Search

Guoxia Zhou,1,2,&ast; Yuecheng Yang,1,2,&ast; Yunkui Zhang,1,2,&ast; Congxia Pan,1,2 Xing Wu,1,2 Jun Zhang1,2 1Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of Oncology, Fudan University Shanghai Medical College, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Zhang, Department of Anesthesiology, Fudan University Shanghai Cancer Center, No. 270, Dong-An Road, Shanghai, 200032, People’s Republic of China, Tel +86-021-64175590, Fax +86-021-64174774, Email snapzhang@aliyun.comObjective: To investigate the efficacy of ultrasound-guided interscalene brachial plexus block in the treatment of shoulder pain following hepatectomy.Design: A randomized controlled trial.Methods: We conducted a single-center, randomized controlled trial. Forty-four patients with shoulder pain scores of at least 5 were randomly assigned to two groups: the treatment group, which received 0.5% ropivacaine (5mL) combined with dexamethasone (5 mg) (n=22), and the control group, which received normal saline (5mL) (n=22). The intervention was performed in the postanesthesia care unit after shoulder pain was identified by using the visual analogue scale. The shoulder pain was re-evaluated 15 minutes after intervention. The incidence of effective pain relief, defined as at least 75% reduction in pain intensity, was the primary outcome. Secondary outcomes included shoulder pain intensity within 2 days after surgery, the timing of the first rescue analgesia, total additional analgesic use, arterial oxygen saturation, intervention-related adverse reactions, and patient satisfaction regarding shoulder pain.Results: The incidence of effective pain relief was significantly higher in the treatment group compared to the control group (15 (68.2%) vs 2 (9.1%), P< 0.001). The interscalene brachial plexus block not only prolonged the time to first analgesic request (P < 0.001), but also reduced the number of analgesic requests (P < 0.001). In the comparison between groups, arterial oxygen saturation was lower in the control group than that in the treatment group, attributed to the use of sufentanil for remedial analgesia (92.4% vs 94.5%, P=0.014).Conclusion: Interscalene brachial plexus block can effectively relieve post-hepatectomy shoulder pain without clinically significant hypoxemia.Keywords: interscalene brachial plexus block, hepatectomy, referred pain, phrenic nerve

Chi Pan,1,&ast; Yawen Gu,2,&ast; Qingtao Ni2 1Department of General Surgery, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, 225300, People’s Republic of China; 2Department of Oncology, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, 225300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingtao Ni, Department of Oncology, Jiangsu Taizhou People’s Hospital, Taihu Road 366, Taizhou, 225300, People’s Republic of China, Tel +8618852656280, Email niqingtao@njmu.edu.cnObjective: This study examined the potential risk value of the serum albumin to globulin ratio (AGR) in patients with breast cancer (BC).Methods: This study employed a retrospective design, enrolling 332 patients with BC and 38 patients without BC treated at Taizhou People’s Hospital between September 2015 and May 2021. Multivariate Cox proportional hazard regression models were used to identify potential risk factors. A prognostic nomogram was developed based on the multivariate analyses. The receiver operating characteristic curve determined the optimal cutoff value for AGR.Results: The results indicated a statistically significant decrease in AGR among patients with BC. Significant disparities were observed in globulin and AGR levels between the two cohorts. AGR was significantly associated with tumor size and stage, with a marked decline in advanced stages of BC. Additionally, AGR and aspartate transaminase/Alanine aminotransferase (AST/ALT) emerged as significant diagnostic indicators for invasive carcinoma and advanced stages (II–IV) of BC. Specifically, AGR exhibited an area under the curve of 0.645 (P < 0.003), highlighting the discriminatory capacity of serum globulin levels in distinguishing between BC and non-BC cohorts.Conclusions: The AGR, routinely assessed due to its simplicity, objectivity, and cost-effectiveness, holds promise as a potential risk factor for BC and may have practical implications in clinical settings.Keywords: albumin to globulin ratio, risk factor, breast cancer, retrospective study

