Safety and immunogenicity of a subtype C ALVAC-HIV (vCP2438) vaccine prime plus bivalent subtype C gp120 vaccine boost adjuvanted with MF59 or alum in healthy adults without HIV (HVTN 107): A phase 1/2a randomized trial.

BACKGROUND: Adjuvants are widely used to enhance and/or direct vaccine-induced immune responses yet rarely evaluated head-to-head. Our trial directly compared immune responses elicited by MF59 versus alum adjuvants in the RV144-like HIV vaccine regimen modified for the Southern African region. The RV144 trial of a recombinant canarypox vaccine vector expressing HIV env subtype B (ALVAC-HIV) prime followed by ALVAC-HIV plus a bivalent gp120 protein vaccine boost adjuvanted with alum is the only trial to have shown modest HIV vaccine efficacy. Data generated after RV144 suggested that use of MF59 adjuvant might allow lower protein doses to be used while maintaining robust immune responses. We evaluated safety and immunogenicity of an HIV recombinant canarypox vaccine vector expressing HIV env subtype C (ALVAC-HIV) prime followed by ALVAC-HIV plus a bivalent gp120 protein vaccine boost (gp120) adjuvanted with alum (ALVAC-HIV+gp120/alum) or MF59 (ALVAC-HIV+gp120/MF59) or unadjuvanted (ALVAC-HIV+gp120/no-adjuvant) and a regimen where ALVAC-HIV+gp120 adjuvanted with MF59 was used for the prime and boost (ALVAC-HIV+gp120/MF59 coadministration). METHODS AND FINDINGS: Between June 19, 2017 and June 14, 2018, 132 healthy adults without HIV in South Africa, Zimbabwe, and Mozambique were randomized to receive intramuscularly: (1) 2 priming doses of ALVAC-HIV (months 0 and 1) followed by 3 booster doses of ALVAC-HIV+gp120/MF59 (months 3, 6, and 12), n = 36; (2) 2 priming doses of ALVAC-HIV (months 0 and 1) followed by 3 booster doses of ALVAC-HIV+gp120/alum (months 3, 6, and 12), n = 36; (3) 4 doses of ALVAC-HIV+gp120/MF59 coadministered (months 0, 1, 6, and 12), n = 36; or (4) 2 priming doses of ALVAC-HIV (months 0 and 1) followed by 3 booster doses of ALVAC-HIV+gp120/no adjuvant (months 3, 6, and 12), n = 24. Primary outcomes were safety and occurrence and mean fluorescence intensity (MFI) of vaccine-induced gp120-specific IgG and IgA binding antibodies at month 6.5. All vaccinations were safe and well-tolerated; increased alanine aminotransferase was the most frequent related adverse event, occurring in 2 (1.5%) participants (1 severe, 1 mild). At month 6.5, vaccine-specific gp120 IgG binding antibodies were detected in 100% of vaccinees for all 4 vaccine groups. No significant differences were seen in the occurrence and net MFI of vaccine-specific IgA responses between the ALVAC-HIV+gp120/MF59-prime-boost and ALVAC-HIV+gp120/alum-prime-boost groups or between the ALVAC-HIV+gp120/MF59-prime-boost and ALVAC-HIV+gp120/MF59 coadministration groups. Limitations were the relatively small sample size per group and lack of evaluation of higher gp120 doses. CONCLUSIONS: Although MF59 was expected to enhance immune responses, alum induced similar responses to MF59, suggesting that the choice between these adjuvants may not be critical for the ALVAC+gp120 regimen. TRIAL REGISTRATION: HVTN 107 was registered with the South African National Clinical Trials Registry (DOH-27-0715-4894) and ClinicalTrials.gov (NCT03284710).

Vaccine Efficacy of ALVAC-HIV and Bivalent Subtype C gp120-MF59 in Adults.

BACKGROUND: A safe, effective vaccine is essential to eradicating human immunodeficiency virus (HIV) infection. A canarypox-protein HIV vaccine regimen (ALVAC-HIV plus AIDSVAX B/E) showed modest efficacy in reducing infection in Thailand. An analogous regimen using HIV-1 subtype C virus showed potent humoral and cellular responses in a phase 1-2a trial in South Africa. Efficacy data and additional safety data were needed for this regimen in a larger population in South Africa. METHODS: In this phase 2b-3 trial, we randomly assigned 5404 adults without HIV-1 infection to receive the vaccine (2704 participants) or placebo (2700 participants). The vaccine regimen consisted of injections of ALVAC-HIV at months 0 and 1, followed by four booster injections of ALVAC-HIV plus bivalent subtype C gp120-MF59 adjuvant at months 3, 6, 12, and 18. The primary efficacy outcome was the occurrence of HIV-1 infection from randomization to 24 months. RESULTS: In January 2020, prespecified criteria for nonefficacy were met at an interim analysis; further vaccinations were subsequently halted. The median age of the trial participants was 24 years; 70% of the participants were women. The incidence of adverse events was similar in the vaccine and placebo groups. During the 24-month follow-up, HIV-1 infection was diagnosed in 138 participants in the vaccine group and in 133 in the placebo group (hazard ratio, 1.02; 95% confidence interval, 0.81 to 1.30; P = 0.84). CONCLUSIONS: The ALVAC-gp120 regimen did not prevent HIV-1 infection among participants in South Africa despite previous evidence of immunogenicity. (HVTN 702 ClinicalTrials.gov number, NCT02968849.).

