Rapid Initiation of Antiretroviral Therapy Under the Treat-All Policy Reduces Loss to Follow-Up and Virological Failure in Routine Human Immunodeficiency Virus Care Settings in China: A Retrospective Cohort Study (2016-2022).

Following the World Health Organization's guidelines for rapid antiretroviral therapy (ART) initiation [≤7 days after human immunodeficiency virus (HIV) diagnosis], China implemented Treat-All in 2016 and has made significant efforts to provide timely ART since 2017. This study included newly diagnosed HIV adults from Tianjin, China, between 2016 and 2022. Our primary outcome was loss to follow-up (LTFU) at 12 months after enrollment. The secondary outcome was 12-month virological failure. The association between rapid ART and LTFU, as well as virological failure, was assessed via Cox regression and logistic regression. A total of 896 (19.1%) of 4688 participants received ART ≤7 days postdiagnosis. The rate of rapid ART has increased from 7.5% in 2016 to 33.3% by 2022. The rapid ART group had an LTFU rate of 3.3%, as opposed to 5.0% in the delayed group. The rapid ART group had a much reduced virological failure rate (0.6% vs. 1.8%). Rapid ART individuals had a reduced likelihood of LTFU [adjusted hazard ratio: 0.65, 95% confidence intervals (CI): 0.44-0.96] and virological failure (adjusted odds ratio: 0.35, 95% CI: 0.12-0.80). The real-world data indicated that rapid ART is practicable and beneficial for Chinese people with HIV, providing evidence for its widespread implementation and scaling up.

Prevalence of and prognosis for poor immunological recovery by virally suppressed and aged HIV-infected patients.

Background: Antiretroviral therapy (ART) prolongs lifespan and decreases mortality of HIV infected patients. However, many patients do not achieve optimal immune reconstitution. The influence of non-optimal immune recovery on non-AIDS related diseases is not well defined in aged HIV-infected patients receiving ART. Methods: A retrospective study was conducted at Tianjin Second People's Hospital, China to evaluate the association of an inadequate immunological response and non-AIDS diseases in HIV infected patients ≥60 years of age and virally suppressed for at least 2 years by ART. Results: The study included patients (n = 666) who initiated ART between August 2009 and December 2020. The prevalence of patients with an inadequate immunological response was 29.6%. The percentage of non-AIDS diseases such as hypertension, cardiovascular disease (CVD), diabetes, tumor, and chronic kidney disease (CKD) was 32.9, 9.9, 31, 4.1, and 13%, respectively. In addition to baseline CD4+ T cell counts, CVD and tumor were associated with poor immune reconstitution in aged Chinese HIV-1 infected patients. The adjusted odds ratios (95% confidence interval) were AOR 2.45 (95% CI: 1.22-4.93) and 3.06 (95% CI: 1.09-8.56, p = 0.03). Inadequate immunological response was associated with greater mortality (AOR: 2.83, 95% CI: 1.42-5.67, p = 0.003) in this cohort. Conclusion: These results tend to demonstrate appropriate drug selection at ART initiation and prevention of non-AIDS complications during ART decreased mortality of and an inadequate immunological response in aged HIV infected patients.

Effect of boxers' social support on mental fatigue: Chain mediating effects of coach leadership behaviors and psychological resilience.

BACKGROUND: Athletic fatigue is an inescapable issue in competitive sports. It belongs to a physiological response that is triggered when competitive athletes are trained to a critical point. OBJECTIVE: The study aims to explore the relationships involving boxers' social support, mental fatigue, coach leadership behaviors and psychological resilience. METHODS: 1050 boxers were selected in several provinces across China and investigated on the basis of the Social Support Questionnaire for Athletes, Mental Fatigue Scale, Psychological Resilience Scale, and Leadership Scale for Sport. RESULTS: Boxers' social support was negatively correlated with mental fatigue and psychological resilience, while it was positively correlated with coach leadership behaviors. Apart from direct effects on mental fatigue, other impacts are imposed by boxers' social support via mediating effects such as coach leadership behaviors and psychological resilience. The total effect value was -0.18, the direct effect value was -0.08, and the indirect effect value was -0.12; furthermore, coach leadership behaviors and psychological resilience play a mediating role, accounting for 65.57% of the total. CONCLUSION: In order to alleviate the stress from intense competitive training and abate mental fatigue, competitive athletes may be encouraged in subsequent training to seek all-sided social support for social interpersonal relationships. While clarifying the mechanism how the external environment affects individuals, this paper explains the principle of social support on athletes' psychological fatigue and identifies mutual influences between coaches and athletes.

