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Chunhua Wang,1 Haifeng Jin,1 Hua Xue,1 Yanwei Zhang2 1Department of Gastroenterology, Bethune International Peace Hospital, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Diagnostic Radiology, Bethune International Peace Hospital, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Chunhua Wang; Haifeng Jin, Department of Gastroenterology, Bethune International Peace Hospital, No. 398 Zhongshan West Street, Qiaoxi Disctrict, Shijiazhuang, Hebei, People’s Republic of China, Email crown99@126.com; jinhfhfjin@163.comPurpose: Hepatic portal venous gas is not a specific disease and is often only an imaging manifestation in patients with acute abdomen. However, its appearance often indicates serious disease and poor prognosis. It is not difficult to distinguish typical portal venous gas from biliary tract gas on computed tomography because of their relatively different distribution within the liver. But the difference is not absolute.Case Description: An 82-year-old female was admitted to the emergency department due to epigastric pain, nausea and vomiting for 1 day. Intrahepatic gas was found on computed tomography (CT), which was initially diagnosed as portal venous gas, and contrast-enhanced abdominal CT was performed 3 hours after the first plain CT scan and revealed a significant reduction of intrahepatic gas, then diagnosed as biliary tract gas. Two days later, enhanced abdominal CT showed that biliary tract gas had disappeared. Continuous gastrointestinal decompression, anti-infection, rehydration and other treatments were given. After treatment, abdominal pain, nausea, vomiting and other symptoms of the patient were gradually relieved. The patient refused gastroenteroscopy and was discharged after 13 days of hospitalization.Conclusion: Portal venous gas and biliary tract gas may have similar CT findings and be misdiagnosed, and enhanced CT examination is necessary to confirm the diagnosis.Keywords: hepatic portal venous gas, biliary tract gas, acute gastroenteritis, computed tomography, case report

Four body-size and fourteen head-size measurements were taken from each Chinese alligator (Alligator sinensis) according to the measurements adapted from Verdade. Regression equations between body-size and head-size variables were presented to predict body size from head dimension. The coefficients of determination of captive animals concerning body- and head-size variables can be considered extremely high, which means most of the head-size variables studied can be useful for predicting body length. The result of multivariate allometric analysis indicated that the head elongates as in most other species of crocodilians. The allometric coefficients of snout length (SL) and lower ramus (LM) were greater than those of other variables of head, which was considered to be possibly correlated to fights and prey. On the contrary, allometric coefficients for the variables of obita (OW, OL) and postorbital cranial roof (LCR), were lower than those of other variables.

Huan-Ju Shih,1 Hong Xue,1 Hua Min,1 Janusz Wojtusiak,1 Jongwha Chang2 1Department of Health and Human Services, George Mason University, Fairfax City, VA, USA; 2Department of Pharmaceutical Sciences, Irma Lerma Rangel School of Pharmacy, Texas A&M University, College Station, TX, USACorrespondence: Jongwha Chang, Department of Pharmaceutical Sciences, Irma Lerma Rangel School of Pharmacy, Texas A&M University, College Station, TX, 77843, USA, Tel +1-979-436-0664, Email jc2345@tamu.eduObjective: The study utilized a cross-sectional dataset to identify demographic and health factors associated with patient utilization of mHealth applications for engaging with healthcare providers. The focus was on adults with chronic health conditions as the primary app user group. The goal was to reveal specific barriers and facilitators to app adoption among smartphone users, with the aim of highlighting opportunities for upgrades that promote patient empowerment as a prerequisite for shared decision-making (SDM).Methods: Data from the Health Information National Trends Survey (HINTS 5, Cycle 4, 2020) with 3865 respondents (≥ 18 years old) stratified analyses and weighted logistic regression were used.Results: The study found that individuals having a wellness app on a smartphone increased the likelihood (OR 2.68, CI: 2.02– 3.56, p-value < 0.0001) of discussing health conditions with providers. Furthermore, individuals with multiple chronic health conditions were more likely (OR 1.93, CI 1.26– 2.95, p-value < 0.01) to use apps to use mobile health applications to engage with healthcare providers. Other significant variables affecting app usage such as race, marital status, and educational level.Conclusion: Due to difficulties obtaining in-person healthcare, the COVID-19 epidemic forced a swift deployment of mHealth technologies. Even in the absence of a crisis, mobile health applications continue to be crucial for improving patient-provider engagement and developing novel approaches to healthcare delivery. During the pandemic, people with numerous chronic diseases used apps to stay in touch with doctors and maintain their reliance on these platforms. Nonetheless, different smartphone users continue to use mHealth application in different ways. The findings revealing barriers in mHealth app adoption among certain patient subgroups suggest opportunities for developers, in collaboration with users and providers, to enhance inclusion and acceptability when upgrading mHealth application platforms.Keywords: mobile health, digital equity, post-SARS Cov2 care management, healthcare policy, chronic care

