Thyroid-stimulating hormone and total bile acids can predict adverse pregnancy outcome among patients with gestational hypertension.

OBJECTIVE: To investigate the correlation between serum thyroid-stimulating hormone (TSH) and total bile acid (TBA) levels in gestational hypertension and their combined predictive value for pregnancy outcome. METHODS: A total of 194 patients with gestational hypertension (GH), treated from June 2020 to May 2022, were included in this study. The patients were divided into two subgroups based on pregnancy outcome: an adverse pregnancy outcome group (77 cases) and a normal pregnancy outcome group (117 cases). Additionally, 50 healthy pregnant women undergoing routine prenatal checkups during the same period served as the control group. In this study, serum TBA and TSH levels were measured and compared between the control and GH groups as well as between adverse pregnancy outcome and normal pregnancy outcome groups. The independent risk factors for adverse pregnancy outcome were screened using logistic regression, and their predictive value for pregnancy outcome in patients with GH was analyzed using receiver operating characteristic (ROC) curves. RESULTS: Serum TSH and TBA levels were significantly higher in the GH group compared to the normal group (both P < 0.001). Logistic regression analysis revealed that age, body mass index (BMI), TSH, and TBA were independent risk factors for adverse pregnancy outcome. ROC curve analysis showed that combined TSH and TBA for predicting adverse pregnancy outcome had an Area Under the Curve (AUC) of 0.896, surpassing the AUCs of each individual index (0.843 for TSH and 0.765 for TBA), which indicates a stronger predictive value (P < 0.001). CONCLUSION: The combined measurement of serum TBA and TSH can serve as a valuable predictive tool for pregnancy outcome in patients with gestational hypertension.

Elevations in presepsin, PCT, hs-CRP, and IL-6 levels predict mortality among septic patients in ICU.

BACKGROUND: Aim to investigate the predictive value of changes in presepsin (PSEP), procalcitonin (PCT), high-sensitivity C-reactive protein (hsCRP), and interleukin-6 (IL-6) levels to for mortality in septic patients in intensive care unit (ICU). METHOD: This study enrolled septic patients between November 2020 and December 2021. Levels of PSEP, PCT, hsCRP, and IL-6 were measured on 1st (PSEP_0, PCT_0, hsCRP_0, IL-6_0) and 3rd day (PSEP_3, PCT_3, hsCRP_3, IL-6_3). Follow-up was performed on days 3, 7, 14, 21, and 28 after enrollment. The outcome was all-cause death. RESULTS: The study included 119 participants, and the mortality was 18.5%. In univariable Cox proportional-hazards regression (Cox) analysis, △PSEP (= PSEP_3- PSEP_0) > 211.49 pg/ml (hazard ratio (HR) 2.70, 95% confidence interval (CI) 1.17-6.22), △PCT (= PCT_3- PCT_0) > -0.13 ng/ml (HR 7.31, 95% CI 2.68-19.80), △hsCRP (= hsCRP_3- hsCRP_0) > -19.29 mg/L (HR 6.89, 95% CI 1.61-29.40), and △IL-6 (= IL-6_3- IL-6_0) > 1.00 pg/ml (HR 3.13, 95% CI 1.35-7.24) indicated an increased risk of mortality. The composite concordance index for alterations in all four distinct biomarkers was highest (concordance index 0.83, 95% CI 0.76-0.91), suggesting the optimal performance of this panel in mortality prediction. In decision curve analysis, compared with the APACHE Ⅱ and SOFA scores, the combination of the four biomarkers had a larger net benefit. Interestingly, IL-6 was predominantly produced by monocytes upon LPS stimulation in PBMCs. CONCLUSIONS: △PSEP, △PCT, △hsCRP, and △IL-6 are reliable biomarkers for predicting mortality in septic patients in ICU, and their combination has the best performance.

Epidemic Features and Megagenomic Analysis of Childhood Mycoplasma Pneumoniae post COVID-19 Pandemic: A 6-year Study in Southern China.

