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Yujia Huang,1,2,* Yinan Li,2,* Tong Su,3 Hao Wang,2 Shuyu Xu,2 Jingzhou Xu,2 Siqi Zheng,4 Jing Du,2 Yajing Wang,2 Ruike Zhang,2 Yao Meng,2 Xin Guo,2 Lei Xiao,2 Yunxiang Tang3 1Psychology Department, The Second Naval Hospital of Southern Theater Command, Sanya, People’s Republic of China; 2Department of Medical Psychology, Faculty of Psychology, Naval Medical University, Shanghai, People’s Republic of China; 3Faculty of Psychology, Naval Medical University, Shanghai, People’s Republic of China; 4Department of Psychology, TongJi University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lei Xiao; Yunxiang Tang, Email xiaolei0237@163.com; tangyun7633@sina.comObjective: To investigate the effects of sleep quality, sleep deprivation, and napping on facial emotion recognition (FER) accuracy and speed.Methods: This research included a cross-sectional study (102 qualified participants) and a randomized controlled study (26 in the napping group and 24 in the control group). The stimuli for the FER task were obtained from the Chinese Facial Affective Picture System (CFAPS). Four facial expressions (fearful, disgusted, sad, and angry) were used. The Pittsburgh Sleep Quality Index (PSQI), Self-Rating Anxiety Scale, and Self-Rating Depression Scale were used to measure participants’ sleep quality and psychological conditions. In Study 1, FER ability was compared between good and poor sleepers. In Study 2, all participants were sleep-deprived for one night, and completed the FER task before and after sleep deprivation. After different interventions (ie, napping for one hour, or walking around for ten minutes), the participants completed the third FER task.Results: Study 1: Poor sleepers were able to recognize sad expressions more accurately compared with good sleepers. Study 2: 30-h sleep deprivation had no significant effect on the accuracy (ACC). Napping after sleep deprivation improved the FER ACC of upper-face expressions and marginally significantly improved the FER ACC of disgusted expressions.Conclusion: Better sleep quality was linked to lower FER accuracy, particularly in recognizing sad expressions, while no significant differences in recognition speed were observed. Additionally, 30 hours of sleep deprivation did not affect FER accuracy, but napping after sleep deprivation improved accuracy for upper-face and marginally for disgusted expressions.Keywords: facial emotion recognition, sleep quality, facial features, facial emotion, sleep deprivation, sleep loss

Jun Du,1,* Zijie An,2,* Kun Zhu2 1Department of Oncological Surgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, People’s Republic of China; 2Department of Orthopaedics, The First Affiliated Hospital of Bengbu Medical University, Bengbu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kun Zhu, Department of Orthopaedics, The First Affiliated Hospital of Bengbu Medical University, Bengbu, People’s Republic of China, Email zk19870128@163.comObjective: To investigate the therapeutic efficacy of totally laparoscopic total gastrectomy (TLTG) versus laparoscopy-assisted total gastrectomy (LATG) in gastric cancer (GC) treatment, as well as their effects on postoperative inflammation and glucose and lipid metabolic status.Methods: Clinical data of 68 individuals with GC who underwent LATG (n=31) and TLTG (n=37) from January 2020 to December 2022 were procured. This included intraoperative blood loss, operative time, incision length, number of lymph nodes dissected, postoperative complication rates, and recovery indicators, such as inflammation, glucose metabolism, and lipid metabolism.Results: The TLTG cohort demonstrated significant advantages in intraoperative blood loss, operative time, and incision length compared to the LATG cohort. Furthermore, TLTG was superior in reducing the incidence of complications. Nevertheless, no substantial variation was observed in the quantity of lymph nodes dissected. Additionally, TLTG showed benefits in postoperative recovery, including better control of the inflammatory response, reduction of complication risks, shorter hospital stay, and alleviation of postoperative pain. TLTG also exhibited a reduced impact on inflammation and demonstrated greater effectiveness in improving postoperative glucose and lipid levels.Conclusion: TLTG surgery is associated with superior clinical outcomes in the treatment of GC compared to LATG, particularly in reducing surgical trauma and accelerating postoperative recovery. Furthermore, TLTG facilitates the resolution of postoperative inflammatory responses and the amelioration of metabolic disorders. The findings from this investigation advocate for the broader adoption of TLTG in the surgical treatment of GC.Keywords: totally laparoscopic total gastrectomy, laparoscopy-assisted total gastrectomy, gastric cancer, inflammatory markers, glucose and lipid metabolism

Juan Sun, Juxiang Shen, Lei Liu, Juan Du Department of Medical Technology, Jiangsu College of Nursing, Huai’an, Jiangsu Province, People’s Republic of ChinaCorrespondence: Juan Sun, Department of Medical Technology, Jiangsu College of Nursing, Huaian, 223001, People’s Republic of China, Tel +8615162765063, Email 15162765063@163.comBackground: Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus, causing a serious economic burden worldwide. Traditional Chinese Medicine (TCM) is playing an increasingly important role in the treatment of DN. The purpose of this study was to comprehend the main themes and developments in relevant research throughout the last 11 years.Methods: We looked for publications in the Web of Science Core Collection database (WOS) and the Chinese National Knowledge Infrastructure (CNKI) between 2013 and 2024. CiteSpace 6.3.R1 software was used to analyze the co-authorship of countries/regions, organizations, and co-occurrence of keywords. In addition, burst detection was applied to predict research hotspots and future trends.Results: A total of 530 articles were included. The overall trend of published articles is increasing. China is the country with the highest number of publications and the highest impact. The research institutions are relatively scattered, with Beijing University of Traditional Chinese Medicine having the highest number of publications. The cooperation among institutions is mainly between universities of traditional Chinese medicine and their affiliated hospitals, and the cross-regional cooperation is not common. The research hotspots are the efficacy of TCM on DN and its mechanism of action, the exploration of TCM and formulas related to the treatment of DN, and the identification and typing of DN in TCM. The research frontiers lie in the control of oxidative stress and the effects of TCM on gut microbiota. In addition, the use of network pharmacology to explore the targets of Chinese herbal formulas for the treatment of this disease has also become popular.Conclusion: TCM provides more possibilities for the treatment of DN. Researchers can refer to the research hotspots and trends in this paper for future research direction, on the one hand, they can focus on the study of the clinical efficacy of TCM and its improvement of renal function, on the other hand, they can also start from the pharmacological mechanism of TCM for the treatment of DN. Among them, improving oxidative stress in human body and regulating gut microbiota are the directions that can be studied.Keywords: diabetes nephropathy, traditional Chinese medicine, citespace, bibliometric analysis, visualization

Baoliang Liu,1,* Haotian Zheng,1,* Guoyuan Ma,1,2 Hongchang Shen,3 Zhaofei Pang,3 Gemu Huang,4 Qingtao Song,4 Guanghui Wang,1,2 Jiajun Du1,2 1Department of Thoracic Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 3Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 4Research and Development Department, Amoy Diagnostics Co., LTD., Xiamen, Fujian, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guanghui Wang; Jiajun Du, Email wangguanghui66@email.sdu.edu.cn; dujiajun@sdu.edu.cnBackground: Lung cancer is the most common type of cancer in the world. In lung adenocarcinoma (LUAD), studies on receptor tyrosine kinase ROS proto-oncogene 1 (ROS1) have mainly focused on the oncogenic effects of its fusion mutations, whereas ROS1 has been reported to be aberrantly expressed in a variety of cancers and can extensively regulate the growth, survival, and proliferation of tumor cells through multiple signaling pathways. The comprehensive analysis of ROS1 expression has not been fully investigated regarding its predictive value for LUAD patients.Methods: Gene expression profiles collected from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases were used to build and validate prognostic risk models. The association of ROS1 with overall survival and the immune landscape was obtained from the Tumor Immune Estimation Resource (TIMER) database. The following analyses were performed using the R package to determine the model’s validity: pathway dysregulation analysis, gene set enrichment analysis, Gene Oncology analysis, immune invasion analysis, chemotherapy, radiotherapy, and immunotherapy sensitivity analysis. Finally, we conducted a pan-cancer analysis and performed in vitro experiments to explore the regulatory role of intercellular adhesion molecule 5 (ICAM5) in the progression of LUAD.Results: We constructed a 17-gene model that categorized patients into two risk groups. The model had predictive accuracy for tumor prognosis and was specific for patients with high ROS1 expression. Comprehensive analysis showed that patients in the high-risk group were characterized by marked dysregulation of multiple pathways (eg, unfolded protein response), immune suppression of the tumor microenvironment, and poor benefit from immunotherapy and radiotherapy compared with patients in the low-risk group. PLX4720 may be a suitable treatment for the high-risk patient population. The ICAM5 gene has been demonstrated to inhibit the proliferation, cell cycle, invasion, and migration of LUAD cells.Conclusion: We constructed a 17-gene prognostic risk model and found differences in immune-related cells, biological processes, and prognosis among patients in different risk groups based on the correlation between ROS1 and immunity. Personalized therapy may play an essential role in treatment. We further investigated the role of ICAM5 in inhibiting the malignant bioactivity of LUAD cells.Keywords: ROS1, ICAM5, LUAD, immune, prognostic model

Zhengwen Feng,1 Hui Li,1 Xiaolei Chen,1 Tiancheng Zhang,2 Yanxiang Chen,3 Shuang Shao,1,* Juan Du1,* 1School of General Practice and Continuing Education, Capital Medical University, Beijing, People’s Republic of China; 2Department of General Practice, Dahongmen Community Health Service Center, Beijing, Fengtai District, People’s Republic of China; 3Department of general practice, Changying Community Health Service Center, Beijing, Chaoyang District, People’s Republic of China*These authors contributed equally to this workCorrespondence: Juan Du; Shuang Shao, School of General Practice and Continuing Education, Capital Medical University, 10 You’ Anmen Outer West 1 st Street, Beijing, 100069, People’s Republic of China, Email cuckoo@ccmu.edu.cn; shaoshuang@ccmu.edu.cnPurpose: Our study aimed to explore the current status of patient participation in medication safety from the perspectives of general practitioners (GPs), pharmacists, and outpatients in Beijing, China.Patients and Methods: A qualitative study using semi-structured in-depth individual interviews with GPs, pharmacists, and outpatients. Subjects were identified by purposive sampling until code saturation. Semi-structured qualitative interviews were conducted with GPs, pharmacists, and patients from community health service centers in three urban districts of Beijing, China. The interviews were transcribed verbatim and the text was analysed using thematic analysis techniques including familiarising with data, generating initial codes, searching for themes, reviewing themes, defining and naming themes, and producing the report.Results: A total of eight GPs, seven pharmacists, and 18 outpatients were interviewed. Data analysis led to the generation of five key themes: (1) mutual trust between patient and GP, (2) communication with healthcare professionals, (3) acquisition of knowledge about medication safety, (4) implementation of medication self-management at home, and (5) different attitudes toward participation in medication decisions. Patients participated in medication safety in multiple ways. However, insufficient knowledge about medication safety, lack of awareness of the patient’s role in ensuring medication safety, shortage of consultation lengths, and being misled by some information were problems with patient participation in medication safety.Conclusion: This exploratory study contributes to our initial understanding of patient participation in medication safety. There were still many issues and barriers in the process of patient participation. Appropriate policies and measures, such as providing various forms of patient education, ensuring sufficient physician-patient communication, giving full play to the role of pharmacists, and making judicious use of digital health tools should be taken to improve medication safety by fully utilising the role of patients.Plain Language Summary: Medication safety is a significant concern around the world. Patient participation in the medication process is effective in reducing the incidence of medication errors and improving medication safety. However, the role of outpatients with chronic conditions in ensuring medication safety is often neglected. This study aims to explore the perspectives and experiences of GPs, pharmacists, and outpatients by qualitative interviews in Beijing, China. The study involved a series of interviews with eight GPs, seven pharmacists, and 18 outpatients living with noncommunicable diseases. The interview revealed five themes: (1) mutual trust between patient and GP, (2) communication with healthcare professionals, (3) acquisition of knowledge about medication safety, (4) implementation of medication self-management at home, and (5) different attitudes toward participation in medication decisions. The findings might help propose suggestions for patient participation in medication safety. Integrating these findings into future studies can help healthcare professionals formulate interventions and better support patients in participating in the medication process.Keywords: medication safety, patient participation, patient safety, qualitative study, noncommunicable disease, community health service centers

Liping Zou,1,* Wanli Kang,2,* Chunhui Guo,3,* Juan Du,4,* Qing Chen,1 Zhengyu Shi,1 Xianzhen Tang,1 Li Liang,1 Peijun Tang,5 Qing Pan,6 Qingdong Zhu,7 Song Yang,8 Zhanlin Chang,9 Zhouli Guo,1 Guihui Wu,1 Shenjie Tang2 1Department of Tuberculosis, Public Health Clinical Center of Chengdu, Chengdu, People’s Republic of China; 2Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People’s Republic of China; 3Department of Tuberculosis, Harbin Chest Hospital, Harbin, People’s Republic of China; 4Department of Tuberculosis, Wuhan Pulmonary Hotel, Wuhan, People’s Republic of China; 5Department of Tuberculosis, the Fifth People’s Hospital of Suzhou, Suzhou, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Anqing Municipal Hospital, Anqing, People’s Republic of China; 7Department of Tuberculosis, the Fourth People’s Hospital of Nanning, Nanning, People’s Republic of China; 8General Internal Medicine Department, Chongqing Public Health Medical Center, Chongqing, People’s Republic of China; 9Department of Surgery, the Third People’s Hospital of Tibet Autonomous Region, Lasa, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guihui Wu, Department of Tuberculosis, Public Health Clinical Center of Chengdu, Jingjusi 18 Street, Jingjiang District, Chengdu, Sichuan, People’s Republic of China, Tel +86-28-8455-0573, Email wghwgh2584@sina.com Shenjie Tang, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, 101149, People’s Republic of China, Tel +86-13621028338, Email tangsj1106@vip.sina.comObjective: Rifampin-resistant tuberculosis (RR-TB) remains a serious global public health concern. We assessed treatment outcomes and associated influencing factors among RR-TB patients in China.Methods: This research enrolled 1339 patients who started RR-TB treatment between May 2018 and April 2020 in China retrospectively. Data were collected from the electronic medical records. Multivariable logistic regression analysis was used to identify the influencing factors related to unfavorable outcomes.Results: Of the 1339 RR-TB patients, 78.8% (1055/1339) achieved treatment success (cured or treatment completed), 5.1% (68/1339) experienced treatment failure, 1.1% (15/1339) died during treatment, 10.1% (135/1339) were lost to follow-up, and 4.9% (66/1339) were not evaluated. About 67.7% (907/1339) of patients experienced at least one adverse event (AE). The most common AE was hypohepatia (507/1339, 37.9%), followed by hyperuricemia (429/1339, 32.0%), anemia (368/1339, 27.5%), electrolyte disturbance (318/1339, 23.7%), peripheral neuritis (245/1339, 18.3%), and gastrointestinal reactions (203/1339, 15.2%). Multivariate analysis showed that age ≥ 60 years [adjusted odds ratio (aOR): 1.96, 95% confidence interval (CI): 1.39– 2.77], national minority (aOR: 2.36, 95% CI: 1.42– 3.93), smoking (aOR: 1.50, 95% CI: 1.10– 2.04), cardiopathy (aOR: 2.90, 95% CI: 1.33– 6.31), tumors (aOR: 9.84, 95% CI: 2.27– 42.67), immunocompromise (aOR: 2.17, 95% CI: 1.21– 3.91), re-treated TB (aOR: 1.46, 95% CI: 1.08– 1.97), and experienced gastrointestinal reactions (aOR: 2.27, 95% CI: 1.52– 3.40) were associated with unfavorable outcomes. Body mass index (BMI) ≥ 18.5 kg/m2, regimens containing bedaquiline and experienced adverse events (AEs) such as hypohepatia, leukopenia, peripheral neuritis, and optic neuritis were associated with favorable outcomes.Conclusion: High rates of treatment success were achieved for RR-TB patients at tertiary tuberculosis hospitals in China. Age ≥ 60 years, national minority, smoking status, comorbidities, re-treated TB, and experienced gastrointestinal reactions were independent prognostic factors for unfavorable treatment outcomes.Keywords: RR-TB, treatment outcomes, influencing factors, China

