Epidemiology, clinical presentation, pathophysiology, and management of long COVID: an update.

The increasing number of coronavirus disease 2019 (COVID-19) infections have highlighted the long-term consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection called long COVID. Although the concept and definition of long COVID are described differently across countries and institutions, there is general agreement that it affects multiple systems, including the immune, respiratory, cardiovascular, gastrointestinal, neuropsychological, musculoskeletal, and other systems. This review aims to provide a synthesis of published epidemiology, symptoms, and risk factors of long COVID. We also summarize potential pathophysiological mechanisms and biomarkers for precise prevention, early diagnosis, and accurate treatment of long COVID. Furthermore, we suggest evidence-based guidelines for the comprehensive evaluation and management of long COVID, involving treatment, health systems, health finance, public attitudes, and international cooperation, which is proposed to improve the treatment strategies, preventive measures, and public health policy making of long COVID.

The phenotype and prediction of long-term physical, mental and cognitive COVID-19 sequelae 20 months after recovery, a community-based cohort study in China.

Long-term sequelae clustering phenotypes are important for precise health care management in COVID-19 survivors. We reported findings for 1000 survivors 20 months after diagnosis of COVID-19 in a community-based cohort in China. Sequelae symptoms were collected from a validated questionnaire covering 27 symptoms involved in five organ systems including self-reported physical condition, dyspnea, cognitive function and mental health. The generalized symptoms were reported with the highest rate (60.7%), followed by the mental (48.3%), cardiopulmonary (39.8%), neurological (37.1%; cognitive impairment, 15.6%), and digestive symptoms (19.1%). Four clusters were identified by latent class analysis: 44.9% no or mild group (cluster 1), 29.2% moderate group with mainly physical impairment (cluster 2), 9.6% moderate group with mainly cognitive and mental health impairment (cluster 3), and 16.3% severe group (cluster 4). Physical comorbidities or history of mental disorders, longer hospitalization periods and severe acute illness predicted severe group. For moderate group, adults less than 60 years, with physical comorbidities and severe acute illness were more likely to have physical symptoms, while adult women with longer hospitalization stays had increased risk of cognitive and mental health impairment. Overall, among more than half of community COVID-19 survivors who presented moderate or severe sequelae 20 months after recovery, three-tenth had physical vulnerability that may require physical therapy aiming to improve functioning, one-tenth mental or cognitive vulnerable cases need psychotherapy and cognitive rehabilitation, and one-sixth severe group needs multidisciplinary clinical management. The remaining half is free to clinical intervention. Our findings introduced an important framework to map numerous symptoms to precise classification of the clinical sequelae phenotype and provide information to guide future stratified recovery interventions.

Prognostic effects of previous cancer history on patients with major salivary gland cancer.

OBJECTIVES: To explore the prognostic effects of previous cancer history on patients with major salivary gland cancer (SGC). SUBJECTS AND METHODS: SGC patients with (sec-SGC) and without (one-SGC) a previous cancer from the SEER database were identified. Cox proportional hazards regression (CoxPH) models were used to compare the prognosis between sec-SGC and one-SGC patients. Subgroup analyses for sec-SGC patients by gender, previous cancer types, previous cancer histology, and cancer diagnosis interval (CDI) were performed. Two CoxPH models were constructed to distinguish sec-SGC patients with different prognostic risks. RESULTS: 9098 SGC patients were enrolled. Overall, sec-SGC patients (adjusted HR [aHR] = 1.26, p < 0.001), especially those with a CDI ≤ 5 years (aHR = 1.47, p < 0.001), had worse overall survival (OS) than one-SGC patients. In subgroup analysis, only sec-SGC patients with a previous head and neck cancer who were female (aHR = 2.38, p = 0.005), with a CDI ≤ 5 years (aHR = 1.65, p = 0.007) or with a previous squamous cell carcinoma (aHR = 6.52, p < 0.001) had worse OS. Our models successfully differentiated all sec-SGC patients into high-, intermediate- and low-risk groups with different prognosis. CONCLUSIONS: Sec-SGC patients with different previous cancer types, gender, CDI and previous cancer histology had varied prognosis. The models we constructed could help differentiate the prognosis of sec-SGC patients with different risks.

lncRNA MAGI2-AS3 suppresses castration-resistant prostate cancer proliferation and migration via the miR-106a-5p/RAB31 axis.