Life span-associated ferroptosis-related genes identification and validation for hepatocellular carcinoma patients as hepatitis B virus carriers.

BACKGROUND: Hepatitis B virus (HBV)-infected population accounts for approximately 50% of all hepatocellular carcinoma (HCC) cases and has a relatively poor prognosis. Although the significant role of ferroptosis in the development and therapeutic response of various cancers has been validated, the key ferroptosis-related genes (FRGs) on the stratification of HBV-associated HCC are still unclear. METHODS: Through the random forest, GSVA and Cox regression analyses, we established a comprehensive prognostic system covering multiple FRGs to elevate the predictive accuracy for the survival rate of HBV-related HCC using information obtained from public databases. The association between key FRGs and the immune microenvironment was evaluated, and the molecular mechanism was identified by GSEA and SNV analyses. Finally, the differential expression of key FRGs was validated by immunohistochemistry staining of patient tissue microarrays. RESULTS: Within the top 10 key FRGs, EPAS1 and GABARAPL1 were taken as protective factors, and SQLE, RAD51AP1, RPL8, CAPG, RRM2, SLC1A5, SLC38A1, and SRC were the other eight dangerous markers. Cox regression analysis combined with clinicopathological features indicated the independent prognostic efficacy of GSVA complex score based on these FRGs. In addition, key FRGs were related to immune and metabolic-related functions. Especially, the immunohistochemical analysis of SQLE in 50 clinical samples showed significantly higher expression in HBV+ HCC tissues. CONCLUSIONS: These results indicate that 10 FRGs may be potential biomarkers and therapeutic targets for long-term survival in HBV-related HCC.

Initiating antiretroviral therapy within 2 weeks of anti-Pneumocystis treatment does not increase mortality or AIDS-defining events in patients with HIV-associated moderate to severe Pneumocystis pneumonia: results of a prospective observational multicenter study.

BACKGROUND: The mortality rate remains high among patients with coinfection with Pneumocystis pneumonia (PCP) and HIV. The timing for initiation of antiretroviral therapy (ART) after a diagnosis of moderate to severe PCP remains controversial, however. We therefore designed the present study to determine the optimal timing for ART initiation in AIDS-associated PCP (AIDS/PCP) patients. METHODS: This was a multicenter, observational, prospective clinical trial. Eligible participants were recruited from 14 hospitals in mainland China, and assigned to an Early ART arm (initiation of ART ≤ 14 days after PCP diagnosis) and a Deferred ART arm (initiation of ART > 14 days after PCP diagnosis). The primary outcomes were death and the incidence of AIDS-defining events at week 48. The secondary outcomes were the changes in CD4+ T-cell counts from baseline values at weeks 12, 24, and 48, the virological suppression rate at week 24 and week 48, the rate of development of PCP-associated immune reconstitution inflammatory syndrome (PCP/IRIS), and the rate of adverse events over 48 weeks. RESULTS: The present study was performed using the data of 363 participants, with 169 participants in the Early ART arm, and 194 participants in the Deferred ART arm. Immunological and virological outcomes were found to be similar in both treatment arms. At week 48, there were no significant differences for the incidence of mortality (20 vs. 26, p = 0.860), and AIDS-defining events (17 vs. 26, p = 0.412). Over 48 weeks, the rates of PCP/IRIS (2 vs. 3, p = 1.000), adverse events (70 vs. 72, p = 0.465), and grade 3 or 4 adverse events (28 vs. 34, p = 0.919) did not reach statistical significance. A significant difference observed between two study arms was that 11 participants (55.0%) in the Early ART arm compared to 23 participants (88.5%) in the Deferred ART arm (p = 0.026) succumbed before ART had ever been started. CONCLUSIONS: Early ART initiation results in no increase in mortality, AIDS-defining events, IRIS, adverse events, and immunological or virological outcomes. These results support the early initiation of ART in patients with moderate to severe AIDS/PCP. Clinical trial registration The present trial was registered at Chinese Clinical Trial Registry (ChiCTR1900021195). Registered 1 February 2019, http://www.chictr.org.cn/showproj.aspx?proj=35362 .

