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Qiaoting Huang,1 Changzheng Shi,2 Saurabh Sonkusare,3 Congrui Li,1 Valerie Voon,3 Jiyang Pan1 1Department of Psychiatry, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 2Medical Imaging Center, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 3Department of Psychiatry, University of Cambridge, Cambridge, UKCorrespondence: Jiyang Pan, Department of Psychiatry, The First Affiliated Hospital of Jinan University, 613 West Huangpu Avenue, Guangzhou, 510630, People’s Republic of China, Tel +86 20 38688651, Email jiypan@163.com Valerie Voon, Department of Psychiatry, University of Cambridge, Box 189, Level E4, Addenbrooke’s Hospital, Cambridge, CB2 0QQ, UK, Tel +44 1223 765088, Email vv247@cam.ac.ukPurpose: Converging evidence implicates the putamen in sleep-wake regulation. However, its role remains unclear. We hypothesized that metabolic abnormalities in the putamen are linked to insomnia disorder, which has not been previously addressed, and investigated putaminal N-acetylaspartate (NAA), choline (Cho), and creatine (Cr) in patients with insomnia disorder compared to healthy controls.Participants and Methods: In the present study, the concentrations of NAA, Cho, and Cr in the putamen of 23 patients with insomnia disorder and 18 healthy controls were determined using proton magnetic resonance spectroscopy. Sociodemographic, psychometric, and polysomnography data were obtained from all participants.Results: We found that the mean NAA/Cr ratio of the right putamen was significantly greater in the insomnia group compared to the control group and also greater than the left putamen within the insomnia group. The NAA/Cr ratio of the right putamen distinguished insomnia disorder from normal sleep with 78.3% sensitivity and 61.1% specificity. Furthermore, this ratio positively correlated with both objective and subjective insomnia severity and sleep quality.Conclusion: Our findings provide critical evidence for the dysfunctional putaminal metabolism of NAA/Cr in insomnia disorder, suggesting that the abnormal NAA/Cr ratio of the right putamen is linked to wakefulness in patients with insomnia disorder and may serve as a potential biomarker of insomnia disorder.Keywords: insomnia disorder, wakefulness, putamen, proton magnetic resonance spectroscopy, NAA/Cr ratio, polysomnography

Congenital diarrheal disorders (CDD) are a group of rare inherited intestinal disorders, among which CDD7 was recently identified to be associated with only 24 mutations in gene coding for diacylglycerol-acyltransferase 1 (DGAT1).

Shengping Gong,1 Cong Shi2 1Cancer Radiotherapy and Chemotherapy Center, the First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, People’s Republic of China; 2Laboratory of Stem Cell Transplantation, the First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315000, People’s Republic of ChinaCorrespondence: Cong Shi, Email shicong5103@sina.comBackground: Immune imbalance appears to have a critical role in tumor growth according to emerging research. Peripheral lymphocyte subsets are considered to reflect the systemic immune response and clinical prognosis. The prognostic value of lymphocyte subpopulations in myelodysplastic syndrome (MDS) patients remains unclear.Methods: A total of 94 MDS patients were enrolled for the study. X-tile software was performed to determine the prognostic significance of various lymphocyte subpopulations, CD3, CD4, CD8, CD4/CD8 ratio, natural killer cell (NK) and CD19. Among them, the appropriate threshold of NK percent could be found only. Patients were divided into the high NK percent group and the low NK percent group. The prognostic significance was determined by univariate and multivariate Cox hazard models.Results: MDS patients with lower NK level had significantly shorter overall survival (OS). Based on univariate analysis, male gender (P = 0.030), lower HB (< 10 g/dl, P = 0.029), higher BM blast (> 5%, P < 0.0001), higher-risk IPSS-R cytogenetic (P = 0.032) and lower NK percent (P < 0.0001) were significantly associated with shorter OS. Multivariate Cox proportional hazards regression analysis indicated that low NK was also independent adverse prognostic factor for OS in MDS.Conclusion: Decreased NK level predicts poor prognosis independent of the IPSS-R and provide a novel evaluation factor for MDS patients.Keywords: myelodysplastic syndrome, lymphocyte subsets, prognostic, IPSS-R, natural killer cell

Li Zhang,1,2 Zimu Yu,3 Yunfeng Zhang,1 Hengyu Wang,4,5 Juntao Cheng,6 Chao Shi1 1Department of Oncology, Gaoxin Branch Of The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, People’s Republic of China; 2First School of Clinical Medicine, Jiangxi Medical College, Nanchang University, Nanchang, 330031, People’s Republic of China; 3Medical College of Zhengzhou University, Zhengzhou University, Zhengzhou, 450001, People’s Republic of China; 4Queen Mary College, Nanchang University, Nanchang, 330031, People’s Republic of China; 5School of Biological and Biomedical Sciences, Queen Mary University of London, London, UK; 6Peking University First Hospital, Peking University, Beijing, 100034, People’s Republic of ChinaCorrespondence: Chao Shi, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Donghu District, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel +86 151 7049 8679, Email ndyfy4540@ncu.edu.cnPurpose: Although brain metastasis (BM) from gastric cancer (GC) is relatively uncommon, its incidence has been increasing owing to advancements in treatment modalities. Unfortunately, patients diagnosed with BM from gastric cancer have poor life expectancy. Our study aims to establish a predictive model for brain metastasis in advanced gastric cancer patients, thus enabling the timely diagnosis of brain metastasis.Patients and Methods: The clinicopathological features of a cohort which included 40 GC patients with brain metastasis, 32 of whom from the First Affiliated Hospital of Nanchang University, 2 from Gaoxin Branch of the First Affiliated Hospital of Nanchang University, remaining 6 from Anyang District Hospital, and 80 non-metastatic advanced GC patients from the First Affiliated Hospital of Nanchang University between 2018 and 2022. Data were retrospectively analyzed.Results: Age, tumor size, differentiation, lymph node grade, tumor location, Lauren classification, liver metastasis, carbohydrate antigen 199 (CA199), lactate dehydrogenase (LDH), and human epidermal growth factor receptor 2 (Her-2) were associated with BM. A nomogram integrated with nine risk factors (tumor size, differentiation, lymph node grade, tumor location, Lauren classification, liver metastasis, CA-199, LDH, and Her-2) showed good performance (Area Under Curve 0.95, 95% CI: 0.91– 0.98).Conclusion: We developed and validated a nomogram that achieved individualized prediction of the possibility of BM from GC. This model enables personalized imaging review schedules for timely brain metastasis detection in advanced gastric cancer patients.Keywords: brain metastasis, gastric cancer, nomogram, risk factors

Yaping Wang,1 Yiyi Zhao,1 Chaolu Shi,2 Juanqing Li,1,3,4 Xiufeng Huang1,3,4 1Zhejiang University, Womens Hospital, Sch Med, Department Obstet & Gynecol, Hangzhou, Zhejiang, People’s Republic of China; 2Cixi maternity&health Care Hospital, Department Obstet & Gynecol Ningbo, Ningbo, Zhejiang, People’s Republic of China; 3Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 4Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Juanqing Li; Xiufeng Huang, Email ljq0313@zju.edu.cn; huangxiufeng@zju.edu.cnPurpose: The aim of this study was to investigate the risk factors of postmenopausal special uterine leiomyoma pathological types or leiomyosarcoma and to develop a nomogram for clinical risk assessment, ultimately to reduce unnecessary surgical interventions and corresponding economic expenses.Methods: A total of 707 patients with complete information were enrolled from 1 August 2012 to 1 August 2022. Univariate and multivariate logistic regression models were used to analyse the association between variables and special uterine leiomyoma pathological types or leiomyosarcoma in postmenopausal patients. A nomogram for special uterine leiomyoma pathological types or leiomyosarcoma in postmenopausal patients was developed and validated by bootstrap resampling. The calibration curve was used to assess the accuracy of the model and receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were compared with the clinical experience model.Results: The increasing trend after menopause, the diameter of the largest uterine fibroid, serum carcinoembryonic antigen 125 concentration, Serum neutrophil to lymphocyte ratio, and Serum phosphorus ion concentration were independent risk factors for special uterine leiomyoma pathological types or leiomyosarcoma in postmenopausal patients. We developed a user-friendly nomogram which showed good diagnostic performance (AUC=0.724). The model was consistent and the calibration curve of our cohort was close to the ideal diagonal line. DCA indicated that the model has potential value for clinical application. Furthermore, our model was superior to the previous clinical experience model in terms of ROC and DCA.Conclusion: We have developed a prediction nomogram for special uterine leiomyoma pathological types or leiomyosarcoma in postmenopausal patients. This nomogram could serve as an important warning signal and evaluation method for special uterine leiomyoma pathological types or leiomyosarcoma in postmenopausal patients.Keywords: special uterine leiomyoma pathological types, leiomyosarcoma, postmenopausal women, prediction nomogram, bootstrap

Fujian Ji, Chunyu Shi, Zhenbo Shu, Zhongmin Li Department of Gastrointestinal and Colorectal Surgery, China-Japan Union Hospital of Jilin University, Changchun, 130033, People’s Republic of ChinaCorrespondence: Zhongmin Li, Email lizhongmin1211@jlu.edu.cnAbstract: Pyroptosis, a pro-inflammatory and lytic programmed cell death pathway, possesses great potential for antitumor immunotherapy. By releasing cellular contents and a large number of pro-inflammatory factors, tumor cell pyroptosis can promote dendritic cell maturation, increase the intratumoral infiltration of cytotoxic T cells and natural killer cells, and reduce the number of immunosuppressive cells within the tumor. However, the efficient induction of pyroptosis and prevention of damage to normal tissues or cells is an urgent concern to be addressed. Recently, a wide variety of nanoplatforms have been designed to precisely trigger pyroptosis and activate the antitumor immune responses. This review provides an update on the progress in nanotechnology for enhancing pyroptosis-based tumor immunotherapy. Nanomaterials have shown great advantages in triggering pyroptosis by delivering pyroptosis initiators to tumors, increasing oxidative stress in tumor cells, and inducing intracellular osmotic pressure changes or ion imbalances. In addition, the challenges and future perspectives in this field are proposed to advance the clinical translation of pyroptosis-inducing nanomedicines. Keywords: pyroptosis, programmed cell death, nanomaterial, immunotherapy

Bingcong Zhao,1,2 Zhigang Li,3 Chuan Shi,4 Yan Liu,5 Yang Sun,3 Bin Li,1,2 Jie Zhang,6 Zhizhong Gong,7 Yuanzheng Wang,8 Xuehong Ma,9 Xinjing Yang,10 Huili Jiang,3 Yuanbo Fu,1,2 Xin Wang,1,2 Yang Li,6 Hengchia Liu,6 Tuya Bao,3 Yutong Fei11– 13 1Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Key Laboratory of Acupuncture Neuromodulation, Beijing, People’s Republic of China; 3School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Psychological Assessment Center, Peking University Sixth Hospital, Beijing, People’s Republic of China; 5Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 6Department of Psychosomatic Medicine, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 7Division of Medical Affairs, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 8Department of Integrative TCM and Western Medicine, Peking University First Hospital, Beijing, People’s Republic of China; 9Department of Acupuncture & Moxibustion, Dongfang Hospital, the Second Clinical Medical College of Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 10Department of Traditional Chinese Medicine, South China Hospital of Shenzhen University, Shenzhen, People’s Republic of China; 11Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 12Institute of Excellence in Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 13Beijing GRADE Centre, Beijing, People’s Republic of ChinaCorrespondence: Tuya Bao, School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, No. 11, Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, People’s Republic of China, Email tuyab@263.net Yutong Fei, Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, No. 11, Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, People’s Republic of China, Email feiyt@bucm.edu.cnPurpose: Anxious depression (AD) is a common, distinct depression subtype. This exploratory subgroup analysis aimed to explore the effects of acupuncture as an add-on therapy of selective serotonin reuptake inhibitors (SSRIs) for patients with AD or non-anxious depression (NAD).Patients and Methods: Four hundred and sixty-five patients with moderate-to-severe depression from the AcuSDep pragmatic trial were included in analysis. Patients were randomly assigned to receive MA+SSRIs, EA+SSRIs, or SSRIs alone (1:1:1) for six weeks. AD was defined by using dimensional criteria. The measurement instruments included 17-items Hamilton Depression Scale (HAMD-17), Self-Rating Depression Scale (SDS), Clinical Global Impression (CGI), Rating Scale for Side Effects (SERS), and WHO Quality of Life-BREF (WHOQOL-BREF). Comparison between AD and NAD subgroups and comparisons between groups within either AD or NAD subgroups were conducted.Results: Eighty percent of the patients met the criteria for AD. The AD subgroup had poorer clinical manifestations and treatment outcomes compared to those of the NAD subgroup. For AD patients, the HAMD response rate, remission rate, early onset rate, and the score changes on each scale at most measurement points on the two acupuncture groups were significantly better than the SSRIs group. For NAD patients, the HAMD early onset rates of the two acupuncture groups were significantly better than the SSRIs group.Conclusion: For AD subtype patients, either MA or EA add-on SSRIs showed comprehensive improvements, with small-to-medium effect sizes. For NAD subtype patients, both the add-on acupuncture could accelerate the response to SSRIs treatment. The study contributed to the existing literature by providing insights into the potential benefits of acupuncture in combination with SSRIs, especially for patients with AD subtypes. Due to its limited nature as a post hoc subgroup analysis, prospectively designed, high-quality trials are warranted.Clinical Trials Registration: ChiCTR-TRC-08000297.Keywords: anxious depression, non-anxious depression, acupuncture, SSRIs, subgroup analysis

