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Ge Song,1,&ast; Zhigong Wei,2,&ast; Yiyan Pei,1 Zheran Liu,1 Yu Min,1 Huilin Li,1 Kun Gao,1 Junyou Ge,3 Yan Qing,3 Youneng Wei,3 Ye Chen,2,4 Xingchen Peng1 1Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 3Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd., Chengdu, People’s Republic of China; 4Division of Abdominal Tumor Multimodality Treatment, West China Hospital, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xingchen Peng, Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, No. 37 Guo Xue Alley, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-13458502834, Fax +86-28-85423278, Email pxx2014@scu.edu Ye Chen, Division of Abdominal Tumor Multimodality Treatment, Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, No. 37 Guo Xue Alley, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-18980605508, Fax +86-028-85422589, Email huaxichenye@163.comPurpose: Immunotherapy has become the primary option for recurrent and metastatic nasopharyngeal cancer (R/M NPC) after failure of chemotherapy, but without good prognostic indicators. Our study aimed to assess the potential of the systemic immune-inflammation index (SII) in predicting the effectiveness of PD-L1 inhibitor therapy for R/M NPC.Patients and Methods: The study cohort comprises of a prospective Phase 2 clinical trial population undergoing PD-L1 inhibitor for R/M NPC at 42 hospitals in China between 2019 and 2021. The SII is classified into high and low states based on the optimal threshold determined by the ROC curve. We assessed the relationship between SII status and objective remission rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) using regression analyses and Kaplan–Meier method. We performed sensitivity analyses to confirm the results.Results: Our study analyzed 153 patients from one of the largest cohorts to date of R/M NPC treated with PD-L1 inhibitor and found that SII showed a significant association with prognosis. We found higher ORR and DCR in the SII-Low group. Univariate analyses demonstrated that SII independently predicted DCR (OR, 0.43; 95% CI, 0.22– 0.84; p = 0.001), PFS (HR, 1.85; 95% CI, 1.31– 2.62; p < 0.001) and OS (HR, 1.92; 95% CI, 1.29– 2.85; p < 0.001). After adjusting for covariates, multivariate analysis remains relevant. [DCR (OR, 0.47; 95% CI, 0.22– 0.99; p = 0.048), PFS (HR, 1.72; 95% CI, 1.2– 2.47; p =0.003); OS (HR, 2.08; 95% CI, 1.38– 3.13; p < 0.001)]. Sensitivity analyses also support this conclusion.Conclusion: SII may well provide predictive value for the efficacy and prognosis of patients with R/M NPC treated with PD-L1 inhibitor. Patients with high status of SII may have a poorer therapeutic effect and survival.Keywords: systemic immune response, nasopharyngeal carcinoma prognosis, immunotherapy, efficacy

Guoqiang Xu,1,2,&ast; Xiaona Song,2,&ast; Xiaotang Wang,1,2,&ast; Rui Xue,1,2 Xiaoru Yan,1,2 Litao Qin,1,2 Xiaoqi Chang,1,2 Jiping Gao,1 Zhaoyang Chen,1 Guohua Song1 1Laboratory Animal Center Shanxi Key Laboratory of Experimental Animal Science and Human Disease Animal Model, Shanxi Medical University, Taiyuan, People’s Republic of China; 2School of Basic Medical Science, Shanxi Medical University, Taiyuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guohua Song, Laboratory Animal Center, Shanxi Key Laboratory of Experimental Animal Science and Human Disease Animal Model, Shanxi Medical University, Road Xinjian 56, Taiyuan, 030001, People’s Republic of China, Tel +86-351-4135919, Email ykdsgh@sxmu.edu.cnPurpose: Oral squamous cell carcinoma is the most common type of malignant tumor in the head and neck region. Despite advancements, metastasis and recurrence rates remain high, and patient survival has not significantly improved. Although miRNA therapies are promising for cancer gene therapy, their applications in treating oral cancer are limited. Targeted medication delivery systems based on nanotechnology offer an efficient way to enhance oral cancer treatment efficacy.Methods: We synthesized nanosilver (AgNPs) and loaded them with the tumor suppressor miR-181a-5p. In vitro experiments were conducted to investigate the inhibitory effects of AgNPs and their composites on the malignant behavior of oral cancer cell lines. The xenograft experiment was utilized to examine their effects on tumorigenesis and the potential molecular mechanisms involved.Results: The nanosilver exhibited a spherical morphology with a size distribution ranging from 50 to 100 nm. They exhibited a distinct absorption peak at 330 nm and could be excited to emit green fluorescence. The biocompatible AgNPs effectively shielded miRNA from degradation by RNase and serum. The nanocomposites significantly inhibited the proliferation, invasion, migration, and colony formation of oral cancer cell lines. Notably, treatment with the nanocomposites resulted in substantial tumor growth suppression in the xenograft model. Mechanistically, these composites directly targeted BCL2 and exerted their antitumor effects by suppressing the β-catenin signaling pathway and other downstream genes without inducing acute toxicity.Conclusion: Collectively, the findings demonstrate that the miR-181a-5p/AgNPs combination significantly impedes the growth and progression of oral cancer both in vitro and in vivo, highlighting a pivotal role for the β-catenin signaling pathway. This multifaceted approach holds promise as a prospective therapeutic strategy for oral cancer management in the future. Keywords: silver nanoparticles, nanocomposite, combination therapy, β-catenin signaling pathway

Jiali Teng,1 Qian Li,1 Guihang Song,2 Youli Han1 1School of Public Health, Capital Medical University, Beijing, People’s Republic of China; 2Department of Medical Services Management, Gansu Healthcare Security Administration, Lanzhou, Gansu, People’s Republic of ChinaCorrespondence: Youli Han, School of Public Health, Capital Medical University, 10 Xi Toutiao Road, Youanmenwai District, Beijing, People’s Republic of China, 100069, Email hanyouli@ccmu.edu.cn Guihang Song, Department of Medical Services Management, Gansu Healthcare Security Administration, 101 Guangchangnan Road, Chengguan District, Lanzhou, Gansu, People’s Republic of China, 730030, Email 285601604@qq.comPurpose: To control medical costs and regulate the behavior of providers, China has formed an original widely piloted case-based payment under the regional global budget, called the Diagnosis-Intervention Packet (DIP). This study aimed to evaluated the impact of the DIP payment reform on medical costs, quality of care, and medical service capacity in a less-developed pilot city in Northwest China.Patients and Methods: We used the de-identified case-level discharge data of hospitalized patients from January 2021 to June 2022 in pilot and control cities located in the same province. We performed difference-in-differences (DID) analysis to examine the differential impact of the DIP reform for the entire sample and between secondary and tertiary hospitals.Results: The DIP payment reform resulted in a significant decrease of total expenditure per case in the entire sample (5.5%, P < 0.01) and tertiary hospitals (9.3%, P < 0.01). In-hospital mortality rate decreased significantly in tertiary hospitals (negligible in size, P < 0.05), as did all-cause readmission rate within 30 days in the entire sample (1.1 percentage points, P < 0.01) and secondary hospitals (1.4 percentage points, P < 0.01). Proportion of severe patients increased significantly in the entire sample (1.2 percentage points, P < 0.05) and tertiary hospitals (2.5 percentage points, P < 0.01). We did not find the DIP reform was associated with a significant change in relative weight per case.Conclusion: The DIP payment reform in the less-developed pilot city achieved short-term success in controlling medical costs without sacrificing the quality of care for the entire sample. Compared with secondary hospitals, tertiary hospitals experienced a greater decline in medical costs and received more severe patients. These findings hold lessons for less developed countries or areas to implement case-based payments and remind them of the variations between different levels of hospitals.Keywords: DIP payment, medical costs, quality of care, medical service capacity, less developed city, case-based payment

