OBJECTIVE: This study aimed to investigate the prevalence of HIV pretreatment drug resistance (PDR) and the transmission clusters associated with PDR-related mutations in newly diagnosed, treatment-naive patients between 2020 and 2023 in Dehong prefecture, Yunnan province, China. METHODS: Demographic information and plasma samples were collected from study participants. PDR was assessed using the Stanford HIV Drug Resistance Database. The Tamura-Nei 93 model within HIV-TRACE was employed to compute pairwise matches with a genetic distance of 0.015 substitutions per site. RESULTS: Among 948 treatment-naive individuals with eligible sequences, 36 HIV subtypes were identified, with unique recombinant forms (URFs) being the most prevalent (18.8%, 178/948). The overall prevalence of PDR was 12.4% (118/948), and resistance to non-nucleotide reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) was 10.7%, 1.3%, and 1.6%, respectively. A total of 91 clusters were identified, among which eight showed evidence of PDR strain transmission. The largest PDR-associated cluster consisted of six CRF01_AE drug-resistant strains carrying K103N and V179T mutations; five of these individuals had initial CD4+ cell counts < 200 cells/μL. CONCLUSION The distribution of HIV subtypes in Dehong is diverse and complex. PDR was moderately prevalent (12.4%) between 2020 and 2023. Evidence of transmission of CRF01_AE strains carrying K103N and V179T mutations was found. Routine surveillance of PDR and the strengthening of control measures are essential to limit the spread of drug-resistance HIV strains.
Humans ; HIV Infections/virology* ; China/epidemiology* ; Drug Resistance, Viral ; Male ; Adult ; Female ; Middle Aged ; HIV-1/genetics* ; Anti-HIV Agents/therapeutic use* ; Myanmar/epidemiology* ; Young Adult ; Prevalence ; Adolescent ; Mutation

Objective To investigate the status of population dynamics and distribution changes of Aedes aegypti in Guangdong Province.Methods Continuous monitoring was conducted from May 2018 to July 2024 in Wushi Town and Qishui Town,Leizhou City,Zhanjiang City,Guangdong Province.Additionally,a survey of the distribution of Ae.aegypti along the Leizhou Peninsula coast was carried out.Results The density of Ae.aegypti in Zhanjiang showed a gradual decline from 2018 to 2024.The last detection of adult Ae.aegypti in Wushi Town was in September 2021,and the last larva was found in October 2023.No Ae.aegypti was detected in Qishui Town during surveys from 2021 to 2024.A survey of 18 coastal villages in the Leizhou Peninsula revealed no detections of Ae.aegypti.Conclusions This study provides a basis for understanding the distribution and population density fluctuations of Ae.aegypti,assessing its invasion risk,and scientifically conducting relevant prevention and control efforts.

Background: and Purpose Intravenous tenecteplase (TNK) efficacy has not been well demonstrated in acute ischemic stroke (AIS) beyond 4.5 hours after onset. This study aimed to determine the effect of intravenous TNK for AIS within 4.5 to 24 hours of onset. Methods: In this pilot trial, eligible AIS patients with diffusion-weighted imaging (DWI)-fluid attenuated inversion recovery (FLAIR) mismatch were randomly allocated to intravenous TNK (0.25 mg/kg) or standard care within 4.5–24 hours of onset. The primary endpoint was excellent functional outcome at 90 days (modified Rankin Scale [mRS] score of 0–1). The primary safety endpoint was symptomatic intracranial hemorrhage (sICH). Results: Of the randomly assigned 80 patients, the primary endpoint occurred in 52.5% (21/40) of TNK group and 50.0% (20/40) of control group, with no significant difference (unadjusted odds ratio, 1.11; 95% confidence interval 0.46–2.66; P=0.82). More early neurological improvement occurred in TNK group than in control group (11 vs. 3, P=0.03), but no significant differences were found in other secondary endpoints, such as mRS 0–2 at 90 days, shift analysis of mRS at 90 days, and change in National Institutes of Health Stroke Scale score at 24 hours and 7 days. There were no cases of sICH in this trial; however, asymptomatic intracranial hemorrhage occurred in 3 of the 40 patients (7.5%) in the TNK group. Conclusion This phase 2, randomized, multicenter study suggests that intravenous TNK within 4.5–24 hours of onset may be safe and feasible in AIS patients with a DWI-FLAIR mismatch.

