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Jingxia Mao,1,2,&ast; Guibo Yang,1,3,&ast; Qin Su,1,4,&ast; Zhonghong Zeng,1 Jueying Lin,2 Lin Kong,3 Lidun Zhang,4 Lidan Liu,1 Yihua Yang,1 Hongbo Wu1 1Guangxi Reproductive Medical Center, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Obstetrics, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 3Department of Obstetrics, The Maternity and Child Health Care of Guangxi Zhuang Autonomous Region, Nanning, People’s Republic of China; 4Department of Obstetrics, The First People’s Hospital of Yulin, Yulin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongbo Wu; Yihua Yang, Guangxi Reproductive Medical Center, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China, Email 19587200@qq.com; workyyh@163.comObjective: To assess the safety and efficiency of in vitro fertilization/ intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) on maternal and neonatal perinatal outcomes in women (≥ 40y) with singleton pregnancies.Methods: This multi-center retrospective cohort study, carried out from January 2018 to June 2023, enrolled 1762 women (≥ 40y) with singleton pregnancies of at least 28 weeks. Participants were divided into two groups: the IVF/ICSI-ET group (204 cases) and the spontaneous conception (SC) group (1558 cases). After 1:2 propensity score matching (PSM), the two groups were compared for maternal and neonatal outcomes. The SC group (1558 cases) was further divided by age into the < 43 years group (1195 cases) and the ≥ 43 years group (363 cases) for subgroup analysis.Results: Adverse maternal and neonatal outcomes were comparable between the IVF/ICSI-ET group and the SC group, with a higher cesarean section rate (78% vs 67.5%, P =0.013), an increased maternal ICU admissions rate (5.5% vs 1.3%, P =0.008), and a lower birth defects rate (1.1% vs 4.6%, P =0.037) in the IVF/ICSI-ET group. Subgroup analysis showed that women aged ≥ 43 years had higher incidences of gestational diabetes, gestational hypertension, cesarean section, and neonatal asphyxia compared to women aged < 43 years.Conclusion: This study indicated IVF/ICSI-ET is relatively safe for women ≥ 40 years with singleton pregnancies. However, advanced maternal age deteriorated maternal and neonatal outcomes, and IVF/ICSI-ET further heightened the risk of cesarean section and maternal ICU admissions. Therefore, enhanced care and vigilance are crucial for women over 40 undergoing IVF/ICSI-ET.Keywords: in-vitro fertilization, intracytoplasmic sperm injection, advanced maternal age, maternal outcomes, neonatal outcomes

Shaoli Shi,1 Guangyao Li,2 Xiaoli Zhu,2 Lingming Kong2 1Psychiatry Department, The 5th People’s Hospital of Luoyang, Luoyang, Henan Province, 471027, People’s Republic of China; 2Treatment & Prevention Center, No. 904th Hospital, Changzhou, Jiangsu Province, 213003, People’s Republic of ChinaCorrespondence: Lingming Kong, Treatment & Prevention Center, No. 904th Hospital, North Peace Road 55, No. 904th Hospital, Changzhou, Jiangsu, 213003, People’s Republic of China, Email lingmk123@163.comBackground: Adolescent group may be prone to a variety of behavioral disorders, one of which is nonsuicidal self-injury (NSSI), NSSI intervention is limited for its unknown mechanism, so this study aimed to explore the factors associated with and pathological mechanism underlying NSSI from the perspective of family dysfunction, alexithymia, circRNA_103636 in a sample of Chinese adolescents.Methods: A total of 200 MDD adolescents with NSSI and 200 healthy controls were enrolled via a convenient sampling method in clinical settings. The Family APGAR Index (APGAR), Toronto Alexithymia Scale (TAS-20), and Adolescent Nonsuicidal Self-injury Assessment Questionnaire (ANSSIAQ) were used for mental assessment of the study group and control group participants. Real-time quantitative reverse transcription PCR (qRT–PCR) was utilized to detect circRNA_103636 expression in peripheral blood mononuclear cells (PBMCs).Results: There were significant between-group differences of 134 patients (67%) in the study group and 42 patients in the control group (21%) with moderate or severe family dysfunction (P< 0.01). The APGAR score was lower, and the difficulty identifying feeling (DIF), difficulty describing feeling (DDF) and externally oriented thinking (EOT) scores of the TAS-20 and ΔCt value of circRNA_103636 were greater in the study group than in the control group. NSSI behavior and NSSI function were negatively correlated with the APGAR score and positively correlated with DIF, DDF, and the EOT of TAS-20 and the ΔCt value of circRNA_103636. Multiple regression analysis confirmed that EOT, circRNA_103636 expression, and APGAR were predictors of ANSSIAQ, which could explain 40.5% of the variance. Similarly, the alexithymia and circRNA_103636 expression mediated the correlation between family dysfunction and NSSI in the study group, and these mediating effects accounted for 27.25% and 23.33%, respectively, of the total effect. Taken together, family dysfunction, alexithymia, and circRNA_103636 expression have predictive effects on NSSI and alexithymia, circRNA_103636 expressions are mediators between family dysfunction and NSSI in Chinese adolescent.Conclusion: Here, we established a new model for NSSI in which exposure to family dysfunction could induce pathological process by modulating personality traits and epigenetic regulators.Keywords: nonsuicidal self-injury, family dysfunction, alexithymia, circRNA_103636, epigenetics

Zixu Zhang,1,2 Muhan Chen,1,2 Jiahua Wang,1,2 Mo Liu,1,2 Ruibo Guo,1,2 Lu Zhang,1,2 Liang Kong,1,2 Yang Liu,1,2 Yang Yu,1– 3 Xuetao Li1,2 1School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, 116600, People’s Republic of China; 2Shenyang Key Laboratory of Chinese Medicine targeted Delivery Key laboratory, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, People’s Republic of China; 3Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, 110032, People’s Republic of ChinaCorrespondence: Xuetao Li; Yang Yu, School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, 116600, People’s Republic of China, Tel +86411 8589 0170, Fax +86411 8589 0128, Email lixuetao1979@163.com; yuqn0702@163.comIntroduction: Resistance of intracellular pathogens is a challenge in microbial therapy. Methicillin-resistant Staphylococcus aureus (MRSA), which is able to persist inside the cells of infected tissues, is protected from attack by the immune system and many antimicrobial agents. To overcome these limitations, nano-delivery systems can be used for targeted therapy of intracellular MRSA.Methods: Hyaluronic acid-modified azithromycin/quercetin micelles (HA-AZI/Qe-M) were synthesized by thin film hydration. The micelles were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and Fourier transform infrared spectroscopy (FTIR), and the drug loading (DL) and encapsulation efficiency (EE) were detected by high performance liquid chromatography (HPLC). The uptake ability of RAW264.7 cells was investigated, and its distribution in mice was evaluated by in vivo imaging. The inhibitory effect of the micelles against MRSA in vitro and its ability to eliminate intracellular bacteria were evaluated. Bacterial muscle-infected mice were constructed to evaluate the therapeutic effect of the micelles on bacterial infections in vivo and the biocompatibility of the micelles was investigated.Results: HA-AZI/Qe-M had suitable physical and chemical properties and characterization. In vitro antibacterial experiments showed that HA-AZI/Qe-M could effectively inhibit the growth of MRSA, inhibit and eliminate the biofilm formed by MRSA, and have an excellent therapeutic effect on intracellular bacterial infection. The results of RAW264.7 cells uptake and in vivo imaging showed that HA-AZI/Qe-M could increase the cellular uptake, target the infection site, and prolong the treatment time. The results of in vivo antibacterial infection experiments showed that HA-AZI/Qe-M was able to ameliorate the extent of thigh muscle infections in mice and reduce the expression of inflammatory factors.Conclusion: HA-AZI/Qe-M is a novel and effective nano-drug delivery system that can target intracellular bacterial infection, and it is expected to be safely used for the treatment of MRSA infection.Keywords: MRSA, hyaluronic acid, antibiotics, micelles, azithromycin, quercetin

Yanzhi Feng,1– 4,&ast; Litao Liang,1– 4,&ast; Wenbo Jia,1– 4 Jinyi Wang,1– 4 Chao Xu,1– 4 Deming Zhu,1– 4 Bin Xu,1– 4 Wenhu Zhao,1– 4 Xiangyu Ling,1– 4 Yongping Zhou,5 Lianbao Kong,1– 4,&ast; Wenzhou Ding1– 4,&ast; 1Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, National Health Commission Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, Jiangsu, People’s Republic of China; 3Jiangsu Provincial Medical Innovation Center, Nanjing, Jiangsu, People’s Republic of China; 4Jiangsu Provincial Medical Key Laboratory, Nanjing, Jiangsu, People’s Republic of China; 5Jiangnan University Medical Center, JUMC, Department of Hepatobiliary, Wuxi, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenzhou Ding; Lianbao Kong, Hepatobiliary Centre, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People’s Republic of China, Email dingwenzhou@njmu.edu.cn; lbkong@njmu.edu.cnBackground: Circular RNAs (circRNAs) have been shown to play a crucial role in the initiation and development of Hepatocellular carcinoma (HCC). However, the mechanism and function of circ_0007386 in HCC are still unknown.Methods: Circ_0007386 expression level in HCC tissues, and HCC cell lines was further analyzed by qRT-PCR. Agarose gel electrophoresis and Sanger sequencing were used to figure out the structure of circ_0007386. The involvement of circ_0007386 in HCC development was evaluated by experimental investigations conducted in both laboratory settings (in vitro) and living organisms (in vivo). RNA immunoprecipitation, Western blotting, luciferase reporter assay and fluorescence in situ hybridization (FISH) were applied for finding out the interaction among circ_0007386, miR-507 and CCNT2. To assess the connection between circ_0007386 and lenvatinib resistance, lenvatinib-resistant HCC cell lines were employed.Results: The expression of circ_0007386 was found to increase in HCC tissues, and it was observed to be associated with a worse prognosis. Overexpression of circ_0007386 stimulated HCC cells proliferation, invasion, migration and the epithelial–mesenchymal transition (EMT) while silencing of circ_0007386 resulted in the opposite effect. Mechanistic investigations revealed that circ_0007386 acted as a competing endogenous RNA of miR-507 to prevent CCNT2 downregulation. Downregulating miR-507 or overexpressing CCNT2 could reverse phenotypic alterations that originated from inhibiting of circ_0007386. Importantly, circ_0007386 determines the resistance of hepatoma cells to lenvatinib treatment.Conclusion: Circ_0007386 advanced HCC progression and lenvatinib resistance through the miR-507/ CCNT2 axis. Meanwhile, circ_0007386 served as a potential biomarker and therapeutic target in HCC patients. Keywords: hepatocellular carcinoma, circ_0007386, miR-507, CCNT2, Lenvatinib

Ling Tang,1 Yu-Jia Wang,2 Yuan-Yuan Wang,2 Shu-Tong Li,3 Liang Kong,3 Xue-Tao Li,3 Ling-Ling Ma,1 Xiu-Xiu Liu1 1Department of Obstetrics and Gynecology, Affiliated Zhongshan Hospital of Dalian University, Dalian, People’s Republic of China; 2Department of Pharmacy, Affiliated Zhongshan Hospital of Dalian University, Dalian, People’s Republic of China; 3School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, 116600, People’s Republic of ChinaCorrespondence: Ling-Ling Ma; Xiu-Xiu Liu, Department of Obstetrics and Gynecology, Affiliated Zhongshan Hospital of Dalian University, Dalian, People’s Republic of China, Email 826269013@qq.com; 1225949002@qq.comPurpose: Ovarian cancer is a fatal gynecologic malignancy with a high rate of abdominal metastasis. Chemotherapy still has a poor clinical prognosis for ovarian cancer patients, with cell proliferation and angiogenesis leading to invasion, migration, and recurrence. To overcome these obstacles, we constructed a novel HA-modified paclitaxel and diosgenin liposome (PEG-TK-HA-PDLPs) using two novel functional materials, DSPE-PEG2000-HA and DSPE-PEG2000-TK-PEG5000, to specifically deliver the drugs to the tumor site in order to reduce OC cell proliferation and anti-angiogenic generation, thereby inhibiting invasion and migration.Methods and Results: PEG-TK-HA-PDLPs were prepared by film dispersion, with ideal physicochemical properties and exhibits active targeting for enhanced cellular uptake. The ZIP synergy score for PTX and Dios was calculated using the online SynergyFinder software to be 3.15, indicating synergy. In vitro results showed that PEG-TK-HA-PDLPs were highly cytotoxic to ID8 cells, induced ID8 cell apoptosis, and inhibited ID8 cell migration and invasion. In vivo studies showed that PEG-TK-HA-PDLPs could prolong the circulation time in the blood, accumulate significantly in the tumor site, and effectively fight against angiogenesis with significant anti-tumor effects.Conclusion: The production of PEG-TK-HA-PDLPs is an effective strategy for the treatment of OC.Keywords: ovarian cancer, functional liposomes, paclitaxel, diosgenin, ROS-response, HA

