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Background and purposeAcidification of the tumor microenvironment from abnormal metabolism along with angiogenesis to meet metabolic demands are both hallmarks of malignant brain tumors; however, the interdependency of tumor acidity and vascularity has not been explored. Therefore, our aim was to investigate the association between pH-sensitive amine chemical exchange saturation transfer echoplanar imaging (CEST-EPI) and relative cerebral blood volume (CBV) measurements obtained from dynamic susceptibility contrast (DSC) perfusion MRI in patients with gliomas.Materials and methodsIn this retrospective study, 90 patients with histologically confirmed gliomas were scanned between 2015 and 2018 (median age, 50.3 years; male/female ratio = 59:31). pH-weighting was obtained using chemical exchange saturation transfer echo-planar imaging estimation of the magnetization transfer ratio asymmetry at 3 ppm, and CBV was estimated using DSC-MR imaging. The voxelwise correlation and patient-wise median value correlation between the magnetization transfer ratio asymmetry at 3 ppm and CBV within T2-hyperintense lesions and contrast-enhancing lesions were evaluated using the Pearson correlation analysis.ResultsGeneral colocalization of elevated perfusion and high acidity was observed in tumors, with local intratumor heterogeneity. For patient-wise analysis, median CBV and magnetization transfer ratio asymmetry at 3 ppm within T2-hyperintense lesions were significantly correlated (R = 0.3180, P = .002), but not in areas of contrast enhancement (P = .52). The positive correlation in T2-hyperintense lesions remained within high-grade gliomas (R = 0.4128, P = .001) and in isocitrate dehydrogenase wild-type gliomas (R = 0.4300, P = .002), but not in World Health Organization II or in isocitrate dehydrogenase mutant tumors. Both magnetization transfer ratio asymmetry at 3 ppm and the voxelwise correlation between magnetization transfer ratio asymmetry and CBV were higher in high-grade gliomas compared with low-grade gliomas in T2-hyperintense tumors (magnetization transfer ratio asymmetry, P = .02; Pearson correlation, P = .01). The same trend held when comparing isocitrate dehydrogenase wild-type gliomas and isocitrate dehydrogenase mutant gliomas (magnetization transfer ratio asymmetry, P = .04; Pearson correlation, P = .01).ConclusionsA positive linear correlation between CBV and acidity in areas of T2-hyperintense, nonenhancing tumor, but not enhancing tumor, was observed across patients. Local heterogeneity was observed within individual tumors.

Qingwei Li,1 Haiyin Zhang,2 Guozhen Lin,3 Shenxun Shi,4 Yingli Zhang,5 Jianlin Ji,6 Lipeng Yang,7 Jun Yao,1 Wenyuan Wu1 1Department of Psychiatry, Tongji Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Clinical Psychology, Shanghai Mental Health Center, Shanghai, People’s Republic of China; 3Department of Psychiatry, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Psychiatry Department, Fudan University Affiliated Huashan Hospital, Shanghai, People’s Republic of China; 5Department of Depressive Disorders, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, People’s Republic of China; 6Department of Psychological Medicine, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 7Department of Neurology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, People’s Republic of ChinaCorrespondence: Wenyuan Wu, Department of Psychiatry, Tongji Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China, Email wuwy@tongji.edu.cnPurpose: To determine the relative safety and efficacy of different doses of tandospirone in treating generalized anxiety disorder (GAD).Patients and Methods: This parallel randomized controlled trial enrolled patients with GAD from eight centers in China. The patients were randomly assigned to 60 mg/day or 30 mg/day tandospirone groups. The primary endpoint was the overall response rate after receiving 6-week treatment. The secondary endpoints included significant response rate, clinical recovery rate, change in the Hamilton Anxiety Scale (HAMA) total score, HAMA subscale score, Hamilton Depression Scale-17 (HAMD-17), Clinical Global Impression-Severity Scale (CGI-S) score, and Impression-Improvement scale (CGI-I) score.Results: No significant difference was found in the overall response rate between the two groups (65.7% vs 58.4%, p = 0.213). A higher significant response rate and change in the HAMA total score were found in the 60 mg/day group. The reduction in the CGI-S score and percentage of patients with a CGI-I score of ≤ 2 were higher in 60 mg/day group. The reduction in HAMA somatic anxiety factor, cardiovascular symptom factor, gastrointestinal symptom factor, and HAMD-17 score were more significant in the 60 mg/day group. The incidence of total adverse events was higher in the 60 mg/day group than in the 30 mg/day group. No significant difference was found in the proportion of withdrawal due to adverse events.Conclusion: Both 60 mg/day and 30 mg/day tandospirone show good efficacy in treating patients with GAD. High doses of tandospirone may have advantages in relieving the somatic symptoms but also present disadvantages due to their high level.Trial Registration: The trial registration no. was NCT01614041.Keywords: generalized anxiety disorder, tandospirone, randomized controlled trial, safety, efficacy

Zhenming Zhang,1,* Zhentao Hu,1,* Yujie Qin,2,* Jun Qian,3 Song Tu,1,3 Jiaxi Yao3,4 1Department of General Surgery II, Hexi University Affiliated Zhangye People’s Hospital, Zhangye, Gansu, 734000, People’s Republic of China; 2Department of Endoscopy Center, Hexi University Affiliated Zhangye People’s Hospital, Zhangye, Gansu, 734000, People’s Republic of China; 3Institute of Urology, Hexi University, Zhangye, Gansu, 734000, People’s Republic of China; 4Department of Urology, Hexi University Affiliated Zhangye People’s Hospital, Zhangye, Gansu, 734000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jiaxi Yao; Song Tu, Department of Urology, Zhangye People’s Hospital, affiliated to Hexi University, No. 67, Xihuan Road, Ganzhou District, Zhangye City, Gansu, 734000, People’s Republic of China, Tel +86-18093616382, Email 16111210057@fudan.edu.cn; zytusong@126.comPurpose: To determine an accurate method of inspecting low anastomotic leakages and application of transurethral prostate resection instrumentation for treating low rectal anastomotic leakage.Patients and Methods: Clinical data of eight patients treated for anastomotic leakage after rectal cancer surgery at Zhangye People’s Hospital (affiliated to Hexi University), from August 2019 to November 2021, were retrospectively analyzed. Transanal prostate resection instrumentation was used to assess the leakage and surrounding conditions. Using prostate resection instrumentation, the presacral and perirectal residual cavities were washed and removed, and indwelling suprapubic presacral, transanal presacral, and rectal drainage tubes were placed. Continuous presacral saline irrigation and drainage and open negative-pressure suction in the rectal cavity were performed until the patients’ fistula healed.Results: Of the eight patients with anastomotic leakages, one had grade B and seven had grade C International Study Group of Rectal Cancer anastomotic leakage classifications following Dixon operation. Transanal prostate resection instrumentation showed that the leakage of the one patient with grade B was less than a third of the circumference of the anastomosis. Among the seven patients with grade C, one leakage was less than a third of the anastomotic circumference. One patient had complete separation of the anastomosis and one distal colon necrosis, which necessitated immediate descending colostomy. Conservative treatment was successful in six patients; the conservative overall cure rate was 75%, and the median healing time was 43 (21– 68) days.Conclusion: Transanal examination of rectal anastomotic leakage using prostate resection instrumentation is comprehensive, easy to perform, provides clear visualization, accurately guides catheter placement, and can be combined with continuous open negative-pressure drainage, which is a safe, convenient, and effective method for treating low rectal leakage.Keywords: anastomotic leakage, prostate resection instrumentation, catheter, negative-pressure drainage

