Threshold and combined effects of heavy metals on the risk of phenotypic age acceleration among U.S. adults.

Accumulation of heavy metals in the body has been shown to affect the phenotypic age (PhenoAge). However, the combined and threshold effects of blood heavy metals on the risk of PhenoAge acceleration (PhenoAgeAccel) are not well understood. A cross-sectional study was conducted using blood heavy metal data (N = 7763, age ≥18 years) from the 2015-2018 National Health and Nutrition Examination Survey. PhenoAgeAccel was calculated from actual age and nine biomarkers. Multiple regression equations were used to describe the relationship between heavy metals and PhenoAgeAccel. Least Absolute Shrinkage and Selection Operator (LASSO) regression modeling was used to explore the relationship between the combined effects of heavy metals and PhenoAgeAccel. Threshold effect and multiple regression analyses were performed to explore the linear and nonlinear relationships between heavy metals and PhenoAgeAccel. Threshold effect analysis showed that blood mercury (Hg) concentration was linearly associated with PhenoAgeAccel. In contrast, lead (Pb), cadmium (Cd), manganese (Mn), and combined exposure were nonlinearly associated with PhenoAgeAccel. In addition, the combination of Pb, Cd, Hg, and Mn significantly affected PhenoAgeAccel. The risk of PhenoAgeAccel was increased by 207% (P < 0.0001). Meanwhile, a threshold relationship was found between blood Pb, Cd, Mn, and the occurrence of PhenoAgeAccel. Overall, our results indicate that combined exposure to heavy metals may increase the risk of PhenoAgeAccel. This study underscores the need to reduce heavy metal pollution in the environment and provides a reference threshold for future studies.

Mindfulness-Based Therapy for Military Populations with Chronic Pain: A Systematic Review.

Background: Due to the limited role of chronic pain medication in military personnel and the distress caused to the military population, mindfulness-based therapy has been considered for the follow-up treatment of military personnel with chronic pain. The purpose of this review is to explore the effect and the implementation of mindfulness-based therapy for the military population with chronic pain. Methods: The keywords for the search included "mindfulness" AND ("pain" OR "chronic pain") AND ("military" OR "veteran"). The PubMed, Embase, and Cochrane Library databases were searched. The Cochrane Collaboration tool was used to independently assess the risk of bias of the included randomized controlled trials, and the Newcastle-Ottawa Scale was used to independently assess the risk of bias of the included case-control studies. Results: A total of 175 papers were identified; 65 duplicates were excluded, and 59 papers that did not meet the inclusion criteria were excluded after reading the titles and abstracts. The remaining 51 papers were read in full, 42 of which did not meet the inclusion criteria. Nine papers met the inclusion criteria and were included in the study. The nine studies included 507 veterans and 56 active-duty female military personnel. All pain interventions were mindfulness-based therapy, and all of them were integrated into or adapted from standard mindfulness courses. The results all showed that after mindfulness-based therapy, the relevant indicators improved. Conclusions: Mindfulness-based therapy is an effective treatment method for the military population with chronic pain. The review indicates that future research should focus on the best setting for mindfulness-based therapy, including the course content and time.

Progress in overactive bladder: novel avenues from psychology to clinical opinions.

Rationale: Overactive bladder (OAB) is a common, distressing condition that worsens with age and impacts quality of life significantly. As a results of its clinical symptoms, patients suffer from serious physical and mental health issues, have a poor quality of life, and participate in a serious economic burden. The key social-psychological factors include living habits, eating habits, and personality characteristics on this disease, even though the pathogenesis of OAB is complex. However, there is few cognitions and research on OAB in the field of psychology. Methods/Search Strategy: Between 2000 and 2022, two electronic databases were systematically searched in accordance with Cochrane library guidelines (PubMed/Medline, Web of Science). An analysis of the remaining articles with relevant information was conducted using a data extraction sheet. An itemized flow diagram was adopted and used to report systematic reviews and meta-analysis. A systematic review of studies published from 2000 to 2022 in English language were conducted and included in the review. The intended audience: Urological surgeon and psychologists majoring in urinary diseases. Implication: As a result of this information, we are able to develop a better understanding of the role of psychological factors in the development of OAB and suggest potential therapeutic directions for OAB patients. This may benefit the recovery of OAB patients.

