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Xiaojuan Wu, Guoyue Zhang, Xianzhi Du Department of Respiratory Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of ChinaCorrespondence: Xianzhi Du, Department of Respiratory Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China, Tel +86 023 62887761, Email dxzdjy868@sina.comBackground: Chronic obstructive pulmonary disease (COPD) is caused by exposure to noxious external particles, air pollution, and the inhalation of cigarette smoke. Airway mucus hypersecretion particularly mucin5AC (MUC5AC), is a crucial pathological feature of COPD and is associated with its initiation and progression. In this study, we aimed to investigate the effects of cigarette smoke extract (CSE) on MUC5AC expression, particularly the mechanisms by which reactive oxygen species (ROS) induce MUC5AC expression.Methods: The effects of CSE on the expression of MUC5AC and mucin5B (MUC5B) were investigated in vitro in Calu-3 cells. MUC5AC and MUC5B expression levels were measured using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), immunofluorescence staining, and enzyme-linked immunosorbent assay (ELISA). Total cellular levels of ROS and Ca2+ were determined using DCFH-DA and Fluo-4 AM. Subsequently, the expression levels of IP3R, IRE1α, p-IRE1α and XBP1s were measured by Western blotting. Gene silencing was achieved by using small-interfering RNAs.Results: Our findings revealed that exposure to CSE increased MUC5AC levels and upregulated ROS, IP3R/Ca2+ and unfolded protein response (UPR)-associated factors. In addition, knockdown of IP3R using siRNA decreased CSE-induced Ca2+ production, UPR-associated factors, and MUC5AC expression. Furthermore, 10 mM N-acetyl-l-cysteine (NAC) treatment suppressed the effects of CSE, including ROS generation, IP3R/ Ca2+, UPR activation, and MUC5AC overexpression.Conclusion: Our results suggest that ROS regulates CSE-induced UPR and MUC5AC overexpression through IP3R/ Ca2+ signaling. Additionally, we identified NAC as a promising therapeutic agent for mitigating CSE-induced MUC5AC overexpression.Keywords: chronic obstructive pulmonary disease, mucin5AC, cigarette smoke extract, reactive oxygen species, unfolded protein response, IP3R, Ca2+

Xian Du,1,* Jun Hu,1,* Jianhua Xue,1 Yuan Zhuang,2 Xuefeng Tang,1 Zhiyue Xu1 1Health Examination Center, Shanghai Health and Medical Center (Huadong Sanatorium), Wuxi, People’s Republic of China; 2The Affiliated Hospital of Nantong University, Nantong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhiyue Xu; Xuefeng Tang, Health Examination Center, Shanghai Health and Medical Center (Huadong Sanatorium), 67 Dajishan, Wuxi, 214065, People’s Republic of China, Email hepenxiaozi@163.com; 978665164@qq.comPurpose: Fatigue was a common symptom of non-alcoholic fatty liver disease (NAFLD), which seriously affected patients’ quality of life. The aim of this study was to detect fatigue rate and to evaluate factors associated with fatigue in NAFLD patients.Patients and Methods: A cross-sectional study was carried out from the Huadong Sanatorium between April 2022 and May 2023, and 133 NAFLD patients were included in this study. They completed Fatigue Severity Scale to assess fatigue, the Hospital Anxiety and Depression Scale to estimate psychological status, and the Pittsburgh Sleep Quality Index for sleep quality. Data were analyzed by independent samples t-tests, χ 2 tests and logistic regression models.Results: We found that 51.1% of NAFLD patients had fatigue. Exercise, anxiety, depression, subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disorders, daytime dysfunction and overall sleep quality were related to fatigue among NAFLD patients. Moreover, logistic regression models indicated anxiety, habitual sleep efficiency and sleep disorders as important predictors of fatigue.Conclusion: This was the first time to explore demographic, clinical, psychological and sleeping correlated factors for fatigue in Chinese NAFLD patients. Our study showed that more than half of NAFLD patients had fatigue, and anxiety, habitual sleep efficiency and sleep disorders were significantly associated with fatigue in NAFLD. The findings indicated that it was very necessary to pay more attention to fatigue of NAFLD patients, especially those with negative emotions and poor sleep quality by favorable intervention to relieve fatigue symptoms, so as to improve quality of life.Keywords: non-alcoholic fatty liver disease, fatigue, exercise, anxiety, sleep

Hang Jin,1,2,* Zhongqiang Yan,3,* Xin Ge,4,* Qi Wang,2 Hui Wang,2 Xinying Du,2 Hongbo Liu,2 Chaojie Yang,2 Ying Xiang,2 Sai Tian,2 Shaofu Qiu,1,2 Yu Zhou5 1School of Public Health, Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Infectious Disease Control and Prevention, Center for Disease Control and Prevention of Chinese PLA, Beijing, People’s Republic of China; 3Department of Disease Prevention and Control, The Second Medical Center of PLA General Hospital, Beijing, People’s Republic of China; 4School of Public Health, Anhui Medical University, Hefei, People’s Republic of China; 5Department of Clinical Laboratory, National Clinical Research Center for Geriatric Diseases, The Second Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shaofu Qiu, Center for Disease Control and Prevention of Chinese PLA, Beijing, People’s Republic of China, Email qiushf0613@hotmail.com Yu Zhou, Department of Clinical Laboratory, National Clinical Research Center for Geriatric Diseases, The Second Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China, Email zhouy427@163.comPurpose: This study conducted an phenotypic and whole-genome sequencing analysis with Klebsiella aerogenes to elucidate its clinical epidemiological characteristics, antimicrobial resistance (AMR) phenotype, biofilm formation ability and hemolytic activity testing, AMR genes and phylogenetic relationships, so as to provide a further understanding of the intra-hospital strain transmission.Methods: Samples were collected from a hospital in Beijing between 2020 and 2022. All strains underwent bacterial identification, antimicrobial susceptibility testing (AST) using the VITEK-2 compact system. Biofilm formation ability and hemolytic activity were tested. Second-generation sequencing was applied to all strains, with those carrying the blaKPC gene were selected for third-generation sequencing. Whole-genome analysis identified resistance genes, plasmid types, MLST typing, and phylogenetic relationships. Plasmids were assembled to detect plasmid structures and AMR gene location.Results: Among the 42 K. aerogenes isolates, 21 were carbapenem-resistant K. aerogenes (CRKA). All strains exhibited strong biofilm formation and no hemolytic activity. Most were sourced from sputum (83.3%). CRKA demonstrated extensive resistance to antibiotics, particularly β-lactamase inhibitors and Cefotetan. This resistance pattern was closely associated with the presence of an IncFII(pHN7A8) plasmid, which carried multiple resistance genes, including blaKPC-2, blaCTX-M-65, blaTEM-1, rmtB and a large number of mobile elements. The majority of CRKA strains clustered within the same branch of the phylogenetic tree, exhibiting minimal single nucleotide polymorphism (0– 13 SNPs) differences, and they shared the same sequence type (ST292), resistance genes, and plasmids, originating from different departments, suggesting clonal transmission among the hospital.Conclusion: Our research reveals that the clonal transmission of CRKA occurs across various departments within the hospital. The widespread resistance observed in CRKA, attributed to the presence of blaKPC and ESBLs genes, underscores the need for heightened vigilance to prevent the further dissemination of CRKA within the hospital and, potentially, throughout the wider community.Keywords: Klebsiella aerogenes, carbapenem resistance, blaKPC-2, clonal transmission

Xin Liu,1,* Ruofan Xi,1,* Xinran Du,1 Yi Wang,1 Linyan Cheng,1 Ge Yan,1 Hanzhi Lu,1 Te Liu,2 Fulun Li1 1Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Te Liu; Fulun Li, Email liute1979@shutcm.edu.cn; drlifulun@163.comBackground: Psoriasis is a common chronic inflammatory skin condition. The emergence of psoriasis has been linked to dysbiosis of the microbiota on the skin surface and an imbalance in the immunological microenvironment. In this study, we investigated the therapeutic impact of topical thymopentin (TP5) on imiquimod (IMQ)-induced psoriasis in mice, as well as the modulatory influence of TP5 on the skin immune milieu and the skin surface microbiota.Methods: The IMQ-induced psoriasis-like lesion mouse model was used to identify the targets and molecular mechanisms of TP5. Immunofluorescence was employed to identify differences in T-cell subset expression before and after TP5 therapy. Changes in the expression of NF-κB signaling pathway components were assessed using Western blotting (WB). 16S rRNA sequencing and network pharmacology were used to detect changes in the skin flora before and after TP5 administration.Results: In vivo, TP5 reduced IMQ-induced back inflammation in mice. H&E staining revealed decreased epidermal thickness and inflammatory cell infiltration with TP5. Masson staining revealed decreased epidermal and dermal collagen infiltration after TP5 administration. Immunohistochemistry showed that TP5 treatment dramatically reduced IL-17 expression. Results of the immunoinfiltration analyses showed psoriatic lesions with more T-cell subsets. According to the immunofluorescence results, TP5 dramatically declined the proportions of CD4+, Th17, ROR+, and CD8+ T cells. WB revealed that TP5 reduced NF-κB pathway expression in skin tissues from IMQ-induced psoriasis model mice. 16S rRNA sequencing revealed a significant increase in Burkholderia and Pseudomonadaceae_Pseudomonas and a significant decrease in Staphylococcaceae_Staphylococcus, Aquabacterium, Herbaspirillum, and Balneimonas. Firmicutes dominated the skin microbial diversity after TP5 treatment, while Bacteroidetes, Verrucomicrobia, TM7, Proteobacteria, Actinobacteria, Acidobacteria, Gemmatimonadetes, and other species dominated in the IMQ group.Conclusion: TP5 may treat psoriasis by modulating the epidermal flora, reducing NF-κB pathway expression, and influencing T-cell subsets.Keywords: psoriasis, thymopentin, 16S rRNA sequencing, T-cell subsets

Qiwen Yu,1 Chaopeng Mei,1 Mengwei Cui,1 Qianqian He,1 Xudong Liu,2 Xiaoxiao Du2 1Department of Emergency Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 2Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of ChinaCorrespondence: Xiaoxiao Du, Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Erqi, Zhengzhou, Henan, People’s Republic of China, Email xiaoxiao5811@126.comBackground: Nepetoidin B (NB) has been reported to possess anti-inflammatory, antibacterial, and antioxidant properties. However, its effects on liver ischemia/reperfusion (I/R) injury remain unclear.Methods: In this study, a mouse liver I/R injury model and a mouse AML12 cell hypoxia reoxygenation (H/R) injury model were used to investigate the potential role of NB. Serum transaminase levels, liver necrotic area, cell viability, oxidative stress, inflammatory response, and apoptosis were evaluated to assess the effects of NB on liver I/R and cell H/R injury. Quantitative polymerase chain reaction (qPCR) and Western blotting were used to measure mRNA and protein expression levels, respectively. Molecular docking was used to predict the binding capacity of NB and mitogen-activated protein kinase phosphatase 5 (MKP5).Results: The results showed that NB significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, liver necrosis, oxidative stress, reactive oxygen species (ROS) content, inflammatory cytokine content and expression, inflammatory cell infiltration, and apoptosis after liver I/R and AML12 cells H/R injury. Additionally, NB inhibited the JUN protein amino-terminal kinase (JNK)/P38 pathway. Molecular docking results showed good binding between NB and MKP5 proteins, and Western blotting results showed that NB increased the protein expression of MKP5. MKP5 knockout (KO) significantly diminished the protective effects of NB against liver injury and its inhibitory effects on the JNK/P38 pathway.Conclusion: NB exerts hepatoprotective effects against liver I/R injury by regulating the MKP5-mediated P38/JNK signaling pathway.Keywords: liver ischemia/reperfusion injury, nepetoidin B, MKP5, JNK/P38 pathway

Lini Chen,&ast; Weiyong Qin,&ast; Jiangdong Wu, Guilin Zhao, Xiaoqing Jiang, Minghui Li, Zijin Huang,&ast; Xueke Du&ast; Department of Anesthesiology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zijin Huang; Xueke Du, Department of Anesthesiology, the Second Affiliated Hospital of Guangxi Medical University, No. 166 of Daxue East Road, Nanning, Guangxi, 530007, People’s Republic of China, Tel +86-13768114848 ; Tel +86-17307711159, Email batistuta921@163.com; duxueke@gxmu.edu.cnPurpose: This study aims to evaluate the effect of remimazolam on induction and maintenance of general anesthesia in kidney transplant patients.Methods: 120 patients undergoing kidney transplant were divided into two groups: Propofol group (Group P) and Remimazolam group (Group R). Anesthesia induction: remimazolam had injected IV at a dose of 0.15– 0.35 mg/kg in Group R, while propofol had injected IV at a dose of 2.0– 2.5 mg/kg in Group P. Anesthesia maintenance: remimazolam was injected IV at a dose of 0.3– 1.0 mg·kg− 1·h− 1 and propofol was injected IV at a dose of 1– 12 mg·kg− 1·h− 1 in Group R, propofol was injected IV at a dose of 3– 12 mg·kg− 1·h− 1 in Group P. All patients have the same remaining anesthesia durgs.Results: Compared with Group P, in Group R the time of disappearance of the eyelash reflex and the time to drop to 60 in BIS was longer (P < 0.05), the time of awakening was shorted (P < 0.05), the MAP of T6 was fluctuated less (P < 0.05), the incidence of hypotension and injection pain during induction was reduced (P < 0.001), the incidence of intraoperative bradycardia during operation was reduced (P < 0.05), the dosages of sedatives drug during maintenance was reduced (P < 0.05). There was no statistically significant difference in postoperative renal function between the two groups of patients (P > 0.05).Conclusion: Remimazolam can be safely and effectively used for the induction and maintenance of general anesthesia in kidney transplant patients.Keywords: remimazolam, propofol, general anesthesia, kidney transplant