Prediction of programmed death-1 expression status in non-small cell lung cancer based on intratumoural and peritumoral computed tomography (CT) radiomics nomogram.

AIMS: This study aimed to predict the expression of programmed death-1 (PD-1) in non-small cell lung cancer (NSCLC) using intratumoral and peritumoral computed tomography (CT) radiomics nomogram. MATERIALS AND METHODS: Two hundred patients pathologically diagnosed with NSCLC from two hospitals were retrospectively analyzed. Of these, 159 NSCLC patients from our hospital were randomly divided into a training cohort (n=96) and an internal validation cohort (n=63) at a ratio of 6:4, while 41 NSCLC patients from another medical institution served as the external validation cohort. The radiomic features of the gross tumor volume (GTV) and peritumoral volume (PTV) were extracted from the CT images. Optimal radiomics features were selected using least absolute shrinkage and selection operator regression analysis. Finally, a CT radiomics nomogram of clinically independent predictors combined with the best rad-score was constructed. RESULTS: Compared with the 'GTV' and 'PTV' radiomics models, the combined 'GTV + PTV' radiomics model showed better predictive performance, and its area under the curve (AUC) values in the training, internal validation, and external validation cohorts were 0.90 (95% confidence interval [CI]: 0.83-0.97), 0.85 (95% CI: 0.74-0.96) and 0.78 (95% CI: 0.63-0.92). The nomogram constructed by the rad-score of the 'GTV + PTV' radiomics model combined with clinical independent predictors (prealbumin and monocyte) had the best performance, with AUC values in each cohort being 0.92 (95% CI: 0.85-0.98), 0.88 (95% CI: 0.78-0.97), and 0.80 (95% CI: 0.66-0.94), respectively. CONCLUSION: The intratumoral and peritumoral CT radiomics nomogram may facilitate individualized prediction of PD-1 expression status in patients with NSCLC.

Associations between abdominal obesity indices with hypertension in type 2 diabetes mellitus: Chinese visceral adiposity index.

PURPOSE: This research was performed to evaluate the relationship between hypertension (HTN) and abdominal obesity index in patients with type 2 diabetes mellitus (T2DM). METHODS: Totally 1657 participants with T2DM (mean age 54 ± 12 years; 38.02% female) were enrolled. They were divided into the groups of HTN (n = 775) and non-HTN (n = 882). Anthropometric and biochemical indicators were measured and collected. A bioelectrical impedance analyzer was used to measure visceral and subcutaneous fat areas. RESULTS: Compared with the HTN group, the non-HTN group had a lower level of Chinese visceral adiposity index (CVAI) (p < 0.001). Meanwhile, among tertiles of CVAI, as CVAI increased, the proportion of patients with HTN increased, which was 33.51%, 44.30%, and 62.50%, respectively. CVAI was shown to have a significant positive correlation with HTN. (r = 0.258, p < 0.001). CVAI was independently related to an elevated risk of HTN by binary logistic regression analyses, and the OR was (95% CI) 1.013 (1.010-1.016, p < 0.001) after adjustment. The area under the receiver operating characteristic curve (AUC) of CVAI predicted HTN in T2DM patients was greater than those of other abdominal obesity indices (p < 0.001). CONCLUSION: We found that CVAI was highly positively correlated with HTN in T2DM. Compared with other indices of abdominal obesity, such as WC, BMI, WHR, VAI, and LAP, the CVAI showed superior discriminative ability in T2DM complicated with HTN. Therefore, more attention should be paid to CVAI in T2DM.

FBXO28 reduces high-fat diet-induced hyperlipidemia in mice by alleviating abnormal lipid metabolism and inflammatory responses.

