S-nitrosylation of EMMPRIN influences the migration of HSCs and MMP activity in liver fibrosis.

The mechanism of extracellular matrix metalloproteinase inducer (EMMPRIN) in the regulation of liver fibrosis has not been clarified. This study aims to investigate the role of EMMPRIN S-nitrosylation (SNO) in the regulation of hepatic stellate cell (HSC) migration and matrix metalloproteinase (MMP) activities in liver fibrosis. The results from the tissue microarrays and rat/mouse liver tissues suggest that EMMPRIN mRNA and protein levels in the fibrotic livers are lower than those in the corresponding normal control livers, but higher SNO level of EMMPRIN in fibrotic liver area was shown by immunohistochemistry, immunofluorescence staining, and biotin-switch assay conversely in vivo. Primary EMMPRIN comes from hepatocytes and liver sinus epithelial cells (LSECs) rather than quiescent HSCs. To mimic the uptake of extrinsic EMMPRIN, supernatants from mouse primary hepatocytes/293 cells transfected with EMMPRIN wild-type plasmids (WT) and EMMPRIN SNO site (cysteine 87) mutation plasmids (MUT) were collected and added to JS-1/LX2 cell medium. The MUT EMMPRIN diminishes SNO successfully, enhances the activities of MMP2 and MMP9, and subsequently increases HSC migration. In conclusion, SNO of EMMPRIN influences HSC migration and MMP activities in liver fibrosis. This finding may shed light on the possible regulatory mechanism of MMPs in ECM accumulation in liver fibrosis.

Mesoporous polydopamine based biominetic nanodrug ameliorates liver fibrosis via antioxidation and TGF-ß/SMADS pathway.

Early intervention of liver fibrosis can prevent its further irreversible progression. Both excess reactive oxygen species (ROS) and transforming growth factor beta(TGF-ß)/drosophila mothers against decapentaplegic protein (SMADS) pathway balance disorder promote the progression of hepatic stellate cell (HSC) activation, but existing therapeutic strategies failed to focus on those two problems. A new biomimetic mesoporous polydopamine nandrug (MPO) was constructed for liver fibrosis therapy with multiple targets and reliable biosafety. The MPO was formed by mesoporous polydopamine (mPDA) which has the effect of ROS elimination and encapsulated with anti-fibrotic drug -oxymatrine (OMT) which can intervene liver fibrosis targeting TGF-ß/SMADSpathway. Particularly, the nanodrug was completed by macrophage-derived exosome covering. The MPO was confirmed to possess a desired size distribution with negative zeta potential and exhibite strong ROS scavenger ability. Besides, in vitro studies, MPO showed efficient endocytosis and superior intracellular ROS scavenging without cytotoxicity; in vivo studies, MPO effectively cleared the excessive ROS in liver tissue and balanced the TGF-ß/SMADS pathways, which in turn inhibited HSC activation and showed superior anti-liver fibrosis therapeutic efficiency with good biological safety. Taken together, this work showed highlights the great potential of the MPO for ameliorating liver fibrosis via ROS elimination and TGF-ß/SMADS balancing.

Y-box binding protein 1 promotes chromatin accessibility to aggravate liver fibrosis.