Targeted therapy based on ubiquitin-specific proteases, signalling pathways and E3 ligases in non-small-cell lung cancer.

Lung cancer is one of the most common malignant tumours worldwide, with the highest mortality rate. Approximately 1.6 million deaths owing to lung cancer are reported annually; of which, 85% of deaths occur owing to non-small-cell lung cancer (NSCLC). At present, the conventional treatment methods for NSCLC include radiotherapy, chemotherapy, targeted therapy and surgery. However, drug resistance and tumour invasion or metastasis often lead to treatment failure. The ubiquitin-proteasome pathway (UPP) plays an important role in the occurrence and development of tumours. Upregulation or inhibition of proteins or enzymes involved in UPP can promote or inhibit the occurrence and development of tumours, respectively. As regulators of UPP, ubiquitin-specific proteases (USPs) primarily inhibit the degradation of target proteins by proteasomes through deubiquitination and hence play a carcinogenic or anticancer role. This review focuses on the role of USPs in the occurrence and development of NSCLC and the potential of corresponding targeted drugs, PROTACs and small-molecule inhibitors in the treatment of NSCLC.

Correlation Analysis between Retention of Gd-DTPA in the Cystic Area of Brain Metastasis and MRI Signs.

Objective: The aim of this study is to investigate gadolinium-diethylenetriaminepentacetate (Gd-DTPA) retention in the cystic area of brain metastasis and its correlation with MRI signs. Methods: Clinical and MRI data of 76 patients with brain metastasis in the cystic area were collected. The contrast signal intensity (CSI) of the cystic area and edema area in the plain scan, enhanced scan, and plain scan after enhancement within 1 month (hereafter referred to as "enhanced plain scan") were analyzed to determine whether Gd-DTPA was retained in these areas. The lesions with higher CSI values on the enhanced plain scan were classified as the Gd-DTPA retention group and the remaining lesions as the Gd-DTPA-free group. The two groups were compared to determine significant differences in primary lesion type, tumor size, tumor location, capsule wall thickness and morphology, peritumoral edema, and renal function. Results: A total of 123 lesions were detected. The CSI of the enhanced plain scan exceeded that of the plain scan and enhanced scan in the cystic area (P < 0.05). There were 54 lesions (43.9%) with Gd-DTPA retention in the cystic area and 69 lesions (56.1%) without Gd-DTPA retention. Significant differences were observed in tumor size and cystic wall thickness between the two groups (P < 0.05), while no significant differences in primary lesion type, cystic wall shape, peritumoral edema, or function were observed. Conclusion: The retention of Gd-DTPA was found in the cystic area of some brain metastases, which was correlated with tumor size and cystic wall thickness.

Evaluation of anthropometric indices as a predictor of diabetes in Dong and Miao ethnicities in China: A cross-sectional analysis of China Multi-Ethnic Cohort Study.

BACKGROUND: Although it is known that obesity is inseparable from diabetes, many anthropometric indices are used for determining obesity. At the same time, research on the predictive indices of diabetes in Chinese minority populations is lacking. Therefore, this study determines the relationship between different anthropometric indices and diabetes, and identifies the best index and best cut-off values for predicting diabetes. METHOD: In total, 11,035 Dong and Miao ethnic participants (age: 30-79 years) from the China Multi-Ethnic Cohort study were included. The logistic regression model was used to examine the relationship between the different anthropometric indices and diabetes risk. The receiver operating characteristic curve and the area under the curve (AUC) were used to identify the best predictor of diabetes. RESULTS: In multivariate adjusted logistic regression models, body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), a body shape index (ABSI), body roundness index (BRI), and visceral adiposity index (VAI) were positively correlated with diabetes risk. Among Chinese Dong men and women and Miao men, WHR had the largest AUC (0.654/0.719/0.651). Among Miao women, VAI had the largest AUC(0.701). The best cut-off values of WHR for Dong men and women and Miao men were 0.94, 0.92, and 0.91, respectively. The best cut-off value of VAI for Miao women was 2.20. CONCLUSION: Obesity indicators better predict diabetes in women than men. WHR may be the best predictor of diabetes risk in both sex of Dong ethnicity and Miao men, and VAI may be the best predictor of diabetes risk in Miao women.