With the atypical rise of Mycoplasma pneumoniae infection (MPI) in 2023, prompt studies are needed to determine the current epidemic features and risk factors with emerging trends of MPI to furnish a framework for subsequent investigations. This multicentre, retrospective study was designed to analyse the epidemic patterns of MPI before and after the COVID-19 pandemic, as well as genotypes and the macrolide resistance-associated mutations in MP sampled from pediatric patients in Southern China. Clinical data was collected from 133674 patients admitted into investigational hospitals from June 1, 2017, to November 30, 2023. Metagenomic next-generation sequencing (mNGS) data were retrieved based on MP sequence positive samples from 299 pediatric patients for macrolide resistance-associated mutations analysis. Pearson's chi-squared test was used to compare categorical variables between different time frames. The monthly average cases of pediatric common respiratory infection diseases were increased without enhanced public health measures after the pandemic, especially for influenza, respiratory syncytial virus infection, and MPI. The contribution of MPI to pneumoniae was similar to that in the outbreak in 2019. Compared mNGS data between 2019-2022 and 2023, the severity of MP did not grow stronger despite higher rates of macrolide-resistance hypervariable sites, including loci 2063 and 2064, were detected in childhood MP samples of 2023. Our findings indicated ongoing surveillance is necessary to understand the impact of post pandemic on MP transmission disruption on epidemic season and severity of clinical outcomes in different scenarios.

Effect of intraoperative and/or postoperative esketamine administration on preventing postpartum depression: A systematic review and meta-analysis.

This systematic review and meta-analysis aimed to evaluate the impact of intraoperative and/or postoperative esketamine application on the prevention of postpartum depression (PPD). PubMed, Embase, and Web of Science were thoroughly searched for eligible randomized controlled trials (RCTs) regarding the application of esketamine for postnatal depression prevention. Nine RCTs including 1277 participants were involved in the final analysis. It was found that intraoperative and/or postoperative administration of esketamine significantly reduced the PPD incidence and the Edinburgh Postnatal Depression Scores in the early postoperative period. Meanwhile, esketamine lowered the occurrence of postoperative nausea and vomiting with no influence on other psychiatric symptoms.

Microglial AT1R Conditional Knockout Ameliorates Hypoperfusive Cognitive Impairment by Reducing Microglial Inflammatory Responses.

Chronic cerebral hypoperfusion (CCH) can cause vascular cognitive impairment and dementia. AT1R, angiotensin II type I receptor, plays a vital role in central nervous system pathologies, but its concrete function in vascular dementia is still unclear. Herein, we investigated the effects of AT1R during CCH by conditional knockout of the microglial AT1R and candesartan treatment. Using the bilateral carotid artery stenosis (BCAS) model, we found that the AT1R is crucial in exacerbating CCH-induced cognitive impairment via regulating microglial activation. The levels of AT1R were increased in the hippocampus and the hippocampal microglia after CCH induction. Microglial AT1R conditional knockout ameliorated cognitive impairment by reducing inflammatory responses and microglial activation, and so did candesartan treatment. However, we observed restoration of cerebral blood flow (CBF) but no significant neuronal loss in the hippocampus at 28 days after BCAS. Finally, we screened three hub genes (Ctss, Fcer1g, Tyrobp) associated with CCH. Our findings indicated that microglial expression of AT1R is critical for regulating neuroinflammation in CCH, and AT1R antagonism may be a feasible and promising method for ameliorating CCH-caused cognitive impairment.

Efficacy of 1-hour postload plasma glucose as a suitable measurement in predicting type 2 diabetes and diabetes-related complications: A post hoc analysis of the 30-year follow-up of the Da Qing IGT and Diabetes Study.

