A genome-wide association study of Chinese and English language phenotypes in Hong Kong Chinese children.

Dyslexia and developmental language disorders are important learning difficulties. However, their genetic basis remains poorly understood, and most genetic studies were performed on Europeans. There is a lack of genome-wide association studies (GWAS) on literacy phenotypes of Chinese as a native language and English as a second language (ESL) in a Chinese population. In this study, we conducted GWAS on 34 reading/language-related phenotypes in Hong Kong Chinese bilingual children (including both twins and singletons; total N = 1046). We performed association tests at the single-variant, gene, and pathway levels. In addition, we tested genetic overlap of these phenotypes with other neuropsychiatric disorders, as well as cognitive performance (CP) and educational attainment (EA) using polygenic risk score (PRS) analysis. Totally 5 independent loci (LD-clumped at r2 = 0.01; MAF > 0.05) reached genome-wide significance (p < 5e-08; filtered by imputation quality metric Rsq>0.3 and having at least 2 correlated SNPs (r2 > 0.5) with p < 1e-3). The loci were associated with a range of language/literacy traits such as Chinese vocabulary, character and word reading, and rapid digit naming, as well as English lexical decision. Several SNPs from these loci mapped to genes that were reported to be associated with EA and other neuropsychiatric phenotypes, such as MANEA and PLXNC1. In PRS analysis, EA and CP showed the most consistent and significant polygenic overlap with a variety of language traits, especially English literacy skills. To summarize, this study revealed the genetic basis of Chinese and English abilities in a group of Chinese bilingual children. Further studies are warranted to replicate the findings.

Effect and Safety of Herbal Medicine Foot Baths in Patients with Diabetic Peripheral Neuropathy: A Multicenter Double-Blind Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect and safety of foot baths with Tangbi Waixi Decoction (TW) in treating patients with diabetic peripheral neuropathy (DPN). METHODS: It is a multicenter double-blinded randomized controlled trial. Participants with DPN were recruited between November 18, 2016 and May 30, 2018 from 8 hospitals in China. All patients received basic treatments for glycemic management. Patients received foot baths with TW herbal granules either 66.9 g (intervention group) or 6.69 g (control group) for 30 min once a day for 2 weeks and followed by a 2-week rest, as a therapeutic course. If the Toronto Clinical Scoring System total score (TCSS-TS) ⩾6 points, the patients received a total of 3 therapeutic courses (for 12 weeks) and were followed up for 12 weeks. The primary outcome was change in TCSS-TS score at 12 and 24 weeks. Secondary outcomes included changes in bilateral motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of the median and common peroneal nerve. Safety was also assessed. RESULTS: Totally 632 patients were enrolled, and 317 and 315 were randomized to the intervention and control groups, respectively. After the 12-week intervention, patients in both groups showed significant declines in TCSSTS scores, and significant increases in MNCV and SNCV of the median and common peroneal nerves compared with pre-treatment (P<0.05). The reduction of TCSS-TS score at 12 weeks and the increase of SNCV of median nerve at 24 weeks in the control group were greater than those in the intervention group (P<0.05). The number of adverse events did not differ significantly between groups (P>0.05), and no serious adverse event was related with treatment. CONCLUSION: Treatment of TW foot baths was safe and significantly benefitted patients with DPN. A low dose of TW appeared to be more effective than a high dose. (Registry No. ChiCTR-IOR-16009331).

Scrutinizing science to save lives: uncovering flaws in the data linking L-type calcium channels blockers to CRAC channels and heart failure.

Hypertension is estimated to affect almost 1 billion people globally and significantly increases risk of myocardial infarction, heart failure, stroke, retinopathy and kidney disease. One major front line therapy that has been used for over 50 years involves L-type Ca 2+ channel blockers (LCCBs). One class of LCCBs is the dihydropyridine family, with amlodipine being widely prescribed regardless of gender, race, ethnicity or age. In 2020, Johnson et al. 7 reported that all LCCBs significantly increased the risk of heart failure, and attributed this effect to non-canonical activation of store-operated Ca 2+ entry. A major approach on which they based many of their arguments was to measure cytosolic Ca 2+ using the fluorescent Ca 2+ indicator dye fura-2. We recently demonstrated that amlodipine is highly fluorescent within cells and overwhelms the fura-2 signal, precluding the use of the indicator dye with amlodipine 24 . Our meta-analyses and prospective real world study showed that dihydropyridines were not associated with an increase in heart failure, likely explained by the lack of consideration by Johnson et al. 7 of well-known confounding factors such as age, race, obesity, prior anti-hypertensive treatment or diabetes 24 . Trebak and colleagues have responded to our paper with a forthright and unwavering defence of their work 27 . In this paper, we carry out a forensic dissection of Johnson et al., 7 and conduct new experiments that address directly points raised by Trebak et al. 27 . We show that there are major flaws in the design and interpretation of their key experiments, that fura-2 cannot be used with amlodipine, that there are fundamental mathematical misunderstandings and mistakes throughout their study leading to critical calculations on heart failure that are demonstrably wrong, and several of their own results are inconsistent with their interpretation. We therefore believe the study by Johnson et al. 7 is flawed at many levels and we stand by our conclusions.