Hongmei Xue,1 Jiquan Li,1 Li Ma,1 Xuxin Yang,1 Lingling Ren,1 Zhijun Zhao,1 Jianling Wang,1 Yuanbo Zhao,1 Zhongzhi Zhao,1 Xuefei Zhang,1 Zhiguo Liu,2 Zhenjun Li2 1Department of Brucellosis Prevention and Control, Qinghai Institute for Endemic Disease Prevention and Control, Xining, Qinghai, People’s Republic of China; 2National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of ChinaCorrespondence: Zhiguo Liu; Zhenjun Li, Email wlcblzg@126.com; lizhenjun@icdc.cnObjective: Brucellosis is a serious public health issue in Qinghai (QH), China. Surveying the seroprevalence and isolation of B. abortus strains from marmots is key to understanding the role of wildlife in the maintenance and spread of brucellosis.Methods: In this study, a set of methods, including a serology survey, bacteriology, antibiotic susceptibility, molecular genotyping (MLST and MLVA), and genome sequencing, were employed to characterize the two B. abortus strains.Results: The seroprevalence of brucellosis in marmots was 7.0% (80/1146) by serum tube agglutination test (SAT); one Brucella strain was recovered from these positive samples, and another Brucella strain from a human. Two strains were identified as B. abortus bv. 1 and were susceptible to all eight drugs examined. The distribution patterns of the accessory genes, virulence associated genes, and resistance genes of the two strains were consistent, and there was excellent collinearity between the two strains on chromosome I, but they had significant SVs in chromosome II, including inversions and translocations. MLST genotyping identified two B. abortus strains as ST2, and MLVA-16 analysis showed that the two strains clustered with strains from northern China. WGS-SNP phylogenetic analysis showed that the strains were genetically homogeneous with strains from the northern region, implying that strains from a common lineage were spread continuously in different regions and hosts.Conclusion: Seroprevalence and molecular clues demonstrated frequent direct or indirect contact between sheep/goats, cattle, and marmots, implying that wildlife plays a vital role in the maintenance and spread of B. abortus in the Qinghai–Tibet Plateau.Keywords: Brucella abortus, marmots, isolated, MLST, MLVA, WGS-SNP, QH

Zhimeng Wang,&ast; Yao Lu,&ast; Pengfei Wang, Chen Fei, Shuhao Li, Hanzhong Xue, Zhong Li, Qian Wang, Kun Zhang, Teng Ma Department of Orthopedics and Traumatology, Honghui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, 710000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kun Zhang; Teng Ma, Department of Orthopedics and Traumatology, Honghui Hospital, Xi’an Jiaotong University, No. 555, East Youyi Road, Xi’an, Shaanxi, 710000, People’s Republic of China, Email hhzhangkun@163.com; gukemat@163.comIntroduction: This study aimed to examine the impacts of DOACs compliance and prescribing preferences on clinical outcomes in elderly hip fracture patients with isolated calf deep vein thrombosis (ICDVT).Methods: We conducted a retrospective cohort study that evaluated 702 patients who underwent surgical treatment combined with ICDVT in an academic university hospital between January 2016 and October 2021. DOACs compliance was investigated through telephone and outpatient follow-up, and ICDVT clinical outcomes were collected 30 and 90 days post-discharge, respectively. Variables of interest were collected through the electronic medical record system, and data were analyzed after adjusting for predictors of non-completely dissolved (CD) of ICDVT.Results: The DOACs compliance survey revealed that 375 (53.42%) patients were fully adherent, 270 (38.46%) were fairly adherent, and 57 (8.12%) were poorly adherent. Approximately 62% of patients had ICDVT dissipation within 30 days after discharge, reaching 94% within 90 days. DOACs QD/BID regimen is often based on economic status, activity capacity, discharge destination and post-operative weight-bearing activities (p< 0.05).The mechanism of injury, ASA classification, surgical technique and timing of ICDVT formation were significantly correlated with DOACs 14/28 days regimen (p< 0.05).Multivariate analysis revealed that rural patients [OR 1.518 (95% CI, 1.117– 2.236)], pre-operative ICDVT[OR 2.816 (95% CI, 1.862– 4.259)] and thrombus length [OR 1.157 (95% CI, 1.263– 1.821)] were ICDVT risk factors for non-CD. Furthermore, DOACs fair compliance [OR 0.087 (95% CI, 0.042– 0.178)], DOACs full compliance [OR 0.283 (95% CI, 0.139– 0.579)], and hospitalization duration [OR 0.793 (95% CI, 0.694– 0.907)] were ICDVT protective factors for CD.Conclusion: Better compliance with DOACs benefits early ICDVT dissipation, but final clinical outcomes have to be validated with longer follow-up periods. When managing elderly patients with hip fractures, indications for anticoagulation should be considered and individualized protocols should be used.Keywords: hip fractures, direct oral anticoagulant, calf deep vein thrombosis, compliance, elderly