BACKGROUND: Hyperlipidemia is a lipid metabolism disorder with increasing incidence and prevalence worldwide. Abnormal lipid metabolism and inflammation are two significant characteristics of hyperlipidemia. The purpose of this study was to explore the role and mechanism of F-box only protein 28 (FBXO28) in hyperlipidemia. METHODS: Mice were fed with high-fat diet (HFD) to elicit obesity, and 3T3-L1 preadipocytes were stimulated with MDI cocktail (IBMX, DEX and insulin) to evoke differentiation. In vivo and in vitro role of FBXO28 in hyperlipidemia was investigated by hematoxylin-eosin and oil Red O staining, the lipid biochemistry measurement, enzyme-linked immunosorbent assay, reverse transcription quantitative polymerase chain reaction and western blotting assays. The mechanism of FBXO28 explored by co-immunoprecipitation, immunofluorescence, ubiquitination and cycloheximide assays. RESULTS: Low expression of FBXO28 was found in hyperlipidemia in silico, in vivo and in vitro. Upregulation of FBXO28 declined the body weight, fat accumulation, and serum lipid content in HFD-fed mice. Abnormal lipid accumulation, and the level of liposynthetic genes and beta-oxidation related genes were improved by overexpression of FBXO28 both in HFD-elicited mice and MDI-treated 3T3-L1 preadipocytes. Besides, overexpression of FBXO28 declined HFD-induced the level of proinflammatory factors and F4/80. Mechanically, FBXO28 directly bound RAB27A and promoted its ubiquitinated degradation. Thus, upregulation of RAB27A inverted the improved role of FBXO28 in abnormal lipid metabolism and inflammation in vivo and in vitro. CONCLUSION: FBXO28 ameliorated abnormal lipid metabolism and inflammation through the ubiquitinated degradation of RAB27A, thereby attenuating HFD-induced hyperlipidemia. The results could promote the treatment of hyperlipidemia, and the relevant diseases.

[Comparison of robotic-assisted single-incision-plus-one-port laparoscopic pyeloplasty and single-incision laparoscopic pyeloplasty in the treatment of pediatric ureteropelvic junction obstruction].

Objective: To compare the efficacy of robotic-assisted single-incision-plus- one-port laparoscopic pyeloplasty (R-SILP+1) with single-incision laparoscopic pyeloplasty (SILP) in pediatric ureteropelvic junction obstruction (UPJO). Methods: The clinical data of 47 children with UPJO who underwent surgery from October 2020 to September 2022 in the Department of Pediatric Surgery of Fujian Provincial Hospital were retrospectively analyzed. According to the surgical method chosen by parents, the children were divided into R-SILP+1 group and SILP group. Baseline data, operative time, intraoperative anastomosis time, volume of blood loss, postoperative hospitalization time, complications, total costs, preoperative and postoperative renal parenchymal thickness (PT), anterior posterior diameter of renal pelvis (APD), and differential renal function (DRF) before and after operation were compared between the two groups, and the clinical efficacy of the two kinds of operation was evaluated. Results: Among the 47 children, 27 were in R-SILP+1 group, including 16 males and 11 females, aged (6.6±3.5) years; 20 were in SILP group, including 12 males and 8 females, aged (6.5±3.5) years. The operations were successful in both groups without conversion to open operation. There were no significant differences between the two groups in baseline data, volume of blood loss, complications, APD and PT at postoperative 6 months, APD, PT and DRF at postoperative 12 months (all P>0.05). Compared with the SILP group, the operative time [(153.0±14.4) vs (189.9±32.6) minutes, P<0.001], intraoperative anastomosis time [(68.8±16.8) vs (97.5±12.0) minutes, P<0.001], postoperative hospitalization time [(6.0±1.3) vs (9.0±1.3) d, P<0.001] were shorter, but the total cost was higher[(57 390±7 664) vs (30 183±4 219) yuan RMB, P<0.001]. Conclusions: Compared with the SILP group, R-SILP+1 can achieve considerable efficacy in treating pediatric UPJO, and has certain advantages in shortening operative time, intraoperative anastomosis time, and postoperative hospitalization time. However, the cost is high.

[Comparison of the population covered by the 2024 version of the WHO's hepatitis B prevention and treatment guidelines and the Chinese antiviral treatment guidelines].

