Autophagy inhibitors 3-MA and BAF may attenuate hippocampal neuronal necroptosis after global cerebral ischemia-reperfusion injury in male rats by inhibiting the interaction of the RIP3/AIF/CypA complex.

Our previous study found that receptor interacting protein 3 (RIP3) and apoptosis-inducing factor (AIF) were involved in neuronal programmed necrosis during global cerebral ischemia-reperfusion (I/R) injury. Here, we further studied its downstream mechanisms and the role of the autophagy inhibitors 3-methyladenine (3-MA) and bafilomycin A1 (BAF). A 20-min global cerebral I/R injury model was constructed using the 4-vessel occlusion (4-VO) method in male rats. 3-MA and BAF were injected into the lateral ventricle 1 h before ischemia. Spatial and activation changes of proteins were detected by immunofluorescence (IF), and protein interaction was determined by immunoprecipitation (IP). The phosphorylation of H2AX (γ-H2AX) and activation of mixed lineage kinase domain-like protein (p-MLKL) occurred as early as 6 h after reperfusion. RIP3, AIF, and cyclophilin A (CypA) in the neurons after I/R injury were spatially overlapped around and within the nucleus and combined with each other after reperfusion. The survival rate of CA1 neurons in the 3-MA and BAF groups was significantly higher than that in the I/R group. Autophagy was activated significantly after I/R injury, which was partially inhibited by 3-MA and BAF. Pretreatment with both 3-MA and BAF almost completely inhibited nuclear translocation, spatial overlap, and combination of RIP3, AIF, and CypA proteins. These findings suggest that after global cerebral I/R injury, RIP3, AIF, and CypA translocated into the nuclei and formed the DNA degradation complex RIP3/AIF/CypA in hippocampal CA1 neurons. Pretreatment with autophagy inhibitors could reduce neuronal necroptosis by preventing the formation of the RIP3/AIF/CypA complex and its nuclear translocation.

Oxytocin infusion for maintenance of uterine tone under prophylactic phenylephrine infusion for prevention of post-spinal hypotension in cesarean delivery: a prospective randomised double-blinded dose-finding study.

BACKGROUND: Prior studies have shown that, when administered as an intravenous bolus to prevent uterine atony, prophylactic phenylephrine infusion increased the dose requirement of oxytocin and second-line uterotonics. For the prevention of uterine atony, oxytocin should be delivered by continuous infusion. Here, we aimed to determine the ED50 and ED90 parameters (the effective doses for 50 and 90% patients without uterine atony) of oxytocin for co-infusion with prophylactic phenylephrine during cesarean delivery. METHODS: In this prospective randomized double-blinded dose-finding study, one hundred patients were divided into four groups to receive 2.5, 5.0, 7.5, or 10 IU/h oxytocin infusion, after the umbilical cord was clamped during the study period. The uterine tone was evaluated and defined as either adequate or inadequate. Probit regression analysis was applied to calculate the ED50 and ED90 of oxytocin infusion. Uterine tone, the percentage of patients who needed additional oxytocin bolus, second-line uterotonics, side effects, estimated blood loss, and neonatal outcomes were monitored. RESULTS: The estimated ED50 and ED90 values of the oxytocin infusion doses for the prevention of uterine atony were 1.9 IU/h (95% CI -4.6-3.8) IU/h and 9.3 IU/h (95% CI 7.3-16.2) IU/h, respectively. Across groups, there was a significant linear trend between the infusion dose and the percentage of patients who required additional oxytocin (p-value = 0.002). No differences were observed in the incidence of side effects and neonatal outcomes. CONCLUSION: Under the conditions of this study, the ED90 of oxytocin infusion for the prevention of uterine atony was 9.3 IU/h, which is higher than the current recommendation. This finding is helpful for clinical practice, because of the routine use of phenylephrine in cesarean delivery. Further studies are needed to determine the appropriate initial bolus of oxytocin after neonatal delivery. TRIAL REGISTRATION: The study was registered on the Chinese Clinical Trial Register (register no. ChiCTR2200059556 ).

Association of overweight, obesity and risk of urinary incontinence in middle-aged and older women: a meta epidemiology study.

