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Hupo Bian,1 Shaoqi Zhu,2 Yonghua Zhang,3 Qiang Fei,4 Xiuhua Peng,1 Zanhui Jin,1 Tianxiang Zhou,5 Hongxing Zhao1,6 1Department of Radiology, The First Affiliated Hospital of Huzhou Normal University, Huzhou, Zhejiang, People’s Republic of China; 2Department of Endocrinology, The First Affiliated Hospital of Huzhou Normal University, Huzhou, Zhejiang, People’s Republic of China; 3Department of Radiology, The Wuxing District People’s Hospital, Huzhou, Zhejiang, People’s Republic of China; 4Department of Radiology, The Linghu People’s Hospital, Huzhou, Zhejiang, People’s Republic of China; 5Department of Urinary Surgery, The First Affiliated Hospital of Huzhou Normal University, Huzhou, Zhejiang, People’s Republic of China; 6Huzhou Key Laboratory of Precise Diagnosis and Treatment of Urinary Tumors, Huzhou, Zhejiang, 313000, People’s Republic of ChinaCorrespondence: Hongxing Zhao, Department of Radiology, The First Affiliated Hospital of Huzhou Normal University, No. 158, Plaza Back Road, Wuxing District, Huzhou City, Zhejiang Province, People’s Republic of China, Email zhx2113408@126.comObjective: A bibliometric analysis was conducted using VOSviewer and CiteSpace to examine studies published between 2009 and 2023 on the utilization of artificial intelligence (AI) in chronic obstructive pulmonary disease (COPD).Methods: On March 24, 2024, a computer search was conducted on the Web of Science (WOS) core collection dataset published between January 1, 2009, and December 30, 2023, to identify literature related to the application of artificial intelligence in chronic obstructive pulmonary disease (COPD). VOSviewer was utilized for visual analysis of countries, institutions, authors, co-cited authors, and keywords. CiteSpace was employed to analyze the intermediary centrality of institutions, references, keyword outbreaks, and co-cited literature. Relevant descriptive analysis tables were created using Excel2021 software.Results: This study included a total of 646 papers from WOS. The number of papers remained small and stable from 2009 to 2017 but started increasing significantly annually since 2018. The United States had the highest number of publications among countries/regions while Silverman Edwin K and Harvard Medical School were the most prolific authors and institutions respectively. Lynch DA, Kirby M. and Vestbo J. were among the top three most cited authors overall. Scientific Reports had the largest number of publications while Radiology ranked as one of the top ten influential journals. The Genetic Epidemiology of COPD (COPDGene) Study Design was frequently cited. Through keyword clustering analysis, all keywords were categorized into four groups: epidemiological study of COPD; AI-assisted imaging diagnosis; AI-assisted diagnosis; and AI-assisted treatment and prognosis prediction in the COPD research field. Currently, hot research topics include explainable artificial intelligence framework, chest CT imaging, and lung radiomics.Conclusion: At present, AI is predominantly employed in genetic biology, early diagnosis, risk staging, efficacy evaluation, and prediction modeling of COPD. This study’s results offer novel insights and directions for future research endeavors related to COPD.Keywords: chronic obstructive pulmonary disease, artificial intelligence, visual analysis, bibliometric analysis

Haotian Chen, Juan Zhi, Lei Wang, Zibin Jin, Jin Xu, Fei Xing, Chao Wen, Qianyu Wang, Chunmei Chen, Weiou Li, Ermeng Xu, Jie An, Lingxin Wei Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Lingxin Wei, Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 33 Badachu Road, Shijingshan District, Beijing, 100144, People’s Republic of China, Tel +86 010 85557917, Email weilx3934@sina.comPurpose: Esketamine have anesthetic and analgesic properties. This study aimed to observe the enhancing effect of subanesthetic doses of esketamine (0.15– 0.3 mg/kg/h) with dexmedetomidine and remifentanil during anesthesia for liposuction surgery.Patients and Methods: A total of 155 subjects were randomized with a 1:1 ratio to Group E (esketamine-dexmedetomidine/remifentanil, n=78) or Group C (saline-dexmedetomidine/remifentanil group, n=77). The primary outcome was satisfaction of patient and surgical team with the procedure. The secondary outcomes were the postoperative Athens Insomnia Scale (AIS) and Hospital Anxiety and Depression Scale (HADS) scores, hemodynamic and respiratory changes, drug consumption, adverse event rates, and predictors associated with patient satisfaction.Results: Patient and surgical team satisfaction with the procedure was significantly higher in Group E than in Group C (4.7 ± 0.6 vs 4.2 ± 0.7, P < 0.001; 4.7 ± 0.5 vs 4.4 ± 0.7, P = 0.005). The postoperative AIS (4 [1, 6] vs 5 [2, 9], P = 0.012) and HADS-A (1 [0, 3] vs 2 [0, 6], P = 0.012) scores were significantly lower in Group E than in Group C. Hemodynamic and respiratory parameters were more stable in Group E than in Group C, with the lower opioids consumption of sufentanil (0 [0, 4] vs 5 [2.5, 7.7], P < 0.001) and remifentanil (700 [480, 900] vs 800 [500, 1200], P = 0.023) in Group E compared to Group C. On ordinal logistics regression, postoperative sleep quality (OR, 0.70; 95% CI, 0.62– 0.79), anxiety level (OR, 0.77; 95% CI, 0.62– 0.95) and recovery time in post-anesthesia care unit (PACU) (OR, 0.69; 95% CI, 0.56– 0.98) were identified as significant predictors associated with patient satisfaction.Conclusion: A subanesthetic dose of esketamine (0.15– 0.3 mg/kg/h) as an adjuvant can improves the sedative and analgesic effects of dexmedetomidine and remifentanil during anesthesia for liposuction surgery.Clinical Trial Registration: ChiCTR2400080363.Keywords: esketamine, sedation, analgesia, satisfaction, liposuction

Yi Tang,1,&ast; Zemin Wei,1,&ast; Ning Li,2 Chao Jiang,2 Chen Liang,1 Lulu Sun,2 Lufeng Tian,3 Zhengyu Jin,4 Zhe Wu,2,&ast; Hao Sun4,&ast; 1Department of Endocrinology, Fushun Central Hospital, Fushun, Liaoning Province, People’s Republic of China; 2Department of Radiology, Fushun Central Hospital, Fushun, Liaoning Province, People’s Republic of China; 3Department of Internal Medicine, Fushun Central Hospital, Fushun, Liaoning Province, People’s Republic of China; 4Department of Radiology, State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Sun, No. 1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing, 100730, People’s Republic of China, Tel +86-10-69159537, Email sunhao_robert@126.com Zhe Wu, Fushun Central Hospital, Xincheng Road, Shuncheng District, Fushun, Liaoning Province, 113006, People’s Republic of China, Tel +86-156-42018778, Email wuzhe0306@163.comPurpose: To examine the risk of type 2 diabetes mellitus in non-obese patients with pancreatic fatty infiltration through abdominal computed tomography (CT) quantitation.Patients and Methods: We carried out a retrospective analysis of abdominal CT and inpatient medical records of 238 inpatients from July 2019 to April 2021. The patients were divided into a normal non-obese group (BMI < 25, n = 135) and diabetic non-obese group (BMI < 25, n = 103). Abdominal CT-related parameters included body width; mean CT values of the pancreas, liver, and spleen; difference between pancreas and spleen CT values (P−S); pancreas-to-spleen attenuation ratio (P/S); and liver-to-spleen attenuation ratio (L/S). Logistic regression was used to estimate the risk factors for comorbid diabetes in a non-obese population.Results: The P-values of the pancreas CT value, P−S, P/S, body width, and L/S were all < 0.05 and correlated to comorbid diabetes in non-obese patients. Worsening pancreatic fatty infiltration increased the risk of developing diabetes. Using a P/S of 1.0 as reference, every successive decrease in this ratio by 0.1 increases patient risk by 3.981, 4.452, 6.037, and 12.937 times.Conclusion: The risk of developing type 2 diabetes mellitus in non-obese patients increases with the degree of pancreatic fatty infiltration as assessed by CT.Keywords: computed tomography, non-obese patients, pancreatic fatty infiltration, type 2 diabetes mellitus

Michael H Storandt,1 Zhaohui Jin,2 Amit Mahipal3 1Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA; 2Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA; 3Department of Medical Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH, USACorrespondence: Amit Mahipal, University Hospitals Seidman Cancer Center, Case Western Reserve University, 11100 Euclid Ave, Cleveland, OH, 44106, USA, Tel +1 216-844-3951, Email Amit.mahipal@UHhospitals.orgAbstract: Advanced biliary tract cancers (BTCs) have historically been managed with chemotherapy but, in recent years, this treatment paradigm has begun to shift with the introduction of immune checkpoint inhibitors in addition to standard of care chemotherapy. The tumor microenvironment of BTC may be enriched with regulatory T lymphocytes and immune checkpoint expression in some patients. Durvalumab, an anti-programmed death ligand-1 (PD-L1) antibody, in combination with gemcitabine and cisplatin, has now received United States Food and Drug Administration approval for treatment of advanced BTC. Regulatory approval was based on the Phase III, randomized TOPAZ-1 trial that demonstrated survival benefit with addition of durvalumab to gemcitabine plus cisplatin compared to chemotherapy alone. The combination of chemotherapy and immunotherapy was well tolerated, and a subset of patients were able to achieve a durable response, with a 2-year overall survival rate of 23.6%. However, limitations remain in identifying which patients are most likely to benefit from immune checkpoint inhibition. Future study should aim to identify biomarkers predictive of substantial benefit, as well as the role of immune checkpoint inhibition in combination with targeted therapies and radiotherapy in the management of advanced BTC.Keywords: durvalumab, immunotherapy, cholangiocarcinoma, bile duct cancers

Zhuhua Jin,1,2 Lei Zhu,3 Shuping Zhou,2,4 Chao Lu2,4 1Department of Information Management, First Affiliated Hospital of Anhui University of Science and Technology, First People’s Hospital of Huainan, Huainan, Anhui Province, People’s Republic of China; 2School of Economics and Management, Anhui University of Science and Technology, Huainan, 232001, People’s Republic of China; 3Department of Neurology, First Affiliated Hospital of Anhui University of Science and Technology, First People’s Hospital of Huainan, Huainan, Anhui Province, People’s Republic of China; 4First Affiliated Hospital of Anhui University of Science and Technology, First People’s Hospital of Huainan, Huainan, Anhui Province, People’s Republic of ChinaCorrespondence: Lei Zhu, Department of Neurology, Department of Neurology, First Affiliated Hospital of Anhui University of Science and Technology, First People’s Hospital of Huainan, Huainan, Anhui Province, People’s Republic of China, Email salimai@126.com Chao Lu, First Affiliated Hospital of Anhui University of Science and Technology, First People’s Hospital of Huainan, Huainan, Anhui Province, People’s Republic of China, Email 765385306@qq.comBackground: Post-stroke Fatigue (PSF) after Intracerebral Hemorrhage (ICH) is a long-term symptom in stroke survivors. However, the pathogenesis of PSF remains inadequately understood and sufficient evidence-based treatments are lacking. Mobile health (mHealth) technology offers a promising approach to expanding access to high-quality and culturally tailored evidence-based mental care.Aim: This study examined the role of mHealth called iHealth in the management of PSF after ICH.Methods: A total of 225 patients diagnosed with intracerebral hemorrhage (ICH) were included in the study and randomly assigned to either the Mobile Health Intervention Group (mHI Group) or the non-Mobile Health Intervention Group (non-mHI). The management involved the utilization of a digital healthcare application named iHealth, which incorporated digital questionnaires, fatigue scale tests, and online videos for the purpose of administering the Patient Fatigue Reporting Measurement Information System (PFRMIS) short form as part of the initial patient assessment following ICH. The study was conducted remotely via video conferencing over a 12-week period in mHI Group, with fatigue assessments being conducted 3 months post-ICH onset in two groups.Results: Following the administration of PSF by iHealth, Univariate Logistic analyses indicated a significant association between fatigue and the type of activity, with patients who were sedentary or did nothing experiencing higher levels of fatigue (β=2.332, p< 0.001; β=2.517, p< 0.001). Multivariate Logistic analyses demonstrated a positive association between the intensity of physical activity and decreased emotional well-being and family support, as well as increased fatigue. (p=0.001, p=0.002, p=0.001). The FSS results demonstrated a significantly reduced incidence of PSF in the MHI group in comparison to non-mHI group following the conclusion of the programme. (13.1% vs 40%, p< 0.001).Conclusion: This study explored the effectiveness of the iHealth app for PSF following ICH, indicating that iHealth is a clinically valuable tool that warrants further dissemination.Keywords: post-stroke fatigue, mobile health intervention, fatigue severity scale, intracerebral hemorrhage, iHealth

Jun’e Ma,1,* Zhenhui Wang,1,* Chuanjin Luo,2 Jin’ou Xi,1 Xiaojing Wang,1 Yan Hu,1 Chengliang Zhu,3 Zhengjiang Jin1 1Department of Clinical Laboratory, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430070, People’s Republic of China; 2State Key Laboratory of Virology College of Life Sciences, Wuhan University, Wuhan, 430060, People’s Republic of China; 3Department of Clinical Laboratory, Institute of Translational Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhengjiang Jin, Department of Clinical Laboratory, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430070, People’s Republic of China, Email king199735@126.com Chengliang Zhu, Department of Clinical Laboratory, Institute of Translational Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China, Email zhuchengliang@whu.edu.cnPurpose: To understand the epidemiology and clinical features of Ureaplasma urealyticum (UU) infection in hospitalized neonates due to vertical transmission from mother to child.Methods: Respiratory secretions were collected from neonates hospitalized in the neonatology department of the Maternal and Child Health Hospital of Hubei Province from July 2020 to June 2022, and PCR was used to detect UU-DNA in respiratory secretions. The neonates were divided into UU-positive and UU-negative groups, the epidemiological and clinical characteristics of two groups, were statistically analyzed.Results: A total of 7257 hospitalized neonates were included in this study, of whom 561 were UU positive and 6696 were UU negative, with a UU detection rate of 7.73%. The detection rate among female neonates was higher than male neonates, and the highest detection rate was found in the period from 1– 7 days after birth; the detection rate was highest in spring and fall, and the lowest in winter, but the overall difference was not statistically significant (P> 0.05). Compared with the UU-negative group, neonates in the UU-positive group were more likely to be preterm, have a lower birth weight, be delivered vaginally, and have maternal preterm rupture of membranes. In addition, neonates in the UU-positive group were more likely to be co-infected with pathogens and to have complications related to UU infections, which were all statistically significant (P< 0.05).Conclusion: Neonatal UU infections are detected more frequently in female infants, with the highest detection rate occurring in 1– 7 days after birth, and the most prevalent periods for infection being spring and fall. Vaginal delivery and premature rupture of membranes may lead to an increased risk of vertical UU transmission from mother to child, and UU infection is strongly associated with preterm labor, low birth weight, pathogen co-infection, and related complications.Keywords: Ureaplasma urealyticum, neonates, infection, epidemiology, clinical characteristics, co-infection