Enhao Huang,1,2,&ast; Huadao Li,2,3,&ast; Hanghang Han,1,2,&ast; Lianshan Guo,4 Yubing Liang,3 Zijin Huang,1 Ke Qin,5 Xueke Du1 1Department of Anesthesiology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530007, People’s Republic of China; 2Key Laboratory for Basic Science and Prevention of Perioperative Organ Dysfunction, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China; 3Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China; 4Department of Emergency, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530007, People’s Republic of China; 5Guilin People’s Hospital, Guilin, Guangxi Zhuang Autonomous Region, 541100, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ke Qin; Xueke Du, Email qinke303@163.com; duxueke@gxmu.edu.cnPurpose: The primary objective of this study was to develop an innovative nanomedicine-based therapeutic strategy to alleviate Postoperative Neurocognitive Disorder (PND) in patients undergoing surgery.Patients and Methods: To achieve this goal, polydopamine-coated Kaempferol-loaded Metal-Organic Framework nanoparticles (pDA/KAE@ZIF-8) were synthesized and evaluated. The study involved encapsulating Kaempferol (KAE) within ZIF-8 nanoparticles, followed by coating with polydopamine (PDA) to enhance biocompatibility and targeted delivery. The characterization of these nanoparticles (NPs) was conducted using various techniques including Scanning Electron Microscopy, Fourier-Transform Infrared Spectroscopy, X-ray Diffraction, and Ultraviolet-Visible spectroscopy. The efficacy of pDA/KAE@ZIF-8 NPs was tested in both in vitro and in vivo models, specifically focusing on their ability to penetrate the blood-brain barrier and protect neuronal cells against oxidative stress.Results: The study found that pDA/KAE@ZIF-8 NPs efficiently penetrated the blood-brain barrier and were significantly taken up by neuronal cells. These nanoparticles demonstrated remarkable Reactive Oxygen Species (ROS) scavenging capabilities and stability under physiological conditions. In vitro studies showed that pDA/KAE@ZIF-8 NPs provided protection to HT-22 neuronal cells against H2O2-induced oxidative stress, reduced the levels of pro-inflammatory cytokines, and decreased apoptosis rates. In a PND mouse model, the treatment with pDA/KAE@ZIF-8 NPs significantly improved cognitive functions, surpassing the effects of KAE alone. This improvement was substantiated through behavioral tests and a noted reduction in hippocampal inflammation.Conclusion: The findings from this study underscore the potential of pDA/KAE@ZIF-8 NPs as an effective nanotherapeutic agent for PND. This approach offers a novel direction in the postoperative care of elderly patients, with the potential to transform the therapeutic landscape for neurocognitive disorders following surgery. The application of nanotechnology in this context opens new avenues for more effective and targeted treatments, thereby improving the quality of life for patients suffering from PND.Keywords: nanomedicine, reactive oxygen species, blood-brain barrier

Zhihao Zhao,1,&ast; Diya Qi,1,&ast; Zeqing Zhang,2,&ast; Xin Du,3 Fengyun Zhang,2 Ruicong Ma,4 Yi Liang,1 Yuewu Zhao,1 Ying Gao,1 Yu Yang2 1Department of Cardiology, the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou First People’s Hospital, Xuzhou, People’s Republic of China; 2Department of Cardiology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China; 3Department of Neurology, the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou First People’s Hospital, Xuzhou, People’s Republic of China; 4Graduate School, Dalian Medical University, Dalian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Gao, Department of Cardiology, the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou First People’s Hospital, Xuzhou, People’s Republic of China, Tel +86-13951461302, Email xzyygaoying@163.com Yu Yang, Department of Cardiology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China, Tel +86-15651359875, Email xuzhouyangyu@163.comPurpose: The aim of this study was to explore the relationship between inflammatory cytokines and the risk of heart failure (HF) readmission in patients with heart failure with preserved ejection fraction (HFpEF).Patients and Methods: We enrolled 429 patients with HFpEF admitted to the cardiology department in our hospital from January 2020 to July 2022. The patients were divided into the readmission or non-readmission groups according to whether they were readmitted for heart failure within 1 year of discharge. The clinical features and laboratory date of the subjects were collected and analyzed. Multivariate cox regression analysis was used to identify predictors of HF readmission. In addition, receiver operating characteristic (ROC) curves were used to determine the prognostic value of each factor.Results: The levels of IL-1β, IL-6, IL-10, IL-17, TNF-α, NT-proBNP, heart rate, total cholesterol and NYHA class were significantly higher in the readmission group than in the non-readmission group (p < 0.05). IL-1β, IL-6, IL-17, TNF-α, NT-proBNP, heart rate and NYHA class were identified as independent predictors of HF readmission.Conclusion: Inflammatory markers, including IL-1β, IL-6, IL-17 and TNF-α were related to the HF readmission in patients with HFpEF.Keywords: heart failure with preserved ejection fraction, inflammation, cytokine, readmission, risk assessment

Jiarun Mi, Xinyu Du, Yilixiati Aili, Mingkun Li, Yuanli Liu School of Health Policy and Management, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of ChinaCorrespondence: Yuanli Liu, School of Health Policy and Management, Chinese Academy of Medical Sciences and Peking Union Medical College, Dongdansantiao, Dongcheng District, Beijing, 100730, People’s Republic of China, Tel +86-13522592907, Email liuyuanli_pumc@163.comBackground: Trust is a major factor affecting patient-physician relationship and healthcare quality. However, there has been a lack of comprehensive study on the extent of and major factors affecting patient trust in healthcare providers of China, the world’s largest developing country. The objective of this study is to elucidate the current status of outpatient trust in physicians in China and its influencing factors, providing empirical evidence to enhance doctor-patient trust and improve doctor-patient relationships.Methods: Between December 2017 and January 2018, 28,760 patients seeking care at the outpatient departments of 136 tertiary hospitals were interviewed, where they were asked to rate their trust in physicians. We applied a multilevel logistic regression model to explore the association between patients trust and characteristics of hospitals, physicians and patient characteristics. We conducted a series of sensitivity analysis to check the robustness of our findings.Results: Among 28,760 participants included in this study, 91.54% expressed trust in their physicians, while 7.52% showed moderate trust. Only 0.94% expressly distrusted or strongly distrusted their physicians. Outpatients of hospitals with convenient payment, volunteer guidance and enough seats available in the rest and waiting area showed higher levels of trust. Physicians who had a senior title, showed patience and protection of the patient’s privacy were more likely to be trusted by their patients in the outpatient setting. Compared to their female counterparts, male outpatients showed a higher degree of trust.Conclusion: While this study highlights an overall high level of Trust in physicians (TIP) among patients in China’s tertiary hospitals, it is found to vary with patient demographic factors as well as provider’s attributes. Hospitals with a more keen sense of protecting patients privacy and better meeting patients’ need for efficient and caring service provision process appeared to yield a higher level of trust.Keywords: trust in physicians, national survey, outpatients

Xue Du,1,2 Qi Dong,1,2 Le Sun,1,2 Xiaoyi Chen,1,2 Jun Jiang3 1College of Educational Science, Chongqing Normal University, Chongqing, People’s Republic of China; 2Key Laboratory of Applied Psychology, Chongqing Normal University, Chongqing, People’s Republic of China; 3Department of Basic Psychology, School of Psychology, Third Military Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Xue Du, Tel +86-23-65910354, Email 714789425@qq.com; duxue@cqnu.edu.cnBackground: It is well known that parents play an important role in the family, particularly the mental health literacy of parents is essential for the growth and development of children. As the parents of children with special needs, they are facing more difficulties and psychological pressure, resulted in more mental health problems.Purpose: The current study examined the effect of social support on mental health literacy, and its underlying mechanisms regarding the mediating role of coping styles and moderating role of social comparison.Methods: Using a cross-sectional design, 165 parents of children with special needs (22– 67 years old, M=37.72, SD=8.78) participated in the study. The general information questionnaire, Mental Health Literacy Scale (MHLS), Social Support Rating Scale, Simplified Coping Style Questionnaire, and Social Comparison Orientation Scale were used.Results: We found that objective support positively predicted the mental health literacy, positive coping style played a mediating role between objective support and mental health literacy. In addition, the relationship between objective support and positive coping styles was moderated by social comparisons; for lower levels of opinion social comparison, the effect of objective support on positive coping styles was significantly stronger.Conclusion: We revealed the underlying mechanisms between social support and mental health literacy. The present study has profound implications for mental health literacy services for parents who have children with special needs.Keywords: parents of children with special needs, social support, mental health literacy, coping styles, social comparison orientation

Wenli Liu,&ast; Shuran Zheng,&ast; Xiaogang Du&ast; Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaogang Du, Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, Chongqing, 400016, People’s Republic of China, Tel +13452058896, Fax +86 023 89012019, Email dxgcxm@163.comPurpose: To evaluate the association of the systemic immune-inflammatory index (SII) and systemic inflammatory response index (SIRI) with the clinical and pathological features and progression of diabetic kidney disease (DKD).Patients and Methods: We analyzed 303 patients with type 2 diabetes mellitus (T2DM), classifying them into distinct groups: T2DM, early DKD (EDKD), and clinical DKD (Cli-DKD). Variations in SII and SIRI levels across these groups and their association with renal function were assessed. Logistic regression analysis was used to identify independent risk factors for DKD. Additionally, in 43 patients with biopsy-confirmed DKD, we analyzed the relationship between SII, SIRI, and pathological changes. Kaplan–Meier survival analysis and the Cox proportional hazards model were used to assess the influence of SII and SIRI levels on outcomes in patients with DKD.Results: SII and SIRI were significantly higher in the Cli-DKD group than in the T2DM and EDKD groups, and were positively correlated with the urinary albumin-creatinine ratio and negatively correlated with estimated glomerular filtration rate. Notably, SIRI was identified as an independent risk factor for DKD development. Additionally, a lower SII score was associated with a higher cumulative survival rate.Conclusion: This study demonstrates an association between SII, SIRI, and renal function in patients with T2DM. A high SIRI was an independent risk factor for DKD, while an elevated SII was associated with an increased risk of kidney disease progression in biopsy-confirmed DKD cases. Our findings underscore the potential implications of utilizing SII and SIRI as cost-effective and readily available inflammatory indicators for monitoring DKD in primary care settings.Keywords: diabetes, renal complications, inflammatory markers, prognosis, immune response, biomarkers

Fenge Li,1,2,&ast; Yupeng Wang,1,&ast; Jin Yan,1,&ast; Huancheng Wu,3 Xueming Du,1 Weihong Feng,1 Xiaoqing Zhang,4 Yongming Xue,4 Huaqing Wang,5,6 Wenxin Liu7 1Department of Oncology, Tianjin Beichen Hospital Tianjin People’s Republic of China; 2Core Laboratory, Tianjin Beichen Hospital, Tianjin, People’s Republic of China; 3Department of Neurosurgery, Tianjin Beichen Hospital, Tianjin, People’s Republic of China; 4Department of Basic Research, Suzhou Lanma Biotechnology Co, Suzhou, People’s Republic of China; 5Department of Oncology, Tianjin Union Medical Center, Tianjin, People’s Republic of China; 6Department of Translational Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, People’s Republic of China; 7Department of Gynecological Oncology, Tianjin Medical Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenxin Liu, Department of Gynecological Oncology, Tianjin Medical Cancer Institute and Hospital, Huanhuxi Road, Tiyuanbei, Hexi District, Tianjin, People’s Republic of China, Tel +8618622221101, Email wenxin1973@163.com Huaqing Wang, Department of Translational Medicine, Tianjin Union Medical Center of Nankai University, Jieyuan Road No. 190, Nankai District, Tianjin, People’s Republic of China, Tel +8618622221223, Email huaqingw@163.comIntroduction: Tumor-infiltrating lymphocytes (TILs) therapy is one of the most promising adoptive T cell therapies, which has shown great clinical efficacy against several solid malignancies. Nevertheless, clinical response to TILs mono-therapy in Asian patients with recurrent cervical cancer has not been well reported.Case Presentation: Here, we report two patients who were diagnosed with metastatic cervical cancer and tumor progression following multiple conventional treatments. In particular, one of the patients has a history of severe myelosuppression after chemotherapy. The patients received lymphodepletion therapy, which consisted of cyclophosphamide (30mg/kg) for 2 days, followed by Fludarabine (25mg/m2) for 5 days, approximately 24 hr before receiving intravenous autologous TILs infusion. These two patients then received high doses of IL-2 for 10 days with the purpose of maintaining T cell survival and proliferation. Patient 1 experienced clinical partial response (PR) at 6 weeks post TILs infusion and a 33% tumor shrinkage at 12 weeks follow-up, and patient 2 was evaluated as stable disease (SD) at 6 weeks post treatment. Mild and manageable adverse events were observed and soon subsided after the TILs treatment. A time-course study examining the peripheral blood cell count and cytokine secretion demonstrated the persistence of infused TILs and long-term immune response.Conclusion: These results suggest that TILs mono-therapy can be a promising treatment strategy for Asian patients with late-stage metastatic cervical cancer even with severe myelosuppression. TILs infusion can induce persistence and a long-term systematic immune response that reversed peripheral CD4+T and CD8+T percentages implying that TILs infusion increased cytotic T cell responses, which is consistent with clinical responses in these patients. Trial registration number: NCT05366478.Keywords: tumor-infiltrating lymphocytes, clinical response, immune response, metastatic cervical cancer, treatment

