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Dong Wu,1,&ast; Bingyu Long,1,&ast; Bangxiao Huang,1,&ast; Xiaomei Zhong,1 Xiaoer Chen,1 Xiaoping Shen,1 Qiu Huang,1 Wenchao Zhang,1 Jiayuan Wu,2 Min Chen,1 Dongming Li,1 Bin Wu,1 Dong Lv,3 Dan Huang,1 Xuanna Zhao1 1Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, People’s Republic of China; 2Department of Clinical Research, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, People’s Republic of China; 3Department of Psychiatry, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuanna Zhao; Dan Huang, Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, No. 57, South of Renmin Road, Zhanjiang, Guangdong, 524013, People’s Republic of China, Email 792665234@qq.com; 287538250@qq.comBackground: Education and living environment are related to mental health. But the independent and combined effects of them on mental health among patients with chronic obstructive pulmonary disease (COPD) are uncertain.Methods: The independent and combined effects of education and living environment on mental health were assessed by binary logistic regression in 1064 COPD patients. Additive interaction was assessed with the relative excess risk ratio (RERI), attribution percentage (AP), and synergy index (SI).Results: Our results shown that low education level and urban living environment were independently associated with higher risks for anxiety (odds ratio [OR]: 1.56, 95% confidence interval [CI] 1.06– 2.29 and OR:2.15, 95% CI 1.51– 2.05) or depression (OR:1.62, 95% CI 1.17– 2.27 and OR: 2.01, 95% CI 1.46– 2.75) among COPD patients. The combination effect of them was also associated with higher risks for anxiety (OR: 7.90, 95% CI 3.83– 16.29, P < 0.001) or depression (OR: 11.79, 95% CI 5.77– 24.10, P < 0.001) among these patients. Furthermore, we observed strong synergistic additive interactions between them for anxiety (SI: 11.57, 95% CI 1.41– 95.27; RERI: 6.31, 95% CI 1.60– 11.01; AP: 0.8, 95% CI 0.66– 0.94) and depression (SI: 31.31, 95% CI 1.59– 617.04; RERI: 10.44, 95% CI 2.66– 18.23; AP: 0.89, 95% CI 0.8– 0.97).Conclusion: Low education levels and living in urban areas had an independent and synergistic effects on mental health among COPD patients.Keywords: anxiety, China, COPD, depression, education, living environment

Dan Lv,1 Yuling Liu,1 Ruying Tang,1 Sai Fu,1 Shasha Kong,1 Qian Liao,1 Hui Li,1,2 Longfei Lin1 1Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, People’s Republic of China; 2Institute of Traditional Chinese Medicine Health Industry, China Academy of Chinese Medical Sciences, Jiangxi, 330006, People’s Republic of ChinaCorrespondence: Hui Li; Longfei Lin, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Nanxiaojie 16, 8 Dongzhimennei Ave, Beijing, 100700, People’s Republic of China, Tel +86-10-64032658, Email hli1967@icmm.ac; lflin@icmm.ac.cnAbstract: The potential anti-cancer effect of traditional Chinese medicine (TCM) monomers has been widely studied due to their advantages of well-defined structure, clear therapeutic effects, and easy quality control during the manufacturing process. However, clinical trial information on these monomers is scarce, resulting in a lack of knowledge regarding the research progress, efficacy, and adverse reactions at the clinical stage. Therefore, this study systematically reviewed the clinical trials on the anti-cancer effect of TCM monomers registered in the Clinicaltrials.gov website before 2023.4.30, paying special attention to the trials on tumors, aiming to explore the research results and development prospects in this field. A total of 1982 trials were started using 69 of the 131 TCM monomers. The number of clinical trials performed each year showed an overall upward trend. However, only 26 monomers entered into 519 interventional anti-tumor trials, with vinblastine (194, 37.38%) and camptothecin (146, 28.13%) being the most used. A total of 45 tumors were studied in these 519 trials, with lymphoma (112, 21.58%) being the most frequently studied. Clinical trials are also unevenly distributed across locations and sponsors/collaborators. The location and the sponsor/collaborator with the highest number of performed trials were the United States (651,32.85%) and NIH (77). Therefore, China and its institutions still have large room for progress in promoting TCM monomers in anti-tumor clinical trials. In the next step, priority should be given to the improvement of the research and development ability of domestic enterprises, universities and other institutions, using modern scientific and technological means to solve the problems of poor water solubility and strong toxic and side effects of monomers, so as to promote the clinical research of TCM monomers.Keywords: traditional Chinese medicine monomers, anti-cancer, interventional clinical trials, research progress, adverse reactions