Chunxia Shi,1– 3,&ast; Xiaoning Liu,4,&ast; Zouxi Du,2,3,5 Limin Tian2,3 1School of Medicine, Jiangsu University, Zhenjiang, People’s Republic of China; 2Department of Endocrinology, Gansu Provincial Hospital, Lanzhou, People’s Republic of China; 3Clinical Research Center for Metabolic Diseases, Lanzhou, Gansu Province, People’s Republic of China; 4Institution of Health Statistics and Epidemiology, School of Public Health, Lanzhou University, Lanzhou, People’s Republic of China; 5The First School of Clinical Medicine, Lanzhou University, Lanzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Limin Tian, Department of Endocrinology, Gansu Provincial Hospital, Donggang West Road, Lanzhou, Gansu, 730000, People’s Republic of China, Tel +86-15293184257, Email tlm7066@sina.comPurpose: This study aims to investigate the relationship between thyroid and type 1 diabetic nephropathy (T1DN) in euthyroid populations, focusing on thyroid hormone sensitivity.Methods: A cross-sectional study was conducted between January 2016 and December 2021, including 357 euthyroid patients with type 1 diabetes mellitus (T1DM). Parameters representing thyroid hormone sensitivity were assessed, including the thyroid feedback quantile-based index (TFQI), parameter thyroid feedback quantile index (PTFQI), thyroid stimulating hormone index (TSHI), thyrotropin thyroxine resistance index (TT4RI), and free triiodothyronine/free thyroxine (FT3/FT4). Logistic regression and restricted cubic spline regression were performed to detect the association between thyroid hormone sensitivity and the risk of T1DN.Results: The study found a negative correlation between the risk of T1DN and FT3/FT4 in euthyroid T1DM patients (OR 0.71, 95% CI 0.51– 0.97, P < 0.01). PTFQI (P< 0.05), TSHI (P< 0.05), and TT4RI (P< 0.01) showed an M-shaped nonlinear relationship with the risk of T1DN. Elevated risk of T1DN was associated with PTFQI, TSHI, and TT4RI values outside the range of zero, 2.3– 3.88, and 27.56– 32.19, respectively.Conclusion: This study confirms the relationship between impaired thyroid hormone sensitivity and the risk of T1DN in euthyroid patients. It emphasizes the importance of evaluating thyroid hormone sensitivity in T1DM patients, even when their thyroid function appears normal, to promptly prevent the occurrence of T1DN.Keywords: euthyroid, sensitivity to thyroid hormones, type 1 diabetic nephropathy

Qiang Fu,1 Na Han,1 Na Li,2 Ling Gui,3 Chen Shi,4 Peipei Rong,5 Fan Zeng,1 He Rao,6 Yuan Chen1 On behalf of Cancer Rehabilitation and Palliative Treatment Professional Committee of Hubei Anti Cancer Association1Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China; 2Cancer Center, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People’s Republic of China; 3Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China; 4Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 5Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People’s Republic of China; 6Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of ChinaCorrespondence: Qiang Fu; Yuan Chen, Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Qiaokou District, Wuhan, Hubei, 430030, People’s Republic of China, Email fqiang2016@163.com; chenyuan008@163.comAbstract: Pain is one of the most common clinical symptoms of cancer patients, seriously affecting the quality of life of patients and bringing heavy mental and economic burden to families and society. The treatment of cancer pain in China is facing numerous challenges, one of which includes the irrational usage of analgesic drugs in clinical practice. As a strong opioid analgesic, transdermal fentanyl patch has been widely used due to its convenient clinical application and obvious therapeutic effect. Several basic-level hospitals and even general hospitals in China fail to appropriate the application of drugs in clinical application due to the lack of understanding of the pharmacological characteristics and clinical application of fentanyl transdermal patch by medical staff, seriously affecting the treatment quality. Therefore, it is imperative to strengthen the rational use and management of fentanyl transdermal patches. Accordingly, the initiation by the Cancer Rehabilitation and Palliative Treatment Professional Committee of the Hubei Anti-cancer Association launched the compilation of the “Guidelines for Rational Clinical Use of Fentanyl Transdermal Patch” (from now on referred to as the “Guidelines”) in Hubei Province, China. The experts in the preparation group are experts in many disciplines, such as medicine, pharmacy, and nursing. The expert group determines the outline, prepares the required regulations, and revises it repeatedly. Moreover, these experts put forward suggestions for revision to strictly control the accuracy and scientific authenticity of the contents of the “Guide”. Finally, all experts of the preparation team certify and finalize the draft. This “Guide” prepared by experts of the Cancer Rehabilitation and Palliative Treatment Professional Committee of the Hubei Anti-cancer Association and the expert advisory group with joint efforts, aims to play a positive role in promoting the rational clinical use of fentanyl transdermal patch, reducing the mental and economic burden of patients, and ensuring medical quality and medical safety.Keywords: fentanyl transdermal patch, reasonable application, medication guidelines

Min Yi,1 Yuebin Cao,2 Jiangjun Wang,3 Chenyi Shi,1 Yalin Cheng,1 Yanlin Cao1 1Institute of Medical Information and Library, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100020, People’s Republic of China; 2Health Commission of Hunan Province, Changsha, 410008, People’s Republic of China; 3China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of ChinaCorrespondence: Yanlin Cao, Institute of Medical Information and Library, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 3 Yabao Street, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel +86-010-52328845, Email cao.yanlin@imicams.ac.cnBackground: Medical disputes are a recurrent and pressing issue in hospitals, posing significant challenges to the functioning of medical institutions. We aimed to investigate whether receiving rule of law publicity on short video platforms is relevant to preventing medical disputes among healthcare professionals.Methods: We collected the data from 37,978 medical professionals from 130 tertiary public hospitals. Participants were classified into two groups according to the presence of receiving rule of law publicity on short video platforms. A subgroup analysis was performed before and after propensity score analysis, and multiple logistic regression was used to identify risk factors for medical disputes.Results: Among all participants, 46.1% (17,506/37,978) experienced medical disputes. Before propensity score analysis, the prevalence of medical disputes among participants who received rule of law publicity on short video platforms was similar to that among participants who did not (P = 0.639). However, after propensity score analysis, participants who received the rule of law publicity on short video platforms did not show a benefit effect. These participants had a significantly higher rate of suffering from medical disputes than participants who did not receive publicity on this platform (P=0.020). Multiple logistic regression analysis confirmed that receiving the rule of law publicity through short video platforms (P=0.010) or MicroBlog (P = 0.016), and previously facing legal issues outside of medical work (P < 0.001) were risk factors for medical disputes; participating in legal training organized by hospitals (P=0.004) and the hospital rule of law being very good (P=0.045) were protective factors.Conclusion: Medical disputes are a common occurrence within the healthcare profession. However, using short video platforms to promote the rule of law is not an effective method to prevent disputes. Instead, healthcare professionals can benefit from participating in legal training and having a well-established rule of law within the hospital construct.Keywords: healthcare professionals, medical disputes, rule of law publicity, short video platforms, construction of hospital rule of law

Mingping He,1,&ast; Wenzheng Han,1,&ast; Chuan Shi,1 Ming Wang,1 Junheng Li,2 Wei He,2 Xinxin Xu,3 Qian Gan,1 Shaofeng Guan,1 Liang Zhang,1 Yang Chen,1 Xifeng Chang,1 Tianqi Li,1 Xinkai Qu1 1Department of Cardiology, Huadong Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 2Department of Nuclear Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 3Clinical Research Center for Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenzheng Han; Xinkai Qu, Department of Cardiology, Huadong Hospital Affiliated to Fudan University, No. 221, Yan’an Road (W), Shanghai, People’s Republic of China, Email wzhan_cardiology@foxmail.com; qxkchest@126.comBackground: Microvascular dysfunction in patients with non-obstructive epicardial coronary may aggravate patient’s symptoms or lead to various clinical events.Objective: To investigate the correlation between dynamic single photon emission computed tomography (D-SPECT) derived coronary flow reserve (CFR) and TIMI frame count (TFC) in patients with non-obstructive epicardial coronary patients.Methods: Patients with suspected or known stable CAD who were recommended to undergo invasive coronary angiography were prospectively enrolled in this study. Those who had non-obstructive coronary received TIMI frame count (TFC) and D-SPECT. A cut-off value of > 40 was defined as slow flow referred to TFC.Results: A total of 47 patients diagnosed with non-obstructive coronary were enrolled. The mean age of patients was 66.09 ± 8.36 years, and 46.8% were male. Dynamic SPECT derived coronary flow reserve (CFR) was significantly correlated with TIMI frame count in 3 epicardial coronary (LAD: r=− 0.506, P = 0.0003; LCX: r= − 0.532, P = 0.0001; RCA: r= − 0.657, P < 0.0001). The sensitivity and specificity of CFR in identifying abnormal TIMI frame count < 40 was 100.0% and 57.6% in LAD, 62.5% and 87.0% in LCX, 83.9% and 75.0% in RCA, respectively. The optimal CFR cut-off values were 2.02, 2.47, and 1.96 among the three vessels.Conclusion: In patients with non-obstructive coronary, CFR derived from D-SPECT was strongly correlated with TFC. This study demonstrates that that CFR may be an alternative non-invasive method for identifying slow flow in non-obstructive coronary.Keywords: dynamic single photon emission computed tomography, thrombolysis in myocardial infarction frame count, slow flow, non-obstructive coronary, coronary flow reserve

Chun Zhang,1,2 Changzhou Shi,1 Pengzhao Chang,1 Shuang Bian,1,2 Bangbang Li,1 Jingjing Li,1,2 Pingfu Hou2,3 1School of Medical Imaging, Xuzhou Medical University, Xuzhou, 221004, People’s Republic of China; 2Department of Radiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, People’s Republic of China; 3Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of ChinaCorrespondence: Pingfu Hou; Jingjing Li, Email houpf612@xzhmu.edu.cn; qingchao0124@163.comPurpose: Magnetic resonance imaging (MRI) has been a valuable and widely used examination technique in clinical diagnosis and prognostic efficacy evaluation. The introduction of MRI contrast agent (CA) improves its sensitivity obviously, particularly with the development of nano-CA, which presents higher contrast enhancement ability. However, systematical evaluation of their toxicity is still limited, hampering their further translation in clinics.Methods: In this paper, to systematically evaluate the toxicity of nano-CA, Gd-doped mesoporous carbon nanoparticles (Gd-MCNs) prepared by a one-step hard template method were introduced as a model and clinically used MRI CA, Magnevist (Gd-DTPA) as control. Their in vitro blood compatibility, cellular toxicity, DNA damage, oxidative stress, inflammation response as well as in vivo toxicity and MR imaging behaviors were studied and compared.Results: The experimental results showed that compared with Gd-DTPA, Gd-MCNs displayed negligible influence on the red blood cell shape, aggregation, BSA structure, macrophage morphology and mitochondrial function. Meanwhile, limited ROS and inflammatory cytokine production also illustrated the cellular compatibility of Gd-MCNs. For in vivo toxicity evaluation, Gd-MCNs presented acceptable in vivo biosafety even under 12 times injection for 12 weeks. More importantly, at the same concentration of Gd, Gd-MCNs displayed better contrast enhancement of tumor than Gd-DTPA, mainly coming from its high MRI relaxation rate which is nearly 9 times that of Gd-DTPA.Conclusion: In this paper, we focus on the toxicity evaluation of MRI nano-CA, Gd-MCNs from different angles. With Gd-DTPA as control, Gd-MCNs appeared to be highly biocompatible and safe nanoparticles that possessed promising potentials for the use of MRI nano-CA. In the future, more research on the long-term genotoxicity and the fate of nanoparticles after being swallowed should be performed.Graphical Abstract: Keywords: MRI, nano-contrast agent, cytotoxicity, tissue toxicity, immunotoxicity

Weimin Fang,1,2,&ast; Jinghao Wang,3,&ast; Xiaocong Ma,1,2 Ni Shao,1,2 Kunlin Ye,1,2 Dong Zhang,1,2 Changzheng Shi,1,2 Liangping Luo1,2 1Medical Imaging Center, the First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, People’s Republic of China; 2The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, Jinan University, Guangzhou, Guangdong, People’s Republic of China; 3Department of Pharmacy, the First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Changzheng Shi, Medical Imaging Center, The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, People’s Republic of China, Email tsczcn@jnu.edu.cn Liangping Luo, Medical Imaging Center, The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, People’s Republic of China. Department of Radiology, The Fifth Affiliated Hospital of Jinan University, Guangzhou, Guangdong, People’s Republic of China, Email tluolp@jnu.edu.cnBackground: Olaparib, a poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor has demonstrated promising efficacy in patients with triple-negative breast cancer (TNBC) carrying breast cancer gene (BRCA) mutations. However, its impact on BRCA wild-type (BRCAwt) TNBC is limited. Hence, it is crucial to sensitize BRCAwt TNBC cells to olaparib for effective clinical practice. Novobiocin, a DNA polymerase theta (POLθ) inhibitor, exhibits sensitivity towards BRCA-mutated cancer cells that have acquired resistance to PARP inhibitors. Although both of these DNA repair inhibitors demonstrate therapeutic efficacy in BRCA-mutated cancers, their nanomedicine formulations’ antitumor effects on wild-type cancer remain unclear. Furthermore, ensuring effective drug accumulation and release at the cancer site is essential for the clinical application of olaparib.Materials and Methods: Herein, we designed a progressively disassembled nanosystem of DNA repair inhibitors as a novel strategy to enhance the effectiveness of olaparib in BRCAwt TNBC. The nanosystem enabled synergistic delivery of two DNA repair inhibitors olaparib and novobiocin, within an ultrathin silica framework interconnected by disulfide bonds.Results: The designed nanosystem demonstrated remarkable capabilities, including long-term molecular storage and specific drug release triggered by the tumor microenvironment. Furthermore, the nanosystem exhibited potent inhibitory effects on cell viability, enhanced accumulation of DNA damage, and promotion of apoptosis in BRCAwt TNBC cells. Additionally, the nanosystem effectively accumulated within BRCAwt TNBC, leading to significant growth inhibition and displaying vascular regulatory abilities as assessed by magnetic resonance imaging (MRI).Conclusion: Our results provided the inaugural evidence showcasing the potential of a progressively disassembled nanosystem of DNA repair inhibitors, as a promising strategy for the treatment of BRCA wild-type triple-negative breast cancer.Keywords: olaparib, novobiocin, tumor microenvironment, disulfide bonds, drug release, magnetic resonance