Zheng Wang,1,2 Xin Du,1 Jianzeng Dong1 1Department of Cardiology, Capital Medical University Affiliated Anzhen Hospital, Beijing, 100029, People’s Republic of China; 2Department of Intensive Care Unit, Peking University International Hospital, Beijing, 102206, People’s Republic of ChinaCorrespondence: Jianzeng Dong; Xin Du, Department of Cardiology, Capital Medical University Affiliated Anzhen Hospital, No. 2 of Anzhen Road, Chaoyang District, Beijing, 100029, People’s Republic of China, Tel +86 13911828375 ; +86 13370103558, Fax +86 1084005363, Email jz_dong@126.com; duxinheart@sina.comObjective: To describe the effects of various fluid strategies on mechanical ventilation time and other outcomes in patients with diastolic dysfunction undergoing non-cardiac surgery.Methods: After evaluation, 192 Intensive Care patients met the inclusion criteria. Based on infusion volume and fluid balance, we categorized patients into quartiles using two grouping methodologies. The first quartiles for total infusion volume on day one of ICU admission after surgery were as follows: Q1 ≤ 2.02 mL/kg/h; Q2 > 2.02 to 2.69 mL/kg/h; Q3 > 2.69 to 3.86 mL/kg/h; Q4 > 3.86 mL/kg/h. The second quartiles for fluid balance divided by actual body weight multiplied by the corresponding number of hours were as follows: G1 ≤ − 0.07 mL/kg/h; G2 > − 0.07 to 0.56 mL/kg/h; G3 > 0.56 to 1.54 mL/kg/h; G4> 1.54 mL/kg/h. The primary outcome was mechanical ventilation time. The research utilized both univariate and multivariate negative binomial regression models.Results: The fourth group (Q4 and G4) had a significant impact on mechanical ventilation time(P< 0.05).There were also significant differences between Q4 or G4 and some other groups in terms of ICU time, ICU cost, total hospital time, and total hospital cost (P < 0.05).After negative binomial regression analysis,Q2 and Q4 were approximately 2.406 times (95% CI 1.153– 5.017, P = 0.019) and 3.532 times (95% CI 1.812– 6.883, P < 0.01) longer than Q1 respectively, when grouped by infusion volume, but there was no significant difference between G groups. And Q4 or G4 also differed significantly from other parameters of clinical outcomes (P < 0.05).Conclusion: For patients admitted to the ICU following non-cardiac surgery with left ventricular diastolic dysfunction, the greater the fluid infusion or fluid balance, the greater the mechanical ventilation time, ICU or hospital time, and cost.Keywords: fluid strategies, left ventricular diastolic dysfunction, non-cardiac surgery, mechanical ventilation time, perioperative period

Yan Fang,1,2,&ast; Chuang Xiao,1,&ast; Lueli Wang,1,&ast; Youlan Wang,3 Jun Zeng,1 Yaping Liang,1 Rong Huang,1 Yunke Shi,2 Sha Wu,1 Xiaohua Du,2 Shibo Sun,2 Min Li,2 Yuanyuan Zheng,2 Hongxiang Wu,1 Qiuzhe Guo,4 Weimin Yang1 1School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, People’s Republic of China; 2The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 3Kunming Institute of Medical Sciences, Kunming, People’s Republic of China; 4Fuwai Yunnan Cardiovascular Hospital, Kunming, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiuzhe Guo; Weimin Yang, Email drguoqz@163.com; ywmbessie@yeah.netBackground: Sepsis is initiated by the dysfunctional response of the host immune system to infection. Septic shock and acute lung injury (ALI) are the main etiology of death caused by sepsis. Glucocorticoids, which are commonly used in clinic to antagonize the inflammatory response of sepsis, may cause serious side effects. Isoforskolin (ISOF) from the plant Coleus forskohlii stimulates adenylyl cyclase, increases the cAMP level and inhibits inflammatory response. The aim of this study was to investigate the synergistic effect of ISOF with dexamethasone (DEX) to prevent and ameliorate septic inflammation.Methods: Lipopolysaccharide (LPS) of 30 and 5 mg/kg (iv.) was used to induce sepsis and ALI mice model respectively in vivo. BEAS-2B cells stimulated by LPS were applied as cell model in vitro. The cumulative survival of mice with LPS-induced sepsis and the histopathological changes of lungs in mice with acute lung injury were observed, and the secretion of pro-inflammatory cytokines was analyzed by ELISA. The expression of RGS2 in BEAS-2B cells was detected by immunoblotting assay and PCR.Results: In the sepsis mice model, ISOF (10 mg/kg) combined with DEX (10 mg/kg.) (ip.) pretreatment significantly increased mice survival rate from 33.3% to 58.3%, which was significantly higher than that of ISOF or DEX treated alone. In the ALI mice model, ISOF, DEX pretreatment alone and combined application attenuated pulmonary pathological changes in ALI mice. Furthermore, ISOF, DEX alone or combined administration decreased MPO, MDA, IL-6, and IL-8 levels, while significantly synergistic effects were observed in the combined treatment group compared with ISOF or DEX alone. In BEAS-2B cells, combined pretreatment with ISOF and DEX significantly decreased the expression of IL-8 and increased the expression of RGS2.Conclusion: The results indicated that ISOF in combination with DEX synergistically improves survival rate and attenuates ALI in mice model through anti-inflammatory and antioxidant effects.Keywords: isoforskolin, sepsis, acute lung injury, pulmonary inflammation, glucocorticoids, regulator of G-protein signaling 2

Ming-Yue Zhu,&ast; Rong Li,&ast; Jie Xu, Fei She, Xin Du, Wei Zhang Department of Emergency Medicine, the Fourth Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Zhang, Department of Emergency Medicine, the Fourth Medical Center, Chinese PLA General Hospital, No. 51 Fucheng Road, Haidian District, Beijing, 100048, People’s Republic of China, Tel +86 010-66867373, Email zhangw8642@126.comObjective: To clarify variations of diagnosis and treatment in the emergency care of critically ill patients not infected with novel coronavirus (COVID-19) prior to and amidst the COVID-19 pandemic.Methods: A retrospective cohort study was conducted to compare and analyze the diagnosis and treatment data of critically ill patients with non-COVID-19 infection who were admitted to the emergency department of the Fourth Medical Center of Chinese PLA General Hospital from January 2019 to November 2022. The variations in emergency care of the pandemic were summarized, and the influence of the pandemic on emergency care was assessed.Results: A total of 6634 critically ill patients with non-COVID-19 infection were included in this study. These patients were elderly, high incidence of chronic diseases, and extended emergency duration during the pandemic. Notably, the proportion of patients requiring intensive care was twofold higher compared to the period before the pandemic. Throughout the pandemic, patients experienced prolonged emergency durations, increased overall costs and daily expenses per patient. Further investigation revealed that elderly patients exhibited worse medical conditions, requiring lengthier emergency treatment and incurring escalated healthcare expenses. However, the presence of pre-existing chronic diseases did not appear to influence disease severity, nor extended emergency durations or heightened healthcare expenditures. Irrespective of the pandemic phase—be it short-term, medium-term, or long-term emergency care—greater healthcare spending was necessary.Conclusion: There was no difference in the disease spectrum of emergency critical ill patients with non-COVID-19 infection prior to and amidst the COVID-19 pandemic, nor the duration and expenditure in prior chronic illness patients. However, the disease severity and emergency duration have led to an increase in the total cost and economic intensity of emergency care for all patients during the epidemic. Especially, elderly patients required longer emergency duration, greater healthcare spending, and more inpatient medical resources than usual.Keywords: novel coronavirus epidemic, emergency, elderly

Qitao Chen, Qiuwei Tao, Qilin Zhu, Jing Zhu, Xufeng Du Department of Dermatology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, People’s Republic of ChinaCorrespondence: Xufeng Du, Department of Dermatology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, No. 299 Qingyang Road, Wuxi, People’s Republic of China, Tel +86 19952290906, Email docdxf@126.comPurpose: Androgenetic alopecia (AGA) is a common dermatological condition, with reported associations between serum vitamin D and sex hormone levels. However, the relationship between these factors and the severity of hair loss remains unclear.Patients and Methods: Our cross-sectional study included 310 AGA patients who visited the dermatology clinic and underwent trichoscopy examinations throughout 2021. We collected data on serum sex hormones and 25(OH)D levels during their consultations. TrichoScan analysis was used to characterize and quantify AGA severity based on hair density and vellus hair proportions in the central scalp area, which were then correlated with the collected indicators.Results: The study findings reflect the basic demographic characteristics of AGA patients in the Chinese population. We discovered a significant negative correlation between serum SHBG levels and AGA severity in women, but no association was found in men. Serum testosterone, estradiol, dehydroepiandrosterone sulfate, and 25(OH)D levels showed no significant correlation with the severity of androgenetic alopecia, regardless of gender.Conclusion: To our knowledge, this is the first study to investigate the relationship between serum sex hormones, vitamin D, and AGA severity using trichoscopic scalp hair features.Keywords: androgenetic alopecia, TrichoScan, vitamin D, sex hormones

Mingzhen Li,1 Bing Zhang,2 Lichuan Guo,2 Yuan Zhang,2 Xiaoyan Du,3 Bingyi Wang,3 Zheng Xu,4 Ning Sun,4 Ruibin Chen,4 Wanwen Han,4 Liming Chen,1 Zhenqiang Song1 1Department of Endocrinology, NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, People’s Republic of China; 2Department of Information Management, NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, People’s Republic of China; 3Department of Medical, Happy Life Technology Co Ltd, Beijing, People’s Republic of China; 4Department of Yutang, Andon Health Co., Ltd, Tianjin, People’s Republic of ChinaCorrespondence: Zhenqiang Song, Department of Endocrinology, NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, No. 6 North Huanrui Road, Beichen District, Tianjin, People’s Republic of China, Tel +86-18602276218, Fax +86-022-59562017, Email zsong@tmu.edu.cnBackground: Our previous study demonstrated that digital diabetes care model (DDCM) created by multidisciplinary care team (MDCT) can improve glycemic control for patients with diabetes than usual care. Therefore, we aimed to explore long-term glycemic control with DDCM and influencing factors in type 2 diabetic cohort, in order to make a portrait for diabetes with goal-achieved HbA1c in clinics.Methods: A total of 1198 outpatients with type 2 diabetes using DDCM for at least 12 months were recruited as a cohort. Medical records and specific DDCM indexes were collected. The influencing factors for glycemic control were explored by multivariate logistic regression analysis, followed by an internal and external validation.Results: A total of 887 patients were finally included. HbA1c target-achieving rate was increased from 39.83% at baseline to 71.79% after 3-month follow-up. A shorter duration of diabetes, more frequent self-monitoring of blood glucose, lower HbA1c level at baseline, and less frequent emergency out-of-hospital follow-ups were influencing factors for HbA1c < 7% at 12-month follow-up. AUC of the prediction model was 0.790, with a sensitivity of 69.7% and specificity of 76.1%. Internal and external validation in patients using the DDCM monitored by MDCT indicated that the DDCM was robust (AUC =0.783 and 0.723, respectively).Conclusion: Our findings made a portrait for T2DM with goal-achieved HbA1c in our DDCM. It is important to recognize associated factors for health providers to make personalized intervention in clinical practice.Keywords: digital diabetes care model, glycemic control, type 2 diabetes management

Liping Shi,1,2 Xiaoqing Du,3 Jing Li,1,2 Guoqiang Zhang1,2 1Department of Dermatology, The First Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Candidate Branch of National Clinical Research Center for Skin Diseases, Shijiazhuang, People’s Republic of China; 3Department of Dermatology, Bethune International Peace Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Guoqiang Zhang, The First Hospital of Hebei Medical University, 89 Donggang Road, Yuhua District, Shijiazhuang City, Hebei Province, People’s Republic of China, Tel +8618633888122, Email zlx090702@163.comObjective: This study aimed to identify hub genes and common pathways shared between psoriasis and cardiovascular disease (CVD) using bioinformatics analysis and predict the transcription factors (TFs) of hub genes.Methods: GSE133555 data from the Gene Expression Omnibus (GEO) database were used to identify differentially expressed genes (DEGs) between involved and uninvolved skin lesions in psoriasis, employing the limma package in R. Additionally, CVD-related genes were obtained from the GeneCards database. The intersection of DEGs and CVD-related genes yielded CVD-DEGs. Gene Ontology and signaling pathway analyses were performed using the clusterProfiler package in R. Hub genes were identified by intersecting six algorithms in the CytoHubba plugin of Cytoscape. To identify potential biomarkers, the GSE14905 dataset was subjected to receiver operating characteristic analysis, resulting in the identification of eight central hub genes. Finally, the NetworkAnalyst web tool was used to identify the TFs of the eight hub genes.Results: We identified 92 significant DEGs out of 1825 CVD-related genes in psoriasis obtained from the GSE13355 and GeneCard data. Functional enrichment analysis revealed the involvement of these genes in various signaling pathways, including the interleukin-17 signaling, tumor necrosis factor signaling, lipid and atherosclerosis, chemokine signaling, and cytokine signaling pathways in the immune system. The eight hub genes identified included interleukin-1 beta, C-X-C motif chemokine ligand 8, signal transducer and activator of transcription 3, C-C motif chemokine ligand 2, arginase 1, C-X-C motif chemokine receptor 4, cyclin D1, and matrix metallopeptidase 9, with forkhead box C1 also identified as an associated TF of these genes. These hub genes and TF may act as key regulators in the context of CVD.Conclusion: This study identified several hub genes and signaling pathways associated with both CVD and psoriasis. These findings lay the groundwork for potential therapeutic interventions for patients with psoriasis affected by CVD.Keywords: psoriasis, cardiovascular disease, signaling pathway, gene expression omnibus

Wan Y, Lv M, Zhou K, et al. Nat Sci Sleep. 2023;15:511-522. The authors wish to advise that an unauthorized version of the Chinese MMSE was used by the study team without permission. The MMSE is a copyrighted instrument and may not be used or reproduced in whole or in part, in any form or language, or by any means without written permission of PAR (www.parinc.com). The issue was resolved between the authors and PAR. The authors confirm that no test items from the unauthorized version of the Chinese MMSE are included in the article.