Yang Qian, Chenting Cai, Mengqing Sun, Dan Lv, Yun Zhao The First Affiliated Hospital of Ningbo University, Ningbo, People’s Republic of ChinaCorrespondence: Dan Lv, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang Province, People’s Republic of China, Email fylvdan@nbu.edu.cnAbstract: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is the exacerbation of a range of respiratory symptoms during the stable phase of chronic obstructive pulmonary disease (COPD). AECOPD is thus a dangerous stage and key event in the course of COPD, as its deterioration and frequency seriously affects the quality of life of patients and shortens their survival. Acute exacerbations occur and develop due to many factors such as infection, tobacco smoke inhalation, air pollution, comorbidities, airflow limitation, various biomarkers, history of previous deterioration, natural killer cell abnormalities, immunoglobulin G deficiency, genetics, abnormal muscle and nutritional status, negative psychology, and seasonal temperature changes. There is relatively limited research on the impact of the role of standardized management on the alleviation of AECOPD. However, with the establishment of relevant prevention and management systems and the promotion of artificial intelligence technology and Internet medical approaches, long-term effective and standardized management of COPD patients may help to achieve the quality of life and disease prognosis in COPD patients and reduce the risk of AE.Keywords: chronic obstructive pulmonary disease, acute exacerbation, related risk factors

Qiang Wei,1,&ast; Dong Lv,1,2,&ast; Shuna Fu,3,&ast; Dongmei Zhu,1 Minxiao Zheng,1 Si Chen,3 Shihang Zhen4 1Department of Psychology, Jianghan University, WuHan, People’s Republic of China; 2School of Business Administration, Huaqiao University, Quanzhou, People’s Republic of China; 3Department of Applied Psychology & Human Development, University of Toronto, Toronto, Canada; 4College of Economics and Management, Northwest Agriculture and Forestry University, XianYang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiang Wei, Department of Psychology, Jianghan University, WuHan, HuBei, People’s Republic of China, Tel +86-18671454618, Email weiqiang@jhun.edu.cn Dong Lv, School of Business Administration, Huaqiao University, Quanzhou, FuJian, People’s Republic of China, Tel +86-15798002728, Email lvdong@stu.hqu.edu.cnBackground: Tourism consumption is a topic with heated debates in tourism research, and pricing tourism products is a crucial task for tourism managers. Different types of tourist attractions offer different experiences to tourists, which affect their price perceptions and purchase decisions.Methods: This study combined questionnaires and event-related potentials (ERPs) measures to explore the magnitude of psychological conflict and the degree of emotional arousal that consumers experience when faced with different prices of goods in different scenic types.Results: The questionnaire results showed that attraction type influenced consumers’ price perceptions and that consumers were willing to pay higher prices for products in attractions. The ERP results implied that in the early stage of cognition, attraction type did not affect consumers’ perceptual processing, while price information attracted consumers’ cognitive attention. In the late stage of cognition, attraction type, and price information jointly influenced consumers’ decision-making, and consumers tended to accept high prices of products in entertainment attractions and cultural attractions, but consumers were more sensitive to the price of products in cultural attractions and less tolerant to price increases.Conclusion: The study elucidated how price information influenced consumers’ purchase decisions of tourism products at different stages of the dual-process theory, which can assist tourism managers in devising different pricing strategies and positioning strategies based on the attributes of attractions, to enhance product sales and revenues. This would further the vision of the World Tourism Organization (UNWTO) of “tourism fostering economic development”.Keywords: tourist attractions, price perception, neuromarketing, event-related potentials, P2, LPP

Dongsheng Hong,1,2 Duo Lv,1 Jiaying Wu,1 Xin Li,1 Qingwei Zhao,1 Xiaoyang Lu,1 Lu Li2 1Key Laboratory for Drug Evaluation and Clinical Research of Zhejiang Province, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Social Medicine of school of Public Health, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Xiaoyang Lu, Key Laboratory for Drug Evaluation and Clinical Research of Zhejiang Province, the First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, People’s Republic of China, Email luxiaoyang@zju.edu.cn Lu Li, Department of Social Medicine of school of Public Health, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou, 310058, People’s Republic of China, Email lilu@zju.edu.cnBackground: DIP is a new medical insurance payment system developed in China which was implemented in Guangzhou in January 2018, but few studies have focused on its intervention effect on the drug burden of elderly hypertensive patients.Methods: Nine medical institutions in Guangzhou, China, were selected, among which, daily full medical orders of elderly hypertensive inpatients from 2016 to 2020 were randomly collected. To assess the impact of DIP policy intervention on patient drug burden, we took the data after policy implementation in January 2018, as the intervention data, and applied a segmented regression model with interrupted time series to analyze the trend and changes in average daily drug costs per month and medication structure, stratified by age, sex, and inpatient department.Results: A total of 34,276 elderly hypertensive patients’ daily full medical orders were obtained. The immediate level change of drug costs after intervention was − 23.884 RMB/month (P = 0.652), and the trend change was statistically significant (− 15.642 RMB/month, P = 0.002). The relative cumulative effect at the end of the study was − 78.860% (95% CI: − 86.087% to − 69.076%), and the intervention effect was more significant in surgical and male patients. The analysis of drug structure changes showed that after the implementation of the DIP policy intervention, the proportion of anti-infective drugs, anti-tumor drugs, and biological products all showed a significant downward trend (P < 0.05), while nutritional drugs showed a significant upward trend (P = 0.011), but no immediate horizontal change in slope was observed.Conclusion: The typical practice in China showed that DIP policy intervention can improve the drug burden of elderly hypertensive hospitalized patients and has a stable long-term effect, and the intervention effect is not consistent across different clinical department and populations with different characteristics, and it would also cause changes in the medication structure.Keywords: diagnosis-intervention packet policy, daily drug cost, interrupted time series analysis, elderly hypertension, medication structure

