ObjectiveTo investigate the antiviral efficacy of pegylated interferon α-2b （PEG-IFN-α-2b） in patients with HBV-related liver cirrhosis， to assess the safety and tolerability of this regimen， and to provide evidence-based medical evidence for optimizing the treatment strategies for patients with HBV-related compensated liver cirrhosis. MethodsA prospective study was conducted among 115 patients with HBV-related compensated liver cirrhosis and 114 patients with CHB who attended Third People’s Hospital of Taiyuan from January 2023 to March 2024. Treatment-naïve patients received PEG-IFN-α-2b monotherapy， while the patients once treated with nucleos（t）ide analogues （NAs） received PEG-IFN-α-2b add-on therapy. The patients with HBV-related compensated liver cirrhosis were followed up at baseline and at 12， 24， 36， and 48 weeks of treatment. Samples were collected from CHB patients at baseline and at the end of follow-up to assess virological indicators， routine blood test results， and liver function. The chi-square test was used for comparison of categorical data between groups； the independent samples t-test was used for comparison of normally distributed continuous data between two groups， and the one-way repeated measures analysis of variance was used for comparison among different time ponts within the same group，and the Bonferroni was applied for post-hoc pairwise comparisons； the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the Friedman test was used for comparison across different time points within the same group， and the Nemenyi test was utilized for subsequent pairwise comparisons. The multivariate stepwise Logistic regression analysis was used to investigate the influencing factors for clinical cure. ResultsCompared with the CHB group， the HBV-related compensated liver cirrhosis group had a significantly higher mean age （43.50±9.97 years vs 40.90±8.16 years， t=2.160， P=0.032）， a significantly higher proportion of patients with hepatitis B e antigen at baseline （28.70% vs 15.79%， χ²=4.788， P=0.029）， and a significantly lower platelet level ［（178.67±55.07）×10⁹/L vs （194.93±55.79）×10⁹/L， t=2.217， P=0.028］. Compared with the CHB group at the end of follow-up， the HBV-related compensated liver cirrhosis group had significantly lower HBV surface antigen （HBsAg） clearance rate （10.38% vs 33.04%， χ²=14.988， P<0.001） and HBV surface antibody positive rate （0.00% vs 19.64%， χ²=21.041， P<0.001）. Compared with the CHB group at the end of follow-up，the HBV-related compensated liver cirrhosis group had significantly lower aminotransferase levels ［ALT： 31.00（19.00～47.50） U/L vs 40.00（27.00～57.00） U/L， Z=2.433， P<0.05； AST： 31.00（23.00～45.50） U/L vs 37.00（25.00～52.00） U/L， Z=1.963， P<0.05］， but significantly higher level of white blood cells （WBC） ［（4.02±1.56）×10⁹/L vs （3.59±1.24）×10⁹/L， t=2.272， P<0.05］， neutrophils ［（2.39±1.17）×10⁹/L vs （1.87±0.94）×10⁹/L， t=3.284， P<0.05］， and platelets ［（143.93±68.10）×10⁹/L vs （121.88±49.72）×10⁹/L， t=2.588， P<0.05］. A lower level of HBsAg （OR=0.997， 95%CI： 0.996　—　0.999， P<0.001） and previous treatment with NAs （OR=5.889， 95%CI： 2.195　—　17.330， P<0.001） were positive predictive factors for clinical cure， while liver cirrhosis （OR=0.177， 95%CI： 0.063　—　0.470， P<0.001） was a negative predictive factor for clinical cure. During follow-up， no patients experienced acute decompensation or progression to hepatocellular carcinoma， and the main adverse events included fever， fatigue， reductions in WBC and platelets， weight loss， alopecia， and thyroid dysfunction. In the subgroup analysis of HBV-related compensated liver cirrhosis， in both the treatment-naïve patients and the patients previously treated with NAs， there was a significant reduction in HBsAg level from baseline to week 36 of treatment ［treatment-naïve： 99.25 （5.87　—　1 212.35） IU/mL vs 403.47 （36.94　—　2 569.02） IU/mL， P<0.05； previously treated with NAs： 205.94 （14.00　—　737.80） IU/mL vs 427.03 （65.64　—　1 552.65） IU/mL， P<0.05］ and week 48 of treatment ［treatment-naïve： 85.45 （0.58　—　827.56） IU/mL vs 403.47 （36.94　—　2 569.02） IU/mL， P<0.05； previously treated with NAs： 45.28 （0.16　—　267.27） IU/mL vs 427.03 （65.64　—　1 552.65） IU/mL， P<0.05］. There were significant increases in the levels of aminotransferases during treatment， as well as significant reductions in the levels of WBC， neutrophils， platelets， and hemoglobin （all P<0.05）. ConclusionAlthough a finite course of PEG-IFN-α-2b therapy has achieved a relatively low rate of clinical cure in the treatment of HBV-related compensated liver cirrhosis， it can still significantly reduce the level of HBsAg， and this treatment regimen has good safety and tolerability， without accelerating disease progression.