Cang-ai volatile oil ameliorates imiquimod-induced psoriatic skin lesions by suppressing the ILC3s.

ETHNOPHARMACOLOGICAL RELEVANCE: Cang-ai volatile oil (CAVO) is an aromatic Chinese medicine with potent antibacterial and immune regulatory properties. While CAVO has been used to treat upper respiratory tract infections, depression, otomycosis, and bacterial infections in the skin, its effect on psoriasis is unknown. AIM OF THE STUDY: This study explores the effect and mechanism of CAVO in psoriasis intervention. MATERIAL AND METHODS: The effect of CAVO on the expression of IL-6 and IL-1ß was assessed in TNF-α-induced HaCaT cells using enzyme-linked immunosorbent assay (ELISA). Mice were given imiquimod (IMQ) and administered orally with different CAVO doses (0.03 and 0.06 g/kg) for 5 days. The levels of inflammatory cytokines related to group-3 innate lymphoid cells (ILC3s) in the skin were assessed using hematoxylin and eosin (H&E) staining, ELISA, and western blotting (WB). The frequency of ILC3s in mice splenocytes and skin cells was evaluated using flow cytometry. RESULTS: The results demonstrated that CAVO decreased the expression of IL-6 and IL-1ß in TNF-α- induced HaCaT cells. CAVO significantly reduced the severity of psoriatic symptoms in IMQ-induced mice. The expression of inflammatory cytokines in the skin, such as IL-1ß, IL-6, IL-8, IL-22, IL-23, and IL-17 A were decreased, whereas IL-10 levels were increased. The mRNA expressions of TNF-α, IL-23 A, IL-23 R, IL-22, IL-17 A, and RORγt were down-regulated in skin tissues. CAVO also decreased the levels of NF-κB, STAT3, and JAK2 proteins. CONCLUSIONS: CAVO potentially inhibits ILC3s activation to relieve IMQ-induced psoriasis in mice. These effects might be attributed to inhibiting the activation of NF-κB, STAT3, and JAK2 signaling pathways.

Hypofractionated radiotherapy for refractory or relapsed aggressive B-cell lymphoma in the rituximab era.

BACKGROUND: Radiotherapy (RT) is an effective and available local treatment for patients with refractory or relapsed (R/R) aggressive B-cell lymphomas. However, the value of hypofractionated RT in this setting has not been confirmed. METHODS: We retrospectively analyzed patients with R/R aggressive B-cell lymphoma who received hypofractionated RT between January 2020 and August 2022 at a single institution. The objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and acute side effects were analyzed. RESULTS: A total of 30 patients were included. The median dose for residual disease was 36 Gy, at a dose per fraction of 2.3-5 Gy. After RT, the ORR and complete response (CR) rates were 90% and 80%, respectively. With a median follow-up of 10 months (range, 2-27 months), 10 patients (33.3%) experienced disease progression and three died. The 1-year OS and PFS rates for all patients were 81.8% and 66.3%, respectively. The majority (8/10) of post-RT progressions involved out-of-field relapses. Patients with relapsed diseases, no response to systemic therapy, multiple lesions at the time of RT, and no response to RT were associated with out-of-field relapses. PFS was associated with response to RT (P = 0.001) and numbers of residual sites (P < 0.001). No serious non-hematological adverse effects (≥ grade 3) associated with RT were reported. CONCLUSION: These data suggest that hypofractionated RT was effective and tolerable for patients with R/R aggressive B-cell lymphoma, especially for those that exhibited localized residual disease.

Efficacy of a self-management program on quality of life in colorectal cancer patients: A randomized controlled trial.