Qiang Ye,1 Guoping Huang,1 Qin Hu,1 Qin Man,2 Xiaoying Hao,3 Liangyan Liu,4 Qiang Zhong,1 Zhao Jin2 1Department of Clinical Laboratory, West China Second University Hospital, Southern Sichuan Women’s and Children’s Hospital, Zigong, Sichuan, 643000, People’s Republic of China; 2Department of Prenatal Diagnosis Center, West China Second University Hospital, Southern Sichuan Women’s and Children’s Hospital, Zigong, Sichuan, 643000, People’s Republic of China; 3Department of Ultrasound, West China Second University Hospital, Southern Sichuan Women’s and Children’s Hospital, Zigong, Sichuan, 643000, People’s Republic of China; 4Department of Obstetrics, West China Second University Hospital, Southern Sichuan Women’s and Children’s Hospital, Zigong, Sichuan, 643000, People’s Republic of ChinaCorrespondence: Zhao Jin, Department of Prenatal Diagnosis Center, West China Second University Hospital, Southern Sichuan Women’s and Children’s Hospital, No. 49 Da Huang Tong Road, Da’an District, Zigong, Sichuan, 643000, People’s Republic of China, Tel +86-13990094008, Email Jinzhao_work@163.comObjective: This study was to evaluate the performance of noninvasive prenatal testing (NIPT) in detecting fetal chromosome disorders in pregnant women.Methods: From October 1st, 2017, to December 31th, 2022, a total of 15,304 plasma cell free DNA-NIPT samples were collected for fetal chromosome disorders screening. The results of NIPT were validated by confirmatory invasive testing or clinical outcome follow-up. Further, NIPT performance between low-risk and high-risk groups, as well as singleton pregnancy and twin pregnancy groups was compared. Besides, analysis of 111 false-positive cases was performed.Results: Totally, NIPT was performed on 15,086 eligible venous blood samples, of which 179 (1.19%) showed positive NIPT results and 68 were further validated to be true positive samples via confirmatory invasive testing or follow-up of clinical outcomes. For common chromosome aneuploidies, sex chromosome abnormalities (SCA) and other chromosomal aneuploidies, the detection sensitivities of NIPT were all 100%, the specificities were 99.87%, 99.70%, and 99.68% and the positive predictive values (PPVs) were 65.45%, 31.82%, and 10.91%, respectively. No statistically significant variance in detection performance was observed among 2987 high-risk and 12,099 low-risk subjects, as well as singleton and twin pregnancy subjects. The concentration of cell-free fetal DNA of 111 false-positive cases ranged from 5.5% to 33.7%, which was higher than the minimum requirement of NIPT.Conclusion: With stringent protocol, NIPT shows high sensitivity and specificity for detecting fetal chromosome disorders in a large-scale clinical service, helping improving overall pregnancy management.Keywords: noninvasive prenatal testing, fetal chromosome disorders, high risk, twin pregnancy, performance evaluation

Jing Wang,1,&ast; Lisha He,2,&ast; Zhiyan Jin,1,&ast; Guoguang Lu,1 Sufei Yu,1 Lingling Hu,1 Meidan Fang,1 Xiaxia Jin1 1Department of Clinical Laboratory, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Taizhou, Zhejiang Province, People’s Republic of China; 2Department of Ultrasound, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Taizhou, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Meidan Fang; Xiaxia Jin, Department of Clinical Laboratory, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Taizhou, Zhejiang Province, People’s Republic of China, Tel +86 13586102337; +86 15967063239, Email fangmd@enzemed.com; jinxiax@enzemed.comObjective: To explore the early predictors and their predicting value of 28-day mortality in sepsis patients and to investigate the possible causes of death.Methods: 127 sepsis patients were included, including 79 cases in the survival group and 48 cases in the death group. The results of all patients on admission were recorded. After screening the risk factors of 28-day mortality, the receiver operating characteristic curve (ROC) was used to determine their predictive value for the 28-day mortality rate on admission, and the Kaplan-Meier curve was drawn to compare the 28-day mortality rate between groups. Finally, patients with cytokine and lymphocyte subsets results were included for investigating the possible causes of death through correlation analysis.Results: APACHE II (acute physiology and chronic health evaluation II), SOFA (Sequential Organ Failure Assessment) and red blood cell distribution width (RDW) were the risk factors for 28-day mortality in sepsis patients (OR: 1.130 vs.1.160 vs.1.530, P < 0.05). The area under the curve (AUC), sensitivity and specificity of APACHE II, SOFA and RDW in predicting the mortality rate at 28 days after admission in sepsis patients were 0.763 vs 0.806 vs 0.723, 79.2% vs 68.8% vs 75.0%, 65.8% vs 89.9% vs 68.4%. The combined predicted AUC was 0.873, the sensitivity was 89.6%, and the specificity was 82.3%. The Kaplan-Meier survival curve showed that the 28-day mortality rates of sepsis patients with APACHE II≥ 18.5, SOFA≥ 11.5 and RDW≥ 13.8 were 58.5%, 80.5% and 59.0%, respectively. In the death group, APACHE II was positively correlated with SOFA, IL-2, and IL-10, and RDW was positively correlated with PLT, TNF-α, CD3+ lymphocyte count, and CD8+ lymphocyte count.Conclusion: Sepsis patients with high APACHE II, SOFA and RDW levels at admission have an increased 28-day mortality rate. The elevation of these indicators in dead patients are related to immune dysfunction.Keywords: sepsis, APACHE II, SOFA, red blood cell distribution width, mortality, immune dysfunction

Jiaru Wang,1 Peiyao Jia,2 Dong Zhang,2 Ying Zhao,2,3 Xin Sui,1 Zhengyu Jin,1,&ast; Wei Song1,&ast; 1Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Clinical Laboratory, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China; 3Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Song, Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, People’s Republic of China, Tel/Fax +86 10 69159525, Email cjr.songwei@vip.163.comPurpose: To explore the clinical characteristics, diagnosis, and treatment of family outbreak of psittacosis and to improve the success rate of treatment.Patients and Methods: The clinical characteristics, diagnosis, treatment, and outcome of family outbreak of psittacosis, which consists three patients, diagnosed by clinical analysis and metagenomic next-generation sequencing (mNGS) in our hospital were analyzed retrospectively.Results: We report on three instances of clustered atypical pneumonia, which were caused by Chlamydia psittaci during the COVID-19 pandemic. All patients exhibited symptoms of fever and cough, while one patient also experienced gastrointestinal symptoms such as nausea, vomiting, and diarrhea. Laboratory tests indicated no significant increase in leukocytes and neutrophils, but a mild increase in C-reactive protein was observed in all three patients. Chest computed tomography (CT) scans revealed a consolidation shadow in a unilateral lung lobe in all three patients. Both patients were treated with empirical moxifloxacin, yielding unsatisfactory outcomes. mNGS was conducted on sputum samples from one adult patient, revealing the presence of Chlamydia psittaci. Additional doxycycline was prescribed immediately, and then the patients’ temperatures were stabilized, and the lesion in chest CT was absorbed. The pediatric patient exhibited less severe symptoms compared to the adult patients and exhibited a favorable response to azithromycin administration.Conclusion: This study reports a cluster of a family outbreak of atypical pneumonia caused by C. psittaci in China. The occurrence of a family outbreak during the COVID-19 pandemic may be attributed to familial aggregation resulting from the epidemic. The three cases reported in this study did not experience severe complications, which can be attributed to the prompt medical intervention and swift diagnosis. This finding implies the need to enhance patients’ awareness and vigilance towards their health. Additionally, mNGS emerges as a valuable technique for accurately identifying pathogens causing pulmonary infections.Keywords: psittacosis, outbreak, COVID-19, metagenomic next-generation sequencing, pneumonia

Yuchen Li,1,&ast; Yinfeng Gu,1,&ast; Pengyue Yang,1 Yan Wang,1 Xibao Yu,1 Yangqiu Li,1 Zhenyi Jin,1,2 Ling Xu1,3 1Institute of Hematology, School of Medicine, Key Laboratory for Regenerative Medicine of Ministry of Education, Department of Hematology, First Affiliated Hospital, Jinan University, Guangzhou, 510632, People’s Republic of China; 2Department of Pathology, School of Medicine, Jinan University, Guangzhou, 510632, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, 510632, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Xu; Zhenyi Jin, Email lingxu114@163.com; jinzhenyijnu@163.comAbstract: Immunotherapy utilizing T cells that attack tumors is a promising strategy for treatment, but immune suppressive T cell subsets, such as regulatory T cell (Treg), and immune checkpoint molecules, including programmed death-1 (PD-1), can suppress the intensity of a T cell immune reaction and thereby impair tumor clearance. Cluster of differentiation 69 (CD69), known as an early leukocyte activation marker, can be used as a measure or early marker of T cell activation. In recent years, the functions of CD69 in the regulation of Treg/Th17 (T helper cell 17) differentiation and in the tissue retention of T cells have attracted considerable interest. These functions are related to the role of CD69 in immune suppression in tumor environments (TME). In this review, we first summarized current perspectives in the biological function of CD69 and demonstrated that CD69 acts as a regulator of T cell activation, differentiation, retention, and exhaustion. Then, we discussed recent advances in understanding of CD69 deficiency and anti-CD69 antibody administration and shed light on the value of targeting on CD69 for cancer immunotherapy and prognosis prediction.Keywords: CD69, T cell, immunotherapy

Jiaojiao Dong,&ast; Zhousheng Jin,&ast; Hongfei Chen, Nana Bao, Fangfang Xia&ast; Department of Anesthesiology, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, 325000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fangfang Xia, Department of Anesthesiology, The First Affiliated Hospital, Wenzhou Medical University, Shangcai Village, Nanbaixiang Town, Ouhai District, Wenzhou, Zhejiang Province, 325000, People’s Republic of China, Email Helenxia4271@163.comPurpose: We examined whether the addition of sufentanil to local anesthetics improves the quality of continuous femoral nerve block in patients undergoing total knee arthroplasty (TKA).Patients and Methods: With institutional ethical approval and having obtained written informed consent from each, 35 patients scheduled for elective bilateral TKA with ASA I or II physical status were studied. Bilateral femoral perineural catheters were preoperatively inserted. Both-sided catheters were randomly assigned to receive perineural ropivacaine of 0.2% plus 0.5μg/mL sufentanil deemed as RS group or 0.2% ropivacaine alone deemed as R group at the end of surgery. Visual analogue pain scores (VAS) during activity and at rest of each lower limb were recorded at 6,12,18,24,30,36,42 and 48h after surgery. During the first 48 postoperative hours, the number and reason of patients sleep interruption at night, the number of painful compressions, patient satisfaction and morphine requirements were recorded for each lower limb of patients.Results: Pain scores of RS group on movement were significantly lower than R group, but no difference was noted at rest. When compared to R group, RS group had a lower incidence of sleep interruption at night, fewer painful compressions, higher satisfaction scores and less morphine requirement.Conclusion: The addition of sufentanil to ropivacaine improved analgesia quality of continuous femoral nerve block after arthroplasty. Keywords: continuous femoral nerve block, ultrasound guidance, total knee arthroplasty, analgesia, ropivacaine

Shasha Zhang,1,&ast; Jinchun Li,2,&ast; Li Wan,1 Jing Yu,2 Sumei Chen,2 Zhengjiang Jin3 1Department of Pharmacy, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430070, People’s Republic of China; 2Department of Neonatology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430070, People’s Republic of China; 3Department of Clinical Laboratory, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430070, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhengjiang Jin, Department of Clinical Laboratory, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430070, People’s Republic of China, Email king199735@126.comPurpose: To determine the clinical features, laboratory findings, antibiotic treatment, and outcomes of neonatal listeriosis in a specialized tertiary hospital in Wuhan, China.Patients and Methods: We retrospectively analyzed the medical records of patients diagnosed with neonatal listeriosis at Maternal and Child Health Hospital of Hubei Province from January 2015 to December 2022. Listeriosis was indicated by positive culture for Listeria monocytogenes (LM).Results: A total of 11 cases were included in our study. The incidence rate of neonatal listeriosis was 2.06 per 100,000 live births. Seventy-three percent of the cases were born prematurely, caused early onset sepsis. Respiratory distress (100%) was the most common and earliest symptom, followed by fever (64%) and rashes (27%). The levels of C-reactive protein (CRP) and procalcitonin (PCT) were elevated in 100% of the cases. The median time-to-positivity (TTP) of the culture was 15 hours (range 9– 28hours). Of the 11 neonates, 6 were cured, 2 showed improvement, and 3 died, with a mortality rate of 27%. There were statistically significant differences in Apgar score at 5 minutes (p=0.037) and CRP (p=0.025) between the survival group and fatality group. Ampicillin was sensitive to LM isolates and effective for therapy if initiated early.Conclusion: Neonatal listeriosis is a rare but severe infection with a high mortality rate. Early identification and appropriate use of effective antibiotics are particularly critical for achieving positive outcomes. Apgar score and CRP are relevant indices for prognosis. Ampicillin is the first-line therapy and can be empirically administered to neonates suspected of having listeriosis.Keywords: neonatal listeriosis, Listeria monocytogenes, clinical features, antibiotic treatment, Apgar score, C-reactive protein