Min Zhu,1 Yuyu Sun,1 Huawei Xue,1 Gang Wu,1 Zhen Wang,1 Junfeng Shi,1 Jiye Ma,1 Baorong Gu,1 Xiaoling Yan2 1Department of Spine Surgery, Nantong Third People’s Hospital, Affiliated Nantong Hospital 3 of Nantong University, Nantong, People’s Republic of China; 2Department of Chemotherapy, Affiliated Hospital of Nantong University, Nantong, People’s Republic of ChinaCorrespondence: Xiaoling Yan, Department of Chemotherapy, Affiliated Hospital of Nantong University, Nantong, 226001, People’s Republic of China, Email 5200007@ntu.edu.cnBackground: Osteosarcoma is a malignant tumor originating from the skeletal system. There is no effective treatment other than surgery and chemotherapy, which seriously endangers the health of children and adolescents. NEK6 is a novel discovered Serine/Threonine protein kinase that can regulate cell cycle and activate several oncogenic pathways.Methods: NEK6 expression in pan-cancer including sarcoma was evaluated using analysis tools of TIMER, UALCNA and GEPIA with TCGA database, and its association with overall survival in patients with sarcoma was also analyzed. TargetScan, tarbase, microT-CDS and Starbase online software were used to predict NEK6-targeted miRNAs, including miR-26a-5p. Tumor tissues from patients with osteosarcoma were collected for NEK6 and miRNA detection using RT-qPCR. NEK6 down-regulated by siRNAs or miR-26a-5p in osteosarcoma cells was detected by RT-qPCR, Western blot and Immunofluorescence staining assays. Effects of NEK6 knockdown on proliferation, migration, invasion and apoptosis of osteosarcoma cells were detected by CCK-8, wound healing, transwell and flow cytometry, respectively. The expressions of STAT3, metastasis and apoptosis-related genes were detected by Western blot.Results: High expression of NEK6 and low expression of miR-26a-5p were lowly expressed in osteosarcoma and they were negative correlation. NEK6 has been confirmed as a direct target for miR-26a-5p. In addition, NEK6 down-regulated by siRNAs or miR-26a-5p led to inhibition of cell proliferation, migration and invasion while promoting cell apoptosis. The levels of phosphorylated STAT3 and metastasis genes (MMP-2, MMP-9) were inhibited, while apoptotic gene Bax was promoted and Bcl2 was inhibited by miR-26a-5p upregulation.Conclusion: NEK6 can promote osteosarcoma progression via activating STAT3 signaling pathway, which is inhibited by miR-26a-5p, suggesting that NEK6 is a potential oncogene and miR-26a-5p is a suppressor of osteosarcoma. The strategy of inhibiting of NEK6 by miR-26a-5p may be an effective approach for osteosarcoma therapy.Keywords: osteosarcoma, NEK6, miR-26a-5p, STAT3 signaling pathway

Huan Xue,1,&ast; Hao-Jie Xing,1,&ast; Bin Wang,1 Chao Fu,1 Yu-Shan Zhang,1 Xi Qiao,1 Chao Guo,1 Xiao-Li Zhang,1 Bin Hu,1 Xin Zhao,1 Li-Jiao Deng,1 Xiao-Chan Zhu,1 Yi Zhang,1 Yun-Feng Liu2 1Department of Pharmacology, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China; 2Department of Endocrinology, First Hospital of Shanxi Medical University, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Zhang; Yun-Feng Liu, Tel +86-18835102847 ; +86-18703416169, Email yizhang313@163.com; nectarliu@163.comPurpose: The glucagon-like peptide-1 receptor (GLP-1R) is an effective therapeutic target for type 2 diabetes mellitus (T2DM) and non-alcoholic steatohepatitis (NASH). Research has focused on small-molecule GLP-1R agonists because of their ease of use in oral formulations and improved patient compliance. However, no small-molecule GLP-1R agonists are currently available in the market. We aimed to screen for a potential oral small-molecule GLP-1R agonist and evaluated its effect on blood glucose and NASH.Methods: The Connectivity map database was used to screen for candidate small-molecule compounds. Molecular docking was performed using SYBYL software. Rat pancreatic islets were incubated in different concentrations glucose solutions, with cinchonine or Exendin (9– 39) added to determine insulin secretion levels. C57BL/6 mice, GLP-1R−/− mice and hGLP-1R mice were used to conduct oral glucose tolerance test. In addition, we fed ob/ob mice with the GAN diet to induce the NASH model. Cinchonine (50 mg/kg or 100 mg/kg) was administered orally twice daily to the mice. Serum liver enzymes were measured using biochemical analysis. Liver tissues were examined using Hematoxylin-eosin staining, Oil Red O staining and Sirius Red staining.Results: Based on the small intestinal transcriptome of geniposide, a recognized small-molecule GLP-1R agonist, we identified that cinchonine exerted GLP-1R agonist-like effects. Cinchonine had a good binding affinity for GLP-1R. Cinchonine promoted glucose-dependent insulin secretion, which could be attenuated significantly by Exendin (9– 39), a specific GLP-1R antagonist. Moreover, cinchonine could reduce blood glucose in C57BL/6 and hGLP-1R mice, an effect that could be inhibited with GLP-1R knockout. In addition, cinchonine reduced body weight gain and food intake in ob/ob-GAN NASH mice dose-dependently. 100 mg/kg cinchonine significantly improved liver function by reducing the ALT, ALP and LDH levels. Importantly, 100 mg/kg cinchonine ameliorated hepatic steatosis and fibrosis in NASH mice.Conclusion: Cinchonine, a potential oral small-molecule GLP-1R agonist, could reduce blood glucose and ameliorate NASH, providing a strategy for developing small-molecule GLP-1R agonists.Graphical Abstract: Keywords: glucagon-like peptide-1 receptor, cinchonine, drug repurposing, non-alcoholic steatohepatitis, type 2 diabetes mellitus

