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Chunjiao Lu,* Xuewei Wu,* Xin Meng,* Yi Liu, Ting Yang, Yan Zeng, Yang Chen, Yishan Huang, Zhou Fang, Xiaojun Yang, Juanjuan Luo Engineering Research Center of Key Technique for Biotherapy of Guangdong Province, Shantou University Medical College, Shantou, 515041, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaojun Yang; Juanjuan Luo, Shantou University Medical College, 22 Xinling Road, Shantou, 515041, People’s Republic of China, Email yangx@stu.edu.cn; 15jjluo1@stu.edu.cnIntroduction: The potential toxic effects of wastewater discharges containing silver nanoparticles (AgNPs) and their release into aquatic ecosystems on aquatic organisms are becoming a major concern for environmental and human health. However, the potential risks of AgNPs to aquatic organisms, especially for cardiac development by Focal adhesion pathway, are still poorly understood.Methods: The cardiac development of various concentrations of AgNPs in zebrafish were examined using stereoscopic microscope. The expression levels of cardiac development-related genes were analyzed by qRT-PCR and Whole-mount in situ hybridization (WISH). In addition, Illumina high-throughput global transcriptome analysis was performed to explore the potential signaling pathway involved in the treatment of zebrafish embryos by AgNPs after 72 h.Results: We systematically investigated the cardiac developing toxicity of AgNPs on the embryos of zebrafish. The results demonstrated that 2 or 4 mg/L AgNPs exposure induces cardiac developmental malformations, such as the appearance of pericardial edema phenotype. In addition, after 72 h of exposure, the mRNA levels of cardiac development-related genes, such as myh7, myh6, tpm1, nppa, tbx5, tbx20, myl7 and cmlc1, were significantly lower in AgNPs-treated zebrafish embryos than in control zebrafish embryos. Moreover, RNA sequencing, KEGG (Kyoto Encyclopedia of Genes) and Genomes and GSEA (gene set enrichment analysis) of the DEGs (differentially expressed genes) between the AgNPs-exposed and control groups indicated that the downregulated DEGs were mainly enriched in focal adhesion pathways. Further investigations demonstrated that the mRNA levels of focal adhesion pathway-related genes, such as igf1ra, shc3, grb2b, ptk2aa, akt1, itga4, parvaa, akt3b and vcla, were significantly decreased after AgNPs treatment in zebrafish.Conclusion: Thus, our findings illustrated that AgNPs could impair cardiac development by regulating the focal adhesion pathway in zebrafish.Keywords: AgNPs, focal adhesion, cardiac development, zebrafish

Yun Zhong,1– 3 Yufei Zhao,4 Xin Meng,2 Fan Wang,2 Lei Zhou1 1Department of Dermatology, the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Department of Dermatology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 3Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 4Department of Gastrointestinal Surgery, Laboratory of Surgery, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Lei Zhou, Department of Dermatology, the Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Tianhe District, Guangzhou, Guangdong, 510630, People’s Republic of China, Tel +020-85253333, Fax +020-85253336, Email zhoulei53@mail.sysu.edu.cnBackground: Rosacea, a recurring dermatological disorder, demands effective therapeutic approaches. Traditional Chinese medicine, particularly Liangxue Siwu Decoction (LXSWD), has shown promise in managing inflammatory skin diseases, such as rosacea. This study focuses on uncovering LXSWD’s specific effects on the inflammatory symptoms of rosacea.Objective: Our research investigates LXSWD’s therapeutic effectiveness in rosacea treatment and delves into its underlying mechanisms.Methods: Network pharmacology was utilized to identify LXSWD’s key components and their targets in rosacea management, which were then validated by molecular docking. An in vivo rosacea-like model in LL-37-induced mice was developed, subdividing them into control, model, and LXSWD groups. The LXSWD group received oral administration (25.0 g/kg/day) for six days before model induction. Post-treatment evaluations included skin tissue analyses to verify our network pharmacology predictions.Results: Key active ingredients in LXSWD, such as quercetin, kaempferol, and luteolin, were identified alongside central target proteins like TNF and MMPs. Our molecular docking study confirmed the interactions between these ingredients and targets. Analyses through GO and KEGG pathways indicated LXSWD’s role in mitigating inflammation, particularly influencing the TNF and IL-17 pathways. LXSWD treatment in vivo markedly alleviated LL-37-induced symptoms in mice, showing a marked reduction in inflammatory cytokines (p < 0.05) and modulation of crucial genes (p < 0.05). These results, supported by immunofluorescence analysis and Western blot, underline the modulatory effects of LXSWD on MMPs, offering significant protection against rosacea’s inflammation alterations (p < 0.05).Conclusion: Integrating network pharmacology, molecular docking, and in vivo experiments, this study elucidates LXSWD’s potential mechanisms in rosacea treatment. It offers a novel theoretical framework for its clinical use in managing rosacea.Keywords: Liangxue siwu decoction, molecular docking, network pharmacology, rosacea, skin inflammation

Ting Dai,&ast; Qimeihui Wang,&ast; Lingyu Zhu, Qiang Luo, Jiayu Yang, Xia Meng, Hui Wang, Zhixia Sun Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Wang; Zhixia Sun, Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, 130033, People’s Republic of China, Email whui66@jlu.edu.cn; sunzx@jlu.edu.cnIntroduction: The effective accumulation of nanoparticles (NPs) in the tumour area is an important goals of current nanotechnology research, and a targeted nanoplatform is an effective solution. So we designed a multifunctional sound-sensitive targeted NP that combines a sonosensitizer to enable precisely targeted, deep-penetration sonodynamic therapy (SDT) in combination with multimodal imaging for the diagnosis and monitoring of renal cell carcinoma (RCC).Methods: ZnPP@PP NPs (ZnPP@PLGA- PFP NPs) were prepared via a double emulsion method, and G250 was covalently attached to the NPs shell via the carbon diimide method. Physicochemical property tests were conducted on the ZnPP@G-PP NPs, including tests of particle size, potential distribution, encapsulation efficiency and drug loading capability. We assessed the targeting ability, the production of reactive oxygen species (ROS) and permeability of the NPs in vitro. Moreover, we evaluated the nanoparticle’s multimodal imaging capabilities and therapeutic ability against RCC, both in vitro and in vivo.Results: The Znpp@G-PP NPs were successfully constructed, and their general properties showed uniform particle size, negative potential and good stability. The nanoparticles were successfully loaded with ZnPP and connected with G250, showing tumor-specific targeting ability. Under LIFU irradiation, the nanoparticles produced 1O2 by SDT. For RCC, PA/US multi-modal imaging of Znpp@G-PP NPs provide diagnostic information and monitor therapies in real time in 786-O RCC xenografts, with good biocompatibility. With the UTMD, nanoparticles can be effectively targeted into the tumor cells and penetrate into the tumor interior, significantly improving the SDT effect. Experiments in vitro and in vivo showed that the combination of the nanoparticles and LIFU could suppress the tumor, and the therapeutic effect was confirmed by immunohistochemistry.Conclusion: ZnPP@G-PP NPs provide a promising theranostic strategy for RCC and a platform for further research on improving the efficacy of diagnosis and treatment.Keywords: targeted therapy, deep-penetration, sonodynamic therapy, multimodal imaging

Hanrui Fan,1 Ping Xu,1 Enming Zhang,1 Xi Meng,2 Jianmei Xia,3 Yong Fei,3 Ming Yao3 1Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Zhejiang Sci-Tech University, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Anesthesiology and Pain, The First Hospital of Jiaxing, Jiaxing, Zhejiang, People’s Republic of ChinaCorrespondence: Yong Fei, Department of Anesthesiology and Pain, The First Hospital of Jiaxing, 1882 Zhong-Huan-South Road, Jiaxing, 314000, People’s Republic of China, Email jxfy6666662022@163.comBackground: Current studies mostly suggest that hyperhidrosis is caused by relative sympathetic hyperactivity. Sympathetic radiofrequency thermocoagulation is widely used in clinics. Previous studies have demonstrated that surgery at T3 is effective and safe compared with higher levels, so craniofacial hyperhidrosis in our hospital is selected to be treated at T3. However, some patients pursue repeat medical treatment due to an increase in hyperhidrosis at the original site after surgery. Previous studies have demonstrated the significance of Perfusion index (PI) value in the recurrence of palmar hyperhidrosis, but there is no relevant study on craniofacial hyperhidrosis.Methods: Clinical data from patients with craniofacial hyperhidrosis, who underwent T3 sympathetic radiofrequency thermocoagulation at Jiaxing First Hospital (Jiaxing, China) between January 1, 2018 and December 31, 2021, were analyzed. Recurrence in patients 1 year after surgery was recorded through a case search and telephone follow-up system that registered patient information. Clinical data were analyzed using binary logistic regression analysis to investigate risk factors associated with recurrence in patients with craniofacial hyperhidrosis 1 year after surgery.Results: Of 83 patients included in the present study, 34 (40%) experienced increased craniofacial sweating 1 year after surgery. Results of univariate logistic regression analysis revealed that computed tomography (CT) scan count, increase in pulse index (PI) at the fingertips, and differences in forehead temperature were potential risk factors for postoperative recurrence in patients with craniofacial hyperhidrosis (p< 0.2), and the results were consistent on both sides. Three potential risk factors were included in the multivariate logistic regression analysis and results revealed that the risk for recurrence was reduced by 48% (left side) and 67% (right side) for every 1 unit increase in PI value.Conclusion: A small increase in PI was an independent risk factor for recurrence of hyperhidrosis in patients with craniofacial hyperhidrosis after undergoing T3 sympathetic radiofrequency thermocoagulation.Keywords: ephidrosis, craniofacial hyperhidrosis, sympathetic radiofrequency thermocoagulation

Licai Miao,1,&ast; Zihao Xu,1,&ast; Junhao Sui,1,&ast; Xiangyu Meng,1,&ast; Shicheng Huo,2 Shu Liu,1 Mengchen Chen,1 Zhong Zheng,1 Xiaobin Cai,3 Hao Zhang1 1Department of Orthopedics, Changhai Hospital Affiliated to the Navy Military Medical University, Shanghai, 200433, People’s Republic of China; 2Department of Orthopedic Surgery, Spine Center, Changzheng Hospital, Navy Medical University, Shanghai, 200003, People’s Republic of China; 3Department of Orthopedics Shanghai Tenth People’s Hospital Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaobin Cai, Department of Orthopedics Shanghai Tenth People’s Hospital Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China, Tel +8613122575295, Email caixbjn@163.com Hao Zhang Department of Orthopedics, Changhai Hospital Affiliated to the Navy Military Medical University, Tel +8613917856377, Email zhanghsmmu@126.comPurpose: Skin injury, often caused by physical or medical mishaps, presents a significant challenge as wound healing is critical to restore skin integrity and tissue function. However, external factors such as infection and inflammation can hinder wound healing, highlighting the importance of developing biomaterials with antibiotic and wound healing properties to treat infections and inflammation. In this study, a novel photothermal nanomaterial (MMPI) was synthesized for infected wound healing by loading indocyanine green (ICG) on magnesium-incorporated mesoporous bioactive glass (Mg-MBG) and coating its surface with polydopamine (PDA).Results: In this study, Mg-MBG and MMPI was synthesized via the sol-gel method and characterized it using various techniques such as scanning electron microscopy (SEM), the energy dispersive X-ray spectrometry (EDS) system and X-ray diffraction (XRD). The cytocompatibility of MMPI was evaluated by confocal laser scanning microscopy (CLSM), CCK8 assay, live/dead staining and F-actin staining of the cytoskeleton. The antibacterial efficiency was assessed using bacterial dead-acting staining, spread plate method (SPM) and TEM. The impact of MMPI on macrophage polarization was initially evaluated through flow cytometry, qPCR and ELISA. Additionally, an in vivo experiment was performed on a mouse model with skin excision infected. Histological analysis and RNA-seq analysis were utilized to analyze the in vivo wound healing and immunomodulation effect.Conclusion: Collectively, the new photothermal and photodynamic nanomaterial (MMPI) can achieve low-temperature antibacterial activity while accelerating wound healing, holds broad application prospects.Keywords: infection-related wounds, magnesium-doped bioactive glass, photothermal therapy, photodynamic therapy, immunomodulation

Yongpeng Huang, Hui Tang, Xiangyan Meng, Dongxin Liu, Yanli Liu, Bo Chen, Zhiyun Zou State Key Laboratory of NBC Protection for Civilian, Beijing, People’s Republic of ChinaCorrespondence: Bo Chen; Zhiyun Zou, Email NBC_BoChen@163.com; zouzhiyun65@163.comIntroduction: Nanoparticles have the advantages of improving the solubility of poorly water-soluble drugs, facilitating the drug across biological barriers, and reducing macrophage phagocytosis in pulmonary drug delivery. However, nanoparticles have a small aerodynamic particle size, which makes it difficult to achieve optimal deposition when delivered directly to the lungs. Therefore, delivering nanoparticles to the lungs effectively has become a popular research topic.Methods: Nanoaggregate microparticles were used as a pulmonary drug delivery strategy for the improvement of the bioavailability of cyclosporine A (CsA). The nanoaggregate microparticles were prepared with polyvinyl pyrrolidone (PVP) as the excipient by combining the anti-solvent method and spray drying process. The physicochemical properties, aerodynamic properties, in vivo pharmacokinetics and inhalation toxicity of nanoaggregate microparticles were systematically evaluated.Results: The optimal nanoparticles exhibited mainly spherical shapes with the particle size and zeta potential of 180.52 nm and − 19.8 mV. The nanoaggregate microparticles exhibited irregular shapes with the particle sizes of less than 1.6 μm and drug loading (DL) values higher than 70%. Formulation NM-2 as the optimal nanoaggregate microparticles was suitable for pulmonary drug delivery and probably deposited in the bronchiole and alveolar region, with FPF and MMAD values of 89.62% and 1.74 μm. In addition, inhaled NM-2 had Cmax and AUC0-∞ values approximately 1.7-fold and 1.8-fold higher than oral cyclosporine soft capsules (Neoral®). The inhalation toxicity study suggested that pulmonary delivery of NM-2 did not result in lung function damage, inflammatory responses, or tissue lesions.Conclusion: The novel nanoaggregate microparticles for pulmonary drug delivery could effectively enhance the relative bioavailability of CsA and had great potential for clinical application. Keywords: pulmonary drug delivery, dry powder inhalers, nanoaggregate microparticles, aerosol performance, pharmacodynamic study, inhalation toxicity