Y-box binding protein 1 (YBX1) has been reported to be involved in the transcriptional regulation of various pathophysiological processes, such as inflammation, oxidative stress, and epithelial-mesenchymal transformation. However, its precise role and mechanism in regulating hepatic fibrosis remain unclear. In this study, we aimed to investigate the effects of YBX1 on liver fibrosis and its potential mechanism. The expression of YBX1 in human liver microarray, mice tissues and primary mouse hepatic stellate cells (HSCs) was validated to be upregulated in several hepatic fibrosis models (CCl4 injection, TAA injection, and BDL). Hepatic-specific Ybx1 overexpression exacerbated the liver fibrosis phenotypes in vivo and in vitro. Moreover, the knockdown of YBX1 significantly improved TGF-ß-induced fibrosis in the LX2 cell (a hepatic stellate cell line). Assay for Transposase-Accessible Chromatin with high throughput sequencing (ATAC-seq) of hepatic-specific Ybx1 overexpression (Ybx1-OE) mice with CCl4 injection showed increasing chromatin accessibility than CCl4 only group. Functional enrichments of open regions in the Ybx1-OE group indicated that extracellular matrix (ECM) accumulation, lipid purine metabolism, and oxytocin-related pathways were more accessible in the Ybx1-OE group. Accessible regions of the Ybx1-OE group in the promoter also suggested significant activation of genes related to liver fibrogenesis, such as response to oxidative stress and ROS, lipid localization, angiogenesis and vascular development, and inflammatory regulation. Moreover, we screened and validated the expression of candidate genes (Fyn, Axl, Acsl1, Plin2, Angptl3, Pdgfb, Ccl24, and Arg2), which might be potential targets of Ybx1 in the pathogenesis of liver fibrosis.

Risk prediction model based on blood biomarkers for predicting moderate to severe endoscopic activity in patients with ulcerative colitis.

Object: We explored developing an internal validation model to predict the moderate to severe endoscopic activity of ulcerative colitis (UC) patients based on non-invasive or minimally-invasive parameters. Methods: Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and Mayo endoscopic subscore were performed for UC patients who met the criteria from January 2017 to August 2021 through the electronic database of our center. Logistic regression and a least absolute shrinkage and selection operator (Lasso) regression model were performed to screen the risk factors of moderate to severe UC activity. The nomogram was established subsequently. Discrimination of the model was evaluated using the concordance index (c-index), and the calibration plot and 1,000 Bootstrap were used to evaluate the model's performance and conduct internal validation. Results: Sixty-five UC patients were included in this study. According to UCEIS criteria,45 patients were moderate to severe endoscopic activity. 26 potential predictors of UC were analyzed by logistic and Lasso regression showed that vitamin D (Vit D), albumin (ALB), prealbumin (PAB), and fibrinogen (Fbg) were the best predictors of moderate to severe endoscopic activity of UC. We used these 4 variables to develop a dynamic nomogram prediction model. The c-index was 0.860, which means good discrimination. The calibration plot and Bootstrap analysis showed that the prediction model accurately distinguished the moderate to severe endoscopic activity in UC patients. The prediction model was verified using a cohort of UC patients with moderate to severe activity defined by the Mayo endoscopic subscore, and it was found that the model still had good discrimination and calibration (c-index = 0.891). Conclusion: The model containing Vit D, ALB, PAB, and Fbg was a good tool for evaluating UC activity. The model is simple, accessible, and user-friendly, which has broad application prospects in clinical practice.

Dynamic Reach Deficit Is a Predictive Factor of Inferior Outcomes After Modified Broström Procedure for Lateral Ankle Instability.

BACKGROUND: Only a few studies have analyzed functional predictive factors for inferior outcomes after modified Broström procedure (MBP). The aim of the current study is to identify the influence of the preoperative dynamic reach deficit on the surgical outcomes of MBP. METHODS: Sixty-one patients with lateral ankle instability who underwent MBP were included in the current study and followed up for a median of 24 months. The Karlsson scores and the reaches of the Star Excursion Balance Test (SEBT) were evaluated before surgery and during the last follow-up. A total of 19 prognostic factors were analyzed. The relationship between the variables and inferior outcomes (Karlsson score < 90) in the bivariate analysis was tested through the Mann-Whitney U test or the Fisher exact test. A multivariate logistic regression model was developed to investigate the influence of the selected factors on inferior outcomes. RESULTS: Thirty-two of the patients had superior outcomes, and the rest had inferior outcomes. The age, gender, and body mass index of the groups with superior and inferior outcomes did not differ. Preoperative dynamic reach deficit (P = .032), osteochondral lesion of the talus (P = .004), and decreased preoperative Karlsson score (P = .004) were independent predictors of inferior outcomes. CONCLUSION: Patients with preoperative dynamic reach deficit, osteochondral lesion of the talus, or decreased preoperative Karlsson score have inferior outcomes after MBP. LEVEL OF EVIDENCE: Level III, case-control study.

