Voriconazole plus flucytosine is not superior to amphotericin B deoxycholate plus flucytosine as an induction regimen for cryptococcal meningitis treatment.

BACKGROUND: The efficacy and side effects of voriconazole plus 5-flucytosine (Vori + 5-FC) versus amphotericin B deoxycholate plus 5-flucytosine (AmBd + 5-FC) as an induction treatment for cryptococcal meningitis are unknown. METHODS: Forty-seven patients treated with Vori + 5-FC and 92 patients treated with AmBd + 5-FC were included in the current study after propensity score matching (PSM) at a ratio of 1:2. Two-week laboratory test results and 90-day mortality were compared between the two groups. RESULTS: After 2 weeks of induction treatment, the CSF Cryptococcus sterile culture rate was 57.1% in the Vori + 5-FC group and 76.5% in the AmBd + 5-FC group (p = .026). No difference was found in the normalization of CSF indicators (glucose, total protein, intracranial pressure and India ink sterile rate) between the two groups. Both the Vori + 5FC regimen and AmBd + 5-FC regimen obviously decreased haemoglobin concentrations, platelet counts and serum potassium levels (all p ≤ .010). Notably, the Vori + 5FC regimen did not influence serum creatinine levels (p = .263), while AmBd + 5FC increased serum creatinine levels (p = .019) after 2-week induction treatment. The Vori + 5-FC group and AmBd + 5-FC group had similar 90-day cumulative survival rates (89.9% vs. 87.8%, p = .926). CONCLUSION: The Vori + 5-FC regimen was associated with low 2-week CSF sterile culture and was not superior to AmBd + 5-FC as induction therapy in terms of the 90-day cumulative survival rate of CM patients.

Immunogenicity and safety of COVID-19 vaccines among people living with HIV: A systematic review and meta-analysis.

Available data suggest that the immunogenicity of COVID-19 vaccines might decrease in the immunocompromised population, but data on vaccine immunogenicity and safety among people living with HIV (PLWH) are still lacking. The purpose of this meta-analysis is to compare the immunogenicity and safety of COVID-19 vaccines in PLWH with healthy controls. We comprehensively searched the following databases: PubMed, Cochrane Library, and EMBASE. The risk ratio (RR) of seroconversion after the first and second doses of a COVID-19 vaccine was separately pooled using random-effects meta-analysis. Seroconversion rate was lower among PLWH compared with healthy individuals after the first (RR = 0.77, 95% confident interval (CI) 0.64-0.92) and second doses (RR = 0.97, 95%CI 0.95-0.99). The risk of total adverse reactions among PLWH is similar to the risk in the healthy group, after the first (RR = 0.87, 95%CI 0.70-1.10) and second (RR = 0.83, 95%CI 0.65-1.07) doses. This study demonstrates that the immunogenicity and safety of SARS-CoV-2 vaccine in fully vaccinated HIV-infected patients were generally satisfactory. A second dose was related to seroconversion enhancement. Therefore, we considered that a booster dose may provide better seroprotection for PLWH. On the basis of a conventional two-dose regimen for COVID-19 vaccines, the booster dose is very necessary.

Factors Affecting the Prognosis of Patients with Acute Cerebrovascular Occlusion with High National Institutes of Health Stroke Scale Scores Treated with SWIM Technology.