Kunjie Zheng,1– 3 Xiaolong Li,1– 3 Yihua Rong,2 Xuejing Wang,4 Liping Hou,2 Wei Gu,2 Xiaoyu Hou,3 Yunpeng Guan,5 Lifang Liu,6 Jianlin Geng,2 Guangyao Song1,3 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Endocrinology, Hengshui People’s Hospital, Hengshui, Hebei, People’s Republic of China; 3Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of China; 4Hengshui People’s Hospital Statistical Office, Hengshui, Hebei, People’s Republic of China; 5Department of Endocrinology, Shijiazhuang People’s Hospital, Shijiazhuang, Hebei Province, People’s Republic of China; 6Department of Endocrinology, Baoding First Central Hospital, Baoding, Hebei, People’s Republic of ChinaCorrespondence: Guangyao Song, Department of Endocrinology, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, Hebei, 050051, People’s Republic of China, Email sguangyao2@163.comPurpose: Elevated serum gamma-glutamyltranspeptidase (GGT) is an independent marker of the activation of systemic inflammation, while conditions associated with elevated triglyceride (TG) levels, such as type 2 diabetes, non-alcoholic fatty liver disease, obesity, and metabolic syndrome, are associated with an increased inflammatory burden. Moreover, serum liver enzymes (GGT, alanine aminotransferase [ALT], aspartate aminotransferase [AST], and alkaline phosphatase [ALP]) are associated with metabolic syndrome and its components, including hypertriglyceridemia. However, the relationship between liver enzymes and postprandial hypertriglyceridemia (PHTG) remains unclear. Therefore, in this study we conducted oral fat tolerance tests (OFTTs) to understand the differences in serum liver enzyme levels among individuals with different lipid tolerance levels and their correlation with PHTG.Patients and Methods: For the OFTT, we enrolled 202 non-diabetic volunteers whose fasting triglyceride (TG) levels were less than 1.7 mmol/L in this case-control study. The participants were categorized into two groups according to the TG levels at the 0- and 4-h OFTT: a postprandial normal TG (PNTG) group and a PHTG group. Routine fasting serum biochemical indices, liver enzyme (GGT, ALT, AST, and ALP) levels, and 0- and 4-h OFTT lipid levels were assessed.Results: The PHTG group had significantly higher serum GGT and ALT levels and a lower AST/ALT ratio than those in the PNTG group. However, no significant difference was observed in AST and ALP levels compared with the PNTG group. After adjusting for major confounders, logistic regression analysis indicated a significant correlation between serum GGT and PHTG (odds ratio = 1.168, P < 0.001), but not with ALT level, AST level, AST/ALT ratio, and ALP level. The receiver operating characteristic curve analysis demonstrated that the serum GGT level was an effective predictor of PHTG.Conclusion: Serum GGT levels are significantly associated with PHTG risk and serve as an effective biomarker for early identification.Keywords: gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, inflammation, triglyceride, oral fat tolerance test

Jing Zhang,1,2 Yilin Hou,1 Zhaozi Zhang,1 Yihe Shi,1 Zhimin Wang,1 Guangyao Song1,2 1Department of Internal Medicine, Graduate School of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Guangyao Song; Jing Zhang, Email sguangyao2@163.com; gina_zhangjing@163.comBackground: Peroxidation is one of the important causes of insulin resistance (IR), and vitamin E is a natural antioxidant, and there may be some correlation between serum vitamin E levels and insulin resistance.Purpose: The correlation between serum vitamin E and insulin resistance in type 2 diabetes mellitus (T2DM) population.Methods: Two hundred and forty-two people (119 with T2DM) were included. One hundred and nineteen patients with T2DM were selected as the case group, and 123 people with non-T2DM were selected as the control group. People insulin resistance was detected by the homeostasis model assessment method (HOMA-IR) greater than 2.69 were included in the diabetic insulin resistance group, and those with HOMA-IR less than 2.69 were included in the diabetic non-insulin resistance group. Record the general body indicators, biochemical indicators, hepatic function indicators, vitamin E, and other indicators. Correlation analysis, logistic regression, trend analysis, and restricted cubic spline (RCS) were performed using SPSS 25.0 and R 4.1.1 software. Correlation analysis, logistic regression, trend analysis, restricted cubic spline (RCS) analysis were conducted on general body indicators, biochemical indicators, hepatic function indicators, vitamin E, and other indicators.Results: The logistic regression results showed that after adjusting for confounding factors, vitamin E was an independent influencing factor for insulin resistance in T2DM patients (P < 0.001). The trend analysis results show that with the decrease of serum vitamin E levels, the risk of insulin resistance in T2DM patients gradually increases. The RCS results showed that the risk of insulin resistance was significantly increased when the serum vitamin E level was lower than 10,575.23 ng/mL.Conclusion: Serum vitamin E levels are lower in T2DM patients than in healthy populations; Vitamin E is an independent influencing factor for HOMA-IR in T2DM patients. The risk of insulin resistance gradually increases in T2DM patients as serum vitamin E levels decrease. Vitamin E is a risk factor for insulin resistance at serum vitamin E levels below 10,575.23 ng/mL. At higher serum vitamin E levels than 10,575.23 ng/mL, vitamin E is a protective factor for insulin resistance.Keywords: Vitamin E, type 2 diabetes mellitus, insulin resistance, oxidative stress

Tingting Zhang,1,&ast; Lan Yao,1,&ast; Tao Li,2 Haoxin Tian,3 Guirong Song4 1Nursing Department, the First Hospital Affiliated to Dalian Medical University, Dalian, People’s Republic of China; 2Department of Neurology, the First Hospital Affiliated to Dalian Medical University, Dalian, People’s Republic of China; 3The First Clinical College, Dalian Medical University, Dalian, People’s Republic of China; 4Department of Health Statistics, School of Public Health, Dalian Medical University, Dalian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guirong Song, Email songsara2016@dmu.edu.cnBackground: Promoting participation and autonomy (PA) in society has been highlighted as an ultimate goal of rehabilitation for people with chronic diseases by the World Health Organization, but few studies have focused on PA in people with Parkinson’s disease (PD). Therefore, this study aimed to determine the level of PA in PD patients and investigate the associated psychological and behavioural factors.Methods: PD patients were recruited from the Department of Neurology of the First Hospital Affiliated with Dalian Medical University using convenience sampling for this cross-sectional study. A questionnaire covering social-demographic and disease-related characteristics, Chinese version of Impact on Participation and Autonomy (IPA) Questionnaire, Connor-Davidson Resilience Scale (CD-RISC), Self-rating Depression Scale (SDS), Self-rating Anxiety Scale (SAS), Medical Coping Modes Questionnaire (MCMQ), Social Support Rating Scale (SSRS), Hoehn-Yahr Staging System and Unified Parkinson’s Disease Rating Scale (UPDRS) were used for investigation. A multivariate stepwise linear regression analysis was used to determine the factors that influence IPA.Results: A total of 326 PD patients responded to all the questionnaires. The patients had a mean IPA score of 46.6 (SD 21.79). Multiple linear regression analyses revealed that UPDRS II (β = 0.35, p < 0.001) had the strongest correlation with IPA, followed by tenacity, which was the second strongest factor (β = − 0.25, p < 0.001). Hoehn-Yahr stage (β = 0.19, p < 0.001) and availability of social support (β =− 0.12, p =0.001) were also strong factors.Conclusion: The average level of PA among PD patients was at the lower middle-level. Among PD patients, physical function, psychological resilience and social support were the strongest factors associated with PA. These findings provide valuable insights into PD patients’ PA and can help medical professionals identify the early risks of restricted PA among PD patients, implement interventions to promote PA and ultimately achieve rehabilitation.Keywords: participation and autonomy, psychological resilience, social support, Parkinson’s disease, medical coping modes

