Liver Fibrosis in the Natural Course of Chronic Hepatitis B Viral Infection: A Systematic Review with Meta-Analysis.

BACKGROUND: Quantitative data are limited on the natural course of liver fibrosis in patients with chronic HBV infection (CHB). AIMS: To estimate the prevalence of fibrosis status including non-fibrosis, significant fibrosis, advanced fibrosis, and cirrhosis throughout the natural course of CHB. METHODS: We searched Cochrane library, EMBASE, PubMed, SCOPUS, Web of Science, and ScienceDirect from January 1993 to November 2019 for studies with histologic data on liver fibrosis in CHB natural course. CHB course was defined based on current criteria for identifying infection phases as recommended by international clinical practice guidelines, including the HBeAg-positive immune-tolerant, HBeAg-positive immune-active, HBeAg-negative immune-inactive, HBeAg-negative immune-reactive, and HBsAg-negative phases. Pooled prevalence rate of fibrosis status at each phase was obtained from random-effect meta-analyses. RESULTS: Thirty-three studies with 9,377 adult participants (23.8-49.0 age years; 45.5-88.6% males) were eligible and finally included. The estimated prevalence of non-fibrosis, significant fibrosis, advanced fibrosis, and cirrhosis was, for HBeAg-positive immune-tolerant phase: 31.2% (95%CI 15.6-46.7), 16.9% (95%CI 7.8-26.1), 5.4% (95%CI 0.0-11.2), and 0.0% (95%CI 0.0-1.5); HBeAg-positive immune-active phase: 6.9% (95%CI 3.6-10.2), 50.6% (95%CI 39.2-61.9), 32.1% (95%CI 24.2-40.0), and 12.8% (95%CI 8.6-17.0); HBeAg-negative immune-inactive phase: 32.4% (95%CI 0.0-100.0), 24.8% (95%CI 4.5-45.1), 3.0% (95%CI 0.0-8.3), and 0.0% (95%CI 0.0-1.0); and HBeAg-negative immune-reactive phase: 6.3% (95%CI 3.5-9.2), 50.3% (95%CI 38.9-61.7), 30.3% (95%CI 20.9-39.6), and 10.0% (95%CI 6.6-13.5), respectively. There was only one study for HBsAg-negative phase, thus not allowing further meta-analyses. CONCLUSIONS: Fibrosis risk persists through CHB natural course. These data can support risk estimation in clinical practice and provide reference for noninvasive investigation.

The CEBPE rs2239633 genetic polymorphism on susceptibility to childhood acute lymphoblastic leukemia: an updated meta-analysis.

OBJECTIVES: We performed an updated meta-analysis to clarify the relationship between the CEBPE rs2239633 polymorphism and the childhood acute lymphoblastic leukemia (CALL) susceptibility. METHODS: All the case-control studies were updated on October 5, 2020, through Web of Science, PubMed, Cochrane Library, Embase, and China National Knowledge Infrastructure (CNKI) electronic database. The heterogeneity in the study was tested by the Q test and I2, and then the random ratio or fixed effect was utilized to merge the odds ratios (OR) and 95% confidence interval (CI). We also performed sensitivity analysis to estimate the impact of individual studies on aggregate estimates. Publication bias was investigated by using funnel plot and Egger's regression test. All statistical analyses were performed using Stata 12.0. RESULTS: A total of 20 case-control studies were selected, including 7014 patients and 16,428 controls. There was no association of CEBPE rs2239633 polymorphism with CALL (CC vs CT + TT: OR = 1.08, 95% CI = 0.94-1.26; CC + CT vs TT: OR = 1.10, 95% CI = 0.94-1.30; C vs T: OR = 1.02, 95% CI = 0.92-1.13). In the subgroup analysis by ethnicity, there is no significant association of this polymorphism and CALL risks among Asian and Caucasian populations in the three genetic models (CC vs CT + TT, CC + CT vs TT, and C vs T). CONCLUSION: This meta-analysis found no significant association between the CEBPE rs2239633 polymorphism and susceptibility to CALL.

Alanine aminotransferase influencing performances of routine available tests detecting hepatitis B-related cirrhosis.