Objective: This study aims to compare the antiviral treatment similarities and differences in the population covered by the 2024 version of the World Health Organization's (WHO) hepatitis B prevention and treatment guidelines and the current Chinese hepatitis B prevention and treatment guidelines, so as to explore their impact on the indications for antiviral therapy in Chinese patients with chronic hepatitis B (CHB). Methods: The information of patients with chronic hepatitis B virus infection who did not receive antiviral treatment was collected through the registration database of the China Clinical Research Platform for Hepatitis B Elimination. Descriptive statistics were conducted on the demographic, blood, biochemical, and virological levels of patients according to the treatment recommendations of the two versions of the guidelines. The Mann-Whitney U test and χ2 test were used to compare the differences and proportional distribution of the treatment populations covered by the two guidelines. The χ2 test was used to analyze the coverage rate of different antiviral treatment indications. Results: A total of 21,134 CHB patients without antiviral treatment were enrolled. 69.4% of patients met the 2024 versions of the WHO guidelines' recommendations. 85.0% of patients met the current Chinese hepatitis B prevention and treatment guidelines. The WHO guidelines for antiviral therapy indications were met in younger patients with higher levels of ALT, AST, and APRI scores, as well as greater proportion of patients with higher viral loads (P<0.001). The WHO guidelines recommended a cut-off value of APRI>0.5, which raised the proportion of patients on antiviral therapy from 6.6% to 30.9%. 45.7% of patients met the antiviral indications for HBV DNA >2000 IU/ml with abnormal transaminase (ALT>30 U/L for males and ALT>19 U/L for females). The reduced APRI diagnostic cut-off value and ALT treatment threshold had further increased the treatment coverage rate by 91.6% in patients with chronic HBV infection in line with the 2024 versions of WHO guidelines. Conclusion: The reduction of the APRI diagnostic cut-off value and the ALT treatment threshold, based on the current hepatitis B guidelines of China, will further improve the treatment coverage of CHB patients.

[Advances in warfarin's anticoagulation therapy in Chinese population after mechanical valve replacement].

Warfarin is an irreplaceable oral anticoagulant for patients with mechanical heart valves, the stable pharmacogenetic-based warfarin dose prediction algorithms have improved the effectiveness and safety of warfarin anticoagulation therapy. Genetic factors are the main factors affecting the stable dose of warfarin. Single nucleotide polymorphisms such as VKORC1 and CYP2C9 affect the anticoagulation effect of warfarin through pharmacodynamic or pharmacokinetic pathways. Age, body surface area, combined use of drugs, and other nongenetic factors also affect the stable dose of warfarin. Previously published algorithms for warfarin dose prediction included mainly the white race, and most algorithms were constructed using traditional multiple linear regression. However, domestic studies have used machine learning methods to construct warfarin dose prediction algorithms based on the Chinese Han post-mechanical valve replacement population and have achieved better prediction efficiency. This article reviews the advances of warfarin anticoagulation influencing factors and the clinical application of stable dose prediction algorithms.

[Analysis of the therapeutic effect of aspiration thrombectomy for early carotid stent thrombosis].

Objective: To investigate the clinical characteristics and the efficacy of thrombus aspiration in patients with early intrastent thrombosis (EST) following carotid artery stenting (CAS). Methods: This study is a retrospective case series, collecting clinical data of five patients who developed EST after CAS in the Department of Neurosurgery, Beijing Chaoyang Hospital, Capital Medical University from January 2021 to September 2023.All patients were male, with an age of (64.0±11.9) years (range:48 to 77 years), accounting for 2.0% (5/244) of CAS procedures during the same period.Among them, three patients did not receive standard dual antiplatelet therapy before the procedure, and one had an inadequate ADP inhibition rate (45.6%).Four patients received XACT carotid stents, while one received a Wallstent carotid stent.All five patients showed significant residual stenosis ranging from 43% to 55% after CAS.Emergency thrombus aspiration was performed in all cases, and data regarding perioperative conditions, vascular patency, and clinical outcomes were collected. Results: The interval between CAS and the occurrence of EST ranged from 3 hours to 14 days.The main clinical symptoms included sudden onset of consciousness disorders and contralateral limb weakness.None of the patients received preoperative intravenous thrombolysis, and thrombus aspiration was performed during the procedure to restore vascular patency.Four cases underwent balloon angioplasty during the procedure, and two cases utilized overlapping stents.Two patients experienced intraoperative embolization of thrombus to the C2 segment.In one case, the embolized thrombus was retrieved using an intracranial thrombectomy stent, while in another case, it was aspirated using a guiding catheter.Postoperatively, all patients had a thrombolysis in cerebral infarction grade of 3, and symptoms improved in four cases.One patient showed no improvement in symptoms, and MRI revealed extensive new infarction in the right frontal and insular regions, adjacent to the right lateral ventricle.Regular follow-up examinations after discharge did not reveal restenosis or embolism within the stent.The follow-up period ranged from 7.6 to 21.2 months, with modified Rankin scale scores of 0 to 1 point in four cases and 2 points in one case, indicating good recovery in all patients. Conclusions: Acute intrastent thrombosis is a rare complication after carotid artery stenting.The combined use of percutaneous thrombus aspiration and endovascular techniques, such as balloon angioplasty and stent overlapping, can rapidly restore vessel patency with favorable outcomes.However, further large-scale clinical studies are needed to confirm the effectiveness of these treatments for acute intrastent thrombosis.