Aims: The aim of this meta-analysis is to evaluate the potential correlation between obesity and overweight, and the vulnerability to urinary incontinence (UI) in women aged middle-aged and above. Methods: We searched PubMed, Cochrane Library, and Embase for observational studies published between the inception of the databases and April 25, 2023. A fixed-effects model was used when the P>0.1 and the I2 ≤ 50%. In cases where I2 ≥ 50% (indicating significant heterogeneity), a random-effects model was applied. For the purpose of evaluating publication bias, a funnel plot and Egger's test were used. Stata 14.0 was used for all statistical analyses. Findings: This meta-analysis includes 16 observational studies, covering29,618 individuals. The pooled analysis shows that being overweight(25 kg/m2≤BMI<30kg/m2) in middle-aged and elderly women is more likely to develop UI (OR=1.27; 95% CI: 1.17-1.37; I2 = 51.8%, P=0.013). Middle-aged and elderly women with obesity(30 kg/m2≤BMI<35 kg/m2) are significantly more likely to develop UI (OR=1.60; 95% CI: 1.42-1.81; I2 = 71.8%, P=0.000). In addition, the results indicated a higher probability of UI in middle-aged and older women with obesity class II (BMI≥35 kg/m2) (OR=1.85; 95% CI: 1.59-2.16; I2 = 48.1%, P=0.103). In subgroup analysis, there is no direct relationship between the obesity in middle-aged and elderly women and an increased risk of stress urinary incontinence (SUI) (OR=1.31; 95% CI: 0.99-1.74; I2 = 63.7%, P=0.011). In middle-aged and elderly women with obesity are more likely to develop urgent urinary incontinence (UUI) (OR=2.11; 95% CI: 1.54-2.89; I2 = 80.2%, P=0.000). Conclusion: In this meta-analysis, overweight and obesity are associated with an increased risk of UI in middle-aged and elderly women. Obesity and overweight are independent risk factors for UI, as demonstrated by this study. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023421986.

Efficacy and safety of daratumumab in the treatment of relapsed/refractory multiple myeloma: A meta-analysis of randomized controlled trials.

BACKGROUND: Daratumumab as a monoclonal antibody has shown promising results in the treatment of relapsed/refractory multiple myeloma (RRMM). However, the efficacy and safety of daratumumab-based regimens compared to control regimens have not been fully established. METHODS: The search was conducted using electronic databases (PubMed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials databases) up to December 2022. We conducted a meta-analysis of randomized controlled trials that evaluated the efficacy and safety of daratumumab in the treatment of RRMM. Data were extracted from eligible studies and were presented as hazard ratio or risk ratio (RR) with 95% confidence interval (CI). RESULTS: A total of 5 randomized controlled trials comprising 2003 patients were included in this meta-analysis. The results showed that daratumumab-based regimens significantly improved progression-free survival compared to control regimens (hazard ratio = 0.44, 95% CI 0.32-0.60, P < .00001). Additionally, daratumumab-based regimens significantly improved overall response rate compared to control regimens (RR = 1.25, 95% CI 1.16-1.36, P < .00001). the rate of minimal residual disease was also significantly higher in the daratumumab-based regimens (RR = 6.10, 95% CI 4.09-9.11, P < .00001). However, there was an increased risk of pneumonia, upper respiratory tract infections, and diarrhea in the daratumumab-based regimens. CONCLUSION: Our results suggest that daratumumab-based regimens are effective in the treatment of RRMM, improving progression-free survival, minimal residual disease, and overall response rate. However, there is an increased risk of pneumonia, upper respiratory tract infections, and diarrhea. Further studies are needed to determine the long-term safety and efficacy of daratumumab in the treatment of multiple myeloma.

Acteoside improves adipocyte browning by CDK6-mediated mTORC1-TFEB pathway.

Adipocyte browning increases energy expenditure by thermogenesis, which has been considered a potential strategy against obesity and its related metabolic diseases. Phytochemicals derived from natural products with the ability to improve adipocyte thermogenesis have aroused extensive attention. Acteoside (Act), a phenylethanoid glycoside, exists in various medicinal or edible plants and has been shown to regulate metabolic disorders. Here, the browning effect of Act was evaluated by stimulating beige cell differentiation from the stromal vascular fraction (SVF) in the inguinal white adipose tissue (iWAT) and 3T3-L1 preadipocytes, and by converting the iWAT-SVF derived mature white adipocytes. Act improves adipocyte browning by differentiation of the stem/progenitors into beige cells and by direct conversion of mature white adipocytes into beige cells. Mechanistically, Act inhibited CDK6 and mTOR, and consequently relieved phosphorylation of the transcription factor EB (TFEB) and increased its nuclear retention, leading to induction of PGC-1α, a driver of mitochondrial biogenesis, and UCP1-dependent browning. These data thus unveil a CDK6-mTORC1-TFEB pathway that regulates Act-induced adipocyte browning.

