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Zhaobai Lao,1,* Xuliang Fang,1,* Shuchao Shen,1,* Yuliang Zhang,2,* Xin Chen,1 Helou Zhang,1 Yishan Bian,1 Chengcong Zhou,1 Ronghua Bao,2 Taotao Xu,3 Hongting Jin,1 Fangda Fu,1 Chengliang Wu,1 Changfeng Hu,4 Hongfeng Ruan1 1Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, 310053, People’s Republic of China; 2Hangzhou Fuyang Hospital of TCM Orthopedics and Traumatology, Hangzhou, Zhejiang, 311400, People’s Republic of China; 3Department of Orthopaedics, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, 310053, People’s Republic of China; 4College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China*These authors contributed equally to this workCorrespondence: Changfeng Hu, College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China, Email zhudianzhuifeng@163.com Hongfeng Ruan, Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310053, People’s Republic of China, Email rhf@zcmu.edu.cnPurpose: Systemic lupus erythematosus (SLE) is an autoimmune disorder marked by immune system dysregulation and autoantibodies production, causing widespread inflammation and damage across various body systems. Despite the prevalent back pain in SLE patients, the link between SLE and intervertebral disc (IVD) degeneration, a primary contributor to back pain, remains inadequately understood. This study explored the impact of SLE on IVD degeneration using the MRL/lpr mouse model, which effectively replicates human SLE manifestations.Methods: The study utilized MRL/lpr mice to investigate the effects of SLE on IVD degeneration. The mice were evaluated for typical SLE phenotypes and indicators of IVD degeneration, including IVD height, IVD score, tissue integrity, extracellular matrix degradation, and apoptosis of IVD cells. Additionally, the study examined nucleus pulposus (NP) pyroptosis and inflammatory cytokine secretion. Mechanistic analysis focused on the antioxidant pathway, specifically the expression levels of NRF2, HO-1, KEAP1, and the phosphorylation levels of p65.Results: MRL/lpr mice displayed typical SLE phenotypes and exacerbated profiles of IVD degeneration, including reduced IVD height, lower IVD score, significant IVD tissue impairment, extracellular matrix degradation, and increased apoptosis of IVD cells. Notably, SLE stimulated NP pyroptosis and excessive secretion of inflammatory cytokines. Mechanistic analysis indicated that the progression of SLE impedes the antioxidant pathway by downregulating NRF2 and HO-1 expression, upregulating KEAP1, and enhancing phosphorylation levels of p65.Conclusion: Our findings highlight the mechanistic link between SLE and IVD degeneration, suggesting potential therapeutic targets for mitigating back pain in SLE patients.Keywords: systemic lupus erythematosus, intervertebral disc degeneration, nucleus pulposus, pyroptosis, NRF2/KEAP1/NF-κB pathway

Yuying Ge,1,* Yuepeng Xie,2,* Junlei Chai,3,* Weifeng Ji,4,* Xiulong Lou,1 Kun Tian,2 Ronghua Bao,3 Chengliang Wu,1 Hongfeng Ruan1 1Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, People’s Republic of China; 2The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3Hangzhou Fuyang Hospital of TCM Orthopedics and Traumatology, Hangzhou, People’s Republic of China; 4Department of Orthopaedics, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongfeng Ruan; Chengliang Wu, Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310053, People’s Republic of China, Fax +86 571 86613684, Email rhf@zcmu.edu.cn; wcl@zcmu.edu.cnBackground: Intervertebral disc (IVD) degeneration (IVDD) is highly prevalent among the elderly population and stands as a leading cause of low back pain. Our prior studies have highlighted the therapeutic potential of Liuwei Dihuang decoction (LWDHD) and its component Cornus officinalis (CO)-derived compounds in alleviating IVDD and osteoarthritis, suggesting beneficial effects of CO in treating degenerative osteoarthropathies. However, uncertainty remains regarding the optimal CO dosage within LWDHD and its potential mechanism for effectively treating IVDD.Objective: To ascertain the optimal dosage of CO within LWDHD for enhancing its therapeutic efficacy in treating IVDD, through a comparison of its effects across varied dosages using a mouse IVDD model.Methods: Eight-week-old male C57BL/6J mice were subjected to a lumbar spine instability surgery to induce an IVDD model and received a modified LWDHD formulation containing varied dosages of CO (original dose of CO, or 5- or 10-time dose of CO (referred to as 1 × CO, 5 × CO, and 10 × CO)) for 8 weeks. The therapeutic efficacy on IVDD was evaluated through changes in lumbar spine function, histopathological morphology, extracellular matrix metabolism, nucleus pulposus cell viability, sensory nerve ingrowth, and nucleus pulposus (NP) cell pyroptosis.Results: Augmenting CO levels in LWDHD led to a dose-dependent increase in the levels of CO-sourced active compounds in the plasma of mice. The modified LWDHD formulations, particularly the 5 × CO, exhibited a favorable pharmacological effect on lumbar function, structural integrity, ECM composition, NP cell viability, and sensory nerve ingrowth. Importantly, all 3 formulations notably mitigated NP cell pyroptosis by activating NRF2/KEAP1 pathway, with the 5 × CO formulation exhibiting superior efficacy. Additionally, a comprehensive score analysis indicated that 5 × CO formulation achieved the highest score.Conclusion: These data underscore that elevating the dosage of CO to a specific threshold can enhance the effectiveness of LWDHD in treating IVDD.Keywords: intervertebral disc degeneration, liuwei dihuang decoction, nucleus pulposus cell, pyroptosis, Cornus officinalis

