Seven novel linear polyketides,talaketides A-G(1-7),were isolated from the rice media cultures of the mangrove sed-iment-derived fungus Talaromyces sp.SCSIO 41027.Among these,talaketides A-E(1-5)represented unprecedented unsaturated lin-ear polyketides with an epoxy ring structure.The structures,including absolute configurations of these compounds,were elucidated through detailed analyses of nuclear magnetic resonance(NMR)and high-resolution mass spectrometry(HR-MS)data,as well as elec-tronic custom distributors(ECD)calculations.In the cytotoxicity screening against prostate cancer cell lines,talaketide E(5)demon-strated a dose-dependent inhibitory effect on prostate cancer PC-3 cell lines,with an IC50 value of 14.44 μmol·L-1.Moreover,com-pound 5 significantly inhibited the cloning formation of PC-3 cell lines and arrested the cell cycle in S-phase,ultimately inducing ap-optosis.These findings indicate that compound 5 may serve as a promising lead compound for the development of a potential treat-ment for prostate cancer.

Active surveillance means patients are monitored closely without active treatment immediately. Many studies have shown that active surveillance, as a relatively safe method for prostate cancer patients, can reduce overtreatment, and is one of the main methods for very low risk, low risk and a small proportion of intermediate risk men with a life expectancy more than 10 years. The follow-up process of active surveillance includes regularly repeat needle biopsy, PSA test, digital rectal examination, multiparametric magnetic resonance imaging (mpMRI), etc. However, the monitoring standard and frequency are still not unified. There is still a lack of active surveillance data in China, and further research is needed.

BACKGROUND: Hepatitis B surface antigen (HBsAg) clearance is vital for a functional cure of hepatitis B virus (HBV) infection. However, the incidence and predictors of HBsAg seroclearance in patients co-infected with HBV and human immunodeficiency virus (HIV) remain largely unknown in Guangdong, China. METHODS: Between 2009 and 2019, patients co-infected with HBV/HIV undergoing antiretroviral therapy (ART) in Guangzhou Eighth People's Hospital affiliated to Guangzhou Medical University were retrospectively reviewed with the endpoint on December 31, 2020. The incidence and risk factors for HBsAg seroclearance were evaluated using Kaplan-Meier and multivariate Cox regression analyses. RESULTS: A total of 1550 HBV/HIV co-infected patients were included in the study, with the median age of 42 years and 86.0% (1333/1550) males. Further, 98.3% (1524/1550) received ART containing tenofovir disoproxil fumarate (TDF) plus lamivudine (3TC). HBV DNA was examined in 1283 cases at the last follow-up. Over the median 4.7 years of follow-up, 8.1% (126/1550) patients achieved HBsAg seroclearance, among whom 50.8% (64/126) obtained hepatitis B surface antibody, 28.1% (137/488) acquired hepatitis B e antigen seroconversion, and 95.9% (1231/1283) undetectable HBV DNA. Compared with patients who maintained HBsAg positive, cases achieving HBsAg seroclearance showed no differences in age, gender, CD4 + T cell count, alanine aminotransferase (ALT) level, or fibrosis status; however, they presented lower HBV DNA levels, lower HBsAg levels, and higher rates of HBV genotype B at the baseline. Multivariate analysis showed that baseline HBsAg <1500 cutoff index (COI) (adjusted hazard ratio [aHR], 2.74, 95% confidence interval [95% CI]: 1.48-5.09), ALT elevation >2 × upper limit of normal during the first six months after receiving ART (aHR, 2.96, 95% CI: 1.53-5.77), and HBV genotype B (aHR, 3.73, 95% CI: 1.46-9.59) were independent predictors for HBsAg seroclearance (all P <0.01). CONCLUSIONS Long-term TDF-containing ART has high anti-HBV efficacy including relatively high overall HBsAg seroclearance in HBV/HIV co-infected patients. Lower baseline HBsAg levels, HBV genotype B, and elevated ALT levels during the first six months of ART are potential predictors of HBsAg seroclearance.
Male ; Humans ; Adult ; Hepatitis B Surface Antigens ; Hepatitis B virus/genetics* ; HIV Infections/drug therapy* ; HIV ; DNA, Viral ; Incidence ; Coinfection/drug therapy* ; Retrospective Studies ; Tenofovir/therapeutic use* ; Lamivudine/therapeutic use* ; Hepatitis B, Chronic/drug therapy*

Objective:To understand the incubation periods of infections of Omicron variants BA.2 and BF.7 in two COVID-19 epidemics and related factors in Beijing and provide basic parameters for the establishment of 2019-nCoV dynamic transmission model.Methods:The COVID-19 cases with specific exposure time and onset time in the Omicron variant BA.2 infection epidemic in April 2022 and in the Omicron variant BF.7 infection epidemic in October 2022 in Beijing were included in the analysis. The rank-sum test was conducted to estimate the differences in the incubation period between two types of infections. The incubation period distribution of the Omicron variant infection was fitted by using Weibull, Gamma and lognormal distributions. Multivariate analysis of variance was conducted to assess the effects of age, sex, variant type and vaccination status on the incubation periods.Results:A total of 64 cases of variant BA.2 infection and 58 cases of variant BF.7 infection were included. The M( Q1,Q3) of the incubation period was 3.00 (3.00, 4.00) days for BA.2 infection and 3.00 (2.00, 3.25) days for BF.7 infection. The lognormal distribution was the best fit. Multivariate analysis of variance showed that there were some differences in the incubation periods between two types of infections of Omicron variants, and the incubation period of variant BF.7 infection was shorter than that of variant BA.2 infection. Conclusion:Omicron variant BF.7 infection had shorter incubation period compared with Omicron variant BA.2 infection.