Guolan Wu,1– 3 Huili Zhou,1,2 Duo Lv,1,2 Ruling Zheng,4 Lihua Wu,1 Songxia Yu,1,2 Jiejing Kai,1,2 Nana Xu,1,2 Lie Gu,5 Nanfang Hong,5 Jianzhong Shentu1,2 1Department of Clinical Pharmacy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3Polytechnic Institute, Zhejiang University, Hangzhou, People’s Republic of China; 4The Fifth Affiliated Hospital, College of Medicine, Guangzhou Medical University, Guangzhou, People’s Republic of China; 5Hainan Honz Pharmaceutical Co. Ltd, Haikou, Hainan, People’s Republic of ChinaCorrespondence: Jianzhong Shentu, Email stjz@zju.edu.cnPurpose: Suramin is a multifunctional molecule with a wide range of potential applications, including parasitic and viral diseases, as well as cancer.Methods: A double-blinded, randomized, placebo-controlled single ascending dose study was conducted to investigate the safety, tolerability, and pharmacokinetics of suramin in healthy Chinese volunteers. A total of 36 healthy subjects were enrolled. All doses of suramin sodium and placebo were administered as a 30-minute infusion. Blood and urine samples were collected at the designated time points for pharmacokinetic analysis. Safety was assessed by clinical examinations and adverse events.Results: After a single dose, suramin maximum plasma concentration (Cmax) and area under the plasma concentration–time curve from time zero to the time of the last measurable concentration (AUClast) increased in a dose-proportional manner. The plasma half-life (t1/2) was dose-independent, average 48 days (range 28– 105 days). The cumulative percentages of the dose excreted in urine over 7 days were less than 4%. Suramin can be detected in urine samples for longer periods (more than 140 days following infusion). Suramin was generally well tolerated. Treatment-emergent adverse events (TEAEs) were generally mild in severity.Conclusion: The PK and safety profiles of suramin in Chinese subjects indicated that 10 mg/kg or 15 mg/kg could be an appropriate dose in a future multiple-dose study.Keywords: suramin, clinical pharmacokinetics, antiviral, safety, drug repurposing

Huihui Xu,1,2,&ast; Teng Li,1,2,&ast; Xiaoming Zhang,1,3 Hongqiang Li,4 Diyu Lv,4 Yiyuan Wang,4 Fangjie Huo,5 Jianwen Bai,4,6 Chunmei Wang4,6 1Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, People’s Republic of China; 2University of Chinese Academy of Sciences, Beijing, 100000, People’s Republic of China; 3Shanghai Huashen Institute of Microbes and Infections, Shanghai, 200052, People’s Republic of China; 4Department of Emergency Medicine and Critical Care, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, People’s Republic of China; 5Department of Respiratory Medicine, Xi’an No. 4 hospital, Xi’an, 710004, People’s Republic of China; 6Department of Emergency Medicine and Critical Care, Shanghai East Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, 211166, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunmei Wang; Jianwen Bai, Department of Emergency Medicine and Critical Care, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120, People’s Republic of China, Tel +8613761004402 ; +8613386057150, Email wcm1702@163.com; baijianwen1019@163.comPurpose: Sepsis is a condition that derives from a dysregulated host response to infection. Although B lymphocytes play a pivotal role in immune response, little is known about status of their terminally differentiated cells, antibody-secreting cells (ASCs) during immunosuppressive phase of sepsis, especially in elderly patients. Our aim was to extensively characterize the immune functions of ASCs in elderly septic patients.Patients and Methods: Clinical and laboratory data were collected on days 1, 3, and 7 of hospitalization. Circulating ASCs were evaluated by flow cytometry from fresh whole blood in elderly septic patients at the onset of disease. RNA sequencing analyzed ASCs gene expression profile. Receiver operating characteristic (ROC) curve analysis and logistic regression predicted the survival rate of 28-day mortality.Results: A total of 103 septic patients were enrolled. The number and proportion of ASCs among total lymphocytes dramatically increased in septic patients, and RNA sequencing analysis showed that ASCs from septic patients exhibited a different gene expression profile. Furthermore, we found these ASCs could promote the function of T cells. Logistic regression analysis showed ASCs population was an independent outcome predictor in septic shock patients.Conclusion: Our study revealed the complex nature of immune disorders in sepsis and identified circulating ASCs population as a useful biomarker for predicting mortality in elderly septic patients, which provided a novel clue to combat this severe disease.Keywords: biomarker, antibody-secreting cells, prognosis, sepsis, septic shock

