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Dong-Xia Wu,1,&ast; Jing-Xian Hu,2,&ast; Jian-Hong Ma,1,&ast; Ke-Yi Chang,1,&ast; Yun Zhang,1 Xiao-Li Quan,1 Jia-Ning Han,1 Hai-Jing Long,1 Chen Chen,1 Wei Zhai,1 Huan-Huan Guo,1 Li-Li Zhang,2 Xiao-Lan Wang2 1Department of Infection and Immunology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China; 2Department of Nursing, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li-Li Zhang; Xiao-Lan Wang, Department of Nursing, Beijing Youan Hospital, Capital Medical University, No. 8 of Xitoutiao, Fengtai District, Beijing, 100069, People’s Republic of China, Tel/Fax +86 010 8399 7143, Email lillizhang3200z@163.comPurpose: To investigate and analyse the status quo of the self-management of patients living with HIV/AIDS (PLWHA) and its influencing factors and to provide the basis for formulating intervention strategies.Methods: In this cross-sectional study, 300 PLWHA who visited the Infection Center of Beijing Youan Hospital, Capital Medical University between September 2021 and December 2021 were enrolled using the convenience sampling method. Demographic characteristics and disease-related data were collected for each participant. The HIV/AIDS Self-Management Scale was used to evaluate the self-management ability of PLWHA.Results: A total of 251 male and 49 female PLWHA were included in this study, with an average age of 39.08 ± 12.09 years and an average disease duration of 9.61 ± 37.04 months. Univariate analysis showed that the PLWHA’s place of residence, educational level, physical condition, family relations, duration of HIV disease, receipt or not of antiviral therapy and knowledge of disease had an influence on the scores of the HIV Self-Management Scale (all p < 0.05). The results of the self-management scores indicated that the total score for self-management was 41.5 ± 6.4 points, with a scoring rate of 69.6%, which was at a medium level. Long-term self-management had the highest scoring rate (12.2 ± 2.5 points), followed by daily health management (22.3 ± 4.3 points), and social support for self-management had the lowest scoring (5.1 ± 0.9 points). Multivariable analysis showed that the self-management ability of PLWHA was related to educational level, duration of disease and family relations (R2 = 0.67, F = 121.7, p < 0.05).Conclusion: The self-management level of patients with AIDS, especially the social support of daily health management and self-management, needs to be further improved. Educational level, duration of disease and family relations are important factors influencing the self-management of PLWHA.Keywords: HIV/AIDS, AIDS, self-management

Xuan Wang,1,&ast; Jing-Xian Hu,2,&ast; Ying Wang,1 Fang Wang,1 Xuan Wu,1 Fei Wang,1 Yan-Chao Zhao,1 Xiao-Lan Wang,2 Li-Li Zhang2 1Second Department of Hepatology Center for Liver Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China; 2Department of Nursing, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li-Li Zhang; Jing-Xian Hu, Department of Nursing, Beijing Youan Hospital, Capital Medical University, No. 8 of Xitoutiao, Youanmen wai, FengtaiDistrict, Beijing, 100069, People’s Republic of China, Email zhanglyliy@163.com; 819211326@mail.ccmu.edu.cnObjective: This study explores the correlation between coping style, quality of life, and illness uncertainty in the family caregivers of patients with liver cancer.Methods: Employing convenience sampling, 210 family caregivers of patients with liver cancer who met the admission criteria were selected from a grade A infectious disease hospital in Beijing between January and December 2022. A cross-sectional survey was conducted using the Simplified Coping Style Questionnaire, Caregiver Quality of Life, and the Mishel Uncertainty in Illness Scale for Family Members. This study analysed the correlations between coping styles, quality of life, and illness uncertainty in these caregivers.Results: The study found that family caregivers of patients with liver cancer had average scores for illness uncertainty (83.44 ± 11.86), coping style (33.19 ± 9.79; both positive [23.02 ± 6.81] and negative [10.17 ± 5.05]), and quality of life (169.53 ± 32.46). A negative association was observed between illness uncertainty in these caregivers and positive coping style (r = − 0.207, p = 0.003), physical status (r = − 0.182, p = 0.008), psychological status (r = − 0.200, p = 0.004), and social adaptation (r = − 0.229, p = 0.001).Conclusion: The study concludes that illness uncertainty in family caregivers of patients with liver cancer is at a moderate level. Furthermore, there is a notable correlation between illness uncertainty, coping style, and quality of life in these caregivers.Keywords: liver cancer, family caregivers, uncertainty in illness, coping style, quality of life