Yahui Wan,1 Mengdi Lv,2 Kaili Zhou,1 Zheng Li,3 Xueyun Du,1 Wei Wu,4 Rong Xue4 1Departments of Neurology, Tianjin Medical University General Hospital Airport Hospital, Tianjin, 300308, People’s Republic of China; 2Departments of Neurology, Tianjin First Central Hospital, Tianjin, 300190, People’s Republic of China; 3Departments of Neurology, Binhai Hospital, Peking University, Tianjin, 300450, People’s Republic of China; 4Departments of Neurology, Tianjin Medical University General Hospital, Tianjin, 300052, People’s Republic of ChinaCorrespondence: Rong Xue, Departments of Neurology, Tianjin Medical University General Hospital, Tianjin, 300052, People’s Republic of China, Email xuerong1403@126.comPurpose: To evaluate the correlation between sleep microstructure, autonomic nervous system activity, and neuropsychological characteristics in chronic insomnia (CI) patients with obstructive sleep apnea (OSA).Patients and Methods: Forty-five CI-OSA patients, forty-six CI patients and twenty-two matched healthy control subjects (HCs) were enrolled. CI-OSA patients were then divided into two groups: mild OSA and moderate-to-severe OSA. All participants completed neuropsychological tests, which included the Hamilton Depression and Anxiety Scales (HAMD and HAMA), the Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index (ISI), the Epworth Sleepiness Scale (ESS), and the Mini-mental State Examination (MMSE). The autonomic nervous system activity and sleep microstructure were examined by the PSM-100A.Results: The CI-OSA patients exhibited higher scores on the PSQI, ESS, ISI, HAMA, and HAMD than HCs and CI patients (all p < 0.01). The CI-OSA patients had a lower proportion of stable sleep, REM sleep and a higher proportion of unstable sleep ratio (all p < 0.01) than HCs and CI patients (all p < 0.01). The CI-OSA patients had higher ratios of LF and LF/HF, and lower ratios of HF and Pnn50% (all p < 0.01) than HCs and CI patients (all p < 0.01). Compared to CI-mild OSA patients, the CI-moderate-to-severe OSA patients presented with a higher ESS scores, higher ratios of LF and LF/HF, and lower ratios of HF (all p < 0.05). In CI-OSA patients, higher HAMD scores were correlated with decreased MMSE scores (r=− 0.678, p < 0.01). A higher LF ratio was correlated with higher HAMD and HAMA scores (r=0.321, p=0.031, r =0.449, p =0.002), and a higher HF ratio was correlated with lower HAMD and HAMA scores (r=− 0.321, P =0.031, r =− 0.449, p =0.002).Conclusion: OSA exacerbates the abnormalities of sleep microstructure and the autonomic nervous dysfunction in CI patients. Dysfunction of the autonomic nervous system could contribute to mood deterioration in CI with OSA patients.Keywords: chronic insomnia, obstructive sleep apnea, OSA, depression, sleep microstructure, autonomic function

Lini Chen,&ast; Yongguo Xie,&ast; Xueke Du, Weiyong Qin, Lifu Huang, Junmin Dai, Ke Qin,&ast; Jianfeng Huang&ast; Department of Anesthesiology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ke Qin; Jianfeng Huang, Department of Anesthesiology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, People’s Republic of China, Tel/Fax +8613878103578 ; +8613978896039, Email qinke303@163.com; 295812612@qq.comBackground: Ciprofol is currently used for painless gastrointestinal endoscopy and anesthesia induction. However, whether it is superior to propofol and its optimal dose remains unknown.Methods: A total of 149 patients, 63 males and 86 females, aged 18– 80 years, BMI 18– 28 kg/m2, ASA I–III, were divided randomly into four groups: propofol group (group P, n = 44), ciprofol 0.2mg/kg group (group C2, n = 38), ciprofol 0.3mg/kg group (group C3, n = 36) and ciprofol 0.4 mg/kg group (group C4, n = 31). Groups C2, C3 and C4 had injected IV with ciprofol 0.2, 0.3 and 0.4 mg/kg, respectively. Group P had injected IV with propofol 1.5mg/kg. The time for disappearance of the eyelash reflex, gastrointestinal endoscopy time, recovery time, and the Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) score at awakening (T1), 15 minutes after awakening (T2) and 30 minutes after awakening (T3) were recorded.Results: Compared with group P, the time to fall asleep was significantly shortened, and the incidence of nausea and vomiting and injection pain was significantly lower in groups C2, C3 and C4 (P < 0.05). There was no significant difference in recovery time and recovery quality between each group (P > 0.05). Compared with group P and C4, the incidence of hypotension and respiratory depression was significantly lower in groups C2 and C3 (P < 0.05).Conclusion: The appropriate dose of ciprofol for painless gastrointestinal endoscopy is more advantageous than propofol in hemodynamics and respiratory stability, with less injection pain and nausea and vomiting, which is worthy of clinical promotion.Keywords: ciprofol, propofol, painless gastrointestinal endoscopy

Dao-Lin Wu,1,2,&ast; Chun-Li Luo,3,&ast; Xu Du,1 Pei-Pei Li,1 Min Jiang,1 Tao Liu,2,4 Yun Sun1,2 1School of Nursing, Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China; 2Clinical Medical College and the First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China; 3School of Nursing, Chongqing Medical University, Chongqing, People’s Republic of China; 4Department of Oncology, Clinical Medical College and the First Affiliated Hospital of Chengdu Medical College, Key Clinical Specialty of Sichuan, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yun Sun, No. 783, Xindu Avenue, Xindu District, Chengdu, Sichuan, People’s Republic of China, Email sy83016603@163.com Tao Liu, No. 783, Xindu Avenue, Xindu District, Chengdu, Sichuan, People’s Republic of China, Email liutao520513@163.comObjective: Readiness for hospital discharge is an important indicator of patients’ transition from illness to health and can predict rehabilitation and prognosis. Identifying factors that influence readiness for discharge is crucial for developing effective nursing interventions. Therefore, this study aims to investigate the current status of discharge readiness and its influencing factors in elderly patients with chronic obstructive pulmonary disease (COPD).Methods: A total of 311 elderly inpatients diagnosed with COPD were enrolled in this investigation at a tertiary hospital in Chengdu between December 2021 and June 2022. Questionnaires were designed to collect general information, disease-related information, and responses to the Readiness for Hospital Discharge Scale (RHDS) and the Quality of Discharge Teaching Scale (QDTS). Univariate and multivariate linear regression analyses were employed to further analyze factors related to discharge readiness and the correlation between discharge readiness and the quality of discharge guidance.Results: The total score of discharge readiness of elderly COPD patients was 77.72 ± 11.86 with a mean score of 6.48 ± 0.19 for each item. The quality of discharge instructions was 110.54 ± 15.66, with a mean score of 6.12 ± 0.15 for each item. Discharge preparation was positively correlated with the quality of discharge guidance. Multivariate analysis showed that marital status, admission mode, length of stay in hospital, Classification of Severity of Airflow Limitation, mMRC classification, number of medications taken with discharge, presence of inhalers in medication orders, mode of home oxygen therapy, and quality of discharge guidance were independent factors of discharge readiness in elderly COPD patients (P < 0.05).Conclusion: Both discharge readiness and the quality of discharge guidance for elderly COPD patients in China are currently suboptimal and need further improvement. The survey findings provide valuable insights that can guide future management practices and interventions aimed at improving discharge readiness.Keywords: chronic obstructive pulmonary disease, discharge readiness, quality of discharge guidance, nursing care

Jie Ren,1,&ast; Jingzhou Wang,2,&ast; Xingchen Yao,1 Yue Wu,1 Ming Shi,1 Xiangjun Shi,3 Xinru Du1 1Department of Orthopaedics, Beijing Chao-yang Hospital, Beijing, 100020, People’s Republic of China; 2Department of Orthopaedics, Beijing Daxing District People’s Hospital, Beijing, 102600, People’s Republic of China; 3Department of Hematology, Beijing Chao-yang Hospital, Beijing, 100020, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinru Du, Department of orthopaedics, Beijing Chao-yang Hospital, No. 8 of Gongti South Road, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel +86 13683156652, Email duxinru@163.comObjective: To explore the role of sclerosteosis (SOST) gene expression in the occurrence and development of multiple myeloma (MM) complicated with sarcopenia.Methods: Analysis of the SOST expression in skeletal muscle tissue of patients with MM using high-throughput sequencing combined with transcriptomics; observation of morphological changes of the mouse C2C12 myoblasts co-cultured with SP2/0 myeloma cells in Transwell; observation of the SOST expression in the C2C12 myoblasts using the immunofluorescence labeling method; and assessment of the changes in exercise capacity of mice with MM using ethology; and the measurement of the SOST expression in muscles of mice using immunohistochemistry.Results: The transcription level of the SOST gene in the muscle tissue was significantly higher in patients with MM and sarcopenia than in patients with MM without sarcopenia and elderly patients with sarcopenia; the area of C2C12 mouse myoblasts co-cultured with SP2/0 myeloma cells was 167,904 ± 8653.7 pix; this was significantly lower than the area of 402,994 ± 13,575.0 pix in the control group (CG); the fluorescence intensity of SOST in the cells of the experimental group (EG) was 159,389 ± 10,534 AU; this was significantly higher than the intensity of 26,338 ± 6059 AU in the CG; the differences in results of the coat-hanger test, the tail suspension test, the weight-bearing forced swimming test, and the grip strength test between the tumor-bearing mice in the EG and the CG were statistically significant; and the quantitative result of SOST expression in the muscle tissue of the EG mice was 11,515 ± 1573 pix; this was significantly higher than the result of 3399 ± 798.8 pix in the CG.Conclusion: The SOST gene expression was significantly higher in muscle of mice in EG than in CG; and increased SOST gene expression might be a pathogenesis of MM complicated with sarcopenia.Keywords: multiple myeloma, SOST, multiple myeloma mouse model, ethology, sarcopenia, myoblast differentiation

In this paper, Ag contained in the lead-silver slag was recovered during the melt-vaporization process. The existing Ag state in the soot was analyzed, the influence of the reaction temperature, the carbon ratio, and the reaction time on the removal rate of the silver was investigated, and the process conditions were optimized using reaction surface methodology. Silver chloride, silver metal, silver sulfide, silver oxide, and silver sulfate are the main silver phases in lead-silver slag, of which silver chloride and silver sulfide are the main phases. The silver oxide (Ag2O) and the silver chloride (AgCl) in the leadsilver slag volatilize to soot, the silver sulfide (Ag2S) is oxidized by oxygen to silver sulfate (Ag2SO4), and elemental silver volatilizes with Pb and Zn to form alloys. The silver is ultimately present as Ag, AgCl, Ag2O and Ag2SO4 in the soot. The removal rate of the silver gradually increases with increasing reaction temperature and tends to remain stable at 1300°C. With a gradual increase in the carbon content, the removal rate of silver first increases and then decreases. The highest value is 80.12 wt% when the carbon content is 16.30 wt%. As the holding time increases, the silver removal rate gradually increases and then stabilizes at 79.97 wt% even at a holding time of 150 minutes. The optimum process conditions for silver removal are a reaction temperature of 1340°C, a carbon content of 16.10 wt%, and a holding time of 165 minutes. The average removal rate of silver under these conditions is 80.42 wt%. The research in this article provides a theoretical basis for the removal and utilization of silver from lead and silver residues.