Yongde Zhou,1,&ast; Xiaoxiao Wang,2,3,&ast; Zhengqian Li,2,4 Yu Ma,5 Cuiping Yu,1 Yao Chen,1 Jian Ding,1 Jianfeng Yu,1 Rongsong Zhou,5 Ning Yang,2,4 Taotao Liu,2,4 Xiangyang Guo,2,4 Ting Fan,1 Chengmei Shi2,4 1Department of Anesthesiology, Tsinghua University Yuquan Hospital, Beijing, 100040, People’s Republic of China; 2Department of Anesthesiology, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 3Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 4Beijing Center of Quality Control and Improvement on Clinical Anesthesia, Beijing, 100191, People’s Republic of China; 5Department of Neurosurgery, Tsinghua University Yuquan Hospital, Beijing, 100040, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chengmei Shi, Department of Anesthesiology, Peking University Third Hospital, Beijing, 100191, People’s Republic of China, Tel +86-13811592813, Email shichengmei@bjmu.edu.cn Ting Fan, Department of Anesthesiology, Tsinghua University Yuquan Hospital, Beijing, 100040, People’s Republic of China, Tel +86-13681100715, Email 13681100715@163.comBackground: A simple, rapid, and effective cognitive screening test appropriate for fast-paced settings with limited resources and staff is essential, especially preoperatively. This study aimed to develop and validate the short versions of Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) for predicting postoperative delirium (POD) in patients with Parkinson’s disease (PD) who were scheduled for surgery.Methods: The current study was a secondary analysis of data collected from 128 inpatients scheduled for deep brain stimulation of the subthalamic nuclei (STN-DBS) lasting > 60 min, at Tsinghua University Yuquan Hospital, China. Preoperative cognitive screening was performed during the preoperative visit using the MMSE and MoCA. The optimal MMSE and MoCA cut-off scores for detecting PD-MCI was 27 and 23 respectively. The POD was assessed twice a day on the first postoperative day until discharge by the confusion assessment method. The backward conditional logistic regression analysis was used to organize the reduced versions of the MMSE or MoCA. Also, the areas under the receiver operating characteristic curves (AUCs) were examined using the DeLong test.Results: 125/128 PD patients were included in the analysis, and 27 (21.6%) developed POD. The MMSE reduced version (orientation to time, attention and calculation, and comprehension) demonstrated performance similar to the original MMSE in predicting POD (z=0.820, p=0.412). The AUC of the original MoCA and the short MoCA (visuospatial and executive attention and orientation) were 0.808 and 0.826, respectively. There was no significantly difference in the AUC values between the tests (z=0.561, p=0.575).Conclusion: Our simplified MMSE and MoCA could be efficiently used to identify patients at risk for POD. Also, short cognitive tests could be considered while predicting POD in fast-paced preoperative settings with limited resources and staff.Plain Language Summary: Routine preoperative cognitive screening is very important in predicting postoperative delirium.MMSE and MoCA are the most commonly used cognitive testing method which normally takes a long time.The short variant of MMSE and MoCA show a predictive performance similar to the original tests.Keywords: Parkinson’s disease, preoperative cognitive impairment, mini-mental state examination, Montreal Cognitive Assessment, postoperative delirium

Chunxia Shi, Pan Cao, Yukun Wang, Qingqi Zhang, Danmei Zhang, Yao Wang, Luwen Wang, Zuojiong Gong Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of ChinaCorrespondence: Zuojiong Gong, Department of Infectious Diseases, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, People’s Republic of China, Email zjgong@163.comAbstract: PANoptosis is a new cell death proposed by Malireddi et al in 2019, which is characterized by pyroptosis, apoptosis and necroptosis, but cannot be explained by any of them alone. The interaction between pyroptosis, apoptosis and necroptosis is involved in PANoptosis. In this review, from the perspective of PANoptosis, we focus on the relationship between pyroptosis, apoptosis and necroptosis, the key molecules in the process of PANoptosis and the formation of PANoptosome, as well as the role of PANoptosis in diseases. We aim to understand the mechanism of PANoptosis and provide a basis for targeted intervention of PANoptosis-related molecules to treat human diseases.Keywords: PANoptosis, pyroptosis, apoptosis, necroptosis

Yiyi Zhu,1 Lingling Wu,2– 5 Shuling Ye,6– 9 Yaoyang Fu,2– 5 Huimin Huang,1 Jianbo Lai,2– 5 Chuan Shi,6– 9 Shaohua Hu1– 5,10 1School of Mental Health, Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Psychiatry, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3The Key Laboratory of Mental Disorder’s Management in Zhejiang Province, Hangzhou, People’s Republic of China; 4Brain Research Institute of Zhejiang University, Hangzhou, People’s Republic of China; 5Zhejiang Engineering Center for Mathematical Mental Health, Hangzhou, People’s Republic of China; 6Peking University Sixth Hospital, Beijing, People’s Republic of China; 7Peking University Institute of Mental Health, Beijing, People’s Republic of China; 8NHC Key Laboratory of Mental Health (Peking University), Beijing, People’s Republic of China; 9National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, People’s Republic of China; 10Department of Neurobiology, NHC and CAMS Key Laboratory of Medical Neurobiology, School of Brain Science and Brian Medicine, and MOE Frontier Science Center for Brain Science and Brain-Machine Integration, Zhejiang University School of Medicine, Hangzhou, 310058, People’s Republic of ChinaCorrespondence: Shaohua Hu, School of Mental Health, Wenzhou Medical University, Wenzhou, People’s Republic of China, Email dorhushaohua@zju.edu.cn Chuan Shi, Peking University Sixth Hospital, Beijing, 100191, People’s Republic of China, Email shichuan@bjmu.edu.cnBackground: Emotional blunting is prevalent in patients with mood disorders and adversely affects the overall treatment outcome. The Oxford Depression Questionnaire is a validated psychometric instrument for assessing emotional blunting. We aimed to evaluate the reliability and validity of the Chinese version of the ODQ (ODQ) in Chinese patients with mood disorders.Methods: 136 mood disorders patients and 95 healthy control participants were recruited at the First Affiliated Hospital of Zhejiang University, School of Medicine. Patients were assessed using the ODQ, Beck Depression Inventory-II (BDI-II), and Montgomery-Asberg Depression Rating Scale (MADRS). Internal consistency reliability and test-retest reliability were analyzed. Confirmatory factor analysis and correlation analysis were used to evaluate construct and convergent validity.Results: A total of 136 patients with mood disorders and 95 healthy controls participated in this study. Cronbach α values were 0.928 (ODQ-20) and 0.945 (ODQ-26). Test-retest reliability coefficients were 0.798 (ODQ-20) and 0.836 (ODQ-26) (p< 0.05); intraclass correlation coefficient values were 0.777 (ODQ-20) and 0.781 (ODQ-26) (p< 0.01). The score of ODQ was positively correlated with BDI-II and MADRS (r=0.326~0.719, 0.235~0.537, p< 0.01). The differences in the ODQ scores between the patient and control groups were statistically significant.Conclusion: The reliability, structural validity, and criterion validity of the ODQ applied to patients with mood disorders meet the psychometric requirements, and the scale can be used to assess emotional blunting in Chinese patients with mood disorders.Keywords: emotional blunting, Chinese, mood disorder, psychometrics, validation

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

Yongde Zhou,1 Yu Ma,2 Cuiping Yu,1 Yao Chen,1 Jian Ding,1 Jianfeng Yu,1 Rongsong Zhou,2 Xiaoxiao Wang,3 Ting Fan,1 Chengmei Shi4 1Department of Anesthesiology, Tsinghua University Yuquan Hospital, Beijing, People’s Republic of China; 2Department of Neurosurgery, Tsinghua University Yuquan Hospital, Beijing, People’s Republic of China; 3Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, People’s Republic of China; 4Department of Anesthesiology, Peking University Third Hospital, Beijing, People’s Republic of ChinaCorrespondence: Chengmei Shi; Ting Fan, Email shichengmei@bjmu.edu.cn; 13681100715@163.comObjective: This study aimed to explore possible biomarkers of postoperative delirium (POD) of Parkinson’s disease (PD) patients received deep brain stimulation (DBS) of the subthalamic nuclei.Materials and methods: This nested case control study analyzed perioperative plasma and cerebral spinal fluid (CSF) of patients (n = 40) who developed POD undergone DBS surgery (n = 10) and those who did not (n = 30). Blood sample was collected before surgery and on the first day postoperative, CSF sample was collected at the beginning of the operation. POD was assessed by the Confusion Assessment Method (CAM) twice a day between 7:00 am and 7:00 pm after the surgery until discharge. Plasma and CSF sample from the two groups were analyzed to investigate possible biomarkers for POD in PD patients.Results: There was no difference between POD and Non-POD groups on the concentration of Interleukin 6 and Tumor Necrosis Factor-α in CSF, preoperative plasma and postoperative plasma. There was no difference between POD and Non-POD groups on the concentration of S100 calcium-binding protein β protein (S100β) and Neurofilament light chain (NFL) in preoperative plasma and postoperative plasma. The concentration of C-reactive protein (CRP), NFL and S100β were significant higher in POD group than non-POD group in CSF. The concentration of CRP was significantly higher in POD group than non-POD group in preoperative plasma and postoperative plasma. CSF concentration of S100β might be a potential biomarker for POD via the receiver operating characteristic curve analysis and the area under the curve value of 0.973.Conclusion: For PD patients received DBS surgery, CSF S100β might be a marker for aiding detection of high-risk patients with delirium. This requires further confirmation in clinical trials.Keywords: Parkinson’s disease, deep brain stimulation, cerebrospinal fluid, postoperative delirium, biomarker

Lei Yang,1,2 Weimin Dang,2,3 Xin Yu,1,2 Yi He,4,5 Chuan Shi,1,2 Jialong Yi,1,2 Lu Gao,6 Siheng Li,7 Tianhang Zhou,1,2 Yantao Ma1,2 1Department of Clinical Research, Peking University Sixth Hospital (Institute of Mental Health), Beijing, People’s Republic of China; 2NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, People’s Republic of China; 3The Division of Medical Affairs, Peking University Sixth Hospital (Institute of Mental Health), Beijing, People’s Republic of China; 4Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing, People’s Republic of China; 5Department of Psycho-Oncology, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China; 6Department of Stomatology, Beijing Children’s Hospital, Capital Medical University, Beijing, People’s Republic of China; 7Department of Neurology, Peking University First Hospital, Beijing, People’s Republic of ChinaCorrespondence: Xin Yu, Peking University Sixth Hospital, No. 51 Hua Yuan Bei Road, Haidian District, Beijing, 100191, People’s Republic of China, Tel +86 13718747842, Fax +86-10-62026310, Email yuxin@bjmu.edu.cnIntroduction: Processed betel quid product chewing is a public health problem in areca non-plant areas in China. However, there is no valid instrument to screen for betel quid use disorder (BQUD) in mainland China. We developed a self-administered screening test for betel quid use disorders (SST-BQUD) and tested its reliability and validity in a sample of betel quid chewers (BQCers) in Hunan, China.Methods: Items of SST-BQUD were selected from the test results of an item pool, which includes 52 questions related to the psycho-social and behavioral presentations of BQUD. All participants, in a self-administered manner, completed the item pool. A subsample completed the re-test one week later. Two psychiatrists interviewed all participants to ascertain the presence of BQUD. The receiver Operating Characteristic curve was used to determine the best cut-off value to discriminate BQUD.Results: One hundred and twelve BQCers were recruited. Based on the statistical analysis of receiver operating characteristic (ROC) curves, 14 yes/no questions were selected for SST-BQUD. As indicated by Cronbach’s α coefficient, the internal consistency was 0.876. The area under the curve of SST-BQUD was 0.881, representing a satisfactory diagnostic value. The one-week re-test reliability test was 0.771 (P< 0.001), suggesting good stability over time. The optimal cut-off score for BQUD screening was six, with a sensitivity of 0.921 and a specificity of 0.716, implying the satisfactory accuracy of SST-BQUD to screen for BQUD.Conclusion: The standard version of SST-BQUD consists of 14 items. The total score of SST-BQUD was the sum of affirmative answers, with higher scores denoting a more severe BQUD symptom. If one answered six or more times “yes” to these 14 questions, they can be classified with BQUD. The SST-BQUD is a valid screening method for BQUD among BQCers in betel quid processed area.Keywords: betel quid use disorders, screener, development, validity, diagnostic test