Yuling Liang,1,* Yuqing Xie,1,* Xiaoli Liu,1 Lihua Yu,1 Huiwen Yan,1 Zimeng Shang,1 Yuan Wu,1 Xue Cai,2 Wanxin Shi,2 Juan Du,3 Zhiyun Yang1 1Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China; 2Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 3Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China*These authors contributed equally to this workCorrespondence: Juan Du, Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China, Email duj656@163.com Zhiyun Yang, Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China, Tel +86-10-84322148, Email yangzhiyun2016@163.comPurpose: Traditional Chinese medicine (TCM) therapy is an important means to treat hepatocellular carcinoma (HCC), Astragalus (Latin name: Hedysarum Multijugum Maxim; Chinese name: Huangqi, HQ) and Atractylodes (Latin name: Atractylodes Macrocephala Koidz; Chinese name: Baizhu, BZ) (HQBZ), a classic herb pair, is often used in combination to HCC. However, the main components and potential mechanisms of HQBZ therapy in HCC remain unclear. This study aimed to identify the potential active ingredients and molecular mechanisms of action of HQBZ in HCC treatment.Methods: The HQBZ-Compound-Target-HCC network and HQBZ-HCC transcriptional regulatory network were constructed to screen the core active compound components and targets of HQBZ therapy for HCC. Molecular docking techniques are used to verify the stability of binding core active compound components to targets. GO and KEGG enrichment analysis were used to explore the signaling pathway of HQBZ in HCC treatment, the mechanism of HQBZ treatment of HCC was verified based on in vivo H22 tumor bearing mice and in vitro cell experiments.Results: Network pharmacology and molecular docking studies showed that HQBZ treatment of HCC was related to the targeted regulation of IL-6 and STAT3 by the active compound biatractylolide, KEGG pathway enrichment analysis suggest that HQBZ may play a role in the treatment of HCC through IL-6/STAT3 signaling pathway. In vitro experiment results proved that HQBZ could regulate IL-6/STAT3 signaling pathway transduction on CD8+T cells, inhibit CD8+T cell exhaustion and restore the function of exhausted CD8+T cells. In vivo experiment results proved that HQBZ can regulate IL-6/STAT3 signaling pathway transduction in H22 liver cancer model mouse tumor tissue, increased the proportion of tumor infiltrating CD8+T cells.Conclusion: This study found that HQBZ may play a therapeutic role in HCC by targeting IL-6 and STAT3 through biatractylolide, its mechanism of action is related to regulating IL-6/STAT3 signaling pathway, reversing T cell failure and increasing tumor infiltration CD8+T cells.Keywords: Astragalus–Atractylodes herb pair, hepatocellular carcinoma, IL-6/STAT3 signaling pathway, molecular docking, network pharmacology

Juan Du,1,* Li-Li Shi,2,* Wei-Wei Jiang,3 Xue-Ai Liu,3 Xin-Hong Wu,3 Xiang-Xiang Huang,3 Ming-Wei Huo,3 Ling-Zhi Shi,3 Jingjian Dong,2 Xiaohong Jiang,2 Renyu Huang,4 Qing-Ri Cao,3 Wenzhou Zhang1 1Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, People’s Republic of China; 2College of Medicine, Jiaxing University, Jiaxing, People’s Republic of China; 3College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, People’s Republic of China; 4College of Social Science, Soochow University, Institute of Culture and Tourism Development, Soochow University, Suzhou, 215123, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenzhou Zhang, Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, People’s Republic of China, Email hnzzzwzx@sina.com Qing-Ri Cao, College of Pharmaceutical Sciences, Soochow University, 199 Ren-Ai Road, Suzhou Industrial Park, Jiangsu, 215123, People’s Republic of China, Email qrcao@suda.edu.cnBackground: The commercial docetaxel (DTX) formulation causes severe side effects due to polysorbate 80 and ethanol. Novel surfactant-free nanoparticle (NP) systems are needed to improve bioavailability and reduce side effects. However, controlling the particle size and stability of NPs and improving the batch-to-batch variation are the major challenges.Methods: DTX-loaded bovine serum albumin nanoparticles (DTX-BSA-NPs) were prepared by a novel thermal-driven self-assembly/microfluidic technology. Single-factor analysis and orthogonal test were conducted to obtain the optimal formulation of DTX-BSA-NPs in terms of particle size, encapsulation efficiency (EE), and drug loading (DL). The effects of oil/water flow rate and pump pressure on the particle size, EE, and DL were investigated to optimize the preparation process of DTX-BSA-NPs. The drug release, physicochemical properties, stability, and pharmacokinetics of NPs were evaluated.Results: The optimized DTX-BSA-NPs were uniform, with a particle size of 118.30 nm, EE of 89.04%, and DL of 8.27%. They showed a sustained release of 70% over 96 hours and an increased stability. There were some interactions between the drug and excipients in DTX-BSA-NPs. The half-life, mean residence time, and area under the curve (AUC) of DTX-BSA-NPs increased, but plasma clearance decreased when compared with DTX.Conclusion: The thermal-driven self-assembly/microfluidic combination method effectively produces BSA-based NPs that improve the bioavailability and stability of DTX, offering a promising alternative to traditional formulations. Keywords: DTX-BSA nanoparticles, thermal-driven self-assembly, microfluidic technology, in-vitro release, pharmacokinetics

Jun Du,1 Qing-long Gu,1 Ying-xia Lu,1 Lei Zhang,2 Xiao-jun Zhan,1 Zhan Wang1 1Department of Otolaryngology, Head and Neck Surgery, Children’s Hospital Capital Institute of Pediatrics, Beijing, 100000, People’s Republic of China; 2Department of Hematopathology, Children’s Hospital Capital Institute of Pediatrics, Beijing, 100000, People’s Republic of ChinaCorrespondence: Qing-long Gu, Department of Otolaryngology, Head and Neck Surgery, Children’s Hospital Capital Institute of Pediatrics, No. 2 Yabao Road, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel +86-13810091816, Email qinglonggugql@126.comObjective: To evaluate the safety and feasibility of tonsillectomy and/or adenoidectomy (T&A) in pediatric patients with prolonged activated partial thromboplastin time (APTT) and coagulation factor deficiency.Methods: A prospective study was admitted to the children undergoing T&A at our institution between October 2019 and January 2020, specifically focusing on preoperative coagulation function. Within this group, we identified 5 patients exhibiting prolonged APTT and coagulation factor deficiencies, constituting the experimental group, and 10 patients matched by gender and age with normal blood coagulation function were selected as the control group. Comparative analyses between the two groups were conducted, focusing on surgical duration, intraoperative bleeding volume, duration of hospital stay, and postoperative complications such as active bleeding across the groups. At the six-month postoperative mark, a reassessment of coagulation functions and factor assays was conducted within the experimental group.Results: No statistically significant differences were discovered in terms of surgical duration or bleeding volume when comparing the experimental subgroups with their respective control counterparts. Furthermore, there were no incidences of postoperative active bleeding observed in any of the groups. Notably, postoperative APTT values (32.7 ± 1.7s) exhibited a significant disparity compared to preoperative levels (43.7 ± 1.8s, p < 0.01). Coagulation factors demonstrated normalization, evidenced by a significant difference in postoperative Factor XII levels (40.2 ± 5.4%) compared to preoperative levels (63.1 ± 5.9%, p < 0.01).Conclusion: Prolonged APTT with FXII factor deficiency does not show a significant bleeding tendency and is not a contraindication for T&A surgery. Post T&A surgery, children with abnormal coagulation function and deficient clotting factors show significant improvement compared to pre-surgery. It is important to consider that chronic inflammation in adenoids and tonsils may contribute to the prolongation of APTT and the manifestation of Factor XII deficiency.Keywords: adenoidectomy, children, factor XII deficiency, prolonged APTT, tonsillectomy

Hai Xu,1 Conghui Hao,1 Xinxin Wang,2 Jingjing Du,1 Tianyu Zhang,1 Xiaobao Zhang2,3 1Department of Anesthesiology, Graduate Training Base of Lianyungang First People’s Hospital of Jinzhou Medical University, Lianyungang, Jiangsu, People’s Republic of China; 2Department of Anesthesiology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, Jiangsu, People’s Republic of China; 3Department of Anesthesiology, The First Affiliated Hospital of Kangda College of Nanjing Medical University, Lianyungang, Jiangsu, People’s Republic of ChinaCorrespondence: Xiaobao Zhang, Department of Anesthesiology, The First Affiliated Hospital of Kangda College of Nanjing Medical University, Lianyungang, Jiangsu, People’s Republic of China, Email hotdog100@163.comBackground: Magnesium sulfate, an intravenous adjuvant, has recently attracted immense attention in multimodal analgesia. Previous studies confirmed the crucial role of magnesium sulfate in postoperative pain and nociceptive hypersensitivity. However, the effect of magnesium sulfate in multimodal analgesia on the quality of recovery (QoR) for elderly patients has not been thoroughly studied. Therefore, the present experiment aimed to investigate the effect of continuous intravenous magnesium sulfate on the quality of postoperative recovery in elderly patients undergoing total knee arthroplasty (TKA).Patients and Methods: In this study, a total of 148 patients scheduled to undergo unilateral total knee arthroplasty were randomized into a magnesium sulfate group (Group M, n=68) and a control group (Group C, n=66) using a double-blind, randomized controlled trial. Before induction of anesthesia, Group M received intravenous magnesium sulfate (40 mg/kg) for 15 min, followed by a continuous infusion (15 mg/kg) until the end of the procedure. In the same manner, Group C received an infusion of the same amount of isotonic saline using the same method as the Group M.Results: Compared with Group C, Group M had significantly better QoR-15 scores on postoperative day 1(POD1) than Group C (P < 0.05). Analysis of the dimensions of QoR-15 scores indicated that Group M exhibited notably reduced levels of pain, and higher levels of emotional state and physical comfort than Group C (P < 0.05). Furthermore, Group C had significantly higher numerical rating scale (NRS) scores at POD1 than Group M (P < 0.05).Conclusion: For elderly patients undergoing knee arthroplasty, magnesium sulfate can be used as an adjuvant in a multimodal analgesic regimen to reduce early postoperative pain and improve the quality of early postoperative recovery.Keywords: magnesium sulfate, quality of recovery, postoperative pain, multimodal analgesic regimen, total knee arthroplasty

Naigeng Wang,1 Fei Li,2 Jing Du,3 Jianhong Hao,1 Xin Wang,2 Yueru Hou,3 Zhenguo Luo1 1Department of Anesthesiology, Honghui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China; 3Second Clinical Medical College, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People’s Republic of ChinaCorrespondence: Zhenguo Luo, Email luozhenguo@stu.xjtu.edu.cnBackground: This study aims to investigate the protective effect of quercetin against global cerebral ischemia‒reperfusion (GCI/R) injury in rats and elucidate the underlying mechanism.Methods: A GCI/R injury rat model was established using a four-vessel occlusion (4-VO) method. An oxygen–glucose deprivation/reoxygenation (OGD/R) injury model was induced in BV2 cells. The extent of injury was assessed by evaluating neurological deficit scores (NDS) and brain water content and conducting behavioral tests. Pathomorphological changes in the prefrontal cortex were examined. Additionally, the study measured the levels of inflammatory cytokines, the degree of microglial activation and polarization, and the protein expression of Toll-like receptor 4 (TLR4) and TIR-domain-containing adaptor inducing interferon-β (TRIF).Results: Quercetin pretreatment significantly ameliorated neurological impairment, improved learning and memory abilities, and reduced anxiety in rats subjected to GCI/R injury. Furthermore, quercetin administration effectively mitigated neuronal injury and brain edema. Notably, it suppressed microglial activation and hindered polarization toward the M1 phenotype. Simultaneously, quercetin downregulated the expression of TLR4 and TRIF proteins and attenuated the release of IL-1β and TNF-α.Conclusion: This study highlights the novel therapeutic potential of quercetin in alleviating GCI/R injury. Quercetin demonstrates its neuroprotective effects by inhibiting neuroinflammation and microglial activation while impeding their transformation into the M1 phenotype through modulation of the TLR4/TRIF pathway.Keywords: quercetin, cerebral ischemia, neuroprotection, neuroinflammation