Cuiyun Wu,1 Lin Zheng,1 Jie Yao2 1Department of Clinical Laboratory, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, Guangdong, People’s Republic of China; 2Department of Laboratory Medicine and Medical Research Center, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, Guangdong, People’s Republic of ChinaCorrespondence: Jie Yao, Department of Laboratory Medicine and Medical Research Center, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), No. 1, Jiazi Road, Lunjiao, Shunde District, Foshan City, Guangdong Province, 528308, People’s Republic of China, Tel +86 757 22318169, Email jie.yao413@yahoo.comBackground: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection is associated with high mortality and has become a major public problem threatening patients. This study aimed to explore risk factors for death in patients with Klebsiella pneumoniae (KP) and identify risk factors for CRKP infection.Methods: The study retrospectively analyzed clinical characteristics and microbiological data from patients infected with KP from January 2019 to October 2021 to identify risk factors and mortality, using multivariate logistic regression analysis and Cox regression analysis.Results: A total of 214 KP inpatients were enrolled in our study. The in-hospital mortality rate was significantly higher in patients infected with CRKP (13/68, 19.12%) than carbapenem-susceptible KP (CSKP) (2/146, 1.37%) and the difference was statistically significant (P= 0.03). Multivariate Cox regression analysis showed CRKP isolation (HR 12.26, 95% CI 2.43– 61.68, P = 0.002), lower TP (HR 10.50, 95% CI 1.33– 82.76, P = 0.03), antibiotic days of therapy > 15 (HR 0.08, 95% CI 0.01– 0.56, P= 0.01) and length of stay (LOS) (HR 0.03, 95% CI 0.002– 0.61, P= 0.02) were independent risk factors for death from KP. Additionally, intensive care unit (ICU) stay (OR 21.69, 95% CI 4.50– 118.76, P< 0.001) and previous carbapenem exposure (OR 5.26, 95% CI 1.38– 21.19, P= 0.02) are independent risk factors for CRKP.Conclusion: Our findings showed that patients infected with CRKP have a higher in-hospital mortality rate. Identifying the independent risk factors for CRKP infection may contribute to the management of CRKP and reduce the mortality of KP patients.Keywords: carbapenem-resistant, Klebsiella pneumoniae, risk factors, mortality

Cong Luo,1 Jiaxin Yao,1 Haoran Bi,2 Zhen Li,1 Ju Li,3 Guosong Xue,3 Ke Li,3 Shenyang Zhang,3 Kun Zan,3 Wenqing Meng,3 Zunsheng Zhang,3 Hao Chen3 1Graduate School, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 2Department of Biostatistics, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 3Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of ChinaCorrespondence: Zunsheng Zhang; Hao Chen, Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, 99 Huaihai West Road, Quanshan District, Xuzhou, Jiangsu, People’s Republic of China, Tel +86-13913473179 ; +86-15252006510, Email 13913473179@163.com; haochen-2008@hotmail.comBackground: Inflammation is closely associated with prognosis in patients with aneurysmal subarachnoid hemorrhage (aSAH), which is orchestrated by inflammatory cytokines. Therefore, this study aimed to investigate the levels of inflammatory cytokines in the early stage of aSAH and their predictive value for prognosis.Methods: In this retrospective study, 206 patients with aSAH were recruited and assigned to a severe group (WFNS grade ≥ 4) and a mild group (WFNS grade < 4) according to the severity of patients on admission. Flow cytometry was performed to detect the levels of 12 inflammatory cytokines in the serum of patients. Then, patients were grouped into a poor prognosis group (mRS score ≥ 4) and a good prognosis group (mRS score < 4) based on their prognosis after 3 months of discharge to compare the relationship between cytokines and prognosis. Propensity score matching (PSM) was utilized to control confounding factors. The correlation between inflammatory factors and prognosis was determined using Spearman correlation, and the predictive efficacy of inflammatory factors was tested by a receiver operating characteristic curve.Results: Serum IL-1β, IL-5, IL-6, IL-8, IL-10, IFN-γ, and TNF-α levels were significantly higher in the mild group than in the severe group and in the poor prognosis group than in the good prognosis group. After PSM, the differences in IL-1β, IL-5, IFN-α, and IFN-γ levels disappeared between the two groups, whereas IL-2, IL-6, IL-8, IL-10, and TNF-α levels remained higher in the poor prognosis group than in the good prognosis group. Additionally, IL-2, IL-6, IL-8, and IL-10 levels were positively correlated with mRS scores. Moreover, the predictive value was found to be the highest for IL-6 and the lowest for TNF-α.Conclusion: Inflammation degree was related to the severity of aSAH. Inflammatory markers, including IL-6, IL-10, IL-8, IL-2, and TNF-α, might predict the poor prognosis of aSAH.Keywords: aneurysmal subarachnoid hemorrhage, inflammation, cytokine, prognosis, propensity score matching

Quan Lu,1,2,&ast; Mei-feng Yang,3,&ast; Yu-jie Liang,4,&ast; Jing Xu,5 Hao-ming Xu,5 Yu-qiang Nie,5 Li-sheng Wang,1,2 Jun Yao,1,2 De-feng Li1,2 1Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University), Shenzhen, Guangdong, People’s Republic of China; 2Department of Gastroenterology, Shenzhen People’s Hospital (The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People’s Republic of China; 3Department of Hematology, Yantian District People’s Hospital, Shenzhen, Guangdong, People’s Republic of China; 4Department of Child and Adolescent Psychiatry, Shenzhen Kangning Hospital, Shenzhen, Guangdong, People’s Republic of China; 5Department of Gastroenterology and Hepatology, Guangzhou First People’s Hospital (School of Medicine of South China University of Technology), Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Yao; De-feng Li, Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University), No. 1017, Dongmen North Road, Luohu District, Shenzhen, 518020, People’s Republic of China, Tel +86 755 25533018, Email yao.jun@szhospital.com; ldf830712@163.comAbstract: As a main digestive organ and an important immune organ, the intestine plays a vital role in resisting the invasion of potential pathogens into the body. Intestinal immune dysfunction remains important pathogenesis of inflammatory bowel disease (IBD). In this review, we explained the interactions among symbiotic flora, intestinal epithelial cells, and the immune system, clarified the operating mechanism of the intestinal immune system, and highlighted the immunological pathogenesis of IBD, with a focus on the development of immunotherapy for IBD. In addition, intestinal fibrosis is a significant complication in patients with long-term IBD, and we reviewed the immunological pathogenesis involved in the development of intestinal fibrogenesis and provided novel antifibrotic immunotherapies for IBD.Keywords: inflammatory bowel disease, immune system, immunological pathogenesis, immunotherapy