The effects of adolescent physical activity participation on cell phone dependence: The mediating role of self-control.

BACKGROUND: The rapid development of science and technology and the swift improvement of people's material living standards enabled smartphones to be indispensable of people's daily lives. OBJECTIVE: The purpose of this paper was to examine the influence of self-control in adolescents' participation in physical activity on cell phone dependence. METHODS: The Physical Activity Rating Scale (PARS-3), the Self-Control Scale, and the Cell Phone Dependence Scale were used to measure the influence of self-control in adolescents' participation in physical activity on cell phone dependence among 649 adolescents. RESULTS: The results show: (1) There were significant differences (p < 0.01) in the physical activity levels of adolescents under different gender, birthplace, and education background. (2) Each dimensional variable of physical activity was negatively correlated with the cell phone dependence variable, and positively correlated with each variable of self-control, and the self-control variables were negatively correlated with cell phone dependence. (3) Self-control was partially mediating the effects of physical activity on cell phone dependence, with the mediating effect accounting for 39.68%. CONCLUSIONS: Adolescents' participation in physical exercise activities will improve self-control and ultimately reduce cell phone dependence. Curbing the negative and malignant events of cell phone addiction among adolescents, timely investigation of mobile phone and Internet addiction, pathological formation mechanisms and intervention measures are important measures to reshape the healthy lifestyle of adolescents and have great practical significance for the prosperity and development of families, society, nation and country.

Therapeutic lumbar puncture and lumbar drainage: which is more effective for the management of intracranial hypertension in HIV patients with cryptococcal meningitis? Results of a prospective non-randomized interventional study in China.

OBJECTIVE: This study aimed to evaluate the effectiveness of therapeutic lumbar drainage (LD) compared to therapeutic lumbar puncture (LP) for the management of intracranial hypertension (ICH) among HIV-positive patients with cryptococcal meningitis (CM). METHODS: The study was a multicenter prospective non-randomized interventional clinical trial. One hundred and sixteen HIV-associated CM patients were identified who presented with ICH (≥250 mmH2O). The LP group comprised 76 cases, while the LD group consisted of 40 cases. We compared mortality, intracranial pressure (ICP) normalization rate, and clinical symptom remission at 10 weeks, between the two groups. RESULTS: The cumulative mortality at week 10 was 22.4% in the LP group and 20% in the LD group (p = .927), without any significant difference in mortality between the two groups. Improvement after treatment at 2-weeks, ICP normalization, and headache reversal event occurrence in the two groups showed no significant difference (p > .05). The incidence of CSF Cryptococcus clearance at two weeks in the LD group was significantly higher than in the LP group (p < .05). The frequency of invasive lumbar therapeutic procedures in the LP group during the first week was higher than that of the LD group (p < .05). Localized infection at the puncture site occurred more frequently in the LD group than in the LP group (p < .05). CONCLUSION: For HIV-positive CM patients with an elevated ICP, LD and LP are comparably effective and safe options to normalize ICP. LP increases the frequency of invasive lumbar therapeutic procedures but does not incur more risk of infection events at the puncture site, while LD may accelerate CSF Cryptococcus clearance but may induce more frequent localized infection. TRIAL REGISTRATION: This study was registered as one of 12 trials under a general project at the Chinese Clinical Trial Registry (ChiCTR1900021195).

No Statistically Apparent Difference in Antifungal Effectiveness Observed Among Trimethoprim/Sulfamethoxazole Plus Clindamycin or Caspofungin, and Trimethoprim/Sulfamethoxazole Monotherapy in HIV-Infected Patients with Moderate to Severe Pneumocystis Pneumonia: Results of an Observational Multicenter Cohort Study.