The performances of routine tests such as FIB-4 and APRI in detecting cirrhosis and significant fibrosis in chronic hepatitis B (CHB) have been shown to be discrepant between studies. Novel tests such as red cell distribution width-platelet ratio (RPR), γ-glutamyl transpeptidase to platelet ratio (GPR) and easy liver fibrosis test (eLIFT) are introduced recently. To evaluate the aminotransferase influence on the performance of these routine tests, a total of 1005 CHB patients who underwent liver biopsies and routine tests were retrospectively analysed. The diagnostic cut-offs referring to likelihood ratio were determined for excluding or including cirrhosis diagnosis and also for ruling in significant fibrosis diagnosis. The performances of RPR, FIB-4, eLIFT and APRI in detecting cirrhosis seemed improved at higher ALT levels, while GPR was conversely impaired. The likelihood ratio was âˆ for APRI cut-off 2 diagnosing cirrhosis in ALT < 2 upper limit of normal (ULN), 14.6 for APRI cut-off 1.5 determining significant fibrosis in ALT ≤ 5ULN and 20.6 for FIB-4 cut-off 3.2 diagnosing ≥ F3 in the total cohort, respectively. The optimal cut-offs for cirrhosis diagnosis were increased with higher ALTs by tests which included aminotransferase, but not for RPR. The proportions of patients classified as having cirrhosis or no cirrhosis stratified by ALT level cut-offs were superior. Stepwise applying RPR, GPR and eLIFT would determine 60% of patients as having cirrhosis or no cirrhosis with an accuracy of 93.0%. In conclusion, the performance of aminotransferase comprising tests in detecting cirrhosis in CHB were influenced by ALT levels. Thus, ALT stratified cut-offs may be a preferred alternative. In resource-limited settings, stepwise applying routine tests could be recommended as a preferred measurement for cirrhosis detection.

Stepwise application of fibrosis index based on four factors, red cell distribution width-platelet ratio, and aspartate aminotransferase-platelet ratio for compensated hepatitis B fibrosis detection.

BACKGROUND AND AIM: Fibrosis index based on four factors (FIB-4) and aspartate aminotransferase-platelet ratio (APRI) were validated with unsatisfactory efficiency. Routine hematology index red cell distribution width-platelet ratio (RPR) had been tried in liver fibrosis detection. This study tries to evaluate the stepwise application of FIB-4, RPR, and APRI in detecting chronic hepatitis B (CHB) fibrosis. METHODS: A total of 246 compensated CHB patients who underwent liver biopsies, transient elastography, and routine blood tests including complete blood count were included. Dual cut-offs were determined to exclude or include cirrhosis diagnosis. Performance of stepwise combining routine biomarkers including RPR, FIB-4, and APRI were statistically analyzed. RESULTS: The Metavir F0, F1, F2, F3, and F4 were identified in 2.4%, 22.0%, 32.1%, 24.0%, and 19.5% of the eligible patients, respectively. The area under receiver operating characteristics curves for detecting significant fibrosis and cirrhosis were 0.853 and 0.883 for transient elastography; 0.719 and 0.807 for FIB-4; 0.638 and 0.791 for RPR; 0.720 and 697 for APRI; and 0.618 and 0.760 for mean platelet volume-platelet ratio, respectively. The proportion of patient determined as cirrhosis or non-cirrhosis was 65.9% by transient elastography, 36.9% by FIB-4, 30.5% by RPR, and 19.5% by APRI, respectively. These numbers for determining significant fibrosis were 49.6%, 24.2%, 21.5%, and 23.6% in the same order. Detected by stepwise application of FIB-4, RPR, and APRI, 41.5% and 52.8% of patients could be determined the state of significant fibrosis and cirrhosis, respectively. CONCLUSIONS: In source-limited settings without transient elastography, stepwise applying FIB-4, RPR, and APRI could free nearly half of CHB patients from liver biopsies in detecting significant fibrosis and cirrhosis.

Oral administration of honokiol attenuates airway inflammation in asthmatic mouse model.

