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Yuhao Zhao,&ast; Shun Zhao,&ast; Yuchen Shi, Qin Ma, Ze Zheng, Ping Wang, Jinghua Liu Center for Coronary Artery Disease (CCAD), Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ping Wang; Jinghua Liu, Email wang_ping@vip.sina.com; liujinghua@vip.sina.comBackground: There is limited research on the long-term prognosis of percutaneous coronary intervention (PCI) in coronary chronic total occlusion (CTO) patients who have previously undergone coronary artery bypass grafting (CABG). Additionally, the prognostic value of a novel systemic immune inflammation index (SII) in this specific patient population remains unclear.Methods: To adjust for differences in baseline features and minimize bias, 335 pairs of patients with or without prior CABG undergone PCI were obtained after probability score matching (PSM) in a single-center cohort. The clinical characteristics were collected, and the primary outcomes were major cardiovascular events (MACE), which included all-cause death, nonfatal MI and unplanned revascularization, were recorded during the follow-up period after discharge. The group with prior CABG were divided according to the median level of SII: Lower SII group (SII ≤ 570.10, N = 167) and higher SII group (SII ≥ 570.10, N = 168).Results: The SII values were significantly higher in the prior CABG group than in the without prior CABG group [570.10 (444.60, 814.12) vs 519.65 (446.86, 565.84), P < 0.001, respectively]. The survival Kaplan–Meier analysis showed that patients with prior CABG was significantly associated with a higher risk of MACE than patients without prior CABG (P = 0.016) in the long-term follow-up. As SII levels increased, the cumulative risk of MACE became significantly higher in the patients with prior CABG (P = 0.023) stratified by the median value of SII. The Cox proportional hazards regression model analysis indicated that the level of SII (hazard ratio = 2.035, 95% CI, 1.103– 3.753, P = 0.023) emerged as independent predictors of MACE. The restricted cubic spline (RCS) analysis illustrated that the HR for MACE increased with increasing SII.Conclusion: SII is a reliable predictor of long-term cardiovascular events after PCI in CTO patients with prior CABG, suggesting that SII may be helpful in identifying high-risk patients who need more aggressive treatment and follow‐up strategies.Keywords: systemic immune inflammation index, coronary chronic total occlusion, coronary artery bypass grafting, percutaneous coronary intervention, major adverse cardiovascular events

Rong Yang,1,&ast; Qing Ma,1,2,&ast; Xiaolin Zhang,3 Qian Zhao,1,4,5 Suilan Zeng,6 Hechun Yan,7 Yi Lei,1,5 Shanye Yi,1 Xin Chen,8 Nianxi Wu9 1General Practice Ward/International Medical Center Ward, General Practice Medical Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2West China School of Nursing, Sichuan University, Chengdu, People’s Republic of China; 3Preventive Health Section, Dayi County Shaqu Street Community Health Service Center, Chengdu, People’s Republic of China; 4Teaching & Research Section, General Practice Medical Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 5General Practice Medical Center and General Practice Research Institute, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 6Guan Ge Center Health Center, Guangan, People’s Republic of China; 7Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, People’s Republic of China; 8Big Buddha Street Community Health Service Center, Leshan, People’s Republic of China; 9Chongqing Magic MedTech Co., Ltd., Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qian Zhao, Email 27355151@qq.comPurpose: Osteoporosis is a major health concern among the elderly, underscoring the importance of investigating its prevalence across different geographical regions. There is a current research gap regarding the incidence of osteoporosis and its variation by altitude within Sichuan, China. This study aimed to assess the prevalence of osteoporosis among populations residing at different altitudes in western Sichuan Province.Basic Procedures: This study utilized data from a population-based cohort in Sichuan, China. Representative locations were selected, and cluster random sampling was employed to conduct cohort studies across multiple sites in southwestern China. T Baseline data were collected from populations in Mianzhu, Kangting, and Sertar between July 2020 and August 2021. To assess differences in osteoporosis incidence among populations at different altitudes and with varying characteristics, we applied Chi-square and rank-sum tests.Main Findings: The study involved 4074 participants, including 1404 males (34.46%) and 791 individuals diagnosed with osteoporosis (19.42%). The prevalence of osteopenia in mid-altitude and high-altitude regions was 20.05% and 16.28%, respectively, while the prevalence of osteoporosis was significantly different, at 25.85% in mid-altitude areas compared to 13.00% in high-altitude areas (P < 0.001). Further analysis identified statistically significant differences in the prevalence of osteopenia and osteoporosis among females (P< 0.001), middle-aged (P=0.015) and elderly populations (P=0.038), as well as among individuals who were underweight (P=0.011), normal weight (P< 0.001), overweight (P< 0.001), and obese (P=0.038). As altitude increased, the prevalence of osteoporosis decreased in all groups except the elderly, while the prevalence of osteopenia decreased among women and across various BMI categories, but increased among middle-aged and elderly individuals. Additionally, in high-altitude regions, Kangting recorded an 18.10% prevalence of osteopenia and a 14.26% prevalence of osteoporosis, compared to Sertar, which exhibited a 6.54% prevalence of osteopenia and a 6.23% prevalence of osteoporosis, indicating significant differences (P< 0.001).Conclusion: This study demonstrates that higher altitudes are associated with a decreased prevalence of osteopenia and osteoporosis, particularly among females and middle-aged individuals. These results emphasize the importance of developing region-specific osteoporosis prevention strategies.Keywords: osteoporosis, aging, prevalence, altitude, Sichuan province

Guangzan Yu, Lulu Liu, Qian Ma, Fusheng Han, Hua He Cardiac Division of Emergency Intensive Care Unit, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, People’s Republic of ChinaCorrespondence: Hua He, Email hehua430@163.comBackground: A large number of studies have demonstrated links between chronic obstructive pulmonary disease (COPD) and cardiovascular diseases (CVDs). However, the causal relationship between COPD and CVDs and the reverse causality remains divergent.Methods: Exposure and outcome data from the largest available genome-wide association studies were extracted for Mendelian randomization (MR) studies. Univariate MR analysis was performed using IVW as the primary analysis method, and multiple sensitivity analyses were used to enhance the robustness of the results. Furthermore, this was followed by mediation MR analysis of positive results after excluding confounding factors with multivariable MR analysis.Results: The MR estimation based on IVW method indicated a strong association between genetically determined COPD and heart failure (HF) (OR = 1.117, 95% CI: 1.066– 1.170, p < 0.001), coronary heart disease (CHD) (OR = 1.004, 95% CI: 1.002– 1.006, p < 0.001), essential hypertension (EH) (OR = 1.009, 95% CI: 1.005– 1.013, p < 0.001) as well as Stroke (OR = 1.003, 95% CI: 1.001– 1.004, p < 0.001). The results of multivariable MR analysis revealed that COPD is not significantly associated with CHD after adjusting for IL-6, LDL, or total cholesterol (p> 0.05). Our findings indicated that BMI, smoking initiation, smoking status, obesity, and FEV1 played a role in the causal effect of COPD on HF, EH, and Stroke.Conclusion: We found positive causal relationships between COPD and HF, EH, and Stroke essentially unaffected by other confounding factors. The causal relationship exhibited between COPD and CHD was influenced by confounding factors. BMI, obesity, initiation of smoking, smoking status, and FEV1 were the mediators between COPD and CVDs.Keywords: chronic obstructive pulmonary disease, cardiovascular diseases, Mendelian randomization

Xiaoqing Liu,1,2 Qiaoqiao Ma,1 Jianfei Li,1 Zijun Huang,3 Xin Tong,2 Ting Wang,2 Hualong Qin,2 Wenjie Sui,2 Jing Luo2 1School of Nursing, Suzhou Medical College of Soochow University, Suzhou, People’s Republic of China; 2Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 3School of Computer Science and Technology, Soochow University, Suzhou, People’s Republic of ChinaCorrespondence: Jing Luo, Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Gusu District, Suzhou, Jiangsu, 215006, People’s Republic of China, Email luobojenny@163.comBackground: Rapid recovery after lung cancer surgery is challenging. Exercise is a low-cost, effective method to expedite recovery. Despite numerous exercise interventions, many fail to consider patient perspectives, leading to low adherence and short-term effects. Understanding lung cancer patients’ perspectives on postoperative exercise and exploring their exercise-related concerns and needs are crucial for enhancing the effectiveness of exercise-based rehabilitation programs.Objective: This study aims to analyze lung cancer patients’ perspectives on postoperative exercise in their daily lives, exploring their concerns and needs related to postoperative exercise to help healthcare professionals develop personalized exercise plans.Methods: An internet crawling technique collected online inquiries from Baidu webpages about postoperative physical activity in lung cancer patients, using “lung cancer”, “surgery”, and ”exercise” as keywords. The data was encoded, categorized, and analyzed using a large-scale semantic analysis platform in natural language processing and information retrieval to examine term frequency, sentiment tendencies, and attributes in the inquiry texts.Results: Initially, 2727 queries were retrieved; after screening, deduplication, and cleansing, 201 unique queries were identified. Queries related to “modes of exercise” constituted the largest proportion. The most frequently occurring words in the word frequency analysis were “lung”, “ cancer”, “should”, “can”, “long”, “early”, and “surgery”, “exercise”, “respiratory”. Postoperative lung cancer patients demonstrate significant interest in whether they should engage in exercise, as well as in the appropriate types and duration of such activities, indicating a strong need for detailed guidance and knowledge related to exercise. The sentiment analysis showed a positive score of 87.5% and a negative score of 12.5%, indicating that postoperative lung cancer patients view exercise positively and have an enthusiastic attitude towards it. Among the positive sentiment attributes, “good” was the most frequently mentioned term, whereas “bad” and “surprising” were the most prevalent terms within the negative sentiment attributes.Conclusion: Postoperative physical activity receives limited attention from lung cancer patients, who emphasize their preferences for exercise modalities. Their inquiries often reflect psychological concerns, such as fear and helplessness caused by symptoms. Understanding patients’ perspectives on postoperative physical activity within their real-life contexts can help integrate psychological support into exercise plans. This integration could guide healthcare professionals in developing more personalized postoperative exercise regimens for lung cancer patients.Keywords: lung cancer, surgery, exercise, web crawling technology, needs, concern

Qingqing Ma,1,2,&ast; Guoju Luo,1,&ast; Fei Wang,1,&ast; Haolong Li,1 Xiaomeng Li,1,3 Yongmei Liu,1 Zhan Li,1 Ye Guo,1 Yongzhe Li1 1Department of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Medical Laboratory Innovation Unit, Chinese Academy of Medical Sciences, Shenyang, People’s Republic of China; 3Department of Clinical Laboratory, Peking University People’s Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ye Guo; Yongzhe Li, Department of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1 Shuai-Fu-Yuan, Dongcheng District, Beijing, 100730, People’s Republic of China, Email 4227582@163.com; yongzhelipumch@126.comPurpose: This study investigated potential predictive models associated with natural killer (NK) cell mitochondrial membrane potential (MMP or ΔΨm) in predicting death among critically ill patients with COVID-19.Patients and Methods: We included 97 patients with COVID-19 of different severities attending Peking Union Medical College Hospital from December 2022 to January 2023. Patients were divided into three groups according to oxygen and mechanical ventilation use during specimen collection and were followed for survival and death at 3 months. The lymphocyte subpopulation MMP was detected via flow cytometry. We constructed a joint diagnostic model by integrating identified key indicators and generating receiver operating curves (ROCs) and evaluated its predictive performance for mortality risk in critically ill patients.Results: The NK-cell MMP median fluorescence intensity (MFI) was significantly lower in critically ill patients who died from COVID-19 (p< 0.0001) and significantly and positively correlated with D-dimer content in critically ill patients (r=0.56, p=0.0023). The random forest model suggested that fibrinogen levels and NK-cell MMP MFI were the most important indicators. Integrating the above predictive models for the ROC yielded an area under the curve of 0.94.Conclusion: This study revealed the potential of combining NK-cell MMP with key clinical indicators (D-dimer and fibrinogen levels) to predict death among critically ill patients with COVID-19, which may help in early risk stratification of critically ill patients and improve patient care and clinical outcomes.Keywords: COVID-19, mortality prediction, NK cell, mitochondrial membrane potential, fibrinogen, D-dimer

Ying Lan,1 Die Hu,1 Shijing Huang,1 Qing Ma,1 Li Chen,2,3 Min Xu,1 Qin He1 1Department of Pharmacy, Affiliated Hospital of Southwest Jiaotong University, The Third People’s Hospital of Chengdu, Chengdu, Sichuan, 610031, People’s Republic of China; 2Department of Pharmacology, Faculty of Medicine, University of the Basque Country, UPV/EHU, Leioa, Spain; 3Department of Pharmacy and Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Ying Lan; Li Chen, Email lanying0212@126.com; chenl_hxey@scu.edu.cnPurpose: This study conducted a pharmacovigilance analysis based on the FDA Adverse Event Reporting System (FAERS) database to compare the infection risk of inhaled or nasal Beclomethasone, Fluticasone, Budesonide, Ciclesonide, Mometasone, and Triamcinolone Acetonide.Methods: We used proportional imbalance analysis to evaluate the correlation between ICS /INCs and infection events. The data was extracted from the FAERS database from April 2015 to September 2023. Further analysis was conducted on the clinical characteristics, site of infection, and pathogenic bacteria of ICS and INCs infection adverse events (AEs). We used bubble charts to display their top 5 infection adverse events.Results: We analyzed 21,837 reports of infection AEs related to ICS and INCs, with an average age of 62.12 years. Among them, 61.14% of infection reports were related to females. One-third of infections reported to occur in the lower respiratory tract with Fluticasone, Budesonide, Ciclesonidec, and Mometasone; over 40% of infections reported by Triamcinolone Acetonide were eye infections; the rate of oral infections caused by Beclomethasone were 7.39%. The reported rates of fungal and viral infections caused by beclomethasone were 21.15% and 19.2%, respectively. The mycobacterial infections caused by Budesonide and Ciclesonidec account for 3.29% and 2.03%, respectively. Bubble plots showed that the ICS group had more fungal infections, oral infections, pneumonia, tracheitis, etc. The INCs group had more eye symptoms, rhinitis, sinusitis, nasopharyngitis, etc.Conclusion: Women who use ICS and INCs are more prone to infection events. Compared to Budesonide, Fluticasone seemed to have a higher risk of pneumonia and oral candidiasis. Mometasone might lead to more upper respiratory tract infections. The risk of oral infection was higher with Beclomethasone. Beclomethasone causes more fungal and viral infections, while Ciclesonide and Budesonide are more susceptible to mycobacterial infections.Keywords: data mining, FAERS, ICS, INCs, pharmacovigilance, infections

