The effect of pH shifting on the calcium-fortified milk analogue with chickpea protein.

Milk alternative attracts more attention due to nutrition benefits, but the low solubility and the calcium deficiency of plant protein hinder the development of milk alternatives. Therefore, pH shifting was optimized to improve chickpea protein solubility and calcium fortification while ensuring good digestibility. The results showed that pH shifting reduced the particle size from 2197.67 ± 178.2 nm to 80.2 ± 2 nm, and increased the net ζ potential from -0.48 ± 0.24 to -21.27 ± 0.65 due to the unfolding of secondary protein structure, by which chickpea protein bring better solution stability. Additionally, the whiteness of the solution with chickpea protein increased. The calcium addition kept the solution stable with small particle size despite a slight increase. The microstructure of chickpea protein during digestion was well disrupted even with fortifying calcium. This study provides proof of the positive effect of pH shifting on chickpea protein stability and calcium fortification.

METTL3 mediated ferroptosis in chondrocytes and promoted pain in KOA via HMGB1 m6A modification.

Methyltransferase-like 3 (METTL3) plays a role in the development of knee osteoarthritis (KOA). However, the mechanism underlying the role of METTL3 in KOA is unclear. This work investigated the effects of MELLT3 on ferroptosis and pain relief in in vitro and in vivo KOA models. Chondrocytes were treated with 10 ng/mL interleukin-1ß (IL-1ß) or 5 µM Erastin (ferroptosis inducer). IL-1ß or Erastin treatment inhibited cell viability and glutathione levels; increased Fe2+, lipid reactive oxygen species and malondialdehyde production; and decreased glutathione peroxidase 4, ferritin light chain and solute carrier family 7 member 11 levels. The overexpression of METTL3 facilitated the N6-methyladenosine methylation of high mobility group box 1 (HMGB1). HMGB1 overexpression reversed the effect of sh-METTL3 on IL-1ß-treated chondrocytes. A KOA rat model was established by the injection of monosodium iodoacetate into the joints and successful model establishment was confirmed by haematoxylin and eosin staining and Safranin O/Fast Green staining. METTL3 depletion alleviated cartilage damage, the inflammatory response, ferroptosis and knee pain in KOA model rats, and these effects were reversed by the addition of HMGB1. In conclusion, METTL3 depletion inhibited ferroptosis and the inflammatory response, and ameliorated cartilage damage and knee pain during KOA progression by regulating HMGB1.

Factors influencing the tendency of residual symptoms in patients with depressive disorders: a longitudinal study.

BACKGROUND: Residual symptoms of depressive disorders are serious health problems. However, the progression process is hardly predictable due to high heterogeneity of the disease. This study aims to: (1) classify the patterns of changes in residual symptoms based on homogeneous data, and (2) identify potential predictors for these patterns. METHODS: In this study, we conducted a data-driven Latent Class Growth Analysis (LCGA) to identify distinct tendencies of changes in residual symptoms, which were longitudinally quantified using the QIDS-SR16 at baseline and 1/3/6 months post-baseline for depressed patients. The association between baseline characteristics (e.g. clinical features and cognitive functions) and different progression tendencies were also identified. RESULTS: The tendency of changes in residual symptoms was categorized into four classes: "light residual symptom decline (15.4%)", "residual symptom disappears (39.3%)", "steady residual symptom (6.3%)" and "severe residual symptom decline (39.0%)". We observed that the second class displayed more favorable recuperation outcomes than the rest of patients. The severity, recurrence, polypharmacy, and medication adherence of symptoms are intricately linked to the duration of residual symptoms' persistence. Additionally, clinical characteristics including sleep disturbances, depressive moods, alterations in appetite or weight, and difficulties with concentration have been identified as significant factors in the recovery process. CONCLUSIONS: Our research findings indicate that certain clinical characteristics in patients with depressive disorders are associated with poor recovery from residual symptoms following acute treatment. This revelation holds significant value in the targeted attention to specific patients and the development of early intervention strategies for residual symptoms accordingly.

Identification and experimental verification of immune-related hub genes in intervertebral disc degeneration.