PLATELET-RICH PLASMA VERSUS CORTICOSTEROID IN THE TREATMENT OF KNEE OSTEOARTHRITIS: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS.

The aim of this meta-analysis is to evaluate the clinical effectiveness of intra-articular injections of platelet-rich plasma (PRP) versus corticosteroid (CS) in treating knee osteoarthritis (KOA). A comprehensive search of the PubMed, Embase, and Web of Science databases was conducted for literature on intra-articular PRP and CS injections for the treatment of knee osteoarthritis, with the search period extending to December 2023. The risk of bias was assessed using the Cochrane Risk of Bias tool, and statistical analysis was subsequently carried out using Review Manager 5.4.1 software. The efficacy of PRP versus CS injections across various studies was compared based on the weighted mean difference and 95% confidence interval for scores from the Visual Analogue Scale (VAS), Knee Osteoarthritis Outcome Score (KOOS), and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). In our analysis, we incorporated twelve studies encompassing a total of 801 joints, of which 404 were in the PRP group and 397 in the CS group. PRP group was significantly reduced the VAS score than CS group in 3-month (P=0.003), 6-month (P=0.007) and 9-month (P<0.00001); PRP group was significantly reduced the WOMAC total score compared to CS group in 1-month (P=0.01), 6-month (P=0.003), 9-month (P=0.005) and 12-month (P<0.00001); In 3-month and 6-month, PRP group were significantly increased the KOOS pain relief score (3-month: P=0.002, 6-month: P<0.00001), the KOOS activities of daily living scores (3-month: P<0.00001, 6-month: P<0.00001) and the KOOS quality of life score (3-month: P=0.003, 6-month: P<0.00001) compared to CS group; PRP group also were significantly increased the KOOS sports score in 3-month compared to CS group (P=0.04). The leukocyte-poor PRP (LP-PRP) group was significantly reduced the VAS score compared to CS group (P=0.04). Recent findings indicate that intra-articular injections of PRP yield superior results in alleviating pain and enhancing functionality in individuals with knee osteoarthritis, as opposed to CS injections. During short-term follow-up, no significant difference was observed between knee injections of PRP and CS. However, the benefits of PRP injections primarily become apparent in the medium to long-term management of clinical symptoms, including pain relief, enhancing patients' quality of life, increasing activities of daily living, and improving sports capabilities.

[Infiltration and significance of M1 macrophage in breast cancer: an analysis of METABRIC database and clinical validation].

Objective: To investigate the differences of immune microenvironment between stage T1N3 and stage T3N0 breast cancer patients and explore the relationship between M1 macrophage infiltration and lymph node metastasis in breast cancer. Methods: Clinical information and RNA-sequencing (RNA-Seq) expression data of stage T1N3 (n=9) and stage T3N0 (n=11) breast cancer patients were extracted from Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases. Using CIBERSORT, the proportions of 22 types of immune cells were calculated, and then the differences of immune cell infiltration between stage T1N3 and T3N0 patients were compared. From 2011 to 2022, pathologic specimens were collected from breast cancer patients who underwent curative resection at the Cancer Hospital, Chinese Academy of Medical Sciences, including 77 at stage T1N3 and 58 at stage T3N0.The METABRIC database analysis results were verified by examining the density of M1 macrophages in tissues using dual-staining immunohistochemistry. Results: METABRIC data analysis showed M1 macrophage was the highest proportion, 15.85% in stage T1N3 breast cancer; M2 macrophage was the highest proportion, 13.07% in stage T3N0 breast cancer.M1 macrophage proportions were statistically different between patients with stage T1N3 and stage T3N0 (P=0.010). The dual-staining immunohistochemistry analysis of breast cancer tissues showed M1 macrophage density (median) of 62.0 and 38.0 cells/mm(2) for stage T1N3 and T3N0, respectively. The difference was statistically significant (P=0.002). Conclusion: The density of M1 macrophages is notably higher in stage T1N3 patients and is associated with lymph node metastasis.

[Genomic structure of varicella-zoster virus and its vaccine application status].

With the determination of the whole genome sequence of varicella-zoster virus (VZV) virus, the successful breakthrough of infectious cloning technology of VZV, and the emergence of effective preventive vaccines, which have been proven to be effective and safe, varicella has become a disease preventable by specific immunity. This article will review the genomic structure, epidemiological characteristics, and research application progress of varicella vaccine and herpes zoster vaccine of varicella zoster virus to provide reference for primary prevention of the disease.

