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Background With the rapid spread of the mpox epidemic, cases have emerged in multiple countries, mainly among men who have sex with men. Because of the connectedness of today’s world, countries have to be prepared to face risks in advance. Therefore, this study aimed to investigate awareness of mpox-related knowledge among men who have sex with men in China. Methods With the assistance of the social organizations of men who have sex with men, a cross-sectional survey of men who have sex with men in China was conducted through an online questionnaire between July 1 and July 18, 2022. A nationwide sample of Chinese men who have sex with men (N = 3,257) was recruited. Results Only 36.9% of participants had mpox-related knowledge. Awareness of mpox-related knowledge among respondents was positively associated with those in older age groups (33 to 42 years and 51 years or older) (adjusted odds ratio [AOR] = 1.31; 95% confidence interval [CI]: 1.03–1.67, AOR = 1.61; 95% CI: 1.16–2.24; respectively), married (AOR = 1.55; 95% CI: 1.09–2.19), and those with a graduate degree or above (AOR = 2.14; 95% CI: 1.11–4.13), while negatively associated with those living in the western parts of China (AOR = 0.74; 95% CI: 0.60–0.92), and those who were unsure of their history of Human Immunodeficiency Virus (HIV) status (AOR = 0.44; 95% CI: 0.30–0.63). Conclusion Mpox-related knowledge is fairly low among men who have sex with men in China. China needs to spread knowledge to the public through multiple channels, especially in key populations (men who have sex with men, HIV-infected, etc.), and take preventive measures to effectively avoid outbreaks of mpox.

Mesenchymal stem cells (MSCs) are the most promising multipotent stem cells that can differentiate into osteoblasts, chondrocytes, and adipocytes. This cellular flexibility contributes to widespread clinical use of MSCs in tissue repair and regeneration. The immune system is a key player in regulating bone remodeling. In recent years, the association between the immune system and bone metabolism has become an increasing focus of interest. Metformin, a glucose-lowering drug, exerts powerful impact on metabolic signaling. However, whether metformin can modulate bone metabolism or whether metformin can influence immune milieu by regulation of macrophages has not been thoroughly elucidated. Herein, we specifically explored the complex interactions between macrophages and human umbilical cord mesenchymal stem cells (UC-MSCs) in the context of metformin. Our research demonstrated that metformin not only stimulated osteogenesis of UC-MSCs but also influenced the immune system via promoting M2 but reducing M1 macrophages. Mechanically, we found that metformin-treated M2 macrophages possessed more potent osteoinductive capacity in our coculture system. Molecularly, these metformin-stimulated M2 macrophages facilitated osteogenesis via activating the PI3K/AKT/mTOR pathway. As demonstrated by using PI3K-specific inhibitor LY294002, we found that the pathway inhibitor partly reversed osteoinductive activity which was activated by coculture of metformin-treated M2 macrophages. Overall, our novel research illuminated the cooperative and synergistic effects of metformin and M2 macrophages on the dynamic balance of bone metabolism.

Severe fever with thrombocytopenia syndrome (SFTS) is a viral hemorrhagic fever with high mortality, primarily driven by immune dysregulation. This study aimed to characterize the expression profile of TIM-3 expression on peripheral NK cells in SFTS, explore the role of TIM-3 ⁺ NK cells in disease progression, and evaluate soluble TIM-3 (sTIM-3) and Galectin-9 (sGalectin-9) as prognostic biomarkers. Public single-cell RNA sequencing (scRNA-seq) datasets were analyzed using weighted gene co-expression network analysis (WGCNA). Peripheral blood samples from 21 SFTS patients and 14 healthy donors collected at the First Affiliated Hospital, Zhejiang University School of Medicine, were analyzed by flow cytometry, functional assays, and serological assessments. NK cell cytotoxicity was assessed by granzyme B, perforin, IFN-γ, and TNF-α production. Serum sTIM-3 and sGalectin-9 were measured by Cytometric Bead Array. TIM-3 ⁺ NK cells were significantly increased in SFTS patients, especially in fatal cases. WGCNA identified HAVCR2 (encoding TIM-3) as a mortality-associated hub gene. TIM-3 ⁺ NK cells exhibited enhanced granzyme B and perforin expression, while TIM-3 blockade significantly reduced IFN-γ and TNF-α production. Elevated sTIM-3 and sGalectin-9 levels were correlated with fatal outcomes. Activated TIM-3 ⁺ NK cells were associated with fatal outcomes in SFTS. TIM-3 ⁺ NK cell proportion, sTIM-3, and sGalectin-9 may serve as novel prognostic biomarkers and therapeutic targets.