Allergic asthma is a disease that pathologically characterized by eosinophilia infiltration, airway inflammation and hyper responsiveness. In this study, we evaluated the anti-inflammatory and anti-allergy possibilities of honokiol, a bi-phenolic compound obtained from species of the genus Magnolia, which has long been involved in traditional Chinese prescriptions for asthma-related lung diseases, in an ovalbumin-induced mouse model of allergic asthma. We found honokiol significantly inhibited the eosinophilia infiltration, reduced the airway inflammation and suppressed the production of inflammatory cytokines) as well as the IgE in serum. Moreover, MMP-9 and? (IL-4 and IFN- NF-κB were found to be involved in the honokiol induced biological process. These results suggested that honokiol may be a possible candidate in the treatment of lung asthma related diseases.

Optimization of hepatitis B cirrhosis detection by stepwise application of transient elastography and routine biomarkers.

BACKGROUND AND AIM: Significant inflammation may overestimate liver stiffness and result in false positive diagnosis by transient elastography for chronic hepatitis B (CHB) cirrhosis detection. This study tries to further improve the performance by stepwise combination with routine biomarkers. METHODS: A total of 236 compensated CHB patients with alanine transferase lower than five times upper limit of normal, liver biopsies, transient elastography, and routine blood tests were included. Performance of stepwise combination of transient elastography and routine biomarkers was analyzed. RESULTS: The area under the receiver operating characteristics curve for detecting cirrhosis was 0.876 for transient elastography, 0.794 for fibrosis index based on the four factors (FIB-4), 0.765 for age-platelet index (API), 0.715 for aspartate aminotransferase-platelet ratio index (APRI), and 0.661 for alanine-aspartate aminotransferase ratio, respectively. The numbers for significant fibrosis were 0.844, 0.662, 0.595, 0.695, and 0.510 in the same order. The proportion of patients determined as cirrhosis or non-cirrhosis was 66.5% by transient elastography, 41.1% by FIB-4, 14.4% by API, and 24.2% by APRI, respectively; the numbers for significant fibrosis were 55.5% by transient elastography, 11.9% by APRI, and none by the other serum markers. Stepwise combination of transient elastography and FIB-4/APRI increased positive predictive value of confirming cirrhosis diagnosis from 0.677 to 0.808 and 0.724, respectively; and the proportion of patients being determined in the state of cirrhosis and obviating liver biopsy was up to 76%. CONCLUSION: By transient elastography-based stepwise combination with readily available serum markers, performance of detecting compensated CHB cirrhosis could be significantly improved in terms of diagnosis accuracy and proportion of obviating liver biopsy.

Is transient elastography valuable for high-risk esophageal varices prediction in patients with hepatitis-B-related cirrhosis?

BACKGROUND AND AIM: The aim of this study was to evaluate the clinical value of transient elastography (TE) for high-risk esophageal varices (HREV) prediction in hepatitis-B-related cirrhosis patients. METHODS: A total of 238 patients with hepatitis B cirrhosis were prospectively enrolled. All patients had undergone TE and upper gastrointestinal endoscopy. Diagnostic value was assessed by the area under ROC curve (AUROC), predictive value and likelihood ratio. RESULTS: The size of esophageal varices correlated with liver stiffness with Kendall's tau_b 0.236 overall and 0.425 in patients with ALT ≥ 5 × upper limit of normal (ULN). The AUROC of TE predicting HREV was 0.73 (95% confidence interval 0.66-0.80) overall and 0.92 (0.82-1.01) for patients with ALT ≥ 5 × ULN. In patients with ALT ≥ 5 × ULN, cut-off 36.1 kPa predicted HREV with a 100% negative predictive value (NPV), an indefinite negative likelihood ratio (NLR), a 72.7% positive predictive value (PPV) and a positive likelihood ratio (PLR) of 9.3. The AUROC of HREV-predicting model, constructed by ultrasonography and TE (USLS), was 0.84 (0.77-0.90) in the training set and 0.85 (0.76-0.94) in the validating set. Cut-off 3.30 excluded HREV with NPV 0.946 and NLR 0.10, and cut-off 5.98 determined HREV with PPV 0.870 and PLR 10.24. Using USLS, nearly 50% of patients could avoid endoscopic screening. The model's predictive values were maintained at similar accuracy in the validation set. Differences of AUROC in USLS, liver stiffness/spleen diameter to platelet ratio score and ultrasonic score were not significant. CONCLUSIONS: TE may predict HREV in patients with ALT ≥ 5 × ULN. Overall, the clinical values of TE and USLS for HREV prediction should be evaluated by further studies.