PURPOSE: To test the efficacy of a self-management program based on acceptance and commitment therapy on quality of life, emotional distress, fatigue, physical activity, and fruit and vegetable intake in patients with colorectal cancer. METHODS: The study was a randomized controlled trial. A sample of 156 patients with colorectal cancer (stage I-III) was recruited by convenience sampling and participants were allocated randomly assigned to control or intervention groups. The intervention included a colorectal cancer self-management information booklet, two personal skills training sessions, and 12 follow-up telephone calls. The control group received health education leaflets. Outcome variables were assessed in both groups at baseline and every two months thereafter during the six-month follow-up period. RESULT: The mean age of participants was 62 years (range: 30-89 years). Generalized estimation equations analyses revealed significant differences over time in changes in anxiety (ß = -2.22, p = 0.001), depression (ß = -1.48, p = 0.033), fatigue (ß = 4.46, p = 0.001), physical and functional measures (ß = 6.16, p = 0.005), and colorectal-cancer-specific quality of life (ß = 7.45, p = 0.012). However, there were no significant differences in changes in physical activity or fruit and vegetable intake over time. CONCLUSION: The self-management skills provided by oncology nurses, including symptom management, psychological adjustment, and relaxation exercises, help colorectal cancer patients to overcome the challenges of cancer survivorship, accelerate their recovery, and improve their quality of life. THE TRIAL NUMBER: NCT03853278 registered on ClinicalTrials.gov.

The alleviating effect of Scutellaria amoena extract on the regulation of gut microbiota and its metabolites in NASH rats by inhibiting the NLRP3/ASC/caspase-1 axis.

Background: Scutellaria amoena (SA) is the root of S. amoena C.H. Wright of Labiatae, also known as Scutellaria southwestern. This is mainly distributed in Sichuan, Yunnan, and Guizhou in China. In southwest China, SA is used as an alternative method to genuine medicine for the treatment of allergy, diarrhea, inflammation, hepatitis, and bronchitis. Thus far, studies on the effects of SA on non-alcoholic steatohepatitis (NASH) are lacking. This paper investigated the effect of SA on the regulation of gut microbiota and its metabolites in NASH rats by inhibiting the NOD-like receptor 3 (NLRP3)/apoptosis-associated speck-like protein (ASC)/caspase-1 axis. Methods: A NASH rat model was induced by a high-fat diet (HFD) for 12 weeks, and rats were orally given different doses of SA extracts (150 and 300 mg/kg/d) for 6 weeks. Changes in histological parameters, body weight, organ indexes, cytokines, and biochemical parameters related to NLRP3 in NASH rats were checked. 16S rRNA gene sequencing and UPLC-MS/MS technology were used to analyze the changes in the gut microbiota composition and its metabolites in NASH rats. Results: SA significantly inhibited the HFD-induced increase in body weight, lipid levels, and inflammatory infiltration. SA notably inhibited the HFD-induced increase in the upper and lower factors of NLRP3, such as transforming growth factor (TGF)-ß, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-18, pro-IL-18, IL-1ß, pro-IL-1ß, NLRP3, ASC, and caspase-1. Additionally, mRNA expressions of caspase-1, NLRP3, and ASC were significantly downregulated after SA treatment. The results of the intestinal flora showed that SA could increase the diversity of flora and change its structure and composition in NASH rats by reducing Firmicutes/Bacteroidetes (F/B) ratio, Blautia (genus), Lachospiraceae (family), and Christensenellaceae R-7 group (genus), and increasing Muribaculaceae (family) and Bacteroides (genus). The metabolomics revealed that 24 metabolites were possibly the key metabolites for SA to regulate the metabolic balance of NASH rats, including chenodeoxycholic acid, xanthine, and 9-OxoODE. Nine metabolic pathways were identified, including primary bile acid biosynthesis, bile secretion, purine metabolism, and secondary bile acid biosynthesis. Conclusion: SA can regulate the intestinal microbial balance and metabolic disorder by inhibiting the NLRP3/ASC/caspase-1 axis to relieve NASH.

Identifying the common elements of psychological and psychosocial interventions for preventing postpartum depression: Application of the distillation and matching model to 37 winning protocols from 36 intervention studies.