Objective To explore the diagnostic value of soluble C5b-9 (sC5b-9) for delayed graft function (DGF) following kidney transplantation. Methods Clinical data of 49 kidney transplant recipients who underwent sC5b-9 detection at the Second People’s Hospital of Shanxi Province between January 2024 and December 2025 were retrospectively analyzed. Recipients were divided into the DGF group (n=25) and the non-DGF group (n=24) according to the occurrence of DGF. Baseline characteristics and serum sC5b-9 levels were compared between the two groups. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic efficacy of sC5b-9 for DGF. A restricted cubic spline model was adopted to investigate the association between sC5b-9 and DGF. Results Among the 49 recipients, DGF occurred in 25 patients. Compared with the non-DGF group, the DGF group presented a higher proportion of male patients, a higher incidence of adverse transplant outcomes, and elevated final serum creatinine levels (all P<0.05). Within 30 days after transplantation, sC5b-9 concentrations were significantly higher in the DGF group than those in the non-DGF group (P<0.001). ROC analysis revealed that the area under the curve (AUC) of sC5b-9 for diagnosing DGF was 0.81, with a 95% confidence interval (CI) of 0.68-0.92, and the optimal cutoff value was 265.7 ng/mL. Recipients with elevated sC5b-9 (≥265.7 ng/mL) had a significantly higher incidence of DGF than those with low sC5b-9 levels (<265.7 ng/mL) (P<0.001). Recipients with adverse outcomes exhibited significantly higher sC5b-9 levels than those without adverse outcomes (P<0.001), and the AUC of sC5b-9 for identifying adverse outcomes was 0.82 (95%CI 0.63-0.95). A significant nonlinear correlation was observed between sC5b-9 and final serum creatinine (P<0.001). Conclusions Elevated sC5b-9 is correlated with the development of DGF after kidney transplantation and exhibits favorable diagnostic performance. It may serve as a potential biomarker for predicting early allograft dysfunction and adverse outcomes in kidney transplant recipients.

Triggering receptor expressed on myeloid cells 2 （TREM2） is expressed in resident non-parenchymal cells （NPCs） and is involved in various pathological processes including liver inflammation and immunoregulation. In recent years， TREM2 has attracted attention in the field of acute and chronic liver diseases， and more and more studies have shown that TREM2 is a potential target for the treatment of acute and chronic liver diseases； however， there is a lack of systematic summary for the mechanism of action of TREM2 in acute and chronic liver diseases. Therefore， this article reviews the latest research advances in the regulatory role of TREM2 in acute and chronic liver diseases， in order to provide new ideas for the clinical prevention and treatment of acute and chronic liver diseases.

Objective: To investigate the effect of neurite outgrowth inhibitor extracellular peptide residues 1-40 (NEP1-40) combined with poly (lactic-co-glycolic acid) (PLGA) and gelatin electrospun fiber membrane on facial nerve repair in rats. Methods: According to the principle of random grouping, 108 male SD rats were divided into four groups (n = 27 in each group, approved by the ethics committee), namely, the sham group, control group, PLGA group, and NEP1-40 + PLGA group. A facial nerve fracture model was established for all of the groups except for the sham group. The control group received no further treatment, the PLGA group and the NEP1-40+PLGA group were supported by PLGA membrane, and the NEP1-40+PLGA group received one immediate local injection of NEP1-40 (5 μg/μL) at a dose of 10 μL. Facial nerve function analysis, electrophysiological examination, transmission electron microscope observation, HE staining, and immunohistochemical staining of myelin marker S100β and axonal marker β3-tubulin were used to evaluate the recovery of injured facial nerves of rats at 2, 4 and 8 weeks. Results : At 8 weeks, the facial nerve function score of the NEP1-40+PLGA group was better than that of the control group and PLGA group (P < 0.001), and facial nerve function was significantly restored. Electrophysiological examination of nerve action potentials at the injured facial nerve showed that the amplitude in the NEP1-40+PLGA group was higher than that of the control group and PLGA group (P < 0.001), but there was no significant difference in latency and conduction velocity results between the groups (P > 0.05). At 2, 4, and 8 weeks, transmission electron microscopy showed that the number of myelinated nerve fibers and myelin sheath thickness in the cross-section of the injured facial nerve in the NEP1-40+PLGA group were greater than those in the other groups (P < 0.05). At 8 weeks, HE staining showed that the facial nerves in the control group had partially recovered, but the overall cell distribution was uneven and the boundary with surrounding tissues was slightly blurred. In contrast, the NEP1-40+PLGA group had a relatively uniform cell distribution and a clearer boundary with surrounding tissues. At 2, 4, and 8 weeks, the immunohistochemical results showed that in the cross-section of the injuried facial nerve, NEP1-40 increased the expression of neural markers S100 β and β3-tubulin, especially β3-tubulin, which was close to normal levels (P > 0.05) Conclusion NEP1-40 is beneficial for the generation of new myelin sheaths and axons at the site of injury, and it can promote the repair and regeneration of injured facial nerves to a certain extent, thus accelerating the recovery of injured nerve function.