Yanling Li,&ast; Li Ji,&ast; Tian Liu, Guang Xu, Kaihe Wang, Leixin Mu, Yuying Guo, Qun Ma School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qun Ma, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China, Email maqun99@126.comBackground: Qiguiyin decoction (QGYD) is a traditional Chinese medicine (TCM) and its combined application with levofloxacin (LVFX) has been confirmed effective in the clinical treatment of multidrug-resistant Pseudomonas aeruginosa (MDR PA) infection. This study investigated the therapeutic effect and possible mechanism of QGYD in sensitizing LVFX against MDR PA infection.Materials and Methods: Pulmonary infections were induced in rats by MDR PA. The changes in pharmacokinetics-pharmacodynamics (PK-PD) parameters of LVFX after combined with QGYD were investigated in MDR PA-induced rats. Subsequently, the correlation between PK and PD was analyzed and PK-PD models were established to elucidate the relationship between QGYD-induced alterations in LVFX metabolism and its sensitization to LVFX. Antibody chip technology was used to detect the levels of inflammatory factors, suggesting the relationship between the beneficial effect of immune regulation and the sensitization of QGYD.Results: QGYD significantly enhanced the therapeutic efficacy of LVFX against MDR PA infection. The combination of QGYD changed the PK parameters of LVFX such as Tmax, t1/2, MRT, Vd/F, CL/F and PD parameters such as MIC, AUC0-24h/MIC. Predicted results from PK-PD models demonstrated that the antibacterial effect of LVFX was significantly enhanced with the combination of QGYD, consistent with experimental findings. Antibody chip results revealed that the combination of QGYD made IL-1 β, IL-6, TNF- α, IL-10, and MCP-1 levels more akin to those of the blank group.Conclusion: These findings indicated that QGYD could change the PK-PD behaviors of LVFX and help the body restore immune balance faster. This implied that a potential drug interaction might occur between QGYD and LVFX, leading to improved clinical efficacy when combined.Keywords: multidrug-resistant Pseudomonas aeruginosa infection, combination therapy, PK/PD model, Qiguiyin decoction, levofloxacin

Lili Zhang,1– 3 Yunshu Zhang,2,3 Wentao Guo,2,3 Qi Ma,1,4 Feng Zhang,2,3 Keqing Li,2,3 Qizhong Yi1,4 1The First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 2Hebei Provincial Mental Health Center, Baoding, Hebei Province, People’s Republic of China; 3Hebei Key Laboratory of Major Mental and Behavioural Disorders, Baoding, Hebei Province, People’s Republic of China; 4Xinjiang Clinical Research Center for Mental (Psychological) Disorder, Urumqi, People’s Republic of ChinaCorrespondence: Qizhong Yi, The First Affiliated Hospital of Xinjiang Medical University, No. 137, Liyushan Road, Urumqi, 830054, People’s Republic of China, Tel +86 13079911689, Email qizhongyi@126.com Keqing Li, Hebei Provincial Mental Health Center, No. 572, Dongfeng East Road, Baoding City, Hebei Province, 071000, People’s Republic of China, Tel +86 13703288007, Email like2125@sina.comPurpose: Depressive disorder is a mental health disorder with complicated etiopathogenesis. Environmental stress and neurodevelopment combined with other factors contribute to the occurrence of depression. Especially for the depressive disorder with chronic negative stress, it has characteristics of recurrence and poor curative effect because of unclear mechanism. Here, we investigated the hippocampal structures and functional connectivity (FC) according to resting-state functional magnetic resonance imaging in patients with depression who underwent chronic negative stress.Patients and Methods: A total of 65 patients with depression (34 underwent chronic negative stress and 31 non-underwent chronic negative stress) and 30 healthy controls who did not undergo chronic negative stress were included in the study. The volumes of hippocampal subfields, seed-based FCs between hippocampus and the whole brain voxels, and ROI-wise-based FC between hippocampal subfields were compared among the three groups.Results: In the patients with depression who underwent chronic negative stress, the volumes of right_GC-ML-DG-head, right_CA4-head and right_CA3-head increased, FCs between Temporal_Mid_R, Precuneus_R, Frontal_Sup_R, Temporal_Sup_R, Angular_L, Frontal_Inf_Tri_R, Supp_Motor_Area_R, Precentral_L and hippocampus increased, and FCs between parasubiculum and CA3, and presubiculum and CA1 decreased. When compared to the patients who did not undergo chronic negative stress, the patients who underwent chronic negative stress had larger volumes of right_GC-ML-DG-head and right_CA3-head, higher FCs between Frontal_Sup_R, Frontal_Inf_Tri_R and hippocampus, and lower FCs between presubiculum and CA1.Conclusion: The depression underwent chronic negative stress may experience disrupted hippocampal structures and functional connectivity. It may be one of potential depressive disorder subtypes.Keywords: depressive disorder, chronic stress, hippocampus, functional connectivity

Qin Ma,1 Yao-Bang Liu,2 Tong She,3 Xin-Lan Liu4 1Department of Radiation Oncology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 2Department of Surgical Oncology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 3Hospital of Zhongwei, Zhongwei, People’s Republic of China; 4Department of Medical Oncology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of ChinaCorrespondence: Xin-Lan Liu, Tel +8613709577339, Email nxliuxinlan@126.comObjective: This study determined the cut-off value of Ki-67 expression and discussed the interaction between Ki-67 and histological grade, further explored the prognostic role of Ki-67 in hormone receptor-positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer;.Materials and Methods: We assessed the Ki-67 expression of 956 patients with HR+/HER2 breast cancer diagnosed in the General Hospital of Ningxia Medical University from 2015 to 2019 by immunohistochemistry (IHC), The disease-free survival (DFS) was defined as the time from postoperative to the first local recurrence, distant metastasis or death of the disease. The follow-up by means of inpatient or outpatient medical records and telephone.Results: 22.5% was used as the cut-off for low/high Ki-67 expression in HR+/HER2- breast cancer. Compared with the value of 14%, which is commonly used in clinic at present, the consistency of the two values is moderate (Kappa = 0.484, P< 0.001). The expression of Ki-67 was increased with the grade. (Median: G1:10%; G2:20%; G3:40%. Mean: G1:13%; G2:23%; G3:39%, P < 0.001). Survival analysis was based on all patients for a median of 51 months (24– 89 months), 63 cases had recurrence or metastasis during the follow-up, which 21 cases had low expression of Ki-67 and 42 cases had high expression. The patients with Ki-67 ≥ 22.5% had a 2.969 higher risk of early recurrence and metastasis than the patients with Ki-67 < 22.5%. There were 4 cases of local recurrence, 7 cases of regional lymph node metastasis, and 52 cases of distant metastasis in all patients, the common distant metastases were bone, liver, and lung, and rare metastases were adrenal gland, bone marrow, and pericardium.Conclusion: In HR+/HER2- breast cancer, patients with Ki-67 > 22.5% have a worse prognosis and are more likely to have early recurrence and metastasis.Keywords: Ki-67, breast cancer, cut-off value, histological grade, recurrence and metastasis

Yan Zhang,1,&ast; Qiongyao Yang,2– 4,&ast; Qianru Ma,5,&ast; Yuanxiong Wu,5,&ast; Yue Wang,2– 4 Chuanchuan Chen,2– 4 Yitan Yao,2– 4 Ziqiao Feng,2,3 Xiaoping Yuan,2,3 Shengya Shi,2,3 Kai Zhang2,3 1Department of Pneumology, Second People’s Hospital of Anhui Province, Hefei, People’s Republic of China; 2Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, People’s Republic of China; 3Anhui Psychiatric Center, Anhui Medical University, Hefei, People’s Republic of China; 4School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, People’s Republic of China; 5Department of Psychiatry, Third People’s Hospital of Fuyang, Fuyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kai Zhang, Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, 238000, People’s Republic of China, Tel/Fax +86-551-82324114, Email zhangkai@ahmu.edu.cnPurpose: Masks are designed to reduce the spread of airborne pathogens, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), although wearing a mask has some adverse effects. The primary objective of this study was to explore the effects of surgical masks and N95 respirators on patients diagnosed with anxiety.Methods: Subjects diagnosed with first-episode anxiety disorders were recruited from outpatient departments between February and July, 2023. A self-administered questionnaire was administered at baseline and at follow-up. The questionnaire addressed demographic information, Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Rating Scale (HAM-D) and Insomnia Severity Index (ISI). Subjects were divided into three groups (n=30 each): control (no mask); surgical mask; and N95 respirator. The Kruskal–Wallis test and repeated measures analysis of variance were used to examine associations between face mask use and emotion.Results: Ninety subjects completed the study, of whom 51 (56.67%) were male and 39 (43.33%) were female. Time and group effects were observed in HAM-A score among the 3 groups. After 4 weeks, mean (± SD) HAM-A score decreased from 32.63± 13.37 to 28.07± 9.33 in the control group, increased from 33.67± 12.47 to 36.80± 10.32 in the surgical mask group, and from 32.33± 14.73 to 41.13± 8.29 in the N95 respirator group, with no sex differences among the 3 groups. HAM-A score was significantly higher in the mask groups than that in the control group at follow-up. Only N95 respirator group exhibited significant time effects on HAM-D and ISI scores, with a decreasing trend in HAM-D score and an opposite trend in ISI score.Conclusion: Prolonged mask use may exacerbate anxiety, especially among those wearing N95 respirator masks. In a post-pandemic environment, governments should improve public health beliefs regarding coronavirus disease 2019 and promote the safety of face mask use, thus reducing the physiological and psychological effects of improper mask use.Keywords: anxiety, COVID-19, health beliefs, mask, N95

Longbin Zheng,1,&ast; Tao Fang,2,&ast; Wei Zhang,1 Xiaojing Zhang,1 Zhiqiang Ren,1 Weimin Qin,1 Wenbo Liang,1 Qing Ma,1 Ning Yin1 1Department of Anesthesiology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China; 2Department of Anesthesiology, Xinchang County People’s Hospital, Xinchang, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ning Yin, Department of Anesthesiology, Sir Run Run Hospital, Nanjing Medical University, No. 109 Longmian Avenue, Nanjing, Jiangsu Province, 211112, People’s Republic of China, Email yinning882000@126.comPurpose: Dexmedetomidine (Dex) is a potent and highly selective α 2-adrenergic receptor agonist. Within an appropriate dose range, Dex can effectively attenuate the surgical stress response, provide intraoperative hemodynamic stability, and improve the patient recovery quality. High-dose Dex can delay patient awakening from anesthesia and increase the incidence of bradycardia. This randomized controlled trial aimed to investigate the effects of low-dose intravenous Dex premedication in patients undergoing laparoscopic cholecystectomy (LC).Material and Methods: In total, 100 patients undergoing LC were equally randomized into Group C (premedication with saline) and Group D (premedication with 0.5 μg/kg Dex). The patients were premedicated with saline or Dex, depending on the group, before anesthesia induction. Following this, anesthesia induction and endotracheal intubation was performed, and anesthesia was maintained during surgery. Following the completion of the surgery, the patients were transferred the post-anesthesia care unit (PACU) and stayed there until they met the PACU discharge criteria. The hemodynamic parameters, consumption of anesthetics, surgical duration, postoperative awakening time, extubation time, postoperative pain, and complications were recorded.Results: No significant differences were observed in the heart rate (HR) and mean arterial pressure (MAP) between the two groups before premedication (P> 0.05). The MAP and HR immediately after endotracheal intubation and immediately after extubation were significantly lower in Group D than in Group C (P< 0.05 for both). The incidence of bradycardia was significantly higher in Group D than in Group C (P< 0.05), while atropine was used in neither group. Propofol and remifentanil consumption was significantly lower in Group D than in Group C (P< 0.05). The postoperative awakening and extubation times were significantly shorter in Group D than in Group C (P< 0.05). The postoperative visual analog scale scores for pain and incidence of nausea, vomiting, and cough were significantly lower in Group D than in Group C (P< 0.05 for all).Conclusion: Our data suggest that premedication with dexmedetomidine (0.5 μg/kg) before general anesthesia induction can effectively attenuate intraoperative stress response and postoperative pain, maintain perioperative hemodynamic stability, and decrease the incidence of adverse events, which might be an effective and safe anesthetic protocol during LC worthy of further clinical application.Keywords: dexmedetomidine, laparoscopic cholecystectomy, general anesthesia, premedication

Wenbo Wu,1,&ast; Xiaoli Yu,2,&ast; Jiaxiang Sun,3 Yuanyuan Han,3 Yuanye Ma,1 Guoqing Zhang,1 Qingming Ma,4 Qiang Li,3 Hongfei Xiang1 1Department of Orthopedics, the Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of China; 2Department of Anesthesiology, the Affiliated Hospital of Qingdao University, Qingdao, 266100, People’s Republic of China; 3College of Physics, Center for Marine Observation and Communications, Qingdao University, Qingdao, 266021, People’s Republic of China; 4Department of Pharmaceutics, School of Pharmacy, Qingdao University, Qingdao, 266021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongfei Xiang; Qingming Ma, Tel +86-532-61807860, Email xianghf@qdu.edu.cn; qma@qdu.edu.cnBackground: As a broad-spectrum antitumorigenic agent, doxorubicin (DOX) is commonly used as a chemotherapeutic drug for treating osteosarcoma (OS). Still, it is associated with significant cell toxicity and ineffective drug delivery, whereas the zeolite imidazolate framework is extensively applied in the biomedical field as a carrier owing to its favorable biocompatibility, high porosity, and pH-responsiveness. Therefore, we need to develop a drug delivery platform that can effectively increase the antitumorigenic effect of the loaded drug and concurrently minimize drug toxicity.Methods: In this study, a Fe3O4@ZIF-8 nanocomposite carrier was prepared with ZIF-8 as the shell and encapsulated with Fe3O4 by loading DOX to form DOX- Fe3O4@ZIF-8 (DFZ) drug-loaded magnetic nanoparticles. Then, we characterized and analyzed the morphology, particle size, and characteristics of Fe3O4@ZIF-8 and DFZ by TEM, SEM, and Malvern. Moreover, we examined the inhibitory effects of DFZ in vitro and in vivo. Meanwhile, we established a tumor-bearing mouse model, evaluating its tumor-targeting by external magnetic field guidance.Results: DFZ nanoparticles possessed have a size of ~110 nm, with an encapsulation rate of 21% and pH responsiveness. DFZ exerted a superior cytostatic effect and apoptosis rate on K7M2 cells in vitro compared to DOX(p< 0.01). In animal experiments, DFZ offers up to 67% tumor inhibition and has shown a superior ability to induce apoptosis than DOX alone in TUNEL results(p< 0.01). Tumor-targeting experiments have validated that DFZ can be effectively accumulated in the tumor tissue and enhance anticancer performance.Conclusion: In summary, the DFZ nano-delivery system exhibited a more substantial anti-tumorigenic effect as well as superior active tumor targeting of DOX- Fe3O4@ZIF-8 compared to that of DOX alone in terms of biocompatibility, drug loading capacity, pH-responsiveness, tumor-targeting, and anti-tumorigenic effect, indicating its chemotherapeutic application potential.Keywords: osteosarcoma chemotherapy, zeolite imidazolate framework, PH-responsive, nanocarriers, tumor targeting