Wei Zhang, Yingfei Guo, Fei She, Shuangqing Liu, Xin Du, Hongsheng Liu Department of Emergency Medicine, the Fourth Medical Center, Chinese PLA General Hospital, Beijing, 100048, People’s Republic of ChinaCorrespondence: Hongsheng Liu, Department of Emergency Medicine, the Fourth Medical Center, Chinese PLA General Hospital, 51 Fucheng Road, Haidian District, Beijing, 100048, People’s Republic of China, Tel +86 010-66867373, Email liuhomgss6@163.comObjective: To identify the factors influencing the completion rate of the course of rabies vaccinations without considering the economic factors or the drug supplies.Methods: Rabies vaccination data from the Fourth Medical Center of the PLA General Hospital from January 1 to December 31, 2020, were collected. This includes demographics, information on injury-causing animals, vaccination schemes, and injury assessments. Data on completed the course of rabies vaccinations were compared with data on uncompleted. Internal analysis of Zagreb regimen and Essen regimen was performed. The key factor affecting the completion of the course of rabies vaccinations was analyzed.Results: A total of 1633 patients completed the course of rabies vaccinations, while 462 patients did not. There were differences between the two groups in terms of the vaccination scheme, age, and previous history of rabies vaccinations. The results of a multivariate analysis of variance showed that only the vaccination scheme was significantly correlated with the completion rate of the course of rabies vaccinations. The internal analysis of the vaccination schemes showed that the duration of the vaccination scheme directly affected the completion rate of the course of rabies vaccinations, and the vaccination duration was negatively correlated with the completion rate of rabies vaccinations.Conclusion: The completion rate of the course of rabies vaccinations with Zagreb regimen was higher than Essen regimen. The completion rate was closely correlated with the vaccination scheme, but the duration of the vaccination scheme was the key factor. There was a linear relationship between the vaccination duration and the completion rate of the course of vaccinations, which can be represented by the following linear equation: the completion rate of the course of rabies vaccinations (%) = 98.342– 0.999 × vaccination duration (d). Duration is the critical factor affecting the completion rate. To improve the completion rate of vaccination, it is recommended to use a shorter vaccination duration regimen.Keywords: rabies, the completion rate, vaccination duration

Jing Wen,1,2 Liu He,1 Xin Du,1 Chang-Sheng Ma1 1Department of Cardiology, Capital Medical University Affiliated Anzhen Hospital; National Clinical Research Center for Cardiovascular Diseases, Beijing, People’s Republic of China; 2Department of Geriatrics, Beijing Fengtai Hospital, Beijing, People’s Republic of ChinaCorrespondence: Chang-Sheng Ma; Xin Du, Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, No. 2 Beijing Anzhen Road, Chaoyang District, Beijing, 100029, People’s Republic of China, Tel +86-10-84005363, Fax +86-10-84005361, Email chshma@vip.sina.com; duxinheart@sina.comBackground: It is uncertain whether the effect of hyperglycemia on mortality among patients with acute coronary syndrome (ACS) could be adjusted by other modifiable risk factors. Greater body mass index (BMI) might enhance the effect of fasting blood glucose (FPG) on cardiovascular mortality in patients with ACS.Methods: We retrospectively enrolled patients admitted for ACS from 2008 to 2017 in Beijing and divided them into three BMI groups (normal weight ≤ 25 kg/m2, overweight 25– 29.9 kg/m2, obese ≥ 30 kg/m2). The relationships between the blood glucose levels and all-cause or cardiovascular mortalities and their heterogeneities across the groups were analyzed using Cox regression models.Results: A total of 8,086 patients were enrolled, with 746 all-cause and 496 cardiovascular mortalities recorded during the follow-up period. Each 1 mmol/L increase in FPG was associated with an increased risk of all-cause mortality across all groups (adjusted hazard ratio [HR] 1.06, 95% confidence interval [CI] 1.02– 1.09 for normal weight patients; adjusted HR: 1.09, 95% CI: 1.05– 1.13 for overweight patients; adjusted HR: 1.12, 95% CI: 1.03– 1.22 for obese patients), and was associated with an increased risk of cardiovascular mortality among overweight (adjusted HR: 1.10, 95% CI: 1.05– 1.14) and obese patients (adjusted HR: 1.15, 95% CI: 1.04– 1.26), which was greater (p for heterogeneity = 0.006) than the association in the normal weight group (adjusted HR: 1.03, 95% CI: 0.99– 1.08). Similar results were found among 2,537 patients with ACS diagnosed with diabetes.Conclusion: Greater BMI enhances the effect of FPG on cardiovascular mortality among patients with ACS.Keywords: acute coronary syndrome, mortality, fasting plasma glucose, body mass index

Bingjie Shen, Tianjia Guan, Xinyu Du, Chenyang Pei, Jinhong Zhao, Yuanli Liu School of Health Policy and Management, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Yuanli Liu, School of Health Policy and Management, Chinese Academy of Medical Sciences & Peking Union Medical College, 46 Xizongbu Hutong, Dongcheng District, Beijing, 100005, People’s Republic of China, Tel +86 13522592907, Fax +86 10 65105830, Email yliu@pumc.edu.cnPurpose: Previous studies suggested perceived social support has impact on medication adherence among hypertensive patients, but did not simultaneously elucidate the different contents or key providers of social support that patients perceived. This study was to identify the contents and providers of perceived social support beneficial for improving medication adherence among hypertensive patients in China, which could prove important for targeted interventions.Patients and Methods: Following a multi-stage stratified sampling framework, a total of 903 hypertensive patients from 12 primary health institutions across a middle-income city were recruited from April to June 2021. Medication adherence was measured using the Chinese version of the Morisky, Green and Levine scale; perceived social support was determined using the name generator method. A binary logistic regression model was performed to identify the association between medication adherence and perceived social support. The contents of support included informational, emotional, and instrumental support (finances and caregiving). The support providers included spouse/partner, children, parents, siblings, other relatives, and friends.Results: A total of 506 (56.04%) patients optimally adhered to their antihypertensive medication. Female, older, urban patients, patients with shorter duration of hypertension and antihypertensive medications used showed better adherence (P< 0.05). Optimal medication adherence was positively associated with the overall score of caregiving support (adjusted odds ratio [AOR] = 1.128; 95% confidence interval [CI] = [1.013– 1.257]), informational support from the spouse/partner (AOR = 1.574; 95% CI = [1.112– 2.227]), emotional support from the spouse/partner (AOR = 1.430; 95% CI = [1.032– 1.981]), financial support from the spouse/partner (AOR = 1.439; 95% CI = [1.069– 1.937]) and caregiving support from the spouse/partner (AOR = 1.652; 95% CI = [1.130– 2.414]), whereas optimal medication adherence was negatively associated with caregiving support from friends (AOR = 0.499; 95% CI = [0.286– 0.872]).Conclusion: Informational, emotional, financial and caregiving support from spouses/partners have positive impacts on optimal medication adherence of hypertensive patients of community-level. Community-based interventions designed to improve medication adherence of hypertensive patients should target both patients and their spouses/partners; spouses/partners could be encouraged to provide various support to improve the medication adherence of hypertensive patients.Keywords: medication adherence, perceived social support, spouse, hypertension, China

Mei Li,1 Jing Xu,1,2 Yujue Wang,1 Xiaoye Du,1,2 Teng Zhang,1,2 Yu Chen1– 3 1Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200427, People’s Republic of China; 2Clinical Research Institute of Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 200437, People’s Republic of China; 3Laboratory of Clinical and Molecular Pharmacology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200427, People’s Republic of ChinaCorrespondence: Yu Chen, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Road, Shanghai, 200437, People’s Republic of China, Tel +86 21 5598 1009, Fax +86 21 5598 1009, Email chenyu@shutcm.edu.cnPurpose: Photoreceptors are specialized retinal neurons responsible for phototransduction. Loss of photoreceptors directly leads to irreversible vision impairment. Pharmacological therapies protecting against photoreceptor degeneration are clinically lacking. Oxidative stress and inflammation are common mechanisms playing important roles in the pathogenesis of photoreceptor degeneration. Astragaloside A (AS-A) is a naturally occurring antioxidant and anti-inflammatory agent with neuroprotective activities. However, the photoreceptor protective effects of AS-A remain unknown. The current study thus aims to illustrate the pharmacological potentials of AS-A in protecting against photoreceptor degeneration.Methods: BALB/c and C57/BL6J mice were exposed to bright light and DNA alkylating agent methyl methanesulfonate (MMS) to develop oxidative stress and DNA damage-mediated photoreceptor degeneration, respectively. Microstructural, morphological and functional assessments were performed to directly evaluate the photoreceptor protective effects of AS-A. Ultrastructural and molecular changes in the retina were examined to better understand the pharmacological mechanisms of AS-A in protecting against photoreceptor degeneration.Results: AS-A protected against bright light-induced photoreceptor impairment. Bright light-induced retinal oxidative stress and photoreceptor cell death were attenuated by AS-A treatment. AS-A treatment mitigated bright light-induced DNA damage, activation of poly (ADP-ribose) polymerase (PARP) and nuclear dislocation of high mobility group box 1 (HMGB1) in photoreceptors. AS-A broadly counteracted bright light-altered retinal gene expression profiles. In particular, AS-A decreased the retinal expression of genes involved in necroptosis and inflammatory responses. Bright light-induced microglial activation was also suppressed as a result of AS-A treatment. Furthermore, AS-A attenuated MMS-induced photoreceptor morphological impairment, elevated expression of pro-necroptotic and proinflammatory genes as well as microglial activation in the retina.Conclusion: The work here demonstrates for the first time that AS-A protects against photoreceptor degeneration in part through mitigating oxidative stress and DNA damage-induced necroptosis and inflammatory responses in the retina.Keywords: retinal degeneration, photooxidative stress, photoreceptor protection, programmed cell death, microglial activation

Qianqian Zhao,1 Luyu Zhang,1 Yingying Wang,2 Ye Sun,1 Tianpei Wang,1 Jingjing Cao,1 Meng Qi,3 Xiaoping Du,3 Zengrun Xia,3 Rongqiang Zhang,4 Yin Yang1,5 1School of Nursing, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People’s Republic of China; 2The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 3Ankang R&D Center of Se-Enriched Products, Ankang, Shaanxi, People’s Republic of China; 4School of Public Health, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People’s Republic of China; 5The Second Department of Orthopedics, Xi’an Central Hospital, Xi’an, Shaanxi, People’s Republic of ChinaCorrespondence: Rongqiang Zhang, School of Public Health, Shaanxi University of Chinese Medicine, No.1 Middle Section of Century Avenue, Xianyang, Shaanxi, 712046, People’s Republic of China, Tel/Fax +86-029-38185219 Email Zhangrqxianyang@163.com Yin Yang, The Second Department of Orthopedics, Xi’an Central Hospital, No. 161, West Fifth Road, Xincheng District, Xi’an, Shaanxi, 710003, People’s Republic of China, Email yydoctor@126.comPurpose: Glutathione peroxidase-7 (GPX7) is a newly discovered non-selenium-containing protein with glutathione peroxidase activity, which mainly protects the organism from oxidative damage and is very important for basic biology studies. This study aims to reveal the expression pattern of GPX7 and its prognosis potential from a pan-cancer perspective.Methods: Expression levels of GPX7 in human tumor tissues and normal tissues were evaluated using Human Protein Atlas (HPA), the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) and UALCAN databases. The prognostic potential of GPX7 for 33 TCGA tumors was evaluated by Kaplan–Meier analysis and Cox regression analysis. Subsequently, the Chinese Glioma Genome Atlas (CGGA) dataset was used to further verify the expression of GPX7 and its prognostic potential in glioma. We explored the correlation between GPX7 and immune infiltration, tumor mutational burden (TMB) and microsatellite instability (MSI). Furthermore, a nomogram lower-grade glioma (LGG) was constructed to verify the prognostic outcome of patients. Finally, the relationship between GPX7 and treatment regimens for LGG was also explored.Results: GPX7 was overexpressed in multiple tumors. Elevated expression of GPX7 was associated with poor prognosis of LGG patients (OS hazard ratio (HR) = 1.044, P < 0.0001; DFS HR = 1.035, P < 0.0001; PFS HR = 1.045, P < 0.0001). GPX7 was proved to be an independent prognostic factor of LGG through univariate and multivariate Cox analysis. The nomogram confirmed a better predictability (Concordance index (C-index): 0.845; 95% CI, 0.825– 0.865). GPX7 was positively correlated with TMB in LGG. GPX7 expression was negatively correlated with half-maximal inhibitory concentration (IC50) of temozolomide (TMZ) (spearman= − 0.59, P =1.3e-48).Conclusion: GPX7 was upregulated in multiple tumors, and it was a potential prognostic biomarker in LGG. High-expressed GPX7 can predict the sensitivity of TMZ in LGG patients.Keywords: GPX7, pan-cancer, gene expression, prognosis, biomarker