[Current status and treatment strategies for liver injury before targeted immunotherapy for liver cancer].

The occurrence rate of primary liver cancer in malignant tumors ranks sixth in the world, and the mortality rate ranks third, with a poor prognosis and a five-year survival rate of less than 5%. Most patients with liver cancer in China are found to be in the intermediate and advanced stages, and a targeted immunotherapy combination has become the main treatment option. However, many patients have underlying liver lesions, and their liver function cannot meet the requirements of targeted immunotherapy, which directly affects the treatment of liver cancer patients. Therefore, it is very important to optimize the patient's liver function in a timely manner so as to obtain the opportunity for anti-tumor therapy. This article reviews the current status and response strategies before liver injury related to targeted immune therapy in patients with primary liver cancer.

[Clinical features and long-term prognosis of primary biliary cholangitis in patients with past hepatitis B virus infection].

Objective: To investigate the clinical features and long-term prognosis of primary biliary cholangitis (PBC) in patients with past hepatitis B virus (HBV) infection. Methods: 353 cases with PBC who visited the Liver Disease Center of Beijing Friendship Hospital Affiliated to Capital Medical University between January 2000 and January 2018 were retrospectively analyzed and were divided into the past HBV infection group (156 cases) and the no HBV infection group (197 cases). The two groups' baseline clinical features were compared. Ursodeoxycholic acid response rate after one year, GLOBE score, UK-PBC score, and long-term liver transplantation-free survival rate were compared through outpatient and telephone follow-up. Results: PBC with past HBV infection had a significantly reduced female proportion compared to the no HBV infection group (91.9% vs. 79.5%, P = 0.001). However, there were no statistically significant differences in age, biochemical indices, immunological indicators, platelet count, cirrhosis proportion, and others. Ursodeoxycholic acid biochemical response rate was reduced in patients with past HBV infection at the end of one year of treatment, but the difference was not statistically significant (65.8% vs. 78.2%, P = 0.068). In addition, there were no statistically significant differences between the GLOBE score (0.57 vs. 0.59, P = 0.26) and UK-PBC 5-year (2.87% vs. 2.87%, P = 0.38), 10-year (9.29% vs. 8.2%, P = 0.39) and 15-year liver transplantation rates (16.6% vs. 14.73%, P = 0.39). Lastly, the overall 5-year liver transplantation-free survival rate had no statistically significant difference between the two groups of patients (86.4% vs. 87.5%, P = 0.796). Conclusion: Primary biliary cholangitis had no discernible effect in terms of age at onset, biochemical indices, immunological indicators, cirrhosis proportion, ursodeoxycholic acid response rate after one year, GLOBE score, UK-PBC score, or overall liver transplantation-free survival rate in patients with past hepatitis B virus infections.

[Ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China: a CR-HepB-based real-world study].

Objective: To understand ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China. Methods: Patients with chronic HBV infection:demographic, virologic, hematologic, blood biochemistry, and antiviral treatment data were extracted from the China Registry of Hepatitis B (CR-HepB) database between 2012 and 2022 for descriptive statistics and change trend analysis. Multiple group comparisons were conducted using the Kruskal Wallis H test, while counting data was compared between groups using χ (2) test. Results: A total of 180 012 patients with chronic HBV infection were included, with a median age of 40 years old, and a male proportion accounting for 60.2%. The HBeAg positive rate was 43.3%. Over time, the median age of new patients each year increased from 39 to 47 years, while the HBeAg positive rate decreased from 51.3% to 32.8%. The initial diagnosis of patients was mainly CHB (71.4%), followed by hepatitis B cirrhosis (11.8%), inactive HBsAg carrier status (10.6%), and chronic HBV carrier status (6.2%). Among the newly registered patients every year from 2012 to 2022, the proportion of hepatitis B cirrhosis remained stable, but after 2019, the proportion of CHB increased and the proportion of other diagnoses decreased. The proportion of patients with cirrhosis increased with age in different age groups, with 3.5%, 19.3%, and 30.4% in the < 40, 40-69, and≥70 age groups, respectively. The proportion of women in patients with cirrhosis also increased with age, from 16.1% in those < 30 years old to 44.3% in those≥80 years old. From 2012 to 2022, the proportion of patients receiving first-line nucleos(t)ide analog antiviral treatment increased year by year, from 51.0% in 2012-2013 to 99.8% in 2022. Conclusion: The CR-HepB registration data reflect the changes in clinical characteristics and antiviral treatment patterns in patients with chronic HBV infection in China over the past ten years and can thus provide a reference to promote hepatitis B diagnosis and treatment practice, as well as scientific research.