The article delves into the analysis of large-scale coherent structures in turbulent pipe flows at different Reynolds numbers. By utilizing the Karhunen-Loève decomposition and a unique Voronoi diagram method, the research identifies two categories of structures - wall-attached and detached eddies - based on their characteristics and energy contributions. The study demonstrates that as the Reynolds number increases, the energy distribution of these structures changes, with attached eddies scaling linearly with the wall-normal distance while detached eddies maintain a consistent size. This research sheds light on the spatial distribution of these structures, potentially aiding in understanding the variations in mean velocity between pipe and channel flows and enhancing the modeling of large-scale motions. [Extracted from the article]

Xiaojing Shang,1 Rui Zhang,2 Xiaolai Wang,1 Junxin Yao,1 Xiaoying Zhao,1 Huanming Li3 1Department of Endocrinology, Tianjin Fourth Central Hospital, Tianjin, People’s Republic of China; 2Division of Health Management, Tianjin Fourth Central Hospital, Tianjin, People’s Republic of China; 3Department of Cardiology, Tianjin Fourth Central Hospital, Tianjin, People’s Republic of ChinaCorrespondence: Huanming Li Email lihuanming0716@163.comAim: Elevated serum ferritin has been found to be closely related to type 2 diabetes mellitus. This study aimed to explore the relationship of high serum ferritin to metabolism and chronic complications in type 2 diabetes.Methods: This was a cross-sectional study. A total of 330 type 2 diabetes patients who visited an endocrine clinic were included for the analysis. Serum ferritin and metabolic parameters were recorded. The prevalence of chronic diabetic complications was evaluated. Based on serum ferritin, participants were divided into hyperferritinemia and normal-ferritin groups. Metabolic parameters and prevalence of chronic diabetic complications were compared. The relationship between hyperferritinemia and chronic diabetic complications was explored with multivariate logistic regression models. Data were statistically analyzed by sex.Results: Compared with the normal-ferritin group, the hyperferritinemia group showed higher levels of the serum inflammatory marker CRP and higher prevalence of diabetic retinopathy (DR) and coronary heart disease (CHD), regardless of sex (p< 0.05). Moreover, male patients with hyperferritinemia had increased serum triglyceride, alanine transferase, γ-glutamyltranspeptidase, urea nitrogen, creatinine, and uric acid and higher prevalence of microalbuminuria (p< 0.01). After controlling for demographics and metabolic profiles, hyperferritinemia remained an independent risk factor of DR (male OR 3.957, 95% CI 1.559– 10.041, p=0.004; female OR 2.474, 95% CI 1.127– 5.430, p=0.024) and CHD (male OR 2.607, 95% CI 1.087– 6.257, p=0.032; female OR 2.293, 95% CI 1.031– 5.096, p=0.042).Conclusion: This study found that hyperferritinemia was associated with increased CRP and higher prevalence of DR and CHD in type 2 diabetes. In men, high serum ferritin was also associated with dyslipidemia, hepatic dysfunction, and microalbuminuria.Keywords: diabetes mellitus, type 2, ferritin, metabolism, chronic complication

Juan Pan,1,2,&ast; Rui Tong,1,&ast; Qing Deng,3 Yanni Tian,1 Ning Wang,1 Yanqi Peng,1 Sijia Fei,1 Wei Zhang,4 Jiaqi Cui,1 Chaoying Guo,1 Juanchuan Yao,1 Cui Wei,1 Jing Xu1 1Department of Geriatric Endocrinology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, Shaanxi, People’s Republic of China; 2Department of Endocrinology, Xianyang Central Hospital, Xianyang, 712000, Shaanxi, People’s Republic of China; 3Department of Endocrinology, No. 215 Hospital of Shaanxi Nuclear Industry, Xianyang, 712000, Shaanxi, People’s Republic of China; 4Department of Breast Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Cui Wei; Jing XuDepartment of Geriatric Endocrinology, The First Affiliated Hospital of Xi’an Jiaotong University, #277 West Yanta Road, Xi’an, 710061, Shaanxi, People’s Republic of China, Tel +86 18991232462; Tel +86 18991232462Email doctorweiwei.cui@126.com; 254309205@qq.comBackground: SOCS2 is downregulated in diabetes, which might be related to diabetes. We explored the effect of SOCS2 polymorphisms on the development of type 2 diabetes mellitus (T2DM) and diabetic complications.Methods: The subjects consisted of 500 patients with T2DM and 501 healthy controls. Five variants in SOCS2 were genotyped by Agena MassARRAY system. RT-qPCR profiling was performed to detect the expression of SOCS2 mRNA. Logistic regression analysis was utilized to calculate odds ratio (OR) and 95% confidence intervals (95% CIs).Results: Rs3825199 (OR = 1.44, p = 0.007), rs11107116 (OR = 1.39, p = 0.014) and rs10492321 (OR = 1.48, p = 0.004) had an increased T2DM risk of T2DM. Moreover, the contribution of SOCS2 polymorphisms to T2DM risk was associated with age, gender, smoking, drinking, and BMI. SOCS2 variants also had a reduced risk for T2DM patients with diabetic nephropathy, diabetic retinopathy and coronary heart disease. SOCS2 rs10492321 was the best single locus model. SOCS2 mRNA was downregulated in patients with T2DM compared to healthy controls (p = 0.029).Conclusion: This study firstly reported that rs3825199, rs11107116 and rs10492321 in SOCS2 conferred to an increased risk for the occurrence of T2DM in the Chinese Han population. Moreover, SOCS2 mRNA was downregulated in patients with T2DM, suggesting that SOCS2 might have an important role in the occurrence of T2DM.Keywords: type 2 diabetes mellitus, SOCS2 variants, diabetic complications, life style

Vacuum ultraviolet (VUV) single photon ionization mass spectrometry (SPI-MS) is a vacuum-based technique typically used for the analysis of gas phase and solid samples, but not for liquids due to the challenge in introducing volatile liquids in a vacuum. Here we present the first demonstration of in situ liquid analysis by integrating the System for Analysis at the Liquid Vacuum Interface (SALVI) microfluidic reactor into VUV SPI-MS. Four representative volatile organic compound (VOC) solutions were used to illustrate the feasibility of liquid analysis. Our results show the accurate mass identification of the VOC molecules and the reliable determination of appearance energy that is consistent with ionization energy for gaseous species in the literature as reported. This work validates that the vacuum-compatible SALVI microfluidic interface can be utilized at the synchrotron beamline and enable the in situ study of gas-phase molecules evaporating off the surface of a liquid, which holds importance in the study of condensed matter chemistry.

