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Xuexue Bai,1 Hao Xing,1 Ming Feng,1 Wenbin Ma,1 Shiyong Wang2 1Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Neurosurgery, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Ming Feng; Shiyong Wang, Email pumchfming@126.com; Washiyong@126.comPurpose: We retrospectively analyzed the effect of Bevacizumab (BEV) on recurrent high-grade glioma (rHGG) and examined the relationship between dose and efficacy.Methods: A total of 182 patients with rHGG were included in this study. Patients were divided into a non-BEV group and a BEV group according to the treatment they received, and the BEV group was further divided into a low-dose group and a high-dose group based on the dose. Depending on the number of groups and the characteristics of numerical variables, t-test, ANOVA, or rank-sum test were selected. Categorical variables were compared using the chi-squared test.Results: Progression-free survival (PFS) was lower in the non-BEV group compared to the BEV group, while overall survival (OS) was not different between the two groups. There was no difference in PFS and OS between low-dose group and high-dose group. Notably, we found that patients with longer PFS and OS were more likely to be from the BEV group. In addition, differences in Karnofsky Performance Score (KPS), steroid dose, and brain edema were observed in the non-BEV, low-dose, and high-dose groups from 3 to 12 months after treatment.Conclusion: BEV can improve PFS in patients with rHGG, although its impact on OS is limited. There was no difference in the efficacy of different doses of BEV on rHGG. Interestingly, patients with longer PFS and OS were more likely to be from the BEV group. Based on these findings, long-term low-dose BEV appears to be an effective treatment option for rHGG.Keywords: bevacizumab, temozolomide, recurrent high-grade glioma, progression free survival, overall survival

Cong Wang,1 Lidan Liu,1 Xue Bai2 1Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, People’s Republic of China; 2Department of Health Management, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, People’s Republic of ChinaCorrespondence: Xue Bai, Department of Health Management, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning Province, 110004, People’s Republic of China, Email xbai88@cmu.edu.cnPurpose: The adverse effects and drug abuse issues associated with opioid drugs have made finding a safe and effective alternative a focus of research. Oliceridine has attracted attention for its lower adverse reactions, such as respiratory depression and gastrointestinal issues, compared to traditional opioids, and is considered a promising candidate for addressing the current limitations in opioid therapy. This article explored the knowledge structure of oliceridine through bibliometric analysis, highlighting its clinical applications in managing acute pain and its mechanisms that may reduce addiction risk. Our bibliometric analysis highlighted hotspots and trends in oliceridine research, guiding future studies on its safety and efficacy in pain management.Methods: This study utilized the Web of Science Core Collection database to search for articles related to oliceridine from 2013 to 2024. Systematic analysis was conducted on publication, country, institution, author, journal, references, and keywords. The software Citespace, Vosviewer, and Bibliometrix were employed to visualize bibliometric analysis.Results: From 2013 to 2024, 159 articles on oliceridine were published in 98 journals by 158 institutions from 28 countries. The United States has rapidly developed in this field, providing significant momentum. Keyword clustering analysis revealed that research on oliceridine primarily focused on exploring its molecular and pharmacological mechanisms and conducting clinical studies to evaluate its efficacy and safety in pain management. Analyses of the strongest citation bursts with references and keywords indicated that protein-biased ligands and oliceridine were hotspots. The emergence of divergent views regarding oliceridine’s biased agonism will lead to future hotspots focusing on the underlying mechanisms of biased signaling by G protein-coupled receptors and drug design.Conclusion: Bibliometric analysis provides insights into the current hotspots and emerging areas of oliceridine, which can guide future research. The widespread attention and clinical application of oliceridine lay a solid foundation for further drug development and clinical trials.Keywords: opioid receptors, biased agonism, oliceridine, bibliometrics

Weijun Wan,1,2,* Yunjing Pan,1,2,* Jinshu Pang,1,2 Xiumei Bai,1,2 Lipeng Li,1,2 Tong Kang,1,2 Jiamin Chen,1,2 Rong Wen,1 Dongyue Wen,1 Hong Yang,1– 3 Yun He1,2 1Department of Medical Ultrasound, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China; 2Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor/Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Nanning, 530021, People’s Republic of China; 3Collaborative Innovation Centre of Regenerative Medicine and Medical Bioresource Development and Application Co-constructed by the Province and Ministry, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yun He; Hong Yang, Department of Medical Ultrasound, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China, Email heyun@stu.gxmu.edu.cn; yanghong@gxmu.edu.cnPurpose: The explosive progression of residual hepatocellular carcinoma (HCC) following incomplete thermal ablation is challenging, and the underlying mechanisms require further exploration. We investigated the mechanism by which Forkhead box P4 (FOXP4) promotes the malignant transformation of residual HCC cells through N-deacetylase and N-sulfotransferase 2 (NDST2) after incomplete thermal ablation.Methods: The clinical significance of FOXP4 and NDST2 in HCC was evaluated using big data analysis. FOXP4 expression was detected in clinical samples of HCC. The gene expression levels in an in vitro heat-stressed HCC cell model were determined using quantitative real-time PCR (RT-qPCR) and Western blotting. The effects of the genes on heat-stressed HCC cells were investigated using Cell Counting Kit-8 (CCK-8), scratch, Transwell migration, and invasion assays. Additionally, the regulatory relationship between FOXP4 and NDST2 was validated using the Cleavage Under Targets and Tagmentation (CUT&Tag) experiments and phenotypic assays.Results: High FOXP4 expression was correlated with liver cancer occurrence and development. In the heat-stressed HCC cell model, downregulating FOXP4 inhibited cancer cell progression. Besides, there was a positive association between FOXP4 and NDST2 in liver cancer. Suppressing FOXP4 reduced NDST2 expression in the heat-stressed HCC cells. Furthermore, reducing NDST2 expression weakened the biological behavior of heat-stressed HCC cells.Conclusion: FOXP4 and NDST2 are crucial in the incomplete thermal ablation of residual cancer. FOXP4 might regulate the biological progression of residual HCC after incomplete thermal ablation through NDST2.Keywords: ablation therapy, gene expression regulation, cancer inhibition, hepatocellular carcinoma

Xianglian Bai,1 Aiwu Luo,2 Qin Liu,1 Xiaofeng Ma1 1The Affiliated Nanhua Hospital, Department of Cardiology, Hengyang Medical School, University of South China, Hengyang City, Hunan Province, 421001, People’s Republic of China; 2Department of Health Education, Hengyang Center for Disease Control and Prevention, Hengyang City, 421002, People’s Republic of ChinaCorrespondence: Xiaofeng Ma, The Affiliated Nanhua Hospital, Department of Cardiology, Hengyang Medical School, University of South China, Dongfeng Street, Zhuhui District, Hengyang City, Hunan Province, People’s Republic of China, Tel + 8613786437543, Email 1607251097@qq.comObjective: To explore the influencing factors of left ventricular thrombosis after percutaneous coronary intervention (PCI) in patients with acute ST segment elevation myocardial infarction (STEMI) and construct a column chart model.Methods: A retrospective study was conducted on 331 STEMI patients who underwent PCI between July 2020 and January 2024. According to the principle of approximately 3:1, patients were randomly separated into 245 in the modeling group and 86 in the validation group, and clinical data of patients were collected. Multivariate logistic regression was applied to screen for risk factors. R software was applied to draw column charts. Bootstrap method was applied for internal validation. Hosmer-Lemeshow (H-L) was applied to test the fitting degree of the column chart model. Calibration curve and ROC curve were applied to verify calibration and discrimination, respectively. DCA curve was applied to analyze the clinical practicality of the column chart model.Results: A history of angina pectoris, ventricular aneurysm, alcohol abuse, postoperative TIMI grade ≤ 2, LVEF, and total ischemic time were influencing factors for left ventricular thrombosis in STEMI patients after PCI (P< 0.05). The predicted probabilities of the internal and external validation calibration curves were highly consistent with the actual probabilities, the concordance index of the ROC curve was 0.962 (95% CI: 0.931– 0.994) and 0.958 (95% CI: 0.926– 0.990), respectively, indicating high model calibration and discrimination; H-L inspection showed χ2=11.977, 9.757 (P=0.152, 0.282). DCA curve showed that when the probability range of the high-risk threshold was 0.02~0.99, the column chart model performed better and had a higher net return.Conclusion: The column chart model constructed by risk factors such as history of angina, ventricular aneurysm, history of alcohol abuse, postoperative TIMI ≤ grade 2, LVEF, and total ischemic time has high predictive value and can effectively predict left ventricular thrombosis in STEMI patients after PCI.Keywords: acute ST-segment elevation myocardial infarction, percutaneous coronary intervention, left ventricular thrombosis, influencing factors, column chart

Beibei Luo, Wenbo Xu, Dan Ye, Xuejing Bai, Mengna Wu, Chunting Zhang, Rui Shi Clinical Laboratory, People’s Hospital of Yuxi City, the Sixth Affiliated Hospital of Kunming Medical University, Yuxi City, Yunnan Province, 653100, People’s Republic of ChinaCorrespondence: Wenbo Xu, Clinical Laboratory, People’s Hospital of Yuxi City, the Sixth Affiliated Hospital of Kunming Medical University, 21 Nieer Road, Yuxi City, Yunnan Province, 653100, People’s Republic of China, Email xwb103196@sina.comIntroduction: Dyslipidemia commonly complicates type 2 diabetes mellitus, yet the relationship between glycosylated hemoglobin and blood lipid levels remains uncertain.Methods: This retrospective cross-sectional study included 27,158 participants from the People’s Hospital of Yuxi. Statistical comparisons for continuous variables utilized analysis of variance (ANOVA), while chi-square analysis was employed for categorical variables. Boxplots assessed the concentration, dispersion, and deviation of total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL-C), and high-density lipoprotein (HDL-C) distribution. A linear regression analysis examined the association between HbA1c and lipid profile, complemented by a fitting curve to visualize trends.Results: Participants who developed diabetes exhibited higher age and elevated Body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), TC, TG, LDL-C, and FPG levels compared to those without diabetes (p < 0.001). Linear regression analysis demonstrated significant associations between HbA1c values and TC, TG, LDL-C, and HDL-C (p < 0.001). The plotted curve indicated that as TC, TG, and LDL levels increased, HbA1c levels rose, while HDL levels decreased.Conclusion: HbA1c was positively correlated with TC, TG, LDL-C, and negatively correlated with HDL-C in the population in the central Yunnan Plateau.Keywords: dyslipidemia, HbA1c, lipid profile

Haichuan Miao,1,2 Zhiyong Zhu,2 Huisheng Wang,2 Xizhuang Bai,2 Xi Li2 1Dalian Medical University, Dalian, 116044, People’s Republic of China; 2Department of Sports Medicine and Joint Surgery, The People’s Hospital of Liaoning Province, The People’s Hospital of China Medical University, Shenyang, 110000, People’s Republic of ChinaCorrespondence: Xizhuang Bai; Xi Li, Department of Sports Medicine and Joint Surgery, The People’s Hospital of Liaoning Province, The People’s Hospital of China Medical University, 33 Wenyi Road, Shenhe District, Shenyang, 110000, People’s Republic of China, Email educmu0922@163.com; lixiseki@gmail.comBackground: Robotic-assisted total knee arthroplasty (RATKA) has been reported to enhance operative decision-making. The purpose of this study was intended to assess the predictive accuracy of bone cuts, lower limb alignment, and component size of a novel system for RATKA preoperatively and intraoperatively.Methods: Preoperatively planned bone cuts, limb alignment, and component size were projected using a reconstructed 3D model. Intraoperative bone cuts and postoperative limb alignment were measured. Errors between planned and real bone cuts, limb alignment, and component size were compared.Results: The mean absolute errors for bone cuts and alignment were within 1.40mm/1.30° with a standard deviation (SD) of 0.96mm/1.12°. For all errors of bone cuts and alignment compared with the plan, there were no statistically significant differences except for the lateral distal of femoral cuts (P=0.004). The accuracy for predicting the femoral, tibial, and polyethylene component sizes was 100% (48/48), 90% (43/48), and 88% (42/48), respectively. Regarding all mean absolute errors of bone cuts and alignments, no significant differences were observed among surgeons.Conclusion: The novel robotically-assisted system for RATKA donated reliable operative decision-making based on the predictive accuracy regardless of the surgeon’s level of experience.Keywords: robotic surgery, total knee arthroplasty, resection, implant, level of experience