Predictive Value of Platelet-Related Measures in Patients with Hepatocellular Carcinoma.

Background: Increasing numbers of studies reported platelet (PLT)- related measures could play a creative role in many malignancies, while the prognostic impact of these measures in hepatocellular carcinoma (HCC) remains limited and controversial. It is worth exploring the predictive value of PLT-related measures in HCC. Methods: A total of 279 HCC patients with hepatectomy were analyzed in the retrospective cohort study. The optimal cut-off points of these PLT-related indices were obtained by the receiver operating characteristic (ROC) curve. The associations of these indices with clinical characteristics and overall survival (OS) were evaluated by Kaplan-Meier curves and Cox proportional hazards models. Results: High PLT count and low prognostic nutritional index (low-PNI) were significantly associated with larger tumor size. The low gamma-glutamyl transpeptidase-to-platelet ratio (low-GPR) group was inclined to more hepatitis infections. Survival curves indicated that preoperative high-PLT, low-GPR, and low-PNI had a worse prognosis after surgery in the cohort. In addition, PLT≥220 × 109/L (HR, 2.274; 95% CI, 1.061-4.876; P = .035), PNI≥51.9 (HR, 0.503; 95% CI, 0.265-0.954; P = .035), and GPR≥0.2 (HR, 0.432; 95% CI, 0.204-0.912; P = .028) were identified as independent prognostic factors for survival outcomes in the multivariable analysis. Conclusion: High-PLT, low-GPR, and low-PNI as the preoperative predictors were associated with poor OS in HCC patients with hepatectomy. Our data reveal that they could be simple, easily obtained, and effective predictors for evaluation of survival outcomes in patients.

Efficient electrocatalytic reduction of nitrate to nitrogen gas by a cubic Cu2O film with predominant (111) orientation.

A (111) predominant cubic Cu2O film terminated with nanopyramids was electrodeposited on copper foam as the cathode for electrocatalytic reduction of nitrate. The nitrate removal efficiency reached 94.3% and the selectivity for nontoxic nitrogen gas was 49.2%, 99% and 64.2% in neutral solution, alkaline solution and spiked actual lake water, respectively.

Efficacy and safety of modified Bushen Yiqi formulas (MBYF) as an add-on to formoterol and budesonide in the management of COPD: study protocol for a multicentre, double-blind, placebo-controlled, parallel-group, randomized clinical trial: FB-MBYF Trial.

BACKGROUND: Inhaled glucocorticoid corticosteroid (ICS), long-acting ß2-adrenoceptor agonist (LABA), and other drugs have limited therapeutic effects on COPD with significant individual differences. Traditional Chinese medicine (TCM)-modified Bushen Yiqi formula (MBYF) demonstrates advantages in COPD management in China. This study aims to evaluate the efficacy and safety of MBYF as an add-on to budesonide/formoterol in COPD patients and confirm the related genes affecting the therapeutic effect in the treatment of COPD. METHODS: In this multicentre, randomised, double-blind, placebo-controlled, parallel-group study, eligible patients with COPD will randomly receive a 360-day placebo or MBYF as an adjuvant to budesonide/formoterol in a 1:1 ratio and be followed up with every 2 months. The primary outcomes will be the frequency, times, and severity of acute exacerbation of COPD (AECOPD), COPD assessment test (CAT) score, and pulmonary function tests (PFTs). The secondary outcomes will include the modified Medical Research Council (mMRC) dyspnoea scale, 6-min walking test (6MWT), BODE index, quantitative scores of syndromes classified in TCM, inflammation indices, and hypothalamic-pituitary-adrenaline (HPA) axis function. We will also test the genotype to determine the relationship between drugs and efficacy. All the data will be recorded in case report forms (CRFs) and analysed by SPSS V.20.0. DISCUSSION: A randomized clinical trial design to evaluate the efficacy and safety of MBYF in COPD is described. The results will provide evidence for the combination therapy of modern medicine and TCM medicine, and individual therapy for COPD. TRIAL REGISTRATION: ID:  ChiCTR1900026124 , Prospective registration.