Danmei Lv, Shanshan Shen, Xujiao Chen Department of Geriatrics, Zhejiang Hospital, Hangzhou, 310013, People’s Republic of ChinaCorrespondence: Xujiao Chen, Department of Geriatrics, Zhejiang Hospital, Lingyin Road #12, Hangzhou, 310013, People’s Republic of China, Email lily197459@163.comBackground: In recent years, dynapenic abdominal obesity has received more and more attention. This article aimed to explore the relationship between dynapenic abdominal obesity and fall risk in older adults.Methods: In this cross-sectional study, according to waist circumference (≥ 90 cm for men and ≥ 85 cm for women) and handgrip strength (< 28 kg for men and < 18 kg for women), 551 older adults were divided into four groups: dynapenic abdominal obese (D/AO), dynapenic nonabdominal obese (D/NAO), nondynapenic abdominal obese (ND/AO) and nondynapenic nonabdominal obese (ND/NAO). Fall risk was measured by the Tinetti performance-oriented mobility assessment (POMA). Binary logistic regression was used to explore the relationship between D/AO and fall risk.Results: D/AO was related to POMA score (odds ratio [OR]=3.39; 95% confidence interval [CI]: 1.47– 7.81; P=0.004) after adjusting the confounding variables. However, D/NAO (OR=1.51; 95% CI:0.69– 3.32; P=0.302) and ND/AO (OR=1.48; 95% CI:0.74– 2.99; P=0.272) were not associated with POMA score.Conclusion: This study suggests that older adults with D/AO have a higher risk of falls. Therefore, it is necessary to strengthen the attention to D/AO and relevant interventions should be implemented.Keywords: dynapenic abdominal obesity, fall risk, older adult

Cuixiao Shi,1 Dongmei Lv,1 Kai Zhou,1 Tengchuan Jin,2 Gang Wang,3 Bo Wang,1 Yajuan Li,1 Yuanhong Xu1 1Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China; 2Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, People’s Republic of China; 3The Second Hospital of Anhui Medical University, Hefei, 230601, People’s Republic of ChinaCorrespondence: Yuanhong Xu; Yajuan LiDepartment of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, People’s Republic of ChinaEmail xyhong1964@163.com; liyajuan@ahmu.edu.cnBackground: Human listeriosis is a severe foodborne infection caused by Listeria monocytogenes and the data of patients with this infection are largely limited for the Hefei population.Purpose: This is a retrospective study that evaluated the clinical and laboratory data of patients with listeriosis at a tertiary hospital in Hefei City.Patients and Methods: A total of 24 listeriosis patients were admitted to the First Affiliated Hospital of Anhui Medical University from January 2003 to July 2021. Data from all patients were collected from the hospital’s electronic medical records.Results: The most common symptom of all patients was fever (91.7%), followed by altered consciousness (50.0%), rashes (45.8%), respiratory distress symptoms (37.5%), nuchal rigidity (29.2%), and headaches (20.8%). Laboratory results also indicated elevated C-reactive protein (CRP) (79.1%), hypoproteinemia (75.0%), anemia (62.5%), leukocytosis (45.8%), and neutrophilia (45.8%). The mean value of 5.1 μg/mL (SD, 3.8) for D‐dimer (D‐D) was significantly higher than the normal value ((0.00– 0.50) μg/mL), while both altered consciousness (6 vs 4, P = 0.034) and headaches (4 vs 1, P = 0.036) occurred more frequently in the neurolisteriosis group compared with the bacteremia one. Additionally, the mean maximal body temperature (°C) (40.5 ± 0.7) as well as white blood cell (WBC) (15.3 vs 7.5 × 109/L, P = 0.014) and neutrophil (NEUT#) (13.2 vs 6.1 × 109/L, P = 0.026) counts of neurolisteriosis patients were higher than those of bacteremia (39.4 ± 0.4) (P = 0.001). Of all patients, four (50%) from the maternal-neonatal group remained uncured.Conclusion: Listeriosis is a rare disease with extremely variable clinical characteristics in Hefei City. Our data indicated that unexplained fever, altered consciousness, hypoproteinemia, anemia, elevated CRP and DD should be considered to assist diagnosis of listeriosis for early treatment interventions.Keywords: Listeria monocytogenes, listeriosis, clinical and laboratory characteristics

