators and prognosis of each group were observed and analyzed by ANOVA,t-test,χ2 test or Fisher exact test,respectively. Results: There was no significant difference in mortality, complication rate and complication grade in each type of IPN(all P>0.05). Compared with other types of patients, the length of stay (69(40)days vs. 19(19)days) and hospitalization expenses(323 000(419 000)yuan vs. 60 000(78 000)yuan) were significantly increased in Type Ⅳ IPN(Z=-4.041, -3.972; both P<0.01). The incidence of postoperative residual infection of Type Ⅳ IPN was significantly higher than that of other types (χ2=16.350,P<0.01). There was no significant difference in the mortality of patients with different types of IPN between different treatment groups. The length of stay and hospitalization expenses of patients in the Step-up group were significantly less than those in the Step-jump group(19(20)days vs. 33(35)days, Z=-2.052, P=0.040;59 000(80 000)yuan vs. 122 000(109 000)yuan,Z=-2.317,P=0.020). Among the patients in Type Ⅳ IPN, the hospitalization expenses of Step-up group was significantly higher than that of Step-jump group(330 000(578 000)yuan vs. 141 000 yuan,Z=-2.000,P=0.046). The incidence of postoperative residual infection of Step-up group(17.4%(19/109)) was significantly lower than that of Step-jump group(10/17)(χ2=11.980, P=0.001). Conclusions: Type Ⅳ IPN is more serious than the other three types. It causes longer length of stay and more hospitalization expenses. The step-up approach is safe and effective in the treatment of IPN. However, for infected lesions which are deep in place,difficult to reach by conventional drainage methods, or mainly exhibit "dry necrosis", choosing the step-jump approach is a more positive choice.

[P4HA2 promotes occurrence and progression of liver cancer by regulating the PI3K/Akt/mTOR signaling pathway].

OBJECTIVE: To investigate the role of proline 4-hydroxylase Ⅱ (P4HA2) in the occurrence and progression of liver cancer. METHODS: GEPIA and Human Protein Atlas database were used to predict the expression of P4HA2 in hepatocellular carcinoma (HCC), and K-M plotter online database was used to analyze the relationship between P4HA2 expression and the prognosis of HCC. We also examined the expressions of P4HA2 in HCC cells and normal hepatocytes using qRT-PCR and Western blotting. With lentivirus-mediated RNA interference, P4HA2 expression was knocked down in hepatoma SNU-449 and Hep-3B cells, and the changes in cell proliferation, migration and invasion were assessed using cell counting kit-8 (CCK-8) assay, colony formation test, scratch test and Transwell assay. The changes in the expressions of epithelial-mesenchymal transition (EMT) and PI3K/Akt/mTOR signal pathway-related proteins were detected using Western blotting. RESULTS: Online database analysis showed that the expression of P4HA2 was significantly higher in HCC tissues than in normal liver tissues (P < 0.05). The expression levels of P4HA2 mRNA and protein were also significantly higher in HCC cell lines than in normal hepatocytes (P < 0.01). Lentivirus-mediated RNA interference of P4HA2 significantly lowered the expression levels of P4HA2 mRNA and protein in the hepatoma cells (P < 0.05) and caused obvious inhibition of cell proliferation, migration and invasion. P4HA2 knockdown significantly increased the expression of E-cadherin protein, lowered the expressions of N-cadherin and Snail, and obviously decreased the expressions of phosphorylated PI3K, AKT and mTOR (P < 0.05). CONCLUSION: P4HA2 enhances the proliferation, migration, invasion, and EMT of hepatoma cells by activating the PI3K/Akt/mTOR signaling pathway to promote the occurrence and progression of liver cancer.

[Characteristics and risk factors of functional constipation in children aged 0-4 years in Xi 'an].