Objective:To observe the expression of sirtuin 3 (Sirt3) and mitochondrial damage-associated proteins in lipopolysaccharide (LPS)-induced acute kidney injury mouse model and renal tubular epithelial cells, and to explore the role of Sirt3 in LPS-induced abnormal mitochondrial dynamics in renal tubular epithelial cells.Methods:Eighteen specific pathogen free (SPF) male C57BL/6 mice were randomly assigned to control group, LPS 24 h group and LPS 48 h group. The control group was intraperitoneally injected with physiological saline (0.1 ml/10 g), and LPS 24 h group and LPS 48 h group were intraperitoneally injected with LPS (10 mg/kg) solution. Renal functional indexes of mice were analyzed by automatic biochemical analyzer. The pathological change of the kidney was observed by HE staining, and the expressions of dynamin-related protein-1 (Drp1), optic atrophy type 1 (Opa1) and Sirt3 were evaluated by Western blotting. Expression and distribution of Sirt3 in kidney was assessed by immunohistochemistry. Human renal tubular epithelial cells (HK-2) were exposed to 10 μg/ml LPS for 24 h, and the expression of Drp1, Opa1 and Sirt3 were detected by Western blotting. Cell apoptosis was assessed by Hoechst-33342 staining. After transfection to HK-2 cells with pcDNA3.1-Sirt3 recombinant plasmid, the expressions of Sirt3, Drp1, Opa1 and cell apoptosis were detected by the same methods as above.Results:(1) The levels of blood urea nitrogen and serum creatinine in LPS group were significantly higher than those in control group (both P<0.05), and the pathological changes of kidney were obvious. (2) Compared with the control group, the expression of mitochondrial fission-associated protein Drp1 in renal tissue of LPS group was significantly higher ( P<0.05), and the expression of mitochondrial fusion associated protein Opa1 was significantly lower ( P<0.05). (3) Compared with the control group, the expression of Sirt3 in LPS group was significantly lower ( P<0.05), and immunohistochemistry results showed that Sirt3 was mainly expressed in glomerular vascular endothelial cells and renal tubular epithelial cells. (4) In vitro, LPS stimulation induced increased Drp1 expression in HK-2 cells ( P<0.05), decreased Opa1 and Sirt3 expression (both P<0.05), and increased apoptosis ( P<0.05). (5) LPS-induced mitochondrial dynamics disturbance and apoptosis were alleviated by pcDNA3.1-Sirt3 recombinant plasmid transfection. Conclusions:LPS can induce down-regulation of Sirt3 expression and disturbance of mitochondrial dynamics, and Sirt3 may play a protective role in LPS-induced acute kidney injury by regulating mitochondrial dynamics.

Guideline or consensus for the vaccination of children with special conditions like immunocompromised children may be more suitable for pediatricians.However, the vaccination of children in China is mainly performed by general practitioners or child health care practitioners in community health service centers.They need to master the screening knowledge of contraindications and precautions for the vaccination of children, and make the decision to referral to specialists.Based on the technical guidelines for Immunization of National Health Commission of the People′s Republic of China, Best Practices Guidance of the Advisory Committee on Immunization Practices and contraindications and precautions proposed by the Immunization Action Coalition, 20 suggestions for primary screening of children with vaccination contraindications and referral recommendations for primary care providers were developed by experts from the Integration of Medicine and Prevention in Children of Health Commission of Shenzhen Municipality.

