Neuroprotective Effect and Mechanism of Tanreqing Injection on Ischemic Stroke: Insights from Network Pharmacology and in vivo Experiments.

OBJECTIVE: To explore the neuroprotective effects and mechanism of Tanreqing Injection (TRQ) on treating ischemic stroke based on network pharmacology and in vivo experimental validation. METHODS: The chemical compounds of TRQ were retrieved based on published data, with targets retrieved from PubChem, Therapeutic Target Database and DrugBank. Network visualization and analysis were performed using Cytoscape, with protein-protein interaction networks derived from the STRING database. Enrichment analysis was performed using Kyoto Encyclopedia of Genes Genomes pathway and Gene Ontology analysis. In in vivo experiments, the middle cerebral artery occlusion (MCAO) model was used. Infarct volume was determined by 2,3,5-triphenyltetrazolium hydrochloride staining and protein expressions were analyzed by Western blot. Molecular docking was performed to predict ligand-receptor interactions. RESULTS: We screened 81 chemical compounds in TRQ and retrieved their therapeutic targets. Of the targets, 116 were therapeutic targets for stroke. The enrichment analysis showed that the apelin signaling pathway was a key pathway for ischemic stroke. Furthermore, in in vivo experiment we found that administering with intraperitoneal injection of 2.5 mL/kg TRQ every 6 h could significantly reduce the infarct volume of MCAO rats (P<0.05). In addition, protein levels of the apelin receptor (APJ)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway were increased by TRQ (P<0.05). In addition, 41 chemical compounds in TRQ could bind to APJ. CONCLUSIONS: The neuroprotective effect of TRQ may be related to the APJ/PI3K/AKT signaling pathway. However, further studies are needed to confirm the findings.

Efficacy and safety of Shenmai injection for acute ischemic stroke: a systematic review and meta-analysis.

Background: Ischemic stroke is a serious and sudden cerebrovascular condition that significantly affects individual's health and imposes a substantial economic burden on medical management. Despite its widespread use in China, there is still a lack of reliable evidence regarding the efficacy of Shenmai injection (SMI) in acute ischemic stroke (AIS). We aimed to comprehensively assess the effectiveness and safety of SMI in treating AIS through a systematic review and meta-analysis. Methods: Randomized controlled studies (RCTs) investigating the efficacy of SMI in treating AIS were searched for in eight databases from the inception of each database till January 2024. We utilized the ROB 2.0 to assess the risk of bias. A meta-analysis was conducted using Review Manager 5.4, while sensitivity analyses and publication bias assessments were conducted using Stata 16.1. Results: A total of 17 studies involving 1,603 AIS patients were included in our meta-analysis. Our results showed that SMI plus conventional treatments (CTs) was more effective than CTs alone in improving the total effective rate (RR 1.22, 95% CI: 1.14 to 1.30, p < 0.00001), the Barthel index (BI) (MD 12.18, 95% CI: 10.30 to 14.06, p < 0.00001), and reducing the National Institute of Health Stroke Scale Score (NIHSS) score (MD -3.05, 95% CI: 3.85 to -2.24, p < 0.00001) and Modified Rankin Scale (mRS) (MD -0.68, 95% CI: 0.86 to-0.49, p < 0.00001). In addition, SMI combination therapy was better than CTs alone in decreasing the levels of IL-6, IL-18, and hs-CRP. SMI therapy also enhanced the cerebral hemorheology of patients by reducing levels of fibrinogen and plasma viscosity. However, there was no significant difference in the incidence of adverse events, including elevated transaminase, rash, nausea, bleeding, urticaria, headache, vomiting, chest tightness, and facial flushes. Moreover, no serious adverse effects or life-threatening events were reported. Conclusion: Our study shows that combining SMI with CTs effectively enhances the neurological function of patients with acute cerebral infarction. However, our findings should be interpreted considering the significant heterogeneity and suboptimal quality of the analyzed trials. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024504675, Identifier PROSPERO, CRD42024504675.

Association between surrogate marker of insulin resistance and bone mineral density in US adults without diabetes.