AIM: To evaluate whether 1-hour plasma glucose (1hPG) can be a comparable measurement to 2-hour plasma glucose (2hPG) in identifying individuals at high risk of developing diabetes. METHODS: A total of 1026 non-diabetic subjects in the Da Qing IGT and Diabetes Study were included and classified according to baseline postload 1hPG. The participants were followed up and assessed at 6-, 20- and 30year follow-up for outcomes including diabetes, all-cause and cardiovascular mortality, cardiovascular disease (CVD) events, and microvascular disease. We then conducted a proportional hazards analysis in this post hoc study to determine the risks of developing type 2 diabetes and its complications in a '1hPG-normal' group (1hPG <8.6 mmol/L) and a '1hPG-high' group (≥8.6 mmol/L). The predictive values of 1hPG and 2hPG were evaluated using a time-dependent receiver-operating characteristic (ROC) curve. RESULTS: Compared with the 1hPG-normal group, the 1hPG-high group had increased risk of diabetes (hazard ratio [HR] 4.45, 95% CI 3.43-5.79), all-cause mortality (HR 1.46, 95% CI 1.07-2.01), CVD mortality (HR 1.84, 95% CI 1.16-2.95), CVD events (HR 1.39, 95% CI 1.03-1.86) and microvascular disease (HR 1.70, 95% CI: 1.03-2.79) after adjusting for confounders. 1hPG exhibited a higher area under the ROC curve (AUC) for predicting diabetes than 2hPG during the long-term follow-up (AUC [1hPG vs. 2hPG]: 10 years: 0.86 vs. 0.84, p = 0.08; 20 years: 0.88 vs. 0.87, p = 0.04; 30 years: 0.85 vs. 0.82, p = 0.009). CONCLUSIONS: Elevated 1hPG level (≥8.6 mmol/L) was associated with increased risk of developing type 2 diabetes and its long-term complications, and could be considered as a suitable measurement for identifying individuals at high risk of type 2 diabetes.

The efficacy and safety of aspirin-ticagrelor vs. aspirin-clopidogrel in ischemic stroke patients with cerebral artery stenting.

OBJECTIVE: First, the efficacy and safety of aspirin-ticagrelor after cerebral artery stenting in ischemic stroke patients is controversial. Second, there is a gap in the research on guiding two antiplatelet therapy (DAPT) after stenting based on the CYP2C19 genotype. METHODS: This retrospective study included patients who underwent cerebral artery stenting at the First Affiliated Hospital of Chongqing Medical University from January 2019 to February 2023. We divided them into the aspirin-clopidogrel group and aspirin-ticagrelor group and carefully collected baseline information laboratory data and imaging results from the patients. The efficacy outcomes were 30 days recurrent stroke, 90 days recurrent stroke, and 180 days recurrent stroke, and the safety outcome was intracranial hemorrhage. T-tests or Fisher's tests were performed for study outcomes in both groups of patients. OUTCOME: A total of 372 patients were included. For efficacy outcomes, aspirin-ticagrelor was associated with a reduced risk of 180 days recurrent stroke, in patients with CYP2C19 LOF allele (OR = 0.426, CI = 0.184-0.986, P = 0.042) and CYP2C19 intermediate metabolic genotype (OR = 0.237, CI = 0.026-1.034, P = 0.044), compared with aspirin-clopidogrel. There was no significant difference in the rate of intracranial hemorrhage (ICH) between patients with aspirin-clopidogrel and aspirin-ticagrelor, regardless of overall (OR = 1.221, CI = 0.115-7.245, P = 0.683), CYP2C19 LOF allele carriers (OR = 1.226, CI = 0.411-3.658, P = 0.715), or CYP2C19 intermediate metabolizer (OR = 1.221, CI = 0.115-7.245, P = 0.683). No significant differences were found between the two DAPTs on other efficacy and safety outcomes. CONCLUSION: A cohort study found that aspirin-ticagrelor was significantly superior to aspirin-clopidogrel in reducing 180 days recurrent stroke in CYP2C19 LOF allele carriers and CYP2C19 intermediate metabolizers. There was no significant difference between aspirin-ticagrelor and aspirin-clopidogrel in the risk of intracranial hemorrhage in terms of ICH rates.

Cell-derived nanomaterials for biomedical applications.