Zhao-Ting Gong,1 Yu-Yan Xiong,1,2 Yu Ning,1 Rui-Jie Tang,1 Jun-Yan Xu,3 Wen-Yang Jiang,1 Xiao-Song Li,1 Li-Li Zhang,1 Cheng Chen,1 Qi Pan,1 Meng-Jin Hu,1 Jing Xu,1 Yue-Jin Yang1 1State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100037, People’s Republic of China; 2Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 3Department of Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of ChinaCorrespondence: Yue-Jin Yang, Email yangyjfw@126.comBackground: Exosomes derived from bone marrow mesenchymal stem cells (MSC-exo) have been considered as a promising cell-free therapeutic strategy for ischemic heart disease. Cardioprotective drug pretreatment could be an effective approach to improve the efficacy of MSC-exo. Nicorandil has long been used in clinical practice for cardioprotection. This study aimed to investigate whether the effects of exosomes derived from nicorandil pretreated MSC (MSCNIC-exo) could be enhanced in facilitating cardiac repair after acute myocardial infarction (AMI).Methods: MSCNIC-exo and MSC-exo were collected and injected into the border zone of infarcted hearts 30 minutes after coronary ligation in rats. Macrophage polarization was detected 3 days post-infarction, cardiac function as well as histological pathology were measured on the 28th day after AMI. Macrophages were separated from the bone marrow of rats for in vitro model. Exosomal miRNA sequencing was conducted to identify differentially expressed miRNAs between MSCNIC-exo and MSC-exo. MiRNA mimics and inhibitors were transfected to MSCs or macrophages to explore the specific mechanism.Results: Compared to MSC-exo, MSCNIC-exo showed superior therapeutic effects on cardiac functional and structural recovery after AMI and markedly elevated the ratio of CD68+ CD206+/ CD68+cells in infarcted hearts 3 days post-infarction. The notable ability of MSCNIC-exo to promote macrophage M2 polarization was also confirmed in vitro. Exosomal miRNA sequencing and both in vivo and in vitro experiments identified and verified that miR-125a-5p was an effector of the roles of MSCNIC-exo in vivo and in vitro. Furthermore, we found miR-125a-5p promoted macrophage M2 polarization by inhibiting TRAF6/IRF5 signaling pathway.Conclusion: This study suggested that MSCNIC-exo could markedly facilitate cardiac repair post-infarction by promoting macrophage M2 polarization by upregulating miR-125a-5p targeting TRAF6/IRF5 signaling pathway, which has great potential for clinical translation. Keywords: mesenchymal stem cell, exosomes, nicorandil, macrophage polarization, myocardial infarction

Ling-Ling Zhang,1,2 Zhi-Fang Luo,2 Guang-Jing Yang1,3 1Hunan University of Chinese Medicine, Hunan, People’s Republic of China; 2Department of Operating Room, Chongqing Traditional Chinese Medicine Hospital, Chongqing, People’s Republic of China; 3Department of Nursing, Chongqing Traditional Chinese Medicine Hospital, Chongqing, People’s Republic of ChinaCorrespondence: Guang-Jing Yang, Department of Nursing, Chongqing Traditional Chinese Medicine Hospital, No. 6, Seven Branch Road, Panxi, Jiangbei District, Chongqing, 400021, People’s Republic of China, Tel +86-15998951588, Email yangguangjingygj@126.comObjective: In this study, the clinical application and efficacy of three different methods for placing and repositioning patients in the lithotomy position over the bed using stirrups were evaluated.Methods: A total of 240 surgical patients who underwent surgery in Chongqing Traditional Chinese Medicine Hospital between July and November 2022 were selected as study participants. Using envelopes, they were randomly divided into three groups of 80 cases each using a randomization method. The groups included the traditional over-bed method, the postural trolley-assisted over-bed method, and the direct over-bed method. Using the Kruskal–Wallis rank-sum test, analysis of variance, and multiple linear regression equations, the placement time, over-bed repositioning time, and total time of the three methods for placing and repositioning in the lithotomy position supported by stirrups were analyzed statistically. In addition, we investigated and examined the satisfaction of nurses and doctors with the aforementioned techniques.Results: The placement time, repositioning time, and total time were significantly higher for the traditional over-bed method than for the postural trolley-assisted over-bed method and the direct over-bed method (both P < 0.01). However, there was no statistically significant difference between the postural trolley-assisted over-bed method and the direct over-bed method (P > 0.05). Nurses and doctors reported significantly higher satisfaction with the postural trolley-assisted over-bed method and the direct over-bed method compared to the traditional over-bed method (both P < 0.01). In addition, nurses were more satisfied with the direct over-bed method than the postural trolley-assisted over-bed method (P < 0.05).Conclusion: The results of this study demonstrate that the direct over-bed method is preferred for positioning and repositioning patients in the lithotomy position with the support of stirrups.Keywords: lithotomy position, position placement, postural trolley, repositioning over bed, stirrup

Li-Li Zhang,&ast; Wen-Hao Wang,&ast; Yong-Li Hou Department of Obstetrics and Gynecology, The Second Hospital of Shanxi Medical University, Taiyuan, 030000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong-Li Hou, Department of Obstetrics and Gynecology, The Second Hospital of Shanxi Medical University, No. 382 of Wuyi Road, Xinghualing District, Taiyuan, 030000, People’s Republic of China, Tel +86 03513382151, Email houyonglihyl@126.comObjective: To investigate the risk factors of intraoperative massive hemorrhage in patients with pernicious placenta previa (PPP) and analyze the value of bilateral internal iliac artery balloon occlusion in Cesarean section for these patients.Methods: The clinical data of 134 patients with PPP admitted to the Second Hospital of Shanxi Medical University from January 2012 to January 2019 were analyzed. A logistic regression analysis was used to analyze the risk factors for intraoperative massive hemorrhage in PPP. The study subjects were divided into the intervention group (38 cases) and the routine group (96 cases) according to whether bilateral internal iliac artery balloon occlusion was conducted during the operation. The differences in some clinical indicators were compared between the two groups.Results: The risk factors for intraoperative massive hemorrhage in PPP were age ≥ 35 years, gestational age ≥ 34 weeks, complete placenta previa, and the presence of placenta accreta. The differences in the operation time, postoperative transfer to the intensive care unit, postoperative length of the hospital stay, and neonatal weight and score were not statistically significant between the intervention group and the routine group (P > 0.05 for all). While the intraoperative blood loss and the transfusion volume in the intervention group were lower than in the routine group, the hospitalization cost was higher in the former than in the latter, and the differences were statistically significant (P < 0.05 for all). Moreover, there was no case of hysterectomy in the intervention group, while there were two cases of hysterectomies in the routine group.Conclusion: The risk factors for intraoperative massive hemorrhage in PPP were age ≥ 35 years, gestational age ≥ 34 weeks, complete placenta previa, and the presence of placenta accreta. Internal iliac artery balloon occlusion during PPP could reduce intraoperative blood loss and the hysterectomy rate.Keywords: pernicious placenta previa, internal iliac artery balloon occlusion, intraoperative bleeding, risk factor