Background: Inflammation and immune factors are the core of intervertebral disc degeneration (IDD), but the immune environment and epigenetic regulation process of IDD remain unclear. This study aims to identify immune-related diagnostic candidate genes for IDD, and search for potential pathogenesis and therapeutic targets for IDD. Methods: Gene expression datasets were obtained from the Gene Expression Omnibus (GEO). Differential expression immune genes (Imm-DEGs) were identified through weighted gene correlation network analysis (WGCNA) and linear models for microarray data analysis (Limma). LASSO algorithm was used to identify feature genes related to IDD, which were compared with core node genes in PPI network to obtain hub genes. Based on the coefficients of hub genes, a risk model was constructed, and the diagnostic value of hub genes was further evaluated through receiver operating characteristic (ROC) analysis. Xcell, an immunocyte analysis tool, was used to estimate the infiltration of immune cells. Finally, nucleus pulposus cells were co-cultured with macrophages to create an M1 macrophage immune inflammatory environment, and the changes of hub genes were verified. Results: Combined with the results of WGCNA and Limma gene differential analysis, a total of 30 Imm-DEGs were identified. Imm-DEGs enriched in multiple pathways related to immunity and inflammation. LASSO algorithm identified 10 feature genes from Imm-DEGs that significantly affected IDD, and after comparison with core node genes in the PPI network of Imm-DEGs, 6 hub genes (NR1H3, SORT1, PTGDS, AGT, IRF1, TGFB2) were determined. Results of ROC curves and external dataset validation showed that the risk model constructed with the 6 hub genes had high diagnostic value for IDD. Immunocyte infiltration analysis showed the presence of various dysregulated immune cells in the degenerative nucleus pulposus tissue. In vitro experimental results showed that the gene expression of NR1H3, SORT1, PTGDS, IRF1, and TGFB2 in nucleus pulposus cells in the immune inflammatory environment was up-regulated, but the change of AGT was not significant. Conclusions: The hub genes NR1H3, SORT1, PTGDS, IRF1, and TGFB2 can be used as immunorelated biomarkers for IDD, and may be potential targets for immune regulation therapy for IDD.

Lot-to-lot consistency, immunogenicity and safety of a quadrivalent split virion inactivated influenza vaccine in healthy population aged 9-59 years: A randomized, double-blind, controlled, phase IV clinical trial.

OBJECTIVES: This study was to assess the lot-to-lot consistency, immunogenicity and safety of three manufacturing lots of a quadrivalent inactivated influenza vaccine (IIV4). METHODS: A randomized, double-blind, phase IV clinical trial was conducted in healthy children, adolescents and adults aged 9-59 years in Guizhou Province, China. Eligible participants were enrolled and randomized into three groups in a ratio of 1:1:1 to receive a single dose of one of three manufacturing lots of IIV4. Serum samples were collected before and 28 days after vaccination for hemagglutination inhibition (HI) antibody testing. Safety data were collected for up to 28 days after vaccination. The primary objective was to evaluate the lot-to-lot consistency of immune response as assessed by the geometric mean titer (GMT) of HI antibody at 28 days after vaccination. RESULTS: Between November 27, 2022 and December 18, 2022, 1260 eligible participants were enrolled, with similar participant demographics among groups. Immune responses after vaccination were comparable across groups, with the 95% confidence intervals (CIs) of GMT ratios for all 4 strains falling into the equivalence criterion of (0.67, 1.5). The seroconversion rates (SCRs) and seroprotection rates (SPRs) met the US Center or Biologics Evaluation and Research (CBER) criteria for all strains for each lot (lower limit of 95% CI of SCR ≥ 40% and SPR ≥ 70%). The incidences of solicited and unsolicited adverse reactions were similar among three groups, most of which (91.9%) were mild or moderate in severity. A total of 11 serious adverse events were reported during the study, and all were considered unrelated to vaccination. CONCLUSION: The three manufacturing lots of IIV4 demonstrated consistent immunogenicity. IIV4 can elicit satisfactory immune responses for all four strains and no safety concerns were identified. CLINICAL TRIAL REGISTRATION: Identifier No. NCT05512494.

Global, regional, and national burdens of HIV/AIDS acquired through sexual transmission 1990-2019: an observational study.