Liang Shan,1– 4 Fengling Wang,1 Dandan Zhai,1 Xiangyun Meng,1 Jianjun Liu,1 Xiongwen Lv2– 4 1Department of Pharmacy, The Second People’s Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, Anhui, 230011, China; 2Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, 230032, China; 3Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, Anhui, 230032, China; 4The Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, 230032, ChinaCorrespondence: Jianjun Liu, Department of Pharmacy, The Second People’s Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, Anhui, 230011, China, Tel/Fax +86 0551 62965335, Email Jianjun_liu2020@163.com Xiongwen Lv, Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, 230032, China, Tel/Fax +86 0551 65161000, Email Xiongwen_lv2019@163.comBackground: Biliary atresia (BA) is a severe neonatal progressive cholangiopathy of unknown etiology. A timely Kasai portoenterostomy (KPE) improves survival of the native liver in patients with BA, although liver transplantation remains the ultimate treatment for most (60%– 80%) patients. However, postoperative adverse effects of liver transplantation may be significant. In addition, patients require lifelong immunosuppressive therapy after liver transplantation.Case Summary: Here, we report a case of a newborn female baby (birthday: 10– 03-2018) with congenital BA (confirmed at 76 days of life) who survived KPE (first surgery at 85 days of life) and underwent successful living-related liver transplantation (LRLT) (second surgery at 194 days of life). Additionally, we reviewed the existing literature on BA. After KPE (at 85 days of life), the liver function of the baby did not improve, and the indicators of liver and kidney function showed a trend of aggravation, indicating that the liver function had been seriously damaged before KPE (at 85 days of life), demonstrating the urgent need for liver transplantation surgery. The female baby survived after part of her father’s liver was successfully transplanted into her body (at 194 days of life). The patient recovered successfully. No other diseases were found at the 4-year follow-up, and all indices of liver and kidney functions tended to be normal.Conclusion: This case highlights the following. Postoperative alkaline phosphatase was consistently above the normal range, although the reason for this was unclear; neither tacrolimus nor cyclosporine A has formulations designed specifically for infants, which does not meet the needs of clinical individualized medication, suggesting that these anti-rejection drugs are future development directions. Only one case of congenital BA has been found thus far in Hefei, and this case has extremely important reference significance for the prevention, treatment, and diagnosis of BA in Hefei, Anhui province. Keywords: biliary atresia, Kasai portoenterostomy, living-related liver transplantation, immunosuppressive drug, therapeutic drug monitoring

Xiaofei Wang,1,2,&ast; Jihang Dai,2,&ast; Zhimin Wu,1,2 Yuxia Yang,2 Jian Zhang,2 Xiangji Meng,1,2 Wenkang Liu,2 Wenyong Fei,2 Jingcheng Wang2 1The Graduate School, Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 2Department of Orthopedics, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenyong Fei; Jingcheng Wang, Email sbydyx105@126.com; yzwangjingcheng@163.comObjective: To compare the clinical efficacy of artificial total hip arthroplasty(THA) for femoral neck fracture between direct anterior approach(DAA) in lateral position and posterior lateral approach(PLA).Methods: Comparison of 200 cases of patients who underwent THA collected between September 2019 and August 2021 was done. Incision length, intraoperative bleeding, operative time, difference in postoperative haemoglobin from preoperative levels, length of hospital stay, postoperative time to get off the floor, visual analogue score (VAS) for pain, preoperative and postoperative Harris scores for the hip, and measurements of the acetabular abduction angle and anterior acetabular tilt angle at 6 months postoperatively were collected, and all the cases were followed up for at least 2 years.Results: Compared with the PLA group, the DAA group had a shorter incision length, less intraoperative blood loss, less postoperative haemoglobin reduction compared with the preoperative period, a shorter hospital stay and an earlier first time to get off the floor after surgery, however, the comparison of operative times was not statistically significant; Patients in the DAA group had a lower VAS in the early postoperative period compared to PLA; Patients in the DAA group had higher hip Harris scores at 6 weeks and 6 months postoperatively; There was no significant difference in acetabular abduction angle and acetabular anterior tilt angle between the two groups at 6 months postoperatively.Conclusion: Compared to PLA, DAA in THA is minimally invasive, has less pain, less bleeding, earlier time out of bed, shorter hospital stay, better early hip function, faster rehabilitation, and better joint stability.Keywords: direct lateral approach, DAA, femoral neck fractures, total hip arthroplasty, THA, Hip function, postoperative rehabilitation

Feng Lu,1,&ast; Yangyang Wang,2,&ast; Fangyu Miao,3 Chengzhou Han,2 Xiangming Meng2 1Department of Emergency Medicine, Affiliated Huishan Hospital of Xinglin College, Nantong University, Wuxi Huishan District People’s Hospital, Wuxi, 214187, People’s Republic of China; 2Department of Otolaryngology, Affiliated Huishan Hospital of Xinglin College, Nantong University, Wuxi Huishan District People’s Hospital, Wuxi, 214187, People’s Republic of China; 3Information Centre, Affiliated Huishan Hospital of Xinglin College, Nantong University, Wuxi Huishan District People’s Hospital, Wuxi, 214187, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangming Meng, Department of Otolaryngology, Affiliated Huishan Hospital of Xinglin College, Nantong University, Wuxi Huishan District People’s Hospital, 2 Zhanqian North Road, Luoshe Town, Huishan District, Wuxi, 214187, People’s Republic of China, Email xiangming_meng@hotmail.comPurpose: This study aimed to investigate the clinical characteristics of acute epiglottitis (AE) patients in East China and examine the correlation between the incidence of AE and the 24 solar terms (24 STs).Methods: A retrospective, observational study was conducted on patients diagnosed with AE between January 2014 and December 2021 at a single-center medical institution in East China. The clinical characteristics of patients with AE and their correlation with the 24 STs were investigated.Results: A total of 287 patients with AE were included in this study, among which there were 179 males (62.37%) and 108 females (37.63%), with a mean age of 47.79 ± 13.83 years (range 16– 87 years). Of these patients, 100 (34.84%) had at least one comorbidity and the most common comorbidities were hypertension, smoking and type 2 diabetes. The duration of hospitalization was 3 days (IQR, 1– 16 days). All patients, except for one who required tracheal intubation, were cured with intravenous antibiotic administration and the combined use of corticosteroids. The incidence of AE showed significant fluctuations between the 24 STs and the highest number of cases occurred during the Summer solstice (24 cases, 8.36%).Conclusion: The incidence of AE was seen to increase annually in this study. The main features of AE are sore throat, dysphagia, odynophagia and fever, which may be accompanied by inflammation in surrounding areas. A clear correlation exists between the incidence of AE and the fluctuations within the 24 STs, notably with the peak incidence observed during the Summer solstice, which approximately corresponds to June 21 to July 7 in the Gregorian calendar.Keywords: acute epiglottitis, 24 solar terms, seasonal variations, incidence, summer solstice

Guanshuai Guo,1,2,&ast; Xi Chen,1,2,&ast; Jingran Zhang,1,2 Xiangmin Meng,3 Aifeng Jia,4 Xinli Xing,5 Fenglei Huang,6 Xumei Zhang,2,7 Juan Liu,8 Shuying Li,3,9 Qiang Zhang1,2 1Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin, People’s Republic of China; 2Tianjin Key Laboratory of Environment, Nutrition and Public Health, School of Public Health, Tianjin Medical University, Tianjin, People’s Republic of China; 3Department of Endocrinology, Tianjin Xiqing Hospital, Tianjin, People’s Republic of China; 4Department of Obstetrics and Gynecology, Tianjin Xiqing Hospital, Tianjin, People’s Republic of China; 5Department of Obstetrics and Gynecology, Women’s and Children’s Health Center of Dongchangfu District, Liaocheng, People’s Republic of China; 6Department of Reproductive Health, Women’s and Children’s Health Center of Dongchangfu District, Liaocheng, People’s Republic of China; 7Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin, People’s Republic of China; 8Department of Biomedical Information and Library, Tianjin Medical University, Tianjin, People’s Republic of China; 9NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shuying Li, Department of Endocrinology, Tianjin Xiqing Hospital, Tianjin, 300380, People’s Republic of China, Email lsy_tj2006@163.com Qiang Zhang, Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin, 300070, People’s Republic of China, Tel +86 022 83336633, Email qiangzhang@tmu.edu.cnPurpose: This study aimed to explore the association between N-6 adenine-specific DNA methyltransferase 1 (N6AMT1) single nucleotide polymorphisms (SNPs) and gestational diabetes mellitus (GDM) and the modification of the relationship by folate and vitamin B12.Methods: A cross-sectional study involving 1303 pregnant women (262 GDM and 1041 non-GDM) was performed in Tianjin, China. Nine SNPs in N6AMT1 were genotyped, and serum folate, vitamin B12, and homocysteine (Hcy) levels were measured. The logistic regression models determined the odds ratios (ORs) for SNPs in N6AMT1 and the gene-nutrition interactions on GDM.Results: N6AMT1 rs7282280, rs1048546, and rs1997605 were related to GDM under the dominant model after adjusting for multiple covariates. Individuals carrying the N6AMT1 rs7282280 TC/TT genotypes had a lower risk of developing GDM, regardless of serum folate and vitamin B12 levels. However, rs1048546 TG/GG genotypes were associated with lower GDM risk when serum folate ≥ 6.0 ng/mL. Pregnancies with the risk genotypes in N6AMT1 and higher serum folate or lower vitamin B12 are more prone to GDM. The study also showed a statistically significant additive interaction between N6AMT1 rs1997605 GG genotypes and lower vitamin B12 (RERI: 2.54; 95% CI: 0.17, 4.92).Conclusion: SNPs in N6AMT1 were found to be associated with GDM, and serum folate and vitamin B12 levels can modify their associations.Keywords: N6AMT1, folate, vitamin B12, gene-nutrition interaction, gestational diabetes mellitus

Xiaoying Meng,1,2 Fei Li,2 Wenpei Wu,3 Juncang Wu1,2 1Department of Neurology, Hefei Hospital Affiliated to Anhui Medical University (Hefei Second People’s Hospital), Hefei, Anhui, 230011, People’s Republic of China; 2The Fifth Clinical School of Medicine, Anhui Medical University, Hefei, Anhui, 230032, People’s Republic of China; 3Department of Neurology, Hefei Second People’s Hospital Affiliated to Bengbu Medical College, Hefei, Anhui, 230011, People’s Republic of ChinaCorrespondence: Juncang Wu, Department of Neurology, Hefei Hospital Affiliated to Anhui Medical University (Hefei Second People’s Hospital), Hefei, Anhui, 230011, People’s Republic of China, Email wujuncang126@126.comPurpose: To investigate the quantitative assessment of carotid plaque by each parameter of dual-layer detector spectral CT and its diagnostic value in patients with acute cerebral infarction.Patients and Methods: Eighty-three patients with carotid atherosclerotic plaques who underwent spectral CT scanning were retrospectively included. Forty-two patients with acute ischaemic stroke (AIS) were included in the study group, and 41 patients without AIS were included in the control group. We compared the detection of carotid plaques in the two groups and the differences in the spectral quantitative parameters of the plaques in the two groups, and their diagnostic efficacy was obtained.Results: The detection rate of carotid plaques in the AIS group was higher than that in the non-AIS group (p< 0.05); the carotid plaques in the AIS group mainly consisted of non-calcified plaques, while those in the non-AIS group mainly consisted of calcified plaques. The effective atomic number (Zeff), slope of the energy spectrum curve (λH), electron density (ED), and iodine-no-water value of the carotid plaques in the AIS group were lower than those in the non-AIS (p< 0.05). For the differentiation of the carotid plaques in the AIS group from those in the non-AIS group, the area under the curve (AUC) of Zeff amounted to 0.637 (cut-off value: 11.865; sensitivity: 72.5%; specificity: 56.2%), the AUC of λH amounted to 0.628 (cut-off value: 19.56; sensitivity: 76.3%; specificity: 51.6%), and that for ED amounted to 0.624 (cut-off value: 110.45; sensitivity: 60.0%; specificity: 64.1%), AUC of iodine-no-water value amounted to 0.645 (cut-off value: 9.125; sensitivity: 61.3%; specificity: 65.6%).Conclusion: In summary, the quantitative parameters of dual-layer detector spectral CT can be used to assess plaque stability and have certain value in the diagnosis of AIS. The quantitative parameters can effectively differentiate carotid plaques in AIS and non-AIS patients.Keywords: ischemic stroke, carotid plaque, spectral CT, effective atomic number, iodine density values, anhydrous iodine values, electron density

Yuying Zhou,1,&ast; Wu Xue,2,&ast; Xinyu Meng,2,&ast; Adheesh Bhandari,2,3,&ast; Hanqian Zeng,4 Rajan KC,5 Suzita Hirachan,6 Erjie Xia2 1Department of Oncology and Hematology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou, Zhejiang, People’s Republic of China; 2Department of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 3Department of Surgery, Breast and Thyroid Unit, Primera Hospital, Kathmandu, Nepal; 4Department of Surgical Oncology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Zhejiang Province, People’s Republic of China; 5Central Department of Zoology, Tribhuvan University, Kirtipur, Kathmandu, Nepal; 6Department of General Surgery, Breast and Thyroid Unit, Tribhuvan University, Teaching Hospital, Kathmandu, Nepal&ast;These authors contributed equally to this workCorrespondence: Erjie Xia, Department of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China, Tel +86 577 5557 8527, Email erjiexia1@126.com Yuying Zhou, Department of Oncology and Hematology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou, Zhejiang, People’s Republic of China, Tel +8615757194239, Email yuying_ne@163.comBackground: Breast cancer (BC) is increasingly becoming the primary reason for death in women, which sounded the alarm. Thus, finding a novel management target for BC is imminent.Materials and Methods: The data on gene expression and clinicopathological characteristics were downloaded from The Cancer Genome Atlas (TCGA). The expression of GNPNAT1 in 40 paired breast cancer and adjacent tissues was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Univariate and Multivariate logistic regression methodology was applied to analyze the prognostic factors for lymph node metastasis (LNM). Based on the status of breast cancer-relative receptors, patients were distributed into six groups, and then the Kaplan-Meier survival analysis with a Log rank test was applied to investigate the involvement among the expression of GNPNAT1 and overall survival (OS).Results: We found higher expression of GNPNAT1 was connected with poor survival in breast cancer by COX regulation analysis. GO, KEGG, and GSEA analysis prompted that GNPNAT1 was connected with the defense mechanism of cells, cell proliferation, and division. Immunization infiltration analysis showed that high GNPNAT1 was negatively connected with 16 immunization infiltration cell types and positively connected with four immunization infiltration cell types.Conclusion: As a whole, our results indicated that GNPNAT1 might be a probable biomarker for diagnosis and prognosis in breast cancer.Keywords: GNPNAT1, biomarker, breast cancer, diagnosis, prognosis

