ObjectiveTo investigate the significance of different non-treatment thresholds or upper limits of normal （ULN） of alanine aminotransferase （ALT） in evaluating significant liver pathological injury in patients with chronic hepatitis B virus （HBV） infection， and to provide guidance for clinical diagnosis and treatment. MethodsThis study was conducted among 733 patients with chronic HBV infection who were hospitalized in Ningbo No. 2 Hospital from January 2015 to December 2023 and underwent liver biopsy and histopathological examination， and all patients had a persistent ALT level of ≤40 U/L and positive HBV DNA （>30 IU/mL）. According to the treatment threshold or ULN of ALT， the patients were divided into group 1 with 575 patients （≤35 U/L for male patients， ≤25 U/L for female patients）， group 2 with 430 patients （≤30 U/L for male patients， ≤19 U/L for female patients）， group 3 with 443 patients （≤27 U/L for male patients， ≤24 U/L for female patients）， group 4 with 446 patients （≤25 U/L）， group 5 with 158 patients （>35 U/L for male patients， >25 U/L for female patients）， and group 6 with 145 patients （>30 — ≤35 U/L for male patients， >19 — ≤25 U/L for female patients）. Groups 2， 5， and 6 were compared to analyze the severity of liver pathological injury in patients with different ALT levels and the constituent ratio of patients with significant liver pathological injury， and groups 1， 2， 3， and 4 were compared to investigate the value of different ULN or non-treatment thresholds of ALT in determining liver inflammation grade （G）， liver fibrosis stage （S）， and the treatment indication based on liver pathology. The independent-samples t test was used for comparison of normally distributed continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test or the Tambane’s test was used for further comparison between two groups； the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between multiple groups and further comparison between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups； a Ridit analysis was used for comparison of ranked data. A multivariate Logistic regression analysis （forward stepwise） was performed with whether liver pathology met the treatment indication （≥G2 and/or ≥S2） as the dependent variable and related factors with a significant impact on the dependent variable （P <0.05） as the independent variable. The receiver operating characteristic （ROC） curve was plotted， and the area under the ROC curve （AUC）， as well as sensitivity， specificity， positive predictive value， negative predictive value， positive likelihood ratio， and negative likelihood ratio， was used to assess the diagnostic value of different non-treatment thresholds of ALT. ResultsAmong the 733 patients， 259 （35.33%） had ≥G2 liver inflammation， 211 （28.79%） had ≥S2 liver fibrosis， and 306 （41.75%） had treatment indication （≥G2 and/or ≥S2）. There was a significant difference in liver inflammation grade （G0 — G4） between groups 2， 5， and 6 （χ²=22.869， P <0.001）， and there were also significant differences in the constituent ratios of patients with ≥G2 or ≥G3 liver inflammation between the three groups （χ²=21.742 and 14.921， P<0.001 and P=0.001）. There was a significant difference in liver fibrosis stage （S0 — S4） between groups 2， 5， and 6 （χ²=16.565， P<0.001）， and there were also significant differences in the constituent ratios of patients with ≥S2， ≥S3 or S4 liver fibrosis between the three groups （χ²=13.264， 13.050， and 6.260， P=0.001， 0.001， and 0.044）. There were significant differences between groups 2， 5， and 6 in the constituent ratios of patients with or without treatment indication based on liver pathology （χ²=20.728， P<0.001）. There were significant differences between groups 2， 5， and 6 in the constituent ratio of male patients （χ²=24.836， P<0.05）， age （F=5.710， P<0.05）， ALT （F=473.193， P<0.05）， aspartate aminotransferase （AST） （F=107.774， P<0.05）， ALT/AST ratio （F=40.167， P<0.05）， γ-glutamyl transpeptidase （GGT） （H=15.463， P<0.05）， aspartate aminotransferase-to-platelet ratio index （APRI） （H=63.024， P<0.05）， and LIF-5 （5 indicators for liver inflammation and fibrosis） （H=46.397， P<0.05）. In groups 1 — 4， compared with the patients without treatment indication， the patients with treatment indication had a significantly lower constituent ratio of patients with positive HBeAg， significantly lower levels of platelet count （PLT） and HBV DNA， and significantly higher age， ALT， AST， GGT， APRI， FIB-4， and LIF-5 （all P<0.05）. The Logistic regression analysis showed that age （odds ratio ［OR］=1.044， 95% confidence interval ［CI］： 1.025 — 1.063， P<0.001）， GGT （OR=1.022， 95%CI： 1.007 — 1.038， P=0.003）， and HBV DNA （OR=0.839， 95%CI： 0.765 — 0.919， P<0.001） were influencing factors for treatment indication based on liver pathology in group 1； HBeAg （OR=1.978， 95%CI： 1.269 — 3.082， P=0.003）， age （OR=1.048， 95%CI： 1.025 — 1.071， P<0.001）， GGT （OR=1.016， 95%CI： 1.001 — 1.031， P=0.041）， and PLT （OR=0.995， 95%CI： 0.991 — 1.000， P=0.049） were influencing factors in group 2； age （OR=1.040， 95%CI： 1.014 — 1.066， P=0.002）， ALT （OR=1.047， 95%CI： 1.005 — 1.092， P=0.029）， HBV DNA （OR=0.817， 95%CI： 0.736 — 0.907， P<0.001）， and LIF-5 （OR=7.382， 95%CI： 1.151 — 47.330， P=0.035） were influencing factors in group 3； age （OR=1.054， 95%CI： 1.031 — 1.077， P<0.001）， ALT （OR=1.061， 95%CI： 1.016 — 1.107， P=0.008）， and HBV DNA （OR=0.825， 95%CI： 0.743 — 0.917， P<0.001） were influencing factors in group 4. The diagnostic performance for identifying ≥G2 liver inflammation， ≥S2 liver fibrosis， and treatment indication in groups 1 — 4 had an AUC of >0.7； group 1 showed the lowest sensitivity （28.76%） and the highest specificity， positive predictive value， positive likelihood ratio， and negative likelihood ratio in judging treatment indication； group 2 had the highest sensitivity and negative predictive value and the lowest negative likelihood ratio； groups 3 and 4 had similar diagnostic indicators. ConclusionIn patients with chronic HBV infection and a persistently low ALT level， the severity of liver histopathological injury and the constituent ratio of significant liver histopathological injury decrease with the reduction in ALT level. A higher non-treatment threshold or ULN of ALT can help to identify the patients requiring treatment （with a higher specificity）， while a lower non-treatment threshold or ULN of ALT can help to identify the patients who do not require treatment （with a higher sensitivity）.