Xiaoying Zhao,1 Chunhong Shi,2,3 Lihua Zhao1 1Handan First Hospital, Handan, 056000, People’s Republic of China; 2School of Nursing, Xiangnan University, Chenzhou, People’s Republic of China; 3Affiliated Hospital of Xiangnan University, Chenzhou, 423000, People’s Republic of ChinaCorrespondence: Chunhong Shi, School of Nursing, Xiangnan University, 889 Chenzhou Avenue, Suxian District, Chenzhou, 423000, People’s Republic of China, Tel +86 15907354840, Fax +86-735-2325007, Email shichunhong@xnu.edu.cnPurpose: This study explored nurses’ intentions, awareness and barriers in reporting adverse events in tertiary hospitals in China. We also analyzed its associated factors to increase the chance to evaluate preventable errors, enhance care delivery, and improve patient outcomes.Patients and Methods: A cluster sampling method was used to recruit 1382 nurses from two tertiary hospitals in Chenzhou and Handan City. An online structured questionnaire was used to collect data, which included general information questionnaire (eight questions), reporting awareness questionnaire (eight items with scores ranging from 0 to 8), reporting intention questionnaire (15 items with scores ranging from 0 to 15), and reporting barriers questionnaire (22 items with scores ranging from 22 to 110).Results: We received 1565 completed questionnaires from 1734 potential participants (a response rate of 90.25%), with 1382 valid questionnaires, yielding an effective rate of 88.31%. The scores of reporting awareness, reporting intention, and reporting barriers in adverse events for nurses in tertiary hospitals were 8 (1), 15 (0), and 83.04 (± 12.21) out of 110, respectively. Reporting awareness and barriers to adverse events were positively correlated with nurses’ intention to report adverse events (rs = 0.237 and 0.361, respectively; P < 0.001). Regression analyses showed that reporting awareness and barriers in adverse events and professional title influenced nurses’ intention to report adverse events (P < 0.05) in tertiary hospitals.Conclusion: Nurses in tertiary hospitals have a strong intention to report adverse events. The higher the reporting awareness of adverse events or the fewer perceived reporting barriers, the stronger the nurses’ intention to report. Hospital managers should deliver patient safety education and training for nurses, to increase their reporting awareness and decrease their perceived reporting barriers, improve their intention to report adverse events.Keywords: nurse, adverse events, patient safety, safety culture

Dan-Dan Wang,1,2,&ast; Chi-Yi He,3,&ast; Yi-Jin Wu,1,2 Liang Xu,4 Chao Shi,1 Opeyemi Joshua Olatunji,5 Jian Zuo,1,6,7 Cong-Lan Ji8 1Xin’an Medicine Research Center, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital), Wuhu, 241000, People’s Republic of China; 2The Key Laboratory of Anti-Inflammatory and Immune Medicine, Ministry of Education, Institute of Clinical Pharmacology, Anhui Medical University, Hefei, 230032, People’s Republic of China; 3Department of Gastroenterology, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital), Wuhu, 241000, People’s Republic of China; 4Department of Rheumatology, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital), Wuhu, 241000, People’s Republic of China; 5Traditional Thai Medical Research and Innovation Center, Faculty of Traditional Thai Medicine, Prince of Songkla University, Hat Yai, 90110, Thailand; 6Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution, Wannan Medical College, Wuhu, 241000, People’s Republic of China; 7Anhui Provincial Engineering Laboratory for Screening and Re-evaluation of Active Compounds of Herbal Medicines in Southern Anhui, Wuhu, 241000, People’s Republic of China; 8School of Pharmacy, Anhui College of Traditional Chinese Medicine, Wuhu, 241000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Cong-Lan Ji; Jian Zuo, Email 37709103@qq.com; zuojian8178@163.comBackground: Exact roles of many metabolic regulators in rheumatoid arthritis (RA) are to be clarified. This study aimed to further characterize the impacts of silent information regulator 1 (SIRT1) status changes on this disease.Methods: Fluctuation pattern of SIRT1 expression in adjuvant-induced arthritis (AIA) rats was monitored using periodically collected white blood cells. Another bath of AIA rats were treated by SIRT1 agonist resveratrol. Blood from these rats was used to separate monocytes and plasma, which were subjected to polymerase chain reaction (PCR), enzyme linked immunosorbent assay (ELISA), and biochemical analyses. Clinical implication of SIRT1 activation was verified by treating AIA rat monocytes with SIRT1 agonist and overexpression vector in vitro.Results: SIRT1 deficiency occurred in AIA rats, which was accompanied with down-regulation of interleukin 10 (IL-10) and arginase-1 (ARG-1). Resveratrol eased oxidative stress and increased IL-10 production in vivo. Results of ELISA analysis demonstrated that resveratrol attenuated AIA severity in rats. Furthermore, it restored the altered levels of triglyceride, lactate and pyruvate in blood. Resveratrol promoted IL-10 production, and suppressed glycolysis of AIA monocytes cultured in vitro. SIRT1 overexpression similarly reshaped differentiation profile of AIA monocytes, evidenced by changes in metabolism indicators, IL-10 production and AMP-activated protein kinase (AMPK) pathway status. Although overexpressing SIRT1 in normal cells did not affect glycolysis significantly, it attenuated AMPK antagonist-caused abnormality.Conclusion: SIRT1 deficiency is implicated in AIA-related immune abnormality and metabolism alteration. Activating this signaling with resveratrol would impair the inflammatory polarization of monocytes, and consequently ease the severity of RA.Keywords: inflammation, metabolic reprogramming, monocytes, resveratrol, rheumatoid arthritis

Cong Shi,1,&ast; Shengping Gong,2,&ast; An Wu,3 Tingting Niu,1 Ningning Wu,1 Yi Zhang,1 Guifang Ouyang,3 Qitian Mu1 1Laboratory of Stem Cell Transplantation, Ningbo First Hospital, Ningbo, Zhejiang, People’s Republic of China; 2Cancer Radiotherapy and Chemotherapy Center, Ningbo First Hospital, Ningbo, Zhejiang, People’s Republic of China; 3Hematology Department, Ningbo First Hospital, Ningbo, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guifang Ouyang; Qitian Mu, Email nbhematology@163.com; muqitian@163.comBackground: Myelodysplastic syndrome (MDS) is a group of heterogeneous myeloid clonal diseases originating from hematopoietic stem cells. It has been demonstrated that fibrinogen (FIB) is associated with disease risk in several cancer types. Coagulation and fibrinolysis problems are widespread in MDS patients. Therefore, FIB might be one of these indicators. We thus examined the role of FIB levels in the prognosis of MDS.Methods: A cohort of 198 MDS patients were retrospectively analyzed to explore the prognostic value of the plasma FIB levels at diagnosis. Patients were divided into the high FIB group and low FIB group. The prognostic significance of FIB was determined by univariate and multivariate Cox hazard models.Results: In our cohort, the FIB levels in 198 MDS patients were higher than those in 100 healthy donors (3.9 g/L vs 2.9 g/L, P < 0.0001). MDS patients with high FIB levels had significantly shorter overall survival (OS; P = 0.001) and decreased leukemia-free survival (LFS; P = 0.036). Multivariate cox proportional hazards regression analysis indicated that, in addition to older age, gender, lower HB, poorer karyotype for OS, lower NE, and higher bone marrow blast percentage for OS and LFS, elevated FIB level was also an independent adverse prognostic factor for OS (P = 0.045) but not for LFS (P = 0.188).Conclusion: Elevated FIB levels may be associated with mortality risk among MDS patients and could predict disease progress and patient prognosis. Thus, assessment of FIB levels may promote the determination of the prognosis of MDS patients.Keywords: myelodysplastic syndrome, IPSS-R, prognostic, overall survival, fibrinogen

Ning Wang,1 Meifang Song,2 Haike Gu,2 Yiyuan Gao,1 Ge Yu,3 Fang Lv,4 Cuige Shi,5 Shangming Wang,5 Liwen Sun,1 Yang Xiao,6 Shucheng Zhang1 1Department of Health Quality Center, National Research Institute for Family Planning, Beijing, People’s Republic of China; 2Beijing Radiation Center, Beijing Academy of Science and Technology, Beijing, People’s Republic of China; 3Department of Gynecology, Harbin Medical University Cancer Hospital, Harbin, People’s Republic of China; 4Reproductive Medicine Center, Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Soochow University, Soochow, People’s Republic of China; 5Department of Cell Biology, National Research Institute for Family Planning, Beijing, People’s Republic of China; 6Graduate School of Chinese Academy of Agricultural Sciences, Beijing, People’s Republic of ChinaCorrespondence: Shucheng Zhang; Yang Xiao, Tel/Fax +86 10 62197760 ; +86 10 82109683, Email shuchengzz87@email.cn; xiao_y87sd@163.comObjective: The objective of this study is to reduce the dimension of several indicators with a strong correlation when conducting semen quality analysis in a small number of comprehensive variables that could retain most of the information in the original variables.Methods: A total of 1132 subjects were recruited from the Maternal and Child Health Institutions of seven provinces in mainland China. They completed the questionnaire and provided semen samples. Visualization of the correlation between variables was realized by using a function chart and correlation in the PerformanceAnalytics package of the R programming language (version 3.6.3 [2020-02-29]). Factor analysis was conducted using the principal function in the psych package of R. Principal component analysis, combined with varimax rotation, was used in the operation of the model, and two common factors were selected and measured to provide values for the common factor. The score coefficient was estimated using the regression method.Results: The contribution rates of the two common factors to variable X were 43.7% and 33.98%, respectively. When the two common factors were selected, approximately 78% of the information of the original variables could be explained. The correlation coefficients between the first common factor (the quantitative factor) and sperm density, total sperm count, and semen volume were 0.824, 0.984, and 0.544, respectively. The correlation coefficients between the second common factor (the quality factor) and sperm motility and the percentage of forward-moving (progressive spermatozoa) sperm were 0.978 and 0.976, respectively.Conclusion: The correlation between the original variables of a semen quality analysis was strong and suitable for dimensionality reduction by factor analysis. Factor analysis and dimensionality reduction provide a fast and accurate assessment of semen quality. Patients with low fertility or infertility can be identified and provided with corresponding treatments.Keywords: semen quality analysis, factor analysis, score coefficient, dimensionality reduction

Chunyan Li,1 Chunhong Shi2 1School of Nursing, Hunan University of Chinese Medicine, Changsha, People’s Republic of China; 2School of Nursing, Xiangnan University, Chenzhou, People’s Republic of ChinaCorrespondence: Chunhong Shi, Tel +86 15907354840, Fax +86 735 2325007, Email shichunhong@xnu.edu.cnPurpose: Adverse events threaten residents’ safety. Risk management is important to provide proper care and maintain quality in residential aged care facilities (RACFs). However, there is little data on adverse events, risk management, and risk early warning in RACFs in the Chinese mainland. This study aimed to fill this gap by investigating the prevalence of the aforementioned aspects and related factors in China.Participants and Methods: Using a cross-sectional design, a field survey of 272 RACFs in Hunan Province was conducted from January 25 to June 1, 2020. Data were collected using four main tools on prevalence of nursing adverse events, risk management, risk early warning, and general information. Descriptive statistics were described by frequency (percentage) and median (interquartile range). Mann–Whitney U-test and Kruskal–Wallis H-test, and Spearman coefficient were used for statistical analysis.Results: RACFs experienced an average of five (15) adverse events in 2019, with falls and pressure ulcers being the most common. The total average score of risk management in RACFs was 4.72 (0.98) out of 5, with the environment and personnel management dimensions scoring the highest with 4.75 (1) and the service management dimension scoring the lowest with 4.60 (1). Only 72.79% had trained their staff on ethical and legal knowledge and 84.56% had utilized pre-hospital first aid. Further, 30% to 40% were unprepared for contingency plans of suicide, electric shock, gas poisoning, and drowning. There were significant risk management differences among the following variables: facilities’ locations, accreditation with the Practice Certificate of Social Welfare Facilities, bed-size, nursing hours per resident day, requirement for nursing staff with certificates, and payment for nursing staff (p < 0.05).Conclusion: RACFs are facing safety challenges with a high prevalence of nursing adverse events. These facilities need to improve risk early warning and management to ensure residents’ safety.Keywords: safety measures, quality of nursing care, nursing homes, geriatric care