AIM: Postpartum depression is prevalent worldwide and seriously endangers maternal and child health. Previous studies have demonstrated the effectiveness of psychological and psychosocial intervention programmes in preventing postpartum depression. However, the literature offers limited practice guidance. Therefore, this study aimed to deeply analyse prior findings to gather rich evidence-based information on this topic. METHODS: Using the distillation and matching model, we conducted a systematic review of psychological and psychosocial interventions used to effectively prevent postpartum depression. Four researchers trained in coding system independently read eligible studies and identified reliable (Cohen's kappa >0.40) and frequently occurring (frequency ≥3 winning study groups) practice elements. RESULTS: Our review included 36 studies containing 37 winning study groups. Fourteen practice elements were identified and subsequently divided into six categories: postpartum practical problems-related, social support-related, interpersonal psychotherapy-related, cognitive behavioural therapy-related, labour trauma-related and non-specific techniques. The most common practice elements were baby care skills and mother-infant bonding/interaction enhancement. Inter-rater reliability averaged 0.86, ranging from 0.48 to 1. CONCLUSION: The practice elements identified in this study provide rich evidence-based information that can guide clinical practitioners in selecting or developing effective, realistically available intervention programmes.

Extracts from Seseli mairei Wolff attenuate imiquimod-induced psoriasis-like inflammation by inhibiting Th17 cells.

Objective: Seseli mairei Wolff extracts (SMWE) are widely used to treat psoriasis as a Chinese medicine, but their effect and mechanism are unclear. This study verified the effect of SMWE on psoriasis by regulating Th17 cells. Methods: HaCaT cells were treated with IL-17A in vitro to evaluate the effect of SMWE on psoriasis. In vivo, the mice psoriasis model was established using imiquimod (IMQ, 62.5 mg/d), and intragastrically treated with the different drugs for six days. The severity of skin inflammation was evaluated with Psoriasis Area and Severity Index (PASI) scores and pathology. The levels of inflammation cytokines were assessed with immunofluorescence, immunochemistry, ELISA, and real-time PCR. The number of Th17 cells was determined with flows. Results: SMWE inhibited the proliferation of HaCaT cells and reduced the IL-17A-induced IL-6 production in vitro. In vivo, SMWE deduced the levels of IL-1ß, IL-6, IL-8, IL-17A, IL-17F, IL-22, IL-23, and TNF-α, while increasing the level of IL-10 compared to the model group. SMWE also inhibited the levels of NF-κB, JAK2, and STAT3 proteins, while declining the expressions of Gr-1, and MPO. Interestingly, SMWE significantly decreased the number of Th17 cells. Conclusion: SMWE inhibited the proliferation of HaCaT cells and attenuated the development of psoriasis lesions by inhibiting Th17 cells to regulate the levels of inflammation cytokines.

Dynamic Change of Novel Systemic Inflammation Markers to Predict Maternal-Neonatal Prognosis After Cervical Cerclage.

Objective: Cervical cerclage is an effective method to prevent preterm birth. However, the clinical indicators that can predict cervical cerclage remain limited. This study aimed to explore whether dynamically inflammatory markers are valuable biomarkers for the prognosis of cervical cerclage. Methods: This study included 328 participants. Inflammatory markers were calculated using maternal peripheral blood before and after the cervical cerclage procedure. The Chi-square test, linear regression, and logistic regression were performed to evaluate the dynamic change of inflammatory markers with the prognosis of cervical cerclage. And the optimal cut-off values of inflammatory markers were calculated. Results: Totally 328 pregnant women were analyzed in the study. 223 (67.99%) participants obtained successful cervical cerclage. This study revealed that the maternal age, the baseline BMI (cm2/kg), the times of gravida, the rate of recurrent abortion, the PPROM, cervical length shorter (<1.5cm), cervical dilation (≥2cm), the bulging membrane, the Pre-SII, the Pre-SIRI, the Post-SII, the Post-SIRI, and the ΔSII were significantly associated with outcomes after cervical cerclage (all P<0.05). Pre-SII, Pre-SIRI, Post-SII, Post-SIRI, and ΔSII levels were mainly related to maternal-neonatal outcomes. Furthermore, the results demonstrated that the ΔSII level had the highest OR (OR=14.560; 95% CI (4.461-47.518)). In addition, we revealed that Post-SII and ΔSII levels had the highest AUC (0.845/0.840) and relatively higher sensitivity/specificity (68.57/92.83% and 71.43/90.58%) and PPV/ NPV (81.82/86.25% and 78.13/87.07%) compared with other indicators. Conclusion: This study suggested that the dynamic change of SII level and SIRI level are important biochemical markers to predict the prognosis of cervical cerclage and maternal-neonatal prognosis, especially the Post-SII and ΔSII levels. They can help to determine candidates for cervical cerclage before surgical procedure and enhance postoperative surveillance.

An Explainable Student Fatigue Monitoring Module with Joint Facial Representation.