Zhenzhu Wu,1 Jie Li,1 Peipei Fang,1 Chenwei Pan,1 Yi Chen2 1Department of Infectious Disease, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325000, People’s Republic of China; 2Department of Gastroenterology, Wenzhou People’s Hospital, Wenzhou, Zhejiang, 325000, People’s Republic of ChinaCorrespondence: Yi Chen; Zhenzhu Wu, Email alivefish1993@qq.com; 15003890524@163.comBackground: The prevalence of pyogenic liver abscess (PLA) is increasing worldwide. However, evaluation on its economic burden is still lack.Methods: A retrospective study that included all patients identified PLA from 2017 to 2020 was conducted. Clinical information and hospital costs were collected through the electronic medical records. We evaluated the economic burden using disability-adjusted life years (DALYs). Differences in socioeconomic burdens between Klebsiella pneumoniae-caused liver abscesses (KPLA) and non-Klebsiella pneumoniae-caused liver abscesses (non-KPLA) were compared.Results: We found 327 patients identified PLA in the study, including 146 with KPLA and 181 with non-KPLA. The demographic characteristics, median hospital stay, severity, and in-hospital mortality were similar between the two groups. The median total in-hospital cost was higher in the non-KPLA than in the KPLA group, although no statistical difference was found (&dollar;3607.2 vs &dollar;3424.6; P = 0.446). The median DALY loss was significantly higher in the KPLA than in the non-KPLA group [1.49 (0.97– 2.30) vs 1.27 (0.87– 1.89); P = 0.033)], and male patients presented a higher average DALY loss than female patients. KPLA had a substantially greater median indirect economic loss than the non-KPLA group [&dollar;1442.8 (915.9– 17,221.5) vs &dollar;1232.5 (764.6– 15,473.0); P = 0.028], and indirect economic loss exhibited a significant increase from 2017 to 2020 in patients with PLA. No differences were found in the socioeconomic burden between the two groups [&dollar;8019.6 (4200.3– 21,832.1) vs &dollar;7436.4 (4023.2– 19,063.9); P = 0.172].Conclusion: The economic burden of PLA is significant, particularly in patients with KP. Patients with KPLA experienced increased DALY loss and indirect economic loss than non-KPLA. PLA must be prioritized as the indirect economic burden rises annually.Keywords: pyogenic liver abscess, Klebsiella pneumoniae, socioeconomic burden, disability-adjusted life years

Mingxing Guo,1,&ast; Chen Pan,1,&ast; Ying Zhao,1 Wanyi Xu,1 Ye Xu,1 Dandan Li,1 Yichen Zhu,2 Xiangli Cui1 1Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangli Cui, Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China, Email xianglicui@ccmu.edu.cn Yichen Zhu, Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China, Email yczhu@ccmu.edu.cnBackground: The risk of transplant recipient infection is unknown when the preservation solution culture is positive.Methods: We developed a prediction model to evaluate the infection in kidney transplant recipients within microbial contaminated preservation solution. Univariate logistic regression was utilized to identify risk factors for infection. Both stepwise selection with Akaike information criterion (AIC) was used to identify variables for multivariate logistic regression. Selected variables were incorporated in the nomograms to predict the probability of infection for kidney transplant recipients with microbial contaminated preservation solution.Results: Age, preoperative creatinine, ESKAPE, PCT, hemofiltration, and sirolimus had a strongest association with infection risk, and a nomogram was established with an AUC value of 0.72 (95% confidence interval, 0.64– 0.80) and Brier index 0.20 (95% confidence interval, 0.18– 0.23). Finally, we found that when the infection probability was between 20% and 80%, the model oriented antibiotic strategy should have higher net benefits than the default strategy using decision curve analysis.Conclusion: Our study developed and validated a risk prediction model for evaluating the infection of microbial contaminated preservation solutions in kidney transplant recipients and demonstrated good net benefits when the total infection probability was between 20% and 80%.Keywords: risk prediction model, kidney transplant, nomogram, risk factors