Objective: We aimed to explore the factors affecting the prognosis of patients with acute cerebrovascular occlusion with high National Institutes of Health Stroke Scale (NIHSS) scores treated with the SWIM (Solitaire™ stent retriever-assisted thrombectomy with immediate mechanical aspiration) technique using an intracranial support catheter. Methods: A retrospective analysis was conducted in 72 patients with acute cerebrovascular occlusion who underwent SWIM surgery in the Affiliated Hospital of Chengde Medical University in China between January 2020 and June 2022. The patients were divided into a good prognosis group (Modified Rankin Score [mRS] 0 to 2; n = 30) and a poor prognosis group (mRS score 3 to 6; n = 42) on their mRS scores 3 months after surgery. The THRIVE (TICI, hemorrhage, reocclusion, infarction, vessel, and embolism) score at different time points before and after the SWIM procedure and the postoperative revascularization rate were compared in the 2 NIHSS score groups. Univariate and logistic regression analyses were performed to identify the risk factors that affected the prognosis of patients with acute cerebrovascular occlusion treated with the SWIM procedure. Results: The NIHSS score difference at various time points after SWIM surgery in patients with low to moderate NIHSS scores was significantly higher than in patients with high NIHSS scores (P < .05). The postoperative revascularization rate in patients with high NIHSS scores was 74.36%, which was not significantly different from that in patients with low to moderate scores (84.85%; P > .05). The poor prognosis in patients with acute cerebrovascular occlusion after SWIM surgery was related to age, hypertension, NIHSS score, Glasgow Coma Scale (GCS) score, Essen Stroke Risk Score (ESRS), onset-to-treatment time (OTT) and Alberta Collateral Grading Scale (ACGS) score (P < .05). Logistic regression analysis showed that age, admission NIHSS score and ACGS score were independent risk factors that affected the prognosis in patients with acute cerebrovascular occlusion treated with the SWIM procedure (P < .05). Conclusion: The prognosis in patients with acute cerebrovascular occlusion with high NIHSS scores after SWIM surgery was poor. Advanced age, high NIHSS score and ACGS score were independent risk factors that affected the prognosis in patients with acute cerebrovascular occlusion treated with the SWIM procedure. Overall, incorporating these findings into clinical practice promotes personalized approaches, interdisciplinary collaboration and timely interventions to optimize outcomes in patients undergoing the SWIM procedure for acute cerebrovascular occlusion.

A novel U-shaped relationship between mitochondrial mass and risk of incomplete immune reconstitution in HIV-infected patients on antiviral therapy.

Mitochondrial mass (MM) is considered an essential parameter of the immune system, but the association of MM with incomplete immune reconstitution (IIR) in people living with HIV (PLWH) remains unclear. Here, we tested 2148 blood samples from 1999 PLWH by flow cytometry in China between August 2021 and February 2022. A novel U-shaped relationship, determined by multivariable smooth curve fitting and piecewise-linear mixed-effect model, was observed between the ratio of MM to SD (MM/SD) and IIR, with a threshold cutoff of 2.8. For MM/SD <2.8, per SD increment of MM was independently associated with 30%, 30%, 20%, and 20% decreased risk of CD4+ T-cell counts <500 cells/µL after 4 years of treatment and CD4+ T-cell counts <350 cells/µL after 4, 5, 6 years of treatment, respectively. Our study suggested that increasing MM may indicate the low risk of IIR for PLWH with MM/SD <2.8.

Differences in cytokine and chemokine profiles in cerebrospinal fluid caused by the etiology of cryptococcal meningitis and tuberculous meningitis in HIV patients.

The roles of cytokines and chemokines in HIV-associated cryptococcal meningitis (HCM) and HIV-associated tuberculous meningitis (HTBM) are debatable. In sum, 34 HIV-infected patients without meningitis, 44 HCM patients and 27 HTBM patients were enrolled for study. The concentrations of 22 cytokines/chemokines in cerebrospinal fluid (CSF) were assayed at admission. Principal component analysis (PCA), Pearson's and logistic regression analyses were used to assess the role of cytokines/chemokines in HCM and HTBM. We found the levels of T helper (Th)17, Th1 [interleukin (IL)-12p40, interferon (IFN)-γ, tumor necrosis factor (TNF)-α and TNF-ß and Th2 (IL-2/4/5/6/10)] cytokines were elevated in patients with meningitis compared with those in HIV-infected patients without central nervous system (CNS) infection. Furthermore, the IL-1Ra, IL-12p40, IL-17α and monocyte chemotactic protein-1 (MCP-1) levels were higher in HCM patients, while the IFN-γ, regulated upon activation, normal T cell expressed and secreted (RANTES) and interferon-inducible protein-10 (IP)-10 levels were higher in HTBM patients. Elevated CSF concentrations of IL-17a, TNF-ß, IL-5, IL-12p40 and IL-1Rα were closely related to meningitis, but elevated IP-10, MCP-1, RANTES and IFN-γ levels and CSF white blood cells (WBCs) were protective factors against HCM. Our study suggested that HIV-infected patients with low CSF WBCs have a high risk of HCM. Th1, Th2 and Th17 cytokines/chemokines mediate differences in the pathogenesis of HCM and TBM. Overexpressed proinflammatory MCP-1, RANTES, IFN-γ and IP-10 in CSF are protective factors against HCM but not HTBM.