Xue Bai,1,2,&ast; LiTing Yang,1,2,&ast; Ruxin Liu,1,2 YuJiao Tang,1,2 Long Yang,1,2 Lingna Ma,1,2 MengFei Chen,2 Ling Zhang2 1Department of Emergency, The Third Clinical Medical College of Ningxia Medical University, Yinchuan, People’s Republic of China; 2Department of Emergency, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: MengFei Chen; Ling Zhang, Tel +86 13389513801 ; +86 13895318660, Email prayer_821@sina.com; zhangling_7015@sina.comObjective: Cellular pyroptosis is a pro-inflammatory mode of programmed cell death that has been identified in recent years, and studies have shown that the LncRNA SOX2OT regulates myocardial injury during sepsis, but the exact regulatory mechanism is unclear. The aim of this study was to assess the role of SOX2OT in regulating cardiomyocyte injury during sepsis cardiomyopathy.Methods: Rat cardiomyocytes, C57BL/6 mice, and transgenic mice were divided into four groups: control, LPS, LPS+ knockout LncRNA SOX2OT, and LPS+ overexpression LncRNA SOX2OT. Inflammatory factor levels were detected by qPCR. Associated proteins and gene expression were detected by Western blotting and qPCR. Dual luciferase was used to detect the target genes of SOX2OT. Nrf2 and EZH2 knockdown and overexpression cell lines were established, and the expression of related genes was detected by qPCR.Results: Results In this study, we found that SOX2OT knockdown exacerbated LPS-induced levels of inflammatory factors and procalcitoninogen (PCT), and increased the expression of pyroptosis-related proteins and LDH. The results of dual luciferase reporter gene assay showed that EZH2 is the target gene of SOX2OT, and overexpression of SOX2OT decreased the expression of EZH2; we also found that knockdown of EZH2 in H9c2 cells decreased the expression of Nrf2, which was positively correlated with the expression level of NLRP3. Further in vivo results showed that overexpression of SOX2OT attenuated SIMD (sepsis-induced myocardial dysfunction), as evidenced by improved myocardial structural integrity and reduced inflammatory cell infiltration. The expression of pyroptosis-related proteins and LDH was significantly increased in the mice in the LPS group; this effect was reversed by overexpression of SOX2OT, and potentiated by knockdown of SOX2OT.Conclusion: Our data reveal a novel mechanism by which SOX2OT inhibits cardiomyocyte sepsis through the EZH2/Nrf-2/NLRP3 pathway, thereby attenuating septic myocardial injury, which may contribute to the development of new therapeutic strategies.Keywords: SOX2OT, EZH2, Nrf2, sepsis, pyroptosis

Tingting Qin, Xingming Li, Kun Qiao, Xinyuan Bai, Mingyu Gu, Yao Wang School of Public Health, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Xingming Li, School of Public Health, Capital Medical University, No. 10 Xitoutiao, Youanmenwai, Fengtai District, Beijing, 100069, People’s Republic of China, Email xingmingli@ccmu.edu.cnPurpose: Group Model Building (GMB) is a qualitative method that refers to a participatory process. This project aims to identify barriers and facilitators of hypertension management in primary health care in China, through which, the leverage point for intervention may be found.Methods: The GMB was used to identify the factors influencing hypertension management. Graphs over time and causal loop diagram (CLD) were main tools of GMB. To propose the influencing factors, key stakeholders were invited to participate in a workshop. During the workshop, stakeholders were encouraged to plot the graphs over time of the variables about research issues and give a descriptive explanation. And based on this, a CLD was initially developed to establish a model of the interaction of factors. After the workshop, the research group further improved the CLD through repeated mutual discussions, and gave feedback to the participants. The Vensim PLE 9.0 software package was used to build CLD.Results: A total of 14 key stakeholders were invited to participate in the workshop. Finally, 26 influencing factors were identified, which were divided into three dimensions, including the institutional, the community health workers (CHWs), and the patient level. And 5 reinforcing loops and 4 balancing loops were formed in the CLD. Promoting the building of the Medical Community/Regional Medical Association, implementing the family doctor contract service (FDCS), and enhancing the motivation of CHWs may be potential leverage points for hypertension management in China.Conclusion: By using GMB, we have identified key factors in the management of hypertension in primary health care and provided comprehensive suggestions to overcome the obstacles.Keywords: group model building, hypertension management, primary health care, causal loop diagram, system dynamics

Xiaoxi Deng,1,&ast; Xiaofei Guo,1,&ast; Xiaojie Chen,2 Xinyu Zeng,1 Jiamin Guo,1 Xin Bai,1 Ping Zhang,1 Yuan Wang1 1Department of Pathology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, 100102, People’s Republic of China; 2Department of Emergency, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, 100102, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuan Wang, Ping Zhang, Department of Pathology, Wangjing Hospital, China Academy of Chinese Medical Sciences, 6 Wangjing Zhonghuan South Road, Chaoyang District, Beijing, 100102, People’s Republic of China, Tel +86 010-84739040, Email yuanwangwwwy@126.com; zhang787ping@126.comBackground: Acute myocardial infarction (AMI) is a severe acute coronary syndrome, demonstrating a trend toward affecting younger individuals in recent years. The association between early-onset myocardial infarction and single nucleotide polymorphism necessitates further exploration and evaluation.Case description: We present a case of a patient experiencing early-onset and recurrent myocardial infarction. The patient underwent stent implantation for myocardial infarction at the age of 53 and subsequently encountered two more myocardial infarctions within a span of 16 years. Following interventional therapy, genetic testing was conducted to assess the efficacy of subsequent anti-heart failure medications, with the aim to preemptively address heart failure risks. Genetic testing revealed a mutation in the angiotensin-converting enzyme (ACE) gene (rs577350502, g.63488533C>A), characterized by an intron-deletion single nucleotide variant.Conclusion: While this variant has not been previously reported to be associated with any specific disease, we hypothesize that it may contribute to the susceptibility and risk of myocardial infarction and coronary heart disease in the patient under consideration. This observation underscores the significance of investigating the insertion/deletion polymorphisms of the ACE gene in the context of AMI and emphasizes the necessity for further validation of this variant and other genetic markers associated with AMI in related diseases.Keywords: ACE, case reports, gene mutations, myocardial infarction, SNV

Guoqiang Yang,1– 3 Jiraporn Kantapan,3 Maryam Mazhar,4,5 Qiongdan Hu,1,5,6 Xue Bai,5,7 Yuanxia Zou,1,3 Honglian Wang,1 Sijin Yang,4,5 Li Wang,1,5 Nathupakorn Dechsupa3 1Research Center for Integrated Chinese and Western Medicine, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 2Acupuncture and Rehabilitation Department, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 3Molecular Imaging and Therapy Research Unit, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand; 4National Traditional Chinese Medicine Clinical Research Base and Drug Research Center of the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 5Institute of Integrated Chinese and Western Medicine, Southwest Medical University, Luzhou, People’s Republic of China; 6Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand; 7Department of Neurology and National Traditional Chinese Medicine Clinical Research Base, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, People’s Republic of ChinaCorrespondence: Li Wang; Nathupakorn Dechsupa, Email wangli120@swmu.edu.cn; nathupakorn.d@cmu.ac.thBackground: Intracerebral hemorrhage (ICH), a devastating form of stroke, is characterized by elevated morbidity and mortality rates. Neuroinflammation is a common occurrence following ICH. Mesenchymal stem cells (MSCs) have exhibited potential in treating brain diseases due to their anti-inflammatory properties. However, the therapeutic efficacy of MSCs is limited by the intense inflammatory response at the transplantation site in ICH. Hence, enhancing the function of transplanted MSCs holds considerable promise as a therapeutic strategy for ICH. Notably, the iron-quercetin complex (IronQ), a metal-quercetin complex synthesized through coordination chemistry, has garnered significant attention for its biomedical applications. In our previous studies, we have observed that IronQ exerts stimulatory effects on cell growth, notably enhancing the survival and viability of peripheral blood mononuclear cells (PBMCs) and MSCs. This study aimed to evaluate the effects of pretreated MSCs with IronQ on neuroinflammation and elucidate its underlying mechanisms.Methods: The ICH mice were induced by injecting the collagenase I solution into the right brain caudate nucleus. After 24 hours, the ICH mice were randomly divided into four subgroups, the model group (Model), quercetin group (Quercetin), MSCs group (MSCs), and pretreated MSCs with IronQ group (MSCs+IronQ). Neurological deficits were re-evaluated on day 3, and brain samples were collected for further analysis. TUNEL staining was performed to assess cell DNA damage, and the protein expression levels of inflammatory factors and the cGAS-STING signaling pathway were investigated and analyzed.Results: Pretreated MSCs with IronQ effectively mitigate neurological deficits and reduce neuronal inflammation by modulating the microglial polarization. Moreover, the pretreated MSCs with IronQ suppress the protein expression levels of the cGAS-STING signaling pathway.Conclusion: These findings suggest that pretreated MSCs with IronQ demonstrate a synergistic effect in alleviating neuroinflammation, thereby improving neurological function, which is achieved through the inhibition of the cGAS-STING signaling pathway.Keywords: mesenchymal stem cells, IronQ, intracerebral hemorrhage, cGAS/STING/NFκB, inflammatory response

Runing Zhou,1 Xiyu Sun,2 Mingyue Guo,1 Huimin Zhang,1 Xuanfu Chen,1 Meixu Wu,1 Haozheng Liang,1 Xiaoyin Bai,1 Gechong Ruan,1 Hong Yang1 1Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China; 2Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of ChinaCorrespondence: Hong Yang, Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, 100730, People’s Republic of China, Tel +86-10-69155014, Email yangh@pumch.cnAim: The diagnosis of inflammatory bowel disease (IBD) worldwide is complicated and results in diagnostic delay. However, the diagnostic interval of IBD and the factors associated with diagnostic delay in patients in China have not been determined.Methods: We retrospectively analyzed clinical data of hospitalized IBD patients in Peking Union Medical College Hospital from January 1998 to January 2018. Patients were divided into non-delayed and delayed groups according to their diagnostic interval.Results: A total of 516 and 848 patients were confirmed to have Crohn’s disease (CD) and ulcerative colitis (UC), respectively. The median diagnostic intervals were 6 and 20 months in patients with UC and CD, respectively (P< 0.05). A decreasing trend in the diagnostic interval for IBD was observed over time, from 9 months to 1 month in UC patients and from 30 months to 3 months in CD patients. The longest diagnostic interval was 29.5 months in CD patients with first symptoms at the age of 51– 60 years and 12.5 months in UC patients at the age of 41– 50 years. In patients with CD, intestinal obstruction (OR=2.71), comorbid diabetes (OR=4.42), and appendectomy history (OR=2.18) were risk factors for diagnostic delay, whereas having fever as the first symptom may reduce its risk (OR=0.39). In patients with UC, the misdiagnosis of chronic enteritis (OR=2.10) was a risk factor for diagnostic delay.Conclusion: The diagnostic interval for IBD has decreased over the years. Some clinical manifestations, such as initial symptoms and age at symptom onset, may help to shorten this interval. Diseases such as tuberculosis and infectious enteritis should be considered during differentiation.Keywords: inflammatory bowel disease, diagnostic delay, China

Yin-Ling Xiu, Kai-Xuan Sun, Qian Zhang, Yu-Hong Xiao, Xue Bai, Yong Chen, Meng-Si Zhao, Yue-Xin Yu Center of Reproductive Medicine, General Hospital of Northern Theatre Command, Shenyang, 110016, People’s Republic of ChinaCorrespondence: Yue-Xin Yu, Center of Reproductive Medicine, General Hospital of Northern Theater Command, No. 83, Wenhua Road, Shenhe District, Shenyang, 110016, People’s Republic of China, Tel +86-18809881296, Email yuyuexinpingan@163.comAim: To compare the pregnancy outcomes of frozen-thawed embryo transfer (FET) cycles among women with repeated implantation failure (RIF) treated with various endometrial preparation protocols.Methods: A total of 605 women with RIF were retrospectively recruited between January 2017 and December 2020 from Northern Theater General Hospital. Patients were divided into natural cycles, hormone replacement therapy (HRT) cycles, depot gonadotropin-releasing hormone (GnRH) agonist-HRT, and endometrial scratching (ES) plus depot GnRH agonist-HRT. The primary endpoint was clinical pregnancy rate, while secondary endpoints included live birth rate and pain assessment.Results: Of the 605 recruited patients, 63 were undergoing natural cycles, 281 were treated with HRT cycles, 141 treated with depot GnRH agonist-HRT, and 120 treated with ES combined with depot GnRH agonist-HRT. There were significant differences among protocols on clinical pregnancy rate (P=0.029), while no significant difference was observed among protocols on live birth rates (P=0.108). Multivariate analyses suggested that HRT (odds ratio [OR]: 0.50; 95% confidence interval [CI]: 0.28– 0.89; P=0.019) and depot GnRH agonist-HRT (OR: 0.49; 95% CI: 0.27– 0.91; P=0.021) cycles were associated with a lower clinical pregnancy rate as compared with natural cycles, while no significant difference between ES combined with depot GnRH agonist-HRT and natural cycles for clinical pregnancy rates (OR: 0.72; 95% CI: 0.38– 1.36; P=0.313). Moreover, the HRT (OR: 0.70; 95% CI: 0.39– 1.28; P=0.239), depot GnRH agonist-HRT (OR: 0.67; 95% CI: 0.35– 1.29; P=0.229), and ES combined with depot GnRH agonist-HRT (OR: 1.11; 95% CI: 0.58– 2.14; P=0.754) cycles had no significant effects on live birth rate as compared with natural cycles. A total of 87.50% patients treated with ES combined with depot GnRH agonist-HRT reported pain during the procedure.Conclusion: ES and depot GnRH agonists could be considered for RIF women with high-quality blastocysts, 14 days after verified transplantation failure.Keywords: endometrial scratching, depot GnRH agonist, repeated implantation failure, blastocysts, clinical pregnancy rate, live birth rate