Ci-Qiu Yang,* Fei Ji,* Hong-Fei Gao, Liu-Lu Zhang, Mei Yang, Teng Zhu, Min-yi Chen, Jie-qing Li, Kun Wang Department of Breast Cancer, Cancer Center, Guangdong Provincial People’s Hospital & Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kun WangDepartment of Breast Cancer, Cancer Center, Guangdong Provincial People’s Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, People’s Republic of ChinaTel/Fax +86 20-83827812-80420Email gzwangkun@126.comBackground: Nipple-sparing mastectomy (NSM) is becoming increasingly accepted as a treatment for breast disease; however, nipple-areolar complex (NAC) necrosis, a frequent severe postoperative complication, inhibits the popularity of this procedure. This study reports the technical aspects and short-term postoperative outcomes of NSM.Methods: A single-center, retrospective review of 110 patients treated with NSM at our institution from November 2015 to September 2018 was performed. The primary outcome was the incidence of NAC necrosis.Results: A total of 130 NSMs performed on 110 patients were included in our study. Median patient age was 42 years. We performed a sharp dissection by using a scalpel, raising 3–5 mm thick flaps, and continuing onto the undersurface of the NAC. None of the 110 patients appeared to have NAC necrosis or mastectomy skin flap necrosis. However, discoloration or ischemia of the NAC with eschar formation presented between postoperative days 3 and 7 in six nipples; four nipples were ischemic, and two were discolored. No infection was detected in any of the 110 patients. All NACs were intact after an average follow-up of 30 months, and no local or systemic recurrence was detected in those breast cancer cases.Conclusion: NSM can be safely performed in properly selected patients. Nipple necrosis was avoided using a special surgical technique, and other complications occurred at an acceptable rate.Keywords: nipple-sparing mastectomy, breast cancer, nipple-areolar complex, sharp dissection

Tianmei Si,1,2 Jianmin Zhuo,3 Yu Feng,4 Huafei Lu,5 Di Hong,5 Lili Zhang51National Clinical Research Center for Mental Disorders & The Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, People’s Republic of China; 2Peking University Institute of Mental Health/The Sixth Hospital, Beijing, People’s Republic of China; 3Janssen (China) Research & Development Center, Johnson & Johnson (China) Investment Ltd., Shanghai, People’s Republic of China; 4Department of Neuroscience, Janssen Pharmaceutical Companies of Johnson and Johnson, Singapore; 5Medical Affairs, Xi’an Janssen Pharmaceuticals, Beijing, People’s Republic of ChinaBackground: The subgroup analysis of a primary study (NCT01051531) evaluated the effect of long-term paliperidone palmitate once-monthly (PP1M) therapy in Chinese patients with recent-onset schizophrenia responding unsatisfactorily to previous oral antipsychotics.Patients and methods: This 18-month, open-label study consisted of 3 phases – screening (7 days), treatment (18 months) and end-of-study/withdrawal visit. All enrolled patients (18–50 years) received PP1M: 150 mg eq. (day 1), 100 mg eq. (day 8) followed by a once-monthly flexible dose (50, 75, 100 or 150 mg eq.). Efficacy and safety were assessed.Results: Among the 118 enrolled Chinese patients, 68 completed the treatment (mean age: 25.6 years; male: 54.7%). A clinically meaningful change from baseline to day 548 was observed in Positive and Negative Syndrome scale (primary endpoint, mean [SD]: −15.3 [20.76]), Personal and Social Performance scale (15.9 [19.65]), Clinician Global Impression-schizophrenia score (−1.2 [1.54]) and Medication Satisfaction Questionnaire score (0.9 [1.73]). Commonly reported treatment-emergent adverse events (TEAEs) included insomnia (13.9%), injection-site pain (13.9%), upper respiratory tract infection (13.0%), restlessness (13.0%) and akathisia (13.0%). Serious TEAEs were reported in 9.3% patients with schizophrenia being most common (6.5%) and one death (suicide) was observed.Conclusion: Efficacy of PP1M corroborate findings from earlier studies and no new safety concerns emerged in this Chinese subgroup of patients with schizophrenia.Keywords: Chinese patients, long-acting injectable, maintenance therapy, paliperidone palmitate once-monthly, schizophrenia

Lanlan Zhang,1 Chengzhong Wang,1 Wei Li2 1Department of Pediatric Neurology, Yancheng Maternal and Child Health Hospital, 2Department of Medical Imaging, Jiangsu Vocational College of Medicine, Yancheng, China Objective: To evaluate clinical efficacy, safety, and tolerability of levetiracetam as mono- or adjunctive therapy in the treatment of children and adolescents with epilepsy.Materials and methods: We performed a meta-analysis of randomized controlled trials published from January 2007 to December 2016 in the databases Web of Science, Medline, Embase, Cochrane Library, and PubMed, Bing, Baidu, Google Scholar, Chinese National Knowledge Infrastructure (CNKI), and Wanfang Data. All of the studies eligible were compared for the efficacy, safety, and tolerability of levetiracetam with other antiepileptic drugs (AEDs) in epilepsy.Results: Thirteen randomized controlled trials on a total of 1,013 patients met the inclusion criteria in present study. Compared with other AEDs (oxcarbazepine, valproate, sulthiame, carbamazepine, and placebo), we found that levetiracetam had a comparable seizure-free rate (RR 1.16, 95% CI 1.03–1.31; P=0.30). Regarding seizure-frequency reduction ≥50% from baseline, levetiracetam also seemed equivalent to other AEDs (RR 1.08, 95% CI 1.01–1.16; P=0.35). In spite of patients treated with levetiracetam having a lower incidence of side effects compared with patients treated with other AEDs (RR 0.90, 95% CI 0.77–1.06), the difference between them was minute and not statistically significant (P=0.22).Conclusion: Based on this meta-analysis, it seemed that levetiracetam had comparable effects concerning efficacy, tolerability, and adverse events. Nevertheless, 13 studies were insufficient to draw a conclusion that levetiracetam is effective as mono- and adjunctive therapy for all types of epilepsy syndromes and seizures. Larger-sample and more well-designed trials are needed to justify the widespread use of levetiracetam in the treatment of children and adolescents. Keywords: levetiracetam, epilepsy, children, antiepileptic drug, RCT, efficacy