Prostate cancer (PCa) is a common malignant cancer in elderly males in Western countries. Whole-genome sequencing confirmed that long non-coding RNAs (lncRNAs) are frequently altered in castration-resistant prostate cancer (CRPC) and promote drug resistance to cancer therapy. Therefore, elucidating the prospective role of lncRNAs in PCa oncogenesis and progression is of remarkable clinical significance. In this study, gene expression in prostate tissues was determined using RNA-sequencing datasets, and the gene diagnostic and prognostic values of CRPC were analyzed using bioinformatics. Further, the expression levels and clinical significance of MAGI2 Antisense RNA 3 (MAGI2-AS3) in PCa clinical specimens were evaluated. The tumor-suppressive activity of MAGI2-AS3 was functionally explored in PCa cell lines and animal xenograft models. MAGI2-AS3 was found to be aberrantly decreased in CRPC and was negatively correlated with Gleason score and lymph node status. Notably, low MAGI2-AS3 expression positively correlated with poorer survival in patients with PCa. The overexpression of MAGI2-AS3 significantly inhibited the proliferation and migration of PCa in vitro and in vivo. Mechanistically, MAGI2-AS3 could play a tumor suppressor function in CRPC through a novel miR-106a-5p/RAB31 regulatory network and could be a target for future cancer therapy.

A systematic review and meta-analysis on the prevalence of stigma in infectious diseases, including COVID-19: a call to action.

Infectious diseases, including COVID-19, are crucial public health issues and may lead to considerable fear among the general public and stigmatization of, and discrimination against, specific populations. This meta-analysis aimed to estimate the pooled prevalence of stigma in infectious disease epidemics. We systematically searched PubMed, PsycINFO, Embase, MEDLINE, Web of Science, and Cochrane databases since inception to June 08, 2021, and reported the prevalence of stigma towards people with infectious diseases including SARS, H1N1, MERS, Zika, Ebola, and COVID-19. A total of 50 eligible articles were included that contributed 51 estimates of prevalence in 92722 participants. The overall pooled prevalence of stigma across all populations was 34% [95% CI: 28-40%], including enacted stigma (36% [95% CI: 28-44%]) and perceived stigma (31% [95% CI: 22-40%]). The prevalence of stigma in patients, community population, and health care workers, was 38% [95% CI: 12- 65%], 36% [95% CI: 28-45%], and 30% [95% CI: 20-40%], respectively. The prevalence of stigma in participants from low- and middle-income countries was 37% [95% CI: 29-45%], which is higher than that from high-income countries (27% [95% CI: 18-36%]) though this difference was not statistically significant. A similar trend of prevalence of stigma was also observed in individuals with lower education (47% [95% CI: 23-71%]) compared to higher education level (33% [95% CI: 23-4%]). These findings indicate that stigma is a significant public health concern, and effective and comprehensive interventions are needed to counteract the damaging effects of the infodemics during infectious disease epidemics, including COVID-19, and reduce infectious disease-related stigma.

A systematic review and meta-analysis on prevalence of and risk factors associated with depression, anxiety and insomnia in infectious diseases, including COVID-19: a call to action.

Infectious disease epidemics have become more frequent and more complex during the 21st century, posing a health threat to the general public and leading to psychological symptoms. The current study was designed to investigate the prevalence of and risk factors associated with depression, anxiety and insomnia symptoms during epidemic outbreaks, including COVID-19. We systematically searched the PubMed, Embase, Web of Science, OVID, Medline, Cochrane databases, bioRxiv and medRxiv to identify studies that reported the prevalence of depression, anxiety or insomnia during infectious disease epidemics, up to August 14th, 2020. Prevalence of mental symptoms among different populations including the general public, health workers, university students, older adults, infected patients, survivors of infection, and pregnant women across all types of epidemics was pooled. In addition, prevalence of mental symptoms during COVID-19 was estimated by time using meta-regression analysis. A total of 17,506 papers were initially retrieved, and a final of 283 studies met the inclusion criteria, representing a total of 948,882 individuals. The pooled prevalence of depression ranged from 23.1%, 95% confidential intervals (95% CI: [13.9-32.2]) in survivors to 43.3% (95% CI: [27.1-59.6]) in university students, the pooled prevalence of anxiety ranged from 25.0% (95% CI: [12.0-38.0]) in older adults to 43.3% (95% CI: [23.3-63.3]) in pregnant women, and insomnia symptoms ranged from 29.7% (95% CI: [24.4-34.9]) in the general public to 58.4% (95% CI: [28.1-88.6]) in university students. Prevalence of moderate-to-severe mental symptoms was lower but had substantial variation across different populations. The prevalence of mental problems increased over time during the COVID-19 pandemic among the general public, health workers and university students, and decreased among infected patients. Factors associated with increased prevalence for all three mental health symptoms included female sex, and having physical disorders, psychiatric disorders, COVID infection, colleagues or family members infected, experience of frontline work, close contact with infected patients, high exposure risk, quarantine experience and high concern about epidemics. Frequent exercise and good social support were associated with lower risk for these three mental symptoms. In conclusion, mental symptoms are common during epidemics with substantial variation across populations. The population-specific psychological crisis management are needed to decrease the burden of psychological problem and improve the mental wellbeing during epidemic.