Yuanyuan Wang,1 Ruibo Guo,2 Ming Zou,1 Lingling Jiang,1 Liang Kong,2 Sen Zhao,1 Xuan Zhang,1 Wei Wang,1 Baoli Xu1 1Department of Pharmacy, Affiliated Zhongshan Hospital of Dalian University, Dalian, People’s Republic of China; 2School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, People’s Republic of ChinaCorrespondence: Baoli Xu, Department of Pharmacy, Affiliated Zhongshan Hospital of Dalian University, No. 6 Jiefang Street, Dalian, 116001, Liaoning, People’s Republic of China, Tel +86411 6289 3215, Email xubaoli1981@hotmail.comIntroduction: Rheumatoid arthritis (RA) is an inflammatory immune-mediated disease that involves synovitis, cartilage destruction, and even joint damage. Traditional agents used for RA therapy remain unsatisfactory because of their low efficiency and obvious adverse effects. Therefore, we here established RA microenvironment-responsive targeted micelles that can respond to the increase in reactive oxygen species (ROS) levels in the joint and improve macrophage-specific targeting of loaded drugs.Methods: We here prepared ROS-responsive folate-modified curcumin micelles (TK-FA-Cur-Ms) in which thioketal (TK) was used as a ROS-responsive linker for modifying polyethylene glycol 5000 (PEG5000) on the micellar surface. When micelles were in the ROS-overexpressing inflammatory microenvironment, the PEG5000 hydration layer was shed, and the targeting ligand FA was exposed, thereby enhancing cellular uptake by macrophages through active targeting. The targeting, ROS sensitivity and anti-inflammatory properties of the micelles were assessed in vitro. Collagen-induced arthritis (CIA) rats model was utilized to investigate the targeting, expression of serum inflammatory factors and histology change of the articular cartilage by micelles in vivo.Results: TK-FA-Cur-Ms had a particle size of 90.07 ± 3.44 nm, which decreased to 78.87 ± 2.41 nm after incubation with H2O2. The micelles exhibited in vitro targeting of RAW264.7 cells and significantly inhibited inflammatory cytokine levels. Pharmacodynamic studies have revealed that TK-FA-Cur-Ms prolonged the drug circulation and exhibited augmented cartilage-protective and anti-inflammatory effects in vivo.Conclusion: The unique ROS-responsive targeted micelles with targeting, ROS sensitivity and anti-inflammatory properties were successfully prepared and may offer an effective therapeutic strategy against RA.Keywords: rheumatoid arthritis, ROS-responsive, curcumin, folate, micelles

Lingming Kong,1,&ast; Liqin Miu,2,&ast; Wenwei Yao,2 Zhiyuan Shi3 1Mental Health Research Center, No. 904th Hospital, Changzhou, Jiangsu, 213003, People’s Republic of China; 2Psychiatry Department, the 2nd People’s Hospital of Jintan District, Changzhou, Jiangsu, 213200, People’s Republic of China; 3College of Clinical Medicine, Yangzhou University, Yangzhou, Jiangsu, 225009, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lingming Kong, Mental Health Research Center, North Peace Road 55, No. 904th Hospital, Changzhou, Jiangsu, 213003, People’s Republic of China, Email lingmk123@163.comPurpose: Mild cognitive impairment (MCI) and depressive disorder (DD), which are associated with unhealthy lifestyles, are prevalent worldwide. This study aimed to investigate the effects of regular aerobic exercise on cognitive function, depression, and the regulatory role of neurotrophic growth factors for providing scientific basis in preventing MCI and DD in healthy individuals.Patients and Methods: Eighty members of the fitness center and 80 community residents were recruited, who were administered by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Patient Health Questionnaire (PHQ-9). Brain-derived neurotrophic factor (BDNF) and glial cell-line-derived neurotrophic factor (GDNF) in the peripheral blood were detected by enzyme-linked immunosorbent assay (ELISA).Results: The RBANS and other factor scores, except for visuospatial abilities, were higher and PHQ-9 scores were lower in the study group than in the control group. The concentrations of BDNF and GDNF in the study group were higher than those in the control group. RBANS and its factor scores positively and PHQ-9 negatively correlated with BDNF and GDNF levels. Finally, multiple regression analysis showed that BDNF, as a predictor of RBANS, could explain 59.90% of its variance and that GDNF was a predictor of PHQ-9 could explain 12.30% of the variance.Conclusion: Regular aerobic exercise can improve cognitive function and depressive symptoms by increasing the BDNF and GDNF levels.Keywords: cognitive impairment, depression level, brain derived neurotrophic factor, glial cell line-derived neurotrophic factor, aerobic exercise

Ran Sang,1,2 Manxue Jiang,1,2 Qiuju Zhao,2 Lingti Kong1,2 1Department of Pharmacy, The First Affiliated Hospital of Bengbu Medical University, Bengbu, 233004, People’s Republic of China; 2School of Pharmacy, Bengbu Medical University, Bengbu, 233030, People’s Republic of ChinaCorrespondence: Lingti Kong, Department of Pharmacy, The First Affiliated Hospital of Bengbu Medical University, 287 Changhuai Road, Longzihu District, Bengbu, Anhui, 233004, People’s Republic of China, Tel +865523086297, Email konglingtiklt7@126.comBackground: The excessive use of intravenous infusion in China was once a serious problem, but in recent years, attention has been paid to the phenomenon, and the government has implemented several policies to solve the problem, which has been gradually improved.Aim: This study focuses on evaluating the impact of ongoing interventions and improvements in outpatient intravenous infusion therapy.Methods: From January 2016 to December 2022, we conducted a study to gather annual data on intravenous infusion prescriptions. A data questionnaire, encompassing information on departments, clinical diagnosis, and infusion drugs, was developed for this purpose. We analyzed the changing trends of Top 10 clinical departments with higher intravenous infusion usage rates and Top 10 drugs used. We also evaluated the compliance of intravenous infusion prescriptions with management regulations and drug instructions, for further intervention in the future.Results: The analysis of intravenous infusion prescription rates revealed a gradual decrease from 10.89% to 5.63%. This reduction was statistically significant (P < 0.05). High levels of intravenous infusion use were consistently observed in emergency surgery and emergency medicine. Commonly administered drugs via infusion included antibacterial drugs, tumor medications, proton pump inhibitors, and injections of traditional Chinese medicine. Inappropriate prescriptions are often characterized by issues related to drug dosage, usage, indication, and selection. Trend analysis of unreasonable types revealed significant improvements in “Diagnosis incomplete/unwritten”, “Solvent selection”, “Dosing frequency”, and “Treatment without indication” (P < 0.05).Conclusion: The findings of this study indicate a gradual improvement in the situation regarding intravenous infusion. However, there are still prevalent instances of unreasonable practices that need to be addressed.Keywords: cross-sectional study, evaluation, analysis, intravenous infusion prescriptions, outpatient

Ziran Wang,1,&ast; Lingjun Kong,1,&ast; Rui Zhang,1 Xiaobo Yang,2 Zhe Cao,3 Tengda Xu,4 Han Zhang,1 Yaling Dou1 1Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3Hunan Light of Life Biotechnology Co., Ltd., Ningxiang, Hunan, People’s Republic of China; 4Department of Health Management, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yaling Dou, Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China, Email douyl@pumch.cnObjective: To evaluate the diagnostic performance of aldo-keto reductase family 1 member B10 (AKR1B10) in a Beijing cohort with hepatocellular carcinoma (HCC).Methods: This study included 521 subjects who visited Peking Union Medical College Hospital from June 2017 to May 2023, including 109 cases of HCC, 165 cases of healthy controls, 106 cases of benign liver diseases, and 141 cases of other cancers. Serum AKR1B10 levels were measured and compared across various groups. Diagnostic performances of serum AKR1B10 and other tumor markers were assessed using receiver operator characteristic (ROC) curves. In addition, a subset of HCC patients who underwent surgical resection were recruited for clinical follow-up study.Results: We found that serum AKR1B10 expression was higher in patients with HCC relative to other control groups. The association between serum AKR1B10 and clinical features of HCC was not observed. Serum AKR1B10 showed a high diagnostic performance for HCC, and when combined with AFP, the diagnostic effectiveness was significantly improved. Specifically, serum AKR1B10 showed superior diagnostic effectiveness for AFP-negative HCC. The clinical follow-up study indicated a gradual decrease in serum AKR1B10 after surgery.Conclusion: Our study demonstrated that serum AKR1B10 is a promising biomarker for HCC, and when used in combination with AFP can significantly improve the detection rate of HCC.Keywords: AKR1B10, AFP, hepatocellular carcinoma, diagnostic performance

Miao Zhu,1 Juan Zhao,1 Xiaoli Zhu,2 Qi Cheng,2 Shuyou Zhang,2 Lingming Kong2 1Psychiatry Department, The Oriental People’s Hospital of Xuzhou, Xuzhou, 221004, People’s Republic of China; 2Psychological Intervention Center, No.904 Hospital, Changzhou, 213003, People’s Republic of ChinaCorrespondence: Lingming Kong, Psychological Intervention Center, No.904th Hospital, Peace Road 55, Changzhou, Jiangsu, 213003, People’s Republic of China, Tel +86 519 83064556, Fax +8651983064560, Email lingming123@163.comPurpose: Late-onset depression (LOD) with poor treatment response has high incidence and mortality in the China’s aged people, this study aims to explore the correlation between health-promoting lifestyle, meaning in life, interleukin-6 (IL-6) and LOD for providing scientific basis of LOD prevention and rehabilitation.Patients and Methods: A total of 496 LOD patients (study group) and healthy older adults (control group) were enrolled and investigated by using the Health-promoting lifestyle Profile-II, revised (HPLP-IIR), Meaning in Life Questionnaire-Chinese Version (MLQ-C), and Hamilton Depression Scale (HAMD). The interleukin-6 (IL-6) in the circulating blood was detected by utilizing ELISA kit.Results: The results showed that the scores of all factors in HPLP-IIR and MLQ were significantly lower and IL-6 level was higher in the study group than the control group. Scores of most factors in HPLP-IIR and MLQ negatively and IL-6 positively correlated with scores of subscales and total HAMD score. Meaning in life and IL-6 partially mediated the relationship between health-promoting lifestyles and depression severity in the study group, with the mediating effect explains 15.76% and 22.64% of the total effect, respectively.Conclusion: Health-promoting lifestyles, meaning in life, and IL-6 are predictors of LOD, and an unhealthy lifestyle could induce LOD through the mediating effect of meaning in life and IL-6 in older adults.Keywords: late-onset depression, meaning in life, health-promoting lifestyle, older adult

Qigang Huang, Yingwei Ding, Chao Fang, Hao Wang, Laifa Kong Department of Emergency Medicine, Zhejiang University Medical College Affiliated Jinhua Hospital, Jinhua, Zhejiang, People’s Republic of ChinaCorrespondence: Laifa Kong, Department of Emergency Medicine, Zhejiang University Medical College Affiliated Jinhua Hospital, Jinhua, Zhejiang, People’s Republic of China, Email h1585897@163.comAbstract: Sepsis is a syndrome in multi-organ dysfunction triggered by a deleterious immunological reaction of the body to a condition caused by infection, surgery, or trauma. Currently, sepsis is thought to be primarily associated with abnormal immune responses resulting in organ microcirculatory disturbances, cellular mitochondrial dysfunction, and induced cell death, although the exact pathogenesis of sepsis is still inconclusive. In recent years, the role of abnormal metabolism of trace nutrients in the pathogenesis of sepsis has been investigated. Ferroptosis is a type of cell death that relies on iron and is characterized by unique morphological, biochemical, and genetic features. Unlike other forms of cell death, such as autophagy, apoptosis, necrosis, and pyroptosis, ferroptosis is primarily driven by lipid peroxidation. Ferroptosis cells may be immunogenic, amplify inflammatory responses, cause more cell death, and ultimately induce multi-organ failure. An increasing number of studies have indicated the significance of ferroptosis in sepsis and its role in reducing inflammation. The effectiveness of sepsis treatment has been demonstrated by the use of drugs that specifically target molecules associated with the ferroptosis pathway, including ferroptosis inhibitors. Nevertheless, there is a scarcity of studies investigating the multi-organ dysfunction caused by ferroptosis in sepsis. This article presents a summary and evaluation of recent progress in the role of ferroptosis through molecularly regulated mechanisms and its potential mechanisms of action in the multi-organ dysfunction associated with sepsis. It also discusses the current challenges and prospects in understanding the connection between sepsis and ferroptosis, and proposes innovative ideas and strategies for the treatment of sepsis.Keywords: sepsis, ferroptosis, organ damage, lipid peroxidation, treatment