Deyi Huang,1 Xingan Yang,2 Hongbiao Ruan,3 Yushui Zhuo,1 Kai Yuan,4 Bowen Ruan,1 Fang Li1 1Department of Ultrasound, The People’s Hospital of Yuhuan, Yuhuan City, Zhejiang Province, People’s Republic of China; 2Department of Ultrasound, Taizhou Hospital of Zhejiang Province, Linhai City, Zhejiang Province, People’s Republic of China; 3Department of Cardiology, The People’s Hospital of Yuhuan, Yuhuan City, Zhejiang Province, People’s Republic of China; 4Department of Clinical Laboratory, The People’s Hospital of Yuhuan, Yuhuan City, Zhejiang Province, People’s Republic of ChinaCorrespondence: Fang Li, Department of Ultrasound, The People’s Hospital of Yuhuan, No. 18, Changle Road, Yuhuan City, Zhejiang Province, 317600, People’s Republic of China, Tel +8613967672898, Email 3260772796@qq.comIntroduction: Chronic coronary artery disease (CAD) management often relies on myocardial contrast echocardiography (MCE), yet its effectiveness is limited by subjective interpretations and difficulty in distinguishing hibernating from necrotic myocardium. This study explores the integration of machine learning (ML) with radiomics to predict functional recovery in dyskinetic myocardial segments in CAD patients undergoing revascularization, aiming to overcome these limitations.Methods: This prospective study enrolled 55 chronic CAD patients, dividing into training (39 patients, 205 segments) and testing sets (16 patients, 68 segments). Dysfunctional myocardial segments were identified by initial wall motion scores (WMS) of ≥ 2 (hypokinesis or higher). Functional recovery was defined as a decrease of ≥ 1 grade in WMS during follow-up echocardiography. Radiomics features were extracted from dyssynergic segments in end-systolic phase MCE images across five cardiac cycles post- “flash” impulse and processed through a five-step feature selection. Four ML classifiers were trained and compared using these features and MCE parameters, to identify the optimal model for myocardial recovery prediction.Results: Functional improvement was noted in 139 out of 273 dyskinetic segments (50.9%) following revascularization. Receiver Operating Characteristic (ROC) analysis determined that myocardial blood flow (MBF) was the most precise clinical predictor of recovery, with an area under the curve (AUC) of 0.770. Approximately 1.34 million radiomics features were extracted, with nine features identified as key predictors of myocardial recovery. The random forest (RF) model, integrating MBF values and radiomics features, demonstrated superior predictive accuracy over other ML classifiers. Validation of the RF model on the testing dataset demonstrated its effectiveness, evidenced by an AUC of 0.821, along with consistent calibration and clinical utility.Conclusion: The integration of ML with radiomics from MCE effectively predicts myocardial recovery in CAD. The RF model, combining radiomics and MBF values, presents a non-invasive, precise approach, significantly enhancing CAD management.Keywords: coronary artery disease, myocardial contrast echocardiography, radiomics, machine learning, myocardial recovery prediction, random forest