The role of HPV status in patients with overlapping grey zone cancer in oral cavity and oropharynx.

PURPOSE: We aimed to explore the clinicodemographic characteristics and prognosis of grey zone squamous cell cancer (GZSCC) located in the overlapping or ambiguous area of oral cavity and oropharynx and to identify valuable factors that would improve its differential diagnosis and prognosis. METHODS: Information of GZSCC patients in the Surveillance, Epidemiology, and End Results (SEER) database were compared to patients with oral cavity (OCSCC) and oropharyngeal (OPSCC) squamous cell carcinomas with corresponding HPV status, respectively. Kaplan-Meier method with log-rank test and multivariate Cox regression analysis were applied to assess associations between clinical characteristics and overall survival (OS). A predictive model integrating age, gender, marital status, HPV status and staging variables was conducted to classify GZSCC patients into three risk groups and verified internally by tenfold cross validation. RESULTS: A total of 3318 GZSCC, 10792 OPSCC and 6656 OCSCC patients were identified. HPV-positive GZSCC patients had the best 5-year OS as HPV-positive OPSCC (81% vs. 82%). However, the 5-year OS of HPV-negative/unknown GZSCC (43%/42%) were the worst among all groups, indicating that HPV status and the overlapping nature of tumors were valuable prognostic predictors in GZSCC patients. Compared with the strategy of dividing GZSCC into two groups by HPV status, the predictive model integrating more variables could additionally identify a unique high-risk GZSCC group with the lowest OS rate. CONCLUSIONS: GZSCC patients had distinct clinical characteristics and prognosis compared with OPSCC and OCSCC, integrating HPV status and other clinical factors could help distinguish GZSCC and predict their prognosis.

[Guideline for the Standardized Construction of Sleep Medicine Centers in China: Undertaking the Mission of Medicine of the Era and Caring for People's Sleep Health].

Humans spend one third of their life sleeping. Sleep, a vital life process, is an essential part of human health. In response to people's growing needs concerning sleep health, sleep medicine was born and is growing rapidly, and there is also an upsurge in the construction of sleep medicine centers in China and other countries. Unfortunately, there are no Chinese standards available for the construction of sleep medicine centers and the sleep medicine centers already constructed are of varied quality. In view of this academic problem, Professor Lu Lin, an academician of Chinese Academy of Sciences and the president of Peking University Sixth Hospital, organized Chinese experts with outstanding achievements in the field of sleep medicine to draft "Guideline for the Standardized Construction of Sleep Medicine Centers in China". This guideline mainly introduces the overall status of standardized construction of sleep medicine centers and the status of the construction of specialized sleep medicine centers in China, aiming to guide the construction of high-quality and high-standard sleep medicine centers in China, to promote the development of sleep medicine, and to safeguard people's sleep health.

Lycopene enhances the sensitivity of castration-resistant prostate cancer to enzalutamide through the AKT/EZH2/ androgen receptor signaling pathway.