Objective : To study the expression and clinical significance of Wnt signal secretory protein DKK1 in cervical cancer. Methods : Reverse transcription polymerase chain reaction (RT⁃PCR) was used to detect the expression of DKK1 mRNA in 30 pairs of cervical cancer tissues and adjacent normal tissues. The expression of DKK1 protein was detected by immunohistochemistry in 60 cases of cervical cancer and 30 cases of normal cervical tissue , and the relationship between the expression and clinicopathological characteristics of cervical cancer was analyzed. Results : The expression of DKK1 in cervical cancer tissues was lower than that in adjacent tissues and normal cervical tissues (P < 0. 05) . The expression of DKK1 was closely related to clinicopathological stage , tissue differentiation , lymph node metastasis and depth of invasion (P < 0. 05) . Conclusion The expression of DKK1 is low in cervical cancer and plays an important role in the occurrence and development of cervical cancer.

BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER NCT02063100 on ClinicalTrials.gov.

FGFC1 (Fungi fibrinolytic compound1) is a bisindole compound with good biological activity, which was first derived from the Stachybotrys longispora FG216. However, the anti-tumor effects of FGFC1 have not been reported. This study investigated the effect and mechanism of FGFC1 on the proliferation, apoptosis, migration and invasion of non-small cell lung cancer (NSCLC) cells.Firstly, PC9, H1975, HCT116, HeLa and 293T cells were treated with different concentrations of FGFC1, and the cell counting kit-8 assay was used to determine relative cell viability; flow cytometry was used to evaluate apoptosis; real-time PCR and Western blotting analysis were performed to measure the expression of apoptosis-related genes in PC9 cells; wound healing and Transwell invasion assays were used to measure the ability of migration and invasion; Western blotting was performed to measure the expression of kinase proteins involved in the PI3K/Akt/mTOR signaling pathway, exploring the influence of FGFC1 on this signaling pathway. We found that FGFC1 selectively inhibited the proliferation of PC9 cells. It also up-regulated the expression of apoptosis-promoting protein cleaved-caspase-3 and cleaved-PARP, and induced apoptosis in a dose-dependent manner (P < 0. 05). FGFC1 also significantly inhibited the migratory and invasive capacity of PC9 cells in a dose-dependent manner (P < 0. 05). Further studies confirmed that FGFC1 could inhibit the activation of the PI3K/Akt/mTOR signaling pathway with the down-regulation of the protein expression levels of p-PI3K, p-Akt and p-mTOR. Thus, we conclude that FGFC1 inhibited the proliferation of PC9 and H1975 cells, induced the apoptosis and inhibited the migration and invasion of PC9 cells, which may take place through down-regulating the PI3K/Akt/mTOR signaling pathway. These findings suggest that FGFC1 might be a new therapeutic target in NSCLC treatment in the future.

