Abstract: Objective　To investigate the distribution characteristics of HCV genotypes and subtypes in patients with HIV (human immunodeficiency virus, HIV)/HCV co-infection in Kunming based on the nucleocapsid protein gene sequence of HCV (hepatitis C virus). Methods　Serum was collected from HIV/HCV co-infected patients with household registration in 14 county-level cities, districts and counties under the jurisdiction of Kunming, who admitted to Yunnan Provincial Infectious Disease Hospital from March to August 2019. The viral RNA was extracted from the serum, reverse transcribed to synthesize cDNA, and the HCV nucleocapsid protein gene-specific primers were used for nested PCR amplification. The positive amplification products were sequenced, bioinformatics software such as DNAstar and MEGAX were used for sequence analysis. Results　A total of 64 samples from co-infected patients with clinical diagnosis of suspected HIV/HCV were collected and amplified by HCV nucleocapsid protein gene-specific primers, of which 17 samples were amplified positively. The results of sequence analysis showed that the sequences of 9 cases were located in the same evolutionary branch as the HCV 3b subtype sequence, and the nucleotide homology was 93.3%-95.2%; the sequences of 5 cases were located in the same evolutionary branch as the HCV 1b subtype sequence, and the nucleotide homology was 96.8%-97.6%; the sequence of one case and the subtype sequence of HCV 3a gene were located in the same evolutionary branch, and the nucleotide homology was 95.2%; the sequence of one case and HCV 6n gene subtype sequence were located in the same evolutionary branch, and the nucleotide homology was 97.9%; One case was located in the same evolutionary branch as the HCV 6u gene subtype sequence, and the nucleotide homology was 98.4%. Conclusions　HCV 1b, HCV 3a, HCV 3b, HCV 6n and HCV 6u genotypes or subtypes of HCV are prevalent in Kunming, and HCV 3b is the most prevalent genotype.

Male infertility caused by idiopathic oligoasthenospermia (OAT) is known as idiopathic male infertility. Glutathione S-transferase (GST) and fluoride may play important roles in idiopathic male infertility, but their effects are still unknown. Our study examined the relationship between GST polymorphisms and fluoride-induced toxicity in idiopathic male infertility and determined the underlying mechanism. Sperm, blood, and urine samples were collected from 560 males. Fluoride levels were measured by a highly selective electrode method, and GST genotypes were identified using polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP). Semen parameters, DNA fragmentation index (DFI), mitochondrial membrane potential (MMP), and oxidative stress (OS) biomarkers were statistically assessed at the P < 0.05 level. Compared with healthy fertile group, semen parameters, fluoride levels, OS biomarkers, sex hormone levels, and MMP and DFI levels were lower in the idiopathic male infertility group. For glutathione S-transferase M1 (GSTM1[-]) and glutathione S-transferase T1 (GSTT1[-]) or glutathione S-transferase P1 (GSTP1) mutant genotypes, levels of semen fluoride, OS, MMP, and DFI were considerably higher, and the mean levels of sperm parameters and testosterone were statistically significant in GSTM1(+), GSTT1(+), and GSTP1 wild-type genotypes. Both semen and blood fluoride levels were associated with oxidative stress in idiopathic male infertility patients. Elevated fluoride in semen with the genotypes listed above was linked to reproductive quality in idiopathic male infertility patients. In conclusion, GST polymorphisms and fluorine may have an indicative relationship between reproductive quality and sex hormone levels, and OS participates in the development of idiopathic male infertility.
Humans ; Male ; Fluorides/adverse effects* ; Semen ; Polymorphism, Genetic ; Glutathione Transferase/genetics* ; Glutathione S-Transferase pi/genetics* ; Infertility, Male/genetics* ; Genotype ; Biomarkers ; Genetic Predisposition to Disease ; Case-Control Studies