INTRODUCTION: Pneumocystis pneumonia is a common opportunistic infection in patients with HIV/AIDS, and is a leading cause of death in this population. Early selection of effective treatment is therefore critical to reduce mortality. We conducted a clinical trial to compare the effectiveness and safety of three different antifungal treatment regimens in HIV-infected patients with moderate to severe PCP. METHODS: Our study was a multicenter, observational prospective clinical trial. We recruited 320 HIV-infected patients with moderate to severe PCP, and stratified these subjects into a trimethoprim/sulfamethoxazole (TMP-SMX) monotherapy group, a TMP-SMX plus clindamycin group, and a TMP-SMX plus caspofungin group. Patients were invited to participate in 12 weeks of follow-up. Outcomes included the difference in overall mortality and the proportion of overall positive response to treatment in the three groups at weeks 4 and 12, the difference in treatment duration, and the proportion of adverse events among the three groups during the study period. RESULTS: The probability of survival not statistically different among three treatment groups. Mortality in the TMP-SMX monotherapy group (group 1) was 15/115 (13.04%) vs. 20/83 (24.10%) in the TMP-SMX plus clindamycin group (group 2) vs. 24/107 (22.43%) in the TMP-SMX plus caspofungin group (group 3) at week 12 (p = 0.092). The overall positive response rate to treatment in the three groups was 24.14%, 34.94%, and 38.32%, respectively, at week 4, and 33.91%, 38.55%, and 44.86%, respectively, at week 12. No significant difference in the overall positive response rate to treatment at either week 4 or week 12 was noted (p = 0.061, p = 0.246). Rates of changes to therapy were 6.50% (8/123) in group 1, 3.40% (3/87) in group 2, and 2.70% (3/110) in group 3, and did not differ significantly among the three groups (p = 0.376). There were also no significant differences in adverse events among the three treatment groups of patients with moderate to severe PCP. CONCLUSIONS: Our results indicate that there are no significant statistical differences among the three studied treatment regimens in terms of antifungal effectiveness in HIV-infected patients with moderate to severe PCP. TMP-SMX monotherapy is a convenient, cheap, and effective therapeutic drug regimen to treat HIV-infected patients with moderate to severe PCP, and is an appropriate treatment strategy in resource-limited settings. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov , ID: ChiCTR1900021195. Registered on February 1, 2019.

Consequences of HIV/Syphilis Co-Infection on HIV Viral Load and Immune Response to Antiretroviral Therapy.

INTRODUCTION: Although syphilis is a frequent co-infection in patients with human immunodeficiency virus (HIV) infection, the influence of syphilis on immune response and virologic failure in HIV-infected patients following initiation of antiretroviral therapy (ART) is not well-defined. METHODS: A retrospective study was conducted at Tianjin Second People's Hospital to evaluate the prevalence of syphilis and immune status in 4171 ART-naïve patients. The study included patients who initiated ART between August 2009 and June 2019. RESULTS: The prevalence of syphilis was 40.1% in all ART-naïve patients and 42.5% in ART-naïve men who have sex with men. HIV/syphilis co-infection was associated with higher virologic failure (odds ratio (95% confidence interval): 1.30 (1.04, 1.63)). Patients with HIV/syphilis co-infection had lower median CD4+ T cell counts and CD4/CD8 ratios at baseline. After initiation of ART, patients co-infected with HIV/syphilis had smaller increases in CD4+ T cell counts and CD4/CD8 ratios than patients infected only with HIV. The rate of recurrence of syphilis or reinfection was 9% (n = 128) during seven years of ART. CONCLUSION: HIV/syphilis co-infection had a negative impact on immune recovery and antiretroviral effectiveness. RPR titer and HIV viral load should be monitored in patients co-infected with HIV/syphilis, especially in patients with high RPR titers.

HIV-1 Genetic Diversity and High Prevalence of Pretreatment Drug Resistance in Tianjin, China.