Yiting Hua,1,2,* Yutong Zhou,1,2,* Ziyue Qin,1,2 Yuan Mu,1,2 Ting Wang,1,2 Haoyu Ruan1,2 1Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Branch of National Clinical Research Center for Laboratory Medicine, Nanjing, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haoyu Ruan; Ting Wang, Department of Laboratory Medicine, the First Affiliated Hospital, Nanjing Medical University, 300 Guang Zhou Road, Nanjing, Jiangsu Province, 210029, People’s Republic of China, Email rhy1170871576@163.com; wangting0622@njmu.edu.cnBackground: The surge in the number of patients diagnosed with COVID-19 since China’s open-door policy has placed a huge burden on the public healthcare system, especially the intensive care system. This study’s objective was to discover possible clinical outcome predictors in COVID-19 patients treated in intensive care units (ICUs) and to provide useful information for future preventative efforts and therapies.Methods: This retrospective study included 173 COVID-19 critically ill patients and reviewed the 28-day survival outcome in the First Affiliated Hospital of Nanjing Medical University. Competing risk analysis was performed to predict the cumulative incidence function (CIF) of mortality in hospital. The independent prognostic factors were identified by applying the Fine–Gray proportional subdistribution hazard model. Receiver operating characteristic (ROC) curves were used to evaluate model efficacy, and calibration curves were used to validate the model. Finally, we compared the competing risk model with the traditional proportional hazards model (Cox regression model) using CIF.Results: Of these 173 patients, 66 (38.2%) survived, 55 (31.8%) died, and 52 (30.0%) discharged. In univariate analysis, 12 variables were significantly correlated with mortality. In multivariate analysis, Age, Neutrophil ratio, Direct Bilirubin (DBIL) and Renal disease were independent predictors of 28-day outcome. The ROC curve of the multivariate prediction model showed an AUC (area under the curve) of 0.790. The results of the calibration curve and the concordance index (C-index) show that the model has good discriminatory power. The competing risk model we applied was more accurate than the Cox model.Conclusion: We presented a more accurate multivariate prediction model for 28-day in-hospital mortality for ICU COVID-19 patients using a competing risk model.Keywords: COVID-19, 28-day mortality, competing-risk analysis, ICU

Zhiguo Zhang,1,2,* Fangda Fu,1,2,* Yishan Bian,1,2,* Huihao Zhang,1,2 Sai Yao,1,2 Chengcong Zhou,1,2 Yuying Ge,2 Huan Luo,3 Yuying Chen,4 Weifeng Ji,1 Kun Tian,1 Ming Yue,5 Weibin Du,6 Hongting Jin,1 Peijian Tong,1 Chengliang Wu,1,2 Hongfeng Ruan1,2 1Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, People’s Republic of China; 2The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 4The Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 5Department of Physiology, College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 6Research Institute of Orthopedics, The Affiliated Jiangnan Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongfeng Ruan; Chengliang Wu, Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310053, People’s Republic of China, Fax +86 571 86613684, Email rhf@zcmu.edu.cn; wcl@zcmu.edu.cnBackground: With the rapid growth of the elderly population, the incidence of osteoarthritis (OA) increases annually, which has attracted extensive attention in public health. The roles of dietary intake in controlling joint disorders are perhaps one of the most frequently posed questions by OA patients, while the information about the interaction between dietary intake and OA based on scientific research is limited. α-Chaconine is the richest glycoalkaloid in eggplants such as potatoes. Previous evidence suggests that α-Chaconine is a toxic compound to nervous and digestive systems with potentially severe and fatal consequences for humans and farm animals, but its effect on OA development remains obscure.Objective: To determine whether α-Chaconine deteriorates OA progression through sensory innervation and chondrocyte pyroptosis via regulating nuclear factor-κB (NF-κB) signaling, providing evidence for a possible linkage between α-Chaconine and OA progression.Methods: We established a mouse OA model by destabilization of medial meniscus (DMM) surgery and then intra-articular injection of 20 or 100 μM α-Chaconine into the OA mice for 8 and 12 weeks. The severity of OA progression was evaluated by histological staining and radiographic analyses. The expressions of matrix metabolic indicators, Col2, Mmp3, and Mmp13, as well as pyroptosis-related proteins, Nlrp3, Caspase-1, Gsdmd, IL-1β, IL-18, were determined by immunohistochemistry. And the changes in sensory nerve ingrowth and activity of NF-κB signaling were determined by immunofluorescence.Results: We found that α-Chaconine could exacerbate mouse OA progression, resulting in subchondral sclerosis, osteophyte formation, and higher OARSI scores. Specifically, α-Chaconine could augment cartilage matrix degradation and induce chondrocyte pyroptosis and nerve ingrowth. Mechanistical analysis revealed that α-Chaconine stimulated NF-κB signaling by promoting I-κB α phosphorylation and p65 nuclear translocation.Conclusion: Collectively, our findings raise the possibility that α-Chaconine intake can boost chondrocyte pyroptosis and nerve ingrowth to potentiate OA progression by activating NF-κB signaling.Graphical Abstract: Keywords: α-Chaconine, osteoarthritis, pyroptosis, nerve ingrowth, NF-κB signaling