Meiju Deng,1,2,&ast; Yongqin Zeng,2,3,&ast; Ying Liu,2 Xiaolei Wang,1,2 Na Chen,1,2 Mengyuan Zhang,1,4– 6 Meiqing Jiang,1,4– 6 Hongxin Zhao,2 Juan Du1,4– 6 1Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China; 2Clinical Center for HIV/AIDS, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China; 3Department of Nephrology, The Affiliated Hospital Guizhou Medical University, Guiyang, Guizhou, 550004, People’s Republic of China; 4Beijing Institute of Infectious Diseases, Beijing, 100015, People’s Republic of China; 5National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China; 6National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Beijing, 100015, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Juan Du; Hongxin Zhao, Email duj656@ccmu.edu.cn; Drzhao66@ccmu.edu.cnBackground: The aging of the immune system is associated with various diseases. It is worth exploring the changes of the immune system in aging. Previous studies have shown that aged T cells have enhanced expression of co-inhibitory molecules. However, it remains unclear whether aged NK cells exhibit similar characteristics to aged T cells. The objective of our research was to clarify this aspect.Patients and Methods: This study included 98 adults aged 24– 90 years (50 males and 48 females). We detected the subset of peripheral blood NK cells and the expression of various receptors on NK cells among donors of different age groups by flow cytometry. Immune subsets were initially defined by forward and side-scatter characteristics and then staining with the appropriate marker.Results: The absolute number and subset distribution of NK cells were not associated with age. However, CD57 expression and CD69 expression were correlated with age. Furthermore, we found that PD-1 was up-regulated on NK cells in older people, associated with aging, while no such change was observed in other co-inhibitory molecules, including 2B4, CTLA-4, TIM-3, BTLA, CD70, CD39, CD160, and TIGIT. PD-1+ NK cells expressed high levels of CD57 and CD69, indicating PD-1+ NK cells displayed a phenotype of over-activation and aging.Discussion: This study indicated that PD-1+ NK cells were one of the characteristics of NK cells in older people.Conclusion: This study indicated that PD-1+ NK cells were one of the characteristics of NK cells in older people. Those findings provided new ideas to explore the underlying drivers of NK aging.Keywords: PD-1, NK cell, aging, co-inhibitory molecules

Long Lv,1,&ast; Jinghu Du,1,&ast; Daorong Wang,2 Zeqiang Yan2 1Department of General Surgery, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, People’s Republic of China; 2Department of Gastroenterology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Daorong Wang; Zeqiang Yan, Department of Gastroenterology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, People’s Republic of China, Tel +13581425716 ; +13597505970, Email 415004128@qq.com; yzqi48959@163.comBackground: Gastric cancer (GC) is a common fatal malignancy. The aim of this study was to explore and validate the tumor-suppressive role and mechanism of Radix Bupleuri in GC.Methods: The active constituents of Radix Bupleuri were screened using TCMSP database. SwissTargetPrediction database was used to predict potential target genes of the compounds. GeneCards, TTD, DisGeNET, OMIM, and PharmGKB databases were used to search for GC-related targets. STRING database and Cytoscape 3.10 software were used for protein–protein interaction network construction and screening of core targets. DAVID database was used for GO and KEGG analyses. Core targets were validated using molecular docking. Cell proliferation and apoptosis were detected using CCK-8 and flow cytometry after GC cells were treated with isorhamnetin. The mRNA and protein expression levels of genes were detected using qRT PCR and Western blot. The metastasis potential of GC cells was evaluated in a nude mouse model.Results: A total of 371 potential targets were retrieved by searching the intersection of Radix Bupleuri and GC targets. Petunidin, 3’,4’,5’,3,5,6,7-Heptamethoxyflavone, quercetin, kaempferol, and isorhamnetin were identified as the main bioactive compounds in Radix Bupleuri. SRC, HSP90AA1, AKT1, and EGFR, were core targets through which Radix Bupleuri suppressed GC. The tumor-suppressive effect of Radix Bupleuri on GC was mediated by multiple pathways, including PI3K-AKT, cAMP, and TNF signaling. The key compounds of Radix Bupleuri had good binding affinity with the core target. Isorhamnetin, a key component of Radix Bupleuri, could inhibit proliferation and metastasis, and induces apoptosis of GC cells. In addition, isorhamnetin could also reduce the mRNA expression of core targets, and the activation of PI3K/AKT pathway.Conclusion: This study identified potential targets and pathways of Radix Bupleuri against GC through network pharmacology and molecular docking, providing new insights into the pharmacological mechanisms of Radix Bupleuri in GC treatment. Keywords: gastric cancer, Radix Bupleuri, network pharmacology, molecular docking

Yunzhi Xiang,&ast; Guanghui Wang,&ast; Baoliang Liu, Haotian Zheng, Qiang Liu, Guoyuan Ma, Jiajun Du Institute of Oncology, Shandong Provincial Hospital, Shandong University, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiajun Du, Shandong Provincial Hospital, No. 324 Jingwu Road, Huaiyin District, Jinan, 250000, People’s Republic of China, Email dujiajun@sdu.edu.cnBackground: In recent years, the immunotherapy of lung adenocarcinoma has developed rapidly, but the good therapeutic effect only exists in some patients, and most of the current predictors cannot predict it very well. Tumor-infiltrating macrophages have been reported to play a crucial role in lung adenocarcinoma (LUAD). Thus, we want to build novel molecular markers based on macrophages.Methods: By non-negative matrix factorization (NMF) algorithm and Cox regression analysis, we constructed macrophage-related subtypes of LUAD patients and built a novel gene signature consisting of 12 differentially expressed genes between two subtypes. The gene signature was further validated in Gene-Expression Omnibus (GEO) datasets. Its predictive effect on prognosis and immunotherapy outcome was further evaluated with rounded analyses. We finally explore the role of TRIM28 in LUAD with a series of in vitro experiments.Results: Our research indicated that a higher LMS score was significantly correlated with tumor staging, pathological grade, tumor node metastasis stage, and survival. LMS was identified as an independent risk factor for OS in LUAD patients and verified in GEO datasets. Clinical response to immunotherapy was better in patients with low LMS score compared to those with high LMS score. TRIM28, a key gene in the gene signature, was shown to promote the proliferation, invasion and migration of LUAD cell.Conclusion: Our study highlights the significant role of gene signature in predicting the prognosis and immunotherapy efficacy of LUAD patients, and identifies TRIM28 as a potential biomarker for the treatment of LUAD.Keywords: lung adenocarcinoma, macrophage, TRIM28, prognosis, immunotherapy

Yunhong Ren,1,&ast; Yinhao Guo,2,&ast; Jing Tang,2 Ling He,1 Meiling Li,1 Xuemei Huang,1 Qin Lu,1 Baoxia Sun,1 Haixia Feng,1 Huan Liu,1 Juan Du,1 Jun Li1 1Mianyang Key Laboratory of Anesthesia and Neuroregulation, Department of Anesthesiology, Mianyang Central Hospital, Mianyang, Sichuan, 621000, People’s Republic of China; 2Department of Anesthesiology, North Sichuan Medical College, Nanchong, Sichuan, 637000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Li; Juan Du, Mianyang Key Laboratory of Anesthesia and Neuroregulation, Department of Anesthesiology, Mianyang Central Hospital, Mianyang, Sichuan, People’s Republic of China, Email lj89199@163.com; 1151941061@qq.comPurpose: This study aimed to investigate the effects of different psychological personalities and pain catastrophizing levels on postoperative analgesia in patients undergoing cesarean section.Patients and Methods: Puerperas who underwent cesarean section at our hospital between January and August 2023 were recruited into the study and assessed using the Eysenck Personality Questionnaire-Revised Short Scale (EPQRSC) and Pain Catastrophizing Scale (PCS). Data on the numerical pain intensity at rest and during activity 24 h after surgery, number and dosage of analgesia pumps, and satisfaction with analgesia were recorded. According to the numerical pain score during activity 24 h post-operation, the patients were divided into the analgesia incomplete group (≥ 4) and control group (< 4). Univariate analysis, Spearman correlation analysis, and binary logistic regression analysis were used to evaluate the influence of personality characteristics and PCS on postoperative analgesia.Results: A total of 778 women were included in the study. The incidence of inadequate analgesia was 89.8%. The satisfaction rate of analgesia was 66.8%. Univariate analysis showed that extraversion; neuroticism; PCS; numbers of previous cesarean delivery; ASA; analgesic satisfaction; and 24-h analgesia pump compressions and dosage were associated with postoperative analgesia after cesarean section (P< 0.05). Using binary logistic regression analysis, the first cesarean section (odds ratio [OR]=0.056, 95% confidence interval [CI]=1.913– 19.174), the number of 24-h analgesic pump compressions (OR=8.464, 95% CI=0.356– 0.604), extraversion (OR=0.667, 95% CI=0.513– 0.866), neuroticism (OR=1.427, 95% CI=1.104– 1.844), and PCS (OR=7.718, 95% CI=0.657– 0.783) were factors affecting postoperative analgesia.Conclusion: The incidence of inadequate analgesia after a cesarean section was high (89.8% on the first day after surgery). Formulating accurate analgesia programs for women undergoing cesarean section with extraversion, neuroticism personality characteristics, and pain catastrophizing behaviors is necessary for improving their postoperative analgesia effects and satisfaction and promoting postpartum comfort.Keywords: aftercare, anesthetics, breast feeding, fear, personal satisfaction, postpartum depression

Wentao Zhong,1– 3,&ast; Qianyu Wang,2,&ast; Xiaofei Shen,4,&ast; Yuan Lv,2,3 Liang Sun,2 Ran An,5 Hongyan Zhu,5 Huiyun Cai,2 Gang Chen,2,3 Aijun Liu,5 Junfeng Du1– 3 1The Second School of Clinical Medicine, Southern Medical University, Guangdong, 510515, People’s Republic of China; 2Department of General Surgery, The 7th Medical Center, Chinese PLA General Hospital, Beijing, 100700, People’s Republic of China; 3Medical Department of General Surgery, The 1st Medical Center, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 4Division of Gastric Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, People’s Republic of China; 5Department of Pathology, the 7th Medical Center, Chinese PLA General Hospital, Beijing, 100700, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Aijun Liu, Department of Pathology, The 7th Medical Center, Chinese PLA General Hospital, NO. 5, Nanmen Cang, Beijing, 100700, People’s Republic of China, Email aliu301@126.com Junfeng Du, Department of General Surgery, the 7th Medical Center, Chinese PLA General Hospital, NO. 5, Nanmen Cang, Beijing, 100700, People’s Republic of China, Email dujf66@126.comPurpose: To demonstrate the intrinsic association of Neutrophil extracellular traps (NETs) with outcome and neoadjuvant therapy response of locally advanced rectal cancer (LARC), and the mechanisms.Patients and Methods: We enrolled 240 patients with LARC who underwent surgery without neoadjuvant therapy in two independent sets (training and validation), and 153 patients who received neoadjuvant therapy with biopsy followed by surgery. Immunohistochemistry, immunofluorescence staining and bioinformatics analysis were performed in formalin-fixed paraffin-embedded sections. NETs were identified by costaining for myeloperoxidase and citrullinated histone H3.Results: NETs were associated with recurrence-free survival in the surgical training and validation sets. High-NET density predicted poor postoperative survival of patients with LARC. Multivariate analysis identified NETs, TNM stage, and neutrophil-to-lymphocyte ratio as independent prognostic factors for recurrence-free survival. Low-NETs LARC demonstrated increased CD8+ T cell and lower T regulatory cell infiltration, which indicated a tumor immune microenvironment with strong antitumor capacity. High-NET density was associated with epithelial–mesenchymal transition, which is considered to contribute to tumor progression. In the neoadjuvant therapy cohort, high-NET density on biopsy was significantly associated with reduced likelihood of complete/near complete response.Conclusion: NET was an independent prognostic factor in LARC that were associated with patients’ survival, and NET density in pretreatment biopsies was an independent predictive biomarker of response to neoadjuvant therapy. This biomarker may be helpful in predicting survival in LARC with improved accuracy and selecting patients who will respond to neoadjuvant therapy.Keywords: NETs, tumor microenvironment, locally advanced rectal cancer, outcome

Man Li,&ast; Fang Wang,&ast; Xinxin Li, Xiaolan Ding, Juan Du Department of Dermatology, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fang Wang; Juan Du, Department of Dermatology, Peking University People’s Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, People’s Republic of China, Fax +861088325474, Email wfangxixi@sina.com; dujuan223@126.comBackground: Dermoscopic and ultrastructural features of vitiligo-associated leukotrichia (VAL) have not been well studied. This study is aimed at the dermoscopic and ultrastructural features of VAL.Methods: We present a cross-sectional study of VAL-related dermoscopic signs and their relationship with disease stages and duration of leukotrichia. Characteristics of hair surface and finer details including melanosomes, macrofibrils, and remnant nucleus were observed under Electron Microscopy (EM).Results: One hundred and forty samples on distinct sites from 100 patients were collected. Among 75 VAL from the scalp, the prevalence of diameter diversity of leukotrichia (52.6% vs 8.1%), Pohl-Pinkus constrictions (34.2% vs 0), and depigmented hair roots signs (34.2% vs 8.1%) in patients with progressive vitiligo was much higher than that in patients with stable vitiligo (all P< 0.05). The EM result of VAL showed that melanosomes were smaller with vesicles formation, reduced counts, and incomplete shape, and macrofibrils were irregularly arranged with widened spaces and vesicles formation.Limitations: No conclusions about the histopathologic characteristics or dermoscopic-histopathologic correlation of the VAL.Conclusion: The dermoscopic signs of diameter diversity of leukotrichia, Pohl-Pinkus constrictions, and depigmented hair roots are related to progressive vitiligo. The process of melanin synthesis and formation of VAL are impaired at the early stage of VAL under Electron microscopy.Keywords: vitiligo, leukotrichia, dermoscopy, electron microscopy, diameter diversity, Pohl-Pinkus constrictions, melanosomes

Conghui Hao,1 Hai Xu,1 Jingjing Du,1 Tianyu Zhang,1 Xiaobao Zhang,2 Zhibin Zhao,2 Hengfei Luan2 1Department of Anesthesiology, Graduate Training Base of Lianyungang First People’s Hospital of Jinzhou Medical University, Lianyungang, Jiangsu, People’s Republic of China; 2Department of anesthesiology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, The First People’s Hospital of Lianyungang, Lianyungang, Jiangsu, People’s Republic of ChinaCorrespondence: Hengfei Luan, The Affiliated Lianyungang Hospital of Xuzhou Medical University, The First People’s Hospital of Lianyungang, No. 6 East Zhenhua Road, Lianyungang, Jiangsu, People’s Republic of China, Email luanhengfei1027@163.comPurpose: Opioid analgesics may delay discharge and affect postoperative quality of recovery because of their significant adverse effects, such as hyperalgesia, postoperative nausea and vomiting (PONV), shivering and urine retention. We aimed to compare the quality of postoperative recovery (QoR) between patients undergoing laparoscopic cholecystectomy surgeries with opioid-free anesthesia (OFA) and those with opioid-based anesthesia (OA).Patients and Methods: 80 adult patients undergoing laparoscopic cholecystectomy were randomly allocated to an opioid-free anesthesia group (Group OFA) or an opioid-based anesthesia group (Group OA). The primary outcome was the quality of postoperative recovery using QoR-15 scale on postoperative day 1 (POD 1) and 2 (POD 2). The secondary outcomes included the incidence of opioid-related adverse symptoms, perioperative hemodynamic data, duration of post-anesthesia care unit (PACU) stay and duration of extubation, and the incidences of hypotension and bradycardia.Results: A statistically significant difference in total QoR-15 was observed between the two groups on POD 1 and POD 2 (91.00 (90.00, 92.00) vs 113.00 (108.25, 115.00), 106.00 (104.00, 112.00) vs 133.00 (130.00, 135.00), P < 0.001). The incidence of opioid-related symptoms was significantly different between the two groups on POD 1 (P < 0.05). There were between-group differences in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at T3 (P 0.05). There was no difference in heart rate between the two groups at all observed time points, either (P > 0.05).Conclusion: We concluded that the quality of recovery of patients receiving OFA was superior to those receiving OA after laparoscopic cholecystectomy.Keywords: opioid-free anesthesia, opioid-based anesthesia, postoperative recovery, laparoscopic cholecystectomy