Enzalutamide is an effective drug for the treatment of castration-resistant prostate cancer (CRPC), but acquired enzalutamide resistance is usually unavoidable within the short term in many patients. Lycopene, a safe and effective phytochemical, has been documented to have anticancer activity in a variety of tumors, especially for prostate cancer (PCa). The aim of this study was to provide data support for the combination of lycopene and enzalutamide in the treatment of CRPC. To this end, tissues from patients with primary prostate cancer (PPC) and CRPC were examined by immunohistochemical analysis and found that p-AKT and p-EZH2 were overexpressed in CRPC. Furthermore, Kaplan-Meier survival analysis showed that the high expression of p-AKT and p-EZH2 may be related to the poor prognosis of patients. In addition, the expression of p-AKT, p-EZH2 and androgen receptor (AR) were significantly down-regulated in 22RV1 and C4-2B cells and the proliferation and invasion of CRPC cells were inhibited after treatment with lycopene, while SC79 (an AKT agonist) markedly rescue this effect. Of note, a combination of lycopene and enzalutamide significantly inhibited the proliferation and invasion of CRPC cells in vitro, as well as tumor growth and bone metastasis in vivo. These results suggest that the enhanced antitumor effects of enzalutamide by lycopene may be related to the reduction of AR protein levels through lycopene-mediated inhibition of AKT/EZH2 pathway, which may provide a new approach to improve the efficacy of enzalutamide in CRPC.

Solitary fibrous tumors in prostate: a case report with review of the literature.

BACKGROUND: Solitary fibrous tumor (SFT) is a relatively rare type of mesenchymal neoplasm that occurs most frequently in the pleura. However, SFT originating from the prostate is particularly uncommon and only approximately 39 cases were reported before. Herein, we reported a rare case of a patient diagnosed with prostate SFT and presented a literature review.Case presentation: A 50-year-old Asian with irritative urinary symptoms was admitted to our hospital and almost all the evidence indicated that benign prostate hyperplasia (BPH) caused his symptoms. Therefore, transurethral resection of the prostate (TURP) was performed, but histopathological and Immunohistochemical (IHC) assessments showed that spindle cells arranged disorderly in the TURP specimen with a cluster of differentiation 34 (CD34), B-cell lymphoma-2 (Bcl-2), and signal transducer and activator of transcription 6 (STAT6) highly expressed and SFT was diagnosed. Finally, the patient underwent a radical prostatectomy and there was no disease progression observed thereafter. CONCLUSIONS: Prostate SFT is extremely rare, and to our knowledge, this is the first case of prostate SFT that is difficult to differentiate from small volume BPH. IHC examinations are of great diagnostic value. Radical resection of the tumor appears to be the most effective method at present and continuous follow-up is highly recommended.

MicroRNA-199b-3p suppresses malignant proliferation by targeting Phospholipase Cε and correlated with poor prognosis in prostate cancer.

OBJECTIVES: MicroRNA-199b-3p (miR-199b-3p) plays a crucial role in the malignant development of various cancers, but little known in prostate cancer (PCa). The aim of our study was to demonstrate the function of miR-199b-3p in PCa. METHODS: Quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect miR-199b-3p expression in PCa and benign prostatic hyperplasia (BPH) tissue samples. In addition, we examined the relationship between the poor prognosis in PCa and miR-199b-3p. Western blot was used to analyze the expression of Phospholipase Cε (PLCε). CCK8 and colony-forming assays were applied to detect the proliferation of PCa. EdU assay is used to detect PCa cells uptake of EdU. Luciferase reporter assay was applied to analyze the binding between miR-199b-3p and PLCε. RESULTS: It has been shown that miR-199b-3p in PCa was significantly lower than that in benign prostatic hyperplasia and correlated with poor prognosis. Meanwhile, upregulation of miR-199b-3p can prominently inhibit the proliferation of PCa cells, while its down-regulation triggered opposite result. PLCε was identified as the downstream binding target gene and negatively associated with that of miR-199b-3p. CONCLUSION: miR-199b-3p suppresses malignant proliferation by inhibiting PLCε in prostate cancer in vitro and vivo.

Renal cancer-derived exosomes induce tumor immune tolerance by MDSCs-mediated antigen-specific immunosuppression.

