Serum Metabonomics Study of Difference in Lymph Node Metastasis of Pancreatic Ductal Adenocarcinoma Based on LC-MS / 肿瘤防治研究

Objective To investigate the differential metabolites of lymph node metastasis in pancreatic ductal carcinoma (PDAC) and provide new ideas for the pathogenesis, early diagnosis and treatment of metastatic pancreatic cancer. Methods Forty serum specimens of patients with pancreatic ductal carcinoma were collected and divided into lymph node metastasis group (18 cases) and non-metastasis group (22 cases). Thirty-one serum specimens were also collected from the healthy control group. Liquid chromatographytandem mass spectrometry was used to analyze the differential metabolites and metabolic pathways between patients with PDAC and healthy controls as well as between lymph node metastasis and non-metastasis groups. Results Principal component analysis and partial least squares-discriminant analysis revealed statistically significant differences in metabolites and metabolic pathways between patients with PDAC and the healthy controls and between lymph node metastasis and non-metastasis groups. The differences in profiles were also statistically significant. Seventy-six different metabolites and 11 metabolic pathways were screened between patients with PDAC and the healthy controls, among which phenylalanine metabolism and histidine metabolism were the two most influential metabolic pathways. Four different metabolites were screened between lymph node metastasis and non-metastasis groups, and the expression of ethopropazine and phenylalanine were upregulated but the expression of tetrahydrodeoxycorticosterone and oxprenolol were downregulated. Conclusion Metabolites are significantly altered in the lymph node metastasis group of patients with PDAC compared with the non-metastasis group. Ethopropazine, phenylalanine, tetrahydrodeoxy corticosterone, and oxprenolol are potential biomarkers of lymph node metastasis in patients with PDAC.

Ketogenic diet improves low temperature tolerance in mice by up-regulating PPARα in the liver and brown adipose tissue / 生理学报

The aim of the present study was to investigate the effects of short-term ketogenic diet on the low temperature tolerance of mice and the involvement of peroxisome proliferator-activated receptor α (PPARα). C57BL/6J mice were divided into two groups: normal diet (WT+ND) group and ketogenic diet (WT+KD) group. After being fed with normal or ketogenic diet at room temperature for 2 d, the mice were exposed to 4 °C low temperature for 12 h. The changes in core temperature, blood glucose, blood pressure of mice under low temperature condition were detected, and the protein expression levels of PPARα and mitochondrial uncoupling protein 1 (UCP1) were detected by Western blot. PPARα knockout mice were divided into normal diet (PPARα-/-+ND) group and ketogenic diet (PPARα-/-+KD) group. After being fed with the normal or ketogenic diet at room temperature for 2 d, the mice were exposed to 4 °C low temperature for 12 h. The above indicators were also detected. The results showed that, at room temperature, the protein expression levels of PPARα and UCP1 in liver and brown adipose tissue of WT+KD group were significantly up-regulated, compared with those of WT+ND group. Under low temperature condition, compared with WT+ND, the core temperature and blood glucose of WT+KD group were increased, while mean arterial pressure was decreased; The ketogenic diet up-regulated PPARα protein expression in brown adipose tissue, as well as UCP1 protein expression in liver and brown adipose tissue of WT+KD group. Under low temperature condition, compared to WT+ND group, PPARα-/-+ND group exhibited decreased core temperature and down-regulated PPARα and UCP1 protein expression levels in liver, skeletal muscle, white and brown adipose tissue. Compared to the PPARα-/-+ND group, the PPARα-/-+KD group exhibited decreased core temperature and did not show any difference in the protein expression of UCP1 in liver, skeletal muscle, white and brown adipose tissue. These results suggest that the ketogenic diet promotes UCP1 expression by up-regulating PPARα, thus improving low temperature tolerance of mice. Therefore, short-term ketogenic diet can be used as a potential intervention to improve the low temperature tolerance.

Membrane dual-targeting probes: A promising strategy for fluorescence-guided prostate cancer surgery and lymph node metastases detection

Fluorescence-guided surgery (FGS) with tumor-targeted imaging agents, particularly those using the near-infrared wavelength, has emerged as a real-time technique to highlight the tumor location and margins during a surgical procedure. For accurate visualization of prostate cancer (PCa) boundary and lymphatic metastasis, we developed a new approach involving an efficient self-quenched near-infrared fluorescence probe, Cy-KUE-OA, with dual PCa-membrane affinity. Cy-KUE-OA specifically targeted the prostate-specific membrane antigen (PSMA), anchored into the phospholipids of the cell membrane of PCa cells and consequently showed a strong Cy7-de-quenching effect. This dual-membrane-targeting probe allowed us to detect PSMA-expressing PCa cells both in vitro and in vivo and enabled clear visualization of the tumor boundary during fluorescence-guided laparoscopic surgery in PCa mouse models. Furthermore, the high PCa preference of Cy-KUE-OA was confirmed on surgically resected patient specimens of healthy tissues, PCa, and lymph node metastases. Taken together, our results serve as a bridge between preclinical and clinical research in FGS of PCa and lay a solid foundation for further clinical research.