Songhui Li,1,&ast; Wenfeng Zhao,2,&ast; Lei Xia,3 Lingyi Kong,1 Lei Yang1 1Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 210009 People’s Republic of China; 2Department of Biochemistry, School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009 People’s Republic of China; 3Bloomage Biotechnology Corporation Limited, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lingyi Kong, Jiangning Campus, China Pharmaceutical University, No. 639 Longmian Avenue, Chunhua Street, Jiangning District, Nanjing City, Jiangsu Province, People’s Republic of China, Fax +86-25-8327-1405, Email cpu_lykong@126.com Lei Yang, Jiangning Campus, China Pharmaceutical University, No. 639 Longmian Avenue, Chunhua Street, Jiangning District, Nanjing City, Jiangsu Province, People’s Republic of China, Tel +86-13813925076, Email dorothy19802003@gmail.comAbstract: Helicobacter pylori infection often occurs in early childhood, and can last a lifetime if not treated with medication. H. pylori infection can also cause a variety of stomach diseases, which can only be treated with a combination of antibiotics. Combinations of antibiotics can cure H. pylori infection, but it is easy to relapse and develop drug resistance. Therefore, a vaccine is a promising strategy for prevention and therapy for the infection of H. pylori. After decades of research and development, there has been no appearance of any H. pylori vaccine reaching the market, unfortunately. This review summarizes the aspects of candidate antigens, immunoadjuvants, and delivery systems in the long journey of H. pylori vaccine research, and also introduces some clinical trials that have displayed encouraging or depressing results. Possible reasons for the inability of an H. pylori vaccine to be available over the counter are cautiously discussed and some propositions for the future of H. pylori vaccines are outlined.Graphical Abstract: Keywords: Helicobacter pylori vaccines, antigen, adjuvant, delivery system, clinical trials

Fangfang Xu,1,&ast; Lijun Shen,2,&ast; Yongguang Yang,2 Limin Kong,3 Wufan Zu,4 Dandan Tian,5 Xuanchao Cao,1 Gairong Huang1 1Key Laboratory of Geriatrics, Institute of Geriatrics, Department of Geriatric Medicine, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Clinical Medical Research Center, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 3Department of General Medicine, Xinxiang Medical University, the Sixth People’s Hospital of Zhengzhou, Zhengzhou, People’s Republic of China; 4Department of Immunology, School of Basic Medical Science, Xinxiang Medical University, Xinxiang, People’s Republic of China; 5Department of Hypertension, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gairong Huang; Fangfang Xu, Email gaironghuang163@163.com; xffxff0924@163.omBackground: ANGPTL3, 4 and 8 have been reported to be involved in the regulation of lipid and glucose metabolism. The aim of this study was to investigate the expression of ANGPTL3, 4, 8 in hypertensive patients with or without overweight/obesity, T2D, and hyperlipidemia, and the possible association between their expression and the status of the aforementioned comorbidities.Methods: Plasma levels of ANGPTL3, 4, and 8 in 87 hospitalized patients with hypertension were measured using ELISA kits. Associations between circulating ANGPTLs levels and the most common additional cardiovascular risk factors were assessed using multivariate linear regression analyses. Pearson’s correlation analysis was used to examine the association between ANGPTLs and clinical parameters.Results: In the context of hypertension, (1) although not statistically significant, circulating ANGPTL3 levels were higher in the overweight/obese group than in the normal weight group; (2) circulating levels of ANGPTL3 and ANGPTL8 were significantly lower in patients with T2D than in non-diabetic patients; (3) circulating ANGPTL3 levels were significantly higher in the hyperlipidemic group than in the non-hyperlipidemic group. ANGPTL3 was associated with T2D and hyperlipidemia status, whereas ANGPTL8 was independently associated with T2D status. In addition, circulating ANGPTL3 levels were positively correlated with TC, TG, LDL-C, HCY, and ANGPTL8, and circulating ANGPTL4 levels were positively correlated with UACR and BNP.Conclusion: Changes in circulating ANGPTL3 and ANGPTL8 levels have been observed in hypertensive patients with the most common additional cardiovascular risk factors, suggesting a role in the common comorbidities of hypertension and cardiovascular disease. Hypertensive patients with overweight/obesity or hyperlipidemia may benefit from therapies targeting ANGPTL3.Keywords: angiopoietin-like proteins, hypertension, cardiovascular risk factors, overweight/obesity, type 2 diabetes, hyperlipidemia

Ziran Wang,1 Jintu Chen,2 Jingjing Song,3 Lingjun Kong,1 Xuanzhi Wang,4 Tengda Xu,5 Songbai Lin,5 Yaling Dou1 1Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Department of Clinical Laboratory, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian, People’s Republic of China; 3Department of Clinical Laboratory, Anhui Provincial Maternal and Child Health Hospital, Hefei, Anhui, People’s Republic of China; 4Department of Medical Laboratory, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 5Department of Health Management, Peking Union Medical College Hospital, Beijing, People’s Republic of ChinaCorrespondence: Yaling Dou, Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China, Email douyl@pumch.cnObjective: To determine the plasminogen activator inhibitor-1 (PAI-1) 4G/5G (rs1799889) genotype of the subjects in a robust detection method and to explore the association of the PAI-1 4G/5G polymorphism with susceptibility to diabetes mellitus (DM) and hypertension (HTN) as well as clinical characteristics.Methods: This study recruited 208 patients (68 patients were diagnosed with DM, 70 patients with HTN and 70 patients with DM combined with HTN) and 132 healthy controls (HC). A subset of the population was selected to evaluate the accuracy of the Real-time PCR (RT-PCR) method for detecting PAI-1 4G/5G polymorphism by using the sequencing method as the gold standard. Furthermore, the association of the PAI-1 4G/5G polymorphism with genetic susceptibility to DM and HTN was explored. Moreover, variations in clinical characteristics among individuals with various PAI-1 genotypes were also analyzed in the DM group, the HTN group and the DM+HTN group.Results: There was a high concordance between the RT-PCR method and the sequencing method in determining the PAI-1 4G/5G polymorphism. No association was observed between the PAI-1 4G/5G polymorphism and susceptibility to DM, HTN and DM+HTN, respectively. There were no statistical differences in all study indicators among individuals that carrying various genotypes in the HC group. There were several variations in clinical characteristics among individuals harboring different PAI-1 4G/5G genotypes in the DM group, the HTN group and the DM+HTN group.Conclusion: The RT-PCR method can accurately identify the PAI-1 4G/5G genotype in different individuals. The PAI-1 4G/5G polymorphism may not be associated with genetic susceptibility to DM, HTN and DM+HTN, but differences in clinical characteristics among individuals with various genotypes may provide a reference for disease assessment and personalized treatment of patients.Keywords: diabetes mellitus, hypertension, plasminogen activator inhibitor-1, gene polymorphism

Lingchao Kong,1,2,* Lingling Gao,1,2,* Hong Zhang,1,2 Xin Wang,1,2 Jun Zhang1,2 1Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun Zhang, Department of Anesthesiology, Shanghai Cancer Center, Fudan University and Department of Oncology, Shanghai Medical College, Fudan University, No. 270 Dong’An Road, Xuhui District, Shanghai, 200032, People’s Republic of China, Tel +86-21-64175590, Fax +86-21-64174774, Email snapzhang@aliyun.comPurpose: This study aimed to investigate whether preoperative computerized tomography-guided hookwire localization-associated pain could affect acute and chronic postsurgical pain (CPSP) in patients undergoing video-assisted thoracoscopic surgery (VATS).Methods: We enrolled 161 adult patients who underwent elective VATS; sixty-nine patients experienced hookwire localization (Group A) and 69 did not (Group B). Group A was further subdivided into the multiple localization group (n=35, Group Amultiple) and the single localization group (n=34, Group Asingle) according to the number of hookwires. The numerical rating scale (NRS) was used preoperatively, during recovery at the post-anesthesia care unit (PACU), and the first two days, 3 and 6 months postoperatively. Furthermore, multivariate regression analysis was used to identify the risk factors associated with CPSP. The postoperative adverse events, length of hospital stay, and satisfaction in pain management were also recorded.Results: The incidence and severity of acute postoperative pain were similar between Group A and Group B (p > 0.05). The incidence (56.5% vs 30.4%, p = 0.002) and the NRS scores (2.0 [2.0– 3.0] vs 1.0 [1.0– 2.0], p = 0.011) for CPSP were significantly higher in Group A than in Group B at 3 months postoperatively. On subgroup analysis, compared with Group Asingle, the intensity of CPSP (2.0 [2.0– 3.0] vs 2.0 [1.0– 2.0], p = 0.005) in Group Amultiple was slightly higher at 3 months postoperatively. Conversely, the CPSP incidence (60.0% vs 29.4%, p = 0.011) was significantly higher at 6 months postoperatively in Group Amultiple. The multivariate regression analysis further validated hookwire localization as a risk factor for CPSP (odds ratio: 6.199, 95% confidence interval 2.049– 18.749, p = 0.001). Patient satisfaction relating to pain management at 3 months postoperatively was lower in Group A (p = 0.034).Conclusion: The preoperative pain stress of hookwire localization increased the incidence and intensity of CPSP rather than acute pain at 3 months postoperatively, especially in patients with multiple hookwires.Keywords: chronic postsurgical pain, postoperative acute pain, hookwire localization, video-assisted thoracoscopic surgery, lung cancer

BaoPing Luo,1 Ying Zhang,2 LingXia Kong,3 YanHong Zhao,4 MeiJin Yuan1 1Department of Nursing, The First Affiliated Hospital of Hebei North University, Zhangjiakou, People’s Republic of China; 2Education Office, The First Affiliated Hospital of Hebei North University, Zhangjiakou, People’s Republic of China; 3Department of Breast Surgery, The First Affiliated Hospital of Hebei North University, Zhangjiakou, People’s Republic of China; 4Department of Operation Room, The First Affiliated Hospital of Hebei North University, Zhangjiakou, People’s Republic of ChinaCorrespondence: BaoPing Luo, Department of Nursing, The First Affiliated Hospital of Hebei North University, No. 12 Changqing Road, Qiaoxi District, Zhangjiakou, 075000, People’s Republic of China, Tel +86-0313-8043526, Fax +86-0313-8043535, Email luobaoping2022@163.comObjective: To explore the establishment of an objective, standardised and operable comprehensive evaluation and assessment system for clinical nurses based on the support of an information technology platform and to realise the assessment management of tier nurses before and after promotion.Methods: By reviewing the literature and combining the findings with the actual situation of nursing work in hospitals, the clinical nurse comprehensive evaluation assessment criteria were designed and assessed for nurses at different levels in terms of their medical ethics, attendance, performance, theoretical study, professional skills and teaching and then supported by the information technology platform to achieve timely and quick assessment.Results: In 2021, 999 nurses out of the 1037 clinical nurses in our institution completed the assessment. Overall, 888 passed the assessment, 111 failed, and 38 did not complete the assessment due to various reasons. Moreover, 367 nurses were promoted based on the comprehensive evaluation assessment results, and the 111 nurses who failed the assessment had their promotion delayed in accordance with the regulations.Conclusion: The assessment indexes of the clinical nurse comprehensive evaluation assessment system are objective, scientific and operable. They could be used as the basis for nurse promotion and assessment management after promotion and could become a powerful aid for nurse promotion management to realise closed-loop management of nurse hierarchy. The support of information platform makes the operation of the assessment system faster and more convenient and improves the management efficiency.Keywords: information platform, nurse hierarchy, evaluation and assessment system, nursing management

Jingwen Zhang,1 Linglingli Kong,2 Juan Ni1 1Department of Anesthesiology, West China Second University Hospital, Sichuan University, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, Sichuan, People’s Republic of China; 2Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Juan Ni, Department of Anesthesiology, West China Second University Hospital, Sichuan University, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, No. 20, Section 3, South of Renmin Road, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86 18180609890, Fax +86 2885503752, Email nijuankiki@163.comPurpose: This study aimed to test the effect of different doses of intravenous lidocaine on the median effective dose (ED50) and 95% effective dose (ED95) of propofol-induction dose and identify the optimal dose.Patients and Methods: Patients undergoing first-trimester uterine aspiration were screened and randomly enrolled into the following groups: saline (L0), 0.5 mg/kg lidocaine (L0.5), 1.0 mg/kg lidocaine (L1.0), and 1.5 mg/kg lidocaine (L1.5). Anesthesia was induced with 1.0 μg/kg fentanyl. Prepared lidocaine or saline solution was injected later according to allocation, followed by propofol. The dose of propofol for each patient was determined using the up-and-down sequential study design. The primary end point was the ED50 and ED95 of the propofol-induction dose. The total propofol doses, awakening time, and adverse events were recorded.Results: The ED50 (95% confidence interval) of propofol was significantly lower in groups L1.0 and L1.5 than group L0 (1.6 [1.5– 1.7] mg/kg and 1.8 [1.6– 1.9] mg/kg, versus 2.4 [2.3– 2.5] mg/kg, respectively; p< 0.001). There was no significant difference in ED50 between groups L1.0 and L1.5 (p> 0.05). However, surprisingly, the ED50 was significantly higher in group L0.5 than L0 (2.8 [2.6– 3.0] mg/kg vs 2.4 [2.3– 2.5] mg/kg; p< 0.05). The total doses of propofol in groups L1.0 and L1.5 were lower than those in groups L0 and L0.5 (p< 0.05). The systolic blood pressure (SBP) decline after anesthesia induction in group L0.5 was greater than that in group L0 (p< 0.01). The incidence of respiratory depression in group L0.5 was greater than that in groups L0 and L1.0 (p< 0.05).Conclusion: In patients who underwent first-trimester uterine aspiration, intravenous lidocaine 1.0 mg/kg prior to propofol injection significantly reduced the ED50 of propofol induction dose without severe side effects, equivalent to the effect of 1.5 mg/kg dose. We recommend 1.0 mg/kg as the optimal dose.Keywords: lidocaine, propofol, uterine aspiration, median effective dose