The ever-growing use of nature-derived materials creates exciting opportunities for novel development in various therapeutic biomedical applications. Living cells, serving as the foundation of nanoarchitectonics, exhibit remarkable capabilities that enable the development of bioinspired and biomimetic systems, which will be explored in this review. To understand the foundation of this development, we first revisited the anatomy of cells to explore the characteristics of the building blocks of life that is relevant. Interestingly, animal cells have amazing capabilities due to the inherent functionalities in each specialized cell type. Notably, the versatility of cell membranes allows red blood cells and neutrophils' membranes to cloak inorganic nanoparticles that would naturally be eliminated by the immune system. This underscores how cell membranes facilitate interactions with the surroundings through recognition, targeting, signalling, exchange, and cargo attachment. The functionality of cell membrane-coated nanoparticles can be tailored and improved by strategically engineering the membrane, selecting from a variety of cell membranes with known distinct inherent properties. On the other hand, plant cells exhibit remarkable capabilities for synthesizing various nanoparticles. They play a role in the synthesis of metal, carbon-based, and polymer nanoparticles, used for applications such as antimicrobials or antioxidants. One of the versatile components in plant cells is found in the photosynthetic system, particularly the thylakoid, and the pigment chlorophyll. While there are challenges in consistently synthesizing these remarkable nanoparticles derived from nature, this exploration begins to unveil the endless possibilities in nanoarchitectonics research.

We have highlighted the Cell-derived Nanomaterials for Biomedical Applications through the lenses of our team who have experiences with working on cell membrane, thylakoids, and studying the impact of nanoparticles on biological phenomenon such as nanomaterialsinduced endothelial leakiness (NanoEL). In this review, we have discussed the progress and the wide potential of nanoarchitectonics in plant systems, animal cells and microorganisms. Due to our unique backgrounds, our take on this topic may be the novelty of the review.

Development of an Evaluation System for the Prophylactic Use of Antimicrobial Drugs in the Perioperative Period of Class I Surgical Incisions in Neurosurgery.

BACKGROUND: This study aimed to establish a precise preoperative high-risk factor scoring system and algorithm for antibiotic prophylaxis decision-making, provide guidance for the judicious use of AMP, refine interventions, and ensure the appropriate application of AMP for class I incisions in neurosurgery. METHODS: According to PRISMA guidelines, literature searches, study selection, methodology development, and quality appraisal were performed. The quality of evidence across the study population was assessed using the Newcastle-Ottawa Scale. A two-round Delphi expert consultation method involved 15 experts from leading tertiary hospitals in China. Establishing an algorithm of SOPs for perioperative antimicrobial prophylaxis in Class I neurosurgical incisions. RESULTS: Thirteen studies, encompassing 11,936 patients undergoing clean neurosurgical procedures, were included. 791 patients experienced SSI, resulting in an average incidence of 6.62%. Identified risk factors significantly associated with an increased incidence of postoperative SSI (P < 0.05) included emergency surgery, preoperative hospitalization ≥7 days, intraoperative blood loss ≥300 mL, operation time ≥4 hours, diabetes mellitus, cerebrospinal fluid leakage, and repeat surgery. Sensitivity analysis demonstrated robust results for emergency surgery, intraoperative blood loss ≥300 mL, operation time ≥4 hours, cerebrospinal fluid leakage, and repeat surgery. Established a risk assessment system for Class I neurosurgical incisions by the Delphi method. Additionally, we have formulated an algorithm of SOPs for perioperative antimicrobial prophylaxis in Class I neurosurgical incisions. CONCLUSIONS: The established index for AMP utilization and SOPs in the preoperative period of class I neurosurgical incisions proves valuable, contributing to improved patient outcomes in neurosurgical procedures.

Edge Substitution Effects of Histidine Tautomerization Behaviors on the Structural Properties and Aggregation Properties of Aß(1-42) Mature Fibril.