Correlation of TRAF4 and RSK4 Protein Expression Levels in Gastric Cancer Tissues with Recurrence After Laparoscopic Radical Resection / 肿瘤防治研究

Objective To investigate the relationships between the expression levels of tumor necrosis factor receptor associated factor 4 (TRAF4) and ribosomal S6 protein kinase 4 (RSK4) protein in gastric cancer tissues and the recurrence after laparoscopic radical gastrectomy. Methods In total, 176 patients were divided into the recurrence and non-recurrence group, and the expression levels of TRAF4 and RSK4 protein in cancer and adjacent tissues and in gastric cancer tissues in the recurrence and non-recurrence group were compared. The influencing factor of recurrence and the efficacy of TRAF4 and RSK4 protein expression in predicting recurrence were analyzed. Results The positive expression rate of TRAF4 protein in gastric cancer tissues was higher than that in adjacent tissues (P < 0.05) and that in the recurrence group was higher than that in the non-recurrence group (P < 0.05). The positive expression rate of RSK4 protein in gastric cancer tissues was lower than that in adjacent tissues (P < 0.05) and that in the recurrence group was lower than that in non-recurrence group (P < 0.05). The largest tumor diameter 5 cm, poor differentiation, TNM Ⅲ stage, depth of invasion T3-T4, lymph node metastasis, absence of adjuvant chemotherapy after operation, positive expression of TRAF4 and RSK4 protein, and regular diet w influenced the post-operative recurrence (all P < 0.05). The accuracy of TRAF4 and RSK4 protein in gastric cancer tissues in combined predicting the recurrence was 83.52%. Conclusion The expression of TRAF4 protein is high, and the RSK4 protein is low in gastric cancer tissue, which are related to recurrence.

Association between metabolism-related chronic disease combination and prevalence of non-alcoholic fatty liver disease in community residents in Shanghai / 中华流行病学杂志

Objective: To explore the combination of metabolism-related chronic diseases associated with the prevalence of non-alcoholic fatty liver disease (NAFLD) in community residents in Shanghai. Methods: The baseline data of Shanghai Suburban Adult Cohort and Biobank were used to understand the prevalence of five metabolism-related chronic diseases, including obesity, hypertension, hyperlipidemia, gout and diabetes, based on questionnaire survey, physical examination and blood biochemical detection. NAFLD was diagnosed by B-ultrasound detection and questionnaire. Multivariable logistic regression model was used to analyze the association of 31 metabolism-related chronic diseases combinations with the prevalence of NAFLD. Results: The median age (Q1, Q3) of 65 477 subjects was 60 (51, 66) years, and men accounted for 40.6%. The overall prevalence of NAFLD was 38.2%, and the prevalence of HAFLD in patients without any of the five metabolism-related chronic diseases was 12.0%. The chronic disease combination with the strongest association with NAFLD was obesity + hypertension + hyperlipidemia + gout + diabetes in the total population (OR=37.94, 95%CI: 31.02-46.41), in women (OR=36.99, 95%CI: 28.78-47.54) and in age group ≥60 years (OR=36.19, 95%CI: 28.25-46.36). The chronic disease combination with the strongest association with NAFLD was obesity + hyperlipidemia + gout + diabetes in men (OR=50.70, 95%CI: 24.62-104.40) and in age group <60 years (OR=49.58, 95%CI: 24.22-101.47). Conclusions: The prevalence of NAFLD in community residents in Shanghai was high. Attention needs to be paid to health of obese people and weight loss should be promoted for them. Community health education should be strengthened for patients complicated with gout, diabetes, hyperlipidemia and hypertension and it is necessary to correct abnormal serum uric acid, blood sugar, blood lipids and blood pressure in a timely manner to reduce the risk of NAFLD.