Model-Based Reasoning of Clinical Diagnosis in Integrative Medicine: Real-World Methodological Study of Electronic Medical Records and Natural Language Processing Methods.

BACKGROUND: Integrative medicine is a form of medicine that combines practices and treatments from alternative medicine with conventional medicine. The diagnosis in integrative medicine involves the clinical diagnosis based on modern medicine and syndrome pattern diagnosis. Electronic medical records (EMRs) are the systematized collection of patients health information stored in a digital format that can be shared across different health care settings. Although syndrome and sign information or relative information can be extracted from the EMR and content texts can be mapped to computability vectors using natural language processing techniques, application of artificial intelligence techniques to support physicians in medical practices remains a major challenge. OBJECTIVE: The purpose of this study was to investigate model-based reasoning (MBR) algorithms for the clinical diagnosis in integrative medicine based on EMRs and natural language processing. We also estimated the associations among the factors of sample size, number of syndrome pattern type, and diagnosis in modern medicine using the MBR algorithms. METHODS: A total of 14,075 medical records of clinical cases were extracted from the EMRs as the development data set, and an external test data set consisting of 1000 medical records of clinical cases was extracted from independent EMRs. MBR methods based on word embedding, machine learning, and deep learning algorithms were developed for the automatic diagnosis of syndrome pattern in integrative medicine. MBR algorithms combining rule-based reasoning (RBR) were also developed. A standard evaluation metrics consisting of accuracy, precision, recall, and F1 score was used for the performance estimation of the methods. The association analyses were conducted on the sample size, number of syndrome pattern type, and diagnosis of lung diseases with the best algorithms. RESULTS: The Word2Vec convolutional neural network (CNN) MBR algorithms showed high performance (accuracy of 0.9586 in the test data set) in the syndrome pattern diagnosis of lung diseases. The Word2Vec CNN MBR combined with RBR also showed high performance (accuracy of 0.9229 in the test data set). The diagnosis of lung diseases could enhance the performance of the Word2Vec CNN MBR algorithms. Each group sample size and syndrome pattern type affected the performance of these algorithms. CONCLUSIONS: The MBR methods based on Word2Vec and CNN showed high performance in the syndrome pattern diagnosis of lung diseases in integrative medicine. The parameters of each group's sample size, syndrome pattern type, and diagnosis of lung diseases were associated with the performance of the methods. TRIAL REGISTRATION: ClinicalTrials.gov NCT03274908; https://clinicaltrials.gov/ct2/show/NCT03274908.

Efficacy and safety of Jia Wei Bushen Yiqi formulas as an adjunct therapy to systemic glucocorticoids on acute exacerbation of COPD: study protocol for a randomized, double-blinded, multi-center, placebo-controlled clinical trial.

BACKGROUND: Systemic glucocorticoids are effective for the management of chronic obstructive pulmonary disease (COPD) exacerbation but have serious adverse effects. Traditional Chinese medicine (TCM) can bring additional benefits to these patients but has few adverse effects. The present study aims to evaluate the efficacy and safety of Jia Wei Bushen Yiqi (JWBY) formulas in patients who suffer from COPD exacerbations and to investigate whether the short-term (5-days) systemic glucocorticoid therapy is non-inferior to the long-term (9-day) regime. METHODS: In this multi-center, randomized, double-blinded trial, eligible inpatients with COPD exacerbation are randomly assigned to four groups (A, B, C, and D). Group A will receive placebo plus 5-day prednisone, group B will receive placebo plus 9-day prednisone, group C will receive JWBY formulas plus 5-day prednisone, and group D will receive JWBY formulas plus 9-day prednisone. The primary outcomes are the time interval to the patient's next exacerbation during a 180-day following up and the COPD assessment test (CAT) during treatment. Secondary outcomes include lung function, TCM syndrome assessment, laboratory tests, and safety. The changes of the hypothalamic pituitary adrenaline axis (HPA axis) and inflammatory cytokine will be measured as well. DISCUSSION: By demonstrating the advantages of utilizing TCM and an appropriate duration of systemic glucocorticoids, this effectiveness comparison trial will provide new references to physicians on how to improve the management of COPD exacerbation. The results of HPA axis and inflammation cytokine measurements will shed light on the molecular mechanisms and entail further mechanism studies. TRIAL REGISTRATION: www.chictr.org.cn ChiCTR1900023364. Registered on 24 May 2019.