BACKGOUND: Although Myeloid-derived suppressor cells (MDSCs) have a prominent ability to suppress the immune responses of T lymphocytes and propel tumor immune escape, a lack of profound systemic immunesuppression in tumor-bearing mice and tumor patients. The underlying mechanism of these remains unclear. METHODS: For this purpose, renal cancer-derived exosomes (RDEs) were first labeled with PKH67 and been observed the internalization by MDSCs. Flow cytometry analysis showed the proportion and activity change of MDSCs in spleen and bone marrow induced by RDEs. Further, western blot experiments were used to verify triggered mechanism of MDSCs by RDEs. Finally, proliferation and cytotoxicity of cytotoxic T lymphocytes (CTLs) co-cultured with MDSCs in vitro and a series of experiments in vivo were performed to demonstrate the specific inhibitory effect of RDEs-induced MDSCs. RESULTS: This study suggested that RDEs crucially contributed to presenting antigenic information, activating and driving specific immunosuppressive effect to MDSCs. HSP70, which is highly expressed in RDEs, initiate this process in a toll like receptor 2 (TLR2)-dependent manner. Importantly, RDEs-induced MDSCs could exert an antigen-specific immunosuppression effect on CTL and specific promote renal tumors-growth and immune escape in consequence. CONCLUSION: The immunosuppression mediated by MDSCs which is induced by RDEs is antigen-specific. HSP70, which is highly expressed in RDEs, plays a pivotal role in this process. Targeted abrogating the function of MDSCs, or eliminating the expression of HSP70 in exosomes, or blocking the crosstalk between them provides a new direction and theoretical support for future immunotherapy. Video abstract.

Phospholipase Cε Regulates Prostate Cancer Lipid Metabolism and Proliferation by Targeting AMP-Activated Protein Kinase (AMPK)/Sterol Regulatory Element-Binding Protein 1 (SREBP-1) Signaling Pathway.

BACKGROUND Metabolic reprogramming is a common characteristic of numerous kinds of tumors, including prostate cancer (PCa). Tumor metabolism such as lipid metabolism provides sufficient lipids for tumor cell division and rapid growing as well as a vital source for formation of new cellular membranes. Phospholipase Cε (PLCε) is an oncogene that can drive proliferation, progression, and lipid metabolism of tumors, but its effect in lipid metabolism of PCa is not clear. MATERIAL AND METHODS Benign prostatic hyperplasia (BPH) and PCa tissue specimens were assessed for SREBP-1, FASN, and PLCε by immunohistochemistry, and PLCε was knocked-down by a lentiviral short hairpin RNA. The mRNA and protein level expression of related factors were tested by qPCR and Western blot analyses. Cell proliferation was assessed by clone formation, CCK-8, and Ki-67 assays. Nile red and oil red O staining were performed to detect endogenous lipid levels. Immunofluorescence was used to localize the protein of SREBP-1. Finally, a tumor xenograft assay of nude mice was performed to assess the role of PLCε in prostate tumor generation. RESULTS We found that overexpression of PLCε indicates low PFS in PCa and is involved in metastasis of PCa, and that the PLCε/AMPK/SREBP-1 signaling network promotes the progression of PCa through lipid metabolism in vivo and in vitro. CONCLUSIONS This study is the first to discover the lethal role of PLCε in lipid metabolism and malignant behavior of PCa, elucidation PCa occurrence and progression.

Public awareness and knowledge of factors associated with dementia in China.

BACKGROUND: Dementia is a global public health priority. Many modifiable factors have been shown to influence the development of dementia, but these factors are not adequately known by the general public. This study aimed to assess public awareness of the factors that are associated with dementia in China. METHODS: A cross-sectional study was conducted from May to October 2019 using an Internet-based questionnaire. Data on basic sociodemographic characteristics were collected, and the knowledge of risk and protective factors for dementia was investigated. Logistic regression analysis was performed to compare levels of the knowledge of factors associated with dementia across populations with different demographic characteristics. RESULTS: Data from 3338 respondents were analyzed. The percentages of participants who accurately identified the risk factors of dementia were follows: 84.24% for negative affect, 65.07% for alcohol use, 56.68% for smoking, 48.74% for hypertension, and 42.66% for diabetes. The percentages of participants who accurately identified the protective factors for dementia were follows: 90.00% for exercise, 84.69% for social activity, 80.92% for intelligence games, 74.45% for reading, and 6.14% for antihypertensive or hypolipidemic drugs. The majority of Chinese people correctly recognized the role of lifestyle factors in the development of dementia but not medical factors. The levels of knowledge of the factors associated with dementia were significantly distinct across populations with different characteristics. The following sociodemographic characteristics were associated with more comprehensive knowledge of dementia risk and protective factors: women, young age, high education levels, nonmanual jobs, and contact with patients with dementia. CONCLUSIONS: Public awareness and knowledge of risk and protective factors for dementia in China are still insufficient. More efforts are needed to publicize information to reduce the risk of dementia.