Background Sexual transmission accounts for a substantial proportion of HIV infections. Although some countries are experiencing an upward trend in HIV infections, there has been a lack of studies assessing the global burden of HIV/AIDS acquired through sexual transmission. We assessed the global, regional, and national burdens of HIV/AIDS acquired through sexual transmission from 1990 to 2019. Methods Data on deaths, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALY) of HIV/AIDS acquired through sexual transmission in 204 countries and territories from 1990 to 2019 were retrieved from the Global Burden of Disease Study (GBD) 2019. The burdens and trends were evaluated using the age-standardised rates (ASR) and estimated annual percentage change (EAPC). Results Globally, HIV/AIDS acquired through sexual transmission accounted for ~695.8 thousand (95% uncertainty interval 628.0-811.3) deaths, 33.0million (28.7-39.9) YLLs, 3.4million (2.4-4.6) YLDs, and 36.4million (32.2-43.1) DALYs in 2019. In 2019, Southern sub-Saharan Africa (11350.94), Eastern sub-Saharan Africa (3530.91), and Western sub-Saharan Africa (2037.74) had the highest ASR of DALYs of HIV/AIDS acquired through sexual transmission per 100,000. In most regions of the world, the burden of HIV/AIDS acquired through sexual transmission has been increasing from 1990 to 2019, mainly in Oceania (EAPC 17.20, 95% confidence interval 12.82-21.75), South Asia (9.00, 3.94-14.30), and Eastern Europe (7.09, 6.35-7.84). Conclusions HIV/AIDS acquired through sexual transmission results in a major burden globally, regionally, and nationally.

Telitacicept: A novel horizon in targeting autoimmunity and rheumatic diseases.

BLyS and APRIL have the capability to bind to B cells within the body, allowing these cells to evade elimination when they should naturally be removed. While BLyS primarily plays a role in B cell development and maturation, APRIL is linked to B cell activation and the secretion of antibodies. Thus, in theory, inhibiting BLyS or APRIL could diminish the population of aberrant B cells that contribute to SLE and reduce disease activity in patients. Telitacicept functions by binding to and neutralizing the activities of both BLyS and APRIL, thus hindering the maturation and survival of plasma cells and fully developed B cells. The design of telitacicept is distinctive; it is not a monoclonal antibody but a TACI-Fc fusion protein generated through recombinant DNA technology. This fusion involves merging gene segments of the TACI protein, which can target BLyS/APRIL simultaneously, with the Fc gene segment of the human IgG protein. The TACI-Fc fusion protein exhibits the combined characteristics of both proteins. Currently utilized for autoimmune disease treatment, telitacicept is undergoing clinical investigations globally to assess its efficacy in managing various autoimmune conditions. This review consolidates information on the mechanistic actions, dosing regimens, pharmacokinetics, efficacy, and safety profile of telitacicept-a dual-targeted biological agent. It integrates findings from prior experiments and pharmacokinetic analyses in the treatment of RA and SLE, striving to offer a comprehensive overview of telitacicept's research advancements.

Bioinformatic analysis indicated that STARD4-AS1 might be a novel ferroptosis-related biomarker of oral squamous cell carcinoma.