Trimethylamine-N-oxide is an independent risk factor for hospitalization events in patients receiving maintenance hemodialysis.

Background: Hospitalization is a significant outcome measurement for maintenance hemodialysis pantients. Trimethylamine-N-oxide (TMAO), created by gut microflora from dietary l-carnitine and choline, cleared by the kidney, has been implicated in the causation of cardiovascular diseases in patients with chronic kidney disease. However, whether it associates with hospitalization risk for these patients is unclear.Methods: In this study, 69 patients undergoing outpatient dialysis were enrolled. Enzyme-linked immunosorbent assay was used to quantitate the baseline plasma TMAO levels in patients. The patients were divided into a high TMAO level group (TMAO ≥ 15 µmol/L) and a low TMAO level group (TMAO < 15 µmol/L). During the 1-year follow-up, 1-year dialysis-related data and all-cause hospitalization events were recorded.Results: The incidence of hospitalization events was significantly higher in the high TMAO level group than in the low TMAO level group (91 per 100 patient-year vs. 32 per 100 patient-year). The Kaplain-Meier survaial analysis showed that the incidence of hospitalization events in the high TMAO level group was significantly higher than that in the low TMAO level group (log-rank p = 0.0004). After adjustment age, sex, CK-MB and albumin, the results of multivariate Cox proportional hazard analysis showed that high TMAO level was an independent risk factor for hospitalization in maintenance hemodialysis patients.Conclusion: TMAO is an independent risk factor for hospitalization events in patients receiving maintenance hemodialysis. It may be a new therapeutic target for improving the outcomes of these patients.

ASB3 knockdown promotes mitochondrial apoptosis via activating the interdependent cleavage of Beclin1 and caspase-8 in hepatocellular carcinoma.

Apoptosis and autophagy are distinct cellular processes that can be highly interconnected. The cross talk between the two processes is indispensable in determining the overall cell fate. Although the apoptosis-promoting effect of caspases has been demonstrated, the roles of autophagy-related proteins and even autophagy itself in regulating apoptosis remain poorly understood. In our present study, we found that downregulation of ubiquitin E3 ligase ASB3 led to enhanced mitochondrial apoptosis as well as autophagy, which synergistically promoted cell death in hepatocellular carcinoma (HCC). We observed the activation of caspase-8 and decrease of autophagy protein Beclin1 in apoptotic cells that were depleted of ASB3. Beclin1 was mainly cleaved by activated caspase-8 and active Beclin1 initiated mitochondrial apoptosis via locating its C-terminal fragment to mitochondria. In addition, knocking down of Beclin1 markedly blocked the apoptosis, indicating its essential role in the process. Notably, our study indicated that enhanced autophagy level might be involved in the activation of caspase-8 and promote the apoptosis. Taken together, our results demonstrated that ASB3 can regulate mitochondrial pathway of apoptosis by controlling caspase-8 mediated cleavage of Beclin1 in HCC. Therefore, ASB3 may potentially serve as a novel target for HCC therapy, especially when combined with autophagy agonist.

Kidney-Qi deficiency diagnosed by Deng's diagnosis standard was not correlated with aging based on clinical observation of 90 participants.