Hui Gao,1,&ast; Nan Jiang,2,&ast; Qiannan Niu,3 Shenglin Mei,4,5 Håvard Jostein Haugen,6 Qianli Ma6,7 1Department of Stomatology, the Eighth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Department of Community Dentistry, Institute of Clinical Dentistry, University of Oslo, Oslo, Norway; 3State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi Province, People’s Republic of China; 4Xingrui Dental Clinic, Xi’an, Shaanxi Province, People’s Republic of China; 5Department of Physics & Materials Science, City University of Hong Kong, Hong Kong, People’s Republic of China; 6Department of Biomaterials, Institute of Clinical Dentistry, University of Oslo, Oslo, Norway; 7Department of Immunology, School of Basic Medicine, Fourth Military Medical University, Xi’an, Shaanxi Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Håvard Jostein Haugen; Qianli Ma, Department of Biomaterials, Institute of Clinical Dentistry, University of Oslo, Oslo, 0317, Norway, Email h.j.haugen@odont.uio.no; qianlima@odont.uio.noIntroduction: Titanium (Ti) and its alloys are widely utilized in endosseous implants. However, their clinical efficacy is marred by complications arising from bacterial infections owing to their inadequate antibacterial properties. Consequently, enhancing the antibacterial attributes of implant surfaces stands as a pivotal objective in the realm of implantable materials research.Methods: In this study, we employed sequential anodization and plasma immersion ion implantation (PIII) technology to fabricate a silver-embedded sparsely titania nanotube array (SNT) on the near-β titanium alloy Ti-5Zr-3Sn-5Mo-15Nb (TLM) implants. The surface characteristics, antimicrobial properties, biocompatibility, and osteogenic activity of the silver-nanomodified SNT implant (SNT Ag) surface, alongside peri-implant inflammatory responses, were meticulously assessed through a combination of in vitro and in vivo analyses.Results: Compared with polished TLM and SNT, the silver-embedded SNT (SNT Ag) surface retained the basic shape of nanotubes and stably released Ag+ at the ppm level for a long time, which demonstrated an effective inhibition and bactericidal activity against Staphylococcus aureus (SA) while maintaining ideal cytocompatibility. Additionally, the subtle modifications in nanotubular topography induced by silver implantation endowed SNT Ag with enhanced osteogenic activity and mitigated inflammatory capsulation in soft tissue peri-implants in a rat model.Conclusion: Incorporating a silver-embedded SNT array onto the implant surface demonstrated robust antibacterial properties, impeccable cytocompatibility, exceptional osteogenic activity, and the potential to prevent inflammatory encapsulation around the implant site. The Silver-PIII modification strategy emerges as a highly promising approach for surface applications in endosseous implants and trans-gingival implant abutments.Keywords: implant surface modification, silver PIII, anti-bacterial activity, cytocompatibility, osteogenic differentiation, host inflammatory response

Yifan Yang,1,&ast; Huayu Yang,1,&ast; Zongli Diao,2 Xu Liu,2 Lan Yao,1 Liyan Wang,2 Xiaotian Shi,1 Xu Li,1 Qing Ma1 1Department of Geriatrics, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Nephrology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qing Ma, Department of Geriatrics, Beijing Friendship Hospital, Capital Medical University, 95, Yong-an Road, Xicheng District, Beijing, 100050, People’s Republic of China, Tel +86 10 63137641, Fax +86 10 63138730, Email maqing3@163.comPurpose: Frailty is an important geriatric syndrome associated with aging and adverse events, especially in patients with severe infection. To help guide prognosis for elderly patients undergoing maintenance hemodialysis (MHD) who experience acute infection, this study investigated whether baseline (pre-infection) frailty may be associated with adverse outcomes in elderly patients undergoing MHD who suffer SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection.Patients and Methods: Patients (aged ≥ 60 y) receiving MHD had been assessed for overall frailty and the 5 frailty components based on the Fried Frailty Phenotype scale within 3 months prior to SARS-CoV-2 infection.Results: There were 59 and 98 patients in the frail and non-frail groups, respectively. Three months after SARS-CoV-2 infection, 21 (13.4%) and 45 (28.7%) patients had died or were in hospital. The multivariate COX proportional risk model suggested that the all-cause mortality rate in patients judged overall frail or with low activity was significantly higher compared with that of the non-frail (P = 0.049; 0.003). The multivariate logistic regression analysis showed that hospitalization 3 months after SARS-CoV-2 infection was associated with both overall frailty and low activity (OR 2.276, 95% CI: 1.034– 5.010, P = 0.041; OR 2.809, 95% CI: 1.311– 6.020, P = 0.008, respectively).Conclusion: Overall frailty and specifically low activity were significantly associated with all-cause mortality and hospitalization in this elderly MHD population after SARS-CoV-2 infection. Early assessment of frailty and effective interventions are recommended to improve the prognosis of patients receiving MHD who are at higher risk of acute infection.Keywords: SARS-CoV-2, COVID-19, hemodialysis, frailty, elderly, prognosis

Lingyan Qin,&ast; Qingwei Ma,&ast; Chunrong Zhang, Zuojie Lu, Luchao Liu, Zhihu Huang Department of Clinical Laboratory, Minzu Hospital of Guangxi Zhuang Autonomous Region, Affiliated Minzu Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhihu Huang, Department of Clinical Laboratory, Minzu Hospital of Guangxi Zhuang Autonomous Region, Affiliated Minzu Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530001, People’s Republic of China, Tel +86-0771-3112210, Fax +86-0771-863112210, Email hoftiger@126.comPurpose: This paper aims to study the relationship between lipoprotein-associated phospholipase A2 (Lp-PLA2) and GDM (gestational diabetes mellitus) by detecting Lp-PLA2 level and its gene polymorphism.Patients and Methods: From January to June 2022, 82 GDM patients treated in our hospital were included as an experimental group, and 89 healthy pregnant women during the same period were selected as the control group. Lp-PLA2 concentration and TG, TC, HDL-C, and LDL-C levels were tested with specialized instruments in clinical laboratories. The PLA2G7 gene polymorphisms (rs1805017, rs1805018, and rs76863441) were detected by fluorescent probe method and sequencing.Results: Lp-PLA2 concentration was significantly higher in GDM group than control group (P< 0.05). Among three polymorphism loci of PLA2G7 gene (rs1805017, rs1805018, and rs76863441) the significant associations were only found in GT genotype of rs76863441 loci (P< 0.05).Conclusion: Pregnant women with high levels of Lp-PLA2 concentration are more likely to develop GDM, especially those with PLA2G7 rs76863441 polymorphism. Lp-PLA2 concentration and PLA2G7 rs1805017 polymorphism may be a novel marker for GDM diagnosis and prediction.Keywords: gestational diabetes mellitus, PLA2G7, Lp-PLA2, gene polymorphism

Cui Wang,1,&ast; Qing Ma,2,&ast; Xijie Yu1 1Laboratory of Endocrinology & Metabolism/Department of Endocrinology & Metabolism, Rare Disease Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, 610041, People’s Republic of China; 2General Practice Ward/International Medical Center Ward, General Practice Medical Center, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, Sichuan Province, 610041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xijie Yu, Department of Endocrinology and Metabolism, Laboratory of Endocrinology and Metabolism, Rare Disease Center, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, Sichuan Province, 610041, People’s Republic of China, Tel +86 2885422362, Fax +86 2885423459, Email xijieyu@hotmail.comAbstract: Bile acids play a crucial role in promoting intestinal nutrient absorption and biliary cholesterol excretion, thereby protecting the liver from cholesterol accumulation and bile acid toxicity. Additionally, bile acids can bind to specific nuclear and membrane receptors to regulate energy expenditure and specific functions of particular tissues. Vascular calcification refers to the pathological process of calcium-phosphate deposition in blood vessel walls, which serves as an independent predictor for cardiovascular adverse events. In addition to aging, this pathological change is associated with aging-related diseases such as atherosclerosis, hypertension, chronic kidney disease, diabetes mellitus, and osteoporosis. Emerging evidence suggests a close association between the bile acid network and these aforementioned vascular calcification-associated conditions. Several bile acids have been proven to participate in calcium-phosphate metabolism, affecting the transdifferentiation of vascular smooth muscle cells and thus influencing vascular calcification. Targeting the bile acid network shows potential for ameliorating these diseases and their concomitant vascular calcification by regulating pathways such as energy metabolism, inflammatory response, oxidative stress, and cell differentiation. Here, we present a summary of the metabolism and functions of the bile acid network and aim to provide insights into the current research on the profound connections between the bile acid network and these vascular calcification-associated diseases, as well as the therapeutic potential.Keywords: bile acid, vascular calcification, aging, farnesoid X receptor, FXR, the G protein-coupled membrane receptor, TGR5

Tianjun Wei,1,2 Wei Wei,2 Qiang Ma,2 Zhongbing Shen,2 Kebing Lu,2 Xiangming Zhu1,2 1School of Continuing Education, Anhui Medical University, Hefei, 230032, People’s Republic of China; 2Department of Ultrasound, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241001, People’s Republic of ChinaCorrespondence: Xiangming Zhu, School of Continuing Education, Anhui Medical University, NO. 81 Meishan Road, Shushan District, Hefei City, Anhui Province, 230032, People’s Republic of China, Tel +86 553-5739808, Email xiangmingzhudr@yeah.netBackground and Objectives: Papillary thyroid carcinoma (PTC) is a prevalent histological type of thyroid cancer; however, noninvasive assessment of cervical lymph node metastasis (LNM) poses a challenge. This study aims to develop a novel clinical-radiomics nomogram that utilizes ultrasound (US) images to predict the presence of cervical LNM metastasis in patients with PTC.Methods: A total of 423 patients with PTC were recruited to participate in this study between January 2020 and December 2022, of which 282 were classified into the training group and 141 patients were classified into the validation set. Contrast-enhanced ultrasound (CEUS) and B-mode ultrasound (BMUS) images were subjected to radiomic analysis, leading to the extraction of 912 radiomic features. Thereafter, a radiomics score (Radscore) was developed to effectively integrate the information derived from BMUS and CEUS modalities. Univariate and multivariate backward stepwise logistic regression analysis techniques were used to construct the clinical and clinical-radiomics models, respectively.Results: The findings revealed that the clinical-radiomics nomogram incorporated age, sex, CEUS Radscore, and US-reported LNM as risk factors. The nomogram demonstrated good performance using data from the training (AUC = 0.891) and validation (AUC = 0.870) sets. The decision curve analysis implied that this nomogram exhibited good clinical utility, which was further supported by the results of the calibration curves and Hosmer-Lemeshow test.Conclusion: The CEUS Radscore-based clinical radiomics nomogram could serve as a valuable tool for predicting cervical LNM metastasis in patients with PTC, thereby tailoring individualized treatment strategies for them.Keywords: lymph node metastasis, radiomics, papillary thyroid carcinoma, contrast-enhanced ultrasound, B-mode ultrasound

Bei Chen,1,2,&ast; Mingzhi Yan,1,2,&ast; Huijing Gao,1,2 Qin Ma,3 Lihua Li,4 Guodong Lü,1,2 Yuehong Gong,1,2 Limei Wen,1,2 Shaoquan Xu,5 Jianhua Wang,1,2 Jun Zhao1,2 1First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 2State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 3HuaShiDan Pharmaceutical Company Limited, Urumqi, Xinjiang, People’s Republic of China; 4Xinjiang Urumqi Maternal and Child Health Hospital, Urumqi, Xinjiang, People’s Republic of China; 5College of Pharmacy, Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Zhao; Jianhua Wang, First Affiliated Hospital of Xinjiang Medical University, State Key Laboratory of Pathogenesis, Prevention, and Treatment of Central Asian High Incidence Diseases, Urumqi, Xinjiang, 830011, People’s Republic of China, Email zhaojun700326@163.com; jhw716@sohu.comIntroduction: Cystic echinococcosis (CE) is a chronic zoonotic parasitic disease caused by the larvae of the Echinococcus granulosus sensu lato (s.l.) cluster. The current existing drugs have limited therapeutic efficacy against cystic echinococcosis, and thus, there is an urgent need to develop new drugs.Methods: In this study, 7 harmine (HM) derivatives were screened and the effects of HM derivatives on E. granulosus sensu stricto (s.s.) were evaluated by in vitro and mouse experiments. The safety of the HM derivatives was assessed by cytotoxicity assays, acute toxicity study in animals and subacute toxicity study.Results: These results show that the HM derivatives H-2-168 and DH-004 exhibited more significant antiparasitic effects at an initial concentration of 40 μM. The results of further studies showed that H-2-168 and DH-004 had dose-dependent effects against protoscoleces and had satisfactory therapeutic outcomes in vivo. Electron microscopy observations demonstrated that H-2-168 and DH-004 caused severe disruption of the parasite ultrastructure. Notably, the results of the acute toxicity and subchronic toxicity studies showed that H-2-168 and DH-004 had significantly improved safety. In addition, we found that H-2-168 and DH-004 induced DNA damage in E. granulosus s.s., which may be the mechanism by which these drugs produce their therapeutic effects.Discussion: Overall, the data from this work demonstrate that H-2-168 and DH-004 are highly effective candidate compounds with low toxicity for the treatment of CE and will provide a new therapeutic strategy for CE pharmacological treatment.Graphical Abstract: Keywords: harmine derivatives, β-carboline, Echinococcus granulosus sensu stricto, cystic echinococcosis, DNA damage