Xiaojiao Zheng,1,2 Xiuyi Lv,1 Linyan Zhu,1 Kejun Xu,1 Cong Shi,1 Lining Cui,1 Huiqing Ding1 1Department of Obstetrics and Gynecology, Ningbo First Hospital, Ningbo, Zhejiang, 315035, People’s Republic of China; 2Department of Biochemistry & Genetics, The National Education Base for Basic Medical Sciences, Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, 310058, Zhejiang Province, People’s Republic of ChinaCorrespondence: Lining Cui; Huiqing Ding Email 1935148739@qq.com; 1209256240@qq.comBackground: Mounting evidence indicates altered circadian rhythm represents a critical factor affecting carcinogenesis and tumor progression. The circadian gene neuronal PAS domain protein 2 (NPAS2) constitutes a newly discovered prognostic biomarker. NPAS2 dysregulation is found in multiple malignancies, although its functions in uterine corpus endometrial carcinoma (UCEC) remain largely unknown.Objective: To evaluate NPAS2’s roles in UCEC and to explore the underlying mechanisms.Methods: NPAS2 transcription levels, patient prognosis, different clinical stages and target microRNAs in UCEC cases were comparatively assessed based on public databases, including UALCAN, GEPIA, TIMER, Kaplan–Meier plotter, starBase database, LinkedOmics and String. Then, qRT-PCR and immunohistochemical analysis were applied to analyze the expression of NPAS2 in UCEC tissue samples. CCK-8, clonogenic assay and flow cytometry were carried out for detecting cell viability, colony formation ability and cell apoptosis, respectively.Results: NPAS2 was upregulated in tissue samples from UCEC cases compared with the corresponding control specimens. NPAS2 overexpression was associated with decreased overall (OS), disease free (DFS) and relapse free (RFS) survival in UCEC. In addition, NPAS2 overexpression was associated with clinical stage, tumor grade, estrogen receptor status, myometrial invasion in UCEC. Furthermore, NPAS2 knockdown or overexpression altered cell proliferation and apoptosis in UCEC. Moreover, NPAS2 showed significant negative correlations with miR-17-5p and miR-93-5p, and positive correlations with miR-106a-5p and miR-381-3p in UCEC.Conclusion: NPAS2 overexpression is associated with poor prognosis and clinicopathological characteristics in UCEC and promotes proliferation and colony formation while inhibiting apoptosis. Finally, NPAS2 is associated with several miRNAs in UCEC.Keywords: NPAS2, circadian rhythm, cell cycle, apoptosis, uterine corpus endometrial carcinoma

Tao Ouyang,1,&ast; Junxia Liu,2,&ast; Chengyang Shi,3 Lisheng Zhu,4 Xiaopeng Guo1 1Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Cancer Medical Center, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao OuyangDepartment of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of ChinaTel +86 18720931226Email ouyt1996@163.comXiaopeng GuoDepartment of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China, +86 13667216827Email guoxiaopenghe@163.comPurpose: This study aims to compare the efficacy of drug-eluting bead transarterial chemoembolization (DEB-TACE) versus conventional TACE (cTACE), both combined with apatinib, and to establish predictive nomograms to support individualized survival prediction in hepatocellular carcinoma (HCC) patients.Patients and Methods: This retrospective study assessed HCC patients from June 2015 to December 2019. Patients were classified as DEB-TACE plus apatinib (D-apatinib) and cTACE plus apatinib (c-apatinib). The endpoints were overall survival (OS) and progression-free survival (PFS). The nomograms were constructed, and the C-index, receiver operating characteristic (ROC) curve, and calibration curves were used to validate the nomograms. Propensity score matching (PSM) analysis was applied to reduce patient selection bias.Results: A total of 174 patients were included. After PSM analysis, 58 pairs of patients were selected. Before PSM analysis, the median OS and PFS were 21.0 and 8.0 months in the D-apatinib group, respectively, which were better than the 18.0 and 5.0 months observed in the c-apatinib group (P < 0.05). The complete response (CR) rate and objective response rate (ORR) of the D-apatinib group were higher than those of the c-apatinib group. The C-index values of the nomograms in the D-apatinib group and the c-apatinib group were 0.826 and 0.802, and the area under the curve (AUC) values in the ROC curve were 0.934 and 0.892. After PSM analysis, the survival of patients treated with D-apatinib was better than that of patients treated with c-apatinib (P < 0.05). The C-index values were 0.854 and 0.794 in the D-apatinib group and the c-apatinib group, respectively, and the AUC values were 0.960 and 0.890. The incidence of adverse events was higher in the c-apatinib group.Conclusion: DEB-TACE in combination with apatinib showed better treatment effectiveness for unresectable HCC. The nomograms can identify HCC patients who may benefit most from the treatment.Keywords: hepatocellular carcinoma, DEB-TACE, cTACE, apatinib, nomogram, PSM

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

Wenjuan Yan,1,&ast; Qi Zhang,1,&ast; Yingjie Zhu,1 Nan Jing,1 Youhua Yuan,1 Yi Zhang,2 Siying Ren,3 Dongmei Hu,4 Wenmin Zhao,5 Xiaojuan Zhang,6 Caiqin Shi,7 Meiyun Wang,8 Yi Li1 1Department of Clinical Microbiology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou, Henan, People’s Republic of China; 2Department of Clinical Laboratory, Zhengzhou Central Hospital, Affiliated to Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 3Department of Clinical Laboratory, Kaifeng People’s Hospital, Kaifeng, Henan, People’s Republic of China; 4Department of Clinical Laboratory, Zhumadian First People’s Hospital, Zhumadian, People’s Republic of China; 5Department of Clinical Laboratory, Kaifeng Central Hospital, Kaifeng, Henan, People’s Republic of China; 6Department of Clinical Laboratory, Gongyi People’s Hospital, Zhengzhou, Henan, People’s Republic of China; 7Department of Microbiology Laboratory, KingMed Diagnostics, Zhengzhou, Henan, People’s Republic of China; 8Department of Medical Imaging, Henan Provincial People’s Hospital & the People’s Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi LiDepartment of Clinical Microbiology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou, Henan, People’s Republic of ChinaTel +86 159 39039006Email liyilabmed@henu.edu.cnPurpose: To evaluate polymyxin-resistant Klebsiella pneumoniae and Escherichia coli prevalence and characteristics in the Henan province, China.Materials and Methods: A total of 2301 bacterial isolates collected at six hospitals were assessed. Their response to polymyxin was evaluated by minimum inhibitory concentration (MIC) analysis, and the mobilized colistin resistance (mcr) and carbapenemase gene were explored. Mutations on mgrB, phoPQ, pmrAB, and crrAB in polymyxin-resistant K. pneumoniae were detected by PCR. phoP, phoQ, pmrK, pmrA, pmrB, and pmrC transcriptional levels were quantified by RT-qPCR. Pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing were performed to determine the phylogenetic relationship between the polymyxin-resistant isolates.Results: Of the E. coli and K. pneumoniae isolates identified, 0.3% and 1.4% were polymyxin-resistant, respectively, with MICs of 4– 64 μg/mL. All polymyxin-resistant isolates were susceptible to tigecycline. Four E. coli isolates were mcr-1-positive and one was carbapenem-resistant, carrying blaNDM-5 and mcr-1. One K. pneumoniae isolate was mcr-1-positive and nine were carbapenem-resistant (PRCRKP), carrying blaKPC-2 but not mcr-1. The five E. coli isolates belonged to four sequence types (ST2, ST132, ST632, and ST983). All PRCRKP isolates belonged to ST11. However, all 16 isolates belonged to different PFGE types with < 95% genetic similarity. Insertion sequences in mgrB were detected in nine (81.8%) polymyxin-resistant K. pneumoniae samples. Colistin resistance was linked with pmrHFIJKLM operon upregulation, with phoP, phoQ, and pmrK being overexpressed in all but one of the polymyxin-resistant K. pneumoniae samples. Furthermore, 33.3% of patients carrying polymyxin-resistant isolates had previously used polymyxin, and 66.7% patients displayed good clinical outcomes.Conclusion: The K. pneumoniae polymyxin resistance rate was slightly higher than that of E. coli and mcr-1 was more common in E. coli than in K. pneumoniae. Moreover, the insertion of ISkpn14 into mgrB may be the main contributor to polymyxin-resistance in K. pneumoniae in Henan.Keywords: polymyxin, Escherichia coli, Klebsiella pneumoniae, mcr, Henan province

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

Debao Li,1,* Keyang Li,2,* Hongliang Dong,2 Dongmei Ren,1 Dandan Gong,2 Fuguo Jiang,1 Chunhua Shi,1 Junmin Li,1 Qi Zhang,3 Wenjuan Yan,3 Yi Li3 1Department of Clinical Laboratory, Jiaozuo People’s Hospital, Jiaozuo, Henan, People’s Republic of China; 2Department of Clinical Pharmacy, Jiaozuo People’s Hospital, Jiaozuo, Henan, People’s Republic of China; 3Department of Clinical Laboratory, Henan Provincial People’s Hospital, Zhengzhou, Henan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenjuan Yan; Yi LiDepartment of Clinical Laboratory, Henan Provincial People’s Hospital, Weiwu Road 7#, Jinshui District, Zhengzhou, 450003, Henan, People’s Republic of ChinaTel +86 15225061830; +86 15939039006Email yanwenjuan2008@126.com; liyilabmed@henu.edu.cnPurpose: Carbapenem-resistant Klebsiella pneumoniae (CRKP) represents a serious problem worldwide. Herein, we describe the evolution of ceftazidime–avibactam (CZA) resistance by sequencing clinical isolates from a patient with CRKP infection undergoing CZA treatment.Patients and Methods: In this study, six CRKP strains were isolated from sputum and blood samples of a patient with CRKP infection after intracerebral hemorrhage. Two strains were selected for whole-genome analysis.Results: Drug susceptibility testing showed that the MIC of CZA for CRKP strains isolated after 6 days of CZA treatment was 64-fold higher than that for three CRKP strains isolated before CZA treatment (4 vs > 256 μg/mL), whereas the MIC of imipenem and meropenem was 128-fold (> 32 vs 0.25 μg/mL) and 16-fold (> 32 vs 2 μg/mL) lower relatively, respectively. Multilocus sequence typing showed that all six CRKP strains isolated from the patient were ST11 and pulsed-field gel electrophoresis confirmed that they were of the same clone. Two strains were selected for whole-genome analysis. The aspartic acid residue at position 179 in the Ω loop was replaced by a tyrosine residue in the resistant strain, and the plasmid carried a blaKPC-2 to blaKPC-33 mutation. The results of the modified carbapenem inactivation method and the carbapenemase inhibitor enhancement and colloidal gold enzyme immunochromatographic assays for blaKPC-33 were negative.Conclusion: This is the first report from Henan to show that treatment with CZA for 6 days can cause mutations and change the phenotype from CZA sensitive to resistant. Therefore, routine testing for drug susceptibility and carbapenemase phenotypes should be conducted during treatment with CZA, and genotype determination is essential.Keywords: ceftazidime–avibactam, drug resistance, carbapenem-resistant Klebsiella pneumoniae, K. pneumoniae carbapenemase-2, ST11

Chen Shi,1,2 Xiong Wang,1,2 Changdong Diao,1,2 Haixia Zhu,1,2 Qi Yuan,1,2 Jinmei Liu,1,2 Shijun Li,1,2 Ming Gu,1,2 Yu Zhang1,2 1Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology (HUST), Wuhan, People’s Republic of China; 2Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan, 430022, People’s Republic of ChinaCorrespondence: Ming Gu; Yu ZhangDepartment of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology (HUST), Wuhan, People’s Republic of ChinaEmail gimyonline@163.com; whxhzy@163.comObjective: Although temozolomide has been extensively used to treat various tumors, there is a lack of large-cohort studies on temozolomide’s toxicity profile. The toxicity profiles and associated factors in patients treated with temozolomide-containing regimens were analyzed.Patients and Methods: Patients treated with temozolomide-containing regimens in the Affiliated Union Hospital of Huazhong University of Science and Technology from January 2008 to December 2019 were included. A retrospective analysis of the clinical data of patients treated with temozolomide-containing regimens was performed. Univariate chi-square test and multivariate logistic regression analysis were employed to identify factors associated with the occurrence of toxicities.Results: Among the 1057 patients received temozolomide-containing regimens, 922 patients were included in our analyses. Of the 922 patients, 484 patients (52.5%) experienced toxicities. Univariate analysis revealed that radiotherapy, chemotherapy cycle, chemotherapy regimen, and clinical stage were significantly associated with the toxicity during temozolomide treatment (P < 0.05). The chemotherapy regimen, chemotherapy cycle, and clinical stage were significantly associated with the overall occurrence of toxicities (P < 0.05). A chemotherapy regimen, chemotherapy cycle, and clinical stage were associated with the hematological system’s toxicities, whereas gender, age, clinical diagnosis, and clinical stage were related to gastrointestinal toxicities (P < 0.05). Clinical diagnosis, chemotherapy regimen, and age were associated with liver toxicity (P < 0.05).Conclusion: Toxicities are common among patients receiving temozolomide-containing regimens. Clinicians should be aware of factors associated with toxicities to minimize the impact of the toxicity.Keywords: temozolomide, toxicity, hematological system, gastrointestinal system, liver toxicity

Yuan Ge,1 Chunhong Shi,2 Bin Wu,1 Yannan Liu,3 Ling Chen,1 Yuegui Deng4 1School of Nursing, Guangxi University of Chinese Medicine, Nanning, 530200, People’s Republic of China; 2School of Nursing, Xiangnan University, Chenzhou, 423000, People’s Republic of China; 3Nursing School, Hunan University of Medicine, Huaihua, 418000, People’s Republic of China; 4Nursing Department, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, 530022, People’s Republic of ChinaCorrespondence: Chunhong ShiSchool of Nursing, Xiangnan University, 889 Chenzhou Avenue, Suxian District, Chenzhou, 423000, Hunan, People’s Republic of ChinaTel +86 15907354840Fax +86-735-2325007Email shichunhong@xnu.edu.cnPurpose: This study explored the impact of COVID-19 on the mental health and adaptation of behavior of Zhuang women in China to provide more specific guidance for the social and medical practice of pregnant women during public health emergencies.Participants and Methods: This cross-sectional study recruited 446 pregnant Zhuang women from obstetric outpatient clinics in four tertiary hospitals and online maternity schools in Nanning, Guangxi, between February 24 and March 1, 2020. Self-designed questionnaires and the Self-Rating Anxiety Scale were used.Results: During the COVID-19 pandemic, the prevalence rate of anxiety among women was 36.77%, and some adaptation of behavior was observed. Logistic regression analysis showed that pregnant women who had an annual household income of less than $7,000, were primiparous, went out for prenatal examination, wanted to self-monitor during pregnancy but did not know how to do it, believed that they should be strictly isolated at home and cancel prenatal examinations, and expected to receive pregnancy healthcare through teleconsultation services showed a higher risk of anxiety. Nevertheless, pregnant Zhuang women who were 22– 35 years old, undergraduate-educated, and in their second trimester were less likely to suffer from anxiety.Conclusion: The COVID-19 pandemic has a significant psychological impact on pregnant women from ethnic minorities. Factors related to quarantine and social isolation policies appear to drive changes in behaviors and anxiety disorders. Multidisciplinary mental health services and culturally sensitive interventions are necessary for minority pregnant women, especially for low-income primiparous women in the first or third trimester.Keywords: pregnant women, minority, psychological, behavior, coronavirus disease 2019