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

Sirong Zhu,1,&ast; Chao Sun,1,&ast; Longjiang Zhang,1 Xiaoan Du,1 Xiaodong Tan,1,2 Shuzhen Peng3 1School of Public Health, Wuhan University, Wuhan, Hubei, People’s Republic of China; 2School of Nursing, Wuchang University of Technology, Wuhan, Hubei, People’s Republic of China; 3The People’s Hospital of Huangpi, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaodong Tan; Shuzhen Peng, Email 00300469@whu.edu.cn; 1718274898@qq.comPurpose: This study aimed to analyze the incidence trend and further explore the risk factors influencing the survival among patients of malignant skin cancer in America.Methods: Age-adjusted incidence rates, annual percentage change (APC) of different sex and ethnicity in 1973– 2015 and patient records were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate analysis and multivariate Cox regression were used to analyze risk factors influencing the survival in skin cancer patients. Survival curves and nomograms were constructed to evaluate the survival prediction by R.Results: The overall age-adjusted incidence of skin cancer increased in America from 1973 to 2005 (APC = 2.8%, 95% CI: 2.6– 2.9%, P < 0.05), particularly in white patients, 66-year-old people, and males. The 3- and 5-year overall survival (OS) rates were 51.4% and 33.8%, respectively. Independent predictors for short OS include age over 65, white ethnicity, other marital status and no surgery (P < 0.05). Stage was not an independent factor of survival (P > 0.05). The nomogram with a C-index of 0.72 (95% CI: 0.71– 0.73) matched an appropriate calibration curve.Conclusion: Incidence of skin cancer in America was on the rise during 1973– 2015 based on SEER database. Age, ethnicity, marital status and surgical history were related with survival of malignant skin cancer. Nomograms were effective tools for predicting the survival prognosis.Keywords: malignant skin cancer, primary site surgery, SEER, incidence, overall survival, nomogram

Yulan Huang,&ast; Shitong He,&ast; Yitian Chen, Junli Sheng, Yuling Fu, Xialin Du, Yalong Yang, Honglin Liu, Zhenyu Han, Yingqi Huang, Qian Wen, Chaoying Zhou, Xinying Zhou, Shengfeng Hu, Li Ma Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Ma; Shengfeng HuInstitute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, People’s Republic of China, Email mali_61648322@smu.edu.cn; hushengfeng@smu.edu.cnBackground: As deubiquitinases (DUBs), ubiquitin C-terminal hydrolase (UCH)-L1 has been shown to play a crucial role in regulating diverse biological processes. However, its function in macrophage polarization remains unclear.Methods: We performed in vivo and in vitro experiments to investigate the role of ubiquitin carboxyl-terminal hydrolase L1 (UCHL1), a kind of DUBs, in macrophage differentiation by using UCHL1-deficiency mice.Results: We demonstrated that LPS stimulation induced UCHL1 expression in macrophages. The deficiency of UCHL1 expression decreased the expression of CD80 and CD86 but increased the expression of CD206. The expression of TNF-α, IL-6, iNOS, and IL-10 was downregulated, while that of Arg1, Ym1, and Fizz1 was upregulated in UCHL1 deficient macrophages. Moreover, we observed that UCHL1 promoted the degradation of p110α through autophagy, but paradoxically increased the activity of AKT, thereby promoting polarization of macrophages into pro-inflammatory states.Conclusion: In this study, we identified UCHL1 as a positive regulator of M1 macrophage polarization. Our findings may help in developing therapeutic interventions for the treatment of inflammatory diseases and pathogenic infections.Keywords: UCHL1, macrophages, AKT, p110α, autophagy

Yi Zhou,1 Qiwen Huo,1 Shaoying Du,1 Xiaoyang Shi,1 Qisong Shi,2 Shanshan Cui,3 Cuina Feng,4 Xiaojing Du,1 Yan Wang1 1School of Nursing, Hebei University, Baoding, Hebei, People’s Republic of China; 2Department of Cardiovascular Medicine, The Second Hospital of Baoding, Baoding, Hebei, People’s Republic of China; 3Department of General Medicine, Affiliated Hospital of Hebei University, Baoding, Hebei, People’s Republic of China; 4Department of Cardiovascular Medicine, Affiliated Hospital of Hebei University, Baoding, Hebei, People’s Republic of ChinaCorrespondence: Yan WangSchool of Nursing, Hebei University, 342 Yuhuadong Road, Baoding, Hebei, 071000, People’s Republic of China, Tel/Fax +86 3125075605, Email chjanwy@163.comPurpose: Medication non-adherence is a major public health issue. Recent evidence suggests that depression, inadequate social support, and lower levels of self-efficacy are associated with poor medication adherence. However, the mechanism underlying the association among depression, social support, self-efficacy and medication adherence is unclear. This study aims to examine the mediating role of social support and self-efficacy between depression and medication adherence in older patients with coronary heart disease.Patients and Methods: Data were collected from 238 hospitalized older patients with coronary heart disease. Depression, social support, self-efficacy, and medication adherence were assessed using structured questionnaires. A serial multiple mediation model was tested using the PROCESS macro for SPSS.Results: A total of 238 older patients with CHD with a mean age of 70.5 years were involved in this cross-sectional study. Depression was negatively correlated with medication adherence in older patients with coronary heart disease. Social support and self-efficacy were positively associated with medication adherence, and fully mediated the relationship between depression and medication adherence. Three mediation paths were included in the model: (a) social support, (b) chain combination of social support and self-efficacy, and (c) self-efficacy.Conclusion: Social support and self-efficacy explain the association of depression and medication adherence in older CHD patients and may be the keys target for enhanced intervention to improve medication adherence in older CHD patients with depression.Keywords: coronary heart disease, depression, medication adherence, self-efficacy, social support

Qiongjie Yu,&ast; Xuedan Du,&ast; Zhen Fang, Xiaolu Mao, Jinting Wu, Bin Wang, Wenfeng Li Department of Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenfeng LiDepartment of Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of ChinaEmail lwf720325@126.comPurpose: Inflammatory biomarkers and clinical pathological factors have been reported to predict survival of patients with non-small cell lung cancer (NSCLC). The goal of this study was to identify risk factors for early recurrence in patients with pIIIA-N2 NSCLC who had undergone radial resection.Methods: A retrospective analysis was conducted on 238 patients with pIIIA-N2 NSCLC who underwent surgical treatment at the First Affiliated Hospital of Wenzhou Medical University between December 2006 and August 2018. The early recurrence (ER) group included patients who recurred within one year of curative resection, while the non-early recurrence (NER) group included patients who did not recurrence or recurrence beyond one year. The univariate and multivariate Cox proportional risk analyses were used to identify prognostic factors associated with early recurrence, while the chi-square test was used for categorical data. Overall survival and recurrence-free survival were assessed by Kaplan–Meier estimates.Results: A total of 69 patients experienced an early recurrence, while the remaining 169 patients did not relapse within one year. ER patients had a much worse prognosis than NER patients, with median survival times of 20.6 and 83.1 months, respectively. Multivariate analysis showed that smoking status, tumor size, metastatic lymph node ratio (LNR) and platelet-to-lymphocyte ratio (PLR) were independent risk factor of early recurrence. Patients with early recurrence were more likely to develop bone metastases.Conclusion: Smoking history, large tumour size, and elevated LNR and PLR values in pIIIA-N2 NSCLC patients after complete resection may have a significant risk of early recurrence. Based on these independent risk indicators, this prediction model may successfully predict early recurrence and advise individual treatment.Keywords: non-small cell lung cancer, early recurrence, risk factors, inflammatory biomarkers, prognosis

Luyu Zhang,1 Qianqian Zhao,1 Leilei Mao,2 Huanze Li,1 Miaoqing Zhuang,1 Jiayi Wang,1 Yue Liu,1 Meng Qi,3 Xiaoping Du,3 Zengrun Xia,3 Na Sun,4 Qiling Liu,4 Hongfang Chen,1,5,6 Rongqiang Zhang4 1School of Nursing, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People’s Republic of China; 2School of Information Engineering, Chang’an University, Xi’an, Shaanxi, People’s Republic of China; 3Ankang R & D Center of Se-enriched Products, Ankang, Shaanxi, People’s Republic of China; 4School of Public Health, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People’s Republic of China; 5Shaanxi Academy of Tradional Chinese Medicine, Xi’an, Shaanxi, People’s Republic of China; 6Shaanxi Provincial Hospital of Chinese Medicine, Xi’an, Shaanxi, People’s Republic of ChinaCorrespondence: Hongfang ChenShaanxi Academy of Tradional Chinese Medicine, Shaanxi Provincial Hospital of Chinese Medicine, No. 4 Xihua Gate, Xi’an, Shaanxi, 710003; School of Nursing, Shaanxi University of Chinese Medicine, No. 1 Middle Section of Century Avenue, Xianyang, Shaanxi, 712046, People’s Republic of ChinaEmail 13892881695@163.comRongqiang ZhangSchool of Public Health, Shaanxi University of Chinese Medicine, No. 1 Middle Section of Century Avenue, Xianyang, Shaanxi, 712046, People’s Republic of ChinaTel/Fax +86-029-38185219Email Zhangrqxianyang@163.comPurpose: Selenophosphate synthetase 2 (SEPHS2) has been shown to regulate selenoprotein biosynthesis by catalyzing the synthesis of active selenium donor selenophosphate. SEPHS2 influences the survival of tumor cells. However, few studies have explored the expression level and prognostic of SEPHS2 in various cancers.Methods: The expression of SEPHS2 in human tumor tissues and normal adjacent tissues was analyzed in The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Human Protein Atlas (HPA), and UALCAN databases. Cox regression analysis and Kaplan–Meier curve analysis were performed to analyze the association of SEPHS2 expression with the prognosis of cancer patients. The expression and prognosis of SEPHS2 in gliomas were further verified using the Chinese Glioma Genome Atlas (CGGA) dataset. The relationship between SEPHS2 and immune infiltration, tumor mutational burden (TMB), microsatellite instability (MSI), and neoantigens was comprehensively explored using a TCGA cohort. The mechanism by which SEPHS2 regulates tumor progression was explored by using the STRING database. A nomogram was constructed using the R software to predict the overall survival (OS) of patients with brain lower grade glioma (LGG).Results: SEPHS2 was highly expressed in many cancers including LGG. Its high expression was significantly associated with poor OS, disease-free survival (DFS), and progression-free survival (PFS). Univariate and multivariate Cox analyses showed that SEPHS2 was an independent prognostic factor for LGG. Concordance index and calibration curves revealed that the nomogram had good predictive performance (concordance index: 0.791; 95% CI: 0.732– 1). A significant correlation was found between SEPHS2 and immune infiltration, TMB, MSI, and tumor neoantigens across diverse cancers. Enrichment analysis showed that SEPHS2 may regulate the PPAR signaling pathway.Conclusion: SEPHS2 expression regulates tumor development and it is a potential treatment target and prognostic biomarker, especially for lower grade glioma.Keywords: SEPHS2, selenoprotein, cancer, prognosis, biomarker

Lixiao Liu,1,&ast; Xuedan Du,2,&ast; Jintao Fang,3,&ast; Jinduo Zhao,1 Yong Guo,3 Ye Zhao,1 Chengyang Zou,1 Xiaojian Yan,1 Wenfeng Li2 1Department of Obstetrics and Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2Department of Chemoradiation Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 3Department of Urinary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenfeng Li; Xiaojian Yan Email liwenfeng@wmu.edu.cn; yxjbetter2016@hotmail.comBackground: Interferon plays a crucial role in the pathogenesis and progression of tumors. Clear cell renal cell carcinoma (ccRCC) represents a prevalent malignant urinary system tumor. An effective predictive model is required to evaluate the prognosis of patients to optimize treatment.Materials and Methods: RNA-sequencing data and clinicopathological data from TCGA were involved in this retrospective study. The IFN-γ response genes with significantly different gene expression were screened out. Univariate Cox regression, LASSO regression and multivariate Cox regression were used to establish a new prognostic scoring model for the training group. Survival curves and ROC curves were drawn, and nomogram was constructed. At the same time, we conducted subgroup analysis and experimental verification using our own samples. Finally, we evaluated the relatedness between the prognostic signature and immune infiltration landscapes. In addition, the sensitivity of different risk groups to six drugs and immune checkpoint inhibitors was calculated.Results: The IFN-γ response-related signature included 7 genes: C1S, IFI44, ST3GAL5, NUP93, TDRD7, DDX60, and ST8SIA4. The survival curves of the training and testing groups showed the model’s effectiveness (P = 4.372e-11 and P = 1.08e-08, respectively), the ROC curves showed that the signature was stable, and subgroup analyses showed the wide applicability of the model (P< 0.001). Multivariate Cox regression analysis showed that the risk model was an independent prognostic factor of ccRCC. A high-risk score may represent an immunosuppressive microenvironment, while the high-risk group exhibited poor sensitivity to drugs.Conclusion: Our findings strongly indicate that the IFN-γ response-related signature can be used as an effective prognostic indicator of ccRCC.Keywords: interferon gamma, nomogram, prognostic signature, drug sensitivity, qPCR