Background: Oral squamous cell carcinoma (OSCC) stands as the predominant form of oral cancer, marked by a poor prognosis. Ferroptosis, a type of programmed cell death, plays a critical role in the initiation and progression of various cancers. Long non-coding RNAs (lncRNAs) are prominent in modulating cancer development. Nevertheless, the prognostic significance of ferroptosis-related lncRNAs (FRLs) in OSCC remains inadequately explored. This study aims to develop a predictive signature based on FRLs to forecast the prognosis of OSCC patients. Methods: We gathered expression profiles of FRLs along with clinical data from The Cancer Genome Atlas (TCGA) and FerrDb databases. A prognostic model based on 10 FRLs were constructed using Cox regression analyses with LASSO algorithms, and their predictive power was evaluated. Then, the model was used to investigate functional enrichment, immune landscape, m6A genes, somatic variations, and drug response in different risk cohorts of patients. Finally, the expression and function of STARD4-AS1 (steroidogenic acute regulator protein-related lipid transfer domain containing 4-antisense RNA 1), a potential prognostic marker for OSCC screening based on our bioinformatics analysis, were investigated in vitro. Results: We developed a signature comprising 10 FRLs to stratify patients into two risk cohorts according to their calculated risk scores. Patients classified as high-risk exhibited significantly poorer prognoses compared to those in the low-risk cohort. Furthermore, survival analysis, patient risk heat plot, and risk curve verified the accuracy of the signature. The role of this signature in OSCC was well investigated using immune microenvironment, mutational, and gene set enrichment analysis (GSEA). Moreover, seven drugs, including cisplatin and docetaxel, were identified as potential treatments for patients with high-risk cancers. In addition, the knockdown of STARD4-AS1 in OSCC cell lines markedly inhibited cell proliferation and migration and induced ferroptosis. Conclusion: Using this signature may improve overall survival predictions in OSCC, throwing new light on immunotherapies and targeted therapies. Moreover, STARD4-AS1 might regulate the process of ferroptosis and could be used as a novel biomarker of OSCC.

Novel Halogenated Curcumin-Mediated Photodynamic Inactivation for the Preservation of Small Yellow Croaker (Larimichthys polyactis).

A novel class of halogenated curcumin, X-Cur (X = F, Cl, or Br), was synthesized, and its photosensitivity was evaluated. The results showed that Br-Cur with the highest singlet oxygen (1O2) generation capacity exhibited a better photodynamic inactivation (PDI) effect on the small yellow croaker (Larimichthys polyactis) than curcumin. This was attributed to the heavy atom effect of Br, which resulted in Br-Cur having the smallest singlet-triplet energy difference ΔEst(S1-T3) (0.140 eV) and the largest spin-orbit coupling value (0.642262 cm-1). When L. polyactis was treated with 0.025 wt % Br-Cur and exposed to blue LED irradiation (450 nm, 20 mW/cm2) for 20 min, the increase in the total volatile basic nitrogen content (28.23 ± 2.38 mg/100 g on day 6), pH, and total viable count (6.13 ± 0.06 log CFU/g on day 6) could be effectively controlled. Accordingly, Br-Cur is a promising photosensitizer for PDI preservation.

Acne treatment: research progress and new perspectives.

Acne is a chronic inflammatory skin disease that primarily affects adolescents and is attributed to various factors, including hormonal changes, genetic predisposition, and environmental influences. It typically manifests in areas rich in sebaceous glands such as the face, chest, and back. Symptoms of acne can range from mild to severe and may present as pimples, pustules, nodules, cysts, and scarring. The appearance of acne can significantly impact both the physical and mental well-being of patients, potentially leading to feelings of anxiety, depression, and social withdrawal. The pathogenesis of acne is multifaceted involving genetic predisposition as well as environmental factors such as hormonal imbalances, inflammation, abnormal follicular sebaceous unit keratinization, proliferation of follicular microorganisms like Propionibacterium acnes, increased sebum production, and dietary influences. Traditional treatment methods for acne include topical drug therapy, oral drug therapy, photoelectric therapy, and chemical peeling. With ongoing research into the pathogenesis of acne, treatment methods are rapidly evolving with novel antibiotics, probiotics, biological agents, topical anti-androgen drugs, topical vitamin A acid metabolism blockers, antimicrobial peptides, immunotherapy, micro-needling, and micro-needling patches. This article aims to provide a comprehensive review of recent advancements in acne treatment.

Enantiodivergent Cyclization of Racemic Cyclohexadienones via Parallel Kinetic Asymmetric Transformation.

Strategies that fully convert available racemic substrates into valuable enantioenriched products are urgently needed in organic synthesis. Reported herein is the first parallel kinetic asymmetric transformation of racemic cyclohexadienones. Racemic cyclohexadienones are first diastereoselectively converted into a new pair of racemic transient dienol intermediates, which are then parallel protonated by chiral phosphoric acid to deliver two sets of hydroindole products bearing a quaternary stereocenter with generally excellent enantioselectivity.

Curcumin-loaded food-grade nano-silica hybrid material exhibiting improved photodynamic effect and its application for the preservation of small yellow croaker (Larimichthys polyactis).

