The immune reconstitution after initiation of highly active antiretroviral therapy (HAART) among HIV-infected individuals substantially affects patients’ prognosis. However, the dynamic characteristics and predictors of reconstitution outcome remain unclear. In this study, the HIV/AIDS patients with sustained virological suppression (viral load < 50 copies/ml) after HAART were enrolled. The patients were subgrouped into immunological non-responders (INRs) (< 200 cells/μl), immunological inadequate responders (IIRs) (200 ~ 500 cells/μl) and immunological responders (IRs) (> 500 cells/μl) according to the CD4 cell count after two-year HAART. The immune reconstitution data based on the CD4+ and CD8+ cell counts with 8-year follow-up were collected for analysis. The CD4+ cell counts in the immunological responders (IRs) were significantly higher than in the immunological non-responders (INRs) and immunological inadequate responders (IIRs) (P < 0.001). The overall CD4+ cell count and CD4/CD8 ratio in the IRs increased faster than the IIRs and INRs. The CD4+ cell count growth at 0.5 year and 1 year after HAART in the IRs was significantly higher than the IIRs and INRs. The ROC curve demonstrated that 1 year CD4+ cell count had the highest predictive value, with the best cut-off value of 188 cells/μl, the predictive sensitivity was 81.0%, the predictive specificity was 85.2%, false positive rate was 14.8%, false negative rate was 19.0%, positive predictive value (IR) was 63.0%, negative predictive value (INR) was 93.5%. Taken together, our findings suggest that early initiation of HAART can reduce the immune reconstitution failure. The combination of baseline CD4+ cell count and baseline CD4/CD8 ratio may serve as a valid predictor of immune reconstitution prognosis after HAART.

Non-melanoma skin cancers (NMSCs), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), have shown significant global increases in burden, particularly among older adults, with wide regional, gender, and socio-demographic disparities. However, no previous study has comprehensively analyzed these trends using integrated multi-model approaches. A comprehensive analysis of global non-melanoma skin cancer (NMSC) data from 1990 to 2021 was performed, including trend analysis, frontier analysis, and decomposition analysis to compare the burden of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) across regions, genders, and socio-demographic groups. Temporal trends in incidence, prevalence, and disability-adjusted life years (DALYs) were identified using epidemiological decomposition techniques. To forecast future disease burden from 2022 to 2050, eight machine learning models (Prophet, ARIMA, TBATS, ElasticNet, ETS, VAR, HoltWinters, and Theta) were applied, and the most optimal predictive models for BCC and SCC were selected based on performance metrics. From 1990 to 2021, the global burden of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) among older adults increased substantially. The incidence of BCC rose by 291.85%, with an age-standardized rate (ASR) increase of 62.79%, while SCC incidence increased by 322.77%, with a 67.42% rise in ASR. High Socio-Demographic Index (SDI) regions showed the largest ASR increases for BCC (102.73%) and SCC (107.31%), whereas low SDI regions demonstrated more modest changes or declines (BCC: – 2.86%, SCC: – 3.08%). Gender disparities were observed, with males accounting for 56.47% of SCC cases globally. Decomposition analysis revealed that population growth was the primary driver of increased NMSC burden, contributing 62.52-83.92% of the rise in incidence and DALYs, while epidemiological changes accounted for up to 52.2% in high SDI regions. Frontier analysis highlighted significant regional disparities, with high SDI regions, such as North America, exhibiting the highest age-standardized incidence rates for BCC (2,923.22 per 100,000) and SCC (1,805.33 per 100,000), whereas low SDI regions, like sub-Saharan Africa, showed minimal burdens near frontier values. Finally, disease burden forecasting for 2022 to 2050 using machine learning models predicted a slight decrease in the incidence rates of BCC (from 314.00 to 308.73 per 100,000) and SCC (from 157.67 to 148.16 per 100,000). Disability-adjusted life years (DALYs) are projected to decline for SCC (79.32 to 75.20 per 100,000) but increase slightly for BCC (0.136 to 0.151 per 100,000). These projections underscore the need for tailored strategies to address the growing burden of NMSC. The growing global burden of NMSCs, particularly in high SDI regions and among older adults, underscores the urgent need for tailored prevention, resource allocation, and management strategies. Machine learning-based approaches provide robust insights into global trends and future challenges for BCC and SCC.

Talaromycosis caused by Talaromyces marneffei infection is a fatal systemic mycosis in immunosuppressed individuals such as patients with acquired immune deficiency syndrome (AIDS). Cytokines and immunocytes play a central role against fungus infection. However, how the host immune system respond to infection and treatment has not been reported to date. Fourty-one Talaromyces marneffei co-infected AIDS patients were followed up, their immunocytes and cytokine profiles were obtained at different antifungal treatment stages, and data on clinical features and laboratory examinations were collected. Correlation analysis was used to identify factors associated with host immunity against Talaromyces marneffei infection in AIDS patients. Common signs of the patients were lymphadenopathy, hepatomegaly, and splenomegaly. CD4⁺ T cells were extremely low in all enrolled patients. Moreover, significant increases of pro-inflammatory cytokines (IL-12, IL-17A, TNF-α, IFN-γ, IL-18, and IL-1β), anti-inflammatory cytokines (IL-10), and chemokines (IP-10) were observed in talaromycosis before treatment (P < 0.05), comparing to both AIDS patients and healthy controls. The cytokines IL-6, IL-8, TNF-α, IL-18, IL-17A, IL-7, IP-10, and IL-1β reached peak levels three days after initial antifungal therapy, and then gradually decreased. The symptoms of the patients gradually decreased. Furthermore, patients who died showed the highest levels of IL-6, TNF-α, IL-8, IL-1β, and IP-10, which were 1.4- to 164-fold higher than in surviving patients. Our findings indicate that innate immune cell-derived cytokines are critical for host defense against AIDS-associated Talaromyces marneffei infection; furthermore, excessive inflammatory cytokines are associated with poor outcomes.