This study examines the relationship between TyG-BMI, an indicator of insulin resistance, and bone mineral density in US adults without diabetes, revealing a positive association. The findings suggest that higher TyG-BMI levels may be linked to a lower risk of osteoporosis, providing a basis for future research in this area. OBJECTIVE: Patients with osteoporosis are often diagnosed with type 2 diabetes or prediabetes. Insulin resistance is a prediabetic state, and triglyceride glucose-body mass index (TyG-BMI) has been recognized as a potential predictor of it, valuable in assessing prediabetes, atherosclerosis, and other diseases. However, the validity of TyG-BMI in osteoporosis studies remains inadequate. PURPOSE: The purpose of this study was to evaluate the relationship between TyG-BMI and BMD as well as the effect of TyG-BMI on the odds of developing osteoporosis in US adults without diabetes. METHODS: National Health and Nutrition Examination Survey data were obtained. The relationship between TyG-BMI and BMD was evaluated via multivariate linear regression models. Smoothed curve fitting and threshold effect analysis explored potential non-linear relationships, and age, gender, and race subgroup analyses were performed. In addition, multivariate logistic regression models were employed to analyze its potential role in the development of osteoporosis. RESULTS: In a study of 6501 participants, we observed a significant positive correlation between the TyG-BMI index and BMD, even after adjusting for covariates and categorizing TyG-BMI. The study identified specific TyG-BMI folding points-112.476 for the total femur BMD, 100.66 for the femoral neck BMD, 107.291 for the intertrochanter BMD, and 116.58 for the trochanter BMD-indicating shifts in the relationship's strength at these thresholds. While the association's strength slightly decreased after the folding points, it remained significant. Subgroup analyses further confirmed the positive TyG-BMI and BMD correlation. Multivariate linear regression analyses indicated a lower osteoporosis risk in participants with higher TyG-BMI levels, particularly in menopausal women over 40 and men over 60. CONCLUSION: This study suggests a positive correlation between BMD and TyG-BMI in US adults without diabetes. Individuals with higher levels of TyG-BMI may have a lower risk of osteoporosis.

Impact of remote ischemic postconditioning on acute ischemic stroke in China: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Acute ischemic stroke (AIS) is a significant health burden in China, affecting a sizable portion of the population. Conventional pharmacological treatments frequently fall short of desirable outcomes. Therefore, exploring alternative therapies is crucial. Remote ischemic postconditioning (RIPostC) is a noninvasive and cost-effective adjunctive therapy. This study aimed to investigate the efficacy and safety of RIPostC as an adjunctive therapy for AIS to inform clinical practice. METHODS: A comprehensive search was conducted across the PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang, Weipu (VIP), and China Biology Medicine disc (CBM) databases up to October 2023. All included studies underwent bias risk assessment using the Cochrane risk-of-bias assessment tool. The primary outcome measure was the National Institute of Health Stroke Scale (NIHSS), with secondary outcomes including the Barthel index (BI), D-dimer, C-reactive protein (CRP), fibrinogen (FIB), brain-derived neurotrophic factor (BDNF), modified Rankin scale (mRS), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels. The data were analyzed using fixed-effects and random-effects models in Review Manager, with mean differences (MDs) and 95% confidence intervals (CIs) calculated for each outcome. The grading of recommendations, assessment, development, and evaluations (GRADE) approach was used to evaluate the level of evidence for each outcome measure. RESULTS: This meta-analysis included 38 studies, encompassing 4334 patients. Compared with the control group, the RIPostC group had significantly lower NIHSS scores, serum CRP, D-dimer, IL-6, TNF-α, and FIB levels, and increased BDNF levels. Moreover, it improved the patient's BI and mRS scores. According to the GRADE approach, the quality of evidence for mRS was deemed "moderate," while the NIHSS, BI, and CRP were rated as "low" quality. IL-6, TNF-α, FIB, D-dimer, and BDNF received "very low" quality ratings. CONCLUSION: The findings suggest that RIPostC activates endogenous protective mechanisms, providing benefits to patients with AIS.

The association between lower extremity function and cardiovascular diseases risk in older Chinese adults: Longitudinal evidence from a nationwide cohort.

BACKGROUND: Older adults in China are at a high risk of cardiovascular diseases (CVD), and impaired lower extremity function (LEF) is commonly observed in this demographic. This study aimed at assessing the association between LEF and CVD, thus providing valuable insights for clinical practice and public health policies. METHODS: A sample of 4,636 individuals was included from the China Health and Retirement Longitudinal Study (CHARLS) dataset. Logistic regression and cox proportional hazard regression model was utilized to study the association between LEF and CVD incidence. Cross-lagged panel models were utilized to investigate the potential causal association between LEF and CVD over time. RESULTS: Poor LEF was significantly associated with a higher risk of CVD in the total population [OR (95 % CI): 1.62 (1.27-2.05), P < 0.001]. Individuals with poor LEF demonstrated an increased risk of developing CVD [HR (95 % CI): 1.11 (1.02-1.23), P < 0.05], particularly stroke, compared to those with good LEF. And those with poor LEF had higher risks for heart disease [1.21 (1.00-1.45), P < 0.05] and stroke [1.98 (1.47-2.67), P < 0.001]. CONCLUSION: The results suggest the potential usefulness of the Short Physical Performance Battery (SPPB) for classifying stroke risk in older Chinese adults, which also suggested that preventing and/or improving LEF may be beneficial for reducing stroke incidence and promoting healthy aging for older adults.