Wenpei Wu,1,2,&ast; Zhi Geng,3– 5,&ast; Aimei Wu,2,&ast; Xinyi Chen,6,7 Xiaoying Meng,2 Qianyun Zhang,2 Zheng Tan,2 Hong Yue,2 Juncang Wu1,2 1Department of Neurology, Hefei Second People’s Hospital Affiliated to Bengbu Medical University, Hefei, Anhui, 230011, People’s Republic of China; 2Department of Neurology, Hefei Second People’s Hospital, Hefei, Anhui, 230011, People’s Republic of China; 3Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 4Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Hefei, People’s Republic of China; 5Collaborative Innovation Centre of Neuropsychiatric Disorder and Mental Health, Hefei, 230000, People’s Republic of China; 6Department of Neurology, Hefei Hospital Affiliated to Anhui Medical University (Hefei Second People’s Hospital), Hefei, Anhui, 230011, People’s Republic of China; 7The Fifth Clinical School of Medicine, Anhui Medical University, Hefei, Anhui, 230011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Juncang Wu; Hong Yue, Intersection of Guangde Road and Leshui Road, Hefei, Anhui, 230011, People’s Republic of China, Tel/Fax +86 551 13956076148 ; +86 551 18949855780, Email wujuncang126@126.com; yuehong01@foxmail.comBackground and Purpose: The role of serum uric acid (UA) level in patients suffering from stroke remains controversial. Our aim was to investigate the effect of UA level on clinical outcomes in patients with intracerebral hemorrhage (ICH).Methods: In the retrospective cohort study, we analyzed data from 250 patients with intracerebral hemorrhage (85 women and 165 men) to investigate the difference in UA levels between patients with a good prognosis and those with a poor prognosis. Additionally, we analyzed the impact of UA levels on the risk of short-time prognosis of ICH patients.Results: Patients with a good prognosis presented with significantly lower levels of UA (348.71 ± 84.97 μmol/L) than those with poor prognosis (393.06 ± 148.46 μmol/L). Furthermore, multivariate logistic regression model demonstrated that a high UA level was a likely risk factor for worse prognosis among patients suffering in ICH (odds ratio [95% confidence interval], 1.006 [1.0012, 1.0108]; P = 0.015). Additionally, UA has a threshold effect value of 363.9 μmol/L and was presented in levels that were in a nonlinear relationship with incidence rate of short-time prognosis outcome of ICH patients.Conclusion: Our findings indicate that higher UA levels can increase the risk of poor clinical prognosis in patients with ICH and high UA levels are not conductive to the clinical prognosis of patients with ICH. These findings provide a new perspective on the treatment and prevention of ICH.Keywords: intracerebral hemorrhage, uric acid, oxidative stress, follow-up, nonlinear relationship, prognosis

Mengqi Wang,1,&ast; Shuting Lan,1,&ast; Wenqi Zhang,1,&ast; Qin Jin,2 Hua Du,3 Xiaomei Sun,1 Lijun He,1 Xiangyun Meng,1 Liya Su,1 Gang Liu1 1Key Laboratory of Medical Cell Biology, Department of Achievement Transformation, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, People’s Republic of China; 2Department of Pathology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People’s Republic of China; 3Department of Pathology, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gang Liu, Email 20190043@immu.edu.cnIntroduction: The anti-cancer potency of copper-doped carbon quantum dots (Cu-CDs) against breast cancer progression needs more detailed investigations.Methods: With urea and ethylene glycol applied as carbon sources and copper sulfate used as a reactive dopant, Cu-CDs were synthesized in the current study by a one-step hydrothermal synthesis method, followed by the characterization and biocompatibility evaluations of Cu-CDs. Subsequently, the anti-cancer potency of Cu-CDs against breast cancer progression was confirmed by these biochemical, molecular, and transcriptomic assessments, including viability, proliferation, migration, invasion, adhesion, clonogenicity, cell cycle distribution, apoptosis, redox homeostasis, and transcriptomic assays of MDA-MB-231 cells.Results: The biocompatibility of Cu-CDs was confirmed based on the non-significant changes in the pathological and physiological parameters in the Cu-CDs treated mice, as well as the noncytotoxic effect of Cu-CDs on normal cells. Moreover, the Cu-CDs treatments not only decreased the viability, proliferation, migration, invasion, adhesion, and clonogenicity of MDA-MB-231 cells but also induced the redox imbalance, cell cycle arrest, and apoptosis of MDA-MB-231 cells via ameliorating the mitochondrial dysfunctions and regulating the MAPK signaling pathway.Conclusion: Our findings confirmed the biosafety and excellent anti-cancer potency of Cu-CDs against breast cancer progression by tapping into mechanisms that disrupt malignant behaviors and oxidative homeostasis of breast cancer cells.Keywords: copper, carbon quantum dots, breast cancer, oxidative stress, MAPK signaling pathway

Sisi Zhang,1 Miao Yu,2 Yu Zhang,2 Conying Liang,2 Dayi Hu,1 Dao Wen Wang,1 Xiaoping Meng2 1Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Department of Cardiology and Cardiac Rehabilitation, Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, 130000, People’s Republic of ChinaCorrespondence: Xiaoping Meng, Department of Cardiology and Cardiac Rehabilitation, Affiliated Hospital of Changchun University of Chinese Medicine, &num;1473 Gongnong Road, Chaoyang District, Changchun, 130000, People’s Republic of China, Email xiopingmeng@126.comPurpose: This study aimed to translate and cross-culturally adapt the cardiac rehabilitation barriers scale to the Chinese, and examine its reliability and validity among the older population.Methods: An approach comprising translation, cultural adaptation, reliability, and validity examination in the Chinese version was conducted in two hospitals in Jilin, China. The t-tests were used to compare the sex differences between each item. Participants included Chinese individuals > 60 who were eligible for the cardiac rehabilitation program.Results: In total, 325 participants completed the questionnaire with an average age of 61.23 ± 9.68 years. The item-total correlations were 0.432 to 0.678. Factor analysis of CRBS-C (Kaiser Meyer Olkin = 0.867, Bartlett’s test p = 0.000) revealed four factors: logistical factors, comorbidities/functional status, perceived need/healthcare factors, and work/time conflict. The confirmatory factor analysis (CFA) indicated a good model fit (χ 2/df = 1.84, RMSEA = 0.051, CFI = 0.953, TLI = 0.945, SRMR=0.046). Cronbach’s alpha was 0.88 for the scale, ranging from 0.801 to 0.88 for each item, which indicates the internal reliability was acceptable.Conclusion: The Chinese version of the CRRS has acceptable reliability and validity in the Chinese elderly population.Keywords: cardiac rehabilitation, internal reliability, cross-cultural adaptation, exploratory factor analysis, confirmatory factor analysis

Nan Du,1,2 Xiaojing Meng,1,2 Jingwei Li,2 Li Shi,2 Xulai Zhang1,2 1Affiliated Psychological Hospital of Anhui Medical University, Hefei Fourth People’s Hospital, Hefei, 230022, People’s Republic of China; 2Anhui Clinical Center for Mental and Psychological Diseases, Hefei Fourth People’s Hospital, Hefei, 230022, People’s Republic of ChinaCorrespondence: Xulai Zhang, Hefei Fourth People’s Hospital, 316 Mei shan Road, Hefei, Anhui, 230032, People’s Republic of China, Email xulaizhang@163.comBackground: Schizophrenia (SCZ) is a severe mental illness, Cognitive deficits and negative symptoms (NS) are prevalent in individuals with SCZ and are crucial indicators of functional recovery. It is well known that cognitive symptoms and negative symptoms are interrelated and that negative symptoms can affect the ability to take cognitive tests. However, the specific relationship between attention, working memory (WM), and NS in stable SCZ remains unclear. This study aims to explore these associations and provide valuable insights for the subsequent treatment of SCZ.Methods: We conducted a comprehensive assessment of 145 patients with stable SCZ using the Chinese Brief Neurocognitive Suite of Tests (C-BCT) and the Positive and Negative Symptom Scale (PANSS).Results: Patients with abnormal cognition exhibited significantly higher PANSS total scores, cognitive symptom scores, and NS than those with normal cognition (P< 0.05). Pearson’s correlation analysis revealed significant positive correlations between digital breadth(DB) and continuous operation(CO) (r=0.389, P< 0.001), as well as a significant negative correlation between DB and NS (r=− 0.291, P< 0.001). Moreover, CO showed a negative correlation with NS (r=− 0.173, P< 0.05). However, no significant correlations were found between the digital breadth-anterograde score and CO or NS (r=0.148, P> 0.05; r=− 0.068, P> 0.05). Notably, NS were identified as a mediator in the relationship between attention and WM (effect size=0.024).Conclusion: Our findings highlight significant associations between WM, attention, and NS in individuals with stable SCZ. Moreover, attention not only directly impacts WM but also indirectly influences it through NS. Addressing cognitive deficits and NS in the treatment of SCZ may lead to improved overall outcomes for affected individuals.Keywords: stable schizophrenia, working memory, attention, negative symptom, intermediary effect

Yue Zhang, Ruoxin Pan, Duoduo Gu, Xiaoqi Meng, Tingwei Liu, Yang Xu Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, 210029, People’s Republic of ChinaCorrespondence: Yang Xu, Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, Jiangsu Province, 210029, People’s Republic of China, Tel/Fax +86-13851856794, Email yangxu@njmu.edu.cnBackground and Aim: Clinical manifestations of rosacea include transient or persistent facial erythema, telangiectasia, papules, and pustules. The existing assessment tools primarily evaluate the facial area to assess the severity of rosacea. However, in addition to the face, telangiectasia, erythema, and flushing can occur in the ear. Here, we investigated the correlation between the dermoscopic characteristics of capillaries in the earlobe and auricle and the types and severity of rosacea.Materials and Methods: Experienced dermatologists evaluated the clinical type, medical history, severity, and distribution pattern of facial erythema. The clinical severity of rosacea was assessed using the standard grading system (SGS), clinician’s erythema assessment (CEA), and investigator’s global assessment (IGA). Relationships of the clinical types and severity with the dermoscopic characteristics of capillaries in the earlobe and auricle were further analyzed.Results: In total, 145 patients with rosacea were enrolled in this study. We found that SGS, CEA, and IGA correlated well with the dermoscopic features of capillaries in the earlobe (R = 0.357, 0.357, and 0.314, respectively) (p < 0.001) and auricle (R = 0.423, 0.443, and 0.374, respectively) (p < 0.001). However, there was no significant correlation between the features and types of rosacea.Conclusion: The dermoscopic characteristics of capillaries in the earlobe and auricle can be used as indicators of the clinical severity of rosacea, regardless of the clinical subtype.Keywords: skin conditions, ear, dermoscopy, blood vessels

Peng Yu,1– 4 Ranran Kan,1,3 Xiaoyu Meng,1,3 Zhihan Wang,1,3 Yuxi Xiang,1,3 Beibei Mao,1,3 Xuefeng Yu1,3 1Department of Endocrinology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Endocrinology, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Branch of National Clinical Research Center for Metabolic Diseases, Hubei, People’s Republic of China; 4Key Laboratory for Molecular Diagnosis of Hubei Province, Wuhan, People’s Republic of ChinaCorrespondence: Xuefeng Yu, Department of Internal Medicine, Tongji Hospital, Huazhong University of Science and Technology, No. 1095, Jiefang Road, Wuhan, 430030, People’s Republic of China, Tel +8602783663331, Email xfyu188@163.comBackground: In China, the spectrum of causes for CKD has been changing in recent years, and the proportion of CKD caused by cardiometabolic diseases, such as diabetes and hypertension continues to increase. Thus, predicting CKD based on cardiometabolic risk factors can to a large extent help identify those at increased risk and facilitate the prevention of CKD. In this study, we aimed to develop a nomogram for predicting CKD risk based on cardiometabolic risk factors.Methods: We developed a nomogram for predicting CKD risk by using a subcohort population of the 4C study, which was located in central China. The prediction model was designed by using a logistic regression model, and a backwards procedure based on the Akaike information criterion was applied for variable selection. The performance of the model was evaluated by the concordance index (C-index), and Hosmer‒Lemeshow goodness-of-fit test. The bootstrapping method was applied for internal validation.Results: During the 3-years follow-up, 167 cases of CKD developed. By using univariate and multivariate logistic regression models, the following factors were identified as predictors in the nomogram: age, sex, HbA1c, baseline eGFR, low HDL-C levels, high TC levels and SBP. The bootstrap-corrected C-index for the model was 0.84, which indicated good discrimination ability. The Hosmer‒Lemeshow goodness-of-fit tests yielded chi-square of 13.61 (P=0.192), and the calibration curves demonstrated good consistency between the predicted and observed probabilities, which indicated satisfactory calibration ability.Conclusion: We developed a convenient and practicable nomogram for the 3‑year risk of incident CKD among a population in central China, which may help to identify high-risk individuals for CKD and contribute to the prevention of CKD.Keywords: CKD, cardiometabolic risk factors, nomogram