Larger biopsies evaluation of transient elastography for detecting advanced fibrosis in patients with compensated chronic hepatitis B.

BACKGROUND AND AIM: Although larger biopsies sample had been recommended for the study of non-invasive liver fibrosis assessment, few studies with larger biopsies for transient elastography (TE) detecting liver fibrosis had been reported. The present study tries to re-evaluate the performance of TE for detecting advanced fibrosis (≥F3) with larger biopsies in patients with compensated chronic hepatitis B. METHODS: A total of 375 compensated patients were analyzed, who had undergone liver biopsy, reliable TE and routine blood tests. RESULTS: The area under the receiver operating characteristic curve (AUC) was influenced by liver biopsy sample: 0.873 (95% confidence interval 0.838-0.909) in total patients, 0.880 (0.844-0.917) in length ≥ 15 mm, 0.897 (0.863-0.932) in length ≥ 20 mm and 0.911 (0.874-0.949) in length ≥ 25 mm. In patients with sample length ≥ 20 mm, the cutoffs to exclude and confirm advanced fibrosis were 7.1 kPa and 12.7 kPa, respectively. Stratified by alanine aminotransferase of two times the upper limit of normal (ALT 2 × ULN), transient elastography detecting advanced fibrosis with the most efficiency by 72.5% of patients obviated from liver biopsy. In patients with normal bilirubin and ALT < 2 × ULN, the area was 0.921 (0.860-0.982), and cutoffs for excluding and confirming diagnosis were 7.4 kPa and 10.6 kPa, respectively; 80% of patients could be classified with or without advanced fibrosis (AF). In patients with normal bilirubin and ALT ≥ 2 × ULN, the corresponding numbers were 0.885 (0.824-0.947), 7.5 kPa, 12.7 kPa and 79.2%, respectively. CONCLUSIONS: Inadequate sample study would underestimate the efficiency of TE on detecting advanced fibrosis. With ALT 2 × ULN stratified cutoffs, TE determined nearly 80% of patients with normal bilirubin as AF or non-AF and obviated them from liver biopsies.

Preoperative nutritional evaluation of prostate cancer patients undergoing laparoscopic radical prostatectomy.

BACKGROUND AND OBJECTIVE: Prostate cancer (PCa) is one of the most common malignant tumors in men. Geriatric Nutritional Risk Index (GNRI) is an objective index for evaluating nutritional status of elderly people over 65 years old. The aim of the current study was to explore the correlation and predictive value between GNRI and postoperative recovery and complications in PCa patients undergoing laparoscopic radical prostatectomy (LRP). METHODS: Taking 98 as the GNRI boundary value, 96 PCa patients (aged≥65 y) undergoing LRP in the Department of Urology, Affiliated Hospital of North Sichuan Medical College from January 2018 to December 2020 were grouped into malnutrition group (MNg, 34 patients, 35.4%) and normal nutrition group (NNg, 62 patients, 64.6%). Basic information, laboratory examination indexes, operation conditions, postoperative complications and postoperative recovery indexes of patients were recorded and retrospectively analyzed. Clavien-Dindo Classification System (CDCS) was used to assess postoperative complications. T-test was used to analyze differences between the two groups. ROC curve was generated to determine the predictive value of GNRI for postoperative complications. RESULTS: Percentage of complications was significantly higher in MNg group compared with that in NNg group (P < 0.01). The average grade based on CDCS was significantly lower in NNg group compared with that in MNg group (P < 0.01). Body weight, Body Mass Index (BMI), preoperative hemoglobin value (HGB), serum albumin (ALB) values of MNg and NNg were significantly positively correlated with GNRI (P<0.01). Incidence and severity of postoperative complications of MNg patients were significantly higher compared with those of NNg patients (P<0.05). Average hospitalization cost of MNg patients was higher in MNg patients compared with that of NNg patients (P<0.05). Duration of post-anesthesia care unit (PACU), duration of antibiotic use and duration of indwelling drainage tube were longer in MNg patients compared with those in NNg patients (P<0.05). Furthermore, volume of indwelling drainage tube was higher in MNg patients compared with that in NNg patients (P<0.05). CONCLUSION: GNRI is an effective and reliable tool for evaluation of preoperative nutritional status of prostate cancer patients. The findings showed that GNRI is correlated with postoperative recovery and complications, and is an effective predictive marker.