Cauchy combination methods for the detection of gene-environment interactions for rare variants related to quantitative phenotypes.

The characterization of gene-environment interactions (GEIs) can provide detailed insights into the biological mechanisms underlying complex diseases. Despite recent interest in GEIs for rare variants, published GEI tests are underpowered for an extremely small proportion of causal rare variants in a gene or a region. By extending the aggregated Cauchy association test (ACAT), we propose three GEI tests to address this issue: a Cauchy combination GEI test with fixed main effects (CCGEI-F), a Cauchy combination GEI test with random main effects (CCGEI-R), and an omnibus Cauchy combination GEI test (CCGEI-O). ACAT was applied to combine p values of single-variant GEI analyses to obtain CCGEI-F and CCGEI-R and p values of multiple GEI tests were combined in CCGEI-O. Through numerical simulations, for small numbers of causal variants, CCGEI-F, CCGEI-R and CCGEI-O provided approximately 5% higher power than the existing GEI tests INT-FIX and INT-RAN; however, they had slightly higher power than the existing GEI test TOW-GE. For large numbers of causal variants, although CCGEI-F and CCGEI-R exhibited comparable or slightly lower power values than the competing tests, the results were still satisfactory. Among all simulation conditions evaluated, CCGEI-O provided significantly higher power than that of competing GEI tests. We further applied our GEI tests in genome-wide analyses of systolic blood pressure or diastolic blood pressure to detect gene-body mass index (BMI) interactions, using whole-exome sequencing data from UK Biobank. At a suggestive significance level of 1.0 × 10-4, KCNC4, GAR1, FAM120AOS and NT5C3B showed interactions with BMI by our GEI tests.

Comparison of epidural dexmedetomidine to fentanyl in reducing ropivacaine dose in Programmed Intermittent Epidural Bolus plus Patient Controlled Epidural Analgesia during labor: A randomized, double-blind, controlled study.

Background: Dexmedetomidine has been documented to reduce the dose of both intrathecal local anesthetic during cesarean delivery, and the concentration of ropivacaine needed for inducing analgesia during labor. However, few studies have compared adjuvant dexmedetomidine to fentanyl on how they impact the dose of ropivacaine required during labor. The aim of the current study was to evaluate the efficacy of epidural dexmedetomidine at doses of 0.3, 0.4, or 0.5 and 2 µg/ml of fentanyl (the traditional clinical concentration), when added to epidural 0.125% ropivacaine. Methods: This was a randomized, double-blinded study that comprised one hundred eighty-eight patients, allocated into four groups receiving either epidural fentanyl at 2 µg/ml, or dexmedetomidine at 0.3, 0.4, or 0.5 µg/ml for labor analgesia. The primary outcome was the amount of ropivacaine necessary per hour. Secondary outcomes included visual analogue pain scale (VAS), motor block (Bromage Scale), side effects, patient satisfaction, and neonatal outcomes. Results: At the completion of the study, data from 165 participants were analyzed. The mean hourly amount of epidural ropivacaine administered was 16.2 ± 3.3, 14.0 ± 3.1, 13.1 ± 3.7 and 12.1 ± 2.5 ml/h in the 2 µg/ml fentanyl group, and the 0.3, 0.4 and 0.5 µg/ml dexmedetomidine groups, respectively. There was a significant difference among groups in the mean hourly consumption of epidural ropivacaine (P < 0.0001 for 1 way ANOVA). The frequency of PCEA (patient-controlled epidural analgesia) was significantly higher in the fentanyl group than in the three dexmedetomidine groups (P < 0.001), and similar among the dexmedetomidine groups. The mean values of the VAS among all groups were similar over time, P > 0.05. The incidence of pruritus in the fentanyl group was 17.5%, whereas no patient experienced pruritus in any of the dexmedetomidine groups, P < 0.0001. Conclusion: The study demonstrated that epidural dexmedetomidine (0.3 and 0.4 µg/ml) was superior to standard dose epidural fentanyl in reducing the mean hourly amount of ropivacaine administered, and minimizing opioid-related side effects. Further large and multicenter studies would be necessary to confirm the benefits of dexmedetomidine, and potentially serve as an alternative to opioids for routine use in labor analgesia. Clinical trial registration: [http://www.chictr.org.cn/showproj.aspx?proj=62846], identifier [ChiCTR2000039067].

Kernel-based gene-environment interaction tests for rare variants with multiple quantitative phenotypes.