The efficacy and safety of ketamine in the treatment of super-refractory status epilepticus: a systematic review.

BACKGROUND: Ketamine, as an anesthetic, has been considered for terminating status epilepticus (SE); however, due to the urgency and severity of the condition, there are currently no randomized controlled trials internationally assessing the efficacy of ketamine for treating super-refractory status epilepticus. Similarly, there appears to be a lack of systematic reviews addressing this topic in the literature. Therefore, this systematic review aims to explore the effectiveness and safety of ketamine for terminating super-refractory status epilepticus. METHODS: We conducted a systematic search on PubMed, EMBASE, and Web of Science databases. Manuscripts unrelated to the research on super-refractory status epilepticus were excluded, as were manuscripts published in non-English languages. The quality assessment and risk of bias were evaluated using the MINORS criteria. Data extraction was limited to qualitative synthesis due to the unsuitability of the data for meta-analysis. RESULTS: Out of 782 studies retrieved from electronic databases, 11 met the inclusion criteria. Among them, 10 studies were retrospective, and 1 study was prospective. Patient data for inclusion were sourced from the case registries of the researchers' respective hospitals. Across all included studies, the administration of ketamine significantly reduced the duration of status epilepticus and demonstrated higher safety compared to patients not receiving ketamine treatment for super-refractory status epilepticus. Additionally, early administration of ketamine correlated with improved treatment outcomes. The risk of bias across all studies was deemed low. CONCLUSION: This systematic review suggests that ketamine may be a feasible treatment option for super-refractory status epilepticus. However, given the critical nature of super-refractory status epilepticus, clinicians should prioritize its termination over evaluating the efficacy of specific medications, ensuring patient safety remains paramount. If feasible in real-world medical settings, future research should focus on designing randomized controlled trials to observe the specific efficacy and mechanisms of ketamine. Careful validation is necessary before considering ketamine as a first-line treatment for super-refractory status epilepticus.

The development and external validation of a web-based nomogram for predicting overall survival with Ewing sarcoma in children.

Background: Ewing sarcoma remains the second most prevalent primary aggressive bone tumor in teens and young adults. The aim of our study was to develop and validate a web-based nomogram to predict the overall survival for Ewing sarcoma in children. Methods: A total of 698 patients, with 640 cases from the Surveillance, Epidemiology, and End Results (the training set) and 58 cases (the external validation set), were included in this study. Cox analyses were carried out to determine the independent prognostic indicators, which were further included to establish a web-based nomogram. The predictive abilities were tested through the concordance index, calibration curve, decision curve analysis, and area under the receiver operating characteristic curve. Results: As suggested by univariate and multivariate Cox analyses, age, primary site, tumor size, metastasis stage (M stage), and chemotherapy were included as the independent predictive variables. The area under the receiver operating characteristic curve values, calibration curves, concordance index, and decision curve analysis from training and validation groups suggested the model has great clinical applications. Conclusion: We developed a convenient and precise web-based nomogram to evaluate overall survival for Ewing sarcoma in children. The application of this nomogram would assist physicians and patients in making decisions.

Association of congestive heart failure with mortality in individuals with rheumatoid arthritis: a cohort study.

OBJECTIVE: Rheumatoid arthritis (RA) is a risk factor for congestive heart failure (CHF). Evidence is lacking regarding the relationship between CHF and mortality among American adults with RA. We aimed to investigate the relationship between CHF and mortality in patients with RA. METHODS: We extracted the corresponding data from the National Health and Nutrition Examination Survey (NHANES) database and calculated the hazard ratios (HR) and 95% CIs between CHF and mortality from all causes, cardiovascular disease (CVD), and cancer by using a Cox proportional risk model. RESULTS: A total of 2045 participants with a mean age of 60.32 ± 13.96 years were included; 57.60% were female. During a median follow-up period of 109 months, there were 602 deaths. After adjusting for potential confounders, compared with participants who are non-CHF, those with CHF had 60% (HR 1.60, 95% CI 1.27-2.01) and 110% (1.45, 1.45 to 3.06) higher all-cause mortality and CVD mortality, respectively. Furthermore, a significant association between CHF and all-cause mortality can also be observed in female individuals and those aged 65 and above. There was no significant association between CHF and cancer mortality. CONCLUSIONS: In this cohort study of US adults with RA, CHF was significantly associated with an increased risk of all-cause or CVD-related death. This finding underscores the importance of CHF in the management of patients with RA and may provide future information on maintaining the health status of patients with RA. Key messages • The study findings demonstrate a significant increase in overall mortality and cardiovascular mortality among individuals with RA who develop CHF. • This knowledge can assist healthcare professionals in identifying high-risk patients who could benefit from targeted monitoring and early intervention to prevent or manage CHF.