Diversity of genotypes and prevalence of pretreatment drug resistance (PDR) are challenges for the epidemic control and vaccine development of HIV-1. However, little is known about the situation in Tianjin. Blood samples were collected from newly diagnosed, antiretroviral treatment (ART)-naive HIV/AIDS patients from January 2016 to November 2019. The target fragment in the pol gene was sequenced after RNA extraction and gene amplification. The HIV-1 genotype was identified by phylogenetic analysis. Drug resistance was carried out using the Stanford University HIVdb algorithm. A total of 305 pol sequences from 279 non-PDR individuals and 35 PDR individuals were successfully amplified. The most prevalent genotype was CRF01_AE (65.6%, 200/305), followed by CRF07_BC (22.0%, 67/305) and B (3.0%, 9/305). A variety of circulating recombinant forms (CRFs) and unique recombinant forms were found. The overall incidence of PDR was 11.5% (35/305), with 9.8% (30/305) to non-nucleoside reverse transcriptase (RT) inhibitors (NNRTIs). The most frequent mutation pattern against NNRTIs was V179D/E/T (6.9%, 21/305), with M184V (1.0%, 3/305) and K65R (1.0%, 3/305) against nucleoside RT inhibitors (NRTIs). M64L (0.1%, 1/305) was the sole mutation found against protease inhibitors (PIs). Eight variants generated at least low-level resistance to NNRTIs (2.6%, 8/305), which was much higher than that to NRTIs (1.6%, 5/305) and PIs (0/305) (p < .05). Genotypic drug resistance testing before initiating ART in newly diagnosed HIV/AIDS patients may be necessary in Tianjin, China. The non-NNRTI-based regimen may be preferred as initial therapy in Tianjin.

Characterization of a New HIV-1 CRF01_AE/CRF07_BC Recombinant Virus in Tianjin, China.

HIV is notorious for its rapid evolution since its transmissions from monkey to human. Currently, HIV contains multiple subtypes, circulating recombinant forms (CRFs) and unique recombinant forms (URFs). Here, from an HIV-positive mother and her child in Tianjin, China, we identified a novel HIV-1 second-generation recombinant virus (TJ20170316 and TJ20170317) between CRF01_AE and CRF07_BC. Near full-length genomes (NFLGs) were obtained from both samples, and they shared very close sequences, except some point mutations. Phylogenetic analyses of the NFLGs showed that they consist of CRF01_AE backbone and part CRF07_BC sequences. Recombinant Identification Program and Simplot software identified four breakpoints in gag, pol, vif, and tat genes in TJ20170316, totally different from other reported CRFs and URFs. The emergence of such URFs in Tianjin, China, highlights the complexity of HIV-1 epidemic and more measures should be taken to prevent HIV transmissions.

Trends in the incidence of AIDS and epidemiological features in Tianjin, China from 2005 to 2016.

The objective of this study was to assess the epidemiological trends among patients with AIDS in Tianjin, China. A long-term surveillance study was conducted from 2005 to 2016 in Tianjin, China. All patients with AIDS registered in Tianjin from 2005 to 2016 were recruited to this study. Demographic information and clinical features were recorded. A total of 3062 patients with AIDS who were treated with antiretroviral therapy were included in this study. Among AIDS patients, men were more likely to be younger than women (age, 37.84 years vs. 43.27 years; P < 0.001). The incidence of AIDS increased by 39.6% annually over the past 12 years overall. There was the greatest increase (by 44.7%) for homosexual route. Moreover, the proportion of patients aged < 30 years increased considerably over the 12-year study period, while there was a decrease in the proportion of patients aged ≥ 35 years. The frequency of homosexual transmission increased by 86% from before 2011 to 2016, but the frequency of heterosexual transmission decreased by 49%. The frequency of transmission through intravenous drug use decreased in men and patients aged 25-29 years. For those infected through homosexual transmission, there was a significant increase in the numbers of patients aged 20-24 years and 25-29 years. It is important for developing countries to effectively prevent and control the transmission of HIV/AIDS; in particular, it is crucial to promote disease education and sexual protection among young men.

Effects of CTR4 deletion on virulence and stress response in Cryptococcus neoformans.