Ultrasonic spleen thickness-based indexes surpass Baveno VI criteria in high-risk gastroesophageal varices detection.

AIMS: To evaluate the efficiency of ultrasonic spleen thickness (UST), routine variables and (expanded) Baveno VI criteria for high-risk gastroesophageal varices (HRGOV) detection in cirrhotic patients. METHODS: In total, 305 cirrhotic patients were retrospectively enrolled in the deriving cohort and 328 cirrhotic patients with hepatitis B sustained viral response were prospectively enrolled in the validation cohort. HRGOV was defined as medium and severe gastroesophageal varices (GOV), mild GOV with red signs or Child-Pugh C. The cut-offs for HRGOV were determined by likelihood ratio indicating strong evidences. Algorithms of Spleen thickness-Age-Liver stiffness measurement (LSM, by Fibroscan®)-Albumin (SALA) and Spleen thickness-Platelet-Albumin (SPA) were derived by multivariate analyses. RESULTS: The area under receiver operating characteristics curve of SALA, SPA, UST, platelet, and LSM were 0.849, 0.835, 0.808, 0.746, and 0.655 in the deriving cohort, and improved to 0.901, 0.904, 0.858, 0.876, and 0.811 in the validation cohort, respectively. While SALA, SPA, UST, platelet, Baveno VI criteria (BVI), and expanded BVI spared 46.6%, 38.0%, 29.2%, 21.0%, 12.1%, and 23.6% esophagogastroduodenoscopy in the deriving cohort, these numbers were improved to 68.1%, 66.8%, 27.1%, 37.8%, 36.0%, and 61.0% in the validating cohort, respectively; however, the negative likelihood ratio of expanded BVI was up to 0.16. SPA spared less esophagogastroduodenoscopy than SALA, which can be supplemented by stepwise applying UST and SPA. Sequentially combining UST and SALA, BVI and SALA exempted additional 10-5% endoscopies. CONCLUSIONS: SPA, without LSM, improves HRGOV detection comparing with BVI. UST based algorithms combination can achieve the best efficiency especially in sustained virus response hepatitis B.

[Transient elastography accurately predicts the severity of disease in patients with chronic hepatitis B].

OBJECTIVE: To evaluate the value of transient elastography (TE) for predicting severity of liver fibrosis in patients with chronic hepatitis B (CHB). METHODS: A total of 969 patients with CHB was enrolled and recruited for analysis, which had been received TE scan, including 258 patients of liver biopsy, and 117 patients of gastric endoscopy. RESULTS: A total of 35 patients was excluded from analysis due to TE failure or unreliable TE. Liver stiffness measurement (LSM) was independently influenced by bilirubin, AST, liver fibrosis and inflammation, ultrasonic score and albumin. TE predicted Child-Pugh C, B/C, liver fibrosis S4, ≥ S3 and ≥ S2 with respective area under receiver operating characteristics curves (AUROC) 0.907 (95%CI 0.886 - 0.928), 0.920(95%CI 0.899 - 0.940), 0.871(95%CI 0.819 - 0.923), 0.852(95%CI 0.805 - 0.899) and 0.807(95%CI 0.749 - 0.865), respectively. While LSM < 32.2 kPa excluded Child-Pugh C with 99.4% probability, LSM ≥ 35.3 kPa determined Child-Pugh B/C with positive predictive value (PPV) 0.820. For compensated CHB, cut-offs of LSM 23.3, 15.2 and 10.8 kPa diagnosed cirrhosis, liver fibrosis ≥ S3 and ≥ S2 with positive likelihood ratio nearly 10.0 and PPV 0.692, 0.882 and 0.980, respectively; and cut-offs 8.8 kPa, 6.6 kPa excluded cirrhosis, liver fibrosis ≥ S3 with negative likelihood ration nearly 0.1 and negative predictive value 0.977 and 0.903, respectively. Correlation coefficient between LSM and grades of esophageal varices was only 0.180, and AUROC for TE predicting EV was of no clinical value. CONCLUSION: TE relatively make accurate prediction in the severity of liver fibrosis and classification of Child-Pugh. Patients with LSM ≥ 10.8 kPa should be considered for receiving antivirus treatment.