Hui Zhang,1 Zhigeng Jin,1 Hao Wang,2 Yutao Guo,1,3 Gregory YH Lip3,4 1Medical School of Chinese PLA, Department of Pulmonary Vessel and Thrombotic Disease, Sixth Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Department of Cardiology, Second Medical Centre, National Clinical Research Centre for Geriatric Diseases, Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, UK; 4Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, DenmarkCorrespondence: Yutao Guo, Department of Pulmonary Vessel and Thrombotic Disease, Six Medical Center, Chinese PLA General Hospital, 5 Fucheng Road, Beijing, 100048, People’s Republic of China, Email dor_guoyt@hotmail.comBackground: Guideline-recommended integrated care based on the ABC (Atrial fibrillation Better Care) pathway for “general” patients with atrial fibrillation (AF) improves clinical outcomes, as demonstrated in our prior mobile Atrial Fibrillation Application (mAFA)-II cluster randomized trial. The present study aims to investigate whether mAFA III-supported structured follow-up rehabilitation packages adapted to patient risk profiles and different treatment patterns (eg, for patients receiving drug treatment only, AF ablation, or left atrial appendage occlusion [LAAO]) will improve guideline adherence and reduce the risk of adverse cardiovascular events.Methods and Analysis: In this prospective, observational mAFA III pilot cohort study, patients with AF aged ≥ 18 years will be enrolled using the mAFA III App for self-management. Assuming an annual rate of composite outcome of “ischaemic stroke or systemic embolism, all-cause death and cardiovascular hospitalization” of 29.3% for non-ABC pathway compliance compared with 20.8% for ABC pathway compliance, at least 1475 patients would be needed to detect the outcome of the A, B and C components of the ABC pathway, assuming a withdrawal rate of 20% in the first year. The primary endpoint is adherence to guidelines regarding the A, B and C components of the ABC pathway. Ancillary analyses will be performed to determine the impact of the ABC pathway using smart technologies on the outcomes among the “high-risk” population (eg, ≥ 75 years old, with multimorbidities, with polypharmacy) and the application of artificial intelligence machine-learning AF risk prediction management in assessing AF recurrence. The individualised anticoagulants with AF burden will be monitored by smart devices.Trial Registration Number: ISRCTN13724416.Keywords: atrial fibrillation, rehabilitation, mobile health

Huan Zhang,1,2,&ast; Cheng Yu,1,&ast; Yuanling Cheng,1 Zhi Chen,2 Min Chen,2 Wangan He,1 Zhigang Jin,1 Shaoqian Cai,1 Lijuan Yu2 1Department of Cardiology, China Resources & Wisco General Hospital, Wuhan University of Science and Technology, Wuhan, People’s Republic of China; 2Wuhan University of Science and Technology Medical College, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaoqian Cai; Zhigang Jin, Department of Cardiology, China Resources & Wisco General Hospital, Wuhan University of Science and Technology, Wuhan, Hubei, 430080, People’s Republic of China, Email caishaoqian0716@163.com; 1634046380@qq.comBackground: With the disappointing results associated with the use of cardiac myosin inhibitors in the treatment of hypertrophic cardiomyopathy (HCM), the development of new therapies in clinical trials for HCM has rapidly increased. We assessed the characteristics of therapeutic intervention in HCM registered on ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP).Methods: We conducted a cross-sectional, descriptive study of clinical trials for therapeutic intervention in HCM registered on ClinicalTrials.gov and ICTRP.Results: This study analyzed 137 registered trials. Regarding study designs of these trials, 77.37% were purpose of treatment, 59.12% were randomized, 50.36% were parallel assignment, 45.26% were performed with masking, 48.18% recruited less than 50 participants, and 27.74% were Phase 2 trials. In total, 67 trials were new drug trials, of which 35 drugs were tested in these trials, and 13 trials involved treatment with mavacamten. Of these 67 clinical drug trials, 44.78% of trials involved the study of amines, and 16.42% involved 1-ring heterocyclic compounds. Regarding the NCI Thesaurus Tree, 23.81% of trials involved myosin inhibitors, 23.81% of trials involved drugs belonging to agents affecting the cardiovascular system, and 20.63% were involved in testing cation channel blockers. The drug-target network showed that myosin-7, potassium voltage-gated channel subfamily h member 2, beta-1 adrenergic receptor, carnitine o-palmitoyltransferase 1, and liver isoform were the most targeted pathways of the clinical trials analyzed in the drug-target network.Conclusion: The number of clinical trials investigating therapeutic interventions for HCM has increased in recent years. Ultimately, recent HCM therapeutic clinical trials generally did not incorporate either randomized controlled trials or masking and were small studies recruiting fewer than 50 participants. Although recent research has focused on targeting myosin-7, the molecular signaling mechanisms involved in the pathogenesis of HCM have the potential to elucidate novel target pathways.Keywords: clinical trials, obstructive hypertrophic cardiomyopathy, nonobstructive hypertrophic cardiomyopathy, myosin-7, amines, myosin inhibitors

Yang Wang,1,&ast; Zheng Wang,1,&ast; Xiao Wu,1,&ast; Song Zhu,2,&ast; Qiru Guo,1 Zhong Jin,1 Zixian Chen,3 Delai Zhang,2 Wangming Hu,1 Huan Xu,1 Liangqin Shi,1 Lan Yang,1 Yong Wang1 1College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 3School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong Wang, College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China, Tel +86 18280350393, Email yongwang1008@hotmail.com; wangyong@cdutcm.edu.cnPurpose: Dysfunction of endothelium is associated with multiple pathological vascular diseases. However, how to regulate reendothelialization after vascular injury is not well defined. This study aims to determine whether and how Paeonol controls reendothelialization following artery injury.Methods: The endothelium of murine carotid artery was denuded by catheter guide wires injury. H&E staining and IF staining were performed to determine whether Paeonol is critical for reendothelialization. BRDU Incorporation Assay, Boyden Chamber Migration Assay, Tube Formation Assay, and Spheroid Sprouting Assay were used to investigate whether Paeonol is involved in regulating proliferation and migration of endothelial cells. The underlying mechanism of how Paeonol regulates reendothelialization was determined by Molecular docking simulation and CO-IP Assay.Results: Paeonol treatment significantly inhibits neointima formation in carotid artery ligation model by promoting proliferation and migration of endothelial cells. Mechanistically, Paeonol enhances c-Myc expression, consequently interacts with VEGFR2 results in activating VEGF signaling pathway, and eventually promotes reendothelialization after vascular injury.Conclusion: Our data demonstrated that Paeonol plays a critical role in regulating vascular reendothelialization, which may be therapeutically used for treatment of pathological vascular diseases.Graphical Abstract: Keywords: Paeonol, c-Myc, VEGFR2, vascular injury, reendothelialization

Neil Daksla,1 Ashley Wang,1 Zhaosheng Jin,1 Abhishek Gupta,1 Sergio D Bergese1,2 1Department of Anesthesiology, Stony Brook University Health Science Center, Stony Brook, NY, 11794-8480, USA; 2Department of Neurosurgery, Stony Brook University Health Science Center, Stony Brook, NY, 11794-8480, USACorrespondence: Sergio D Bergese, Department of Anesthesiology, Stony Brook University School of Medicine, Health Sciences Center, Level 4, Room 060, Stony Brook, NY, 11794, USA, Tel +1 631 444-2979, Fax +1 631 444-2907, Email sergio.bergese@stonybrookmedicine.eduAbstract: Despite current advances in acute postoperative pain management, prevalence remains high. Inadequate treatment could lead to poor outcomes and even progression to chronic pain. Opioids have traditionally been the mainstay for treatment of moderate to severe acute pain. However, their use has been associated with opioid-related adverse events (ORAEs), such as respiratory depression, sedation, nausea, vomiting, pruritus, and decreased bowel motility. In addition, their liberal use has been implicated in the current opioid epidemic. As a result, there has been renewed interest in multimodal analgesia to target different mechanisms of action in order to achieve a synergistic effect and minimize opioid usage. Oliceridine is a novel mu-opioid receptor agonist that is part of a new class of biased ligands that selectively activate G-protein signaling and downregulate β-arrestin recruitment. Since G-protein signaling has been associated with analgesia while β-arrestin recruitment has been associated with ORAEs, there is potential for a wider therapeutic window. In this review, we will discuss the clinical evidence behind oliceridine and its potential role in acute postoperative pain management. We have systematically searched the PubMed database using the keywords oliceridine, olinvyk, and trv130. All articles identified were reviewed and evaluated, and all clinical trials were included.Keywords: postoperative pain, opioids, multimodal analgesia, opioid-related adverse events, biased agonism

Giacomo Scorsese,1,&ast; Zhaosheng Jin,1,&ast; Seth Greenspan,1 Christopher Seiter,1 Yujie Jiang,1,2 Michael B Huang,3 Jun Lin1 1Department of Anesthesiology, Stony Brook University Health Science Center, Stony Brook, NY, 11794-8480, USA; 2Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, 98195-6540, USA; 3Health Sciences Library, Stony Brook University, Stony Brook, NY, 11794-8034, USA&ast;These authors contributed equally to this workCorrespondence: Giacomo Scorsese, Department of Anesthesiology, Stony Brook University Health Science Center, Stony Brook, NY, USA, Tel +1631637-1457, Fax +1631444-2907, Email Scorseseg@gmail.comIntroduction: Thoracic epidural analgesia (TEA) and thoracic paravertebral blocks (PVB) are well-established techniques for pain management in thoracotomy. Here, we examine the efficacy of various thoracic fascial plane blocks vs TEA and PVB for intraoperative and postoperative analgesia for video assisted thoracoscopy surgery (VATS) with network meta-analysis.Methods: A search for prospective randomized control studies using adult patients undergoing VATS with general anesthesia. The interventions of interest were any regional anesthesia techniques used for postoperative pain control after VATS. Primary outcomes of interest were 24-hour opioid requirement and 24-hour pain scores. A Bayesian network meta-analysis was conducted.Results: We identified 42 studies that fulfilled our inclusion criteria. For patients who underwent VATS, TEA (MD = − 27MME, 95% CI = − 46.2 to − 9MME), ESP (MD = − 20MME, 95% CI – 33 to − 7.9MME), PVB (MD = − 15MME, 95% CI = − 26 to − 4.5MME) demonstrated significant opioid sparing efficacy, as well as reduction in cumulative 24-hour static pain scores. However, exclusion of one study due to high risk of bias revealed that TEA did not significantly reduce opioid consumption, nor did it reduce the incidence of PONV, pulmonary complications, or LOS when compared to ESP, SAP, PVB, ICN, or PECS blocks.Conclusion: Our findings suggest that TEA did not provide superior pain relief compared to ESP, SAP, PVB, ICN, or PECS blocks following VATS. Therefore, we propose ESP as a suitable intervention for the prevention of postoperative pain after VATS.Keywords: fascial plane blocks, thoracic epidurals, post-operative analgesia, postoperative nausea and vomiting, video assisted thoracoscopic surgery

Michael H Storandt,1 Amit Mahipal,2 Sri Harsha Tella,2 Anuhya Kommalapati,2 Zhaohui Jin2 1Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA; 2Department of Medical Oncology, Mayo Clinic, Rochester, MN, USACorrespondence: Zhaohui Jin, Department of Medical Oncology, Mayo Clinic, 200 1st St SW, Rochester, MN, 55905, USA, Tel +1 507-293-0487, Email jin.zhaohui@mayo.eduAbstract: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. Most patients with HCC have advanced disease at initial diagnosis, and sorafenib has been the only systemic treatment option for more than a decade in patients with advanced, unresectable HCC. However, there has been a dramatic change in the treatment algorithm in the last several years, given new drug approvals in the field. Most importantly, the combination of atezolizumab and bevacizumab has demonstrated clinically meaningful benefits in terms of response rate, progression-free survival, and overall survival compared to sorafenib in the first-line setting. Recently a phase III trial showed that the combination of durvalumab with a single dose of tremelimumab improved overall survival compared to sorafenib, while durvalumab monotherapy was found to be noninferior to sorafenib, making it an attractive alternative single agent in selected patient populations. As immunotherapy makes its way into the therapeutic landscape of HCC, other novel targeted therapies, such as lenvatinib, cabozantinib, ramucirumab, and regorafenib, have also been approved by regulatory authorities for treatment of advanced, unresectable HCC. This review article focuses on the first-line systemic treatment options for HCC while addressing some of the most important questions aimed at optimization of HCC treatment.Keywords: hepatocellular carcinoma, advanced hepatocellular carcinoma