Previous studies have suggested that gene-environment interactions (GEIs) between a common variant and an environmental factor can influence multiple correlated phenotypes simultaneously, that is, GEI pleiotropy, and that analyzing multiple phenotypes jointly is more powerful than analyzing phenotypes separately by using single-phenotype GEI tests. Methods to test the GEI for rare variants with multiple phenotypes are, however, lacking. In our work, we model the correlation among the GEI effects of a variant on multiple quantitative phenotypes through four kernels and propose four multiphenotype GEI tests for rare variants, which are a test with a homogeneous kernel (Hom-GEI), a test with a heterogeneous kernel (Het-GEI), a test with a projection phenotype kernel (PPK-GEI) and a test with a linear phenotype kernel (LPK-GEI). Through numerical simulations, we show that correlation among phenotypes can enhance the statistical power except for LPK-GEI, which simply combines statistics from single-phenotype GEI tests and ignores the phenotypic correlations. Among almost all considered scenarios, Het-GEI and PPK-GEI are more powerful than Hom-GEI and LPK-GEI. We apply Het-GEI and PPK-GEI in the genome-wide GEI analysis of systolic blood pressure (SBP) and diastolic blood pressure (DBP) in the UK Biobank. We analyze 18,101 genes and find that LEUTX is associated with SBP and DBP (p = 2.20×10-6) through its interaction with hemoglobin. The single-phenotype GEI test and our multiphenotype GEI tests Het-GEI and PPK-GEI are also used to evaluate the gene-hemoglobin interactions for 22 genes that were previously reported to be associated with SBP or DBP in a meta-analysis of genetic main effects. MYO1C shows nominal significance (p < 0.05) by the Het-GEI test. NOS3 shows nominal significance in DBP and MYO1C in both SBP and DBP by the single-phenotype GEI test.

Association of CHA2DS2-VASC Score with in-Hospital Cardiovascular Adverse Events in Patients with Acute ST-Segment Elevation Myocardial Infarction.

Background: Acute ST-elevation myocardial infarction (STEMI) is a common clinical critical illness, and accurate, reliable, simple, and easy-to-remember tools are needed in clinical practice to quickly identify the risk of this condition in STEMI patients. This study investigates the predictive value of the admission CHA2DS2-VASc score for in-hospital MACE in STEMI patients. Methods: A total of 210 STEMI patients who visited the Chest Pain Center of the Second People's Hospital of Hefei from December 2019 to December 2021 were retrospectively analyzed. They were divided into MACE and non-MACE groups. The receiver operating characteristic curve (ROC) was used to assess the predictive value of the CHA2DS2-VASc score for MACE events during hospitalization. Results: The CHA2DS2-VASc score was higher in the MACE group than in the non-MACE group (P < 0.05), and multivariate logistic regression analysis showed that the CHA2DS2-VASc score was an independent risk factor for MACE events during hospitalization in STEMI patients (OR = 1.391, 95%CI 1.044-1.853, P=0.024); ROC curve analysis showed that the area under the curve (AUC) of the CHA2DS2-VASc score was 0.744, the sensitivity was 0.64, the specificity was 0.694, and the optimal cutoff value was 3.5 in predicting the risk of MACE events during hospitalization in STEMI patients. There were no significant differences between the GRACE score (0.744 VS.0.827) and TIMI score (0.744VS.0.745) (P > 0.05). Conclusion: The CHA2DS2-VASc score can successfully predict the occurrence of in-hospital MACE events in STEMI patients.

The Value of Serum YKL-40 and TNF-α in the Diagnosis of Acute ST-Segment Elevation Myocardial Infarction.