Combined prognostic nutritional index and albumin-bilirubin grade to predict the postoperative prognosis of HBV-associated hepatocellular carcinoma patients.

This study aims to evaluate the predictive value of the prognostic nutritional index (PNI) and albumin-bilirubin grade (ALBI) for the postoperative prognosis of hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) patients undergoing radical hepatectomy (RH). Besides, we seek to identify novel prognosis indicators for HBV-HCC patients. Between April 2009 and March 2015, this work enrolled 868 patients diagnosed with HBV-HCC and undergoing RH in the Liver Surgery Department, West China Hospital, Sichuan University (WCHSU). The basic information, laboratory examination indicators, pathological reports, and follow-up data of patients were included. SPSS 22.0 statistical software was used for statistical data analyses. Platelet (PLT), alpha-fetoprotein (AFP), maximum diameter (max-D), number of tumors (Number), degree of differentiation (DD), Microvascular invasion situation (MVI), satellite focus situation (SF), PNI, and ALBI were the independent risk factors for both overall survival (OS) and disease-free survival (DFS) of HBV-HCC patients undergoing RH. Taking PNI = 46 and ALBI = - 2.80 as cut-off values, the OS and DFS of the PNI-high group were significantly higher than those of the PNI-low group. Meanwhile, the OS and DFS of the ALBI-low group were significantly higher than those of the ALBI-high group; the OS and DFS of the PNI-high + ALBI-low group were significantly higher than those of the PNI-low + ALBI-high group. Xie prognostic index (XPI) was the independent risk factor for both OS and DFS of HBV-HCC patients undergoing RH. The OS and DFS of the XPI-high group were significantly higher than those of the XPI-low group. This paper reveals that preoperative PNI and ALBI can predict the OS and DFS of HBV-HCC patients undergoing RH. Their impact on the prognosis of HBV-HCC patients is insignificant, however, it cannot be ignored. XPI can precisely predict the prognosis of HBV-HCC patients undergoing RH, nonetheless, its effect requires additional research for validation.

Preoperative nutritional evaluation of patients with hepatic alveolar echinococcosis.

OBJECTIVE: This study is aimed at determining the preoperative nutritional status of patients with hepatic alveolar echinococcosis (HAE), and subsequently establish a concise and reasonable nutritional evaluation indicator. The established evaluation method could be used for clinical preoperative risk assessment and prediction of post-operation recovery. METHODS: The basic patient information on height, body weight, BMI and hepatic encephalopathy of 93 HAE patients were examined. Subsequently, abdominal ultrasonography, blood coagulation and liver function tests were done on the patients. Liver function was assessed using the Child-Pugh improved grading method while nutritional status was evaluated using the European Nutrition Risk Screening 2002 (NRS 2002) method. Additional parameters including hospitalization time, the hemoglobin (HGB) level on the 3rd day after the operation, and the number of postoperative complications of HAE patients were also recorded. RESULTS: The NRS 2002 score was negatively correlated with body weight, body mass index (BMI)and albumin (ALB) (P<0.01), and positively correlated with the transverse and longitudinal diameters of the lesions (P<0.01). A worse grading of liver function was associated with a low ALB and a high NRS 2002 score (P<0.01). Results of the NRS 2002 score indicate that the hospitalization time of the normal nutrition group was significantly shorter than that of the malnourished group (P < 0.05). The HGB level of the control group on the 3rd day after the operation was significantly higher than that of the malnourished group (P < 0.05), and the number of postoperative complications was lower than that of malnutrition group (P < 0.05). CONCLUSION: Malnutrition is common in HAE patients. The nutritional status of HAE patients is related to many clinical factors, such as Child-Pugh classification of liver function, size of the lesion, and ALB among others. Although both BMI and ALB can be used as primary screening indicators for malnutrition in HAE patients, NRS 2002 is more reliable and prudent in judging malnutrition in HAE patients. Therefore, BMI and ALB are more suitable for preoperative risk assessment and prediction of postoperative recovery.