Lijun Fan,1,2 Hui Xue,1 Qian Wang,3 Yuhan Yan,4 Wei Du1 1School of Public Health, Southeast University, Nanjing, People’s Republic of China; 2School of Public Health, Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Guangdong Provincial Geriatrics Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China; 4General Hospital of Eastern Theater Command, Nanjing, People’s Republic of ChinaCorrespondence: Wei Du, School of Public Health, Southeast University, Nanjing, 210009, People’s Republic of China, Email duwei@seu.edu.cn Yuhan Yan, General Hospital of Eastern Theater Command, Nanjing, 210009, People’s Republic of China, Email yanyuhan0215@163.comObjective: The identification of older patients at risk of repeated emergency department (ED) visits is crucial for managing preventable adverse outcomes. This study aims to identify risk factors associated with ED revisits and to develop and validate a nomogram for predicting risk of geriatric ED revisits.Methods: This was a cohort study comprising 553 older patients, who attended the two tertiary hospitals EDs in China from August 2018 to February 2019 and were prospectively followed for any unplanned revisit within 1 year after discharge. Patients were randomly assigned to a training or validation set at a ratio of 2:1. Stepwise selection procedure was applied to select factors associated with ED revisits for inclusion in a multivariable logistic model from which a nomogram was elaborated. Discrimination, calibration and clinical utility of the nomogram were assessed using C-statistic, calibration plot, Hosmer-Lemeshow test, and decision curve analysis (DCA).Results: The final nomogram included four predictors for ED revisits: age, BMI, frailty and polypharmacy. Older patients having revisits were more likely to be frail (OR = 1.17, p = 0.031), have polypharmacy (OR = 1.69, p = 0.049) or BMI < 18.5 kg/m2 (OR = 2.45, p = 0.025), and were less likely to be older than 90 years (OR = 0.21, p = 0.002). The nomogram demonstrated acceptable discrimination ability in the training (C-index = 0.661) and validation sets (C-index = 0.651), satisfactory calibration (p > 0.05), and good clinical applicability.Conclusion: A nomogram incorporating four obtainable variables was constructed to individualize ED readmission risk in older patients. These patients may benefit from early triage and better-targeted care if considering the nomogram as a clinical decision aid.Keywords: nomogram, risk prediction, emergency department revisit, acute care, older adults

Jie Li,1,&ast; Siwen Chen,1,&ast; Hui Xue,2,&ast; Haoyi Wang,3,&ast; Tianwei Huang,4 Hongya Xie,5 Jiang He,6 Cai Ke,3 Zhaonan Yu,3 Bin Ni4 1Department of General Medical Ward, First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Oncology Medical Ward, Hanzhong Central Hospital, Hanzhong, People’s Republic of China; 3Hangzhou D.A. Medical Laboratory, Hangzhou, People’s Republic of China; 4Department of Thoracic Surgery, First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 5Department of Thoracic Surgery, Suzhou Municipal Hospital, Suzhou, People’s Republic of China; 6Department of Thoracic Surgery, Suzhou Wuzhong People’s Hospital, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Ni, Department of Thoracic Surgery, First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China, Tel +86 17774015977, Email bin_ni@163.com Zhaonan Yu, Hangzhou D.A. Medical Laboratory, Hangzhou, People’s Republic of China, Tel +86 15558078770, Email yuzhaonan870213@163.comIntroduction: From an oncologic perspective, genetic detection is becoming a frontline clinical test, used to identify actionable alterations for targeted therapy, monitor molecular clonal tumor evolution, indicate disease progression and prognosis, and predict medication efficacy and resistance. From analysis of both tumor tissue and cell-free DNA from a large cohort of non-small cell lung cancer patients in East-China, we characterized the full spectrum of genomic alterations.Methods: The study comprised 3000 unpaired samples including 1351 tumor tissue DNA (tDNA) and 1649 cell-free circulating tumor DNA (cfDNA) samples, from which 67 cancer-related genes were sequenced and the genetic alteration profiles were depicted. Integrative molecular analyses identified the frequently mutated genes, uncovered co-occurring somatic alterations, described the distribution of hotspot variants, analyzed the frequency of variant alleles, and notably distinguished actionable, novel variants.Results: The most commonly affected genes were EGFR, TP53, KRAS, CDKN2A, and PIK3CA in both tDNA and cfDNA samples. EGFR and CTNNB1, PIK3CA and PTEN, ERBB2 and SMO were found to have frequent co-occurring alterations in tDNA samples, while EGFR and SMO, KRAS and PDGFRA, PIK3CA and KDR were in cfDNA samples. A large number of primary druggable variants were identified in tDNA samples, while numerous drug-resistance variants, rare actionable variants, and non-EGFR actionable variants were detected in cfDNA samples. Novel variants were enriched in KDR, KIT, TP53, ABL1, FGFR1 in tDNA samples while the majority of novel variants were distributed in PDGFRA, EGFR, KIT, ROS1, BRCA2 in cfDNA samples. Variant allele frequency in tDNA samples was significantly (P < 0.001) higher than that in cfDNA samples.Conclusion: The results revealed considerable differences in the alteration characteristics between the two kinds of specimens. To date, this study represents the largest real-world investigation of its kind, derived from the largest number of patients in East-China. It reinforced and expanded the mechanism of molecular analysis of neoplastic genetic profiles.Keywords: real world study, non-small cell lung cancer patients in East-China, tumor tissue DNA, cell-free circulating tumor DNA, next-generation-sequencing, genetic alteration