hsa-miR-191-5p inhibits replication of human immunodeficiency virus type 1 by downregulating the expression of NUP50.

MicroRNAs (miRNAs) are important host molecules involved in human immunodeficiency virus type 1 (HIV-1) infection. Antiretroviral therapy (ART) can affect the miRNA expression profile, but differentially expressed miRNAs still remain to be identified. In this study, we used gene chips to analyze miRNA expression profiles in peripheral blood mononuclear cells from ART-naive HIV-1 patients and those receiving ART, as well as from uninfected individuals. We measured differences in miRNA expression by quantitative polymerase chain reaction (qPCR) in an expanded sample. We found significant differences in the expression of has-miR-191-5p among the three groups (P < 0.05). Furthermore, we showed that hsa-miR-191-5p has an inhibitory effect on HIV-1 replication in cell models in vitro. We identified CCR1 and NUP50 as target molecules of hsa-miR-191-5p and found that hsa-miR-191-5p inhibits the expression of CCR1 and NUP50. Knockdown of NUP50 resulted in significant inhibition of HIV-1 replication. In summary, our research shows that hsa-miR-191-5p expression is reduced in HIV-1-infected patients and acts an inhibitor of HIV-1 infection via a mechanism that may involve targeted repression of NUP50 expression.

Clinical features and Outcomes of Cryptococcemia patients with and without HIV infection.

BACKGROUND: The effects of cryptococcemia on patient outcomes in those with or without HIV remain unclear. METHODS: One hundred and seventy-nine cryptococcemia patients were enrolled in this retrospective study. Demographic characteristics, blood test results and outcome were compared between the two groups. RESULTS: The diagnosis time of Cryptococcus infection was 2.0(0-6.0) days for HIV-infected patients, 5.0 (1.5-8.0) days for HIV-uninfected patients (p = .008), 2.0 (1.0-6.0) days for cryptococcal meningitis (CM) patients and 6.0 (5.0-8.0) days for non-CM patients (p < .001). HIV infection [adjusted odds ratio (AOR) (95% confidence interval): 6.0(2.3-15.9)], CRP < 15 mg/L [AOR:3.7(1.7-8.1)) and haemoglobin > 110 g/L [AOR:2.5(1.2-5.4)] were risk factors for CM development. Forty-six (25.7%) patients died within 90 days. ICU stay [AOR:2.8(1.1-7.1)], hypoalbuminemia [AOR:2.7(1.4-5.3)], no anti-cryptococcal treatment [AOR:4.7(1.9-11.7)] and altered consciousness [AOR:2.4(1.0-5.5)] were independent risk factors for 90-day mortality in all patients. HIV infection did not increase the 90-day mortality of cryptococcemia patients when anti-Cryptococcus treatment was available. Non-Amphotericin B treatment [AOR:3.4(1.0-11.2)] was associated with 90-day mortality in HIV-infected patients, but age ≥ 50.0 years old [AOR:2.7(1.0-2.9)], predisposing disease [AOR:4.1(1.2-14.2)] and altered consciousness [AOR:3.7(1.1-12.9)] were associated with 90-day mortality in HIV-uninfected patients who accepted anti-Cryptococcus treatment. CONCLUSION: HIV infection increased the incidence of CM rather than mortality in cryptococcemia patients. The predictive model was completely divergent in HIV-infected and HIV-uninfected patients, suggesting that novel strategies for diagnosis and treatment algorithms are urgently needed.