Liqun Yang,1– 3 Zhimei Zhang,3 Yunfeng Zhen,3 Jing Feng,3 Jinhu Chen,3 Guangyao Song1– 3 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei Province, People’s Republic of China; 2Hebei Key Laboratory of Metabolic Disease, Shijiazhuang, Hebei Province, People’s Republic of China; 3Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei Province, People’s Republic of ChinaCorrespondence: Guangyao Song, Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei Province, People’s Republic of China, Tel +86-0311-8598-8556, Email sguangyao2@163.comPurpose: Energy metabolism is regulated by SIRT3, no research has been done on the connection between lipid metabolism in the oral fat test and SIRT3 polymorphism. Thus, we conducted a case-control study to investigate the connection between postprandial lipid and SIRT3 polymorphism.Patients and Methods: 402 non-obese Chinese subjects were enrolled and their postprandial lipid response to oral fat tolerance test (OFTT) was observed to understand the relationship between rs11246020 gene and postprandial triglyceride metabolism.Results: In a binary logic regression model, a protective effect of the T allele of the rs11246020 SIRT3 for postprandial hypertriglyceridemia was shown (OR=0.417, 95% CI = 0.219– 0.794, p=0.008). Compared to the CC genotype, individuals with the TT+CT variant of the rs11246020 SIRT3 gene demonstrated significantly lower levels of homeostasis model assessment of insulin resistance (HOMA-IR) (p=0.04), postprandial plasma glucose (PPG) (p=0.037), fasting plasma glucose (FPG) (p=0.02), and 4-hour triglyceridemia (Tg) (p=0.032).Conclusion: The C allele of rs11246020 SIRT3 gene may be a risk factor to increased possibility of postprandial triglyceridemia after an oral fat test, which involved in the mechanism of glucose and insulin metabolism.Keywords: sirtuin, postprandial hypertriglyceridemia, insulin resistance, genetics

Tingxue Zhang,1,2 Yilin Hou,1,2 Min Liu,2 Xiaoyu Hou,1,2 Yong Tang,2 Luping Ren,2 Guangyao Song1,2 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Guangyao Song, Tel +86-0311-8598-8556, Email sguangyao2@163.comPurpose: To investigate the effects of different angiopoietin-like proteins (ANGPTLs) on postprandial hypertriglyceridemia (PPT) by analyzing changes in serum lipid, ANGPTL3, ANGPTL4, and ANGPTL8 levels before and after a high-fat diet in individuals with normal fasting lipid and oral glucose tolerance test results.Patients and Methods: Exactly 103 volunteers were recruited for an oral fat tolerance test (OFTT). Blood samples were obtained at 0, 2, and 4 h after eating to detect relevant indicators. PPT was defined as triglyceride (TG) levels ≥ 2.5 mmol/L. According to the test results, the participants were divided into two groups: postprandial normal triglycerides (PNT) and PPT. The levels of blood lipids and ANGPTL3, ANGPTL4, and ANGPTL8 were compared between the two groups.Results: There were differences in the body mass index (BMI), waist circumference (WC), fasting total cholesterol (TC), TG, low-density lipoprotein cholesterol (LDL-C), triglyceride-rich lipoprotein cholesterol (TRL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), ApoA1/ApoB, fasting blood glucose (FBG), fasting insulin (FINS), ANGPTL4, and ANGPTL8 between the two groups. In the PNT group, the TG level increased from baseline at 2 and 4 h, TRL-C increased from baseline at 4 h, and ANGPTL8 decreased from baseline at 2 and 4 h. After OFTT, the levels of TG, TRL-C, ANGPTL3, and ANGPTL4 in the PPT group gradually increased; ANGPTL8 gradually decreased. Fasting ANGPTL3 was positively associated with age, TC, HDL-C, TRL-C, and ApoA1, and negatively associated with systolic blood pressure. Fasting ANGPTL4 was positively correlated with weight, WC, BMI, TC, TG, LDL-C, TRL-C, non-HDL-C, ApoB, FBG, and FINS, and negatively correlated with ApoA1/ApoB and fasting ANGPTL8. Binary logistic regression analysis indicated that ANGPTL4 and ANGPTL8 were significant predictors of PPT.Conclusion: PPT occurrence is closely associated with changes in ANGPTL4 and ANGPTL8 levels.Keywords: dyslipidemia, serum lipid, ANGPTL proteins, oral fat tolerance test, postprandial normal triglyceride

Xiaolong Li,1– 3 Kunjie Zheng,1– 3 Wei Gu,1– 3 Xiaoyu Hou,1,3 Yunpeng Guan,1 Lifang Liu,1,3,4 Liping Hou,2 Jianlin Geng,2 Guangyao Song1,3 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Endocrinology, Harrison International Peace Hospital, Hengshui, Hebei, People’s Republic of China; 3Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 4Department of Endocrinology, Baoding First Central Hospital, Baoding, Hebei, People’s Republic of ChinaCorrespondence: Guangyao Song, Tel +86-0311-8598-8556, Email sguangyao2@163.comPurpose: The relationship between blood lipids and fibroblast growth factor (FGF) 21 in the postprandial period remains unclear. To investigate this, we observed the changes in blood lipid levels after an oral fat tolerance test (OFTT) and examined the short-term effects on FGF21.Patients and Methods: A total of 158 non-diabetic adult volunteers who underwent OFTT were randomly recruited from the Hebei General Hospital. Participants were stratified into three groups according to fasting and 4-h postprandial triglyceride levels: normal fat tolerance (NFT), impaired fat tolerance (IFT), and hypertriglyceridemia (HTG). Blood samples were collected at 2-h intervals for 6 h. Circulating total cholesterol levels, triglycerides, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, free fatty acids (FFA), and FGF21 were assessed.Results: Fasting FGF21 levels increased progressively in the NFT, IFT, and HTG groups and were strongly correlated with FFA levels (r = 0.531, P < 0.001). During the OFTT, the FFA and FGF21 levels decreased and then increased after reaching a nadir at 2 and 4 h, respectively. After adjusting for potential risk factors, the FFA incremental area under the curve (iAUC) was an independent influencing factor of FGF21 iAUC (P = 0.005).Conclusion: Fasting FGF21 levels showed a strong positive correlation with FFA. During OFTT, changes in FGF21 levels were closely associated with alterations in FFA exogenously changed by OFTT. Moreover, they were linearly related to each other. Therefore, the serum FGF21 level is positively correlated to the FFA level in the postprandial period.Keywords: fibroblast growth factor 21, free fatty acid, lipids, dyslipidemia, postprandial state, oral fat tolerance test

Xiaoling Liu, Ermei Zhong, Jinzhi Li, Chunxia Huang, Weixin Liu, Liping Zeng, Ge Song, Ronghua Jiang, Yu Liu NHC Key Laboratory of Male Reproduction and Genetics, Guangdong Provincial Reproductive Science Institute (Guangdong Provincial Fertility Hospital), Guangzhou, 510600, People’s Republic of ChinaCorrespondence: Ge Song, NHC Key Laboratory of Male Reproduction and Genetics, Guangdong Provincial Reproductive Science Institute (Guangdong Provincial Fertility Hospital), No. 17 Mei Dong Road, Guangzhou, 510600, People’s Republic of China, Tel/Fax +86-020-87301316, Email gzdhmjyd@163.comBackground: This study aimed to explore the current situation of anxiety and depression on day of transfer in couples receiving in vitro fertilization and embryo transfer (IVF-ET) with donor sperm and analyze its influencing factors.Methods: This study selected 187 IVF-ET administered couples who received donor sperm from our Hospital from August 2021 to July 2022. On the day of IVF-ET with donor sperm transplantation, patients were investigated with general data questionnaire, self-rating anxiety scale (SAS) and self-rating depression scale (SDS) to analyze their anxiety and depression scores and their influencing factors.Results: Scores of anxiety and depression on the day of transplantation in patients receiving IVF-ET with donor sperm were 43.98± 6.80 and 46.03± 10.61 respectively, which were higher compared to levels of Chinese health norm (P< 0.05). The anxiety score of patients’ spouses was 41.23± 6.69 and depression score was 44.23± 11.65, which were higher compared to levels of Chinese health norm (P< 0.05). Score of anxiety and depression of women was significantly higher compared to those of their spouse (P< 0.05). Anxiety and depression scores of women in non-pregnant group were significantly higher compared to those in pregnant group (P< 0.05). Regression analysis showed that education level and annual family income were influencing factors of anxiety and depression scores of IVF-ET with donor sperm couples on the day of transfer, and number of eggs taken and transfer times were influencing factors of depression scores of IVF-ET with donor sperm patients on the day of transfer.Conclusion: Psychological state of couples receiving IVF-ET with donor sperm was significantly affected, especially in female side. Medical staff should focus on patients with low education level, low family income, and more times of transfer and egg retrieval, and take targeted intervention measures to keep them in good psychological state, which is conducive to improving pregnancy outcome.Keywords: in vitro fertilization and embryo transfer with donor sperm, day of transfer, anxiety, depression, psychological state