Prevalence and Site of Concomitant Osteochondral Injuries in Patients With Acute Lateral Patellar Dislocation: A Systematic Review and Meta-analysis.

Background: Osteochondral injuries (OCIs) are common in patients with acute lateral patellar dislocation, which can produce both short- and long-;term adverse effects. However, the pattern of these injuries warrants further analysis, especially in relation to patient age. Purpose: To determine the overall prevalence of concomitant OCIs as well as the prevalence differences based on location and age after acute lateral patellar dislocations. Study Design: Systematic review; Level of evidence, 4. Methods: A comprehensive search of PubMed, Embase, Web of Science, and Cochrane Library was completed from inception to July 20, 2022. All articles reporting the prevalence of OCI were included. The sample characteristics such as age, study design, magnetic resonance imaging diagnostic data, and the number of patients with OCI were extracted. The Methodological Index for Non-Randomized Studies (MINORS) was used for quality assessment. The overall and per-;site injury rates were calculated, and the prevalence was stratified by age-;group (≤16 and >16 years) and compared. Results: The systematic review included 39 studies involving 3354 patients. MINORS scores were 11.94 ± 1.98 and 16 ± 3.46 in the noncomparative and comparative studies, respectively. The overall prevalence of bone bruises and OCI was 89.6% (95% CI, 77.4%-97.7%) and 48.8% (95% CI, 39.0%-58.7%), respectively. In both overall and >16-year-old patients, the lateral femoral condyle (LFC) was the most common site of bone bruise (90.5% [95% CI, 84.0%-95.6%] and 91.5% [95% CI, 84.3%-96.9%], respectively); however, the medial patellar bruise was more common in patients ≤16 years (89.2% [95% CI, 82.9%-94.4%]). Among the pooled sites of OCI, the medial patella accounted for the largest proportion (36.9% [95% CI, 28.0%-46.3%]). OCIs were more common in patients >16 years (52.6% [95% CI, 39.4%-65.6%]) than in patients ≤16 years (46.6% [95% CI, 33.2%-60.3%]). Conclusion: Bone bruises on the LFC were most prevalent overall and in patients >16 years, whereas bone bruises on the medial patella were more prevalent in patients ≤16 years. OCIs were frequently seen in patients >16 years, with the most common site being the medial patella.

Associations of the serum vitamin D with mortality in postmenopausal women.

PURPOSE: Current evidence on the association of serum vitamin D with mortality in postmenopausal women is limited and inconsistent. Therefore, the purpose of this study was to examine the relationship between serum vitamin D and mortality in postmenopausal women. METHODS: In this study, we used data from the NHANES (2001-2018) and conducted a multivariate Cox regression model to examine associations between serum vitamin D and all-cause mortality, cardiovascular mortality (CVD), and cancer mortality. RESULTS: In a median follow-up period of 8.3 years, 1905 deaths of all causes were reported, 601 were due to CVD, and 385 deaths were due to cancer. After multivariable adjustment, higher serum vitamin D levels were significantly associated with a reduced risk of death. Compared to participants with lower vitamin D levels (<25 nmol/L), those with higher vitamin D levels (≥75.0 nmol/L) had a lower risk of all-cause mortality (hazard ratio 0.60, 95 % confidence interval 0.49 to 0.74), a lower risk of cardiovascular mortality (0.51, 0.35 to 0.74), and a lower risk of cancer mortality (0.43, 0.28 to 0.67). Moreover, we observed an L-shaped dose-response relationship of serum vitamin D levels with all-cause mortality, and cancer mortality, with this inflexion point being 55.9 nmol/L, and 51.2 nmol/L, respectively. CONCLUSIONS: Higher concentrations of serum vitamin D substantially correlated with a reduction in mortality risk from all-cause, CVD, and cancer in postmenopausal women. These results imply that upholding adequate vitamin D levels may help prevent premature death in postmenopausal women.

Efficacy and safety of Chinese herbal medicine in post-stroke epilepsy: a systematic review and meta-analysis.