Fang Wen,1,&ast; Shantong Jiang,1– 4,&ast; Ping Yuan,1– 5,&ast; Jinbo Liu,1– 4 Xiu Bai,1 Hongwei Zhao,1– 4,6,7 Xin Chen,1– 4,7 Yan-Bing Gong,5 Roland Asmar,8 Hongyu Wang1– 4,6,7 1Department of Vascular Medicine, Peking University Shougang Hospital, Beijing, People’s Republic of China; 2Vascular Health Research Center of Peking University Health Science Center (VHRC-PKUHSC), Beijing, People’s Republic of China; 3Beijing Shijingshan District Key Clinical Specialty of Vascular Medicine, Beijing, People’s Republic of China; 4Heart and Vascular Health Research Center of Peking University Clinical Research Institute (HVHRC-PUCRI), Beijing, People’s Republic of China; 5Department of Scientific Research, Peking University Shougang Hospital, Beijing, People’s Republic of China; 6State Key Laboratory of Vascular Homeostasis and Remodeling, (Peking University), Beijing, People’s Republic of China; 7Heart and Vascular Health Research Center of Chengdu Medical College (HVHRC-CMC), Chengdu, People’s Republic of China; 8Foundation-Medical Research Institutes, Beirut, Lebanon&ast;These authors contributed equally to this workCorrespondence: Hongyu Wang, Department of Vascular Medicine, Peking University Shougang Hospital, Beijing, 100144, People’s Republic of China, Email dr.hongyuwang@foxmail.comAbstract: Cardiovascular disease(CVD) has become a major disease burden affecting people’s health in China. Blood vessels are very important for human health and are the “sentinel” for the development of many cardiovascular and cerebrovascular diseases. The key to effectively preventing fatal, disabling heart, brain and peripheral vascular events lies in controlling traditional and non-traditional risk factors for vascular health from the source, and early assessment and intervention of early vascular lesions. Since 2004, China government promoted the early detection technology of vascular lesions and vascular medicine, and proposed the Beijing Vascular Health Stratification (BVHS) to provide suggestions for the examination, evaluation and management of risk factors, and to provide new ideas for lifelong maintenance of vascular health. This review mainly introduces the establishment and development of the clinical discipline of “vascular medicine” in the past 20 years in China, introduces the indicators for detecting vascular function and structure and the predictive value of vascular events, and carries out intelligent and digital management of vascular health throughout the life cycle of individualized prevention, treatment and rehabilitation for people with different parts or degrees of lesions, effectively reducing the occurrence and development of cardiovascular and cerebrovascular diseases, and the prospect of new technology in maintaining vascular health.Keywords: heart and vascular health, vascular medicine, early assessment, digital, Beijing vascular health stratification

Cong Wang,1 Lidan Liu,1 Xue Bai2 1Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, People’s Republic of China; 2Department of Health Management, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, People’s Republic of ChinaCorrespondence: Xue Bai, Department of Health Management, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning Province, 110004, People’s Republic of China, Tel +8618940252079, Email xbai88@cmu.edu.cnPurpose: The global incidence of primary dysmenorrhea is continuously increasing, and understanding its research trends is crucial for effective pain management and women’s health. Therefore, this study aims to perform a comprehensive bibliometric analysis of primary dysmenorrhea research to identify hotspots, explore emerging trends, and provide valuable insights for future research endeavors.Material and Methods: All of the relevant studies on primary dysmenorrhea in the Web of Science™ Core Collection database were searched for bibliometric analysis. Biclustering analysis using gCLUTO software was performed to identify research hotspots. Social network analysis with Ucinet was employed to reveal knowledge structure. Evolutionary analysis using SciMAT was utilized to predict thematic trends.Results: A total of 903 papers were analyzed, indicating a gradual increase in research on primary dysmenorrhea in recent years, with the scope of research expanding and diversifying. We identified seven hotspots, three treatment nodes, and four thematic trends. Research hotspots focused on epidemiological studies, adolescent primary dysmenorrhea, drug and non-drug treatments. Within the realm of treatments, we have identified three treatment nodes: acupuncture, acupressure, and ibuprofen. The evolution of research has witnessed a shift from traditional epidemiological studies toward a more diverse research landscape. Adolescent primary dysmenorrhea is expected to remain a prominent research topic while dietary supplements and lifestyle are predicted to gain more attention. An emerging theme is the study of variation and polymorphism of circadian rhythm genes concerning primary dysmenorrhea.Conclusion: This bibliometric analysis provides valuable insights into the current state of research on primary dysmenorrhea, offering a clearer understanding of the field’s landscape. The identified hotspots, knowledge structure, and thematic trends can serve as valuable references for future investigations in this area. The research holds significant scientific importance and innovative value in elucidating the mechanisms of primary dysmenorrhea and finding more effective treatment approaches.Graphical Abstract: Keywords: primary dysmenorrhea, pain management, women’s health, bibliometric analysis

Wen Wen,1 Zhanyi Zhang,2 Jianqing She,2 Xiaofang Bai,3 Yan Wu,2 Li Gao,2 Juan Zhou,2,4,5 Zuyi Yuan2,4,5 1Department of Ultrasound, Clinical Medical College, First Affiliated Hospital of Chengdu Medical College, Chengdu, People’s Republic of China; 2Department of Cardiovascular Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 3Department of Ultrasound, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 4Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 5Key Laboratory of Molecular Cardiology, Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaCorrespondence: Juan Zhou; Zuyi Yuan, Email zj.7332@mail.xjtu.edu.cn; zuyiyuan@mail.xjtu.edu.cnBackground: White blood cell (WBC) indices are strongly associated with cardiovascular disease, but data on the prognostic values of these parameters in patients with acute coronary syndrome (ACS) following percutaneous coronary intervention (PCI) are sparse. The current study aimed to investigate the relationship between baseline WBC indices levels and the incidence of heart failure (HF) in ACS patients after PCI and explore the predictive values over a 2-year follow-up period.Methods: A total of 416 consecutive ACS patients treated with PCI were enrolled and received a median of 27.7 months follow-up. Univariate and multivariate Cox regression analyses and the receiver operating characteristic (ROC) curves were performed.Results: Baseline lymphocyte (LYMPH) count, eosinophil (EO) count and eosinophil percentage (EO %) were higher in patients who experienced HF over a 2-year follow-up. In multivariate Cox proportional hazards analysis, LYMPH count, EO count and EO % were independently associated with the occurrence of HF (hazard ratio [HR] = 12.876, P = 0.025; HR = 16.625, P = 0.004; HR = 1.196, P = 0.031, respectively). The area under the ROC curve of baseline EO count predicting the occurrence of HF in ACS patients following PCI was 0.625 (P = 0.037). For patients aged 60 years and above, who had PCI or history of coronary artery bypass grafting, the higher EO count, the higher the risk of HF.Conclusion: Elevated baseline LYMPH count, EO count and EO % were independently associated with the incidence of HF in ACS patients following PCI, suggesting that WBC indices might be available, simple, and cost-efficient biomarkers with predictive value, especially for patients aged more than 60 years.Keywords: heart failure, acute coronary syndrome, lymphocytes, eosinophils, independent predictive factors

Xueying Bai, Ji Luo Department of Thoracic Surgery, The First Hospital of China Medical University, Shenyang, 110001, People’s Republic of ChinaCorrespondence: Xueying Bai, Email baixueying9914@163.comBackground: Invasive candidiasis (ICs) is one of the common causes of death in patients with solid tumors. However, studies on the clinical characteristics of ICs with solid tumors are limited.Methods: The purpose of this study was to retrospectively analyse the clinical characteristics, laboratory results and risk factor prediction of inpatients with ICs and solid tumors. We reviewed the clinical data and candida specimen information of hospitalized patients diagnosed with solid tumors combined with ICs at the First Hospital of China Medical University from January 2016 to December 2020. Multivariate logistic regression analysis was used to assess the prognostic factors associated with mortality in these patients.Results: A total of 243 ICs patients with solid tumors were included in this study. The average ± SD age was 62.8 ± 11.7 (range: 27– 93 years old), of which nearly 41% were ≥ 65 years old (99/243, 40.7%), and most were male (162/243, 66.6%). Most patients had malignant tumors of the digestive system. The most common candida was Candida parapsilosis (101/243, 41.5%), followed by Candida guilliermondii (83/243, 34.1%), Candida albicans (32/243, 13.1%), Candida glabrata (17/243, 6.9%), Candida tropicalis (7/243, 2.8%) and Candida krusei (3/243, 1.2%). Multivariate logistic regression analysis showed that the length of stay in the ICU, urinary catheter, total parenteral nutrition, stay in the ICU, renal failure and neutrophil count were prognostic factors related to death.Conclusion: In this study, based on the clinical data of solid tumor patients with ICs in the past 5 years, the results showed that the length of stay in the ICU, urinary catheter, total parenteral nutrition, stay in the ICU, renal failure and neutrophil count were identified as the main prognostic factors. This study can be used to help clinicians carry out early intervention for high-risk patients.Keywords: invasive candidiasis, solid tumors, epidemic, single center, prognosis

Ting Xiong,1 Xinyue Bai,1 Xingyi Wei,1 Lezheng Wang,1 Fei Li,2 Hui Shi,3 Yue Shi2 1School of Exercise and Health, Shanghai University of Sport, Shanghai, 200438, People’s Republic of China; 2School of Athletic Performance, Shanghai University of Sport, Shanghai, 200438, People’s Republic of China; 3Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of ChinaCorrespondence: Yue Shi, School of Athletic Performance, Shanghai University of Sport, No. 399, Changhai Road, Shanghai, 200438, People’s Republic of China, Tel +86-21- 18521361033, Fax +86-21-65508050, Email shiyue910@sina.comAbstract: Chronic respiratory diseases (CRD), is a group of disorders, primarily chronic obstructive pulmonary disease and asthma, which are characterized by high prevalence and disability, recurrent acute exacerbations, and multiple comorbidities, resulting in exercise limitations and reduced health-related quality of life. Exercise training, an important tool in pulmonary rehabilitation, reduces adverse symptoms in patients by relieving respiratory limitations, increasing gas exchange, increasing central and peripheral hemodynamic forces, and enhancing skeletal muscle function. Aerobic, resistance, and high-intensity intermittent exercises, and other emerging forms such as aquatic exercise and Tai Chi effectively improve exercise capacity, physical fitness, and pulmonary function in patients with CRD. The underlying mechanisms include enhancement of the body’s immune response, better control of the inflammatory response, and acceleration of the interaction between the vagus and sympathetic nerves to improve gas exchange. Here, we reviewed the new evidence of benefits and mechanisms of exercise intervention in the pulmonary rehabilitation of patients with chronic obstructive pulmonary disease, bronchial asthma, bronchiectasis, interstitial lung disease, and lung cancer.Keywors: chronic respiratory disease, exercise training, chronic obstructive pulmonary disease, asthma, interstitial lung disease, bronchiectasis, lung cancer