Wenting Gong,1,&ast; Wen Tang,2,&ast; Lan Luo,3 Furong Zhang,1 Chenyang Cai,1 Jiangyan Zhang,1 Xiaolin Wu,4 Jianping Shang,4 Xiaolan Shu,2 Ting Wang,5 Danna Tu,6 Zhengjiang Jin,7,&ast; Ronghao Zheng4,&ast; 1Department of pharmacy, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Pediatric Intensive Care Unit, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Department of Child Health, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4Department of Pediatric Nephrology, Rheumatology, and Immunology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 5Department of Pediatric Neurology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 6Department of Pediatric Cardiology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 7Department of Clinical Laboratory, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ronghao Zheng, Department of Pediatric Nephrology, Rheumatology, and Immunology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, 745 Wu luo Road, Hongshan District, Wuhan, 430070, Hubei Province, People’s Republic of China, Tel +86 02787169267, Email hytwo2001@126.com Zhengjiang Jin, Department of Clinical Laboratory, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, 745 Wu luo Road, Hongshan District, Wuhan, 430070, Hubei Province, People’s Republic of China, Email king199735@126.comPurpose: To explore the trends and correlation between antibiotics consumption and antimicrobial resistance in children in a specialist hospital from 2016– 2021 in China.Patients and Methods: This retrospective study investigated data on the consumption of antibiotics and antimicrobial resistance in children. Antibiotics consumption was expressed as defined daily doses (DDDs)/1000 patient-days based on the Guidelines for Anatomical Therapeutic Chemical. The trends in antibiotics consumption and antimicrobial resistance rates were analyzed by linear regression, while Spearman correlation analysis was employed to evaluate their correlations.Results: An increasing trend in the annual consumption of carbapenems and monobactams was detected (all P< 0.05). A significant upward trend was detected in the annual resistance rates of Enterococcus faecium to ciprofloxacin, Streptococcus pneumonia to ceftriaxone, Acinetobacter baumannii to carbapenems, Enterobacter cloacae to carbapenems, Pseudomonas aeruginosa to ceftazidime, and Escherichia coli to cefepime, while the annual resistance rates of Escherichia coli to carbapenems had a significant downward trend (all P< 0.05). The consumption of cephalosporin/β-lactamase inhibitor (C/BLI) combinations and carbapenems had significant positive correlations with the resistance rates of Acinetobacter baumannii to carbapenems (r=0.763, P< 0.001; r=0.806, P< 0.001), Enterobacter cloacae to carbapenems (r=0.675, P< 0.001; r=0.417, P=0.043), and Pseudomonas aeruginosa to ceftazidime (r=0.625, P=0.001; r=0.753, P< 0.001), respectively. Also, increasing consumption of monobactams was related to the upward resistance rates of Acinetobacter baumannii to carbapenems (r=0.557, P=0.005) and Enterobacter cloacae to carbapenems (r=0.507, P= 0.011).Conclusion: This study demonstrated significant positive associations between antibiotics consumption and specific antimicrobial resistance rates. The current findings pointed out some directions to pursue in controlling the prevalence of certain resistant bacterial strains in children.Keywords: antibiotic consumption, antimicrobial resistance, correlation, children

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

Dian Zhang,1,2,&ast; Minshan Feng,1,&ast; Wei Liu,3,&ast; Jie Yu,1 Xu Wei,1 Kexin Yang,1 Jiawen Zhan,1 Wei Peng,1,2 Mingyi Luo,1,2 Tao Han,1 Zhefeng Jin,1 He Yin,1 Kai Sun,1 Xunlu Yin,1 Liguo Zhu1 1Department of Spinal Surgery, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Department of Nursing, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xunlu Yin; Liguo Zhu, Department of Spine, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing, 100102, People’s Republic of China, Email yin_xun_lu@163.com; zhlg95@aliyun.comAbstract: Neck pain and low back pain are major challenges in public health, and intervertebral disc (IVD) biomechanics is an important multidisciplinary field. To date, no bibliometric literature review of the relevant literature has been performed, so we explored the emerging trends, landmark studies, and major contributors to IVD biomechanics research. We searched the Web of Science core collection (1900– 2022) using keywords mainly composed of “biomechanics” and “intervertebral disc” to conduct a bibliometric analysis of original papers and their references, focusing on citations, authors, journals, and countries/regions. A co-citation analysis and clustering of the references were also completed. A total of 3189 records met the inclusion criteria. In the co-citation network, cluster #0, labeled as “annulus fibrosus tissue engineering”, and cluster #1, labeled as “micromechanical environment”, were the biggest clusters. References by MacLean et al and Holzapfel et al were positioned exactly between them and had high betweenness centrality. There existed a research topic evolution between mechanobiology and mechanical repair strategies of IVDs, and the latter had been identified as an emerging trend in IVD biomechanics. Numerous landmark studies had contributed to several fields, including mechanical testing of normal and pathological IVDs, mechanical evaluation of new repair strategies and development of finite element model. Adams MA was the author most cited by IVD biomechanics papers. Spine, the European Spine Journal, and the Journal of Biomechanics were the three journals where the most original articles and their references have been published. The United States has contributed most to the literature (n = 1277 papers); however, the research output of China is increasing. In conclusion, the present study suggests that IVD repair is an emerging trend in IVD biomechanics.Keywords: emerging trend, co-citation, CiteSpace, annulus fibrosus

Zhengjiang Jin,1,&ast; Zhenhui Wang,1,&ast; Jinchun Li,2 Lu Yi,1 Nian Liu,1 Lan Luo3 1Department of Clinical Laboratory, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430070, People’s Republic of China; 2Department of Neonatology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430070, People’s Republic of China; 3Department of Child Health, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430070, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lan Luo, Department of Child Health, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430070, People’s Republic of China, Email luolanlili@163.comPurpose: To determine the distribution and antibiotic resistance patterns among pathogens that cause neonatal sepsis (NS) and to assess trends in antibiotic resistance.Patients and methods: A total of 864 patients with sepsis admitted to a neonatal intensive care unit (NICU) between 2014 and 2021 were enrolled. Data on neonate age and sex, pathogenic microbes, and antimicrobial susceptibility were collected. Univariate and linear regression analyses were performed to determine the differences and trends in antibiotic resistance rates.Results: The overall incidence rate of NS was 4.59 cases per 1000 live births. Of these cases, 255 (29.5%) were early-onset neonatal sepsis (EONS) and 609 (70.5%) were late-onset neonatal sepsis (LONS). A total of 670 (70.5%) gram-positive cocci and 171 (19.8%) gram-negative bacilli were identified. Among the 552 coagulase-negative Staphylococcus (CoNS) strains, the rate of oxacillin resistance was 70.6%, but no strains were resistant to linezolid, vancomycin or tigecycline. Among the antibiotic resistance patterns of the top three gram-negative pathogens, K. pneumoniae showed the highest rates of resistance, with resistance rates of 37.9% and 39.4% to ertapenem and imipenem, respectively, while E. coli and Enterobacter cloacae showed high levels of susceptibility to both. With regard to the trends in resistance among important pathogens, the rates of resistance to rifampicin, ciprofloxacin, levofloxacin, moxifloxacin and clindamycin by Staphylococcus epidermidis significantly decreased (p< 0.05) during the study period. E. coli strains exhibited a significant increase in ceftriaxone resistance during the study period (p< 0.05).Conclusion: CoNS was the main microbe that caused NS, followed by E. coli. The bacterial isolates showed varying levels of resistance to the antimicrobial drugs tested. Thus, periodic surveillance in hospital settings to monitor changes in pathogens and antibiotic resistance is important.Keywords: neonatal sepsis, NICU, microorganisms, antibiotic resistance

Ke Song,1 Yiran Hu,1,2 Wei Chen,1 Wei Hua,2 Zening Jin1 1Department of Cardiology and Macrovascular Disease, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 2Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Zening Jin, Department of Cardiology and Macrovascular Disease, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Beijing, 100070, People’s Republic of China, Email zening_jin@126.com Wei Hua, Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, North Lishi Road No.167, Beijing, 100073, People’s Republic of China, Tel +86 010-59975832, Email drhuaweifw@sina.comBackground: Not all patients with heart failure derive consistent benefit from prophylactic implantable cardioverter-defibrillator (ICD). We aimed to evaluate the role of MADIT-ICD benefit score in risk-stratifying in Asian patients with left ventricular ejection fraction (LVEF) ≤ 35%.Methods: In this two-center, retrospective study, a total of 136 patients with LVEF ≤ 35% who received an ICD for primary prevention were enrolled. The endpoints were defined as the ventricular tachycardia ≥ 200bpm (VT) or ventricular fibrillation (VF) and non-arrhythmic death. Based on the MADIT-ICD benefit score system, all patients were categorized into three groups: highest benefit group (n = 41), intermediate benefit group (n = 80), and lowest benefit group (n = 15).Results: Forty patients experienced VT/VF and seven died of non-arrhythmic causes during a median follow-up of 44.8 ± 28.9 months. Kaplan–Meier curves showed that patients in highest benefit group had a worse VT/VF occurrence compared to those in other groups. In the highest benefit group, the predicted risk of VT/VF was 17-fold higher than the risk of non-arrhythmic mortality (41.5% vs 2.4%, P < 0.001). In the intermediate benefit group, the predicted risk of VT/VF was 4.2-fold higher than the risk of non-arrhythmic mortality (26.3% vs 6.3%, P = 0.001). In the lowest benefit group, however, the difference in the corresponding predicted risks was attenuated without statistically significant (13.3% vs 5.1%, P = 0.56).Conclusion: We demonstrate that MADIT-ICD benefit score can be used for the assessment of ICD primary prevention benefits in Asian patients with LVEF ≤ 35%.Keywords: implantable cardioverter-defibrillator, primary prevention, risk score, risk stratification, heart failure with reduced ejection fraction

Chunchun Gan,1 Zhan Jin,1 Gaobo Hu,1 Zheming Li,2 Minli Yan3 1Quzhou College of Technology, Quzhou, Zhejiang, 324000, People’s Republic of China; 2College of Pharmacy, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Neurology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, 310000, Zhejiang, People’s Republic of ChinaCorrespondence: Minli Yan, Department of Neurology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, 310000, Zhejiang, People’s Republic of China, Tel +86-571-87077785, Email yanminli.victory@163.com Zheming Li, College of Pharmacy, Hangzhou Medical College, Hanzhou, People’s Republic of China, Email lizheming90@163.comPurpose: Post-traumatic stress disorder (PTSD) is a result of trauma exposure and is related to psychological suffering as a long-lasting health issue. Further analysis of the networks and genes involved in PTSD are critical to the molecular mechanisms of PTSD.Methods: In this study, we aimed to identify key genes and molecular interaction networks involved in the pathogenesis of PTSD by integrating mRNA and miRNA data.Results: By integrating three high-throughput datasets, 5606 differentially expressed genes (DEGs) were detected, including five differentially expressed miRNAs (DEmiRNAs) and 5525 differentially expressed mRNAs (DEmRNAs). Nineteen upregulated and 46 downregulated DEmRNAs were identified in both GSE64813 and GSE89866 datasets, while five upregulated DEmiRNAs were found in the GSE87768 dataset. Functional annotations of these DEmRNAs indicated that they were mainly enriched in blood coagulation, cell adhesion, platelet activation, and extracellular matrix (ECM)-receptor interaction. Integrated protein-protein and miRNA-protein interaction networks among the DEGs were established with the help of 65 nodes and 121 interactions. Finally, 286 small molecules were obtained based on the Drug-Gene Interaction database (DGIdb). Three genes, prostaglandin-endoperoxide synthase 1 (PTGS1), beta-tubulin gene (TUBB1), and cyclin-dependent kinase inhibitor 1A (CDKN1A), were the most promising targets for PTSD therapy. Additionally, the present study also provided a higher performance diagnostic model for PTSD based on 17 DEmRNAs, which was validated in two independent datasets, GSE109409 and GSE63878.Conclusion: Our data provides a new molecular aspect that ECM-receptor interaction and the platelet activation process could be the potential molecular mechanism of PTSD, and the genes involved in this process may be promising therapeutic targets. A higher-performance diagnostic model for PTSD has also been identified.Keywords: differentially expressed genes, post-traumatic stress disorder, TCGA, prognosis, drug-gene interaction database

Chunting Liang &ast;, Tongtong Huang &ast;, Xiaofeng Zhang, Huaqing Rao, Zhiru Jin, Xiaoxiong Pan, Jingtao Li, Yingying Mo, Yongzhi Cai, Ji Wu Department of Ultrasonic Medicine, The First Hospital Affiliated to Guangxi Medical University, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ji Wu, Department of Ultrasonic Medicine, The First Hospital Affiliated to Guangxi Medical University, Nanning, 530021, People’s Republic of China, Email gxnnwuji@126.comPurpose: To study the thrombolytic effect and safety of cRGD urokinase liposomes (cRGD-UK-LIP) in rats with acute pulmonary microthromboembolism (APMTE), and explore the application value of echocardiography (ECHO) in animal models.Patients and Methods: Ninety-six SD rats were randomized into 6 groups (16/group): normal control, sham operation, APMTE, normal saline (NS), free urokinase (UK), cRGD-UK-LIP. Four groups (APMTE, NS, UK, cRGD-UK-LIP) of rats were injected with autologous thrombus to induce APMTE. Samples were injected into 3 groups (NS, UK, cRGD-UK-LIP) of rats after modeling. Echocardiography was used to assess right ventricle (RV) function and morphology in rats. Six rats in each group were randomly selected and pulmonary artery pressure (PAP) of them was measured through ECHO-guided transthoracic puncture. Finally, the rats were killed and their tissues were taken for pathological examination.Results: Compared with normal control or sham operation group, rats in APMTE group had enlarged RV, decreased RV function, increased PAP, and lung tissue of them showed postthromboembolic appearance. There was no significant difference between NS group and APMTE group. RV morphology and function of rats in the UK group and cRGD-UK-LIP group were better and vessels with residual thrombus in these 2 groups were less than APMTE group, especially in the cRGD-UK-LIP group. In terms of PAP, only cRGD-UK-LIP group was significantly lower than APMTE group. No hyperemia, bleeding and swelling were observed in heart, liver and kidney of rats in each group.Conclusion: A rat model of APMTE was successfully established. cRGD-UK-LIP has better thrombolytic effect than free urokinase and it is safe. Echocardiography is not merely an important way to evaluate the morphology and function of RV, transthoracic puncture measurement under the guidance of it can be an effective way to monitor PAP in animal models.Keywords: cRGD urokinase liposomes, acute pulmonary microthromboembolism, targeted thrombolysis, right ventricle, echocardiography, pulmonary artery pressure

