ObjectiveTo investigate the therapeutic effects of direct-acting antiviral agents (DAAs) combined regimens for hepatitis C virus (HCV) patients in Dehong Prefecture, Yunnan Province from 2022 to 2024, to analyze the characteristics of treatment failure patients, so as to provide a basis for discovering more effective treatment regimens in the future. MethodsData on HCV prevention and treatment in Dehong Prefecture was extracted from the China Disease Control and Prevention Information System. A total of 617 patients with HCV antiviral therapy were included, and the differences in variable characteristics among patients with different genotypes were analyzed using comparative statistical tests, including basic socio-demographic characteristics, biochemical testing indicators, and information on previous treatment and current treatment. In addition, the cure rate of HCV patients with diverse characteristics was compared, and the potential causes of treatment failure were explored simultaneously. ResultsThe cure rate of HCV was 96.8%, and statistically significant differences were observed in aspartate transaminase (AST) and alanine transaminase (ALT) levels, previous antiviral therapy history and initial treatment regimens among patients with different HCV genotypes (all P<0.05). Among the multi-type combination regimens, the cure rate of sofosbuvir (SOF)-containing regimens was 97.00%, that of velpatasvir (VEL)-containing regimens was 95.45%, and the cure rate of other treatment regimens, including the regimens with ribavirin (RIB) intervention, was 93.10%. Among the patients with treatment failure, 45.00% had genotype 3, 40.00% had abnormal abdominal ultrasound results, and all presented with elevated baseline AST test levels. ConclusionThe clinical treatment of HCV patients should consider the differences in genotype and biochemical test results. DAAs combined regimens for HCV have achieved a high cure rate in Dehong Prefecture and are applicable to HCV patients with diverse clinical characteristics, providing research evidence for wider application.

Objective:To analyze the epidemic characteristics and trends of newly reported HIV-infected people among Chinese and Burmese in Dehong Dai and Jingpo Autonomous Prefecture (Dehong Prefecture) of Yunnan Province, China, from 2000 to 2023, and provide evidence for formμlating AIDS prevention and control measures for the Burmese living in Dehong.Methods:The data were obtained from the Chinese Disease Control and Prevention Information System. The distribution of HIV-infected people with different population characteristics was analyzed, and the Joinpoint regression model was used to analyze the temporal trend of crude detection rate in different genders, ethnicities, and ages.Results:From 2000 to 2023, 24 989 newly HIV infections were reported in Dehong Prefecture, of which 14 594 (58.4%) were Chinese and 10 395 (41.6%) were Burmese. Compared with Chinese, Burmese women (32.9%, 3 416/10 395), those aged 20-29 (40.9%, 4 248/10 395), and Jingpo people (26.7%, 2 773/10 395) accounted for a higher proportion. The new diagnosis rate of Chinese nationals increased from 1.0/10 000 in 2000 to 15.4/10 000 in 2004, and then showed a downward trend, falling to 1.2/10 000 in 2023. Among them, compared with other age groups, Dai and other ethnic groups and women, the new diagnosis rate among 20-49 age group, Jingpo and men were relatively higher, at 1.7/10 000, 2.3/10 000 and 1.3/10 000 respectively. Regarding the method of detection, the Chinese HIV-infected people were mainly detected by key population testing (35.7%), while the Burmese HIV-infected people by key population testing (28.9%) and physical examination for entry-exit personnel (25.3%). The transmission routes of both nationalities were mainly heterosexual transmission, but compared with Chinese HIV-infected persons, the proportion of Burmese infected persons through non-marital non-commercial transmission was relatively higher (66.4% vs. 60.6%). The proportion of Chinese nationals with a first CD4 +T lymphocyte (CD4) counts of <200 cells/μl (28.9%) was higher than that of Burmese nationals (19.8%). Conclusions:The rising trend of HIV infection among Chinese and Burmese people in Dehong Prefecture from 2000 to 2023 slowed down. The new diagnosis rate was higher in the 20-49 age group, Jingpo and men. Compared with Burmese HIV-infected people, the proportion of Chinese HIV-infected people with first CD4 counts <200 cells/μl was relatively higher. Comprehensive interventions should be further carried out for Myanmar nationals, and efforts should be made to expand testing for Chinese nationals.

