AIM: To investigate the dynamic variety of frequency and function of FoxP3~+ regulatory T cells in patients with acute hepatitis B (AHB). METHODS: Peripheral blood mononuclear cells (PBMCs) from 15 AHB patients at acute phase (week 1 of illness), convalescent phase (primary occurrence of both ALT level normalization and HBsAg negative conversion), resolved phase (at least 8 weeks after both ALT normalization and HBsAg seroconversion, and 15 health subjects were analyzed for FoxP3 (Forkhead/winged helix transcription factor) mRNA expression in MACS magnetic beads-purified CD4~+ T cells by real-time RT-PCR assay. The effects of Treg cells on the proliferation of CD4~+CD25~- T cells were examined by a ~3[H]-thymidine incorporation assay. RESULTS: AHB patients presented a significantly higher FoxP3 mRNA expression at convalescent phase than acute phase (t=-6.04, P<0.01) and resolved phase (t=4.45, P<0.01), and healthy controls (t=3.44, P<0.01). We also observed that the suppression efficiency of Treg cells on proliferation of CD4~+CD25~- T cells was lower at acute phase than convalescent phase (t=-5.30, P<0.01) and resolved phase (t=-3.20, P<0.05), but there was no significant difference between healthy controls and any phase of AHB. CONCLUSION: AHB patients presented lower circulating Treg frequency and suppression function at acute phase, and both of them are increased at convalescent phase, and then return to normal level along with disease resolved. This follow-up study furthers our understanding of Treg' s role in immunopathogenesis of hepatitis B.

Liver sinusoidal endothelial cells (LSECs) are the highest proportion of liver non-parenchymal cells with fenestrae structure and high endocytic ability maintaining liver homeostasis and playing an indispensable role in the physiology and patholo-gy of the liver.LSECs are involved in the regulation of patholog-ical process in nonalcoholic fatty liver disease(NAFLD),alco-holic fatty liver(AFL),hepatocellular carcinoma(HCC),liverregeneration and liver fibrosis mainly via antiinflammation,endocytosis,secretion of angiocrine signals and maintaining thequiescence phenotype of HSCs.This review highlights the physiological function of LSECs and the different roles in different pathological conditions,which aims to provide a new perspectivefor the treatment of liver diseases through targeting LSECs.

Objective: To observe the joint effect of school and family tobacco control on middle school students, and to explore its effectiveness in reducing second-hand smoke exposure in middle school students’ families, as so asto provide a new way of thinking for controlling smoking among middle school sudents. Methods: A questionnaire survey was conducted on the study of 2 125 primary and high school students in four middle schools in the Dongcheng District of Beijing by means of a stratified group sampling method. Personal information of students, tobacco control environment around the family, school and surrounding ares, as well as the knowledge, attitude and behavior of students related to tobacco control was collected. Results: The exposure rate of second-hand smoke in the families of middle and high school students in Dongcheng District of Beijing was 33.41%. Smoking by at least one parent was positively correlated with second-hand smoke exposure in the student’s home (OR=22.88, P<0.05). Among the students who saw the "clear no-smoking label" on campus, the exposure rate (4.92%) when the smoking restriction was set on the home was lower than that of those who did not have a regulation in the home (58.94%) (χ2=452.57, P<0.01). The results of Logistic regression showed that there was a combination of family smoking restrictions and second-hand smoke exposure in middle and high school students who had seen the smoking ban on campus (OR=0.08) and had the school’s tobacco control education (OR=0.08). Conclusion The joint tobacco control measures between school and family can effectively reduce the exposure rate of second-hand smoke in middle school students’ families, which is better than the effect of tobacco control alone.

Ziziphi Spinosae Semen (ZSS), a traditional Chinese medicine, is used in clinics for the treatment ofinsomnia in China and other Asian countries. Herein, we described for the first time a comparative pharmacokinetics study of the six major compounds of ZSS in normal control (NC) and para-chlor-ophenylalanine (PCPA)-induced insomnia model (IM) rats that were orally administered the aqueous extract of ZSS. An ultra-high-performance liquid chromatography coupled with quadrupole orbitrap mass (UHPLC-Q-Orbitrap-MS) method was developed and validated for the simultaneous determination of coclaurine, magnoflorine, spinosin, 6'''-feruloylspinosin, jujuboside A (JuA), and jujuboside B (JuB) in ZSS in rat plasma. The established approach was successfully applied to a comparative pharmacokinetic study. The systemic exposures of spinosin and 6'''-feruloylspinosin were decreased in the IM group compared to the NC group, while plasma clearance (CL) was significantly increased. The Tmax values of JuA and JuB in IM rats were significantly lower than those in NC rats. The T1/2 of JuA in the IM group was significantly accelerated. The pharmacokinetic parameters of coclaurine and magnoflorine were not evidently affected between the two groups. These results indicate that the pathological state of insomnia altered the plasma pharmacokinetics of spinosin, 6'''-feruloylspinosin, JuA, and JuB in the ZSS aqueous extract, providing an experimental basis for the role of ZSS in insomnia treatment. The comparative pharmacokinetics-based UHPLC-Q-Orbitrap-MS using full-scan mode can therefore provide a reliable and suitable means for the screening of potentially effective substances applied as quality markers of ZSS.