Objective: To investigate the epidemiological characteristics of human brucellosis in Jiande City, Zhejiang Province from 2005 to 2024, so as to provide the evidence for strengthening the prevention and control of brucellosis. Methods: Data on brucellosis cases and surveillance in Jiande City from 2005 to 2024 were collected through the Chinese Disease Prevention and Control Information System, the annual brucellosis surveillance reports from the Jiande Center for Disease Control and Prevention, and the annual summaries of brucellosis prevention and control efforts. The epidemiological characteristics of human brucellosis were analyzed using a descriptive epidemiological method. Results: A total of 1 125 individuals were monitored in Jiande City from 2005 to 2024, with 18 seropositive cases identified and the seropositivity rate of 1.60%. The average annual seropositivity rate from 2015 to 2024 was 3.35%, which was significantly higher than that of 0.57% from 2005 to 2014 (P<0.05). There were 10 confirmed brucellosis cases and 8 asymptomatic infections, with no reported deaths. The peak incidence occurred between March and August. Among the 16 towns (streets) in Jiande City, 8 reported brucellosis cases. Of the brucellosis cases, 14 were male and 4 were female, with a male-to-female ratio of 3.5∶1. The majority of cases (13 cases) were aged between 40 and 60 years. Occupational exposure was identified in 16 cases, all of whom were infected through direct hand contact with the excreta, secretions, or animal products of infected sheep or cattle. The primary source of infection was sheep, followed by cattle. Five strains of Brucella were isolated and cultured, all identified as Brucella melitensis biovar 3. Conclusions The brucellosis epidemic in Jiande City remained at a sporadic and low prevalence level from 2005 to 2024, with an increasing trend observed from 2015 to 2024. Male occupational groups aged 40 to 60 years were the key population for brucellosis prevention and control, and sheep were the primary source of infection.

Objective To understand the surveillance situation of poliovirus in Guangzhou from 2011 to 2024, and to further strengthen polio surveillance and ensure the continued maintenance of a polio-free status. Methods An analysis was conducted on the discovery and investigation results of six cases of vaccine-derived poliovirus (VDPV) detected in Guangzhou. Results A total of 6 VDPV incidents were reported in Guangzhou from 2011 to June 2024, among which 5 incidents were from sewage sample testing in the Liede Sewage Treatment Plant in Guangzhou, all of which were confirmed as VDPV, with 1 for type I, 1 for type II, and 3 for type III. In addition, one confirmed HFMD case was identified as a type VDPV II carrier. No presence of any wild poliovirus (WPV), VDPV cases, or circulating VDPV (cVDPV) was reported. Conclusion Guangzhou City has maintained a high level of vigilance and effectiveness in the monitoring and prevention of polio. Continuously strengthening the construction of the polio monitoring network, optimizing vaccination strategies, and comprehensively improving public health awareness are still the focus of the prevention and control work in the future.