Association between sedentary behavior and force expiratory volume in 1 second reduction in middle-aged and elderly adults in communities / 中华流行病学杂志

Objective: To analyze the relationship between sedentary behavior and the force expiratory volume in 1 second (FEV1) reduction in middle-aged and elderly people in communities. Methods: The participants aged ≥40 years were randomly selected from a natural population cohort in Songjiang District, Shanghai, for pulmonary function tests and survey by using international physical activity questionnaire, a generalized additive model was used to analyze the association between sedentary behavior and FEV1 reduction in the study population and different sex-age subgroups. Results: A total of 3 121 study subjects aged ≥40 years were included. The prevalence of FEV1 reduction was 14.8%, which was higher in men than in women. There were 24.8% participants were completely sedentary. The prevalence of FEV1 reduction in women aged <60 years in complete sedentary group was 2.04 (95%CI: 1.11-3.72) times higher than that in non-complete sedentary group. In men aged <60 years, the prevalence of FEV1 reduction increased with daily sedentary time (OR=1.16, 95%CI: 1.04-1.29), and the prevalence of FEV1 reduction was also higher in those with sedentary time >5 hours/day than those with sedentary time ≤5 hours/day (OR=3.02, 95%CI: 1.28-7.16). The sensitivity analysis also found such associations. Conclusions: FEV1 reduction rate in age group <60 years was associated with sedentary behavior. Complete sedentary behavior or absence of moderate to vigorous physical activity played important roles in FEV1 reduction in women, while men were more likely to be affected by increased sedentary time, which had no association with physical activity. Reducing sedentary time to avoid complete sedentary behavior, along with increased physical activity, should be encouraged in middle-aged and elderly adults in communities to improve their pulmonary function.

Efficacy and safety of low-dose rituximab in treatment of pediatric nephrotic syndrome: a prospective randomized controlled trial / 中国当代儿科杂志

OBJECTIVES@#To study the efficacy and safety of repeated application of rituximab (RTX) at a low dose (200 mg/m2) versus the recommended dose (375 mg/m2) for remission maintenance in frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS).@*METHODS@#A randomized controlled trial was conducted for 29 children with FRNS/SDNS who received systemic treatment in the Department of Nephrology, Anhui Provincial Children's Hospital, from September 2020 to December 2021. These children were divided into a recommended dose group (n=14) and a low dose group (n=15) using a random number table. The two groups were compared in terms of general characteristics, changes in CD19 expression after RTX treatment, number of relapses, glucocorticoid dose, adverse reactions of RTX, and hospital costs.@*RESULTS@#After RTX treatment, both the low dose group and the recommended dose group achieved B-lymphocyte depletion and had significant reductions in the number of relapses and glucocorticoid dose (P<0.05). The low dose group had a comparable clinical effect to the recommended dose group after RTX treatment (P>0.05), and the low dose group had a significant reduction in hospital costs for the second, third, and fourth times of hospitalization (P<0.05). There were no serious adverse reactions in either group during RTX treatment and late follow-up, and there was no significant difference in adverse reactions between the two groups (P>0.05).@*CONCLUSIONS@#Repeated RTX treatment at a low dose has comparable clinical efficacy and safety to that at the recommended dose and can significantly reduce the number of FRNS/SDNS relapses and the amount of glucocorticoids used, with little adverse effect throughout the treatment cycle. Therefore, it holds promise for clinical application.

Acupoint Injection Decreases Anesthetic Cosumption during Combined Spinal-Epidural and Patient-Controlled Epidural Labor Analgesia / 中国结合医学杂志

OBJECTIVE@#To explore if acupoint injection can improve analgesic effects or delivery outcomes in parturients who received combined spinal-epidural analgesia (CSEA) and patient-controlled epidural analgesia (PCEA) for labor analgesia.@*METHODS@#A total of 307 participants were prospectively collected from July 2017 to December 2019. The participants were randomized into the combined acupoint injection with CSEA plus PCEA group (AICP group, n=168) and CSEA plus PCEA group (CP group, n=139) for labor analgesia using a random number table. Both groups received CSEA plus PCEA at cervical dilation 3 cm during labor process, and parturients of the AICP group were implemented acupoint injection for which bilateral acupoint of Zusanli (ST 36) and Sanyinjiao (SP 6) were selected in addition. The primary outcome was Visual Analogue Scale (VAS) score, and the secondary outcomes were obstetric outcomes and requirement of anesthetics doses. Safety evaluations were performed after intervention.@*RESULTS@#The VAS scores were significantly lower in the AICP group than in the CP group at 10, 30, 60, and 120 min after labor analgesia (all P<0.05). The latent phase of the AICP group was shorter than that of the CP group (P<0.05). There were less additional anesthetics consumption, lower incidences of uterine atony, fever, pruritus and urinary retention in the AICP group than those in the CP group (all P<0.05).@*CONCLUSION@#Acupoint injection combined CSEA plus PCEA for labor analgesia can decrease the anesthetic consumption, improve analgesic quality, and reduce adverse reactions in the parturients. (Registration No. ChiMCTR-2000003120).