Introduction Atopic dermatitis (AD) is one of the most common skin diseases, and it may be associated with skin cancer risk. However, there is a controversy pertaining to whether it implies a greater or decreased risk of skin cancers. We aimed to study the relationship between AD and skin cancer risk. Methods PubMed and Embase databases from their inception to 4 August 2021 were systematically searched. Results We evaluated 16 studies involving a total of 9,638,093 participants examining the contribution of AD to skin cancers. Random-effects model was applied to estimate the overall effect sizes. The pooled analysis of 16 studies indicated that AD was significantly associated with an overall increased risk of skin cancer. Subgroup pooled analyses showed that AD was statistically associated with an increased risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). With regard to cohort study, AD was statistically associated with an increased risk of nonmelanoma skin cancer (NMSC), BCC, and SCC, but not melanoma risk. Sensitivity analysis revealed that excluding each study in turn did not alter the overall combined results. No publication bias existed among the studies. Conclusion It can be concluded that AD is associated with risk of skin cancers; however, this association still needs to be verified in well-designed, worldwide trials (especially prospective, non-Western studies). The mechanism of AD leading to skin cancer is not clear, and further research is needed to explore the possibility of a potential pathogenesis.

Background: Yunnan has the highest rates of HIV in China. Other treatable sexually transmitted infections (STIs) are associated with accelerated HIV transmission and poor ART outcomes, but are only diagnosed by syndromic algorithms. Methods: We recruited 406 HIV-positive participants for a cross-sectional study (204 ART-naive and 202 receiving ART). Blood samples and first-voided urine samples were collected. Real-time polymerase chain reaction methods were used for diagnosing Chlamydia trachomatis (CT), Neisseria gonorrhea (NG) and Mycoplasma genitalium (MG). Syphilis and herpes simplex virus type 2 (HSV-2) tests were also performed. Results: Among the 406 participants, the overall prevalence of STIs was 47.0% and 45.1% in ART-naive individuals and 49.0% in individuals receiving ART, respectively. The testing frequencies were 11.6% (11.8% vs. 11.4%), 33.2% (29.4% vs. 37.1%), 3.2% (3.4% vs. 3.0%), 2.0% (3.4% vs. 0.5%) and 4.7% (6.4% vs. 3.0%) for active syphilis, HSV-2, CT, NG and MG, respectively. The percentage of multiple infections in both groups was 10.8% (22/204) in ART-naive participants and 9.9% (20/202) in participants receiving ART. Female sex, an age between 18 and 35 years, ever injecting drugs, homosexual or bisexual status, HIV/HBV coinfection, and not receiving ART were identified as risk factors. Self-reported asymptomatic patients were not eliminated from having a laboratory-diagnosed STI. Conclusions: The STI prevalence was 47.0% (45.1% vs. 49.0%), and HSV-2, syphilis and MG were the most common STIs in HIV-infected individuals. We found a high prevalence (6.4%) of MG in ART-naive individuals. HIV-positive individuals tend to neglect or hide their genital tract discomfort; thus, we suggest strengthening STI joint screening and treatment services among HIV-infected individuals regardless of whether they describe genital tract discomfort.

Background: Psoriasis is a common inflammatory skin disease that has a great impact on patients’ physical and mental health. However, the causes and underlying molecular mechanisms of psoriasis are still largely unknown.Methods: The expression profiles of genes from psoriatic lesion samples and skin samples from healthy controls were integrated via the sva software package, and differentially expressed genes (DEGs) between psoriasis and healthy skin were screened by the limma package. Furthermore, GO and KEGG pathway enrichments for the DEGs were performed using the Clusterprofiler package. Protein–protein interaction (PPI) networks for the DEGs were then constructed to identify hub genes. scGESA analysis was performed on a single-cell RNA sequencing dataset via irGSEA. In order to find the cytokines correlated with the hub genes expression, single cell weighted gene co-expression network analyses (scWGCNA) were utilized to build a gene co-expression network. Furthermore, the featured genes of psoriasis found in suprabasal keratinocytes were intersected with hub genes. We then analyzed the expression of the intersection genes and cytokines in the integrated dataset. After that, we used other datasets to reveal the changes in the intersection genes’ expression levels during biological therapy. The relationship between intersection genes and PASI scores was also explored.Results: We identified 148 DEGs between psoriatic and healthy samples. GO and KEGG pathway enrichment analysis suggested that DEGs are mainly involved in the defense response to other organisms. The PPI network showed that 11 antiviral proteins (AVPs) were hub genes. scGSEA analysis in the single-cell transcriptome dataset showed that those hub genes are highly expressed in keratinocytes, especially in suprabasal keratinocytes. ISG15, MX1, IFI44L, and IFI27 were the characteristic genes of psoriasis in suprabasal keratinocytes. scWGCNA showed that three cytokines—IL36G, MIF, and IL17RA—were co-expressed in the turquoise module. Only interleukin-36 gamma (IL36G) was positively correlated with AVPs in the integrated dataset. IL36G and AVPs were found co-expressed in a substantial number of suprabasal keratinocytes. Furthermore, we found that the expression levels of IL36G and the 4 AVPs showed positive correlation with PASI score in patients with psoriasis, and that these levels decreased significantly during treatment with biological therapies, but not with methotrexate.Conclusion: IL36G and antiviral proteins may be closely related with the pathogenesis of psoriasis, and they may represent new candidate molecular markers for the occurrence and severity of psoriasis.