Xiaoyue Yang,1 Rui Hu,1 Zhen Wang,1 Yilin Hou,1 Guangyao Song1,2 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, 050017, People’s Republic of China; 2Endocrinology Department, Hebei General Hospital, Shijiazhuang, Hebei, 050051, People’s Republic of ChinaCorrespondence: Guangyao Song, Endocrinology Department, Hebei General Hospital, 361 Zhongshan East Road, Shijiazhuang, People’s Republic of China, Tel +86 13930119808, Email sguangyao2@163.comBackground: Adequate intake of folic acid (FA) has been proven essential for metabolism, cellular homeostasis, and antioxidant effects in diabetic patients. Our aim was to evaluate the association between serum folate levels and the risk of insulin resistance in patients with type 2 diabetes mellitus (T2DM) and to provide new ideas and approaches for reducing the risk of T2DM.Methods: This was a case–control study involving 412 participants (206 with T2DM). Anthropometric parameters, islet function, biochemical parameters and body composition of T2DM group and control group were determined. Correlation analysis and logistic regression were used to evaluate the risk factors associated with the onset of insulin resistance in T2DM.Results: The folate levels in type 2 diabetic patients with insulin resistance were significantly lower than those in patients without insulin resistance. Logistic regression showed that FA and high-density lipoprotein were independent influencing factors for insulin resistance in diabetic patients (P < 0.05). After adjusting for confounding factors, the degree of insulin resistance in diabetic patients was in a significant inverse relationship with folate levels (P< 0.05). We also found that below the serum FA threshold of 7.09 ng/mL insulin resistance was significantly more elevated.Conclusion: Our findings suggest that the risk of insulin resistance increases with the decrease in serum FA levels in T2DM patients. Monitoring folate levels in these patients and FA supplementation are warranted preventive measures.Keywords: folic acid, type 2 diabetes mellitus, insulin resistance, Chinese

While the mitigating effects of trees on shallow landslide occurrence are well recognised, the impact of landslides on tree community structure and tree-tree interactions have received much less research attention. The structures of tree communities before and after landslides were compared in a 25-ha subtropical forest plot. Tree-tree interactions were examined by analysing the pre- and post-landslide spatial point patterns of large (DBH ≥ 20 cm) and small (1 cm ≤ DBH < 20 cm) tree cohorts. In landslide scarps, 35 (34%) of 104 large trees and 467 (13%) of 3.072 small trees survived. Large (L) and small (S) tree cohorts were paired together for spatial analyses, including pre-landslide (PL) (LPL-SPL), surviving (S) (LS-SS), and missing (M) large-small tree paired cohorts (LM-SM). We randomly selected trees from the pre-landslide tree cohorts to create two virtual paired cohorts, the L34%-S13% and L66%-S87% paired cohorts, whose population sizes were identical to the field-observed LS-SS and LM-SM paired cohorts respectively, but with random spatial patterns. Post-landslide survival rates of trees increased monotonically with DBH. Large trees dislodged by landslides scarcely reduced small-tree survival. Evidence for this included: (i) the distance from small trees to the nearest large trees of the LM-SM paired cohort did not differ significantly from that of the virtual L66%-S87% paired cohort; (ii) survival rates of small trees near LM individuals did not differ significantly from those without large trees nearby. Surviving large trees had positive effects on the survival of small trees, indicated by: (i) the distance from small trees to the nearest large trees of the LS-SS paired cohort was significantly lower than that of the virtual L34%-S13% paired cohort; (ii) SS individuals clumped around LS individuals, whereas the virtual L34%-S13% spatial relationship was random. Large trees prevent landslide dislodgement of adjacent small trees through the nurse-plant effect. Our study suggests that landslide damage in sloping forests may be reduced simply by constantly maintaining a critical density of large trees.

Zhiru Xiu,1 Yiquan Li,1 Jinbo Fang,1 Jicheng Han,1 Shanzhi Li,1 Yaru Li,1,2 Xia Yang,1 Gaojie Song,3 Yue Li,1 Ningyi Jin,1,4,5 Yilong Zhu,1 Guangze Zhu,1 Lili Sun,6 Xiao Li1,4,7 1Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 2Medical College, Yanbian University, Yanji, People’s Republic of China; 3Medical College, Jiujiang· University, Jiujiang, People’s Republic of China; 4Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, People’s Republic of China; 5Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, People’s Republic of China; 6Department of Head and Neck Surgery, Tumor Hospital of Jilin Province, Changchun, People’s Republic of China; 7College of Life Sciences, Shandong Normal University, Jinan, People’s Republic of ChinaCorrespondence: Lili Sun; Xiao Li, Boshuo Road, 1035, Jingyue Economic & Technological Development Zone, Changchun, Jilin, 130122, People’s Republic of China, Tel +86-431-86985923, Fax +86-431-87985861, Email skylee6226@163.com; linjiaxiaoya@163.comObjective: To explore the effects of Esculetin on liver cancer and explore potential mechanisms of Esculetin-inducing cells death.Methods: Esculetin’s effects on the proliferation, migration and apoptosis of HUH7 and HCCLM3 cells were detected by using CCK8, crystal violet staining, wound healing, TranswellTM and Annexin V-FITC/PI. Flow cytometry, fluorescence staining, Western blot, T-AOC, DPPH radical scavenging assay, hydroxyl radical’s inhibitory capability and GSH test were used to examine the esculetin’s effects on the ROS level, the oxidation-related substances and proteins’ expression in hepatoma cells. In vivo experiment was performed by xenograft model. Ferrostatin-1 was used to determine the death way of hepatoma cells induced by esculetin. Live cell probe, Western blot, Fe2+ content, MDA, HE staining, Prussian blue staining and immunohistochemistry were used to examine the ferritinophagy-related phenomenon induced by esculetin in hepatoma cells. The relationship between esculetin and NCOA4-mediated ferritinophagy was confirmed through gene silence and overexpression, immunofluorescence staining and Western blot.Results: Esculetin suppressed the proliferation, migration and apoptosis of HUH7 and HCCLM3 cells significantly, influenced the oxidative stress level, altered the autophagy and iron metabolism levels in cells, and produced a ferritinophagy-related phenomena. Esculetin increased the levels of cellular lipid peroxidation and reactive oxygen species. In vivo, esculetin could decrease tumour volume, promote LC3 and NCOA4 expressions, suppresse hydroxyl radical‘s inhibiting capacity and GSH, increase Fe2+ and MDA levels, decrease antioxidant proteins expression in tumour tissue. In addition, Esculetin could also increase the iron deposition of tumour tissues, promote ferritinophagy, and induce tumours’ ferroptosis.Conclusion: Esculetin has an inhibitory effect on liver cancer in vivo and in vitro through triggering NCOA4 pathway-mediation ferritinophagy.Keywords: esculetin, ferritinophagy, liver cancer, anti-tumour, NCOA4