Pengwen Ouyang,1 Zhijie Zhou,2 Chanyuan Pan,3 Peijuan Tang,1 Sheng Long,1 Xiangjian Liao,1 Qiong Liu,1 Liangyi Xie1 1Department of Clinical Laboratory, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, People’s Republic of China; 2Department of Respiratory Medicine, The Affiliated Zhuzhou Hospital of Xiangya School of Medicine, Central South University, Zhuzhou, People’s Republic of China; 3Department of Respiratory Medicine, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, People’s Republic of ChinaCorrespondence: Liangyi Xie, Email lyxie78@hunnu.edu.cnPurpose: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is closely related to respiratory tract infection. The aim of this study was to investigate the clinical features and prognostic factors of CRKP-induced pneumonia in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients.Methods: A single-centre, retrospective case-control study on COPD patients hospitalized for acute exacerbation and CRKP-induced pneumonia was conducted from January 1, 2016, to December 31, 2022. The mortality rate of acute exacerbation due to CRKP-induced pneumonia was investigated. The patients were divided into the CRKP-induced pneumonic acute exacerbation (CRKPpAE) group and the non-CRKP-induced pneumonic acute exacerbation (non-CRKPpAE) group, and the clinical characteristics and prognostic factors were compared using univariate analysis and multivariate analysis.Results: A total of 65 AECOPD patients were included, composed of 26 patients with CRKPpAE and 39 patients with non-CRKPpAE. The mortality rate of CRKPpAE was 57.69%, while non-CRKPpAE was 7.69%. Compared with non-CRKPpAE, a history of acute exacerbation in the last year (OR=8.860, 95% CI: 1.360– 57.722, p=0.023), ICU admission (OR=11.736, 95% CI: 2.112– 65.207, p=0.005), higher NLR levels (OR=1.187, 95% CI: 1.037– 1.359, p=0.013) and higher D-dimer levels (OR=1.385, 95% CI: 1.006– 1.905, p=0.046) were independently related with CRKPpAE. CRKP isolates were all MDR strains (26/26, 100%), and MDR strains were also observed in non-CRKP isolates (5/39, 12.82%).Conclusion: Compared with non-CRKPpAE, CRKPpAE affects the COPD patient’s condition more seriously and significantly increases the risk of death.Keywords: chronic obstructive pulmonary disease, acute exacerbation, carbapenem-resistant K. pneumoniae, pneumonia

Qiankun Luo,1,&ast; Yifei Dong,1,&ast; Pan Liu,1,&ast; Chao He,2 Lei Chen,1 Kailun Zhang,1 Changjie Pan,1 Yahui Gao,1 Tao Qin1 1Department of Hepatobiliary and Pancreatic Surgery, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, Henan, People’s Republic of China; 2Department of Hepatobiliary and Pancreatic Surgery, Henan University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Qin, Department of Hepatobiliary and Pancreatic Surgery, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, No. 7, Weiwu Road, Jinshui District, Zhengzhou, Henan, 450003, People’s Republic of China, Tel +86 13949116088, Email qtgoodfreecn@zzu.edu.cnIntroduction: Chemotherapy combined with immune checkpoint inhibitors (ChIM) is used to treat advanced pancreatic ductal adenocarcinoma (PDAC). However, the efficacy of ChIM is similar to that of chemotherapy alone.Methods: To assess potential factors affecting the effectiveness of ChIM, we analyzed the clinical data of 359 patients with PDAC who visited the hospital during June 2017 to December 2022.Results: Surgical resection, diabetes, and ChIM were risk factors for pancreatic exocrine insufficiency (PEI). The adjusted odds ratio of ChIM was 2.63 (95% confidence interval (CI) 1.492– 4.626) (P = 0.001). The incidence of PEI in the ChIM group (76.9%) was significantly higher than that of the chemotherapy group (60.2%) (P = 0.004). Survival analysis showed that ChIM did not improve the survival rate of patients with PDAC (hazard ratio (HR) 0.92, 0.707– 1.197) (P = 0.534) in comparison with that of the chemotherapy group. However, in patients without PEI, those receiving ChIM showed a higher 1-year overall survival (OS) rate of 70.8% (two-sided, P = 0.045) and a median OS of 22.0 months (95% CI 11.5– 32.5). Moreover, pancreatic enzyme replacement therapy significantly improved the OS of patients with PDAC (HR = 0.73, 95% CI = 0.561– 0.956) (P = 0.022).Conclusion: Immune checkpoint inhibitors (ICIs) increased the incidence of PEI in patients with PDAC. The OS was not different between patients receiving chemotherapy and ChIM due to irregular PERT treatment. The finding show that pancreatic enzyme replacement therapy may improve the response rate of patients with PDAC to ICIs.Keywords: pancreatic cancer, pancreatic exocrine insufficiency, immune checkpoint inhibitors, pancreatic enzyme replacement therapy