Daqiu Wang,1 Xin Meng,2 Lei Liu,1 Aiping Wang2 1Liaoning University of Traditional Chinese Medicine, Shenyang, People’s Republic of China; 2The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Aiping Wang, Department of Public Service, the First Affiliated Hospital of China Medical University, No. 155, Nanjing North Street, Heping District, Shenyang, Liaoning Province, People’s Republic of China, Tel + (0086)02483282288, Fax + (0086)02483282288, Email jianghaoran88@hotmail.comPurpose: To explore how elderly patients with chronic conditions identify and cope with suspected adverse drug events (ADEs) in northern China with the aim of encouraging the elderly to participate in medication safety monitoring.Patients and Methods: A purposive sampling method was adopted to select 15 elderly patients with chronic conditions from a medical center in northern China for semi-structured-interviews, and the data were collated and analyzed through thematic framework analysis.Results: Five major themes and 12 subthemes were refined, namely (1) lack of knowledge: poor awareness of the medications and ambiguous knowledge of ADEs, (2) barriers to identifying suspected ADEs: unawareness and uncertainty, seeking alternative explanations, and limited access to information, (3) the basis for identifying suspected ADEs: time cues and actively seeking communication (4) coping with suspected ADEs: cope with it themselves, not talking to the health care provider on their own initiative and actively seeking communication, and (5) expectations: desire for more reliable information and hope to be safeguarded for medication safety.Conclusion: Due to the lack of relevant knowledge and limited access to information, the elderly were limited in identifying suspected ADEs, but they were positive towards participating in medication safety monitoring and hoped to obtain reliable medication information and detailed medication assessment by enhancing communication with medical professionals in order to achieve medication safety.Keywords: the elderly, adverse drug events, medication safety, qualitative study

Chen Li,1,&ast; Jun Hao,2,&ast; Chuangshi Wang,2 Jie Yang,1 Yitian Zheng,1 Kuo Zhang,3 Wen Hui,4 Xiangbin Meng,1 Jun Gao,1 Wei Li,2 Yi-Da Tang1,5 1Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, People’s Republic of China; 2Medical Research and Biometrics Center, National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 4Department of Science and Technology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 5Research Unit of Medical Science Research Management/Basic and Clinical Research of Metabolic Cardiovascular Diseases, Chinese Academy of Medical Sciences, Beijing People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Li; Yi-Da Tang, Email liwei@mrbc-nccd.com; tangyida@bjmu.edu.cnObjective: The incidence rate of thyroid diseases increased worldwide. This study aims to overview the changing landscape of drug clinical trials on thyroid disease during 2009– 2022.Methods: The detailed information of thyroid disease drug trials registered on the National Medical Products Administration (NMPA) Registration and Information Disclosure Platform for Drug Clinical Studies was searched and collected. The thyroid drug clinical trials were analyzed by the characteristics, time trends, indications, and geographical distribution.Results: Sixty-five thyroid disease drug clinical trials were launched from 2009 to 2022 in China, which included 21 trials in nontumorous thyroid disease and 44 trials in thyroid carcinoma. The number of registered trials of thyroid diseases including thyroid carcinoma and nontumorous thyroid disease increased steadily from 2009 to 2020. Bioequivalence studies accounted for the largest proportion (32[49.2%]), while phase I and Phase II studies both only accounted for 18.5% (12/65). A significant difference was observed in the trials phase, and randomization between thyroid carcinoma and nontumorous thyroid disease. In terms of clinical indications and drug mechanisms, the number of trials in multi-target tyrosine kinase inhibitors for thyroid carcinoma (n=35) ranked first, followed by thyroid hormone for hypothyroidism (n=7), thyrotropin for thyroid carcinoma (n=6). Sixty-five trials were led by 36 principal investigator (PI) units, and more than 30% of PI-leading units were located in Shanghai (n=7) and Beijing (n=4).Conclusion: During the past 13 years, the development of thyroid diseases drugs trials has achieved certain progress in thyroid carcinoma, especially the molecular targeted therapy, yet the development of drug trials on nontumorous thyroid disease was very slow.Keywords: thyroid disease, thyroid carcinoma, nontumorous thyroid disease, China, drug clinical trial

Yujun Xiong,1,&ast; Haoqi Yan,2,&ast; Lang Qu,3 Shuqi Wang,4 Xiangda Meng,5 Xingyun Zhu,6 Pan Zhang,1 Su Yuan,2 Jihua Shi1 1Department of Gastroenterology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Department of Anesthesiology, Fuwai Hospital, National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences; Peking Union Medical College, Beijing, 100037, People’s Republic of China; 3Department of Anesthesiology, Shanghai General Hospital, Shanghai, People’s Republic of China; 4Department of Otolaryngology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 5Department of Neurosurgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 6Department of Endocrinology, Beijing Jishuitan Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Su Yuan, Department of Anesthesiology, Fuwai Hospital, Chinese Academy of Medical Sciences; Peking Union Medical College, Xicheng District, Beijing, People’s Republic of China, Email fuwaiys@126.com Jihua Shi, Department of Gastroenterology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 100370, People’s Republic of China, Email shijihua1981@sina.comBackground: Gastrointestinal (GI) endoscopy becomes more and more common now in order to diagnose and treat GI diseases, and anesthesia/sedation plays an important role. We aim to discuss the developmental trends and evaluate the research hotspots using bibliometric methods for GI endoscopy anesthesia/sedation in the past two decades.Methods: The original and review articles published from 2001 to December 2022 related to GI endoscopy anesthesia/sedation were extracted from the Web of Science database. Four different softwares (CiteSpace, VOSviewer, and Bibliometrix, Online Analysis Platform of Literature Metrology (Bibliometric)) were used for this comprehensive analysis.Results: According to our retrieval strategy, we found a total of 3154 related literatures. Original research articles were 2855, and reviews were 299. There has been a substantial increase in the research on GI endoscopy anesthesia/sedation in recent 22 years. These publications have been cited 66,418 times, with a mean of 21.04 citations per publication. The US maintained a leading position in global research, with the largest number of publications (29.94%), and China ranked second (19.92%). Keyword burst and concurrence showed that conscious sedation, colonoscopy and midazolam were the most frequently occurring keywords.Conclusion: Our research found that GI endoscopy anesthesia/sedation was in a period of rapid development and demonstrated the improvement of medical instruments and surgical options that had significantly contributed to the field of GI endoscopy anesthesia/sedation. The US dominates this field, and the selection and dosage of sedative regimens have always been the foci of disease research to improve comfort and safety, while adverse events and risks arouse attention gradually. In the past 20 years, hotspots mainly focus on upper gastrointestinal endoscopy, gastroscopy, and esophagogastroduodenoscopy. These data would provide future directions for clinicians and researchers regarding GI endoscopy anesthesia/sedation.Keywords: gastrointestinal endoscopy anesthesia, sedation, bibliometric analysis, CiteSpace, VOSviewer

Lijun Zuo,1 Yanhong Dong,2 Yuesong Pan,3 Hongyi Yan,3 Xia Meng,3 Hao Li,3 Xingquan Zhao,1 Yilong Wang,1 Yongjun Wang,1 Xiaoling Liao1 1Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Alice Lee Centre for Nursing Studies, Yong Loo Lin School of Medicine, National University of Singapore, Clinical Research Centre, Singapore, 117597, Singapore; 3National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Xiaoling Liao, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No. 119, South Fourth Ring West Road, Fengtai District, Beijing, 100070, People’s Republic of China, Tel +86-010-59978350, Fax +86-010-59973383, Email liao828@sina.comObjective: Cognitive impairment after stroke/transient ischemic attack (TIA) has a high prevalence. Cystatin C (CysC) has been found as a novel biomarker of neurodegenerative diseases, such as dementia and Alzheimer’s disease. We aimed to explore the possible correlations of serum CysC level with cognitive impairment in patients who had mild ischemic stroke and TIA after 1 year.Methods: We measured serum CysC level in 1025 participants with a minor ischemic stroke/TIA from enrolled from the Impairment of Cognition and Sleep (ICONS) study of the China National Stroke Registry-3 (CNSR-3). They were divided into four groups according to quartiles of baseline CysC levels. Patients’ cognitive functions were assessed by Montreal Cognitive Assessment (MoCA)-Beijing at day 14 and at 1 year. Multiple logistic regression models were performed to evaluate the relationship between CysC and post-stroke cognitive impairment (PSCI) at 1-year follow-up.Results: Cognitive impairment was defined as MoCA-Beijing ≤ 22. Most patients were in 60s (61.52± 10.97 years old) with a median (interquartile range) National Institute of Health Stroke Scale(NIHSS) score of 3.00 (4.00) and greater than primary school level of education, and 743 participants (72.49%) were male. Among the 1025 participants, 331 participants (32.29%) patients suffered PSCI at 1-year follow-up. A U-shaped association was observed between CysC and 1-year PSCI [quartile (Q)1 vs Q3: adjusted odds ratio (aOR) 2.69, 95% CI 1.67– 4.34, p < 0.0001; Q2 vs Q3: aOR 1.63, 95% CI 1.03– 2.57, p = 0.0354; Q4 vs Q3: aOR 1.83, 95% CI 1.16– 2.87, p = 0.009]. Moreover, the U-shaped trends were also found between CysC level and the subscores of attention, recall, abstraction and language in MoCA.Conclusion: CysC showed a U-shaped correlation with 1-year overall cognitive function. It is probable that measurement of the serum CysC level would aid in the early diagnosis of PSCI.Keywords: mild stroke, post stroke cognitive impairment, cystatin C

Yuhong Gan,1 Xiaobin Meng,1 Nanfeng Lei,1 Hong Yu,1 Qingkao Zeng,2 Qingyan Huang3,4 1Department of Clinical Pharmacy, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 2Department of Intensive Care Unit, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 3Center for Precision Medicine, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 4Guangdong Provincial Engineering and Technology Research Center for Clinical Molecular Diagnostics and Antibody Therapeutics, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of ChinaCorrespondence: Qingyan Huang, Center for Precision Medicine, Guangdong Provincial Engineering and Technology Research Center for Clinical Molecular Diagnostics and Antibody Therapeutics, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, No. 63 Huangtang Road, Meijiang District, Meizhou, 514031, People’s Republic of China, Tel +86 753 2131 591, Email Huangqingyan03@163.comPurpose: This study aimed to investigate the pharmacokinetics and target attainment of meropenem and compare the effect of meropenem dosing regimens in critically ill patients.Patients and Methods: Thirty-seven critically ill patients who were administered meropenem in intensive care units were analyzed. Patients were classified according to their renal function. Pharmacokinetic parameters were assessed based on Bayesian estimation. The target attainment of 40%fT > MIC (fraction time that the free concentration exceeds the minimum inhibitory concentration) and 100%fT > MIC with the pathogen MIC of 2 mg/L and 8 mg/L were specially focused. Furthermore, the effects of standard dosing (1g meropenem, 30 min intravenous infusion every 8h) and non-standard dosing (dosage regimens except standard dosing) were compared.Results: The results showed that the values of meropenem clearance (CL), central volume of distribution (V1), intercompartmental clearance (Q), and peripheral volume of distribution (V2) were 3.3 L/h, 9.2 L, 20.1 L/h and 12.8 L, respectively. The CL of the patients among renal function groups was significantly different (p < 0.001). The tow targets attainment for the pathogen MIC of 2 mg/L and 8 mg/L were 89%, 73%, 49% and 27%, respectively. The severe renal impairment group has higher fraction of target attainment than the other group. The standard dosing achieved the target of 40%fT > 2/8 mg/L (85.7% and 81%, respectively) and patients with severe renal impairment achieved the target fraction of 100% for 40%fT > MIC. Additionally, there was no significant difference between standard and non-standard dosing group in target attainment.Conclusion: Our findings indicate that renal function is an important covariate for both meropenem pharmacokinetics parameters and target attainment. The target attainment between standard and non-standard dosing group was not comparable. Therefore, therapeutic drug monitoring is indispensable in the dosing adjustment for critically ill patients if it is available.Keywords: meropenem, critically ill patients, pharmacokinetics, therapeutic drug monitoring

Hongyu Zhou,1,2 Weiqi Chen,1,2 Yue Suo,1,2 Xia Meng,1,2 Xingquan Zhao,1,2 Mengxing Wang,1,2 Liping Liu,1,2 Hao Li,1,2 Yuesong Pan,1,2 Yongjun Wang1– 4 1Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, People’s Republic of China; 4Research Unit of Artificial Intelligence in Cerebrovascular Disease, Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Yongjun Wang; Yuesong Pan, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China, Email yongjunwang@ncrcnd.org.cn; yuesongpan@ncrcnd.org.cnBackground: There is a close brain–kidney interaction following ischemic cerebrovascular disease. The new-onset kidney injury after stroke leads to severe neurological deficits and poor functional outcomes. We aimed to validate the Nelson equation for predicting the new-onset and long-term kidney function decline in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA).Methods: A total of 3169 patients were enrolled in the Third China National Stroke Registry, whose baseline estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2. The outcome of interest was the incident eGFR< 60 mL/min/1.73 m2 at 3 months. The prediction equation of participants with or without diabetes was validated respectively. The receiver operating characteristic curve (AUC) evaluated prediction performance. The Delong test compared the Nelson equation performance with the O’Seaghdha equation and the Chien equation. Continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were determined to evaluate the incremental effect.Results: During the 3-mo follow-up period, among 1151 patients with diabetes, there were 31 cases (2.7%) of reduced eGFR. Meanwhile, among 2018 non-diabetic patients, there were 23 cases (1.1%) of reduced eGFR. The Nelson equation showed good discrimination and was well-calibrated in patients with diabetes (AUC 0.82, Hosmer-Lemeshow test p = 0.67) or without diabetes (AUC 0.82, Hosmer-Lemeshow test p = 0.09). The performance of the Nelson equation was superior to other equation, as increased continuous NRI (diabetic, 0.64; non-diabetic, 1.13) and IDI (diabetic, 0.10; non-diabetic, 0.13) to the Chien equation.Conclusion: The Nelson equation reliably predicted the risks of the new-onset and long-term kidney function decline in patients with AIS or TIA, which could help clinicians screen high-risk patients and improve clinical care.Keywords: stroke, transient ischemic attack, kidney disease, prognosis, risk factors