Yu Hu,1– 3 Hui Guo,1– 3 Shuai Cheng,1– 3 Junpeng Sun,2,4 Jiaqun Du,2,4 Xiaobang Liu,2,4 Ying Xiong,5 Liqing Chen,6 Chang Liu,3,6 Chao Wu,2,4 He Tian1– 3 1School of Basic Medicine, Jinzhou Medical University, Jinzhou, Liaoning, 121001, People’s Republic of China; 2Liaoning Provincial Collaborative Innovation Center for Medical Testing and Drug Research, Jinzhou Medical University, Jinzhou, Liaoning, 121001, People’s Republic of China; 3Key Laboratory of Medical Tissue Engineering of Liaoning Province, Jinzhou Medical University, Jinzhou, Liaoning, 121001, People’s Republic of China; 4Pharmacy School, Jinzhou Medical University, Jinzhou, Liaoning, 121001, People’s Republic of China; 5Laboratoire Catalyse et Spectrochimie (LCS), Normandie Université, ENSICAEN, UNICAEN, CNRS, Caen, 14050, France; 6Department of Endocrinology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 121000, People’s Republic of ChinaCorrespondence: He Tian; Chao Wu, Email tianhe@jzmu.edu.cn; wuchao@jzmu.edu.cnBackground: Oxidative stress induced reactive oxygen species (ROS) and aggregation of amyloid β (Aβ) in the nervous system are significant contributors to Alzheimer’s disease (AD). Cerium dioxide and manganese oxide are known as to be effective and recyclable ROS scavengers with high efficiency in neuroprotection.Methods: A hollow-structured manganese-doped cerium dioxide nanoparticle (LMC) was synthesized for loading Resveratrol (LMC-RES). The LMC-RES were characterized by TEM, DLS, Zeta potential, and X-ray energy spectrum analysis. We also tested the biocompatibility of LMC-RES and the ability of LMC-RES to cross the blood-brain barrier (BBB). The antioxidant effects of LMC-RES were detected by SH-SY5Y cells. Small animal live imaging was used to detect the distribution of LMC-RES in the brain tissue of AD mice. The cognitive abilities of mice were tested by water maze and nesting experiments. The effects of LMC-RES in reducing oxidative stress and protecting neurons was also explored by histological analysis.Results: The results showed that LMC-RES had good sustained release effect and biocompatibility. The drug release rate of LMC-RES at 24 hours was 80.9 ± 2.25%. Meanwhile, LMC-RES could cross the BBB and enrich in neurons to exert antioxidant effects. In Aβ-induced SH-SY5Y cells, LMC-RES could inhibits oxidative stress through the Nrf-2/HO-1 signaling pathway. In AD model mice, LMC-RES was able to reduce ROS levels, inhibit Aβ-induced neurotoxicity, and protect neurons and significantly improve cognitive deficits of AD mice after drug administration.Conclusion: LMC-RES can effectively across the BBB, reduce oxidative stress, inhibit Aβ aggregation, and promote the recovery of neurological function.Keywords: cerium dioxide nanoparticles, manganese, oxidative stress, resveratrol, Alzheimer’s disease

Jingjing Du,1 Yiqing Tao,2 Jiaxing Yang,1 Jiachang Cai,1 Hongwei Zhou,1 Rong Zhang,1 Yanyan Hu1 1Department of Clinical Laboratory, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, People’s Republic of China; 2Department of Orthopedics, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Rong Zhang; Yanyan Hu, Department of Clinical Laboratory, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, 310009, People’s Republic of China, Email zhang-rong@zju.edu.cn; yanyanhu@zju.edu.cnAbstract: Brucellosis is a zoonotic disease caused by Brucella spp., with the highest prevalence found in the northern cities of China. In this case report, we present an occurrence of spinal infection caused by B. melitensis in a 67-year-old man residing in a non-endemic area of southern China. The patient initially presented with chest and back pain, which was not accurately diagnosed and treated at a local hospital. Subsequently, due to worsening pain, he was admitted to our hospital. To determine the cause of the infection, we performed CT-guided aspiration biopsy and collected biopsy tissue for metagenomic next-generation sequencing (mNGS) on the second day of hospitalization. Imaging investigations revealed involvement of the thoracic vertebrae, specifically thoracic 4– 7 with the main focus on 5– 6, accompanied by stenosis of the intervertebral space. The mNGS results indicated that the spine infection was caused by B. melitensis. The patient’s history as a shepherd and a positive Rose Bengal plate test (RBPT) further supported the diagnosis of brucella spondylitis. In order to alleviate pain and restore spinal function, the patient underwent posterior internal fixation of the thoracic spine. Treatment was initiated with cefoperazone/sulbactam, followed by doxycycline. Subsequently, the patient was switched to a combination therapy of rifampicin and doxycycline for a duration of six weeks. The patient responded well to treatment, and his condition remained stable. In conclusion, brucellosis is a common disease that can be easily misdiagnosed. This case report highlights the potential value of mNGS in early and rapid diagnosis. We believe that mNGS can serve as an effective tool to improve the diagnosis of spine infections caused by this pathogen.Keywords: spine infection, Brucella melitensis, metagenomic next-generation sequencing, Rose Bengal plate test

Jing Du, Xin Zhao, Xiumei Xu, Zhichao Zhang, Xiaomei Zhang Department of Endocrinology and Metabolism, Peking University International Hospital, Beijing, People’s Republic of ChinaCorrespondence: Xiaomei Zhang, Department of Endocrinology and metabolism, Peking University International Hospital, No. 1 Life Garden Road Zhongguancun Life Science Garden Changping District, Beijing, People’s Republic of China, Tel/Fax +86-010-69006105, Email z.x.mei@163.comPurpose: To explore the association between thyroid parameters and subclinical atherosclerosis (AS) in hospitalised euthyroid patients with type 2 diabetes mellitus (T2DM).Patients and Methods: A retrospective analysis was conducted involving 1245 inpatients with T2DM. Free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) levels were measured, and carotid artery ultrasonography was performed. Thyroid hormone (TH) sensitivity was evaluated using thyroid feedback quantile-based index (TFQI), TSH index (TSHI), thyrotropin thyroxine resistance index (TT4RI), and free triiodothyronine/free thyroxine ratio (FT3/FT4).Results: In inpatients with T2DM having normal thyroid function, the incidence of subclinical AS declined with increasing levels of FT3, FT4, and FT3/FT4 (P trend < 0.05). Logistic regression analysis revealed that FT4 (OR, 0.914; 95% CI, 0.845– 0.989), FT3 (OR, 0.374; 95% CI, 0.277– 0.504), and FT3/FT4 (OR, 0.036; 95% CI, 0.013– 0.061) were independently associated with subclinical AS (P < 0.05). However, TSH, TFQI, TSHI, and TT4RI levels were not associated with subclinical AS (P > 0.05). FT3/FT4 demonstrated superior predictive accuracy for subclinical AS than that of FT3 or FT4 alone (P < 0.001), with a cutoff point of 0.25.Conclusion: In euthyroid inpatients with T2DM, subclinical AS exhibited negative correlation with FT3, FT4, and FT3/FT4 levels, independent of other risk factors for AS. Additionally, FT3/FT4 ratio had a good predictive value for subclinical AS.Keywords: thyroid hormone, thyroid hormone sensitivity, euthyroid, diabetes mellitus, atherosclerosis

Canbin Dong,1,&ast; Fang Liu,1,&ast; Zuda Liao,2 Lanmei Lin,1 Runnan Wang,1 Juan Du,1 Wen Huang1 1Department of Dermatology, Huashan Hospital, Fudan University, Shanghai Institute of Dermatology, Shanghai, People’s Republic of China; 2Medical Insurance Office of Huashan Hospital Affiliated, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Juan Du; Wen Huang, Department of Dermatology, Huashan Hospital, Fudan University, Shanghai Institute of Dermatology, Shanghai, 200040, People’s Republic of China, Tel +86-21-52889999, Fax +86-21-52887782, Email dujuan@huashan.org.cn; huangwen2@huashan.org.cnBackground: There are still some gaps in the summary and generalization of cosmetic-related adverse reaction reports.Objective: The aim of this study is to summarize and analyze the occurrence of cosmetic adverse reactions in Shanghai Han population by using available survey data.Materials and Methods: Collection, statistics and analysis of patients with cosmetic adverse reactions in Shanghai Huashan Hospital from 2017 to 2021.Results: Among the 1004 patients, most of them (96.71%) were diagnosed as cosmetic contact dermatitis, which often occurred within 3 days of using cosmetics (51.79%). A total of 260 patients were tested with patch test, but the compliance rate was only 18.08%. Among them, 240 patients underwent additional European standard allergen tests, and positive allergens were detected in 210 cases (87.5%). Univariate analysis revealed that dosage form (emulsion and cream), age (≤ 25 years) and the allergic ingredients triethanolamine, rose oil, propylene glycol, thiomersal and musk ambrette are associated with the occurrence of cosmetic adverse reactions within seven days. A logit prediction model was also successfully constructed: Logit (P) = 1.710– 0.796× 1 + 1.185× 2 − 3.650X3-1.335X4.Conclusion: This study complements the data reported on cosmetic adverse reactions in the Chinese Han population and suggests that in future clinical diagnosis and data collection, emphasis should be placed on patch testing, combining the patch test with cosmetic protoplast with the European standard allergen test to improve the detection rate.Keywords: adverse reaction reporting, cosmetics, contact dermatitis, personal care products, patch tests

Xiaoyu Pan,1,&ast; Huazheng Zhu,2,&ast; Jinglong Du,1 Guangtao Hu,1 Baoru Han,1 Yuanyuan Jia1 1College of Medical Informatics, Chongqing Medical University, Chongqing, People’s Republic of China; 2College of Intelligent Technology and Engineering, Chongqing University of Science and Technology, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanyuan Jia, Email yyjia@cqu.edu.cnAim: The Coronavirus Disease 2019 (COVID-19) pandemic has increased the public health burden and brought profound disaster to humans. For the particularity of the COVID-19 medical images with blurred boundaries, low contrast and different infection sites, some researchers have improved the accuracy by adding more complexity. Also, they overlook the complexity of lesions, which hinder their ability to capture the relationship between segmentation sites and the background, as well as the edge contours and global context. However, increasing the computational complexity, parameters and inference speed is unfavorable for model transfer from laboratory to clinic. A perfect segmentation network needs to balance the above three factors completely. To solve the above issues, this paper propose a symmetric automatic segmentation framework named MS-DCANet. We introduce Tokenized MLP block, a novel attention scheme that uses a shift-window mechanism to conditionally fuse local and global features to get more continuous boundaries and spatial positioning capabilities. It has greater understanding of irregular lesion contours. MS-DCANet also uses several Dual Channel blocks and a Res-ASPP block to improve the ability to recognize small targets. On multi-modality COVID-19 tasks, MS-DCANet achieved state-of-the-art performance compared with other baselines. It can well trade off the accuracy and complexity. To prove the strong generalization ability of our proposed model, we apply it to other tasks (ISIC 2018 and BAA) and achieve satisfactory results.Patients: The X-ray dataset from Qatar University which contains 3379 cases for light, normal and heavy COVID-19 lung infection. The CT dataset contains the scans of 10 patient cases with COVID-19, a total of 1562 CT axial slices. The BAA dataset is obtained from the hospital and includes 387 original images. The ISIC 2018 dataset is from the International Skin Imaging Collaborative (ISIC) containing 2594 original images.Results: The proposed MS-DCANet achieved evaluation metrics (MIOU) of 73.86, 97.26, 89.54, and 79.54 on the four datasets, respectively, far exceeding other current state-of-the art baselines.Conclusion: The proposed MS-DCANet can help clinicians to automate the diagnosis of COVID-19 patients with different symptoms.Keywords: multi-modality COVID-19 lesion segmentations, laboratory to clinic, multi-scale feature learning, depthwise separable convolution

Ran Li,1,2,&ast; Chen Liu,1,2,&ast; Chaoqiong Wan,1,2 Tiantian Liu,1,2 Rongrong Zhang,1,2 Jie Du,1 Xiangyu Wang,1,2 Xiaofeng Jiao,1,2 Ruifang Gao,1,2 Bing Li1 1Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, People’s Republic of China; 2Department of Pediatric and Preventive Dentistry, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ruifang Gao; Bing Li, Email gruifang_26@163.com; libing-1975@163.comPurpose: Oral squamous cell carcinoma (OSCC) is a malignant disease with serious impacts on human health and quality of life worldwide. This disease is traditionally treated through a combination of surgery, radiotherapy, and chemotherapy. However, the efficacy of traditional treatments is hindered by systemic toxicity, limited therapeutic effects, and drug resistance. Fibroblast activation protein (FAP) is a membrane-bound protease. Although FAP has limited expression in normal adult tissues, it is highly expressed in the tumor microenvironment of many solid cancers – a characteristic that makes it an ideal target for anticancer therapy. In this study, we constructed a nano-drug delivery system (NPF@DOX) targeting FAP to increase the therapeutic efficiency of synergistic chemo-photothermal therapy against OSCC.Methods: We utilized PEGylated nano-graphene oxide (NGO) to link doxorubicin (DOX) and fluorescently-labeled, FAP-targeted peptide chains via hydrogen bonding and π–π bonding to enhance the targeting capability of NPF@DOX. The synthesis of NPF@DOX was analyzed using UV–Vis and FT–IR spectroscopy and its morphology using transmission electron microscopy (TEM). Additionally, the drug uptake efficiency in vitro, photo-thermal properties, release performance, and anti-tumor effects of NPF@DOX were evaluated and further demonstrated in vivo.Results: Data derived from FT–IR, UV–Vis, and TEM implied successful construction of the NPF@DOX nano-drug delivery system. Confocal laser scanning microscopy images and in vivo experiments demonstrated the targeting effects of FAP on OSCC. Furthermore, NPF@DOX exhibited a high photothermal conversion efficiency (52.48%) under near-infrared radiation. The thermogenic effect of NPF@DOX simultaneously promoted local release of DOX and apoptosis based on a pH-stimulated effect. Importantly, FAP-targeted NPF@DOX in combination with PTT showed better tumor suppression performance in vivo and in vitro than did either therapy individually.Conclusion: NPF@DOX can precisely target OSCC, and combined treatment with chemical and photothermal therapy can improve the therapeutic outcomes of OSCC. This method serves as an efficient therapeutic strategy for the development of synergistic anti-tumor research.Keywords: fibroblast activation protein, nano-graphene oxide, photothermal therapy, oral squamous cell carcinoma, targeted combination therapy