Chunran Pan,&ast; Wenjie Hou,&ast; Xiaofeng Deng, Jiawei Liu, Ruimin Chi, Xingru Shang, Tao Xu, Xiaoxia Hao Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoxia Hao, Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095&num;, Jie-Fang Avenue, Qiaokou District, Wuhan, 430030, People’s Republic of China, Tel +86 1-597-296-0593, Fax +86- 27-83662640, Email haoxiaoxia@hust.edu.cnAbstract: Intervertebral disc degeneration (IDD) is considered as a dominant contributor to low back pain (LBP), causing severe pain, limited range of lumbar motion, physical dysfunction, and restriction of social activity. However, the specific pathological mechanisms underlying IDD remain elusive, and effective strategies to delay the pathogenesis of IDD are still unclear and limited. In recent years, some studies have found that nuclear factor erythroid 2-related factor 2 (Nrf2), an important antioxidant transcription factor, may play crucial roles in the pathogenesis and progression of age-related diseases including IDD. Nrf2 can maintain redox homeostasis and protecting nucleus pulposus (NP) cells against oxidative stress, inflammatory response, extracellular matrix (ECM) catabolism, cell senescence and cell death involving in the progression of IDD. In this review, we aim to systematically describe the vital roles and pathological mechanism of Nrf2 signaling axis in the pathogenesis of IDD, which may put forward potential therapeutic strategies for the prevention and treatment of IDD by targeting Nrf2.Keywords: Nrf2, intervertebral disc degeneration, nucleus pulposus cells, oxidative stress

Nada Alsuhebany,1– 3 Congshan Pan,4 Eileen Holovac,5 Brian Do,6 Ali McBride7 1College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Kingdom of Saudi Arabia; 2King Abdulaziz Medical City, National Guard Health Affairs, Riyadh, Kingdom of Saudi Arabia; 3King Abdullah International Medical Research Center, Riyadh, Kingdom of Saudi Arabia; 4Department of Oncology Pharmacy, University of Arizona Cancer Center, Tucson, AZ, USA; 5Department of Oncology Pharmacy, VA Loma Linda Healthcare System, Loma Linda, CA, USA; 6Department of Oncology Pharmacy, Southern Arizona VA Hlth Care, Tucson, AZ, USA; 7WW HEOR Markets, Bristol-Myers Squibb, New York City, NY, USACorrespondence: Nada Alsuhebany, Department of Clinical Pharmacy, College of Pharmacy, King Saud Bin Abdulaziz University for Health Sciences, PO Box 3660, Riyadh, 11481, Kingdom of Saudi Arabia, Tel +966500828585, Email nalsuhebany@gmail.comPurpose: The pharmacology, pharmacokinetics, pharmacodynamics, clinical efficacy, and safety of zanbrutinib are described.Summary: Mantle cell lymphoma (MCL) is a mature B-cell lymphoma that is typically associated with unfavorable outcomes, and virtually all patients with MCL have refractory or relapsed disease despite aggressive treatment. The treatment paradigm for MCL has transformed dramatically over the past decade owing to rapid advancements in immunotherapy and molecular-targeted therapies. Zanubrutinib, a second-generation Bruton’s tyrosine kinase inhibitor (BTKI) designated for mature B-cell non-Hodgkin’s lymphoma (NHL), has drastically improved the survival outcomes in relapsed/refractory (R/R) MCL patients. This selective BTKI is a small molecule that functions by forming a covalent bond in the active site of BTK. The inhibition of BTK activity is essential for the signaling of B-cell antigen receptor (BCR) and cytokine receptor pathways. In a preclinical study, zanubrutinib inhibited malignant B-cell proliferation and reduced tumor growth. Zanubrutinib was granted FDA-accelerated approval based on the results of Phase I and II trials. The investigator-assessed overall response rate was 83.7%, of which 78% of patients achieved complete response. The median duration of response was 19.5 months, and the median progression-free survival was 22.1 months. The most common (≥ 20%) all-grade adverse events were low neutrophil count (46.5%), upper respiratory tract infection (38.4%), rash (36.0%), low white blood cell count (33.7%), and low platelet count (32.6%).Conclusion: Zanubrutinib is a selective, next-generation, orally active, irreversible BTK inhibitor. The selectivity of zanubrutinib and its superior efficacy, with a well-tolerated safety profile, have proven to be attractive options for other malignancies.Keywords: zanubrutinib, mantle cell lymphoma, Bruton’s tyrosine kinase inhibitor