Yalan Yang,1,&ast; Dao Xin,2,&ast; Huike Wang,1,&ast; Lulu Guan,1 Xiangrui Meng,1 Taiying Lu,1 Xiwen Bai,3 Feng Wang1 1Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Medical Oncology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Translational Medicine, Nanchang University Queen Mary School, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Wang, Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China, Email zzuwangfeng@zzu.edu.cnPurpose: Neoadjuvant immunochemotherapy (nICT) for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC) has attracted widespread attention recently, whose safety and clinical benefit was observed in clinical researches. This study aimed to develop and validate a novel predictor systemic inflammation-tumor markers index (SITI) to predict the pathological complete response (pCR) for resectable LA-ESCC patients receiving nICT.Patients and Methods: A total of 147 LA-ESCC patients who underwent nICT followed by surgery from February 2020 to April 2022 were included in the study. The dynamic change of inflammatory indexes was compared at baseline, after two cycles of nICT and postoperative one month. Least absolute shrinkage and selection operator (LASSO) regression was performed to avoid collinearity and identify key indexes, with SITI constructed. After univariate and multivariate stepwise forward logistic analyses, a nomogram for pCR prediction was developed.Results: 41(27.9%) patients achieved pCR among 147 resectable LA-ESCC patients received nICT. Compared with baseline, most inflammatory indexes were significantly decreased at postoperative one month. 5 key indexes were identified and then a predictive index named SITI was constructed. The result showed that lower SITI and earlier clinical tumor node metastasis (cTNM) stage were more likely to achieve pCR. The nomogram for pCR prediction had excellent discrimination performance (C-index = 0.791).Conclusion: The SITI is an independent predictor for pCR in resectable LA-ESCC patients received nICT. To our knowledge, our nomogram is the first model using systemic inflammation-tumor markers for pCR prediction and may be a promising predictor to effectively differentiate pCR for nICT in LA-ESCC patients.Keywords: esophageal squamous cell carcinoma, neoadjuvant therapy, immunotherapy, pathologic complete response, inflammation, nomogram

Lin Li,1– 3,&ast; Yuwei Zhang,1,3,&ast; Yudan Luo,1 Xianghui Meng,1 Guixiang Pan,4 Han Zhang,1– 3 Yuhong Li,1– 3 Boli Zhang1,3 1Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, People’s Republic of China; 2Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, People’s Republic of China; 3State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, People’s Republic of China; 4Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300250, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuhong Li; Boli Zhang, Tianjin University of Traditional Chinese Medicine, 10 Poyang Lake Road, Jing Hai District, Tianjin, 301617, People’s Republic of China, Email yhltcm@126.com; zhangbolipr@163.comAbstract: Astragali Radix is a significant traditional Chinese medication, and has a long history of clinical application in the treatment of diabetes mellitus (DM) and its complications. AS-IV is an active saponin isolated from it. Modern pharmacological study shows that AS-IV has anti-inflammatory, anti-oxidant and immunomodulatory activities. The popular inflammatory etiology of diabetes suggests that DM is a natural immune and low-grade inflammatory disease. Pharmacological intervention of the inflammatory response may provide promising and alternative approaches for the prevention and treatment of DM and its complications. Therefore, this article focuses on the potential of AS-IV in the treatment of DM from the perspective of an anti-inflammatory molecular basis. AS-IV plays a role by regulating a variety of anti-inflammatory pathways in multiple organs, tissues and target cells throughout the body. The blockade of the NF-κB inflammatory signaling pathway may be the central link of AS-IV’s anti-inflammatory effect, resulting in a reduction in the tissue structure and function damage stimulated by inflammatory factors. In addition, AS-IV can delay the onset of DM and its complications by inhibiting inflammation-related oxidative stress, fibrosis and apoptosis signals. In conclusion, AS-IV has therapeutic prospects from the perspective of reducing the inflammation of DM and its complications. An in-depth study on the anti-inflammatory mechanism of AS-IV is of great significance for the effective use of Chinese herbal medicine and the promotion of its status and influence on the world.Keywords: astragaloside IV, anti-inflammatory property, molecular basis, diabetes, complications

Xiaonan Meng,1,2,&ast; Jie Sun,3,&ast; Qi Liu,4,&ast; Yueping Huang,5 Xianwen Qiu,6 David Jung Seto,7,8 Ying Li,3 Liping Wang,2 Chunying Li,2 Sen Gao,9 Haikuo Yu,10 Jiping Zhao,1 Baixiao Zhao1 1Department of Acupuncture and Moxibustion, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Department of Acupuncture and Moxibustion, Beijing Huguosi TCM Hospital, Affiliated with Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Department of Integrated Chinese and Western Medicine Rehabilitation, Beijing Xiaotangshan Hospital, Beijing, People’s Republic of China; 4Department of General Internal Medicine, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 5School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 6Department of Acupuncture and Moxibustion, Beijing Shichahai Community Healthcare Center, Beijing, People’s Republic of China; 7Division of Integrative Medicine, Department of Medicine, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA; 8Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA; 9Department of Rehabilitation, Beijing Huguosi TCM Hospital, affiliated with Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 10Rehabilitation Department, Xuanwu Hospital Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiping Zhao; Baixiao Zhao, Email zjp7883@sina.com; baixiao100@vip.sina.comBackground: Post-stroke shoulder-hand syndrome (PS-SHS), a common neurological comorbidity after stroke episodes, poses a grave threat on patients’ functional recovery. Preliminary trials have demonstrated that the acupuncture and moxibustion treatment, including a dermal acupuncture tapping method known as plum blossom needling (PBN) can improve pain and motor dysfunctions in patients with PS-SHS. However, there are few reports describing simultaneous moxibustion treatment in combination with PBN. Hence, a novel plum blossom needle device with mild moxibustion (PBNMM) was developed to evaluate its potential efficacy and safety in patients with stage 1 PS-SHS.Materials and Methods: This multicenter, sham-controlled, randomized controlled trial (RCT) will recruit 102 eligible patients with stage 1 PS-SHS from three clinical centers, randomly allocated in a ratio of 1:1:1 to the PBNMM group, PBNMM with no moxa smoke (PBNMM-NMS) group and sham control group. Patients in each group will receive a 30-minute treatment once per day for 4 weeks, with 5 consecutive sessions per week, for a total of 20 sessions. The primary outcome measure will be defined as the decreased scores from baseline in the visual analog scale (VAS) assessment at week 4. Secondary outcome measures will include scores on the Fugl-Meyer Assessment of the Upper Extremity Scale (FMA-UE), the Modified Barthel Index (MBI), and the somatosensory evoked potential (SEP) records. All outcomes will be evaluated at baseline and weeks 4, 5, 6 and 10, and the intention-to-treat analysis will be applied.Conclusion: This study aims to provide robust evidence for the efficacy and safety of the PBNMM for PS-SHS treatment, as well as the specific impact of moxibustion smoke itself in dealing with PS-SHS.Clinical Trial Registration: Chinese Clinical Trial Registry No. ChiCTR2200062441. Registered on 7 August 2022.Keywords: plum blossom needling, mild moxibustion, novel device, post-stroke shoulder-hand syndrome, protocol, randomized controlled trial

Yitian Zheng,1– 3,&ast; Yu Qi,1,&ast; Samuel Seery,4,5 Jie Yang,2,3 Chen Li,2,3 Wenyao Wang,1 Jun Gao,1 Xiangbin Meng,1 Chunli Shao,1 Yi-Da Tang1 1Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, People’s Republic of China; 2Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 4School of Humanities and Social Sciences, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, People’s Republic of China; 5Faculty of Health and Medicine, Division of Health Research, Lancaster University, Lancaster, UK&ast;These authors contributed equally to this workCorrespondence: Yi-Da Tang, Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, 100191, People’s Republic of China, Email tangyida@bjmu.edu.cnObjective: Anti-inflammatory therapies are reported to have additional benefits beyond lipid control for patients with cardiovascular disease. However, no study has focused on the relationship between inflammation status and long-term outcomes for chronic obstructive pulmonary disease (COPD) patients, after percutaneous coronary intervention (PCI).Methods: 277 COPD-PCI patients were divided into two groups according to hsCRP status upon admission. Major adverse cardiac events (MACE) in high hsCRP patients were compared to patients with low hsCRP. Restricted cubic spline (RCS) analysis was performed using MACE hazard ratios (HR) to investigate interrelations with hsCRP, as a continuous variable.Results: Patients in the high hsCRP group incurred more inflammation activation, in terms of higher white blood cell counts, neutrophil, lymphocytes, and had higher smoking rates, compared to those with lower hsCRPs. A significant increase in MACEs was observed in hsCRP high group, compared to the low hsCRP group (HR: 2.47, 95% CI: 1.22– 5.00; p = 0.012). RCS curves suggest that HRs rise beyond 1.0, after the 0.24 juncture for Lg HsCRP (base 10 logarithm with hsCRP), HR per SD: 1.19 (95% CI: 0.96– 1.48). Further subgroup analysis implies that elevated hsCRP is associated with a higher risk of MACEs across the sub-groups tested.Conclusion: HsCRP could be a useful indicator for COPD-CAD patient prognosis, after PCI. This is because hsCRP highlights inflammation activation. More multi-center research, designed for COPD-CAD patients should be conducted to more accurately determine the cut-off value for hsCRP.Keywords: HsCRP, chronic obstructive pulmonary disease, coronary artery disease, percutaneous coronary intervention, outcomes

Chenchen Niu,1 Xiangxiang Meng,2 Fei Xiang1 1School of Management, Qilu University of Technology, Jinan, People’s Republic of China; 2Department of Business Management, Shandong University of Finance and Economics, Jinan, 250353, People’s Republic of ChinaCorrespondence: Chenchen Niu, Tel +86-153-7666-3653, Email ncc0811@163.comPurpose: Drawing on social exchange theory and attribution theory, this study aims to explore the influencing mechanism of paradoxical leadership on organizational citizenship behavior.Participants and Methods: According to the research purpose, this study selects enterprises in the manufacturing, financial and high-tech industries in Shandong Province as the research objects, and collects data on the leaders and employees of the human resources departments and marketing departments in the enterprises. Data were collected from 77 leaders and 473 employees in China by a two-wave questionnaire survey. Hierarchical regression analysis and structural equation model approach were employed to test hypotheses.Results: This study found that perceived insider status and psychological entitlement play mediating roles about paradoxical leadership and organizational citizenship behavior; Collectivism moderates the relationship between paradoxical leadership and perceived insider status, and moderates the positive mediating role played by perceived insider status in the relationship of paradoxical leadership and organizational citizenship behavior; Leader-member exchange differentiation moderates the relationship about paradoxical leadership and psychological entitlement, and moderates negative mediating role played by psychological entitlement in the relationship of paradoxical leadership’s and organizational citizenship behavior.Conclusion: The findings of this study offer guidance for managers to better undermine the negative effects of paradoxical leadership, and improve organizational citizenship behavior.Innovations: First, this study extends the literature on paradoxical leadership by verifying the double-edged sword effect of paradoxical leadership to organizational citizenship behavior. Second, this study enriches one’s understanding of the “black box” underlying the link between paradoxical leadership and its consequences by demonstrating the mediating roles of perceived insider status and psychological entitlement. Third, by verifying the moderating roles of collectivism and leader-member exchange differentiation, this study provides insights into the boundary conditions of the impact of paradoxical leadership.Keywords: paradoxical leadership, organizational citizenship behavior, perceived insider status, psychological entitlement, collectivism, leader-member exchange differentiation

Xiaoning Zhao, Xiaoqian Li, Ying Wang, Weijie Xiao, Baihui Zhang, Xin Meng, Xijia Sun The Department of Anesthesiology, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Xijia Sun, The Department of Anesthesiology, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China, Tel +86 15840015620, Email xijia0822@163.comBackground: Patients undergoing video-assisted thoracoscopic surgery (VATS) frequently suffered postoperative acute and chronic pains. In recent years, intrathoracic intercostal nerve block (INB) is regularly used thanks to its safety and accuracy, especially under the circumstance of lacking ultrasound or in face of the contraindications of the thoracic paravertebral block (TPVB). However, clinical evidence of comparing TPVB and INB for pain management after VATS has been limited and the observation of the chronic pain has been less than clear.Methods: A total of 180 patients undergoing VATS were randomly divided into three groups: A single multi-point paravertebral nerve block (Group P), intrathoracic intercostal nerve block (Group I), and general anesthesia without any regional block (Group C). Postoperative acute pain was scored at rest and coughing by the Visual Analog Scale (VAS) for recording 24h, 48h and 72h after VATS. All patients were interviewed 1, 3 and 6 months after the surgery to investigate both the incidence and intensity of chronic pains.Results: There were significantly less incidence and intensity of acute pain in Group P and Group I, compared to those in Group C. The patients in Group I showed the least incidence and intensity of chronic pain after 3 months compared with those in Group P and Group C. There are 89 of 98 patients suffering pains after 1 month, which grew into chronic pains after 3 months and 78 of them still suffered chronic pains even after 6 months.Conclusion: The intrathoracic INB offers excellent relief from acute and chronic pains, which does as effectively as TPVB. Besides, one-month postoperative pain could increase the risk of a chronic one.Keywords: video-assisted thoracoscopic surgery, acute pain, chronic pain, intrathoracic intercostal nerve block, paravertebral nerve block

Sisi Zhang,1 Houjuan Zuo,1 Xiaoping Meng,2 Dayi Hu1,3 1Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Affiliated Hospital of Changchun Traditional Chinese Medicine, Changchun, People’s Republic of China; 3People’s Hospital of Peking University, Beijing, People’s Republic of ChinaCorrespondence: Xiaoping Meng, Affiliated Hospital of Changchun Traditional Chinese Medicine, Gongnong Avenue No. 1478, Chaoyang District, Changchun, 130000, People’s Republic of China, Tel +86-13180889540, Email xiopingmeng@126.com Dayi Hu, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue No. 1095, Qiaokou District, Wuhan, 430000, People’s Republic of China, Tel +86-13901389171, Email hudayihust@126.comAim: To describe a new model, the Support Life Club (SLC), for participants of Phase II cardiac rehabilitation (CR) programs and to evaluate this model for adherence, completion rates, and clinical outcomes.Methods: This retrospective study involved 391 consecutive patients who participated in an outpatient CR program between September 2016 and May 2020. The intervention group (SLC) was comprised of 198 patients who participated in education, WeChat-based group activity as well as outdoor activities, while the control group (non-intervention) was comprised of 193 cases. All patients attended a 12-week supervised outpatient CR program (three sessions per week, each lasting 40min). The intervention and control groups were compared for completion rates, Cardiopulmonary Exercise Test (CPET) results, Six-minute Walk Test (6MWT) distances, and Patient Health Questionnaire-9 (PHQ-9) scores.Results: Patients in the intervention group attended at least 75% of the exercise training sessions more often than those in the control group (72.5% vs 40.41%, adjusted odds ratio (OR): 27.385; 95% CI: 10.2 to 73.6; P = 0.0000). Analysis of variance (2 × 2 ANOVA) revealed a significant group-by-time interaction in PHQ9 and 6MWT test results (p = 0.000).Conclusion: The addition of SLC to a cardiac rehabilitation program resulted in better outcomes for PHQ9 and 6MWT tests and may be a useful strategy to improve exercise adherence.Keywords: cardiac rehabilitation, support life club, adherence, completion rate, WeChat platform