Nan Li,1 Yu Feng,2 Huafei Lu,3 Shang Li Cai,3 Jianmin Zhuo,4 Tianmei Si,5,6 Lili Zhang3 1Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, People’s Republic of China; 2Regional Medical Affairs, Janssen Pharmaceutical Companies of Johnson and Johnson, Singapore; 3Medical Affairs, Xian Janssen Pharmaceutical Ltd, Beijing, People’s Republic of China; 4Department of Statistics, Janssen China Research and Development, Shanghai, People’s Republic of China; 5National Clinical Research Center for Mental Disorders and The Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, People’s Republic of China; 6Peking University Institute of Mental Health (The Sixth Hospital), Beijing, People’s Republic of China Background: Paliperidone palmitate once-monthly (PP1M) demonstrated symptomatic and functional remission in patients with schizophrenia. This post hoc analysis aimed to identify factors associated with improved clinical outcomes in patients switching to PP1M (75–150 mg eq.).Methods: The improved patient outcomes were observed as Positive and Negative Symptom Scale (PANSS, symptoms) score 70:34.3% (199/581), and Involvement Evaluation Questionnaire (IEQ, caregiver burden) reduction ≥6:50.2% (270/538). Independent variables including demographics, disease duration, employment status, and clinical scores were screened individually using a univariate analysis and subsequently, variables (cutoff p

Hailun Zheng,1,2,* Huang Hong,1,* Lulu Zhang,1,2,* Xiong Cai,1,2 Meng Hu,1,2 Yuepiao Cai,2 Bin Zhou,1 Jiayuh Lin,3 Chengguang Zhao,2 Wanle Hu1 1Department of Coloproctology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 2Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 3Department of Biochemistry and Molecular Biology, University of Maryland Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MA, USA *These authors contributed equally to this work Abstract: Activation of the signal transducer and activator of transcription 3 (STAT3) is observed in multiple cancer types, including gastric cancer, and represents a potential drug target for chemotherapy. Currently, clinically available small-molecule inhibitors targeting STAT3 are lacking. Here, we report that nifuratel, an antiprotozoal and antifungal drug, is a potent inhibitor of STAT3. We found that nifuratel significantly suppressed proliferation and induced apoptosis of gastric cancer cells. Studies of the mechanism of action of nifuratel indicated that it acts by inhibiting the constitutive and interleukin-6-induced STAT3 activation. Taken together, our findings demonstrate that nifuratel may be a novel, clinically accessible STAT3 inhibitor in gastric cancer cells. Keywords: nifuratel, STAT3, gastric cancer, inhibitor, drug

Jingping Zhao,1,* Lehua Li,1,* Jianguo Shi,2 Yi Li,3 Xiufeng Xu,4 Keqing Li,5 Lili Zhang,6 Shangli Cai,6 Yu Feng,6 Jianmin Zhuo,6 Weihong Liu,6 Huafei Lu6 1Department of Psychiatry, The Mental Health Institute, The Second Xiangya Hospital of Central South University, 2Department of Psychiatry, Mental Health Center of Xi’an City, 3Department of Psychiatry, Mental Health Center of Wuhan City, 4Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, 5Department of Psychiatry, The Sixth People’s Hospital of Hebei Province, 6Department of Medical Affairs, Xi’an Janssen Pharmaceutical Ltd., Beijing, People’s Republic of China *These authors contributed equally to this work Rationale: Long-acting injectable (LAI) paliperidone palmitate 1-month formulation (PP1M) has demonstrated acceptable tolerability and favorable clinical outcomes in Western and Asian patients with schizophrenia. Hence, analysis of the outcomes of long-term PP1M treatment specifically in Chinese patients is of interest.Objective: The aim of this study is to evaluate the long-term safety and efficacy of PP1M treatment in Chinese patients with schizophrenia.Methods: In this 25-week, open-label, Phase IV study, patients (18–65 years) diagnosed with schizophrenia and having a baseline Positive and Negative Syndrome Scale (PANSS) total score of 60–120 (inclusive) were enrolled. All patients received injections of PP1M 150 mg eq. (day 1) and 100 mg eq. (day 8), followed by a flexible once-monthly maintenance dosing (75, 100, or 150 mg eq.).Results: Of the 353 patients, 234 (66.3%) completed the study treatment (mean age, 31.1 years; 52.7% men). The PANSS total score (primary end point) improved significantly over the 6-month treatment period (mean [standard deviation] change from baseline to end of treatment, -27.2 [18.30]; P