Dan Lv,1 Zepu Wang,2 Shuai Ji,1 Xiaoxi Wang,1 Huiqing Hou1 1Physical Examination Center, Hebei General Hospital, Shijiazhuang City, Hebei Province, People’s Republic of China; 2Department of Hepatobiliary Surgery, Hebei General Hospital, Shijiazhuang City, Hebei Province, People’s Republic of ChinaCorrespondence: Dan LvPhysical Examination Center, Hebei General Hospital, Shijiazhuang City, Hebei Province, People’s Republic of ChinaEmail ld2449@163.comObject: Studies have shown a link between homocysteine (Hcy) and heart diseases, kidney diseases, cerebrovascular diseases, liver diseases, and other pathological conditions. However, the relationship between Hcy and liver fibrosis (LF) is unclear. Here, we studied the link between plasma Hcy concentration and LF.Methods: We determined and recorded the plasma Hcy concentration, general biochemical parameters, and liver stiffness measurement (LSM) in 1582 subjects, followed by statistical data analyses.Results: During different stages of LF, we found a considerable difference (p < 0.001 unless specified) in body mass index (BMI), sex, age, Hcy, the levels of alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT; P = 0.012), triglycerides (TG; P = 0.006), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FBS), and platelet count (PLT). There was a strong association between the plasma Hcy concentration and the serum biomarkers of LF (P < 0.001) and the values of LSM (P < 0.001).Conclusion: The plasma Hcy concentration was substantially different among different stages of LF. The higher the plasma Hcy concentration, the more evident was the degree of LF.Keywords: liver fibrosis, homocysteine, FibroScan

Cuixiao Shi,1 Lianzi Wang,1 Dongmei Lv,1 Gang Wang,1 Hylemariam Mihiretie Mengist,2 Tengchuan Jin,2 Bo Wang,1 Ying Huang,1 Yajuan Li,1 Yuanhong Xu1 1Department of Clinical Laboratory, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China; 2Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, People’s Republic of ChinaCorrespondence: Yuanhong Xu; Yajuan Li Email xyhong1964@163.com; liyajuan@ahmu.edu.cnBackground: Brucellosis is currently one of the most widespread zoonotic diseases caused by Brucella genus, and the Brucella melitensis is the major pathogen. The number of people infected with Brucella has gradually increased in Anhui Province.Purpose: To retrospectively evaluate the epidemiological, clinical, and laboratory data of brucellosis patients in Anhui Province.Patients and Methods: A total of 109 brucellosis patients were admitted to the First Affiliated Hospital of Anhui Medical University from January 2012 to March 2021. Data from all patients were retrieved from the hospital’s electronic medical system. The final results were grouped and compared according to the presence or absence of bacteremic brucellosis and three phases of brucellosis.Results: The most common symptoms among all 109 brucellosis patients were fever (89.0%), followed by chills (52.3%), arthralgia (48.6%), and weight loss (30.3%), and laboratory results presented with anemia (65.1%), elevate of C-reactive protein (CRP) (91.7%), erythrocyte sedimentation rate (ESR) (86.2%), aspartate aminotransferase (AST) (40.4%), and lactate dehydrogenase (LDH) (43.1%). The percentage of fever (96.1%), arthralgia (58.8%), anorexia (35.3%), leukopenia (31.4%), and the AST (51.0%) were higher in bacteremic than nonbacteremic group. Additionally, the median level of LDH (332.0 mg/L, IQR, 209.0– 553.0) was higher in bacteremic than nonbacteremic group. Nevertheless, the albumin (36.0 mg/L, IQR, 33.9– 38.2) was lower in the bacteremic group. The percentage of fever (94.9%) and the median LDH level (316.0 U/L (IQR,218.0– 517.5)) in the acute phase of brucellosis were higher than the percentage of fever (72.0%) and the median LDH level (209.0 U/L (IQR,162.0– 276.0)) in the subacute phase of brucellosis.Conclusion: Brucellosis has become an important public health issue in Anhui Province. Brucellosis is a disease with diverse clinical manifestations. Our data showed that unexplained fever, arthralgia, and elevated AST and LDH should be considered as a diagnosis of bacteremia brucellosis for early treatment intervention.Keywords: Brucella melitensis, brucellosis, bacteremia, epidemiological, clinical and laboratory features

