Epidemiological study of human papillomavirus infection in 105,679 women in Wuhan, China.

BACKGROUND: Quality assessment of the prevalence and distribution of human papillomavirus (HPV) genotypes could support additional targeted HPV vaccinations. However, the characteristics of HPV infection in Wuhan city are limited in the past decade. We aimed to assess the epidemiology of HPV infection among women and provide a reference for the prevention and treatment of cervical cancer in this region. METHODS: A retrospective study employing 105,679 women attending Wuhan Medical and Health Center for Women and Children for cervical cancer screening from January 2015 to December 2022 was conducted. The HPV genotype was detected by polymerase chain reaction (PCR) and diversion hybridization. The overall incidence and age-specific type distribution of HPV infection and the relationship between HPV infection and cervical cytology were analyzed. RESULTS: The overall HPV infection rate was 16.87% in Wuhan city, and the prevalence rates of high-risk, low-risk and mixed high- and low-risk HPV infections were 13.64%, 1.77% and 1.46%, respectively. The five most prevalent genotypes were HPV52 (4.24%), HPV58 (2.42%), HPV16 (2.34%), HPV53 (1.87%), and HPV39 (1.66%). The prevalence of HPV in women exhibited a "two-peak" pattern, the peaks of which were observed in the < 21 years group (37.4%) and the 61-65 years group (41.72%). Logistic regression analysis revealed no significant difference in the rate of high-grade lesion positivity between single and multiple high-risk HPV infections. Among patients with a high-grade squamous intraepithelial lesion+ (HSIL+) ThinPrep cytologic test (TCT) diagnosis, HPV58 was the most common type, followed by HPV52, HPV16, HPV39 and HPV53. CONCLUSIONS: HPV types 52, 58, 16, 53, and 39 were the most common types in the general female population in Wuhan, and the prevalence of HPV infection varied among different age groups. This study provides a comprehensive overview of the epidemiological characteristics of HPV infection in women, which could support the development of targeted prevention and control strategies for cervical cancer in the region.

Diabetes is a risk factor for the progression and prognosis of COVID-19.

BACKGOUND: To figure out whether diabetes is a risk factor influencing the progression and prognosis of 2019 novel coronavirus disease (COVID-19). METHODS: A total of 174 consecutive patients confirmed with COVID-19 were studied. Demographic data, medical history, symptoms and signs, laboratory findings, chest computed tomography (CT) as well the treatment measures were collected and analysed. RESULTS: We found that COVID-19 patients without other comorbidities but with diabetes (n = 24) were at higher risk of severe pneumonia, release of tissue injury-related enzymes, excessive uncontrolled inflammation responses and hypercoagulable state associated with dysregulation of glucose metabolism. Furthermore, serum levels of inflammation-related biomarkers such as IL-6, C-reactive protein, serum ferritin and coagulation index, D-dimer, were significantly higher (P < .01) in diabetic patients compared with those without, suggesting that patients with diabetes are more susceptible to an inflammatory storm eventually leading to rapid deterioration of COVID-19. CONCLUSIONS: Our data support the notion that diabetes should be considered as a risk factor for a rapid progression and bad prognosis of COVID-19. More intensive attention should be paid to patients with diabetes, in case of rapid deterioration.

Cardiovascular disease potentially contributes to the progression and poor prognosis of COVID-19.

BACKGROUND AND AIM: A novel coronavirus severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) caused pneumonia, Coronavirus Disease 2019 (COVID-19), broke out in Wuhan, China in December 2019, and spread all over the world. Patients with COVID-19 showed huge differences in the hospital stay, progression, and prognosis. As reported, the comorbidities may play an important role in COVID-19. Here, we aim to address the role of cardiovascular disease (CVD) in the progression and prognosis of COVID-19. METHODS AND RESULTS: Eighty-three confirmed COVID-19 patients were divided into CVD (n = 42) and non-CVD (n = 41) group according to their medical history. Medical records including demographic data, medical history, clinical characteristics, laboratory examinations, chest computed tomography (CT), and treatment measures were collected, analyzed, and compared between the two groups. COVID-19 patients with CVD showed (1) more severe pathological changes in the lungs, (2) elevated injury-related enzymes including α-hydroxybutyrate dehydrogenase (HDBH), lactic dehydrogenase (LDH), γ-glutamyltransferase (GGT), creatine kinase (CK), and alanine aminotransferase (ALT), (3) significantly increased uncontrolled inflammation related markers, such as c-reactive protein (CRP), interleukin (IL)-6, serum ferritin, erythrocyte sedimentation rate (ESR), and serum amyloid A (SAA), (4) serious hypercoagulable status reflected by increased D-dimer and serum fibrinogen (FIB), and (5) higher mortality, compared to COVID-19 patients without CVD. CONCLUSIONS: Our data indicated that CVD is a strong risk factor for rapid progression and bad prognosis of COVID-19. More intensive medical care should be applied to patients with CVD to prevent rapid deterioration of the disease.