[Recompensation of complications in patients with hepatitis B virus-related decompensated cirrhosis treated with entecavir antiviral therapy].

Objective: To analyze the occurrence of recompensation conditions in patients with chronic hepatitis B virus-related decompensated cirrhosis after entecavir antiviral therapy. Methods: Patients with hepatitis B virus-related decompensated cirrhosis with ascites as the initial manifestation were prospectively enrolled. Patients who received entecavir treatment for 120 weeks and were followed up every 24 weeks (including clinical endpoint events, hematological and imaging indicators, and others) were calculated for recompensation rates according to the Baveno VII criteria. Measurement data were compared using the Student t-test or Mann-Whitney U test between groups. Categorical data were compared by the χ (2) test or Fisher's exact probability method between groups. Results: 283 of the 320 enrolled cases completed the 120-week follow-up, and 92.2% (261/283) achieved a virological response (HBV DNA 20 IU/ml). Child-Pugh and MELD scores were significantly improved after treatment (8.33 ± 1.90 vs. 5.77 ± 1.37, t = 12.70, P < 0.001; 13.37 ± 4.44 vs. 10.45 ± 4.58, t = 5.963, P < 0.001). During the 120-week follow-up period, 14 cases died, two received liver transplants, 19 developed hepatocellular cancer, 11 developed gastroesophageal variceal bleeding, and four developed hepatic encephalopathy. 60.4% (171/283) (no decompensation events occurred for 12 months) and 56.2% (159/283) (no decompensation events occurred for 12 months and improved liver function) of the patients had achieved clinical recompensation within 120 weeks. Patients with baseline MELD scores > 15 after active antiviral therapy achieved higher recompensation than patients with baseline MELD scores ≤15 [50/74 (67.6%) vs. 109/209 (52.2%), χ (2) = 5.275, P = 0.029]. Conclusion: Antiviral therapy can significantly improve the prognosis of patients with hepatitis B virus-related decompensated cirrhosis. The majority of patients (56.2%) had achieved recompensation. Patients with severe disease did not have a lower probability of recompensation at baseline than other patients.

[Interpretation of the essential updates in guidelines for the prevention and treatment of chronic hepatitis B (Version 2022)].

Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association update the guidelines for the prevention and treatment of chronic hepatitis B (version 2022) in 2022. The latest guidelines recommend more extensive screening and more active antiviral treating for hepatitis B virus infection. This article interprets the essential updates in the guidelines to help deepen understanding and better guide the clinical practice.

[Effect of miR-96-5p targeting IRS1 on apoptosis of PC12 cells induced by aluminum maltol].

Objective: To investigate the effect and mechanism of miR-96-5p on apoptosis of PC12 cells induced by maltol aluminum. Methods: In January 2021, PC12 cells at logarithmic growth phase were divided into blank control group and low, medium and high dose group. Cells in each group were treated with 0, 100, 200 and 400 µmol/L maltol aluminum for 24 hours respectively. Cells were collected and cell apoptosis rates were detected by flow cytometry, miR-96-5p and insulin receptor substrate 1 (IRS1) mRNA expressions were detected by qRT-PCR, and the protein expression levels of cysteine protease 3 (Caspase3) 、activated cysteine protease 3 (Cleaved-caspase3) 、IRS1、phosphorylated protein kinase B (p-AKT) and phosphorylated glucose synthesis kinase 3ß (p-GSK3ß) were detected by western blotting. The target binding relationship between miR-96-5p and IRS1 was detected by double luciferase reporter gene experiment. The miR-96-5p inhibitor cells and negative control cells were constructed after transfecting PC12 cells with miR-96-5p inhibitor for 24 hours. The cells were divided into blank control group, negative control group, aluminum exposure group, aluminum exposure+negative control group, aluminum exposure+miR-96-5p inhibition group, and miR-96-5p inhibition group. After transfecting PC12 cells with miR-96-5p inhibition and IRS1 siRNA for 24 h, the cells were divided into aluminum exposure+miR-96-5p inhibition+negative control group and aluminum exposure+miR-96-5p inhibition+IRS1 inhibition group. The control group was cultured in complete culture medium, and cells in the aluminum exposure group were treated with 200 µmol/L maltol aluminum for 24 hours. Cells in each group were collected and the apoptosis rate, miR-96-5p and IRS1 mRNA expression levels, as well as protein expression levels of Caspase3, Cleaved-caspase3, IRS1, p-AKT, and p-GSK3ß were measured. Results: After 24 hours of exposure, compared with blank control group and low-dose group, the apoptosis rates, relative expressions of Caspase3 and Cleaved-caspase3 proteins, and relative expressions of miR-96-5p in the medium and high-dose groups of PC12 cells were significantly increased, while the relative expression levels of IRS1 mRNA, IRS1, p-AKT and p-GSK3ß proteins were significantly decreased (P<0.05). Targetscan prediction and double luciferase report experiment both proved that IRS1 was a direct target gene of miR-96-5p. In the transfection experiment, compared with the aluminum exposure group, the apoptosis rate, the relative expressions of Caspase3 and Cleaved-caspase3 proteins, the relative expression of miR-96-5p in the aluminum exposure+miR-96-5p inhibition group were significantly decreased, while the relative expression levels of IRS1 mRNA and IRS1, p-AKT and p-GSK3ß proteins were significantly increased (P<0.05). In the IRS1 low expression experiment, compared with the aluminum exposure+miR-96-5p inhibition+negative control group, the apoptosis rate, the relative expressions of Caspase3 and Cleaved-caspase3 proteins in the aluminum exposure+miR-96-5p inhibition+IRS1 inhibition group were significantly increased, while the relative expression levels of IRS1 mRNA and IRS1, p-AKT and p-GSK3ß proteins were significantly decreased (P<0.05) . Conclusion: The increased expression of miR-96-5p and the targeted inhibition of IRS1 may be one of the mechanisms of apoptosis of PC12 cells induced by maltol aluminum exposure.