Histidine behaviors play critical roles in folding and misfolding processes due to the changes in net charge and the various N/N-H orientations on imidazole rings. However, the effect of histidine tautomerization (HIE (Nε-H, ε) and HID (Nδ-H, δ) states) behaviors on the edge chain of Aß mature fibrils remains inadequately understood, which is critical for finding a strategy to disturb fibril elongation and growth. In the current study, eight independent molecular dynamics simulations were conducted to investigate such impacts on the structural and aggregation properties. Our results from three different binding models revealed that the binding contributions of edge substitution effects are primarily located between chains 1 and 2. Histidine states significantly influence the secondary structure of each domain. Further analysis confirmed that the C1_H6//C1_E11 intrachain interaction is essential in maintaining the internal stability of chain 1, while the C1_H13//C2_H13 and C1_H14//C2_H13 interchain interactions are critical in maintaining the interchain stability of the fibril structure. Our subsequent analysis revealed that the current edge substitution leads to the loss of the C1_H13//C1_E11 intrachain and C1_H13//C2_H14 interchain interactions. The N-terminal regularity was significantly directly influenced by histidine states, particularly by the residue of C1_H13. Our study provides valuable insights into the effect of histidine behaviors on the edge chain of Aß mature fibril, advancing our understanding of the histidine behavior hypothesis in misfolding diseases.

Practice guideline on ovarian tissue cryopreservation and transplantation in the prevention and treatment of iatrogenic premature ovarian insufficiency.

Premature ovarian insufficiency (POI) refers to the decline of ovarian function before the age of 40. POI causes a reduction in or loss of female fertility, accompanied by different degrees of menopausal symptoms, which increases the risk of chronic diseases related to early menopause and seriously affects patients' quality of life and health. It is conservatively estimated that at least one million prepubertal girls and women of reproductive age in China are at risk of iatrogenic POI caused by radiotherapy and chemotherapy every year. With the development of medical technology and the breakthrough of scientific and technological advances, preventing and treating iatrogenic POI have become possible. International and national guidelines consider cryopreserved ovarian tissue transplantation to be the most promising method of preserving the ovarian function and fertility of prepubertal girls and women of reproductive age who cannot delay radiotherapy and chemotherapy. In order to guide the clinical application of ovarian tissue cryopreservation and transplantation technology in China, the Guideline Working Group finally included 14 scientific questions and 18 recommendations through a questionnaire survey, field investigation, and consultation of a large number of Chinese and English literature databases in order to provide a reference for colleagues in clinical practice.

Isolation, structure modification, and anti-rheumatoid arthritis activity of isopimarane-type diterpenoids from Orthosiphon aristatus.

Orthosiphon aristatus is a well-known folkloric medicine and herb for Guangdong soup for the treatment of rheumatism in China. Eight isopimarane-type and migrated pimarane-type diterpenoids (1-8), including a new one with a rarely occurring α,ß-unsaturated diketone C-ring, were isolated from O. aristatus. Their structures were determined by spectroscopic methods and quantum chemical calculations. Furthermore, the most abundant compound, orthosiphol K, was structurally modified by modern synthetic techniques to give seven new derivatives (9-15). The anti-rheumatoid arthritis activity of these diterpenoids were evaluated on a TNF-α induced MH7A human rheumatoid fibroblast-like synoviocyte model. Compound 10 showed the most potent activity among these compounds. Based on their inhibitory effects on the release levels of IL-1ß, the preliminary structure-activity relationships were concluded. Furthermore, western blot analysis revealed that 10 could increase the expression of IκBα and decrease the expression of NF-κB p65, and the expression levels of COX-2 and NLRP3 proteins were consequently down-regulated.

Circulating palmitoyl sphingomyelin levels predict the 10-year increased risk of cardiovascular disease death in Chinese adults: findings from the Da Qing Diabetes Study.

