Management for persistent HPV infection and cervical lesions among women infected with HIV: a retrospective observational cohort study.

BACKGROUND: Early diagnosis and treatment of HPV persistent infection and cervical intraepithelial neoplasia, which have yet to be thoroughly characterized in Guangxi, Southwestern China, are the key preventative measures for the development of cervical cancer in women, particularly in HIV-infected women. METHODS: A retrospective study of 181 patients with HPV infection or cervical intraepithelial neoplasia who received surgical excision of lesions and were prospectively enrolled at the Fourth People's Hospital of Nanning between January 2018 and February 2023 was performed. HPV-infected patients were divided into two subgroups: HIV-infected and HIV/HPV-coinfected patients and compare differences between these groups. RESULTS: HPV16, 18, 52, and 58 were the most prevalent HPV genotypes. High-risk HPV was significantly co-infected with multiple genotypes (P = 0.0332). HIV-infected women were predisposed to HPV infection (P < 0.0001), and the development of cervical cancer at a young age (P = 0.0336) compared to HIV-uninfected women and the loop electrosurgical excision procedure (P = 0.0480) is preferred for the treatment. CONCLUSIONS: HIV infection may increase HPV prevalence and lead to cervical cancer development at a young age. The loop electrosurgical excision procedure is an efficient evaluation and treatment strategy for HIV-infected women suffering from cervical intraepithelial neoplasia.

Genomic epidemiology reveals early transmission of SARS-CoV-2 and mutational dynamics in Nanning, China.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are a fatal pathogen resulting in substantial morbidity and mortality, and posing a great threat to human health with epidemics and pandemics. METHODS: Next-generation sequencing (NGS) was performed to investigate the SARS-CoV-2 genomic characterization. Phylogenetic analysis of SARS-CoV-2 genomes was used to probe the evolutionary. Homology protein structure modelling was done to explore potential effect of the mutations. RESULTS: The eighty genome sequences of SARS-CoV-2 obtained from the thirty-nine patients with COVID-19. A novel variant with mutation H625R concomitant with S50L in spike glycoprotein had been identified. Phylogenetic analysis revealed that SARS-CoV-2 variants belong to several distinct lineages. Homology modelling indicated that variant with mutation H625R and S50L increases flexibility of S1 subunit. CONCLUSIONS: SARS-CoV-2 genomes are constantly evolving by accumulation of point mutations. The amino acid H625R in combination with S50L may have a significant impact on the interaction between spike glycoprotein and ACE2.

Clinical utilization of multiple antibodies of Mycobacterium tuberculosis for serodiagnosis evaluation of tuberculosis: a retrospective observational cohort study.

OBJECTIVES: We aimed to investigate clinical uncertainties by characterizing the accuracy and utility of commercially available antibodies of Mycobacterium tuberculosis in the diagnostic assessment of suspected tuberculosis in high-burden countries. METHODS: We conducted a retrospective, descriptive, cohort study among participants aged ≥ 18 years with suspected tuberculosis in Nanning, Guangxi, and China. Participants were tested for M. tuberculosis infection using commercially available antibodies against Mycobacterum tuberculosis. Specificity, sensitivity, negative and positive predictive values, and negative and positive likelihood ratios of the tests were determined. Sputum specimens and bronchoalveolar lavage fluid were sent for mycobacterial culture, Xpert MTB/RIF assay, and cell-free M. tuberculosis DNA or RNA assay. Blood samples were used for IGRAs, T-cell counts (CD3 + CD4+ and CD3 + CD8+), and antibodies to tuberculosis test. RESULTS: Of the 1857 participants enrolled in this study, 1772 were included in the analyses, among which, 1311 were diagnosed with active tuberculosis. The specificity of antibody against 16kD for active tuberculosis was 92.7% (95% confidence interval [CI]: 89.3-95.4) with a positive likelihood ratio for active tuberculosis cases of 3.1 (95% CI: 2.1-4.7), which was higher than that of antibody to Rv1636 (90.5% [95% CI: 86.6-93.5]), antibody to 38kD (89.5% [95% CI: 85.5-92.7]), antibody against CFP-10 (82.6% [95% CI: 77.9-86.7]), and antibody against LAM (79.3% [95% CI: 74.3-83.7]). Sensitivity ranged from 15.8% (95% CI: 13.9-17.9) for antibody against Rv1636 to 32.9% (95% CI: 30.4-35.6) for antibody to LAM. CONCLUSIONS: Commercially available antibodies against to Mycobacterium tuberculosis do not have sufficient sensitivity for the diagnostic evaluation of active tuberculosis. However, antibody against Rv1636 and 16kD may have sufficiently high specificities, high positive likelihood ratios, and correspondingly high positive predictive values to facilitate the rule-in of active tuberculosis.