Background: Poststroke epilepsy (PSE) is a common complication of strokes that seriously affects the recovery and quality of life of patients, and effective treatments are needed. Chinese herbal medicine (CHM) adjunctive therapy is a viable treatment option, but current evidence is insufficient to support its efficacy and safety. This study aimed to evaluate the efficacy and tolerability of CHM adjunctive therapy in the treatment of PSE. Methods: A systematic search of eight databases was conducted to identify PSE-related randomized clinical trials from the inception of each database through October 2023. The methodological quality assessment was conducted by RoB 2.0, meta-analysis was conducted by RevMan 5.3 and Stata 15.1, and evidence quality was evaluated by GRADE. Results: Twenty-three RCTs involving 1,901 PSE patients were identified. We found that orally administered CHM plus conventional Western medicine (CWM) was superior to CWM monotherapy in increasing the 75% responder rate (RR 1.46, 95% CI: 1.31 to 1.62, p < 0.00001), decreasing the seizure duration (MD -1.01, 95% CI: -1.30 to -0.72, p < 0.00001), improving total responder rate (RR 1.29, 95% CI: 1.20 to 1.37, p < 0.00001), reducing epileptiform discharges (EDs) (MD -2.02.46, 95% CI: -2.64 to -1.40, p < 0.00001), and decreasing the number of leads involved in epileptiform discharge (MD -3.92, 95% CI: -5.15 to -2.68, p < 0.00001). Furthermore, intravenously administered CHM plus CWM was superior regarding 75% responder rate (RR 1.39, 95% CI: 1.24 to 1.56, p < 0.00001), total responder rate (RR 1.29, 95% CI: 1.20 to 1.39, p < 0.00001), EDs (MD -3.92, 95% CI: -5.15 to -2.68, p < 0.00001), and the number of leads involved in epileptiform discharge (MD -1.82, 95% CI: -2.62 to -1.02, p < 0.00001). However, regarding the 50%-75% responder rate, there was no statistically significant difference between the two groups for either oral (RR 1.00, 95% CI: 0.77 to 1.29, p = 0.98) or injectable CHM (RR 0.95, 95% CI: 0.67 to 1.33, p = 0.75). Both orally administered CHM plus CWM (RR 0.56, 95% CI: 0.35 to 0.90, p = 0.02) and intravenously administered CHM plus CWM (RR 0.64, 95% CI: 0.45 to 0.90, p = 0.010) caused fewer AEs than CWM. Furthermore, the levels of evidence ranged from low to high due to publication bias and heterogeneity. Conclusion: CHM adjuvant therapy may be an effective and safe therapy for PSE. However, due to the poor quality of clinical data, more well-designed RCTs are needed to confirm these findings. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=364356, identifier PROSPERO (CRD42022364356).

Efficacy and safety of acupuncture in post-stroke constipation: a systematic review and meta-analysis.

Background and objective: Post-stroke constipation (PSC) is a common complication of strokes that seriously affects the recovery and quality of life of patients, and effective treatments are needed. Acupuncture is a viable treatment option, but current evidence is insufficient to support its efficacy and safety. This study aims to evaluate the efficacy and safety of acupuncture in the treatment of PSC. Methods: A systematic search of eight databases was conducted to identify PSC-related randomized clinical trials from the inception of each database through May 2023. Methodological quality assessment was conducted by RoB 2.0, meta-analysis was conducted by RevMan 5.3 and Stata 15.1, and evidence quality was evaluated by GRADE. Moreover, reporting quality of acupuncture interventions was assessed using the Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA). Results: Thirty RCTs involving 2,220 patients were identified. We found that acupuncture was superior to conventional treatment (CT) in improving total responder rate [risk ratio (RR): 1.16, 95% confidence interval (CI): 1.09 to 1.25, p < 0.0001], decreasing constipation symptom scores [standardized mean difference (SMD): -0.65, 95% CI: -0.83 to -0.46, p < 0.00001], increasing serum P substance (SP) levels (SMD: 1.92, 95% CI: 0.47 to 3.36, p = 0.009), reducing the time to first bowel movement (BM) (SMD: -1.19, 95% CI: -2.13 to -0.25, p = 0.01), and lowing serum vasoactive intestinal peptide (VIP) levels (SMD: -2.11, 95% CI: -3.83 to -0.38, p = 0.02). Furthermore, acupuncture plus CT was superior regarding total responder rate (RR: 1.26, 95% CI: 1.17 to 1.35, p < 0.00001), serum SP levels (SMD: 2.00, 95% CI: 1.65-2.35, p < 0.00001), time to first BM (SMD: -2.08, 95% CI: -2.44 to -1.71, p < 0.00001), and serum VIP levels (SMD: -1.71, 95% CI: -2.24 to -1.18, p < 0.00001). However, regarding Bristol Stool Scale (BSS) score, acupuncture plus CT was superior to CT (SMD: -2.48, 95% CI: -3.22 to -1.73, p < 0.00001), while there was no statistically significant difference between acupuncture and CT (SMD: 0.28, 95% CI: -0.02 to 0.58, p = 0.07). Acupuncture causes fewer AEs than CT (RR: 0.13, 95% CI: 0.06 to 0.26, p < 0.00001), though there was no statistically significant difference between acupuncture plus CT vs. CT (RR: 1.30, 95% CI: 0.60 to 2.84, p = 0.51). Conclusion: Acupuncture may be an effective and safe therapy for PSC. However, given the inferior quality of clinical data, additional well-designed RCTs are required to confirm these findings.