Mechanism of levosimendan in treating hypoxic pulmonary hypertension based on network pharmacology and molecular docking technology / 中国药理学通报

Aim To explore the efficacy of levosimendan on hypoxia pulmonary hypertension through animal experiments, and to further explore the potential mechanism of action using network pharmacological methods and molecular docking technique. Methods The rat model of hypoxia pulmonary hypertension was constructed to detect right heart systolic pressure and right heart remodeling index. HE , Masson, and VG staining were core targets were screened out. GO and KEGG pathway enrichment analysis were performed using the DAVID database. Molecular docking of the core targets was performed with the AutoDock software. Results The results of animal experiments showed that levosimendan had obvious therapeutic effect on hypoxia pulmonary hypertension. The network pharmacology results showed that SRC, HSP90AA1, MAPK1, PIK3R1, AKT1, HRAS, MAPK14, LCK, EGFR and ESR1 used to analyze the changes of rat lung histopathology. Search the Swiss Target Prediction, DrugBank Online, BatMan, Targetnet, SEA, and PharmMapper databases were used to screen for drug targets. Disease targets were retrieved from the GeneCards, OMIM databases. The "drug-target-disease" network was constructed after identification of the two intersection targets. The protein interaction network was constructed and the were the key targets to play a therapeutic role. Molecular docking showed good docking of levosimendan with all the top five core targets with degree values. Conclusions Levosimendan may exert a therapeutic effect on hypoxia-induced pulmonary hypertension through multiple targets.

Population genetics analysis of Oncomelania hupensis in Jiaxing， Zhejiang Province， 2022 / 上海预防医学

ObjectiveTo genotype Oncomelania hupensis， based on microsatellites， in different snail-bearing environments in Jiaxing City， Zhejiang Province， for population genetics analysis in order to explore the reasons and influencing factors for the existence or proliferation of snails and to provide scientific basis for effective monitoring and control of snails. MethodsA total of 90 snail samples from three populations were collected in Yaobang Village （YB） and Sanxing Village （SX） in Pinghu City， and Yunhe Farm （YH） in Xiuzhou District， all were selected for snail checking in key snail habitats of Jiaxing City in 2022. DNA of the snails was genotyped and analyzed for population genetics using nine microsatellite loci. ResultsA total of 84 alleles were observed， and the mean number of alleles （Na） was 7.889， 5.667， and 3.778 for YB， SX， and YH respectively； the number of effective alleles （NeA） was 4.807， 3.329， and 2.294， respectively； and the coefficients of inbreeding （FIS） were 0.400， 0.377， and 0.493， respectively. Under the Infinite Allele Model （IAM）， the SX and YH might have a recent bottleneck. The NEstimator and LDNe software calculated effective population sizes （Ne） were above 31.9. AMOVA analysis showed that the variation of snails in the three populations mainly existed among individuals， accounting for 41.4% of the total variation. The value of the index of genetic differentiation between populations （FST） was 0.286， indicating a high degree of genetic differentiation. The results of the principal component analysis and phylogenetic tree were consistent， and the three populations were divided into two lineages， YB and SX were one lineage， and YH belonged to another independent lineage. Population history and dynamics analysis showed that the gene flow of the three populations was insufficient， population divergence history indicated that YH might have diverged from SX first， and YB was produced by the contact fusion of SX and YH. ConclusionThe genetic diversity of snail populations in Jiaxing City is generally low， and the snail populations are unstable， with a great degree of genetic differentiation and insufficient gene flow among populations. This study can provide a basis for evaluating the effectiveness of the control of the snail as well as monitoring the trend of the spread of the snail.