Objective To assess the effect of early nutritional intervention on the patients with respiratory diseases at nutritional risk. Methods A total of 130 patients with respiratory disease who were hospitalized in Shanghai Fifth People’s Hospital, Fudan University between May 2023 and December 2024 and had a nutritional risk screening 2002 score ≥3 points. Based on the initiation time of nutritional intervention, patients were divided into an early group (≤5 days, n＝65) and a late group (＞5 days, n＝65). Results In the early group, prealbumin (P-ALB) and retinol-binding protein (RBP) levels were significantly higher (P＜0.01), C-reactive protein (CRP), procalcitonin (PCT) levels were significantly lower after intervention (P＜0.05). Compared with the late group, the hospital costs were lower and hospital stays were shorter in the early group (P＜0.001). Spearman analysis showed ALB, P-ALB, and total protein (TP) were negatively correlated with hospital costs (r＝－0.37, －0.20, and－0.22, P＜0.05). RBP, ALB, P-ALB, and lymphocyte count (LYM) were negatively correlated with CRP (r＝－0.30, －0.26, －0.37, －0.18, P＜0.01), RBP, ALB, P-ALB, hemoglobin (HB), and TP were negatively correlated with PCT (r＝－0.23,－0.36, －0.40, －0.30, －0.19, P＜0.05). Conclusions For patients with respiratory diseases, early nutritional assessment should be underwent, and for patients with nutritional risk screening 2002 score ≥3 points, early nutritional intervention could improve the nutritional status and alleviate inflammatory response, promote recovery, shorten the hospital stays.

OBJECTIVE: To analyze a Chinese pedigree with Hereditary coagulation factor Ⅻ (FⅫ) deficiency duo to variants of F12 gene and explore its molecular pathogenesis. METHODS: A patient who underwent laparoscopic cystectomy at the Department of Gynecology of the First Affiliated Hospital of Wenzhou Medical University in June 2012 was selected as the study subject. Coagulation factor indexes of the proband and her family members (5 individuals from three generations) were determined. All exons, flanking sequences, 5' and 3' untranslated regions of the F12 gene of the proband and her family members were analyzed by direct sequencing. Three bioinformatics software was used to analyze the conservation, pathogenicity and protein model of the variant. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No. 2012-17). RESULTS: The activated partial thromboplastin time (APTT), FⅫ activity (FⅫ:C) and FⅫ antigen (FⅫ:Ag) of the proband was 180.0 s, 1.0% and 2.1%, respectively. DNA sequencing revealed that she has harbored compound heterozygous variants of the F12 gene, namely c.712_713insT (p.Cys238Leufs *73) in exon 8 and c.1561G>A (p.Glu521Lys) in exon 13. Her mother and younger son were heterozygous for the p.Cys238Leufs*73 variant, while her older son was heterozygous for the p.Glu521Lys variant. Bioinformatic analysis suggested that Cys238 is highly conserved and p.Cys238Leufs*73 is a pathogenic variant, which eventually resulted in a truncated protein. CONCLUSION The c.712_713insT and c.1561G>A compound heterozygous variants of the F12 gene probably underlay the decreased FⅫ level in this pedigree, among which c.712_713insT (NM_000505) was unreported previously.
Adult ; Female ; Humans ; Male ; Middle Aged ; Base Sequence ; China ; Factor XII/genetics* ; Heterozygote ; Mutation ; Pedigree ; Factor XII Deficiency/genetics* ; East Asian People