Online fatigue estimation is, inevitably, in demand as fatigue can impair the health of college students and lower the quality of higher education. Therefore, it is essential to monitor college students' fatigue to diminish its adverse effects on the health and academic performance of college students. However, former studies on student fatigue monitoring are mainly survey-based with offline analysis, instead of using constant fatigue monitoring. Hence, we proposed an explainable student fatigue estimation model based on joint facial representation. This model includes two modules: a spacial-temporal symptom classification module and a data-experience joint status inferring module. The first module tracks a student's face and generates spatial-temporal features using a deep convolutional neural network (CNN) for the relevant drivers of abnormal symptom classification; the second module infers a student's status with symptom classification results with maximum a posteriori (MAP) under the data-experience joint constraints. The model was trained on the benchmark NTHU Driver Drowsiness Detection (NTHU-DDD) dataset and tested on an Online Student Fatigue Monitoring (OSFM) dataset. Our method outperformed the other methods with an accuracy rate of 94.47% under the same training-testing setting. The results were significant for real-time monitoring of students' fatigue states during online classes and could also provide practical strategies for in-person education.

A crystalline-amorphous interface engineering in Fe-doped NixP electrocatalyst for highly efficient oxygen evolution reaction.

OER (oxygen evolution reaction) is a critical reaction in several storage and conversion systems for renewable and clean electrochemical energies, including solar fuel devices, metal-air batteries, as well as regenerative fuel and water splitting cells. Regarding the shortcomings of OER, apart from the sluggish kinetics and high reaction overpotential, the reaction rate and overpotential are difficult to be optimized simultaneously. Herein, a novel hierarchical particle-sheet-structured Fe-doped NixP electrocatalyst is developed, which presents abundant interfaces between crystalline particle and amorphous sheet. The OER overpotential is reduced to 204 mV at 20 mA cm-2 current density, while it is reduced to 225 and 231 mV at 100 and 300 mA cm-2, respectively. The Fe-doped NixP electrocatalyst also shows fast reaction kinetics, whose Tafel slope is a remarkable 25 mV dec-1. For an electrolytic cell whose cathode and anode are Pt/C/NF and Fe-NixP/NF, respectively, a mere 1.446 V voltage is necessary to drive a 10 mA cm-2 current density for achieving overall water-splitting property. Notably, it also works stably at considerably high current densities of 500 and 1000 mA cm-2, representing high potential for commercial applications.

Effects of coping on nurses' mental health during the COVID-19 pandemic: Mediating role of social support and psychological resilience.

BACKGROUND: Fighting against the COVID-19 pandemic, front-line nurses were under unprecedented psychological pressure. Therefore, it is necessary to promptly evaluate the psychological status of nurses during the COVID-19 epidemic period. AIM: To investigate nurses' mental health during the COVID-19 pandemic, and to test the mediating role of social support and psychological resilience between coping and mental health. DESIGN: This was a descriptive, cross-sectional survey which used a structural equation model. METHOD: In total, 711 registered nurses were included. All participants were invited to complete a socio-demographic questionnaire, the general health questionnaire, the trait coping style questionnaire, the perceived social support scale and the Conner-Davidson Resilience scale. RESULTS: In total, 50.1% nurses had high risk of mental health. Positive coping positively affected social support and psychological resilience, while it negatively affected mental health. Negative coping negatively affected social support and psychological resilience, while it positively affected mental health. Social support positively affected psychological resilience, while it negatively affected mental health. In addition, social support mediated coping and psychological resilience, and coping and mental health. Moreover, psychological resilience negatively affected mental health, and it mediated coping and mental health.

Development of a risk score model for the prediction of patients needing percutaneous coronary intervention.

BACKGROUND: The incidence of coronary heart disease (CHD) is increasing worldwide. The need for percutaneous coronary intervention (PCI) is determined by coronary angiography (CAG). As coronary angiography is an invasive and risky test for patients, it will be of great help to develop a predicting model for the assessment of the probability of PCI in patients with CHD using the test indexes and clinical characteristics. METHODS: A total of 454 patients with CHD were admitted to the cardiovascular medicine department of a hospital from January 2016 to December 2021, including 286 patients who underwent CAG and were treated with PCI, and 168 patients who only underwent CAG to confirm the diagnosis of CHD were set as the control group. Clinical data and laboratory indexes were collected. According to the clinical symptoms and the examination signs, the patients in the PCI therapy group were further split into three subgroups: chronic coronary syndrome (CCS), unstable angina pectoris (UAP), and acute myocardial infarction (AMI). The significant indicators were extracted by comparing the differences among the groups. A nomogram was drawn based on the logistic regression model, and predicted probabilities were performed using R software (version 4.1.3). RESULTS: Twelve risk factors were selected by regression analysis; the nomogram was successfully constructed to predict the probability of needing PCI in patients with CHD. The calibration curve shows that the predicted probability is in good agreement with the actual probability (C-index = 0.84, 95% CI = 0.79-0.89). According to the results of the fitted model, the ROC curve was plotted, and the area under the curve was 0.801. Among the three subgroups of the treatment group, 17 indexes were statistically different, and the results of the univariable and multivariable logistic regression analysis revealed that cTnI and ALB were the two most important independent impact factors. CONCLUSION: cTnI and ALB are independent factors for the classification of CHD. A nomogram with 12 risk factors can be used to predict the probability of requiring PCI in patients with suspected CHD, which provided a favorable and discriminative model for clinical diagnosis and treatment.