Fu De Yang,1 Juan Li,1 Yun Long Tan,1 Wei Ye Liang,1 Rongzhen Zhang,1 Ning Wang,1 Wei Feng,1 Shangli Cai,2 Jian Min Zhuo,2 Li Li Zhang2 1Beijing Hui-Long-Guan Hospital, 2Department of Medical Affairs, Xian Janssen Pharmaceutical Ltd, Beijing, People’s Republic of China Objective: The aim of this study was to evaluate the changes in treatment satisfaction after switching to paliperidone extended-release (ER) in Chinese schizophrenia patients dissatisfied with their previous antipsychotic treatment.Methods: In this 8-week, open-label, single-arm, multicenter, prospective study, 1,693 patients dissatisfied with previous antipsychotic medication were enrolled and switched to paliperidone ER tablets (3–12 mg/d) based on clinical judgment. The primary efficacy end point was change in Medication Satisfaction Questionnaire (MSQ) score from baseline to week 8. The secondary end points included percentage of patients with MSQ score ≥4, as well as changes in Clinical Global Improvement-Severity (CGI-S) and Personal and Social Performance (PSP) scores.Results: MSQ scores increased significantly from baseline (mean [standard deviation {SD}]: 2.48 [0.55]) to week 8 (5.47 [0.89], P10 patients) events were extrapyramidal disorder (n=84, 4.96%), poor quality sleep (n=18, 1.06%) and akathisia (n=13, 0.77%). The majority of AEs were mild to moderate in severity. No deaths occurred.Conclusion: Treatment satisfaction improved after switching to paliperidone ER from the previous antipsychotic in Chinese patients with schizophrenia. Keywords: atypical antipsychotics, open label, paliperidone extended-release, schizophrenia, medical satisfaction questionnaire, patient satisfaction, Chinese

Haiping Chen, Meina Li,* Zhixin Dai,* Qiangyu Deng, Lulu Zhang Department of Military Health Management, College of Health Service, Second Military Medical University, Shanghai, People’s Republic of China *These authors contributed equally to this work Objective: Dual practice is defined as a physician’s performance of medical activities in different health care institutions (two or more) simultaneously. This study aimed to examine the perception and acceptance of medical staff and outpatients of dual practice and explore the possible factors affecting people’s perception.Methods: A cross-sectional study was conducted in 13 public hospitals in Shanghai. Participants included medical staff and outpatients. We distributed 1,000 questionnaires to each participant group, and the response rates were 66.7% and 69.4%, respectively. Statistical differences in variables were tested, and multinomial logistic regression methods were employed for statistical analysis.Results: The study included two parts: medical staff survey and outpatient survey. The results of medical staff survey showed that 63.0% of the respondents supported dual practice. Medical staff who belonged to the surgical department or held positive belief of dual practice were more willing to participate in dual practice. Moreover, the publicity activities of dual practice and hospitals’ human resource management system were important factors affecting the willingness of the medical staff. The results of outpatient survey showed that 44.5% of respondents believed that dual practice could reduce difficulty in consulting a doctor. Regarding the perceived benefits of dual practice, the proportion of outpatients who believed that dual practice could meet the demand for health convenience, minor illness, and chronic disease were 45.4%, 42.4%, and 53.7%, respectively. Additionally, demographic characteristics significantly influenced the perception of outpatients.Conclusion: This study confirmed that both medical staff and outpatients generally held positive attitudes toward dual practice. Medical staff who belonged to the surgical department or held positive belief of dual practice were more willing to participate in dual practice. Moreover, the existence of publicity activities and more flexible management system of hospitals’ human resource would promote physicians’ willingness to participate in dual practice. In addition, perception of outpatients of dual practice was affected by demographic characteristics. Keywords: dual practice, perception of medical staff, outpatients’ perception, influential factors, labor supply

LiLi Zhang,1 JiTao Li,2–4 YanJie Zhao,5 Yun’Ai Su,2–4 Tianmei Si2–4 1Medical Affairs, Xian Janssen Pharmaceutical Co, Ltd, 2National Clinical Research Center for Mental Disorders, 3Peking University Sixth Hospital, Institute of Mental Health, 4The Key Laboratory of Mental Health, Ministry of Health, Peking University, 5National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China Background: Paliperidone (9-hydroxyrisperidone), the major active metabolite of risperidone, has been introduced as a novel atypical antipsychotic agent in many countries. It is available both as an oral extended-release (ER) formulation and as a long-acting injection (paliperidone palmitate, PP), which have been approved for treating schizophrenia in the People’s Republic of China since 2009 and 2012, respectively. This systematic review summarizes the efficacy, effectiveness, and safety of paliperidone in the treatment of schizophrenia in the Chinese population. Methods: A systematic literature search was conducted on the databases covering international and Chinese core journals, published from January 1, 2008, to May 22, 2015. Results: A total of 122 publications were retrieved, of which 63 studies were identified for inclusion; most studies were related to paliperidone ER (n=53), nine were related to PP, and one study was related to both agents. Paliperidone ER demonstrated at least comparable efficacy with active comparators, including risperidone, olanzapine, ziprasidone, or aripiprazole, and was found to be superior with respect to the onset of action and improvement in the Personal and Social Performance Scale score. Paliperidone ER appeared to be associated with a lower risk of metabolic syndromes; the most common treatment-emergent adverse events were extrapyramidal symptoms, akathisia, insomnia, and somnolence. Results from interventional and observational studies showed that PP was also an effective and well-tolerated treatment for Chinese patients with schizophrenia. The findings were generally consistent with those observed in non-Chinese populations. Conclusion: Both paliperidone ER and PP were effective and well-tolerated agents for the treatment of schizophrenia in the Chinese population according to the data we reviewed. No new safety signals specific for the Chinese population were raised for paliperidone. Further studies may be needed to collect more data on long-term treatment of schizophrenia in the People’s Republic of China. Keywords: paliperidone, antipsychotics, efficacy, effectiveness, safety