Objective:To investigate the impact of low level viremia (LLV) on the prognosis of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients received anti-retroviral therapy (ART).Methods:From January to December 2015, the HIV/AIDS patients with LLV received ART over one year were recruited in Guangzhou Eighth People′s Hospital, Guangzhou Medical University (LLV group). Patients with viral load (VL) less than 50 copies/mL were matched at ratio of 1∶1 according to gender, age and the transmission route were included in the control group (suppression group). The LLV group was divided into three subgroups according to VL (LLV-1 subgroup was 50-200 copies/mL, LLV-2 subgroup was 201-400 copies/mL, and LLV-3 subgroup was 401-1 000 copies/mL). The influence of LLV on the antiviral response during the following three years was investigated.The Wilcoxon signed rank test, Kruskal-Wallis test and chi-square test were used for statistical analysis.Results:One hundred and thirty-seven patients were enrolled in the LLV group, of whom 111 were males and 26 were females, with age of (39.5±13.5) years old. At the same time, 137 patients were included in the suppression group. There were 93 cases in LLV-1 subgroup, 25 cases in LLV-2 subgroup and 19 cases in LLV-3 subgroup. There were no significant differences in the CD4 + T lymphocyte counts and CD4 + /CD8 + T lymphocyte counts ratios between LLV group and suppression group before ART (both P>0.05). During the three-year follow-up, the cumulative number of viral failures in LLV group (7.3%(10/137)) was significantly higher than that in the suppression group (1.5%(2/137)) ( χ2=5.578, P=0.018). Virological failure occurred in eight patients (8.6%) in the LLV-1 subgroup, two patients (8.0%) in the LLV-2 subgroup, and no patients in the LLV-3 subgroup. There was no statistical significance in the incidence of virological failure among all the subgroups ( P>0.05). At one, two, three years follow-up, the CD4 + T lymphocyte counts increased in both LLV group and suppression group without statistical differences (all P>0.05), and the CD4 + /CD8 + T lymphocyte counts ratios in each LLV group were lower than that in the suppression group ( Z=-3.183, -2.094 and -2.312, respectively, all P<0.05). At one, two, three years follow-up, There were no significant differences in CD4 + /CD8 + T lymphocyte counts ratios among the LLV-1, LLV-2 and LLV-3 subgroups (all P>0.05). Conclusion:HIV/AIDS patients with LLV having received ART over one year are more likely to develop virological failure and delay the recovery of immune function, which requires early relevant interventions.

Objective:To investigate the long-term characteristic changes of virus, immune status, and liver fibrosis markers in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infected patients after receiving direct-antiviral agents (DAAs).Methods:HIV/HCV co-infected patients who visited the Guangzhou Eighth People’s Hospital, Guangzhou Medical University from May 2014 to December 2019 were selected as the research subjects. The changes of virological response rate, peripheral blood CD4 +T lymphocyte level and serological markers of liver fibrosis (APRI score and FIB-4 index) were observed during 144 weeks of follow-up course after the end of DAAs treatment. Kruskal-Wallis test was used for statistical approach. Results:A total of 103 cases were included in the study. There were 87 males (87.5%), with a median age of 44 years. Sustained virological response rate at 12 weeks (SVR12) after DAAs treatment was 97.6%, and the SVR during the entire follow-up period was at least 95.9%. Compared with baseline, CD4 +T lymphocyte count were significantly increased equally at 12 weeks ( Z = -2.283, P = 0.022), 24 weeks (Z = -3.538, P < 0.001), 48 weeks ( Z = -3.297, P = 0.001), 96 weeks ( Z = -3.562, P < 0.001), and 144 weeks ( Z = -2.842, P = 0.004). APRI score ( Z = -6.394, P < 0.001) and FIB-4 index ( Z = -2.528, P = 0.011) were significantly lower than baseline at week 4 of DAAs treatment, and thereafter remained at a low level, without further declination. Conclusion:HIV/HCV co-infected patients can maintain high SVR for a long time, acquire good immune reconstitution, and significantly improve liver fibrosis after DAAs treatment.

Objective:To investigate the predictive value of trigeminal nerve vascular compression grading evaluated by preoperative magnetic resonance imaging (MRI) in patients with trigeminal neuralgia (TN) after microvascular decompression (MVD).Methods:Two hundred and seventy patients with TN accepted MVD in our hospital from January 2015 to December 2017 were chosen in our study; their clinical and MRI data were retrospectively analyzed. By referring to Sindou's method and Jannetta standard, these patients were divided into patients with mild vascular compression ( n=71) and patients with severe vascular compression ( n=199) according to preoperative MRI data; these patients were divided into typical TN patients ( n=219) and atypical TN patients ( n=51) according to their symptomatic characteristics; the differences in prognoses after one year of follow-up were compared among patients from different categories. Results:The degree of intraoperative vascular compression was basically consistent with the preoperative imaging evaluation results, and the intraoperative vascular compression in 256 patients was consistent with preoperative imaging evaluation grading, with a coincidence rate of 94.8% (256/270). The difference in prognosis between patients with mild vascular compression and patients with severe vascular compression was statistically significant ( Z=-3.420, P=0.001), and the mean rank indicated that the prognosis of patients with severe vascular compression was better than that of patients with mild vascular compression (142.01 vs. 117.25). The prognosis difference between typical TN patients and atypical TN patients was statistically significant ( Z=-5.810, P=0.000), and the mean rank indicated that the prognosis of typical TN patients was better than that of atypical TN patients (144.45 vs. 97.08). Conclusions:Preoperative MR imaging evaluation is a reliable method to assess the degree of vascular compression. Patients with severe vascular compression and typical TN have high postoperative pain relief rate after MVD.

Objective Analyze the application status and existed problems of clinical biobank in China,propose possible application mechanisms for clinical biobank.Methods Through questionnaire survey and case analysis combined with relevant literature reports from home and abroad,conduct qualitative analysis to understand the application status and problems of clinical biobank.Results With the rapid development of biobank,its application rate was far from expected.The construction of clinical database lags behind in China will affect the application of samples.The lag of application mechanism will affect the opening and application of the biobank.Conclusions At the beginning of construction,the clinical biobank should take full account of what and how resources can be used,and establish tailored application mechanism.More attention should be paid to the possible benefit of biobank construction.