Objective: To investigate the epidemiology, characteristics and risk factors of functional constipation (FC) in children aged 0-4 years in Xi'an. Methods: From October, 2020 to June, 2021, a prevalence survey was conducted among 2 615 children aged 0-4 years in Xi'an by group sampling. The related factors of FC were investigated by questionnaire designed based on Rome Ⅳ diagnostic criteria.The children were divided into FC group and non-FC group. The prevalence, symptoms and signs of FC were analyzed, and its risk factors were analyzed by multivariate Logistic regression. Results: A total of 2 985 valid questionnaires were handed out, and 2 711 (90.8%) were received back. A total of 2 615 questionnaires were valid, with an effective rate of 96.5%. There were 1 338 males (51.2%) and 1 277 females (48.8%). There were 260 cases in FC group and 2 355 cases in non-FC group. The prevalence of FC in children aged 0-4 years in Xi 'an was 10.6%.There were significant differences in FC prevalence among children of different ages and sex (χ2=14.58,4.39, both P<0.05), but not in urban or rural residence (χ2=3.29, P=0.070). The main symptoms of FC group in the last month were large-diameter feces (73.5%, 191/260), painful defecation or dry and hard defecation (65.8%, 171/260). In the last month, FC group had higher incidences of the Bristol type 1, 2 and 3 stool, fecal retention, prolonged defecation, abdominal pain and incomplete defecation compared with non-FC group, with statistical significance (all P<0.05). Parental history of childhood constipation (OR=2.13, 95%CI 1.55-2.92), fever in the last month (OR=1.86, 95%CI 1.32-2.63), history of constipation (OR=3.24, 95%CI 2.46-4.26) and taking probiotics in the last month (OR=1.45, 95%CI 1.11-1.91) were risk factors of FC in children aged 0-4 years. Stratified with age, the results showed that complementary feeding earlier than 5 months of age or later than 6 months of age (OR=2.42, 95%CI 1.13-5.20), dry stools during the complementary feeding (OR=11.27, 95%CI 5.15-24.66), history of constipation (OR=2.29, 95%CI 1.23-4.29) and taking probiotics in the last month (OR=1.88, 95%CI 1.10-3.23) were risk factors of FC in children aged 0-<1 year, and breastfeeding (OR=0.53, 95%CI 0.29-0.94) was a protective factor of FC in children aged 0-<1 year. Family members' recent constipation history (OR=2.02, 95%CI 1.06-3.85) and past history of constipation (OR=3.06, 95%CI 1.74-5.38) were FC risk factors for children aged 1-<2 years. Parental history of childhood constipation (OR=3.12, 95%CI 2.00-4.85), frequency of eating vegetables less than 3 times per week (OR=3.28, 95%CI 2.00-5.38), history of constipation (OR=3.66, 95%CI 2.42-5.53) and taking antibiotics in the last month (OR=1.65, 95%CI 1.06-2.55) were risk factors for FC in children aged 2-4 years. Conclusions: FC in children aged 0-4 years in Xi'an is mainly manifested with large-diameter feces and painful defecation or dry and hard defecation in the last month. It is associated with a variety of risk factors, which are different in different age groups.

Use of CT-based renal volumetry for the measurement of split renal function: a split glomerular filtration rate prediction model based on unilateral renal volume parameters.

AIM: To develop a split glomerular filtration rate (sGFR) prediction model based on unilateral renal volume parameters using three-dimensional (3D) computed tomography (CT) volumetry. MATERIALS AND METHODS: Clinical data (age, sex, height, weight, serum creatinine level [sCr], and sGFR measured by 99mTc-diethylene triamine pentaacetic acid nuclear renal scintigraphy with the double plasma sample method) of 67 healthy renal donors and 111 patients with hydronephrosis admitted from April 2016 to September 2021 were analysed. The split renal parenchymal volume (sRPV) and split renal calyces and pelvis volume (sRCPV) of 67 unilateral donor left kidneys and 111 hydronephrotic kidneys were measured. Statistical analysis of these parameters was performed to develop and validate the sGFR prediction model. RESULTS: sRPV (p<0.001), sRCPV (p=0.012), age (p=0.015), serum creatinine level (p=0.004), and weight (p=0.006) were significantly associated with the measured sGFR and were included in the sGFR prediction formula, which was constructed as: 68.710 + 0.093 × sRPV-0.041 × sRCPV-0.228 × W-0.219 × A-14.432 × sCr (r2 = 0.416; where A is age, W is weight). The paired difference of internal validation between the measured sGFR (42.34 ± 13.71 ml/min/1.73 m2) and the sGFR estimated by the prediction model (41.46 ± 8.99 ml/min/1.73 m2) was 0.879 ± 11.475 ml/min/1.73 m2 (p=0.492) with a 95% confidence interval of the mean difference of ±2.54 ml/min/1.73 m2. CONCLUSION: The proposed model based on sRPV and sRCPV parameters could be used for estimating split renal function of healthy renal donors and patients with hydronephrosis to some extent. Further studies are required to evaluate and rectify the model.