Han Tang,1,2 Ruibo Wang,3 Pei Yan,1,4 Wei Zhang,1 Feng Yang,1 Shengjie Guo,3 Ting Li,3 Luanxing Yi,5 Xue Bai,6 Shan Lin,7 Yuhai Zhang,1 Lei Shang1 1Department of Health Statistics, School of Public Health, The Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China; 2Department of Clinical Nursing, School of Nursing, The Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China; 3School of Nursing and Health, Zhengzhou University, Zhengzhou, Henan, 450001, People’s Republic of China; 4Department of Operation Room, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China; 5School of Nursing, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, People’s Republic of China; 6Puyang Oilfield General Hospital, Puyang, Henan, 457001, People’s Republic of China; 7Department of Neurology, The 900th Hospital of Joint Logistic Support Force, PLA, Fuzhou, Fujian, 350025, People’s Republic of ChinaCorrespondence: Lei Shang, The Fourth Military Medical University, Changle West Road 169&num;, Xi’an, Shaanxi, People’s Republic of China, Tel +86 029-84774853, Email shanglei@fmmu.edu.cnBackground: Chemotherapy often negatively impacts the nutritional status of breast cancer patients, and healthy dietary behaviors are important for patient wellbeing. With the guidance of the “Knowledge, Attitude and Practice model” (KAP model), the objective of this survey was to determine the frequency with which patients engage in healthy dietary behaviors and to explore the association between healthy dietary behaviors and nutrition literacy and dietary attitudes.Methods: This study included a total of 284 breast cancer patients undergoing chemotherapy from three hospitals spanning three cities in China. Face-to-face interviews were conducted to collect demographic and clinical characteristics as well as the Dietary Nutritional Knowledge, Attitude and Practice Questionnaire (DNKAPQ) and the Nutrition Literacy Measurement Scale for Chinese Adult (NLMS-CA).Results: Participants exhibited medium to high scores for nutrition literacy, dietary attitude and dietary behavior. Nutrition literacy (r = 0.505, p < 0.001) and dietary attitude (r= 0.326, p < 0.001) scores were both positively correlated with the total dietary behavior score. The total nutrition literacy score was positively correlated with the total dietary behavior score (r = 0.286, p < 0.001). In the univariate analysis, age, body mass index, living environment, education level, monthly family income, work status, menopausal status, number of comorbidities, relapse and endocrine therapy were significantly associated with dietary behavior (p < 0.05). In the multiple linear regression analysis, patients’ dietary behavior was significantly associated with nutrition literacy (β = 0.449, p < 0.001) and dietary attitude (β = 0.198, p < 0.001). These two factors accounted for 28.6% of the variation in the patients’ dietary behavior scores.Conclusion: There is an important need for targeted dietary and nutritional interventions designed and implemented by health professionals to improve dietary behaviors. Intervention design and content should take the patients’ nutrition literacy and dietary attitudes into consideration. In particular, women who are older, overweight, unemployed, and postmenopausal and live in rural areas, exhibit fewer comorbidities, have a lower family income and education level, have not relapsed and are currently receiving endocrine therapy are in urgent need of diet-specific intervention.Keywords: attitude, behavior, breast cancer, chemotherapy, dietary, nutrition literacy

Yalan Yang,1,&ast; Dao Xin,2,&ast; Huike Wang,1,&ast; Lulu Guan,1 Xiangrui Meng,1 Taiying Lu,1 Xiwen Bai,3 Feng Wang1 1Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Medical Oncology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Translational Medicine, Nanchang University Queen Mary School, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Wang, Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China, Email zzuwangfeng@zzu.edu.cnPurpose: Neoadjuvant immunochemotherapy (nICT) for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC) has attracted widespread attention recently, whose safety and clinical benefit was observed in clinical researches. This study aimed to develop and validate a novel predictor systemic inflammation-tumor markers index (SITI) to predict the pathological complete response (pCR) for resectable LA-ESCC patients receiving nICT.Patients and Methods: A total of 147 LA-ESCC patients who underwent nICT followed by surgery from February 2020 to April 2022 were included in the study. The dynamic change of inflammatory indexes was compared at baseline, after two cycles of nICT and postoperative one month. Least absolute shrinkage and selection operator (LASSO) regression was performed to avoid collinearity and identify key indexes, with SITI constructed. After univariate and multivariate stepwise forward logistic analyses, a nomogram for pCR prediction was developed.Results: 41(27.9%) patients achieved pCR among 147 resectable LA-ESCC patients received nICT. Compared with baseline, most inflammatory indexes were significantly decreased at postoperative one month. 5 key indexes were identified and then a predictive index named SITI was constructed. The result showed that lower SITI and earlier clinical tumor node metastasis (cTNM) stage were more likely to achieve pCR. The nomogram for pCR prediction had excellent discrimination performance (C-index = 0.791).Conclusion: The SITI is an independent predictor for pCR in resectable LA-ESCC patients received nICT. To our knowledge, our nomogram is the first model using systemic inflammation-tumor markers for pCR prediction and may be a promising predictor to effectively differentiate pCR for nICT in LA-ESCC patients.Keywords: esophageal squamous cell carcinoma, neoadjuvant therapy, immunotherapy, pathologic complete response, inflammation, nomogram

Xue Bai,1– 4,&ast; Jinqiu Feng,1– 4,&ast; Yanchi Liu,1– 4 Yuan Gao,1– 4 Jun Deng,1– 4 Lei Mo1– 4 1School of Psychology, Center for Studies of Psychological Application, Guangzhou, People’s Republic of China; 2Key Laboratory of Brain, Cognition and Education Sciences, (South China Normal University), Ministry of Education, Guangzhou, People’s Republic of China; 3School of Psychology, South China Normal University, Guangzhou, People’s Republic of China; 4School of Psychology, Guangdong Key Laboratory of Mental Health and Cognitive Science, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Mo, School of Psychology, South China Normal University, No. 55, West of Zhongshan Avenue, Tianhe District, Guangzhou, People’s Republic of China, Tel +86 20 85216892, Email molei@m.scnu.edu.cnIntroduction: Parallel distributed processing theory (PDP theory) holds that all brain regions involved in conceptual representation perform a series of activities at the same time. However, the role of emotional experience information in concrete conceptual representation is still unknown. This study further explores whether the emotional experience will also affect the semantic processing of concrete concept representations.Methods: This study used the emotion priming paradigm and semantic judgment task to explore whether emotion priming impacts the processing of animal concepts with different emotional experiences through two experiments. In Experiments 1a and 1b, pleasant or disgusted faces were used as emotional priming stimuli to explore whether the explicit processing of emotions would affect the semantic processing of animal concepts. Experiments 2a and 2b used positive or negative scenery pictures as emotional priming stimuli to explore whether the implicit processing of emotions would affect the semantic processing of animal concepts.Results: The Experiment 1 results showed that the perception of faces promotes the processing of animal words, showing the “word-emotion congruence effect”. Experiment 2a did not show the expected results, while Experiment 2b showed that the general negative perception of scenery pictures could significantly promote the processing of disgusted animal words. The results further proved the “word-emotion congruence effect” shown in the results of Experiment 1 from the perspective of implicit emotion processing. Combining the results of two experiments, it can be proven that emotional experience affects the semantic processing process of concrete concepts.Discussion: Both Experiment 1 and Experiment 2b of this study show the “word-emotion congruence effect”. PDP theory believes that conceptual representation is represented by the activity patterns of billions of neurons distributed in many areas of the brain, and related semantic processing and sensory processing will occur simultaneously. The results of this experiment well support PDP theory.Keywords: embodied cognition, emotional experience, conceptual representation, explicit emotional priming, implicit emotional priming

Zhan Lu,1,2,&ast; Yiyue Huang,1,2,&ast; Juntao Huang,1,2,&ast; Hang-Hang Ni,1,2 Tai Luo,1 Xingyu Wei,1 Xue Bai,1 Lunnan Qi,1– 3 Bangde Xiang1– 3 1Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 2Key Laboratory of Early Prevention and Treatment for Regional High-Frequency Tumors, Ministry of Education, Nanning, People’s Republic of China; 3Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bangde Xiang; Lunnan Qi, Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, 71&num; Hedi Road, Qingxiu District, Nanning, Guangxi, 530021, People’s Republic of China, Tel +86-7715301253 ; +86-135-1788-6990, Email xiangbangde@gxmu.edu.cn; qilunan_gxmu@163.com; wangzhennuo@aliyun.comPurpose: Recent studies indicated the vital role of platelet in enhancing the survival of circulating tumor cells (CTCs) in the blood, thereby stimulating the metastasis of tumors. CTCs have been considered an indicator of early tumor recurrence. Therefore, this study evaluated the prognostic potential of platelet count in predicting the early recurrence of hepatocellular carcinoma (HCC) in the presence of CTCs.Patients and Methods: 127 patients, whose preoperative CTCs were detected, were enrolled in this study. Univariate analysis was performed to identify the significant association of factors with the early recurrence of HCC, followed by multivariate analysis to determine the independent prognostic indicators. The prediction potential was evaluated using receiver operating characteristic (ROC) curves.Results: A total of 81 (63.7%) patients showed early HCC recurrence. The platelet count ≥ 225× 109/L (hazard ratio, HR: 1.679, P = 0.041), CTCs > 5/5 mL (HR: 2.467, P = 0.001), and presence of microvascular invasion (MVI) (HR: 2.580, P = 0.002) were independent factors correlated with the early recurrence of HCC in multivariate analysis. The prognostic potential of the combined CTCs-platelet count (0.738) was better than that of CTCs (0.703) and platelet (0.604) alone. The subgroup analysis, excluding 23 patients with pathological cirrhosis and splenomegaly, showed that the platelet count ≥ 225× 109/L and CTCs > 5/5 mL were also independent factors of early HCC recurrence. The prediction potential of the combined CTCs-platelet count was 0.753, which was better than that of the whole cohort. Kaplan–Meier survival curve analysis indicated that the HCC patients with high platelet or CTCs had the worse recurrence-free survival (RFS).Conclusion: The high platelet count was an independent factor of early HCC recurrence in the presence of CTCs. The combination of preoperative CTCs and platelet count could effectively predict the early recurrence of HCC. The subgroup analysis also showed similar results.Keywords: hepatocellular carcinoma, liver resection, early recurrence, platelet count, circulating tumor cells

Xuefeng Bai,1,* Jiangxin Ma,1,* Xiaohong Wu,1 Lingling Qiu,2 Rongfu Huang,3 Haibin Zhang,1 Huibin Huang,1 Xiaoyu Chen1 1Department of Endocrinology, Second Affiliated Hospital of Fujian Medical University, Quanzhou City, Fujian Province, People’s Republic of China; 2Department of Reproductive Medicine, Second Affiliated Hospital of Fujian Medical University, Quanzhou City, Fujian Province, People’s Republic of China; 3Department of Clinical Laboratory, Second Affiliated Hospital of Fujian Medical University, Quanzhou City, Fujian Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huibin Huang; Xiaoyu Chen, Department of Endocrinology, the Second Affiliated Hospital of Fujian Medical University, No. 950 Donghai Street, Fengze District, Quanzhou City, Fujian Province, 362000, People’s Republic of China, Tel +86-13313872001 ; +86-13600739755, Email huibinhuang@aliyun.com; chenxiaoyu271@163.comObjective: We aimed to identify structural and functional alterations of gut microbiota associated with visceral obesity in adult women with polycystic ovary syndrome (PCOS).Methods: Twenty-seven adults with PCOS underwent stool and fasting blood collection, oral glucose tolerance testing, and visceral fat area (VFA) measurement via dual-bioimpedance technique. Metagenomic analysis was used to analyze gut microbiota.Results: PCOS patients were divided into three groups: visceral obesity group (PCOS-VO, n=9, age 28.33± 5.68 years, BMI 37.06± 4.27 kg/m2, VFA 128.67± 22.45 cm2), non-visceral obesity group (PCOS-NVO, n=10, age 25.40± 4.53, BMI 30.74± 3.95, VFA 52.00± 24.04), normal BMI group (PCOS-NB, n=8, age 27.88± 2.53, BMI 21.56± 2.20, VFA 27.00± 21.18), with no statistical difference in age (P> 0.05) and significantly statistical differences in BMI and VFA (P< 0.05). The groups showed a significant difference in microbial β-diversity between PCOS-VO and PCOS-NVO (P=0.002) and no difference between PCOS-NVO and PCOS-NB (P=0.177). Bacteroidetes was the phylum with the highest relative abundance among all patients, followed by Firmicutes. Those with visceral obesity had a higher abundance of Prevotella, Megamonas, and Dialister genera, positively correlated with metabolic markers (r> 0.4, P< 0.05), and lower abundance of Phascolarctobacterium and Neisseria genera, negatively correlated with metabolic markers (r

Mingfen Wu,1 Xiaohan Xu,2 Rongsheng Zhao,2 Xiangrong Bai,3 Bin Zhu,1 Zhigang Zhao1 1Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 2Department of Pharmacy, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 3Department of Pharmacy, Xuanwu Hospital Capital Medical University, Beijing, 100053, People’s Republic of ChinaCorrespondence: Zhigang Zhao; Bin Zhu, Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Fengtai District, Beijing, 100070, People’s Republic of China, Tel +8601059978036 ; +8601059975444, Fax +8601059976856, Email 1022zzg@sina.com; zbtcm@163.comPurpose: Medication adherence plays an important role in glycemic control in type 2 diabetes mellitus (T2DM) self-management. To analyze the factors influencing medication adherence in T2DM patients and the effect of pharmacist-led interventions, we conducted a study in Beijing, China.Patients and Methods: T2DM patients with hypoglycemic drugs for at least 6 months were enrolled. A pharmacist-led survey was conducted followed by individualized interventions for those non-adherent patients monthly within 3 months. FPG, HbA1c, and 2hPG were measured as the comprehensive glycemic control. Medication adherence was determined according to the patient’s self-reported compliance with prescribed medication during the last 3 months.Results: A total of 763 T2DM patients were included. The average age was 63.26± 11.89 years, with 363 males. After pharmacist intervention, the patients with good adherence increased from 34.21% to 39.06%, while poor adherence decreased from 32.5% to 24.5% (p < 0.001). The average adherence score was a significant increase (p < 0.001) from 27.846± 4.185 to 29.831± 7.065. Furthermore, our study demonstrated that pharmacist-led interventions significantly increased glycemic control (FPG from 42.33% to 53.60%, p < 0.001; 2hPG from 41.68% to 48.75%, p = 0.005; HbA1c from 24.12% to 29.23%, p = 0.024). The results found that body mass index (OR 0.643, 95% CI 0.437– 0.945), use of medications empirically (occasionally (OR=3.066, 95% CI 2.069– 4.543); often (OR=2.984, 95% CI 1.107– 8.044)), following the doctor’s advice to visit (OR 2.129, 95% CI 1.079– 4.202) and lifestyle compliance (OR 2.835, 95% CI 1.094– 7.346) were the independent risk factors of non-adherence (p < 0.05), the area under the ROC curve was 0.716.Conclusion: Self-reported medication adherence and glycemic control in T2DM patients were poor which can be improved by pharmacist-led interventions. Interventions should focus on empirical medication behavior, non-adherence to lifestyle, and failure to follow the doctor’s advice. The recall bias with self-reported results needs further objective data to verify.Keywords: T2DM, medication adherence, glycemic control, current status, risk factor, pharmacist-led interventions