Xiao-Ming Zhang,1,* Jing Jiao,1,* Chen Zhu,1 Na Guo,1 Ying Liu,1 Dongmei Lv,2 Hui Wang,3 Jingfen Jin,4 Xianxiu Wen,5 Shengxiu Zhao,6 Xin-Juan Wu,1 Tao Xu7 1Department of Nursing, Chinese Academy of Medical Sciences - Peking Union Medical College, Peking Union Medical College Hospital (Dongdan Campus), Beijing, 100730, People’s Republic of China; 2Department of Nursing, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 3Department of Nursing, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4Department of Nursing, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 5Department of Nursing, Sichuan Provincial People’s Hospital, Chengdu, People’s Republic of China; 6Department of Nursing, Qinghai Provincial People’s Hospital, Xining, People’s Republic of China; 7Department of Epidemiology and Statistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, 100005, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xin-Juan Wu; Tao Xu Tel/Fax +010 86 6915 6114Email wuxinjuan@sina.com; xutaosd@126.comPurpose: Studies exploring the association of cognitive frailty and mortality have been mainly based on community settings or nursing home settings. The aim of our study was to explore the association between cognitive frailty and 30-day mortality among older Chinese inpatients.Patients and Methods: A national cohort study was performed in different hospitals in China. A baseline survey was conducted from October 2018 and February 2019. Trained investigators collected the 30-day mortality. Cognitive impairment and frailty were defined by the Mini-Cog and FRAIL scale, respectively. Multivariate regression was used to explore the association between cognitive impairment and frailty status with 30-day mortality.Results: Of these participants, there were 3891 (41.91%) women and 5392 (58.09%) men, with an average age of 72.41 (SD=5.72). The prevalence of cognitive frailty was 5.44%. After adjusting for age, gender, education, depression and activities of daily living (ADL), the odds ratios (ORs) for 30-day mortality among inpatients were 3.43 (95% CI: 1.80– 6.55) for cognitive frailty, 1.85 (95% CI: 1.01– 3.41) for frailty only, and 1.43 (95% CI: 0.77– 2.65) for cognitive impairment only compared to the reference group (neither frailty nor cognitive impairment). In addition, the discrimination of 30-day mortality was higher among patients with cognitive frailty (area under the curve =0.676 [95% CI: 0.621– 0.731]) than either frailty (area under the curve =0.644 [95% CI: 0.594– 0.694]) or cognitive impairment (area under the curve = 0.606 [95% CI: 0.556– 0.655]) separately. Stratified analysis showed that these associations still existed when grouped by gender.Conclusion: Our study found that Chinese inpatients with cognitive frailty had a higher risk of 30-day mortality than those without frailty and cognitive impairment, suggesting that clinicians should be encouraged to perform early screening of patients with frailty and cognitive impairment and carry out effective interventions to reverse cognitive frailty syndrome.Keywords: frailty, cognitive impairment, mortality, older adults, Chinese; inpatients

Nana Xu,1,2 Qiao Zhang,1,2 Guolan Wu,1,2 Duo Lv,1,2 Yunliang Zheng1,2 1Research Center of Clinical Pharmacy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Yunliang ZhengThe First Affiliated Hospital, Zhejiang University School of Medicine, 79# Qingchun Road, Hangzhou, Zhejiang 310003, People’s Republic of ChinaEmail ylzheng1984@zju.edu.cnBackground: Vancomycin is the standard therapy for methicillin-resistant Staphylococcus aureus (MRSA) infection; however, nephrotoxicity happened with a high incidence of 15%∼ 40%. Weighting the risk before receiving vancomycin treatment facilitates timely prevention of nephrotoxicity, but no standardized strategy exists for this purpose.Methods: A retrospective cohort study was performed. A total of 524 hospitalized patients treated with vancomycin were included in this study. They were divided into derivation cohort (n=341) and externally validation cohort (n=183) according to their admission time. Using univariate and multivariable logistic regression, we identified potential predictors of vancomycin-associated acute kidney injury (AKI) and developed a risk score by plotting nomogram. The predictive performance of this novel risk score was assessed and validated by discrimination and calibration. Besides, the risk score was also compared with existing prediction models according to integrated discrimination index (IDI) and net reclassification index (NRI).Results: The incidence of AKI was 16.1% (55/341) in the derivation cohort and 16.4% (30/183) in the validation cohort. Three factors (vancomycin serum trough concentration, piperacillin/tazobactam and furosemide) were determined as predictors for vancomycin-associated AKI. The established three-item risk score showed a comparable discrimination in both derivation cohort (AUC=0.793, 95% CI: 0.732– 0.855) and validation cohort (AUC=0.788, 95% CI: 0.698– 0.877). The risk score also demonstrated a good calibration in the derivation cohort (χ2=6.079, P=0.638> 0.05) and validation cohort (χ2=5.665, P=0.686> 0.05). Compared with prediction by Cmin alone, this risk score significantly improved reclassification accuracy (IDI=0.050, 95% CI: 0.024– 0.076, P< 0.001, NRI=0.166, 95% CI: 0.044– 0.289, P=0.007).Conclusion: The established model in this study is a simplified three-item risk score, which provides a robust tool for the prediction of AKI after receiving vancomycin treatment.Keywords: vancomycin, acute kidney injury, prediction model