Increased expression of BCL11B and its recruited chromatin remodeling factors during highly active antiretroviral therapy synergistically represses the transcription of human immunodeficiency virus type 1 and is associated with residual immune activation.

Persistence of human immunodeficiency virus 1 (HIV-1) latency and residual immune activation remain major barriers to treatment in patients receiving highly active antiretroviral therapy (HAART). In the present study, we investigated the molecular mechanisms of persistent HIV infection and residual immune activation in HAART-treated patients. We showed that the expression level of B-cell CLL/lymphoma 11B (BCL11B) was significantly increased in CD4+T cells from HIV-infected patients undergoing HAART, and this was accompanied by increased expression of BCL11B-associated chromatin modifiers and inflammatory factors in comparison to healthy controls and untreated patients with HIV. In vitro assays showed that BCL11B significantly inhibited HIV-1 long terminal repeat (LTR)-mediated transcription. Knockdown of BCL11B resulted in the activation of HIV latent cells, and dissociation of BCL11B and its related chromatin remodeling factors from the HIV LTR. Our findings suggested that increased expression of BCL11B and its related chromatin modifiers contribute to HIV-1 transcriptional silencing, and alteration of BCL11B levels might lead to abnormal transcription and inflammation.

Unique clinical features of cryptococcal meningitis among Chinese patients without predisposing diseases against patients with predisposing diseases.

The clinical features of cryptococcal meningitis (CM) in patients without predisposing diseases (PD) remain unclear. In sum, 162 of the 167 patients without PD and 162 of the 309 patients with PD were enrolled after propensity score matching. Demographic characteristics, symptoms, blood, and cerebrospinal fluid (CSF) characteristics were compared between the two groups. Kaplan-Meier curves and a Cox proportional hazards model were used to assess the factors associated with 10-week mortality. In total, approximately 35.1% of CM patients were without PD. CM patients without PD had blood profiles of higher white blood cells (WBC) [8.9(6.7-11.0) × 109/l], hemoglobin (128.4 ± 20.9 g/l), platelets [(226.2 ± 64.1) × 109/l], and serum albumin (41.2 ± 5.8 g/l) (all P ≤ .001) and CSF profiles of lower glucose (2.0 ± 1.2 mmol/l), pleocytosis [65.0 (18.0-160.0) × 106/l] and higher total protein [0.9 (0.7-1.4)g/l] (all P < .05). CM patients without PD had lower Cryptococcus culture positivity in CSF (62.5% vs. 74.1%, P = .039) but higher 2-week of CSF culture sterilization rates (69.4% vs. 51.3%, P = .031). The overall 10-week survival rate was 84.7% in patients without PD and 81.1% in patients with PD (Log-rank P = .439). CSF glucose <1.5 mmol/l, CSF fungal burden >20 cells/high power field and treatment lacking amphotericin B had a 3-4 times higher risk of death in patients without PD, whereas serum albumin <35 g/l, CSF glucose < 1.5 mmol/l, and CSF WBC <55 × 106 cell/l were risk factors for patients with PD. CM patients without PD had unique blood and CSF profiles, especially, had lower Cryptococcus culture positivity in CSF, and higher 2-week CSF culture sterilization. Low CSF glucose levels, higher fungal burden, and treatment without amphotericin B were risk factors for 10-week mortality.

Chemokine and Cytokine Cascade Caused by Skewing of the Th1-Th2 Balance Is Associated with High Intracranial Pressure in HIV-Associated Cryptococcal Meningitis.