Mingshuang Wu,&ast; Chenxi Pan,&ast; Yi He, Bo Yang Department of Urology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi He; Bo Yang, The Second Affiliated Hospital of Dalian Medical University, 467, Zhongshan Road, Shahekou District, Dalian, 116044, People’s Republic of China, Tel/Fax +86 411 84671291, Email heyi_gzr@163.com; yangbo20160101@163.comPurpose: The goal of this study was to assess the prognostic impact of the lower urinary tract symptoms (LUTS) in advanced prostate cancer (PCa) patients before progression to castration-resistant prostate cancer (CRPC).Methods: A retrospective analysis of the follow-up data for 152 CRPC patients was performed. Severe LUTS symptom was defined as an International Prostate Symptoms Score (IPSS) ≥ 20 at baseline. Cox regression analysis was conducted to assess CRPC prognostic factors. Nomogram model was created and assessed using the concordance index (C-index), calibration curves, receiver operating characteristic (ROC) curves, and decision curve analyses (DCA).Results: The median CRPC free survival of patients with severe LUTS was 20.5 months, significantly longer than that (7.5 months) of less symptomatic patients. Furthermore, severe LUTS, the hemoglobin, albumin, lymphocyte, and platelet (HALP) score, and Gleason sum were determined to be independent prognostic markers and combined to establish a nomogram, which performed well in the customized prediction of CRPC progression at 6th, 12th, 18th and 24th month. The C-index (0.794 and 0.816 for the training and validation cohorts, respectively), calibration curve, and ROC curve all validated the prediction accuracy. DCA curve showed that it could be effective in helping doctors make judgments. The Nomogram-related risk score separated the patients into two groups with notable progression differences.Conclusion: Severe LUTS was significantly associated with decreased risk for rapid progression to CRPC. The developed nomogram could help identify patients who are at a high risk of rapid CRPC progression and provide tailored follow-up and therapeutic advice.Keywords: LUTS, HALP, castration-resistant prostate cancer, nomogram

Mingshuang Wu,1 Yi He,1 Chenxi Pan2 1Department of Urology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 2Department of Breast Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of ChinaCorrespondence: Yi He; Chenxi Pan, The Second Affiliated Hospital of Dalian Medical University, 467, Zhongshan Road, Shahekou District, Dalian, 116044, People’s Republic of China, Tel/Fax +86 411 84671291, Email heyi_gzr@163.com; PCX980205@outlook.comPurpose: Serum lipids were reported to be the prognostic factors of various cancers, but their prognostic value in small cell lung cancer (SCLC) patients remains unclear. This study investigated the relationship between lipid profiles and clinical outcomes in extensive-stage (ES) SCLC by establishing a predictive risk classification model.Patients and Methods: We retrospectively analyzed the prognostic values of pretreatment serum lipids and their derivatives in patients with a confirmed diagnosis ES-SCLC. Independent factors of progression-free survival (PFS) were determined by univariate and multivariate cox analysis. Then, prognostic nomograms were established, of which predictive performance was evaluated by concordance index (C-index), calibration curves, receiver operating characteristic (ROC) curves, and decision curve analyses (DCA).Results: A total of 158 patients was included in this study. Four optimal PFS-related factors, total cholesterol (TC) ≥ 5.30, high-density lipoprotein cholesterol (HDL-C) > 1.30, triglycerides (TG)/HDL-C > 2.18, and ki67 expression > 70%, were included to construct the predictive nomogram. The C-indexes in training and validation sets were 0.758 and 0.792, respectively. ROC curves, calibration plots, and DCA all suggested favorable discrimination and predictive ability. Besides, the nomogram also performed better predictive ability than ki67 expression. Nomogram-related risk score divided the patients into two groups with significant progression disparities.Conclusion: The promising prognostic nomogram based on lipid parameters could help clinicians to conveniently and accurately evaluate the prognosis of ES-SCLC patients and identify high-risk groups, so as to formulate individualized therapeutic regimens and follow-up strategies in time.Keywords: small cell lung cancer, serum lipid, ki67, chemotherapy, nomogram