Yu Cui,&ast; Yao Lu,&ast; Qiang Huang, Congming Zhang, Liang Sun, Cheng Ren, Qian Wang, Teng Ma, Zhong Li, Kun Zhang, Zhimeng Wang, Hanzhong Xue Department of Orthopedics and Trauma, Hong Hui Hospital, Xi’an Jiaotong University College of Medicine, Xi’an, Shaanxi, 710000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhimeng Wang; Hanzhong Xue, Department of Orthopedics and Trauma, Hong Hui Hospital, Xi’an Jiaotong University College of Medicine, Xi’an, Shaanxi, 710000, People’s Republic of China, Email enshuo99@126.com; 13759963709@163.comIntroduction: Research on preoperative blood management in older patients with delayed surgery for intertrochanteric fracture is scarce, especially regarding hematopoiesis and hemostasis. We assessed the effectiveness of optimized blood management programs in older patients undergoing delayed surgery for intertrochanteric fractures.Methods: This retrospective study included 456 patients who underwent delayed surgery for intertrochanteric fractures. According to the optimized blood management plan, the patients were divided into four groups: group A was the control group; group B received 1 g of tranexamic acid (TXA) intravenously at admission; group C underwent sequential TXA treatment after admission until 1 day before surgery (1 g/day); and group D received iron supplements (200 mg/day) in addition to the treatment administered to group C, with or without recombinant human erythropoietin (rHuEPO; 40,000 IU). The primary outcomes were preoperative hidden blood loss (HBL), preoperative allogeneic blood transfusion (ABT) rate, hemoglobin (Hb) change, and actual Hb drop.Results: The Hb reduction, calculated HBL, and hospitalization duration in groups C and D were significantly lower than those in groups A and B. The preoperative ABT rates in groups C and D were significantly lower than those in groups A and B, with no significant difference between groups C and D.Discussion: The results of this study suggested that iron supplementation (with or without rHuEPO) combined with the sequential IV TXA scheme did not show a better clinical effect than the sequential IV TXA scheme in the management of patients undergoing delayed surgery for intertrochanteric fractures. Therefore, further evaluation is needed before recommending iron supplements and rHuEPO in older patients.Keywords: blood management, iron supplements, surgical delay, intertrochanteric fractures, tranexamic acid

Yaoqiang Wu,1 Bo Yu,2 Yaping Li,3 Fuxiang Yu,1 Zhongguo Li,1 Daxin Chen,1 Feng Jiang,1 Jianbo Bo,1 Hongwei Xue,1 Hongyang Lv,1 Haiyang Li1 1Department of General Surgery, Dandong First Hospital, Dandong, Liaoning, People’s Republic of China; 2Department of Gastroenterology, Dandong First Hospital, Dandong, Liaoning, People’s Republic of China; 3Department of Intensive Care Unit, Dandong First Hospital, Dandong, Liaoning, People’s Republic of ChinaCorrespondence: Yaoqiang Wu, Department of General Surgery, Dandong First Hospital, Dandong, Liaoning, People’s Republic of China, Tel/Fax + 86-415-2819133, Email wo612389@163.comPurpose: Colon cancer is the most commonly diagnosed gastrointestinal cancer. This research intended to evaluate the prognostic values of LINC01006 and miR-3199 for colon cancer and their effects on cell physiology.Patients and Methods: LINC01006 and miR-3199 expression levels were determined by RT-qPCR. Patients’ 5-year cumulative survival rate was analyzed by Kaplan–Meier curves with the Log rank test. Chi-square test and multivariate Cox regression analysis were used to access the clinical significance. CCK-8 assay, transwell assay, and TUNEL assays were used to monitor the change of cell proliferation, invasion, migration, and apoptosis.Results: The expression level of LINC01006 was increased while miR-3199 was decreased in colon tissues and cells compared to normal ones. This dysregulated expression was correlated with T stage (P = 0.002) and N stage (P = 0.009). High LINC01006 level (HR = 4.048, 95%: 1.502– 10.911, P = 0.006) or low miR-3199 level (HR = 3.421, 95% CI: 1.254– 9.330, P = 0.016) was outstanding for predicting poor prognosis in patients with colon cancer. Downregulation of LINC01006 reduced cell proliferation, invasion, and migration but induced cell apoptosis (P < 0.05).Conclusion: LINC01006 knockdown showed anti-proliferative, anti-metastatic, and apoptotic-induced effects on colon cancer cells. This study contributes to research on promising prognostic biomarkers of colon cancer and might give way to further investigation of alternative tumor targets.Keywords: colon cancer, LINC01006, miR-3199, prognosis