Two types of curcumin-loaded food-grade nano-silica (F-SiO2) hybrid materials were successfully synthesized using the rotary evaporation method (F-SiO2@Cur) and the adsorption method (Cur@F-SiO2). The microstructure and spectral analyses confirmed that the curcumin in F-SiO2@Cur was loaded within the nanopores in a non-aggregate form rather than being adsorbed onto the surface (Cur@F-SiO2). Additionally, F-SiO2@Cur exhibited remarkable water solubility (1510 ± 50.33 µg/mL) and photostability (a photodegradation ratio of only 59.22 %). Importantly, F-SiO2@Cur obtained a higher capacity for the generation of singlet oxygen (1O2) compared to control groups. Consequently, F-SiO2@Cur-mediated photodynamic inactivation (PDI) group attained the highest score in sensory evaluation and the best color protection effect in PDI experiment of small yellow croaker (Larimichthys polyactis) at 4 °C. Moreover, F-SiO2@Cur could effectively controlled total volatile basic nitrogen (TVB-N) content, pH, and total viable count (TVC), thereby prolonging the shelf life. Therefore, F-SiO2@Cur-mediated PDI is an effective fresh-keeping technology for aquatic products.

Clinical effects of chemical drugs, fecal microbiota transplantation, probiotics, dietary fiber, and acupuncture in the treatment of chronic functional constipation: a systematic review and network meta-analysis.

Currently, there are increasingly diverse treatment modalities for chronic functional constipation (CFC). This study aims to compare the relative efficacy and safety of chemical drugs, fecal microbiota transplantation (FMT), probiotics, dietary fiber, and acupuncture in the treatment of patients with CFC. We searched relevant randomized controlled trials (RCTs) published in five databases up to November 2023. Network meta-analysis (NMA) was carried out using R Studio 4.2.1. Cumulative ranking probability plots, assessed through the surface under the cumulative ranking (SUCRA), were employed to rank the included drugs for various outcome measures. We included a total of 45 RCT studies with 17 118 patients with CFC. From the SUCRA values and NMA results FMT showed the best utility in terms of clinical efficacy, Bristol stool form scale scores, patient assessment of constipation quality of life scores, and the treatment modality with the lowest ranked incidence of adverse effects was electroacupuncture. Subgroup analysis of the chemotherapy group showed that sodium A subgroup analysis of the chemical group showed that sodium picosulfate 10 mg had the highest clinical efficacy. FMT is more promising in the treatment of CFC and may be more effective in combination with the relatively safe treatment of acupuncture.

Genomic investigation of bone tuberculosis highlighted the role of subclinical pulmonary tuberculosis in transmission.

BACKGROUND: Extrapulmonary tuberculosis (EPTB) without symptomatic pulmonary involvement has been thought to be non-transmissible, but EPTB with asymptomatic pulmonary tuberculosis (PTB) could transmit tuberculosis (TB). Genomic investigation of Mycobacterium tuberculosis (Mtb) isolates from EPTB may provide insight into its epidemiological role in TB transmission. METHODS: Between January 2017 and May 2020, 107 Mtb isolates were obtained from surgical drainage of bone TB patients at the Beijing Chest Hospital, and 218 Mtb strains were isolated from PTB cases. These 325 Mtb isolates were whole-genome sequenced to reconstruct a phylogenetic tree, identify transmission clusters, and infer transmission links using a Bayesian approach. Possible subclinical PTB in the bone TB patients was investigated with chest imaging by two independent experts. RESULTS: Among 107 bone TB patients, 10 were in genomic clusters (≤12 SNPs). Phylogenetic analysis suggested that three bone TB patients transmitted the infection to secondary cases, supported by epidemiological investigations. Pulmonary imaging of 44 bone TB patients revealed that 79.5 % (35/44) had radiological abnormalities suggestive of subclinical PTB. CONCLUSIONS: This study provides genomic evidence that bone TB patients without clinically diagnosed PTB can be sources of TB transmission, underscoring the importance of screening for subclinical, transmissible PTB among EPTB cases.