Hongbao Liang,1– 3,&ast; Chenghong Sun,2,3,&ast; Zhong Feng,2– 4 Xianzhen Wang,2 Lingpeng Kong,2,3 Feng Zhu,2,3 Jingchun Yao,2,3 Xiaomei Yuan,3 Zhong Liu,2,3 Guimin Zhang,2,3 Feng Li1 1School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 2Center for Drug Safety Evaluation, Shandong New Time Pharmaceutical Co., Ltd., Linyi, People’s Republic of China; 3State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Lunan Pharmaceutical Group Co., Ltd., Linyi, People’s Republic of China; 4School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Li, Shandong University of Traditional Chinese Medicine, No. 4655 Daxue Road, Jinan, 250355, People’s Republic of China, Tel +86 139 6914 1796, Email 13969141796@163.com Guimin Zhang, Lunan Pharmaceutical Group Co., Ltd., State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, No. 209 Hongqi Road, Linyi, 276006, People’s Republic of China, Tel +86 539-5019206, Email lunanzhangguimin@yeah.netBackground: To improve the dissolution and bioavailability of the component-based Chinese medicine of Ginkgo biloba leaves (GBCCM), a novel nanocrystalline solid dispersion of GBCCM (GBCCM NC-SD) was first prepared.Methods: GBCCM mainly containing high pure flavonoid aglycones (FAs) and terpenoid lactones (TLs) was used as the model drug. PVP K30 and SDS were used as solubilizers, combined stabilizers and carriers, and GBCCM NC-SD was prepared by high-pressure homogenization combined with freeze-dryer. Morphology and crystal characteristic of GBCCM NC-SD were analyzed. The dissolution and bioavailability evaluation were performed to investigate the feasibility of GBCCM NC-SD by in vitro dissolution and in vivo integrated pharmacokinetic models.Results: After homogenizing for 30 cycles under the pressure of 650 bar and freeze-drying, GBCCM NC-SD with uniform quality would be obtained. The particle size, PDI and zeta potential were found to be 335.9 ± 32.8 nm, 0.29 ± 0.02 and − 28.4 ± 0.7 mV respectively. Based on charged aerosol detector (CAD) technology, a new chromatographic method for simultaneous detection of eight components in GBCCM was developed. In vitro drug release study showed that the cumulative dissolution of FAs and TLs in GBCCM NC-SD increased from 12.77% to 52.92% (P < 0.01) and 90.91% to 99.21% (P < 0.05) respectively. In comparison with physical mixture of GBCCM and stabilizer (PM), the integrated pharmacokinetics AUC0-t of FAs and TLs in GBCCM NC-SD were significantly increased (P < 0.05), and the T1/2 of TLs was also significantly prolonged (P < 0.05).Conclusion: This study demonstrated that novel GBCCM NC-SD was prepared using Polyvinylpyrrolidone K30 (PVP K30) and Sodium dodecyl sulfate (SDS) as a synergetic stabilizer and also provided a feasible way to improve the dissolution and oral bioavailability of poorly soluble candidate antihypertensive drugs.Keywords: Ginkgo biloba, flavonoid aglycones, terpenoid lactones, nanocrystalline solid dispersion, integrated pharmacokinetics, charged aerosol detector

Wei Xie,1 Yongqiang Shu,1 Xiang Liu,1 Kunyao Li,1 Panmei Li,1 Linghong Kong,1 Pengfei Yu,2 Ling Huang,1 Ting Long,1 Li Zeng,1 Haijun Li,1,3 Dechang Peng1,3 1Medical Imaging Center, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 2Big Data Research Center, The Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 3PET Center, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of ChinaCorrespondence: Dechang Peng; Haijun Li, The First Affiliated Hospital of Nanchang University, No. 17, Yongwai Zheng Street, Donghu District, Nanchang City, Jiangxi Province, 330006, People’s Republic of China, Tel +86 79186427560 ; +86 18970025300, Email pengdcdoctor@163.com; haijunli1990@163.comPurpose: This study aimed to explore the alterations in spontaneous brain activity in obstructive sleep apnea (OSA) using percent amplitude of fluctuation (PerAF) and investigate the relationship between abnormal spontaneous brain activity and cognitive impairment in OSA.Patients and Methods: Overall, 52 patients with moderate to severe OSA and 61 healthy controls (HCs) were eventually enrolled in this study. All participants underwent resting-state functional magnetic resonance (rs-fMRI) and T1-weighted imaging. The PerAF was calculated and compared between patients with OSA and HCs, with voxel level P < 0.001 and cluster level P < 0.05 corrected with Gaussian Random Field was be considered statistically different. A partial correlation analysis was used to assess the relationship between altered PerAF and clinical assessments in patients with OSA.Results: Compared to HCs, patients with OSA had significantly lower PerAF values in the right rectal gyrus and left superior frontal gyrus, but higher PerAF values in the right cerebellum posterior lobe and left middle frontal gyrus. The PerAF values of some specific regions in patients with OSA correlated with sleep efficiency and Montreal Cognitive Assessment scores. Additionally, support vector machine analysis showed that PerAF values in all differential brain regions could differentiate patients with OSA from HCs with good accuracy.Conclusion: Specific brain areas in OSA patients may exhibit aberrant neuronal activity, and these anomalies may be linked to decreased cognitive performance. This discovery offers fresh perspectives on these patients’ neurocognition.Keywords: cerebellum, cognitive function, frontal lobe, functional magnetic resonance imaging, percent amplitude of fluctuation

Zhengshuo Jin,1,2,&ast; Zhouxian Pan,2,&ast; Ziran Wang,3,&ast; Lingjun Kong,3 Min Zhong,3 Yongshi Yang,2 Yaling Dou,3 Jin-Lyu Sun2 1Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, People’s Republic of China; 2Allergy Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yaling Dou; Jin-Lyu Sun, Email douyl@pumch.cn; sunjinlv@pumch.cnBackground and Objective: Asthma and allergic rhinitis have been reported to be strongly associated with genetic factors. The aim of this study was to evaluate the accuracy of the TaqMan-MGB (minor groove binder) qPCR method for detecting CYSLTR1 rs320995 (T927C) and GSDMB rs7216389 (G1199A) gene polymorphisms as well as to explore the association of CYSLTR1 rs320995 and GSDMB rs7216389 polymorphisms with genetic susceptibility of Chinese patients with asthma and allergic rhinitis.Methods: In this study, 310 asthmatic patients and 60 healthy individuals were recruited in Peking Union Medical College Hospital. The CYSLTR1 rs320995 (T927C) and GSDMB rs7216389 (G1199A) gene polymorphisms in each group were analyzed by TaqMan-MGB qPCR and DNA sequencing which was regarded as the gold standard. After the validation of this method, additional 71 patients with allergic rhinitis and 72 patients with asthma combined with allergic rhinitis were selected and tested by using TaqMan-MGB qPCR.Results: The TaqMan-MGB qPCR results were fully consistent with DNA sequencing results (Kappa = 1, P< 0.001). In addition, the results of the TaqMan-MGB qPCR assay were not affected by bilirubin and lipids. We found differential distribution of CYSLTR1 rs320995 genotypes in female patients with asthma combined with allergic rhinitis (χ2=6.172, P=0.046, statistical power = 0.591). Specifically, the TT genotype is more frequent in women suffering from asthma with allergic rhinitis, whereas the TC genotype is more prevalent in healthy women. However, no such associations were observed in the GSDMB rs7216389 polymorphism.Conclusion: We have established a reliable TaqMan-MGB qPCR method for the detection of CYSLTR1 rs320995 and GSDMB rs7216389 polymorphisms. Moreover, the CYSLTR1 rs320995 polymorphism may be associated with genetic susceptibility of Chinese female patients with asthma and allergic rhinitis. Multicenter studies with larger sample sizes are required in the future.Keywords: asthma, allergy treatment, gene polymorphism, CYSLTR1, GSDMB

Junyuan Deng, Yujie Guo, Jichun Gu, Jiali Du, Lei Kong, Boan Tao, Ji Li, Deliang Fu Department of Pancreatic Surgery, Pancreatic Disease Institute, Huashan Hospital, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Ji Li, Department of Pancreatic Surgery, Pancreatic Disease Institute, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China, Email liji@huashan.org.cnPurpose: Pancreatic cyst neoplasm (PCN) is a precursor of pancreatic cancer. Previous studies reported PCN was often concurrent with diabetes. We aim to examine the association between diabetes with PCN malignancy and to detect the potential role of diabetes in PCN management and treatment.Patients and Methods: A total of 224 patients who were diagnosed with the three major types of PCN (IPMN, MCN, and SCN) and underwent surgical resection were selected. Patients were divided into three groups (normal group, new-onset diabetes group (NODM) (< 4years), and long-standing diabetes group (LSDM) (> 4years)) according to diabetic history and diagnostic time interval. Diabetes, fast blood glucose level, HbA1c, and insulin resistance level were measured. Malignant PCN (mPCN) radiological features (worrisome features and high-risk stigmata) were analyzed. Pathological features (PCN type, dysplasia grade, tumor stage, and tumor volume) and immunohistology of Ki67 and SMAD4 were performed. Diagnostic efficacy of each variable was determined by the ROC curve. mPCN diagnosis was the main outcome in diagnostic prediction and overall survival as the glucose controlling outcome variables.Results: Diabetes groups (NODM and LSDM) showed difference with the normal group in age, weight loss, malignancy, CA19-9 value, CEA value, Ki-67 value, tumor volume, pathological grade, and a lowered pancreatic fistula risk. NODM was related to insulin resistance, weight loss, and SMAD4 mutation. NODM (87.3%) and high insulin resistance rate (93.6%) significantly increased the sensitivity of radiological evidence-based mPCN diagnosis. Moreover, long-standing diabetes and elevated HbA1c led to reduced survival in mPCN patients than the normal PCN group. Anti-diabetic drugs showed limited influence on PCN malignancy and tumor volume.Conclusion: NODM in PCN patients was associated with malignancy, insulin resistance, weight loss, and SMAD4 mutation. Prediabetic status and NODM diagnosis enhanced the diagnostic accuracy of radiological standards (worrisome features and high-risk stigmata). Stable glucose surveillance is necessary for mPCN patients’ survival.Keywords: pancreatic cyst neoplasms, diabetes mellitus, pancreatic cancer, cancer diagnostic model

Shuangqing Chen,1,2 Shicheng Liu,1 Siwei Xu,3 Shumin Cao,4,5 Zhaohui Han,1,2 Lingxin Kong,1,5 Dahu Ren,1,5 Guochen Duan6 1Department of Thoracic Surgery, Hebei General Hospital, Shijiazhuang, 050057, People’s Republic of China; 2Graduate School, Hebei North University, Zhangjiakou, 075000, People’s Republic of China; 3Department of Thoracic Surgery, The First Hospital of Hebei Medical University, Shijiazhuang, 050057, People’s Republic of China; 4Department of Oncology, Hebei General Hospital, Shijiazhuang, 050057, People’s Republic of China; 5Graduate School, Hebei Medical University, Shijiazhuang, 050011, People’s Republic of China; 6Department of Thoracic Surgery, Children’s Hospital of Hebei Province, Shijiazhuang, 050000, People’s Republic of ChinaCorrespondence: Guochen Duan, Children’s Hospital of Hebei Province, No. 133 Jianhua South Street, Yuhua District, Shijiazhuang, 050000, People’s Republic of China, Tel +8613513380703, Email duanguoc@126.com Shicheng Liu, Hebei General Hospital, No. 348, Heping West Road, Xinhua District, Shijiazhuang, 050000, People’s Republic of China, Tel +861309388955, Email 1309388955@qq.comBackground: The routine clinical nutritional and inflammatory indicators such as serum albumin, total cholesterol and lymphocytes have been widely investigated in the prognosis of small cell lung cancer (SCLC). The Naples prognostic score (NPS), based on nutritional and inflammatory status, has been identified as a prognostic impactor in several malignancies. However, the prognostic role of NPS in SCLC has not been elucidated. This study aims to evaluate the prognostic effect of NPS in SCLC patients.Patients and Methods: Patients with SCLC were recruited at Hebei General Hospital between April 2015 and August 2021. Pretreatment clinical and laboratory data were obtained. Participants were assigned into three groups according to NPS (group 0: NPS=0, group 1: NPS=1 or 2, group 2: NPS=3 or 4). Kaplan-Meier and Cox regression analysis were performed to assess the prognostic significance of NPS. The RMS package in R software was used to draw the nomogram predictive model.Results: A total of 128 patients were enrolled. The median progression-free survival (PFS) and overall survival (OS) was 7.2 and 12.3 months, respectively. The median PFS and OS was 12.3 vs 19.8 months, 7.6 vs 14.1 months and 6.0 vs 8.45 months for the three groups respectively. There were significant differences in both OS and FPS among the three groups. Survival analysis showed that NPS was significantly correlated with both OS and PFS (P< 0.05). Lower NPS is associated with longer OS and PFS. Multivariate analysis showed that NPS has an independent prognostic impact on OS (P< 0.05). The nomogram predictive model showed that NPS has good predictive power for survival rates.Conclusion: NPS is an independent prognostic factor for OS in SCLC patients. Low NPS may predict longer OS. Therefore NPS plays a vital role in the nomogram predictive model of survival rates in SCLC patients.Keywords: small cell lung cancer, Naples prognostic score, prognostic factor, nomogram predictive model