Yuying Ge,1,* Yuying Chen,2,* Chijiao Guo,1,* Huan Luo,3 Fangda Fu,1,4 Weifeng Ji,1,4 Chengliang Wu,1,4 Hongfeng Ruan1,4 1The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 2The Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 4Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chengliang Wu, Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310053, People’s Republic of China, Email wcl@zcmu.edu.cn Hongfeng Ruan, Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310053, People’s Republic of China, Email rhf@zcmu.edu.cnAbstract: Low back pain (LBP) is a common problem worldwide, resulting in great patient suffering and great challenges for the social health system. Intervertebral disc (IVD) degeneration (IVDD) is widely acknowledged as one of the key causes of LBP. Accumulating evidence suggests that aberrant pyroptosis of IVD cells is involved in the pathogenesis of IVDD progression, however, the comprehensive roles of pyroptosis in IVDD have not been fully established, leaving attempts to treat IVDD with anti-pyroptosis approaches questionable. In this review, we summarize the characteristics of pyroptosis and emphasize the effects of IVD cell pyroptosis on the pathological progression of IVDD, including secretion of cytokines, nucleus pulposus cell apoptosis and autophagy, accelerated extracellular matrix degradation, annulus fibrosus rupture, cartilage endplate calcification, vascularization, sensory and sympathetic fiber neoinnervation, and infiltrating lymphatic vessels. Finally, we discuss several interventions used to treat IVDD by targeting pyroptosis. This review provides novel insights into the crucial role of IVD cell pyroptosis in IVDD pathogenesis, and could be informative for developing novel therapeutic approaches for IVDD and LBP.Keywords: low back pain, intervertebral disc degeneration, pyroptosis, inflammasome, anti-pyroptotic approach

Huanrong Ruan,1,2 Hailong Zhang,1– 3 Zhenzhen Feng,1– 3 Xuanlin Li,1,2 Weihong Han,1,2 Yimei Si,1,2 Jiansheng Li1– 3 1Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou, Henan, 450046, People’s Republic of China; 2Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, Henan, 450046, People’s Republic of China; 3Department of Respiratory Diseases, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, 450003, People’s Republic of ChinaCorrespondence: Jiansheng Li, Henan University of Chinese Medicine, No. 156 Jinshui East Road, Zhengzhou, 450046, People’s Republic of China, Tel +86 371 65676568, Fax +86 371 65944307, Email li_js8@163.comObjective: To assess the completeness of reporting in randomized controlled trials (RCTs) of acupuncture therapy (AT) for chronic obstructive pulmonary disease (COPD).Methods: We systematically searched PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Chongqing VIP (CQVIP), WANFANG Data, and China Biology Medicine (CBM) for studies published from their inception to May 8, 2021. The completeness of reporting was evaluated by CONSORT statement and STRICTA guidelines. Univariate and multivariate regression analyses were performed to preliminarily explore the factors related to completeness of reporting.Results: A total of 44 RCTs were included. The overall quality score (OQS) based on the CONSORT statement and STRICTA guidelines ranged from 3 to 26 and 7 to 14, with a median of 10 and 11, respectively. Among the 35 items of the CONSORT statement, 10 items were fully reported with reporting rate > 70%, and 11 items were poorly reported at a rate < 5%. Among the 17 items of the STRICTA guidelines, 10 items were adequately reported with > 70%, and only 3 items were incompletely reported at a rate < 20%. The agreement of most items was determined as “good”, “substantial”, or “moderate”. By regression analysis, publication language (β coefficient: 6.432, 95% CI: 3.202 to 9.663, P < 0.001) and funding source (β coefficient: 3.159, 95% CI: 1.045 to 5.273, P =0.004) acted as independent predictors of completeness of reporting according to the CONSORT statement. However, no variables associated with the STRICTA guidelines were identified.Conclusion: The completeness of reporting of AT for COPD was inadequate. The condition relatively improved for trials with publication in the English language and funding source. By recommendation, reports should be strictly standardized in accordance with the CONSORT statement and STRICTA guidelines to improve the clinical research evidence of AT for COPD.Keywords: chronic obstructive pulmonary disease, acupuncture therapy, randomized controlled trials, completeness of reporting