Li-Qiang Cai,1,2 Lei Huang,1,2 Li-Li Wei,1,2 Jia-Shu Yao,1,2 Luo-Yi Xu,1,2 Wei Chen1,2 1Department of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Center for Sleep Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Wei ChenDepartment of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, East Qingchun Road 3, Hangzhou, Zhejiang, 310016, People’s Republic of ChinaTel +86-571-87887800Email srrcw@zju.edu.cnObjective: This study aimed at investigating the correlation between estradiol and sleep apnea among women with major depressive disorders during the perimenopausal and postmenopausal periods.Methods: A total of 84 perimenopausal and postmenopausal women diagnosed with depression, and who had been subjected to whole-night polysomnography (PSG) were retrospectively studied. They were assigned into two groups based on the presence of OSA (apnea–hypopnea index (AHI)≥ 5) (OSA vs non-OSA). The correlation between estradiol levels and apnea–hypopnea index were assessed by logistic regression models after adjusting for age, body mass index (BMI), Hamilton Depression Rating Scale (HAMD), Pittsburgh Sleep Quality Index (PSQI), apnea frequency and progesterone.Results: Among the 84 patients, 45.23% had OSA. Estradiol levels were significantly elevated in non-OSA than in OSA patients (p< 0.05). Univariate analysis revealed that elevated estradiol levels are associated with reduced odds of OSA (odds ratio [OR] 0.92, 95% confidence interval [CI] 0.875– 0.966, p = 0.001). Multivariate analyses showed that low estradiol levels (OR = 0.859, 95% CI 0.826– 0.991, p = 0.031), higher HAMD scores (OR = 1.212, 95% CI 1.012– 1.453, p = 0.037), higher apnea frequency (OR = 2.493, 95% CI 1.389– 4.473, p = 0.002) and higher BMI (OR=1.635, 95% CI 1.136– 2.353, p = 0.008) are correlated with OSA.Conclusion: The ratio of depressed perimenopausal to postmenopausal women comorbid OSA was high. Higher BMI, low estradiol levels, high apnea frequency and high HAMD scores were correlated with OSA diagnosis and could be potential diagnostic markers for OSA in depressed perimenopausal and postmenopausal women. Reduced estradiol levels were correlated with an increased risk of OSA among depressed perimenopausal and postmenopausal women.Keywords: major depressive disorder, estradiol, obstructive sleep apnea, menopause, polysomnography

Jian-Yao Wang,1,&ast; Jing Lao,2,&ast; Yu Luo,3 Jing-Jie Guo,2 Hao Cheng,2 Hong-Yan Zhang,2 Jun Yao,4 Xiao-Peng Ma,1 Bin Wang1 1Department of General Surgery, Shenzhen Children’s Hospital, Shenzhen, 518026, Guangdong Province, People’s Republic of China; 2Shenzhen Children’s Hospital of China Medical University, Shenzhen, 518026, Guangdong Province, People’s Republic of China; 3Zhuhai Campus of Zunyi Medical University, Zhuhai, 519090, Guangdong Province, People’s Republic of China; 4Department of Gastroenterology, Jinan University of Medical Sciences, Shenzhen Municipal People’s Hospital, Shenzhen, 518020, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao-Peng Ma; Bin Wang Tel +86-075583008073Email 1345012907@qq.com; szwb1967@126.comPurpose: This study aimed to identify novel methylation-regulated genes as diagnostic biomarkers and therapeutic targets for hepatoblastoma (HB).Materials and Methods: The DNA methylation data of 19 HB tumor samples and 10 normal liver samples from the GSE78732 dataset and gene expression profiling data of 53 HB tumor samples and 14 normal liver samples from the GSE131329 dataset and 31 HB tumor samples and 32 normal liver samples from the GSE133039 dataset were downloaded form the Gene Expression Omnibus database. Next, differentially methylated genes (DMGs) and differentially expressed genes (DEGs) were identified. Venn diagrams were used to identify methylation-regulated genes. The VarElect online tool was selected to identify key methylation-regulated genes, and a protein–protein interaction (PPI) network was constructed to show the interactions among key methylation-regulated genes and DEGs. Finally, Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed to investigate the potential regulatory mechanisms of key methylation-regulated genes.Results: A total of 457 DMGs and 1597 DEGs were identified between the HB and normal liver samples. After DMGs and DEGs overlapping, 22 hypomethylated and upregulated genes and 19 hypermethylated and downregulated genes in HB were screened. Survival analysis revealed that 13 methylation-regulated genes were associated with the prognosis of liver cancer. Moreover, SPP1, UHRF1, and HEY1 were selected as the key DNA methylation-regulated genes. The PPI network revealed that all of them could affect TP53, while both UHRF1 and HEY1 could influence BMP4. Enrichment analysis suggested that the DEGs were involved in TP53-related pathways, including the cell cycle and p53 signaling pathway. Finally, SPP1, UHRF1, and HEY1 were hypomethylated and upregulated in the HB samples compared with those in the normal liver samples.Conclusion: SPP1, UHRE1, and HEY1 may play important roles in HB and be used as biomarkers for its diagnosis and treatment.Keywords: DNA methylation, gene, hepatoblastoma, biomarker, tumor