Gai Ge,1 Jingzhe Shang,2,3 Tian Gan,1 Zhiming Chen,1 Chun Pan,1 Youming Mei,1 Siyu Long,4 Aiping Wu,2,3 Hongsheng Wang1,5,6 1Laboratory of Mycobacteria, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, People’s Republic of China; 2Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 3Suzhou Institute of Systems Medicine, Suzhou, People’s Republic of China; 4Department of Dermatology, Beijing Chao-Yang Hospital & Capital Medical University, Beijing, People’s Republic of China; 5National Center for Sexually Transmitted Disease and Leprosy Control, China Centers for Disease Control and Prevention, Nanjing, People’s Republic of China; 6Centre for Global Health, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Hongsheng Wang, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 12 Jiang-wang-miao Street, Nanjing, Jiangsu Province, People’s Republic of China, Tel/Fax +86 258 5478953, Email whs33@vip.sina.comPurpose: Psoriasis (Ps) and leprosy are chronic inflammatory skin disorders, characterised by enhanced innate and adaptive immunity. Ps and leprosy rarely coexist. The molecular immune mechanism of the Ps and leprosy rarely coexistence is unclear.Patients and Methods: RNA-sequencing (RNA-seq) was performed on 20 patients with Ps, 5 adults with lepromatous leprosy (L-lep), and 5 patients with tuberculoid leprosy (T-lep) to analyse the differentially expressed genes (DEGs) between them. Moreover, the biological mechanism of Ps and leprosy was explored by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, Gene Ontology (GO) analysis, Gene Set Enrichment Analysis analysis, and protein–protein interaction (PPI) analyses. Finally, 13 DEGs of 10 skin biopsies of Ps patients, 6 samples of L-lep patients, 6 samples of T-lep patients and 5 healthy controls were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR).Results: The PPI network was constructed and primarily associated with immune response, IL-17 signalling, and Toll-like receptor pathway between Ps and leprosy. Th17 markers (interleukin (IL)- 19, IL-20, IL-36A, IL-36G, IL-22, IL-17A, and lipocalin-2 (LCN2) had higher expression in Ps than in L-lep and T-lep, whereas macrophage biomarkers (CLEC4E and TREM2), SPP1, and dendritic cell (DC)-related hallmarks (ITGAX) and TNF-a had significantly lower expression across Ps and T-lep than in L-lep.Conclusion: To put it simply, Ps patients with IL-17A, IL-19, IL-20, IL-36A, IL-36G, and IL-22 in conjunction with LCN2 with up-graduated expression might be not susceptible to L-lep. However, high levels of CLEC4E, TREM2, and SPP1 in L-lep patients indicated that they unlikely suffered from Ps.Keywords: psoriasis, leprosy, Th17 cell, macrophage, IL-17A, CLEC4E