BACKGROUND: Higher levels of palmitoyl sphingomyelin (PSM, synonymous with sphingomyelin 16:0) are associated with an increased risk of cardiovascular disease (CVD) in people with diabetes. Whether circulating PSM levels can practically predict the long-term risk of CVD and all-cause death remains unclear. This study aimed to investigate whether circulating PSM is a real predictor of CVD death in Chinese adults with or without diabetes. METHODS: A total of 286 and 219 individuals with and without diabetes, respectively, from the original Da Qing Diabetes Study were enrolled. Blood samples collected in 2009 were used as a baseline to assess circulating PSM levels. The outcomes of CVD and all-cause death were followed up from 2009 to 2020, and 178 participants died, including 87 deaths due to CVD. Cox proportional hazards regression was used to estimate HRs and their 95% CIs for the outcomes. RESULTS: Fractional polynomial regression analysis showed a linear association between baseline circulating PSM concentration (log-2 transformed) and the risk of all-cause and CVD death (p < 0.001), but not non-CVD death (p > 0.05), in all participants after adjustment for confounders. When the participants were stratified by PSM-tertile, the highest tertile, regardless of diabetes, had a higher incidence of CVD death (41.5 vs. 14.7 and 22.2 vs. 2.9 per 1000 person-years in patients with and without diabetes, respectively, all log-rank p < 0.01). Individuals with diabetes in the highest tertile group had a higher risk of CVD death than those in the lowest tertile (HR = 2.73; 95%CI, 1.20-6.22). CONCLUSIONS: Elevated PSM levels are significantly associated with a higher 10-year risk of CVD death, but not non-CVD death, in Chinese adults with diabetes. These findings suggest that PSM is a potentially useful long-term predictor of CVD death in individuals with diabetes.

Functional fitness and risk factors of older patients with diabetes combined with sarcopenia and/or frailty: A cross-sectional study.

AIM: To learn the functional fitness levels in older adults with diabetes combined with sarcopenia and/or frailty. DESIGN: A cross-sectional investigation study. METHODS: A total of 205 participants with type 2 diabetes were recruited from September 2019 to August 2020. All patients underwent diagnostic screening for sarcopenia and frailty, and were divided into combined group (the patients who had sarcopenia and/or frailty) and non-combined group (the patient who had no sarcopenia and/or frailty). The diagnostic criteria for sarcopenia applied was proposed by the Asian Working Group on Sarcopenia in 2019 and frailty status was assessed using FRAIL Scale. Functional fitness was measured using the Senior Fitness Test and compared between combined and non-combined groups. Biochemical data of blood routine, glycolipid, and hepatorenal function tests were acquired from medical records. Logistic regression analysis was applied to explore the factors associated with the sarcopenia and/or frailty in the older adults with diabetes. RESULTS: Compared with non-combined group, the participants in combined group exhibited shorter 6-min walk distance, fewer repetitions of arm curls and chair stands, smaller back scratch and chair sit-and-reach values, and longer time in the 8-ft up-and-go test. The patients in the combined group had significantly lower level of red blood cell, haemoglobin, haematocrit, and higher level of platelet and blood urea nitrogen. Apart from calf circumference, physical activity, and insulin injection treatment, 6-min walk distance was the factor associated with diabetes combined with sarcopenia and/or frailty.

Influence of a diet and/or exercise intervention on long-term mortality and vascular complications in people with impaired glucose tolerance: Da Qing Diabetes Prevention Outcome study.

AIM: We aimed to investigate the long-term influence of a diet and/or exercise intervention on long-term mortality and cardiovascular disease (CVD) events. METHODS: The Da Qing Diabetes Prevention Study had 576 participants with impaired glucose tolerance (IGT) randomized to diet-only, exercise-only and diet-plus-exercise intervention group and control group. The participants underwent lifestyle interventions for 6 years. The subsequent Da Qing Diabetes Prevention Outcome Study was a prospective cohort study to follow-up the participants for up to 24 years after the end of 6-year intervention. In total, 540 participants completed the follow-up, while 36 subjects lost in follow-up. Cox proportional hazards analysis was applied to assess the influence of lifestyle interventions on targeted outcomes. RESULTS: Compared with controls, the diet-only intervention in people with IGT was significantly associated with a reduced risk of all-cause death [hazard ratio (HR) 0.77, 95% confidence interval (CI) (0.61-0.97)], CVD death [HR 0.67, 95% CI (0.46-0.97)] and CVD events [HR 0.72, 95% CI (0.54-0.96)]. The diet-plus-exercise intervention was significantly associated with a decreased risk of all-cause death [HR 0.64, 95% CI (0.48-0.84)], CVD death [HR 0.54, 95% CI (0.30-0.97)] and CVD events [HR 0.68, 95% CI (0.52-0.90)]. Unexpectedly, the exercise-only intervention was not significantly associated with the reduction of any of these outcomes, although there was a consistent trend towards reduction. CONCLUSIONS: A diet-only intervention and a diet-plus-exercise intervention in people with IGT were significantly associated with a reduced risk of all-cause death, CVD death and CVD events, while an exercise-only intervention was not. It suggests that diet-related interventions may have a potentially more reliable influence on long-term vascular complications and mortality.