Lv L, Liu Y, Zhang P, et al. Int J Nanomedicine. 2018;13:5605–5623. It was brought to the authors’ attention that FITC and OCN images had been misused with images from their previous Biomaterials article (2015; 39: 193—205). The authors reviewed their original data and found a mistake had occurred during the assembly of the FITC and OCN images in Figure 1D and H on pages 5609 and 5610. The immunofluorescence experiments, from which the FITC and OCN images were obtained, were performed together with the study published in their 2015 Biomaterials article. The authors intended to further describe the underlying mechanism of why nanotubes were much better in osteogenesis than smooth Ti surface by RNA sequencing and high-throughput analyses based on the results of their earlier study. The purpose of Figure 1 was to provide an overview of how 70nm nanotubes were better than smooth Ti surface in cell adhesion and osteogenic ability but images from the wrong treatment groups were selected in error. The authors had retained all original data and were able to make corrections without impacting the results and conclusions of the article. The authors apologize for any inconvenience caused. The correct Figure 1 is as follows. Figure 1 Surface characterization, cell morphology, and osteoinductive ability of TiO2 nanotubes.Abbreviations: OM, osteoinduction medium; PM, proliferation medium.Notes: (A) Scanning electron microscopic (SEM) observation of TiO2 nanotubes and smooth Ti surfaces. (B) Atomic force microscopy (AFM) images of TiO2 nanotubes and Ti surfaces. (C) Photographs of contact-angle measurement of water. (D) Confocal micrographs of human adipose-tissue-derived stem cells (hASCs) on TiO2 nanotubes and Ti surfaces after 2, 4, and 24 hours of culture. (E) SEM observation of cell morphology on TiO2 nanotubes and Ti surfaces after 2, 4, and 24 hours of culture. (F) Cell spreading area on TiO2 nanotubes and Ti surfaces after 2, 4, and 24 hours of culture. (G) Gene expression of osteogenic-related genes quantified by quantitative real-time PCR. *P

Ruihuan Du,1 Gang Xu,1,2 Xujue Bai,1 Zhonghai Li1,2 1Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China; 2Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopedic Diseases, Dalian, People’s Republic of ChinaCorrespondence: Zhonghai Li, The Third Department of the First Affiliated Hospital of Dalian Medical University, No. 5 Longbin Road, Development Zone, Dalian, 116011, People’s Republic of China, Tel +86-18098876419, Fax +86-411-83635963, Email lizhonghaispine@126.comAbstract: Facet joint osteoarthritis (OA) is the most frequent form of facet joint syndrome. Medical history, referred pain patterns, physical examination, and diagnostic imaging studies (standard radiographs, magnetic resonance imaging, computed tomography and single-photon emission computed tomography) may suggest but not confirm lumbar facet joint (LFJ) syndrome as a source of low back pain (LBP). However, the diagnosis and treatment of facet joint syndrome is still controversial and needs further study. It is widely acknowledged that block with local anesthetic is perhaps the most effective method to establish a diagnosis of pain from LFJ. Particularly, there are different rates of success among different populations selected for diagnostic block with various positive criteria. Currently, in addition to conservative treatments for pain such as painkillers, functional exercises, and massage, there are many other methods, including block, denervation of the nerves that innervate the joints by radiofrequency, freezing or endoscopy, and injections. Due to the limited duration of pain relief from neurolysis of medial branch, many scholars have recently turned their targets to dorsal roots and LFJ capsules. Therefore, we reviewed the latest research progress of facet joint syndrome from diagnosis to treatment.Keywords: low back pain, medial branch, block, radiofrequency, neurolysis

Yumin Chen,1 Wei Xiong,2,3 Ying Zhang,1 Xue Bai,1 Guoliang Cheng,1 Yifan Zhang,1 Rui Chen,1 Yinghui Guo,1 Hui Kong,1 Yue Zhang,4 Huihua Qu,5 Yan Zhao1 1School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Institutes of Health Research, Mayinglong Pharmaceutical Group Co., Ltd, Wuhan, Hubei, People’s Republic of China; 4School of Life Sciences, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 5Centre of Scientific Experiment, Beijing University of Chinese Medicine, Beijing, People’s Republic of ChinaHuihua QuCentre of Scientific Experiment, Beijing University of Chinese Medicine, No. 11 Bei San Huan Dong Lu, Chaoyang District, Beijing, People’s Republic of China, Email quhuihuadr@163.comCorrespondence: Yan Zhao, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 Bei San Huan Dong Lu, Chaoyang District, Beijing, People’s Republic of China, Email zhaoyandr@163.comBackground: At present, people are susceptible to developing depression and anxiety disorders in response to stress. However, there is no specific medicine for anxiety. Os Draconis (OD, named “Long gu” in Chinese) are fossilized bones that have been used in traditional Chinese medicine to treat neurological diseases for thousands of years. Thus, we conducted this study to determine the biological basis for the anxiolytic effect of OD.Methods: In this study, novel carbon dots (OD-CDs) from OD decoctions were discovered and separated. OD-CDs were anatomized using nanomaterials characterization methods to characterize the morphological structure, optical properties, and functional group properties. Four behavioural tests were conducted to observe the behavioural activities of mice, including the open field test (OFT), light/dark box test (LDT), elevated plus maze test (EPMT), and novelty-suppressed feeding test (NSFT), to determine its anxiolytic effects. Moreover, we assessed the possible mechanisms of the OD-CDs by detecting hormones associated with the hypothalamic-pituitary-adrenal (HPA) axis.Results: OD-CDs were spherical and monodispersed with a narrow size distribution between 1 and 5 nm and had a yield of 3.67%. OD-CDs increased the activity time of mice in the central zone in the OFT. The mice in the experimental group showed more frequent activity in the light compartment and the open arms, in LDT and EPMT, respectively. In addition, OD-CDs shortened the feeding latency in the NSFT. Furthermore, the results after OD-CDs intervention showed a significant increase in serum serotonin (5-HT) and norepinephrine (NE). In addition, the concentrations of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ATCH), and corticosterone (CORT) were decreased.Conclusion: These results demonstrate a definite anxiolytic effect of OD-CDs and reveal the possible mechanism of action of OD-CDs’ anxiolytic effect, which supports the research of OD for neurological disorders and a promising new trend of therapeutic approach and drug development.Graphical Abstract: Keywords: Os Draconis, carbon dots, anti-anxiety, HPA axis

Cong Wang,1 Li-Dan Liu,1 Xue Bai2 1Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Health Management, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Xue Bai, Department of Health Management, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, 110004, People’s Republic of China, Email xbai88@cmu.edu.cnBackground: Postoperative pain in children has been overlooked for a long time. The knowledge structure, research hotspots and trends related to postoperative pain in children are unclear and have not been systematically summarized.Purpose: We aimed to analyze the current state of research on postoperative pain in children and to conduct in-depth mining of the knowledge structure.Methods: The PubMed database for publications on postoperative pain in children between 1950 and 2021 was searched. Bibliographic Item Co-Occurrence Matrix Builder (BICOMB) was performed to obtain the co-word matrix and co-occurrence matrix. The H-index method was used to extract high-frequency main Medical Subject Headings (MeSH) terms/subheadings.Results: The high-frequency MeSH terms were analyzed by biclustering, strategic diagram and social network analyses. Totally, 4022 publications were retrieved. The analysis showed that 60 countries or regions published relevant documents, with the United States publishing the most significant number of papers. Totally, 811 journals published relevant papers, with Pediatric Anesthesia ranking first. Moreover, we extracted 43 high-frequency main MeSH terms/subheadings and clustered them into five categories: overview, aetiology and epidemiology, pharmacotherapy, opioid administration and dosing, and prevention and control of postoperative pain in children.Conclusion: Pharmacological treatments, pain prevention and control are the focus of research and are becoming increasingly mature. Opioid stewardship and regional anesthesia is the trend and focus of future research. Our study offers a better understanding of the current status and knowledge structure of postoperative pain in children and provides a reference for improving postoperative pain management in children in the future.Keywords: bibliometrics, visualization analysis, postoperative pain, children, status, trends

Xuchen Bai,1 Md Nahin Hossain,2 Nilesh Kumar,3 Md Yahin Hossain4 1China Institute of Education and Social Development, Beijing Normal University, Beijing, People’s Republic of China; 2Army Institute of Business Administration Savar, Savar, Bangladesh; 3School of Business Administration, Zhejiang Gongshang University, Hangzhou, People’s Republic of China; 4Department of Business Studies, University of Information Technology and Sciences, Dhaka, BangladeshCorrespondence: Md Nahin Hossain; Nilesh Kumar, Email md.nahinhossainsaad@yahoo.com; nileshk@live.comPurpose: The purpose of this study is to understand how perceived fear, course quality, and self-determination of learners influence the retention rate of massive open online courses (MOOCs) during the time of pandemic.Methodology: The proposed developed model is comprised of IS success, expectation confirmation and self-determination theories. Data were collected from 284 respondents and the structural equation modeling was applied to interpret and analyze the data. Additionally, importance-performance maps were plotted to prioritize essential findings.Findings: The findings revealed that course quality, identified and integrated regulation (motivation) all significantly affect perceived usefulness and satisfaction to influence learners’ retention intention. Moreover, the importance performance map analysis (IPMA) exhibited that integrated regulations and course quality are very significant factors with very limited focus. Therefore, developers should improve the performance of these two factors to overcome the dropout rate.Originality: This research analyzed the effect of the course quality, learners’ determination and fear of the pandemic as the determining factors. Besides, the impacts of motivational factors (integrated, identified, introjected and external) from determination theory were also investigated on the learner’s satisfaction. Finally, these factors were tested in the context pandemic that gave us new insights, which are not similar to pre-pandemic phase; ie, learners prefer course quality rather than system quality, because they demand new skill and knowledge to increase competitive advantage.Keywords: self-determination theory, higher education, distance education, COVID-19 and MOOCs, perceived fear

Xuexue Bai,1 Xiaomin Liu,2 Jun Wen1 1Neurosurgery, The First Affiliated Hospital, Jinan University, Guangzhou, People’s Republic of China; 2Neurosurgery, Tianjin Huanhu Hospital, Tianjin, People’s Republic of ChinaCorrespondence: Xiaomin Liu; Jun Wen, Email liuxiaomin619@163.com; willwenjun0905@163.comObjective: We investigated the role of bevacizumab (BV) in high-grade meningiomas (HGMs) by retrospective analysis.Methods: We retrospectively analyzed the clinical data of 139 patients with HGMs. The chi-square test was used to compare progression-free survival (PFS) and overall survival (OS) between patients who received BV and those who did not. According to whether they received BV treatment, we divided the patients into the BV group and non-BV group, and the effect of BV on PFS and OS was compared. In addition, we compared Karnofsky performance status (KPS) and steroid doses between the BV and non-BV groups.Results: There were statistically differences in PFS and OS between the BV and non-BV groups at 12 and 36 months after surgery (P< 0.05). However, there was no significant difference in PFS and OS between the two groups at 60 months postoperatively (P> 0.05). Using survival curves drawn by the Kaplan Meier method, we found that the PFS and OS of the BV group were greater than those of the non-BV group, and the difference was statistically significant (P< 0.05).Conclusion: BV could improve PFS and OS at 12 and 36 months after surgery in patients with HGMs. In addition, BV was associated with lower preoperative steroid use.Keywords: bevacizumab, meningiomas, peritumoral brain edema, progression-free survival, overall survival