Clinical investigation and research on Axis Ⅱ evaluation of patients with temporomandibular disorders / 中华口腔医学杂志

Objective: To screen the physical, psychological and behavioral factors related to patients with temporomandibular disorders (TMD) by using Axis Ⅱ assessment instruments of diagnostic criteria for TMD(DC/TMD). And to provide a reference to establish personalized diagnosis and treatment plans for TMD patients so as to prevent TMD and reduce predisposing factors. Methods: A total of 141 TMD patients, who were admitted in the Department of Oral and Maxillofacial Surgery in School and Hospital of Stomatology, Wuhan University from October 2018 to February 2021 were selected. There were 121 females and 20 males, with an average age of 30 years. A total of 90 healthy people were included as controls. A full-time psychologist conducted relevant questionnaire surveys. The questionnaires include general clinical survey forms and TMD symptom questionnaire. In addition, Axis Ⅱ assessment instruments include graded chronic pain scale, jaw functional limitation scale, oral behaviors checklist, patient health questionnaire-9 (depression), generalized anxiety disorder scale, patient health questionnaire-15 (physical symptoms), etc. The main observational indicators include: pain level, pain impact rates, overall classification of chronic pain, limited chewing function score, limited motor function score, limited communication function score, total jaw function restricted score, depression score, anxiety score, somatic symptom score and oral behavior score.The survey data were imported into SPSS 22.0 software for statistical analysis. Results: In the TMD group 60.3% (85/141) patients had various degrees of pain, 24.1% (34/141) of those with pain effect grades from 1 to 3 and 61.0% (86/141) showed chronic pain overall grades from Ⅰ to Ⅳ. The chewing function restricted score was 2.67(1.17, 4.25), motor function restricted score was 4.25(1.75, 6.12), communication function restricted score was 1.13(1.00, 2.25) and total jaw function restricted score was 2.56(1.47, 4.15) respectively. Patients with mild depression or above accounted for 59.6%(84/141), patients with mild anxiety or above accounted for 56.7%(80/141), 46.1%(65/141) patients had somatization symptoms. Statistical differences (P<0.05) were determined between TMD group and control group in various scores of jaw function, oral behavior grading, depression, anxiety, and physical symptoms. Physical symptoms had significantly statistical difference between different diagnostic classification(P<0.05). Meanwhile, among the different chronic pain levels in the TMD group, there were statistical differences in the various scales of mandibular dysfunction, depression, anxiety, and somatization. In the TMD group, other significant differences were noticed between males and females in terms of the average score of mouth opening, verbal and facial communication, the total score of mandibular dysfunction as well as physical symptoms (P<0.05). Conclusions: Compared with the healthy people, patients with TMD had more abnormal oral behaviors, different restriction of the mandibular functional activities. At the same time, depression, anxiety, and somatization were more serious. Patients with osteoarthritis and subluxation of temporomandibular joint were more likely to suffer physical symptoms. TMD patients suffering from pain had more severe mandibular dysfunction and symptoms of depression, anxiety, and somatization.

Betulin Targets Lipin1/2-Meidated P2X7 Receptor as a Therapeutic Approach to Attenuate Lipid Accumulation and Metaflammation

The present study focused on the potential mechanism of betulin (BT), a pentacyclic triterpenoid isolated from the bark of white birch (Betula pubescens), against chronic alcohol-induced lipid accumulation and metaflammation. AML-12 and RAW 264.7 cells were administered ethanol (EtOH), lipopolysaccharide (LPS) or BT. Male C57BL/6 mice were fed Lieber-DeCarli liquid diets containing 5% EtOH for 4 weeks, followed by single EtOH gavage on the last day and simultaneous treatment with BT (20 or 50 mg/ kg) by oral gavage once per day. In vitro, MTT showed that 0-25 mM EtOH and 0-25 μM BT had no toxic effect on AML-12 cells. BT could regulate sterolregulatory-element-binding protein 1 (SREBP1), lipin1/2, P2X7 receptor (P2X7r) and NOD-like receptor family, pyrin domains-containing protein 3 (NLRP3) expressions again EtOH-stimulation. Oil Red O staining also indicated that BT significantly reduced lipid accumulation in EtOH-stimulated AML-12 cells. Lipin1/2 deficiency indicated that BT might mediate lipin1/2 to regulate SREBP1 and P2X7r expression and further alleviate lipid accumulation and inflammation. In vivo, BT significantly alleviated histopathological changes, reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and triglyceride (TG) levels, and regulated lipin1/2, SREBP1, peroxisome proliferator activated receptor α/γ (PPARα/γ) and PGC-1α expression compared with the EtOH group. BT reduced the secretion of inflammatory factors and blocked the P2X7rNLRP3 signaling pathway. Collectively, BT attenuated lipid accumulation and metaflammation by regulating the lipin1/2-mediated P2X7r signaling pathway.