Isoflavone‑enriched soybean leaves (Glycine max) restore loss of dermal collagen fibers induced by ovariectomy in the Sprague Dawley rats / 한국실험동물학회지

Phytoestrogens, such as isoflavones, are known for their capacity to simulate various physiological impacts of estro‑ gen in the human body. Our research evaluated the effects of isoflavone-enriched soybean leaves (IESL) on collagen fiber loss prompted by ovariectomy in Sprague Dawley (SD) rats, thereby simulating menopausal changes in women.IESL, bolstered with an increased concentration of isoflavones through a metabolite farming process, contained a significantly higher amount of isoflavones than regular soybean leaves. Our results indicate that the administration of IESL can counteract the decrease in relative optical density and dermal thickness of collagen fibers caused by ova‑ riectomy in SD rats, with more pronounced effects observed at higher isoflavone dosages. These outcomes suggest that soybean leaves rich in isoflavones may hold potential benefits in combating collagen degradation and skin aging symptoms related to menopause. Further research is needed to fully understand the exact molecular pathways at play and the potential clinical relevance of these findings.

Secondary type 1 narcolepsy after traumatic brain injury: a case report / 中华神经科杂志

Type 1 narcolepsy is a rare central nervous system disorder that is believed to result from the interaction of environmental and genetic factors. Traumatic brain injury (TBI) is one of the most common causes of secondary narcolepsy. Currently, there are very few reports on post-TBI narcolepsy, and this patient is the first reported case of HLA-DQB1 *06:02-positive type 1 narcolepsy following TBI in China. The clinical data of this patient are retrospectively analyzed to improve the understanding of the diagnosis and pathogenesis of the disease among clinicians.

Changes and predictive value of degree centrality in patients with narcolepsy type 1 based on resting-state functional magnetic resonance imaging / 中华神经科杂志

Objective:To investigate the abnormal changes of the nodal centrality of the whole-brain network in patients with narcolepsy type 1 (NT1) through the degree centrality (DC) technique of resting-state magnetic resonance and the predictive value for NT1.Methods:From September 2019 to November 2021, 18 NT1 patients who were first diagnosed and never accepted managements and 18 age-, sex-matched healthy controls recruited by advertisement in the Second Affiliated Hospital of Nanchang University were required for resting-state functional magnetic resonance imaging scans and clinical scale assessment, including Epworth Sleepiness Scale (ESS), Self-rating Anxiety Scale, Self-rating Depression Scale, Pittsburgh Sleep Quality Index, Insomnia Severity Scale and Multidimensional Fatigue Inventory-20 (MFI-20). The differences in DC values between the NT1 patients and healthy controls were analyzed using the DC method. Then, the correlation between DC values in differential brain regions and clinical characteristics of NT1 was explored through Pearson correlation analysis. The receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of the DC values in the differential brain regions for NT1 patients.Results:Compared with the healthy controls, the DC value of the right superior temporal gyrus was increased, while the DC values of the bilateral middle frontal gyrus and the right precuneus were decreased in the NT1 patients (all P<0.05, Gaussian random-field correction). The DC value of the right superior temporal gyrus in the NT1 patients was positively correlated with the ESS score ( r=0.82, P<0.001) and MFI-20 score ( r=0.48, P=0.040). The DC value of the right middle frontal gyrus was positively correlated with the disease course ( r=0.51, P=0.032). The ROC curve showed that the area under the curve of NT1 predicted by the DC value of the right superior temporal gyrus was 0.95. And the areas under the curve of non-NT1 predicted by the DC values of the left middle frontal gyrus, right middle frontal gyrus, and right precuneus were 0.86, 0.84 and 0.87, respectively. Conclusions:NT1 patients have abnormal resting-state DC in the default network, executive network core brain regions, and superior temporal gyrus. And the DC value in the right superior temporal gyrus may be a potential biomarker of NT1 patients.

Clinical Application of Vibration Controlled Transient Elastography in Patients with Chronic Hepatitis B.

Evaluation of the extent and progression of liver fibrosis and cirrhosis is of critical importance in the management and prognosis of patients with chronic hepatitis B. Due to the limitation of liver biopsy, non-invasive methods, especially liver stiffness measurement (LSM) by vibration controlled transient elastography, have been developed and widely applied for liver fibrosis assessment. LSM aims to reduce, but not to substitute, the need for liver biopsy for fibrosis/cirrhosis diagnosis. While LSM may have potential utility in monitoring treatment response, its applications in prediction of liver complications in terms of portal hypertension and esophageal varices, as well as disease prognosis, have been gradually validated. Here, we review the latest clinical applications of LSM in patients with chronic hepatitis B.