Sihang Cheng,1,2 Xiang Yu,2 Siyun Liu,3 Zhengyu Jin,1 Huadan Xue,1 Zhiwei Wang,1 Ping Xie2 1Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Department of Radiology, Sichuan Provincial People’s Hospital, Sichuan Academy of Medical Sciences, Chengdu, People’s Republic of China; 3Pharmaceutical Diagnostics, GE Healthcare, Beijing, People’s Republic of ChinaCorrespondence: Zhiwei Wang; Ping Xie Tel +8610 69159562; +8628 87393976Email zhiweiwang1981@sina.com; haoyanx@163.comObjective: To develop and validate a prognostic nomogram in eastern patients with hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) receiving trans-arterial chemoembolization with drug-eluting beads (DEB-TACE).Methods: This retrospective study included 200 patients with training cohort (n = 118) from institution 1 and test cohort (n = 82) from institution 2. All these patients received first-line DEB-TACE between October 2016 and October 2018. Multivariate Cox proportional hazard regression analysis was performed on the training cohort to reveal the independent prognostic factors, and then prognostic nomograms were developed. In order to evaluate the performance of the nomogram comprehensively in both the training and test cohorts, C-index, Kaplan–Meier curve with Log rank test, receiver operating characteristic curve (ROC), calibration plot, and decision curve analysis (DCA) were performed.Results: Tumor number, serum γ-glutamyl transferase (GGT) level, and level of PVTT were independent risk factors of prognosis. A nomogram was constructed to predict 6-, 12- and 18-month overall survival (OS) based on these identified prognostic factors. C-indexes of the nomogram were 0.88 (95% confidence interval [CI], 0.79– 0.97) in the training cohort and 0.87 (95% CI, 0.75– 0.99) in the test cohort. The Kaplan–Meier curve analysis showed that the nomogram was able to separate patients into low- and high-risk subgroups. ROC curves for the nomogram at 6-, 12- and 18-month showed satisfied discrimination, with an AUC of 0.765, 0.803 and 0.809 in the training cohort, respectively, and 0.772, 0.724 and 0.746 in the test cohort, respectively. The calibration curve demonstrated good agreement between predicted and actual survival rates in the training and test cohorts. The decision curve showed good performance of the nomogram in terms of clinical application.Conclusion: We developed and validated a nomogram that was accurate and clinically useful in eastern patients with HBV-associated HCC with PVTT who underwent DEB-TACE.Keywords: hepatocellular carcinoma, portal vein tumor thrombus, trans-arterial chemoembolization, drug-eluting beads, nomogram

The Millennium Eruption of Changbaishan Volcano is heralded as one of the largest explosive eruptions in the Late Holocene and produced huge quantities of tephra. The petrogeochemical method estimates that the Millennium Eruption emitted up to 45 Tg of sulfur into the atmosphere—more than in the Tambora eruption in 1815 CE, which caused "a year without a summer" across the Northern Hemisphere in 1816 CE. Despite such massive emissions, evidence for this eruption's climate impact in East Asia remains elusive. To explain this contradiction, this study used 67 high‐resolution tree‐ring‐width records from the Northern Hemisphere spanning the past two millennia, complemented by volcanic sensitivity experiments conducted with the Community Earth System Model. Results reveal a prevailing decreasing/negative trend in the proxy records during the potential eruption period, with 945 CE marking the most notable negative anomaly, suggesting that the Millennium Eruption likely occurred in 945 CE rather than 946 CE. Sensitivity experiments, corroborated by proxy records, demonstrate that the Millennium Eruption induced substantial negative temperature anomalies at middle and high latitudes, alongside an increase in Meiyu‐Baiu‐Changma precipitation in the middle and lower reaches of the Yangtze River and southwestern Japan and a decrease in precipitation in India, northern China, and the South China Sea in the first post‐eruption year. This study offers a novel perspective on the climate impact of the Millennium Eruption, reconciling previous discrepancies regarding its climate impact. Plain Language Summary: About a thousand years ago, the Changbaishan volcano erupted with incredible force, ranking as one of the largest historical eruptions in the past 2000 yrs. Despite its size, evidence for this eruption's climate impact in East Asia has remained elusive. We delved into this mystery by examining detailed high‐resolution proxy records and performing climate model simulations. Our findings suggest that the climate effects of the eruption may have been unexpectedly strong, with the Millennium Eruption potentially occurring in 945 CE that is earlier than previously thought. The Millennium Eruption triggered notable cooling at middle and high latitudes, increased Meiyu‐Baiu‐Changma precipitation in the middle and lower reaches of the Yangtze River and southwestern Japan, and reduced precipitation in India, northern China, and the South China Sea. This research helps us understand how large volcanic eruptions can interact with other natural factors to influence our climate. Key Points: Sulfur emissions of the Millennium Eruption estimated from a petrogeochemical method are inconsistent with the signal from ice‐core samplesA consistent negative response in the high‐resolution paleoclimate records suggests a significant climate impact of the Millennium EruptionThe eruption enhanced the Meiyu‐Baiu‐Changma precipitation while diminishing precipitation in India, northern China, and the South China Sea [ABSTRACT FROM AUTHOR]