Background: Acute ST-segment elevation myocardial infarction (STEMI) is a serious cardiovascular disease that poses a great threat to the life and health of patients. Therefore, early diagnosis is important for STEMI patient treatment and prognosis. The purpose of this study was to investigate the value of serum YKL-40 and TNF-α in the diagnosis of STEMI. Methods: From October 2020 to February 2022, 120 patients with STEMI were admitted to the Chest Pain Center of the Second People's Hospital of Hefei, and 81 patients with negative coronary angiography were selected as the control group. Serum YKL-40 and TNF-α concentrations were measured by sandwich ELISA. Pearson correlation was used to analyze the correlation between serum YKL-40, TNF-α, and serum troponin I (cTnI) in STEMI patients; multivariate logistic regression analysis was used to screen independent risk factors for STEMI. Three diagnostic models were constructed: cTnI univariate model (model A), combined serum YKL-40 and TNF-α model other than cTnI (model B), and combined cTnI and serum YKL-40 and TNF-α model (model C). We assessed the clinical usefulness of the diagnostic model by comparing AUC with decision curve analysis (DCA). Results: Serum YKL-40 and TNF-α in the STEMI group were significantly higher than those in the control group (P < 0.001). On Pearson correlation analysis, there was a significant positive correlation between serum YKL-40, TNF-α, and cTnI levels in STEMI patients. Multivariate logistic regression analysis showed that serum YKL-40 and TNF-α were independent risk factors for the development of STEMI. The results of ROC analysis showed that the area under the curve (AUC) of serum YKL-40 for predicting the occurrence of STEMI was 0.704. The AUC of serum TNF-α for predicting the occurrence of STEMI was 0.852. The AUC of cTnI as a traditional model, model A, for predicting the occurrence of STEMI was 0.875. Model B predicted STEMI with an AUC of 0.851. The addition of serum YKL-40 and serum TNF-α to the traditional diagnostic model composed of cTnI constituted a new diagnostic model; that is, the AUC of model C for predicting the occurrence of STEMI was 0.930. Model C had a better net benefit between a threshold probability of 70-95% for DCA. Conclusion: In this study, we demonstrate the utility of serum YKL-40 and TNF-α as diagnostic markers for STEMI and the clinical utility of diagnostic models by combining serum YKL-40 and TNF-α with cTnI.

Resveratrol suppresses microglial activation and promotes functional recovery of traumatic spinal cord via improving intestinal microbiota.

Spinal cord injury (SCI) can change the intestinal microbiota pattern and corresponding metabolites, which in turn affect the prognosis of SCI. Among many metabolites, short-chain fatty acids (SCFAs) are critical for neurological recovery after SCI. Recent research has shown that resveratrol exerts anti-inflammatory properties. But it is unknown if the anti-inflammatory properties of resveratrol are associated with intestinal microbiota and metabolites. We thus investigate the alteration in gut microbiota and the consequent change of SCFAs following resveratrol treatment. The SCI mouse models with retention of gut microbiota (donor) and depletion of gut microbiota (recipient) were established. Fecal microbiota transplantation from donors to recipients was performed with intragastrical administration. Spinal cord tissues of mice were examined by H&E, Nissl, and immunofluorescence stainings. The expressions of the inflammatory profile were examined by qPCR and cytometric bead array. Fecal samples of mice were collected and analyzed with 16S rRNA sequencing. The results showed that resveratrol inhibited the microglial activation and promoted the functional recovery of SCI. The analysis of intestinal microbiota and metabolites indicated that SCI caused dysbiosis and the decrease in butyrate, while resveratrol restored microbiota pattern, reversed intestinal dysbiosis, and increased the concentration of butyrate. Both fecal supernatants from resveratrol-treated donors and butyrate suppressed the expression of pro-inflammatory genes in BV2 microglia. Our result demonstrated that fecal microbiota transplantation from resveratrol-treated donors had beneficial effects on the functional recovery of SCI. One mechanism of resveratrol effects was to restore the disrupted gut microbiota and butyrate.

FAM198B promotes colorectal cancer progression by regulating the polarization of tumor-associated macrophages via the SMAD2 signaling pathway.

Colorectal cancer (CRC) is one of the most common malignant tumors. Tumor-associated macrophages (TAMs) promote the progression of CRC, but the mechanism is not completely clear. The present study aimed to reveal the expression and function of FAM198B in TAMs, and the role of FAM198B in mediating macrophage polarization in CRC. The role of FAM198B in macrophage activity, cell cycle, and angiogenesis was evaluated by CCK-8 assay, flow cytometry, and vasculogenic mimicry assay. The effects of FAM198B on macrophage polarization were determined by flow cytometry. The function of FAM198B-mediated macrophage polarization on CRC progression was evaluated by transwell assays. Bioinformatic analyses and rescue assays were performed to identify biological functions and signaling pathways involved in FAM198B regulation of macrophage polarization. Increased FAM198B expression in TAMs is negatively associated with poor CRC prognosis. Functional assays showed that FAM198B promotes M2 macrophage polarization, which leads to CRC cell proliferation, migration, and invasion. Mechanistically, FAM198B regulates the M2 polarization of macrophages by targeting SMAD2, identifying the SMAD2 pathway as a mechanism by which FAM198B promotes CRC progression through regulating macrophage polarization. These findings provide a possible molecular mechanism for FAM198B in TAMs in CRC and suggest that FAM198B may be a novel therapeutic target in CRC.