Existing M. tuberculosis antigens do achieve a limited sensitivity and negative predictive value to rule out a diagnosis of tuberculosis.M. tuberculosis antigens may help to rule in a diagnosis of active or latent tuberculosis in clinical setting among the high burden tuberculosis countries.This study is the largest retrospective, descriptive, cohort study to evaluate the clinical utilization of existing M. tuberculosis antigens integrating M. tuberculosis immunogens in patients with suspected active tuberculosis in high-burden country.

Clinical characteristics of platelet-mediated killing circulating parasite of major human malaria.

OBJECTIVE: Microscopy was used to characterize platelet-Plasmodium-infected erythrocyte interactions in patients infected with Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale or Plasmodium malariae, and to investigate the relationship between platelet-associated parasite killing and parasite clearance. METHODS: Data from 244 malaria patients admitted to the Fourth People's Hospital of Nanning between 1 January 2011 and 30 September 2022, and 45 healthy controls, were collected prospectively and assessed retrospectively. Characteristics of platelet-erythrocyte interactions were visualized by microscopy, and blood cell count and clinical profiles of these participants were obtained from the electronic medical records. ANOVA, contingency tables and Cox proportional hazards regression models were used to do statistical analysis on the subgroups. RESULTS: Platelet enlargement and minor pseudopodia development were observed. Platelets were found directly attaching to parasitized erythrocytes by all Plasmodium species studied, especially mature stages, and lysis of parasitized erythrocytes was connected to platelet-mediated cytolysis. Platelet counts were correlated inversely with parasitaemia and duration of parasite clearance. Artemisinin combination therapy was more effective than artemisinin alone in clearing Plasmodium in patients with thrombocytopenia. CONCLUSIONS: Platelet-parasitized erythrocytes cell-to-cell contacts initiated platelet-associated parasite killing and helped to limit Plasmodium infection in cases of human malaria. The weakening platelet-associated parasite killing effects could be counteracted by artemisinin combination therapy in patients with thrombocytopenia.

HighlightsPlatelets directly attaching to parasitized erythrocytes.Platelets correlated inversely with parasitaemia and duration of parasite clearance.Artemisinin combination therapy was more effective than artemisinin alone.Weakening killing effects may counteract by artemisinin combination therapy.

Biochemical characteristics of patients with imported malaria.

Objectives: This study aimed to investigate the clinical and biochemical profiles of patients with imported malaria infection between 1 January 2011 and 30 April 2022 and admitted to the Fourth People's Hospital of Nanning. Methods: This cohort study enrolled 170 patients with conformed imported malaria infection. The clinical and biochemical profiles of these participants were analyzed with malaria parasite clearance, and signs and symptoms related to malaria disappearance were defined as the primary outcome. A multivariable logistic regression model was used to evaluate the odds ratios (ORs) with 95% confidence intervals (CIs) for cerebral malaria. The Cox model was used to estimate the hazard ratios (HRs) with 95% CIs for parasite clearance. Results: Adenosine deaminase and parasitemia were found to be independent risk factors for severe malaria in patients with imported malaria (OR = 1.0088, 95% CI: 1.0010-1.0167, p = 0.0272 and OR = 2.0700, 95% CI: 1.2584-3.4050, p = 0.0042, respectively). A 0.5-standard deviation (SD) increase of variation for urea (HR = 0.6714, 95% CI: 0.4911-0.9180), a 0.5-SD increase of variation for creatinine (HR = 0.4566, 95% CI: 0.2762-0.7548), a 0.25-SD increase of variation for albumin (HR = 0.4947, 95% CI: 0.3197-0.7653), a 0.25-SD increase of variation for hydroxybutyrate dehydrogenase (HR = 0.6129, 95% CI: 0.3995-0.9402), and a 1.0-SD increase of variation for ferritin (HR = 0.5887, 95% CI: 0.3799-0.9125) were associated with a higher risk for increased parasite clearance duration than a low-level change. Conclusions: Aspartate aminotransferase, urea, creatinine, albumin, hydroxybutyrate dehydrogenase, and ferritin are useful biochemical indicators in routine clinical practice to evaluate prognosis for imported malaria.

Viral Dynamic Surveillance in COVID-19 Patients: A Cohort Study.

Background: Coronavirus disease 2019 (COVID-19) is a potentially fatal pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially those of novel SARS-CoV-2 variants and infection has affected over 700 million people globally. Methods: This retrospective, descriptive study included 118 patients admitted with SARS-CoV-2 infection as confirmed by real-time reverse transcription polymerase chain reaction. Results: The median duration of detectable SARS-CoV-2 infection in patients with high ALT, AST, and PLT/LYMPH, or low CD4+, CD8+, and PLT/MONO was considerably longer. In the risk factor model, multivariate analysis was performed for the estimation of ALT (HR, 0.54; 95% CI, 0.36-0.81), AST (HR, 0.56; 95% CI, 0.34-0.93), CD4+ (HR,0.77; 95% CI, 0.48-1.24), CD8+ (HR,0.64; 95% CI, 0.37-1.11), PLT/LYMPH (HR, 1.16; 95% CI, 0.76-1.77), and PLT/MONO (HR, 0.64; 95% CI, 0.43-0.94). Conclusions: The longer viral RNA duration was associated with a higher International Prognostic Index score (p = 0.0013), demonstrating for the first time that multivariate features of the bioindicators closely associated with SARS-CoV-2-infected patients clear the virus.