OBJECTIVE: To explore the genetic pathogenesis of X-linked agammaglobulinemia in two patients for clinical diagnosis and family counseling. METHODS: Data was collected from the patients' family including clinical information, blood immunoglobulin level, as well as classification and subgrouping of B lymphocytes. Gene mutations were screened by whole exome sequencing (WES) through next-generation sequencing (NGS), the result was verified with Sanger sequencing. RESULTS: A BTK c.1627T>C (p.Ser543Pro) variant was found in the pedigree. The phenotype and variant have co-segregated in the pedigree. The variant was not found in population database. The variant has affected in the kinase domain which contained no benign variants and is harmful as predicted through bioinformatic analysis. CONCLUSION BTK c.1627T>C (p.Ser543Pro) is a pathogenic variant contributing to X-linked agammaglobulinemia in this pedigree. Above finding has provided reproduction guidance for this family.
Agammaglobulinaemia Tyrosine Kinase/genetics* ; Agammaglobulinemia/genetics* ; DNA Mutational Analysis ; Genetic Diseases, X-Linked ; Humans ; Mutation ; Pedigree

Objective:To investigatethe heterogeneity of career growth recognition amongphysicians at the stage of standardized training and the growth characteristics of clinical physicians in the early stage, and to provide a reference for improving the quality of standardized training.Methods:The trainees who received standardized residency trainingwere randomly selected from three grade A tertiary hospitals in Chongqing, China. Mplus7.4 was used for latent profile analysis to explain the relationship between explicit continuous indicators, and the subtypes of career growth recognition were analyzed.Results:Career growth recognition at the stage of standardized training was classifiedinto three subtypes of all-round growth recognition, high resource and expectation recognition, and unclassified growth recognition, among which the subtype of unclassified growth recognition accounted for the highest percentage of 40.27% (207 trainees).Conclusions:Physicians at the stage of standardized training show obvious uncertainty aboutcareer growth recognition, and it is necessary to strengthen the education on career growth recognition during standardized training and design a development pathway based on the characteristics of career growth recognition.

Objective:To investigate the genetic subtypes and drug resistance monitoring of newly reported human immunodeficiency virus (HIV) infection/AIDS virus in Anhui Province from 2020 to 2023.Methods:An observational design study was used to collect blood samples from patients diagnosed with HIV/AIDS in the AIDS Prevention and Control Department of Anhui Provincial Center for Disease Control and Prevention from January 2020 to December 2023.The HIV-1 pol gene was amplified by reverse transcription-nested PCR, and the genetic subtypes were identified by phylogenetic tree analysis using MEGA 7.0 software. The mutation sites of drug resistance were analyzed by the online software tool of Stanford University′s HIV Drug resistance database. The influencing factors of drug resistance before treatment were analyzed by multivariate logistic analysis.Results:A total of 335 plasma samples were collected, and 332 HIV-1 pol gene sequences were obtained successfully. The main gene subtypes were CRF01-AE, accounting for 35.55% (118/332), followed by CRF07-BC, B and B+C types [29.22% (97/332), 11.74% (39/332), 9.93% (33/332)]. The total drug resistance rate before treatment was 30.12%(32/100), and the drug resistance rate of protease inhibitor (PIs) in HIV-1 was 6.33% (21/332). The drug resistance rate of nucleoside reverse transcriptase inhibitors (NRTI) before treatment was 6.33% (21/332). The drug resistance rate of non-nucleoside reverse transcriptase inhibitors (NNRTI) before treatment was 17.47% (58/332).The comparison of drug resistance rate of different drug types showed statistical significance ( χ2=30.435, P<0.05).Among the 100 cases of drug resistance, the main mutation point of HIV-1 protease inhibitor was Q58E (21.00%), and the main mutation point of nucleoside reverse transcriptase inhibitor was M184V/I (6.00%). Non-nucleoside reverse transcriptase inhibitor resistance mutation points mainly K103N (22.00%).There were statistically significant differences in the starting time of antiviral therapy, the number of CD4 +T cells at baseline and the drug resistance rate of gene subtypes (the chi-square values are respectively 24.152, 32.516, 11.652, P<0.05).Multivariate logistic analysis showed that the baseline CD4 +T cell count was <200/μl, subtype B, subtype B+C, CRF01-AE subtype, CRF55-01B subtype and 01-BC subtype was the influential factor of drug resistance before treatment (the chi-square values are respectively 4.577, 8.202, 4.416, 5.206, 7.603 and 4.804, P<0.05). Conclusion:The newly reported HIV/AIDS population in Anhui Province from 2020 to 2023 has a variety of viral gene subtypes, and NNRTIs are the main types of drug resistance gene mutations before treatment. Attention should be paid to the number of baseline CD4 +T cells, the duration of antiviral treatment, and the distribution of gene subtypes to reduce the drug resistance of HIV/AIDS patients before treatment.