Peter L Latchman,1 Qin Yang,2 Lingsong Kong,3 Hengbo Zhang,4 Josephine Sebagisha,5 Ronald E De Meersman6 1Department of Health and Movement Sciences, Southern Connecticut State University, New Haven, CT, USA; 2School of Health Promotion and Kinesiology, Texas Woman’s University, Denton, TX, USA; 3Department of Kinesiology, University of Massachusetts, Amherst, MA, USA; 4College of Physical Education, Hunan First Normal University, Changsha, People’s Republic of China; 5Clinical Department St. James School of Medicine, Chicago, IL, USA; 6Department of Rehabilitation and Regenerative Medicine, Columbia University, New York, NY, USACorrespondence: Peter L Latchman, Department of Health and Movement Sciences, Southern Connecticut State University, 501 Crescent Street, New Haven, CT, 06515, USA, Tel +1 203-392-6081, Fax +1 203-392-6093, Email latchmanp1@southernct.eduPurpose: Measuring heart rate recovery (HRR) holds valuable cardiovascular information and requires minimal technical skill and cost. Understanding the associations between HRR and more robust cardiovascular indicators, such as central systolic blood pressure (CSBP), can provide valuable cardiovascular information with less involvement. CSBP is a strong predictor of certain cardiovascular diseases. The study aims to examine the association between measures of HRR and CSBP and the augmentation index (AIx) in a group of young, healthy individuals and based on sex.Participants and Methods: One-hundred and seven participants (men – 55, women – 52) were measured for HRR at one minute (HRR1) and two minutes (HRR2) after maximum oxygen consumption (VO2max) testing, CSBP, and the AIx at a heart rate of 75 beats∙min− 1 (AIx@75).Results: The Pearson correlation indicated no association between HRR1, HRR2, and CSBP in men and women combined: r = 0.06, P = 0.53; r = 0.05, P = 0.59, respectively, or based on sex: men = r = 0.01, P = 0.95; r = 0.04, P = 0.79, respectively, and women = r = − 0.05, P = 0.75; r = − 0.09, P = 0.52, respectively. However, there were associations between HRR1 and AIx@75 in men and women combined: r = − 0.37, P < 0.001, and based on sex: men = r = − 0.31, P = 0.02, and women = r = − 0.38, P < 0.01.Conclusion: Measures of HRR were not associated with CSBP in a combined group of young men and women or based on sex. Most measures of HRR, especially those established by parasympathetic nervous activity, were associated with lower AIx@75. Though measures of HRR might be good indicators of cardiovascular disease, they might not be good indicators of CSBP in young, healthy individuals.Keywords: heart rate recovery, central blood pressure, central systolic blood pressure, augmentation index, sex

Lingwei Kong,1,&ast; Yu Wang,1,&ast; Hairu Ji,2 Zhehong Li,1 Yupeng Sun,1 Yanchao Liu,1 Sheng Cao,1 Jingxin Zhao,1 Litao Shi,1 Yu Jin1 1Department of Orthopedics, The Affiliated Hospital of Chengde Medical College, Chengde, Hebei, 067000, People’s Republic of China; 2Pathology Teaching and Research Section, Chengde Medical College, Chengde, Hebei, 067000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu Jin Tel +86 13832428328Email 358620793@qq.comAbstract: In recent years, hypervirulent Klebsiella pneumoniae (hvKp) has received greater attention. It mainly infects diabetic patients and typically causes a hepatic abscess. Here, we report a case of hvKp that caused forearm muscle and soft tissue infection in addition to bacteremia, hepatic and pulmonary abscess, and hyperglycemia. The patient’s condition stabilized after comprehensive treatment. She eventually recovered and was discharged after several debridement and flap operations. At 9 months of follow-up, no signs of infectious recurrence were noted, and the hyperglycemia resolved. Here, we detail important clinical features of a severe hvKp case diagnosed in an otherwise healthy individual. This report underscores the potential of hvKp to cause deep tissue infection and present with clinical symptoms similar to gas gangrene. Symptom onset in the setting of hvKp infection is usually gradual and misdiagnosis is common. The diagnosis of hvKp should be routinely considered in the clinical setting, and be strongly suspected when presenting with characteristic epidemiological, clinical and laboratory features. Although diabetes is a predisposing factor to hvKp infection, hyperglycemia appeared to manifest as a consequence of hvKp infection in this patient.Keywords: hypervirulent K. pneumoniae, hvKp, soft tissue infection, liver abscess, lung abscess, diabetes

Haijun Li,1,2 Lan Li,3 Linghong Kong,1 Panmei Li,1 Yaping Zeng,1 Kunyao Li,1 Wei Xie,1 Yongqiang Shu,1 Xiang Liu,1 Dechang Peng1,2 1Medical Imaging Center, The First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, People’s Republic of China; 2PET Center, The First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, People’s Republic of China; 3Jiangxi Provincial Institute of Parasitic Diseases Control, Nanchang City, Jiangxi Province, People’s Republic of ChinaCorrespondence: Dechang PengThe First Affiliated Hospital of Nanchang University, No. 17, Yongwai Zheng Street, Donghu District, Nanchang City, 330006, Jiangxi Province, People’s Republic of ChinaTel +86 79186427560Email pengdcdoctor@163.comPurpose: Previous studies have demonstrated abnormal local spontaneous brain activity in the conventional frequency bands (0.01– 0.08 Hz) in obstructive sleep apnea (OSA). However, it is not clear whether these abnormalities are associated with the specific frequency band of low-frequency oscillations or whether it can be improved with a continuous positive airway pressure (CPAP) treatment. This study aimed to investigate the regional homogeneity (ReHo) in specific frequency at baseline (pre-CPAP) and after one month of CPAP adherence treatment (post-CPAP) in OSA patients.Methods: Twenty-one patients with moderate-to-severe OSA and 21 age- and sex-matched healthy controls (HCs) were included in the final analysis. ReHo was calculated in three different frequency bands (typical frequency band: 0.01– 0.1 Hz; slow-5 band: 0.01– 0.027 Hz; slow-4 band: 0.027– 0.073 Hz), respectively. A partial correlational analysis was performed to assess the relationship between altered ReHo and clinical evaluation.Results: OSA patients revealed increased ReHo in the brainstem, bilateral inferior temporal gyrus (ITG)/fusiform, and right-cerebellum posterior lobe (CPL), and decreased ReHo in the bilateral inferior parietal lobule (IPL), right superior temporal gyrus (STG), and left precentral gyrus (PG) compared to HC groups in different frequency bands. Significantly changed ReHo in the bilateral middle temporal gyrus (MTG), PG, medial frontal gyrus (MFG), supplementary motor area (SMA), CPL, IPL, left superior frontal gyrus (SFG), ITG, MTG, and right STG were observed between post-CPAP and pre-CPAP OSA patients, which was associated with specific frequency bands. The altered ReHo in specific frequency bands was correlated with Montreal cognitive assessment score, Epworth sleepiness scale, and apnea hypopnea index in pre-CPAP OSA patients.Conclusion: These findings indicate that OSA has frequency-related abnormalities of spontaneous neural activity before and after short-term CPAP treatment, which might contribute to a better understanding of local neural psychopathology and may serve as potential biomarkers for clinical CPAP treatment.Keywords: obstructive sleep apnea, treatment, frequency band, local connectivity, resting-state functional magnetic resonance imaging

Zhenzhen Liu,1 Xiao Ma,2 Saif Ullah,1 Jitao Song,2 Lingjian Kong,1 Deliang Li,1 Chao Pan,2 Bingrong Liu1 1Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Gastroenterology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of ChinaCorrespondence: Bingrong LiuDepartment of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jianshe Road, Zhengzhou, 450052, People’s Republic of ChinaTel/Fax +86-15713815559Email fccliubr@zzu.edu.cnPurpose: To evaluate the role of endoscopic retrograde appendicography for the diagnosis of acute appendicitis.Patients and Methods: We retrospectively analyzed 33 patients (20 men and 13 women, average age 44± 18 years) with suspected acute appendicitis between December 2016 and November 2018. Endoscopic direct-vision imaging or fluoroscopic endoscopic retrograde appendicography was performed to separate suspected acute appendicitis from actual acute appendicitis. The success rate, complications, and recurrence rate were recorded.Results: Acute appendicitis was ruled out by normal endoscopic retrograde appendicography in 8 (24%) and confirmed in 23 patients (70%). In 2 patients (6%), appendiceal orifice cannulation failed. Colonoscopic findings in acute appendicitis were mucosal hyperemia and edema of appendiceal orifice (83%), outpouring of pus from the appendiceal orifice (74%), and swollen cecal mucosa (61%). Appendicograpic findings were either normal or in acute disease showed diffuse luminal dilation (diameter: 0.8± 0.4 mm), partial stenosis (43%), stiffness or inflexibility (87%) and filling defects (22%). There were no complications during or after follow-up for a median of 13 months (IQR: 9– 24 months).Conclusion: Endoscopic retrograde appendicography appears to be a reliable and safe method to confirm or exclude the diagnosis of acute appendicitis and prevent unnecessary appendectomy.Keywords: acute appendicitis, endoscopic retrograde appendicography, diagnosis, appendicography

Guangyao Ye,1,* Chunyan Lin,1,* Yu Zhang,1 Zihan Ma,2 Yuebo Chen,1 Lingsi Kong,1 Liyong Yuan,1 Tao Ma3 1Department of Anesthesiology, Ningbo No.6 Hospital, Ningbo, 315040, People’s Republic of China; 2School of Medicine, Ningbo University, Ningbo, 315211, People’s Republic of China; 3Department of Anesthesiology and Pharmacology, Xuzhou Medical University, Xuzhou, 221000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liyong YuanDepartment of Anesthesiology, Ningbo No.6 Hospital, Ningbo, 315040, People’s Republic of ChinaEmail yuanl1973@yeah.netTao MaDepartment of Anesthesiology and Pharmacology, Xuzhou Medical University, Xuzhou, 221000, People’s Republic of ChinaEmail Matao201006@126.comContext: Quercetin (que) is one abundant flavonol with a variety of biological activities. Previous studies have shown quercetin can reduce neuropathic pain in rats with chronic constriction injury (CCI).Objective: To evaluate the effects of quercetin on neuropathic pain in CCI model and explore its underlying mechanism in vivo.Materials and Methods: CCI model was established by ligating the sciatic nerve of right leg on the SD rats. They were divided into ten groups: sham group, CCI model, sham+ que, CCI+ que group (30, 60, 120 mg/kg), CCI+ AICAR, CCI+ que+ compound C, CCI+etoricoxib, and the control group. They were administered for 28 days, and were performed the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) during the experiment. At the end of the experiment, sciatic nerves and spinal cord segments of rats were collected, ELISA detected the expression of inflammatory factors, detected the microglia and astrocytes with fluorescence, and Western blot detected AMPK/MAPK pathway.Results: Que could increase the MWT of CCI rats, improve the TWL of plantar, and reduce the inflammatory cells at the ligation site of the sciatic nerve. Also, que could reduce the levels of TNF-α, IL-6, and IL-1β. Western blotting results showed that p-38 MAPK, p-ERK, and p-JNK were activated in the spinal dorsal horn of CCI model group. After treatment with que and AMPK agonists, the phosphorylation levels of related proteins were inhibited. In addition, the analgesic effect of que was abolished when the AMPK inhibitor was added.Discussion and Conclusion: Quercetin alleviated the inflammatory response of sciatic nerve and spinal dorsal horn in rats induced by CCI. Quercetin alleviates neuralgia in CCI rats by activating AMPK pathway and inhibiting MAPK pathway and its downstream targets, p-38, p-ERK, and p-JNK.Keywords: quercetin, neuropathic pain, AMPK, MAPK, CCI

Huimin Zhao,1 Bei Wu,2 Linglin Kong,1 Junyao Fan,1 Quan Wang,1 Jie Li,1 Jing Mao1 1School of Nursing, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Rory Meyers College of Nursing and NYU Aging Incubator, New York University, New York, NY, USACorrespondence: Jie Li; Jing MaoSchool of Nursing, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Qiaokou District, Wuhan 430030, People’s Republic of ChinaTel +86 18971097091; +86 13317135988Fax +86 02783692635; +86 02783692657Email Lijie@hust.edu.cn; maojing@hust.edu.cnPurpose: This cross-sectional study aimed to describe personal growth and to analyze its associated factors among patients with chronic obstructive pulmonary disease (COPD) in China.Patients and Methods: A total of 364 Chinese COPD hospitalized patients were included in the study between November 2016 and April 2018. Participants provided demographic information and completed the Growth Through Uncertainty Scale (GTUS), the Multidimensional Scale of Perceived Social Support (MSPSS), and the modified Medical Research Council dyspnoea scale (mMRC).Results: The mean total score on the GTUS was 142.34 (SD = 7.61). The multiple linear regression analysis showed that factors including educational level, average monthly income, social support, and breathlessness can influence personal growth (R2 = 0.427, F = 44.420, p < 0.001), explaining 42.7% of the variance.Conclusion: COPD patients tend to report a moderate level of personal growth in China. Educational level, average monthly income, social support, and breathlessness were significant factors associated with personal growth. Medical workers should be aware of the level of personal growth among COPD patients and make tailored interventions to facilitate COPD patients’ personal growth, such as increasing social support and decrease breathlessness.Keywords: breathlessness, China, COPD, personal growth, social support