Yilin Hou,1,2 Xiaoyu Hou,1,2 Qian Nie,3 Qiuyang Xia,1,2 Rui Hu,1,2 Xiaoyue Yang,1,2 Guangyao Song,2,4 Luping Ren2,4 1Graduate School, Hebei Medical University, Shijiazhuang, Hebei, 050017, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, 050051, People’s Republic of China; 3Health Examination Center, Hebei General Hospital, Shijiazhuang, Hebei, 050051, People’s Republic of China; 4Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, 050017, People’s Republic of ChinaCorrespondence: Guangyao Song; Luping Ren, Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, 050051, People’s Republic of China, Email sguangyao2@163.com; renluping1122@163.comPurpose: The aim of this study was to evaluate the association of bone turnover markers (BTMs) with type 2 diabetes mellitus (T2DM) and microvascular complications.Methods: A total of 166 T2DM patients and 166 non-diabetic controls matched by gender and age were enrolled. T2DM patients were sub-classified into groups based on whether they had diabetic peripheral neuropathy (DPN), diabetic retinopathy (DR), and diabetic kidney disease (DKD). Clinical data including demographic characteristics and blood test results [serum levels of osteocalcin (OC), N-terminal propeptide of type 1 procollagen (P1NP), and β-crosslaps (β-CTX)] were collected. Logistic regression and restrictive cubic spline curves were performed to examine the association of BTMs with the risk of T2DM and microvascular complications.Results: After adjusting for family history of diabetes, sex and age, an inverse association was observed between elevated serum OC levels [O, p < 0.001] and increased serum P1NP levels , p < 0.001] with the risk of T2DM. Moreover, there was an inverse linear association of serum OC and P1NP levels with the risk of T2DM. However, β-CTX was not associated with T2DM. Further analysis showed a nonlinear association between OC and the risk of DR, while P1NP and β-CTX were not correlated with DR. Serum concentrations of BTMs were not associated with the risks of DPN and DKD.Conclusion: Serum OC and P1NP levels were negatively correlated with T2DM risk. Particularly, serum OC levels were associated with DR risk. Given that BTMs are widely used as markers of bone remodeling, the present finding provides a new perspective for estimating the risk of diabetic microvascular complications.Keywords: bone turnover markers, type 2 diabetes mellitus, microvascular complications

Zhanjie Li,1,&ast; Tangying Liang,2,&ast; Junji Zhang,3 Ge Song,4 Yinzhi Leng,5 Li Qiao,6 Yiyang Zhan,7 Weihong Zhang1 1Department of Infection Control, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 3Department of Infection Control, Suzhou Municipal Hospital, Suzhou, Jiangsu, People’s Republic of China; 4Department of Infection Control, Changzhou No. 2 People’s Hospital Affiliated to Nanjing Medical University, Changzhou, Jiangsu, People’s Republic of China; 5Department of Infection Control, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 6Department of Quality Management, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 7Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yiyang Zhan, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, People’s Republic of China, Tel +86-18912972893, Email yiyangzhan@sina.com Weihong Zhang, Department of Infection Control, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, People’s Republic of China, Tel +86-13585108553, Email zhangweihong@jsph.org.cnObjective: To analyze the characteristics and occurrence scenarios of occupational exposure of staff in the Shanghai Lingang Fangcang Shelter Hospital.Methods: We collected the data of 80 staff with occupational exposure (including doctors, nurses, cleaning, security guards, and maintenance staff) in the Shanghai Lingang Fangcang Shelter Hospital from April 5 to May 20, 2022. The basic information of occupational exposure, factors influencing different occupational exposure types, ways to discover occupational exposure, discovery places of occupational exposure, and specific occurrence scenarios were compiled and analyzed among these data.Results: Occupational exposure mainly occurred in nurses (37, 46.25%), and cleaning (21, 26.25%). After the occurrence of occupational exposure, 20 staff (25%) did not know the occurrence time. Moreover, occupational exposure types were listed from high to low proportion as follows: broken protective clothing (56, 70%), mask loosening or displacement (13, 16.25%), skin exposure (6, 7.5%), and sharp object injuries (5, 6.25%). Occupational exposure was discovered mainly through self-discovery (56, 70%), while other discovery ways were majorly colleague discovery (12, 15%) and infection control supervisor discovery (12, 15%). Furthermore, occupational exposure was discovered principally in the public area (53.75%) and the office area (25%) of the cabin, but the proportion of mask loosening or displacement (38.46%) and skin exposure (50%) was also high in the first unloading area. Broken protective clothing occurred in the following scenarios: scratching while working in the cabin (37, 66.07%) and not knowing its occurrence time (25%). The occurrence scenarios of mask loosening or displacement were mainly not knowing its occurrence time (6, 46.15%), self-discovery (3, 23.08%), and at the time of removal (3, 23.08%).Conclusion: Targeted training and prevention of occupational exposure should be performed to decrease infection risk and ensure staff safety in Fangcang shelter hospitals.Keywords: Fangcang shelter hospital, occupational exposure, characteristics, scenarios, SARS-CoV-2 Omicron

Aifan Li,1,&ast; Tianyi Han,2,&ast; Yongfang Li,1 Gaiqing Yang,3 Yuchao Zhang,4 Yanyang Huang,2 Baixue Zhou,2 Guoying Song,2 Ying He2 1Department of Neurology, The First People’s Hospital of Zhengzhou, Zhengzhou, 450000, People’s Republic of China; 2Department of Medical Genetics and Cell Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, People’s Republic of China; 3Department of Geriatric Medicine, the Center Hospital of Zhengzhou Affiliated Zhengzhou University, Zhengzhou, 450004, People’s Republic of China; 4Department of Genetics, First Affiliated Hospital of Xinxiang Medical College, Xinxiang, 453100, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying He; Guoying Song, Department of Medical Genetics and Cell Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, People’s Republic of China, Tel +86-13938517041 ; +86-13633827880, Email heying39@163.com; songguoying226@zzu.edu.cnBackground and Purpose: Studies have shown that matrix metalloproteinase (MMP-2,3,9) plays an important role in the pathologic process of ischemic stroke (IS). The aim of this study was to investigate the relationship between C1306T, 1612– 5A/6A, C-1562T polymorphisms of MMP-2,3,9 genes and IS in Chinese Han population.Methods: The polymorphisms of MMP-2(C1306T), − 3(1612– 5A/6A), − 9(C-1562T) gene were detected by PCR-RFLP and SNaPshot sequencing. Then, stratified analysis was used to study the relationship between IS subtypes and MMP-2,3,9 polymorphisms.Results: For the MMP-2 gene C1306T polymorphism, TT genotype and T allele were significantly associated with a reduced risk of IS (P = 0.015, P = 0.003, respectively). T allele was significantly associated with a reduced risk of small artery occlusion (SAO) subtype compared with the control group (P = 0.012, OR = 0.550, 95% CI = 0.065– 1.291). For the MMP-3 gene-1612 (5A/6A) polymorphism, 5A/5A genotype was significantly increased in the IS group (P = 0.011, OR = 0.370, 95% CI = 0.168– 0.814), especially in the large-artery atherosclerosis (LAA) subtype (P = 0.001, OR = 2.345) as compared to the control group.Conclusion: Our study suggested that the T allele of MMP-2 may be a protective factor of IS, especially in SAO subtype, while the 5A/5A gene of MMP-3 may increase the risk of IS, especially in LAA subtype in Chinese Han population.Keywords: ischemic stroke, matrix metalloproteinase, polymorphism, association study

Lu Liu,1 Guoxuan Song,2 Zhiqiang Song1 1Department of Dermatology, Southwest Hospital, Third Military Medical University, Chongqing, 400038, People’s Republic of China; 2First School of Clinical Medicine, Changsha Medical College, Changsha, 410219, People’s Republic of ChinaCorrespondence: Zhiqiang Song, Department of Dermatology, Southwest Hospital, Third Military Medical University, No. 29 Gaotanyan Str., Chongqing, 400038, People’s Republic of China, Tel +86 023 68754290, Email zhiqiang.song@hotmail.comAbstract: In atopic dermatitis (AD), recent research advances have portrayed a complex disease profile based on different subtypes/phenotypes and underlying molecular mechanisms/endotypes. Extrinsic and intrinsic subdivision is one of the most common types, defined in terms of total serum immune globulin E (IgE) and/or specific IgE to food and environmental allergens. Extrinsic AD is the most common type (80%), with high IgE, impaired skin barrier, as well as high incidence of comorbid atopic diseases, whereas intrinsic AD accounted for 20% of AD, with normal IgE and intact barrier function. Clinical studies have shown that extrinsic AD was a classic Th2-based inflammatory dermatitis, while the intrinsic subtype presented increased Th1/Th17/Th22 but normal Th2 cytokines. Protein sensitization, a classic Th2 response, has been clearly characterized in extrinsic AD, while metal hapten induces intrinsic AD’s sensitization, which may be associated with suprabasin deficiency. In this review, we aimed to further expand our knowledge about similarities and differences between these two subtypes, which will expand our capability to further dissect pathophysiology of AD and enable us to develop personalized medicine approaches.Keywords: intrinsic atopic dermatitis, extrinsic atopic dermatitis, epidermal barrier, immune dysfunction, immune globulin E