What is an appropriate caesarean delivery rate for China: a multicentre survey.

OBJECTIVE: To assess the current status of caesarean delivery (CD) in China, propose reference CD rates for China overall, and by regions, investigate the main indications for CDs and identify possible areas for safe reduction. DESIGN: A multicentre cross-sectional study. SETTING: A total of 94 hospitals across 23 provinces in China. POPULATION: A total of 73 977 randomly selected deliveries. METHODS: We used a modified Robson classification to characterise CDs in subgroups and by regions, and the World Health Organization (WHO) C-Model to calculate reference CD rates. MAIN OUTCOME MEASURES: CD rates in China. RESULTS: In 2015-2016, the overall CD rate in China was 38.9% (95% CI 38.6-39.3%). Considering the obstetric characteristics of the population, the multivariable model-based reference CD rate was estimated at 28.5% (95% CI 28.3-28.8%). Accordingly, an absolute reduction of 10.4% (or 26.7% relative reduction) may be considered. The CD rate varied substantially by region. Previous CD was the most common indication in all regions, accounting for 38.2% of all CDs, followed by maternal request (9.8%), labour dystocia (8.3%), fetal distress (7.7%) and malpresentation (7.6%). Overall, 12.7% of women had prelabour CDs, contributing to 32.8% of the total CDs. CONCLUSIONS: Nearly 39% of births were delivered by caesarean in China but a reduction of this rate by a quarter may be considered attainable. Repeat CD contributed more than one-third of the total CDs. Given the large variation in maternal characteristics, region-specific or even hospital-specific reference CD rates are needed for precision management of CD. TWEETABLE ABSTRACT: The caesarean rate in 2015-2016 in China was 38.9%, whereas the reference rate was 28.5%.

[A case of CHARGE syndrome confirmed by ophthalmology].

A 31-month-old female patient presented to our department of Ophthalmology in Xijing Hospital with insufficiency closed eyelid in left eye and photophobia for one month. Unsteady gait with asymmetrical face, bilateral auricle deformity and deafness could be observed on the pediatric patient. Esotropia in left eye combined, left facial nerve palsy, with binocular anisometropia was checked out after general eye examination. Echocardiography revealed that she was treated with ligation of the ductus arteriosus. A de novo pathogenic variant, c.3392T>C, was identified in CHD7 gene, which supported the diagnosis of CHARGE syndrome. (Chin J Ophthalmol, 2021, 57: 618-620).

[Blue light regulates the expression of brain derived neurotrophic factor in the habenula nucleus of depression-like rats induced by light deprivation].

Objective: To investigate the regulatory effect of blue light on the expression of brain derived neurotrophic factor (BDNF) in the habenula nucleus of depression-like rats induced by light deprivation. Methods: male SD rats were exposed to white light (white light control group, 20 rats) and constant darkness (depression model group, 60 rats), respectively. 18 days later rats in depression model group were randomly divided into three groups: depression model group (treated with constant darkness), blue light group (treated with blue light) and red light group (treated with red light). Rats in white light control group were kept in white light. All rats exposed to light were in a standard 12∶12 h Light/Dark condition at 20 lx for 36 days. Sucrose preference test was applied to evaluate depression-like symptoms of rats. The c-fos+cells in the habenula nucleus, intergeniculate leaflet and ventral lateral geniculate nucleus were detected. The phosphoylation of cAMP-response element binding protein (CREB) and the relative BDNF protein level in the habenula nucleus were measured. Results: Sucrose intake per kg body weight increased in rats exposed to blue light and returned to the level of control group (P>0.05). Sucrose intake per kg body weight in red light group and depression model group were lower than control group (P<0.05). More c-fos+cells were detected in the habenula nucleus, intergeniculate leaflet and ventral lateral geniculate nucleus from blue light group than those from depression model group (P<0.05). The relative BDNF protein level and the phosphoylation of CREB in the habenula nucleus from blue light group were higher than those from depression model group (P<0.05). Conclusion: Blue light could relieve depression-like symptoms in light-deprived rats. Exposure to blue light could activate neurons in the habenula nucleus to which intrinsically photosensitive retinal ganglion cells projected. Blue-light-mediated antidepressant effect might involve in the activation of CREB/BDNF signal transduction pathways in the habenula nucleus.