Yunli Xing, Ying Sun, Mei Tang, Wei Huang, Jia Luo, Qing Ma Department of Geriatrics, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Qing Ma, Department of Geriatrics, Beijing Friendship Hospital, Capital Medical University, No. 95, Yongan Road, Xicheng District, Beijing, 100050, People’s Republic of China, Tel +86 13801019331, Fax +86 10 6313 8040, Email maqing3@163.comBackground: Advanced age increases the risk for severe COVID-19. However, the risk factors for mortality from COVID-19 in very elderly patients (≥ 80-years-old) are unknown.Objective: Investigate the relationship of mortality with the clinical characteristics of very elderly COVID-19 patients.Materials and Methods: Very elderly patients who were hospitalized with COVID-19 from December 3, 2022 to January 1, 2023 were retrospectively examined. Sociodemographic and clinical variables were recorded and survival was recorded after 30 days.Results: We examined 181 patients (median age: 90.84 years; 114 older than 90 years). The median Barthel index was 30.69, and 55.8% of patients had severe or critical COVID-19 pneumonia. Forty-two patients (33.2%) received a high-flow nasal cannula or non-invasive ventilation, and only 4.4% received mechanical ventilation. The overall mortality was 35.9%, and there was no significant difference in mortality for the 80 to 90-year-old group and the over 90-year-old group (37.7% vs 32.8%, P=0.508). A multivariate analysis showed that the Barthel index (OR, 0.975; 95% CI, 0.962– 0.989), serum creatinine (SCr) level (OR, 1.003; 95% CI, 1.000– 1.006), white blood cell (WBC) count (OR, 1.160; 95% CI, 1.056– 1.276), D-dimer level (OR, 1.060; 95% CI, 1.009– 1.113), and corticosteroid use (OR, 0.268; 95% CI, 0.124– 0.582) were significantly and independently related to 30-day mortality. A binary classification model based on the multivariate analysis had good predictive value (area under the curve, 0.794).Conclusion: Very elderly COVID-19 patients have a high risk for mortality. The Barthel index, SCr, WBC count, D-dimer level, and corticosteroid use were independently associated with mortality.Keywords: COVID-19, over-80-year-old, characteristic, mortality

Xianqin Song,1 Yu Song,1 Quanping Ma,2 Kehua Fang,3 Xiaotian Chang1 1Medical Research Center of the Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China; 2Clinical Laboratory, The fourth People’s Hospital of Jinan, Jinan, Shandong, People’s Republic of China; 3Clinical Laboratory of the Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of ChinaCorrespondence: Xiaotian Chang, Medical Research Center of the Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China, Tel/Fax +86 0532-82917331, Email changxt@126.comPurpose: Vascular calcification is a hallmark of atherosclerosis (AS). We and others confirmed that carbonic anhydrase I (CA1) and CA2 increased expression and catalyzed calcium deposition in atherosclerotic aortas. Macrophages have been demonstrated to be strongly related to AS. This study aimed to clarify how and which macrophage subtypes regulate CA1 and CA2 expression to stimulate aortic calcification.Methods and Results: THP-1 cells were induced to form M0, M1 and M2 macrophage subtypes. These cells and their culture supernatants were separately incubated with human vascular smooth muscle cells (VSMCs). Calcification was strongly increased in VSMCs treated with β-GP, a chemical inducer of cellular calcification, following incubation with M1 macrophages or their culture supernatants, and was much higher than that in VSMCs treated with β-GP alone. Meanwhile, the expression of CA1 and CA2, as well as calcification marker genes, including Runx2, BMP-2 and ALP, was increased in VSMCs during this process. TNF-α levels were also increased in the culture medium of M1 macrophages. M0 and M2 macrophages or their supernatants did not significantly stimulate calcification in VSMCs. Following transfection with anti-CA1 or CA2 siRNAs, β-GP-induced VSMCs showed decreased calcification, but the calcification level was partially increased when those VSMCs were incubated with the supernatants of M1 macrophages, while CA1 and CA2 expression as well as TNF-α levels were also elevated. When VSMCs were treated with TNF-α without β-GP induction, calcification and the expression of CA1 and CA2 were also significantly increased.Conclusion: The results of this study suggest that M1 macrophages can increase CA1 and CA2 expression to promote atherosclerotic calcification in VSMCs by secreting TNF-α.Keywords: atherosclerosis, calcification, carbonic anhydrase I, carbonic anhydrase II, macrophages, TNF-&#x03B1

Chunli Fan,1,2,&ast; Quanfu Ma,1,2,&ast; Xufeng Wu,2 Xuan Dai,2 Qiuzi Peng,2 Hongning Cai1,2 1Department of Scientific Research and Teaching Management Department, Maternal and Child Health Hospital of Hubei Province, Wuhan, 430070, People’s Republic of China; 2Department of Cervical Cancer Prevention Center, Maternal and Child Health Hospital of Hubei Province, Wuhan, 430070, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiuzi Peng; Hongning Cai, Email 1078380199@qq.com; chn@hbfy.comObjective: To evaluate the diagnostic value of DNA methylation detection of multiple gene loci in cervical cancer.Methods: A total of 61 cases requiring cervical biopsy were selected from the outpatient clinic of Maternal and Child Health Hospital of Hubei Province between January 2018 and December 2019. The patients were divided into four groups based on histopathologic diagnosis: cervical cancer (CC) group, high-grade squamous intraepithelial lesion (HSIL) group, low-grade squamous intraepithelial lesion (LSIL) group, and control group. HPV examination, liquid-based cytology examination, and DNA methylation detection at multiple gene sites were performed. The positive rate of DNA methylation, sensitivity, specificity, area under the curve (AUC), and other efficacy indexes were calculated to evaluate the diagnostic value of DNA methylation detection at multiple gene loci in cervical cancer.Results: The positive rates of DNA methylation in CC, HSIL, LSIL, and control groups were 100%, 88%, 83% and 17%, respectively. The ZNF671 gene had the highest positive rate among the cervical lesion group, with rates of 57%, 76%, and 100% in LSIL, HSIL, and CC groups respectively. The combination of DNA methylation detection at multiple gene loci showed the highest diagnostic efficacy for HSIL and cervical cancer, with AUC value of 0.850 (95% CI:0.746– 0.954), a Youden index of 0.654, and a sensitivity and specificity of 85% and 85.4%, respectively. The diagnostic efficacy of the combined detection was significantly higher than that of HPV examination and liquid-based cytology examination (P < 0.05).Conclusion: DNA methylation detection at multiple gene loci is highly effective and diagnostic tool for cervical cancer, and has potential application value in clinical practice.Keywords: multiple gene loci, DNA methylation detection, HSIL and cervical cancer, diagnostic efficacy

Xiaoxiao Xu, Bin Zhou, Jun Liu, Qianli Ma, Tengyu Zhang, Xiang Wu The First Hospital of Ningbo University, Ningbo, 315211, People’s Republic of ChinaCorrespondence: Xiang Wu, The First Hospital of Ningbo University, Ningbo, 315211, People’s Republic of China, Email fywuxiang2@nbu.edu.cnPurpose: Ru360, a selective inhibitor of mitochondrial calcium uptake, maintains mitochondrial calcium homeostasis. To evaluate whether mitochondrial calcium uniporter (MCU)-mediated mitochondrial function is associated with the pathological process of Postoperative cognitive dysfunction (POCD), elucidate its relationship with neuroinflammation, and observe whether the relevant pathological process can be improved with Ru360.Methods: Aged mice underwent experimental open abdominal surgery after anesthesia. Open field tests, Novel object recognition tests and Y Maze Tests were used to conduct behavioral experiments. The reactive oxygen species (ROS) content, the levels of inflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), intra-mitochondrial calcium, mitochondrial membrane potential (MMP) and the activity of antioxidant superoxide dismutase (SOD) in the hippocampus of mice were detected using kits. The expression of proteins was detected using Western blot.Results: After treatment with Ru360, MCU-mediated mitochondrial dysfunction was inhibited, neuroinflammation was reduced, and the learning ability of the mice was improved after surgery.Conclusion: Our study demonstrated that mitochondrial function plays a crucial role in the pathology of POCD, and using Ru360 to improve mitochondrial function may be a new and necessary direction for the treatment of POCD.Keywords: postoperative cognitive dysfunction, mitochondria, Ru360, mitochondrial calcium uniporter, neuroinflammation

Xiaotian Shi, Shan Wang, Jieqiong Hu, Fei Chen, Heng Zhang, Yifan Yang, Xv Li, Qing Ma Department of Geriatrics, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Qing Ma, Email maqing3@163.comObjective: Determine the relationship of renal function with frailty using different formulas for estimated glomerular filtration rate (eGFR).Methods: Individuals who were 60-years-old or more (n=507) were recruited from August 2020 to June 2021, and the FRAIL scale was used to classify them as non-frail or frail. The three equations used to compute the eGFR were based on serum creatinine (eGFRcr), cystatin C (eGFRcys), or SCr+CysC (eGFRcr-cys). Renal function was classified using eGFR and defined as normal (≥ 90 mL/min/1.73m2), mild damage (59– 89 mL/min/1.73m2), or moderate damage (≤ 60 mL/min/1.73m2). The relationship of frailty with renal function was analyzed. A subset of participants (n=358) was used to analyze changes in eGFR from 1 January 2012 to 31 December 2021 according to frailty and using the different eGFR equations.Results: There were significant differences between the eGFRcr-cys and eGFRcr values in the frail group (P< 0.05), but not the non-frail group; however, the differences between the eGFRcr-cys and eGFRcys values were significant in the frail and non-frail groups (P< 0.001). Based on each eGFR equation, the prevalence of frailty increased as eGFR decreased (P< 0.001), but there was no significant relationship after adjusting for age or the age-adjusted Charlson co-morbidity index. There were temporal declines in eGFR in all three frailty groups (robust, pre-frail, and frail), especially in the frail group (2.226 mL/min/1.73m2 per year; P< 0.001).Conclusion: For older individuals who are frail, the eGFRcr value may not provide accurate estimates of renal function. Frailty is associated with a rapid decline in kidney function.Keywords: elderly, frailty, kidney function, serum creatinine, cystatin C

Bin Zhang,1,&ast; Yanyan Song,1,&ast; Qian Ma,2,&ast; Jian Yang,1 Lei Bai1 1Department of Cardiovascular Surgery, General Hospital of Ningxia Medical University, Yinchuan, People’s Republic of China; 2Department of Anesthesiology, Tumor Hospital, General Hospital of Ningxia Medical University, Yinchuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Bai, Email baileibl02h@126.comObjective: To investigate the changes and significance of perioperative expression levels of kidney injury molecule-1 (KIM-1), neutrophil gelatinase-related lipocalin (NGAL), and heme oxygenase-1 (HO-1) in patients with acute kidney injury (AKI) after cardiac valve replacement under cardiopulmonary bypass.Methods: A total of 80 patients were divided into the AKI group and non-AKI group based on the postoperative occurrence of AKI. The expression levels of urinary KIM-1, NGAL, serum creatinine, urea nitrogen, and HO-1 were compared between the two groups before surgery and at 12 h, 24 h, and 48 h after surgery.Results: There were 22 patients with postoperative AKI (AKI group), the incidence of postoperative AKI were 27.5%, and there were 58 patients without AKI (non-AKI group). There was no significant difference in general clinical data between the two groups (P > 0.05). Compared between AKI group and preoperative group, KIM-1, NGAL, HO-1, blood creatinine, and BUN levels were significantly increased, with significant differences (P < 0.05). Compared with non-AKI groups, KIM-1, NGAL, HO-1, blood creatinine, and blood urea nitrogen levels increased at all time points, but the difference was not significant (P > 0.05). Compared with AKI group and non-AKI group, KIM-1, NGAL, HO-1, blood creatinine, and BUN levels increased significantly, the differences were statistically significant (P < 0.05).Conclusion: AKI can easily occur after cardiac valve replacement and postoperative expression levels of KIM-1, NGAL, and HO-1 can be early warning indicators of postoperative AKI.Keywords: acute kidney injury, cardiac valve replacement, heme oxygenase-1, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin

Qian Ma,1,&ast; Lei Chang,2,&ast; Wenwen Wang,2,&ast; Lingyi Che,1 Xiaoqin Song,3 Gailing Li,2 Ying Zhang,2 Yibing Chen,1 Zhuoyu Gu,4 Xin Ge5 1Genetics and Prenatal Diagnosis Center, First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 2Department of Gynecology and Obstetrics, First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 3Physical Examination Center, First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 4Department of Thoracic Surgery, First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 5Department of Breast Surgery, First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450052, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xin Ge, Department of Breast Surgery, First Affiliated Hospital, Zhengzhou University, 1 Jianshe Road East, Zhengzhou, Henan, 450052, People’s Republic of China, Email Gexin1981@126.com Zhuoyu Gu, Department of Thoracic Surgery, First Affiliated Hospital, Zhengzhou University, 1 Jianshe Road East, Zhengzhou, Henan, 450052, People’s Republic of China, Email guzhuoyu@hotmail.comBackground: It was indicated that tumor intrinsic heterogeneity and the tumor microenvironment (TME) of ovarian cancer (OV) influence immunotherapy efficacy and patient outcomes. Leucyl and cystinyl aminopeptidase (LNPEP) encodes a zinc-dependent aminopeptidase, which has been proved to participant in the vesicle-mediated transport and class I MHC mediated antigen processing and presentation. However, the function of LNPEP in TME of OV and its potential molecular mechanisms have not been determined. Therefore, we aimed to investigate a prognostic biomarker which may be helpful in identifying TME heterogeneity of ovarian cancer.Methods: In this study, bioinformatics databases were used to explore the expression profile and immune infiltration of LNPEP. Bioinformatics analyses of survival data and interactors of LNPEP were conducted to predict the prognostic value of LNPEP in OV. The protein levels of LNPEP were validated by Western blot and immunohistochemistry.Results: Based on the TCGA data, our data displayed that the mRNA expression of LNPEP was markedly down-regulated in ovarian cancer than that in para-cancer tissues, contrary to the protein level. Importantly, high LNPEP expression was associated with poor prognosis in patients with OV. Furthermore, Cox regression analysis showed that LNPEP was an independent prognostic factor in OV. GO and KEGG pathway analyses indicated the co-expressed genes of LNPEP were mainly related to a variety of immune-related pathways, including Th1 and Th2 cell differentiation, Th17 cell differentiation, and immunoregulatory interaction. Our data also demonstrated that the expression of LNPEP was strongly correlated with immune infiltration levels, immunomodulators, chemokines and chemokine receptors.Conclusion: In our study, we identified and established a prognostic signature of immune-related LNPEP in OV, which will be of great value in predicting the prognosis of clinical trials and may become a new therapeutic target for immunological research and potential prognostic biomarker in OV.Keywords: LNPEP, ovarian cancer, prognosis, immune infiltration, tumor microenvironment