Runnan Wang,1 Dong Li,2 Jiwei Zhang,1 Guirong Song,1 Qigui Liu,1 Xiao Tang1 1School of Public Health, Dalian Medical University, Dalian City, Liaoning Province, People’s Republic of China; 2School of Marxism, Dalian Ocean University, Dalian City, Liaoning Province, People’s Republic of ChinaCorrespondence: Xiao Tang, School of Public Health, Dalian Medical University, Dalian City, Liaoning Province, People’s Republic of China, Tel +86-411-86110328, Email miss_tang@163.comPurpose: Adolescent depression has become a public health issue in China. Family environment and school life play important roles in shaping adolescent mental health. Our study aimed to examine the effect of parent-adolescent communication, school-life experiences, learning difficulties, and confidence in the future on depressive symptoms. We also examined the mediating effects of school-life experiences, learning difficulties, and confidence in the future on the relationship between parent-adolescent communication and depressive symptoms.Methods: Data on depressive symptoms, parent-adolescent communication, and mediating variables were obtained from the China Education Panel Survey (CEPS), including baseline data (2013– 2014) and follow-up data (2014– 2015). Mixed-effect models were used to evaluate the effects of parent-adolescent communication, school-life experiences, learning difficulties, and confidence in the future on depressive symptoms, and path analyses were performed to determine the mediating roles of school-life experiences, learning difficulties, and confidence in the future on the relationship between parent-adolescent communication and adolescent depressive symptoms.Results: More father-adolescent communication, better school-life experiences, and higher confidence in the future were protective factors for depressive symptoms among all boys and girls, and learning difficulties were a risk factor for depressive symptoms among all boys and girls. School-life experiences, learning difficulties, and confidence in the future had statistically significant mediating effects on the relationship between parent-adolescent communication and depressive symptoms.Conclusion: More father-adolescent communication, higher confidence in the future, better school-life experiences, and fewer academic difficulties were associated with lower levels of depressive symptoms. Both mother-adolescent communication and father-adolescent communication affected depressive symptoms through their effects on school-life experience, learning difficulties, and confidence in the future. This finding highlighted the importance of parent-adolescent communication and its impact on depression.Keywords: depression, communication, adolescent, CEPS

Yue Liu,1,2 Bidong Fu,2 Zichuan Yu,2 Gelin Song,2 Hong Zeng,2 Yiyang Gong,2 Yongqi Ding,2 Da Huang3 1Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330000, People’s Republic of China; 2Second College of Clinical Medicine, Nanchang University, Nanchang, Jiangxi Province, 330000, People’s Republic of China; 3Department of Thyroid Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330000, People’s Republic of ChinaCorrespondence: Da Huang, Department of Thyroid Surgery, Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel +86 13576113993, Email danmo0904@163.comPurpose: Hepatocellular carcinoma (HCC) is a malignancy with high incidence, but its prognosis is not optimistic. KRBA1 is a member of the KRAB family and participates in the regulation of gene transcription. However, no studies have focused on the role of KRBA1 in HCC.Patients and Methods: In this study, we first analyzed the expression of KRBA1 in HCC using TCGA and ICGC databases and validated by Immunohistochemistry in clinical HCC samples. The Wilcoxon rank-sum test was used to determine the relationship between KRBA1 expression and clinicopathological features. Subsequently, we used Kaplan-Meier online website analysis and Cox regression model to predict the prognostic value of KRBA1 in HCC patients. Furthermore, the functions of KRBA1 were identified by enrichment analysis. TIMER and GSCALite were used to investigate the relationship between KRBA1 expression in HCC and immune infiltration and drug targets, respectively. Finally, the relationship between KRBA1 expression and m6A modification in HCC was analyzed using the TCGA and ICGA datasets.Results: The results showed that KRBA1 was upregulated in HCC and was associated with many clinicopathological features. High KRBA1 causes poor overall survival and may be an independent risk factor for HCC. KRBA1 tends to be hypermethylated and associated with poor prognosis in HCC compared with normal tissues. Enrichment analysis indicates that KRBA1 is associated with cell cycle and immune processes, and TIMER analysis shows that KRBA1 expression is associated with infiltration levels and immune characteristics of various immune cells. Silenced KRBA1 evidently reduced three chemokine expression in HCC cells. Drug sensitivity analysis showed that KRBA1 was sensitive to 39 drug small molecules. KRBA1 showed a strong positive correlation with five m6A related genes.Conclusion: KRBA1 is a prognostic biomarker associated with HCC immunity and m6a modification, serving as an effective target for the diagnosis and treatment of HCC.Keywords: KRBA1, prognosis, biomarker, immune infiltration, hepatocellular carcinoma, m6A modification

Yong Gao,1,&ast; Baobao Cai,1,&ast; Lingdi Yin,1,&ast; Guoxin Song,2 Zipeng Lu,1 Feng Guo,1 Jianmin Chen,1 Chunhua Xi,1 Jishu Wei,1 Junli Wu,1 Wentao Gao,1 Kuirong Jiang,1 Yi Miao1,3 1Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China; 2Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China; 3Pancreas Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Miao, Email miaoyi@njmu.edu.cnBackground: Undifferentiated carcinoma of pancreas with osteoclast-like giant cells is an extremely rare tumor in pancreas. It is relatively difficult to have preoperative diagnosis due to the lack of specific tumor markers and pre-operative images.Methods: In the present study, database of the pancreas center in the First Affiliated Hospital of Nanjing Medical University was retrospectively screened. A total of thirteen cases diagnosed as undifferentiated carcinoma of pancreas with osteoclast-like giant cells were included. Their clinical data and treatments were collected.Results: Thirteen patients include eight males and five females, and the median age was 67 (60– 72) years old. The lesions were found in more than half patients through health examination with no symptoms. NSE was elevated in eight cases (66%). CT scan revealed that cystic and solid lesions often had thick (4/5), contrast-enhanced (5/5) wall with smooth edges (5/5) and the boundary of lesions mainly with solid composition (4/10) is not well demarcated with normal pancreatic parenchyma. All patients received surgical resection. Eight patients had adjuvant chemotherapy and only one patient had adjuvant radiotherapy. The median survival time was 13 months. Five patients had postoperative metastasis or recurrence of tumor and four of them had died of this disease during follow-up.Conclusion: Our data showed that elevated level of NSE and characteristic pre-operative images might provide aid with the pre-operative diagnosis for undifferentiated carcinoma of pancreas with osteoclast-like giant cells. Patients with suspected diagnosis should receive surgical intervention as soon as possible, supplemented with postoperative chemotherapy, in order to prolong the survival of patients.Keywords: pancreatic cancer, undifferentiated carcinoma of pancreas, osteoclast-like giant cells, retrospective, pre-operative image