Jinchun Li,1 Shiwen Xia,1 Yong Liu,1 Shasha Zhang,2 Zhengjiang Jin3 1Department of Neonatology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430070, China; 2Department of Pharmacy, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430070, China; 3Department of Clinical Laboratory, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430070, ChinaCorrespondence: Shiwen Xia, Tel +86 027-65395034, Fax +86 027-87163133, Email shiwenxia66@163.com; Xshiwen745@outlook.comPurpose: To evaluate the microorganisms involved in neonatal septicemia and its antibiotic susceptibility pattern and to further investigate the factors associated with the length of intensive care unit (ICU) stay in neonatal septicemia.Patients and Methods: A total of 297 infants with septicemia at neonatal ICU (NICU), Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology from 2016 to 2020 were enrolled. Identification of bacterial species was done using the standard positive blood culture. Data included demographics, signs at time of septicemia, laboratory values, patient sources, complications, microbiologic characteristics, and the duration of ICU stay. Univariate and multivariate gamma regression analyses were applied to determine the variables associated with ICU stay.Results: The result demonstrated that the main causative pathogens of neonatal septicemia in our hospital were Gram-positive bacteria, among which Staphylococcus epidermidis (100 isolates, 47.17%) was the main conditional pathogens; Escherichia coli (27 isolates, 49.09%) was most frequently isolated among Gram-negative pathogens. Gram-positive bacteria had higher susceptibility to vancomycin, tigecycline and linezolid. Escherichia coli was susceptive to piperacillin (27/27, 100.00%), cefotetan (27/27, 100.00%), meropenem and imipenem (27/27, 100.00%). Streptococcus agalactiae (95% CI: 0.140– 0.539), for patients who were transferred from other hospital (95% CI: 0.016 to 0.354), septicemia during hospitalization (95% CI: 0.411 to 0.825), the use of antibacterial drug during pregnancy (95% CI: 0.362 to 2.136), feeding intolerance (95% CI: 0.127 to 0.437), bradycardia (95% CI: 0.196 to 0.838), septicemia newborns have complications (95% CI: 0.063 to 0.291), the onset age (95% CI: 0.006 to 0.023), TRIPS score (95% CI: 0.005 to 0.016), and CRP level (95% CI: 0.002 to 0.005) were related to prolonged ICU stay days.Conclusion: This study summarized common pathogens and associated drug sensitivity, and factors influencing ICU stay length. Prevention and control policy in the NICU should be strengthened.Keywords: NICU, neonatal septicemia, microorganisms, antibiotic susceptibility

Yucheng Fu, Guoyu He, Zhuochao Liu, Jun Wang, Zhusheng Zhang, Qiyuan Bao, Junxiang Wen, Zhijian Jin, Weibin Zhang Department of Orthopedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, People’s Republic of ChinaCorrespondence: Weibin ZhangDepartment of Orthopedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, People’s Republic of ChinaTel +86-21-64370045, Ext 666983Fax +86-21-54660217Email zhangweibin10368@163.comBackground: Inflammatory response took part in the progression of tumor and was regarded as the hallmark of cancer. However, the prognostic relationship between osteosarcoma and inflammatory response-associated genes (IRGs) was unclear. This research aimed to explore the correlations between osteosarcoma prognosis and IRG signature.Methods: The inflammatory response-associated differentially expressed messenger RNAs (DEmRNAs) were screened out through Gene Expression Omnibus (GEO) and Molecular Signature Database (MSigDB) databases. Univariate and multivariate cox regression analyses were utilized to construct the IRG signature. The prognostic value of signature was investigated through Kaplan–Meier (KM) survival curve and nomogram. DEmRNAs among high and low inflammatory response-associated risks were identified and functional enrichment analyses were conducted. ESTIMATE, CIBERSORT and single-sample gene set enrichment analyses (ssGSEA) were implied to reveal the alterations in immune infiltration. All the above results were validated in Target database. The expression of IRGs was also validated in different cell lines by quantitative real-time PCR (qRT-PCR) and osteosarcoma patient samples by immunohistochemistry.Results: The IRG signature that consisted of two genes (MYC, CLEC5A) was established. In training and validation datasets, patients with lower risk scores survived longer and the IRG signature was confirmed as the independent prognostic factor in osteosarcoma. The nomogram was constructed and the calibration curves demonstrated the reliability of this model. Functional analysis of risk score-associated DEmRNAs indicated that immune-related pathways and functions were significantly enriched. ssGSEA revealed that 14 immune cells and 11 immune functions were significantly dysregulated. The qRT-PCR results indicated IRGs were significantly differently expressed in osteosarcoma and osteoblast cell lines. The immunohistochemistry analyses of patients’ samples revealed the same result.Conclusion: The novel osteosarcoma inflammatory response-associated prognostic signature was established and validated in this study. This model could serve as the biomarker and therapeutic target for osteosarcoma in the future.Keywords: osteosarcoma, inflammatory response, metastasis, prognosis, immune

Weimin Luan,1,2,&ast; Xiqian Qi,3,&ast; Feng Liang,2 Xiaotao Zhang,2 Ziyang Jin,2 Ligen Shi,2 Benyan Luo,1 Xuejiao Dai1 1Department of Neurology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Neurology, Ningbo Municipal Hospital of T.C.M., Ningbo, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuejiao Dai; Benyan LuoDepartment of Neurology, First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang, 312000, People’s Republic of ChinaTel/Fax +86-571-87235101Email x.dai@zju.edu.cn; luobenyan@zju.edu.cnPurpose: Age-related increase in myelin loss may be responsible for brain atrophy, and the mechanism is not completely understood. We aim to comprehensively delineate oligodendrocyte heterogeneity in young and aged mice and to reveal the underlying mechanism for myelin loss during aging.Methods: Diffusion tensor imaging and immunofluorescent staining were performed to verify the demyelination in the aged brains of both rodents and human. Further, the single-cell RNA sequencing data of all brain cells from young and aged mice were deeply analyzed to identify the subsets of oligodendrocyte lineage cells. Cell-to-cell interaction analysis was performed to detect the mechanism of observed changes in oligodendrocyte generation.Results: Oligodendrocytes were observed to up-regulate several senescence associated genes in aged brain. Four clusters of oligodendrocyte precursor cells (OPCs) were identified in both young and aged brains. The number of those OPCs in basal state was significantly increased, while the OPCs in the procedure of differentiation were immensely decreased in aged brain. Furthermore, it was identified that activated microglia in the aged brain released inflammatory factors to suppress OPC differentiation. Stat1 might be a potential target to transform senescent microglia into tissue repair type to promote oligodendrocyte generation.Conclusion: These results provided a perspective on how age activated microglia could impede remyelination and might give a new therapeutic target for age-related remyelinating diseases.Keywords: remyelination, oligodendrocyte precursor cells, microglia, oligodendrocytes, single cell RNA sequencing

Shaohua Chen,1,2 Ziyao Jin,3 Linfeng Xin,4 Lv Lv,2 Xuemei Zhang,3 Yizhen Gong,5 Jianlun Liu1 1Department of Breast Surgery, Guangxi Medical University Cancer Hospital, Nangning, People’s Republic of China; 2Department of Breast and Thyroid Surgery, Affiliated Hospital of Guilin Medical University, Guilin, People’s Republic of China; 3Department of Pathology, Affiliated Hospital of Guilin Medical University, Guilin, People’s Republic of China; 4Clinical Medicine, Guilin Medical University, Guilin, People’s Republic of China; 5Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nangning, People’s Republic of ChinaCorrespondence: Jianlun Liu Email 631228181@qq.comObjective: We aimed to investigate the expression, diagnostic and prognostic values, and potential molecular mechanisms of the origin recognition complex (ORC) in breast cancer (BC).Methods: Kaplan–Meier estimation was used to assess the prognostic value of ORC genes, and Oncomine, TCGA, GEO and ULCAN databases were used to analyze their expression in BC. Wilcoxon rank-sum tests were used to evaluate the relationship between ORC gene expression levels and BC clinicopathological features. Receiver operating characteristic (ROC) curves were used to assess the diagnostic value of ORC genes in BC. Survival analysis was performed using Kaplan–Meier estimation and Cox regression. A nomogram was constructed to predict 1-, 3-, and 5-year survival probabilities in BC. Gene set enrichment analysis (GSEA) and immune infiltration were used to investigate potential molecular mechanisms of the ORC.Results: ORC1L and ORC6L were highly expressed in BC compared with healthy tissue, while ORC5L expression patterns were inconsistent; no significant differences in ORC2L, ORC3L or ORC4L expression were observed between BC and healthy tissues. ORC1L and ORC6L expression levels were significantly correlated with age, tumor (T) stage and molecular subtype; ORC5L expression was significantly correlated with age and number of nearby lymph nodes with cancer (N stage). ORC6L expression had the highest diagnostic value in BC and was an independent prognostic factor for poor overall survival (OS). ORC6L may be involved in cell cycle progression and may regulate cancer signaling pathways, including NF-κB, P53, and WNT, in BC. ORC6L expression was also associated with immune infiltration.Conclusion: ORC1L and ORC6L are highly expressed in BC; ORC6L has a high diagnostic value and is an independent prognostic factor for poor OS. ORC6L may be involved in the initiation and progression of BC by regulating cell cycle progression, promoting cancer signaling pathway activation, and influencing tumor immune cell infiltration.Keywords: origin recognition complex, breast cancer, prognostic biomarker, nomogram, gene set enrichment analysis, immune infiltration

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

Yu Zhang,1,2,&ast; Xin Zhang,3,&ast; Zhuoyi Jin,2 Huiyan Chen,4 Chenjing Zhang,2 wangyue Wang,2 Jiyong Jing,5 Wensheng Pan1,2 1Department of Clinical Medicine, Medical College of Soochow University, Suzhou, 215006, People’s Republic of China; 2Department of Gastroenterology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, People’s Republic of China; 3Department of Pathology, Laboratory Medicine Center, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, People’s Republic of China; 4School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, People’s Republic of China; 5Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wensheng PanDepartment of Gastroenterology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College; Institute of Gastrointestinal Diseases, Hangzhou Medical College; Zhejiang Provincial Engineering Laboratory of Diagnosis, Treatment and Pharmaceutical Development of Gastrointestinal Tract Tumors, No. 158 Shangtang Road, Hangzhou, 310014, People’s Republic of ChinaTel/Fax +86 57685893430Email wspan223@163.comJiyong JingZhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, No. 158 Shangtang Road, Hangzhou, 310014, People’s Republic of ChinaEmail jiyong_jing@126.comPurpose: Colorectal cancer (CRC) can develop via a hypermutagenic pathway characterized by frequent somatic DNA base-pair mutations. Alternatively, the immunogenicity of tumor cells themselves may influence the anticancer activity of the immune effector cells. Impaired DNA repair mechanisms drive mutagenicity, which then increase the neoantigen load and immunogenicity. However, no studies have analyzed immune checkpoint protein expression, particularly programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1), in adenoma–carcinoma progression and its relationship with the emergence of other DNA repair gene mutation.Materials and Methods: We investigated mutations of 10 genes involved in DNA repair function: XRCC1, TP53, MLH1, MSH, KRAS, GSTP, UMP, MTHF, DPYD, and ABCC2. We performed sequencing to determine mutations and immunohistochemistry of immune checkpoints in clinical samples and determined changes in XRCC1 expression during progression through the adenoma–carcinoma pathway. We further investigated the prognostic associations of gene XRCC1 according to the expression, mutational profile, and immune profile using The Cancer Genome Atlas-colon adenocarcinoma (TCGA-COAD) dataset.Results: From clinical samples, XRCC1 mutation demonstrated the strongest association with adenomas with a mutation frequency of 56.2% in adenomas and 34% in CRCs (p =0.016). XRCC1 was abnormally expressed and altered by mutations contributing to adenoma carcinogenesis. High expression of XRCC1, CD4, FOXP3, and PD-1/PD-L1 showed an overall upward trend with increased lesion severity (all p < 0.01). PD-1/PD-L1 expression and CD4+ intraepithelial lymphocytes (IELs) correlated with cytological dysplasia progression, specifically in patients with wild-type XRCC1 (all p < 0.01), whereas FOXP3 expression was independently associated with adenoma–carcinoma progression. From TCGA-COAD analysis, XRCC1 expression was associated with patients survival, tumor-infiltrating lymphocytes and immune marker expression.Conclusion: Increased IEL density and PD-1/PD-L1 expression correlate with cytological dysplasia progression and specifically with the XRCC1 mutation status in CRC. Our findings support a stepwise dysplasia-carcinoma sequence of adenoma carcinogenesis and an XRCC1 hypermutated phenotypic mechanism of lesions.Keywords: adenoma–carcinoma, immune environment, PD-1/PD-L1, tumor-infiltrating lymphocytes, XRCC1

Jing Han,&ast; Ruofei Jia,&ast; Chengzhi Yang,&ast; Zening Jin Department of Cardiology and Macrovascular Disease, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zening JinDepartment of Cardiology and Macrovascular Disease, Beijing Tiantan Hospital, No. 119 South Fourth Ring West Road, Beijing, 100070, People’s Republic of ChinaEmail jin_zening@ccmu.edu.cnAim: The coronavirus (COVID-19) outbreak in 2019 has negatively impacted the care of patients with other life-threatening diseases, including acute myocardial infarction (AMI). However, there is little published information concerning the depth of the impact on the clinical management and outcome following AMI.Methods: We enrolled patients with AMI who received urgent primary percutaneous coronary intervention at the Beijing Tiantan Hospital (Beijing, China) between December 1, 2019 and April 10, 2020. Patients were divided into 2 cohorts, the pre-COVID-19 group (from December 1, 2019 to January 31, 2020) and during-COVID-19 group (from February 1, 2020 to April 10, 2020) for analysis. The door-to-balloon (D to B) time, total hospitalization stay (days) and coronary care unit (CCU) hospitalization days were calculated. New York Heart Association heart functional class (NYHA class), re-hospitalization and death ratio in patients were assessed between the two cohorts.Results: A total of 148 AMI patients were enrolled in this study comprising 53 patients pre-COVID-19 group and 95 patients during-COVID-19 group. Patients with AMI during-COVID-19 group had longer symptom onset to hospital time (4.5 [2.0– 9.3] vs 3.0 [2.0– 5.0] hours, p = 0.013) and D to B time (96 [74– 119] vs 67 [52– 81] minutes, p < 0.001); the D to B time shortened during the study period. The two cohorts did not have significantly different number of hospitalization days, re-hospitalization rates, peak cTnI, BNP or death rates. For the one-year follow-up, the patients in the during-COVID-19 group were classified as NYHA class III–IV more frequently (9 [9.7%] vs 0 [0%], p=0.004).Conclusion: The COVID-19 pandemic significantly affected one measure of critical care of patients with AMI, NYHA classification, which may have resulted in increased medical expenses.Keywords: acute myocardial infarction, COVID-19 pandemic, in-hospital outcome, New York Heart Association heart functional class