Jie Zhang,1,* Zhongneng Xu,2,* Lianhua Kong,3,* Hong Gao,1 Yueming Zhang,1 Yulong Zheng,1 Yufeng Wan1 1Department of Respiratory Diseases, The Affiliated Huai’an Hospital of Xuzhou Medical University, Huai’an 203302, Jiangsu, People’s Republic of China; 2Department of Cardiothoracic Surgery, Huai’an Hospital Affiliated to Nanjing Medical College and Huai’an First People’s Hospital, Huai’an 223002, Jiangsu, People’s Republic of China; 3Department of Infectious Disease, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yufeng Wan; Yulong Zheng Tel +86 13776707363; +86 15805230282Email ggwanyufeng@163.com; ha183@163.comPurpose: The aim of this study was to investigate the role of miRNA-486-5p in chronic obstructive pulmonary disease (COPD) progression and the underlying molecular mechanisms.Materials and Methods: Aberrant miRNA expression profiles between smokers and nonsmokers, and those between COPD patients and normal subjects were analyzed using microarray datasets and reverse-transcriptase quantitative polymerase chain reaction (qPCR). Enzyme-linked immunosorbent assay was used to determine the levels of inflammatory cytokines in cell supernatants. Expression levels of inflammatory cytokines, HAT1, TLR4, and miR-486-5p, were determined using qPCR or Western blotting. Luciferase reporter assays and fluorescence in situ hybridization were used to confirm the regulatory interaction between miR-486-6p and HAT1.Results: miR-486-5p was significantly upregulated in the COPD and smoker groups compared to the control group, as demonstrated using bioinformatics analysis and validated using qPCR assay of alveolar macrophages and peripheral monocytes. Moreover, miR-486-5p expression was significantly correlated with the expression of IL-6, IL-8, TNF-α, and IFN-γ. Luciferase reporter assays confirmed that miR-486-5p directly targeted HAT1, and cellular localization showed that miR-486-5p and HAT1 were highly expressed in the cytoplasm. miR-486-5p overexpression led to a significant upregulation of TLR4 and a significant downregulation of HAT1. Inversely, miR-486-5p inhibition led to a significant downregulation of TLR4 and a significant upregulation of HAT1. HAT1 knockdown using siRNA significantly upregulated the expression of TLR4, IL-6, IL-8, TNF-α, and IFN-γ.Conclusion: miR-486-5p was differentially expressed in the alveolar macrophages of COPD patients. miR-486-5p overexpression may enhance the TLR4-triggered inflammatory response in COPD patients by targeting HAT1.Keywords: smoking, chronic obstructive pulmonary disease, miR-486-5p, toll-like receptor 4, histone acetyltransferase 1

Yu Cao,1,* Huajian Zhu,1,* Ruoyu He,2 Limin Kong,3 Jiaan Shao,1 Rangxiao Zhuang,2 Jianjun Xi,2 Jiankang Zhang1 1School of Medicine, Zhejiang University City College, Hangzhou, Zhejiang Province, 310015, People’s Republic of China; 2Department of Pharmaceutical Preparation, Hangzhou Xixi Hospital, Hangzhou, Zhejiang Province, 310023 People’s Republic of China; 3Department of Pharmacy, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang Province, 310003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianjun XiDepartment of Pharmaceutical Preparation, Hangzhou Xixi Hospital, Hangzhou, Zhejiang Province 310023, People’s Republic of ChinaEmail xjianjun@foxmail.comJiankang ZhangSchool of Medicine, Zhejiang University City College, Hangzhou, Zhejiang Province 310015, People’s Republic of ChinaEmail zjk0125@yeah.netAbstract : Proteasome is vital for intracellular protein homeostasis as it eliminates misfolded and damaged protein. Inhibition of proteasome has been validated as a powerful strategy for anti-cancer therapy, and several drugs have been approved for treatment of multiple myeloma. Recent studies indicate that proteasome has potent therapeutic effects on a variety of diseases besides cancer, including parasite infectious diseases, bacterial/fungal infections diseases, neurodegenerative diseases and autoimmune diseases. In this review, recent developments of proteasome inhibitors for various diseases and related structure activity relationships are going to be summarized.Keywords: proteasome inhibitor, infectious diseases, autoimmune diseases, neurodegenerative diseases, drugs

Ya Zhao,1 Peihuan Li,1 Xiang Wang,2 Luya Kong,3 Yan Wu,1 Xinchun Liu1 1Department of Clinical Psychology, Third Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 2Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 3School of Public Health, Changsha Medical University, Changsha, People’s Republic of ChinaCorrespondence: Xinchun LiuDepartment of Clinical Psychology, Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Yuelu District, Changsha, Hunan 410013, People’s Republic of ChinaTel +86-731-886-186-67Fax +86-731-888-619-10Email angelaliu23@sina.comBackground/Purpose: Maladaptive emotion regulation is a strong predictor of depression or anxiety. Behavioral emotion regulation has a direct influence on coping with negative emotion. Although it is interesting to explore more about the behavioral emotion regulation, most of the existing measures can not assess it separately. The Behavioral Emotion Regulation Questionnaire (BERQ) has made important gain in addressing conceptual confusion between cognitive and behavioral emotion regulation. As there is a lack of single and stable measure to assess behavioral emotion regulation in mainland China, we translated the BERQ into Chinese to fit this gap.Methods: We evaluated the psychometric properties of the Chinese version of the BERQ (BERQ-C) based on a sample of Chinese university students (n=816). Factor analysis was performed to assess the construct validity of the BERQ-C. To test its reliability and validity, all the participants were invited to complete BERQ-C, GAD-7, PHQ-9, and CERQ-C. Of the initial samples, 138 students participated in the second measurement with completing BERQ-C twice.Results: Confirmatory factor analysis supported the five-factor model. The internal consistence (Cronbach’s α = 0.71 ∼ 0.85), the split-half reliability (Spearman-Brown coefficient = 0.66 ∼ 0.85), and the test–retest stability (ICC = 0.55 ∼ 0.67) are all acceptable. The criterion-related validity is good.Conclusion: The BERQ-C is a promising instrument to assess behavioral emotion regulation among the Chinese university students. Future studies are needed to explore the questionnaire’s psychometric properties among wider range of population especially for patients.Keywords: emotion regulation, coping, assessment, Chinese university students

Liang Kong,1 Shi-meng Zhang,2 Jia-hao Chu,3 Xin-ze Liu,1 Lu Zhang,1 Si-yu He,1 Si-min Yang,3 Rui-jun Ju,3 Xue-tao Li1 1School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, People’s Republic of China; 2Department of Neurology, Linyi People’s Hospital, Linyi 276003, People’s Republic of China; 3Department of Pharmaceutical Engineering, Beijing Institute of Petrochemical Technology, Beijing 102617, People’s Republic of ChinaCorrespondence: Xue-tao LiSchool of Pharmacy, Liaoning University of Traditional Chinese Medicine, Shengming 1 Road 77, Double D Port, Dalian 116600, People’s Republic of ChinaTel +86411 8589 0170Fax +86411 8589 0128Email lixuetao1979@163.comRui-jun JuDepartment of Pharmaceutical Engineering, Beijing Institute of Petrochemical Technology, Qingyuan North Road 19, Beijing 102617, People’s Republic of ChinaTel +8610 8129 2387Fax +8610 8129 2124Email juruijun@bipt.edu.cnBackground: Non-small cell lung cancer (NSCLC) is one of the most lethal types of cancer with highly infiltrating. Chemotherapy is far from satisfactory, vasculogenic mimicry (VM) and angiogenesis results in invasion, migration and relapse.Purpose: The objective of this study was to construct a novel CPP (mmp) modified vinorelbine and dioscin liposomes by two new functional materials, DSPE-PEG2000-MAL and CPP-PVGLIG-PEG5000, to destroy VM channels, angiogenesis, EMT and inhibit invasion and migration.Methods and Results: The targeting liposomes could be enriched in tumor sites through passive targeting, and the positively charged CPP was exposed and enhanced active targeting via electrostatic adsorption after being hydrolyzed by MMP2 enzymes overexpressed in the tumor microenvironment. We found that CPP (mmp) modified vinorelbine and dioscin liposomes with the ideal physicochemical properties and exhibited enhanced cellular uptake. In vitro and in vivo results showed that CPP (mmp) modified vinorelbine and dioscin liposomes could inhibit migration and invasion of A549 cells, destroy VM channels formation and angiogenesis, and block the EMT process. Pharmacodynamic studies showed that the targeting liposomes had obvious accumulations in tumor sites and magnificent antitumor efficiency.Conclusion: CPP (mmp) modified vinorelbine plus dioscin liposomes could provide a new strategy for NSCLC.Keywords: vinorelbine, dioscin, non-small cell lung cancer, multi-functional liposomes, tumor microenvironment, MMP2 enzymes

Tianshu Wu,1 Xue Liang,1 Keyu He,2 Xi Liu,1 Yimeng Li,1 Yutong Wang,1 Lu Kong,1 Meng Tang1 1Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, People’s Republic of China; 2Blood Transfusion Department, Zhongda Hospital, Southeast University, Nanjing 210009, People’s Republic of ChinaCorrespondence: Tianshu Wu Email ninatswu@126.comIntroduction: Since CdTe quantum dots (QDs) are still widely considered as advanced fluorescent probes because of their far superior optical performance and fluorescence efficiency over non-cadmium QDs, it is important to find ways to control their toxicity.Methods: In this study, the adverse effects of two cadmium-containing QDs, ie, CdTe QDs and CdTe@ZnS QDs, on the nervous system of nematode C. elegans, the hippocampus of mice, and cultured microglia were measured in order to evaluate the neuroinflammation caused by cadmium-containing QDs and the potential mechanisms.Results: Firstly, we observed that cadmium-containing QD exposure-induced immune responses and neurobehavioral deficit in nematode C. elegans. In the mice treated with QDs, neuroinflammatory responses to QDs in the hippocampus, including microglial activation and IL-1ß release, occurred as well. When investigating the mechanisms of cadmium-containing QDs causing IL-1ß-mediated inflammation, the findings suggested that cadmium-containing QDs activated the NLRP3 inflammasome by causing excessive ROS generation, and resulted in IL-1ß release.Discussion: Even though the milder immune responses and neurotoxicity of CdTe@ZnS QDs compared with CdTe QDs indicated the protective role of ZnS coating, the inhibitions of NLRP3 expression and ROS production completely reduced the IL-1ß-mediated inflammation. This provided valuable information that inhibiting target molecules is an effective and efficient way to alleviate the toxicity of cadmium-containing QDs, so it is important to evaluate QDs through a mechanism-based risk assessment.Keywords: quantum dot, Caenorhabditis elegans, hippocampus, BV2 cells, interleukin-1ß, NLRP3 inflammasome

Liang Kong,1 Xue-tao Li,1 Ying-nan Ni,1 Hong-he Xiao,1 Ying-jia Yao,2 Yuan-yuan Wang,3 Rui-jun Ju,4 Hong-yan Li,1 Jing-jing Liu,1 Min Fu,1 Yu-tong Wu,1 Jing-xian Yang,1 Lan Cheng1 1School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, People’s Republic of China; 2College of Life and Health Sciences, Northeastern University, Shenyang 110819, People’s Republic of China; 3Department of Pharmacy, The Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning 116001, People’s Republic of China; 4Department of Pharmaceutical Engineering, Beijing Institute of Petrochemical Technology, Beijing 102617, People’s Republic of ChinaCorrespondence: Jing-xian Yang; Lan Cheng Email jingxianyang0520@163.com; sychenglan@163.comIntroduction: Osthole (Ost) is a coumarin compound that strengthens hippocampal neurons and neural stem cells against Aβ oligomer-induced neurotoxicity in mice, and is a potential drug for the treatment of Alzheimer’s disease (AD). However, the effectiveness of the drug is limited by its solubility and bioavailability, as well as by the low permeability of the blood-brain barrier (BBB). In this study, a kind of transferrin-modified Ost liposomes (Tf-Ost-Lip) was constructed, which could improve the bioavailability and enhance brain targeting.Methods: Tf-Ost-Lip was prepared by thin-film hydration method. The ability of liposomal formulations to translocate across BBB was investigated using in vitro BBB model. And the protective effect of Tf-Ost-Lip was evaluated in APP-SH-SY5Y cells. In addition, we performed pharmacokinetics study and brain tissue distribution analysis of liposomal formulations in vivo. We also observed the neuroprotective effect of the varying formulations in APP/PS-1 mice.Results: In vitro studies reveal that Tf-Ost-Lip could increase the intracellular uptake of hCMEC/D3 cells and APP-SH-SY5Y cells, and increase the drug concentration across the BBB. Additionally, Tf-Ost-Lip was found to exert a protective effect on APP-SH-SY5Y cells. In vivo studies of pharmacokinetics and the Ost distribution in brain tissue indicate that Tf-Ost-Lip prolonged the cycle time in mice and increased the accumulation of Ost in the brain. Furthermore, Tf-Ost-Lip was also found to enhance the effect of Ost on the alleviation of Alzheimer’s disease-related pathology.Conclusion: Transferrin-modified liposomes for delivery of Ost has great potential for AD treatment.Keywords: transferrin, osthole, liposomes, blood-brain barrier, Alzheimer’s disease

In this study, the experimental vapor–liquid equilibria data of the ternary Pb–Sn–Sb alloy system are determined using a new experimental method. The experimental VLE data passed the thermodynamic consistency test (Van Ness test), suggesting that the experimental results are reliable. The activities of the components of Pb–Sn–Sb ternary alloy and those of the corresponding three constituent binaries were calculated using the Wilson equation. The predicted values are in good agreement with the data determined from the experiments, and the average relative deviation and average standard deviation were smaller than ± 4.00% and ± 0.03 for all constituent binaries, respectively, which indicates that the Wilson equation is reliable for calculating the activity of the components of the Pb–Sn–Sb ternary alloy. The VLE data of the Pb– Sn and Sb–Sn binary alloys and Pb–Sn–Sb ternary alloy were calculated based on the VLE theory and the Wilson equation. The calculated VLE data were in good agreement with the data determined from the experiments, indicating that this method is reliable for calculating the VLE of alloy systems. The proposed study offers a valid method for analyzing the composition of products that are dependent on the distillation temperature and system pressure during vacuum distillation, which is of great significance to the experimental design of this process.