OBJECTIVE: To screen for small molecular compounds with selective inhibitory activity against cutaneous melanoma cells with BAP1 deletion. METHODS: Cutaneous melanoma cells expressing wild-type BAP1 were selected to construct a BAP1 knockout cell model using CRISPR-Cas9 system, and small molecules with selective inhibitory activity against BAP1 knockout cells were screened from a compound library using MTT assay. Rescue experiment was carried out to determine whether the sensitivity of BAP1 knockout cells to the candidate compounds was directly related to BAP1 deletion. The effects of the candidate compounds on cell cycle and apoptosis were detected with flow cytometry, and the protein expressions in the cells were analyzed with Western blotting. RESULTS: The p53 activator RITA from the compound library was shown to selectively inhibit the viability of BAP1 knockout cells. Overexpression of wild-type BAP1 reversed the sensitivity of BAP1 knockout cells to RITA, while overexpression of the mutant BAP1 (C91S) with inactivated ubiquitinase did not produce any rescue effect. Compared with the control cells expressing wild-type BAP1, BAP1 knockout cells were more sensitive to RITA-induced cell cycle arrest and apoptosis (P < 0.0001) and showed an increased expression of p53 protein, which was further increased by RITA treatment (P < 0.0001). CONCLUSION Loss of BAP1 results in the sensitivity of cutaneous melanoma cells to p53 activator RITA. In melanoma cells, the activity of ubiquitinase in BAP1 is directly related to their sensitivity to RITA. An increased expression of p53 protein induced by BAP1 knockout is probably a key reason for RITA sensitivity of melanoma cells, suggesting the potential of RITA as a targeted therapeutic agent for cutaneous melanoma carrying BAP1-inactivating mutations.
Humans ; Melanoma ; Skin Neoplasms ; Tumor Suppressor Protein p53 ; Apoptosis ; Cell Division ; Tumor Suppressor Proteins/genetics* ; Ubiquitin Thiolesterase/genetics*

ObjectiveTo investigate the factors that influence the first CD4+T lymphocyte counts in newly reported HIV-infected cases aged 50 and above in Dehong Prefecture of Yunnan Province during 2016 to 2021， and to understand the patient immune status and disease progression so as to provide scientific basis for HIV prevention and control strategies in the future. MethodsData was collected from the national HIV/AIDS information system. Multivariate logistic regression was used for the analysis of factors affecting the first CD4+T lymphocyte counts. ResultsA total of 642 cases of HIV infection were newly reported， among them， 571 cases had CD4+T lymphocyte counts and 200 cases （35.03%） had CD4+T lymphocyte counts <200 cells·μL^-1. Patients who were in the 50-59 age group， male， divorced or widowed， and less educated were more likely to have CD4+T lymphocyte counts <200 cells·μL^-1. Compared with active testing consultants， forced reeducation through labor or drug rehabilitation cases were less likely to have CD4+T lymphocyte counts <200 cells·μL^-1. ConclusionThere is no obvious upward trend in newly reported HIV infected persons aged 50 years and above in Dehong Prefecture during 2016 to 2021. However， the situation of CD4+T lymphocyte counts <200 cells·μL^-1 is still serious. Attention should be paid to the key groups： male， Chinese nationality， farmers， Han nationality， married or divorced， junior high school education or below， and heterosexual transmission. It is necessary to strengthen the intervention in people aged 50 and above and improve the detection efficiency.

ObjectiveThis study aimed to investigate the HIV genotypic subtypes and molecular transmission clusters among men who have sex with men （MSM） with newly reported HIV infections in Dehong Dai and Jingpo Autonomous Prefecture （Dehong Prefecture）， Yunnan Province， China， between 2010 and 2019. The study aimed to identify potential high-risk transmitters and provide reference data for screening， management， and intervention of infection sources. MethodsPlasma samples from newly reported HIV-positive MSM individuals in Dehong Prefecture between 2010 and 2019 were collected. The viral pol gene fragments were amplified， sequenced， and genotyped. Genetic distances （GD） between pairwise sequences were analyzed and calculated. MEGA 7.0 and Gephi were used for phylogenetic and molecular transmission network analysis. ResultsA total of 159 newly reported HIV infections among MSM were included in the study， with successful genotyping of 100 cases. Nine HIV-1 subtypes were identified， with the most prevalent being CRF01_AE subtype （52%）， followed by CRF07_BC subtype （31%）， CRF55_01B subtype （10%）， and others （7%）. Cluster analysis revealed a total network access rate of 67%， forming three transmission clusters. CRF01_AE subtype formed two transmission clusters with 38 and 3 infected individuals， while CRF07_BC subtypes formed one transmission cluster with 26 infected individuals. The transmission network within the CRF01_AE clusters exhibited a more complex relationship. Significant differences in educational level were observed between the two main transmission clusters. ConclusionThe predominant HIV subtypes among newly reported MSM cases in Dehong Prefecture between 2010 and 2019 were CRF01_AE and CRF07_BC. Significant cultural differences are observed between the main transmission clusters. Continued monitoring of genotypic subtypes and targeted interventions within transmission clusters are warranted.