Xiaoling Zhang, Xuting Jin, Jiajia Ren, Jueheng Liu, Haichang Ma, Xiaoming Fang, Huifan Zhang, Yujie Zhao, Yanli Hou, Yanni Luo, Lei Guo, Qi Ma, Ya Gao, Jingjing Zhang, Jiamei Li, Xiaochuang Wang, Gang Wang Department of Critical Care Medicine, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, People’s Republic of ChinaCorrespondence: Xiaochuang Wang; Gang Wang, Department of Critical Care Medicine, the Second Affiliated Hospital of Xi’an Jiaotong University, 157 Xi 5 Lu, Xi’an, Shaanxi, 710004, People’s Republic of China, Tel +86-029-8767-9630 ; +86-029-8767-9633, Email dr_xc_wang@163.com; gang_wang@xjtu.edu.cnPurpose: In patients with carbapenem-resistant Gram-negative bacteria (CRGNB) infection, the impact of appropriate empirical antibiotic treatment (AEAT) initialized before culture results were available remains controversial. We aimed to investigate the effect of AEAT on the prognosis of critically ill patients with hospital-acquired pneumonia (HAP) caused by CRGNB.Patients and Methods: Patients with CRGNB-infected HAP and received empirical antibiotic treatment (EAT) for at least 3 days in the intensive care unit (ICU) of a tertiary teaching hospital in China from February 2017 to September 2021 were included in the retrospective cohort study. Patients were categorized into AEAT and inappropriate empirical antibiotic treatment (IEAT) groups based on whether they received EAT covering CRGNB. The associations of AEAT with ICU and 28-day mortality were assessed using multivariable logistic regression model.Results: A total of 94 patients were enrolled, including 29 patients in AEAT group and 65 patients in IEAT group. Patients in AEAT group had a higher Sequential Organ Failure Assessment (SOFA) score (P = 0.003), levels of procalcitonin (PCT) (P = 0.001), and lactic acid (LAC) (P = 0.026); while patients in the IEAT group had a higher platelet count (PLT) (P = 0.001). There was no significant difference in the length of ICU stay between the two groups (P = 0.051). Compared with IEAT, AEAT was associated with an increased risk of 28-day mortality in the univariable logistic regression model (OR: 2.618, 95% CI: 1.063– 6.448). However, after adjusted for SOFA score, PLT, PCT, and LAC level, the association between AEAT and 28-day mortality diminished (OR: 1.028, 95% CI: 0.353– 2.996). AEAT showed no significant association with ICU mortality in neither univariable (OR: 1.167, 95% CI: 0.433– 3.142) nor multivariable (OR: 0.357, 95% CI: 0.097– 1.320) models.Conclusion: AEAT showed no significant influence on ICU or 28-day mortality in critically ill patients with HAP caused by CRGNB infection.Keywords: appropriate empirical antibiotics, hospital-acquired pneumonia, carbapenem-resistant, gram-negative bacteria, ICU mortality

Qianqing Ma,1,&ast; Chunyun Shen,2,&ast; Yankun Gao,3,&ast; Yayang Duan,1 Wanyan Li,4 Gensheng Lu,5 Xiachuan Qin,1 Chaoxue Zhang,1 Junli Wang2 1Department of Ultrasound, the First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Department of Ultrasound, Wuhu No. 2 People’s Hospital, Wuhu, People’s Republic of China; 3Department of Radiology, the First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 4Department of Ultrasound, Linquan Country People’s Hospital, Fuyang, People’s Republic of China; 5Department of Pathology, Wuhu No. 2 People’s Hospital, Wuhu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junli Wang, Department of Ultrasound, Wuhu No. 2 People’s Hospital, No. 259 Jiuhuashan Road, Jinghu District, Wuhu, Anhui, 241001, People’s Republic of China, Tel +86 18055317022, Email wjl980134@163.com Chaoxue Zhang, Department of Ultrasound, the First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Shushan District, Hefei, Anhui, 230022, People’s Republic of China, Tel +86 13955158023, Email zcxay@163.comBackground: Breast cancer is the most common tumor globally. Automated Breast Volume Scanner (ABVS) and strain elastography (SE) can provide more useful breast information. The use of radiomics combined with ABVS and SE images to predict breast cancer has become a new focus. Therefore, this study developed and validated a radiomics analysis of breast lesions in combination with coronal plane of ABVS and SE to improve the differential diagnosis of benign and malignant breast diseases.Patients and Methods: 620 pathologically confirmed breast lesions from January 2017 to August 2021 were retrospectively analyzed and randomly divided into a training set (n=434) and a validation set (n=186). Radiomic features of the lesions were extracted from ABVS, B-ultrasound, and strain elastography (SE) images, respectively. These were then filtered by Gradient Boosted Decision Tree (GBDT) and multiple logistic regression. The ABVS model is based on coronal plane features for the breast, B+SE model is based on features of B-ultrasound and SE, and the multimodal model is based on features of three examinations. The evaluation of the predicted performance of the three models used the receiver operating characteristic (ROC) and decision curve analysis (DCA).Results: The area under the curve, accuracy, specificity, and sensitivity of the multimodal model in the training set are 0.975 (95% CI:0.959– 0.991),93.78%, 92.02%, and 96.49%, respectively, and 0.946 (95% CI:0.913 − 0.978), 87.63%, 83.93%, and 93.24% in the validation set, respectively. The multimodal model outperformed the ABVS model and B+SE model in both the training (P < 0.001, P = 0.002, respectively) and validation sets (P < 0.001, P = 0.034, respectively).Conclusion: Radiomics from the coronal plane of the breast lesion provide valuable information for identification. A multimodal model combination with radiomics from ABVS, B-ultrasound, and SE could improve the diagnostic efficacy of breast masses.Keywords: radiomics, automated breast volume scanner, strain elastography, ultrasound, breast cancer

Longbin Zheng,1,&ast; Yiteng Wang,2,&ast; Qing Ma,1,&ast; Wenbo Liang,1 Xiaojing Zhang,1 Zhiqiang Ren,1 Weimin Qin,1 Fan Meng,1 Yuhong Li,1 Guoxiang Fan,1 Ning Yin1 1Department of Anesthesiology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China; 2Department of Anesthesiology, Xinchang County People’s Hospital, Xinchang, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ning Yin, Department of Anesthesiology, Sir Run Run Hospital, Nanjing Medical University, No. 109 Longmian Avenue, Nanjing, Jiangsu Province, 211112, People’s Republic of China, Email yinning882000@126.comPurpose: Patients with obesity are more susceptible to hypoxemia. Anesthetic management for patients with obesity undergoing painless gastroscopy presents a severe challenge for anesthesiologists. Esketamine is a NMDA antagonist that has been proven to be beneficial for ameliorating respiratory depression owing to its sympathomimetic effect; however, there are no relevant reports on its use in patients with obesity. We designed a randomized controlled trial to evaluate whether esketamine can be the ideal adjuvant to propofol sedation in patients with obesity undergoing painless gastroscopy.Patients and Methods: A total of 104 patients with obesity undergoing painless gastroscopy were randomly divided into group C (propofol+saline) and group S (propofol+esketamine 0.25 mg/kg). Anesthesia was induced by 2 mg/kg propofol with saline or esketamine. The consumption of propofol, hemodynamic parameters, duration of procedure, induction time, postoperative awakening time, and orientation recovery time were recorded. Adverse events and satisfaction scores were also recorded.Results: Propofol consumption was 274.4± 22.6 mg and 201.3± 16.6 mg in groups C and S, respectively. The induction time of groups C and S were 25.4± 2.3 s and 17.8± 1.9 s, respectively. The postoperative awakening times of groups C and S were 6.2± 1.1 min and 4.8± 1.3 min, respectively. Hemodynamic parameters were more stable in group S than in group C. The incidence of adverse events such as injection pain, hypoxemia, hypotension, bradycardia, choking, and body movement were significantly lower in group S. The satisfaction scores of the endoscopist and anesthesiologist were (4.58± 0.49 vs 3.71± 0.83) and (4.75± 0.44 vs 3.33± 0.92), respectively.Conclusion: The combination of propofol and esketamine (0.25 mg/kg) improves the safety and reduces the incidence of adverse events in patients with obesity during painless gastroscopy. Thus, this method is worthy of clinical application.Clinical Trials Registration: ChiCTR 2200062547.Keywords: esketamine, propofol, patients with obesity, painless gastroscopy

Qi Zhang,1,&ast; Wenjuan Yan,1,&ast; Yingjie Zhu,2,&ast; Nan Jing,1 Shanmei Wang,1 Youhua Yuan,1 Bing Ma,1 Junhong Xu,1 Yafei Chu,1 Jiangfeng Zhang,1 Qiong Ma,1 Baoya Wang,1 Wenbo Xu,1 Liqiang Zhu,3 Ying Sun,2 Caiqin Shi,4 Juan Fang,5 Yi Li,1 Shengqun Liu6 1Department of Clinical Microbiology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, and People’s Hospital of Henan University, Zhengzhou, People’s Republic of China; 2Department of Clinical Microbiology, Henan No.3 Provincial People’s Hospital, Zhengzhou, People’s Republic of China; 3Department of Clinical Microbiology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 4Department of Microbiology Laboratory, KingMed Diagnostics Group Co., Ltd, Zhengzhou, People’s Republic of China; 5Department of Research and Development, Autobio Diagnostics Co., Ltd, Zhengzhou, People’s Republic of China; 6Department of Anesthesia and Perioperative Medicine, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, and People’s Hospital of Henan University, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Li; Shengqun Liu, Department of Anesthesia and Perioperative Medicine, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, and People’s Hospital of Henan University, Weiwu Road 7, Zhengzhou, Henan, 450003, People’s Republic of China, Tel +8613526882118, Fax +8637187160318, Email liyilabmed@henu.edu.cn; tim2002627@163.comPurpose: To evaluate the performance of five widespread commercial products for colistin and polymyxin B susceptibility testing in China for mcr-positive and -negative Escherichia coli and Klebsiella pneumoniae.Methods: A total of 132 E. coli and 83 K. pneumoniae strains (including 68 mcr-1-positive E. coli and 28 mcr-8-positive K. pneumoniae) were collected. We analysed the performance of colistin susceptibility (with Vitek 2 and Phoenix M50) and the performance of polymyxin B susceptibility (with DL-96II, MA120, and a Polymyxin B Susceptibility Test strip; POL E-strip). Broth microdilution was used as the gold standard. Categorical agreement (CA), essential agreement (EA), major error (ME), and very major error (VME) were calculated for comparisons.Results: For E. coli, the total CA, EA, ME, and VME to colistin were as follows: Vitek 2, 98.5%/98.5%/0%/2.9%; and Phoenix M50, 98.5%/97.7%/0%/2.9%. The total CA, EA, ME, and VME to polymyxin B were as follows: POL E-strip, 99.2%/63.6%/1.6%/0%; MA120, 70.0%/-/0%/58.8%; and DL-96II, 80.2%/-/1.6%/36.8%. Only Vitek 2 and Phoenix M50 presented satisfactory performances for mcr-1-positive E. coli. For K. pneumoniae, the total CA, EA, ME, and VME to colistin were as follows: Vitek 2, 73.2%/72.0%/0%/61.6%; and Phoenix M50, 74.7%/74.7%/0%/58.3%. The total CA, EA, ME, and VME to polymyxin B were as follows: POL E-strip, 91.6%/74.7%/2.1%/16.7%; MA120, 92.8%/-/2.1%/13.9%; and DL-96II, 92.2%/-/2.1%/8.3%. All systems were unsatisfactory for mcr-8-positive K. pneumoniae. When the susceptibility of mcr-negative strains was tested, all systems presented excellent performance.Conclusion: Vitek 2 and Phoenix M50 with colistin for E. coli showed acceptable performance regardless of mcr-1 expression, while DL-96II, MA120, and the POL E-strip performed worse for mcr-1-positive strains. Furthermore, mcr-8 greatly affected the performance of all systems with both colistin and polymyxin B for K. pneumoniae isolates.Keywords: polymyxin B, colistin, mobilised colistin resistance, broth microdilution, susceptibility testing, semi-automated systems

Xiachuan Qin,1,2 Xiaomin Hu,2 Weihan Xiao,2 Chao Zhu,3 Qianqin Ma,1 Chaoxue Zhang1 1Department of Ultrasound, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Department of Ultrasound, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College (University), Nan Chong, People’s Republic of China; 3Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of ChinaCorrespondence: Chaoxue Zhang, Department of Ultrasound, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China, Tel +86-13955158023, Email zcxay@163.comObjective: Distinguishing the degree of differentiation, hepatocellular carcinoma (HCC) has important clinical significance in the therapeutic decision-making and patient prognosis evaluation.Methods: We developed a deep-learning radiomics (DLR) model based on contrast-enhanced ultrasound (CEUS) to evaluate the differentiation of HCC noninvasive. We retrospectively analyzed HCC patients who had undergone resection and CEUS one week preoperatively between November 2015 and August 2022. Enrolled patients were randomly divided into training (n=190) and testing (n=82) cohorts in a 7:3 ratio. The depth of learning and radiological characteristics reflecting the differentiation degree of HCC were extracted, and the least absolute shrinkage and selection operator(LASSO) was used for feature selection to obtain the most valuable features and then build a DLR model based on the useful features.Results: The deep-learning Radiomics model could accurately predict the degree of differentiation of HCC; the area under the curve of the DLR model in the training and testing cohorts was 0.969 and 0.932, respectively. The accuracy, sensitivity, and specificity of the CEUS-based DLR model for predicting the differentiation of HCC were 0.915, 0.938, and 0.900, respectively, in the testing cohort. The decision curve analysis confirmed that the combined model predicted good overall net income for differentiation.Conclusion: The CEUS-based DLR model provides an easy-to-use, visual, and personalized tool for predicting the differentiation of HCC and can help doctors formulate more favorable treatment plans for patients.Keywords: hepatocellular carcinoma, differentiated, contrast-enhanced ultrasound, deep-learning, radiomics

In this work, the effect of extrusion process on the mechanical properties and the stress corrosion cracking (SCC) resistance of 7N01 aluminum alloys were systematically investigated by tensile testing, slow strain rate testing (SSRT), electrochemical experiment, scanning electron microscopy (SEM), electron backscattered diffraction (EBSD), and transmission electron microscope (TEM) observation, respectively. The results showed that with the increase of extrusion temperature, the SCC resistances of the alloys deteriorated, and this tendency was also proved by the electrochemical experiments including polarization curves and EIS results. The Microstructure observation results revealed that recrystallization played an important role on the SCC resistances of the alloys: the new recrystallization grain boundaries with higher grain boundary energy and wider PFZ could magnify the difference of electrochemical property between grain boundary area and the grain interior, thus raising the stress corrosion crack sensitivity of the alloys.