The Predictive Effect of Negative Psychological Emotions of Anxiety and Depression on the Poor Prognosis of CHD Patients with Stent Implantation and the Improvement of Clinical Intervention Measures.

OBJECTIVE: To explore the predictive effect of negative emotions such as anxiety and depression on the poor prognosis of coronary heart disease (CHD) patients with stent implantation and to seek the improvement of clinical intervention measures. METHODS: A total of 303 patients with CHD and PCI were recruited from February 2019 to April 2021. The risk factors of CHD such as anxiety and depression, age, sex, smoking and drinking, BMI, hypertension, diabetes, dyslipidemia, and family history of CHD were collected. Meanwhile, clinical data such as laboratory examination, angiography, diseased vessels, and stent types were collected. The patients were followed up for 1 year, and the medical records, hospitalization records, or death records were checked by telephone interview once a month. Major adverse cardiovascular events (MACE) such as emergency and causes, readmission times and causes, new nonfatal myocardial infarction, stent restenosis, heart failure, arrhythmia, and death were recorded. The incidence of anxiety and depression in patients after PCI was counted, and Cox regression was applied to analyze the influence and prediction of anxiety and depression on MACE in patients with CHD stent implantation and improve clinical intervention measures. RESULTS: Compared with those without MACE, anxiety (56.25% vs 30.63%), depression (62.5% vs 22.88%, P < 0.01), anxiety combined with depression (46.88% vs 15.50%, P < 0.01), and hypertension history (71.8% vs 39.11%, P < 0.01) were more common in patients with MACE. Uncorrected Cox proportional hazard regression found that people with anxiety had a higher risk of developing MACE than those without anxiety (HR 3.181, P < 0.01). Multiple Cox proportional hazard regression analysis of anxiety showed that anxiety was an independent predictor of cumulative MACE (P < 0.01). The risk of developing MACE in patients with anxiety was 3.742 times higher than that in patients without anxiety (P < 0.01). Uncorrected Cox hazard regression analysis showed that people with depression had a higher risk of developing MACE than those without depression (HR 5.434, P < 0.01). Furthermore, the results also uncovered that depression was an independent predictor of cumulative MACE (P < 0.01). The risk of MACE in patients with depression was 3.087 times higher than that in patients without depression (P < 0.01). Cox hazard regression showed that the risk of MACE in patients with anxiety and depression was significantly higher than that in patients without anxiety and depression (HR 4.642, P < 0.01). After screening, it was found that anxiety with depression could predict the occurrence of MACE (P < 0.01). The risk of MACE in patients with anxiety and depression was 3.702 times higher than that in patients without anxiety and depression (P < 0.01). Cox regression analysis showed that the risk of MACE with only anxiety and depression was 2.793 times higher than that without anxiety and depression (95% CI 0.914 8.526), with no statistical significance (P > 0.05), and the risk of MACE with depression without anxiety was significantly higher than that without anxiety and depression (P < 0.01). The risk of MACE in patients with anxiety and depression was 7.303 times higher than that in patients without anxiety and depression (P < 0.01). CONCLUSION: Negative emotions such as anxiety and depression can increase the risk of poor prognosis of patients with CHD. Therefore, in clinical work, in addition to routine treatment and nursing during hospitalization, it is recommended to screen patients with depression in CHD patients. Medical staff should use simple and effective assessment tools in time and take active measures to improve the depression of patients. This trial is registered with ChiCTR2200055645.

The Transient Receptor Potential Channel, Vanilloid 5, Induces Chondrocyte Apoptosis via Ca2+ CaMKII-Dependent MAPK and Akt/ mTOR Pathways in a Rat Osteoarthritis Model.