Yi Lu,1,* Bang Hu,2,* Haitao Dai,3,* Bao Wang,1 Jiayin Yao,4 Xinhua Yao1 1Department of Anesthesiology, The Affiliated TCM Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, People’s Republic of China; 2Department of Colorectal Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 3Department of Interventional Radiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 4Department of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinhua YaoDepartment of Anesthesiology, The Affiliated TCM Hospital of Guangzhou Medical University, 16th Zhuji Road, Guangzhou, Guangdong Province, 510130, People’s Republic of ChinaTel +86 13719289709Email yxh200210@126.comJiayin YaoDepartment of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital of Sun Yat-Sen University, 26th Yuancun Second Road, Guangzhou, Guangdong Province, 510655, People’s Republic of ChinaTel +86 13826462890Email yjyin@mail3.sysu.edu.cnBackground: Identifying patients at high risk of developing chronic postsurgical pain (CPSP) is of extreme importance in order to help launch appropriate therapeutic strategies and intensive initiation of pain management.Aim: In this study, we aimed to conduct a multi-center retrospective cohort study to establish a prognostic model and a nomogram to predict the risks of CPSP in elderly patients who underwent hip arthroplasty at 6 months postoperatively.Methods: We collected data from 736 patients aged > 65 years who had undergone hip arthroplasty from October 1, 2016 to September, 30, 2018 at multiple tertiary referral centers in Guangzhou, China. All data were randomly stratified into a training set and a testing set at a ratio of 8:2. Data were analyzed via multiple logistic regression analysis with receiver operating characteristic (ROC) curves and areas under the curve. This model was further validated by estimating calibration and discrimination. A nomogram was ultimately developed.Results: A total of 736 eligible patients were enrolled, 27.20% of whom developed CPSP within 6 months postoperatively. Preoperative pain in the surgical area (OR=2.456, 95% CI:1.814– 3.327, P< 0.001), preoperative depression state (OR=1.256, 95% CI:1.146– 1.378, P< 0.001), surgical type (OR=7.138, 95% CI:3.548– 14.364, P< 0.001), acute postoperative numerical rating scale score (OR=5.537, 95% CI:3.607– 8.499, P< 0.001) and analgesic type (patient-controlled epidural analgesia: OR=0.129, 95% CI:0.055– 0.299, P< 0.001; patient-controlled intravenous analgesia: OR=0.033, 95% CI:0.011– 0.097, P< 0.001) were identified as independent significant factors associated with CPSP. A prognostic model was established and further validated. An ROC curve confirmed the predictive ability of this model with a high sensitivity value of 92.12% (95% CI:86.90– 95.74) and specificity value of 91.72% (95% CI:88.77– 94.11). A nomogram was developed to simplify the use of the predictive model in clinical practice.Conclusion: This prognostic model could be of great value in clinical practice, serving as the basis for early personalized analgesic management of elderly patients undergoing hip arthroplasty.Keywords: chronic postsurgical pain, CPSP, prognostic model, nomogram, retrospective study

Jijin Yao,1,2,&ast; Ying Wang,3,&ast; Yujing Lin,4 Yingying Yang,5 Jingjing Wan,3 Xiaohua Gong,1 Fanwei Zhang,3 Wangjian Zhang,6 Tia Marks,7 Siyang Wang,1 Hongjun Jin,2 Hong Shan2,8 1The Cancer Center of the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, People’s Republic of China; 3Department of Nuclear Medicine, Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, People’s Republic of China; 4Department of Pathology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong Province, 519001, People’s Republic of China; 5Department of Pharmacy, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, People’s Republic of China; 6Department of Medical Statistics, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 7Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, Rensselaer, NY, 12144, USA; 8Department of Interventional Medicine, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongjun JinGuangdong Provincial Key Laboratory of Biomedical Imaging, Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, People’s Republic of ChinaEmail jinhj3@mail.sysu.edu.cnHong ShanDepartment of Interventional Medicine, Guangdong Provincial Key Laboratory of Biomedical Imaging, Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, People’s Republic of ChinaEmail shanhong@mail.sysu.edu.cnIntroduction: To evaluate the role of maximal standardized uptake values (SUVmax) and total lesion glycolysis (TLG) from serial 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for early prediction of neoadjuvant chemotherapy (NAC) response in locoregionally advanced nasopharyngeal carcinoma (LANPC).Methods: A total of 121 LANPC patients who completed pretreatment 18F-FDG PET/CT between June 2017 and July 2020 were retrospectively included. The median age of all the participants was 50 years old (range: 19– 74 years), with 94 (77.7%) males and 27 (22.3%) females. The SUVmax from the primary tumor site (SUVmax-PT) and the total lesion glycolysis from the primary tumor site (TLG-PT) were recorded. Tumor response was calculated according to the Response Evaluation Criteria in Solid Tumor (RECIST) 1.1 Criteria at two-week post-secondary NAC cycle. Patients who achieved an objectively partial or full reaction after two cycles of NAC were defined as ‘responders’, and patients who obtained stability or progression were classified as ‘non-responders’.Results: After two cycles of NAC, 96 patients were categorized as “responders” and 25 patients as “non-responders”. The optimal thresholds of the SUVmax-PT were 11.8 and 38.5 for the TLG-PT. Non-responders were significantly associated with high SUVmax-PT (HR, 3.49; 95% CI, 1.17– 10.36; p = 0.024) and TLG-PT (HR, 4.45; 95% CI, 1.44– 13.78; p = 0.010) in multivariate analysis. Recursive partitioning analysis (RPA) categorized patients into three prognostic groups based on SUVmax-PT and TLG-PT: high-response group, intermediate-response group, and low-response group, with corresponding favorable response rates of 94%, 80%, and 55%, respectively. Moreover, a nomogram was created based on metabolic parameters that precisely projected an individual’s response of NAC (C-index, 0.787; 95% CI, 0.533– 1.000).Conclusion: Pretreatment 18F-FDG PET/CT to measure SUVmax-PT and TLG-PT could be a useful non-invasive method for early indication of NAC efficacy. The nomogram based on PET/CT parameters may potentially provide direction for treatment decisions based on NAC levels.Keywords: nasopharyngeal carcinoma, neoadjuvant chemotherapy, tumor response, PET/CT, nomogram