Xinxin Li, Yifang Sun, Juan Du, Fang Wang, Xiaolan Ding Department of Dermatology, Peking University People’s Hospital, Beijing, People’s Republic of ChinaCorrespondence: Xiaolan Ding, Department of Dermatology, Peking University People’s Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, People’s Republic of China, Tel +8613522658992, Fax +861088325474, Email Lancyding@126.comAbstract: Vitiligo is an acquired autoimmune skin disorder, clinically characterized by distinct white macules and patches resulting from progressive melanocyte destruction. JAK-STAT pathway plays an important role in the loss of epidermal melanocytes. Baricitinib can block the JAK-STAT pathway and the downstream chemokines as a new JAK1/2 inhibitor. In this report, we describe the successful treatment of 2 patients with oral baricitinib combined with NB-UVB phototherapy, which provides a good alternative and supplementary to treat refractory vitiligo.Keywords: IFN-γ signaling pathway, Janus kinase inhibitor, baricitinib, vitiligo

With a view to understanding the performance of the blast furnace slag with high Al2O3 content, the effects of w(MgO)/w(Al2O3), w(CaO)/w(SiO2), and w(Al2O3) on the melting performance (melting characteristic temperature and melting heat) of the blast furnace slag with high Al2O3 content were investigated by the differential scanning calorimeter (DSC) method. Experimental results indicate that melting end temperature (Tend) for almost all the slags has no obvious change with the increase of w(MgO)/w(Al2O3), w(CaO)/w(SiO2) and w(Al2O3) of the slag will raise Tend of the slag. When (w(MgO)/w(Al2O3), R, and w(Al2O3) are high, the melting onset temperature (Tonset) of the slag increases with the increase of any variables. When w(CaO)/w(SiO2) is low, Tonset of the slag decreases with the increase of w(Al2O3). w(MgO)/w(Al2O3), w(CaO)/w(SiO2), and w(Al2O3) within the scope of this study and all these factors lead to the increase of the slag melting heat.

Joanne Du,1 Catherine Roth,2 Sujana Dontukurthy,3 Joseph D Tobias,2,4 Giorgio Veneziano2,4 1The Ohio State University College of Medicine, Columbus, OH, USA; 2Department of Anesthesiology & Pain Medicine, Nationwide Children’s Hospital, Columbus, OH, USA; 3Department of Anesthesiology, Valley Children’s Hospital, Madera, CA, USA; 4Department of Anesthesiology & Pain Medicine, The Ohio State University College of Medicine, Columbus, OH, USACorrespondence: Giorgio Veneziano, Department of Anesthesiology & Pain Medicine, Nationwide Children’s Hospital, 700 Children’s Dr, Columbus, OH, 43205, USA, Tel + 1 614-722-4200, Email Giorgio.Veneziano@nationwidechildrens.orgPurpose: Awake spinal anesthesia continues as an alternative to general anesthesia for infants. Standard clinical practice includes the manual palpation of surface landmarks to identify the desired intervertebral space for lumbar puncture (LP). The current study investigates the accuracy of manual palpation for identifying the intended intervertebral site for LP, using ultrasonography for confirmation and to determine the interspace where the conus medullaris ends.Patients and Methods: After informed parental consent, patients less than one year of age undergoing spinal anesthesia for lower abdominal, urologic, or lower extremity surgical procedures were included. Patients were held in the seated position and an attending pediatric anesthesiologist or pediatric anesthesiology fellow declared the vertebral interspace intended for needle insertion, palpated surface landmarks, and placed a mark at the site. A research anesthesiologist then determined the actual vertebral interspace of the marked site and the location of the conus medullaris using ultrasonography. The time to complete both techniques (manual palpation and ultrasonography) was recorded.Results: The study cohort included 50 infants (median age of 7 months). Sixteen vertebral interspaces (32%) were inaccurately marked. One was marked two spaces higher than intended, ten were marked one space higher than intended, and five were marked one space lower than intended. In one patient, the intended vertebral interspace for the lumbar puncture overlaid the conus medullaris. The median time required was 25 seconds (IQR 14.3, 32) for palpation and 39 seconds (IQR 29, 63.8) for ultrasonography.Conclusion: Manual palpation of surface landmarks to determine the correct interspace for LP for spinal anesthesia in infants is inaccurate. The time required to perform spinal ultrasonography in infants for determination of the optimal site for LP is brief and may be useful in ensuring accurate identification of the correct interspace and the location of the conus medullaris.Keywords: spinal anesthesia, infant, ultrasonography, palpation, lumbar puncture, conus medullaris

Jie Du,1 Jing Niu,1 Lanxiang Ma,2 Yongjie Sui,1 Shuili Wang3 1Department of Health Examination Center, Shaanxi Provincial People Hospital, Xi’an, People’s Republic of China; 2Department of Cardiology, Shaanxi Provincial Corps Hospital, Chinese People’s Armed Police Forces, Xi’an, People’s Republic of China; 3Department of Respiratory Medicine, Shaanxi Provincial People Hospital, Xi’an, People’s Republic of ChinaCorrespondence: Lanxiang Ma, Department of Cardiology, Shaanxi Provincial Corps Hospital, Chinese People’s Armed Police Forces, Xi’an, People’s Republic of China, Tel +86-15991765901, Email mztjzx2250@163.comPurpose: High blood urea nitrogen (BUN) is associated with an elevated risk of mortality in various diseases, such as heart failure and pneumonia. Heart failure and pneumonia are common comorbidities of chronic obstructive pulmonary disease (COPD) exacerbation. However, data on the relationship of BUN levels with length of stay (LOS) in patients with pneumonic COPD exacerbation are sparse. The purpose of this study was to evaluate the correlation between BUN levels and LOS in a cohort of patients with pneumonic COPD exacerbation.Patients and Methods: The present study was a multicentre, retrospective cohort study. A total of 1226 patients with pneumonic COPD exacerbation were included through a validated algorithm derived from the 10th revision of the International Classification of Diseases and Related Health Problems (ICD-10). It should be noted that the entire study was completed by Shiroshita et al, who uploaded the data to the DATADRYAD website. The author only used these data for secondary analysis.Results: After adjusting for potential confounders (age, gender), a nonlinear relationship was detected between BUN levels less than 40 mg/dl and LOS. The effect sizes and the confidence intervals on the left and right sides of the inflection point were 0.27 (0.16, 0.39) and − 0.17 (− 0.34, 0.01), respectively.Conclusion: High levels of BUN in the hospital may be associated with increased LOS. BUN was positively related to LOS when BUN was less than 40 mg/dl.Keywords: pneumonia, chronic obstructive pulmonary disease, exacerbation, blood urea nitrogen, length of stay

Haiqing Fan &ast;, Yue Yu &ast;, Jinhui Du, Likun Liu, Yilin Luo, Hui Yu, Xin Liao Department of Medical Imaging, The Affiliated Hospital of Guizhou Medical University, Guiyang City, Guizhou Province, 550004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xin Liao, Department of Medical Imaging, The Affiliated Hospital of Guizhou Medical University, No. 29 Guiyi Street, Yunyan District, Guiyang City, Guizhou Province, 550004, People’s Republic of China, Tel +86 13765065226, Email liaoxinlxlx@126.comObjective: To investigate the clinical, imaging, and pathological features of gliosarcoma.Methods: The clinical data of 14 patients with gliosarcoma confirmed by surgery and pathology at our hospital between 2010 and 2021 were analyzed retrospectively, and the relevant literature was reviewed.Results: In all 14 cases, the gliosarcoma was located in the supratentorial brain parenchyma and involved a single lesion. There were more male patients (64.3%) than female patients (35.7%), and 57.1% of all the patients were 40– 60 years of age. The prognosis of all 14 patients was poor, and the average survival time was approximately seven months. The computed tomography findings revealed mostly mixed density lesions, and some cases were complicated with bleeding. The magnetic resonance imaging revealed irregularly shaped mass lesions of different sizes, with uneven or circular enhancement. Cystic degeneration and necrosis could be seen in all the masses, some of which showed signs of bleeding and were surrounded by different degrees of edema and space-occupying effects. The pathological examination revealed that the tumors had bidirectional differentiation of the glial and sarcoma components, while the immunohistochemistry examination revealed glial fibrillary acidic protein-positive and reticular fiber-positive staining in the sarcoma.Conclusion: The clinical manifestations of gliosarcoma are nonspecific, but imaging reveals that the condition has certain characteristics, typically consisting of a huge supratentorial mass, with an irregular heterogeneous periphery or obvious mass-like augmentation after enhancement. The final diagnosis depends on the results of a pathological examination.Keywords: brain, gliosarcoma, computed tomography, magnetic resonance imaging, pathology

Yanmei Ma,1– 3,&ast; Jing Du,4,&ast; Zhihua Yin,1,3 Hanying Dai,2 Yazhi Wei,1,3 Yuhao Xia,2,4 Lingyun Li,2 Zhizhong Ye,1,3 Zhong Huang2,3 1Shenzhen Futian Hospital for Rheumatic Diseases, Shenzhen, 518040, People’s Republic of China; 2Biological Therapy Institute, Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Immunology, Health Science Center, Shenzhen University, Shenzhen, 518055, People’s Republic of China; 3Joint Research Laboratory for Rheumatology of Shenzhen University Health Science Center and Shenzhen Futian Hospital for Rheumatic Diseases, Shenzhen, 518055, People’s Republic of China; 4Department of Laboratory Medicine, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhizhong Ye, Shenzhen Futian Hospital for Rheumatic Diseases, Shenzhen, 518040, People’s Republic of China, Email yezhizhong2000@163.com Zhong Huang, Department of Immunology, Biological Therapy Institute of Shenzhen University, Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen University Health Science Center, Shenzhen, 518055, People’s Republic of China, Tel +86-755-86671943, Email zhuang809@126.comIntroduction: Ankylosing spondylitis (AS) is a common form of chronic inflammatory rheumatic disease. Metallothionein-1 (MT-1) has been known to play an immunosuppressive role in various noninfectious inflammatory diseases, especially osteoarthritis and rheumatoid arthritis, thus inhibiting inflammation and pathogenesis in various diseases. However, whether MT-1 is related to AS is unclear. Here, we examined the levels of MT-1 in patients with AS and its correlation with the disease activity, complication, clinical indexes, and inflammatory cytokines and attempted to explain the effect of MT-1 on inflammation in AS.Methods: The messenger RNA (mRNA) and protein expression of MT-1 in patients with AS were detected through real-time polymerase chain reaction and enzyme-linked immunosorbent assay. The associations between serum MT-1 protein level and clinical indexes or proinflammatory cytokines in AS were analyzed using the Spearman correlation test.Results: The mRNAs and serum protein levels of MT-1 were significantly higher in patients with AS, especially in patients with active AS and patients with osteoporosis (OP) than in healthy controls (HCs), and no difference was observed between patients with inactive AS and HCs. Serum MT-1 levels positively correlated with disease activity, proinflammatory cytokines, and clinical indexes Ankylosing Spondylitis Disease Activity Score with C-Reactive Protein, C-reactive protein level, and erythrocyte sedimentation rate in patients with AS.Conclusion: MT-1 expression was upregulated in patients with active AS but not in those with inactive AS and positively correlated with clinical indexes, especially in OP, as well as with proinflammatory cytokines tumor necrosis factor–alpha, interleukin (IL)-1β, and IL-6 in patients with AS.Keywords: metallothionein-1, ankylosing spondylitis, noninfectious inflammatory diseases, inflammation cytokines, regulatory cytokines

Hongcheng Zhang,1,2,&ast; Qiwen Dai,1,2,&ast; Maogui Zeng,1 Yingying Liu,1 Jian Du,2 Wensheng Pang,2 Juan Hu,1,2 Liwu Chen1 1The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, 350003, People’s Republic of China; 2The School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Juan Hu; Liwu Chen, The Second Affiliated Hospital Fujian University of Traditional Chinese Medicine, Fuzhou, 350003, People’s Republic of China, Email huj@fjtcm.edu.cn; chenlw_2022@163.comBackground: Fuzheng Yiliu decoction (FZYLD), a Chinese formula consisting of four herbs, can be clinically used as an adjuvant therapy after surgery or palliative treatment for advanced liver cancer.Methods: This study identified the endogenous and exogenous metabolites of FZYLD in rat serum to characterize the underlying mechanism of its antitumor activity, as well as relieving cancer-related weakness. An orthotopic transplantation rat model of HepG2 cells was established and administered with FZYLD by gastric perfusion for 14 days. Cardiopulmonary function and tail suspension test were used to evaluate the bodily weakness of hepatocellular carcinoma (HCC) rats. Tumor weight and size were measured to calculate inhibition ratios. Serum of different concentrations of FZYLD was used to culture the 2-[N-(7-nitrobenz-2-oxa-1, 3-diaxol-4-yl) amino]-2-deoxyglucose-labeled HepG2 cells. IC50 value was measured using MTT assay. Endogenous and exogenous metabolites in rat serum were detected using nuclear magnetic resonance or LC-MS/MS spectroscopy.Results: FZYLD improved cardiopulmonary function, decreased immobility time in tail suspension test, and yielded tumor inhibition ratios of up to 27%. Serum endogenous markers, such as lipoproteins (high- and low-density lipoproteins), glucose, and valine, and lactic acid metabolic disturbance were recovered, to some extent, in HCC rats. Exogenous metabolites, diosgenin, apigenin-7-O-acetyl-β-D-glucoside, calycosin-7-glucoside, calycosin, ganoderic-acid-A, formononetin, and methylnissolin, became detectable in the blood. FZYLD-containing serum substantially inhibited the proliferation of HepG2-cells. IC50 value was found to be 24.31%. Further, we confirmed that FZYLD could revert energy and lipid metabolism disorders and that its constituents could be bioactive components that induce apoptosis in cancer cells.Conclusion: The present study explained the mechanism of the effect of FZYLD on body empty, fatigue, and low immunity in patients with cancer, offering an efficient way for research of natural compounds in traditional Chinese medicine.Graphical Abstract: Keywords: HCC rat model, Fuzheng Yiliu decoction, regulation of metabolic balance, ameliorating cancer-related weakness, anti-liver tumor