Bone mineral density is associated with composite dietary antioxidant index among US adults: results from NHANES.

This cross-sectional study investigated the relationship between composite dietary antioxidant index (CDAI) and individual dietary antioxidant intakes, including vitamins A, C, and E, zinc, selenium, and carotenoids, and bone mineral density (BMD) in the US population aged 20 years older. We found a positive correlation between CDAI and femoral BMD. Moreover, higher intakes of vitamin C, vitamin E, selenium, zinc, and carotenoids were associated with higher femoral BMD. INTRODUCTION: While individual dietary antioxidants have shown beneficial effects on bone metabolism, the diverse and potentially interacting nature of dietary components may limit the accuracy of evaluating their impact on bone health. Thus, this study aims to investigate the association between CDAI and BMD. Additionally, we explore the relationship between the intake of individual components of the CDAI and BMD. METHODS: The CDAI is a novel index evaluating total dietary antioxidant intake, considering vitamins A, C, and E, zinc, selenium, and carotenoids. A cross-sectional analysis was conducted using data from participants aged ≥ 20 in the National Health and Nutrition Examination Survey (2005-2010, 2013-2014, and 2017-2018). We utilized multivariate linear regression models to examine the relationship between CDAI, individual dietary antioxidants, including vitamins A, C, and E, zinc, selenium, carotenoids, and femoral BMD. RESULTS: The final analysis included 10,584 participants with a mean age of 50.73 ± 16.65 years. After multivariate adjustment, the second to fourth quartiles of CDAI (- 2.00-0.04, 0.04-2.54, and 2.54-70.78) exhibited higher femoral BMD compared to the first quartile of CADI (- 7.34 to - 2.00). Multiple regression analysis revealed that higher intakes of vitamin C, vitamin E, selenium, zinc, and carotenoids were associated with higher femoral BMD. CONCLUSIONS: CDAI serves as a comprehensive tool for evaluating the overall antioxidant capacity of antioxidants in diets. Additionally, our study shows a positive correlation between CDAI and BMD, which indicates that the combined intake of dietary antioxidants may help reduce the risk of osteoporosis in adults.

Marital status independently predicts the overall survival in young adult patients with lymphoma: A population-based, propensity-matched study.

We predicted that marital status may have predictive effects on young adult patients with cancer. A total of 37,028 young adult patients (20-39 years old) newly diagnosed with lymphoma by positive histology between 1988 and 2015 were collected from the Surveillance, Epidemiology, and End Results database. Patients were separated into married and unmarried groups. Multivariate regression was utilized to explore the association between marital status and overall survival, and propensity score matching and an inverse probability of treatment weighting were applied to corroborate our results. Among 37,028 eligible lymphoma patients, 12,827 married patients, and 12,827 unmarried patients, had equal propensity scores and were eventually recruited in this research. Moreover, married patients reported enhanced 10-year overall survival in the original group and the matched cohort. The multivariable Cox regression analysis revealed a vital advantageous influence of married status on overall mortality, with an adjusted hazard ratio (HR) of 0.54 (95% CI, 0.51-0.57, P < .001) and the association remained robust after propensity score matching (HR, 0.53, 95% CI 0.51-0.55, P < .001) and inverse probability of treatment weighting (HR, 0.53, 95% CI 0.51-0.56, P < .001) after adjusting for confounding factors. Marital status had predictive significance for overall survival in young adult patients with lymphoma.

A novel primary osteoporosis screening tool (POST) for adults aged 50 years and over.

PURPOSE: This study aimed to develop and validate a simple primary osteoporosis screening tool (POST) based on adults aged 50 years and older. METHODS: This study included participants aged ≥50 from the National Health and Nutrition Examination Survey. Osteoporosis was defined according to bone mineral density values. The POST was developed based on methods from previous studies. Moreover, we plotted the receiver operating characteristic curves to calculate the area under the curve (AUC) and determine the optimal cut-off value according to the weighted Youden index. In addition, we compared the performances in identifying individuals with osteoporosis between the POST and the Osteoporosis Self-assessment Tool (OST). Finally, we also assessed the performance of the POST in the Chinese population. RESULTS: Finally, a total of 6665 individuals were included in this study. The AUC values of the POST for identifying individuals with osteoporosis in the development cohort and the validation cohort were 0.81 (95% CI: 0.79-0.83) and 0.81 (95% CI: 0.77-0.84), respectively. Moreover, a POST-score ≥7 was determined as the threshold to identify individuals with osteoporosis, in which the sensitivity was greater than 90%. In addition, the POST showed significantly higher sensitivity than the OST. Finally, the POST showed an AUC of 0.75 (95% CI: 0.65-0.85) among 94 Chinese subjects aged ≥50 years old. CONCLUSIONS: POST is a convenient and effective tool for osteoporosis screening among adults aged 50 years and over, which might provide new methodological support for future osteoporosis screening.