Objective:To characterize the epidemiology of respiratory syndrome across healthcare facilities of different types and tiers in Beijing City, to compare pathogen-testing modalities and their associations with adverse outcomes, and to identify key factors associated with progression to severe illness, thereby informing regional prevention, control, and clinical optimization.Methods:The multicenter observational cohort study was performed using outpatient and emergency department data from five sentinel hospitals in Beijing (Beijing Xiaotangshan Hospital, Beijing Chaoyang District Shuangqiao Hospital, Beijing Haidian Hospital, Beijing You′an Hospital, Capital Medical University (Beijing You′an Hospital), and Beijing Ditan Hospital, Capital Medical University (Beijing Ditan Hospital)) from October 1st, 2023 to April 9th, 2025. Dual-target (two-plex) and triple-target (three-plex) respiratory specimens were collected. Demographic characteristics, visit information, pathogen-testing modalities and results were collected, and the epidemiologic features of patients who progressed to severe illness between the influenza high-incidence season (December to May) and the non-influenza season (June to November) were compared. Categorical variables were analyzed using the chi-square test. Multivariable logistic regression was used to estimate associations between covariates and risk of progression to severe illness.Results:Among the 192 131 cases, patients visited at Beijing You′an Hospital were concentrated in the 16 to 44 year age group, accounting for 66.79%(32 532/48 708). Beijing Xiaotangshan Hospital had a broad age distribution, with older adults comprising up to 22.35% (885/3 960). Of the 47 349 respiratory specimens across the five hospitals, Beijing You′an Hospital had the highest positivity rate for dual-target testing (46.76%(1 585/3 390)), while Beijing Haidian Hospital conducted the largest number of this tests ( n=12 514). For triple-target testing, Beijing You′an Hospital again had the highest positivity rate (45.03%(2 835/6 296)), whereas Beijing Ditan Hospital tested the most specimens ( n=12 011; positivity rate was 29.73%(3 571/12 011)). The influenza season within the same period (November 2023 to January 2024) exhibited a bimodal pattern, with alternating circulation of influenza viruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Among 32 744 outpatients/emergency patients who progressed to severe illness, significant seasonal differences were observed by sex, age, comorbidity status, and infection type ( χ2=6.60, 189.24, 32.71 and 189.99, respectively; all P<0.05). After adjustment for sex, age group, comorbidities, and infection type, testing modality remained significantly associated with risk of progression (dual-target testing, odds ratio ( OR)=0.116, 95% confidence interval ( CI) 0.111 to 0.122, P<0.001); no testing, OR=0.063, 95% CI 0.060 to 0.065, P<0.001). Conclusions:The epidemiological pattern of respiratory pathogens undergo significant changes after October 2023, which is characterized by alternating waves of influenza viruses and SARS-CoV-2 with pronounced seasonality and diversity. Substantial inter-hospital differences are observed in testing modalities and positivity rates. Risk of progression to severe illness varies significantly by sex, age, comorbidity burden, and infection type, and is closely associated with the testing modality. These findings support strengthening multiplex pathogen testing and targeted surveillance of high-risk groups to improve early identification and precise control of febrile-respiratory syndromes.