Jiamin Cheng,1,&ast; Yinyin Li,1,&ast; Xiaohui Wang,2,&ast; Zheng Dong,1 Yan Chen,1 Rui Zhang,1 Jiagan Huang,1 Xueyuan Jin,1 Jianfei Yao,2 Aifang Ge,2 Lele Song,2,3,&ast; Yinying Lu,1 Zhen Zeng1 1Comprehensive Liver Cancer Department, The Fifth Medical Center of the Chinese PLA General Hospital, Beijing, 100039, People’s Republic of China; 2HaploX Biotechnology, Shenzhen, Guangdong Province, People’s Republic of China; 3Department of Radiotherapy, The Eighth Medical Center of the Chinese PLA General Hospital, Beijing, 100091, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yinying Lu; Zhen ZengComprehensive Liver Cancer Department, The Fifth Medical Center of the Chinese PLA General Hospital, Beijing, 100039, People’s Republic of ChinaEmail luyinying1973@163.com; zengzhen1970@sina.comBackground: Immunotherapy combined with VEGF inhibitor has become the new first-line therapy for advanced or metastatic hepatocellular carcinoma (HCC). However, the biomarkers for response and prognosis stratification of HCC first-line combined immunotherapy have not been clarified.Methods: Here, we obtained the genomic alteration data from pre-therapeutic samples of 103 HCC patients using a 605-gene NGS test, and obtained the transcriptional and T cell receptor (TCR) diversity data from 18 patients who underwent the first-line combined immunotherapy using RNAseq and TCR sequencing, respectively. Patients received sorafenib/sintilimab or lenvatinib/sintilimab combined first-line therapy and the response was assessed at 3– 6 cycles of therapy.Results: No stratification of response was found in high-frequency key driver gene mutations, including TP53 and TERT. However, significantly higher ratio of progression (PD) was found in patients carrying MDM4 amplification. Similarly, FGF/3/4/19 amplifications could also result in high ratio of PD. The mRNA and lncRNA levels of eight genes related to hepatic metabolism and immune microenvironment exhibited significant differences between PR/SD and PD group, including DGKI, TNFSF14, CHST4, ACTIN1, PFKP, SLC51B, LCK and ERN1, suggesting stratification of response. Furthermore, moderate correlation was identified between the stratification genes (CHST4, SLC51B and ERN1) and immune factors (TIGIT, CD34, ICAM1, CCL5, CXCL9 and CXCL10), suggesting potential roles of these factors in immunoregulation. Strong linear correlation was found between any two of the three indexes for TCR CDR3 diversity, including Shannon–Wiener Index, Simpson index and evenness. However, no significant difference was found in the three indexes between the PR/SD and PD group, suggesting no stratification of response by these indexes.Conclusion: We identified several potential biomarkers for response stratification in the first-line combined immunotherapy. MDM4 was capable of predicting disease progression, and a panel mRNA and lncRNA of eight genes may also predict the response. Further validation is needed to verify these biomarkers.Keywords: hepatocellular carcinoma, HCC, immunotherapy, mRNA, lncRNA, TCR, sintilimab, sorafenib, lenvatinib

Jinzhi Meng,1 Xing Huang,1 Yue Qiu,1 Miao Yu,2 Jinfeng Lu,2 Jun Yao1 1Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of ChinaCorrespondence: Jun Yao Tel +860771-5319091Email yaojun800524@126.comBackground: Skin cutaneous melanoma (SKCM) is the most malignant tumor among skin cancers. Immunotherapy has shown a great role in the advantageous prognosis of SKCM. However, only a small percentage of people can benefit from immunotherapy. To date, there has been insufficient evidence to reveal the prognostic value of m6A in SKCM and its relationship with the infiltration of immune cells and the efficacy of immunotherapy.Methods: Here, we synthetically analyzed 23 m6A regulators from SKCM samples collected from the TCGA and GEO databases. We defined three m6A modification patterns and constructed m6A scores using principal component analysis (PCA).Results: We found significant differences in overall survival (OS) and immune infiltration between different m6A subclusters. Besides, m6A score was positively correlated with regulatory T-cell and helper T-cell content, which may account for the association of high m6A scores with superior prognosis. Multivariate Cox regression analysis revealed that the m6A score was an independent prognostic indicator. Moreover, patients with high m6A scores showed a better response to immunotherapy, and this result was further validated in two independent immunotherapy cohorts receiving anti-PD-1/PD-L1 therapy.Conclusion: The findings suggested the m6A score can screen suitable candidates for immunotherapy and can predict immunotherapy response. This analysis of different m6A patterns in a large sample of SKCM expanded our understanding of TME and provided new ideas for prognostic assessment and personalized immunotherapy strategies for SKCM patients.Keywords: skin cutaneous melanoma, immunotherapy, M6A-related genes, prognosis

Wenqing Yu,1,&ast; Ningfei Ji,2,&ast; Chengjing Gu,3,&ast; Juan Yao,4 Mingdong Ding,1 Daming Zhou,1 Mao Huang,2 Mingshun Zhang5,6 1Department of Infectious Diseases, Taizhou People’s Hospital Affiliated to Nantong University, Taizhou, Jiangsu, 225300, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China; 3Department of Pharmacy, Taizhou People’s Hospital Affiliated to Nantong University, Taizhou, Jiangsu, 225300, People’s Republic of China; 4Department of Oncology, Huaian Hospital of Huaian City, Huaian, Jiangsu, 223200, People’s Republic of China; 5Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu, 211166, People’s Republic of China; 6NHC Key Laboratory of Antibody Technique, Nanjing Medical University, Nanjing, Jiangsu, 211166, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chengjing GuDepartment of Pharmacy, Taizhou People’s Hospital Affiliated to Nantong University, Taizhou, Jiangsu, 225300, People’s Republic of ChinaTel +86 0523-86606290Email chengjingyu706@163.comWenqing YuDepartment of Infectious Diseases, Taizhou People’s Hospital Affiliated to Nantong University, Taizhou, Jiangsu, 225300, People’s Republic of ChinaEmail wenqinggu706@126.comBackground: RORγt+Foxp3+ (Th17-like) Tregs are a plastic Treg subset implicated in immune-related diseases; however, the mechanism of Treg phenotypic transformation in malignant pleural effusion (MPE) has not been elucidated.Methods: The percentage of CD4+CD25+Foxp3+Helios+ and RORγt+Foxp3+ Tregs from peripheral blood and pleural effusion mononuclear cells were measured. The level of interferon regulatory factor 4 (IRF4) mRNA expression was detected by quantitative real-time reverse transcription polymerase chain reaction. The effects of IRF4 on the induction of Tregs from patients with non-small cell lung cancer (NSCLC) were evaluated in vitro. Correlation assays between IRF4 expression and the frequency of RORγt+Foxp3+ Tregs were performed.Results: The frequency of CD4+CD25+Foxp3+Helios+ Tregs and CD4+RORγt+ Th17 cells was both increased in the MPE of NSCLC patients. The group of double-positive Foxp3+RORγt+ Treg phenotype were identified in the pleural effusion. A significant increase in the frequency of Foxp3+RORγt+ Tregs was found in MPE compared with the non-malignant pleural effusion (NPE). Compared to NPE, the relative level of IRF4 expression was increased in the MPE. IRF4 expression was positively associated with the frequency of Foxp3+RORγt+ Tregs in the PE. In vitro, the level of Helios mRNA and protein expression was reduced in induced Tregs following IRF4 over-expression. Additionally, the level of RORγt protein expression was substantially increased. However, ectopic Helios expression in induced Tregs reversed the effects induced by enhanced IRF4 expression.Conclusion: IRF4 may serve as a potential molecule that promotes the conversion of regulatory T cells from MPE to a Th17-like phenotype by modulating Helios.Keywords: malignant pleural effusion, lung cancer, IRF4, regulatory T cells, phenotypic transformation