Wei Sun,1,2,&ast; Songyi Xu,3,&ast; Tianlun Shen,1,3,&ast; Guangyao Li,1 Jingfeng Zhang,2 Chunshu Pan,1,2 Wei Lu,1,2 Xiangrui Liu,1 Jianjun Zheng,2 Jun Ling,1,3 Jihong Sun1 1Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Radiology, Ningbo No. 2 Hospital, Ningbo, People’s Republic of China; 3MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jihong Sun, Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Tel +86 13857176538, Email sunjihong@zju.edu.cn Jianjun Zheng, President of Ningbo No. 2 Hospital, Ningbo, People’s Republic of China, Tel +86 574 83870280, Email zhjjnb2@163.comPurpose: Chemotherapy treatments for cancer are always accompanied by a low concentration of drug delivered in the tumor area and severe side effects including systemic toxicity. Improving the concentration, biocompatibility, and biodegradability of regional chemotherapy drugs is a pressing challenge in the field of materials.Methods: N-Phenyloxycarbonyl-amino acids (NPCs) which exhibit significant tolerance to nucleophiles, such as water and hydroxyl-containing compounds, are promising monomers for the synthesis of polypeptides and polypeptoids. Cell line and mouse models were used to comprehensively explore how to enhance the tumor MRI signal and evaluate the therapeutic effect of Fe@POS-DOX nanoparticles.Results: In this study, poly(3,4-dihydroxy-L-phenylalanine)-b-polysarcosine (PDOPA-b-PSar, simplified as POS) was synthesized by the block copolymerization of DOPA-NPC with Sar-NPC. Fe@POS-DOX nanoparticles were prepared in order to utilize the strong chelation of catechol ligands to iron (III) cations and the hydrophobic interaction between DOX and DOPA block to deliver chemotherapeutics to tumor tissue. The Fe@POS-DOX nanoparticles exhibit high longitudinal relaxivity (r1 = 7.06 mM− 1·s− 1) and act as T1-weighted magnetic resonance (MR) imaging contrast agents. Further, the main focus was improving tumor site-specific bioavailability and achieving therapeutic effects through the biocompatibility and biodegradability of Fe@POS-DOX NPs. The Fe@POS-DOX treatment exhibited excellent antitumor effects.Conclusion: Upon intravenous injection, Fe@POS-DOX delivers DOX specifically to the tumor tissues, as revealed by MR, and leads to the inhibition of tumor growth without overt toxicity to normal tissues, thus displaying considerable potential for use in clinical applications.Graphical Abstract: Keywords: poly (α-amino acid)s, polypeptides, polypeptoids, MRI, chemotherapy, nanoparticles

Various health problems of people with intellectual disabilities (ID) are associated with their physical inactivity. The present study aimed at the understanding of physiological and psychological responses toward exergaming in seven young adults with mild to moderate ID after a single-session and a multiple-session condition, respectively. Their heart rate (HR), the rating of perceived exertion (RPE), and physical activity enjoyment scale (PACES) were measured on control and exergaming sessions. The significant increased HR, which may represent the increased physical activity levels that led to energy expenditure, was observed after a single-session and a multiple-session condition. In addition, the significant increase in RPE and PACES were evident after a single-session condition but a multiple-session condition. The feeling of physical fatigue seems to be distracted by external motivators (e.g. music). However, the positive affectivity to exercise was not noted when exercise was scheduled as their daily routines. This phenomenon might explain the high prevalence of physical inactivity among this population.

Geothermal heat mining simulations using supercritical CO2 (sCO2) were performed in this research. Working fluid selection criteria for power generation using sCO2 from a geothermal reservoir are then presented for subcritical, superheated and supercritical organic Rankine cycles (ORCs). Meanwhile, method of working fluid classification for ORC is proposed. To get the most feasible ORC design, this study introduces the concept of “turning point” for isentropic and dry working fluids, as well as minimum turbine inlet temperature for wet working fluids. A thermodynamic model was developed with capabilities to obtain the optimal working fluid mass flow rate, evaporation temperature, superheated temperature, and supercritical pressure, to evaluate the thermal performance of the three ORC approaches using hot produced sCO2. With this model, thirty potential working fluids with critical temperatures in the range from 50 to 225 °C were screened for utilizing hot produced sCO2 considering physical properties, environmental and safety impacts, and thermodynamic performances. Finally, the thermodynamic results were compared for all possible working fluids.