Objective:To characterize the epidemiology of respiratory syndrome across healthcare facilities of different types and tiers in Beijing City, to compare pathogen-testing modalities and their associations with adverse outcomes, and to identify key factors associated with progression to severe illness, thereby informing regional prevention, control, and clinical optimization.Methods:The multicenter observational cohort study was performed using outpatient and emergency department data from five sentinel hospitals in Beijing (Beijing Xiaotangshan Hospital, Beijing Chaoyang District Shuangqiao Hospital, Beijing Haidian Hospital, Beijing You′an Hospital, Capital Medical University (Beijing You′an Hospital), and Beijing Ditan Hospital, Capital Medical University (Beijing Ditan Hospital)) from October 1st, 2023 to April 9th, 2025. Dual-target (two-plex) and triple-target (three-plex) respiratory specimens were collected. Demographic characteristics, visit information, pathogen-testing modalities and results were collected, and the epidemiologic features of patients who progressed to severe illness between the influenza high-incidence season (December to May) and the non-influenza season (June to November) were compared. Categorical variables were analyzed using the chi-square test. Multivariable logistic regression was used to estimate associations between covariates and risk of progression to severe illness.Results:Among the 192 131 cases, patients visited at Beijing You′an Hospital were concentrated in the 16 to 44 year age group, accounting for 66.79%(32 532/48 708). Beijing Xiaotangshan Hospital had a broad age distribution, with older adults comprising up to 22.35% (885/3 960). Of the 47 349 respiratory specimens across the five hospitals, Beijing You′an Hospital had the highest positivity rate for dual-target testing (46.76%(1 585/3 390)), while Beijing Haidian Hospital conducted the largest number of this tests ( n=12 514). For triple-target testing, Beijing You′an Hospital again had the highest positivity rate (45.03%(2 835/6 296)), whereas Beijing Ditan Hospital tested the most specimens ( n=12 011; positivity rate was 29.73%(3 571/12 011)). The influenza season within the same period (November 2023 to January 2024) exhibited a bimodal pattern, with alternating circulation of influenza viruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Among 32 744 outpatients/emergency patients who progressed to severe illness, significant seasonal differences were observed by sex, age, comorbidity status, and infection type ( χ2=6.60, 189.24, 32.71 and 189.99, respectively; all P<0.05). After adjustment for sex, age group, comorbidities, and infection type, testing modality remained significantly associated with risk of progression (dual-target testing, odds ratio ( OR)=0.116, 95% confidence interval ( CI) 0.111 to 0.122, P<0.001); no testing, OR=0.063, 95% CI 0.060 to 0.065, P<0.001). Conclusions:The epidemiological pattern of respiratory pathogens undergo significant changes after October 2023, which is characterized by alternating waves of influenza viruses and SARS-CoV-2 with pronounced seasonality and diversity. Substantial inter-hospital differences are observed in testing modalities and positivity rates. Risk of progression to severe illness varies significantly by sex, age, comorbidity burden, and infection type, and is closely associated with the testing modality. These findings support strengthening multiplex pathogen testing and targeted surveillance of high-risk groups to improve early identification and precise control of febrile-respiratory syndromes.

Hepatitis B virus(HBV)infection is the main risk factor for the development and progres-sion of hepatocellular carcinoma(HCC).Through re-peated inflammatory stimulation,liver cells regen-eration,fibrosis,and scar formation,it may eventu-ally progress to HCC.Antiviral treatment reduces the incidence of HBV-related HCC and the risk of postoperative recurrence by reducing HBV DNA lev-el,thereby improving prognosis.Many recent stud-ies have found that different kinds of nucleos(t)ide analogues(NAs)may have differential improve-ments in the prevention of HBV-related HCC occur-rence and postoperative recurrence.This article re-views the differential improvement of different cat-egories of NAs in HBV-related HCC and the possible mechanisms.