Xin Meng,1 Ziling Zeng,2 Yunda Wang,3 Shuai Guo,1 Chunjuan Wang,2 Baojie Wang,1 Shougang Guo1,2 1Department of Neurology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 3Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Shougang Guo, Department of Neurology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jing Wu Road, Huaiyin District, Jinan, Shandong, 250021, People’s Republic of China, Tel +86-13220585081, Fax +86-531-87937741, Email guoshougang1124@163.comPurpose: To evaluate the efficacy and safety of low dosages of rituximab (RTX) in the treatment of MuSK-antibody-positive MG patients.Patients and Methods: We retrospectively analyzed the data of MuSK-antibody-positive MG patients who were treated with low dosages of RTX from January 2018 to October 2021. The long-term treatment response to RTX was assessed by Myasthenia Gravis Foundation of America (MGFA) post-interventional status (PIS), Myasthenia Gravis Status and Treatment Intensity (MGSTI), dosage of steroid, MG-related activities of daily living (MG-ADL) and myasthenic muscle score (MMS) at the end of follow-up.Results: Clinical improvement was observed in all eight patients with follow-up for 8 to 29 months after treatment. At the last visit, complete stable remission had been achieved in one patient, pharmacologic remission in three patients, minimal manifestations status in three patients and improved in one patient based on the MGFA-PIS criteria. MGSTI level 2 or better had been reached in six (75%) patients at the last visit. The steroid dosage decreased from 60 mg at baseline to 15 mg at the last follow-up (p = 0.011). The average MG-ADL score decreased from 11 (range 7 to 15) to 0 (range 0 to 3; p = 0.011), and the MMS improved from 38.5 (range 24 to 60) to 100 (range 90 to 100; p = 0.012). These differences were all statistically significant. During RTX treatment and subsequent follow-up, 1 patient reported minor post-infusion malaise.Conclusion: Low-dose RTX is effective and safe for treating anti-MuSK antibody positive MG patients. A long-term response is observed after treatment. Larger prospective studies are required to provide further evidence.Keywords: myasthenia gravis, rituximab, low-dose, muscle-specific kinase

Xiangji Meng,1,&ast; Lei Zhang,2,&ast; Qi Wang,3 Jimin Chen,2 Chunmei Zhang,2 Rongjie Tao,4 Yong Wang5,6 1Department of Neurosurgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, People’s Republic of China; 2Department of Translational Medicine, Genecast Biotechnology Co., Ltd, Wuxi, Jiangsu, 214104, People’s Republic of China; 3Department of Paediatrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China; 4Department of Medical Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, People’s Republic of China; 5Shandong Cancer Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250117, People’s Republic of China; 6Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, Peoples’ Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong Wang, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, No. 440, Jiyan Road, Jinan, Shandong, 250117, People’s Republic of China, Email doctorwy@163.com Rongjie Tao, Department of Medical Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, People’s Republic of China, Email rongjietao@163.comAbstract: Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal tumor that can develop in numerous organs, most commonly in the lungs and rarely in the brain. Here, we reported a 55-year-old patient with nasopharyngeal IMT and the recurrence in the skull base, slope and pterygoid sinus who underwent cranial base and slope tumor resection. Postoperative magnetic resonance imaging (MRI) and multiplex immunohistochemistry (mIHC) showed tumor recurrence and metastasis to the intracalvarium. While genetic testing revealed no significant related gene mutations, tertiary mutations in NSD1 and SOX9 genes were identified in the tumor tissues. The patient achieved partial remission after receiving 7 cycles of immunotherapy (toripalimab 240 mg for 1 cycle followed by 6 cycles of sintilimab 200 mg), and MRI examination indicated an almost complete remission of intracranial IMT after 16 cycles of immunotherapy. In summary, the novel class of immune-targeted agents may be effective in clinical management of rare intracranial IMT.Keywords: inflammatory myofibroblastic tumor, sintilimab, multiplex immunohistochemistry, magnetic resonance imaging, immunotherapy

Xiaonan Meng,1 Liping Wang,1 Chunying Li,1 Sen Gao,2 Haikuo Yu,3 Lufen Zhang,4 Jie Sun5 1Acupuncture Department, Beijing Huguosi TCM Hospital, affiliated with Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Rehablitation Department, Beijing Huguosi TCM Hospital, affiliated with Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Rehabilitation Department, Xuanwu Hospital Capital Medical University, Beijing, People’s Republic of China; 4School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 5Rehabilitation Department of Integrated Chinese and Western Medicine, Beijing Xiaotangshan Hospital, Beijing, People’s Republic of ChinaCorrespondence: Jie Sun, Rehabilitation Department of Integrated Chinese and Western Medicine, Beijing Xiaotangshan Hospital, No. 390 Spring Road, Changping District, Beijing, 102211, People’s Republic of China, Email jiesun1109@gmail.comObjective: This study aims to evaluate the safety and efficacy of various levels of moxibustion smoke concentration (MSC), represented by particulate matter 10mm (PM10), on pain and motor dysfunction in patients with stage 1 post-stroke shoulder-hand syndrome (SHS).Materials and Methods: In this multi-center, sham-controlled, single-blind, randomized controlled trial (RCT), a total of 140 eligible patients with stage 1 post-stroke SHS will be recruited from March 2022 to February 2023 and randomly allocated to five groups in a ratio of 1:1:1:1:1. Moxibustion, in addition to standard medical care, will be applied to subjects in all groups. No acupoints on the affected upper limb will be utilized. Moxibustion smoke therapy, with varying levels of MSC, will be applied to the five groups as follows: (A) sham control group, (B) zero MSC group, (C) low MSC group, (D) medium MSC group, and (E) high MSC group. Patients in each group will be treated for 20 minutes per session, with five sessions each week, over a course of six weeks, with a total follow-up interval of eight weeks. The primary outcome measure will be a visual analog scale (VAS) assessment of the intensity of regionalized pain in the affected upper limb. Secondary outcome measures will include scoring on the Fugl-Meyer Assessment of the Upper Extremity Scale (FMA-UE), the Modified Barthel Index (MBI) and the measurement of somatosensory evoked potential (SEP). All participants will be evaluated before treatment, during treatment (ie, at two weeks and four weeks), immediately after concluding treatment (ie, at six weeks) and at two weeks post-treatment (ie, at eight weeks). Intention-to-treat analysis will be applied.Trial Registration Number: ChiCTR2100043076.Keywords: moxibustion smoke concentration, shoulder-hand syndrome, stroke, protocol, randomized controlled trial

Guitao Zhang,1 Zixiao Li,1– 3 Hongqiu Gu,1– 3 Runhua Zhang,1,2 Xia Meng,1,2 Hao Li,1,2 Yilong Wang,1,2 Xingquan Zhao,1,2 Yongjun Wang,1– 6 Gaifen Liu1,2 On behalf of Chinese Stroke Center Alliance investigators1Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3National Center for Healthcare Quality Management in Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, People’s Republic of China; 5Research Unit of Artificial Intelligence in Cerebrovascular Disease, Chinese Academy of Medical Sciences, Beijing, 2019RU018, People’s Republic of China; 6Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, People’s Republic of ChinaCorrespondence: Yongjun Wang; Gaifen Liu, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Fengtai District, Beijing, 100070, People’s Republic of China, Tel +86 10-59978350 ; +86 10-59976746, Email yongjunwang@ncrcnd.org.cn; liugaifen@ncrcnd.org.cnPurpose: To investigate the effectiveness of dysphagia screening and subsequent swallowing rehabilitation in elderly stroke patients with malnutrition risk.Patients and Methods: Based on the Chinese Stroke Center Alliance (CSCA) from August 1, 2015 to July 21, 2019, we compared the in-hospital adverse outcomes among stroke patients (including ischemic stroke, intracranial hemorrhage, and subarachnoid hemorrhage) over 70 years old with and without dysphagia screening. The primary outcome was in-hospital all-cause mortality. Secondary outcomes were the composite endpoint of discharge against medical advice (DAMA) or in-hospital death.Results: Among 365,530 stroke patients ≥ 70 years old with malnutrition risk in the CSCA, documented dysphagia screening was performed for 288,764 (79.0%) participants. Of these, 41,482 (14.37%) patients had dysphagia, and 33,548 (80.87%) patients received swallowing rehabilitation. A total of 1,694 (0.46%) patients experienced in-hospital death. After adjustment for traditional risk factors, dysphagia screening was associated with a low risk of all-cause mortality in stroke patients [adjusted odds ratio (aOR): 0.75, 95% confidence interval (CI):0.65– 0.87]. Compared to patients with dysphagia who did not receive swallowing rehabilitation, patients reveiving swallowing rehabilitation had a reduced risk of in-hospital death (aOR:0.39, 95% CI: 0.33– 0.46). Additionally, dysphagia screening had a lower risk for the composite endpoint of DAMA or in-hospital death (aOR:0.83,95% CI: 0.80– 0.87), as did subsequent swallowing rehabilitation (aOR:0.43,95% CI: 0.40– 0.47). Similar results were observed in the sensitivity analysis through inverse probability of treatment weighting, propensity score matching, and excluding patients without National Institutes of Health Stroke Scale scores. A similar association was observed between dysphagia management and adverse clinical outcomes in ischemic stroke and intracranial hemorrhage patients.Conclusion: Dysphagia screening and swallowing rehabilitation were associated with a reduced risk of in-hospital death and composite outcome of DAMA or in-hospital death for stroke patients with malnutrition risk. Future research should concentrate on improving the quality of medical care for dysphagia management to improve patients’ outcomes.Keywords: stroke, malnutrition risk, dysphagia screening, in-hospital death, discharge against medical advice

Yu Wang,1,2,&ast; Jiejie Li,1,2,&ast; Yuesong Pan,1,2 Mengxing Wang,1,2 Jinxi Lin,1,2 Xia Meng,1,2 Xiaoling Liao,1,2 Yongjun Wang1– 3 1Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2China National Clinical Research Center for Neurological Diseases, Beijing, People’s Republic of China; 3Research Unit of Artificial Intelligence in Cerebrovascular Disease, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongjun Wang, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China; China National Clinical Research Center for Neurological Diseases, Beijing, People’s Republic of China, Tel +86 10-59978351, Fax +86 10-59978316, Email yongjunwang@ncrcnd.org.cnBackground and Purpose: The relationship between inflammatory markers and cognitive decline in a poststroke setting is still unclear. We aimed to investigate the association between interleukin-6 (IL-6) and cognitive decline after acute ischemic stroke and transient ischemic attack (TIA).Methods: In this prespecified prospective substudy of the Impairment of CognitiON and Sleep after acute ischemic stroke or transient ischemic attack in Chinese patients (ICONS) study, a total of 1003 patients with baseline IL-6 levels and completed standard 3-month and 1-year cognitive function evaluation were included. Cognitive decline was defined according to a reduction of Montreal Cognitive Assessment (MoCA) ≥ 2 between 3 months and one year. Multivariable logistic regression analysis was used to determine the association.Results: Totally, 238 (23.73%) patients had post-stroke cognitive decline at one year. IL-6 levels were classified into four groups according to their quartile. Patients in the highest quartile of IL-6 level had higher risk of cognitive decline than those in the first quartile (25.90% vs 16.80%, adjusted OR, 1.95; 95% CI, 1.13– 3.38, P = 0.0167), after adjusting for potential risk factors.Conclusion: Elevated IL-6 levels were independently associated with reduction of Montreal Cognitive Assessment after ischemic stroke and TIA.Keywords: inflammation, biomarker, stroke, transient ischemic attack, cognitive decline

Xiangxiang Meng,1 Niu Chenchen,2 Fu Liang,3 Yao Ocean Liu4 1Bank of Jining, Jining, 272000, People’s Republic of China; 2School of Management, Qilu University of Technology, Jinan, 250014, People’s Republic of China; 3Department of Business Management, Shandong University of Finance and Economics, Jinan, 250353, People’s Republic of China; 4School of Professional Studies, New York University, New York City, NY, USACorrespondence: Niu Chenchen Tel +86-153-7666-3653Email ncc0811@163.comPurpose: According to attribution theory, the purpose of this paper is to examine the relationship between paradoxical leadership and employees’ compulsory organizational citizenship behavior, research the mediating and moderating effects of work pressure perception and leadership member exchange differentiation.Participants and Methods: The data collection work was carried out with 329 employees as the research object, and empirical tests were carried out using confirmatory factor analysis and hierarchical regression analysis methods.Results: The results of the empirical test show that: paradoxical leadership has a significant positive effect on employees’ compulsory organizational citizenship behavior; work pressure perception plays a mediating role between paradoxical leadership and employee’s compulsory organizational citizenship behavior; leadership member exchange differentiation plays a moderating role between paradoxical leadership and work pressure perception. Paradoxical leadership will lead employees to adopt compulsory organizational citizenship behavior. Moreover, organizations should reduce employees’ perception of work pressure and leadership member exchange differentiation.Conclusion: The results of the study provide positive suggestions for reducing the compulsory organizational citizenship behavior of employees by focusing on the behavior of paradoxical leadership, thereby promoting the improvement of corporate performance.Innovations: 1) The research on the influence of paradoxical leadership on compulsory organizational citizenship behavior reveals the “dark side” of the influence of paradoxical leadership on employee behavior. 2) By introducing work pressure perception, this paper reveals the mechanism of action between paradoxical leadership and compulsory organizational citizenship behavior, which provides a new research perspective for understanding the formation mechanism of employees adopting compulsory organizational citizenship behavior. 3) This paper confirms that leadership member exchange differentiation can positively moderate the relationship between paradoxical leadership and work pressure perception.Keywords: attribution theory, paradoxical leadership, compulsory organizational citizenship behavior, work pressure perception, leadership member exchange differentiation