Jun Wang,1– 3 Linlin Yang,4 Linquan Yang,4 Fei Zhou,1 Hang Zhao,2 Jing Liu,2 Huijuan Ma,1,2,4,&ast; Guangyao Song1,2,&ast; 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Endocrinology and Metabolic Diseases, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of China; 3Department of Emergency, Baoding First Central Hospital, Baoding, Hebei, People’s Republic of China; 4Hebei Key Laboratory of Metabolic Diseases, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huijuan Ma, Hebei Key Laboratory of Metabolic Diseases, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, 050051, Hebei, People’s Republic of China, Email huijuanma76@163.com Guangyao Song, Department of Endocrinology and Metabolic Diseases, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, 050051, Hebei, People’s Republic of China, Email sguangyao2@163.comPurpose: To investigate changes in the protein expression profile of white adipose tissue in low-birth weight (LBW) mice with high-fat diets using tandem mass tag (TMT) and liquid chromatography-mass spectrometry (LC-MS/MS) and parallel reaction monitoring (PRM).Methods: Institute of Cancer Research (ICR) mice were used to establish an LBW model using malnutrition during pregnancy. Male pups were randomly selected from LBW and normal-birth weight (NBW) offspring, then all given a high-fat diet. Blood glucose, serum insulin, total cholesterol (TC) and triglyceride (TG) levels were measured. The weight ratio of liver, muscle, and adiposity index were calculated. Hematoxylin and eosin staining was used to visualize adipose tissue morphology. Oil red O staining of liver and TG content of muscle were used to determine ectopic lipid deposition. TMT combined with LC-MS/MS was used to analyze protein expression in white adipose tissue. PRM and Western blot were used to verify the expression of CD36, SCD1, PCK1 and PPARγ.Results: Compared with NBW mice, fasting blood glucose, insulin and HOMA-IR significantly increased in LBW mice, indicating insulin resistance and impaired glucose regulation; TC, TG, adipocyte size, and adiposity index were increased in LBW mice, suggesting obesity and disorder of lipid metabolism. We observed ectopic lipid deposition in liver and muscle. There were 996 differentially expressed proteins (DEPs) in the LBW/NBW groups. Peroxisome proliferator-activated receptor (PPAR) was a relatively important signaling pathway regulating metabolic process in functional enrichment analysis of DEPs. Up-regulated expression of CD36, SCD1, and PCK1 in the adipose tissue of LBW mice was observed through PPAR pathways cluster analysis. And PRM and Western blot assay validated the proteomics findings.Conclusion: When exposed to high-fat diets, LBW mice exhibited insulin resistance and disorder of lipid metabolism compared with NBW mice. The expression of PPARγ was elevated, as well as upstream CD36, downstream SCD1 and PCK1 of the PPARγ in the adipose tissue of LBW mice. It was suggested that the activation in CD36/PPARγ/SCD1 and CD36/PPARγ/PCK1 pathways may induce adipose dysfunction, thereby increasing susceptibility to insulin resistance.Keywords: low birth weight, adipose tissue, insulin resistance, lipid metabolism

Yuling Xing,1,2 Jinhu Chen,1,2 Jing Liu,1,2 Guangyao Song,1,3 Huijuan Ma1,3 1Department of Endocrinology, Hebei General Hospital, Shijiazhuang, 050017, People’s Republic of China; 2Graduate School of Hebei Medical University, Shijiazhuang, 050017, People’s Republic of China; 3Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, 050017, People’s Republic of ChinaCorrespondence: Huijuan MaDepartment of Endocrinology, Hebei General Hospital, Shijiazhuang, 050017, People’s Republic of China, Tel +86 18032838686, Email huijuanma76@163.comPurpose: To investigate the association between serum uric acid-to-creatinine ratio (SUA/Cr) and the risk of developing metabolic-associated fatty liver disease (MAFLD) in patients with type 2 diabetes mellitus (T2DM).Patients and Methods: Overall, 1434 patients with T2DM who were admitted to Hebei General Hospital from January 2019 to December 2019 were selected as the study subjects. According to abdominal ultrasound findings, patients were divided into two groups: MAFLD group and non-MAFLD group. A total of 734 patients were diagnosed with MAFLD. Participants were divided into three study groups according to the SUA/Cr ratio. Chi-square test and one-way analysis of variance were used to perform a comparison between groups. The relationship between SUA/Cr ratio and MAFLD risk was analyzed using correlation analysis and regression analysis. Furthermore, subgroup analyses were performed to verify the robustness of the results.Results: The detection rate of MAFLD in patients with T2DM was 51.2%, and the detection rate of progressive liver fibrosis in T2DM patients with MAFLD was 36.6%. A significantly higher SUA/Cr ratio was seen in the MAFLD group than in the non-MAFLD group. After adjusting for confounding factors, multivariate logistic regression analysis revealed that the SUA/Cr ratio was an independent risk factor for MAFLD development. Stronger correlations were found in participants with a body mass index ranging between 23 and 28 kg/m2, HbA1C > 7%, or female sex.Conclusion: An elevated SUA/Cr index is independently correlated with an increased risk of MAFLD in Chinese adults with T2DM.Keywords: metabolic-associated fatty liver disease, type 2 diabetes, SUA/Cr

Jian Wang,1 Ge Zhao,2 Guang Song,3 Jing Liu2 1Department of Anesthesiology, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Obstetrics, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China; 3Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Jing LiuDepartment of Obstetrics, The First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Heping District, Shenyang, Liaoning Province, 110001, People’s Republic of ChinaTel +86 24 8328 2599Email liujing9936@163.comObjective: Cesarean section (CS) is one of the most frequently performed major surgical interventions. Local anesthetic techniques, a universal component of perioperative multimodal analgesia, are reportedly effective in reducing pain scores and opioid requirements. However, the optimal local anesthetic technique for postoperative CS pain remains unclear.Methods: Six databases were searched, and a Bayesian network meta-analysis was performed. The outcomes included cumulative morphine consumption and pain scores at four time points, time to first analgesic request, postoperative nausea and vomiting, pruritus, and sedation.Results: Sixty-eight studies with 5039 pregnant women were included. Six local anesthetic techniques were involved, including transversus abdominis plane block (TAPB), ilioinguinal and iliohypogastric nerve block, quadratus lumborum blocks, transversalis fascia plane block, erector spinae block, and wound infiltration. Compared to inactive controls, TAPB reduced cumulative morphine consumption at 6, 12, 24, and 48 h, pain scores at 6, 12, and 24 h (with the exception of 24 h at rest), the risk of postoperative nausea and vomiting, and sedation. Compared with inactive controls, ilioinguinal and iliohypogastric nerve block reduced cumulative morphine consumption at 6 and 24 h and pain scores at 6, 12, and 24 h during movement. Compared with inactive controls, quadratus lumborum blocks reduced cumulative morphine consumption at 24 and 48 h and pain scores at 6 and 12 h and lengthened the time to first analgesic request. Compared with inactive controls, wound infiltration reduced cumulative morphine consumption at 12 and 24 h, pain scores at 12 and 24 h during movement, and risk of sedation. Compared with inactive controls, erector spinae block reduced pain scores at 6 and 12 h. Transversalis fascia plane block was found to have similar outcomes to inactive controls.Conclusion: TAPB is the most comprehensive local anesthetic technique for postoperative CS analgesia in the absence of intrathecal morphine.Keywords: Cesarean section, postoperative pain, network meta-analysis, local anesthesia

Xiao Tang,1 Hongya Zhang,1 Yanxiang Zhao,2 Fang Lei,1 Qigui Liu,1 Dongmei Hu,1 Guorong Li,1 Guirong Song1 1Department of Health Statistics, School of Public Health, Dalian Medical University, Dalian City, Liaoning Province, 116044, People’s Republic of China; 2Department of Mathematics, George Washington University, Washington, DC, USACorrespondence: Guirong SongDepartment of Health Statistics, School of Public Health, Dalian Medical University, No. 9 South Road, Lvshun District, Dalian City, Liaoning Province, 116044, People’s Republic of ChinaTel +86-411-86110328Email songsara110@163.comBackground: Obesity is well recognized as a risk factor for cardiometabolic diseases. The development of obesity is a dynamic process that can be described as a multistate process with an emphasis on transitions between weight states. However, it is still unclear what convenient biomarkers predict transitions between weight states. The aim of this study was to show the dynamic nature of weight status in adults stratified by age and sex and to explore blood markers of metabolic syndrome (MetS) that predict transitions between weight states.Methods: This study involved 9795 individuals aged 18 to 56 at study entry who underwent at least two health check-ups in the eight-year period of study in the health check-up centre of our institution. Weight, height and biochemical indices were measured at each check-up. The participants were divided into four groups based on age and sex (young male, middle-aged male, young female and middle-aged female groups). A multistate Markov model containing 3 states (healthy weight, overweight and obesity) was adopted to study the longitudinal weight data.Results: Young people were more likely to transit between weight states than middle-aged people, and middle-aged people were more resistant to recover from worse states. The mean sojourn time in obesity was greatest in the middle-aged male group (6.23 years), and the predicted rate of obesity beginning with healthy weight was greatest in the young male group (13.7%). In multivariate models, age group and triglyceride (TG) and high-density lipoprotein cholesterol (HDL) levels were significant for specific transitions in females, whereas age group and HDL levels were significant in males. In females, if HDL levels increased 1 mmol/L, the probability of progression from healthy weight to overweight decreased by 37.0% (HR= 0.63), and the probabilities of recovery (overweight to healthy weight and obesity to overweight) increased by 62.0% (HR= 1.62) and 1.23-fold (HR= 2.23), respectively. In males, if TG levels increased 1 mmol/L, the risk of progression from healthy weight to overweight increased by 24.0% (HR= 1.24). Each unit increase in HDL levels was associated with a 0.99-fold (HR= 1.99) increase in the chance of recovery from overweight to healthy weight and with a 0.37-fold (HR= 0.63) decrease in the risk of progression from healthy weight to overweight.Conclusion: The weight status of young people was less stable than that of middle-aged people. Males were more likely to become overweight and more resistant to recover from worse states than females. Young males with healthy weight were more likely to develop obesity than other healthy weight groups. Blood lipid levels, especially HDL, were predictors of weight transitions in adults. Prevention and intervention measures should be applied early.Keywords: obesity, multistate Markov model, triglyceride, high-density lipoprotein cholesterol, low density lipoprotein cholesterol