Wei Zhang,1,2,&ast; Ying Chen,1,2,&ast; Yuntao Zhang,1,2 Rongrong Wang,3 Weili Wang,1,2 Xueli Bai,1,2 Tingbo Liang1,2,4,5 1Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Liver Transplant Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3Department of Clinical Pharmacy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 5Key Lab of Combined Multi-organ Transplantation of the Ministry of Health, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tingbo Liang, Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China, Tel +86-571-87236688, Fax +86-571-87236739, Email liangtingbo@zju.edu.cnObjective: Perioperative prophylaxis, commonly with a third-generation cephalosporin plus ampicillin or piperacillin-tazobactam, is usually employed to prevent infections in liver transplantation (LT) recipients. Patients with a high Model for End-Stage Liver Disease (MELD) score have an increased infection risk after LT. However, whether carbapenems could be used as surgical prophylaxis in these high-risk patients remains unclear. Therefore, this study aimed at comparing the effectiveness of carbapenems with that of cephalosporin or piperacillin-tazobactam for surgical prophylaxis in high-risk LT recipients with a MELD score ≥ 30.Design or Methods: This retrospective study included adult patients with a MELD score ≥ 30 who underwent LT between May 2018 and September 2020. We comparatively analyzed the infection rate and outcome between patients using cefoperazone-sulbactam or piperacillin-tazobactam and those using carbapenems as surgical prophylaxis.Results: This study included 105 LT recipients. Seventy-eight and 27 patients used non-carbapenem and carbapenem antibiotics, respectively, as surgical prophylaxis. The corresponding infection incidence rates within 30 days were 38.5% and 66.7% (p = 0.011). Multivariate analysis revealed that reoperation and the Child–Pugh score were independent risk factors for infections within 30 days after LT. The following four risk factors were associated with the 180-day post-LT survival: MELD score, vascular complication, intra-abdominal bleeding, and infection with carbapenem-resistant organisms (CROs). There was no significant difference in CRO infection incidence between the carbapenem and non-carbapenem groups (18.5% vs 11.5%; p = 0.345).Conclusion: Carbapenem use as surgical prophylaxis was not associated with infection incidence within 30 days after LT, 180-day post-LT survival or CRO infection. Therefore, carbapenems are not superior to cephalosporin or piperacillin-tazobactam for perioperative antibiotic prophylaxis in LT recipients with a MELD score ≥ 30.Keywords: perioperative prophylaxis, liver transplantation, infection, carbapenems, carbapenem-resistant organisms

Yuting Pu,1,2 Shuangyang Li,2 Lingxue Wang,2 Bangjiang Fang,1 Xue Bai2 1LongHua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China; 2Department of Neurology and National Traditional Chinese Medicine Clinical Research Base, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of ChinaCorrespondence: Xue Bai, Department of Neurology and National Traditional Chinese Medicine Clinical Research Base, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China, Email baixue@swmu.edu.cnPurpose: To investigate the association of serum high-sensitivity C-reactive protein (hs-CRP) with the severity of neurological deficits and prognosis in patients with acute cerebral infarction (ACI).Patients and Methods: In this retrospective analysis, 119 patients with ACI were recruited from January to December 2020. The serum hs-CRP level was measured by a latex-enhanced immunoturbidimetric assay. The severity of neurological deficits and prognosis of ACI patients were assessed using the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS). Multivariate logistic analysis was performed and receiver operating characteristic (ROC) curves were plotted to evaluate the value of hs-CRP in predicting the prognosis of ACI.Results: The patients with a more favorable prognosis (mRS score 0– 2) had a lower median serum hs-CRP level than those with a worse prognosis (mRS score 3– 6) (3.32 IQR: 1.51, 8.04 to 17.93 IQR:16.02, 19.01; P< 0.001). After adjusting for potential confounders, multivariable linear regression showed that serum hs-CRP level was independently associated with NIHSS score (Beta = 0.952, P< 0.001) and mRS score (Beta=0.878, P< 0.001). Multivariate logistic analysis revealed that high hs-CRP level was an independent predictor of the poor prognosis in patients with ACI (adjusted1 OR = 1.995; 95% CI = 1.499– 2.655; adjusted2 OR = 2.75; 95% CI = 1.015– 7.457). ROC curve analysis indicated that the area under the curve for hs-CRP to predict poor prognosis was 0.986. The cutoff value, sensitivity, and specificity were 11.835 mg/L, 95%, and 92.5%, respectively. In terms of ischemic stroke subtypes, the serum hs-CRP level was higher in large-artery atherosclerosis (LAA) patients than in those with small-artery occlusion (SAO) and cardioembolism (CE). In addition, the patients with LAA had higher scores of NIHSS and mRS than those with SAO and CE.Conclusion: Serum hs-CRP level is an independent predictor of prognosis, and an efficient index to discriminate patients with ACI, especially for those with LAA.Keywords: acute cerebral infarction, high-sensitivity C-reactive protein, neurological deficits

Weili Wang,1,2,&ast; Rongrong Wang,3,&ast; Yuntao Zhang,1,2 Lei Zeng,1,2 Haisen Kong,4 Xueli Bai,1,2 Wei Zhang,1,2 Tingbo Liang1,2,5,6 1Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Liver Transplant Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3Department of Clinical Pharmacy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4Department of Laboratory Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 5Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 6Key Laboratory of Combined Multi-organ Transplantation of the Ministry of Health, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tingbo Liang, Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China, Email liangtingbo@zju.edu.cnObjective: There are few therapeutic options for infections caused by carbapenem-resistant Enterobacterales (CRE) in children following liver transplantation. Ceftazidime-avibactam (CAZ-AVI), a recently licensed antibacterial in China, was utilized as a salvage therapy against CRE in our center, and its efficacy and safety were therefore assessed.Methods: The retrospective, observational study was conducted at the First Affiliated Hospital of Zhejiang University. Pediatric liver transplantation patients (≤ 12 years) who received CAZ-AVI as a salvage therapy against CRE infections were included from January 2020 to December 2021. Clinical success and all-cause death during hospitalization were the primary outcomes. Recurrence of infection, drug-related adverse events, and changes in inflammatory biomarkers were collected.Results: Six children were enrolled, with a median age of 10.1 (interquartile range (IQR) 5.5– 13.8) months. Primary intraperitoneal infections occurred in all patients, with five patients developing bloodstream infections. KPC carbapenemases were detected in most isolates, and the susceptibility results showed general sensitivity to tigecycline, polymyxin B, and CAZ-AVI. Tigecycline-based therapy was taken as the initial treatment and withdrawn because of clinical failure (5 cases) or cholestasis (1 case). After CRE infection, the median time to convert to CAZ-AVI was 7.5 (IQR 7.0– 8.8) days, and the median CAZ-AVI treatment length was 21.0 (IQR 20.3– 28.5) days. Clinical success was achieved in all patients, with a zero percent all-cause death rate. No CRE infections recurred throughout hospitalization, and no resistance to CAZ-AVI was detected. Patients experienced vomiting (1/6), skin rash (1/6), and a transient increase in cystatin C (2/6), γ-glutamyltransferase (2/6), and alkaline phosphatase (3/6).Conclusion: CAZ-AVI was shown to be a successful salvage treatment for CRE infection in pediatric liver transplant recipients, with minor and temporary drug-related side effects.Keywords: ceftazidime-avibactam, carbapenem-resistant Enterobacterales, pediatric liver transplantation, salvage treatment, effectiveness, safety

Yangfan Zhuang,1 Hao Tu,1 Quanrui Feng,2 Huiming Tang,3 Li Fu,1 Yuchang Wang,1 Xiangjun Bai1 1Trauma Center/Department of Emergency and Traumatic Surgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Department of Intensive Care Unit, First Hospital of Wuhan, Wuhan, Hubei Province, People’s Republic of China; 3Department of Intensive Care Unit, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Xiangjun Bai, Trauma Center/Department of Emergency and Traumatic Surgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China, Email whtj_bxj@163.comPurpose: Currently, assessing trauma severity alone in geriatric trauma patients (GTPs) cannot accurately predict the risk of serious adverse outcomes during hospitalization. As an emerging concept in recent years, frailty syndrome is closely related to the poor prognosis of many diseases in elderly patients, including trauma. A logistic model for predicting adverse outcomes in elderly trauma patients during hospitalization was constructed in elderly patients, and the predictive efficacy of the model was verified.Patients and Methods: Trauma patients aged ≥ 65 years between June 2020 and September 2021 were selected and randomly divided into a training set and validation set at a ratio of 3:1. Mid arm muscle circumference (MAMC) was measured to determine the degree of frailty. LASSO regression was used to screen appropriate variables for the construction of a prognostic model. The logistic regression model was established and presented in the form of a nomogram. Calibration curves and ROC curves were used to verify the performance of the model.Results: A total of 209 patients were enrolled, including 143 (68.4%) males and 66 (31.6%) females, with an average age of 70.8 ± 4.8 years. Ageless Charlson comorbidity index, BT unit, ISS, GCS, MAMC, prealbumin and lactic acid levels were screened by LASSO regression to construct a prognostic model. The AUC of the ROC analysis prediction model was 0.89 (95% CI 0.80– 0.97) in the validation set. The results of the Hosmer–Lemeshow test for the validation set were χ 2 = 11.23, P = 0.189.Conclusion: The prognostic model of adverse outcomes in GTPs has good accuracy and differentiation, which can improve the prediction results of risk stratification of GTPs during hospitalization by medical staff and provide a new idea for prognostic prediction.Keywords: geriatric trauma patients, frailty, MAMC, prognostic model for adverse outcomes

Yangfan Zhuang,1 Quanrui Feng,2 Huiming Tang,3 Yuchang Wang,1 Zhanfei Li,1 Xiangjun Bai1 1Trauma Center/Department of Emergency and Traumatic Surgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Department of Intensive Care Unit, First Hospital of Wuhan, Wuhan, Hubei, People’s Republic of China; 3Department of Intensive Care Unit, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Xiangjun Bai, Trauma Center/Department of Emergency and Traumatic Surgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China, Email whtj_bxj@163.comPurpose: The Geriatric Trauma Outcome Score (GTOS) has been developed and indicate to be a valid prognostic tool for the prediction of mortality in geriatric trauma patients (GTPs) during hospitalization. However, the predictive value of the GTOS for morbidity is still unclear. We aimed to evaluate the association between GTOS, morbidity and mortality in GTPs.Patients and Methods: We performed a retrospective cohort study between June 1, 2016, and May 31, 2020, and collected data for patients aged 65 years or older. These patients were treated at the Trauma Center of Tongji Hospital, Wuhan, China. Clinical data were retrieved from the trauma registry. The GTOS was calculated with the following formula: age + ISS &ast; 2.5 + 22 (if any packed red blood cells were transfused within 24 hours after admission). The outcomes were mortality, morbidity, length of hospital stay (LOS), and functional outcome at discharge.Results: A total of 485 patients were enrolled: 214 (44.1%) were classified into the low-GTOS group, and 271 (55.9%) were classified into the high-GTOS group. The median (IQR) age was 68 (66– 71) years; 361 (74.4%) were male. The most common mechanism of injury was vehicle collision (66.4%), followed by falls < 2 m (19.6%). The median (IQR) ISS was 18 (14– 22). The median (IQR) GCS was 13 (9– 15). A high GTOS was associated with high rates of all-cause mortality (13.3% vs 0.9%, P < 0.001), complications (88.2% vs 31.8%, P < 0.001), unplanned intubation (19.2% vs 1.4%, P < 0.001), and unplanned admissions to the intensive care unit (8.5% vs 0.5%, P < 0.001). In multivariable logistic regression analysis, GTOS was associated with morbidity (OR 1.07, 95% CI, 1.05– 1.09, p < 0.001) and mortality (OR 1.04, 95% CI, 1.02– 1.06, p < 0.001).Conclusion: The GTOS is an independent predictor of morbidity and mortality in GTPs, and it will help us identify patients at high risk on admission.Keywords: Geriatric Trauma Outcome Score, geriatric trauma patients, predictive value

Xianlei Zhao,1,2 Xiaoxia Bai,1 Yongmei Xi1,2 1Division of Human Reproduction and Developmental Genetics, the Women’s Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, 310006, People’s Republic of China; 2Institute of Genetics and Department of Human Genetics, Zhejiang Provincial Key Laboratory of Genetic & Developmental Disorders, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, 310058, People’s Republic of ChinaCorrespondence: Yongmei Xi, Email xyyongm@zju.edu.cnAbstract: In high prevalence settings, mother-to-child transmission is responsible for more than 50% of chronic Hepatitis B Virus (HBV) infections with 1– 9% of newborns of HBV-carrying mothers acquiring HBV in early life. Little is known about the routes and cellular mechanisms by which HBV intrauterine transmission occurs. Clinical studies indicate that placental trophoblasts can be infected with HBV. In vitro studies using primary trophoblast and cell lines support this hypothesis. Several cellular parameters, including the differentiation state of the trophoblasts, cytokine secretion, and the surface molecules involved in virus entry, may influence the receptivity of trophoblastic cells to HBV. In HBV-infected trophoblastic cells, a reduction of apoptosis and increased production of antiviral cytokines has been observed, presumably via an HBx antigen-Akt or TLRs-MyD88-NF-kB pathway. Trophoblast HBV infection occurrence involves complex pathological processes with little currently known of the related mechanisms within infected cells. Whilst much focus has been on the placental routes of infection, through trophoblasts in particular, other routes have also been suggested. In this article, we review the models for HBV mother-to-child transmission and discuss the possible mechanisms of HBV intrauterine transmission with particular emphasis upon the involvement of placental trophoblast infection.Keywords: hepatitis B virus, intrauterine infection, trophoblastic cell, mother-to-child transmission