PURPOSE: Serum cytokines/chemokines play important roles in cryptococcal meningitis, but it is unclear whether cytokines/chemokines in cerebrospinal fluid (CSF) contribute to high intracranial pressure (HICP) in HIV-associated cryptococcal meningitis (HCM). METHODS: CSF cytokines/chemokines were assayed in 17 HIV-uninfected patients, 26 HIV-infected patients without CNS infection, and 39 HCM patients at admission. Principal component analysis and correlation and logistic regression analyses were used to assess the relationships between these parameters. RESULTS: The CSF Th1, Th2, and macrophage cytokines showed an obvious increase in HCM patients as compared to the HIV-uninfected patients and HIV-infected patients without CNS infection. CSF IL-6, GM-CSF, and IL-8 were positively correlated with CSF fungal burden. Serum CD4 count, CSF Th1 cytokines (TNF-α, TNF-ß, IL-12, IL-1ß, IL-12, IL-1α, TNF-α, TNF-ß, IL-12, IL-1γ, and IL-12) and Th2 cytokines (IL-4 and IL-10) contribute to HICP. CONCLUSION: Overall, the present findings indicated that both pro- and anti-inflammatory cytokines of Th1, Th2, and macrophage origin contributed to the development of HCM. Specifically, the chemokine and cytokine cascade caused by skewing of the Th1-Th2 balance and reduced CD4 count were found to be important contributors to HICP. Summary. Our research suggested that chemokine and cytokine cascade caused by skewing of the Th1-Th2 balance in HIV-infected patients played more important role than Cryptococcus numbers and size in CSF on the development of high intracranial pressure in HIV-associated cryptococcal meningitis, providing a new understanding of mechanisms of HCM.

Retinoblastoma binding protein 4 represses HIV-1 long terminal repeat-mediated transcription by recruiting NR2F1 and histone deacetylase.

Human immunodeficiency virus (HIV) transcription is closely associated with chromatin remodeling. Retinoblastoma binding protein 4 (RBBP4) is a histone chaperone implicated in chromatin remodeling. However, the role of RBBP4 in HIV-1 infection and the underlying mechanism remain elusive. In the present study, we showed that RBBP4 plays a negative regulatory role during HIV-1 infection. RBBP4 expression was significantly increased in HIV-1-infected T cells. RBBP4 binds to the HIV-1 long terminal repeat (LTR)， represses HIV-1 LTR-mediated transcription through recruiting nuclear receptor subfamily 2 group F member 1(NR2F1) and histone deacetylase 1 and 2 (HDAC1/2) to HIV-1 LTR, and further controls local histone 3 (H3) deacetylation and chromatin compaction. Furthermore, the occupancy of RBBP4, HDAC1/2, and NR2F1 on LTR in HIV-latent J-lat cells was significantly higher than that in HIV-1-activated cells. In conclusion, our results establish RBBP4 as a new potent antiretroviral factor, which may provide theoretical basis for the treatment of HIV in the future.

Butyrylcholinesterase Levels on Admission Predict Severity and 12-Month Mortality in Hospitalized AIDS Patients.

BACKGROUND: Butyrylcholinesterase (BChE) is synthesized mainly in the liver and an important marker in many infectious/inflammatory diseases, but its role in acquired immunodeficiency syndrome (AIDS) patients is not clear. We wished to ascertain if BChE level is associated with the progression/prognosis of AIDS patients. METHODS: BChE levels (in U/L) were measured in 505 patients; <4500 was defined as "low" and ≥4500 as "normal." Associations between BChE level and CD4 count, WHO stage, body mass index (BMI), C-reactive protein (CRP) level, and duration of hospitalization were assessed. Kaplan-Meier curves and Cox proportional hazards model were used to assess associations between low BChE levels and mortality, after adjustment for age, CD4 count, WHO stage, and laboratory parameters. RESULTS: A total of 129 patients (25.5%) had a lower BChE level. BChE was closely associated with CD4 count, WHO stage, CRP level, and BMI (all P < 0.001). Eighty-four patients (16.6%) died in the first year of follow-up. One-year survival was 64.5 ± 4.5% for patients with low BChE and 87.6 ± 1.8% for those with normal BChE (log-rank, P < 0.001). After adjustment for sex, age, BMI, WHO stage, and CD4 count, as well as serum levels of hemoglobin, sodium, and albumin, the hazard ratio was 1.8 (95% confidence interval, 1.0-3.2) for patients with a low BChE compared with those with a normal BChE (P = 0.035). CONCLUSION: BChE level is associated with HIV/AIDS severity and is an independent risk factor for increased mortality in AIDS patients.