Effects of Tylophora yunnanensis Schltr on regulating the gut microbiota and its metabolites in non-alcoholic steatohepatitis rats by inhibiting the activation of NOD-like receptor protein 3.

ETHNOPHARMACOLOGICAL RELEVANCE: Tylophora yunnanensis Schltr (TYS) is widely distributed in Yunnan, Guizhou, and other places in China. It is commonly used by folks to treat hepatitis and other liver-related diseases; however, its mechanism of action is still unclear. AIM OF THE STUDY: This study aimed to determine the effects of TYS on regulating gut microbiota and its metabolites in non-alcoholic steatohepatitis (NASH) rats by inhibiting the activation of NOD-like receptor protein3 (NLRP3). MATERIAL AND METHODS: An HFD-induced rat model was established to investigate if the intragastric administration of TYS could mediate gut microbiota and their metabolites to ultimately improve the symptoms of NASH. The improving effects of TYS on NASH rats were assessed by measuring their body weight, lipid levels, histopathology, and inflammatory factor levels in the rat models. The regulatory effects of TYS on NLRP3 in the NASH rats were analyzed using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), which determined the levels of NLRP3-related factors. The changes in the composition of the gut microbiota of NASH rats were analyzed using 16S rRNA gene sequencing technology. Meanwhile, the Ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used for the non-targeted analysis of metabolites in the cecum contents. RESULTS: The results showed that TYS could improve NASH by decreasing the body weight and levels of lipid, AST, ALT, LPS, FFA, VLDL, IL-1ß, IL-6, TNF-α, TGF-ß, NLRP3, ASC, and Caspase-1 in the NASH rats. The analysis of gut microbiota showed that TYS could improve the diversity and abundance of gut microbiota and alter their composition by decreasing the Firmicutes/Bacteroidetes (F/B) ratio and relative abundances of Lachnospiraceae, Christensenellaceae, Blautia, etc. while increasing those of Muribaculaceae, Rumiaococcus, Ruminococcaceae, etc. The analysis of metabolites in the cecum contents suggested that the arachidonic acid metabolism, bile secretion, serotonergic synapse, Fc epsilon RI signaling pathway, etc. were regulated by TYS. The metabolites enriched in these pathways mainly included chenodeoxycholic acid, prostaglandin D2, TXB2, 9-OxoODE, and 13(S)-HOTrE. CONCLUSIONS: These findings suggested that TYS could alleviate the NASH symptoms by decreasing the body weight, regulating the lipid levels, reducing the inflammatory response, and inhibiting the expression levels of NLRP3, ASC, and Caspase-1 in the NASH rats. The changes in the composition of gut microbiota and their metabolic disorder were closely related to the activation of NLRP3. TYS could significantly inhibit the activation of NLRP3 and regulate the composition of gut microbiota and the disorder of metabolites during NASH modeling.