OBJECTIVE: To verify the Traditional Chinese Medicine (TCM) theory that kidney-Qi deficiency (KQD) is considered to be the main cause of aging using cross-sectional study. METHODS: Demographic and lifestyle characteristics of 90 healthy participants were collected with a self-administered questionnaire. KQD syndrome was diagnosed according to Deng's diagnosis standard. Creatinine-adjusted urinary 8-hydroxy-2'-deoxyguanosine (8-OH-dG) and 8-isomeric-prostaglandin2α (8-iso-PGF2α), salivary advanced oxidation protein products (AOPPs), malondialdehyde (MDA) and dehydroepiandrosterone-sulfate (DHEA-S) were selected as aging markers and measured using enzyme-linked immunosorbent assay. RESULTS: No significant differences were observed in participant characteristics between the KQD group and non-KQD (NKQD) group (P > 0.05). Levels of 8-OH-dG, 8-iso-PGF2α, AOPPs, and MDA increased with age, except for a slight decrease in 8-OH-dG in the older group. The increase in 8-iso-PGF2α was significant (P < 0.05). DHEA-S significantly decreased with increasing age (P < 0.01). 8-OH-dG levels were higher in the KQD group compared with the NKQD group. Levels of urinary 8-iso-PGF2α, salivary AOPPs, and MDA in the KQD group were lower than in the NKQD group. Salivary DHEA-S was higher in the KQD group compared with the NKQD group. However, differences between KQD group and NKQD group were not significant. CONCLUSION: The current results suggested that KQD syndrome, as diagnosed by Deng's standard, does not underlie the aging phenotype.

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Effects of Loki zupa in Patients With Chronic Asthma.

The purpose of this study was to evaluate the efficacy and safety of Uyghur medical formula Loki zupa in patients with chronic asthma. Adult patients with chronic asthma randomly received placebo or Loki zupa as add-on to inhaled corticosteroids (ICS) maintenance treatment. Loki zupa or mimics was administered orally 10 ml per time, three times a day for 8 weeks. The primary endpoints were asthma control test (ACT) score and peak expiratory flow (PEF). The secondary endpoints were acute exacerbation rate, lung function, night waking days, and symptom-free days in the near 2 weeks, Asthma Quality of Life Questionnaire (AQLQ) score and some inflammatory cytokines in peripheral blood. A total of 240 adult patients with chronic asthma were enrolled, and 218 patients were randomized to placebo (n = 109) or Loki zupa (n = 109) in addition to ICS for 8 weeks. Treatment with Loki zupa resulted in significant improvement in ACT score compared to the placebo group (p = 0.002). Furthermore, oral taken of Loki zupa increased the PEF obviously (p = 0.026). Loki zupa treatment did not improve the forced expiratory volume in 1 s (FEV1, p = 0.131) and FEV1/FVC compared to the placebo treatment (p = 0.805). The placebo group had higher rates of acute exacerbations than the Loki zupa group (6.3% vs. 0, p = 0.027). Subjects randomized to Loki zupa had increased daytime symptom-free days within 2 weeks than placebo (p = 0.016). However, Loki zupa had no effect on night waking days in the near 2 weeks (p = 0.369) and AQLQ score (p = 0.113). No significant effect was found on inflammatory cytokines (IL-2, IL-4, IL-5, IL-10, IL-13, IL-17, IL-33, IFN-γ, and TGF-ß) between the two groups (p > 0.05). No adverse events and severe asthma exacerbations were recorded in the two groups (p > 0.05). Loki zupa add-on to standard ICS produced clinically significant improvements in ACT score, PEF, daytime symptom-free days and acute exacerbation in patients with chronic asthma. Clinical trial: This study is registered at http://www.chictr.org.cn/ with identifier number ChiCTR-IPR-16008106.

The Analysis of Constitutions of Traditional Chinese Medicine in Relation to Cerebral Infarction in a Chinese Sample.