Objective:To investigate the genetic subtypes and drug resistance monitoring of newly reported human immunodeficiency virus (HIV) infection/AIDS virus in Anhui Province from 2020 to 2023.Methods:An observational design study was used to collect blood samples from patients diagnosed with HIV/AIDS in the AIDS Prevention and Control Department of Anhui Provincial Center for Disease Control and Prevention from January 2020 to December 2023.The HIV-1 pol gene was amplified by reverse transcription-nested PCR, and the genetic subtypes were identified by phylogenetic tree analysis using MEGA 7.0 software. The mutation sites of drug resistance were analyzed by the online software tool of Stanford University′s HIV Drug resistance database. The influencing factors of drug resistance before treatment were analyzed by multivariate logistic analysis.Results:A total of 335 plasma samples were collected, and 332 HIV-1 pol gene sequences were obtained successfully. The main gene subtypes were CRF01-AE, accounting for 35.55% (118/332), followed by CRF07-BC, B and B+C types [29.22% (97/332), 11.74% (39/332), 9.93% (33/332)]. The total drug resistance rate before treatment was 30.12%(32/100), and the drug resistance rate of protease inhibitor (PIs) in HIV-1 was 6.33% (21/332). The drug resistance rate of nucleoside reverse transcriptase inhibitors (NRTI) before treatment was 6.33% (21/332). The drug resistance rate of non-nucleoside reverse transcriptase inhibitors (NNRTI) before treatment was 17.47% (58/332).The comparison of drug resistance rate of different drug types showed statistical significance ( χ2=30.435, P<0.05).Among the 100 cases of drug resistance, the main mutation point of HIV-1 protease inhibitor was Q58E (21.00%), and the main mutation point of nucleoside reverse transcriptase inhibitor was M184V/I (6.00%). Non-nucleoside reverse transcriptase inhibitor resistance mutation points mainly K103N (22.00%).There were statistically significant differences in the starting time of antiviral therapy, the number of CD4 +T cells at baseline and the drug resistance rate of gene subtypes (the chi-square values are respectively 24.152, 32.516, 11.652, P<0.05).Multivariate logistic analysis showed that the baseline CD4 +T cell count was <200/μl, subtype B, subtype B+C, CRF01-AE subtype, CRF55-01B subtype and 01-BC subtype was the influential factor of drug resistance before treatment (the chi-square values are respectively 4.577, 8.202, 4.416, 5.206, 7.603 and 4.804, P<0.05). Conclusion:The newly reported HIV/AIDS population in Anhui Province from 2020 to 2023 has a variety of viral gene subtypes, and NNRTIs are the main types of drug resistance gene mutations before treatment. Attention should be paid to the number of baseline CD4 +T cells, the duration of antiviral treatment, and the distribution of gene subtypes to reduce the drug resistance of HIV/AIDS patients before treatment.

Objective To compare the difference of cutpoint and clinical significance of HbA1C for the diagnosis of abnormal glucose metabolism in two population groups with different ages.Methods According to oral glucose tolerance test(OGTT),the cutpoint and clinical significance of HbA1C for the diagnosis of type 2 diabetes and impaired glucose regulation(IGR)were investigated in the two population groups.Results The mean HbA1C of 1 064 young subjects in an academy and 1 671 aged subjects in a community were 5.31% ±0.41% and 5.79% ±0.71%,respectively.The cutpoints of HbA1C for diagnosis of diabetes were 5.7%(specificity 86.7%,sensitivity 66.7%)and 5.9%(specificity 73.8%,sensitivity 80.1%)in the two population groups,and 5.6% for diagnosis of IGR (specificity 82.8%,sensitivity 55.8%)and 5.7%(specificity 60.9%,sensitivity 64.3%),respectively.87.8%,78.7%,and 38.5% were diagnosed diabetes by current OGTT criteria at HbA1C levels of ≥5.7%,≥5.9%,and≥6.5%,IGR being 61.6%,39.6%,and 4.1%,and normal glucose tolerance being 24.4%,10.0%,and 0.4%.Conclusion The cutpoints of HbA1C for diagnosis of diabetes and IGR are different in populations with different ages and HbA1C levels.As one of diagnostic criteria for diabetes,HbA1C 6.5% with relatively higher specificity and lower sensitivity must be combined with fasting blood glucose,random blood glucose,and OGTT.