Efficacy and safety of the modified Zhiwang decoction combined with methotrexate in early rheumatoid arthritis: study protocol for a randomised controlled trial.

INTRODUCTION: Rheumatoid arthritis (RA) is a progressive inflammatory autoimmune disease characterised by chronic systemic inflammation, which can cause swelling, stiffening and destruction of articular cartilage and bone. Early diagnosis and treatment of RA can improve outcomes and slow the progression of joint damage. Preliminary exploratory research had hinted an expected effect of modified Zhiwang decoction (MZWD) in treating early RA. However, few randomised clinical trials have evaluated the effectiveness of MZWD in early RA. Therefore, a parallel-group randomised controlled trial was designed to evaluate the efficacy and safety of MZWD combined with methotrexate (MTX) on early RA. METHODS AND ANALYSIS: This is a prospective, parallel-group, single-centre randomised controlled clinical study. A total of 150 patients will be randomly assigned to either the treatment (n=75) or control group (n=75). The treatment group will receive MZWD and MTX, and the control group will receive MTX for 12 weeks. The primary outcome of this study is Disease Activity Score-28, and the secondary outcomes are Fatigue Scale-14, Visual Analogue Scale pain scores and traditional Chinese medicine symptom scores. Safety outcomes, including adverse events and results of ECG and laboratory tests, will be monitored. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Clinical Research Ethics Committee of the China-Japan Friendship Hospital (no. 2022-KY-124) on 8 July 2022. The findings will be disseminated in peer-reviewed publications. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT05508815).

Algorithm as Recommending Source and Persuasive Health Communication: Effects of Source Cues, Language Intensity, and Perceived Issue Involvement.

Algorithms are now playing significant roles in online health information selection and recommendation. A question arises as to when and why people would be persuaded by the content they recommend. We conducted a 4 (recommending source: algorithm, other users, a friend, the CDC) x 2 (language intensity: high vs. low) experiment to find out. Participants (N = 299) were exposed to a health-related public service announcement embedded in a social media post. The results showed that overall, an algorithm induced a similar level of compliance intention compared with other recommending sources. We also found a significant three-way interaction when comparing the effects of the algorithm and the CDC: for individuals with low issue involvement, the algorithm was less persuasive when paired with a message with high language intensity. In contrast, for high-involvement individuals, the algorithm elicited more fear than the CDC when recommending an assertive message, partially leading to more compliance intention.

Does high-normal blood pressure lead to excess cardiovascular disease events and deaths in Chinese people? A post-hoc analysis of the 30-year follow-up of the Da Qing IGT and Diabetes Study.