Introduction Previous studies have reported inconsistent findings regarding the associationbetween ALK and ROS1 rearrangements in lung cancer and thromboembolic risk. This retrospective study aimed to investigate this association in advanced lung adenocarcinoma patients with ALK, ROS1, RET rearrangements, and EGFR mutations. Materials and Methods We retrospectively collected information on patients with advanced lung adenocarcinoma in the First Affiliated Hospital of Zhejiang University School of Medicine from January 2013 to March 2021. All patients with confirmed ALK, ROS1, or RET rearrangements, as well as a comparison cohort of those with EGFR mutation, were included. Clinical characteristics were analyzed, and the association between driver genes and TE risks was analyzed using competing risk and logistic regression. Results A total of 546 patients were included in the study. Among them, those with ROS1 rearrangements exhibited the highest cumulative incidence of thromboembolic events (TEs), reaching 17.5% ± 0.2% during the peri‐diagnostic period (within 6 months following diagnosis). Regardless of the entire follow‐up or the peri‐diagnostic period, ROS1 rearrangements were significantly associated with an increased risk of TEs. Multivariate analysis revealed ROS1 rearrangements, the number of comorbidities, the size of mediastinal lymph nodes, and elevated C‐reactive protein (CRP) levels as TE risk factors during the peri‐diagnostic period. Throughout the follow‐up period, ROS1 rearrangements and hypertension were independent TE risk factors. In addition, the development of TE significantly affected the overall survival of patients with EGFR mutations. Conclusion ROS1 rearrangements were significantly associated with an increased risk of TE. In this retrospective study of 546 lung adenocarcinoma patients with four different driver genes, ROS1 rearrangements were associated with the increased risk of thromboembolic events (TEs), particularly during the peri‐diagnostic period (6 months before and after diagnosis). Risk factors of TEs during the peri‐diagnostic period included ROS1 rearrangements, multiple comorbidities, enlarged mediastinal lymph nodes, and elevated CRP levels.

This study investigates the longitudinal dynamic changes in immune cells in COVID-19 patients over an extended period after recovery, as well as the interplay between immune cells and antibodies. Leveraging single-cell mass spectrometry, we selected six COVID-19 patients and four healthy controls, dissecting the evolving landscape within six months post-viral RNA clearance, alongside the levels of anti-spike protein antibodies. The T cell immunophenotype ascertained via single-cell mass spectrometry underwent validation through flow cytometry in 37 samples. Our findings illuminate that CD8 + T cells, gamma-delta (gd) T cells, and NK cells witnessed an increase, in contrast to the reduction observed in monocytes, B cells, and double-negative T (DNT) cells over time. The proportion of monocytes remained significantly elevated in COVID-19 patients compared to controls even after six-month. Subpopulation-wise, an upsurge manifested within various T effector memory subsets, CD45RA + T effector memory, gdT, and NK cells, whereas declines marked the populations of DNT, naive and memory B cells, and classical as well as non-classical monocytes. Noteworthy associations surfaced between DNT, gdT, CD4 + T, NK cells, and the anti-S antibody titer. This study reveals the changes in peripheral blood mononuclear cells of COVID-19 patients within 6 months after viral RNA clearance and sheds light on the interactions between immune cells and antibodies. The findings from this research contribute to a better understanding of immune transformations during the recovery from COVID-19 and offer guidance for protective measures against reinfection in the context of viral variants.