Ying Zhu,1–3,* Lei Fu,2,* Wang Jing,2 Li Kong,2,4 Jinming Yu2,4 1Department of Clinical Medicine, Weifang Medical University, Weifang, Shandong Province, People’s Republic of China; 2Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Jinan, People’s Republic of China; 3Heze Medical College Affiliated Hospital, Heze, Shandong Province, People’s Republic of China; 4Shandong Academy of Medical Sciences, Jinan, Shandong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jinming YuDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, 440 Jinan Road, Jinan 250117, Shandong Province, People’s Republic of ChinaTel +86 05 318 798 4777Fax +86 05 318 798 4079Email sdyujinming@163.comIntroduction: Adjuvant radiotherapy in non–small-cell lung cancer (NSCLC) remains controversial,Whether the mutation status of epidermal growth factor receptor (EGFR) will affect the recurrence and survival of patients with resected NSCLC is rarely reported. Our purpose is to study the effect of postoperative radiotherapy on patients with stage IIIA(N2) NSCLC with EGFR mutation.Methods: Total of of 115 patients diagnosed with stage IIIA(N2) resected NSCLC were analyzed retrospectively. Their EGFR mutations were detected by real-time quantitative PCR and DNA sequencing technology together.Results: At a median follow-up of 34.2 months for the postoperative adjuvant radiotherapy (PORT) group and 31.0 months for the non-PORT group, PORT group significantly improved progression free survival (PFS) and overall survival (OS). The median PFS and OS in the EGFR mutant group were not significantly longer than those in the EGFR wild-type group. The number of chemotherapy cycles, postoperative radiotherapy and the number of metastatic lymph nodes were independent factors influencing long-term survival.Conclusion: Our retrospective analysis showed that PORT can improve survival of patients with stage IIIA(N2) NSCLC. EGFR-mutant group with stage IIIA(N2) NSCLC has a tendency of a higher survival than the wild-type EGFR group, but there was no significant difference for both groups. The EGFR mutation status was not associated with PFS or OS of stage IIIA(N2) NSCLC.Keywords: non-small cell lung cancer, N2-stage, adjuvant radiotherapy, EGFR mutations

Copy number variation (CNV) is a main cause of male infertility, yet its influence still remains elusive in that of females. To investigate the correlation between CNV and female infertility, we applied whole-genome CNV analyses by next generation Sequencing (NGS), and analyzed 324 female infertility samples in Xinjiang Province, People's Republic of China. We identified 29 CNVs in total, of which 10 were novel CNVs. We found these CNVs mostly in chromosome X. The CNVs from one sample overlapped the POF1B gene that was related to premature ovarian failure (POF). The rest of these CNVs overlapped important functional genes related to neuropathy, brain, skin and retina, and the relationship between these CNVs and fertility needs to be studied further. We also found recurrent CNVs located on Xp22.31 and 22ql 1.21 in five and three cases, respectively. Our study first identified and characterized CNVs (CNVs preference, recurrent CNVs) in female infertility, also provided genetic evidence and references for future study and infertility etiology research.

Lei Wang,1–3 Jiyi Hu,2,4 Xiaoli Liu,2,5 Weiwei Wang,2,5 Lin Kong,1,2 Jiade J Lu2,41Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Fudan University Cancer Hospital, Shanghai 201315, People’s Republic of China; 2Shanghai Engineering Research Center of Proton and Heavy Ion Radiation Therapy, Shanghai, People’s Republic of China; 3Department of Radiation Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Shanghai 201315, People’s Republic of China; 5Department of Medical Physics, Shanghai Proton and Heavy Ion Center, Shanghai 201315, People’s Republic of ChinaCorrespondence: Lin KongDepartment of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Fudan University Cancer Hospital, 4365 Kangxin Road, Pudong, Shanghai 201321, People’s Republic of ChinaEmail lin.kong@sphic.org.cnJiade J LuDepartment of Radiation Oncology, Shanghai Proton and Heavy Ion Center, 4365 Kangxin Road, Pudong,Shanghai 201321, People’s Republic of ChinaTel +86 213 829 6505Email jiade.lu@sphic.org.cnPurpose: To identify the specific dose advantage of intensity-modulated carbon-ion radiation therapy (IMCT) over photon-based intensity-modulated radiation therapy (IMRT) in the treatment of locally recurrent nasopharyngeal carcinoma (NPC).Materials and methods: Ten patients with locally recurrent NPC underwent IMCT and IMRT planning. Target definition followed the recommendations of the International Commission on Radiation Units and Measurements (ICRU) reports no. 50, 62 and 83. The real treatment plans which were delivered to patients were designed on the Siemens Syngo planning system while the control plans for dosimetric comparison were generated from the Varian Medical Systems. The optimization constraints of the two designs were basically the same. Target coverage was evaluated using the following parameters: Dmin, Dmax, D1, D2, D50, D95, D98 and D99. Target dose distribution and conformality were evaluated using the homogeneity index and conformity index. Normal tissue sparing of organs at risk (OARs) were evaluated using Dmean, D1 and Dmax. SPSS 22.0 software was used for data analysis.Results: Both IMCT and IMRT plans met clinical prescription dose requirements. Target coverage of D1, D2, D50, D95, D98, D99 were not significantly different between the two plans (P>0.05). The two plans showed satisfactory coverage of the target without significant difference. There was no significant difference in terms of the homogeneity and conformability between the two plans. Dosimetric parameters for the brain stem, spinal cord, parotid gland, optic chiasm, eyeball, lens, temporal lobe and inner ear were significantly reduced in the IMCT plan (P

Zhe Wang,1,2 Minghuan Li,2 Feifei Teng,2 Li Kong,2 Jinming Yu2 1School of Medicine, Shandong University, Jinan, Shandong, China; 2Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, Shandong, China Purpose: The prognostic value of tumor location in pulmonary adenocarcinoma (ADC) is controversial. We compared the prognosis and relevant data between central-type ADC (CT-ADC) and peripheral-type ADC (PT-ADC) in order to identify the reasons for the different outcomes between them and to improve the treatment strategy and prognosis of these two types.Patients and methods: Data of 256 patients with pathologically diagnosed ADC were retrospectively reviewed. The prognostic factors for disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS) were analyzed using univariate and multivariate analyses.Results: A total of 124 and 132 patients had CT-ADC and PT-ADC, respectively. CT-ADC was associated with an earlier age, poorer Karnofsky Performance Status (KPS), higher rates of advanced stage, bone metastasis, contralateral pulmonary metastasis, and pleural effusion. Besides, CT-ADC showed a trend toward lower rate of EGFR mutation. Patients with CT-ADC had a significantly shorter PFS/DFS and OS than did those with PT-ADC. Multivariate analysis revealed that advanced stage, central-type location, EGFR wild-type, no surgery, presence of COPD, and interstitial lung disease (ILD) were independent poor prognostic factors for OS. The rate of surgery was significantly lower in patients with CT-ADC. Among patients with ILD or COPD, OS is shorter in patients with central- than peripheral-type tumors.Conclusion: CT-ADC is associated with poorer survival than PT-ADC and the lower rate of surgery in patients with CT-ADC is an important reason for this. Tumor location of pulmonary ADC plays a critical role in predicting prognosis and choosing therapeutic strategies. Keywords: lung cancer, EGFR, surgery, clinical stage, comorbidity

Kong L, Zhang S, Chu J, et al. Int J Nanomedicine. 2020;15:6451–6468. The authors have advised due to an error at the time of figure assembly, Figure 6A on page 6463 is incorrect. The correct Figure 6 is shown in Download Article. The authors apologize for this error and advise it does not affect the results of the paper. Read the original article

Jian Lu,1,* Changjun Sun,2,* Jiangbo Bai,1,* Siyu Tian,1,* Bing Zhang,1 Dehu Tian,1 Lingde Kong1 1Department of Orthopedics, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, China; 2Department of Emergency, The Second Hospital of Tangshan City, Tangshan, Hebei 063000, China *These authors contributed equally to this work Background: This study was conducted to determine whether sagittal lordotic alignment and clinical outcomes could be improved by the correction of segmental kyphosis after single-level anterior cervical discectomy and fusion (ACDF) surgery.Patients and methods: We retrospectively reviewed patients who underwent single-level ACDF surgery in our hospital between January 2014 and February 2017. Basic characteristics of patients included age at surgery, gender, diagnosis, duration of symptoms, and location of target level. Pre- and postoperative radiographs at the 6-month follow-up were used to evaluate the following parameters, such as segmental angle, C2–C7 angle, T1 slope, and C2–C7 sagittal vertical axis (SVA). Postoperative clinical outcomes were assessed by the Neck Disability Index and VAS. According to the segmental angle of postoperative radiographs, patients were divided into noncorrection group and correction group.Results: A total of 181 patients (99 males and 82 females) were analyzed in our study. There were 32 patients in the noncorrection group and 149 patients in the correction group. There was no significant difference in demographic and clinical data between the two groups before surgery. However, patients in the correction group showed larger C2–C7 angle and lower C2–C7 SVA after surgery in comparison with those in the noncorrection group. Besides, changes in the segmental angle were positively correlated with changes in C2–C7 angle and negatively correlated with changes in C2–C7 SVA.Conclusion: Surgical correction of segmental kyphosis in single-level cervical surgery contributed to balanced cervical alignment in comparison with those without satisfactory correction. However, we could not demonstrate that the correction of segmental alignment is associated with a better recovery in clinical outcomes. Keywords: segmental kyphosis, sagittal alignment, single level, cervical spine, anterior cervical discectomy and fusion

Fengchun Wu,1,2,* Yue Zhang,2,3,* Yongzhe Yang,2–4 Xiaobing Lu,1,2 Ziyan Fang,1 Jianwei Huang,1 Lingyin Kong,3 Jun Chen,5,6 Yuping Ning,1,2 Xiaobo Li,7,8 Kai Wu2,3,5,6,9 1Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China; 2Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, China; 3Department of Biomedical Engineering, School of Materials Science and Engineering, South China University of Technology (SCUT), Guangzhou, China; 4School of Medicine, South China University of Technology (SCUT), Guangzhou, China; 5Guangdong Engineering Technology Research Center for Diagnosis and Rehabilitation of Dementia, Guangzhou, China; 6National Engineering Research Center for Healthcare Devices, Guangzhou, China; 7Department of Biomedical Engineering, New Jersey Institute of Technology, NJ, USA; 8Department of Electric and Computer Engineering, New Jersey Institute of Technology, NJ, USA; 9Department of Nuclear Medicine and Radiology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan *These authors contributed equally to this work Background: Structural and functional brain abnormalities in schizophrenia (SZ) have been widely reported. However, a few studies have investigated both structural and functional characteristics in SZ patients at different stages to understand the neuropathology of SZ. Methods: In this study, we recruited 44 first-episode drug-naive SZ (FESZ) patients, 44 medicated chronic SZ (CSZ) patients, and 56 normal controls (NCs) and acquired their structural and resting-state functional magnetic resonance imaging (MRI). We then made group comparisons on structural and functional characteristics, including regional gray matter volume (GMV), regional homogeneity, amplitude of low-frequency fluctuation, and degree centrality. A linear support vector machine (SVM) combined with a recursive feature elimination (RFE) algorithm was implemented to discriminate three groups.Results: Our results indicated that the regional GMV was significantly decreased in patients compared with that in NCs; CSZ patients have more diffused GMV decreases primarily involved in the frontal and temporal lobes when compared with FESZ patients. Both FESZ and CSZ patients showed significant functional alterations compared with NCs; when compared with FESZ patients, CSZ patients showed significant reductions in functional characteristics in several brain regions associated with auditory, visual processing, and sensorimotor functions. Moreover, a linear SVM combined with a RFE algorithm was implemented to discriminate three groups. The accuracies of the three classifiers were 79.80%, 83.16%, and 81.71%, respectively. The performance of classifiers in this study with multimodal MRI was better than that of previous discriminative analyses of SZ patients with single-modal MRI.Conclusion: Our findings bring new insights into the understanding of the neuropathology of SZ and contribute to stage-specific biomarkers in diagnosis and interventions of SZ. Keywords: multimodal MRI, schizophrenia, support vector machine, SVM, classification