Fei Gao,1,&ast; Lingtong Shan,2,&ast; Chong Wang,3,&ast; Xiaoqi Meng,4 Jiapeng Chen,5 Lixiang Han,6 Yangyang Zhang,3 Zhi Li6 1Cardiovascular Department, Huaiyin Hospital of Huai’an City, Huai’an, Jiangsu, People’s Republic of China; 2Department of Thoracic Surgery, Sheyang County People’s Hospital, Yancheng, Jiangsu, People’s Republic of China; 3Department of Cardiovascular Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 4The Second Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 5Xinglin College, Nantong University, Nantong, Jiangsu, People’s Republic of China; 6Department of Cardiovascular Surgery, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhi LiDepartment of Cardiovascular Surgery, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People’s Republic of ChinaTel +86 13770606815Email zhili_cths@163.comYangyang ZhangDepartment of Cardiac Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 Huaihai West Road, Shanghai, 200120, People’s Republic of ChinaTel +86 13818132320Email zhangyangyang_wy@vip.sina.comObjective: To evaluate the powers of European Heart Surgery Risk Assessment System II (EuroSCORE II) and the Society of Thoracic Surgeons (STS) score in predicting in-hospital and medium-term mortality of patients undergoing coronary artery bypass grafting (CABG).Methods: Totally 1628 Chinese patients were included between January 2000 and January 2018. Their perioperative clinical data were collected and the patients were closely followed up. According to the length of follow-up time, the total cohort was divided into 1-year, 2-year, 3-year, 4-year and 5-year groups. The in-hospital and medium-term risk prediction of EuroSCORE II and STS score were comparatively assessed by calibration, discrimination, decision curve analysis (DCA), net reclassification index (NRI), integrated discrimination improvement (IDI) and Bland-Altman analysis.Results: About 36 (2.21%) patients died during hospitalization. Both EuroSCORE II and STS score performed extremely well in predicting in-hospital mortality (area under curve = 0.900 and 0.879, respectively). However, calibration and discrimination analyses showed gradual decrease when these two risk evaluation systems were used to predict mortality during the follow-up period. At the same time, the predictive ability of EuroSCORE II was better than STS score. DCA curves showed that the performances of the two evaluation systems were roughly equal between the threshold probability of 0% to 20%. The percentage of correct reclassification of EuroSCORE II was 21.64% higher than that of STS score in predicting 2-year postoperative mortality. The IDI index showed that the predictive capabilities of these two systems were roughly equivalent. Bland-Altman analysis showed no significant difference between the values of the two systems.Conclusion: EuroSCORE II and STS score have excellent predictive powers in predicting in-hospital mortality of patients undergoing CABG. In particular, EuroSCORE II is superior in calibration and discrimination. The prediction efficiency of the two risk evaluation systems is still acceptable for two-year postoperative mortality, but decreases year by year.Keywords: EuroSCORE II, STS score, coronary artery bypass grafting, in-hospital mortality, medium-term prognosis

Lei Xia,1,&ast; Li Wen,1,2,&ast; Xiangxi Meng,1 Nina Zhou,1 Xiaoyi Guo,1 Teli Liu,1 Xiaoxia Xu,1 Feng Wang,1 Hua Zhu,1 Zhi Yang1 1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, 100142, People’s Republic of China; 2Guizhou University School of Medicine, Guiyang, Guizhou, 550025, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hua Zhu; Zhi YangKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, 100142, People’s Republic of ChinaTel +86 010-88196196; +86 010-88196495Email zhuhuananjing@163.com; pekyz@163.comBackground: In recent years, nuclear medicine imaging and therapy for prostate cancer have radically changed through the introduction of radiolabeled prostate-specific membrane antigen (PSMA)-binding peptides. However, these small molecular probes have some inherent limitations, including high nephrotoxicity and short circulation time, which limits their utility in biological systems.Methods and Results: In this study, organic melanin nanoparticles were used to directly label the long half-life radionuclide 124I (t1/2=100.8 h), and PSMA small molecular groups were efficiently bonded on the surface of nanoparticles to construct the PSMA-targeted long-retention nanoprobe 124I-PPMN, which has the potential to increase tumor uptake and prolong residence time. The results showed that the nanoprobe could substantially aggregate in the tumors of prostate cancer xenograft mice and was visible for more than 72 h. Positron Emission Computed Tomography (PET) imaging showed that the nanoprobe could be used for precise imaging of prostate cancer with high expression of PSMA. In addition, organic melanin nanoparticles labeled with an elemental radionuclide achieved a stable, metal-free structure. Cell experiments and mouse toxicity experiments indicated that the nanoprobe has high safety.Conclusion: The new nanoprobe constructed in this study has high specificity and biocompatibility. In the future, combined with the multifunctional potential of melanin nanoparticles, this nanoprobe is expected to be used in the integrated theranostics of prostate cancer.Keywords: prostate cancer, 124I, PET, PSMA, melanin nanoparticles

Jianyun Long, Xupin Xie, Dong Xu, Changpin Huang, Yongchang Liu, Xiaohu Meng, Xuchao Cai, Xin Fang Department of Vascular Surgery, Affiliated Hangzhou First People’s Hospital, ZheJiang University School of Medicine, Hangzhou, Zhejiang, 310014, People’s Republic of ChinaCorrespondence: Xin FangDepartment of Vascular Surgery, Affiliated Hangzhou First People’s Hospital, ZheJiang University School of Medicine Hangzhou, Zhejiang, 310014, People’s Republic of ChinaTel +86 571-56005600Email hzfhfx@126.comObjective: Red blood cell distribution width (RDW) is a predictor of adverse outcomes in aortic aneurysms. Recent recommendations suggest that combining RDW with other biomarkers could yield better results. We, therefore, propose evaluating the biomarker of vascular aging, albumin with RDW to predict the risk of aortic aneurysms. This study aims to explore whether the combination of RDW with albumin can effectively predict the prognosis of aortic aneurysm patients.Methods: This retrospective cohort study was conducted among adults (age > 18) with aortic aneurysms in the Medical Information Mart for Intensive Care Database III V1.4 (MIMIC-III). RAR was measured according to the red blood cell distribution width and albumin. The primary outcome was the 30-day mortality rate, and the secondary outcome was the 90-day and one-year mortality rates. Estimation of hazard ratios (HR) was obtained from Cox regression models for all-cause mortality related to red cell distribution width-to-albumin ratio (RAR) values.Results: In total, 312 patients were involved, with an average age of 74.9 ± 10.9 years and an average RAR value of 5.4 ± 1.6 mL/g. In 30 days for all-cause mortality, the HR (95% CI) in the highest RAR group (> 5.8 mL/g) in tertiles was 2.54 (1.25, 5.14) in the unadjusted model, with a significant difference compared with the reference group (P < 0.05). After adjusting for race, gender and age, there was still a correlation (P < 0.05), and the HR (95% CI) was 2.51 (1.23, 5.10). Further adjustment of possible covariates showed similar correlation in model 3 (P < 0.05), and HR (95% CI) was 2.66 (1.17, 6.01). Multivariable logistic regression shows that RAR is an independent risk factor for the outcome of aortic aneurysms after adjusting the covariates. In the subgroup analysis, we analyzed the patient’s complications, and no significant interaction was observed.Conclusion: RAR is a risk factor for patients with aortic aneurysms. However, more in-depth research is warranted to further analyze and substantiate our findings on the role of RAR in aortic aneurysm patients.Keywords: red blood cell distribution width–albumin ratio, aortic aneurysms, retrospective cohort study, MIMIC-III

Junwei Tong,1– 3,&ast; Xiangui Meng,1– 3,&ast; Qingyang Lv,1– 3,&ast; Hongwei Yuan,1– 3 Weiquan Li,1– 3 Wen Xiao,1– 3 Xiaoping Zhang1– 3 1Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Shenzhen Huazhong University of Science and Technology Research Institute, Shenzhen, 518000, People’s Republic of China; 3Institute of Urology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoping Zhang; Wen XiaoDepartment of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei Province, 430022, People’s Republic of ChinaFax +86 85776343Email xzhang@hust.edu.cn; xiaowenx11@163.comBackground: Increasing evidence indicated that the aberrant expression of the cytoplasmic FMR1-interacting protein (CYFIP) family might possess critical role and potential functions in cancer. But the role of CYFIP2 in clear cell renal cell carcinoma (ccRCC) is still uncharacteristic.Methods: We investigated the Cancer Genome Atlas Kidney Clear Cell Carcinoma (TCGA-KIRC) database for the expression profile, clinicopathological variables, clinical prognosis information, and promoter methylation levels of CYFIPs in ccRCC. The aberrant CYFIP2 protein expression was validated by the Human Protein Atlas (HPA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to uncover CYFIP2 mRNA levels in 28 pairs of ccRCC cancer tissues. Kaplan–Meier analysis, univariate and multivariate Cox proportional hazard regression were performed to assess CYFIPs’ prognosis value. Gene set enrichment analysis (GSEA) was used to determined hallmark functions, gene ontology of CYFIP2. TIMER database was utilized to assess the correlation with immune infiltration in ccRCC.Results: Results showed CYFIP2 was downregulated in ccRCC, relative to paired normal tissues in TCGA-KIRC database and 28 pairs of clinical samples (P < 0.0001). Similarly, a decreased CYFIP2 protein expression was confirmed by ccRCC tissues. The results showed CYFIP2 was negatively regulated by promoter DNA methylation. Survival analysis results showed CYFIP2 could be an independent biomarker for ccRCC and its reduction predicted a poor overall survival (OS) and disease-free survival (DFS). GSEA showed CYFIP2 was involved in metabolic pathways and epithelial–mesenchymal transition (EMT). Immune infiltration analysis revealed that a list of immune markers was significantly correlated with CYFIP2 expression especially with CD4+ cells and CD8+ cells in ccRCC.Conclusion: These results show that CYFIP2 was downregulated in ccRCC patients and predicted an unfavorable prognosis. CYFIP2 might be a potential novel prognostic molecule, and related to immune infiltration, the metabolism, as well as EMT process in ccRCC. CYFIP2 could act as tumor suppressor gene in ccRCC and positive modulation of CYFIP2 might lead to development of a novel strategy for ccRCC treatment.Keywords: CYFIP2, ccRCC, methylation, prognosis, immune infiltration

Xiangui Meng,1– 3,&ast; Hongwei Yuan,1– 3,&ast; Weiquan Li,1– 3,&ast; Wen Xiao,1– 3 Xiaoping Zhang1– 3 1Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Shenzhen Huazhong University of Science and Technology Research Institute, Shenzhen, 518000, People’s Republic of China; 3Institute of Urology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoping Zhang; Wen XiaoDepartment of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei Province, 430022, People’s Republic of ChinaTel +86-18602752025Fax +86 2785776343Email xzhang@hust.edu.cn; xiaowenx11@163.comBackground: Studies report that conventional treatment of clear cell renal cell carcinoma (ccRCC) is effective, but several advanced patients present with poor prognosis. The current study explored potential new tumor markers and therapeutic targets in advanced ccRCC.Methods: Biomarker gene expression of ccRCC was retrieved from GEO database and the Cancer Genome Atlas Kidney Clear Cell Carcinoma (TCGA-KIRC) database. Gene ontology (GO) analysis and protein–protein interaction (PPI) networks of biomarker genes were constructed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) tool. Kaplan–Meier analysis and receiver operating characteristic curve (ROC) analysis were performed to explore the prognostic and diagnostic roles of these genes. Gene set enrichment analysis (GSEA) analysis was used to determine hallmark functions of the biomarker genes. qRT-PCR was used to verify the reliability of the analysis results in tumor tissues.Results: A total of 21 upregulated genes were identified between advanced ccRCC and early ccRCC (grade III+IV vs grade I+II). Gene ontology analysis showed that the 21 upregulated genes were mainly implicated in biological processes including metabolic and lipid transport. The findings showed that 7 out of the 21 genes were significantly upregulated in 72-paired samples retrieved from the TCGA-KIRC. High expression of 5 genes indicated a poor prognosis of overall survival and disease-free survival in KIRC. Three genes effectively distinguished renal cancer tissue and adjacent renal tissues in a total of 533 ccRCC samples. GSEA showed that the 3 biomarkers were significantly enriched in epithelial–mesenchymal transition, G2M checkpoint, and angiogenesis. The results of qRT-PCR showed that STEAP3, IBSP, and AQP9 had a significant identification effect in ccRCC.Conclusion: The findings showed that 3 biomarkers were significantly upregulated in advanced ccRCC and could be used for diagnosis, prediction, and potential novel therapeutic targets for progression of ccRCC.Keywords: advanced ccRCC, biomarker, progression, differentially expressed genes

Bing Feng,1,&ast; Xinling Meng,2,&ast; Hui Zhou,1,&ast; Liechun Chen,3 Chun Zou,3 Lucong Liang,3 Youshi Meng,3,4 Ning Xu,3,4 Hao Wang,3,4 Donghua Zou3,4 1Department of Neurology, The People’s Hospital of Guiping, Guigang, Guangxi, 537200, People’s Republic of China; 2Department of Endocrinology, The People’s Hospital of Guiping, Guigang, Guangxi, 537200, People’s Republic of China; 3Department of Neurology, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530022, People’s Republic of China; 4Department of Neurology, The First People’s Hospital of Nanning, Nanning, Guangxi, 530022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Wang; Donghua ZouThe Fifth Affiliated Hospital of Guangxi Medical University, 89 Qixing Road, Nanning, Guangxi, 530022, People’s Republic of ChinaTel +86 7712636189Email bswanghao2010@163.com; danvor0922@hotmail.comObjective: Ischemic stroke (IS) is a major cause of severe disability. This study aimed to identify potential biomarkers closely related to IS diagnosis and treatment.Methods: Profiles of gene expression were obtained from datasets GSE16561, GSE22255, GSE112801 and GSE110993. Differentially expressed mRNAs between IS and controls were then subjected to weighted gene co-expression network analysis as well as multiscale embedded gene co-expression network analysis. The intersection of the two sets of module genes was subjected to analyses of functional enrichment and of microRNAs (miRNAs) regulation. Then, the area under receiver operating characteristic curves (AUC) was calculated to assess the ability of genes to discriminate IS patients from controls. IS diagnostic signatures were constructed using least absolute shrinkage and selection operator regression.Results: A total of 234 common co-expression network genes were found to be potentially associated with IS. Enrichment analysis found that these genes were mainly associated with inflammation and immune response. The aberrantly expressed miRNAs (hsa-miR-651-5p, hsa-miR-138-5p, hsa-miR-9-3p and hsa-miR-374a-3p) in IS had regulatory effects on IS-related genes and were involved in brain-related diseases. We used the criterion AUC > 0.7 to screen out 23 hub genes from IS-related genes in the GSE16561 and GSE22255 datasets. We obtained an 8-gene signature (ADCY4, DUSP1, ATP5F1, DCTN5, EIF3G, ELAVL1, EXOSC7 and PPIE) from the training set of GSE16561 dataset, which we confirmed in the validation set of GSE16561 dataset and in the GSE22255 dataset. The genes in this signature were highly accurate for diagnosing IS. In addition, the 8-gene signature significantly correlated with infiltration by immune cells.Conclusion: These findings provide new clues to molecular mechanisms and treatment targets in IS. The genes in the signature may be candidate markers and potential gene targets for treatments.Keywords: ischemic stroke, bioinformatics analysis, miRNAs, immune inflammatory response, candidate markers