Heat shock protein 70 is induced by pepsin via MAPK signaling in human nasal epithelial cells.

BACKGROUND: Recent studies have shown that laryngopharyngeal reflux is associated with chronic rhinosinusitis. Pepsin may be a key factor involved in the injury of nasal mucosal epithelial cells, but the pathogenesis remains unclear. We are to investigate whether a mitogen-activated protein kinase (MAPK) pathway regulates heat shock protein 70 (HSP70) expression in primary cultures of human nasal epithelial cells (HNEpCs) in response to pepsin stimulation. METHODS: HSP70 protein expression levels in HNEpCs were estimated by Western blot analysis after treatment with pepsin. MAPK pathway activity levels were also evaluated to elucidate the mechanism underlying the effects of pepsin on HSP70 in HNEpCs. Inhibitors of signaling pathways were used to determine the contribution of MAPKs in HSP70 response after pepsin stimulation. Cellular apoptosis and cell viability in HNEpCs after treatment with pepsin were measured. RESULTS: The expression of HSP70 increased after stimulation with pepsin and decreased after the removal of pepsin. Pepsin induced activation of p38, extracellular signal-regulated kinase 1/2, and c-Jun N-terminal kinase (JNK) 1/2. Inhibition of JNK1/2 reduced HSP70 expression in HNEpCs. The apoptosis in HNEpCs at 12 h after treatment with pepsin at pH 7.0 increased significantly when compared with the control and pH 7.0 groups. Cell viability decreased following exposure to pepsin at pH 7.0. CONCLUSION: Pepsin, even under neutral pH 7.0, increases the expression of HSP70 in HNEpCs by activating the JNK/MAPK signaling pathway. Increased HSP70 may be the protective mechanism when pepsin presents in the other parts of the body.

Ultrasound-guided puncture drainage versus surgical incision drainage for deep neck space abscesses: a protocol for a systematic review with meta-analysis and trial sequential analysis.

INTRODUCTION: Deep neck space abscesses (DNAs) are serious surgical emergencies, associated with life-threatening complications. Surgical incision and drainage combined with antibiotics is the main treatment for DNAs, but drawbacks still exist. Ultrasound-guided puncture drainage is an alternative treatment for some DNAs with limited clinical evidence. Hence, the optimal drainage technique for the treatment of DNAs remains unclear. Therefore, we will perform a protocol for a systematic review and meta-analysis to identify the efficacy of ultrasound-guided puncture drainage for DNAs. METHODS AND ANALYSIS: PubMed, Ovid Medline, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang database, VIP database and trial registry databases will be searched from inception to September 2023 to identify randomised controlled trials of patients diagnosed with DNAs accepting ultrasound-guided puncture drainage. The primary outcome will be the length of hospital stay. The secondary outcomes will be the cure rate, incidence of retreatment, complications and overall cost to the healthcare system. Fixed-effects or random-effects model will be used according to the statistical heterogeneity. Mean differences or standardised mean differences with 95% CIs for continuous data and risk ratio (RR) with 95% CIs for dichotomous data. The Cochrane risk-of-bias tool 2, Grading of Recommendations Assessment, Development and Evaluation (GRADE) and trial sequential analysis will be conducted to evaluate the evidence quality and control the random errors. Funnel plots and Egger's regression test will be performed to evaluate publication bias. ETHICS AND DISSEMINATION: Ethical approval was not required for this systematic review protocol. The results will be disseminated through peer-reviewed publications. PROSPERO REGISTRATION NUMBER: CRD42023441031.

Causal relationship between gut microbiota and prostate cancer contributes to the gut-prostate axis: insights from a Mendelian randomization study.