Ye Zhao,1,&ast; Lixiao Liu,1,&ast; Jinduo Zhao,1 Xuedan Du,2 Qiongjie Yu,2 Jinting Wu,2 Bin Wang,2 Rongying Ou1 1Department of Obstetrics and Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2Department of Chemoradiation Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rongying OuDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of ChinaTel +86 135662227918Fax +86 577-55578033Email ourongying@163.comIntroduction: Breast cancer is the most common form of cancer worldwide and a serious threat to women. Hypoxia is thought to be associated with poor prognosis of patients with cancer. Long non-coding RNAs are differentially expressed during tumorigenesis and can serve as unambiguous molecular biomarkers for the prognosis of breast cancer.Methods: Here, we accessed the data from The Cancer Genome Atlas for model construction and performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses to identify biological functions. Four prognostic hypoxia-related lncRNAs identified by univariate, LASSO, and multivariate Cox regression analyses were used to develop a prognostic risk-related signature. Kaplan–Meier and receiver operating characteristic curve analyses were performed, and independent prognostic factor analysis and correlation analysis with clinical characteristics were utilized to evaluate the specificity and sensitivity of the signature. Survival analysis and receiver operating characteristic curve analyses of the validation cohort were operated to corroborate the robustness of the model.Results: Our results demonstrate the development of a reliable prognostic gene signature comprising four long non-coding RNAs (AL031316.1, AC004585.1, LINC01235, and ACTA2-AS1). The signature displayed irreplaceable prognostic power for overall survival in patients with breast cancer in both the training and validation cohorts. Furthermore, immune cell infiltration analysis revealed that B cells, CD4 T cells, CD8 T cells, neutrophils, and dendritic cells were significantly different between the high-risk and low-risk groups. The high-risk and low-risk groups could be precisely distinguished using the risk signature to predict patient outcomes.Discussion: In summary, our study proves that hypoxia-related long non-coding RNAs serve as accurate indicators of poor prognosis and short overall survival, and are likely to act as potential targets for future cancer therapy.Keywords: long noncoding RNA, lncRNA, breast cancer, hypoxia, TCGA, prognosis

Qing-E Xie,1– 3,* Xin Du,4,* Mengyao Wang,1,2,5 Fenfen Xie,3 Zuoyang Zhang,6 Yunxia Cao,1,2,5,7,8 Yajing Liu1,2,5,7,8 1Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China; 2NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, Hefei, 230022, People’s Republic of China; 3Department of Histology and Embryology, Anhui Medical University, Hefei, 230032, Anhui, People’s Republic of China; 4 901th Hospital of PLA Joint Logistic Support Force, Heifei, 230031, Anhui, People’s Republic of China; 5Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People’s Republic of China, Hefei, 230032, Anhui, People’s Republic of China; 6Department of Pathology, Anhui Medical University, Hefei, 230032, Anhui, People’s Republic of China; 7Anhui Province Key Laboratory of Reproductive Health and Genetics, Hefei, 230032, Anhui, People’s Republic of China; 8Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, Hefei, 230032, Anhui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yunxia Cao; Yajing Liu Email caoyunxia6@126.com; 13385690561@163.comPurpose: Cumulative evidence has demonstrated that breast cancer was the most commonly diagnosed cancer in women. Despite growing evidence for a link between serotonin and tumorigenesis, research on the expression of serotoninergic systems in the human breast cancer cell and tissue has only rarely been reported.Methods: First, immunofluorescence staining, ELISA and Western blotting were used to detect serotonin and melatoninergic systems in various breast cancer cell types. Then, serotonin expression was evaluated in the cultures of TPBC cell line BT-474 and TNBC cell line MDA-MB-231 using immunofluorescence assay. To further explore the diagnostic role of serotonin in breast cancer, serotonin expression was conducted in the TPBC and TNBC tumor sections by immunostaining analysis.Results: Our results suggested that both human breast cancer cells and human breast epithelial cell line could synthesize serotonin and melatonin. Unlike melatonin, serotonin levels varied significantly between human breast cancer and breast epithelial cell line (p< 0.01). In addition, serotonin N-acetyltransferase (NAT) and acetylserotonin methyltransferase (ASMT), the key enzymes in the pathway of melatonin synthesis from serotonin, were also detectable. In agreement with these findings of human breast cancer cell and human breast epithelial cell line, serotonin expression was also much higher in triple-negative (PR−, ER−, HER-2−) breast cancer (TNBC) and triple-positive breast cancer (TPBC) compared to para-carcinoma tissues (PCTs).Conclusion: Here, we provided evidence that the human breast cancer cell (MCF-7, Bcap-37) and human breast epithelial cell (MCF-10A) could synthesize intrinsic serotonin and melatonin, and serotonin expression was higher in the breast cancer tissue compared with PCT. The findings suggested that serotonin might be used as a predictive marker for breast cancer patients.Keywords: serotonin, melatonin, breast cancer, serotonin N-acetyltransferase, acetylserotonin methyltransferase

Shihua Wang,1 Yimeng Cui,1 Minqi Xiong,1,2 Mei Li,1 Peiwei Wang,1,2 Jingang Cui,1,2 Xiaoye Du,1,2 Yu Chen,1– 3 Teng Zhang1,2 1Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Clinical Research Institute of Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Laboratory of Clinical and Molecular Pharmacology, Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Teng Zhang; Yu ChenShanghai University of Traditional Chinese Medicine, 110 Ganhe Rd, Shanghai, 200437, ChinaTel +86-21-55982301; +86-21-55982302Email zhangteng2089@shutcm.edu.cn; chenyu@shutcm.edu.cnPurpose: Owing to the important mechanistic implications in the pathogenesis of cardiac hypertrophy and heart failure, inflammation has been proposed as a druggable target for the treatment of cardiac hypertrophy and heart failure. Ginseng is a widely used medicinal herb for the treatment of cardiovascular disorders. As one of the major chemical components of ginseng, ginsenoside Rb1 (Rb1) contributes to the cardiovascular effects of ginseng. Meanwhile, anti-inflammatory activity of Rb1 has also been documented. The current work aims to further delineate the pharmacological implications of Rb1 in the treatment of cardiac hypertrophy.Methods: Angiotensin II (Ang II) infusion mouse model was adopted to investigate the effects of Rb1 on cardiac hypertrophic remodeling and associated inflammation in vivo. Furthermore, the mechanisms of actions of Rb1 in modulating the hypertrophic and inflammatory responses were investigated in cardiomyocytes and macrophages, respectively.Results: Rb1 mitigates Ang II–induced cardiac hypertrophy, cardiac inflammation and systemic inflammation in vivo. In cardiomyocytes, Rb1 directly counteracts the pro-hypertrophic effects of Ang II and phenylephrine and maintains the mitochondrial function. In lipopolysaccharide (LPS)-stimulated macrophages, Rb1 decreases the phosphorylation of mitogen-activated protein kinases (MAPKs) and mitogen-activated protein kinase kinase 1/2 (MEK1/2) and reduces the production of inflammation mediators such as interleukin (IL)-1 beta, IL-6 and tumor necrosis factor (TNF). Rb1 also suppresses the expression of pro-hypertrophic microRNA-155 (miR-155) in LPS- or Ang II-stimulated macrophages. Furthermore, in activated macrophages, miR-155 is in part accountable for the suppressive effect of Rb1 on the production of IL-6, an inflammation mediator with pro-hypertrophic functions in the heart.Conclusion: The work here provides novel experimental evidence supporting the notion that Rb1 protects against cardiac hypertrophy in part through suppressing the inflammatory mechanisms that promotes the pathological remodeling of the heart.Keywords: angiotensin II, inflammation, interleukin 6

Qian Xu,1,2,* Ying Fu,3,* Jingshu Ji,3 Xiaoxing Du,1,2 Yunsong Yu1,2 1Department of Infectious Diseases, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, 310016, People’s Republic of China; 2Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, Zhejiang Province, 310016, People’s Republic of China; 3Department of Clinical Laboratory, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, 310016, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yunsong Yu Qingchun East Road No. 3, Hangzhou City, Zhejiang Province, 310016, People’s Republic of ChinaTel/Fax +86-571-86006142Email yvys119@zju.edu.cnIntroduction: Antibiotics for treating infectious diseases caused by carbapenem-resistant Gram-negative pathogens (CR-GNOs) are very limited in clinical practice. We aim to provide supportive evidence by revealing the combined effect of aztreonam (ATM) and amoxicillin/clavulanic acid (AMC) against GNOs with carbapenem resistance mediated by metallo-β-lactamase (MBL).Methods: All isolates were identified by the VITEK system and EDTA inhibitory assays. PCR followed by sequencing was conducted to confirm the genotypes of MBL and extended spectrum β-lactamase (ESBL). Time kill assay was performed to clarify the bactericidal effect of drug combination.Results: A total of 59 MBL-producing CR-GNOs (33 Enterobacteriaceae spp. isolates and 26 Pseudomonadales isolates) were identified and there found three MBL genes, namely, blaIMP, blaNDM and blaVIM, with ratios of 76.2%, 11.8% and 11.8%, respectively. The Enterobacteriaceae spp. isolates were commonly positive for the ESBL genes, including blaTEM (18 isolates), blaSHV (20 isolates) and blaCTX-M-1 (8 isolates), while the P. aeruginosa isolates were positive for blaOXA-10 (11 isolates). The checkerboard microdilution assay was used to detect combination effect of ATM and AMC, which showed synergy (97.0%) and partial synergy (3.0%) in Enterobacteriaceae spp. isolates, and partial synergy (42.3%) and indifference (34.6%) in the Pseudomonadales isolates. Four Enterobacteriaceae spp. isolates were selected for a time-kill assay, and rapid bactericidal effects were observed in the combination groups compared to the control and mono-ATM groups; these effects began in the first hour and continued to the sixth hour, yielding a 5- to 7-fold reduction in Log10 CFU/mL.Discussion: The combination of ATM and AMC would be an available option to control infections caused by MBL-producing CR-GNOs, especially Enterobacteriaceae spp. isolates that coproduce ESBLs, and exhibit significant synergic effects in vitro.Keywords: gram-negative pathogens, carbapenem resistance, metallo-β-lactamase, extended spectrum β-lactamase, aztreonam, amoxicillin/clavulanic acid, combination

Xia Du,1 Cheng-Nan Guo,2 Xiao-Dong Bao3 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2Department of Statistics, School of Public Health and Management, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 3Central Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Xiao-Dong BaoCentral Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325003, People’s Republic of ChinaTel +86 1 881 500 0923Email 512749893@qq.comPurpose: Conventional staging and scoring systems such as the Tumor, Node, and Metastasis; Cancer of the Liver Italian Program; Barcelona Clinic Liver Cancer; and Okuda have failed to predict overall survival (OS) in patients with resected primary hepatocellular carcinoma. Thus, we aimed to establish a novel D-index and nomogram to improve prognostic accuracy.Patients and Methods: We selected 396 patients who underwent liver resection between January 2007 and February 2015 at the First Affiliated Hospital of Wenzhou Medical University. These patients were randomly divided into the training and validation groups in a ratio of 7:3.Results: We generated a nomogram using five independent risk factors, including the D-index (calculated by total bilirubin × tumor size/the ratio of fat-to-muscle area 0.5) in the training set. The predictive performance of the nomogram was similar in both the training and validation cohorts according to the concordance index. The nomogram demonstrated the strongest predictive power for 1-year, 3-year, and 5-year OS, with the area under the receiving operating characteristic curve being 0.8486, 0.7785, and 0.752, respectively. The calibration curves exhibited stable capabilities in both cohorts. The stratification of the Kaplan-Meier curve was significant (P < 0.001).Conclusion: The associated nomogram of the D-index demonstrated a powerful and accurate predictive ability for OS in patients with primary hepatocellular carcinoma.Keywords: primary hepatocellular carcinoma, resection, D-index, nomogram, prognosis

Pengtao Sun,1,* Chunzhi Fan,2,* Rengui Wang,1 Tongwei Chu,3 Xiaoli Sun,1 Dongxue Zhang,4 Xuechao Du5 1Department of Radiology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of China; 2Department of Ultrasound Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China; 3Department of Ultrasound, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of China; 4Department of Endocrinology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of China; 5Department of Radiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100043, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xuechao DuDepartment of Radiology, Beijing Chaoyang Hospital, Capital Medical University, 5 Jingyuan Road, Shijingshan District, Beijing, 100043, People’s Republic of ChinaTel +86 13552588221Email duxuechao@ccmu.edu.cnObjective: To explore potential effects of pancreatic fat content measured by computed tomography (CT) on carotid plaque in patients with type 2 diabetes mellitus (T2DM).Methods: T2DM patients who underwent an un-enhanced CT scan of the upper abdomen and ultrasound of the carotid artery were enrolled. The patients were divided into a non-plaque group and a plaque group (including hypoechoic plaque subgroup and non-hypoechoic plaque subgroup). The CT attenuation of pancreas and spleen were measured. Pancreas-to-spleen attenuation ratio (P/S) and the difference between pancreatic and splenic attenuation (P-S) were calculated. The cutoff values of P/S and P-S were obtained using receiver operating characteristic curves. Logistic regression models were used to evaluate association of P/S or P-S with carotid plaque or hypoechoic plaque.Results: 337 patients were enrolled, including 101 cases in the non-plaque group, 146 cases in the hypoechoic plaque subgroup, and 90 cases in the non-hypoechoic plaque subgroup. P/S and P-S in hypoechoic plaque group were lower than those in non-plaque group, with a cutoff value of P/S and P-S as 0.72 and − 13.33, respectively. After adjusting for risk factors, P/S and P-S correlated with carotid plaque [for low P/S: OR (95% CI): 3.15 (1.47– 6.73), P = 0.0031; for low P-S: OR (95% CI): 2.84 (1.42– 5.66), P = 0.0031] as well as carotid hypoechoic plaque [for low P/S: OR (95% CI): 1.82 (1.07– 3.08), P = 0.0259; for low P-S: OR (95% CI): 1.82 (1.09– 3.02), P = 0.021].Conclusion: T2DM patients with hypoechoic carotid plaque have higher pancreatic fat content than those without. Pancreatic steatosis correlates with carotid plaque and hypoechoic plaque in T2DM patients.Keywords: atherosclerosis, computed tomography, diabetes mellitus, pancreatic steatosis