OBJECTIVE: To investigate the molecular pathogenic mechanisms of a family with hereditary factor Ⅶ (FⅦ) deficiency. METHODS: A family (3 generations, 12 members) with hereditary FⅦ deficiency, in which the proband presented with menorrhagia and was admitted to the First Affiliated Hospital of Wenzhou Medical University in April 2023, was selected as the study subject. Clinical data of the family members were collected. Peripheral venous blood samples were collected from all 12 members for routine coagulation tests and genomic DNA extraction. All exons and flanking sequences of the F7 gene were amplified by PCR and analyzed by Sanger sequencing. Thrombin generation assay was performed to evaluate the coagulation potential of the proband and her parents. Multiple online bioinformatics software tools were used to analyze the conservation and pathogenicity of candidate variants identified in the proband. The pathogenicity of variant was classified according to the Standards and Guidelines for the Interpretation of Sequence Variants released by American College of Medical Genetics and Genomics (ACMG) (hereinafter referred to as ACMG guidelines). Homology modeling of the variant FⅦ protein was performed using homology modeling (SWISS-MODEL). Amino acid sequence alignment between wild-type and variant FⅦ proteins was conducted using MEGA v7, and spatial conformational differences were analyzed using PyMOL to assess the potential impact of the F7 gene variants on the structure and function of the FⅦ protein. This study was approved by the Ethics Committee of the First Affiliated Hospital of Wenzhou Medical University (Ethics No.: KY2022-R193). RESULTS: Coagulation tests showed that the proband's prothrombin time (PT) was significantly prolonged to 33.1 s, and both factor Ⅶ activity (FⅦ:C) and antigen (FⅦ:Ag) levels were reduced to 2%. Her parents, eldest sister, second sister, younger brother, and four children all showed mildly prolonged PT, with FⅦ:C and FⅦ:Ag levels approximately 50% of normal. Genetic sequencing identified compound heterozygous variants in the F7 gene of the proband: a heterozygous missense variant c.722C>A (p.Thr241Asn) in exon 7, and a heterozygous deletion variant c.1261_1261delA (p.Ile421Ser*fs75) in exon 8. Retrieval from domestic and international databases found no previous reports of the latter variant, suggesting it is novel. Familial co-segregation analysis confirmed that these variants were inherited from her father and mother, respectively. The thrombin generation assay demonstrated that the proband had a significantly decreased peak thrombin height (peak ratio: 29.5%), significantly increased thrombin lag time ratio and time-to-peak ratio (3.03 and 2.93, respectively), but only a mildly decreased endogenous thrombin potential (ETP) ratio of 90.7%. Online bioinformatics analysis indicated that threonine-241 (p.Thr241) in the FⅦ protein was not conserved, while isoleucine-421 (p.Ile421) was highly conserved. Both the p.Thr241Asn and p.Ile421Serfs*75 variant sites in the proband's F7 gene were predicted to be pathogenic. According to the ACMG guidelines, the p.Thr241Asn (PM3+PP1+PP3+PP4+PP5) and p.Ile421Ser*fs75 (PM2+PM4 +PP1+PP3+PP4) variants were both classified as "likely pathogenic". Structural analysis of the FⅦ protein indicated that the p.Ile421Ser*fs75 frameshift variant led to the substitution of Cysteine-428 by Alanine, preventing the formation of a critical disulfide bond between amino acid residues 400 and 428 present in the wild-type FVII protein. CONCLUSION The compound heterozygous variants p.Thr241Asn and p.Ile421Ser*fs75 in the F7 gene are likely the genetic etiology responsible for the reduced FⅦ levels in this hereditary FⅦ deficiency family.
Adult ; Female ; Humans ; Male ; Middle Aged ; China ; Factor VII/chemistry* ; Factor VII Deficiency/genetics* ; Heterozygote ; Mutation ; Pedigree ; East Asian People/genetics*

OBJECTIVE: To analyze the phenotype and genotype of a family with hereditary coagulation factor Ⅹ (FⅩ) deficiency and preliminarily explore its molecular pathogenesis. METHODS: A hereditary FⅩ deficiency pedigree presented at the First Affiliated Hospital of Wenzhou Medical University on August 13, 2024 was selected as the study subject. Coagulation parameters of the proband and her family members (7 individuals from 3 generations) were measured using a one-stage clotting assay. All of the 8 exons and flanking sequences of the F10 gene were amplified by PCR and directly sequenced. Bioinformatics software was used to analyze the functional impact and pathogenicity of the variant proteins, as well as the spatial conformational changes and evolutionary conservation of the mutation sites. This study has been approved by the Medical Ethics Committee of the First Affiliated Hospital of Wenzhou Medical University (Ethics No.: KY2022-R193). RESULTS: The proband exhibited significantly abnormal prothrombin time (PT, 33.3 s), activated partial thromboplastin time (APTT, 47.7 s), and FⅩ activity (FⅩ:C, 3%), while other coagulation parameters remained normal. The plasma thromboplastin generation test (PTGT) demonstrated that the proband and her children had lower thromboplastin generation levels compared with the healthy control group, and the proband's thromboplastin generation capacity was more severely impaired. Genetic analysis revealed that the proband, her daughter, and grandson have all harbored a heterozygous missense variant c.212T>C (p.Phe71Ser) in exon 2 of the F10 gene, which was located in the β-sheet core region of the Gla domain. The variant has altered surrounding hydrogen bonds and disrupted calcium-binding sites. Additionally, the proband, her son, and granddaughter have all carried a heterozygous missense variant c.1270G>T (p.Val424Phe) in exon 8, which increased the side-chain volume, leading to steric hindrance in the catalytic domain and impaired coagulation function. Bioinformatics analysis confirmed that both p.Phe71Ser and p.Val424Phe were pathogenic variants, with Phe71 and Val424 being highly conserved residues. CONCLUSION The reduced FⅩ levels in this hereditary FⅩ-deficient family may be attributed to the heterozygous missense variants c.212T>C (p.Phe71Ser) in the exon 2 and c.1270G>T (p.Val424Phe) in the exon 8 of the F10 gene.
Humans ; Female ; Male ; Pedigree ; Adult ; Heterozygote ; Mutation ; Middle Aged ; Factor X/genetics* ; Exons ; Factor X Deficiency/genetics*