Hepatitis B virus(HBV)infection is the main risk factor for the development and progres-sion of hepatocellular carcinoma(HCC).Through re-peated inflammatory stimulation,liver cells regen-eration,fibrosis,and scar formation,it may eventu-ally progress to HCC.Antiviral treatment reduces the incidence of HBV-related HCC and the risk of postoperative recurrence by reducing HBV DNA lev-el,thereby improving prognosis.Many recent stud-ies have found that different kinds of nucleos(t)ide analogues(NAs)may have differential improve-ments in the prevention of HBV-related HCC occur-rence and postoperative recurrence.This article re-views the differential improvement of different cat-egories of NAs in HBV-related HCC and the possible mechanisms.

Developing new therapeutic agents for cancer immunotherapy is highly demanding due to the low response ratio of PD-1/PD-L1 blockade in cancer patients. Here, we discovered that the novel immune checkpoint VISTA is highly expressed on a variety of tumor-infiltrating immune cells, especially myeloid derived suppressor cells (MDSCs) and CD8⁺ T cells. Then, peptide C1 with binding affinity to VISTA was developed by phage displayed bio-panning technique, and its mutant peptide VS3 was obtained by molecular docking based mutation. Peptide VS3 could bind VISTA with high affinity and block its interaction with ligand PSGL-1 under acidic condition, and elicit anti-tumor activity in vivo. The peptide DVS3-Pal was further designed by d-amino acid substitution and fatty acid modification, which exhibited strong proteolytic stability and significant anti-tumor activity through enhancing CD8⁺ T cell function and decreasing MDSCs infiltration. This is the first study to develop peptides to block VISTA/PSGL-1 interaction, which could act as promising candidates for cancer immunotherapy.

Objective:To analyze the phenotypic and genomic characteristics of Salmonella isolates recovered from meat products in Beijing wholesale markets. Methods:A total of 336 Salmonella strains from meat products collected from wholesale markets in Beijing were tested for antimicrobial resistance to 25 antimicrobial compounds by micro-broth dilution method; whole genome data were sequenced, followed by the serotype and ST type prediction by Seqsero2 and SISTR software, and the drug resistance genes and virulence factors were also predicted with CARD and VFDB databases of Abricate software; Salmonella serotyping assay kit and serum agglutination method were used for serotype confirmation of some isolates with different genome prediction results. Results:The resistance rates to Nalidixic acid and Ampicillin were 62.5% (210/336) and 55.1% (185/336), respectively, and all isolates were susceptible to Tigecyclin, Cefoxitin and Carbapenem antimicrobial compounds; 207 isolates (61.6%, 207/336) were multi-drug resistant, some could even be resistant to ten categories of drugs at the same time, and the most common antimicrobial resistance spectrum was NAL-AMP-SAM. A total of 24 serotypes were detected with predominant serotypes of Enteritidis (34.5%, 116/336), Derby (17.3%, 58/336) and Indiana (10.4%, 35/336). A total of 27 ST types were detected, the dominant type was ST11; ST types were in good consistency with serotypes; The detection rates of resistant genes referred to aminoglycosides, fluoroquinolones, β-lactams, sulfonamides and tetracyclines are more than 48%, and the first two reached 100%. The prediction of drug resistance genes was consistent with the results of antimicrobial resistance phenotype. A total of 122 virulence genes were predicted, 74 of which existing among all isolates.Conclusion:Salmonella in meat from the wholesale markets of Beijing has a high proportion of multiple drug resistance, a complex drug resistance spectrum, a variety of serotypes and ST types, and a high carrying rate of drug resistance gene and virulence gene; drug resistance phenotype and genotype are relatively consistent.