Wei Liu, Zenghui Li, Xinyu Zhang, Juanjuan Du, Rui Liang, Yifan Ji, Wei Tang, Xiaoming Zhang Medical Imaging Key Laboratory of Sichuan Province and Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, People’s Republic of ChinaCorrespondence: Xiaoming Zhang; Wei Tang, Medical Imaging Key Laboratory of Sichuan Province and Department of Radiology, Affiliated Hospital of North Sichuan Medical College, No. 1 South Maoyuan Road, Nanchong, Sichuan, 637000, People’s Republic of China, Tel +86 13808271001 ; +86 1369600 2904, Email zhangxm@nsmc.edu.cn; tw-n-g-up@163.comPurpose: To study the CT characteristics of acute pancreatitis (AP) associated with preexisting fatty liver (FL) and the impact of preexisting FL on the severity of AP and persistent systemic inflammatory response syndrome (SIRS).Patients and Methods: A total of 189 patients with AP were divided into AP with and without preexisting FL. The CT features, clinical characteristics, severity of AP, and presence of persistent SIRS between the two groups were compared. Univariate and multivariate analyses were performed to determine the risk factors for predicting SIRS. The diagnostic performances of the risk factors were evaluated by receiver operating characteristic (ROC) curve analysis.Results: Among the 189 patients, 49.7% (94/189) had preexisting FL. On CT, AP patients with preexisting FL were more likely to develop necrosis (23.4% vs 10.5%, p=0.021), local complications (45.7% vs 29.5%, p=0.025) and persistent SIRS (59.6% vs 27.4%, p< 0.001). Multivariate analysis showed that preexisting FL (OR=2.863, 95% CI: 1.264– 6.486, p=0.012), APACHE II≥ 6 (OR=1.334, 95% CI: 1.117– 1.594, p=0.002), and MCTSI ≥ 4 (OR=1.489, 95% CI: 1.046– 2.119, p=0.027) could be independent risk factors for persistent SIRS. The areas under the ROC curve of preexisting FL, APACHE II, and MCISI in diagnosing AP patients with persistent SIRS were 0.664, 0.703, and 0.783, respectively.Conclusion: Patients with preexisting FL were more likely to develop necrosis and local complications on CT and present more severe AP and persistent SIRS. Preexisting FL can be an independent risk factor in predicting the presence of persistent SIRS in patients with AP.Keywords: acute pancreatitis, fatty liver, severity, systemic inflammatory response syndrome, Atlanta classification

Jianpeng Yu,1,&ast; Qi Zhou,1,&ast; Ying Xu,1,&ast; Tieyun Wang,1 Jun Du,1 Lifang Zhao,1 Juan Li,1 Haiyan Wang,1 Qianqian Xu,2 Xueli Lai,1 Zhiyong Guo1 1Department of Nephrology, Shanghai Changhai Hospital, Shanghai, People’s Republic of China; 2Department of Rheumatology and Immunology, Shanghai Changhai Hospital, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xueli Lai; Zhiyong Guo, Email laixueli_changhai@163.com; drguozhiyong@163.comObjective: To investigate the relationship between serum folate (FA) levels and residual renal function (RRF) in continuous ambulatory peritoneal dialysis (CAPD) patients.Methods: Clinical data were collected from 180 hospitalized patients who received CAPD regularly. Patients were divided into the FA deficiency group and the FA non-deficiency group according to serum FA level. Data on age, sex, PD vintage, hemoglobin, mean corpuscular volume, serum FA, total Kt/V, residual kidney Kt/V, peritoneum Kt/V, creatinine clearance (Ccr), ultrafiltration volume, cystatin C (cytC), serum creatinine (Scr), urea nitrogen, retinol-binding protein and the primary disease were gathered from 2 groups. Statistical methods were used to analyze the relationship between serum FA level and RRF.Results: Peritoneal Kt/V, cytC, Scr were higher, and residual kidney Kt/V was lower in FA deficiency group than in non-deficiency group. Univariate correlation showed the peritoneal Kt/V, cytC, Scr negatively correlated with serum FA while residual kidney Kt/V positively correlated with serum FA, and there was a simple linear regression relationship between serum FA and residual kidney Kt/V. Differences were statistically significant (P< 0.05).Conclusion: There is a relationship between serum FA and RRF in CAPD patients. Prospective studies or trials should be performed to clarify the importance of FA supplementation on RRF during peritoneal dialysis.Keywords: folate, continuous ambulatory peritoneal dialysis, residual renal function

Lichuan Zeng,1,&ast; Qu Wang,2,&ast; Haodong Liao,1,&ast; Fengchun Ren,1 Yudong Zhang,1 Jian Du,3 Huaqiang Liao,1 Mingguo Xie,1 Wenbin Wu3 1Department of Radiology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Department of Ultrasound, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 3Department of Geriatrics, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingguo Xie, Department of Radiology, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu, People’s Republic of China, Email 767030837@qq.com Wenbin Wu, Department of Geriatrics, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu, People’s Republic of China, Email wwb1201@vip.sina.comPurpose: We aimed to investigate the prevalence of fluid-attenuated inversion recovery (FLAIR) vascular hyperintensities (FVHs) and the clinical–radiological correlation in transient ischemic attack (TIA) patients.Materials and Methods: We performed a retrospective analysis of TIA patients who had undergone magnetic resonance imaging (MRI) within 24 h of symptom onset. Two independent neuroradiologists investigated the presence of FVHs, large-artery severe stenosis or occlusion (LASO) in magnetic resonance angiograms, and the nature of factors associated with FVH.Results: A total of 207 patients were enrolled in this study. FVHs were detected in 42 (20.3%) patients, in whom atrial fibrillation (AF) was confirmed in 25 (59.5%) cases and LASO was confirmed in 30 (71.4%) cases. The corresponding figures were 33 (20.0%) and 10 (6.1%), respectively, for the 165 FVH-negative patients. Logistic regression analysis showed that time from symptom onset to MRI (odds ratio [OR] = 0.82, 95% CI 0.76– 0.97, p = 0.042), previous stroke (OR = 2.95, 95% CI 1.58– 6.74, p = 0.002), AF (OR = 5.83, 95% CI 2.24– 9.46, p < 0.001), and LASO (OR = 4.28, 95% CI 2.96– 10.28, p < 0.001) were independently associated with FVH. Overall, the sensitivity and specificity of FVH for predicting LASO were 0.75 and 0.93, respectively, and the positive predictive value, negative predictive value, and accuracy were 0.71, 0.94, and 0.89, respectively. The area under the receiver operating characteristic curve was 0.839. FVH-positive TIA patients with LASO had less AF (14 [46.7%] versus 11 [91.7%], p = 0.019) and longer times from symptom onset to MRI (6.8 ± 2.8 h versus 4.8 ± 1.3 h, p = 0.004) than those without LASO.Conclusion: The presence of FVH could be an important marker in TIA patients. Many factors, including LASO, AF, and time from symptom onset to MRI, are associated with the detection of FVH.Keywords: FLAIR vascular hyperintensity, hyperintense vessel, transient ischemic attack, magnetic resonance imaging

Junyuan Deng, Yujie Guo, Jichun Gu, Jiali Du, Lei Kong, Boan Tao, Ji Li, Deliang Fu Department of Pancreatic Surgery, Pancreatic Disease Institute, Huashan Hospital, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Ji Li, Department of Pancreatic Surgery, Pancreatic Disease Institute, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China, Email liji@huashan.org.cnPurpose: Pancreatic cyst neoplasm (PCN) is a precursor of pancreatic cancer. Previous studies reported PCN was often concurrent with diabetes. We aim to examine the association between diabetes with PCN malignancy and to detect the potential role of diabetes in PCN management and treatment.Patients and Methods: A total of 224 patients who were diagnosed with the three major types of PCN (IPMN, MCN, and SCN) and underwent surgical resection were selected. Patients were divided into three groups (normal group, new-onset diabetes group (NODM) (< 4years), and long-standing diabetes group (LSDM) (> 4years)) according to diabetic history and diagnostic time interval. Diabetes, fast blood glucose level, HbA1c, and insulin resistance level were measured. Malignant PCN (mPCN) radiological features (worrisome features and high-risk stigmata) were analyzed. Pathological features (PCN type, dysplasia grade, tumor stage, and tumor volume) and immunohistology of Ki67 and SMAD4 were performed. Diagnostic efficacy of each variable was determined by the ROC curve. mPCN diagnosis was the main outcome in diagnostic prediction and overall survival as the glucose controlling outcome variables.Results: Diabetes groups (NODM and LSDM) showed difference with the normal group in age, weight loss, malignancy, CA19-9 value, CEA value, Ki-67 value, tumor volume, pathological grade, and a lowered pancreatic fistula risk. NODM was related to insulin resistance, weight loss, and SMAD4 mutation. NODM (87.3%) and high insulin resistance rate (93.6%) significantly increased the sensitivity of radiological evidence-based mPCN diagnosis. Moreover, long-standing diabetes and elevated HbA1c led to reduced survival in mPCN patients than the normal PCN group. Anti-diabetic drugs showed limited influence on PCN malignancy and tumor volume.Conclusion: NODM in PCN patients was associated with malignancy, insulin resistance, weight loss, and SMAD4 mutation. Prediabetic status and NODM diagnosis enhanced the diagnostic accuracy of radiological standards (worrisome features and high-risk stigmata). Stable glucose surveillance is necessary for mPCN patients’ survival.Keywords: pancreatic cyst neoplasms, diabetes mellitus, pancreatic cancer, cancer diagnostic model

Jing Du, Yajing Wang, Shuyu Xu, Yujia Huang, Ruike Zhang, Lei Xiao, Jingzhou Xu, Hao Wang, Tong Su, Yunxiang Tang Department of Medical Psychology, Naval Medical University, Shanghai, People’s Republic of ChinaCorrespondence: Tong Su; Yunxiang Tang, Department of Psychology, Naval Medical University, Shanghai, People’s Republic of China, Email sutong-2006@163.com; tangyun7633@sina.comPurpose: Previous epidemiological and psychological studies have assessed the effects of napping on individual performance and health. However, these studies did not distinguish between spontaneous and passive napping due to sleep disorders. Therefore, this study aimed to explore the potential motivation for napping among Chinese college students and to assess the relationship between different nap motivations and sleep.Patients and Methods: This cross-sectional study was conducted at a university in Shanghai in March 2021 using convenience sampling. A total of 564 Chinese college students with self-reported napping habits participated in this study. Exploratory factor analysis (EFA) was employed to analyze 34 self-rated motivations for napping to derive a potential structural model of napping motivation. Correlation and multiple linear regression analyses were performed to determine the influence of nap motivation on sleep behavior.Results: Chinese college students mainly take naps to reduce fatigue, usually in the form of frequent and long naps (6.25 ± 1.24 days; 64.62 ± 23.70 min). A structural model of nap motivation named the I-DREAM model was proposed, consisting of six factors: restorative, induced, mindful, appetitive, dysregulative, and exercise naps. There were also sex differences in nap motivation, as women preferred restorative naps and appetitive naps, while men preferred exercise naps (p < 0.01, p < 0.05). Furthermore, there was a significant correlation between nap motivation on nap duration, frequency and nighttime sleep quality (R2= 2.70– 18.9%).Conclusion: The proposed I-DREAM model implies that there are population differences in napping motivation. Different motivations also have different relationships with napping patterns and nighttime sleep. In understanding the relationship between naps and health status, nap motivation may be an extremely important influencing factor.Keywords: nap, sleep quality, Chinese college student, exploratory factor analysis

Xiaoli Zhu, Jing Wang, Juping Du, Shuaishuai Chen, Shiyong Chen, Jun Li, Bo Shen Department of Laboratory Medicine, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, People’s Republic of ChinaCorrespondence: Bo Shen, Department of laboratory medicine, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Taizhou, Zhejiang, People’s Republic of China, Tel/Fax +86 576 85226374, Email shenb@enzemed.comObjective: Abnormal liver function and liver injury related to COVID-19 during hospitalization has received widespread attention. However, the long-term observation of patients’ liver functions after discharge has not been investigated. This study intends to analyze the abnormal liver function in patients one year after they are discharged.Methods: Serum liver function tests were analyzed for the first time immediately after hospitalization (T1), before discharge (T2), a median of 14.0 (14.0, 15.0) days after discharge (T3) and 1 year (356.0 (347.8, 367.0) days) after discharge (T4). Patients with at least one serum parameter (ALT, AST, ALP, GGT and TB) exceeding the upper limit of reference range were defined as having abnormal liver function.Results: For the 118 COVID-19 patients with a median follow-up time of 376.0 (71.5, 385.3) days from onset to the end of the follow-up after discharge, the proportion with abnormal liver function in T1, T2, T3 and T4 were 32.2%, 45.8%, 54.8% and 28.8%, respectively. The proportion of patients with at least once abnormal liver function detected from T1 to T2, T1 to T3, T1 to T4 was 60.2%, 77.4% and 88.9%, respectively. From T1 to T4, the ALT, AST, GGT and BMI at admission were significantly higher in the patients with persistently abnormal liver function than in the patients with persistently normal liver function. Abnormal liver function was mainly manifested in the elevation of GGT and TB levels. Multivariate logistics regression analysis showed that age and gender-adjusted ALT (odds ratio [OR]=2.041, 95% confidence interval [CI]: 1.170– 3.561, P=0.012) at admission was a risk factor for abnormal liver function in the T4 stage.Conclusion: Abnormal liver function in patients with COVID-19 can persist from admission to one year after discharge, and therefore, the long-term dynamic monitoring of liver function in patients with COVID-19 is necessary.Keywords: COVID-19, serum, liver function, follow-up