OBJECTIVE: To investigate the effect of p-coumaric acid on apoptosis of multiple myeloma cells and its related mechanism. METHODS: Multiple myeloma cell line MM.1s cells were selected and treated with different concentrations of p-coumaric acid (0, 0.4, 0.8, 1.6, 3.2 mmol/L), and the inhibition rate and half inhibition concentration (IC₅₀) were detected by CCK-8 method. Then MM.1s cells were treated with 1/2 IC₅₀, IC₅₀, 2 IC₅₀ and transfected with ov-Nrf-2 and ov-Nrf-2+IC₅₀. The apoptosis, ROS fluorescence intensity and mitochondrial membrane potential of MM.1s cells were detected by flow cytometry, and the relative expressions of cellular Nrf-2 and HO-1 protein were detected by Western blot. RESULTS: P-coumaric acid inhibited the proliferation of MM.1s cells in a dose-dependent manner(r =0.997) with an IC₅₀ value of 2.754 mmol/L. Compared with the control group, apoptosis and ROS fluorescence intensity of MM.1s cells were significantly increased in the 1/2 IC₅₀ group, IC₅₀ group, 2 IC₅₀ group and ov-Nrf-2+IC₅₀ group (P <0.01), the expressions of Nrf-2, HO-1 protein in the IC₅₀ group and 2 IC₅₀ group were significantly decreased (P <0.05). Compared with the IC₅₀ group, the cells apoptosis and ROS fluorescence intensity were significantly decreased (P <0.01), and the expressions of Nrf-2 and HO-1 protein were significantly increased in the ov-Nrf-2+IC₅₀ group (P <0.01). CONCLUSION P-coumaric acid can inhibit the proliferation of MM.1s cells and may target the Nrf-2/HO-1 signaling pathway to affect oxidative stress in MM cells thereby inducing their apoptosis.
Humans ; Reactive Oxygen Species/pharmacology* ; Cell Line, Tumor ; Multiple Myeloma ; Oxidative Stress ; Apoptosis

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Objective: To investigate the quality of life and associated factors in patients with coronary heart disease (CHD) in China. Methods: A cross-sectional study of 25 provinces and cities in China was performed from June to September 2020. A questionnaire was used to collect the socio-demographic and clinical information of patients with CHD, while the European Five-dimensional Quality of Life Scale (EQ-5D) was used to assess the quality of life. Multiple linear regression model was performed to analyze the associated factors. Results: The median age of the 1 075 responders was 60 (52, 67) years, and 797 (74.1%) were men. The EQ-5D and EQ-VAS indices were 0.7 (0.5, 0.8) and 60.0 (40.0, 80.0). Among the five dimensions in the quality of life scale, the frequency of anxiety/depression was the highest (59.8%), while problems in self-care was the lowest (35.8%). In the multiple linear regression model, female, increasing age, obesity, comorbidity(ies), anxiety/depression, social media channels, and receiving the CABG therapy were associated with the lower EQ-5D index (all P<0.05). In addition, increasing age, obesity, comorbidity (ies), depression, anxiety and depression, social media channels, and receiving the CABG therapy were associated with lower EQ-VAS index (all P<0.05). Conclusion: Over half of the patients with CHD in China have a low quality of life, which is related to gender, age, obesity, treatment pathway, the presence or absence of comorbidity (ies), and psychological state. In addition to managing the adverse effects of traditional socio-demographic factors on the quality of life, clinical practices should pay attention to the psychological state of patients. Moreover, establishing a WeChat group for doctor-patient communication could improve the quality of life of CHD patients.
Male ; Humans ; Female ; Quality of Life/psychology* ; Self Report ; Cross-Sectional Studies ; Coronary Disease ; Surveys and Questionnaires ; Obesity

Humans ; Nutrition Surveys ; Diabetes Mellitus, Type 2/chemically induced* ; Environmental Exposure/analysis* ; Environmental Monitoring ; Phthalic Acids/toxicity* ; Environmental Pollutants/toxicity*

Objective To analyze the epidemiological characteristics of hepatitis A in Guangxi from 2010 to 2020, and to provide a scientific basis for formulating effective prevention and control strategies. Methods Descriptive epidemiological method was used to analyze the incidence data of hepatitis A in Guangxi from 2010 to 2020. Results From 2010 to 2020, a total of 8,742 cases of hepatitis A were reported in Guangxi, with an average annual incidence rate of 1.66 /100,000. There were 5 298 male cases (60.60%), and 3,444 female cases (39.40%). The incidence rate decreased from 2.73/100 000 in 2010 to 1.38/100 000 in 2020. The onset seasonality was strong in 2010, but there was no obvious seasonality in other years. A total of 5 891 cases (67.39%) were aged from 25 to 64 years. Farmers accounted for 59.79% of the cases. A total of 7 hepatitis A outbreaks were reported during 2010-2020, including 273 cases，accounting for 3.12% of the total cases．The incidence rates of hepatitis A in Hezhou (3.97/100 000), Wuzhou (2.98/100 000), Hechi (2.44/100 000), Guigang (2.00/100 000) and Beihai (1.79/100 000) were relatively higher than other places. Conclusion The number of reported hepatitis A cases in Guangxi has been declining year by year, and the prevention and control measures of hepatitis A vaccine prevention are effective. The surveillance of hepatitis A should be strengthened, and prevention and control strategies should be formulated for high-risk areas and key populations.