Qian Xie,1,* Shi Gao,1,* Rui Tian,2 Guohao Wang,3,4 Zainen Qin,5 Minglong Chen,1 Wenhui Zhang,1 Qiang Wen,1 Qingjie Ma,1 Lei Zhu1 1Department of Nuclear Medicine, China-Japan Union Hospital of Jilin University, NHC Key Laboratory of Radiobiology, School of Public Health of Jilin University, Changchun, 130033, People’s Republic of China; 2Department of Ophthalmology Second Hospital, Jilin University, Changchun, 130033, People’s Republic of China; 3Cancer Centre, Faculty of Health Sciences, University of Macau, Macau, SAR, 999078, People’s Republic of China; 4Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau, SAR, 999078, People’s Republic of China; 5Department of Oral Radiology, Guangxi Medical University College of Stomatology, Nanning, 530021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qingjie Ma; Lei Zhu, Email maqj@jlu.edu.cn; zeh.ray8@gmail.comIntroduction: Combination therapy is a promising approach to promote the efficacy and reduce the systemic toxicity of cancer therapy. Herein, we examined the potency of a combined chemo-phototherapy approach by constructing a hyaluronidase- and reactive oxygen species-responsive hyaluronic acid nanoparticle carrying a chemotherapy drug and a photosensitizer in a tumor-bearing mouse model. We hypothesized that following decomposition, the drugs inside the nanocomplex will be released in the tumors to provide effective tumor treatment. We aimed to design a smart drug delivery system that can improve traditional chemotherapy drug delivery and enhance the therapeutic efficacy in combination with photodynamic therapy.Methods: Hydrophilic hyaluronic acid (HA) was covalently modified with a hydrophobic 5β-cholanic acid (CA) via an ROS-cleavable thioketal (tk) linker for a targeted co-deliver of 10-Hydroxy camptothecin (HCPT) and Chlorin e6 (Ce6) into tumors to improve the efficiency of combined chemo-photodynamic therapy.Results: The obtained HA-tk-CA nanoparticle carrying HCPT and Ce6, named HTCC, accumulated in the tumor through the enhanced permeable response (EPR) effect and HA-mediated CD44 targeting after intravenous administration. Upon laser irradiation and hyaluronidase degradation, HTCC was disrupted to release HCPT and Ce6 into the tumors. Compared to the monotherapy approach, HTCC demonstrated enhanced tumor growth inhibition and minimized systemic toxicity in a tumor-bearing mouse model.Conclusion: Our results suggested that controlled dual-drug release not only improved tumor drug delivery efficacy, but also reduced systemic side effects. In addition to HCPT and Ce6 delivery, the HA-tk-CA nanocomplex can be used to deliver other drugs in synergistic cancer therapy. Since most current combined therapy uses free drugs with distinct spatiotemporal distributions, the simultaneous co-delivery of dual drugs with a remote on-demand drug delivery nanosystem provides an alternative strategy for drug delivery design.Keywords: chemotherapy, photodynamic therapy, hyaluronic acid, responsive nanoparticle, drug delivery

Yu Guo,1,&ast; Qingyu Ma,1,&ast; Xuan Zhou,1 Juan Yang,2 Kejie He,3 Longbin Shen,4 Canghuan Zhao,3 Zhuoming Chen,4 Celia Ia Choo Tan,5 Jiaxu Chen1 1Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Jinan University, Guangzhou City, People’s Republic of China; 2Division of General Internal Medicine, Mayo Clinic, Rochester, MN, USA; 3Department of Acupuncture, First Affiliated Hospital of Jinan University, Guangzhou City, People’s Republic of China; 4Rehabilitation Medicine Center, First Affiliated Hospital of Jinan University, Guangzhou City, People’s Republic of China; 5Department of Physiotherapy, Singapore General Hospital, Singapore, Singapore&ast;These authors contributed equally to this workCorrespondence: Jiaxu Chen, Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Jinan University, No. 601 Huangpu Road West, Tianhe District, Guangzhou City, People’s Republic of China, Email chenjiaxu@hotmail.comPurpose: To evaluate the efficacy of different non-pharmacologic therapies (NPTs) on relieving depressive symptoms and pain intensity in individuals living with chronic low back pain (LBP) and associated depression.Methods: A comprehensive search of seven English databases and two Chinese databases from inception to the search date will be undertaken. The reference lists of previously published relevant reviews and included trials will also be searched. Only peer-reviewed and published moderate-to-high quality randomized controlled trials (RCTs) for chronic LBP and associated depression treated with NPTs will be considered. Two independent reviewers will identify studies, extract data, assess risk of bias, and evaluate the strength of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Meta-analysis will be conducted to estimate the treatment effect of various NPTs. Heterogeneity will be assessed using Cochrane’s Q and the I-squared statistics. Subgroup and sensitivity analyses will be performed to assess the robustness of findings. A funnel plot will be developed to evaluate reporting bias, and Begg’s and Egger’s tests will be used to assess funnel plot symmetries.Results: This protocol outlines the planned scope and methodology for an upcoming systematic review and meta-analysis, which will provide up-to-date evidence on 1) which NPTs are associated with improvements in depressive symptoms and pain intensity and 2) whether the effects of NPTs on chronic LBP and associated depression vary according to clinical condition, participant, and treatment characteristics.Conclusion: Our meta-analyses of moderate-to-high quality RCTs will help to develop specific recommendations on prescribing NPTs in patients with chronic LBP and associated depression.Study Registration: This protocol is registered on the International Platform of Registered Systematic Review and Meta-analysis (INPLASY) protocols platform as record No. INPLASY202260055.Keywords: non-pharmacologic therapies, chronic low back pain and associated depression, meta-analysis, randomized controlled trial, protocol

Danyang Li,1 Tong Wang,2 Qianli Ma,3 Lu Zhou,1 Yanqing Le,1 Yafei Rao,1 Liang Jin,1 Yuqiang Pei,1 Yaning Cheng,4 Chen Huang,5 Xiaoyan Gai,1 Yongchang Sun1 1Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 2Department of Thoracic Surgery, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 3Department of Thoracic Surgery, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China; 4School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, People’s Republic of China; 5Center of Basic Medical Research, Peking University Third Hospital, Beijing, 100191, People’s Republic of ChinaCorrespondence: Xiaoyan Gai; Yongchang Sun, Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, No. 49 North Garden Road, Haidian District, Beijing, 100191, People’s Republic of China, Email gxy81wfl79@163.com; suny@bjmu.edu.cnBackground: It has been reported that a disintegrin and metalloproteinase 9 (ADAM9) is involved in the pathogenesis of cigarette smoke (CS)-associated chronic obstructive pulmonary disease (COPD). But how CS exposure leads to upregulation of ADAM9 remains unknown.Methods: Patients who underwent lobectomy for a solitary pulmonary nodule were enrolled and divided into three groups: non-smokers with normal lung function, smokers without COPD and smoker patients with COPD. Immunoreactivity of interleukin (IL)-17A and ADAM9 in small airways and alveolar walls was measured by immunohistochemistry. Wild-type and Il17a−/− C57BL/6 mice were exposed to CS for six months, and ADAM9 expression in the airway epithelia was measured by immunoreactivity. In addition, the protein and mRNA expression levels of IL-17A and ADAM9 were assessed in CS extract (CSE) and/or IL-17A-treated human bronchial epithelial (HBE) cells.Results: The immunoreactivity of ADAM9 was increased in the airway epithelia and alveolar walls of patients with COPD compared to that of the controls. The expression of IL-17A was also upregulated in airway epithelial cells of patients with COPD and correlated positively with the level of ADAM9. The results from the animal model showed that Il17a−/− mice were protected from emphysema induced by CS exposure, together with a reduced level of ADAM9 expression in the airway epithelia, suggesting a possible link between ADAM9 and IL-17A. Consistently, our in vitro cell model showed that CSE stimulated the expression of ADAM9 and IL-17A in HBE cells in a dose- and time-dependent manner. Recombinant IL-17A induced ADAM9 upregulation in HBE cells and had a synergistic effect with CSE, whereas blocking IL-17A inhibited CSE-induced ADAM9 expression. Further analysis revealed that IL-17A induced c-Jun N-terminal kinase (JNK) phosphorylation, thereby increasing ADAM9 expression.Conclusion: Our results revealed a novel role of IL-17A in CS-related COPD, where IL-17A contributes to ADAM9 expression by activating JNK signaling.Keywords: chronic obstructive pulmonary disease, a disintegrin and metalloproteinase 9, interleukin-17A, airway epithelium

Zhen Hui,1,&ast; Kelei Guo,2,&ast; Chao Liu,3 Qishuai Ma,3 Weiwei Tian,2 Shujun Yao2 1School of Marxism, Zhaoqing University, Zhaoqing, People’s Republic of China; 2School of Physical Education and Health, Zhaoqing University, Zhaoqing, People’s Republic of China; 3School of Physical Education, Huaibei Normal University, Huaibei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kelei Guo; Chao Liu, Email 2021010043@zqu.edu.cn; 827056169@qq.comPurpose: This study examined the relationship between physical exercise (PE) and prosocial behavior (PSB) and constructed a chain mediation model through the mediating effect of physical education learning motivation (PELM) and emotional intelligence (EI).Methods: Through the stratified random sampling, 1053 students (average age = 14 years, SD = 0.96 years) that complied with the requirements were surveyed from Henan Province in China. PE, EI, PELM, and PSB were assessed using standard scales. For data analysis, Pearson’s correlation analysis, structural equation model test, and bias-corrected percentile Bootstrap method were carried out in turn.Results: (1) There was a significant positive correlation between PE and PSB (r = 0.137), and the direct path between PE and PSB was significant (β = 0.09, t = 4.73, p < 0.01); (2) PE can positively predict EI (β= 0.08, t = 5.27, p < 0.01) and PELM (β= 0.04, t = 2.07, p < 0.05), EI can significantly and positively PSB (β= 0.67, t = 22.12, p < 0.01), PELM can significantly and positively predict PSB (β= 0.05, t =2.20, p< 0.05); (3) EI and physical learning motivation play a significant intermediary role between PE and PSB. The mediating effect consists of three indirect effects: PE → EI → PSB (the mediating effect value is 0.055), PE → PELM → PSB (the mediating effect value is 0.002), PE → EI → PELM → PSB (the mediating effect value is 0.002); (4) The chain mediation effect is significant in girls, but not in boys.Conclusion: (1) PE can positively predict PSB. (2) EI and PELM had significant mediating effects between PE and PSB, including single mediating effects of EI and PELM and chain mediating effects of EI-PELM; (3) There are gender differences in the chain mediation effect.Keywords: physical exercise, emotional intelligence, physical education learning motivation, prosocial behavior, junior school students, COVID-19

Hao Chen,1,2,&ast; Qing Ma,3,&ast; Bo Du,1 Yan Huang,1 Shi-Guang Zhu,1 Sheng-Li Li,4 De-Qin Geng,1 Xing-Shun Xu2,5,6 1Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, People’s Republic of China; 2Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, 215000, People’s Republic of China; 3Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, People’s Republic of China; 4Department of Medical Records and Statistics, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, People’s Republic of China; 5Institute of Neuroscience, Soochow University, Suzhou, 215000, People’s Republic of China; 6Jiangsu Key Laboratory of Neuropsychiatric Diseases, Soochow University, Suzhou, 215000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: De-Qin Geng, Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, People’s Republic of China, Tel +86 18052268197, Email gengdeqingdq@outlook.com Xing-Shun Xu, Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, 215000, People’s Republic of China, Tel +86 13915411326, Email xuxingshunxxs@126.comObjective: The present study aims to analysis the mental health of high-risk health care workers (HHCWs) and low-risk HCWs (LHCWs) who were respectively exposed to COVID-19 wards and non-COVID-19 wards by following up on mental disorders in HCWs in China for 6 months.Methods: A multi-psychological assessment questionnaire was used to follow up on the psychological status of HCWs in the Affiliated Hospital of Xuzhou Medical University in Xuzhou City (a non-core epidemic area) at 6 months after the first evaluation conducted during the COVID-19 epidemic. Based on the risk of exposure to COVID-19 patients, the HCWs were divided into two groups: high-risk HCWs, who worked in COVID-19 wards, and low-risk HCWs, who worked in non-COVID-19 wards.Results: A total of 198 HCWs participated in the study, and 168 questionnaires were selected for evaluation. Among them, 93 (55.4%) were in the HHCW group and 75 (44.5%) were in the LHCW group. Significant differences were observed in salary, profession, and altruistic behavior between the two groups (P < 0.05). There were no significant differences in the anxiety, depression, insomnia, or posttraumatic stress disorder (PTSD) scores between the two groups. Logistic regression revealed that work stress was a major joint risk factor for mental disorders in HCWs. Among all the HCWs, a total of 58 voluntarily participated in psychotherapy; the analysis showed a significant decrease in anxiety, depression, PTSD, work stress, and work risk after attending psychotherapy. There were also significant differences in positive and negative coping styles before and after psychotherapy.Conclusion: In the present follow-up, work stress was the major contributing factor to mental disorders in HCWs. Psychotherapy is helpful in terms of stress management and should be provided to first-line COVID-19 HCWs.Keywords: COVID-19, anxiety, depression, posttraumatic stress disorder, insomnia, work stress

Hai Yin,1 Qiliang Ma,2 Junwei Zhuang,1 Wei Yu,1 Zhongyou Wang3 1School of Biomedical Engineering and Medical Imaging, Xianning Medical College, Hubei University of Science and Technology, Xianning, 437100, People’s Republic of China; 2School of Mathematics and Computer, Wuhan Textile University, Wuhan, 430200, People’s Republic of China; 3School of Computer Science and Technology, Hubei University of Science and Technology, Xianning, 437100, People’s Republic of ChinaCorrespondence: Zhongyou Wang, Email wzy1963@163.comIntroduction: Heart sound signal is an important physiological signal of human body, and the identification and research of heart sound signal is of great significance.Methods: For abnormal heart sound signal recognition, an abnormal heart sound recognition system, combining hidden semi-Markov models (HSMM) with deep neural networks, is proposed. Firstly, HSMM is used to build a heart sound segmentation model to accurately segment the heart sound signal, and then the segmented heart sound signal is subjected to feature extraction. Finally, the trained deep neural network model is used for recognition.Results: Compared with other methods, this method has a relatively small amount of input feature data and high accuracy, fast recognition speed.Discussion: HSMM combined with deep neural network is expected to be deployed on smart mobile devices for telemedicine detection.Keywords: heart sound signal, recognition, hidden semi-Markov, neural network