High-throughput sequencing identifies HIV-1-replication- and latency-related miRNAs in CD4+ T cell lines.

MicroRNAs are potent gene expression regulators involved in regulating various biological processes, including host-pathogen interactions. In this study, we used high-throughput sequencing to investigate cellular miRNA signatures related to HIV-1 replication and latent infection in CD4+ T cell lines, which included HIV-1-replicating H9/HTLV-IIIB, HIV-1-latently-infected CEM-Bru cells, and their parental uninfected H9 and CEM-SS cells. Relatively few miRNAs were found to be modulated by HIV-1 replication or latent infection, while the cell-lineage-specific miRNA difference was more pronounced, irrespective of HIV-1 infection. In silico analysis showed that some of our HIV-1 infection-regulated miRNA profiles echoed previous studies, while others were novel. In addition, some of the miRNAs that were differentially expressed between the productively and latently infected cells seemed to participate in shaping the differential infection state. Thus, the newly identified miRNA profiles related to HIV-1 replication and latency provide information about the interplay between HIV-1 and its host.

Identify Potential Regulators in HIV-1 Latency by Joint microRNA and mRNA Analysis.

BACKGROUND/AIMS: The main obstacle to cure HIV infection is the existence of long-lasting latent reservoirs. Many efforts have been made to understand basal mechanisms of HIV-1 latency, in which miRNAs play an important role. However, integrated analysis of miRNA and mRNA expression in HIV-1 latency is lacking. METHODS AND RESULTS: Global miRNA and mRNA expression was determined by microarrays and quantitative reverse transcription PCR in well-characterized HIV-1 latently and actively infected cells, respectively. Interactions of miRNA-mRNA, mRNA-mRNA, and transcription factor-miRNA pairs were assembled into the function network. Our results show that transcription regulation related genes were mostly enriched in HIV-1 latently infected cells. Gene set enrichment analysis revealed nuclear transport related pathways were up-regulated in the latency group. Network dynamic analysis highlighted many gene-pairs sharing the largest changes in different HIV-1 infection state. 83.33% miRNA-target pairs were validated against database, and RHOB related genes constitute the interface between HIV-1 latency and replication state. CONCLUSION: We show for the first time a joint miRNA and mRNA expression profile related to a HIV-1 latency phenotype, outline a dynamic network of potential regulators involving in HIV-1 latency or replication state, and gain new insights into the source messages for affecting HIV-1 latency.

[Association between androgenetic alopecia and metabolic syndrome: a meta-analysis].

OBJECTIVE: To investigate the association between androgenetic alopecia (AGA) and metabolic syndrome (MS). METHODS: Literature on association between AGA and MS up to December 26, 2013 was searched from PubMed, Web of Knowledge, Scopus, Cochrance library, SinoMed, CNKI, Wanfang and VIP databases, and the studies met the eligibility criteria were selected. Meta-analysis was performed by using StataSE 12.0 software to determine the association between AGA and MS. RESULTS: Four case-control studies and 2 cross-sectional studies met the eligibility criteria, including 950 AGA subjects and 3056 control subjects were entered the analysis. Meta-analysis showed that AGA was significantly correlated with MS (OR=2.70, 95%CI: 1.67-4.37, P<0.01). Stratification analysis showed that AGA was significantly correlated with MS in male (OR=2.30, 95%CI: 1.33-3.98, P<0.01) and female subjects (OR=4.61, 95%CI: 1.26-16.94, P<0.05); and AGA was significantly correlated with MS in European (OR=5.29, 95%CI: 2.86-9.80, P<0.01) and Asian subjects (OR=1.92, 95%CI: 1.18-3.10, P<0.01). CONCLUSION: Based on the available data, AGA may be a risk factor for MS, indicating that AGA patients would be a targeting population for screening of metabolic syndrome.