Comparative analysis of blood components distribution in 24 domestic prefecture-level blood stations / 中国输血杂志

【Objective】 To understand the current situation of blood components distribution in domestic prefecture-level blood stations through analyzing the components distribution data of 24 prefecture-level blood stations in China. 【Methods】 The data of components distribution of 24 blood stations from 2017 to 2020 as well as the data of blood deployment of 24 blood stations from 2019 to 2020 were collected and analyzed. 【Results】 From 2017 to 2020, positive annual growth in red blood cells, plasma and cryoprecipitate was observed in 22, 19 and 15 out of the 24 blood stations, and the annual growth median rate of above three components was 5.24%, 3.80% and 3.25%, respectively. Among the 24 prefecture-level blood stations, 23 carried out the preparation of cryoprecipitate. 【Conclusion】 The distribution of red blood cells, cryoprecipitate and plasma in prefecture-level blood stations is increasing year by year. However, there is a overstock of plasma, and most blood stations need blood employment.

Associations of hyperglycemic emergency and severe hypoglycemia incidences with seasonality and ambient temperature among pregnant women with diabetes: a nested case-control study in Taiwan

BACKGROUND@#Associations of acute glycemic complications with season and ambient temperature have been reported in general population with diabetes. However, little is known about the risks of acute glycemic complications in relation to season and ambient temperature in pregnant women, who are likely to be even more vulnerable. This work aimed to investigate the associations of season and ambient temperature with pregnancies complicated with hyperglycemia emergency or severe hypoglycemia.@*METHODS@#Two separate case-control studies were nested within 150,153 pregnancies by women with type 1, type 2, or gestational diabetes between 2009 and 2014 in Taiwan. Hyperglycemia emergency (mainly diabetic ketoacidosis and hyperosmolar hyperglycemic state) and severe hypoglycemia occurred in 77 and 153 diabetic pregnancies (cases), respectively. Ten control pregnancies were randomly selected for each case by matching each case pregnancy on type of diabetes (i.e., T1DM, T2DM, or GDM), maternal age on the date of acute glycemic complication occurrence (i.e., index date), and "length of gestation at risk" (i.e., period between conception and index date). Meteorological parameters were retrieved from 542 meteorological monitoring stations across Taiwan during 2008-2014. Conditional logistic regression analysis with generalized estimation equation was separately performed to estimate the covariate adjusted odds ratios (ORs) of each of the two acute glycemic complications in association with season and ambient temperature within 30 days prior to the index date.@*RESULTS@#Compared to summer, winter season was associated with a significantly elevated risk of severe hypoglycemia with an OR of 1.74 (95% confidence interval (CI) 1.08-2.79). The OR of hyperglycemic emergency was also elevated in winter season at OR of 1.88, but the significance is only marginal (95% CI 0.97-3.64, p = 0.0598). Subgroup analyses further noted that such seasonal variation was also observed in pregnancies with pre-pregnancy type 1 diabetes and gestational diabetes. On the other hand, ambient temperature was not significantly associated with the two acute glycemic complications.@*CONCLUSIONS@#A moderately but significantly elevated risk of severe hypoglycemia was found in pregnant women with diabetes during winter season, and such increased risk was more evident in pregnancies with T1DM.

Associations between gene polymorphisms of signal transducer and activator of transcription 3 and the susceptibility to hepatitis B virus related liver cirrhosis / 中华预防医学杂志