Objective: To investigate the safety, efficacy, locally control and survival results of transoral Da Vinci robotic surgery for salvage treatment of locally recurrent nasopharyngeal carcinoma. Methods: This retrospective study included 33 patients with locally recurrent nasopharyngeal carcinoma (stage rT1-2, partial rT3) underwent transoral Da Vinci robotic surgery between October 2017 and January 2020. There were 20 males and 11 females, with an average age of (47.9±10.5) years. The lesions were localized in nasopharyngeal cavity in 14 cases, with extending to parapharyngeal space in 6 cases and the floor of sphenoid sinus in 13 cases. Transnasal endoscopy was used to assist surgery if necessary. SPSS 25.0 statistical software was used for statistical analysis. Results: Transoral robotic nasopharyngectomy was successfully performed in all cases without conversion to open surgery, of which 13 cases were combined with transnasal endoscopic surgery. The average operation time was (126.2±30.0) min, ranging from 90 to 180 min. The postoperative pathological margin was R0 (31 cases) and R1 (2 cases), with no tumor residue. Complications of surgery mainly included symptoms of headache, nasal dryness and velopharyngeal insufficiency without nasopharyngeal hemorrhage. Follow-up time was from 3 to 54 months. One case had tumor recurrence 11 months after operation, 1 case had ipsilateral cervical lymph node metastasis 27 months after operation, 2 cases had distant metastasis and 1 case died of nasopharyngeal hemorrhage 3 months after operation. The 1-year, 2-year and 3-year overall survival rates were 97.0%, 96.0% and 92.9%, respectively and the local recurrence free rates were 97.0%, 95.7% and 91.7%, respectively. Conclusion: Transoral robotic nasopharyngectomy is safe and feasible for local recurrent nasopharyngeal carcinoma in selected patients, with higher local control rate and quality of life.
Adult ; Female ; Humans ; Male ; Middle Aged ; Nasopharyngeal Carcinoma/surgery* ; Nasopharyngeal Neoplasms/pathology* ; Neoplasm Recurrence, Local/surgery* ; Quality of Life ; Retrospective Studies ; Robotic Surgical Procedures

OBJECTIVE: To establish an immune gene prognostic model of acute myeloid leukemia (AML) and explore its correlation with immune cells in bone marrow microenvironment. METHODS: Gene expression profile and clinical data of TCGA-AML were downloaded from TCGA database. Immune genes were screened by LASSO analysis to construct prognosis prediction model, and prediction accuracy of the model was quantified by receiver operating characteristic curve and area under the curve. Survival analysis was performed by Log-rank test. Enriched pathways in the different immune risk subtypes were evaluated from train cohort. The relationship between immune prediction model and bone marrow immune microenvironment was verified by flow cytometry in the real world. RESULTS: Patients with low-risk score of immune gene model had better prognosis than those with high-risk score. Multivariate analysis showed that the immune gene risk model was an independent prognostic factor. The risk ratio for AML patients in the training concentration was HR=24.594 (95%CI: 6.180-97.878), and the AUC for 1-year, 3-year, and 5-year overall survival rate was 0.811, 0.815, and 0.837, respectively. In addition, enrichment analysis of differential gene sets indicated activation of immune-related pathways such as cytokines and chemokines as well as autoimmune disease-related pathways. At the same time, real world data showed that patients with high immune risk had lower numbers of CD8⁺T cells and B lymphocytes compared with low immune risk patients. CONCLUSION We constructed a stable prognostic model for AML, which can not only predict the prognosis of AML, but also reveal the dysregulation of immune microenvironment.
Humans ; Leukemia, Myeloid, Acute/genetics* ; Prognosis ; ROC Curve ; Risk Factors ; Transcriptome ; Tumor Microenvironment/genetics*

Objective: To evaluate multidrug resistant loop-mediated isothermal amplification (MDR-LAMP) assay for the early diagnosis of multidrug-resistant tuberculosis and to compare the mutation patterns associated with the Methods: MDR-LAMP assay was evaluated using 100 Results: The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MDR-LAMP were 85.5%, 93.6%, 96.7%, and 74.4% for the detection of resistance to isoniazid and rifampicin, respectively, and 80.5%, 92.3%, 98.6%, and 41.4% for the detection of Conclusion MDR-LAMP is a rapid and accessible assay for the laboratory identification of rifampicin and isoniazid resistance of
Antitubercular Agents ; Bacterial Proteins/genetics* ; Catalase/genetics* ; DNA, Bacterial/analysis* ; DNA-Directed RNA Polymerases/genetics* ; Drug Resistance, Multiple, Bacterial/genetics* ; Isoniazid ; Molecular Diagnostic Techniques/methods* ; Mutation ; Mycobacterium tuberculosis/isolation & purification* ; Nucleic Acid Amplification Techniques/methods* ; Oxidoreductases/genetics* ; Phenotype ; Rifampin ; Whole Genome Sequencing