Yongfang Zhang,1,&ast; Di Wang,2,&ast; Weiqun Liu,1 Yin Zhang,3 Lina Zhou,4 Hanhuan Yuan,5 Jiaming Yao,6 Ming Li7 1Department of Nursing, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, People’s Republic of China; 2Department of Nursing, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China; 3The Party and Government Office, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, People’s Republic of China; 4Department of Publicity, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, People’s Republic of China; 5Infectious Disease Control and Disinfection Management Section, Shanghai Pudong New Area Center for Disease Control and Prevention, Fudan University Pudong Institute of Preventive Medicine, Shanghai, People’s Republic of China; 6Columbia University School of Nursing, New York, NY, USA; 7Dean’s Office, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ming LiShanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, 1500 W Zhouyuan Road, Pudong New Area, Shanghai, 201318, People’s Republic of ChinaTel +86 2168135590 Ext. 6001Fax +86 21-68135715Email liming1070@126.comJiaming YaoColumbia University School of Nursing, 560 W 168th Street, New York, NY, 10032, USATel +1-6463391188Email jy2349@cumc.columbia.eduObjective: To implement epidemic prevention among entry personnel, Shanghai has launched a number of Medical Observation Sites (Observation Site) for which high expectations are set. Ours is one such Observation Site.Methods: As part of a novel project, we did not have any previous experience to use as reference. Despite some challenges, we achieved satisfactory outcomes by establishing a stepwise approach to inbound passenger management, including the division of the working area of the Observation Site, dynamic management of the rooms, closed-loop management of the isolated personnel.Results: As of May 14, 2020, a total of 42 Observation Sites were operational in Pudong New Area. The following are the detailed descriptions of our Temporary Medical Observation Site set up and work flow.Conclusion: Early screening of inbound passengers as well as prompt and dynamic management of information about passengers’ close contacts play an active role in preventing an influx of cases. As a pilot program, we have a model that is effective despite some limitations.Keywords: COVID-19, observation, pandemic, screening, airport, room

Yan Yang,1,2 Jing-hao Yao,1,2 Ling-jie Xu,1,3 Zheng-guang Zhou,1,2 Ming-xi Wang,1,2 Zi-shu Wang,1,2 Fu-you Zhao1,2 1Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, People’s Republic of China; 2Department of Oncology, School of Clinical Medicine, Bengbu Medical College, Bengbu, Anhui, People’s Republic of China; 3School of Nursing, Bengbu Medical College, Bengbu, Anhui, People’s Republic of ChinaCorrespondence: Fu-you ZhaoDepartment of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, Anhui, People’s Republic of ChinaTel +86 552-3086178Email fuyouzhao@bbmc.edu.cnPurpose: To determine whether the teaching method of seminars combined with case-based learning (CBL) is superior to the traditional lecture-based learning (LBL) for teaching cancer pain in medical oncology internship.Methods: Sixty medical and nursing interns in the medical oncology department of our hospital were selected between January 2019 and December 2020. Thirty students received traditional LBL instruction as the control group, and 30 students received combined seminars and CBL instruction as the observation group. The teaching evaluation and assessment was performed by theoretical and practical examinations and questionnaires.Results: In the after-class examination, case analysis, clinical practice and overall scores of the observation group were higher than those of the control group (all p < 0.001). Theoretical knowledge scores did not differ significantly between the two groups (p = 0.470). In the questionnaire regarding attitudes towards opioid use, the observation group had better perceptions of using opioids than the control group (all p < 0.01). In the meantime, students in the observation group outperformed the control group in four aspects: self-learning (p < 0.001), analytical and problem-solving (p < 0.001), clinical thinking (p = 0.001), and clinical practice (p = 0.002) abilities all improved, while stimulating learning interest (p = 0.184) and enhancing theoretical knowledge mastery (p = 0.221) were not significantly different from those of the control group. Overall, students in the observation group were more satisfied with the teaching, teaching methods and teacher performances than the control group (all p < 0.001).Conclusion: Compared to the LBL, the combination of seminars and CBL is a more effective teaching method for cancer pain management, which is worth further study.Keywords: cancer pain teaching, seminar method, case-based learning, lecture-based learning, comparative study

JinJian Yao,1,&ast; Hangfei Wang,2,&ast; Weiling Yu,3,&ast; Yimin Li,4 Zhiqian Luo,2 Biao Wu,5 Wei Zhang,6 Xiaoran Liu,2 Chuanzhu Lv6,7 1Emergency Center, Hainan General Hospital Affiliated to Hainan Medical University, Haikou, Hainan, People’s Republic of China; 2Department of Emergency, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan, People’s Republic of China; 3Oncology Department, Haikou City People’s Hospital, Haikou, Hainan, People’s Republic of China; 4Department of General Surgery, Yang Jiang Hospital of Qiongzhong, Qiongzhong, Hainan, People’s Republic of China; 5Department of Infectious Disease, Hainan General Hospital Affiliated to Hainan Medical University, Haikou, Hainan, People’s Republic of China; 6Emergency and Trauma College of Hainan Medical University, Haikou, Hainan, People’s Republic of China; 7Key Laboratory of Emergency and Trauma, Ministry of Education of Hainan Medical University, Haikou, Hainan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoran LiuDepartment of Emergency, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan, People’s Republic of ChinaTel +8613118901829Email liuxiaoran3192@163.comChuanzhu LvKey Laboratory of Emergency and Trauma, Ministry of Education of Hainan Medical University, Haikou, Hainan, People’s Republic of ChinaTel +8617789830771Email lvchuanzhu677@126.comIntroduction: Close contacts of individuals with COVID-19 may directly gain immunity against SARS-CoV-2 despite lacking a detectable infection. This study examined SARS-CoV-2-specific antibodies levels based on gender, age, and exposure source in close contacts of individuals with COVID-19 and compared antibody levels to patients with an asymptomatic or symptomatic COVID-19 infection.Methods: Two patients had confirmed COVID-19 infections at a community hospital in Qiongzhong, Hainan province. Contact tracing identified all individuals in the community who had been exposed to the two patients during the 14 days before their diagnoses. Close contacts quarantined for 14 days, underwent two SARS-CoV-2 tests, and were screened for SARS-CoV-2-specific antibodies at 7 and 12 weeks after the end of quarantine. SARS-CoV-2-specific antibody levels for the close contacts were compared to those for patients with an asymptomatic or symptomatic COVID-19 infection at 7 and 12 weeks after their diagnoses.Results: Contact tracing identified 10,573 individuals in the community, including 360 (3.4%) close contacts. At 7 weeks, 30 (8.33%) close contacts were positive for SARS-CoV-2-specific antibodies (IgG, n = 26 [7.22%]; IgM, n = 4 [1.11%]), which were lower than the proportion of patients with an asymptomatic (IgG, 100% [12/12]) or symptomatic (IgG, 93.6% [44/47]) COVID-19 infection. SARS-CoV-2-specific IgM antibody levels were significantly higher in close contacts who were exposed through a relative compared to a doctor–patient relationship (P = 0.032). SARS-CoV-2-specific IgG antibody levels were significantly higher in close contacts aged < 18 years vs 18– 64 years (P = 0.014). At 12 weeks, SARS-CoV-2-specific IgG antibody levels among close contacts were significantly lower than among patients with an asymptomatic (P = 0.004) or symptomatic COVID-19 infection (P < 0.001).Conclusion: Immune protection conferred by close contact is short term and unlikely to contribute to herd immunity. There remains an unmet public health need for mass vaccination of populations to increase levels of protective antibodies and achieve and maintain herd immunity.Keywords: SARS-CoV-2, COVID-19, antibody, close contact