TRIM37 is a primate-specific E3 ligase for Huntingtin and accounts for the striatal degeneration in Huntington's disease.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease characterized by preferential neuronal loss in the striatum. The mechanism underlying striatal selective neurodegeneration remains unclear, making it difficult to develop effective treatments for HD. In the brains of nonhuman primates, we examined the expression of Huntingtin (HTT), the gene responsible for HD. We found that HTT protein is highly expressed in striatal neurons due to its slow degradation in the striatum. We also identified tripartite motif-containing 37 (TRIM37) as a primate-specific protein that interacts with HTT and is selectively reduced in the primate striatum. TRIM37 promotes the ubiquitination and degradation of mutant HTT (mHTT) in vitro and modulates mHTT aggregation in mouse and monkey brains. Our findings suggest that nonhuman primates are crucial for understanding the mechanisms of human diseases such as HD and support TRIM37 as a potential therapeutic target for treating HD.

[Application of self-stabilizing zero-profile three-dimensional printed artificial vertebral bodies for treatment of cervical spondylotic myelopathy].

Objective: To evaluate the safety and effectiveness of applying self-stabilizing zero-profile three-dimensional (3D) printed artificial vertebral bodies in anterior cervical corpectomy and fusion (ACCF) for cervical spondylotic myelopathy. Methods: A retrospective analysis was conducted on 37 patients diagnosed with cervical spondylotic myelopathy who underwent single-level ACCF using either self-stabilizing zero-profile 3D-printed artificial vertebral bodies ( n=15, treatment group) or conventional 3D-printed artificial vertebral bodies with titanium plates ( n=22, control group) between January 2022 and February 2023. There was no significant difference in age, gender, lesion segment, disease duration, and preoperative Japanese Orthopedic Association (JOA) score between the two groups ( P>0.05). Operation time, intraoperative bleeding volume, hospitalization costs, JOA score and improvement rate, incidence of postoperative prosthesis subsidence, and interbody fusion were recorded and compared between the two groups. Results: Compared with the control group, the treatment group had significantly shorter operation time and lower hospitalization costs ( P<0.05); there was no significant difference in intraoperative bleeding volume between the two groups ( P>0.05). All patients were followed up, with a follow-up period of 6-21 months in the treatment group (mean, 13.7 months) and 6-19 months in the control group (mean, 12.7 months). No dysphagia occurred in the treatment group, while 5 cases occurred in the control group, with a significant difference in the incidence of dysphagia between the two groups ( P<0.05). At 12 months after operation, both groups showed improvement in JOA scores compared to preoperative scores, with significant differences ( P<0.05); however, there was no significant difference in the JOA scores and improvement rate between the two groups ( P>0.05). Radiographic examinations showed the interbody fusion in both groups, and the difference in the time of interbody fusion was not significant ( P>0.05). At last follow-up, 2 cases in the treatment group and 3 cases in the control group experienced prosthesis subsidence, with no significant difference in the incidence of prosthesis subsidence ( P>0.05). There was no implant displacement or plate-screw fracture during follow-up. Conclusion: The use of self-stabilizing zero-profile 3D-printed artificial vertebral bodies in the treatment of cervical spondylotic myelopathy not only achieves similar effectiveness to 3D-printed artificial vertebral bodies, but also reduces operation time and the incidence of postoperative dysphagia.

Demographic and clinical factors correlated with clinical outcomes among people with HIV treated by antiretroviral therapy: a retrospective cohort study.