Objective:To investigate the distributions of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) genotypes among newly reported HIV/HCV co-infected Burmese patients in Dehong Dai and Jingpo Autonomous Prefecture, Yunnan Province from 2016 to 2019.Methods:A total of 1 289 newly reported HIV/HCV co-infected Burmese patients in Dehong Dai and Jingpo Autonomous Prefecture were collected through the National Acquired Immunodeficiency Syndrome Comprehensive Prevention and Control Data Information System From January 2016 to December 2019. Among them, 996 subjects with a plasma volume of ≥200 μL were selected to perform HIV and HCV genotyping. The HIV pol gene, the HCV core protein-binding envelope protein ( CE1) gene and non-structural protein 5B ( NS5 B) gene were amplified using the nested polymerase chain reaction.The phylogenetic tree was constructed by MEGA 7.0 software to classify the genotypes. Chi-square test was used for statistical analysis. Trend chi-square test was used to analyze the trend of HIV and HCV genotypes. Results:Among the 996 cases with HIV/HCV co-infection, HIV and HCV sequences from a total of 554 subjects (55.6%, 554/996) were successfully obtained, and the genotypes of HIV and HCV were diverse. HIV genotype C (40.3%, 223/554) and BC recombinant (33.6%, 186/554) were the most prevalent, followed by genotype B (6.5%, 36/554) and circulating recombinant form (CRF)01_AE (3.6%, 20/554). HCV genotype 3b was the most prevalent (31.2%, 173/554), followed by genotype 6u (19.5%, 108/554), 1a (17.5%, 97/554), 6n (11.4%, 63/554), 3a (8.7%, 48/554) and 6xg (6.3%, 35/554). The prevalence of HIV genotype C showed a downward trend ( χtrend2=7.23, P<0.001), while the prevalence of BC recombinant showed an upward trend ( χtrend2=5.97, P<0.001), and the proportion of BC recombinant was higher than genotype C in 2019 (54.9%(101/184) vs 21.7%(40/184)). However, there were no statistically significant differences in the proportions of genotype 3b, 6u and 1a from 2016 to 2019 ( χtrend2=1.43, 1.79 and 0.39, respectively, P=0.152, 0.074 and 0.695, respectively). The HIV genotype distribution among patients with different ethnic groups were significantly different ( χ2=22.06, P=0.037). Conclusions:The diversity of HIV and HCV genotypes is high and complex among HIV/HCV co-infected Burmese patients in Dehong Dai and Jingpo Autonomous Prefecture. BC recombinant shows a trend of becoming the predominant HIV genotype among these co-infected patients. Therefore, surveillance of the prevalence of HCV and HIV genotypes in Burmese population needs to be further strengthened.

ObjectiveTo determine the trend and influencing factors of HIV subtypes in newly reported HIV/AIDS cases in Dehong Dai and Jingpo Autonomous Prefecture （Dehong Prefecture） from 2017 to 2019. MethodsRNA extraction was conducted among newly reported HIV/AIDS cases in Dehong Prefecture from 2017 to 2019 whose plasma volume was more than 200 μL. The gag， env and pol genes were amplified by using RT-PCR and then sequenced to determine the subtypes. ResultsA total of 3 287 HIV-infected cases were newly reported in Dehong from 2017 to 2019. The HIV gag， env and pol genotypes were determined in 1 813 cases. The major subtypes were subtype C （28.4%，515/1 813）， recombination form BC （22.0%，398/1 813） and CRF_01AE （18.1%，329/1 813）. Furthermore， the proportion of subtype B， subtype C and CRF01_AE decreased over years， whereas 01/BC， CRF07_BC and CRF08_BC increased over years in both Chinese and Burmese patients （χ²=75.212，P<0.001）. There were significant differences in gender， age， marital status， ethnicity， educational level and transmission route among Chinese and Burmese HIV-infected cases with diverse HIV genotypes （all P<0.05）. ConclusionHIV subtypes in Dehong change over time， which demonstrates that the proportion of BC recombinant subtypes and unique recombinant subtypes increased significantly.