Flavonoids from Scutellaria amoena C. H. Wright alleviate mitochondrial dysfunction and regulate oxidative stress via Keap1/Nrf2/HO-1 axis in rats with high-fat diet-induced nonalcoholic steatohepatitis.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is among the most common liver diseases in the world. Flavonoids from Scutellaria amoena (SAF) are used in the treatment of hepatopathy in China. However, the effect and mechanism against NASH remain unclear. We investigated the alleviating effect of SAF on NASH via regulating mitochondrial dysfunction and oxidative stress. METHODS: The effects of SAF on NASH were evaluated using in vitro and in vivo methods. L02 cells were induced by fat emulsion to establish an adipocytes model, followed by treatment with SAF for 24 h. NASH rat models were established by the administration of a high-fat diet for 12 weeks and were administered SAF for six weeks. Changes in body weight, organ indexes, lipid levels, inflammatory cytokines, mitochondrial indicators, and fatty acid metabolism were investigated. RESULTS: SAF significantly improved body weight, organ indexes, lipid levels, liver injury, and inflammatory infiltration in NASH rats. SAF notably regulated interleukin-6, tumor necrotic factor-alpha, superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), kelch-like ECH-associated protein 1 (Keap1), nuclear factor-erythroid factor 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). Additionally, SAF improved mitochondrial dysfunction, increased the levels of GSH, SOD, ATP synthase, complex I and II, and decreased the level of MDA in liver mitochondria. SAF regulated the expression of ß-oxidation genes, including peroxisome proliferator-activated receptor -gamma coactivator-1alpha (PGC-1α), carnitine palmitoyltransferase-1 (CPT1) A, CPT1B, medium-chain acyl-CoA dehydrogenase, long-chain acyl-CoA dehydrogenase, very long-chain acyl-CoA dehydrogenase, and PPARα. CONCLUSION: SAF can alleviate NASH by regulating mitochondrial function and oxidative stress via the Keap1/Nrf2/HO-1 axis.

Factors influencing physical inactivity status among chinese pregnant women: a cross-sectional study.

BACKGROUND: Regular prenatal physical activity provides numerous health benefits to both mother and fetus. However, little is known about the physical activity status of pregnant women in China and whether they meet the current guidelines for prenatal physical activity. The aims of the study were to assess physical inactivity status and associated factors among pregnant women in Shanghai, China. METHODS: A cross-sectional study of 1636 pregnant women were recruited at a tertiary obstetrics and gynecology hospital in Shanghai. Maternal sociodemographic characteristics and health information were obtained using structured questionnaires or from the electronic medical records. Physical inactivity status was assessed using the International Physical Activity Questionnaire-Short Form. Factors pertinent to physical inactivity were identified by binary logistic regression and were reported with adjusted odds ratios (ORs) and 95% confidence intervals (CIs). All statistical analyses were performed using the SPSS software package. RESULTS: In total, the prevalence of physical inactivity was 47.5%. Walking was the main form of physical activity and only 2.8% of the pregnant women achieved the goal of at least 150 min of moderate-intensity physical activity weekly. Multivariate logistic regression identified a significant negative association of physical inactivity with personal monthly income (adjusted OR 0.648, 95% CI 0.505-0.831), engagement in regular exercise before pregnancy (adjusted OR 0.575, 95% CI 0.464-0.711) and in the second (adjusted OR 0.534, 95% CI 0.411-0.693) or third (adjusted OR 0.615, 95% CI 0.470-0.806) trimester of pregnancy. Women with nausea or vomiting during pregnancy were more likely to be physically inactive during pregnancy (adjusted OR 1.307, 95% CI 1.002-1.705). CONCLUSION: Physical inactivity is highly prevalent among pregnant women in China. Further efforts should be taken to overcome the barriers to prenatal physical activity and to promote moderate- to vigorous-intensity activities among Chinese pregnant women.

The Association between Maternal B Vitamins in Early Pregnancy and Gestational Diabetes Mellitus: A Prospective Cohort Study.

Background: This study evaluated the association between maternal B vitamins in early pregnancy and gestational diabetes mellitus (GDM) risk. Methods: A cohort of 1265 pregnant women was recruited at 8−15 weeks of gestation in 2021−2022 (Shanghai, China). Pregnancies with both serum B vitamin measurements at recruitment and glucose measurements at 24−28 weeks of gestation were included in the final analysis. Results: Of the 1065 pregnancies, in the final analysis, GDM occurred in 121 women (11.36%). In multivariate logistic models, an increased risk trend across serum vitamin B1 quartiles with GDM was observed (p-Trend = 0.001). Compared with women in the lowest quartile of serum vitamin B6, those in the upper two quartiles had approximately twofold higher odds of GDM. Moreover, compared with women with vitamin B12 levels < 150 pmol/L, those with vitamin B12 levels > 150 pmol/L had lower odds of GDM (p = 0.005). The restricted cubic spline regression models also revealed that serum vitamin B6 and vitamin B12 were associated with an increased risk of GDM in a nonlinear fashion. Conclusions: Our study shows that higher maternal serum vitamin B1 and B6 levels in early pregnancy are associated with increased GDM risk, while sufficient vitamin B12 status is associated with lower GDM risk.

Daphnetin contributes to allergen-induced Th2 cytokine expression and type 2-immune responses in atopic dermatitis and asthma.