Hao Wu,1 Min Wei,1 Yu Xu,2 Yuping Li,3 Xue Zhai,4 Peng Su,4 Qiang Ma,3 Hengzhu Zhang3 1Neurosurgery, Graduate School of Dalian Medical University, Dalian, People’s Republic of China; 2Nanotechnology, Jinling Institute of Technology, Nanjing, People’s Republic of China; 3Department of Neurosurgery, Clinical Medical College, Yangzhou University, Yangzhou, People’s Republic of China; 4Department of Advanced Materials, Nanjing University of Posts & Telecommunications, Nanjing, People’s Republic of ChinaCorrespondence: Hengzhu Zhang, 98 Nantong Xi Lu, Yangzhou, Jiangsu Province, People’s Republic of China, Tel +86 18051061558, Fax +86-0514-87373562, Email zhanghengzhu@sina.comAbstract: Glioma is characterized by high mortality and low postoperative survival. Despite the availability of various therapeutic approaches and molecular typing, the treatment failure rate and the recurrence rate of glioma remain high. Given the limitations of existing therapeutic tools, nanotechnology has emerged as an alternative treatment option. Nanoparticles, such as polydopamine (PDA)-based nanoparticles, are embodied with reliable biodegradability, efficient drug loading rate, relatively low toxicity, considerable biocompatibility, excellent adhesion properties, precisely targeted delivery, and strong photothermal conversion properties. Therefore, they can further enhance the therapeutic effects in patients with glioma. Moreover, polydopamine contains pyrocatechol, amino and carboxyl groups, active double bonds, catechol, and other reactive groups that can react with biofunctional molecules containing amino, aldehyde, or sulfhydryl groups (main including, self-polymerization, non-covalent self-assembly, π-π stacking, electrostatic attraction interaction, chelation, coating and covalent co-assembly), which form a reversible dynamic covalent Schiff base bond that is extremely sensitive to pH values. Meanwhile, PDA has excellent adhesion capability that can be further functionally modified. Consequently, the aim of this review is to summarize the application of PDA-based NPs in glioma and to acquire insight into the therapeutic effect of the drug-loaded PDA-based nanocarriers (PDA NPs). A wealthy understanding and argument of these sides is anticipated to afford a better approach to develop more reasonable and valid PDA-based cancer nano-drug delivery systems. Finally, we discuss the expectation for the prospective application of PDA in this sphere and some individual viewpoints.Keywords: glioma, polydopamine, polymeric nanoparticles, photothermal therapy, chemotherapy, synergistic therapy

Maya R Chilbert,1,2 Dylan VanDuyn,3 Sara Salah,1 Collin M Clark,1,2 Qing Ma1 1Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, NY, USA; 2Department of Pharmacy, Buffalo General Medical Center, Buffalo, NY, USA; 3Department of Pharmacy, Buffalo Veterans Affairs Medical Center, Buffalo, NY, USACorrespondence: Maya R Chilbert, Department of Pharmacy Practice, University at Buffalo School of Pharmacy and Pharmaceutical Sciences, 202 Pharmacy Building, Buffalo, NY, USA, Tel +1 716 829-5172, Fax +1 716-829-6093, Email mayahols@buffalo.eduAbstract: Cardiovascular disease is one of the leading causes of death around the world with various efforts being made to reduce risk in patients through preventive measures. One major method for prevention has been managing cholesterol, particularly low-density lipoprotein to decrease atherosclerotic plaque burden, potentially decreasing future cardiac complications. Statins have been the gold standard therapy for hypercholesterolemia treatment due to their ease of dosing, limited drug interactions, and favorable safety profile. Unfortunately, statin therapy alone is not always effective enough to adequately control a patient’s elevated lipid levels and combination therapy may be warranted. Ezetimibe is commonly added to regimens to help augment cholesterol lowering by inhibiting the absorption of cholesterol. The recent approval of a combination tablet of high-intensity rosuvastatin and ezetimibe has introduced a potentially more beneficial option for cholesterol management in addition to the only available combination of moderate intensity simvastatin and ezetimibe. We aimed to identify potential beneficial effects of ezetimibe by comparing its use in combination with high-intensity rosuvastatin compared to a statin therapy alone or in combination with moderate intensity simvastatin through a literature review. The current evidence indicated that combination therapy outperformed statin monotherapy in reduction of low-density lipoprotein cholesterol and patients were more likely to achieve their target low-density lipoprotein cholesterol goal level. This suggests rosuvastatin/ezetimibe combination holds a potential place in therapy for patients requiring a more aggressive reduction in cholesterol to help prevent atherosclerotic disease.Keywords: hypercholesterolemia, hyperlipidemia, cardiac events, lipid biomarkers, atherosclerosis

Xinhua Luo,1,&ast; Jin Zhang,1,&ast; Min Yuan,2 Sihua Mou,1 Mengqiao Xu,1 Dakang Hu,1 Qinfei Ma,1 Lingfen Sun,1 Piaopiao Li,1 Zhiwei Song,1 Lianhua Yu,1 Kai Mu3,4 1Department of Clinical Laboratory Medicine, Taizhou Municipal Hospital Affiliated with Taizhou University, Taizhou, 318000, People’s Republic of China; 2State Key Laboratory for Infectious Diseases Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, People’s Republic of China; 3Beijing Institute of Radiation Medicine, Beijing, 100850, People’s Republic of China; 4Beijing Key Laboratory of New Molecular Diagnosis Technologies for Infectious Diseases, Beijing, 100850, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kai Mu, Beijing Key Laboratory of New Molecular Diagnosis Technologies for Infectious Diseases, Beijing, 100850, People’s Republic of China, Tel +86-010-66874794, Email kai_mu@outlook.com Lianhua Yu, Department of Clinical Laboratory Medicine, Taizhou Municipal Hospital affiliated with Taizhou University, Taizhou, 318000, People’s Republic of China, Email yulianhua64@126.comPurpose: This study aimed to explore the genomic characterization of multidrug-resistant IncHI5-carrying Klebsiella michiganensis strains and detailed genomic dissection of the IncHI5 plasmids.Materials and Methods: Through whole-genome sequencing, the IncHI5 plasmid pK92-qnrS was obtained from a single clinical K. michiganensis isolate K92. All complete genomes of K. michiganensis strains from the Genome database of NCBI were collected and used to construct a maximum likelihood (ML) phylogenetic tree. The epidemiology and geographic distribution of all the K. michiganensis strains were conducted. An extensive comparison of the seven IncHI5 plasmids of K. michiganensis (one from this study, six from GenBank) was applied.Results: This study revealed that all K. michiganensis strains carrying IncHI5 plasmids from different clonal groups were located in the southeast coastal area of China. The backbone regions of IncHI5 plasmids were composed of replicon (repHI5B and repFIB), partition (parABC), and conjugal transfer (tra1/tra2). The main accessory resistant regions of IncHI5 could be divided into two categories, Tn 1696-related region and Tn 6535-related region. These seven IncHI5 plasmids carried multiple drug-resistance genes which were all mediated by the mobile genetic elements (MGEs).Conclusion: Data presented here help to provide an overall in-depth understanding of epidemiology and geographic distribution of IncHI5-carrying K. michiganensis and the structure and evolutionary history of IncHI5 plasmids.Keywords: Klebsiella michiganensis, mobile genetic elements, Tn 1696, Tn 6535, antimicrobial resistance

Xianhua Liao,1 Qianqian Ma,1 Tingfeng Wu,1 Congxiang Shao,1 Yansong Lin,1 Yanhong Sun,2 Shiting Feng,3 Wei Wang,4 Junzhao Ye,1 Bihui Zhong1 1Department of Gastroenterology of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Laboratory of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Department of Radiology of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 4Department of Medical Ultrasonics of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of ChinaCorrespondence: Bihui Zhong; Junzhao Ye, Department of Gastroenterology of the First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan II Road, Yuexiu District, Guangzhou, 510080, People’s Republic of China, Tel +86 135 0307 9262 ; +86 135 0151 9252, Email zhongbh@mail.sysu.edu.cn; yejzh@mail2.sysu.edu.cnPurpose: Effective treatment of dyslipidemia with lipid-lowering agents is pivotal in the management of metabolic-associated fatty liver disease (MAFLD) for preventing cardiovascular complications. We explored the associations between improvements in liver injuries indicated by changes in transaminases and a reduction in lipid levels in MAFLD patients with dyslipidemia and elevated transaminases during lipid-lowering therapies.Methods: This prospective, cohort study enrolled consecutive MAFLD patients with hyperlipidemia and elevated transaminases. Patients were divided into a group receiving lipid-lowering agents and an age-, sex- and baseline lipid level-matched control group without receiving lipid-lowering agents. Clinical visits were performed at the 1st month and then every 3 months for 1 year.Results: This study included 541 MAFLD patients (lipid-lowering group: 325 patients; control group: 216 patients). Compared with controls, there was a substantially greater reduction in alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transpeptidase (GGT), triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) in the lipid-lowering group after 12 months (all P < 0.05). The decrease in ALT was positively correlated with the decrease in TC (r = 0.332), TG (r = 0.180), LDL-c (r = 0.253) and apolipoprotein E (ApoE) (r = 0.119), while the decrease in AST was positively correlated with the decrease in TC (r = 0.228) and LDL-c (r = 0.192) (all P< 0.05). The greater range of reduction in blood lipids (TC/TG/LDL-c), the higher the transaminase and GGT normalization rate (all P< 0.05). Multivariate analysis confirmed that a TG decrease of over 50% remained an independent predictor of transaminase and GGT normalization (OR 2.07, 95% CI 1.12– 3.84, P=0.020).Conclusion: Lipid-lowering to target levels might be beneficial to liver injury improvements in MAFLD patients with dyslipidemia when receiving lipid-lowering agents.Keywords: dyslipidemia, metabolic dysfunction-associated fatty liver disease, alanine aminotransferase, triglyceride, gamma glutamyl transpeptidase, statins

Daidai Wang,1,&ast; Hua Zhang,2,&ast; Lanfang Du,1,&ast; Qiangrong Zhai,1 Guangliang Hu,1 Wei Gao,1 Anyi Zhang,1 Sa Wang,1 Yajuan Hao,1 Kaijian Shang,1,3 Xueqing Liu,1 Yanxia Gao,4 Nijiati Muyesai,5 Qingbian Ma1 1Department of Emergency Medicine, Peking University Third Hospital, Beijing, People’s Republic of China; 2Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, People’s Republic of China; 3Department of Emergency Medicine, Second hospital of Shanxi Medical University, Shanxi, People’s Republic of China; 4Department of Emergency Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 5Department of Emergency Medicine, Xinjiang Ulger Municipal People’s Hospital, Urumqi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingbian Ma; Nijiati Muyesai, Tel +86 15611908229, Email maqingbian@126.com; muyassar11@aliyun.comPurpose: Acute aortic syndrome is a constellation of life-threatening medical conditions for which rapid assessment and targeted intervention are important for the prognosis of patients who are at high risk of in-hospital death. The current study aims to develop and externally validate an early prediction mortality model that can be used to identify high-risk patients with acute aortic syndrome in the emergency department.Patients and Methods: This retrospective multi-center observational study enrolled 1088 patients with acute aortic syndrome admitted to the emergency departments of two hospitals in China between January 2017 and March 2021 for model development. A total of 210 patients with acute aortic syndrome admitted to the emergency departments of Peking University Third Hospital between January 2007 and December 2021 was enrolled for model validation. Demographics and clinical factors were collected at the time of emergency department admission. The predictive variables were determined by referring to the results of previous studies and the baseline analysis of this study. The study’s endpoint was in-hospital death. To assess internal validity, we used a fivefold cross-validation method. Model performance was validated internally and externally by evaluating model discrimination using the area under the receiver-operating characteristic curve (AUC). A nomogram was developed based on the binary regression results.Results: In the development cohort, 1088 patients with acute aortic syndromes were included, and 88 (8.1%) patients died during hospitalization. In the validation cohort, 210 patients were included, and 20 (9.5%) patients died during hospitalization. The final model included the following variables: digestive system symptoms (OR=2.25; P=0.024), any pulse deficit (OR=7.78; P< 0.001), creatinine (μmol/L)(OR=1.00; P=0.018), lesion extension to iliac vessels (OR=4.49; P< 0.001), pericardial effusion (OR=2.67; P=0.008), and Stanford type A (OR=10.46; P< 0.001). The model’s AUC was 0.838 (95% CI 0.784– 0.892) in the development cohort and 0.821 (95% CI 0.750– 0.891) in the validation cohort, and the Hosmer–Lemeshow test showed p=0.597. The fivefold cross-validation demonstrated a mean accuracy of 0.94, a mean precision of 0.67, and a mean recall of 0.13.Conclusion: This risk prediction tool uses simple variables to provide robust prediction of the risk of in-hospital death from acute aortic syndrome and validated well in an independent cohort. The tool can help emergency clinicians quickly identify high-risk acute aortic syndrome patients, although further studies are needed for verifying the prospective data and the results of our study.Keywords: acute aortic syndrome, risk prediction model, emergency department

Qingen Da,1,2,&ast; Mingming Ren,2,&ast; Lei Huang,2 Jianhua Qu,1 Qiuhua Yang,3 Jiean Xu,4 Qian Ma,4 Xiaoxiao Mao,4 Yongfeng Cai,4 Dingwei Zhao,4 Junhua Luo,5 Zilong Yan,1 Lu Sun,2 Kunfu Ouyang,2 Xiaowei Zhang,6 Zhen Han,2 Jikui Liu,1 Tao Wang2 1Department of Hepatobiliary Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, People’s Republic of China; 2Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, People’s Republic of China; 3Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA, USA; 4Shenzhen Graduate School, Peking University, Shenzhen, People’s Republic of China; 5Department of Urological Surgery, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China; 6School of Basic Medical Sciences, Peking University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jikui Liu, Department of Hepatobiliary Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, People’s Republic of China, Email liu8929@126.com Tao Wang, Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, People’s Republic of China, Email szwangtao@126.comObjective: We aimed to explore the prognostic patterns of ferroptosis-related genes in papillary renal cell carcinoma (PRCC) and investigate the relationship between ferroptosis-related genes and PRCC tumor immune microenvironment.Methods: We obtained the mRNA expression and corresponding clinical data of PRCC from the public tumor cancer genome atlas database (TCGA). The PRCC patients were randomly divided into two cohort, training cohort and verification cohort, respectively. Univariate Cox regression, LASSO Cox regression, multivariate Cox regression analysis were utilized to construct ferroptosis signature for PRCC patients. And then, risk prognostic model was established and verified. The correlation of ferroptosis-related signature with survival and immune microenvironment was systematically analyzed.Results: A 4-genes ferroptosis signature (CDKN1A, MIOX, PSAT1, and RRM2) was constructed. Multivariate Cox regression assay indicates that the risk score of ferroptosis signature was an independent prognostic indicator (HR=1.391, p< 0.001). The survival curve shows that the high-risk group has a poorer prognosis than the low-risk group (p< 0.001). The risk prognostic model was established based on prognostic factors of clinical-stage, hemoglobin, and risk score. The time-dependent receiver operating characteristic curve (ROC) analysis proves the predictive capacity of the ferroptosis signature, the 3 years area under the curve (AUC) is 0.890, and the 5 years AUC is 0.733. Further analysis suggested that cell cycle, pentose phosphate pathway, P53 signaling pathway were significantly enriched in the high-risk group. The significantly different fractions of dendritic cells resting, macrophage cells, and T cells follicular helper were observed in risk groups.Conclusion: This study implicates a ferroptosis signature which has a good predict capacity of the prognosis in PRCC patients. Ferroptosis-related genes may have a key role in the process of anti-tumor and serve as therapeutic targets for PRCC.Keywords: papillary renal cell carcinoma, ferroptosis, gene signature, prognosis model, tumor immune microenvironment