Mou-chun Gong,&ast; Wei-qing Chen,&ast; Zhao-qing Jin, Jia Lyu, Li-hao Meng, Hai-yan wu, Fei-hua Chen Department of General Surgery, First People’s Hospital of Hangzhou Lin’an District, Hangzhou, Zhejiang, 311300, People’s Republic of China&ast;These authors contributed equally to this work.Correspondence: Fei-hua ChenDepartment of General Surgery, First People’s Hospital of Hangzhou Lin’an District, 548 Yijin Road, Street Jincheng, Hangzhou, Zhejiang, 311300, People’s Republic of ChinaEmail 13396510518@189.cnBackground: Topoisomerase 2-alpha (TOP2A) has been identified as a hub gene that played an important role in the initiation and progression of thyroid carcinoma (THCA). However, the exact function of TOP2A in papillary thyroid cancer (PTC) remained elusive. The current study aimed to evaluate the TOP2A expression, prognosis significance and key signaling pathways involved in PTC.Methods: We firstly evaluated the expression of TOP2A in PTC via UALCAN, cBioportal, HPA and LinkdedOmics databases. Genetic alteration of TOP2A in PTC was then explored in cBioportal. Prognostic impacts of TOP2A expression on disease-free survival (DFS) of PTC patients were subsequently evaluated using Kaplan–Meier plotter and Gepia databases. Taking gender, age, cancer stage, T, N and M stages into consideration, we compared survival difference between TOP2A high and low expression groups. KEGG pathway analysis in WebGestalt and GSEA analysis were further performed to reveal the potential TOP2A-associated signaling pathways involved in PTC. Finally, the upstream microRNAs of TOP2A were assessed using DIANA, TargetScan, miRDB and miRWALK database, followed by mechanism exploration of upstream microRNAs.Results: 1) The mRNA and protein of TOP2A were highly expressed in PTC tissue compared with normal thyroid tissue. TOP2A expression was associated with patient’s age, N stage and cancer stage (all P< 0.05). TOP2A protein was mainly localized to nucleoplasm. 2) Most of samples occurred the missense substitution, and mutation site was located at K1199E. Nucleotide mutations were mainly presented as G>A (35.29%). 3) TOP2A high expression significantly influenced the DFS of PTC patients (P=0.015). Restricted survival analysis showed that TOP2A high expression caused poorer DFS of female patients (P=0.003) and those with age < 60 years old (P=0.002), early clinical stage (P=0.012), N0 stage (P=0.002) or M0 stage (P=0.040). 4) Pathway analysis suggested that TOP2A positively participated in the cell cycle, oocyte meiosis and p53 signaling pathways (all P< 0.05) involved in thyroid cancer.Conclusion: The expression of TOP2A was higher in PTC tissue, which resulted in a worse DFS of patients with PTC. TOP2A might act as an effective therapeutic target for PTC treatment.Keywords: TOP2A, high expression, poor prognosis, pathway

Cong Zhou,1 Qiang Wu,1 Leqi He,1 Hui Zhang,1 Maosuo Xu,1 Baoyu Yuan,2 Zhi Jin,3 Fang Shen1 1Department of Clinical Laboratory Medicine, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Clinical Laboratory, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Department of Neurology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Fang ShenDepartment of Clinical Laboratory Medicine, Shanghai Fifth People’s Hospital, Fudan University, No. 128, Ruili Road, Minhang District, Shanghai, 200240, People’s Republic of ChinaTel +86 18021073261Email shenfang5th@aliyun.comBackground: The convergence of carbapenem-resistance and hypervirulence in Klebsiella pneumoniae has led to a significant public health challenge. In recent years, there have been more and more reports on carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) isolates.Materials and Methods: Clinical data of patients infected with CR-hvKP from January 2019 to December 2020 in a tertiary hospital were retrospectively evaluated. The number of isolates of Klebsiella pneumoniae, hypermucoviscous Klebsiella pneumoniae (hmKP), carbapenem-resistant hypermucoviscous Klebsiella pneumoniae (CR-hmKP) and carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) collected during the period of 2 years was calculated. The antimicrobial resistance gene, virulence-associated gene, capsular serotype gene and multilocus sequence typing (MLST) of CR-hvKP isolates were detected by PCR.Results: During the study period, a total of 1081 isolates of non-repeat Klebsiella pneumoniae were isolated, including 392 isolates of hypermucoviscous Klebsiella pneumoniae (36.3%), 39 isolates of CR-hmKP (3.6%), and 16 isolates of CR-hvKP (1.5%). About 31.2% (5/16) of CR-hvKP were isolated from 2019, and 68.8% (11/16) of CR-hvKP were isolated from 2020. Among the 16 isolates of CR-hvKP, 13 isolates were ST11 and serotype K64, 1 isolate was ST11 and serotype K47, 1 isolate was ST23 and serotype K1, and 1 isolate was ST86 and serotype K2. The virulence-associated genes entB, fimH, rmpA2, iutA, iucA were present in all of 16 CR-hvKP isolates, followed by mrkD (n=14), rmpA (n=13), aerobactin (n=2), allS (n=1). Sixteen CR-hvKP isolates all carry carbapenemase gene blaKPC-2 and extended-spectrum β-lactamase gene blaSHV. ERIC-PCR DNA fingerprinting results showed that 16 CR-hvKP isolates were highly polymorphic, and there were significant differences in bands among the isolates, presenting a sporadic state.Conclusion: Although CR-hvKP was sporadically distributed, it showed an increasing trend year by year. Therefore, clinical attention should be paid, and necessary measures should be taken to avoid the cloning and transmission of superbacterium CR-hvKP.Keywords: Klebsiella pneumoniae, carbapenem-resistant, hypervirulent, hypermucoviscous, epidemiology

Yang Hu,1 Peng Guo,1 Teng-Hong Lian,1 Li-Jun Zuo,1 Shu-Yang Yu,1 Li Liu,2 Zhao Jin,1 Qiu-Jin Yu,1 Rui-Dan Wang,1 Li-Xia Li,2 Ying-Shan Piao,3 Wei Zhang3– 7 1Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 2Department of Internal Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 3Center for Cognitive Neurology, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 4China National Clinical Research Center for Neurological Diseases, Beijing, 100070, People’s Republic of China; 5Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing, 100069, People’s Republic of China; 6Center of Parkinson’s Disease, Beijing Institute for Brain Disorders, Beijing, 100053, People’s Republic of China; 7Beijing Key Laboratory on Parkinson’s Disease, Beijing, 100053, People’s Republic of ChinaCorrespondence: Wei ZhangCenter for Cognitive Neurology, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of ChinaTel +8613911996107Fax +86-10-59978429Email ttyyzw@163.comBackground: To investigate the clinical characteristics, iron metabolism and neuroinflammation in Parkinson’s disease (PD) patients with excessive daytime sleepiness (EDS).Methods: We studied 379 patients with PD and 30 age-matched controls. All subjects were evaluated by Epworth sleepiness scale (ESS) and a series of rating scales and were divided into PD-EDS and PD-NEDS groups according to ESS score. The concentrations of iron and iron-related proteins and inflammatory cytokines in both cerebrospinal fluid (CSF) and serum were examined.Results: 1. The occurrence rate of EDS in total PD patients was 16.09%. 2. PD-EDS group had significantly severer disease stages, more severe motor and non-motor features of the disease. 3. In CSF, the concentrations of iron and IL-1β in the PD-EDS group were significantly higher and ferritin concentration was prominently lower when compared with the PD-NEDS group and the control group; ESS score was significantly associated with high concentrations of iron and IL-1β and low concentration of ferritin in the PD group. Iron concentration was positively correlated with IL-1β concentration in the PD-EDS group. 4. In serum, no changes were observed in iron and iron-related proteins and inflammatory cytokines among the three groups.Conclusion: EDS was a common symptom in PD patients. PD patients with EDS had more severe motor and some non-motor symptoms. Overloaded iron-relevant inflammation in the brain might be an underlying mechanism of PD-EDS.Keywords: Parkinson disease, excessive daytime sleepiness, clinical features, iron metabolism, inflammation

Zhexiu Jin,1 Xue Yi,2 Jingjing Yang,1 Meili Zhou,1 Peifu Wu,1 Gen Yan3 1Department of Cardiovascular Medicine, The Second Affiliated Hospital of Xiamen Medical College, Xiamen, Fujian Province, 361023, People’s Republic of China; 2Department of Basic Medicine, Xiamen Medical College, Xiamen, Fujian Province, 361023, People’s Republic of China; 3Department of Radiology, The Second Affiliated Hospital of Xiamen Medical College, Xiamen, Fujian Province, 361023, People’s Republic of ChinaCorrespondence: Gen YanDepartment of Radiology, The Second Affiliated Hospital of Xiamen Medical College, Xiamen, Fujian Province, 361023, People’s Republic of ChinaTel +86 592 627 6910Email gyan@stu.edu.cnPurpose: A liposome-coated arsenic–manganese complex, denoted as LP@MnAsx was constructed for the targeted delivery of arsenic trioxide (ATO) against carcinoma.Methods: Arsenite, the prodrug of ATO, was encapsulated within a liposome via electrostatic interaction with the manganese ions. The as-prepared material was characterized with dynamic light scattering and transmission electron microscopy. The entrapment efficiency and drug loading of arsenic in the carrier were measured using inductively coupled plasma spectrometry. The in vitro release of arsenic was evaluated by using the dialysis bag method. Furthermore, the Fenton-like activity and in vitro cytodynamics research of LP@MnAsx were monitored in this work. And the cellular uptake study was used to investigate the in vitro entry mechanism. Furthermore, the cytotoxicity, cell apoptosis and cell cycle study were performed to evaluate the tumor-killing efficiency. Also, the pharmacokinetic and antitumor studies were investigated in HepG2 tumor-bearing nude mice.Results: The as-prepared LP@MnAsx possessed a spherical morphology, uniformly distributed hydrodynamic diameter, and excellent drug-loading efficiency. LP@MnAsx displayed robust stability and sustained-release profile under physiological environments. LP@MnAsx could degrade with high sensitivity to the pH variation in the tumor microenvironment. As such, this could lead to a burst release profile of Mn2+ and arsenite to achieve a synergistic therapy of chemodynamic therapy and chemotherapy. When compared to the carrier-free arsenate, in vitro experiments revealed that LP@MnAsx exhibited enhanced cellular uptake and tumor-killing efficiency. LP@MnAsx also demonstrated significantly enhanced tumor-specific in vivo distribution of arsenic, prolonged systemic circulation lifetime, and increased accumulation at the tumor site.Conclusion: Based on the experimental results, LP@MnAsx is an ideal arsenic-based nanodelivery system, whereby it can improve the non-specific distribution of NaAsO2 in vivo. Thus, this work can expand the research and application of arsenic trioxide against solid tumors.Keywords: arsenic–manganese complex liposome, arsenic trioxide, pH-sensitive, hepatocellular carcinoma

Rongli Cui,* Zhiqiang Song,* Baojun Suo, Xueli Tian, Yan Xue, Lingmei Meng, Zhanyue Niu, Zhu Jin, Hejun Zhang, Liya Zhou Department of Gastroenterology, Peking University Third Hospital, Beijing, 100191, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liya ZhouDepartment of Gastroenterology, Peking University Third Hospital, 49 Road Garden, Haidian District, Beijing, 100191, People’s Republic of ChinaTel +86-13911827827Fax +86-10-82265021Email zhouliya123456@163.comBackground: It has not been fully confirmed whether the detection of Helicobacter pylori resistance gene mutation can replace antibiotic drug sensitivity test to guide the clinical individualized treatment. Therefore, we have studied this aspect and discussed the application value of antibiotic sensitivity gene test.Materials and Methods: The biopsy specimen of gastric mucosa from the patients examined by endoscopy and positive for rapid urease test were collected continuously for histopathological analysis, H. pylori culture, antibiotic drug sensitivity test (E-test drug sensitivity test), and antibiotic sensitivity gene test (high-throughput nucleotide sequencing). The participants received triple plus bismuth solution eradication treatment (esomeprazole 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and bismuth potassium citrate 220 mg, twice daily for 14 days) for follow-up, and the eradication effect was determined.Results: The 551/602 subjects, who met the inclusion criteria, were subjected to culture for H. pylori and antibiotic drug sensitivity determination; among them 506 were cultured successfully. The results showed that the resistance rates of H. pylori were 38.9% for clarithromycin and 31.0% for levofloxacin. In 489 H. pylori strains, the mutations were detected in clarithromycin and levofloxacin resistance genes, indicating the genotype resistance. The resistance genes of clarithromycin and levofloxacin were consistent with phenotype resistance with respect to sensitivity (81.2% and 69.7% for clarithromycin and levofloxacin, respectively) and specificity (88.9% and 93.7% for clarithromycin and levofloxacin, respectively). The eradication rate of H. pylori in the clarithromycin-resistant group was significantly lower than that in the sensitive group (ITT: 52.1% vs 85.0%, P < 0.001).Conclusion: A correlation was established between the resistance genes of clarithromycin and levofloxacin and their phenotypic resistance and clinical efficacy. The detection of H. pylori resistance genes has a good clinical application prospect.Keywords: Helicobacter pylori, drug resistance, clarithromycin, levofloxacin, mutation, high-throughput nucleotide sequencing