Aloperine Suppresses Cancer Progression by Interacting with VPS4A to Inhibit Autophagosome-lysosome Fusion in NSCLC.

Aloperine (ALO), a quinolizidine-type alkaloid isolated from a natural Chinese herb, has shown promising antitumor effects. Nevertheless, its common mechanism of action and specific target remain elusive. Here, it is demonstrated that ALO inhibits the proliferation and migration of non-small cell lung cancer cell lines in vitro and the tumor development in several mouse tumor models in vivo. Mechanistically, ALO inhibits the fusion of autophagosomes with lysosomes and the autophagic flux, leading to the accumulation of sequestosome-1 (SQSTM1) and production of reactive oxygen species (ROS), thereby inducing tumor cell apoptosis and preventing tumor growth. Knockdown of SQSTM1 in cells inhibits ROS production and reverses ALO-induced cell apoptosis. Furthermore, VPS4A is identified as a direct target of ALO, and the amino acids F153 and D263 of VPS4A are confirmed as the binding sites for ALO. Knockout of VPS4A in H1299 cells demonstrates a similar biological effect as ALO treatment. Additionally, ALO enhances the efficacy of the anti-PD-L1/TGF-ß bispecific antibody in inhibiting LLC-derived subcutaneous tumor models. Thus, ALO is first identified as a novel late-stage autophagy inhibitor that triggers tumor cell death by targeting VPS4A.

Recent Advances of Autophagy in Non-Small Cell Lung Cancer: From Basic Mechanisms to Clinical Application.

Lung cancer is characterized by the most common oncological disease and leading cause of cancer death worldwide, of which a group of subtypes known as non-small cell lung cancer (NSCLC) accounts for approximately 85%. In the past few decades, important progression in the therapies of NSCLC has enhanced our understanding of the biology and progression mechanisms of tumor. The application of immunotherapy and small molecule tyrosine kinase inhibitors has brought significant clinical benefits in certain patients. However, early metastasis and the emergence of resistance to antitumor therapy have resulted in the relatively low overall cure and survival rates for NSCLC. Autophagy is a conserved process that allows cells to recycle unused or damaged organelles and cellular components. It has been reported to be related to the progression of NSCLC and resistance to targeted therapy and cytotoxic chemotherapy. Therefore, autophagy is considered as a potential therapeutic target for NSCLC. Mounting results have been reported about the combination of tyrosine kinase inhibitors and inhibitors of autophagy in models of NSCLC. This review aims to provide a comprehensive review on the roles of autophagy in NSCLC, focusing on related clinical data of agents that regulate autophagy in NSCLC. Furthermore, this study will provide a theoretical basis for further improvement of autophagy-based cancer therapy.

Recent advances in the discovery and development of TLR ligands as novel therapeutics for chronic HBV and HIV infections.

INTRODUCTION: Toll-like receptor (TLR) ligands remain as promising antiviral drug candidates for the treatment of chronic viral infections. Basic research on the mechanisms of antiviral activity of TLR ligands in preclinical animal models and clinical testing of drug candidates have been carried out in recent years. Areas covered: This review provides an overview of the preclinical and clinical testing of TLR ligands in two major viral infections: hepatitis B virus (HBV) and human immunodeficiency virus (HIV). Recent results have further demonstrated the potent antiviral activity of various TLR ligands . A TLR7 agonist is in clinical trials for the treatment of chronic HBV infection while a HBV vaccine using a TLR9 ligand as an adjuvant has proven to be superior to conventional HBV vaccines and has been approved for clinical use. Generally, TLR activation may achieve viral control mainly by promoting adaptive immunity to viral proteins. Expert opinion: Recent research in this field indicates that TLR ligands could be developed as clinically effective drugs if the obstacles concerning toxicity and application routes are overcome. TLR-mediated promotion of adaptive immunity is a major issue for future studies and will determine the future development of TLR ligands as drugs for immunomodulation.