Jian Ma,1– 3 Huan Xue,1– 3 Li-Hong He,1– 3 Ling-Yun Wang,1– 3 Xiao-Juan Wang,1– 3 Xun Li,1– 3 Lei Zhang1– 3 1Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, Gansu Province, 730000, People’s Republic of China; 2Key Laboratory of Biological Therapy and Regenerative Medicine Transformation Gansu Province, Lanzhou, Gansu Province, 730000, People’s Republic of China; 3The First Clinical Medical College, Lanzhou University, Lanzhou, Gansu Province, 730000, People’s Republic of ChinaCorrespondence: Xun LiDepartment of General Surgery, The First Hospital of Lanzhou University, 1 Donggang West Road, Chengguan District, Lanzhou, Gansu Province, 730000, People’s Republic of ChinaTel +86 13993138612Email lxdr21@126.comLei ZhangDepartment of General Surgery, The First Hospital of Lanzhou University, Donggang West Road, Chengguan District, Lanzhou, Gansu Province, 730000, People’s Republic of ChinaTel +86 13993181644Email 13993181644@139.comAbstract: Pancreatic cancer, with high morbidity and mortality rates, is one of the most malignant tumors worldwide. Despite extensive research, the prognosis remains poor. Autophagy, a lysosomal-mediated, highly conserved degradation process that removes abnormal proteins and damaged organelles from the body, is upregulated in pancreatic ductal adenocarcinoma. Based on differences in the tumor microenvironment and tumor stage, the functions of autophagy in the pathophysiology and treatment of pancreatic cancer differ. In the initial phase, autophagy inhibits the transformation of precancerous lesions to cancer. However, in the progressive stage, autophagy promotes tumor growth. Autophagy is also one of the main mechanisms of drug resistance during treatment. Here, we describe the role of autophagy in pancreatic cancer progression and discuss relevant treatment strategies for this disease.Keywords: pancreatic ductal adenocarcinoma, cell growth, migration, tumor microenvironment, therapy

Ying-Hua Luo,1,&ast; Cheng Wang,2,&ast; Wan-Ting Xu,3,&ast; Yu Zhang,3 Tong Zhang,3 Hui Xue,3 Yan-Nan Li,3 Zhong-Ren Fu,3 Ying Wang,4 Cheng-Hao Jin3– 5 1Department of Grass Science, College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, 163319, People’s Republic of China; 2Pharmacy Department, Daqing Oilfield General Hospital, Daqing, 163001, People’s Republic of China; 3Department of Biochemistry and Molecular Biology, College of Life Science & Technology, Heilongjiang Bayi Agricultural University, Daqing, 163319, People’s Republic of China; 4College of Food Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, 163319, People’s Republic of China; 5National Coarse Cereals Engineering Research Center, Daqing, 163319, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Cheng-Hao Jin; Ying Wang Email jinchenghao3727@qq.com; wychen156@163.comBackground: 18β-glycyrrhetinic acid (18β-Gly), which is extracted from licorice root, has various pharmacological properties; however, its anti-cancer effects on lung cancer cells have not been fully established.Purpose: In this study, we investigated the underlying molecular mechanisms of 18β-Gly.Results: Our results showed that 18β-Gly had significant cytotoxic effects and no apparent side effects. 18β-Gly induced mitochondria-dependent apoptosis of A549 lung cancer cells. In addition, after treatment with 18β-Gly, intracellular reactive oxygen species (ROS) levels were significantly increased, and G2/M cell cycle arrest and inhibition of cell migration were induced via the mitogen-activated protein kinase (MAPK)/signal transducer and activator of transcription 3 (STAT3)/nuclear factor kappa (NF-κB) signaling pathways. After pretreatment with the ROS scavenger N-acetyl-L-cysteine or MAPK inhibitors, the expression levels of phosphorylated p38 (p-p38), phosphorylated c-Jun N-terminal kinase, inhibitor of nuclear factor kappa B, cleaved caspase-3 (cle-cas-3), cleaved poly (ADP ribose) polymerase (cle-PARP), p-p53, p27, p21, and E-cadherin were decreased; and levels of phosphorylated extracellular signal-regulated kinase, p-STAT3, NF-κB, Bcl-2, cyclin B1, cyclase-dependent kinase 1/2 (CDK1/2), N-cadherin, vimentin, and snail homolog 1 (SNAI 1) were increased. In addition, the percentage of cells in the G2/M phase was decreased, and inhibition of migration was reduced.Conclusion: In summary, 18β-Gly induced apoptosis and G2/M cell cycle arrest and inhibited migration via the ROS/MAPK/STAT3/NF-κB signaling pathways in A549 lung cancer cells. Therefore, 18β-Gly is a novel promising candidate for the treatment of lung cancer.Keywords: 18β-glycyrrhetinic acid, lung cancer, apoptosis, cell cycle arrest, ROS, cell migration