Xianchun Sun,1 Lingting Kong,2 Bingshu Li,2 Yan Zhang,2 Haiyan Yang2 1Department of No. 2 Gastrointestinal Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai 264000, China; 2Department of Emergency, Yantaishan Hospital, Yantai 264000, China Objective: Our study aimed to investigate the interaction between peroxiredoxin 1 (Prx1) and forkhead box O3 (FOXO3) and to explore the role of PI3K/AKT pathway in the development of pancreatic cancer.Material and methods: Human pancreatic normal cells HPDE6-C7 and pancreatic cancer cells PANC-1 were randomly divided into control group, Prx1-silencing (si-Prx1) group, Prx1/FOXO3 dual-silencing (si-Prx1/FOXO3) group, and negative control group. Cell proliferation assay, clone formation assay, and cell apoptosis assay were performed to investigate the effects of Prx1 silencing and FOXO3 silencing on the proliferation and apoptosis ability of pancreatic cancer cells. qRT-PCR and Western blot were performed to study the Prx1 and FOXO3 mRNA in the two cells and FOXO3 protein expression in PANC-1 cells.Result: We found Prx1 silencing could inhibit growth and promote apoptosis of PANC-1 cells. And Prx1 silencing could decrease the Prx1 mRNA level and increase FOXO3 mRNA level. To further explore the role of Prx1 in PI3K/AKT, we study the cell proliferation and apoptosis ability after adding the PI3K inhibitor and PI3K activator. We observed that PI3K inhibitor could inhibit tumor cell growth and promote cell apoptosis. And PI3K inhibitor also downregulated Prx1 protein expression.Conclusion: We concluded that the Prx1 silencing inhibited the growth and promoted apoptosis of pancreatic cancer cells via modulation of PI3K/AKT pathway by targeting FOXO3 gene. Keywords: Prx1, PI3K/AKT pathway, proliferation, apoptosis

Yaofei Jiang,1–4,* Ruoxi Chen,2,* Suming Xu,2,* Jiaxi Li,2,* Fanqi Yu,2 Lingdong Kong,2 Yuhan Sun,2 Yuan Ye,2 Yimin Li,2 Mengqi Yu,2 Jiaming Wu1 1Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jiaxing University, Jiaxing, China; 2Department of General Surgery, The Second Affiliated Hospital, Nanchang University, Nanchang, China; 3Hubei Cancer Clinical Study Centre, 4Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan, China *These authors contributed equally to this work Background/Aims: An updated systematic review and meta-analysis was conducted to assess the effect of prophylactic dexamethasone for tracheal intubation of general anesthesia on ­postoperative sore throat (POST). Methods: Comprehensive literature search of databases for randomized controlled trials (RCTs), including Embase, PubMed, and Cochrane Library, which evaluate the effect of prophylactic dexamethasone on POST was conducted. RevMan 5.0 and STATA 12.0 software were used to perform meta-analyses. Results: Fourteen RCTs totaling 1,837 patients were included for analysis. Compared with placebo, a significant reduction in the incidence of POST (OR 0.44, 95% CI 0.33–0.58, P

Yu-Tuan Wu,1,* Zhou Xu,1,* Ke Zhang,2,* Jiu-song Wu,3,* Xin Li,1,* Bilal Arshad,1 Ying-Cun Li,3 Zhong-Liang Wang,2 Hong-Yuan Li,1 Kai-Nan Wu,1 Ling-Quan Kong1 1Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; 2Department of Orthopedics, Children’s Hospital of Chongqing Medical University, Chongqing 400020, China; 3Department of General Surgery, Children’s Hospital of Chongqing Medical University, Chongqing 400020, China *These authors contributed equally to this work Abstract: The concurrent use of trastuzumab and anthracycline-based neoadjuvant chemotherapy (NAC) has been proposed to improve the pathologic complete response (pCR) rate, although there are conflicting views about its efficacy and safety. The purpose of this study was to evaluate the efficacy and cardiac safety of the concurrent use of trastuzumab and anthracycline-based NAC for human epidermal growth factor receptor 2 (HER2)-positive locally advanced breast cancer. We systematically searched PubMed, Embase, and Cochrane databases from inception until July 1, 2017, for relevant articles. A total of 13 studies were included in the meta-analysis. The results showed that the pCR rate was significantly higher in the concurrent use of trastuzumab and anthracycline group (45%) than that in the nonconcurrent use group (32%) (OR: 2.36, 95% CI: 1.69–3.30, P10% (OR: 1.26, 95% CI: 0.55–2.88, P=0.59), and in terms of cardiac failure (OR: 2.17, 95% CI: 0.24–19.84, P=0.49), when comparing the concurrent use of trastuzumab and anthracyclines with their nonconcurrent use. In conclusion, the concurrent use of trastuzumab and anthracycline-based NAC for certain HER2-positive locally advanced breast cancers significantly improves the pCR rates without obvious increases in the cardiotoxicity. Keywords: breast cancer, HER2, neoadjuvant chemotherapy, trastuzumab, anthracycline

Dong Guo,1,2,* Wang Jing,2,3,* Hui Zhu,2 Minghuan Li,2 Bing Zou,2 Yan Zhang,2 Lei Fu,2 Li Kong,2 Jinbo Yue,2,4 Jinming Yu2,4 1Department of Oncology, Clinical College, Weifang Medical University, Weifang, Shandong Province, People’s Republic of China; 2Department of Radiotherapy, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, Shandong Province, People’s Republic of China; 3Department of Radiotherapy, The First Affiliated Hospital to Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of China; 4Shandong Academy of Medical Sciences, Jinan, Shandong Province, People’s Republic of China *These authors contributed equally to this work Background: Although the role of prophylactic cranial irradiation (PCI) in the treatment of small cell lung cancer (SCLC) has been confirmed, the occurrence of brain metastases (BM) in patients remains a major problem. We designed this study to evaluate the clinical value of carcinoembryonic antigen (CEA) for predicting the incidence of BM and survival in SCLC patients who received PCI.Materials and methods: The records of 128 consecutive SCLC patients, who underwent PCI in our institute between 2005 and 2015, were analyzed. The collected data included clinicopathological features and the levels of CEA, neuron-specific enolase (NSE), cytokeratin 19 fragments (CYFRA21-1), and albumin. Kaplan–Meier and Cox regression analyses were used to determine the factors that affect BM and survival in SCLC patients after PCI.Results: In total, 128 patients were identified, with a median (range) age of 62 (30–83) years. Thirty-two patients developed BM at some time during follow-up. The median levels of CEA, NSE, CYFRA21-1, and albumin were 7.6 ng/mL, 44 ng/mL, 4.6 ng/mL, and 42.1 g/L, respectively. In the multivariate analysis, CEA level (HR: 2.479, 95% CI: 1.101–5.581; P=0.028), advanced clinical stage (HR: 2.929, 95% CI: 1.338–6.413; P=0.007), and NSE level (HR: 3.021, 95% CI: 1.226–7.442; P=0.016) were significantly correlated with BM. CEA (HR: 1.903, 95% CI: 1.133–3.195; P=0.015) and advanced clinical stage (HR: 2.002, 95% CI: 1.227–3.267; P=0.005) were independently associated with worse overall survival in SCLC patients.Conclusion: CEA is an independent predictive factor for the incidence of BM after PCI in SCLC and can be used as a predictor of BM in SCLC. In addition, a high level of CEA indicates a poor prognosis in SCLC patients after PCI. Prospective randomized clinical studies are required to confirm these findings. Keywords: carcinoembryonic antigen, brain metastases, predicting, survival, small cell lung cancer

Ronald Wihal Oei,1,2,* Lulu Ye,1,2,* Fangfang Kong,1,2 Chengrun Du,1,2 Ruiping Zhai,1,2 Tingting Xu,1,2 Chunying Shen,1,2 Xiaoshen Wang,1,2 Xiayun He,1,2 Lin Kong,1,2 Chaosu Hu,1,2 Hongmei Ying1,2 1Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Shanghai, People’s Republic of China *These authors contributed equally to this work Purpose: The aim of this article is to investigate the significance of pretreatment prognostic nutritional index (PNI), systemic immune-inflammation index (SII), and their combination in nasopharyngeal carcinoma (NPC) patients receiving intensity-modulated radiotherapy (IMRT).Materials and methods: A total of 585 patients were included. PNI and SII were calculated within 2 weeks prior to treatment. The optimal cutoff points were determined based on receiver operating characteristics curve analysis. The correlation between variables was analyzed. Kaplan–Meier method and Cox proportional hazards model were performed to evaluate the impact of both indices on overall survival (OS), progression-free survival (PFS) and distant metastasis-free survival (DMFS). Further propensity score matching (PSM) was carried out to minimize the effects of confounders. Results: The optimal cutoff point of 53.0 for PNI and 527.20 for SII were selected. Pearson correlation coefficient showed an inverse correlation between PNI and SII (r = –0.232, P < 0.001). Multivariate analysis demonstrated that pretreatment PNI was an independent prognostic factor for OS (P = 0.047) and DMFS (P = 0.002) while pretreatment SII was an independent prognostic factor for OS (P = 0.003), PFS (P = 0.002), and DMFS (P = 0.002). After PSM, both parameters remained as independent prognosticators of survival. Additional prognostic value was observed in the combined use of PNI and SII.Conclusion: Pretreatment PNI and SII are promising indicators of survival in NPC patients undergoing IMRT. They can be utilized to refine current TNM staging system in predicting prognosis and developing an individualized treatment in these patients. Keywords: prognostic nutritional index, systemic immune-inflammation index, nasopharyngeal carcinoma, intensity-modulated radiotherapy, prognostic factor, survival

Hongfang Zhao,* Siyu Tian,* Lingde Kong,* Jiangbo Bai,* Jian Lu, Bing Zhang, Dehu Tian Department of Orthopedics, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, People’s Republic of China *These authors contributed equally to this work Background: The aim of this study was to investigate the union time of acute middle-third scaphoid fractures following treatments and to analyze the effect of different factors on late union.Patients and methods: We retrospectively reviewed patients with acute middle-third scaphoid fracture at our institution between January 2013 and December 2017. Patient demographics, fracture characteristics, and treatment strategy, such as age, gender, body mass index, habit of smoking, sides of injury, dominant hand, ulnar variance, multiple fractures, and treatment methods, were investigated. Univariate and multivariate analyses were used to identify possible predictive factors.Results: A total of 132 patients with scaphoid fracture were included in our study. Operation was performed in 67 patients (50.8%), and conservative treatment was performed in the other 65 patients (49.2%). The union time was 7.2±0.5 weeks. In the multivariate logistic regression analysis, late diagnosis (odds ratio, 1.247; 95% CI, 1.022–1.521) and conservative treatment method (odds ratio, 1.615; 95% CI, 1.031–2.528) were identified as 2 independent predictors of late union in scaphoid fractures patients. Other parameters were not demonstrated to be predictive factors.Conclusion: Late diagnosis and conservative treatment were two factors associated with late union. Long time of follow-up is necessary for patient with these factors. Keywords: predictive factors, union time, nonunion, scaphoid fractures, multivariable analysis

Xiaofei Wu,1 Yan Tang,1 Xiaohua Zhang,1 Chenchen Wu,2 Lingti Kong3 1Department of Emergency Internal Medicine, the First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, People’s Republic of China; 2Department of Endocrinology, the First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, People’s Republic of China; 3Department of Pharmacy, the First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, People’s Republic of China Objective: We investigated the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of linezolid in patients who had suffered cerebral hemorrhage after lateral ventricular drainage. Materials and methods: Ten patients with cerebral hemorrhage after lateral ventricular drainage with stroke-associated pneumonia who were given linezolid were enrolled. Plasma and cerebrospinal fluid (CSF) samples were taken at appropriate intervals after the first administration of linezolid and assayed by high-performance liquid chromatography (HPLC). Then, PK parameters were estimated, and a Monte Carlo simulation was used to calculate the probability of target attainments (PTAs) for linezolid achieving the PK/PD index at different minimal inhibitory concentrations (MICs). Results: The maximum concentration of linezolid in plasma and CSF was reached at 1.00 h and 3.10 h, respectively. The average penetration of linezolid in CSF was 56.81%. If the area under the plasma concentration vs time curve from zero to the final sampling time (AUC0–24 h)/MIC ≥ 59.1 was applied as a parameter, the PTA of linezolid in plasma could provide good coverage (PTA ≥ 90%) only for pathogens with a MIC of ≤2 µg/mL, whereas it could be achieved in CSF with a MIC of ≤1 µg/mL. If %T > MIC ≥ 40% was applied as a parameter, the PTA of linezolid in plasma/CSF could provide good coverage if the MIC was ≤4 µg/mL. Conclusions: For patients with infection of the central nervous system and who are sensitive to the drug, the usual dosing regimens of linezolid can achieve a good therapeutic effect. However, for critically ill or drug-resistant patients, an increase in dose, the frequency of administration, or longer infusion may be needed to improve the curative effect. Keywords: linezolid, cerebral hemorrhage, plasma, cerebrospinal fluid, pharmacokinetics, pharmacodynamics, Monte Carlo simulation