A machine-learning approach to discerning prevalence and causes of myopia among elementary students in Hubei.

OBJECTIVE: Our aim is to establish a machine-learning model that will enable us to investigate the key factors influencing the prevalence of myopia in students. METHODS: We performed a cross-sectional study that included 16,653 students from grades 1-3 across 17 cities in Hubei Province. We used questionnaires to discern levels of participation in potential factors contributing to the development of myopia. The relative importance of potential contributors was ranked using machine-learning methods. The students' visual acuity (VA) was measured and those with logMAR VA of > 0.0 underwent a autorefraction test to determine students' refraction status. RESULTS: The prevalence of myopia in grades 1, 2, and 3 was 14.70%, 20.54% and 28.93%, respectively. Myopia rates among primary school students in provincial capital city (32.35%) were higher than those in other urban (23.03%) and rural (14.82%) areas. Children with non-myopic parents, only one myopic parent, or both parents having myopia exhibited myopic rates of 16.36%, 25.18%, and 41.37%, respectively. Myopia prevalence was higher in the students who continued to use their eyes at close range for a long time and lower in those engaged longer in outdoor activities. The machine-learning model determined that the top three contributing factors were the students' age (0.36), followed by place of residence (0.34), starting age of education (0.21). CONCLUSION: The overall prevalence of myopia was 21.52%. Children's age and place of residence were the important influencing factors, but genetics and environmental were also played key roles in myopia development.

CDK6 increases glycolysis and suppresses autophagy by mTORC1-HK2 pathway activation in cervical cancer cells.

Cervical carcinoma is a leading malignant tumor among women worldwide, characterized by the dysregulation of cell cycle. Cyclin-dependent kinase 6 (CDK6) plays important roles in the cell cycle progression, cell differentiation, and tumorigenesis. However, the role of CDK6 in cervical cancer remains controversial. Here, we found that loss of CDK6 in cervical adenocarcinoma HeLa cell line inhibited cell proliferation but induced apoptosis as well as autophagy, accompanied by attenuated expression of mammalian target of rapamycin complex 1 (mTORC1) and hexokinase 2 (HK2), reduced glycolysis, and production of protein, nucleotide, and lipid. Similarly, we showed that CDK6 knockout inhibited the survival of CDK6-high CaSki but not CDK6-low SiHa cervical cancer cells by regulation of glycolysis and autophagy process. Collectively, our studies indicate that CDK6 is a critical regulator of human cervical cancer cells, especially with high CDK6 level, through its ability to regulate cellular apoptosis and metabolism. Thus, inhibition of CDK6 kinase activity could be a powerful therapeutic avenue used to treat cervical cancers.

Effects of Golden Plaster on Knee Osteoarthritis: A Multicenter Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Golden plaster is the preferred and most commonly used in China for pain reduction in patients with knee osteoarthritis (OA). However, there was no evidence-based medical evidence about its effect in relieving pain of knee OA patients. Here, a multicenter randomized, double-blind, placebo-controlled trial was performed to evaluate the efficacy and safety of golden plaster for the improvement of pain relief and function's obstacle in patients with knee OA. METHODS: 320 patients with knee OA were enrolled at four hospitals and randomly divided into the treatment group and the control group with 160 subjects in each group. Patients in treatment group were treated with golden plaster, and those in control group with placebo plaster. The study cycle in both groups was 21 days. Patient visits were documented before treatment and 7-, 14-, and 21-day follow-ups after treatment. The outcomes included VAS score, WOMAC score, and adverse events. RESULTS: Compared to the control group, the VAS score in the treatment group was significantly decreased after treatment with golden plaster for 7 days, 14 days, and 21 days. Compared to the control group, the WOMAC score in the treatment group was significantly decreased 14 days and 21 days. The incidence rate of adverse events had no statistical difference between both the groups. CONCLUSIONS: In conclusion, our study, for the first time by carrying on the double-blind and placebo-controlled randomized trial, showed that golden plaster can effectively alleviate the pain of knee and improve the physical function in the patients with knee OA. This trial is registered with ChiCTR-TRC-13003418.

Construction and evaluation of nomogram model for individualized prediction of risk of major adverse cardiovascular events during hospitalization after percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction.