Huihao Zhang,1,&ast; Sai Yao,1,&ast; Zhiguo Zhang,1,&ast; Chengcong Zhou,1 Fangda Fu,1 Yishan Bian,1 Huan Luo,2 Yan Li,1 Shuxin Yan,1 Yuying Ge,1 Yuying Chen,3 Kunyu Zhan,4 Yanzhi Ge,1 Zuxiang Chen,1 Ming Yue,5 Xiaofeng Li,6 Weibin Du,1,7 Hongting Jin,1 Peijian Tong,1 Hongfeng Ruan,1,8 Chengliang Wu1 1Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 3The Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 4The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 5Department of Physiology, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 6Department of Orthopedics and Traumatology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 7Research Institute of Orthopedics, The Affiliated JiangNan Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 8Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongfeng Ruan; Peijian TongInstitute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of ChinaEmail rhf@zcmu.edu.cn; peijiantongzjtcm@163.comPurpose: To explore the pharmacological mechanisms of Liuwei Dihuang Decoction (LWDHD) against intervertebral disc (IVD) degeneration (IVDD) via network pharmacology analysis combined with experimental validation.Methods: First, active ingredients and related targets of LWDHD, as well as related genes of IVDD, were collected from public databases. The protein–protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were performed to predict the core targets and pathways of LWDHD against IVDD. Secondly, the IVDD model of mice treated with LWDHD was selected to validate the major targets predicted by network pharmacology.Results: By searching the intersection of the active ingredient targets and IVDD targets, a total of 110 targets matched the related targets of 30 active ingredients in LWDHD and IVDD were retrieved. PPI network analysis indicated that 17 targets, including Caspase-3, IL-1β, P53, etc., were hub targets. GO and KEGG enrichment analyses showed that the apoptosis pathway was enriched by multiple targets and served as the target for in vivo experimental study validation. The results of animal experiments revealed that LWDHD administration not only restored the decrease in disc height and abnormal degradation of matrix metabolism in IVDD mice but also reversed the high expression of Bax, Caspase-3, IL-1β, P53, and low expression of Bcl-2, thereby inhibiting the apoptosis of IVD tissue and ameliorating the progression of IVDD.Conclusion: Using a comprehensive network pharmacology approach, our findings predicted the active ingredients and potential targets of LWDHD intervention for IVDD, and some major target proteins involved in the predictive signaling pathway were validated experimentally, which gave us a new understanding of the pharmacological mechanism of LWDHD in treating IVDD at the comprehensive level.Keywords: intervertebral disc degeneration, Liuwei Dihuang decoction, network pharmacology, pharmacological mechanisms, apoptosis

Jiansheng Li,1,2,* Hailong Zhang,1,3,* Huanrong Ruan,3 Yimei Si,3 Zikai Sun,4 Hong Liu,5 Jihong Feng,6 Yanqing Wang,7 Lihua Li,8 Li Bai,9 Hui Sun10 1Co-Construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 2Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 3The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 4Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, People’s Republic of China; 5The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 6The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 7Haici Hospital of Qingdao, Qingdao, People’s Republic of China; 8Zhengzhou People’s Hospital, Zhengzhou, People’s Republic of China; 9Shanxi Hospital of Integrated Traditional and Western Medicine, Taiyuan, People’s Republic of China; 10Nanyang City Center Hospital, Nanyang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jiansheng Li No. 156 Jinshui East Road, Zhengdong New District, Zhengzhou, Henan 450046, People’s Republic of ChinaTel +86 371 65676568Fax +86 371 65944307Email li_js8@163.comPurpose: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is an essential occurrence in COPD management and is the leading cause of morbidity and mortality. Chinese herbal medicine is widely used in the treatment of AECOPD, but high quality randomized controlled trials are limited. This study aimed to evaluate the efficacy and safety of Chinese herbal medicine as adjuvant therapy for patients with AECOPD.Methods: This was a randomized, double-blind, placebo-controlled study of 378 participants from eight centers in China. Participants were randomly assigned to receive 10 g of Chinese herbal medicine (according to the type of Traditional Chinese medicine syndrome: Sanhanhuayin, Qingrehuatan, or Zaoshihuatan granules) or placebo, two times per day, for 14 days, in addition to conventional medicine. Participants were followed up for 84 days after the treatment. The primary end point was the COPD assessment test (CAT) score. Secondary end points included the Modified British Medical Research Council (mMRC) questionnaire and the COPD patient-reported outcome scale (COPD-PRO). We also assessed treatment failure and treatment success rate, length of hospitalization, number of patients with acute exacerbations, number of patients readmitted due to AECOPD, and number of deaths and intubation.Results: The between-group difference in the change from baseline for CAT on day 14 (end of treatment) was − 2.11 (95% confidence interval [CI], − 3.198 to − 1.050; P< 0.001), exceeding the minimal clinically important difference. The mMRC and COPD-PRO scores were lower in the intervention group compared to the control group (between-group difference in the change from baseline, − 0.28; 95% CI, − 0.48 to − 0.08; P=0.007 and − 2.51; 95% CI, − 4.087 to − 0.929; P=0.002, respectively) on day 14. The intervention group had a significantly shorter duration of hospital stay than the control group (mean difference, − 1.21days; 95% CI, − 2.041 to − 0.419; P=0.003), significantly lower of number of exacerbations (risk ratio [RR], 0.60; 95% CI, 0.409 to 0.892; P=0.010), and significantly lower number of readmissions due to AECOPD (RR, 0.41; 95% CI, 0.193 to 0.865; P=0.015). Significant differences in the number of treatment failures or successes, deaths, and intubation were not observed. The difference in safety variables and adverse events between the two groups was not observed.Conclusion: Chinese herbal medicine appears to be safe and beneficial for AECOPD and can be considered a complementary treatment for patients with AECOPD.Keywords: acute exacerbations, chronic obstructive pulmonary disease, randomized controlled trial, Chinese herbal medicine