Ping Zheng,1 Kexing Zhang,2 Xifang Lv,1 Chuanhe Liu,3 Qiang Wang,1 Xuetao Bai1 1China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China; 2Department of Immunization Program, Xinwu District Center for Disease Control and Prevention, Wuxi, People’s Republic of China; 3Children’s Hospital, Capital Institute of Pediatrics, Beijing, People’s Republic of ChinaCorrespondence: Qiang Wang; Xuetao Bai, China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, 29 Nanwei Road, Xicheng District, Beijing, 100050, People’s Republic of China, Tel +86 10 50930251, Email wangqiang@nieh.chinacdc.cn; xuetaobai@163.comPurpose: This study aimed to investigate the characteristics of gut bacteria and the derived metabolites among allergic asthmatic children, non-allergic asthmatic children and healthy children without asthma.Methods: Fecal samples were collected from 57 participants, including 20 healthy children, 27 allergic asthmatic children, and 10 non-allergic asthmatic children. 16S rRNA gene sequencing was conducted for analyzing gut bacterial compositions and untargeted metabolomics was used to analyze the alterations of gut microbe-derived metabolites. The associations between gut bacterial compositions and metabolites were analyzed by the method of Spearman correlation.Results: The results showed that the compositions and metabolites of gut microbiome were altered both in allergic and non-allergic asthmatics compared with healthy controls. Chao1 (p = 0.025) index reflected a higher bacterial richness and Simpson (p = 0.024) index showed a lower diversity in asthma group. PERMANOVA analysis showed significant differences among the three groups based on unweighted UniFrac distance (p = 0.001). Both allergic and non-allergic asthmatics showed a higher relative abundance of Proteobacteria and a lower relative abundance of genera from Clostridia. More bacteria were altered in non-allergic asthmatics compared with allergic asthmatics. Metabolomics analysis identified that 42 metabolites were significantly associated with allergic asthma, and 58 metabolites were significantly associated with non-allergic asthma (multiple linear regression, p < 0.05). Histamine was 4 folds up-regulated only in the non-allergic asthma group. The relative abundance of Candidatus Accumulib was significantly correlated with the upregulation of histamine. The relative abundance of genera from Clostridia was significantly correlated with the downregulation of lipid and tryptophan metabolism.Conclusion: The altered gut microbes was associated with the mechanism of asthma attack through metabolites in allergic and non-allergic asthma group, respectively. The result suggested that gut microbiome had an impact on the development of both allergic and non-allergic asthma. The distinct gut microbiome and microbiome-derived metabolites in non-allergic asthma children suggested that gut microbiome might play a critical role in modulation of asthma phenotype.Keywords: gut microbiome, untargeted metabolomics, allergic childhood asthma, non-allergic childhood asthma, 16S rRNA gene sequencing

Xiaojie Bai, Yuanfei Cao, Xin Yan, Kurerban Tuoheti, Guowei Du, Zhao Chen, Huahui Wu, Linfa Guo, Tongzu Liu Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of ChinaCorrespondence: Tongzu LiuDepartment of Urology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, 430071, People’s Republic of ChinaTel +86-27-67813104Fax +86-27-67812667Email liutongzu@163.comPurpose: This study aims to carry out a pan-cancer analysis of kinesin family member 23 (KIF23) and construct a predictive model for the prognosis of clear cell renal cell carcinoma (ccRCC) patients.Methods: We evaluated the differential expression of KIF23 in pan-cancer by The Cancer Genome Atlas (TCGA) and Oncomine database. Then, the correlation between KIF23 with prognosis, clinical grade, stage, immune subtype, tumor mutation burden (TMB), microsatellite instability (MSI) and immune microenvironment was explored by TCGA, an integrated repository portal for tumor-immune system interactions (TISIDB) and cBioPortal. Subsequently, we screened out ferroptosis-related genes (FRGs) related to KIF23 and constructed a risk score model. Univariate Cox analysis was used to determine independent prognostic factors for ccRCC overall survival (OS), and a nomogram was established. Furthermore, gene set enrichment analysis (GSEA) was applied to study the biological functions and pathways of KIF23. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to evaluate the expression of KIF23.Results: KIF23 was highly expressed in most tumors. Further, KIF23 was strongly correlated with prognosis, clinical grade, stage, immune subtype, TMB, MSI and immune microenvironment in different tumors. We found that KIF23 was significantly associated with all aspects of ccRCC. Then, 8 FRGs were identified to construct a risk score model together with KIF23. And a prognostic nomogram prediction model of OS was established. After GSEA analysis, cell cycle, condensed chromosome and other physiological processes were screened out. Finally, qRT-PCR verified the high expression of KIF23 in ccRCC cell lines than normal kidney cell line.Conclusion: KIF23 may act as a pivotal part in occurrence and progression of different tumors. In ccRCC, KIF23 can be a great prognostic biomarker, and the nomogram based on KIF23 may contribute to better treatment plans for ccRCC patients.Keywords: clear cell renal cell carcinoma, ferroptosis, nomogram

Huijuan Chen,1 Xinhua Bai,2 Yang Gao,2 Wenxuan Liu,2 Xuena Yao,2 Jing Wang2 1Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology, Beijing, People’s Republic of China; 2Department of Clinical Laboratory, Beijing Capitalbio Medlab, Beijing, People’s Republic of ChinaCorrespondence: Huijuan Chen Tel +86-10-8722-9999Email m13810539097@163.comBackground: Treatment of pulmonary infections in the intensive care unit (ICU) represents a great challenge, especially infections caused by antibiotic resistance pathogens. A thorough and up-to-date knowledge of the local spectrum of antibiotic resistant bacteria can improve the antibiotic treatment efficiency. In this study, we aimed to reveal the profile of bacteria with antibiotic resistance genes (ARGs) in real-world samples from ICU admission patients with pulmonary infection in Mainland, China, by metagenomic next-generation sequencing (mNGS).Methods: A total of 504 different types of clinical samples from 452 ICU admission patients with pulmonary infection were detected by mNGS analysis.Results: A total of 485 samples from 434 patients got successful mNGS results. Among 434 patients, one or more bacteria with ARGs were detected in 192 patients (44.24%, 192/434), and ≥ 2 bacteria with ARGs were detected in 85 (19.59%, 85/434) patients. The predominant detected bacteria were Corynebacterium striatum (C. striatum) (11.76%, 51/434), Acinetobacter baumannii (A. baumannii) (11.52%, 50/434) and Enterococcus faecium (E. faecium) (8.99%, 39/434). ermX conferred resistance to MSLB and cmx to phenicol were the only two ARGs detected in C. striatum; in A. baumannii, most of ARGs were resistance-nodulation-division (RND)-type efflux pumps genes, which conferred resistance to multi-drug; ermB conferred resistance to MSLB and efmA to multi-drug were the predominant ARGs in E. faecium. Bacteria with ARGs were detected in 50% (140/280) bronchoalveolar lavage fluid (BALF) and 50.5% (48/95) sputum samples, which were significantly higher than in blood and cerebrospinal fluid (CSF) samples.Conclusion: High level of bacteria with ARGs was observed in clinical samples, especially BALF and sputum samples from ICU admission patients with pulmonary infection in Mainland, China. And C. striatum resistant to MSLB and/or phenicol, multi-drug resistance A. baumannii and E. faecium were the lead bacteria.Keywords: intensive care units, pulmonary infection, antibiotic resistant bacteria, antibiotic resistance genes

Hong Zhou,1 Dan Luo,2 Dan Chen,2 Xi Tan,1 Xichen Bai,1 Zhi Liu,1 Xiangliang Yang,1,2 Wei Liu1,2 1College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, Hubei, People’s Republic of China; 2National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan, 430075, Hubei, People’s Republic of ChinaCorrespondence: Wei LiuCollege of Life Science and Technology, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan, 430075, Hubei, People’s Republic of ChinaTel/Fax +86 27 8779 2147Email wliu@hust.edu.cnAbstract: Nanocarrier technology has been effectively applied to the development of drug delivery systems to overcome the limitations of traditional preparation. Its application has been extended to various pharmaceutical fields from injection preparation to oral preparation and external preparation, and now it has appeared in the field of cosmetics for beauty applications. The widespread influence of nanocarrier in the cosmetics industry is due to the fact that nanocarrier can effectively promote the percutaneous penetration and significantly increase skin retention of active components in functional cosmetics. Meanwhile, nanocarrier can effectively improve the water dispersion of insoluble active cosmetic ingredients, enhance the stability of efficacy components and achieve the codelivery of diverse cosmetics active ingredients. In this review, we summarized the current progress of nanocarrier technology in the functional cosmetics, including the types and the routes of dermal/transdermal drug delivery nanocarriers used in the functional cosmetics, the mechanism of nanocarriers promoting the percutaneous penetration of active cosmetic ingredients, the application and efficacy evaluation of different active cosmetic ingredients in nanocarriers and discussing the potential risks to human. This will provide a useful reference for the further development of nanocarriers in the field of functional cosmetics.Keywords: nanocarrier technology, functional cosmetics, active cosmetic ingredients, skin penetration and positioning, efficacy evaluation, codelivery nanocarriers

Xiang Li,1,* Guodong Wang,2,* Kun Yan,1 Shanshan Yin,1 Hongzhi Wang,2 Yanjie Wang,1 Xiumei Bai,1 Yanfen Shen2 1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China; 2Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), ICU, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kun YanKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100042, People’s Republic of ChinaTel + 86 13611176073Fax +86 10-88196195Email ydbz@vip.sina.comHongzhi WangKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), ICU, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, People’s Republic of ChinaTel/Fax +86 10-88196112Email doctorwhz@163.comPurpose: A peripherally inserted central catheter (PICC) is associated with venous thromboembolism (VTE) especially in patients suffering from cancer. We analyzed the incidence, risk factors, and patterns of PICC-related VTE in cancer patients.Patients and Methods: Patients with cancer who underwent PICC placement were evaluated retrospectively. Routine, prospective ultrasound post-PICC placement was used for asymptomatic and symptomatic patients to identify VTE. Multivariable logistic regression models with odds ratios (ORs) were used to examine VTE risk factors.Results: Of 2353 PICCs placed, 165 patients (7.01%) developed PICC-related VTE with a median thrombosis time of 12 days. After adjustment of multivariable analysis, patients with PICC-related VTE were more likely to have a ratio of PICC diameter:vein diameter > 0.35 (adjusted OR, 1.689; 95% CI, 1.023– 2.789) and high level of triglycerides (1.561; 1.096– 2.223). The prevalence of A (adjusted OR, 1.680; 95% CI, 1.009– 2.798), B (1.835; 1.137– 2.961), and AB (3.275; 1.840– 5.829) blood group was significantly higher than that of the O blood group in VTE patients. Venous recanalization was observed in 44.8% (74/165) patients after anticoagulation therapy, and more often in patients with combined deep VTE than in patients with isolated superficial VTE (OR, 17.942; 95% CI, 5.427– 59.316). The recanalization time was 20± 5 (range, 10– 31) days.Conclusion: The non-O blood group, larger ratio of PICC diameter:vein diameter, and high level of triglycerides were significantly associated with PICC-related VTE. Almost half of cases of PICC-related deep VTE could be reversed by anticoagulation treatment.Keywords: recanalization, ultrasound, venous thromboembolism