Bi-Xia Liu,1,* Xi-Jian Dai,2,3,* Heng Liu,4,* Hong-Han Gong,3 Yi-Xiang J Wang,2 Lun-Li Zhang1 1Department of Infectious Diseases, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Imaging and Interventional Radiology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; 3Department of Radiology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 4Department of Radiology, Affiliated Hospital of Zunyi Medical University, Guizhou, People’s Republic of China *These authors contributed equally to this work Abstract: Central nervous system (CNS) cryptococcosis is an opportunistic fungal infection that typically occurs in patients with reduced immunological function, such as patients with AIDS, patients receiving organ transplants, or patients receiving corticosteroid and immunosuppressive therapy. CNS cryptococcosis rarely occurs in immunocompetent patients. CNS cryptococcosis is characterized by meningitis and encephalitis and occasionally forms isolated granulomas. Isolated cerebellar cryptococcoma is a rare condition, especially in immunocompetent patients, and the misdiagnosis rate is high. A definite diagnosis must be based on pathology. To raise awareness of this disease, the clinical data of a patient with cryptococcomas in the right side of the cerebellum are reported. Keywords: cryptococcosis, cerebellar, central nervous system, magnetic resonance imaging, immunosuppressive

Understanding the complexity and dynamics of cancer cells in response to effective therapy requires hypothesis-driven, quantitative, and high-throughput measurement of genes and proteins at both spatial and temporal levels. This study was designed to gain insights into molecular networks underlying the clinical synergy between retinoic acid (RA) and arsenic trioxide (ATO) in acute promyelocytic leukemia (APL), which results in a high-quality disease-free survival in most patients after consolidation with conventional chemotherapy. We have applied an approach inte- grating cDNA micro array, 2D gel electrophoresis with MS, and methods of computational biology to study the effects on APL cell line NM treated with RA, ATO, and the combination of the two agents and collected in a time series. Numerous features were revealed that indicated the coordinated regulation of molecular networks from various aspects of granulocytic differentiation and apoptosis at the transcript and protium levels. These features include an array of transcription factors and cofactors, activation of calcium signaling, stimulation of the IFN pathway, activation of the proteasome system, degradation of the PML-RARE onco protein, restoration of the nuclear body, cell-cycle arrest and gain of apoptotic potential. Hence, this investigation has provided not only a detailed understanding of the combined therapeutic effects of RA/ATO in API but also a road map to approach hematopoietic malignancies at the systems level. [ABSTRACT FROM AUTHOR]

A facile, fast and visible sensing platform for ascorbic acid (AA) detection has been developed based on self-assembled hydrangea-like europium metal-organic framework (HL-EuMOF). HL-EuMOF was synthesized through a simple one-step mixing process with Eu 3+ and 1, 10-phenanthroline-2, 9-dicarboxylic acid at room temperature, which exhibited excellent properties including strong red fluorescence, long decay lifetime (548.623 μs) and good luminescent stability. Based on the specific redox reaction between Fe 3+ and AA, the HL-EuMOF@Fe 3+ was fabricated with "turn-off" response for AA, where the resulting Fe 2+ displayed effective fluorescence quenching ability toward HL-EuMOF. The sensor demonstrated low detection limit (31.94 nM), rapid response time (30 s) and high selectivity. Integration of smartphone-assisted RGB analysis with HL-EuMOF@Fe 3+ permitted convenient and visible quantitative determination of AA level. This approach also presented good detection performances in complex human serum and beverage samples, which could provide a valuable tool for AA detection in biomedical research and food industry., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Salt stress severely affects the growth and yield of apples (Malus domestica Borkh). Although salt-tolerant genes have been extensively studied, documentation on the role of the ATP-dependent phosphofructokinase gene MdPFK5 in salt stress is limited. This study conducted an evolutionary tree and three-dimensional structure analysis of the PFK gene family in Arabidopsis thaliana and MdPFK (MD01G1037400), revealing a close phylogenetic relationship between MdPFK (MD01G1037400) and AtPFK5. Given the similarity in their protein tertiary structures, MdPFK was designated as MdPFK5, suggesting functional similarities with AtPFK5. Further investigation revealed elevated expression levels of MdPFK5 in apple leaves and flowers, particularly showing significant upregulation 120 days after blooming and differential expression beginning at 3 hours of salt stress. Overexpression of MdPFPK5 conferred salt tolerance in both apple calli and transgenic lines of Arabidopsis thaliana. Moreover, NaCl treatment promoted soluble sugar accumulation in apple calli and transgenic lines of Arabidopsis thaliana overexpressing MdPFK5. This study provides new insights into the salt tolerance function of MdPFK5., (© 2024 Scandinavian Plant Physiology Society.)

Epilepsy (EP) is one of the most common neurological diseases in the world. Anemarrhena asphodeloides Bunge. (AA), as a typical heat-cleaning medicine, has been proven to possess the antiepileptic effect in clinical and experimental studies. Anemarrhena asphodeloides steroidal saponins (AAS) are main components. However, the therapeutic effects and underlying mechanisms of AAS against EP are not been fully elucidated. In this study, 63 steroidal saponins were discovered in AAS by UPLC-Q-TOF/MS analysis. Pharmacological and behavioral analysis demonstrated that AAS could significantly lower the Racine classification and reduce the frequency of generalized spike rhythm the rate of tetanic seizures in kainic acid-induced epileptic rats. Hematoxylin and eosin and Nissl staining-indicated AAS could significantly improve hippocampal injury and neuron loss in epileptic rats. TMT proteomic analysis discovered 26 different expressed proteins (DEPs), which were identified as the rescue proteins. After bioinformatic analysis, Heat Shock Protein 90 Alpha Family Class B Member 1 (Hsp90ab1) and Tyrosine 3-Monooxygenase (Ywhab) were screened as key DEPs and verified by western blotting. AAS could significantly inhibited the up-regulation of Hsp90ab1 and Ywhab in EP rats; these two proteins might be the key targets of AAS in treating EP., (© 2024 John Wiley & Sons Ltd.)