Ganlu Ouyang,1 Xibiao Yang,2 Xiangbing Deng,3 Wenjian Meng,3 Yongyang Yu,3 Bing Wu,2 Dan Jiang,4 Pei Shu,1 Ziqiang Wang,3 Jin Yao,2 Xin Wang1 1Department of Radiation Oncology/Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Radiology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 3Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 4Department of Pathology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of ChinaCorrespondence: Xin WangDepartment of Radiation Oncology/Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, No. 37 of Wainan Guoxue Lane, Wuhou District, Chengdu, 610041, People’s Republic of ChinaTel +86 18980602291Email wangxin213@sina.comPurpose: To investigate the potential value of magnetic resonance imaging (MRI) in predicting response relevance to total neoadjuvant treatment (TNT) in locally advanced rectal cancer.Methods: We analyzed MRI of 71 patients underwent TNT from 2015 to 2017 retrospectively. We categorized the response of TNT as CR (complete response) vs non-CR, and high vs moderate vs low sensitivity. Logistic regression analysis was used to identify the best predictors of response. Diagnostic performance was assessed using receiver operating characteristic curve analysis.Results: Post-ICT (induction chemotherapy) ∆TL (tumor length), post-CRT (concurrent chemoradiotherapy) ∆LNN (the numbers of lymph node metastases), post-CCT (consolidation chemotherapy) ∆SDWI (maximum cross-sectional area of tumor on diffusion-weighted imaging), post-CCT ADCT (the mean apparent diffusion coefficient values of tumor) and post-CCT ∆LNV (volume of lymph node) were the best CR predictors. Post-ICT ∆TL, post-CRT EMVI (extramural vascular invasion) and post-CCT ∆ST2 (S on T2-weight) were the best significant factors for high sensitivity.Conclusion: Post-ICT ∆TL may be an early predictor of CR and high sensitivity to TNT. Dynamic analysis based on MRI between baseline and post-CCT could provide the most valuable prediction of CR. The grouping modality of CR vs non-CR may be more suitable for treatment response prediction than high vs moderate vs low sensitivity.Keywords: rectal cancer, total neoadjuvant treatment, MRI, response, TRG

Intense ion beam production is of high importance for various versatile applications from accelerator injectors to secondary ion mass spectrometry (SIMS). For these purposes, different types of ion beams are needed and, accordingly, the optimum plasma to produce the desired ion beams. RF-type plasma features a simple structure, high plasma density and low plasma temperature, which is essential for negative ion beam production. A very compact RF-type ion source using a planar coil antenna has been developed at IMP for negative molecular oxygen ion beam production. In terms of high-intensity positive ion beam production, 2.45 GHz microwave power-excited plasma has been widely used. At IMP, we developed a 2.45 GHz plasma source with both ridged waveguide and coaxial antenna coupling schemes, tested successfully with intense beam production. Thanks to the plasma built with an external planar coil antenna, high O2− production efficiency has been achieved, i.e., up to 43%. With 2.45 GHz microwave plasma, the ridged waveguide can support a higher power coupling of high efficiency that leads to the production of intense hydrogen beams up to 90 emA, whereas the coaxial antenna is less efficient in power coupling to plasma but can lead to attractive ion source compactness, with a reasonable beam extraction of several emA.

Jiayu Yao,1 Xiaotong Liu,1 Yingxu Sun,1 Xin Dong,1 Li Liu,1 Hailun Gu2 1Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, Shenyang, 110122, People’s Republic of China; 2Department of Orthopedics, Shengjing Hospital, China Medical University, Shenyang, 110004, People’s Republic of ChinaCorrespondence: Hailun GuDepartment of Orthopedics, Shengjing Hospital, China Medical University, Shenyang, 110004, People’s Republic of ChinaTel +86-18940257206Email guhailun_@163.comPurpose: The mechanism underlying curcumin’s protective effect on osteoarthritis (OA) has not been clarified. This study aimed to determine whether curcumin exerts a chondroprotective effect by inhibiting apoptosis via upregulation of E2F1/PITX1 and activation of autophagy via the Akt/mTOR pathway by targeting microRNA-34a (miR-34a).Methods: Male Sprague–Dawley rats were fed a normal diet (ND) or high-fat diet (HFD) for 28 weeks. Five rats from each diet group were selected randomly for histological analysis of OA characteristics. Rats fed a HFD were given a single intra-stifle joint injection of the miR-34a mimic agomir-34a or negative control agomir (NC), followed by weekly low-dose (200 μg/kg body weight) or high-dose (400 μg/kg body weight) curcumin intra-joint injections from weeks 29 to 32. The rats’ stifle joints were submitted to histological analysis and to an apoptotic assay. Expression of miR-34a was detected using a real-time RT-PCR. E2F1 and PITX1 protein levels were determined by Western blot analysis, and the expressions of Beclin1, LC3B, p62, phosphorylated (p)-Akt, and p-mTOR were measured using immunofluorescence analysis.Results: We found that rats fed a HFD had OA-like lesions in their articular cartilage and had increased apoptosis of chondrocytes and decreased autophagy compared to rats fed a ND. Curcumin treatment alleviated OA changes, inhibited apoptosis, and upregulated autophagy. Agomir-34a treatment reduced E2F1, PITX1, Beclin1, and LC3B expression and increased p62, p-Akt, and p-mTOR expression in HFD-fed rats given low- or high-dose curcumin. Greater numbers of apoptotic cells, lesser expression of p62, p-Akt, and p-mTOR, and greater expression of E2F1, PITX1, and LC3B were observed in the agomir-34a and high-dose curcumin-treated group than in agomir-34a and low-dose curcumin-treated group.Conclusion: Curcumin’s chondroprotective effect was mediated by its suppression of miR-34a, apparently by reducing apoptosis, via upregulation of E2F1/PITX1, and by augmenting autophagy, likely via the Akt/mTOR pathway.Keywords: curcumin, osteoarthritis, apoptosis, autophagy, microRNA-34a, high-fat diet