Yao Wang,* Xun Li,* Qian Chen, Fangzhou Jiao, Chunxia Shi, Maohua Pei, Luwen Wang, Zuojiong Gong Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zuojiong Gong; Luwen WangDepartment of Infectious Diseases, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, People’s Republic of ChinaEmail zjgong@163.com; wangluw8253@163.comBackground: The glycolysis pathway of M1 macrophages is a key factor affecting the inflammatory response. The aim of this article is to investigate the role of histone deacetylase 6 (HDAC6) in the M1 macrophage glycolysis pathway during acute liver failure (ALF).Methodology: Targeted metabolomics for quantitative analysis of energy metabolites technology was used to detect the characteristics of energy metabolism for 8 ALF patients and 8 normal volunteers. The ALF mice model was intervened with HDAC6 inhibitor ACY-1215. iTRAQ/TMT quantitative proteomics was used to detect protein expression in livers in different mice groups. The liver function, energy metabolites, M1 macrophages, cytokines, and pathological structure, DDX3X, NLRP3 and DNMT1 in liver tissue were detected. The changes of the above molecules were verified in cell groups.Results: ALF patients and mice have significant energy metabolism disorders, accompanied by activation of M1 macrophages. After the intervention of ACY-1215, the activated M1 macrophages and cytokines levels in the mouse liver were reduced. The levels of IDH1, MDH1, and ATP were significantly increased. The expression of DDX3X increased, while the expression of NLRP3 and DNMT1 decreased. ACY-1215 could reduce the model cell apoptosis level and inflammatory response, and improve energy metabolism. It could also promote the expression of DDX3X, and inhibit the expression of NLRP3 and DNMT1.Conclusion: ACY-1215 could inhibit the activation of M1 macrophages by improving the glycolytic pathway through regulating DNMT1 and DDX3X/NLRP3 signals to alleviate ALF.Keywords: HDAC6, M1 macrophage, metabolic reprogramming, acute liver failure

Yuanbo Fu,1,* Mina Wang,1,2,* Bingcong Zhao,1,* Baoli Liu,3 Jie Sun,4 Yaohui Feng,3 Zhengfang Wang,3 Qian Li,3 Chunhong Shi,3 Yabo Xuan,3 Siqi Long,3 Huan Liu,4 Tiange Chi,5 Zehuan Liao,6,7 Bin Li,1 Qingquan Liu3 1The Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Key Laboratory of Acupuncture Neuromodulation, Beijing 100010, People’s Republic of China; 2Beijing University of Chinese Medicine, Beijing 100029, People’s Republic of China; 3Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, People’s Republic of China; 4Beijing Xiao Tang Shan Hospital, Beijing 102200, People’s Republic of China; 5The First Clinical Medical School, Beijing University of Chinese Medicine, Beijing 100029, People’s Republic of China; 6School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore; 7Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm 17177, Sweden*These authors contributed equally to this workCorrespondence: Bin LiBeijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Key Laboratory of Acupuncture Neuromodulation, No. 23 Gallery Street, Beijing 100010, People’s Republic of ChinaEmail libin0314a@126.comQingquan LiuBeijing Hospital of Traditional Chinese Medicine, Capital Medical University, No. 23 Gallery Street, Beijing 100010, People’s Republic of ChinaEmail liuqingquan2003@126.comPurpose: To investigate the psychological impact of cases of coronavirus disease 19 (COVID-19) on medical staff of Beijing Xiaotangshan Hospital.Methods: The 287 online questionnaires were distributed to medical staff working at Beijing Xiaotangshan Hospital, comprising three main sections and 17 questions: basic information, current departmental position, and the 12-item General Health Questionnaire (GHQ-12). The threshold for emotional distress was defined to be a total score of 4 on the GHQ-12 and above.Results: A total of 255 members of medical staff participating in this study presented an emotional distress rate of 17%. Members who were male, aged 50– 59, married with children, positioned as doctors, and in administration were the population with the highest rate of emotional distress. Furthermore, the severity of emotional distress among those under 30 was significantly lower than those aged 30– 39 and 50– 59. Doctors and other occupations shared a lower level of satisfaction on routine activities compared with nurses, so did staff in the administration compared with those who were working in screening or logistic departments. Besides, males and staff of the confirmation department had more difficulty in concentrating than females and those of the screening department, respectively.Conclusion: Medical staff working at Xiaotangshan Hospital underwent relatively low levels of emotional distress thanks to sufficient medical and psychological preparations. However, special attention should be paid to those who were male, married with children, senior, doctors, in administration, and in the confirmation department.Keywords: COVID-19, psychological impact, medical staff, Beijing, GHQ-12

Chengxin Shi,1,* Fengli Yue,2,* Feiyu Shi,1 Qian Qin,1 Lizhao Wang,1 Guanghui Wang,1 Lijun Mu,1 Dan Liu,1 Yaguang Li,1 Tianyu Yu,1 Junjun She1 1Department of General Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, People’s Republic of China; 2College of Basic Medical Sciences, Jilin University, Changchun 130021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Junjun SheDepartment of General Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277, Yanta West Road, Xi’an, Shaanxi 710061, People’s Republic of ChinaTel +86-17765856985Email shejunjun@mail.xjtu.edu.cnBackground: Inflammatory bowel disease (IBD) is characterized by chronic relapsing inflammation of the gastrointestinal tract. Oxidative stress plays a pivotal role in the pathogenesis of IBD. Selenium-containing amino acids reportedly have anti-oxidative and anti-inflammatory properties, but it remains unknown if selenium-containing amino acids can be used to treat IBD. This study aimed to investigate the effects of two selenium-containing amino acids – selenocysteine and selenocystine – on oxidative stress and chronic inflammation in a mouse model of dextran sulfate sodium (DSS)-induced IBD.Methodology: C57BL/6 mice were randomly assigned to the following six groups: control, DSS, DSS+selenocysteine, DSS+selenocystine, DSS+sodium selenite, and DSS+N-acetylcysteine (NAC). IBD was induced by 3% DSS. Pro-inflammatory cytokines [interleukin-1β (IL-1β), monocyte chemotactic protein 1 (MCP-1), IL-6, and tumor necrosis factor-α (TNF-α)] and markers for oxidative and anti-oxidative stress [malondialdehyde (MDA), reactive oxygen species (ROS), superoxide dismutase (SOD), and glutathione peroxidase (GPx)] were measured using immunohistochemical analysis.Results: Selenocysteine and selenocystine significantly attenuated IBD-related symptoms, including preventing weight loss, decreasing disease activity index (DAI) scores, and increasing colon length. Selenocysteine and selenocystine significantly ameliorated the DSS-induced oxidative stress, as demonstrated by a reduction in ROS and MDA activity and an increase in SOD and GPx activity. IL-1, MCP-1, IL-6, and TNF-α levels were significantly increased in the IBD mice, while treatment with the selenium-containing amino acids significantly reduced the levels of these pro-inflammatory cytokines. In vivo safety analysis showed minimal side effects of the selenium-containing amino acids.Conclusion: We found that selenocysteine and selenocystine ameliorated DSS-induced IBD via reducing oxidative stress and intestinal inflammation, indicating that selenium-containing amino acids could be a novel therapeutic option for patients with IBD.Keywords: Inflammatory bowel diseases, colitis, selenium-containing amino acids, selenocysteine, selenocystine, oxidative stress, inflammation

Chunhong Shi,1 Zhihua Guo,2 Chan Luo,3 Changbin Lei,4 Pan Li1 1School of Nursing, Xiangnan University, Chenzhou 423000, People’s Republic of China; 2Nursing Department, Changsha Health Vocational College, Changsha 410100, People’s Republic of China; 3Nursing Department, The First Affiliated Hospital of University of South China, Hengyang 421001, People’s Republic of China; 4Clinical Medicine Research Center, Affiliated Hospital of Xiangnan University, Chenzhou 423000, People’s Republic of ChinaCorrespondence: Changbin LeiClinical Medicine Research Center, Affiliated Hospital of Xiangnan University, No. 25 Renmin West Road, Beihu District, Chenzhou, 423000 Hunan, People’s Republic of ChinaTel +86 13762563779Fax +86-735-2223633Email leichangbin@xnu.edu.cnPan LiSchool of Nursing, Xiangnan University, 889 Chenzhou Avenue, Suxian District, Chenzhou, 423000 Hunan, People’s Republic of ChinaTel +86 17773560292Fax +86-735-2325007Email lipan1020@xnu.edu.cnPurpose: This study aimed to assess the psychological impact of the COVID-19 pandemic among the general public in Hunan Province, China, which could help develop psychological interventions and mental health programs.Participants and Methods: This online cross-sectional study recruited 571 participants through snowball sampling between February 2 and February 5, 2020. Data were collected through a general information questionnaire, the Public Emergency Psychological State Questionnaire, the Simple Coping Style Questionnaire, and the Public Disease Awareness on COVID-19 Scale.Results: The total mean score of the public emergency psychological state of the sample was 0.27 (0.31) points, with only 5.78% of participants (n = 33) developing psychological distress. Avoidant coping style and disease awareness were weakly positively correlated (rs = 0.257, p < 0.01) and weakly negatively correlated (rs = − 0.124, p < 0.01) with psychological responses, respectively. There were significant psychological differences among the following variables: occupation, symptoms of fever or fatigue, discernment of the authenticity of COVID-19 information, and level of concern regarding COVID-19 (p < 0.05).Conclusion: The COVID-19 pandemic appears to have had a minor psychological impact on the general population in Hunan Province. However, psychological health promotion in the general public is still required, especially for employees (such as company employees, migrant workers, and businessmen), individuals with COVID-19-like symptoms, limited discernment competence and unconcerned attitudes.Implications: The initiatives for improving psychological health among the general public could focus on delivering COVID-19 knowledge and alleviating avoidant coping styles. Our findings could provide important insight for the development of psychological support strategies in China, as well as in other places affected by the epidemic.Keywords: coping style, coronavirus disease 2019, disease awareness, psychological health, public health emergency

Chengcheng Pu,1,* Bingjie Huang,1,* Tianhang Zhou,1 Zhang Cheng,1 Yi Wang,2 Chuan Shi,1 Xin Yu1 1Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, People’s Republic of China; 2Neuropsychology and Applied Cognitive Neuroscience Laboratory, CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Department of Psychology, University of Chinese Academy of Sciences, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xin Yu; Chuan ShiPeking University Sixth Hospital, 51 Huayuan North Road, Beijing 100089, People’s Republic of ChinaEmail yuxin@bjmu.edu.cn; shichuan@bjmu.edu.cnObjective: To investigate the gender differences in the efficacy and side effects of three frequently used antipsychotic medicines (risperidone, olanzapine, aripiprazole) for patients with first-episode schizophrenia during the first year of treatment.Methods: A total of 569 patients with first-episode schizophrenia were randomly assigned to risperidone, olanzapine, and aripiprazole groups. All patients were treated according to their actual clinical needs. Clinical efficacies were assessed by the Positive and Negative Symptom Scale (PANSS) and side effects were assessed by the Udvalg for Kliniske Undersogelser Side-Effect scale (UKU). All assessments were completed at baseline and at 1, 2, 3, 6, 9, and 12 months.Results: Males had higher baseline PANSS total scores and PANSS negative and general pathological scores. No significant interactions were found between treatment time and gender in psychopathology improvements in all three groups. In the end of the first year, female patients receiving risperidone reported more dermatological symptoms (rashes) than males, female patients receiving olanzapine reported more autonomic side effects and dermatological symptoms than males, and female patients receiving aripiprazole reported more psychotic side effects than males.Conclusion: Gender differences exhibited in response to antipsychotic treatments for Chinese patients with first-episode schizophrenia. After the first year of antipsychotic treatment, drug-related side effects were more likely presented in female patients than male patients.Keywords: first-episode schizophrenia, gender difference, antipsychotic treatment, treatment response, side effects