Junbin Huang,1,&ast; Lifen Huang,1,&ast; Su Liu,2 Shaofen Lin,2 Yucai Cheng,1 Xiaoyun Jiang,3 Hongman Xue,1 Chikong Li,4 Chun Chen1 1Division of Hematology/Oncology, Department of Pediatrics, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, People’s Republic of China; 2Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, People’s Republic of China; 3Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 518000, People’s Republic of China; 4Division of Haematology/Oncology/BMT, Department of Paediatrics, The Chinese University of Hong Kong, Hong Kong, 999077, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chun ChenDivision of Hematology/Oncology, Department of Pediatrics, The Seventh Affiliated Hospital, Sun Yat-sen University, No. 628 Zhenyuan Road, Guangming District, Shenzhen, 518107, People’s Republic of ChinaTel +86 13719003063Email chemchum@163.comChikong LiDivision of Haematology/Oncology/BMT, Department of Paediatrics, The Chinese University of Hong Kong, 30-32 Ngan Shing Street, Shatin, New Territories, Hong Kong, 999077, People’s Republic of ChinaTel +86 852-9359 0525Email lichikong@126.comObjective: The aim of the present study is to evaluate the efficacy, complications, and contributing factors of immunosuppressive therapy (IST) response in children with acquired aplastic anemia (AA) and to explore optimal therapeutic methods for different clinical AA types.Methods: A total of 130 children diagnosed with acquired AA underwent IST in the Department of Pediatrics at Sun Yat-sen Memorial Hospital and the Department of Pediatrics at Seventh Affiliated Hospital, Sun Yat-sen University, between January 1, 2006, and July 15, 2020. The overall survival (OS), response rates, complications, and response predictors were analyzed. The response rates were compared according to clinical AA type.Results: All 130 children with AA were followed up with for a median of 50.6 months. Among the patients, 25 had non-severe AA (NSAA), 64 had severe AA (SAA), and 41 had very severe AA (VSAA). All patients initially received IST. In 13 patients, the IST failed; these patients received an allo-hematopoietic stem cell transplant as a salvage regimen. The OS rate was 90.3% ± 2.8%, and the response rates at 3, 6, 9, and 12 months were 34.19%, 39.32%, 49.57%, and 66.67%, respectively. The prolonged follow-up period might have led to higher response rates, especially in patients with SAA and VSAA. A multivariate logistic regression analysis of prognostic factors was conducted; the results showed that high red blood cell (RBC) and platelet (PLT) counts were associated with a high overall response rate and that the RBC count at diagnosis is a major contributing factor.Conclusion: With the use of rabbit anti-thymocyte globulin, proper cyclosporine management, and a prolonged IST follow-up period, a higher number of patients with acquired AA than normal achieved response. Proportionally, the number of patients who achieved remission within 12 months was higher in the SAA group (38.18%→ 63.64%) and VSAA group (28.95%→ 65.79%) than in the NSAA group (58.33%→ 75%). Higher RBC and PLT counts at diagnosis can predict a favorable outcome.Keywords: pediatric, aplastic anemia, immunosuppressive therapy, predicting factor

Dandan Luo,1 Meilian Peng,2 Xizhen Wei,1 Diling Pan,3 Huifeng Xue,4 Yuying Xu,1 Binhua Dong2 1Department of Obstetrics, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 2Department of Gynecology, Laboratory of Gynecologic Oncology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 3Department of Pathology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 4Fujian Provincial Cervical Disease Diagnosis and Treatment Health Center, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of ChinaCorrespondence: Binhua DongDepartment of Gynecology, Laboratory of Gynecologic Oncology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, 18 Daoshan Road, Fuzhou, Fujian, People’s Republic of ChinaTel +86-591-87558732Fax +86-591- 87551247Email dbh18-jy@126.comYuying XuDepartment of Obstetrics, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, 18 Daoshan Road, Fuzhou, Fujian, People’s Republic of ChinaTel +86-591-87279515Fax +86-591-87551247Email yyxu703@163.comPurpose: The status of human papillomavirus (HPV) infection in pregnant and non-pregnant women in China remains unclear. This study aimed to compare the prevalence and genotype distributions of HPV between pregnant and non-pregnant women in China.Patients and Methods: A case-control study was conducted of pregnant women during the second trimester and age-matched non-pregnant women attending the Fujian Maternity and Child Health Hospital between January 1, 2017 and December 31, 2018. Participants underwent cervical cytology testing and HPV genotyping. The genotyping test was able to identify 14 high-risk HPV (HR-HPV), four possible HR-HPV, and five low-risk HPV (LR-HPV) types. Further colposcopy and a cervical biopsy were performed if indicated. The primary outcomes were HPV prevalence and genotype distribution.Results: In total, 1077 pregnant and 1077 non-pregnant women were enrolled. Compared with non-pregnant women, pregnant women had a higher prevalence of HPV (24.2% vs 14.8%), HR-HPV (20.2% vs 11.7%), and LR-HPV (8% vs 4.5%) infection. In pregnant women, the most prevalent HPV genotypes were HPV-52 (6.0%), -16 (3.5%), -58 (2.6%), -53 (2.5%), and -51 (2.5%), while in non-pregnant women the most prevalent genotypes were HPV-52 (3.6%), -81 (1.9%), -51 (1.8%), -68 (1.4%), and -16 (1.3%). In women aged ≥ 35 years, HR-HPV (P=0.002) and LR-HPV (P=0.001) prevalence were significantly higher in pregnant women. However, in women aged < 35 years, only HR-HPV prevalence was higher in pregnant women. Pregnant and non-pregnant women with HPV-16 and HPV-58 infection had a high prevalence of high-grade squamous intra-epithelial lesions (HSIL) (HPV-16: P< 0.001 and P=0.005, HPV-58: P=0.043 and P=0.005); but with other HR-HPV genotypes, only non-pregnant women had an increased HSIL prevalence.Conclusion: In China, the HPV prevalence is higher in pregnant women than that in non-pregnant women and is also age- and genotype-dependent. HPV-infected pregnant women aged ≥ 35 years and those with HPV-16 should be closely monitored to enable rapid clinical intervention.Keywords: human papillomavirus, genotype, squamous intraepithelial lesions, cervical cytology, China, pregnant