Accurate diagnosis of colorectal cancer based on histopathology images using artificial intelligence.

BACKGROUND: Accurate and robust pathological image analysis for colorectal cancer (CRC) diagnosis is time-consuming and knowledge-intensive, but is essential for CRC patients' treatment. The current heavy workload of pathologists in clinics/hospitals may easily lead to unconscious misdiagnosis of CRC based on daily image analyses. METHODS: Based on a state-of-the-art transfer-learned deep convolutional neural network in artificial intelligence (AI), we proposed a novel patch aggregation strategy for clinic CRC diagnosis using weakly labeled pathological whole-slide image (WSI) patches. This approach was trained and validated using an unprecedented and enormously large number of 170,099 patches, > 14,680 WSIs, from > 9631 subjects that covered diverse and representative clinical cases from multi-independent-sources across China, the USA, and Germany. RESULTS: Our innovative AI tool consistently and nearly perfectly agreed with (average Kappa statistic 0.896) and even often better than most of the experienced expert pathologists when tested in diagnosing CRC WSIs from multicenters. The average area under the receiver operating characteristics curve (AUC) of AI was greater than that of the pathologists (0.988 vs 0.970) and achieved the best performance among the application of other AI methods to CRC diagnosis. Our AI-generated heatmap highlights the image regions of cancer tissue/cells. CONCLUSIONS: This first-ever generalizable AI system can handle large amounts of WSIs consistently and robustly without potential bias due to fatigue commonly experienced by clinical pathologists. It will drastically alleviate the heavy clinical burden of daily pathology diagnosis and improve the treatment for CRC patients. This tool is generalizable to other cancer diagnosis based on image recognition.

MiR-31 aggravates inflammation and apoptosis in COPD rats via activating the NF-κB signaling pathway.

OBJECTIVE: To study the effect of micro ribonucleic acid (miR)-31 on rats with chronic obstructive pulmonary disease (COPD) by activating the nuclear factor-κB (NF-κB) signaling pathway. MATERIALS AND METHODS: A total of 36 Sprague-Dawley rats were randomly divided into normal group (n=12), model group (n=12) and miR-31 mimics group (n=12). The rats were fed normally in normal group. In model group, the COPD model was first established, followed by intervention using normal saline. In miR-31 mimics group, the COPD model was also first established, followed by intervention using miR-31 mimics. The expression of NF-κB was detected via immunohistochemistry. Protein expressions of B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) were determined through Western blotting. Serum levels of interleukin-6 (IL-6), IL-18 and tumor necrosis factor-α (TNF-α) were measured via enzyme-linked immunosorbent assay (ELISA). Moreover, the apoptosis was examined via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, and the relative expression of miR-31 was detected by means of quantitative polymerase chain reaction (qPCR). RESULTS: The immunohistochemistry results showed that the positive expression of NF-κB was significantly higher in the other two groups than that in normal group (p<0.05), while it was also remarkably higher in miR-31 mimics group than that in model group (p<0.05). The results of Western blotting revealed that the relative protein expression of Bax significantly increased, while that of Bcl-2 notably declined in the other two groups compared with those in normal group (p<0.05). Similarly, the relative protein expression of Bax was upregulated, while that of Bcl-2 was distinctly reduced in miR-31 mimics group compared with those in model group (p<0.05). It was found via ELISA that the model group and miR-31 mimics group had evidently higher levels of IL-6, IL-18 and TNF-α than those in normal group (p<0.05), while miR-31 mimics group also had prominently higher levels than those in model group (p<0.05). In addition, according to the TUNEL assay, the apoptosis rate remarkably increased in the other two groups in comparison with that in normal group (p<0.05), while it remarkably rose in miR-31 mimics group compared with that in model group (p<0.05). Finally, a significantly higher expression of miR-31 was observed in the other two groups than that in normal group via qPCR (p<0.05), and such a higher expression was also found in miR-31 mimics group than that in model group (p<0.05). CONCLUSIONS: MiR-31 aggravates inflammation and apoptosis in COPD rats by activating the NF-κB signaling pathway.