OBJECTIVE: To investigate the relationships between the constitutions of Traditional Chinese Medicine (TCM) and patients with cerebral infarction (CI) in a Chinese sample. METHODS: A total of 3748 participants with complete data were available for data analysis. All study subjects underwent complete clinical baseline characteristics' evaluation, including a physical examination and response to a structured, nurse-assisted, self-administrated questionnaire. A population of 2010 neutral participants were used as the control group. Multiple variable regression (MLR) were employed to estimate the relationship between constitutions of TCM and the outcome. DESIGN: A cross-sectional study was conducted to evaluate the association of body constitution of TCM and CI. SETTINGS/LOCATION: Communications and healthcare centers in Shanghai. SUBJECTS: A total of 3748 participants with complete data were available for data analysis. OUTCOME MEASURES: All study subjects underwent complete clinical baseline characteristics' evaluation, including a physical examination and response to a structured, nurse-assisted, self-administrated questionnaire. A population of 2010 neutral participants were used as the control group. MLR were employed to estimate the relationship between constitutions of TCM and the outcome. RESULT: The prevalence of CI was 2.84% and 4.66% in neutral participants and yang-deficient participants (p = 0.012), respectively. Univariate analysis demonstrated a positive correlation between yang deficiency and CI. After adjustment for relevant potential confounding factors, the MLR detected significant associations between yang deficiency and CI (odds ratio = 1.44, p = 0.093). CONCLUSION: A yang-deficient constitution was significantly and independently associated with CI. A higher prevalence of CI was found in yang-deficient participants as compared with neutral participants.

A Real-World Evidence Study for Distribution of Traditional Chinese Medicine Syndrome and Its Elements on Respiratory Disease.

BACKGROUND: This study aimed to investigate the distribution and characteristics of traditional Chinese medicine (TCM) syndrome and its elements on respiratory diseases (RDs) based on real-world data (RWD). METHODS: A real-world study was performed to explore the relationships among TCM syndrome and RDs based on electronic medical information. A total of 26,074 medical records with complete data were available for data analysis. Factor analyses were used to reduce dimensions of TCM syndrome elements and detect common factors. Additionally, cluster analyses were employed to assess combinations of TCM syndrome elements. Finally, association rule analyses were performed to investigate the structures of TCM syndrome elements to estimate the patterns of TCM syndrome. RESULTS: A total of 27 TCM syndromes were extracted from RWD in this work. There were four TCM syndromes with >5.0% frequency based on the distribution frequency. The top five pathogenesis TCM syndrome elements were Tan, Huo, Feng, Qi_Xu, and Han. Factor analysis, cluster analysis, and association rule analysis demonstrated that Tan, Huo, Feng, Qi_Xu, Shen, and Fei were the core TCM syndrome elements. CONCLUSION: Four common Shi TCM syndromes on RDs were identified: Tan_Re_Yong_Fei, Tan_Zhuo_Zu_Fei, Feng_Re_Fan_Fei, and Feng_Han_Xi_Fei; two core common Xu TCM syndromes (Fei_Shen_Qi_Xu and Fei_Yin_Xu) and two core common Mix TCM syndromes (Fei_Pi_Qi_Xu-Tan_Shi_Yun_Fei and Fei_Shen_Qi_Xu-Tan_Yu_Zu_Fei) were also determined. The core TCM syndrome elements of Tan, Huo, Feng, Qi_Xu, Shen, and Fei were identified in this work.

A Study of Traditional Chinese Medicine Body Constitution Associated with Overweight, Obesity, and Underweight.

OBJECTIVE: The aim of the study was to investigate the associations among the nine types of body constitution in traditional Chinese medicine (TCM) with the outcomes of overweight, obesity, and underweight. METHOD: Participants aged 30 to 90 years were recruited from communities in Shanghai and assessed using a self-administered questionnaire pertaining to their demographics, lifestyles, and self-reported medical history. The data of 3748 participants with complete information was available for the analysis. Multinomial logistic regression (MLR) analysis was performed to determine the associations among the TCM constitution variables and the health outcomes. RESULTS: The standards of classification and determination of the constitution in TCM were used to gauge the patients' constitution type. MLR revealed independent and significant associations among the Qi_Deficient and Yang_Deficient groups with the outcomes of overweight, obesity, and underweight (P < 0.10 for all). MLR revealed independent and significant associations among the Qi_Deficient and Yang_Deficient groups with the outcomes of overweight, obesity, and underweight (P < 0.05 for all). CONCLUSION: Our study revealed significant negative correlations between the Qi_Deficient and Yang_Deficient groups with the outcomes of overweight, obesity, and underweight. On the other hand, positive correlations were found between Phlegm_Dampness and the outcomes of overweight and obesity.