Background: Emergency percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI) helps to reduce the occurrence of major adverse cardiovascular events (MACEs) such as death, cardiogenic shock, and malignant arrhythmia, but in-hospital MACEs may still occur after emergency PCI, and their mortality is significantly increased once they occur. The aim of this study was to investigate the risk factors associated with MACE during hospitalization after PCI in STEMI patients, construct a nomogram prediction model and evaluate its effectiveness. Methods: A retrospective analysis of 466 STEMI patients admitted to our hospital from January 2018 to June 2022. According to the occurrence of MACE during hospitalization, they were divided into MACE group (n = 127) and non-MACE group (n = 339), and the clinical data of the two groups were compared; least absolute shrinkage and selection operator (LASSO) regression was used to screen out the predictors with non-zero coefficients, and multivariate Logistic regression was used to analyze STEMI Independent risk factors for in-hospital MACE in patients after emergency PCI; a nomogram model for predicting the risk of in-hospital MACE in STEMI patients after PCI was constructed based on predictive factors, and the C-index was used to evaluate the predictive performance of the prediction model; the Bootstrap method was used to repeat sampling 1,000 Internal validation was carried out for the second time, the Hosmer-Lemeshow test was used to evaluate the model fit, and the calibration curve was drawn to evaluate the calibration degree of the model. Receiver operating characteristic (ROC) curves were drawn to evaluate the efficacy of the nomogram model and thrombolysis in myocardial infarction (TIMI) score in predicting in-hospital MACE in STEMI patients after acute PCI. Results: The results of LASSO regression showed that systolic blood pressure, diastolic blood pressure, Killip grade II-IV, urea nitrogen and left ventricular ejection fraction (LVEF), IABP, NT-ProBNP were important predictors with non-zero coefficients, and multivariate logistic regression analysis was performed to analyze that Killip grade II-IV, urea nitrogen, LVEF, and NT-ProBNP were independent factors for in-hospital MACE after PCI in STEMI patients; a nomogram model for predicting the risk of in-hospital MACE after PCI in STEMI patients was constructed with the above independent predictors, with a C-index of 0.826 (95% CI: 0.785-0.868) having a good predictive power; the results of H-L goodness of fit test showed χ2 = 1.3328, P = 0.25, the model calibration curve was close to the ideal model, and the internal validation C-index was 0.818; clinical decision analysis also showed that the nomogram model had a good clinical efficacy, especially when the threshold probability was 0.1-0.99, the nomogram model could bring clinical net benefits to patients. The nomogram model predicted a greater AUC (0.826) than the TIMI score (0.696) for in-hospital MACE after PCI in STEMI patients. Conclusion: Urea nitrogen, Killip class II-IV, LVEF, and NT-ProBNP are independent factors for in-hospital MACE after PCI in STEMI patients, and nomogram models constructed based on the above factors have high predictive efficacy and feasibility.

Surgical management of Helveston syndrome (Triad exotropia).

PURPOSE: To evaluate and compare different surgical approaches for the treatment of Helveston syndrome and provide further information for preoperative planning. METHODS: From February 2008 to December 2018, data of 52 patients with Helveston syndrome were retrospectively reviewed. Different surgical approaches were selected based on the extent of A-pattern exotropia, dissociated vertical deviation (DVD), and both superior oblique muscle overaction (SOOA) with fundus photograph intorsion. Eye position, A-pattern, DVD, superior oblique muscle function, and binocular vision function were evaluated pre- and postoperatively. The average follow-up duration was 20.5 months. RESULTS: Nine cases underwent simultaneous horizontal deviation correction with bilateral superior rectus recession, 24 underwent simultaneous horizontal deviation correction with bilateral superior oblique muscle lengthening, and 19 underwent two stages of horizontal deviation correction with superior oblique muscle lengthening, and later bilateral superior rectus recession. A-pattern, DVD, SOOA, and fundus intorsion were all collapsed in all patients postoperatively. Forty-five patients had an orthophoric eye position with considerably aligned ocular movements postoperatively. The total success rate was 86.5%. Postoperatively, eight of the 10 patients with diplopia experienced a recovery of binocular single vision and three had a recovery of rudimentary stereopsis (Titmus 3000-400 s of arc). The compensatory head posture of patients improved significantly postoperatively. CONCLUSIONS: The surgical planning of Helveston syndrome should be designed based on the degree of the A-pattern, SOOA, DVD, and the intorsion in fundus photographs, and the appropriate approach should be selected to improve patient satisfaction.

Effects of sling exercise therapy on post-stroke walking impairment: a systematic review and meta-analysis.