BACKGROUND: As is known, CD4 cell count is a significant parameter predicting HIV progression, opportunistic infections and death in HIV-infected individuals, as well was an important indicator for initiating antiretroviral therapy (ART). In China's National Free Antiretroviral Treatment Program, people with HIV (PWH) on ART can receive a CD4 count test at least once every six months. Importantly, the baseline CD4 count (before ART initiation) is significantly correlated with ART and even prognosis, but the influence of the peak CD4 cell count on ART and/or clinical outcomes is still unknown. METHODS: A retrospective study was conducted among 7965 PWH who received ART from October 2003 to September 2022 at Yunnan Infectious Disease Hospital. Clinical features and laboratory data were collected and analyzed by Chi-square test, univariate and multivariate Cox regression analysis. After elimination of confounding variables, multivariate Cox regression analysis was performed to identify survival-related factors. RESULTS: Of a total of 7965 PWH in the ART treatment cohort who met the inclusion and exclusion criteria, 7939 were finally included in the subsequent analyses. First, it was found that the proportion of clinical variables, including sex, age distribution, interval from diagnosis to ART initiation, marital status, and others, was significantly different between the living and dead groups (P < 0.05). Impressively, significantly more PWH had the higher level of baseline, peak and recent CD4 cell counts in the living group compared to those in the dead group. Due to multicollinearity effect, after excluding confounders, the following factors were found to be significantly associated with mortality by multivariate Cox regression analysis: (1) male sex (hazard ratio (HR) = 1.268 [1.032, 1.559]; P = 0.024); (2) time from HIV confirmation to ART initiation ≥ 6 months (HR = 1.962 [1.631, 2.360]; P < 0.001); (3) peak CD4 cell count: Peak CD4 < 100cells/µL group (HR = 16.093 [12.041, 21.508]; P < 0.001), 100cells/µL ≤ x < 200cells/µL group (HR = 7.904 [6.148, 10.160]; P < 0.001), 200cells/µL ≤ x < 350cells/µL group (HR = 3.166 [2.519, 3.980]; P < 0.001), 350cells/µL ≤ x < 500cells/µL group (HR = 1.668 [1.291, 2.155]; P < 0.001). CONCLUSION: Interestingly, patients in male, time from HIV confirmation to ART initiation ≥ 6 months, or peak CD4 count < 500 cells/µl had inferior clinical outcomes, in other word, a lower peak CD4 cell count significantly increased the risk of death, and peak CD4 cell was independent in predicting the overall survival of PWH. It is important to promote "early diagnosis and treatment of HIV" and regularly monitor CD4 levels in HIV/AIDS to evaluate the efficacy of ART and immune reconstitution, and optimize the ART regimen in time to further reduce the mortality of PWH.

Efficacy of Voluntary Medical Male Circumcision to Prevent HIV Infection Among Men Who Have Sex With Men : A Randomized Controlled Trial.

BACKGROUND: Observational studies suggest that voluntary medical male circumcision (VMMC) may lower HIV risk among men who have sex with men (MSM). A randomized controlled trial (RCT) is needed to confirm this. OBJECTIVE: To assess the efficacy of VMMC in preventing incident HIV infection among MSM. DESIGN: An RCT with up to 12 months of follow-up. (Chinese Clinical Trial Registry: ChiCTR2000039436). SETTING: 8 cities in China. PARTICIPANTS: Uncircumcised, HIV-seronegative men aged 18 to 49 years who self-reported predominantly practicing insertive anal intercourse and had 2 or more male sex partners in the past 6 months. INTERVENTION: VMMC. MEASUREMENTS: Rapid testing for HIV was done at baseline and at 3, 6, 9, and 12 months. Behavioral questionnaires and other tests for sexually transmitted infections were done at baseline, 6 months, and 12 months. The primary outcome was HIV seroconversion using an intention-to-treat analysis. RESULTS: The study enrolled 124 men in the intervention group and 123 in the control group, who contributed 120.7 and 123.1 person-years of observation, respectively. There were 0 seroconversions in the intervention group (0 infections [95% CI, 0.0 to 3.1 infections] per 100 person-years) and 5 seroconversions in the control group (4.1 infections [CI, 1.3 to 9.5 infections] per 100 person-years). The HIV hazard ratio was 0.09 (CI, 0.00 to 0.81; P = 0.029), and the HIV incidence was lower in the intervention group (log-rank P = 0.025). The incidence rates of syphilis, herpes simplex virus type 2, and penile human papillomavirus were not statistically significantly different between the 2 groups. There was no evidence of HIV risk compensation. LIMITATION: Few HIV seroconversions and limited follow-up period. CONCLUSION: Among MSM who predominantly practice insertive anal intercourse, VMMC is efficacious in preventing incident HIV infection; MSM should be included in VMMC guidelines. PRIMARY FUNDING SOURCE: The National Science and Technology Major Project of China.