Research progress of biomarkers in the prediction of anti-PD-1/PD-L1 immunotherapeutic efficiency in lung cancer.

Currently, anti-PD-1/PD-L1 immunotherapy using immune checkpoint inhibitors is widely used in the treatment of multiple cancer types including lung cancer, which is a leading cause of cancer death in the world. However, only a limited proportion of lung cancer patients will benefit from anti-PD-1/PD-L1 therapy. Therefore, it is of importance to predict the response to immunotherapy for the precision treatment of patients. Although the expression of PD-L1 and tumor mutation burden (TMB) are commonly used to predict the clinical response of anti-PD-1/PD-L1 therapy, other factors such as tumor-specific genes, dMMR/MSI, and gut microbiome are also promising predictors for immunotherapy in lung cancer. Furthermore, invasive peripheral blood biomarkers including blood DNA-related biomarkers (e.g., ctDNA and bTMB), blood cell-related biomarkers (e.g., immune cells and TCR), and other blood-related biomarkers (e.g., soluble PD-L1 and cytokines) were utilized to predict the immunotherapeutic response. In this review, the current achievements of anti-PD-1/PD-L1 therapy and the potential biomarkers for the prediction of anti-PD-1/PD-L1 immunotherapy in lung cancer treatment were summarized and discussed.

The central nervous system is a potential reservoir and possible origin of drug resistance in hepatitis B infection.

Background: The significance of hepatitis B virus (HBV) in cerebrospinal fluid (CSF) is unclear. Methods: Synchronous serum and CSF samples were collected from 13 patients. HBV DNA, full-length genome, quasispecies, phylogenetic tree, compartmentalization and mutation of the reverse transcriptase (RT) region were performed based on PCR and sequencing methods. Results: HBV DNA was detected in the CSF of 3 antiviral-naïve individuals and 1 individual after successful antiviral therapy. Complete full-length HBV genomes were isolated from the CSF of 5 individuals, including 2 with undetectable serum HBV DNA. Ten individuals exhibited distinct CSF-serum quasispecies, 8 harbored independent CSF-serum genetic compartmentalization and phylogenetic trees, and 5 lamivudine/entecavir-associated resistance mutations only in the CSF. The frequencies of rtL180M and rtM204I/V mutations in both serum and CSF were higher in HIV-HBV-coinfected individuals than in the HBV-monoinfected ones (serum: rtL180M: 3.9% vs. 0, P = 0.004; rtM204I/V: 21.3% vs. 0, P < 0.001; CSF: rtL180M: 7.6% vs. 0, P = 0.026; rtM204I/V 7.6% vs. 1.6%, P = 0.097). Conclusion: CSF is a potential HBV reservoir, and HBV in CSF harbors distinct evolution and mutation characteristics from those in serum. HIV infection increases the possibility of HBV rtL180M and rtM204I/V mutations in both serum and CSF.

Epigenetic regulation in premature ovarian failure: A literature review.