Jinghai Gao,* Jianhong Dang,* Jing Chu,* Xiaojun Liu, Jing Wang, Jiahao You, Zhijun Jin Department of Obstetrics and Gynecology, Shanghai ChangZheng Hospital, Naval Medical University, Shanghai, 200003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaojun LiuDepartment of Obstetrics and Gynecology, Shanghai ChangZheng Hospital, Naval Medical University, No. 415 Fengyang Road, Huangpu District, Shanghai, 200003, People’s Republic of ChinaTel +8621-81885873Email liuxiaojun@smmu.edu.cnPurpose: To compare perioperative outcomes between robotic single-site surgical technique and conventional laparoendoscopic single-site surgical technique.Methods: This was a retrospective cohort study involving 67 patients who received robotic single-site surgery or laparoendoscopic single-site surgery for the treatment of stage IB1 cervical squamous carcinoma. The robotic single-site radical hysterectomy technique combined with pelvic lymph node dissections were performed in 32 patients while the laparoendoscopic single-site radical hysterectomy technique combined with pelvic lymph node dissections were performed in 35 patients.Results: The enrolled patients had been diagnosed with stage IB1 cervical squamous carcinoma. The perioperative outcomes were mean age (51.63± 8.32 years in the lymph node dissection (RSS group) and 53.14± 8.14 years in the lymph node dissection (LESS group), p=0.453); BMIs (23.76± 2.72 in the RSS group and 23.46± 2.28 in the LESS group, p=0.629); shorter operative times (223.56± 15.43 min in the RSS group and 248.61± 20.89 min in the LESS group, p< 0.01) and less estimated blood loss (217.25± 16.77 mL in the RSS group and 294.74± 24.00 mL in the LESS group, p< 0.01). None of the study participants exhibited postoperative pain. There were no statistically significant differences in the length of hospital stay (p=0.865), perioperative complications (p=0.602), duration of closure and removal of catheter (p=0.518) as well as in pathological diagnoses between the two groups.Conclusion: Robotic single-site surgery can be used in the treatment of early stage cervical cancer as it exhibits acceptable operative times and perioperative outcomes. This surgical technique is feasible and safe.Keywords: cervical squamous cancer, robotic single-site surgery, laparoendoscopic single-site surgery

Chengsheng Ding,1,* Zezhi Shan,2,3,* Mengcheng Li,1 Yang Xia,1 Zhiming Jin1 1Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China; 2Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 3Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yang Xia; Zhiming JinDepartment of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Yishan Road 600, Shanghai, People’s Republic of ChinaTel +86 15057728772; +86 18930177680Email xiayang9999@sina.cn; jzmgyp@hotmail.comBackground: Tumor mutation burden (TMB) is emerging as a new biomarker to monitor the response of cancer patients to immunotherapy. Long non-coding RNAs (lncRNAs) are critical in regulating gene expression and play a significant role in cancer-associated immune responses. However, the association between lncRNA expression patterns and TMB levels and survival outcomes remains unknown in colon cancer.Methods: In colon cancer patients from The Cancer Genome Atlas Program (TCGA), a multi-lncRNAs based classifier for predicting TMB levels was established using the least absolute shrinkage and selection operator (LASSO) method. The association between classifier index and immune-related characteristics of patients was also investigated. Quantitative polymerase chain reaction (qPCR) was used to verify the expression levels of these lncRNAs in normal and CRC cell lines.Results: The multi-lncRNAs based classifier had ability to predict TMB level of patients with accuracy (AUC= 0.70), and the general applicability of this classifier was proved in the validation set (AUC= 0.71) and the pooled set (AUC= 0.70). The classifier index was related to three immune checkpoints (PD1, PD-L1, and CTLA-4), the infiltration level of immune cells, and immune response-related score (IFN-γ score, gene expression profiles (GEP) score, cytolytic activity (CYT) score and MHC score). A nomogram, which integrates classifier and some common clinical information, was able to predict the overall survival of colon cancer patients accurately.Conclusion: LncRNA expression patterns are associated with TMB, which may serve as a classifier to predict the TMB in colon cancer patients. The nomogram could potentially evaluate survival outcomes and provide a reference to better manage colon cancer patients.Keywords: colon cancer, long non-coding RNA, tumor mutation burden, immunotherapy, prognosis

Yinbo Long, Heyang Li, Zhibin Jin, Xiang Zhang Department of Neurosurgery, Cangzhou Central Hospital, Cangzhou City, Hebei Province, 061000, People’s Republic of ChinaCorrespondence: Xiang ZhangDepartment of Neurosurgery, Cangzhou Central Hospital, Cangzhou City, Hebei Province, 061000, People’s Republic of ChinaEmail yb5052@163.comIntroduction: LncRNA SLC16A1-AS1 has been characterized as a critical player in lung cancer, while its role in glioblastoma (GBM) is unknown. By analyzing the TCGA dataset, we observed the upregulation of SLC16A1-AS1 expression in GBM. Therefore, we aimed to investigate the role of SLC16A1-AS1 in this cancer.Methods: GBM tissues and paired non-tumor tissues were collected from 62 GBM patients through biopsy. RT-qPCR was performed to determine the expression of SLC16A1-AS1 and miR-149. Linear regression was used to analyze their correlations. The relationship between SLC16A1-AS1 and miR-149 was assessed by gain and loss of function experiments. Methylation-specific PCR (MSP) and bisulfite sequencing PCR (BSP) were performed to analyze the methylation status of miR-149. Cell proliferation was evaluated by CCK-8 assay and colony formation experiments in GBM cells.Results: We found that SLC16A1-AS1 expression was upregulated in GBM tissues, and the upregulated expression of SLC16A1-AS1 predicted poor survival of GBM patients. MiR-149 was downregulated in GBM tissues and inversely correlated with the expression of SLC16A1-AS1. In GBM cells, overexpression of SLC16A1-AS1 downregulated the expression of miR-149 and increased the methylation of miR-149 gene. In cell proliferation and colony formation assay, overexpression of SLC16A1-AS1 reduced the inhibitory effects of miR-149 on GBM cell proliferation.Conclusion: SLC16A1-AS1 may promote GBM cell proliferation by regulating miR-149 methylation. SLC16A1-AS1 can be considered as a potential diagnostic marker in GBM.Keywords: GBM, SLC16A1-AS1, miR-149, methylation, proliferation

Nan Zhang,1,* Lingfang Zeng,2,* Shouyi Wang,3,* Ronghua Wang,4 Rui Yang,5 Zuolin Jin,6 Hong Tao1 1Department of Stomatology, The First Affiliated Hospital of Xi’an Jiaotong University, Xian, Shanxi, 710061, People’s Republic of China; 2Department of Pediatric Stomatology, Jinan Stomatological Hospital, Jinan, Shandong, 250000, People’s Republic of China; 3Department of Oral and Maxillofacial Surgery, Jinan Stomatological Hospital, Jinan, Shandong, 250000, People’s Republic of China; 4Department of Pediatrics, The First Affiliated Hospital of Xi’an Jiaotong University, Xian, Shanxi, 710061, People’s Republic of China; 5Department of Dental, Xi ‘an Tianrui Institute of Stomatology, Xian, Shanxi, 710061, People’s Republic of China; 6Department of Orthodontics, Oral Hospital of the Fourth Military Medical University, Xian, Shanxi, 710032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zuolin JinDepartment of Orthodontics, Oral Hospital of the Fourth Military Medical University, No. 145, Changle Weste Road, Xian, Shanxi, 710032, People’s Republic of ChinaEmail kn6119@163.comHong TaoDepartment of Stomatology, The First Affiliated Hospital of Xi’an Jiaotong University, No. 227, Yanta West Road, Xian, Shanxi, 710061, People’s Republic of ChinaEmail eu3027@163.comBackground: Oral squamous cell carcinoma (OSCC) is a common cancer especially young people in the world. The long non-coding RNA Fer-1-like protein 4 (FER1L4) has been reported to be closely associated with the progression of various human cancers. However, the role of FER1L4 in OSCC remains unclear.Methods: The expression level of FER1L4 in OSCC tissues and cancer cell lines was detected by using quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was evaluated by cell counting kit-8 (CCK-8) assay and EdU staining assay. Cell invasion and migration were evaluated by Transwell assay. Cell apoptosis was detected by flow cytometry. Luciferase reporter assay was performed to determine the targeting relationship between FER1L4, miR-133a-5p and Prx1. The protein expression of Prx1 was detected by Western blot. In addition, a xenograft tumor model in vivo was constructed to confirm the function of FER1L4.Results: FERIL4 was significantly upregulated in OSCC tissues and cancer cell lines. Moreover, high level of FER1L4 predicted a poor prognosis of OSCC patients. Silencing of FER1L4 not only significantly inhibited cell growth, invasion, migration and induced apoptosis in SCC-9 and HN4 cells in vitro, but also effectively suppressed the tumorigenesis of OSCC cells in vivo. Knockdown of FER1L4 significantly enhanced the expression of miR-133a-5p by sponging it, and then downregulated Prx1 expression.Conclusion: Our study elucidated a new mechanism of lncRNA FER1L4 that promoting OSCC progression by directly targeting miR-133a-5p/Prx1 axis and provided novel therapeutic targets for OSCC.Keywords: OSCC, lncRNA FER1L4, miR-133a-5p, Prx1, tumorigenesis

Jing Nan, Shuai Meng, Hongyu Hu, Ruofei Jia, Zening Jin Department of Cardiology and Macrovascular Disease, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Zening JinDepartment of Cardiology and Macrovascular Disease, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Fengtai District, Beijing 100070, People’s Republic of ChinaEmail Jin_zening@163.comIntroduction: The efficacy of fibrinolysis therapy with deferred percutaneous coronary angioplasty (FPCI) versus primary angioplasty (PPCI) during the coronavirus disease 2019 (COVID-19) pandemic is unclear when medical quarantine is needed.Patients and Methods: Acute ST segment elevation myocardial infarction (STEMI) patients underwent PPCI after finishing the screening protocol from January 23, 2020 to June 10, 2020 while FPCI was applied when COVID-19-confirmed cases reoccurred in Beijing near our hospital from June 11, 2020 to July 20, 2020. The door-to-balloon time (DTB) or door-to-needle time (DTN) as well as in-hospital adverse clinical outcomes were compared between the two groups. A propensity score-matched (PSM) analysis was performed to diminish the potential influence of confounding factors on the clinical outcomes.Results: A total of 126 STEMI patients underwent PPCI after finishing the screening protocol and 17 patients received FPCI before PSM. Patients who received FPCI were younger than patients who underwent PPCI (50.8± 14.0 versus 64.1± 14.2 years, p=0.001), and chronic kidney disease (CKD) was less common in FPCI patients than in patients who underwent PPCI (0% versus 24.6%, p=0.024). The DTN was significantly shorter than DTB (25.8± 4.2 versus 61.1± 10.7, p=0.000) before PSM. The DTN was significantly shorter than DTB (26.9± 4.2 versus 64.9± 23.6, p=0.000); however, the incidence rate of in-hospital ischemia and bleeding adverse clinical outcomes were comparable between the two groups after PSM.Conclusion: Fibrinolysis therapy combined with deferred PCI can reduce the ischemia time and has a similar in-hospital adverse clinical outcome rate compared with patients who underwent primary PCI during the COVID-19 pandemic.Keywords: ST elevation myocardial infarction, fibrinolysis therapy, percutaneous coronary intervention, coronavirus disease 2019, propensity score-matched analysis

Ziqi Jin,1,* Qiong Wu,1,* Shuohua Chen,2,* Jingli Gao,3 Xiaolan Li,3 Xuhui Zhang,4 Yaohan Zhou,1 Di He,1 Zongxue Cheng,1 Yimin Zhu,1,5,6 Shouling Wu7 1Department of Epidemiology & Biostatistics, School of Public Health, Zhejiang University, Hangzhou 310058, Zhejiang, People’s Republic of China; 2Health Care Center, Kailuan Group, Tangshan 063000, People’s Republic of China; 3Department of Intensive Medicine, Kailuan General Hospital, Tangshan 063000, People’s Republic of China; 4Hangzhou Center for Disease Control and Prevention, Hangzhou 310051, Zhejiang, People’s Republic of China; 5Department of Respiratory Diseases, Sir Run Run Shaw Hospital Affiliated to School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310060, People’s Republic of China; 6Department of Pathology, School of Medicine, Zhejiang University, Hangzhou 310058, Zhejiang, People’s Republic of China; 7Department of Cardiology, Kailuan General Hospital, Tangshan, 063000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shouling WuDepartment of Cardiology, Kailuan General Hospital, 57 Xinhua East Road, Tangshan, People’s Republic of ChinaEmail drwusl@163.comYimin ZhuDepartment of Epidemiology & Biostatistics, School of Public Health, Zhejiang University, 388 Yu-Hang-Tang Road, Hangzhou, 310058 Zhejiang, People’s Republic of ChinaTel + 0086-571-88208194Email zhuym@zju.edu.cnBackground: SII and SIRI are two novel systemic inflammation indexes that were suggested in predicting poor outcomes in cancers. However, no studies have examined their effect on cardiovascular diseases (CVDs) and all-cause mortality. Thus, this study aims to investigate associations between SII, SIRI, and the risks for CVDs and all-cause mortality.Methods: A total of 85,154 participants from the Kailuan cohort were included and followed up for incidents of CVDs (including MI, stroke) and all-cause death for 10 years. Multiple Cox regression was used to calculate the adjusted hazard ratios (HRs).Results: During the follow-up period, 4262 stroke events, 1233 MI events, and 7225 all-cause deaths were identified, respectively. Compared with the lowest quantile (Q1) of SII or SIRI, after adjusted for most cardiovascular risk factors, both indexes showed positive associations with the risk for stroke (adjusted HRs in Q4 were 1.264 (95% CI: 1.157,1.382) for SII, 1.194 (95% CI: 1.087,1.313) for SIRI), and all-cause death (adjusted HRs in Q4 were 1.246 (95% CI: 1.165,1.331) for SII, 1.393 (95% CI: 1.296,1.498) for SIRI). Additionally, higher SII and SIRI are also associated with increased risk of hemorrhagic stroke and ischemic stroke. Higher SIRI but not SII exhibited a higher MI risk, the adjusted HR in Q4 was 1.204 (1.013,1.431). The significant association remained after additional adjustment for CRP. Subgroup analysis and sensitivity analysis displayed consistent results except for SIRI with MI, where the association did not arrive at significance in subjects aged ≥ 60.Conclusion: Elevated SII and SIRI increased the risk of stroke, two stroke subtypes, and all-cause death. Higher SIRI, but not SII associated with increased MI incidence, and the association of SIRI was only significant in subjects aged < 60.Keywords: systemic inflammation, prospective study, risk factors, cardiovascular events, mortality