BACKGROUND: Changes in gut microbiota abundance have been linked to prostate cancer development. However, the causality of the gut-prostate axis remains unclear. METHODS: The genome-wide association study (GWAS) data for gut microbiota sourced from MiBioGen (n = 14,306), alongside prostate cancer summary data from PRACTICAL (n = 140,254) and FinnGen Consortium (n = 133,164). Inverse-variance-weighted (IVW) was mainly used to compute odds ratios (OR) and 95% confidence intervals (Cl), after diligently scrutinizing potential sources of heterogeneity and horizontal pleiotropy via the rigorous utilization of Cochran's Q test, the MR-PRESSO method, and MR-Egger. We used meta-analysis methods in random effects to combine the Mendelian randomization (MR) estimates from the two sources. RESULTS: The pooled analyses of MR results show that genus Eubacterium fissicatena (OR = 1.07, 95% CI 1.01 to 1.13, P = 0.011) and genus Odoribacter (OR = 1.14, 95% CI 1.01 to 1.27, P = 0.025) were positively associated with prostate cancer. However, genus Adlercreutzia (OR = 0.89, 95% CI 0.83 to 0.96, P = 0.002), Roseburia (OR = 0.90, 95% CI 0.83 to 0.99, P = 0.03), Holdemania (OR = 0.92, 95% CI 0.86 to 0.97, P = 0.005), Flavonifractor (OR = 0.85, 95% CI 0.74 to 0.98, P = 0.024) and Allisonella (OR = 0.93, 95% CI 0.89 to 0.98, P = 0.011) seems to be a protective factor for prostate cancer. Sensitivity analysis found no significant heterogeneity, horizontal pleiotropy, or reverse causal links in all causal associations. CONCLUSION: This MR study lends support to a causal relationship between genetically predicted gut microbiota and prostate cancer. Research on the gut-prostate axis, along with further multi-omics analyses, holds significant implications for the prevention and treatment of prostate cancer.

Associations between Longitudinal Changes in Sleep Stages and Risk of Cognitive Decline in Older Men.

STUDY OBJECTIVES: To investigate the relationships between longitudinal changes in sleep stages and the risk of cognitive decline in older men. METHODS: This study included 978 community-dwelling older men who participated in the first (2003-2005) and second (2009-2012) sleep ancillary study visits of the Osteoporotic Fractures in Men Study. We examined the longitudinal changes in sleep stages at the initial and follow-up visits, and the association with concurrent clinically relevant cognitive decline during the 6.5-year follow-up. RESULTS: Men with low to moderate (quartile 2, Q2) and moderate increase (Q3) in N1 sleep percentage had a reduced risk of cognitive decline on the Modified Mini-Mental State Examination compared to those with a substantial increase (Q4) in N1 sleep percentage. Additionally, men who experienced a low to moderate (Q2) increase in N1 sleep percentage had a lower risk of cognitive decline on the Trails B compared with men in the reference group (Q4). Furthermore, men with the most pronounced reduction (Q1) in N2 sleep percentage had a significantly higher risk of cognitive decline on the Trails B compared to those in the reference group (Q4). No significant association was found between changes in N3 and rapid eye movement sleep and the risk of cognitive decline. CONCLUSIONS: Our results suggested that a relatively lower increase in N1 sleep showed a reduced risk of cognitive decline. However, a pronounced decrease in N2 sleep was associated with concurrent cognitive decline. These findings may help identify older men at risk of clinically relevant cognitive decline.

Low Bone Mineral Density and the Risk of Benign Paroxysmal Positional Vertigo.

OBJECTIVE: This study aimed to comprehensively analyze the relationship between low bone mineral density (BMD) and the risk of benign paroxysmal positional vertigo (BPPV) based on the large prospective population-based UK Biobank (UKB) cohort. STUDY DESIGN: Prospective population-based cohort study. SETTING: The UKB. METHODS: This prospective cohort study included UKB participants recruited between 2006 and 2010 who had information on BMD and did not have BPPV before being diagnosed with low BMD. Univariable and multivariable logistic regression models were constructed to assess the association between low BMD (overall low BMD, osteopenia, and osteoporosis) and BPPV. We further conducted sex and age subgroup analysis, respectively. Finally, the effects of antiosteoporosis and female sex hormone medications on BPPV in participants with osteoporosis were evaluated. RESULTS: In total, 484,303 participants were included in the final analysis, and 985 developed BPPV after a maximum follow-up period of 15 years. Osteoporosis was associated with a higher risk of BPPV (odds ratio [OR] = 1.37, P = .0094), whereas osteopenia was not. Subgroup analyses suggested that the association between osteoporosis and BPPV was significant only in elderly females (≥60 years, OR = 1.51, P = .0007). However, no association was observed between antiosteoporosis or female sex hormone medications and BPPV in the participants with osteoporosis. CONCLUSION: Osteoporosis was associated with a higher risk of developing general BPPV, especially in females aged ≥ 60 years old, whereas osteopenia was not associated with BPPV.