Lihua Wu,1,2,* Chang Xu,1,2,* Guolan Wu,1,2 Huili Zhou,1,2 Duo Lv,1,2 You Zhai,1,2 Yujie Huang,1,2 Wenling Tang,3 Fangqiong Li,4 Jianzhong Shentu1–3 1Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 2Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 3College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 4Clinical Research Department, Haisco Pharmaceutical Group, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianzhong ShentuResearch Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, People’s Republic of ChinaTel +86 571 87236560Fax +86 571 87214223Email stjz@zju.edu.cnPurpose: A fixed-dose combination (FDC) tablet of melitracen/flupentixol has been widely used for depression. The purpose of this study was to assess the safety profile and the relative bioavailability of two FDC products containing 10 mg melitracen and 0.5 mg flupentixol from two different manufacturers, in order to acquire adequate pharmacokinetic evidence for registration approval of the test formulation.Methods: The study was designed as a single-dose, randomized, open-label, 2-period crossover study under fasted or fed conditions in healthy Chinese subjects. Twenty-four subjects (16 men and 8 women) were selected for fasted study, and another 24 cases (16 men and 8 women) were in fed study. Each subject was randomized at the beginning to receive either a single dose of the reference FDC or the test FDC tablet during the first period. Following two-week washout period, all subjects received the alternate formulation during the second period. Blood samples were collected up to 144 hrs after administration. Pharmacokinetic parameters, including Cmax, Tmax, AUC0-t, AUC0-∞, t½, CL/F, and Vd/F were acquired based on the time versus concentration profiles. Then, the geometric mean ratios (GMR) and corresponding 90% CIs were calculated for the determination of bioequivalence analysis. Safety assessment included changes in vital signs and laboratory tests, physical examination findings, and incidence or reports of adverse events (AEs).Results: The present study has clearly indicated the test and the reference FDC products are bioequivalent in terms of rate and extent of drug absorption. GMR of Cmax, AUC0–t, and AUC0-∞ for both flupentixol and melitracen between the two formulation FDC products, and corresponding 90% CIs, were all within the range of 80% to 125% under fasted or fed conditions. Both the test and the reference FDC products indicated good tolerance in all volunteers. Chinese Clinical Trials Registry identifier: CTR20171256.Keywords: bioequivalence, melitracen, flupentixol, pharmacokinetics, fixed-dose combination tablet

Dingfeng Lv,1 Danyang Zhang,2 Qifa Song21Department of Clinical Laboratory, Ningbo First Hospital, Ningbo, Zhejiang Province, People’s Republic of China; 2Department of Microbiology, Ningbo Municipal Centre for Disease Control and Prevention, Ningbo, Zhejiang Province, People’s Republic of ChinaPurpose: This study was aimed to investigate the dynamics of antimicrobial resistance expansion among different lineages and isolates of S. Typhi.Materials and methods: The S. Typhi isolates were collected from the patients clinically suspected of typhoid fever in Eastern China during 2005–2017. All isolates were tested retrospectively for susceptibility to eight antimicrobials and the genes related to quinolone and ampicillin resistance, including gyrA, ParC, qnrA, qnrB, qnrS, aac(6´)-Ib-cr, qepA and blaTEM. The isolates were subtyped by PFGE.Results: Of 140 isolates, all were susceptible to ciprofloxacin, cefotaxime, chloramphenicol, and trimethoprim-sulfamethoxazole, 95 (68%) were nalidixic acid resistant, and 74 (53%) were ampicillin resistant. The resistance to ampicillin and nalidixic acid was first observed in 2006. Among the 95 nalidixic acid-resistant S. Typhi isolates, 62 possessed S83F mutation in gyrA and 25 possessed D87Y mutation. All ampicillin-resistant isolates harbored gene blaTEM-1. PFGE generated 47 distinguishable clonal lineages. Overall, 64% (89/140) belonged to seven prevalent lineages of clustering isolates. PFGE results illustrated the prevalence of nalidixic acid-resistant lineages increased steadily from 19% during 2005–2012 to 50% during 2013–2014, and thereafter to 74% during 2015–2017 and similar development of ampicillin-resistant lineages increased from 6% to 38%, and also to 39%.Conclusion: The present study indicated the clonal expansion of S. Typhi with ampicillin resistance and reduced ciprofloxacin susceptibility. The findings also suggested that the differential development of antimicrobial resistance to various antimicrobial agents in S. Typhi, showing the rapid increase in ampicillin resistance and reduced ciprofloxacin susceptibility, and the high susceptibility to other traditional antimicrobial agents.Keywords: ampicillin resistance, reduced ciprofloxacin susceptibility, Salmonella Typhi, clonal expansion