WeiGuo Gu,1,2 MingBin Hu,1,2 WeiJia Wang,1 Chao Shi,3 JinHong Mei1 1Department of Pathology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2First Clinical Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 3Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of ChinaCorrespondence: JinHong MeiDepartment of Pathology, The First Affiliated Hospital of Nanchang University, No. 17 Yong Wai Street, Nanchang, Jiangxi 330006, People’s Republic of ChinaEmail mjhdoctor@126.comChao ShiDepartment of Oncology, The First Affiliated Hospital of Nanchang University, No. 17 Yong Wai Street, Nanchang, Jiangxi 330006, People’s Republic of ChinaEmail 43286143@qq.comBackground: Distant metastasis in early T1-2 (diameter≤ 5 cm) stage lung adenocarcinoma (ET-LUAD) patients largely affect treatment strategies in clinical practice. However, the associated mechanism remains unclear and related studies is less. This study aimed to establish and validate a novel nomogram to predict the risk of distant metastasis in ET-LUAD.Methods: A total of 258 patients diagnosed with ET-LUAD and not receiving any treatment were recruited into this study. The patients were randomly divided into a training cohort and validation cohort in a ratio of 1:2. Univariate and multivariate logistic regression analysis was used to select the most significant predictive risk factors associated with distant metastasis in the training cohort. The established nomogram was validated by the consistency index (C-index), calibration curve, and decision curve analysis (DCA).Results: There were 124 patients with confirmed distant metastasis and 134 patients with non-distant metastases ET-LUAD were enrolled in the study. Multivariate logistic hazards regression analysis identified independent risk factors associated with distant metastasis to include platelet-to-lymphocyte ratios (PLR), lactate dehydrogenase (LDH), neural-specific enolase (NSE), carcinoembryonic antigen (CEA) and cytokeratin 19 fragments (Cyfra211), which were included in the establishment of the nomogram. The nomogram achieved a high consistency (C-index=0.792), good calibration, and high clinical application value in the validation cohort.Conclusion: The established nomogram can be used to predict distant metastasis in high-risk ET-LUAD nonmetastasis patients and can also be used by doctors to guide preventive and individualized treatment for ET-LUAD patients.Keywords: lung adenocarcinoma, distant metastasis, nomogram

Xingxing Su,1,* Yishi Yang,1,* Le Ma,2,* Peng Luo,2 Kaicheng Shen,1 Haisu Dai,1 Yan Jiang,1 Ling Shuai,1 Zhipeng Liu,1 Jinshan You,1 Ke Min,1 Chunmeng Shi,2 Zhiyu Chen1 1Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, People’s Republic of China; 2Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing 400038, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhiyu ChenDepartment of Hepatobiliary Surgery, Southwest Hospital, First Affiliated Hospital of the Army Medical University, Chongqing 400038, People’s Republic of ChinaTel +86-13983881219Email chenzhiyu_umn@163.comChunmeng ShiInstitute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing 400038, People’s Republic of ChinaTel +86-13708396812Email shicm@tmmu.edu.cnIntroduction: Pancreatic cancer is one of the deadliest cancers in the world, and pancreatic ductal adenocarcinoma (PDAC) accounts for 90% of all cases. Human positive coactivator 4 (PC4) is a transcriptional coactivator that has been associated with the development and progression of several tumors. However, no studies investigated the potential role of PC4 in PDAC.Methods: We investigated PC4 expression in 81 PDAC tissue samples using immunohistochemistry and studied the impact of PC4 expression and the molecular mechanisms of this altered expression on PDAC tumorigenesis and proliferation both in vitro and in vivo.Results: PC4 overexpression was correlated with a poor outcome in PDAC patients. The RNAi-mediated knockdown of PC4 expression in CFPAC-1 and AsPC-1 cell lines reduced cell proliferation and tumor growth. The loss of PC4 in PDAC inhibits cell growth by inducing cell cycle arrest at the G1/S transition and suppressing the mTOR/p70s6k pathway.Discussion/Conclusion: Our findings reveal for the first time that PC4 exerts oncogenic functions by activating mTOR/p70s6k signaling pathway-mediated cell proliferation, implying that PC4 is a promising therapeutic target for PDAC.Keywords: PC4, PDAC, proliferation, mTOR/p70s6k

Haiyan Wang, 1 Qiuping Xu, 1 Hui Hu, 2 Chunling Shi, 3 Ziyan Lin, 3 Huixi Jiang, 3 Huaipu Dong, 3 Jing Guo 1 1Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong, 250012, People’s Republic of China; 2Osaka Dental University Kusuha School, Hirakata City, Osaka 573-1121, Japan; 3School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, 325027, People’s Republic of ChinaCorrespondence: Jing GuoDepartment of Orthodontics, Room 201, School and Hospital of Stomatology, Shandong University, 44-1 Wenhua West Road, Jinan, Shandong 250012, Mainland ChinaEmail guojing@sdu.edu.cnBackground: Relying on surface topography alone to enhance the osteointegration of implants is still inadequate. An effective way to combine long-term ion release and surface topography to enhance osteogenic property is urgently needed.Purpose: The objective of this study is to fabricate a long-term strontium ion release implant system and confirm the biological function in vitro and in vivo.Methods: The biomimic surface was fabricated through alkali-heat treatment and magnetron sputtering. The in vitro biological function assays were determined by MTT, fluorescence staining, alkaline phosphatase activity, extracellular mineralization, and quantitative real-time polymerase chain reaction assays. The in vivo experiments were detected by micro-CT, HE staining and Masson staining.Results: The biomimic surface structure has been successfully fabricated. The in vitro cell assays determined that AH-Ti/Sr90 possessed the best biological function. The in vivo experiments demonstrated that AH-Ti/Sr90 could promote osteointegration significantly under both in normal and osteoporotic conditions.Conclusion: We determined that AH-Ti/Sr90 possesses the best osteogenic property, long-term ion release capacity and osteointegration promotion ability. It has potential clinic application prospects.Keywords: titanium, alkali-heat treatment, magnetron sputtering, osteogenic differentiation, osteoclast inhibition

Weihua Zhang,1,2,* Na Zhu,3,* Jianbo Lai,1,4 Jingjing Liu,1,5 Chee H Ng,6 Jun Chen,3 Chao Qian,1,7 Yanli Du,1 Chanchan Hu,1,4 Jingkai Chen,1,4 Jianbo Hu,1,4 Zhong Wang,1,4 Hetong Zhou,1,4 Yi Xu,1,4 Yiru Fang,3 Chuan Shi,8– 11 Shaohua Hu1,4 1Department of Psychiatry, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, People’s Republic of China; 2Department of Psychiatry, Taizhou Second People’s Hospital, Taizhou 317200, People’s Republic of China; 3Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai 200030, People’s Republic of China; 4The Key Laboratory of Mental Disorder Management of Zhejiang Province, Hangzhou 310003, People’s Republic of China; 5Department of Psychiatry, Wenzhou Kangning Hospital, Wenzhou 325000, People’s Republic of China; 6The Melbourne Clinic Department of Psychiatry, University of Melbourne, Melbourne, Victoria 3052, Australia; 7Department of Psychiatry, The Seventh Shaoxing People’s Hospital, Shaoxing 312000, People’s Republic of China; 8Department of Psychological Assesssment, Peking University Sixth Hospital, Beijing 100191, People’s Republic of China; 9Peking University Institute of Mental Health, Beijing 100191, People’s Republic of China; 10NHC Key Laboratory of Mental Health, Beijing 100191, People’s Republic of China; 11National Clinical Research Center for Mental Disorders, Beijing 100191, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yiru FangShanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai 200030, People’s Republic of ChinaEmail yirufang@aliyun.comShaohua HuDepartment of Psychiatry, First Affiliated Hospital, Zhejiang University School of Medicine, The Key Laboratory of Mental Disorder Management of Zhejiang Province, 79 Qing Chun Road, Hangzhou 310003, People’s Republic of ChinaEmail dorhushaohua@zju.edu.cnPurpose: The THINC-integrated tool (THINC-it) as a brief screening tool can assesses cognitive impairment in patients with major depressive depression (MDD). Here, we aim to evaluate the reliability and validity of the THINC-it in a bipolar depression (BD-D) group in comparison with a healthy control (HC) group.Materials and Methods: Both groups were matched according to age, gender, years of education, and IQ. All participants completed the THINC-it test, including Spotter, Symbol Check, Codebreaker, Trails, and the Perceived Deficits Questionnaire for Depression-5-item (PDQ-5-D). The concurrent validity and internal consistency of the THINC-it test were analyzed, and 30 healthy controls were randomly sampled to retest THINC-it to verify the reliability of the THINC-it retest. The correlation between THINC-it and Hamilton Depression Scale (HAMD-17) and Sheehan Disability Scale (SDS) was also analyzed.Results: Fifty-eight patients with BD-D and 61 HCs were included for final analysis. There were significant mean difference (MD) standard errors (SE) between two groups in PDQ-5-D, Spotter and Codebreaker (all P< 0.01), Trails (P=0.015). There was no significant difference in Symbol Check (MD (SE)=− 0.01 (0.18), P=0.938; 95% CI=− 0.38 to 0.35). The Cronbach’s α of PDQ-5-D was 0.640. The intraclass correlation coefficient (ICC) was between 0.440 and 0.757. The highest concurrent validity was PDQ-5-D (r=0.812, P< 0.001). PDQ-5-D was positively correlated with HAMD-17 and SDS score (P< 0.01). The objective test had no significant correlation with HAMD-17 and SDS scores (P> 0.05).Conclusion: This study found that THINC-it can accurately present the cognitive impairment of patients with BD-D. It can be potentially applied in assessing the cognitive function of patients with BD-D although Symbol Check may not accurately reflect the level of cognitive function. The concurrent validity and retest reliability are lower than expected, we need to further increase the sample size to study.Keywords: bipolar depression, BD-D, major depressive depression, MDD, THINC-it, cognitive function, reliability, validity

Chunhong Shi,1 Haili Zhu,2 Jun Liu,2 Jian Zhou,2 Weihong Tang2 1School of Nursing, Xiangnan University, Chenzhou 423000, People’s Republic of China; 2Hunan Academy of Traditional Chinese Medicine Affiliated Hospital, Changsha 410006, People’s Republic of ChinaCorrespondence: Haili ZhuHunan Academy of Traditional Chinese Medicine Affiliated Hospital, 58 Lushan Road, Yuelu District, Changsha City, Hunan Province 410006, People’s Republic of ChinaTel +86 188 7499 7609Fax +86 731-88854265Email zhuhaili09@126.comPurpose: Diabetes self-management behaviors are necessary to obtain optimum glycemic control, reduce the risk of complications, and improve health outcomes. The COVID-19 pandemic imposes an additional struggle for self-management by diabetes patients. Although previous studies have reported socio-demographic, behavioral, psychological, and cultural barriers to diabetes self-management, little is known about perceived barriers to diabetes self-management among patients during isolation following their recovery from COVID-19. The purpose of this study was to explore perceived barriers among type 2 diabetes patients during isolation following their recovery from COVID-19.Patients and Methods: A qualitative, exploratory, and descriptive research design was utilized. Semi-structured telephonic interviews were conducted with 12 patients with diabetes who had been discharged from one COVID-19 designated hospital and underwent isolation in the designated facilities in Wuhan City, Hubei Province, China. Data were analyzed using Colaizzi’s seven steps.Results: Barriers to diabetes self-management identified by patients with diabetes during isolation were categorized into five major themes: inadequate knowledge and behavioral beliefs, shortage of resources, suffering from health problems, negative emotions, and lack of support.Conclusion: Perceived barriers to diabetes self-management described by diabetes patients indicated a lack of environmental resources and support strategies to meet their needs. Efforts to remove barriers are important in assisting patients with diabetes to improve their quality of life and health outcomes.Keywords: diabetes mellitus, quarantine, recovery from Coronavirus, treatment

Fang Cheng,1,2 Qiang Li,1,2 Yong Han,1,2 Chen Shi,1,2 Sanlan Wu,1,2 Qiling Xu,1,2 Fang Zeng,1,2 Yu Zhang1,2 1Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People’s Republic of China; 2Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan 430022, People’s Republic of ChinaCorrespondence: Fang Zeng; Yu ZhangDepartment of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People’s Republic of ChinaEmail fancyzeng@126.com; zhangwkp@163.comPurpose: In December 2019, coronavirus disease 2019 (COVID-19) was first identified in Wuhan, and rapidly spread throughout China. Patients with mild symptoms were admitted to Fangcang shelter hospitals for centralized quarantine. We aimed to clarify the medication usage, related adverse reactions, and pharmaceutical interventions in patients with mild COVID-19.Patients and Methods: We innovatively carried out targeted pharmacy services. We provided online and off-line pharmaceutical services to patients in the Fangcang shelter hospital. The use of medication, related adverse reactions, and the effects of pharmaceutical intervention were analyzed.Results: Lower blood lymphocyte count was proposed as the most significant risk factor in patients with mild illness. All patients received antiviral treatment (arbidol, oseltamivir, and ribavirin); 78.4% of patients received antibiotic therapy (moxifloxacin, levofloxacin, and cefdinir); patients in the moderate disease group received more antibiotic therapy than those in the mild disease group. Most of the patients were treated with traditional Chinese medicine. Patients with moderate disease preferred to receive sedative hypnotic therapy. Diarrhea, nausea and vomiting, insomnia, arrhythmia, and constipation were the most common adverse reactions. The rate of mild-to-moderate illness in the pharmaceutical intervention and non-intervention groups was 20.6% and 31.7%, respectively.Conclusion: Most patients with mild illness were treated with antiviral, antibiotic, and Chinese medicine therapy. However, attention should be paid to patients with mild illness presenting with hypertension and low lymphocyte count at the onset; these patients are more likely to develop moderate or severe disease. Moreover, there were many drug-related problems in Fangcang shelter hospital; pharmaceutical care might contribute to alleviate the progress of the patient’s condition. Pharmacists should be prepared to provide skilled and effective services to patients, with the aim to ensure medication safety and promote the overall control of the COVID-19 pandemic.Keywords: COVID-19, Fangcang shelter hospital, medication, drug-related adverse reactions, pharmaceutical care