Yongping Yang,1,* Chenxi Pan,2,* Lingyun Yu,1 Hongxia Ruan,2 Ling Chang,2,3 Jingbo Yang,4 Zihan Zheng,2 Feng Zheng,2,3 Tongjun Liu1,4 1First Bethune Hospital, Jilin University, Changchun, Jilin, People’s Republic of China; 2Dalian Key Laboratory of Immune and Metabolic Kidney Diseases, Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 3Department of Nephrology, Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 4Second Bethune Hospital, Jilin University, Changchun, Jilin, People’s Republic of China*These authors contributed equally to this manuscriptCorrespondence: Tongjun LiuDepartment of Gastrointestinal Surgery, First Bethune Hospital of Jilin University, No.828 Xinmin Street, Changchun, Jilin 130021, People’s Republic of ChinaEmail tongjunliu@163.comFeng ZhengAdvanced Institute for Medical Sciences, Dalian Medical University, 9 West Section, South Road, Lushunkou District, Dalian, Liaoning 116044, People’s Republic of ChinaEmail fzheng63@163.comBackground: Colorectal cancers (CRC) are one of the most common forms of cancer seen worldwide, and also remain difficult to treat despite recent advances in chemotherapy. Although significant progress has been made in recent years towards precision medicine and mutation-guided therapy, common mechanisms that underlie tumor growth and progression remain incompletely understood.Methods: Tumor tissue and nearby unaffected tissue were collected from >15 patients at each stage of CRC, from which we generated representative proteomics profiles of three stages. Bioinformatics analysis was performed to discover common differences that may be shared between the representative profiles and across larger cohorts. Flow cytometry was then used to identify functional consequences of SSBP1 depletion in cell lines, since its expression level was consistently increased in tumor cells across all of the datasets analyzed.Results: Direct comparison of CRC tumor and unaffected tissue at each stage demonstrated that a number of proteins involved in mitochondrial function displayed significantly altered expression patterns. Depletion of SSBP1 in colon cancer cell lines was able to trigger loss of mitochondrial mass and an increase in tumor cell death, and this effect that was further accentuated in the presence of the common chemotherapy drug cisplatin.Conclusion: Mitochondrial biogenesis and maintenance may play an important part in tumor cell survival during CRC progression, and may be a useful target for directed inhibition or adjuvant targeting in the cases of cisplatin resistance.Keywords: SSBP1, colorectal cancer, proteomics

Hong Ruan, Youcheng Yu, Xuehua Guo, Qian Jiang, Ying Luo Department of Stomatology, Zhongshan Hospital, Fudan University, Shanghai, China Background: In this study, simvastatin (SVT) in situ gels were successfully produced by our group. Methods: The preparations were characterized in the following aspects: in vitro gelation, drug release, stability and pharmacodynamics. Results: In this study, drug content of prepared gels was found to be in the range between 89 and 92%. The pH value was in the range between 6.5 and 7.0. The gelation temperature of the prepared thermogelling solutions was 37°C. In vitro release showed that the release of SVT from in situ gels was slow with burst effects at an early stage. Researches indicated that intraorally slow release SVT in situ gels could effectively promote bone regeneration repair of alveolar bone defect. Conclusion: This drug delivery system could prove to be a novel form able to prolong the residence time and to control the release of drug when administered into the oral cavity. Keywords: SVT, in situ gel, thermogelling, gelation, in vitro release, alveolar bone defect

Hai-lin Ruan,1,* Wen-han Ge,2,* Jian-ping Chen,1 Yuan-qun Zhu,3 Wei Huang1 1Department of Emergency, Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, 2Department of Emergency, Huai’an Hospital Affiliated with Xuzhou Medical University, Huai’an, Jiangsu, 3Department of Neurology, Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, China *These authors contributed equally to this work Objective: To evaluate the prognostic value of the Prehospital Index (PHI) for hospitalized patients with acute trauma. Materials and methods: PHI score and the Injury Severity Score (ISS) were determined in 1,802 hospitalized patients with acute trauma. Receiver-operator characteristic (ROC) curves were used to compare the PHI and ISS in subgroups, and corresponding prediction indicators were calculated. Results: There were significant differences in PHI score and ISS between the survival group and the death group (Z=2.674, P=0.007). The area under the ROC curve was 0.871 (95% CI 0.855–0.886) for PHI score and 0.792 (95% CI 0.773–0.811) for ISS. Optimal cutoff points to determine the risk of critical illness were PHI ≥4 and ISS ≥22. The sensitivity of the PHI was superior to the ISS (χ2=6.975, P=0.008), but the specificity and the accuracy of the PHI and ISS showed no significant difference (P>0.05). Conclusion: The PHI is valuable in prognostic prediction of hospitalized patients with acute trauma, and it is superior to the ISS. The PHI has such advantages as being simple in operation, easy to learn, capable of reflecting conditions timely and reliably, and suitable for dynamic evaluation and screening for critical patients with trauma. Keywords: Prehospital Index, trauma, hospitalized patient, Injury Severity Score