Analysis of a Screening System for Diabetic Cardiovascular Autonomic Neuropathy in China.

BACKGROUND The aim of this study was to create a screening system for diabetic cardiovascular autonomic neuropathy (DCAN) in diabetic patients. MATERIAL AND METHODS A Chinese cohort of 455 diabetic participants was recruited between 2011 and 2013. Short-term heart rate variability testing was used to evaluate cardiovascular autonomic function. A simple model was developed using multiple variable regression to include only significant risk factors that were simple and easily assessed. A DCAN score was determined based on the coefficients of the multiple variable model. This score was tested on the entire cohort of 455 diabetic patients and another independent, external cohort of 115 diabetic patients. RESULTS The screening system consisted of age, body mass index, duration of diabetes mellitus, and resting heart rate, and these factors were significantly (P<0.05) associated with DCAN. Receiver operating characteristic (ROC) curve analysis was done. The areas under the ROC curve were 0.798, 0.756, and 0.729 for the total sample, validation cohort, and external set, respectively. A cutoff DCAN score of 12 out of 25 produced optimal results for sensitivity (80.36%), specificity (58.27%), and percentage of patients that needed subsequent testing (43.55%) for the validation set. CONCLUSIONS The study concludes that a simple and practical DCAN screening can be applied for early intervention to delay or prevent the disease in the Chinese population.

Acyloxyacyl hydrolase promotes the resolution of lipopolysaccharide-induced acute lung injury.

Pulmonary infection is the most common risk factor for acute lung injury (ALI). Innate immune responses induced by Microbe-Associated Molecular Pattern (MAMP) molecules are essential for lung defense but can lead to tissue injury. Little is known about how MAMP molecules are degraded in the lung or how MAMP degradation/inactivation helps prevent or ameliorate the harmful inflammation that produces ALI. Acyloxyacyl hydrolase (AOAH) is a host lipase that inactivates Gram-negative bacterial endotoxin (lipopolysaccharide, or LPS). We report here that alveolar macrophages increase AOAH expression upon exposure to LPS and that Aoah+/+ mice recover more rapidly than do Aoah-/- mice from ALI induced by nasally instilled LPS or Klebsiella pneumoniae. Aoah-/- mouse lungs had more prolonged leukocyte infiltration, greater pro- and anti-inflammatory cytokine expression, and longer-lasting alveolar barrier damage. We also describe evidence that the persistently bioactive LPS in Aoah-/- alveoli can stimulate alveolar macrophages directly and epithelial cells indirectly to produce chemoattractants that recruit neutrophils to the lung and may prevent their clearance. Distinct from the prolonged tolerance observed in LPS-exposed Aoah-/- peritoneal macrophages, alveolar macrophages that lacked AOAH maintained or increased their responses to bioactive LPS and sustained inflammation. Inactivation of LPS by AOAH is a previously unappreciated mechanism for promoting resolution of pulmonary inflammation/injury induced by Gram-negative bacterial infection.

Analyzing the association between fish consumption and osteoporosis in a sample of Chinese men.

BACKGROUND: The main purpose of this study was to estimate the associations between frequency of fish food consumption and osteoporosis (OP) in general Chinese men. METHODS: We conducted a large-scale, community-based, cross-sectional study to investigate the associations by using self-report questionnaire to access frequency of fish food intake. A total of 1092 men were available for data analysis in this study. Multiple regression models controlling for confounding factors to include frequency of fish food consumption variable were performed to investigate the relationships for OP. RESULTS: Positive correlations between frequency of fish food consumption and T score were reported (ß = 0.084, P value = 0.025). Multiple regression analysis indicated that the frequency of fish food consumption was significantly associated with OP (P < 0.05 for model 1 and model 2). The men with high frequency of fish food consumption had a lower prevalence of OP. CONCLUSIONS: The findings indicated that frequency of fish food consumption was independently and significantly associated with OP. The prevalence of OP was less frequent in Chinese men preferring fish food habits. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02451397 retrospectively registered 28 May 2015.