Xiang Li,1 Ping Xiang,2 Jianfen Liang,1 Yifan Deng,1 Jingyi Du1 1Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China; 2Department of Medical Quality Management, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of ChinaCorrespondence: Xiang Li, Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China, Tel +86-20-85253132, Fax +86-20-85252297, Email lixiang27@mail.sysu.edu.cnBackground: Being the S-enantiomer of racemic ketamine, esketamine is found to be effective for sedation, analgesia, and treating depression. However, there is no comprehensive bibliometric analysis about esketamine research. In this study, we aimed to determine the scientific output and emerging topics related to esketamine.Methods: Esketamine-related articles and reviews that published between 2000 and 2020 were obtained from the Web of Science Core Collection database, using key word search of “esketamine” “esketamine hydrochloride”, “s-ketamine”, “S(+)-ketamine”, “(S)-ketamine”, or “(–)-ketamine”. Various bibliographic elements were collected, including the annual number of publications, citation frequency, countries/regions, institutions, authors, journals, and keywords. Two sorts of scientometric software, namely VOS viewer and CiteSpace, were used to conduct bibliometric and knowledge-map analyses.Results: A total of 683 publications were included in the current study. We found the number of publications in esketamine research field had increased annually since 2016. The United States was the leader in this field, with the highest publications number (162, 23.72%), total citations (3504/9713, 36.08%) and H-index (40). The most productive institution was Chiba University in Japan, and esketamine-related papers were mainly published in the journal Anesthesia & Analgesia. The keyword co-occurrence analysis showed that keywords relevant to depression were the most frequent. Moreover, all identified keywords could be divided into four clusters, with the research focus gradually shifting from cluster of “anesthesia and analgesia detection” to “depression treatment effect.”.Conclusion: The past two decades have shown a marked increase in esketamine research. The United States maintained a top position worldwide, making the most significant contributions in the field of esketamine research. The contributions and collaborations of Asian countries have continuously increased and is a strong area of growth as well as development in recent years. Additionally, the emerging hotspots of esketamine research concentrate on clarifying its depression treatment effect.Keywords: ketamine, esketamine, bibliometrics, research trends, depression

Xinyu Zhang,1,&ast; Zenghui Li,1,&ast; Wei Liu,1 Juanjuan Du,1 Yun Liu,2 Ningjun Yu,1 Chao Liu,1 Mei Zeng,3 Xiaoming Zhang1 1Medical Imaging Key Laboratory of Sichuan Province and Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, People’s Republic of China; 2Department of Forensic Medicine, North Sichuan Medical College, Nanchong, Sichuan, 637000, People’s Republic of China; 3Institute of Rheumatology and Immunology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoming Zhang, Medical Imaging Key Laboratory of Sichuan Province and Department of Radiology, Affiliated Hospital of North Sichuan Medical College, No.1 South Maoyuan Road, Nanchong, Sichuan, 637000, People’s Republic of China, Tel +86 13808271001, Email zhangxm@nsmc.edu.cn Mei Zeng, Institute of Rheumatology and Immunology, Affiliated Hospital of North Sichuan Medical College, 63 # Wenhua Road, Nanchong, Sichuan, 637000, People’s Republic of China, Tel +86 13990807850, Email zengmei123@gmail.comPurpose: Acute pancreatitis can be classified histologically as interstitial edema pancreatitis (IEP) or as acute necrotizing pancreatitis (ANP). ANP has a higher mortality and long-term or short-term sequelae than IEP. Therefore, this work aims to explore the differences in pathogenesis between ANP and IEP and it has great clinical importance for the treatment and prevention of ANP.Methods: In this work, whole blood samples from IEP and ANP patients were analyzed by whole gene sequencing (WGS). Serum samples from IEP and ANP patients were evaluated via enzyme-linked immunosorbent assay (ELISA). Meanwhile, pancreatic tissues of IEP and ANP rat models were subjected to data independent acquisition (DIA) proteomics assays. Then, the WGS analysis and DIA proteomics assay data were analyzed comprehensively.Results: Six pathways were found to be significantly different in the ANP/IEP groups through WGS analysis. DIA proteomics found eleven different pathways. In both assays, the complement and coagulation cascades pathway was the most significantly different (p < 0.01) pathway between the two groups. WGS analysis showed base mutations in ten genes in the complement and coagulation cascades pathway. These results were consistent with the ten proteins detected by DIA proteomics analysis, which were significantly upregulated in the ANP/IEP groups. In addition, five of these proteins, complement C3, complement Factor I, alpha-2-macroglobulin, complement C9, and serpin family C member 1, were successfully verified by parallel reaction monitoring analysis and ELISA.Conclusion: C3, CFI, A2m, C9, and Serpinc1, which belong to complement and coagulation cascades pathway, may promote pancreatic necrosis and aggravate the severity of ANP.Keywords: acute necrotizing pancreatitis, complement and coagulation cascades pathway, data independent acquisition proteomics, interstitial edema pancreatitis, whole gene sequencing genomics

Piaoliu Yuan,1 Xueying Li,2 Chunyan Tao,1 Xiaojuan Du,1 Chunyu Zhang,1 Junbao Du,1,3 Yaqian Huang,1 Ying Liao1 1Department of Pediatrics, Peking University First Hospital, Beijing, People’s Republic of China; 2Department of Medical Statistics, Peking University First Hospital, Beijing, People’s Republic of China; 3Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, People’s Republic of ChinaCorrespondence: Ying Liao; Yaqian Huang, Department of Pediatrics, Peking University First Hospital, Xi-An Men Street No. 1, West District, Beijing, 100034, People’s Republic of China, Tel +8610-83573238 ; +8610-83575807, Fax +8610-66530532, Email liaoyingwww@163.com; yaqianhuang@126.comPurpose: To explore the value of the longitudinal axis/transverse axis ratio (L/T) of Poincaré plot in selecting children with vasovagal syncope (VVS) who were suitable for metoprolol therapy.Patients and Methods: Children with VVS hospitalized in Peking University First Hospital between January 2012 and June 2019 and treated with metoprolol were retrospectively included as the training set, and children with VVS hospitalized between July 2019 and December 2020 were included as the validation set. The sex, age at admission, height, weight, body mass index, course of disease, syncope symptom score before metoprolol treatment, treatment duration, supine heart rate (HR), supine systolic pressure, supine diastolic pressure, peak HR during the head-up tilt test (HUTT), changes of HR during HUTT, hemodynamic response during HUTT, left ventricular ejection fraction, left ventricular fractional shortening and the L/T of Poincaré plot were compared between responders and nonresponders in the training set. Logistic regression analysis was conducted to explore predictors. Receiver operating characteristic curve was utilized to determine the value of the predictors for selecting potential responders. Finally, the value of the predictors was further verified.Results: In the training set including 105 children, the L/T in responders was distinctly higher than that in nonresponders (P < 0.001), and there was no apparent difference between the two groups in other indexes. The L/T was statistically related to the efficacy of metoprolol (P < 0.001). The L/T > 2.7 yielded a sensitivity of 88.2% and a specificity of 82.8% for indicating responders to metoprolol. Taking L/T > 2.7 to select potential responders in another 43 children with VVS in the validation set, the sensitivity was 96.6%, specificity 71.4%, and accuracy 88.4%.Conclusion: The L/T of Poincaré plot > 2.7 can be a useful tool to select potential responders to metoprolol therapy in children with VVS.Keywords: Poincaré plot, metoprolol, vasovagal syncope, children, Holter

Xiwu Yan,1– 3 Ting Meng,2,3 Huaijun Liu,2 Jinfeng Liu,3 Juan Du,1 Cheng Chang3 1Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, People’s Republic of China; 2Key Laboratory of Cognitive Impairment Research, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, People’s Republic of China; 3Department of Neurology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, People’s Republic of ChinaCorrespondence: Cheng Chang; Xiwu Yan, Department of Neurology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, 210000, People’s Republic of China, Tel +86 13851821996 ; +86 18013930106, Email yxwssg@126.com; chch1967@163.comBackground: Epidemiological studies suggest that the incidence of hypertension in China is causally related to cognitive impairment. However, there is a dearth of information available regarding important factors for the association, including disease duration, therapeutic options, and risk factors associated with mild cognitive impairment (MCI) in patients with hypertension.Methods: We selected a diverse cohort of 572 patients with hypertension and assessed cognitive function using MoCA. Potential risk factors were investigated by a structured questionnaire. Risk factors associated with the hypertension-induced MCI occurring conversion of were analyzed using multifactorial regression analysis.Results: MCI was observed in 256 of 572 individuals, which increased with age (OR=1.15, 95% CI 1.10– 1.20), but was decreased with high education status (OR=0.47, 95% CI 0.32– 0.71). Risk factors independently associated with MCI were diabetes (OR=2.40, 95% CI 1.53– 3.76), hyperlipidemia (OR=1.49, 95%=1.01– 2.16), high salt diet (OR=2.27, 95% CI 1.34– 3.84), and physical activity:> 2h/week (OR=0.65, 95%0.44– 0.94). However, controlling blood pressure to “normal” target values helped decrease the incidence of MCI (OR=0.44, 95% CI 0.30– 0.65): this was not age dependent.Conclusion: Our results suggest that it is necessary to promote the education of the middle-aged and elderly Chinese population to correctly and effectively use anti-hypertensives to control hypertension to a normal range to prevent cognitive.Keywords: hypertension, mild cognitive impairment, control, risk factors

Juan Du,1 Lanlan Zong,2 Mengmeng Li,2 Keke Yu,2 Yonghui Qiao,3 Qi Yuan,2 Xiaohui Pu2 1Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, People’s Republic of China; 2Institute of Pharmacy, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, People’s Republic of China; 3Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, Henan, 450046, People’s Republic of ChinaCorrespondence: Juan Du; Xiaohui Pu, Tel/Fax +86-371-23880680, Email jindalai66@163.com; pgh425@163.comIntroduction: Cancerous tumors are still a major disease that threatens human life, with tumor multidrug resistance (MDR) being one of the main reasons for the failure of chemotherapy. Thus, reversing tumor MDR has become a research focus of medical scientists.Methods: Here, a reduction-sensitive polymer prodrug micelle, mPEG-DCA-SS-PTX (PDSP), was manufactured with a new polymer inhibitor of drug resistance as a carrier to overcome MDR and improve the anti-tumor effect of PTX.Results: The PDSP micelles display good stability, double-responsive drug release, and excellent biocompatibility. The PDSP micelles reduced the cytotoxicity of PTX to normal HL-7702 cells and enhanced that to SMMC-7721 and MCF-7 cells in vitro. Improved sensitivity of A549/ADR to PDSP was also observed in vitro. Furthermore, in vivo experiments show reduced systemic toxicity and enhanced therapeutic efficacy of PTX to H22 subcutaneous tumor-bearing mice.Conclusion: This work proves that the reduction-sensitive polymer prodrug micelles carried by the new polymer inhibitor can be used as an alternative delivery system to target tumors and reverse MDR for paclitaxel and other tumor-resistant drugs.Keywords: anti-multidrug resistance, polymer prodrug micelles, paclitaxel, reduction sensitivity, liver targeting

Jia Ma,1,&ast; Gang Zhao,2,&ast; Jia Du,1 Jiang Li,1 Guangshuai Lin,1 Jianfei Zhang1 1Department of Surgical Oncology, Shaanxi Provincial People’s Hospital, Xi’an, 710068, Shaanxi, People’s Republic of China; 2Department of Surgical Oncology, Pucheng County Hospital, Weinan, 715500, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianfei ZhangDepartment of Surgical Oncology, Shaanxi Provincial People’s Hospital, Xi’an, 710068, Shaanxi, People’s Republic of ChinaTel +86-17391689521Email zhangjfei@21cn.comObjective: This study aimed to investigate the regulatory effect of lncRNA fetal-lethal non-coding developmental regulatory RNA (FENDRR) on gastric cancer (GC) progression.Methods: The expression levels of FENDRR in GC tissues and paracancerous tissues, as well as in gastric normal epithelial cell line and GC cell lines were detected. The Ad-FENDRR or si-FENDRR was transfected into AGS and SGC-7901 cells, and cell proliferation, invasion and apoptosis were determined. Online bioinformatics database predicted and screened miR-421 as a potential target of FENDRR, and SIRT3 was predicted as a target gene of miR-421. The pcDNA-SIRT3 or si-SIRT3 was transfected into AGS cells, and cell proliferation, invasion, apoptosis and Notch-1 protein expression were determined. Ad-FENDRR was transfected into AGS and SGC-7901 cells alone or together with miR-421 mimic to explore the effect of miR-421 on cells. The AGS cells transfected with Ad-FENDRR were injected into the armpits of nude mice to establish subcutaneous xenograft tumor model, and tumor growth was observed.Results: FENDRR expression was downregulated in GC tissues and cell lines. Overexpression of FENDRR or SIRT3 inhibited tumor proliferation and invasion, and promoted apoptosis. The overexpression of Notch-1 reversed the inhibitory effect of SIRT3 on AGS cell. MiR-421 mimic reversed the inhibitory effect of FENDRR on the growth of AGS and SGC-7901 cells. Nude mice injected with FENDRR overexpressing AGS cells had smaller tumor volume and weight and weaker tumor cell proliferation ability.Conclusion: FENDRR inhibits Notch-1 pathway to inhibit GC cell proliferation and invasion by upregulating SIRT3 expression via targeting miR-421.Keywords: gastric cancer, lncRNA FENDRR, miR-421, SIRT3, Notch-1 pathway

Zhenghua Liu, Shize Yang, Siyu Zhou, Shiyao Dong, Jiang Du Department of Thoracic Surgery, The First Affiliated Hospital of China Medical University, Shenyang, 110001, Liaoning Province, People’s Republic of ChinaCorrespondence: Jiang DuDepartment of Thoracic Surgery, The First Affiliated Hospital of China Medical University, No. 155 North Nanjing Street, Heping District, Shenyang, Liaoning Province, People’s Republic of ChinaTel/Fax +86-24-961200Email dujiang02116@163.comPurpose: Lung adenocarcinoma (LUAD) is a most common malignant tumor, even worse for diseases with relatively poor prognosis. Non-coding RNAs have the potential to be biomarkers for the prognosis of various cancers. LncRNA DRAIC and miR-3940-3p have been screened as dysregulated RNAs in LUAD. The clinical significance and biological function of lncRNA DRAIC and miR-3940-3p in LUAD were assessed in this study.Patients and Methods: A total of 122 cases of LUAD patients with complete clinical information were enrolled. The expression levels of lncRNA DRAIC and miR-3940-3p were determined via RT-qPCR in LUAD tissues and cells. The relationship between lncRNA DRAIC or miR-3940-3p expression and the clinicopathological features of patients was analyzed based on the Pearson Chi-square test. For the prognostic value, the Kaplan–Meier plot and multi-variate Cox proportional regression analysis were introduced. Finally, the effect of lnc DRAIC and miR-3940-3p on the LUAD cellular function was investigated by CCK-8 and Transwell assay.Results: lnc DRAIC was upregulated in LUAD tissues and cells, but miR-3940-3p was downregulated. Both of them showed significant associations with and TNM stage, lymph node metastasis, and a poor prognosis. Lnc-DRAIC and miR-3940-3p have the potential as independent prognostic factors for LUAD. Furthermore, the inhibition of lnc DRAIC can inhibit cell proliferation, migration, and invasion of LUAD partly as a ceRNA of miR-3940-3p.Conclusion: lncRNA DRAIC/miR-3940-3p axis may be involved in the progression of LUAD and can be developed to promising prognostic factors, which may provide new insights into the treatment of LUAD.Keywords: lung adenocarcinoma, lncRNA DRAIC, miR-3940-3p, progression, prognosis