BACKGROUND/AIMS: Chondrocyte apoptosis is a central pathological feature of cartilage in osteoarthritis (OA). Accumulating evidence suggests that calcium ions (Ca2+) are an important regulator of apoptosis. Previously, we reported that the transient receptor potential channel vanilloid (TRPV5) is upregulated in monoiodoacetic acid (MIA)-induced OA articular cartilage. METHODS: The protein levels of TRPV5, phosphorylated Ca2+/calmodulin-dependent kinase II (p-CaMKII), and total CaMKII were detected in vivo using western blotting techniques. Primary chondrocytes were isolated and cultured in vitro. Then, p-CAMKII was immunolocalized by immunofluorescence in chondrocytes. Fluo-4AM staining was used to assess intracellular Ca2+. Annexin V-fluorescein isothiocyanate / propidium iodide flow cytometric analysis was performed to determine chondrocyte apoptosis. Western blotting techniques were used to measure the expression of apoptosis-related proteins. RESULTS: We found that ruthenium red (aTRPV5inhibitor)or(1-[N,O-bis-(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperaze (KN-62) (an inhibitor of Ca2+/calmodulin-dependent kinase II (CaMKII) phosphorylation) can relieve or even reverse OA in vivo. We found that TRPV5 has a specific role in mediating extracellular Ca2+ influx leading to chondrocyte apoptosis in vitro. The apoptotic effect in chondrocytes was inhibited by KN-62. We found that activated p-CaMKII could elicit the phosphorylation of extracellular signal-regulated protein kinase 1/2, c-Jun N-terminal kinase, and p38, three important regulators of the mitogen-activated protein kinase (MAPK) cascade. Moreover, we also showed that activated p-CaMKII could elicit the phosphorylation of protein kinase B (Akt) and two important downstream regulators of mammalian target of rapamycin (mTOR): 4E-binding protein, and S61 kinase. CONCLUSION: Our results demonstrate that upregulated TRPV5 may be an important initiating factor that activates CaMKII phosphorylation via the mediation of Ca2+ influx. In turn, activated p-CaMKII plays a critical role in chondrocyte apoptosis via MAPK and Akt/mTOR pathways.

CAV-1 contributes to bladder cancer progression by inducing epithelial-to-mesenchymal transition.

BACKGROUND: The epithelial-to-mesenchymal transition (EMT) is a critical step in tumor metastasis. CAV-1 has been shown to be an oncogene in bladder cancer. However, little is known about the relationship between CAV-1 and EMT in bladder cancer metastasis. METHODS: Immunohistochemical analysis was carried out retrospectively on tumor samples from patients treated for bladder cancer. CAV-1 and E-cadherin expression levels were measured and correlated with clinical features of tumor grade and metastasis. EMT was assessed in bladder cancer cell lines (T24, UMUC3, HT1376, and 5637) using wound healing and in vitro transwell invasion assays, and small interfering RNA was used to knock down CAV-1 and Slug expression. RESULTS: In this study, we show that increased CAV-1 expression induces bladder cancer cell migration and promotes the EMT, which was determined by the reduction of E-cadherin expression and the induction of N-cadherin and vimentin expression. Knockdown of CAV-1 expression with specific small interfering RNA reduced cell migration and EMT. Mechanistically, CAV-1-induced expression of the transcription factor, Slug. Slug knockdown abolished the CAV-1-induced EMT in bladder cancer cells. We further show that Slug expression is mediated by the CAV-1 regulation of the PI3K/AKT signaling. In addition, positive CAV-1 expression was significantly correlated with negative E-cadherin expression, as determined by immunohistochemistry analysis in bladder cancer tissues. CONCLUSIONS: Our results suggest that CAV-1 promotes invasive phenotypes in bladder cancer cells by inducing EMT through up-regulation of Slug expression, which occurs through activation of the PI3K/AKT signaling pathway. This new role for CAV-1 in promoting bladder cancer metastasis presents CAV-1 and related pathways as potential therapeutic targets in invasive bladder cancer.