Radiation injury to the intestine is one of the most common complications in patients undergoing abdominal or pelvic cavity radiotherapy, limiting the clinical application of this treatment. Evidence shows the potential benefits of dietary restriction in improving metabolic profiles and age-related diseases. The present study investigated the effects and mechanisms of dietary restriction in radiation-induced intestinal injury. The mice were randomly divided into the control group, 10 Gy total abdominal irradiation (TAI) group, and groups pretreated with 30% caloric restriction (CR) for 7 days or 24 h fasting before TAI. After radiation, the mice were returned to ad libitum. The mice were sacrificed 3.5 days after radiation, and tissue samples were collected. CR and fasting reduced radiation-induced intestinal damage and promoted intestinal recovery by restoring the shortened colon length, improving the impaired intestinal structure and permeability, and remodeling gut microbial structure. CR and fasting also significantly reduced mitochondrial damage and DNA damage, which in turn reduced activation of the cyclic GMP-AMP synthase/stimulator of interferon gene (cGAS/STING) pathway and the production of type I interferon and other chemokines in the jejunum. Since the cGAS/STING pathway is linked with innate immunity, we further showed that CR and fasting induced polarization to immunosuppressive M2 macrophage, decreased CD8 + cytotoxic T lymphocytes, and downregulated proinflammatory factors in the jejunum. Our findings indicated that CR and fasting alleviate radiation-induced intestinal damage by reducing cGAS/STING-mediated harmful immune responses., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

[ 18 F]3-fluoro-4-aminopyridine ([ 18 F]3F4AP) is the first positron emission tomography (PET) radioligand that targets voltage-gated potassium (K + ) channels in the brain for imaging demyelination. [ 18 F]3F4AP exhibits high brain penetration, favorable kinetics for PET imaging, and high sensitivity to demyelinating lesions. However, recent studies in awake human subjects indicate lower metabolic stability than in anesthetized animals, resulting in reduced brain uptake. Therefore, there is a need for novel radioligands for K + channels with suitable pharmacological properties and enhanced metabolic stability. Recent in vitro studies demonstrate that 5-methyl-3-fluoro-4-aminopyridine (5Me3F4AP) exhibits comparable binding affinity to K + channels, pK a , logD, and membrane permeability as 3F4AP, and a slower enzymatic metabolic rate, suggesting its potential as a K + channel PET tracer. In this study, we describe the radiochemical synthesis of [ 18 F]5Me3F4AP using an isotope exchange method from the corresponding 3-fluoro-5-methyl-4-nitropyridine N-oxide, followed by a palladium on carbon mediated hydrogenation of the nitro and N-oxide groups. This method yielded [ 18 F]5Me3F4AP with high purity and acceptable molar activity. PET/CT studies using naïve mice demonstrate that [ 18 F]5Me3F4AP effectively crosses the blood-brain barrier and has comparable kinetics to [ 18 F]3F4AP. These findings strongly suggest that [ 18 F]5Me3F4AP is a promising candidate for neuroimaging applications and warrant further studies to investigate its sensitivity to lesions and in vivo metabolic stability., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: P.B. is a named inventor on patents related to [(18)F]3F4AP owned by the University of Chicago. P.B. and Y.S. are named inventors on a patent application related to [(18)F]5Me3F4AP filed by MGH. The other authors declare no conflict of interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: To explore the effects of antenatal corticosteroids (ACS) on the outcomes of very premature infants (VPIs) and neurodevelopment during infancy., Methods: A retrospective study was conducted on 190 VPIs admitted to the Department of Pediatrics of the First Affiliated Hospital of Anhui Medical University from January 2020 to December 2022. The infants were categorized into four groups based on ACS usage and dosage: no ACS group ( n =18), single-course group ( n =88), multi-course group ( n =40), and partial-course group ( n =44). The clinical outcomes, Neonatal Behavioral and Neurological Assessment (NBNA) scores at 40 weeks of corrected age, and Gesell Developmental Schedule (Gesell) scores at 1 year of corrected age were compared among the four groups. The impact of timing of ACS use on the Gesell scores of infants at 1 year of corrected age in VPIs with specific gestational ages was analyzed., Results: The incidence rates of neonatal respiratory distress syndrome, bronchopulmonary dysplasia, transient tachypnea of the newborn, and neonatal pneumonia were significantly lower in the partial-course, single-course, and multiple-course groups compared with the no ACS group ( P <0.008). However, there was no significant difference among the partial-course, single-course, and multiple-course groups ( P >0.008). The NBNA scores (behavioral ability, active muscle tone, primitive reflexes, and general assessment) at 40 weeks of corrected age were significantly higher in the no ACS, partial-course, and single-course groups than in the multiple-course group ( P <0.008). The proportion of VPIs with normal neurodevelopment at 1 year of corrected age was significantly higher in the no ACS, partial-course, and single-course groups than in the multiple-course group ( P <0.008). The timing of ACS use had no significant effect on neurodevelopment at a corrected age of 1 year in infants with various gestational ages ( P >0.05)., Conclusions: ACS is crucial for the development of the respiratory system in VPIs, but multiple courses of ACS may cause neurodevelopmental abnormalities. The impact of ACS use on neurodevelopment is independent of gestational age and the timing of ACS use.