Mating-Type Genes Control Sexual Reproduction, Conidial Germination, and Virulence in Cochliobolus lunatus.

Cochliobolus lunatus (anamorph: Curvularia lunata) is a major pathogenic fungus that causes the Curvularia leaf spot of maize. ClMAT1-1-1 and ClMAT1-2-1, the C. lunatus orthologs of C. heterostrophus ChMAT1-1-1 and ChMAT1-2-1, were investigated in the present study to uncover their functions in C. lunatus. Southern blot analysis showed that these mating-type MAT genes exist in the C. lunatus genome as a single copy. ClMAT1-1-1 and ClMAT1-2-1 were knocked out and complemented to generate ΔClmat1-1-1 and ΔClmat1-2-1 and ΔClmat1-1-1-C and ΔClmat1-2-1-C, respectively. The mutant strains had defective sexual development and failed to produce pseudothecia. There were no significant differences in growth rate or conidia production between the mutant and wild-type strains. However, the aerial mycelia and mycelial dry weight of ΔClmat1-1-1 and ΔClmat1-2-1 were lower than those of wild type, suggesting that MAT genes affect asexual development. ClMAT genes were involved in the responses to cell wall integrity and osmotic adaptation. ΔClmat1-2-1 had a lower conidial germination rate than the wild-type strain CX-3. The virulence of ΔClmat1-2-1 and ΔClmat1-1-1 was also reduced compared with the wild-type. Complementary strains could restore all the phenotypes.

Potential biomarkers in the fibrosis progression of nonalcoholic steatohepatitis (NASH).

PURPOSE: Fibrosis is the only histological feature reflecting the severity and prognosis of nonalcoholic steatohepatitis (NASH). We aim to explore novel genes associated with fibrosis progression in NASH. METHODS: Two human RNA-seq datasets were downloaded from the public database. Weighted gene co-expression network analysis (WGCNA) was used to identify their co-expressed modules and further bioinformatics analysis was performed to identify hub genes within the modules. Finally, based on two single-cell RNA-seq datasets from mice and one microarray dataset from human, we further observed the expression of hub genes in different cell clusters and liver tissues. RESULTS: 7 hub genes (SPP1, PROM1, SOX9, EPCAM, THY1, CD34 and MCAM) associated with fibrosis progression were identified. Single-cell RNA-seq analysis revealed that those hub genes were expressed by different cell clusters such as cholangiocytes, natural killer (NK) cells, and hepatic stellate cells (HSCs). We also found that SPP1 and CD34 serve as markers of different HSCs clusters, which are associated with inflammatory response and fibrogenesis, respectively. Further study suggested that SPP1, SOX9, MCAM and THY1 might be related to NASH-associated hepatocellular carcinoma (HCC). Receiver operating characteristic (ROC) analysis showed that the high expression of these genes could well predict the occurrence of HCC. At the same time, there were significant differences in metabolism-related pathway changes between different HCC subtypes, and SOX9 may be involved in these changes. CONCLUSIONS: The present study identified novel genes associated with NASH fibrosis and explored their effects on fibrosis from a single-cell perspective that might provide new ideas for the early diagnosis, monitoring, evaluation, and prediction of fibrosis progression in NASH.