Xingran Du,1,* Jianpeng Xue,2,* Mingzi Jiang,3 Shaoqing Lin,4 Yuzhen Huang,4 Kaili Deng,5 Lei Shu,5 Hanmei Xu,2 Zeqing Li,2 Jing Yao,4 Sixia Chen,4 Ziyan Shen,4 Ganzhu Feng4 1Department of Infectious Disease, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2State Key Laboratory of Natural Medicines, The Engineering Research Center of Synthetic Polypeptide Discovery and Evaluation of Jiangsu Province, China Pharmaceutical University, Nanjing, Jiangsu, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, The First People’s Hospital of Kunshan, Suzhou, Jiangsu, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 5Department of Respiratory Medicine, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ganzhu FengDepartment of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of ChinaTel +86-025-58509837Fax +86-025-58509994Email zhu1635253@163.comBackground: The development of vaccines is a promising and cost-effective strategy to prevent emerging multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) infections. The purpose of this study was to prepare a multiepitope peptide nanovaccine and evaluate its immunogenicity and protective effect in BALB/c mice.Methods: The B-cell and T-cell epitopes of Omp22 from A. baumannii were predicted using bioinformatics methods and identified by immunological experiments. The optimal epitopes were conjugated in series by 6-aminocaproic acid and chemically synthesized multiepitope polypeptide rOmp22. Then, rOmp22 was encapsulated by chitosan (CS) and poly (lactic-co-glycolic) acid (PLGA) to prepare CS-PLGA-rOmp22 nanoparticles (NPs). The immunogenicity and immunoprotective efficacy of the vaccine were evaluated in BALB/c mice.Results: CS-PLGA-rOmp22 NPs were small (mean size of 272.83 nm) with apparently spherical structures, positively charged (4.39 mV) and nontoxic to A549 cells. A high encapsulation efficiency (54.94%) and a continuous slow release pattern were achieved. Compared with nonencapsulated rOmp22, CS-PLGA-rOmp22 immunized BALB/c mice induced higher levels of rOmp22-specific IgG in serum and IFN-γ in splenocyte supernatant. Additionally, lung injury and bacterial burdens in the lung and blood were suppressed, and potent protection (57.14%-83.3%) against acute lethal intratracheal A. baumannii challenge was observed in BALB/c mice vaccinated with CS-PLGA-rOmp22.Conclusion: CS-PLGA-rOmp22 NPs elicited specific IgG antibodies, Th1 cellular immunity and protection against acute lethal intratracheal A. baumannii challenge. Our results indicate that this nanovaccine is a desirable candidate for preventing A. baumannii infection.Keywords: A. baumannii, epitope vaccine, polymeric nanoparticles, PLGA, chitosan

Roushan Liu,1,* Jian Zhang,2,* Xiaoli Du,3 Yingying Lv,1 Xiangyu Gao,1 Yanyan Wang,1 Junrui Wang1 1Department of Laboratory Medicine, Affiliated Hospital of Inner Mongolian Medical University, Hohhot, 010050, People’s Republic of China; 2Department of Laboratory Medicine, Bayannur People’s Hospital, Bayannur City, 015000, People’s Republic of China; 3National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, People’s Republic of China*These authors contributed equally to this workCorrespondence: Junrui WangDepartment of Laboratory Medicine, Affiliated Hospital of Inner Mongolian Medical University, Hohhot, 010050, People’s Republic of ChinaTel +86 13347104892Email wangjunrui123@yeah.netPurpose: This study investigates the phenotypic and genotypic resistance features of OS-MRSA clinical isolates and their distinctive sensitivities to oxacillin.Methods: 1200 clinical isolates of Staphylococcus aureus were enrolled in this study. Automated antibiotics susceptibility tests on VITEK-2 and BD Phoenix-100TM, cefoxitin disc diffusion method, oxacillin broth microdilution method, mecA, and mecC gene detection were performed to identify OS-MRSA. MLST, PFGE, SCCmec, and spa typing methods were employed to determine genotypes of OS-MRSA isolates. Heterogeneous resistance of OS-MRSA isolates was detected using the population analysis profiling method, and PBP2a latex agglutination assay was used to detect the expression of PBP2a protein for 14 OS-MRSA isolates and their highly resistant subpopulations.Results: A total of 14 OS-MRSA isolates (1.17%, 14/1200) were identified, and all of the isolates were confirmed to be positive with the mecA gene and negative with the mecC gene. All of the 14 OS-MRSA isolates were identified as MSSA by VITEK-2, BD Phonenix-100, and oxacillin broth microdilution methods, while 21.43% (3/14) isolates were determined to be MRSA by the cefoxitin disk diffusion method. Genotypes of the 14 OS-MRSA isolates were diverse, and no dominant clones were identified. The prevalence of pvl gene among 14 OS-MRSA isolates was high up to 64.29% (9/14). All of the isolates showed heterogeneous resistance to oxacillin, while frequencies of the oxacillin-resistant subpopulations ranged from 10− 9 to 10− 5 and differed significantly among different isolates.Conclusion: The overall prevalence of OS-MRSA was relatively lower, but lower oxacillin MICs, low testing sensitivity of routine antibiotics susceptibility testing methods and weak PBP2a protein expression were observed in this study. 14 OS-MRSA showed diverse genotypes and universal heterogeneous resistance, and inaccurate laboratory identification and improper antimicrobial usage may promote the induction of highly resistant subpopulations and lead to treatment failure.Keywords: oxacillin sensitive MRSA, molecular typing, heterogeneous resistance

Dongdong Yin,1,2,* Yanfeng Lin,1,3,* Zhonghong Li,1,4,* Hui Ma,5,* Lanfen Lu,6 Kaiying Wang,1,3 Lang Yang,1,3 Xinying Du,1 Peng Li,1 Kezong Qi,2 Hongbin Song1,* 1Center for Disease Control and Prevention of PLA, Beijing, People’s Republic of China; 2Anhui Province Key Laboratory of Veterinary Pathobiology and Disease Control College of Animal Science and Technology, Anhui Agricultural University, Hefei, People’s Republic of China; 3Institute for Disease Control and Prevention, AMMS, Beijing, People’s Republic of China; 4College of Environmental and Chemical Engineering, Nanchang Hangkong University, Nanchang, People’s Republic of China; 5The Sixth Medical Center of PLA General Hospital, Beijing, People’s Republic of China; 6Department of Laboratory Diagnosis, Sun Yat-Sen University Affiliated Zhongshan Hospital, Zhongshan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peng Li; Kezong Qi Email jiekenlee@126.com; qkz@ahau.edu.cnBackground: A carbapenem-resistant Escherichia coli (sequence type 5415) strain was isolated from a male patient through routine surveillance in 2018 in Guangzhou, China.Materials and Methods: Bacteria were isolated from a sputum culture and identified by using the Vitek 2 compact system. The blaNDM-5 gene was amplified and confirmed by sequencing. Antimicrobial susceptibility testing was determined by a Vitek 2 compact system. The blaNDM-5 gene was located by Southern blotting. Whole-genome sequencing was carried out using both Illumina MiSeq and Oxford Nanopore MinION.Results: S1-PFGE and Southern blotting showed that the blaNDM-5 gene was located on a novel 66-kb IncFII [F2:A-:B-] plasmid. Conjugation assays revealed that the blaNDM-5-bearing plasmid was self-transferrable. Genomic sequencing and comparative analysis suggested that plasmid p2947-NDM5 likely originated from a combination of an IncFII-type backbone and the blaNDM-5 flanking genetic elements.Conclusion: This is the first report of an ST5414 E. coli strain expressing an NDM-5 β-lactamase. This study highlights the genetic complexity of blaNDM-5 carrying plasmids and the urgent need for continuous active monitoring.Keywords: Escherichia coli, ST5415, NDM-5, IncFII, carbapenem resistant

Yan Qin,1,* Shiyu Jiang,1,* Peng Liu,1 Jianliang Yang,1 Sheng Yang,1 Xiaohui He,1 Shengyu Zhou,1 Lin Gui,1 Jing Lin,2 Xinhua Du,3 Yuting Yi,3 Yan Sun,1 Yuankai Shi1 1Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, People’s Republic of China; 2Burning Rock Biotech, Guangzhou, Mainland China; 3Geneplus Beijing, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuankai ShiDepartment of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021, People’s Republic of ChinaTel +86 10 8778-8293Fax +86 10 8777-8781Email syuankai@cicams.ac.cnBackground/Aim: TP53 mutation is recognized as a negative prognostic factor for patients with diffuse large B-cell lymphoma (DLBCL). Here, we present the characteristics of TP53mut DLBCL patients following investigation of the effect of a treatment approach on survival of TP53mut DLBCL patients.Methods: A total of 44 DLBCL patients with TP53mut and treated with an R-CHOP regimen were included for analysis. Patients who failed to achieve a complete response (CR) to initial treatment or relapsed in the first 6 months after initial CR were deemed to have primary refractory disease.Results: Among 44 patients harboring TP53 mutations who underwent upfront R-CHOP or R-CHOP–like treatment, 21 (47.7%) had limited-stage and 23 (52.3%) presented advanced-stage disease. Apart from the seven patients receiving upfront surgical resection, 37 had measurable disease under the R-CHOP regimen, with 59.1% (n=26) developing primary refractory disease. Seven limited-stage patients after early complete resection and one with residue resection remained event-free at median follow-up of 37 months. Multivariate analysis revealed that elevated baseline lactate dehydrogenase (LDH), extranodal involvement (two or more), Ann Arbor stage, and locoregional treatment (surgery or radiation therapy) were independent indicators for progression-free survival (PFS). After adjustment for baseline LDH and extranodal involvement, adding locoregional treatment including surgery and radiation to the R-CHOP regimen significantly improved PFS (p=0.008) and overall survival (p=0.017) in limited-stage TP53mut DLBCL patients compared to R-CHOP–only treatment.Conclusion: This study presents the characteristics of TP53-mutated DLBCL and implies a potential benefit of locoregional treatment in limited-stage DLBCL patients with TP53 mutations.Keywords: diffuse large B-cell lymphoma, TP53, surgery, survival, clinical benefit

Sufang Xue,1,* Yi Yang,1,* Pengyu Li,2 Ping Liu,3 Xiangying Du,2 Xin Ma1 1Neurology Department of Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Radiology Department of Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Neurology Department of Hejian People’s Hospital, Cangzhou, Hebei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xin MaNeurology Department of Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China, Tel +86-135-0139-0691Email maxin118@hotmail.comObjective: Vertebral artery dissection (VAD) combined with congenital craniovertebral junction malformation (CVJM) is rare. This study aimed to analyze the etiology, clinical and imaging features, treatment, and prognosis of VAD with CVJM.Methods: Four new cases of VAD with congenital CVJM and 28 similar cases found in the literature were included. Detailed clinical data from all cases were retrospectively analyzed.Results: A total of 32 patients (28 men, four women; mean age 19.01± 12.53 years) were included. Seventeen of 32 cases (53.1%) had had multiple ischemic episodes. The most common neurological symptoms were limb numbness/weakness (20/32), ataxia (15/32), and dizziness/vertigo (12/32). In sum, 31 of 32 cases had multiple infarcts scattered throughout the posterior circulation area on cranial computed tomography or resonance imaging. Dissection had occurred in the V3 segment of the VA in 29/31 cases (93.5%). The most common congenital CVJMs were atlantoaxial dislocation and atlantoaxial subluxation (found in 20/32 cases [62.5%]), while 27/32 cases (84.3%) had multiple combined abnormalities. Seven of eleven cases (63.6%) with initial antiplatelet treatment and one of eleven (9.1%) with initial anticoagulation treatment experienced stoke recurrence. Fusion or vertebral fixation was performed in 16 patients and aneurysm resection in one patient. There was no reported recurrence after surgery in 13 patients with follow-up data.Conclusion: Underlying CVJM is a rare but overlooked etiology in VAD, and is prone to induce recurrent ischemic stroke. Patients with VAD, especially that localized in the V3 segment, should be examined for CVJM. Timely assessment is critical for determining the specific cause and to provide targeted intervention.Keywords: vertebral artery dissection, craniovertebral junction malformation, clinical and imaging features, treatment, prognosis