Objective:To analyze the phenotypic and genomic characteristics of Salmonella isolates recovered from meat products in Beijing wholesale markets. Methods:A total of 336 Salmonella strains from meat products collected from wholesale markets in Beijing were tested for antimicrobial resistance to 25 antimicrobial compounds by micro-broth dilution method; whole genome data were sequenced, followed by the serotype and ST type prediction by Seqsero2 and SISTR software, and the drug resistance genes and virulence factors were also predicted with CARD and VFDB databases of Abricate software; Salmonella serotyping assay kit and serum agglutination method were used for serotype confirmation of some isolates with different genome prediction results. Results:The resistance rates to Nalidixic acid and Ampicillin were 62.5% (210/336) and 55.1% (185/336), respectively, and all isolates were susceptible to Tigecyclin, Cefoxitin and Carbapenem antimicrobial compounds; 207 isolates (61.6%, 207/336) were multi-drug resistant, some could even be resistant to ten categories of drugs at the same time, and the most common antimicrobial resistance spectrum was NAL-AMP-SAM. A total of 24 serotypes were detected with predominant serotypes of Enteritidis (34.5%, 116/336), Derby (17.3%, 58/336) and Indiana (10.4%, 35/336). A total of 27 ST types were detected, the dominant type was ST11; ST types were in good consistency with serotypes; The detection rates of resistant genes referred to aminoglycosides, fluoroquinolones, β-lactams, sulfonamides and tetracyclines are more than 48%, and the first two reached 100%. The prediction of drug resistance genes was consistent with the results of antimicrobial resistance phenotype. A total of 122 virulence genes were predicted, 74 of which existing among all isolates.Conclusion:Salmonella in meat from the wholesale markets of Beijing has a high proportion of multiple drug resistance, a complex drug resistance spectrum, a variety of serotypes and ST types, and a high carrying rate of drug resistance gene and virulence gene; drug resistance phenotype and genotype are relatively consistent.

Objective:To investigate the serotypes and antimicrobial resistance of seven invasive non-typhoidal Salmonella (iNTS) isolates. Methods:For 7 iNTS strains collected, serotype identification, antimicrobial susceptibility testing and whole genome sequencing were performed. We identified, annotated and analyzed the serotypes, MLST types, and antimicrobial resistance genes.Results:Among the 7 tested iNTS isolates, we found one Salmonella Typhimurium strain and two Salmonella Ⅰ 4, [5], 12: i:- strains whose MLST types were ST34, two Salmonella Enteritidis strains, one Salmonella Corvallis strain and one strain of unknown serotype with the antigenic formulae of Ⅰ 4, [5], 12: d:- (ST279 type). Six of seven strains were monophasic and the deletion or pseudogenization of Salmonella Flagellum gene might contribute to the enhancement of Salmonella invasiveness. None was found to be resistant to tigarcycline, aztreonam, amikacin, cephalosporins and carbapenem and one Salmonella Typhimurium strain was found to be co-resistant to eight classes of antimicrobials at the same time. Resistance genes were generally in accord with relative resistant phenotypes. Conclusion:The iNTS strains could show high level multi-drug resistance, indicating that close attention should be paid to the resistance of iNTS though the overall resistance might be relatively not high.

Biosynthesis of nanomaterials has attracted much attention for its excellent characteristics such as low energy consumption, high safety, and environmental friendliness. As we all know, the toxic selenite can be transformed into higher-value nanomaterials by using bacteria. In this study, nano-selenium was synthesized by halophilic Bacillus subtilis subspecies stercoris strain XP in LB medium supplemented with selenite (electron acceptor). The physicochemical characteristics of nano-selenium were analyzed by scanning electron microscope (SEM), X-ray energy dispersive spectral analysis (EDAX), X-ray diffraction (XRD), and fourier transform infrared spectroscopy (FTIR). Meanwhile, the antifungal activity of nano-selenium to strawberry pathogens (fusarium wilt, erythema, and purple spot fungi) was determined. The products from reduction of selenite by strain XP was amorphous spherical selenium nanoparticles (SeNPs) with a diameter range of 135-165 nm. The production of SeNPs was positively correlated with time (0-48 h) and no changes were observed on cell morphology. Selenium was dominant in the surface of SeNPs where the organic elements (C, O, N, and S) existed at the same time. SeNPs were coated with biomolecules containing functional groups (such as -OH, C=O, N-H, and C-H) which were associated with the stability and bioactivity of particles. Although the highest concentration of SeNPs had significant (P<0.05) inhibitory effects on three strains of strawberry pathogens, antifungal activity to erythema and fusarium wilt pathogenic fungi was higher than that to purple spot pathogenic fungi from strawberry. In conclusion, strain XP not only has strong tolerance to high salt stress, but can be also used to synthesize biological SeNPs with good stability and biological activity. Thus, the strain XP has bright perspectives and great potential advantage in pathogens control and green selenium-rich strawberry planting as well as other fields.
Bacillus subtilis ; Fragaria ; Nanoparticles ; Selenious Acid ; Selenium