[Interpretation of 2019 edition of Wilderness Medical Society practice guidelines for prevention and treatment of frostbite].

The Wilderness Medical Society updated and published the Wilderness Medical Society practice guidelines for the prevention and treatment of frostbite in July 2019. The guidelines provide evidence-based recommendations for the prevention and treatment of frostbite, mainly including pathophysiology, classification, prevention, and treatment of frostbite. This paper focuses on the interpretation of the guidelines, aiming at making clinical medical staff understand the new progress of frostbite treatment and providing reference for clinical practice.

[Expression and significance of Nek2B and ß-catenin in triple negative breast cancer].

Objective: To investigate the expression and significance of Nek2B and ß-catenin expression in triple negative breast cancer (TNBC) at molecule levels. Methods: By using the methods of bioinformatics [GEO2R online tool, gene ontology (GO) function analysis, KEGG biological pathway enrichment analysis], the differentially expressed genes were screened from TNBC microarray data.Expression levels of Nek2B and ß-catenin TNBC cell lines were detected by Western blot and qRT-PCR.From January 1, 2007 to December 31, 2012, eighty cases of TNBC were collected from the Second Hospital of Shanxi Medical University. The expression of Nek2B in TNBC tumor tissue was detected by immunohistochemistry and tissue microarray, and the relationship between Nek2B and clinical pathological characteristics of TNBC was analyzed. Results: Through bioinformatics analysis of the cDNA chip sets of 2 TNBC tumors(GSE38959,GSE27447), 998 differentially expressed genes were obtained in the initial screening, and 13 differentially expressed genes were revealed after intersection. The results of biological pathway analysis showed that the common differential expression genes were closely related to Wnt/ß-catenin pathway, among which Nek2 expression showed the greatest difference and was associated with poor prognosis. Expression intensity of Nek2B and repeated ß-catenin in the same TNBC cell line was consistent.The results of immunohistochemistry showed that the high expression of Nek2B was related to the high histological stage (G3;84.3% vs.37.9%, P<0.001), lymph node metastasis group (76.7% vs.54.1%, P=0.032), high Ki-67 positive index group (78.6% vs.52.6%, P=0.007) and ß-catenin positive expression group (72.5% vs.27.3%, P=0.018). Conclusions: The high level of Nek2B expression is related to a poor prognosis in TNBC patients. In TNBC tissues and cells, the expression of Nek2B is correlated with ß-catenin, suggesting that Nek2B may affect the occurrence and development of TNBC by regulating the Wnt/ß-catenin patients signaling pathway.

[Clinical and laboratory characteristics in patients with myeloid neoplasms complicated with clonal T large granular lymphocyte proliferation].

Objective: To analyze the clinical manifestations and laboratory features in patients with myeloid neoplasms complicated with clonal T large granular lymphocyte (T-LGL) proliferation. Methods: The clinical data of 5 patients with myeloid neoplasms complicated with clonal T-LGL proliferation from November 2017 to November 2018 in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College were analyzed retrospectively. Results: The median age was 60 years old. All patients had a history of abnormal peripheral blood cell counts for over 6 months. The absolute lymphocyte count in peripheral blood was less than 1.0×10(9)/L. In addition to the typical T-LGL phenotype, the immunophenotype was heterogenous including CD4(+)CD8(-) in 2 patients, the other 3 CD4(-)CD8(+). Four patients were αß type T cells, the other one was γδ type. STAT3 mutation was detected in 1 patient by next-generation sequencing, the other 4 cases were negative. Conclusions: Clonal T-LGL proliferation with myeloid neoplasm develops in an indolent manner, mainly in elderly patients. Hemocytopenia is the most common manifestation. The diagnosis of T-LGL proliferation does not have specific criteria, that it should be differentiated from other T cell proliferative disorders, such as T-cell clones of undetermined significance. STAT3 or STAT5b mutation may help distinguish.