To investigate the associations between gene polymorphisms of signal transducer and activator of transcription 3 (STAT3) and liver cirrhosis (LC) after hepatitis B virus (HBV) infection. A case-control study was conducted in 243 patients with hepatitis B cirrhosis (HBV-LC, case group) and 486 HBV-infected subjects without LC (non-LC, control group) collected from January 2018 to September 2020 at the Changsha Central Hospital Affiliated to Nanhua University. Three single nucleotide polymorphisms (SNPs) of STAT3 gene, including rs4796793C>G, rs2293152C>G, and rs1053004T>C were selected through literature and biological information database, and the genotypes were detected by real-time fluorescent quantitative PCR (RFQ-PCR). The distribution differences of STAT3 SNPs genotypes between the two groups were compared using Chi-square test and haplotype analysis was conducted by Shesis online. The proportion of HBV C genotype in HBV-LC patients was significantly higher than that in the control group (80.91% vs. 70.79%, χ2=7.109, P=0.008), while the logarithm of ALT was significantly lower than that of the control group (1.78±0.43 vs. 1.95±0.54, t=3.801, P=0.000). The genotypes distributions of rs4796793, rs2293152, and rs1053004 were not significantly different between HBV-LC and non-LC in overall analysis and stratified analysis by gender (χ²=2.610, 1.505, 0.586, 2.653, 2.685, 1.583, 0.351, 5.388, 0.339, respectively, P>0.05 for each). Among the subjects infected with HBV genotype C, rs1053004 CC (vs. TT) significantly increased the risk of HBV-LC [odds ratio (OR) = 1.40, 95% confidence interval (CI): 1.03-1.91]. Among the HBV-infected subjects with HBeAg negative, rs4796793 GG genotype (vs. CC) and G allele (vs. C) significantly increased the risks of HBV-LC (OR = 2.17, 95%CI: 1.11-4.23; OR = 1.45, 95%CI: 1.06-1.97, respectively). Haplotypes analysis showed that the frequency of haplotype C-G-T composed of rs4796793, rs2293152, and rs1053004 was significantly lower in HBV-LC than that in the control group (non-LC) (27.3% vs. 35.6%, χ²=9.949, P = 0.001). The correlation between STAT3 and HBV-LC is different in HBV-infected subjects with different infection status. The HBV-infected subjects carrying haplotype rs4796793C-rs2293152G-rs1053004T of STAT3 gene have significantly decreased risk of LC.

Prediction model of portal pressure for HBV-related cirrhosis based on radiomics feature / 中国医师杂志

Objective:In this study, the liver, spleen, and hepatic portal vein in the portal venous phase images of abdominal enhanced computed tomography (CT) are artificially segmented and annotated, and the radiomics features are extracted from them. A model for predicting portal pressure in patients with hepatitis B virus (HBV) related cirrhosis is constructed by combining radiomics features with clinical indicators.Methods:A total of 171 patients who had abdominal enhancement CT examination and trans-jugular hepatic venous pressure gradient (HVPG) measurement at the same time were enrolled from January 2016 to May 2020 in the Zhongshan Hospital Affiliated to Fudan University. The liver, spleen, and hepatic portal vein in the portal venous phase images of the CT were manually labeled by using ITK-SNAP 3.8 software. The radiomics features of these three sites were extracted using Python programming, and an HVPG prediction model was established.Results:A total of 171 patients was included in the study. The average age was (51.1±10.3)years, of which 134(78.4%) were males, and the average HVPG was 16.87±5.695. A total of 2 553 radiomics features were extracted from three sites of the portal venous phase images of abdominal enhanced CT in each patient. The 2 553 features extracted were screened using LASSO, and by combing with clinical features and radiomics features, the predictive model of HVPG was obtained: m_HVPG=31.622+ 0.028 8T×total bile acids-6.31(portal venous wavelet-LHH_glcm_ClusterShade)=0.253(portal venous wavelet-LHL_glszm_LargeAreaLowGrayLevelEmphasis)-20.9(spleen wavelet-LLH_glcm_Correlation)-0.000 127(liver original_shape_SurfaceArea)+ 2.79(liver wavelet-LLH_glcm_ClusterShade). The coefficient of determination R2 was 0.345. Conclusions:The study suggests that radiomics features of the liver, spleen, and portal venous combined with clinical features may be used as a non-invasive method to assess the portal pressure in patients with HBV-related cirrhosis.

Clinical evaluation of different modalities in emergency endoscopic treatment of esophageal variceal bleeding / 中国医师杂志

Objective:This study aimed to evaluate the rebleeding risk and prognosis of patients being treated after acute esophageal varices bleeding by two different treatment strategies: sclerosing agent combined with tissue glue injection, esophageal varices ligation (EVL), through comparing the therapeutic effects and securities.Methods:A total of 76 patients who underwent endoscopy and received treatment in Zhongshan Hospital Affiliated to Fudan University due to acute esophageal variceal bleeding were included retrospectively. 6 patients with active bleeding and 70 patients with thrombus in esophagus varices under gastroscopy. Among them, 21 cases were treated with sclerosing agent combined with tissue glue injection (sclerosing tissue glue group), and 55 cases were treated with EVL (EVL group). The emergency endoscopic diagnosis and treatment of the two groups were compared, and the risk factors of rebleeding 6 months after endoscopic treatment were analyzed by univariate and multivariate analysis.Results:All patients received endoscopic treatment successfully. During the follow-up period of 6 months after endoscopic treatment, rebleeding occurred in 13 cases. Kaplan Meier analysis showed that the 6-month rebleeding rate in the sclerosing tissue glue group was significantly higher than that in the EVL group (41.6% vs 12.3%, P=0.011). There were 8 deaths in total. Kaplan Meier analysis showed that there was no significant difference in 6-month mortality between the two groups (17.5% vs 10.1%, P=0.616). Multivariate analysis further showed that malignant tumor ( HR=3.700, 95% CI: 1.187-11.536, P=0.024) and treatment mode of esophageal variceal bleeding ( HR=4.834, 95% CI: 1.443-16.193, P=0.011) were independent risk factors for rebleeding 6 months after endoscopic treatment of acute esophageal variceal bleeding. Conclusions:This study found that EVL and the combining injection of lauromacrogol and cyanoacrylate could be used in emergent hemostatic treatment for acute esophageal varices bleeding. Moreover, EVL is the prioritized approach in endoscopic emergency treatment with a lower rebleeding rate and fewer complications. Sclerotherapy combined with tissue glue can be used as one of the measures of emergency treatment, which is not better than ligation.