1. This study determined the effective indicators and proteins involved in long-duration fertility (DF) in chickens.2. Three lines of Chinese Xinhua chickens (900) were compared using seven phenotypic trait indicators, and the best was determined based on repeatability value. Subsequently, differential expression analysis, functional annotation and protein-protein interaction (PPI) network analyses were performed to investigate the pathways and hub proteins. Finally, qPCR analysis was conducted to validate the expression of identified hub proteins, and functional annotation with previously published genes was performed to explain how hub proteins work to maintain the trait.3. The study found that the number of fertilised eggs (FN) and maximum fertilised eggs (MCF) were the most repeatable among the seven indicators. It identified 231 differentially expressed proteins, with 144 being down-regulated and 87 being up-regulated. The differentially expressed proteins exhibited high clustering within various cellular compartments, including the cytosol and cytoplasm and GTP binding. Multiple pathways were identified, including tight and adherens junctions, TGF-beta signalling, autophagy-animal, regulation of actin cytoskeleton and the ribosome that may regulate the trait. Three hub proteins, KRAS, RPL5 (p < 0.001), and HSPA4 (p < 0.01), were significantly differentially expressed between high and low DF groups.4. This study identified FN and MCF as effective indicators for addressing DF. As it is a quantitative trait, KRAS, HSPA4, and RPL5 are potential hub proteins that work with other genes to maintain the trait. [ABSTRACT FROM AUTHOR]

Soil properties, such as clay content, are hypothesized to control decomposition of soil organic carbon (SOC). However, these hypotheses of soil property-C decomposition relationships have not been explicitly tested at large spatial scales. Here, we used a data-assimilation approach to evaluate the roles of soil properties and environmental factors in regulating decomposition of SOC. A three-pool (active, slow, and passive) C-cycling model was optimally fitted with 376 published laboratory incubation data from soils acquired from 73 sites with mean annual temperature ranging from -. 15 to 26. °C. Our results showed that soil physical and chemical properties regulated decomposition rates of the active and the slow C pools. Decomposition rates were lower for soils with high clay content, high field water holding capacity (WHC), and high C:N ratio. Multifactor regression and structural equation modeling (SEM) analyses showed that clay content was the most important variable in regulating decomposition of SOC. In contrast to the active and slow C pools, soil properties or environmental factors had little effect on the decomposition of the passive C pool. Our results show inverse soil property-C decomposition relationships and quantitatively evaluate the essential roles of soil texture (clay content) in controlling decomposition of SOC at a large spatial scale. The results may help model development and projection of changes in terrestrial C sequestration in the future.

© 2014 Nature America, Inc. All rights reserved.Neurodegenerative diseases, such as frontotemporal dementia (FTD), are often associated with behavioral deficits, but the underlying anatomical and molecular causes remain poorly understood. Here we show that

A micromechanical damage mechanics framework is proposed to predict the overall elastoplastic behavior and interfacial damage evolution of fiber-reinforced ductile composites. Progressively debonded fibers are replaced by equivalent voids. The effective elastic moduli of three-phase composites, composed of a ductile matrix, randomly located yet unidirectionally aligned circular fibers, and voids, are derived by using a rigorous micromechanical formulation. In order to characterize the homogenized elastoplastic behavior, an effective yield criterion is derived based on the ensemble area averaging process and the first-order effects of eigenstrains. The resulting effective yield criterion, together with the overall associative plastic flow rule and the hardening law, constitutes the analytical framework for the estimation of effective elastoplastic damage responses of ductile composites containing both perfectly bonded and completely debonded fibers. An evolutionary interfacial fiber debonding process, governed by the internal stresses of fibers and interfacial strength, is incorporated into the proposed framework. The Weibull's function is employed to describe the varying probability of fiber debonding. Further, comparison between predictions and available experimental data are presented to illustrate the potential of the proposed methodology.

ObjectiveThis research focused on examining the distinctive characteristics of nutrient intake and dietary patterns among long-lived elderly individuals. Additionally， the study was aimed to explore the specific dietary components that may impact the skeletal muscle mass in this particular group.MethodsThis study was conducted in the Chongming area of Shanghai， China. A total of 206 long-lived elderly individuals aged 90 or above were recruited. The 3-day 24-hour dietary recall method was used to collect dietary information and general demographic data through face-to-face interviews with professional nutritionists. The skeletal muscle mass index（SMI） was measured by bioelectrical impedance analysis（BIA）， and low skeletal muscle mass was diagnosed based on the 2019 Asian Working Group for Sarcopenia criteria. T-test analysis， chi-square test， and logistic regression were used to analyze the relationship between dietary nutrient intake and skeletal muscle mass.ResultsIn terms of food intake categories， compared with the long-lived elderly people with normal muscle mass， the intake of cereals containing miscellaneous beans and vegetables in the long-lived elderly people with low muscle mass was significantly lower （P