Yongmei Zhang,1,* Xiaoxuan Meng,1,* Yuehao Shen,2,* Jiajia Xie,2 Xi Yu,3 Qiaoshuo Wang,4 Lan Wang1 1School of Nursing, Tianjin Medical University, Tianjin, People’s Republic of China; 2Department of Respiratory Care, General Hospital of Tianjin Medical University, Tianjin, People’s Republic of China; 3Department of Respiratory Care, Tianjin First Center Hospital, Tianjin, People’s Republic of China; 4Department of Cardiac Care, Tianjin Chest Hospital, Tianjin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lan WangSchool of Nursing, Tianjin Medical University, 22 Qi Xiang Tai Road, Heping District, Tianjin, 300070, People’s Republic of ChinaTel +86 22 83336913Fax +86 22 83336900Email wangl0423@tmu.edu.cnPurpose: To analyze the reliability and validity of the Brief international classification of functioning, disability and health (ICF) core set for chronic obstructive pulmonary disease (COPD).Patients and Methods: A cross-sectional study was conducted in four tertiary hospitals in Tianjin, China. A total of 100 patients with COPD were selected to evaluate functioning and disability involving body functions, body structures, activities and participation as well as environmental factors of the Brief ICF core set for COPD. Internal consistency was calculated by Cronbach’s α. Content validity was examined using the content validity index (CVI), scale-level CVI/universal agreement, and scale-level CVI/average agreement (S-CVI/Ave). In addition, construct validity and convergent validity were also examined.Results: The Brief ICF core set for COPD had a high internal consistency, 0.873 for the total scale, with values of 0.750, 0.640, and 0.843 for body functions, body structures, and activity and participation, respectively. The content validity was calculated by the CVI, scale-level CVI/universal agreement, and S-CVI/Ave at values of 0.80– 1, 0.929, and 0.986, respectively. Meanwhile, the ICF core set for COPD had good convergent validity, correlating with the mMRC dyspnea score (r=0.690, P< 0.01), and there were significant correlations between the ICF core set for COPD and COPD clinical severity grade (r=0.363, P< 0.01). A four-factor model of functions and disability in the Brief ICF core set for COPD had the best fit according to confirmatory factor analysis (CFA).Conclusion: The Brief ICF core set for COPD is a reliable and valid convenient instrument for assessing comprehensive problems in the functioning of patients with COPD, which can be used to design and to evaluate rehabilitation strategies.Keywords: international classification of functioning, disability and health, chronic obstructive pulmonary disease, reliability, validity

Fangwei Zhou, Caiming Xu, Yanxiang Sun, Xuehui Meng Humanities and Management School, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Xuehui MengHumanities and Management School of Zhejiang Chinese Medical University, 548# Binwen Road, Binjiang District, Hangzhou, 310051, People’s Republic of ChinaTel/Fax +86 571-86633056Email mengxuehui@aliyun.comPurpose: This study aimed to analyze the status of patient satisfaction in outpatients of tertiary hospitals and the factors affecting patient satisfaction, in order to provide a scientific basis for improving patient satisfaction.Methods: A total of 6480 surveys of outpatients were conducted by a cross-sectional study in 16 tertiary hospitals in the Zhejiang province of China. The main contents of the survey were the basic characteristics of patients. Statistical description, single-factor analysis and binary logistic regression analysis were used to screen influencing factors.Results: Results of this study showed that the total satisfaction score of outpatients was 87.13± 13.47, and higher scored factors in the survey factors were nursing level, the convenience of registration and convenience of appointment diagnosis and treatment. The factors with lower scores were treatment effect, environmental sanitation and comfort and other staffs’ attitudes. Hospital managers should pay attention to the improvement of treatment level, environmental sanitation and comfort and other staffs’ attitudes.Conclusion: In the process of serving outpatients, doctors should pay more attention to patients who are male, 31– 45 years old or over 60 years old, permanent residents, from public institutions, possessed postgraduate education, without medical insurance, and who visiting paediatrics and Chinese medicine hospitals.Keywords: outpatient satisfaction, tertiary hospitals, patient, influencing factor

Peng Yu,1,2 Li Huang,1,2 Zhihan Wang,1,2 Xiaoyu Meng,1,2 Xuefeng Yu1,2 1Department of Internal Medicine, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China; 2Branch of National Clinical Research Center for Metabolic Diseases, Hubei, ChinaCorrespondence: Xuefeng Yu Tel/Fax +8602783663331Email xfyu188@163.comPurpose: Higher serum levels of uric acid (SUA) are associated with an increased risk of developing type 2 diabetes. Meanwhile, insulin resistance and beta-cell dysfunction are critical factors that mediate the progression from normal glucose tolerance to impaired fasting glucose (IFG) and type 2 diabetes. We aimed to investigate the association between SUA levels and insulin resistance and beta-cell dysfunction in individuals without diabetes, thus explicating the role of uric acid in the early stage of the natural history of type 2 diabetes.Patients and Methods: We used cross-sectional data from the China Health and Nutrition Survey to examine the association. Insulin resistance and beta-cell dysfunction were estimated using the homeostasis model assessment of insulin resistance (HOMA-IR) index and homeostasis model assessment of beta-cell function (HOMA-beta) index, respectively. The associations were analyzed by using partial correlation analysis and multivariate logistic regressionl analysis.Results: SUA levels were positively associated with fasting glucose, fasting insulin, HOMA-IR in the total population. After adjustment for age, drinking, smoking, living area, daily dietary nutrient intake, body mass index (BMI), estimated glomerular filtration rate (eGFR), hypertension, and dyslipidemia, compared with participants in the lowest quartile of SUA, the adjusted odds ratios for the fourth quartiles were 1.56(1.09-2.24) for IFG, 1.51(1.27-1.78) for insulin resistance, and 1.06(0.88-1.27) for beta-cell dysfunction. In the subgroup analysis, no interactions were found between serum uric acid and age, drinking status, smoking status, BMI, hypertension, or dyslipidemia (all p for interaction> 0.05).Conclusion: In nondiabetic individuals, SUA levels are independently associated with IFG and insulin resistance, while no significant association exists between SUA and beta-cell dysfunction.Keywords: uric acid, beta-cell function, insulin resistance, nondiabetic

Chengcheng Li,1 Conghui Liao,2 Xuehui Meng,3 Honghua Chen,4 Weiling Chen,4 Bo Wei,5 Pinghua Zhu1 1School of Humanities and Social Sciences, Guangxi Medical University, Nanning, 530021, People’s Republic of China; 2School of Public Health, Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China; 3Department of Health Service Management, Humanities and Management School, Zhejiang Chinese Medical University, Hangzhou, 310000, People’s Republic of China; 4School of Basic Medicine, Guangxi Medical University, Nanning, 530021, People’s Republic of China; 5School of Information and Management, Guangxi Medical University, Nanning, 530021, People’s Republic of ChinaCorrespondence: Pinghua Zhu Email zhupinghua@gxmu.edu.cnPurpose: To identify the factors influencing inpatient satisfaction by fitting the optimal discriminant model.Patients and Methods: A cross-sectional survey of inpatient satisfaction was conducted with 3888 patients in 16 large public hospitals in Zhejiang Province. Independent variables were screened by single-factor analysis, and the importance of all variables was comprehensively evaluated. The relationship between patients’ overall satisfaction and influencing factors was established, the relative risk was evaluated by marginal benefit, and the optimal model was fitted using the receiver operating characteristic curve.Results: Patients’ overall satisfaction was 79.73%. The five most influential factors on inpatient satisfaction, in this order, were: patients’ right to know, timely nursing response, satisfaction with medical staff service, integrity of medical staff, and accuracy of diagnosis. The prediction accuracy of the random forest model was higher than that of the multiple logistic regression and naive Bayesian models.Conclusion: Inpatient satisfaction is related to healthcare quality, diagnosis, and treatment process. Rapid identification and active improvement of the factors affecting patient satisfaction can reduce public hospital operating costs and improve patient experiences and the efficiency of health resource allocation. Public hospitals should strengthen the exchange of medical information between doctors and patients, shorten waiting time, and improve the level of medical technology, service attitude, and transparency of information disclosure.Keywords: random forest, inpatient satisfaction, public hospitals, key influencing factors

Jing Yang,1 Kun Yang,2 Xuxia Meng,1 Penghui Liu,1 Yudong Fu,1 Yibo Wang1 1Ophthalmology, Affiliated Hospital of Qingdao University, Qingdao, 266500, Shandong Province, People’s Republic of China; 2Central Laboratory, Affiliated Hospital of Qingdao University, Qingdao, 266500, Shandong Province, People’s Republic of ChinaCorrespondence: Xuxia Meng Email mengxx@qduhospital.cnPurpose: The lncRNA small nucleolar RNA host gene 1 (SNHG1) is a cerebral infarction-associated gene, its biological role and mechanism in diabetic retinopathy remain to be illuminated. The present study was designed to investigate the role of SNHG1 in high glucose induced human retinal pigment epithelial cells (ARPE-19).Methods: ARPE-19 cells were cultured and exposed to 60 mM high glucose for 48h, and 5.5mM glucose-exposed ARPE-19 cells were used as the control. The levels of the epithelial-mesenchymal transition (EMT) markers E-cadherin, ZO-1, vimentin and α-SMA were measured, and the Cell inflammatory response was evaluated by detecting IL-6 and IL-1β levels. Then, cell migration, proliferation and apoptosis were detected. The expression of the lncRNA SNHG1 in ARPE-19 cells was detected by quantitative real-time PCR. SNHG1 was knocked down by small interfering RNA (siRNA) transfection. The effects of SNHG1 inhibition on inflammation, EMT, migration, proliferation and apoptosis were observed.Results: The results showed that the expression of SNHG1 was significantly increased in ARPE-19 cells exposed to high glucose. Silencing SNHG1 reduced the expression of vimentin, α-SMA, and the expression of inflammatory chemokines IL-6 and IL-1β, inhibited migration and proliferation, elevated the expression of E-cadherin and ZO-1, and promoted apoptosis in ARPE-19 cells.Conclusion: The lncRNA SNHG1 is involved in hyperglycemia-induced EMT and the inflammatory response of ARPE-19 cells and provides a new understanding of the pathogenesis of DR.Keywords: epithelial-mesenchymal transition, small nucleolar RNA host gene 1, retinal pigment epithelial, hyperglycemia

Yu-fan Yang,1,* Hui Wang,1,2,* Nan Song,1,* Ya-hui Jiang,1 Jun Zhang,1 Xiao-wen Meng,1 Xiao-mei Feng,3,4 Hong Liu,5 Ke Peng,1 Fu-hai Ji1 1Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Department of Anesthesiology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, People’s Republic of China; 3Department of Anesthesiology, University of Utah Health, Salt Lake City, UT, USA; 4Transitional Residency Program, Intermountain Medical Center, Murray, UT, USA; 5Department of Anesthesiology and Pain Medicine, University of California Davis Health, Sacramento, CA, USA*These authors contributed equally to this workCorrespondence: Ke Peng; Fu-hai JiDepartment of Anesthesiology, First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, Jiangsu, 215006, People’s Republic of ChinaTel +86-159-6215-5989; +86-512-6797-2352Email pengke0422@163.com; jifuhaisuda@163.comBackground: Endoplasmic reticulum stress (ERS)-mediated myocardial inflammation and apoptosis plays an important role in myocardial ischemia/reperfusion (I/R) injury. Dexmedetomidine has been used clinically with sedative, analgesic, and anti-inflammatory properties. This study aimed to determine the effects of dexmedetomidine pretreatment on inflammation, apoptosis, and the expression of ERS signaling during myocardial I/R injury.Methods: Rats underwent myocardial ischemia for 30 min and reperfusion for 6 h, and H9c2 cardiomyocytes were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) injury (OGD for 12 h and reoxygenation for 3 h). Dexmedetomidine was administered prior to myocardial ischemia in rats or ODG in cardiomyocytes. In addition, the α 2-adrenergic receptor antagonist (yohimbine) or the PERK activator (CCT020312) was given prior to dexmedetomidine treatment.Results: Dexmedetomidine pretreatment decreased serum levels of cardiac troponin I, reduced myocardial infarct size, alleviated histological structure damage, and improved left ventricular function following myocardial I/R injury in rats. In addition, dexmedetomidine pretreatment increased cell viability and reduced cytotoxicity following OGD/R injury in cardiomyocytes. Mechanistically, the cardioprotection offered by dexmedetomidine was mediated via the inhibition of inflammation and apoptosis through downregulating the expression of the ERS signaling pathway, including glucose-regulated protein 78 (GRP78), protein kinase R-like endoplasmic reticulum kinase (PERK), C/EBP homologous protein (CHOP), inositol-requiring protein 1 (IRE1), and activating transcription factor 6 (ATF6). Conversely, the protective effects of dexmedetomidine were diminished by blocking the α 2 adrenergic receptors with yohimbine or promoting PERK phosphorylation with CCT020312.Conclusion: Dexmedetomidine pretreatment protects the hearts against I/R injury via inhibiting inflammation and apoptosis through downregulation of the ERS signaling pathway. Future clinical studies are needed to confirm the cardioprotective effects of dexmedetomidine in patients at risk of myocardial I/R injury.Keywords: myocardial ischemia/reperfusion injury, dexmedetomidine, endoplasmic reticulum stress, inflammation, apoptosis, GRP78/PERK/CHOP