Downregulation of cardiac PIASy inhibits Cx43 SUMOylation and ameliorates ventricular arrhythmias in a rat model of myocardial ischemia/reperfusion injury.

BACKGROUND: Dysfunction of the gap junction channel protein connexin 43 (Cx43) contributes to myocardial ischemia/reperfusion (I/R)-induced ventricular arrhythmias. Cx43 can be regulated by small ubiquitin-like modifier (SUMO) modification. Protein inhibitor of activated STAT Y (PIASy) is an E3 SUMO ligase for its target proteins. However, whether Cx43 is a target protein of PIASy and whether Cx43 SUMOylation plays a role in I/R-induced arrhythmias are largely unknown. METHODS: Male Sprague-Dawley rats were infected with PIASy short hairpin ribonucleic acid (shRNA) using recombinant adeno-associated virus subtype 9 (rAAV9). Two weeks later, the rats were subjected to 45 min of left coronary artery occlusion followed by 2 h reperfusion. Electrocardiogram was recorded to assess arrhythmias. Rat ventricular tissues were collected for molecular biological measurements. RESULTS: Following 45 min of ischemia, QRS duration and QTc intervals statistically significantly increased, but these values decreased after transfecting PIASy shRNA. PIASy downregulation ameliorated ventricular arrhythmias induced by myocardial I/R, as evidenced by the decreased incidence of ventricular tachycardia and ventricular fibrillation, and reduced arrythmia score. In addition, myocardial I/R statistically significantly induced PIASy expression and Cx43 SUMOylation, accompanied by reduced Cx43 phosphorylation and plakophilin 2 (PKP2) expression. Moreover, PIASy downregulation remarkably reduced Cx43 SUMOylation, accompanied by increased Cx43 phosphorylation and PKP2 expression after I/R. CONCLUSION: PIASy downregulation inhibited Cx43 SUMOylation and increased PKP2 expression, thereby improving ventricular arrhythmias in ischemic/reperfused rats heart.

Finding a vocation for validation: taking proteomics beyond association and location.

First established in the seventies, proteomics, chemoproteomics, and most recently, spatial/proximity-proteomics technologies have empowered researchers with new capabilities to illuminate cellular communication networks that govern sophisticated decision-making processes. With an ever-growing inventory of these advanced proteomics tools, the onus is upon the researchers to understand their individual advantages and limitations, such that we can ensure rigorous implementation and conclusions derived from critical data interpretations backed up by orthogonal series of functional validations. This perspective-based on the authors' experience in applying varied proteomics workflows in complex living models-underlines key book-keeping considerations, comparing and contrasting most-commonly-deployed modern proteomics profiling technologies. We hope this article stimulates thoughts among expert users and equips new-comers with practical knowhow of what has become an indispensable tool in chemical biology, drug discovery, and broader life-science investigations.

Metabolic associated fatty liver disease and bone mineral density: a cross-sectional study of the National Health and Nutrition Examination Survey 2017-2018.

This research is a cross-sectional study based on the participants aged 50 years and older from National Health and Nutrition Examination Survey (NHANES) database. The metabolic associated fatty liver disease (MAFLD) population has higher BMD and a lower risk of osteoporosis than those without MAFLD. INTRODUCTION: MAFLD is a new definition presented by panel of experts based on non-alcoholic fatty liver disease in 2020. However, the link between MAFLD and bone mineral density (BMD) is uncertain. Thus, the present study aimed to investigate the relationship between MAFLD and BMD. METHODS: This cross-sectional study included subjects aged ≥ 50 years from the National Health and Nutrition Examination Survey 2017-2018. Multivariate linear regression models were performed to investigate the association between MAFLD and BMD. Moreover, the relationship between MAFLD and osteoporosis was assessed using multiple logistic regression models. RESULTS: Finally, 817 participants (non-MAFLD, n = 436; MAFLD, n = 381) were included in the final analysis. The results demonstrated that participants with MAFLD showed higher femoral BMDs than those without MAFLD, especially among males aged ≥ 50 years and females aged ≥ 65 years. Moreover, the results showed that obese men (BMI ≥ 30 kg/m2) with MAFLD had higher femoral BMDs than the control group according to subgroup analyses stratified by BMI, but this trend was not present in women. In addition, multiple logistic regression models showed that participants with MAFLD had no increased risks of osteoporosis. CONCLUSION: The present study found that the MAFLD population has higher BMD and a lower risk of osteoporosis than those without MAFLD. Because the present study was a cross-sectional study, we could not identify the cause-effect relation between MAFLD and BMD. Therefore, additional research needs to be performed to explore the influences of MAFLD on bone metabolism in the future.