Roles of the high-affinity copper transporter Ctr4 in the virulence of Cryptococcus neoformans remain to be fully determined. Here we demonstrate that Ctr4 plays a necessary role in virulence and tolerance to a number of stress conditions. We first observed, with the method of flame atomic absorption spectrometry, that deletion of CTR4 resulted in a significant decrease in intracellular copper level, confirming the role of Ctr4 as a copper transporter in C. neoformans. Furthermore, CTR4 was critical for the yeast to survive at both elevated and low temperatures, as the growth rate of the ctr4Δ mutant at 4 and 37 °C was significantly decreased. The mutant ctr4Δ also exhibited hypersensitivity to osmotic stress imposed by 2 M NaCl or KCl, indicating the possible crosstalk of Ctr4 with the HOG signalling pathway. Moreover, cell wall and plasma membrane integrity appeared to be impaired in the ctr4Δ strain. The virulence of ctr4Δ in two mouse cryptococcosis models was remarkably reduced either via an intranasal or intravenous inoculation. Our work confirms the roles of Ctr4 in virulence and copper homeostasis as well as other additional novel functions.

[Simulation Analysis of the Pulse Signal on the Electricity Network of Cardiovascular System].

Pulse waves contain abundant physiological and pathological information of human body. Research of the relationship between pulse wave and human cardiovascular physiological parameters can not only help clinical diagnosis and treatment of cardiovascular diseases, but also contribute to develop many new medical instruments. Based on the traditional double elastic cavity model, the human cardiovascular system was established by using the electric network model in this paper. The change of wall pressure and blood flow in artery was simulated. And the influence of the peripheral resistance and vessel compliance to the distribution of blood flow in artery was analyzed. The simulation results were compared with the clinical monitoring results to predict the physiological and pathological state of human body. The result showed that the simulation waveform of arterial wall pressure and blood flow was stabile after the second cardiac cycle. With the increasing of peripheral resistance, the systolic blood pressure of artery increased, the diastolic blood pressure had no significant change, and the pulse pressure of artery increased gradually. With the decreasing of vessel compliance, the vasoactivity became worse and the pulse pressure increased correspondingly. The simulation results were consistent with the clinical monitoring results. The increasing of peripheral resistance and decreasing of vascular compliance indicated that the incidence of hypertension and atherosclerosis was increased.

Negative roles of a novel nitrogen metabolite repression-related gene, TAR1, in laccase production and nitrate utilization by the basidiomycete Cryptococcus neoformans.

The multicopper oxidase laccase is widespread in fungi and has great industrial importance. One puzzle regarding laccase production in the basidiomycetous yeast Cryptococcus neoformans is that it is inhibited by high temperature (e.g., 37 degrees C). In this paper, we report identification of a nitrogen metabolite repression-related gene, TAR1, which is responsible for laccase repression. Disruption of TAR1 results in a significant increase in the level of LAC1 mRNA at 37 degrees C. The putative protein Tar1 shares a moderate level of similarity with the nitrogen metabolite repressors Nmr1 and NmrA from Neurospora crassa and Aspergillus nidulans, respectively. Likewise, Tar1 has a negative role in the utilization of nitrate. Furthermore, the structure of Tar1 is unique. Tar1 lacks the long C-terminal region of Nmr1 and NmrA. It contains the canonical Rossmann fold motif, GlyXXGlyXXGly, whereas Nmr1 and NmrA have variable residues at the Gly positions. Interestingly, the promoter region of TAR1 contains three TTC/GAA repeats which are likely the heat shock factor (Hsf) binding sites, implying that Hsf has a role in laccase inhibition. TAR1 mediation of temperature-associated repression of LAC1 suggests a novel mechanism of laccase regulation and a new function for Nmr proteins. Our work may be helpful for industry in terms of promotion of laccase activity.

[Pathogenicity of the opportunistic pathogenic fungus Cryptococcus neoformans--a review].

The increase of clinical fungal infection causes a wide awareness. Cryptococcus neoformans is one of the major fungal pathogens. In the past 10 years,much progress has been made in its molecular biological research, including the synthesis and mobilization of the virulence factors as well as the signal transduction pathways during pathogeny. All these will help prevent or treat this fungus. We review the virulence factors and the molecular biological research progress.