Advanced platelet-rich fibrin promotes the paracrine function and proliferation of adipose-derived stem cells and contributes to micro-autologous fat transplantation by modulating HIF-1α and VEGF.

Background: The micro-autologous fat transplantation (MAFT) technique has demonstrated its feasibility in multiple medical fields, such as facial rejuvenation. Advanced platelet-rich fibrin (APRF), an autologous platelet concentrated on a fibrin membrane without added external factors, has shown significant potential for tissue restoration. However, the role of APRF in the modulation of MAFT remains unclear. Here, we aimed to explore the effect of APRF on MAFT. Methods: Adipose-derived stem cells (ASCs) were isolated from human gastric subcutaneous fat and treated with APRF. ELISA assays measured cytokines. The proliferation of ASCs was analyzed by CCK-8 assays. The levels of hypoxia-inducible factor-1α (HIF-1α), heat shock protein 70 (HSP70), insulin like growth factor 2 (IGF-2), interleukin-6 (IL-6), interleukin-8 (IL-8), and vascular endothelial growth factor (VEGF) were measured by ELISA assays, quantitative reverse transcription-PCR (qRT-PCR), and Western blot analysis. The effect of APRF/HIF-1α/VEGF on MAFT in vivo was analyzed in Balb/c nude mice. The BALB/c mice were subcutaneously co-transplanted with fat, APRF, and control shRNA, HIF-1α shRNA, or VEGF shRNA into the dorsal area. The serum and protein levels of the above cytokines were analyzed by ELISA assays and Western blot analysis. Lipid accumulation was measured by Oil Red O staining. The expression of CD34 was assessed by immunohistochemical staining. Results: APRF continuously secreted multiple cytokines, including epidermal growth factor (EGF), FGF-2, insulin like growth factor 1 (IGF-1), interleukin-1beta (IL-1ß), interleukin-4 (IL-4), platelet-derived growth factor alpha polypeptide b (PDGF-AB), platelet-derived growth factor beta polypeptide b (PDGF-BB), transforming growth factor-beta (TGF-ß), and VEGF. APRF was able to promote the proliferation of ASCs. APRF dose-dependently activated the expression of HIF-1α, HSP70, IGF-2, IL-6, IL-8, and VEGF in ASCs. APRF regulated the paracrine function of ASCs by modulating HIF-1α and VEGF. APRF increased the survival of MAFT by modulating HIF-1α and VEGF in vivo. Conclusions: APRF promotes the paracrine function and proliferation of ASCs and contributes to MAFT by modulating HIF-1α and VEGF. Our findings provide new insights into the mechanism by which APRF regulates MAFT.

The Effects of Hedgehog Signaling Pathway on the Proliferation and Apoptosis of Melanoma Cells.

BACKGROUND: Studies have found that the abnormality of the Hedgehog signaling pathway is related to the occurrence and development of a variety of tumors, but the effect of this signaling pathway on melanoma cells is still unclear. METHODS: This study aimed to discuss the effect of Hedgehog signaling pathway on the proliferation and apoptosis of human malignant melanoma A375 cells and explore its possible mechanism in the proliferation and apoptosis of melanoma cells. Different concentrations of Hedgehog signaling pathway inhibitor cyclopamine (5, 10, 20 and 40 µM) were used to treat human melanoma A375 cells for 24, 48, and 72 h, and set a blank control group (0 µM). Trypan blue cell counting method was used to detect cell viability. MTT method was used to detect the inhibition rate of cell proliferation. Transwell was used to detect cell invasion, and flow cytometry was used to detect cell apoptosis. RESULTS: Through the trypan blue cell counting method and MTT experiment, it was found that the Hedgehog signaling pathway inhibitor cyclopamine has an inhibitory effect on the proliferation and viability of melanoma A375 cells (P < 0.05), and the proliferation inhibitory effect is enhanced with prolonged action time in a dose- and time-dependent manner. Transwell experiment showed that compared with the blank control group, the invasion and migration ability of the treated melanoma A375 cells are significantly reduced, and the difference is statistically significant (P < 0.05). Cell apoptosis experiment showed that compared with the blank control group, the apoptosis rate of A375 cells is significantly higher after treated by 40 µM cyclopamine for 24 h, and the difference is statistically significant (P < 0.05). Gli1 and Bcl-2 protein are highly expressed in melanoma A375 cells, and their expressions show a downward trend (P < 0.05) after being treated by cyclopamine. CONCLUSION: Cyclopamine inhibits cell proliferation and induces cell apoptosis by downregulating Gli1. Hedgehog signaling pathway can be used as a new target for the treatment of malignant melanoma, and multiple measures can be used to inhibit the signaling pathway to achieve a therapeutic effect.