Objective:To investigate the clinical characteristics and influencing factors of mortality in patients with intra-abdominal candidiasis (IAC).Methods:The retrospective case-control study was conducted. The clinicopathological data of 203 IAC patients who were admitted to 7 medical centers from June 2018 to June 2020 were collected, including 54 cases in Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, 31 cases in Fujian Medical University Union Hospital, 25 cases in Beijing Hospital, 25 cases in the First Affiliated Hospital of Xi'an Jiaotong University, 24 cases in China-Japan Friendship Hospital, 22 cases in General Hospital of Eastern Theater Command of Chinese PLA and 22 cases in Chongqing University Cancer Hospital. There were 130 males and 73 females, aged (64±15)years. Observation indicators: (1) candida infection and treatment of IAC patients; (2) analysis of influencing factors for mortality of IAC patients. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Univariate and multivariate analyses were performed by Logistic regression model. Results:(1) Candida infection and treatment of IAC patients: 134 cases of candida albicans were cultured in the initial abdominal drainage fluid or intraoperative abdominal specimens of 203 patients, and 49 cases were treated with fluconazole. Of 69 cases infected with non candida albicans, 13 cases were treated with fluconazole. The resistance rate of candida albicans to fluconazole was 5.91%(12/203). Of 203 patients, there were 68 cases with infections shock, 53 cases with renal failure, 84 cases with respiratory failure and 63 cases with multiple organ failure, respectively. There were 148 of 203 patients admitted to intensive care unit for 9 days(range, 3-20 days), and the total hospital stay was 28 days(range, 17-50 days). Of 203 patients, 86 cases were cured and discharged, 50 cases were improved and transferred to local hospitals, 32 cases gave up treatment and discharged automatically, 19 cases died, 16 cases had no follow-up data. The mortality was 25.12%(51/203). (2) Analysis of influencing factors for mortality of IAC patients. Results of univariate analysis showed that acute physiology and chronic health evaluation score, sequential organ failure assessment score, the Cr, bilirubin, albumin, procalcitonin, and PLT on the first day of candida positive culture, of the lowest value in a week and the highest in a week, heart disease, diabetes, infections shock, renal failure, respiratory failure, multiple organ failure, anti-fungal therapy were the related factors for mortality of IAC patients ( t=-2.322, Z=-2.550, -2.262, -4.361, t=2.085, Z=-3.734, -5.226, -2.394, -5.542, t=3.462, Z=-4.957, -5.632, 3.670, -5.805, t=3.966, Z=-3.734, -5.727, χ2=4.071, 4.638, 27.353, 18.818, 13.199, 26.251, 13.388, P<0.05). Multivariate analysis showed that the bilirubin, procalcitonin on the first day of candida positive culture and infections shock were independent risk factors for mortality of IAC patients ( odds ratio=1.021, 1.022, 6.864, 95% confidence interval as 1.010-1.033, 1.001-1.044, 1.858-25.353, P<0.05). Conclusions:The common fungus of IAC was candida albicans, and fluconazole can be used as the initial empirical treatment. The prognosis of patients with abdominal candidiasis is poor. Bilirubin, procalcitonin on the first day of candida positive culture and infections shock are indepen-dent risk factors for mortality of IAC patients.

Objectives:To evaluate the impact of diabetes mellitus on prognosis of coronary artery disease patients after implantation of the novel biodegradable polymer drug eluting stents. Methods:PANDA Ⅲ was a perspective, multi-center, "all-comer", randomized controlled trial. Between Dec. 2013 and Sep. 2014, 2 348 patients from 46 centers were enrolled. All the patients underwent percutaneous coronary intervention, among them 1 174 patients implanted with BuMA stent and 1 174 patients implanted with Excel stent. Mean age was 61.2 ±10.6, 1 658 patients (70.6%) were male, 570 (24.2%) patients presented with diabetes mellitus (DM) and 1 778 (75.7%) without DM. Patients were divided into DM and non-DM groups. Primary endpoint was target lesion failure (TLF), including cardiac death, target vessel myocardial infarction and ischemia driven target lesion revascularization. Secondary endpoints included stent thrombosis and major adverse cardiac events (MACE), defined as a composite of death, myocardial infarction and any revascularization. Results:A total of 558 (97.9%) and 1 704 (95.8%) patients completed 2-year follow-up in DM and non-DM groups. Incidence of TLF in the DM and non-DM group was 8.24% vs. 6.81%, P=0.25, and cardiac death rate was significantly higher in the DM group compared with non-DM group:2.87% vs. 1.12%, P=0.004. Incidence of MACE was similar between two group:13.98% vs. 11.38, P=0.10. Myocardial infarction and any revascularization events were numericallyhigher in the DM group compared with non-DM group, but without statistical significance:5.73% vs. 5.11%, P=0.56; 6.45% vs. 5.46%, P=0.38, respectively. Incidence of all-cause death was significantly higher in the DM group compared with non-DM group:4.30% vs. 2.46%, P=0.03. The results were similar after propensity match analysis. Multivariable analysis showed that DM and baseline SYNTAX score were independent factors for 2-year cardiac death. Conclusions:Two-year incidence of TLF is similar in coronary artery disease patients with or without DM post implantation of biodegradable polymer drug eluting stent or Excel stent, however, the rate of death especially cardiac death is significantly higher in the DM group than in the non-DM group.