Chunhong Shi,1 Yinhua Zhang,2 Chunyan Li,1 Pan Li,1 Haili Zhu3 1Nursing Department, XiangNan University, Chenzhou 423000, People’s Republic of China; 2Nursing Department, Hunan University of Chinese Medicine, Changsha 410208, People’s Republic of China; 3Nursing Department, Hunan Academy of Traditional Chinese Medicine Affiliated Hospital, Changsha, 410006, People’s Republic of ChinaCorrespondence: Yinhua Zhang Email zhangyinhua@126.comPurpose: This study aimed to identify risk factors associated with adverse events in residential aged care facilities in China.Patients and Methods: After compiling a list of risk factors for adverse events generated from in-depth interviews with managers of residential aged care facilities, a three-round Delphi method was used to reach consensus. The synthesized risk factors were presented on a Likert scale to the expert panelists three times to validate their responses.Results: The list identified 67 items as risk factors for adverse events, attached to four first-level indexes (ie, environmental facility, nursing staff, older adults’ characteristics, and management factors). The experts’ authority coefficient was 0.87. The positive coefficients were 82.76%, 91.67%, and 100%, and the coordination coefficients were 0.154, 0.297, and 0.313 in the first, second, and third rounds, respectively.Conclusion: Using a Delphi method, this study established a consensus on risk factors contributing to adverse events and developed a risk assessment grade for use in future aged care practice and research. The resulting list is useful in prioritizing risk-reduction activities and assessing intervention or education strategies for preventing adverse events in residential aged care facilities.Impact: This study fills the gap in risk identification in the Chinese residential aged care system to ensure provision of best-practice care to this vulnerable population. Nursing staff and management factors at the top of the list are not only the most common causes of adverse events but also the core elements in creating a secure and error-free environment. This list was intended to support predictive and prevention-oriented decision-making by managers and nursing supervisors to reduce preventable adverse events.Keywords: residential aged care facilities, Delphi survey, risk factors, Aged care, adverse events

Bing-jie Huang,1– 4 Yong Wang,1– 4 Qi Miao,1– 4 Xin Yu,1– 4 Cheng-cheng Pu,1– 4 Chuan Shi1– 4 1Clinical Research Department, Peking University Sixth Hospital, Beijing, People’s Republic of China; 2Institute of Mental Health, Peking University, Beijing, People’s Republic of China; 3NHC Key Laboratory of Mental Health (Peking University), , Beijing, People’s Republic of China; 4National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, People’s Republic of ChinaCorrespondence: Cheng-cheng Pu; Chuan Shi Email pciami@163.com; shichuan@bjmu.edu.cnPurpose: The Negative Symptom Assessment-16 (NSA-16) is an instrument with significant validity and utility for assessing negative symptoms associated with schizophrenia. This study aimed to validate the Chinese version of the NSA-16.Patients and Methods: A total of 172 participants with schizophrenia were assessed with the NSA-16, Scale for Assessment of Negative Symptoms (SANS), Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale for Schizophrenia (CDSS) and Rating Scale for Extrapyramidal Side Effects (RSESE). The factor structure of the NSA-16 was evaluated via exploratory and confirmatory factor analysis. Cronbach’s α and intraclass correlation coefficients were computed. Correlations were evaluated via Spearman correlation coefficient.Results: The original five-factor model of the NSA-16 did not fit our sample. Exploratory factor analysis followed by confirmatory factor analysis suggested a three-factor structure, consisting of communication, emotion and motivation, with 15 items. The NSA with 15 items was termed as the NSA-15. The NSA-15 showed excellent convergent validity by high correlations with the SANS and PANSS total and negative factor scores and good divergent validity by independence from the PANSS positive factor, CDSS and RSESE. The NSA-15 showed good internal consistency, interrater reliability and test–retest reliability.Conclusion: The NSA-15 is best characterized by a three-factor structure and is valid for assessing negative symptoms of schizophrenia in Chinese individuals.Keywords: negative symptoms, schizophrenia, NSA, reliability, validity

Zhiyuan Xu,1,* Hang Lv,2,* Yiping Wang,2 Can Hu,3 Shangqi Chen,3 Yian Du,1 Chengwei Shi,3 Xiangdong Cheng1 1Department of Gastric Surgery, Institute of Cancer and Basic Medicine, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, People’s Republic of China; 2Key Laboratory of Integrated Traditional Chinese and Western Medicine for Diagnosis and Treatment of Digestive System Tumor, Hangzhou 300020, Zhejiang, People’s Republic of China; 3Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiangdong ChengDepartment of Gastric Surgery, Institute of Cancer and Basic Medicine, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, No. 1 Banshan Road, Hangzhou 310022, Zhejiang, People’s Republic of ChinaTel/Fax +86-571-87070965Email chengxd@zcmu.edu.cnObjective: To study the effect of lncRNA HAND2-AS1 on gastric adenocarcinoma (GA) cell property and explore its specific mechanism.Methods: Data on stomach adenocarcinoma (STAD) were analyzed to screen differentially expressed lncRNA HAND2-AS1. RNA22-HAS database and dual luciferase reporter assay were applied to confirm the target relationship between HAND2-AS1/HIF3A and miR-184. The HAND2-AS1 and miR-184 expressions in tissue or cells were determined by qRT-PCR and Western blot. Besides, after GA cells (AGS) cultured in normoxic and hypoxic condition, phosphoenolpyruvate (PEP) and lactic acid were quantified by Phosphoenolpyruvate Fluorometric Assay Kit and Lactic Acid Detection kit, respectively. Additionally, colony formation assay, transwell invasion and migration assays were used to evaluate the abilities of cell invasion, migration, and proliferation in distinct conditions.Results: The HAND2-AS1 and HIF3A expressions were down-regulated and miR-184 expression was up-regulated in GA tissues and cells. Dual luciferase reporter assay confirmed HAND2-AS1 and HIF3A were targeted by miR-184. AGS cell proliferation abilities were restrained by HAND2-AS1 and HIF3A overexpression and enhanced by miR-184, as well as migration and invasion abilities. In addition, HAND2-AS1 rescued enhanced AGS cell proliferation, cell migration, cell invasion abilities and glycolytic process caused by hypoxia via miR-184/HIF3A.Conclusion: LncRNA HAND2-AS1 could inhibit GA cell proliferation, migration and invasion abilities and glycolytic process induced by hypoxia through miR-184/HIF3A signaling.Keywords: gastric adenocarcinoma, lncRNA, cell proliferation, hypoxia, lactic acid

Riping Wu,1,* Qiaolian Li,1,* Fan Wu,2 Chunmei Shi,1 Qiang Chen3 1Fujian Medical University Union Hospital, Fuzhou, Fujian Province, People’s Republic of China; 2Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 3Fujian Medical University Union Hospital, Fuzhou, Fujian Province, People’s Republic of China, Stem Cell Research Institute, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiang Chen; Chunmei ShiDepartment of Medical Oncology, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, People’s Republic of ChinaEmail cqiang8@189.cn; scmscmfz@163.comIntroduction: The peritoneum is the most common metastatic site of gastric cancer and is associated with a dismal prognosis. However, there is no reliable biomarker for predicting peritoneal metastasis (PM).Materials and Methods: Whole-exome sequencing (WES) was performed on formalin-fixed, paraffin-embedded (FFPE) samples from 63 patients with stage I–III gastric cancer and circulating tumor DNA (ctDNA) samples from 10 patients with stage IV gastric cancer. Differentially expressed genes (DEGs) were identified between the PM and non-PM groups and analyzed by multiple bioinformatics analyses. Univariate and multivariate Cox regression analyses were used to identify the risk factors for PM and a risk score model was developed.Results: The number of mutant genes and the tumor mutation burden (TMB) in the PM group were higher than those in the non-PM group (p < 0.05). There was a significant positive correlation between the number of mutant genes and the TMB (R2 = 0.9997). The risk of PM was significantly higher in the high TMB group than in the low TMB group (p = 0.045). Forty-nine DEGs were identified as associated with PM in gastric cancer. CDC27 mutations were associated with a higher risk for PM and poor survival. The CDC27 mutations were located in the Apc3 region, the TPR region, and the phosphorylation region, and new mutation sites were not included in the TCGA database. Multivariable Cox regression analysis demonstrated that pathological T stage, poor tumor differentiation, Borrmann type, and CDC27 mutations were independent predictive factors of PM. A risk score model was constructed that demonstrated good performance.Conclusion: Through WES, we identified 49 DEGs relevant to PM in gastric cancer. CDC27 mutations were independently associated with PM by statistical and bioinformatics analyses. A risk score model was built and was demonstrated to effectively discriminate gastric cancer patients with and without PM.Keywords: gastric cancer, peritoneal metastasis, whole-exome sequencing, CDC27

Changcan Shi,1,* Hongjuan Wu,2,* Ke Xu,3 Ting Cai,3 Kunming Qin,4 Li Wu,1 Baochang Cai1,4 1School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, People’s Republic of China; 2Nanjing Jiangning District Hospital of Traditional Chinese Medicine, Nanjing 211100, People’s Republic of China; 3School of Pharmacy, China Pharmaceutical University, Nanjing 210009, People’s Republic of China; 4Nanjing Haichang Chinese Medicine Group Corporation, Nanjing 210061, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li WuSchool of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, People’s Republic of ChinaEmail wuli@njucm.edu.cnBaochang CaiSchool of Pharmacy Nanjing University of Chinese Medicine, Nanjing 210046, People’s Republic of ChinaEmail bccai@126.comBackground: The clinical use of doxorubicin (DOX) is severely limited due to its cardiotoxicity. Thus, there is a need for prophylactic and treatment strategies against DOX-induced cardiotoxicity.Purpose: The purpose of this study was to develop a liquiritigenin-loaded submicron emulsion (Lq-SE) with enhanced oral bioavailability and to explore its efficacy against DOX-induced cardiotoxicity.Methods: Lq-SE was prepared using high-pressure homogenization and characterized using several analytical techniques. The formulation was optimized by central composite design response surface methodology (CCD-RSM). In vivo pharmacokinetic studies, biochemical analyses, reactive oxygen species (ROS) assays, histopathologic assays, and Western blot analyses were performed.Results: Each Lq-SE droplet had a mean particle size of 221.7 ± 5.80 nm, a polydispersity index (PDI) of 0.106 ± 0.068 and a zeta potential of − 28.23 ± 0.42 mV. The area under the curve (AUC) of Lq-SE was 595% higher than that of liquiritigenin (Lq). Lq-SE decreased the release of serum cardiac enzymes and ameliorated histopathological changes in the hearts of DOX-challenged mice. Lq-SE significantly reduced oxidative stress by adjusting the levels of ROS, increasing the activity of antioxidative enzymes and inhibiting the protein expression of NOX4 and NOX2. Furthermore, Lq-SE significantly improved the inflammatory response through the mitogen-activated protein kinase (MAPK)/nuclear factor-κB (NF-κB) signalling pathway and induced cardiomyocyte apoptosis.Conclusion: Lq-SE could be used as an effective cardioprotective agent against DOX in chemotherapy to enable better treatment outcomes.Keywords: liquiritigenin, submicron emulsion, bioavailability, cardiotoxicity, protective efficacy

In the literature, no detailed description is reported about how to detect if a miscibility gap exists in terms of interaction parameters analytically. In this work, a method to determine the likelihood of the presence of a miscibility gap in a binary substitutional solution phase is proposed in terms of interaction parameters. The range of the last interaction parameter along with the former parameters is analyzed for a set of self-consistent parameters associated with the miscibility gap in assessment process. Furthermore, we deduce the first and second derivatives of Gibbs energy with respect to composition for a phase described with a sublattice model in a binary system. The Al-Zn and Al-In phase diagrams are computed by using a home-made code to verify the efficiency of these techniques. The method to detect the miscibility gap in terms of interaction parameters can be generalized to sublattice models. At last, a system of equations is developed to efficiently compute the Gibbs energy curve of a phase described with a sublattice model.

Lan Li,1 Hui Dai,2 Jun Ke,2 Cen Shi,2 Nan Jiang,2 Chun-Mei Yang3 1Department of Endocrinology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 215006, People’s Republic of China; 2Department of Radiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, People’s Republic of China; 3Department of Endocrinology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, People’s Republic of ChinaCorrespondence: Hui DaiDepartment of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, People’s Republic of ChinaTel/Fax +86512-67780633Email huizi198208@126.comChun-Mei YangDepartment of Endocrinology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, People’s Republic of ChinaTel/Fax +86512-67780633Email muyi1979yang@163.comPurpose: To explore the functional connection strength (FCS) changes of brain networks in diabetic retinopathy (DR) patients and uncover the underlying mechanism.Methods and Materials: Twenty-one patients with DR and 21 age- and sex-matched healthy controls were enrolled from August 2012 to September 2014. Subjects were scanned using 3T MR with blood-oxygen-level dependent (BOLD) and 3-dimension fast spoiled gradient echo (3D-FSPGR) sequences. MR data was analyzed via preprocessing and functional network construction. After a group comparison, components of brain networks with significant group differences were extracted and the FCS of the brain network was evaluated. The brain areas were compared between patients and controls. P-values less than 0.05 were considered statistically significant. Connection strength was evaluated with alphasim, P