Premature ovarian failure (POF), or premature ovarian insufficiency (POI), is a multifactorial and heterogeneous disease characterized by amenorrhea, decreased estrogen levels and increased female gonadotropin levels. The incidence of POF is increasing annually, and POF has become one of the main causes of infertility in women of childbearing age. The etiology and pathogenesis of POF are complex and have not yet been clearly elucidated. In addition to genetic factors, an increasing number of studies have revealed that epigenetic changes play an important role in the occurrence and development of POF. However, we found that very few papers have summarized epigenetic variations in POF, and a systematic analysis of this topic is therefore necessary. In this article, by reviewing and analyzing the most relevant literature in this research field, we expound on the relationship between DNA methylation, histone modification and non-coding RNA expression and the development of POF. We also analyzed how environmental factors affect POF through epigenetic modulation. Additionally, we discuss potential epigenetic biomarkers and epigenetic treatment targets for POF. We anticipate that our paper may provide new therapeutic clues for improving ovarian function and maintaining fertility in POF patients.

Metagenomic Next-Generation Sequencing for the Diagnosis of Suspected Opportunistic Infections in People Living with HIV.

Objective: The diagnosis of suspected opportunistic infections in HIV patients is challenging due to the wide range of potential causes. This study used mNGS to analyse specimens of suspected opportunistic infections in HIV patients from a single centre to explore this method's applicability as a diagnostic tool compared to that of CMTs. Methods: We retrospectively investigated 46 suspected opportunistic infections in people living with HIV(PLWH) Hospitalized at Hangzhou Xixi hospital from January 2020 to August 2021. In total, we collected 49 samples (3 patients provided 2 samples) and sent them out for mNGS. Results: mNGS had a better detection rate for fungi and nontuberculous mycobacteria than that of CMTs. Specifically, the diagnostic detection rate of fungi (11 vs 19, P<0.05) and nontuberculous mycobacteria (1 vs 6, p<0.05) was significantly higher; there was no difference in detection rate for other pathogens (bacteria, Mycobacterium tuberculosis, or viruses). The sensitivity of mNGS was 90.91%, 50%, 0%, 100%, and 100% for detecting fungi, bacteria, Mycobacterium tuberculosis, nontuberculous mycobacteria, and viruses, respectively; the corresponding specificities were 74.29%, 97.73%, 86.36%, 86.67%, and 91.11%. Conclusion: mNGS technology provides an alternative and promising method of identifying suspected opportunistic infections in PLWH. Thus, the best diagnosis strategy may be using a combination of mNGS and CMTs.

Comparing Noninvasive Predictors of Neurosyphilis Among Syphilis Patients With and Without HIV Co-Infection Based on the Real-World Diagnostic Criteria: A Single-Center, Retrospective Cohort Study in China.

Diagnosis of neurosyphilis is currently based on the cerebrospinal fluid (CSF) assessments and CSF-Venereal Disease Research Laboratory (CSF-VDRL) is the traditional "gold standard." In the real world, CSF assessments and CSF-VDRL are not always available. This study aimed to identify noninvasive predictors of neurosyphilis based on real-world clinical parameters and diagnostic criteria in populations with different HIV status. In this retrospective cohort study, syphilis patients with different HIV statuses hospitalized for neurosyphilis screening were retrospectively recruited at an infectious disease hospital. Neurosyphilis was defined by real-world diagnostic criteria. Logistic regression and receiver operating characteristic curve analysis were used to investigate and evaluate predictors of neurosyphilis. In total, 528 patients were enrolled, including 143 syphilis patients without HIV infection and 385 HIV/syphilis-co-infected patients. One hundred twelve and 304 neurosyphilis patients were identified in the HIV-negative and HIV-positive groups, respectively. A high serum toluidine red unheated serum test (TRUST) titer was a robust predictor of neurosyphilis in all participants. An age ≥50 years old [adjusted odds ratio (aOR) = 5.062, 95% confidence interval (CI), 1.449-17.680] in the HIV-negative group and CD4+ T cell count <330/µL (<300 as reference, aOR = 0.552, 95% CI, 0.315-0.966) in the HIV-positive group were predictors of asymptomatic neurosyphilis. In real-world situations, for asymptomatic syphilis patients, relatively old age and a high serum TRUST titer in HIV-negative populations, and CD4+ T cells <330/µL and/or serum TRUST titer >1:64 in HIV-positive populations might predict neurosyphilis.