Objectives: To investigate the characteristics of coronary lesions and evaluate the prognosis post-percutaneous coronary intervention(PCI)in smokers with coronary heart disease. Methods: The data were derived from PANDA III, which was a perspective, multi-center, "all-comer", randomized controlled trial. Between Dec. 2013 and Aug. 2014, 2 348 patients from 46 centers were enrolled. Mean age was (61.2 ±10.6) years old, 1 658 patients (70.6%) were male. All the patients underwent PCI and biodegradable polymer drug eluting stents were implanted as indicated. Patients were divided into non-smoking group, quitter group and smoking-group based on the basis of smoking status at baseline. Primary endpoint was major adverse cardiac events (MACE), including all-cause mortality, myocardial infarction and repeated revascularization. Secondary endpoint were stent thrombosis and target lesion failure (TLF), including cardiac death, target vessel myocardial infarction and ischemia driven target lesion revascularization. Results: Smokers and quitters were more often males. Compared with non-smoking group and quitter group, patients in smoking group were significantly younger (P<0.0001), proportion of hypertension (P=0.0002), diabetes mellitus (P=0.0052) and previous PCI history (P<0.0001) was significantly lower. The incidence of acute myocardial infarction in the smoking group was as high as 41.3% (363/879), which was significantly higher than that of the quitter group and non-smoking group (P<0.0001). A total of 1 130 (96.7%), 286 (95.3%) and 846 (96.2%) patients in the non-smoking group, quitter group and smoking-group completed the 2-year follow-up, respectively. The results of 2-years follow-up showed that MACE rate of non-smoking group, quitter group and smoking-group was 11.23%, 13.64% and 12.21%(P=0.54), respectively. Multivariable cox regression analysis indicated that smoking status was not an independent predictor for all-cause mortality and TLF.

OBJECTIVE:To provide reference and suggestion for relieving the disease burden of hepatitis C (HC) in China,improving medical compensation mechanism of HC treatment and the accessibility of HC drags.METHODS:By reviewing literatures and other relevant information,the epidemic situation of HC,the situation of disease screening and diagnosis,treatment progress,the economic burden of disease,medical insurance compensation in China and international experience on improving the accessibility of HC drugs were all analyzed.RESULTS:The anti-HCV prevalence rate of 1 to 59-year-old population was 0.43％ in China,and the genotype was mainly genotype 1b(58％).Nearly 38.9％ of the patients were not treated.For patients with genotype 1b,the sustained virologic response rate of traditional PEG-interferon combined with ribavirin regimen was 62％,and the effect of new direct-acting antivimls (DAA) regimen was improved significantly;patients receiving new regimen could gain 1.29 QALYs and 0.85 life years.The costs of a single course for traditional and new regimens were 54 960 yuan and 57 810 yuan,respectively.New regimen could save 378 yuan for the cost of disease management for each patient due to evasion of end-stage liver disease.After medical insurance compensation,the cost of self payment had fallen sharply for workers and residents receiving traditional regimen,while new regimen was approved in China in 2017 and had not been covered by medical insurance yet.CONCLUSIONS:New regimen has a cost-effectiveness advantage over traditional regimen.The state should pay more attention to HC patients and take measures to reduce the economic burden of them.By improving the basic medical insurance and special medical assistance fund for HC treatment,the accessibility of the drugs in new HC treatment regimen can be improved.