[The association between carotid atherosclerosis and ischemic stroke in patients with nonvalvular atrial fibrillation].

Objective: To investigate the relationship between indicators of carotid atherosclerosis and onset of ischemic stroke in patients with non-valvular atrial fibrillation (NVAF). Methods: This is a case-control study, a total of 397 NVAF patients with newly diagnosed ischemic stroke (case group) and 3 038 NVAF patients without ischemic stroke (control group) from January 2015 to December 2017 were included in the study. Differences in general clinical features and carotid atherosclerosis indexes between the two groups were compared. Univariate and multivariate logistic regressions were used to analyze the correlation between carotid atherosclerosis indexes and ischemic stroke. Results: Proportions of patients with carotid intima thickening, carotid plaque, stable plaque, unstable plaque, and moderate to severe stenosis were higher in the ischemic stroke group than those in the control group (82.1% vs. 64.4%, 69.3% vs. 50.3%, 43.6% vs. 30.6%, 25.7% vs. 19.7%, and 7.3% vs. 4.0%, respectively, all P <0.05). After adjustment of age, gender, heart failure, hypertension, low density lipoprotein -cholesterol and drug use, multivariate analyses showed that subjects with carotid intima thickening, carotid plaque, stable plaque, unstable plaque, moderate to severe stenosis had 1.766, 2.111, 1.892, 2.256 and 1.824 times the risk for the development of ischemic stroke compared with the subjects without any carotid atherosclerosis indicators. Conclusion: Carotid atherosclerosis, especially with unstable carotid plaque, is associated with ischemic stroke in patients with NVAF.

[Mechanism of renal injury and apoptosis in rats with nephrotic syndrome induced by mercury].

Objective: To investigate the relationship between renal injury and apoptosis in rats with nephrotic syndrome induced by mercury, in order to find out the pathogenesis. Methods: Forty-eight healthy male SPF-grade BN (Brown-Norway) rats were divided into the control group and the exposure group by random number table. The nephrotic syndrome was caused by subcutaneous injection of HgCl(2) (1 mg/ml) in the abdominal weight per kg of body weight. The control group was injected with the same volume of NaCl as the exposure group. Some rats were sacrificed on the 14th, 21st, 28th, and 35th days, and the serum kidney injury indicators creatinine (CRE) and urea nitrogen (BUN) were detected, and the renal tissue mercury content was detected; the in situ terminal transferase labeling technology (TUNEL) was detected Apoptosis, immunofluorescence detection of Cyt C content, Western blot detection of mitochondrial pathway apoptosis-related proteins [B-cell lymphoma 2 (Bcl-2) , Bcl-2 related X protein (BAX) , cysteine proteinase 3 (Caspase 3) ], mitogen-activated protein kinase (MAPK) signaling pathway-related proteins[p38 mitogen-activated protein kinase (P38MAPK) , extracellular regulatory protein kinase (ERK) ] expression. Results: Compared with the control group, the BUN content in the serum of rats in the exposure group was significantly increased on days 7, 21, and 28, the CRE content was significantly increased on 21 days, the CRE content was significantly decreased on 28 and 35 days, and the organ coefficient and renal mercury content were 14 to 35 days. Significantly increased, and the differences were statistically significant (P<0.05) . Compared with the control group, rats in the exposed group showed increased glomerular stroma, tubule dilatation and other renal cell apoptosis at 14 to 35 days, and Cyt C expression was obvious in the exposed groups at 14, 21 days. Compared with the control group, the BAX content of the rats in the exposed group was significantly increased on the 21st day, the content of Caspase 3 in the rats on the 14th and 21st days was significantly increased, and the content of the P38MAPK in the 35th day was significantly increased (P<0.05) . Conclusion: HgCl(2) may cause renal cell damage through the mitochondrial pathway of apoptosis and cause nephrotic syndrome, and the MAPK signaling pathway may regulate this process and exert an inhibitory effect on apoptosis.