Gang Wang,1,* Guobin Song,1,2,* Yuanhong Xu1 1Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 2Department of Clinical Laboratory, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuanhong XuDepartment of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Shushan District, Hefei, Anhui Province, 230022, People’s Republic of ChinaEmail xyhong1964@163.comBackground: Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) is a novel method that can be used to identify pathogens and has potential applications in the detection of drug-resistant bacteria.Purpose: To evaluate the ability of a MALDI-TOF MS-based broth micro-dilution method in detecting the minimum inhibitory concentration (MIC) values of Klebsiella pneumoniae to ceftriaxone and imipenem.Materials and Methods: Sixty strains of K. pneumoniae with different levels of resistance to carbapenems and cephalosporins were randomly collected. The 0.5 McFarland (Mc) concentration of the bacterial suspension was inoculated in cation-adjusted Mueller-Hinton broth (CAMHB) with a final cell turbidity of 5× 105 CFU/mL. The broth was incubated with serial concentrations of antibiotics. After centrifuging the bacterial suspensions, the lysed cells were analyzed by MALDI-TOF MS to identify the growth-promoting or inhibitory effects on K. pneumoniae. The molecular mechanisms of resistance were investigated by PCR and DNA sequencing analysis.Results: The expression of known resistance genes (blaKPC, blaFOX, blaDHA, blaCTX-M and blaTEM) was detected in the 30 carbapenems-resistant strains. The agreement between the MIC values derived from the MALDI-TOF MS analysis and from the broth micro-dilution method was 61.7% for ceftriaxone and 71.7% for imipenem. According to the Clinical and Laboratory Standards Institute (CLSI) breakpoint of resistance to ceftriaxone and imipenem, the 60 isolates were accurately classified as resistant or susceptible isolates with 100% sensitivity and 100% specificity.Conclusion: The transmission and infection of multidrug-resistant bacteria could be better managed and treated with the rapid identification of strains and antimicrobial susceptibility. A MALDI-TOF MS-based susceptibility test could be used to identify resistance of K. pneumoniae within a short time-frame. This approach could potentially be used as a supplementary antimicrobial susceptibility test that could be investigated on more bacterial species combined with different antibiotics.Keywords: Klebsiella pneumoniae, matrix-assisted laser desorption ionization–time of flight mass spectrometry, carbapenemases, extended-spectrum β-lactamases, antimicrobial susceptibility test

Yinhua Tang, Guang Song, Hongcheng Liu, Shuang Yang, Xiaoyi Yu, Lijun Shi Department of Gastroenterology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People’s Republic of ChinaCorrespondence: Lijun ShiDepartment of Gastroenterology, The First Affiliated Hospital of Harbin Medical University, No. 23, Youzheng Street, Harbin, Heilongjiang Province, 150001, People’s Republic of ChinaTel +86-0451-85555119Email 1440588495@qq.comPurpose: Pancreatic cancer (PC) is a malignancy with poor prognosis and controversial treatment options. Long non-coding RNA (lncRNA) is a significant factor in the development of PC. In the current study, the possible effects of HOTAIR on the epithelial–mesenchymal transition (EMT) of PC and the related mechanisms were investigated.Methods: The PC models were induced by 10 mg/100 g dimethylbenzoanthracene (DMBA) in pancreas. Mice were injected with the HOTAIR mimic and HOTAIR shRNA to determine the role of HOTAIR in PC. Subsequently, the expression of HOTAIR in PC cells was assayed. To determine the mechanism of HOTAIR in PC, human PC cell line PANC-1, Miapaca-2 and human normal pancreatic ductal epithelial cell line HPDE6-C7 were transfected with the HOTAIR mimic, the shRNA against HOTAIR, the Wnt/b-catenin activator (LiCl), and the Wnt/b-catenin inhibitor (XAV939), respectively. Moreover, the expressions of the Wnt/β-catenin signaling pathway-related genes (β-catenin, cyclinD1, c-myc, LEF-1 and c-Jun) and the levels of the EMT markers (E-cadherin, N-cadherin and Vimentin) were determined. Finally, the cell biological processes were evaluated by functional experiments.Results: HOTAIR was found to be highly expressed in the PC cells in mice. The expression of β-catenin, cyclinD1, c-myc, LEF-1 and c-Jun, N-cadherin and Vimentin was found to be decreased, while the expression of E-cadherin was found to be increased subsequent to the silencing of HOTAIR in human PC cell lines PANC-1 and Miapaca-2. Additionally, it was observed that the silencing of HOTAIR could inhibit the Wnt/β-catenin signaling pathway to alleviate EMT of tumor cells and inhibit the capacities of cell proliferation, migration, and invasion.Conclusion: The key finding of the present study is that the silencing of HOTAIR could potentially inhibit EMT and growth of PC through the Wnt/β-catenin signaling pathway, providing a novel therapy for PC.Keywords: long non-coding RNA, HOTAIR, Wnt/β-catenin signaling pathway, epithelial–mesenchymal transition, pancreatic cancer

Hang Zhao,1 Yong Tang,1 Chong Zheng,2 Luping Ren,1,* Guangyao Song1,* 1Endocrinology Department, Hebei General Hospital, Shijiazhuang, Hebei, 050051, People’s Republic of China; 2Pediatric Orthopaedics, Shijiazhuang the Third Hospital, Shijiazhuang, Hebei, 050011, People’s Republic of China*These authors contributed equally to this workCorrespondence: Luping Ren; Guangyao Song 348, Heping West Road, Shijiazhuang, Hebei, 050051, People’s Republic of ChinaTel +8631185988975; +8631185988556Email renluping1122@163.com; sguangyao2@163.comPurpose: This study aimed to examine whether 25-hydroxyvitamin D (25OHD) levels (an indicator of vitamin D status) are independently associated with insulin resistance (IR) in patients with type 2 diabetes mellitus (T2DM).Patients and Methods: This was a cross-sectional study. Participants with T2DM were recruited from the Department of Endocrinology in Hebei General Hospital according to inclusion and exclusion criteria. Data on basic characteristics and blood parameters were collected. We used the IR index (20/[fasting C-peptide × fasting plasma glucose]) to evaluate IR. Potential confounding factors were selected from comparisons among different IR index groups of quartiles and were adjusted in different models.Results: We included 172 subjects (121 men and 51 women) whose mean age was 53.2± 10.6 years. Body mass index (BMI), DM course, insulin use, glycated hemoglobin (HbA1c), fasting blood glucose, fasting C-peptide, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (ApoA1), and albumin were differed among different IR-index groups (all P value < 0.05). In models 1 and 2, no or some confounding factors were adjusted for, and we found that there was no relationship between 25OHD and the IR index. In model 3, when all confounding factors (DM course, insulin use, BMI, HbA1c, TG, HDL-C, ApoA1, albumin and other bone turnover markers) were adjusted for, the IR index was increased by 5.6% when 25OHD levels increased by 1 ng/mL (odds ratio: 1.056; 95% confidence interval: 1.009, 1.105).Conclusion: Vitamin D is independently associated with IR in patients with T2DM.Keywords: diabetes mellitus, type 2, vitamin D, insulin resistance