AIM: Whether systolic/diastolic blood pressure (SBP/DBP) values of 130-139/80-89 mmHg should be defined as hypertension has been debated for decades. We aimed to characterize the effect of high-normal BP on cardiovascular disease (CVD) events and deaths. METHODS: In total, 1726 individuals from the original Da Qing IGT and Diabetes Study were enrolled, and divided into the normal BP group (SBP <130 mmHg and DBP <80 mmHg), high-normal BP group (SBP 130-139 mmHg and/or DBP 80-89 mmHg) and hypertension group (SBP ≥140 mmHg and/or DBP ≥90 mmHg). CVD events and their components were assessed from 1986 to 2016. RESULTS: During the 30-year follow-up, the high-normal BP group was not at higher risk for CVD events [hazard ratio (HR) 1.05, 95% confidence interval (CI) 0.84-1.30, p = .68], coronary heart disease (HR 1.12, 95% CI 0.77-1.63, p = .57), stroke (HR 1.05, 95% CI 0.82-1.34, p = .71), or CVD deaths (HR 1.15, 95% CI 0.82-1.60, p = .41) compared with the normal BP group, after adjusting for covariates. However, the hypertension group exhibited significantly increased cardiovascular risk (CVD events, HR 1.91, 95% CI 1.48-2.46, p < .0001; coronary heart disease, HR 1.73, 95% CI 1.12-2.67, p = .01; stroke, HR 1.90, 95% CI 1.43-2.52, p < .0001; CVD deaths, HR 2.07, 95% CI 1.43-3.01, p = .0001) than the normal BP group. Subgroup analyses showed that, regardless of the presence of diabetes, high-normal BP did not increase CVD events compared with normal BP. CONCLUSIONS: This post-hoc study provided no evidence that the high-normal BP increased cardiovascular risk in the Da Qing study population, suggesting that it was reasonable to continue to define hypertension at 140/90 mmHg in China.

SIRT6 Protects Against Lipopolysaccharide-Induced Inflammation in Human Pulmonary Lung Microvascular Endothelial Cells.

Inflammatory response in the pulmonary endothelium drives the pathogenesis of acute lung injury and sepsis. Sirtuin 6 (SIRT6), a member of class III NAD+-dependent deacetylases belonging to the sirtuin family, regulates senescence, metabolism, and inflammation and extends lifespan in mice and model organisms. However, the role of SIRT6 in pulmonary endothelial inflammation is unknown. Thus, we hypothesized that SIRT6 suppresses inflammatory response in human lung microvascular cells (HLMEC) and ensues monocyte adhesion to endothelial cells. Primary HLMECs were treated with control or SIRT6 adenovirus or SIRT6 agonist, with or without lipopolysaccharide (LPS) treatment. We observed that treatment with LPS did not affect the protein expression of SIRT6 in HLMECs. However, adenovirus-mediated SIRT6 overexpression attenuated LPS-induced VCAM1 gene and protein expression, followed by decreased monocyte adhesion to endothelial cells. Similarly, activation of SIRT6 by a recently reported SIRT6 activator UBCS039, but not the regioisomer negative control compound UBCS060, ameliorated LPS-induced VCAM1 mRNA and protein expression as well as monocyte adhesion. Moreover, luciferase assay revealed that SIRT6 adenovirus decreased the activity of NF-κB, the master regulator of vascular inflammation. Taken together, these results indicate that molecular and pharmacological activation of SIRT6 protects against lung microvascular inflammation via suppressing NF-κB activation, implicating the therapeutic potential of the SIRT6 activators for lung disorders associated with microvascular inflammation.

Integrating transcriptome and physiological analyses to elucidate the molecular responses of sorghum to fluxofenim and metolachlor herbicide.

The extensive use of herbicides has raised concerns about crop damage, necessitating the development of effective herbicide safeners. Fluxofenim has emerged as a promising herbicide safener; however, it's underlying mechanism remains unclear. Here, we screened two inbred lines 407B and HYZ to investigate the detoxication of fluxofenim in mitigating metolachlor damage in sorghum. Metolachlor inhibited seedling growth in both 407B and HYZ, while, fluxofenim could significantly restore the growth of 407B, but not effectively complement the growth of HYZ. Fluxofenim significantly increased the activities of glutathione-S-transferase (GST) to decrease metolachlor residue in 407B, but not in HYZ. This implys that fluxofenim may reduce metolachlor toxicity by regulating its metabolism. Furthermore, metolachlor suppressed AUX-related and JA-related genes expression, while up-regulated the expression of SA-related genes. Fluxofenim also restored the expression of AUX-related and JA-related genes inhibited by metolachlor and further increased expression of SA-related genes. Moreover, we noted a significant increase in the content of trans-zeatin O-glucoside (tZOG) and Gibberellin1 (GA1) after the fluxofenim treatment. In conclusion, fluxofenim may reduce the injury of herbicide by affecting herbicide metabolism and regulating hormone signaling pathway.