Daphne koreana Nakai is a cherished medicinal plant in the Changbai Mountain region of China. It can be incorporated into medicinal meals and used for various skin diseases by infiltrating liquor. Daphnetin (7,8-dihydroxycoumarin, Dap.) is a main constituent of D. koreana Nakai, which has been used to treat inflammatory conditions and immune disorders due to its numerous pharmacological activities, including anti-oxidant, anti-inflammatory, analgesic, etc. Atopic dermatitis (AD) and allergic asthma are typical diseases of type 2-immune responses. In the present study, the therapeutic potential of Dap. against AD and allergic asthma was investigated using animal and cell experiments. AD-like lesions were induced by repeated application of 1-chloro-2,4-dinitrobenzene (DNCB) to the shaved dorsal skin of BALB/c mice. Ovalbumin (OVA) induction was utilized to establish a mouse asthma model. A passive cutaneous anaphylaxis (PCA) mouse ear model and immunoglobulin E (IgE)/bovine serum albumin (BSA)-stimulated RBL-2H3 cells were used for in vitro assays. The skin lesions and serum and tissue homogenates of the mice were analyzed using histological analysis, immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA), respectively, in order to investigate the anti-AD effects of Dap. Histological analysis was performed on the allergic asthma model to observe inflammatory cell infiltration in the lung tissues. Total IgE and OVA-specific IgE in the serum were measured by ELISA. The levels of inflammatory cytokines in BALF were detected by ELISA. In addition, ELISA and western blotting were performed for the in vitro analysis of RBL-2H3 cells. The results showed that Dap. inhibited the development of DNCB-induced AD-like lesions in the BALB/c mice by reducing the severity of the lesions, epidermal thickness and mast cell infiltration; this was accompanied by reduced levels of IgE and inflammatory cytokines [interleukin (IL)-4, IL-5, IL-9, IL-13, IL-33 and thymic stromal lymphopoietin (TSLP)]. In the allergic asthma model, Dap. reduced the number of infiltrated inflammatory cells in the lung tissues. Moreover, the levels of total serum IgE and OVA-specific IgE were reduced in the high daphnetin dose groups (Dap., -100 mg kg-1). Dap. administered at a dose of -100 mg kg-1 decreased the levels of inflammatory cytokines (IL-4, IL-5, IL-9, IL-13, IL-33 and TSLP in BALF). Furthermore, Dap. administered to IgE-sensitized mice effectively attenuated the IgE-triggered PCA reaction. In vitro, Dap. decreased the expression levels of histamine, IL-4, IL-6, IL-13, MIP-1α and INF-α, and reduced the protein expression levels of phosphorylated MAPKs, P-Lyn and P-syk in the RBL-2H3 cells. Therefore, Dap. can be represented as a potential therapeutic strategy for the treatment of allergic inflammatory conditions via immunoregulation.

Nuanced Interactions between AKAP79 and STIM1 with Orai1 Ca2+ Channels at Endoplasmic Reticulum-Plasma Membrane Junctions Sustain NFAT Activation.

A-kinase anchoring protein 79 (AKAP79) is a human scaffolding protein that organizes Ca2+/calmodulin-dependent protein phosphatase calcineurin, calmodulin, cAMP-dependent protein kinase, protein kinase C, and the transcription factor nuclear factor of activated T cells (NFAT1) into a signalosome at the plasma membrane. Upon Ca2+ store depletion, AKAP79 interacts with the N-terminus of STIM1-gated Orai1 Ca2+ channels, enabling Ca2+ nanodomains to stimulate calcineurin. Calcineurin then dephosphorylates and activates NFAT1, which then translocates to the nucleus. A fundamental question is how signalosomes maintain long-term signaling when key effectors are released and therefore removed beyond the reach of the activating signal. Here, we show that the AKAP79-Orai1 interaction is considerably more transient than that of STIM1-Orai1. Free AKAP79, with calcineurin and NFAT1 in tow, is able to replace rapidly AKAP79 devoid of NFAT1 on Orai1, in the presence of continuous Ca2+ entry. We also show that Ca2+ nanodomains near Orai1 channels activate almost the entire cytosolic pool of NFAT1. Recycling of inactive NFAT1 from the cytoplasm to AKAP79 in the plasma membrane, coupled with the relatively weak interaction between AKAP79 and Orai1, maintain excitation-transcription coupling. By measuring rates for AKAP79-NFAT interaction, we formulate a mathematical model that simulates NFAT dynamics at the plasma membrane.