1. Fertilisation rate is closely related to the reproductive performance and economic status of chicken laying breeders. In this study, two flocks (n = 1,029 in population I and n = 358 in population II) in the later laying period were used for investigating the individual differences among population fertilisation rates (FRs). 2. The funnel and distal parts of the infundibulum were collected from nine individuals (five with low FR and four with high FR from population II) and RNA-sequencing (RNA-seq) method was used to investigate the transcriptome differences in fertilisation. Differences in fertilisation regulation were investigated by comparing the different parts (funnel and distal) of the infundibulum between the low FR and high FR groups. 3. There were notable individual FR differences in both categories. Some individuals had a relative high FR (≥90%) for a long time (>5 days after AI), contrarily, some individuals lost the ability to fertilise eggs in a very short time. 4. Differentially expressed genes (DEGs), such as DUSP7, PPP1R3B, FYB, OVA, OVALX and OVALY may be associated with sperm functional regulation, fertilisation and early-stage fertilised ovum development processes. DEGs such as AVBD1, AVBD2, AVBD6, NFATC2 and BANK1 indicated a severe immune response to sperm survival and fertilisation in the oviduct. 5. The results suggested that individual differences should be considered in the breeding and reproduction process. The DEGs identified in this study may promote our understanding of different fertilisation regulation in laying breeders. [ABSTRACT FROM AUTHOR]

With the improvement of high complexity and automation level of the aircraft systems，pilots are often ill-prepared to cope with an actual emergency or failure，and their corrective actions may be erroneous，delayed or incomplete. Therefore，there is an urgent need to consider flight crew human factors in system safety assessment. By analyzing the requirements of CCAR25.1309（b）and（c）and failure processing process of flight crew，based on the failure conditions in functional hazard assessment，the methods of requirements capture and analysis of flight crew human factors is proposed. By applying these methods in the aircraft development，the top down design for safety which from failure condition to alert and procedures is achieved，and a complete chain of compliance evidence for human factor of safety is established. The results show that the proposed method can effectively demonstrate airworthiness compliance with human factors of CCAR25.1309 （b）and（c）.

Xuan Zhao,1,&ast; Yang Niu,1,&ast; Xue-Lin Zhao,1,&ast; Hui-Juan Ruan,1 Yi Xiang,1 Ling-Yu Wang,1 Yi Feng,1,2 Qing-Ya Tang1,2 1Department of Clinical Nutrition, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Pediatric Digestion and Nutrition, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qing-Ya Tang; Yi Feng, Email tangqingya@xinhuamed.com.cn; fengyi@xinhuamed.com.cnPurpose: To explore the relationships between serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP) levels and glucolipid metabolism disorders (GLMD) in obese children and adolescents.Patients and Methods: In this cross-sectional study, 105 obese children and adolescents were selected for the detection of TNF-α, IL-6, hs-CRP, and glycolipid metabolism indicators. All participants were divided into elevated TNF-α group (≥ 8.1 pg/mL; n=49) and normal TNF-α group (< 8.1 pg/mL; n=56), elevated IL-6 group (≥ 5.9 pg/mL; n=13) and normal IL-6 group (< 5.9 pg/mL; n=92), elevated hs-CRP group (≥ 3.0 mg/L; n=44) and normal hs-CRP group (< 3.0 mg/L; n=61), respectively.Results: Low-density lipoprotein cholesterol (LDL-C) in the elevated TNF-α group was higher than that in the normal TNF-α group (P=0.010). TNF-α was positively correlated with LDL-C (P=0.005). Fasting insulin (FINS) and homeostasis model assessment of insulin resistance (HOMA-IR) in the elevated IL-6 group were higher than those in the normal IL-6 group (all for P < 0.05), while high-density lipoprotein cholesterol (HDL-C) in the elevated IL-6 group was lower than that in the normal IL-6 group (P< 0.001). IL-6 was positively correlated with FINS, 2-hour postprandial insulin, HOMA-IR and triglyceride (all for P < 0.01), while was negatively correlated with HDL-C (P=0.006). Moreover, hs-CRP was positively correlated with FINS and HOMA-IR (all for P < 0.05).Conclusion: There may be correlations between serum TNF-α, IL-6, hs-CRP levels and GLMD in obese children and adolescents. Attention should be paid to monitoring serum inflammatory factors and preventing their elevation in obese children and adolescents, thus reducing the occurrence of GLMD.Keywords: tumor necrosis factor-alpha, interleukin-6, high-sensitivity C-reactive protein, glucolipid metabolism disorders, obesity, children and adolescents