Correlation between thromboelastography and portal vein thrombosis in patients with cirrhotic esophagogastric varices / 中国医师杂志

Objective:To investigate the correlation between thromboelastography (TEG) and portal vein thrombosis in patients with cirrhotic esophagogastric varices.Methods:210 hospitalized patients with cirrhotic esophagogastric varices treated in Zhongshan Hospital Affiliated to Fudan University from December 2016 to December 2017 were retrospectively included. They were divided into portal vein thrombosis group (PVT group) and non portal vein thrombosis group (NPVT group) according to whether they were complicated with portal vein thrombosis. The correlation between the results of TEG coagulation reaction time (R value), coagulation time (K value), αAngle, maximum amplitude (MA) and coagulation composite index (CI) and portal vein thrombosis was analyzed. The characteristics of coagulation status in patients with portal vein thrombosis in cirrhosis were compared.Results:A total of 91 patients (43.3%) were complicated with portal vein thrombosis. The R value in the PVT group was significantly lower than that of NPVT group [5.49(5.22-5.77) vs 5.98(5.76-6.20), P=0.006]. Logistic regression analysis showed that Child Pugh grade ( OR=2.883, 95% CI: 1.630-5.098, P<0.001) and R value ( OR=0.739, 95% CI: 0.575-0.950, P=0.018) were independently associated risk factors of PVT. The R value of patients was significantly correlated with Child Pugh grade ( r=0.147, P=0.034), platelet ( r=-0.358, P<0.001), prothrombin time (PT) ( r=0.334, P<0.001) and international standardized ratio (INR) ( r=0.328, P<0.001). Conclusions:The decrease of TEG-R value is closely related to PVT in liver cirrhosis.

Practicing clinical research and multidisciplinary team management of portal hypertension / 中国医师杂志

The standard management of portal hypertension and its complications is one important part in achieving the goal of eliminating hepatitis B in 2030. There existing considerable controversy on the management of clinical issues related to portal hypertension: establishing a non-invasive portal pressure prediction model is an urgent need in clinic; emergency management of variceal bleeding is in need of real world evidence; and guidance regarding the management of portal hypertension and its complications is desiderating data validation from Chinese. Designing appropriate and high-quality clinical research on portal hypertension could provide credible evidence for clinical decision, contributing to the precision implement of diagnosis and treatment decisions on portal hypertension and its complications.

Mechanism of protein S-nitrosylation modification mediated severe acute pancreatitis / 中国医师杂志