More than 400 confirmed mpox cases have been reported in China. The mpox vaccination is crucial to mitigate mpox transmission, especially for at-risk populations. This study aimed to determine mpox vaccination hesitancy and its associated factors in Chinese men who have sex with men (MSM). This nationwide cross-sectional study was conducted among 7538 Chinese MSM in 27 MSM social organizations from 21 provinces, municipalities, and autonomous regions of China from 31 July to 4 August 2023. Of them, the rate of mpox vaccination hesitancy was 5.59% (421/7538). The most common reason for mpox vaccination hesitation was concerns of safety and side effects (62.71%, 264/421), followed by concerns of privacy (38.24%, 161/421), thoughts of impossible infection (37.53%, 158/421), no effectiveness in preventing reinfection (30.88%, 130/421), and no worry about infection (12.35%, 52/421). Regarding the concerning characteristics of the vaccines, concerns of vaccine safety ranked first (71.74%, 5408/7538), followed by vaccine effectiveness (14.05%, 1059/7538), vaccine costs (7.35%, 554/7538), and the continuity of vaccine effectiveness (3.91%, 295/7538). The highest odds ratio of mpox vaccination hesitation was seen in MSM who were infected with mpox virus (aOR = 2.38; 95%CI = 1.08, 5.23), followed by those aged ≥60 years (aOR = 2.25; 95%CI = 1.31, 3.88), those who were unemployed (aOR = 1.66; 95%CI = 1.25, 2.19), and those who had an education level of postgraduate and above (aOR = 1.55; 95%CI = 1.01, 2.37). However, MSM who had a higher level of mpox-related knowledge (moderate: aOR = 0.53; 95%CI = 0.36, 0.77; high: aOR = 0.30; 95%CI = 0.23, 0.40) had a lower odds ratio of mpox vaccination hesitation. MSM in China had low hesitancy toward mpox vaccination. The safety and effectiveness of the vaccine and privacy were important aspects of hesitancy. Health education on mpox-related knowledge should be encouraged to promote future vaccination plans.

This work aims to explore the long‐term prognosis of hepatitis B virus‐related acute‐on‐chronic liver failure (HBV‐ACLF). In this prospective study, eligible inpatients with HBV‐ACLF are enrolled and followed up from December 2012 to February 2023, for clinical events, laboratory tests at least every 6 months. Overall, the survival rates at 28 days, 90 days, 1 year, 5 years, and 8 years are 64.7%, 48.8%, 46.1%, 43.8%, and 42.2%, respectively. Among the 8‐year mortality and liver transplant cases, ACLF survivors (who survived over 90 days) accounted for 7.8% (9/115). Among 101 patients who survived for more than 90 days, 97.9% of patients achieve virologic response at 1 year. For HBeAg‐positive patients, the HBeAg seroconversion are 25.5%, 63.6%, and 76.9% at 1, 5, and 8 years, respectively. Alanine aminotransferase, aspartate aminotransferase, total bilirubin, INR, white blood cell count, and albumin levels gradually improve within the first year. Fibrosis biomarkers APRI, FIB‐4 and Chitinase‐3‐like protein 1 (CHI3L1) levels decreases within the first 5 years. The Cox proportional hazards regression reveal that high total bilirubin (HR = 1.008, p = 0.021) is the independent risk factor for 8‐year survival of ALCF survivors. The 90‐day period following of HBV‐ACLF represented a critical juncture for long‐term prognosis, revealing favorable outcomes beyond this timeframe. The 90‐day period following the occurrence of HBV‐ACLF is a critical time point for long‐term prognosis of HBV‐ACLF patients, with favorable outcomes of survival rates, laboratory indicators, virological, and serologic responses and values of liver fibrosis indicators observed beyond this timeframe. Moreover, the high levels of total bilirubin might be the underlying risk factor for 8‐year survival of ALCF patients.

Epithelial-mesenchymal transition (EMT) is one of the most important mechanisms in the initiation and promotion of cancer cell metastasis. The phosphoinositide 3-kinase (PI3K) signaling pathway has been demonstrated to be involved in TGF-β induced EMT, but the complicated TGF-β signaling network makes it challenging to dissect the important role of PI3K on regulation of EMT process. Here, we applied optogenetic controlled PI3K module (named ‘Opto-PI3K’), which based on CRY2 and the N-terminal of CIB1 (CIBN), to rapidly and reversibly control the endogenous PI3K activity in cancer cells with light. By precisely modulating the kinetics of PI3K activation, we found that E-cadherin is an important downstream target of PI3K signaling. Compared with TGF-β treatment, Opto-PI3K had more potent effect in down-regulation of E-cadherin expression, which was demonstrated to be regulated in a light dose-dependent manner. Surprisingly, sustained PI3K activation induced partial EMT state in A549 cells that is highly reversible. Furthermore, we demonstrated that Opto-PI3K only partially mimicked TGF-β effects on promotion of cell migration in vitro . These results reveal the importance of PI3K signaling in TGF-β induced EMT, suggesting other TGF-β regulated signaling pathways are necessary for the full and irreversible promotion of EMT in cancer cells. In addition, our study implicates the great promise of optogenetics in cancer research for mapping input-output relationships in oncogenic pathways.