Zhaosheng Jin,1 Tong J Gan,1 Sergio D Bergese1,2 1Department of Anesthesiology, Stony Brook University Health Science Center, Stony Brook, NY 11794-8480, USA; 2Department of Neurological Surgery, Stony Brook University Health Science Center, Stony Brook, NY 11794-8480, USACorrespondence: Sergio D BergeseStony Brook University Health Science Center, Stony Brook, NY 11794-8480, USATel +1 631-444-2975Email Sergio.Bergese@stonybrookmedicine.eduAbstract: Postoperative nausea and vomiting is one of the most frequent adverse events after surgery and anesthesia. It is distressing for the patient and can lead to other postoperative complications. Management of PONV involves a framework of risk assessment, multimodal risk reduction, and prophylactic measures, as well as prompt rescue treatment. There has been a significant paradigm shift in the approach towards PONV prevention. There have also been several emerging therapeutic options for PONV prophylaxis and treatment. In this review, we will discuss the up-to-date PONV management guidelines and highlight novel therapeutic options which have emerged in the last few years.Keywords: antiemetics, enhanced recovery after surgery, postoperative care, postoperative nausea and vomiting

Jing Nan,1,* Shuai Meng,1,* Hongyu Hu,1,* Ruofei Jia,1 Ce Chen,2 Jianjun Peng,2 Zening Jin1 1Department of Cardiology and Macrovascular Disease, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Cardiology, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianjun PengDepartment of Cardiology, Beijing Shijitan Hospital, Capital Medical University, No. 4 Tieyi Road, Haidian Distict, Beijing 100038, People’s Republic of ChinaTel +86 18811332608Email pjj1972@sina.comZening JinDepartment of Cardiology and Macrovascular Disease, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Fengtai District, Beijing 100070, People’s Republic of ChinaTel +86 15652966904Email jin_zening@ccmu.edu.cnBackground: The clinical value of monocyte count to high-density lipoprotein cholesterol ratio (MHR) in in-stent restenosis (ISR) of patients who have undergone bare metal stent implantation has been studied. However, the predictive value of MHR in ISR for patients who have undergone drug-eluting stent (DES) implantation has not been explored.Methods: Non-ST segment elevation acute coronary syndrome (NSTE-ACS) patients who had undergone DES implantation and coronary angiography follow-up at the Beijing Shijitan Hospital, Capital Medical University, between January 1, 2008, and December 31, 2018, were retrospectively enrolled. Patients were divided into ISR and non-ISR groups depending on the follow-up coronary angiography results. Relative clinical information was recorded and analyzed. The receiver operating characteristic curve analysis was used to determine the optimum cut-off pre-procedural MHR to predict ISR.Results: A total of 214 patients were enrolled in our study. The mean period between two coronary angiography procedures was 25.4± 9.8 months. Percutaneous coronary intervention due to NSTE myocardial infarction, a bifurcation lesion, increased platelet count, and a high MHR were the independent risk factors in multivariate logistic regression analyses.Conclusion: Our results indicated that elevated MHR is an independent and useful predictor of ISR in NSTE-ACS patients who have undergone DES implantation.Keywords: monocyte count to high-density lipoprotein cholesterol ratio, in-stent restenosis, drug-eluting stent

Zuo Tao,* Huandan Suo,* Lei Zhang, Zining Jin, Zhen Wang, Danyu Wang, Ming Wu, Nanxi Peng, Yujie Zhao, Bo Chen Department of Breast Surgery, The First Hospital of China Medical University, Shenyang, Liaoning Province 110001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zuo Tao; Bo ChenDepartment of Breast Surgery, The First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang, Liaoning Province 110001, People’s Republic of ChinaEmail bochen@cmu.edu.cn; taozuocmu@163.comObjective: To study the expression of MRPL13 in breast cancer tissues using TCGA database, analyze the correlation between the expression and clinicopathological characteristics of patients, and explore the role of MRPL13 in the development of breast cancer (BC).Methods: The BC mRNA data and clinical information were downloaded from TCGA database. The correlation between MRPL13 expression and clinicopathological parameters was analyzed. Cox regression multivariate analysis was used to explore the factors affecting the prognosis of BC patients. The UALCAN database was used to analyze the expression level of MRPL13 in BC and its relationship with clinical pathological factors. The GSEA method was used to predict the possible regulatory pathways of MRPL13. Immune responses of MRPL13 expression were analyzed using TISIDB and CIBERSORT. Additionally, GEPIA, K-M survival analysis and data from the HPA were used to validate the outcomes.Results: The expression of MRPL13 in BC tissues was significantly higher than normal counterparts, patients with low MRPL13 expression had a better survival prognosis, also indicated an independent prognostic factor. GSEA analysis showed that the regulation of cell migration, positive regulation of endothelial cell migration, and Notch signaling pathway were enriched in tissues with low expression of MRPL13. Additionally, depleting MRPL13 expression inhibited invasion in MCF-10A and MCF-7 cells. Furthermore, PCR showed that MRPL13 affected VEGFA and MMP gene expression. CIBERSORT analysis revealed that the amount of NK cells decreased when MRPL13 expression was high.Conclusion: The expression of MRPL13 mRNA is upregulated in BC tissues, and the expression level of MRPL13 is significantly related to the clinicopathological factors of patients. High MRPL13 expression is a poor prognostic factor for BC, and it can be used as a molecular marker for prognosis judgment and as a potential therapeutic target.Keywords: cancer genome map, breast cancer, MRPL13, clinical significance

Zhenlin Huang,1,* Yinghui Ding,2,* Lu Zhang,3,* Siyuan He,1 Zhankui Jia,1 Chaohui Gu,1 Tao Wang,1 Hao Li,1 Xiang Li,1 Zhibo Jin,1 Yafei Ding,1 Jinjian Yang1 1Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 45000, People’s Republic of China; 2Department of Otology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 45000, People’s Republic of China; 3Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan 42000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jinjian YangDepartment of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, People’s Republic of ChinaTel +86 13903716991Email hzlinok@outlook.comBackground: Circular RNAs (circRNAs) are novel clusters of endogenous noncoding RNAs (ncRNAs) that are involved in the regulation of multiple biological processes in diverse types of cancers. However, the roles and precise mechanisms of circRNAs in renal cell carcinoma (RCC) occurrence and progression have not been clearly elucidated.Methods: We identified the aberrantly expressed circRNAs in RCC by high-throughput RNA-seq assay and used qRT-PCR to test the expression level of circRNAs in RCC tissues. Loss-of-function experiments were executed to detect the biological roles of circPDK1 in the RCC cells both in vivo and in vitro. RNA Fish, luciferase reporter assays and Western blotting were used to explore the molecular mechanism of circPDK1 function. All data were expressed as the means ± standard error of the mean (SEM). Student’s t-test, one-way ANOVA, Cox regression, an LSD-t-test, Pearson’s chi-squared test, a Log-rank test, and linear regression analyses were used to evaluate the group differences. P

Jiping Xie, Yi Wan, Min Zhang, Zeyu Jin, Yongqiang Yao Third Ward of Breast and Thyoid Surgery Department, Affiliated Zhongshan Hospital of Dalian University, Dalian City, Liaoning Province, People’s Republic of ChinaCorrespondence: Yongqiang YaoThird Ward of Breast and Thyoid Surgery Department, Affiliated Zhongshan Hospital of Dalian University, No. 6 Jiefang Street, Zhongshan District, Dalian 215004, Liaoning Province, People’s Republic of ChinaTel/Fax +86 0411-62897391Email yyq760225@163.comBackground: Breast cancer (BC) remains the most common malignancy among women. Circular RNAs (circRNAs) have been demonstrated to play important roles in human cancers, including BC. In this study, we sought to identify the precise parts of circ_0061825 (circRNA trefoil factor 1, circ_TFF1) in BC pathogenesis.Methods: The expression levels of circ_0061825, miR-593-3p and fibroblast growth factor receptor 3 (FGFR3) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot. Circ_0061825 was characterized using ribonuclease (RNase) R digestion, actinomycin D and subcellular fractionation assays. Cell viability, colony formation, migration, invasion, cell cycle progression and apoptosis were evaluated using Cell Counting Kit-8 (CCK-8), colony formation, wound-healing, transwell and flow cytometry assays, respectively. Targeted relationships among circ_0061825, miR-593-3p and FGFR3 were determined by a dual-luciferase reporter assay. Animal studies were used to assess the impact of circ_0061825 in tumor growth in vivo.Results: Our data indicated that circ_0061825 was overexpressed in BC tissues and cells, and it was mainly localized in the cytoplasm of BC cells. Circ_0061825 knockdown hampered BC cell viability, colony formation, migration, invasion, cell cycle progression and enhanced cell apoptosis in vitro and weakened tumor growth in vivo. Mechanistically, circ_0061825 functioned as a molecular sponge of miR-593-3p, and circ_0061825 knockdown repressed BC cell malignant progression in vitro by miR-593-3p. FGFR3 was a direct target of miR-593-3p, and circ_0061825 modulated FGFR3 expression through sponging miR-593-3p. Moreover, miR-593-3p overexpression hindered BC cell malignant progression in vitro by down-regulating FGFR3.Conclusion: Our current work provided evidence that circ_0061825, an up-regulated circRNA in BC, regulated BC malignant progression at least in part through targeting the miR-593-3p/FGFR3 axis, illuminating a novel therapeutic target for BC management.Keywords: breast cancer (BC), circ_0061825, miR-593-3p, FGFR3

Jie Situ,1,* Hao Zhang,1,* Zi Jin,2 Ke Li,1 Yunhua Mao,1 Wentao Huang1 1Department of Urology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Department of Hepatological Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wentao HuangDepartment of Urology, The Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou 510000, People’s Republic of ChinaEmail lucken_hwt@163.comPurpose: MicroRNA-939 (miR-939) has crucial roles in several types of human cancer. However, the expression profile and precise functions of miR-939 in prostate cancer (PCa) are still unclear. This study aimed to determine miR-939 expression in PCa and explore its roles in PCa tumorigenesis.Methods: miR-939 expression was determined in PCa tissues and cell lines using reverse transcription–quantitative polymerase chain reaction. Cell Counting Kit-8, colony formation, and flow cytometric assays were used to determine the role of miR-939 in PCa cell proliferation and apoptosis in vitro, whereas a tumor xenograft model was generated to evaluate the effect of miR-939 on tumor growth in vivo. Transwell assays were performed to investigate whether miR-939 affects the migration and invasiveness of PCa cells.Results: miR-939 was found to be downregulated in PCa tissues and cell lines, and this downregulation was significantly correlated with tumor stage and lymphatic metastasis. Patients with PCa exhibiting low miR-939 expression had shorter overall survival than those exhibiting high miR-939 expression. Exogenous miR-939 expression suppressed PCa cell proliferation, colony formation, migration, and invasion in vitro; enhanced apoptosis in vitro; and decreased tumor growth in vivo. Investigation of the underlying molecular mechanisms revealed hepatoma-derived growth factor (HDGF) as a direct target gene of miR-939 in PCa. HDGF was found to be significantly upregulated in PCa tissues, and its expression was inversely correlated with miR-939 expression. HDGF silencing and miR-939 upregulation showed similar effects in PCa. Restored HDGF expression counteracted the tumor-suppressive activity of miR-939 overexpression in PCa cells. Furthermore, ectopic miR-939 expression inhibited the WNT/β-catenin pathway activation in PCa both in vitro and in vivo by downregulating HDGF.Conclusion: miR-939 functions as a tumor suppressor during PCa tumorigenesis by directly targeting HDGF and deactivating the WNT/β-catenin pathway, suggesting the miR-939/HDGF/WNT/β-catenin pathway as an effective target for PCa therapy.Keywords: microRNA-939, prostate cancer, hepatoma-derived growth factor, WNT/β-catenin signaling

Xiaoyong Xu,1,* Feihong Song,2,* Xinwei Jiang,1,* Han Hong,1 Qiang Fei,1 Zhengkang Jin,1 Xiang Zhu,1 Binghua Dai,2 Jiamei Yang,2 Chengjun Sui,2 Minhui Xu1 1Department of Hepato-Pancreato-Biliary Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215001, People’s Republic of China; 2Department of Special Treatment and Liver Transplantation, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, People’s Republic of China*These authors contributed equally to this workCorrespondence: Minhui XuDepartment of Hepato-Pancreato-Biliary Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215001, People’s Republic of ChinaEmail xuminhui11@aliyun.comChengjun SuiDepartment of Special Treatment and Liver Transplantation, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, People’s Republic of ChinaEmail suichengjun1978@163.comBackground: Thousands of long non-coding RNAs (lncRNAs) have been functionally verified as crucial regulators of physiological processes and disease progressions, yet their roles in hepatocellular carcinoma (HCC) have not been clearly illuminated.Methods: We analyzed the expression of lncRNA-SNHG14 in TCGA data via bioinformatic analysis and detected its expression in HCC specimens by reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR). Loss-of-function experiments were used to study the biological function of SNHG14 in HCC cells. RT-qPCR, Western blotting and dual-luciferase reporter assay were carried out to investigate the molecular mechanism of SNHG14 in HCC.Results: The upregulation of lncRNA-SNHG14 was observed in HCC tissues compared with normal tissues via RT-qPCR and bioinformatic analysis of TCGA data. Silencing of SNHG14 inhibited cell proliferation and induced cell apoptosis in HCC cells. microRNA-217 (miR-217), the tumor-suppressive miRNA in HCC, was predicted and confirmed as a miRNA sponged by SNHG14 in HCC cells. Via downregulation of miR-217, SNHG14 increased the expression of several miR-217-related oncogenes and subsequently activated oncogene-related signaling pathways in HCC cells. In addition, inhibition of miR-217 reversed SNHG14 silencing induced decrease of cell proliferation and increase of cell apoptosis. Their association was verified in the published microarray dataset and the collected HCC samples.Conclusion: In summary, SNHG14 is involved in the development of HCC via sponging miR-217 and it may be a biomarker for patients with HCC.Keywords: SNHG14, hepatocellular carcinoma, miR-217