We conducted a randomized, open-label, parallel-controlled, multicenter trial on the use of Shuanghuanglian (SHL), a traditional Chinese patent medicine, in treating cases of COVID-19. A total of 176 patients received SHL by three doses (56 in low dose, 61 in middle dose, and 59 in high dose) in addition to standard care. The control group was composed of 59 patients who received standard therapy alone. Treatment with SHL was not associated with a difference from standard care in the time to disease recovery. Patients with 14-day SHL treatment had significantly higher rate in negative conversion of SARS-CoV-2 in nucleic acid swab tests than the patients from the control group (93.4% vs. 73.9%, P = 0.006). Analysis of chest computed tomography images showed that treatment with high-dose SHL significantly promoted absorption of inflammatory focus of pneumonia, which was evaluated by density reduction of inflammatory focus from baseline, at day 7 (mean difference (95% CI), -46.39 (-86.83 to -5.94) HU; P = 0.025) and day 14 (mean difference (95% CI), -74.21 (-133.35 to -15.08) HU; P = 0.014). No serious adverse events occurred in the SHL groups. This study illustrated that SHL in combination with standard care was safe and partially effective for the treatment of COVID-19.
COVID-19 ; Humans ; Medicine, Chinese Traditional ; Research ; SARS-CoV-2 ; Treatment Outcome

Objective To explore the relationship between life events and depression of patients with primary sjgren's syndrome (PSS).Methods 80 patients with PSS complicating depressive disorder were tested by self-rating depression scale(SDS) and life event scale (LES),and compared with the control group including 80 PSS patients with non-depressive disorder matched with age and sex.Then the correlation between SDS and LES were analyzed.Results The total score of life events (32.72 ± 13.93),the score of negative life events (24.36 ±11.24),the score of SDS(58.60 ± 16.78) and the frequency of life events(91.3％) in the research group were higher than those in control group(P ＜ 0.05),but the positive life events score (7.15 ± 5.84) was lower than that in control group (9.76 ± 7.29),and there was statistically significant difference between the two groups (P ＜ 0.05),there were more negative life events,especially on the aspects of family,work and study in the research group.There was positive correlation among the negative life events score,total score of life events and SDS score in the research group(P＜ 0.01),meanwhile,negative correlation was revealed between the score of positive life events and SDS score in the research group(P ＜ 0.05).Conclusion Patients with PSS complicating depressive disorder experienced more negative life events which play an important role in depression of patients with PSS.

Objective To survey the prevalence and the related factors of depression in patients with primary Sj(o)gren's syndrome (pSS),and provide references for early mental intervention.Methods The depression state of 217 patients with pSS was screened with self-rating depression scale (SDS) first and then assessed by Hamilton depression scale (HAMD,17 index).The prevalence of depression was determined based on the diagnosis of psychiatrist based on the 3rd edition of Chinese classification of mental disorders (CCMD Ⅲ).The personality was evaluated by Eysenck personality questionnaire (EPQ),and the life events were questionnaired by life events scale (LES).The general condition was analyzed by self-designed questionnaire.Finally,step-wise multiple factor regression analysis was carried out to determine the risk factors that best accounted for the depression.Results The prevalence rate of depression in patients with pSS was 39.2％ (85/217).There were 5 factors entered the regression equation by multifactor regression analysis.They were severe pain,concerns of doctor and nurse,known of the fact by patients,adverse life events,and neuroticism of EPQ,and the concern of doctor and nurse was negatively correlated.Conclusion More attention from clinicians should be paid to the depression of pSS.Patients with severe pain,lack of attention from doctors and nurses,known of the disease itself,adverse life events and neurotic personality traits are factors related with depression.Recognizing the risk factors early can provide guidance for early psychological intervention.