Walking impairment is a common consequence of stroke, resulting in long-term disability. Trunk muscle strength has been proven to be associated with post-stroke walking performance. As a type of trunk training, sling exercise therapy (SET) has been widely used to improve the trunk function in stroke patients. The purpose of this systematic review was to investigate the efficacy of SET on post-stroke walking impairment. Seven databases were systematically searched for eligible studies from their inception to 1 August 2021. Review Manager 5.3 software was used for this meta-analysis. The overall quality of included studies was evaluated by the physiotherapy evidence database scale. Twenty-five randomized controlled trials involving 1504 patients were included (23 in China and two in South Korea). In summary, SET more effectively improved the walking ability of post-stroke patients than conventional physical therapy or trunk training. The pooled analysis demonstrated that SET had positive effects on the 10 m maximum walking speed, integrated electromyography value of rectus femoris, biceps femoris and gastrocnemius, functional ambulation category, timed up and go test, and step length. At least in East Asia, our findings support SET to manage the post-stroke walking impairment.

A Novel Age-Related Circular RNA Circ-ATXN2 Inhibits Proliferation, Promotes Cell Death and Adipogenesis in Rat Adipose Tissue-Derived Stromal Cells.

Adipose tissue-derived stromal cells are promising candidates investigating the stem cell-related treatment. However, their proportion and utility in the human body decline with time, rendering stem cells incompetent to complete repair processes in vivo. The involvement of circRNAs in the aging process is poorly understood. Rat subcutaneous adipose tissue from 10-week-old and 27-month-old rats were used for hematoxylin and eosin (H and E) staining, TUNEL staining, and circRNA sequencing. Rat adipose tissue-derived stromal cells were cultured and overexpressed with circ-ATXN2. Proliferation was examined using xCELLigence real-time cell analysis, EdU staining, and cell cycle assay. Apoptosis was induced by CoCl2 and examined using flow cytometry. RT-PCR assay and Oil Red O staining were used to measure adipogenesis at 48 h and 14 days, respectively. H and E staining showed that the diameter of adipocytes increased; however, the number of cells decreased in old rats. TUNEL staining showed that the proportion of apoptotic cells was increased in old rats. A total of 4,860 and 4,952 circRNAs was detected in young and old rats, respectively. Among them, 67 circRNAs exhibited divergent expression between the two groups (fold change ≥2, p ≤ 0.05), of which 33 were upregulated (49.3%) and 34 were downregulated (50.7%). The proliferation of circ-ATXN2-overexpressing cells decreased significantly in vitro, which was further validated by xCELLigence real-time cell analysis, EdU staining, and cell cycle assay. Overexpression of circ-ATXN2 significantly increased the total apoptotic rate from 5.78 ± 0.46% to 11.97 ± 1.61%, early apoptotic rate from 1.76 ± 0.22% to 5.50 ± 0.66%, and late apoptosis rate from 4.02 ± 0.25% to 6.47 ± 1.06% in adipose tissue-derived stromal cells. Furthermore, in circ-ATXN2-overexpressing cells, RT-PCR assay revealed that the expression levels of adipose differentiation-related genes PPARγ and CEBP/α were increased and the Oil Red O staining assay showed more lipid droplets. Our study revealed the expression profile of circRNAs in the adipose tissue of old rats. We found a novel age-related circular RNA-circ-ATXN2-that inhibits proliferation and promotes cell death and adipogenesis in rat adipose tissue-derived stromal cells.

Expression and localization of Sox10 during hair follicle morphogenesis and induced hair cycle.

Sox transcription factors play many diverse roles during development, including regulating stem cell states, directing differentiation, and influencing the local chromatin landscape. Sox10 has been implicated in the control of stem/progenitor activity and epithelial-mesenchymal transition, yet it has not been studied in relation to the hair follicle cycle or hair follicle stem cell (HFSC) control. To elucidate the role of Sox10 in hair follicle cycle control, we performed immunohistochemical and immunofluorescence analysis of its expression during hair morphogenesis, the postnatal hair cycle, and the depilation-induced murine hair follicle cycle. During hair follicle morphogenesis, Sox10 was expressed in the hair germ and peg. In telogen, we detected nuclear Sox10 in the hair bulge and germ cell cap, where HFSCs reside, while in anagen and catagen, Sox10 was detected in the epithelial portion, such as the strands of keratinocytes, the outer root sheath (ORS) in anagen, and the regressed epithelial strand of hair follicle in catagen. These results suggest that Sox10 may be involved in early hair follicle morphogenesis and postnatal follicular cycling.