Objective:This study aims to explore the pathogenic roles of protein S-nitrosylation modification in the development of severe acute pancreatitis, and provide new insights into the molecular mechanisms driving acute pancreatitis development.Methods:Thirty two Sprague Dawley (SD) rats were randomly divided into sham operation group, mild acute pancreatitis (MAP) group, severe acute pancreatitis (SAP) group and SAP + N-nitro-L-arginine methyl ester (L-NAME) group (treated with nitric oxide synthase inhibitor), 8 rats in each group. All rats were sacrificed to take blood from heart and pancreatic tissues 24 h after model construction. Total protein S-nitrosylation modification level in pancreatic tissues was quantitated by the biotin-switch method, followed by histological evaluation via hematoxylin and eosin (HE) staining. The serum endotoxin, D-lactic acid, diamine oxidase, interleukin-6 and tumor necrosis factor-ɑ(TNF-ɑ), amylase, alanine aminotransferase, urea nitrogen and calcium ions in rat were detected. Pearson correlation analysis was used to analyze the correlation between each index and protein S-nitrosylation.Results:Compared with the sham operation group, the modification level of protein S-nitrosylation in pancreatic tissue of MAP group increased significantly ( P<0.05); Compared with MAP group, the modification level of protein S-nitrosylation in pancreatic tissue of SAP group increased significantly ( P<0.05); Compared with SAP group, the modification level of protein S-nitrosylation in pancreatic tissue of SAP + L-NAME group decreased significantly ( P<0.05). HE staining showed that the degree of pancreatic necrosis and inflammatory cell infiltration in SAP + L-NAME group were significantly weaker than those in SAP group. The concentrations of serum endotoxin, diamine oxidase, D-lactic acid, IL-6 and TNF-ɑ, amylase, alanine aminotransferase, and urea nitrogen in the MAP group were significantly higher than those in the sham operation group (all P<0.05); The above indexes in SAP group were significantly higher than those in MAP group and sham operation group (all P<0.05); The above indexes in SAP + L-NAME group were significantly lower than those in SAP group (all P<0.05). The serum IL-6 and TNF-ɑ levels in rats with acute pancreatitis were positively correlated with protein S-nitrosylation in pancreatic tissue (all P<0.05). Conclusions:Protein S-nitrosylation modification plays essential roles in the development and progression of severe acute pancreatitis.

Study on the mechanism of Wuzi-Yanzong-Wan-medicated serum interfering with the mitochondrial permeability transition pore in the GC-2 cell induced by atractyloside / 中国天然药物

Wuzi-Yanzong-Wan (WZYZW) is a classic prescription for male infertility. Our previous investigation has demonstrated that it can inhibit sperm apoptosis via affecting mitochondria, but the underlying mechanisms are unclear. The purpose of the present study was to explore the actions of WZYZW on mitochondrial permeability transition pore (mPTP) in mouse spermatocyte cell line (GC-2 cells) opened by atractyloside (ATR). At first, WZYZW-medicated serum was prepared from rats following oral administration of WZYZW for 7 days. GC-2 cells were divided into control group, model group, positive group, as well as 5%, 10%, 15% WZYZW-medicated serum group. Cyclosporine A (CsA) was used as a positive control. 50 μmol·L-1 ATR was added after drugs incubation. Cell viability was assessed using CCK-8. Apoptosis was detected using flow cytometry and TUNEL method. The opening of mPTP and mitochondrial membrane potential (MMP) were detected by Calcein AM and JC-1 fluorescent probe respectively. The mRNA and protein levels of voltage-dependent anion channel 1 (VDAC1), cyclophilin D (CypD), adenine nucleotide translocator (ANT), cytochrome C (Cyt C), caspase 3, 9 were detected by RT-PCR (real time quantity PCR) and Western blotting respectively. The results demonstrated that mPTP of GC-2 cells was opened after 24 hours of ATR treatment, resulting in decreased MMP and increased apoptosis. Pre-protection with WZYZ-medicated serum and CsA inhibited the opening of mPTP of GC-2 cells induced by ATR associated with increased MMP and decreased apoptosis. Moreover, the results of RT-qPCR and WB suggested that WZYZW-medicated serum could significantly reduce the mRNA and protein levels of VDAC1 and CypD, Caspase-3, 9 and CytC, as well as a increased ratio of Bcl/Bax. However, ANT was not significantly affected. Therefore, these findings indicated that WZYZW inhibited mitochondrial mediated apoptosis by attenuating the opening of mPTP in GC-2 cells. WZYZW-medicated serum inhibited the expressions of VDAC1 and CypD and increased the expression of Bcl-2, which affected the opening of mPTP and exerted protective and anti-apoptotic effects on GC-2 cell induced by ATR.

Curriculum teaching design of Military Medical Psychology in medical universities / 中华医学教育探索杂志

This study comprehensively analyzes the course of Military Medical Psychology from 7 aspects including the nature and status, teaching objectives, teaching principles, teaching concepts, classroom teaching, practical teaching and lecturing principles, and finally summarizes the characteristics of the course and points out its shortcomings and prospects. The study found that the Military Medical Psychology is an important interdisciplinary course between medical psychology and military science; the teaching objectives include two categories, the overall goals and classified ones; the teaching principle emphasizes the forces of developing practice ability of service orientation; the teaching concept includes combining the theory with practice, focusing on the students, informatization and lectures; the mode of classroom teaching should be cases-introduction, theory-interpretation and case-analysis; the practical teaching should strengthen teaching skills, emphasize connection, stimulate interest and improve the health; lecturing principles emphasize the focus of content. This study has preliminarily completed the teaching design of the course of Military Medical Psychology, which is conducive to the smooth implementation of this course and the cultivation of professional talents of military medical universities.