Screening and identification of potential hub genes and immune cell infiltration in the synovial tissue of rheumatoid arthritis by bioinformatic approach.

Background: Rheumatoid arthritis (RA) is an autoimmune disease that affects individuals of all ages. The basic pathological manifestations are synovial inflammation, pannus formation, and erosion of articular cartilage, bone destruction will eventually lead to joint deformities and loss of function. However, the specific molecular mechanisms of synovitis tissue in RA are still unclear. Therefore, this study aimed to screen and explore the potential hub genes and immune cell infiltration in RA. Methods: Three microarray datasets (GSE12021, GSE55457, and GSE55235), from the Gene Expression Omnibus (GEO) database, have been analyzed to explore the potential hub genes and immune cell infiltration in RA. First, the LIMMA package was used to screen the differentially expression genes (DEGs) after removing the batch effect. Then the clusterProfiler package was used to perform functional enrichment analyses. Second, through weighted coexpression network analysis (WGCNA), the key module was identified in the coexpression network of the gene set. Third, the protein-protein interaction (PPI) network was constructed through STRING website and the module analysis was performed using Cytoscape software. Fourth, the CIBERSORT and ssGSEA algorithm were used to analyze the immune status of RA and healthy synovial tissue, and the associations between immune cell infiltration and RA-related diagnostic biomarkers were evaluated. Fifth, we used the quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to validate the expression levels of the hub genes, and ROC curve analysis of hub genes for discriminating between RA and healthy tissue. Finally, the gene-drug interaction network was constructed using DrugCentral database, and identification of drug molecules based on hub genes using the Drug Signature Database (DSigDB) by Enrichr. Results: A total of 679 DEGs were identified, containing 270 downregulated genes and 409 upregulated genes. DEGs were primarily enriched in immune response and chemokine signaling pathways, according to functional enrichment analysis of DEGs. WGCNA explored the co-expression network of the gene set and identified key modules, the blue module was selected as the key module associated with RA. Seven hub genes are identified when PPI network and WGCNA core modules are intersected. Immune infiltration analysis using CIBERSORT and ssGSEA algorithms revealed that multiple types of immune infiltration were found to be upregulated in RA tissue compared to normal tissue. Furthermore, the levels of 7 hub genes were closely related to the relative proportions of multiple immune cells in RA. The results of the qRT-PCR demonstrated that the relative expression levels of 6 hub genes (CD27, LCK, CD2, GZMB, IL7R, and IL2RG) were up-regulated in RA synovial tissue, compared with normal tissue. Simultaneously, ROC curves indicated that the above 6 hub genes had strong biomarker potential for RA (AUC >0.8). Conclusions: Through bioinformatics analysis and qRT-PCR experiment, our study ultimately discovered 6 hub genes (CD27, LCK, CD2, GZMB, IL7R, and IL2RG) that closely related to RA. These findings may provide valuable direction for future RA clinical diagnosis, treatment, and associated research.

Association between blood manganese and bone mineral density in US adolescents.

Manganese (Mn) exposure may reduce bone mineral density (BMD); however, studies investigating its effects on BMD are limited, especially among adolescents. Therefore, the present study is aimed at investigating the association between blood Mn levels and BMD in adolescents. This cross-sectional study included participants aged 12-19 years with National Health and Nutrition Examination Survey data collected between 2011 and 2018. Total, trunk bone, lumbar spine, and pelvic BMDs were used as outcome variables. Multivariate linear regression models were used to investigate the association between blood Mn levels and BMD. The relationship between blood Mn level and BMD was assessed using smooth curve fitting. In total, 1,703 participants (mean age 15.62 ± 2.31 years) were considered. Multivariable linear regression models demonstrated that BMD decreased as blood Mn level increased, especially among girls aged 12-15 years. This relationship was also observable in non-Hispanic whites and other races according to subgroup analyses stratified by race. Smooth curve fitting indicated the existence of a non-linear relationship between blood Mn and BMD after confounding variable adjustment. The present study indicated that blood Mn levels were negatively associated with BMD in adolescents, especially in girls aged 12-15 years. Therefore, clinicians should be aware of the potential risk of low bone mass among adolescents with high blood Mn levels.