Xiaowu Zhong,1– 3,&ast; Lihua Yao,1,2,&ast; Lei Xu,3,&ast; Qiang Ma,1,2 Guangcheng Huang,1,2 Miyuan Yang,2 Chuanli Gao,2 Jibing Cheng,1,2 Xi Zhou,2 Qinrong Li,2 Xiaolan Guo1– 3 1Department of Clinical Laboratory, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, People’s Republic of China; 2Department of Laboratory Medicine, North Sichuan Medical College, Nanchong, 637000, People’s Republic of China; 3Translational Medicine Research Center, North Sichuan Medical College, Nanchong, 637000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaolan Guo, Department of Clinical Laboratory, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, People’s Republic of China, Tel +86-817-2282059, Fax +86-817-2282059, Email alan5200@hotmail.comBackground: Lung adenocarcinoma (LUAD) is the most common dangerous malignant tumor and the leading cause of global cancer incidence and mortality. The Solute Carrier 1A (SLC1A) family play a significant part in cellular biological process, inflammation, and immunity. Specific functions of the SLC1A family in lung cancer are still not systematically described.Objective: This study aimed to explore the best biological understanding of SLC1A family in lung cancer.Methods: To study the expression and role of the SLC1A family in lung cancer, researchers used a variety of bioinformatics databases and tools.Results: Aberrant expression of SLC1A family genes were demonstrated and analyzed the association with gender, tumor grade, cancer stages, and nodal metastasis status. The ectopic expression of SLC1A family genes has prognostic value for LUAD patients. Immune infiltration revealed a significant correlation between SLC1A family genes expression in LUAD. SLC1A family genes were involved in manifold biological processes and have different levels of DNA methylation and genetic alteration.Conclusions: These findings suggested that members of the SLC1A family could be a potential target for the development of LUAD therapeutics as well as a reliable indicator of LUAD prognostic value.Graphical Abstract: Keywords: lung adenocarcinoma, SLC1A family, expression, prognosis, bioinformatics analysis

Hui Gao,1,2 Jin Xu,2 Qiang Ma,2 Feng Tang,1 Qin Ga,1 Yuhong Li,3 Wei Guan,3 Ri-Li Ge,1 Ying-Zhong Yang1,2 1Research Center for High Altitude Medical Sciences, School of Medicine, Qinghai University, Qinghai, People’s Republic of China; 2Basic Medical Sciences, School of Medicine, Qinghai University, Qinghai, People’s Republic of China; 3Department of Respiration, Affiliated Hospital, Qinghai University, Qinghai, People’s Republic of ChinaCorrespondence: Ying-Zhong Yang Tel/Fax +86 971 6143168Email yingzhong-yang@hotmail.comPurpose: Steroid hormone metabolism plays an essential role in high-altitude pulmonary edema (HAPE) progression. This study aimed to investigate the association between polymorphism in seven steroid hormone metabolism genes (STAR, HSD3B1, HSD3B2, CYP17A1, CYP21A2, CYP11B1, and CYP11B2) and HAPE susceptibility among Han Chinese.Patients and Methods: A total of 41 tagSNPs in the seven genes were genotyped using Sequenom MassARRAY SNP assays from 169 HAPE patients (HAPE-p) and 309 matched Han Chinese individuals resistant to HAPE (HAPE-r). The genotypic and allele frequencies, odds ratios (ORs), and 95% confidence intervals (95% CIs) were calculated.Results: Four SNPs, including the allele C of rs6203 (p = 0.034, OR [95% CI] = 1.344 [1.022− 1.767]) in HSD3B1, allele G of rs3740397 (p = 0.044, OR [95% CI] = 1.314 [1.007− 1.714]) and allele C of rs10786712 (p = 0.039, OR [95% CI] = 0.751 [0.572− 0.986]) in CYP17A1, and allele T of rs6402 (p = 0.006, OR [95% CI] = 0.504 [0.306− 0.830]) in CYP11B1, were significantly associated with HAPE. The distribution of the genotypes of these SNPs also significantly differed between the HAPE-p and HAPE-r groups. Moreover, six haplotypes (the linkage disequilibrium block including rs10883783, rs4919686, rs3740397, rs3824755, and rs10786712) of CYP17A1 were also significantly associated with HAPE.Conclusion: The four SNPs located in HSD3B1 (rs6203), CYP17A1 (rs3740397 and rs10786712), and CYP11B1 (rs6402) and the six haplotypes of CYP17A1 are likely to have an effect on HAPE.Keywords: steroid hormone metabolism gene, SNP, high-altitude pulmonary edema, susceptibility

Paul W Jones,1 Chanzheng Wang,2 Ping Chen,3 Liping Chen,4 Daoxin Wang,5 Junbo Xia,6 Yang Yang,7 Yingyu Wang,7 Qianli Ma2 1Global Medical, Regulatory and Quality, GlaxoSmithKline plc., Brentford, UK; 2Respiratory Department, Chongqing Xinqiao Hospital, Chongqing, People’s Republic of China; 3Respiratory Department, General Hospital of the Northern Theater Command of the People’s Liberation Army, Shenyang, People’s Republic of China; 4Respiratory Department, The Second Affiliated Hospital of Shenyang Medical College, Shenyang, People’s Republic of China; 5Respiratory Department, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 6Respiratory Department, Hangzhou First People’s Hospital, Hangzhou, Zhejiang, People’s Republic of China; 7Research and Development, GlaxoSmithKline plc., Shanghai, People’s Republic of ChinaCorrespondence: Paul W Jones, Global Medical, Regulatory and Quality, GlaxoSmithKline plc., Brentford, UK, Email paul.8.jones@gsk.comIntroduction: Many patients with chronic obstructive pulmonary disease (COPD) do not report exacerbations and may benefit from simple guidance about when to seek medical attention, so we developed a COPD Exacerbation Recognition Tool (CERT).Methods: The study was run across three sites in China in patients who had an exacerbation within the previous year. Step 1: focus group qualitative study (total 48 patients) captured symptoms associated with an exacerbation. Step 2: cognitive debriefing to ensure items were appropriately worded. Step 3: 150 patients (69 years, 21% female, FEV1 63% predicted, CAT 15, 2 exacerbations in previous year) completed a questionnaire composed of the items from Steps 1 and 2 using two response options – severity during an exacerbation and magnitude of change from usual state. Responses were analysed in terms of frequency and tested for influence of demographic factors. Exploratory factor analysis (EFA) identified key domains. Using these results, an expert panel guided choice of items that formed the CERT.Results: Following Steps 1 and 2, 29 candidate items were selected for Step 3. Response rates with the two response options were very similar. There was minimal influence of demographic factors on response to the items. EFA using the 11 items with the highest response rates identified two principal factors, Factor 1: breathlessness and activity limitation (79.1% of variance), Factor 2: cough and sputum (20.9% of variance). Five items were selected for the CERT based on response rate and EFA factor loading: worsening cough, increased sputum volume, shortness of breath, laborious breathing, and limitation of motion. Sensitivity analysis suggested that worsening of two or more symptoms had good sensitivity and specificity for the presence of an exacerbation.Discussion: The CERT is an evidence-based tool to provide patients with simple-to-follow guidance about when to seek medical attention when their COPD symptoms worsen.Keywords: chronic obstructive pulmonary disease, exacerbations, COPD exacerbation tool

The A7N01-T5 aluminum alloy plates with the thickness of 12 mm were welded with the ER5356 and ER5087 welding wires, respectively, by the method of Metal Inert Gas (MIG) welding. The mechanical properties and microstructures of the welded joints were investigated by micro-hardness measurement, tensile test, energy dispersive spectroscopy (EDS), electron backscattered diffraction (EBSD) and transmission electron microscopy (TEM). The results showed that the tensile strength and elongation of 7N01/5087 welded joint (the 7N01 aluminum alloy plate welded with ER5087 wire) were greater than those of 7N01/5356 welded joint (the 7N01 aluminum alloy plate welded with ER5356 wires), respectively. The high strength and the good elongation of 7N01/5087 welded joint were mainly attributed to the microstructure refinement in the weld zone through adding Zr element to promote the nucleation of Al grains around the Al3Zr sites.

Yaohua Zhai, Chenjiu Pang, Shengtao Sun, Qiufei Ma, Lei Han, Yuwei Gu, Lizhe Gu Henan Provincial People’s Hospital, Henan Eye Hospital, Henan Eye Institute, Zhengzhou, 450003, People’s Republic of ChinaCorrespondence: Chenjiu Pang Email Pangcj999@126.comPurpose: Systematic review of Gemella haemolysans infection associated with ophthalmology, and to summarize the clinical characteristics of Gemellahaemolysans keratitis after refractive surgery.Methods: Case report and literature review.Results: We report an 18-year-old man who developed corneal infection after Trans-PRK, and the culture results of lesion specimens confirmed G. haemolysans keratitis. He was treated with fortified topical antibiotics, and clinical improvement was noted shortly after treatment. Resolution of keratitis was achieved at 1 month. Then, a systematic review of the reported cases of ocular G. haemolysans infection was conducted. We summarized clinical manifestations of G. haemolysans infection in cornea.Conclusion: We reported a case of G. haemolysans keratitis infection after refractive surgery, and reviewed the literature of ocular G. haemolysans infection.Keywords: trans-PRK, refractive surgery, postoperative infection, Gemella haemolysans, bacterial keratitis

Baoya Wang,1 Wenjuan Dong,2 Liyan Ma,3 Yonghui Dong,4 Shanmei Wang,1 Youhua Yuan,1 Qiong Ma,1 Junhong Xu,1 Wenjuan Yan,1 Jing Nan,1 Qi Zhang,1 Wenbo Xu,1 Bing Ma,1 Yafei Chu,1 Jiangfeng Zhang,1 Li Li,1 Yi Li1 1Department of Clinical Microbiology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, and People’s Hospital of Henan University, Zhengzhou, 450003, Henan, People’s Republic of China; 2Department of Clinical Microbiology, Xicheng District Pingan Hospital, Beijing, 100035, People’s Republic of China; 3Department of Clinical Microbiology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People’s Republic of China; 4Department of Osteology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, and People’s Hospital of Henan University, Zhengzhou, 450003, Henan, People’s Republic of ChinaCorrespondence: Yi Li; Li LiDepartment of Clinical Microbiology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, and People’s Hospital of Henan University, Weiwu Road 5, Zhengzhou, 450003, Henan, People’s Republic of ChinaTel +8637165580484Fax +8637187160318Email liyilabmed@henu.edu.cn; hnykylili@126.comObjective: This study aimed to investigate the prevalence, genetic diversity and clinical characteristics of Clostridium perfringens isolates from hospitalized clinical diarrheal patients.Methods: A prospective study was conducted on 1108 patients with diarrhea during hospitalization. Stool samples were cultured for C. perfringens, and the toxin genes were detected by PCR. The available clinical data of 112 patients were analyzed to study the clinical features of various isolates. Multi-locus sequence typing (MLST) was performed to assess phylogenetic relationship between different isolates.Results: A total of 153 (13.8%) isolates were obtained from patients’ stools. C. perfringens type F (49.0%) was the major toxin type in the isolates, followed by type A (n = 59, 38.6%) and type C (n = 14, 9.2%). Patients older than 50 years and those with underlying diseases of cancer, hepatobiliary system, and ulcerative colitis (UC) were more predisposed to C. perfringens type F and type A infection than to type C. The patients infected with type C experienced more severe clinical symptoms compared to those with type A infection. There was a significant association between type FC and foodborne gastrointestinal (GI) diseases (p = 0.018), between type FP and antibiotic-associated diarrhea (AAD) (p < 0.001), and between type A and sporadic diarrhea (SD) (p < 0.001). Phylogenetic analysis indicated that type F isolates carrying a chromosomal cpe gene mainly belonged to ST77 (6/15 isolates). Type F isolates with cpe gene on a plasmid exhibited high genetic diversity.Conclusion: High prevalence and considerable genetic diversity of C. perfringens type F were found in clinical diarrheal patients. Elderly people and patients with cancer, hepatobiliary diseases or UC, or suspected of having food poisoning (FP) may be targeted for routine testing of C. perfringens toxin genes and may benefit from early detection of C. perfringens type C isolates that cause more severe clinical symptoms.Keywords: Clostridium perfringens, toxin type, clinical characteristics, prevalence, MLST

Yuanyuan Li,1,&ast; Dai Zhang,1,&ast; Qing Ma,1 Zongli Diao,2 Sha Liu,2 Xiaotian Shi1 1Department of Geriatrics, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Nephrology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qing MaDepartment of Geriatrics, Beijing Friendship Hospital, Capital Medical University, No. 95, Yong’an Road, Xicheng District, Beijing, 100050, People’s Republic of ChinaTel +86 10 63137641Fax +86 10 63138730Email maqing@ccmu.edu.cnPurpose: To explore the impact of frailty on adverse outcomes in elderly hemodialysis (HD) patients.Patients and Methods: An observational and prospective cohort study was conducted in elderly patients (≥ 60) with HD, with an average 12-month follow-up. Fried frailty phenotype (FFP) was used to define frailty. Negative binomial regression was used to estimate the impact of frailty on the incidence of emergency visits, hospitalizations, acute cardiovascular events, and falls within a year. Cox regression analysis was used to assess the influence of frailty on all-cause mortality in elderly HD patients.Results: Our study enrolled 150 elderly HD patients, and the prevalence of frailty was 34.7%. After adjustment, frailty was independently associated with increased all-cause mortality [hazard ratio (HR)=4.10, 95% CI: 1.09– 15.43, p=0.037] and emergency visits [incidence rate ratio (IRR)=2.78 95% CI: 1.70– 4.60, p< 0.001]. Gait speed was an independent risk factor for all-cause deaths (HR=5.56 95% CI: 1.41– 22.00, p=0.014), emergency visits (IRR=2.52 95% CI: 1.48– 4.33, p< 0.001), and hospitalizations (IRR=2.24, 95% CI: 1.19– 4.21, p=0.010) in elderly HD patients.Conclusion: Frailty was an independent indicator of all-cause mortality and emergency visits in elderly patients with HD.Keywords: elderly people, frailty, hemodialysis, mortality, emergency visits, hospitalizations