Xue Bai,1 Yibo Tang,2 Qiang Li,1 Dan Liu,1 Guimin Liu,1 Xiaolei Fan,2 Zhejun Liu,2 Shujun Yu,1 Tian Tang,1 Shuyan Wang,2 Lingru Li,3 Kailin Zhou,4 Yanfei Zheng,3 Zhenquan Liu1,3 1School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4School of Humanities, Beijing University of Chinese Medicine, Beijing, People’s Republic of ChinaCorrespondence: Yanfei ZhengNational Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of ChinaTel +8618010091957Email yanfei_z@163.comZhenquan LiuSchool of Chinese Materia Medica, National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of ChinaTel +86 13810419708Email lzqbzy@sina.comPurpose: One of the most common types of male infertility is recognized as oligoasthenozoospermia (OA), characterized by low sperm count and quality in males. As a traditional Chinese medicine (TCM), Cuscutae Semen-Mori Fructus coupled-herbs (CSMFCH) has been known to act a curative effect on OA for thousands of years. Nevertheless, the substantial basis and molecular mechanism of CSMFCH in treating OA remain elusive.Methods: Herein, an integrated approach, including network pharmacology, molecular docking, and experiment validation, was utilized to reveal the new candidate active component and mechanism of CSMFCH in treating OA.Results: The results show that kaempferol is the most significant bioactive component of CSMFCH on OA. The mechanism and targets of CSMFCH against OA are relevant to hormone regulation, oxidant stress, and reproductive promotion. In order to validate network pharmacology results, molecular docking and experiment validation were conducted. In detail, molecular docking was employed to verify the strong binding interactions between kaempferol and the core targets. UHPLC-Q-Orbitrap-MS was used to identify kaempferol in the CSMFCH extract. In vitro and in vivo experiments further proved CSMFCH and kaempferol could enhance the mouse Leydig (TM3) and mouse Sertoli (TM4) cell viability, improve the male reproductive organ weights, sperm quality, and decrease testis tissue damage in the OA mouse model induced by CP.Conclusion: Our results not only identify the new candidate active component of CSMFCH in treating OA but also provide new insights into the mechanisms of CSMFCH against OA.Keywords: traditional Chinese medicine, oligoasthenozoospermia, kaempferol, network pharmacology

Zhidan Li,1 Xiaojuan Bai,2 Lulu Han,2 Wen Han,2 Weina Hu3 1Department of Ultrasound, The Fourth Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Gerontology and Geriatrics, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China; 3Department of Cardiology, The Fourth Affiliated Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Weina HuDepartment of Cardiology, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, People’s Republic of ChinaEmail weina_hu2021@126.comXiaojuan BaiDepartment of Gerontology and Geriatrics, Shengjing Hospital of China Medical University, Shenyang, 110004, People’s Republic of ChinaEmail xiaojuan_Bai@126.comBackground: Electromechanical coupling may play a significant role in the association between abnormal myocardial mechanics and heterogeneity of repolarization. This study sought to assess the potential relationship between the left atrial volume index (LAVI), which is an important marker of cardiac diastolic function, and ventricular repolarization variables, such as the QT interval, Tpeak-to-Tend (Tpe) interval and Tpe/QT ratio, in an apparently healthy Chinese population.Methods: This was a community-based cross-sectional study conducted in Shenyang, China. A total of 414 healthy subjects aged 35– 91 years, including 186 men (44.9%), were enrolled. In addition to performing clinical and laboratory measurements, all subjects underwent comprehensive echocardiography and standard 12-lead electrocardiography. Echocardiographic and electrocardiographic results were analysed separately and in a blinded fashion. Correlation and regression analyses were applied to determine associations.Results: Subjects were divided into four groups according to quartile of LAVI levels (< 16.0, 16.0– 18.9, 19.0– 22.5 and > 22.5 mL/m2). Ventricular repolarization variables, such as QT interval and QTc interval, gradually increased with the progression from low to high LAVI levels (P< 0.05). LAVI was positively and significantly correlated with the QT interval, the QTc interval, and the Tpe interval (P< 0.01). After adjusting for age and other possible confounders, LAVI showed significant and independent associations with the QT interval and the QTc interval (P< 0.001; P=0.003).Conclusion: Echocardiographic LAVI is linearly associated with ventricular repolarization variables even in healthy people.Keywords: left atrial volume index, QT interval, Tpe interval, diastolic dysfunction, ventricular repolarization

Yan Sun,1 Ming Deng,2 Xiao Ke,2 Xiangyang Lei,3 Hao Ju,3 Zhiming Liu,3 Xiaosu Bai3,4 1Department of Endocrinology, Southern University of Science and Technology Hospital, Shenzhen, People’s Republic of China; 2Department of Cardiology, Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen Sun Yat-Sen Cardiovascular Hospital, Shenzhen, 518057, People’s Republic of China; 3Department of Endocrinology, Affiliated Longhua People’s Hospital, Southern Medical University, Longhua People’s Hospital, Shenzhen, People’s Republic of China; 4Department of General Practice; Affiliated Longhua People’s Hospital, Southern Medical University, Longhua People’s Hospital, Shenzhen, People’s Republic of ChinaCorrespondence: Xiaosu BaiAffiliated Longhua People’s Hospital, Southern Medical University, Longhua People’s Hospital, No. 2, Jianshe East Road, Bao’an District, Shenzhen, 518109, People’s Republic of ChinaTel +86-755-27741585Email bxsllb@163.comAim: Diabetic nephropathy (DN) is a serious health problem worldwide. Epidermal growth factor (EGF) has suggested as a potential biomarker for the progression of chronic kidney disease. In this study, we examined the effects of EGF on the high glucose (HG)-induced podocyte injury and explored the underlying molecular mechanisms.Methods: The cell proliferation, toxicity, and cell apoptosis of podocytes were determined by CCK-8 assay, lactate dehydrogenase release assay, and flow cytometry, respectively, and protein levels in the podocytes were determined by Western blot assay. Mechanistically, DNA methylation analysis, bioinformatic analysis, methylation‑specific PCR and quantitative real-time PCR were used to analyze functional pathways in differentially methylated genes and the expression of the key methylated genes in the podocytes after different interventions.Results: EGF treatment significantly increased the protein expression level of LC3 and decreased the protein level of P62 in HG-stimulated podocytes, which was attenuated by autophagy inhibitor, 3-methyladenine. EGF increased the cell proliferation and the protein expression levels of nephrin and synaptopodin, but reduced cell toxicity and cell apoptosis and protein expression level of cleaved caspase-3, which was partially antagonized by 3-methyladenine. DNA methylation expression profiles revealed the differential hypermethylation sites and hypomethylation sites among podocytes treated with normal glucose, HG and HG+EGF. GO enrichment analysis showed that DNA methylation was significantly enriched in negative regulation of phosphorylation, cell-cell junction and GTPase binding. KEGG pathway analysis showed that these genes were mainly enriched in PI3K-Akt, Hippo and autophagy pathways. Further validation studies revealed that six hub genes (ITGB1, GRB2, FN1, ITGB3, FZD10 and FGFR1) may be associated with the protective effects of EGF on the HG-induced podocyte injury.Conclusion: In summary, our results demonstrated that EGF exerted protective effects on HG-induced podocytes injury via enhancing cell proliferation and inhibiting cell apoptosis. Further mechanistic studies implied that EGF-mediated protective effects in HG-stimulated podocytes may be associated with modulation of autophagy and PI3K/AKT/mTOR signaling pathway.Keywords: diabetic nephropathy, epidermal growth factor, podocyte injury, autophagy, DNA methylation, PI3K/AKT/mTOR

Zepeng Yu,1,* Xingwei Sun,1,* Xuming Bai,1 Wei Ding,2 WeiDong Wang,2 Liang Xu,3 Wenming Qin,4 Ling Wen,5 Yong Jin1 1Department of Intervention, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu, People’s Republic of China; 2Department of Intervention, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, 214023, Jiangsu Province, People’s Republic of China; 3Department of General Surgery, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, 215500, Jiangsu, People’s Republic of China; 4Department of Anesthesiology, Bazhong Central Hospital, Bazhong, Sichuan, 636000, People’s Republic of China; 5Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yong JinDepartment of Intervention, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu, People’s Republic of ChinaTel +86 13776097707Email 578898234@qq.comLing WenDepartment of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu, People’s Republic of ChinaEmail wenling@suda.edu.cnPurpose: The totally implantable venous access port (TIVAP) provides patients with safe, effective and long-term convenient venous access for the administration of medications such as chemotherapy drugs. The implantation and long-term use of TIVAP are related to thrombosis, infection and other complications. In this study, the medical records of multicentre patients were collected, and the perioperative and postoperative complications were retrospectively analysed to objectively evaluate the safety of the implantation of supraclavicular, ultrasound-guided TIVAP via the brachiocephalic vein (BCV).Patients and Methods: We retrospectively analysed the clinical data of 433 adult patients who had undergone ultrasound-guided TIVAP implantation via the BCV at four hospitals in China from March 2018 to May 2019. The success rates of the first puncture, operation time, and perioperative and postoperative complications were analysed.Results: All the TIVAPs were implanted successfully (100%). The average TIVAP carrying time was 318.15 ± 44.22 days (range: 38– 502 days) for a total of 197,694 catheter days. The success rate of the first puncture was 94.92% (411/433), and the average operation time was 29.66 ± 7.45 min (range: 18– 60 min). The perioperative complications included arterial puncture in 4 patients and pneumothorax in 1 patient. The incidence of postoperative complications was 5.08% (22/433), including poor incision healing (n = 2), catheter-related infection (n = 3), port infection (n = 6), thrombosis (n = 2) and fibrin sheath formation (n = 8). Another patient had infusion disturbance 2 days after the operation, and chest X-ray showed bending at the connection between the catheter and port. No other serious complications occurred, such as catheter rupture and drug leakage. The total incidence of complications was 6.24% (27/433).Conclusion: This study showed excellent tolerance of supraclavicular, ultrasound-guided BCV puncture to implant TIVAP and a low incidence of complications. As a safe and effective method of TIVAP implantation, it can provide a new choice for clinicians.Keywords: complications, totally implantable venous access ports, ultrasound-guided, brachiocephalic vein

Xiaodong Bai, Zhenyu Liu,* Baojun Wang* Department of Orthopedics, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhenyu Liu; Baojun Wang Email doczhyl@163.com; docbjwang@126.comObjective: This study aimed to evaluate asymptomatic flexor pollicis longus (FPL) tendon condition after volar plate fixation for distal radius fracture using shear wave elastography (SWE).Methods: We evaluated 36 distal radius fractures with shear wave elastography to evaluate the FPL tendon after volar plate fixation. Ultrasonography was used to measure the FPL distance to the volar plate in the involved wrists, and the thickness of the FPL tendon in the involved wrists was measured on SWE sonograms taken 12 months postoperatively. Measurements of the involved wrists were compared with those of the intact wrists. The radiographic parameters and Soong grade were collected to analyze the correlation between these indicators and the value of the Young’s modulus and asymptomatic tendon injury.Results: The mean values of the Young’s modulus for involved wrist were lower than for intact wrist tendons. The values of the Young’s modulus were correlated with the FPL distance, radial inclination, and Soong grade. FPL tendons of involved wrists exhibited in the majority a yellow (intermediate) SWE signal, compared to intact wrist tendons, which exhibited a red (hard) signal in the vast majority, and there were significant differences between the involved and intact wrist.Conclusion: FPL tendon may develop asymptomatically changes after volar locking plate fixation of distal radius fractures, which can be detected by SWE effectively. FPL distance, radial accretion, and Soong grade may be the main causes of asymptomatic FPL tendon erosion.Keywords: distal radius fractures, shear wave elastography, flexor pollicis longus tendon, Soong grade, asymptomatic tendon injury

Zihan Zhou,1,2 Dianbin Mu,3 Dexian Zhang,3 Xianbin Zhang,2 Xingchen Ding,2 Jia Yang,2 Xinbin Bai,4 Man Hu2 1Department of Oncology, Weifang Medical University, Weifang, Shandong, People’s Republic of China; 2Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 3Department of Pathology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 4Department of Oncology, Jining Cancer Hospital, Jining, Shandong, People’s Republic of ChinaCorrespondence: Man HuDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jiyan Road 440, Jinan 250117, Shandong, People’s Republic of ChinaTel +86-531-67626152Fax +86-531-67626153Email human5770@163.comObjective: The aim of this study was to evaluate the prognosis effect of PD-L1 in combination with CD8+ tumor-infiltrating lymphocyte (TIL) or HIF-1α in head and neck squamous cell carcinoma (HNSCC).Methods: A total of 63 patients who underwent surgical resection were included in this study. The level of PD-L1, CD8+ TIL, and HIF-1α was determined by immunohistochemical analysis. The survival of patients was evaluated by Kaplan–Meier analysis. The prognostic power of these parameters was evaluated by C-index.Results: We observed that the survival of patients, who had a high level of PD-L1 in tumor cells, was significantly shorter than those who had a low level of PD-L1. However, the survival of patients who had a high level of PD-L1 in tumor microenvironment was significantly longer than patients with a low level of PD-L1 in tumor microenvironment. In addition, high level of CD8+ tumor-infiltrating lymphocyte or low level of HIF-1α level suggests a better prognosis. Moreover, we observed that PD-L1 in combination with CD8+ tumor-infiltrating lymphocyte and HIF-1α could significantly improve the prognostic effect of current TNM stage.Conclusion: The results of this study suggest that the level of PD-L1, CD8+TIL, and HIF-1α are useful prognostic biomarkers for patients with HNSCC. Incorporating these biomarkers into current TNM stage of HNSCC improve the discriminatory capability of TNM stage.Keywords: PD-L1, HIF-1α, CD8+TIL, HNSCC, prognosis