Three undescribed isosteroidal alkaloids (1-3), along with two known ones (4, 5) were isolated from the bulbs of Fritillaria ussuriensis Maxim, their structures were established by comprehensive analyses of the 1D, 2D-NMR and HR-ESI-MS data. Meanwhile, LPS-activated RAW 264.7 macrophages were used to determine the potential anti-inflammatory activity of all the alkaloids in vitro. Among them, compounds 1 and 4 showed significant inhibitory effects against LPS-induced NO production with IC 50 values of 7.79 μM and 11.22 μM, respectively. Compounds 1 and 4 were performed between molecular docking with TLR4/MD2. Based on the results of cell experiments and binding affinities, compound 1 (UG) was chosen for molecular dynamic analysis together with the TLR4/MD2 protein., Competing Interests: Declaration of competing interest The authors declared no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Axis inhibition protein 1 (AXIN1), a scaffold protein interacting with various critical molecules, plays a vital role in determining cell fate. However, its impact on the antiviral innate immune response remains largely unknown. Here, we identify that AXIN1 acts as an effective regulator of antiviral innate immunity against both DNA and RNA virus infections. In the resting state, AXIN1 maintains the stability of the transcription factor interferon regulatory factor 3 (IRF3) by preventing p62-mediated autophagic degradation of IRF3. This is achieved by recruiting ubiquitin-specific peptidase 35 (USP35), which removes lysine (K) 48-linked ubiquitination at IRF3 K366. Upon virus infection, AXIN1 undergoes a phase separation triggered by phosphorylated TANK-binding kinase 1 (TBK1). This leads to increased phosphorylation of IRF3 and a boost in IFN-I production. Moreover, KYA1797K, a small molecule that binds to the AXIN1 RGS domain, enhances the AXIN1-IRF3 interaction and promotes the elimination of various highly pathogenic viruses. Clinically, patients with HBV-associated hepatocellular carcinoma (HCC) who show reduced AXIN1 expression in pericarcinoma tissues have low overall and disease-free survival rates, as well as higher HBV levels in their blood. Overall, our findings reveal how AXIN1 regulates IRF3 signaling and phase separation-mediated antiviral immune responses, underscoring the potential of the AXIN1 agonist KYA1797K as an effective antiviral agent., (© 2024. The Author(s).)

Basal-like breast cancer (BLBC) is the most malignant subtype of breast cancer because of its aggressive clinical behaviour and lack of effective targeted agents. Krüppel-like factor 5 (KLF5) is an oncogenic transcription factor that is highly expressed in BLBC. The deubiquitinase (DUB) BRCA1-associated protein 1 (BAP1) stabilizes KLF5 and promotes BLBC growth and metastasis. Therefore, pharmacological inhibition of the BAP1‒KLF5 axis is an effective therapeutic strategy for BLBC. Here, through screening, we identified a series of tetrahydro-β-carboline derivatives that effectively reduced the protein expression of KLF5 and exhibited strong antitumour activity. Among the investigated compounds, the lead compound LN-439A presented the strongest antitumour activity and inhibitory effect on KLF5 expression. LN-439A suppressed the proliferation and migration of BLBC cells, induced G2/M arrest, and induced apoptosis. Mechanistically, LN-439A functions as a small molecule catalytic inhibitor of BAP1 by binding to the catalytic pocket of BAP1, leading to the ubiquitination and degradation of KLF5. Consistent with this finding, the overexpression of KLF5 suppressed the antitumour effects of LN-439A. In summary, LN-439A is a promising therapeutic agent for BLBC that functions by targeting the BAP1‒KLF5 axis., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Background: Extranodal natural killer/T-cell lymphoma (ENKTCL) has a unique treatment principle. However, the optimal combination of drugs along with radiotherapy (RT) is unknown., Design: Retrospective cohort study., Objectives: We screened multiple drug combinations to identify the most efficacious therapeutic combinations., Methods: We reviewed 3105 patients who received 40 chemotherapy regimens with different combinations of 9 drug classes and/or RT. Least absolute shrinkage and selection operator and multivariable Cox regression analyses were used to screen efficacious single drugs and identify optimal combinations for overall survival (OS). Inverse probability of treatment weighting (IPTW) and multivariable analyses were used to compare survival between treatment regimens., Results: Screening and validation revealed RT, asparaginase (ASP), and gemcitabine (GEM) to be the most efficacious single modality/drug. RT remained an important component of first-line treatment, whereas ASP was a fundamental drug of non-anthracycline (ANT)-based regimens. Addition of RT to non-ANT-based or ASP/GEM-based regimens, or addition of an ASP-drug into ANT-based or GEM/platinum-based regimens, improved 5-year OS significantly. Use of ASP/GEM-based regimens was associated with significantly higher 5-year OS (79.9%) compared with ASP/ANT-based (69.2%, p  = 0.001), ASP/methotrexate-based (63.5%, p  = 0.011), or ASP/not otherwise specified-based (63.2%, p  < 0.001) regimens. The survival benefit of ASP/GEM-based regimens over other ASP-based regimens was substantial across risk-stratified and advanced-stage subgroups. The survival benefits of a combination of RT, ASP, and GEM were consistent after adjustment for confounding factors by IPTW., Conclusion: These results suggest that combining ASP/GEM with RT for ENKTCL is an efficacious and feasible therapeutic option and provides a rationale and strategy for developing combination therapies., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)