Jiangtao Zhang,1,2 Zhongwei Guo,2 Xiaozheng Liu,3 Xize Jia,4 Jiapeng Li,2 Yaoyao Li,1,5 Danmei Lv,1,5 Wei Chen1,5 1Department of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine and the Collaborative Innovation Center for Brain Science, Hangzhou, Zhejiang, China; 2Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China; 3China-USA Neuroimaging Research Institute & Department of Radiology, the Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, China; 4Center for Cognitive Brain Disorders & Zhejiang Key Laboratory for Research in Assessment of Cognitive Impairments, Hangzhou Normal University, Hangzhou, China; 5Key Laboratory of Medical Neurobiology of Chinese Ministry of Health, Hangzhou, Zhejiang, China Background: Depressive symptoms are significant and very common psychiatric complications in patients with Alzheimer’s disease (AD), which can aggravate the decline in social function. However, changes in the functional connectivity (FC) of the brain in AD patients with depressive symptoms (D-AD) remain unclear.Objective: To investigate whether any differences exist in the FC of the posterior cingulate cortex (PCC) between D-AD patients and non-depressed AD patients (nD-AD).Materials and methods: We recruited 15 D-AD patients and 17 age-, sex-, educational level-, and Mini-Mental State Examination (MMSE)-matched nD-AD patients to undergo tests using the Neuropsychiatric Inventory, Hamilton Depression Rating Scale, and 3.0T resting-state functional magnetic resonance imaging. Bilateral PCC were selected as the regions of interest and between-group differences in the PCC FC network were assessed using Student’s t-test.Results: Compared with the nD-AD group, D-AD patients showed increased PCC FC in the right amygdala, right parahippocampus, right superior temporal pole, right middle temporal lobe, right middle temporal pole, and right hippocampus (AlphaSim correction; P

The ecosystem service value on Ximen Island was calculated using the value table of ecosystem services proposed by Xie et al. according to the land use data from 2006–2017. The STIRPAT model was used to analyze the driving mechanisms of ecosystem services on Ximen Island. The results show that the ecosystem service value of Ximen Island has gradually decreased from 2006 to 2017, and the value of ecosystem services has decreased by 15.842 million Yuan over 10 years. Applying the principal component analysis method can effectively eliminate the collinearity problem in the process of regression analysis. The value of ecosystem services has a high correlation with socio-economic variables. The total population, GDP per capita, the increased rate of forestry output, the proportion of primary industry, and the Engel coefficient are all important driving factors that affect the change of valuable ecosystem services on Ximen Island. Among them, the proportion of primary industry is positive, and the other 4 indicators are negative. The rate of increase in forestry output has the greatest negative impact. A 1% increase in the total population, in the GDP per capita, in the rate of forestry output, in the proportion of primary industry, and in the Engel coefficient results in ecosystem service values varying by 0.199%, 0.165%, 0.289%, -0.144%, and 0.252%, respectively.

OBJECTIVE: This study aimed to investigate the relationship between different dietary patterns and diabetic microvascular complications in patients with type 2 diabetes mellitus. PATIENTS AND METHODS: This study was conducted based on the Chinese Chronic Disease and its Risk Factor Surveillance System. A multi-stage stratified sampling method was used to randomly select two districts (Xinghualing District, Taiyuan City, and Yuzi District, Jinzhong City) and two counties (Huguan County, Changzhi City, and Jiang County, Yuncheng City) from the chronic disease surveillance sites in Shanxi Province to collect general information, dietary records, physical measurements, and laboratory tests. In total, 1,227 patients were enrolled according to the study criteria. Factor analysis was performed to construct six dietary patterns, and the relationship between dietary pattern scores and type 2 diabetic microvascular complications was analysed using binary logistic regression after correcting for confounders. RESULTS: (1) Regarding the prevalence of type 2 diabetic microvascular complications and dietary characteristics, the prevalence of microvascular complications in patients with type 2 diabetes mellitus was 55.3% and was higher in urban than in rural areas. The prevalence of diabetic kidney disease (DKD), diabetic retinopathy, and diabetic peripheral neuropathy (DPN) were 21.4%, 12.7%, and 38.0%, respectively. (2) Six dietary patterns were constructed, namely, 'animal protein', 'coarse grains and plant protein', 'nuts and fruits', 'refined grains and vegetables', 'dairy', and 'added sugars', with factor contributions of 15.42%, 9.99%, 8.23%, 8.16%, 7.56%, and 7.28% respectively, explaining 56.64% of the total dietary variation. (3) After adjusting for confounding variables, the results of binary logistic regression indicated that patients in the highest quartile of dietary pattern scores for 'nuts and fruits' experienced a 43.3% lower risk of DKD compared to those in the lowest quartile [odds ratio (OR) = 0.567; 95% confidence interval (CI), 0.359-0.894; p < 0.001]. Similarly, patients in the highest quartile of dietary pattern scores for 'animal protein' had a 42.8% lower risk of DPN compared with those in the lowest quartile (OR = 0.572; 95% CI, 0.388-0.843; p < 0.05). CONCLUSIONS: The results of this study suggest that in patients with type 2 diabetes mellitus, a 'nuts and fruits' dietary pattern reduces the risk of DKD and an 'animal protein' dietary pattern reduces the risk of DPN. [ABSTRACT FROM AUTHOR]