Shaochong Lin,1,2 Junpeng Du,3 Jun Hao,1 Xiaohua Luo,1 Han Wu,1 Huifang Zhang,1 Xinxin Zhao,1 Lida Xu,1 BaoJin Wang1,2 1Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 2Henan International Joint Laboratory of Ovarian Malignant Tumor, Zhengzhou, 450052, People’s Republic of China; 3Department of Pediatric Surgery, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of ChinaCorrespondence: BaoJin WangDepartment of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, No. 7, Kangfu Front Street, Erqi District, Zhengzhou, 450052, People’s Republic of ChinaTel +86 156 3927 7692Fax +86 371-66903480Email 2995269936@qq.comPurpose: Family with sequence similarity 83 (FAM83) is a newly discovered oncogene family, and the members of which can affect the prognosis of patients with malignant tumors via various mechanisms. However, the functions and molecular mechanisms of FAM83 genes in ovarian cancer (OC) have not yet been investigated. This study aimed to explore the clinical significance and prognostic value of FAM83 genes in OC.Materials and Methods: We used a series of bioinformatics databases (Oncomine, GEPIA, cBioPortal, Kaplan–Meier plotter, DAVID and TIMER) to investigate the expression status, prognostic value, genetic alteration and biological function of all eight FAM83 genes in OC. In addition, a tissue microarray cohort (TMA) comprising 99 ovarian tumor tissues and 19 normal ovarian tissues was used to validate the protein expression and clinicopathological significance of FAM83H.Results: Several datasets demonstrated the mRNA levels of FAM83A/D/E/F/H were significantly higher in OC compared with that in normal tissue. Moreover, the upregulation of FAM83D/H has been mutually confirmed in the Oncomine and GEPIA datasets. Kaplan–Meier survival analysis indicated that the FAM83D/H upregulation could predict poor prognosis of OC patients who had shorter overall survival (OS) and progression-free survival (PFS). In addition, cBioportal analysis indicated that the genetic alterations of FAM83 genes might affect the survival outcomes of patients with OC. Furthermore, KEGG analysis suggested that FAM83D/H are involved in the progression of OC through the cell cycle signaling pathway, and they had significant co-expression relationship with cell cycle-related genes. Finally, immunohistochemistry analysis confirmed the high expression of FAM83H protein in OC tissue, suggesting that its expression is positively correlated with the FIGO stage and pathological subtype of OC.Conclusion: This study elucidated the expression status and prognostic value of FAM83 genes in OC and identified that FAM83D/H might be potential targets for the prognostic monitoring and targeted therapy of OC.Keywords: FAM83s, ovarian cancer, prognosis, immunohistochemistry, biomarker

Jianting Du,1,2 Jiekun Qian,1,2 Bin Zheng,1,2 Guobing Xu,1,2 Hao Chen,1,2 Chun Chen1,2 1Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China; 2Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fujian Province University, Fuzhou, Fujian, People’s Republic of ChinaCorrespondence: Chun ChenDepartment of Thoracic Surgery, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, Fujian, 350000, People’s Republic of ChinaTel +86 13805069983Fax +86 591-87113828Email dujt1220@fjmu.edu.cnBackground: Lung cancer (LUCA) is one of the most prevalent human malignancies, and the leading cause of cancer-related deaths worldwide. Previous reports have shown that miR-21-5p plays a vital role in development of various tumors. Here, we explored the relationship between miR-21-5p/PIK3R1 axis and prognosis of patients with lung adenocarcinoma (LUAD).Methods: MiRNAseq data, deposited in The Cancer Genome Atlas (TCGA) database, was downloaded and used to determine patterns of miR-21-5p expression in both LUAD and normal lung tissues. Statistical analyses and data visualization were performed using dbDEMC v3.0 platform, starBase v3.0 database and packages implemented in R software. Next, we employed TargetScan Human, miRDB and DIANA Tools databases to predict miR-21-5p target genes, then analyzed their expression patterns as well as prognostic value in LUAD.Findings: Most human cancers overexpressed miR-21-5p. Specifically, miR-21-5p was significantly upregulated in LUAD tissues relative to normal lung tissues (P < 0.001), and this high expression was significantly correlated with poor patient prognosis (hazard ratio [HR]=1.45, P = 0.014). PIK3R1 was predicted as a miR-21-5p target gene, and both were negatively correlated (r=− 0.218, P < 0.01). Notably, PIK3R1 was significantly downregulated in LUAD, relative to normal lung tissues (P < 0.01), with its overexpression significantly associated with poor prognosis of LUAD patients (HR = 0.62, P = 0.0014).Conclusion: miR-21-5p is a potential prognostic biomarker for LUAD patients. Moreover, it might be playing a role in LUAD progression by regulating PIK3R1 expression.Keywords: lung adenocarcinoma, miR-21-5p, PIK3R1, survival

Yaru Wang,1 Junbao Du,1,2 Xueying Li,3 Ping Liu,1 Yuli Wang,1 Ying Liao,1 Hongfang Jin1 1Department of Pediatrics, Peking University First Hospital, Beijing, 100034, People’s Republic of China; 2Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, 100034, People’s Republic of China; 3Department of Medical Statistics, Peking University First Hospital, Beijing, 100034, People’s Republic of ChinaCorrespondence: Ying Liao; Hongfang JinDepartment of Pediatrics, Peking University First Hospital, Beijing, 100034, People’s Republic of ChinaTel +8610-83573238Fax +8610-66530532Email liaoyingwww@163.com; jinhongfang51@126.comObjective: To investigate the influence of comorbidities on the prognosis of pediatric postural tachycardia syndrome (POTS).Methods: In this retrospective cohort study, 275 children with POTS admitted to the Department of Pediatrics at Peking University First Hospital were recruited from 2016 to 2019 and followed up. The participants were divided into simple POTS (S-POTS, n=156 cases) and POTS with comorbidities (Co-POTS, n=119 cases) groups according to whether they were complicated with comorbidities. A Cox regression analysis was used to identify the prognostic risk factors for children with POTS, while Kaplan–Meier curves were applied to compare the cumulative symptom remission rate (CSRR) between the two groups. The rehospitalization of the children between the two groups was also compared to explore the influence of comorbidities.Results: Twenty-one participants (7.6%) were lost during a median follow-up of 24 months. The Cox regression model showed that comorbidities and body mass index (BMI) were associated with the CSRR of the children with POTS. The CSRR of pediatric POTS alone was 1.748 times higher than that of patients with comorbidities, and the CSRR was decreased by 5.1% for each 1 kg/m2 increase in BMI. The most common comorbidity in children with POTS in this study was allergic disorders, followed by the psychological diseases. The patients in the Co-POTS group had a lower CSRR than those in the S-POTS group (log rank P=0.0001). In addition, compared with those of the S-POTS group, the total number of rehospitalizations was high (P=0.001), and the total hospital stays were long in the Co-POTS group (P< 0.001).Conclusion: Complicating with comorbidities, pediatric patients with POTS had lower CSRR and more rehospitalizations than those without comorbidities. More attention should be given to comorbidities when managing pediatric POTS.Keywords: postural tachycardia syndrome, comorbidity, allergic disorders, prognosis, children

Cong Wei,1,&ast; Xiaoting Zhang,1,&ast; Dan Liang,1 Jilong Yang,1 Jingwen Du,1 Chunyan Yue,1 Lan Deng1,2 1Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, People’s Republic of China; 2Department of Hematology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lan DengDepartment of Hematology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People’s Republic of ChinaTel +86 13724862939Email denglan_76@126.comChunyan YueDepartment of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, People’s Republic of ChinaTel +86 15521117300Email doctor_yy@126.comBackground: Graft-versus-host disease (GVHD) is a main complication following allogeneic hematopoietic stem cell transplantation and is a leading cause of non-relapse-related death. Unsatisfactory response to standard first-line therapy with glucocorticoids is a predictor of a poor prognosis in patients with GVHD. Ruxolitinib is a selective Janus kinases 1/2 inhibitor which has been shown to control acute (a) and chronic (c) GVHD while maintaining graft-versus-tumor effects.Objective: This study aims to evaluate the efficacy and safety of ruxolitinib in the treatment of steroid-refractory GVHD (SR-GVHD) in a population of Chinese patients.Methods: We report the results of 55 patients, including 23 patients with aGVHD and 32 patients with cGVHD, who were treated with ruxolitinib as salvage therapy between August, 2017 and December, 2020.Results: In patients with aGVHD, the overall response rate (ORR) was 86.9%, and the 1-year overall survival (OS) was 82.6% (95% CI, 67.1– 98.1%). The 1-year OS was significantly improved in responders than in non-responders (90.0% vs 33.3%, P=0.004). In patients with cGVHD, the ORR was 78.1%, and the 1-year OS was 81.3% (95% CI, 67.8– 94.8%). There was no significant difference in the 1-year OS between responders and non-responders (84.0% vs 71.4%, P=0.327). Cytopenia, cytomegalovirus-reactivation and infections were common adverse events, particularly in patients with aGVHD.Conclusion: Our real-world data from Chinese patients further confirm that ruxolitinib is a safe and effective treatment for SR-GVHD.Keywords: ruxolitinib, allogeneic hematopoietic stem cell transplantation, graft-versus-host disease, steroid-refractory

Guangchao Han, Min Li, Junfeng Du, Yang Chen, Chen Xu Department of Respiratory and Critical Care Medicine, Cangzhou Central Hospital, Cangzhou, 061000, Hebei, People’s Republic of ChinaCorrespondence: Guangchao HanDepartment of Respiratory and Critical Care Medicine, Cangzhou Central Hospital, No. 16 Xinhua West Road, Cangzhou, 061000, Hebei, People’s Republic of ChinaTel +86-15833371555Email guangchao1020@126.comIntroduction: Chronic obstructive pulmonary disease (COPD) is a progressive condition related to abnormal inflammatory responses. As an inflammatory driver, nucleotide-binding oligomerizing domain-1 (NOD1) is highly expressed in pulmonary inflammatory cells; however, the roles of NOD1 in COPD are unknown.Methods: A COPD mouse model was established by lipopolysaccharides tracheal instillation plus cigarette smoke (CS) exposure. NOD1 activation was induced by C12-iE-DAP (iE) treatment in both control and COPD mice. Inflammatory infiltration, pulmonary histological damage and gene expression were measured to evaluate the lung function of treated mice.Results: The results showed that NOD1 was up-regulated in COPD mice, which significantly exaggerated CS-induced impairment of lung function, demonstrated by increased airway resistance, functional residual capacity and pulmonary damages. Mechanistically, NOD1 activation strongly activated the TLR4/NF-κB signaling pathway and then increased inflammatory responses and promoted the secretion of inflammatory cytokines.Discussion: This study demonstrates that NOD1 is an important risk factor in the progression of COPD; therefore, targeting NOD1 in lung tissues is a potential strategy for COPD treatment.Keywords: COPD, pulmonary damage, inflammation, NOD1, TLR4/NF-κB signaling

Hui Zhang1 &ast;, Dandan Chen2 &ast;, Nianqi Cui,3 Ping Zou,4 Jing Shao,2 Xiyi Wang,5 Yichi Zhang,6 Jiao Du,6 Chunxue Du,6 Guanglan Zhou,6 Deyi Zheng6 1Department of Cardiology, Guizhou Provincial People’s Hospital, Guiyang, People’s Republic of China; 2Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou, People’s Republic of China; 3The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4School of Nursing, Nipissing University, Toronto, Ontario, Canada; 5Shanghai JiaoTong University, School of Nursing, Shanghai, People’s Republic of China; 6Department of Burn and Plastic Surgery, Guizhou Provincial People’s Hospital, Guiyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Deyi ZhengDepartment of Burn and Plastic Surgery, Guizhou Provincial People’s Hospital, Guiyang, People’s Republic of ChinaTel +86 13984826262Email deyizheng@126.comBackground: Despite a flood of research on job satisfaction, few studies have examined how and why social support influences job satisfaction. This study aimed to explore how social support has an indirect effect on job satisfaction by examining its impact on emotional exhaustion and anxiety symptoms among residents of the physicians standardized residency training program in China.Methods: This cross-sectional study adopted questionnaires to collect data from residents in the standardized residency training program in China. The PROCESS macro for SPSS based on ordinary least-squares regression and the bootstrap method was used. The indirect effect of social support was examined using bootstrapping procedures. A serial multiple mediation model was examined in which social support was associated with job satisfaction via emotional exhaustion and anxiety symptoms.Results: There were 269 residents who provided usable data for the analysis. The mean age of residents was 25.98 years old. Close to half (52%) of the participants were female. The total indirect effect of social support on job satisfaction was significant (ab=0.21, SE=0.05, CI=0.12 to 0.32). The specific indirect effect 1 (social support→emotional exhaustion→job satisfaction) was significant (a1b1=0.12, SE=0.04, CI=0.05 to 0.19). The specific indirect effect 2 (social support→anxiety symptoms→job satisfaction) was significant (a2b2=0.07, SE=0.03, CI=0.02 to 0.13).The specific indirect effect 3 (social support→emotional exhaustion→anxiety symptoms→job satisfaction) was also found to be significant through both optimism and work engagement (a1a3b2=0.03, SE=0.01, CI=0.01 to 0.05).Conclusion: It seems critical for hospital management to develop a supportive work environment to improve the effects of emotional exhaustion and anxiety symptoms and to provide sufficient support to improve job satisfaction among residents in standardized residency training programs.Keywords: residents, social support, emotional exhaustion, job satisfaction, anxiety symptoms, standardized residency training programs