Yonghui Hu,1,2 Zhibo Hu,1,2 Wangna Tang,1,2 Wenjie Liu,1,2 Xiaoming Wu,1,2 Congqing Pan1,2 1NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, People’s Republic of China; 2Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University, Tianjin, People’s Republic of ChinaCorrespondence: Congqing Pan; Xiaoming Wu, NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, People’s Republic of China, Email profpancq@163.com; xiaomingwu2014@126.comPurpose: To examine the prevalence of different microvascular complications and investigate the association between thyroid hormones (THs) and these complications in euthyroid patients with type 2 diabetes mellitus (T2DM).Methods: A total of 248 T2DM patients were analyzed retrospectively for the study. All patients received a detailed and standard assessment to identify diabetic peripheral neuropathy (DPN), diabetic nephropathy (DN), and diabetic retinopathy (DR). Multivariate logistic regression was carried out to analyze the association between THs and diabetic microvascular complications.Results: The study found the prevalence of any microangiopathy to be 72.18% (n = 179). At the same time, the prevalence of DPN was 54.84% (n=136), while that of DN was 31.85% (n=79). Likewise, the prevalence of DR was 35.48% (n=88). The odds ratios (ORs) for free triiodothyronine (FT3) developing any microangiopathy, DPN, DN and DR were 0.200, 0.361, 0.310, and 0.588 (P< 0.05), respectively. Also, the ORs for free thyroxine (FT4) developing any microangiopathy, DPN, DN and DR were 0.643, 0.800, 0.702 and 0.726 (P< 0.05), respectively. Lastly, the ORs for thyroid-stimulating hormone (TSH) developing DPN was 1.57 (95% CI: 1.148– 2.137, P=0.005).Conclusion: The study concludes that serum FT3 and FT4 levels are negatively associated with any microangiopathy, DPN, DN and DR in euthyroid patients with T2DM, independent of traditional risk factors. However, the TSH levels are positively associated with DPN. Future larger sample-size studies are needed to confirm the relationship between thyroid hormone levels and microvascular complications in euthyroid patients with T2DM.Keywords: microvascular complications, thyroid hormone, type 2 diabetes mellitus, diabetic peripheral neuropathy, diabetic nephropathy, diabetic retinopathy

Xiuming Zhang,1,&ast; Wei Qiao,1,&ast; Zheng Kang,1 Chunhan Pan,1 Yan Chen,2 Kang Li,1 Wenrong Shen,1 Lei Zhang1 1Department of Radiology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Pathology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Zhang; Wenrong Shen, Email motozl163@163.com; jszlyyct@sohu.comObjective: To investigate computed tomography (CT) features of stage IA invasive mucinous adenocarcinoma (IMA) of the lung and establish a predictive model.Methods: Fifty-three lesions from 53 cases of stage IA IMA between January 2017 and December 2019 were examined, while 141 lesions from 141 cases of invasive non-mucinous lung adenocarcinoma (INMA) served as control cases. Univariate analysis was performed to compare differences in demographics and CT features between the two groups, and multivariate logistic regression analysis was performed to determine primary influencing factors of solitary nodular IMA. A risk score prediction model was established based on the regression coefficients of these factors, and receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive performance of the model.Results: Univariate analysis showed that age, nodule type, maximum nodule diameter, tumor lung interface, lobulation, spiculation, air bronchogram or vacuolar signs, and abnormal vascular changes differed significantly between the two groups (p < 0.05). Compared to INMA, spiculation of IMA was relatively longer and softer. Multivariate logistic regression analysis showed that nodule type, indistinct tumor lung interface, air bronchogram or vacuolar signs, and abnormal vascular changes were the primary influencing factors. A prediction model based on the regression coefficients of these factors was established. ROC curve analysis indicated that the area under the curve was 0.882 (p < 0.05).Conclusion: Compared to INMA, solitary peripheral stage IA nodular IMA were more common in older patients; they more frequently had indistinct tumor lung interface and air bronchogram or vacuolar signs on CT; spiculation was relatively longer and softer; our risk score prediction model based on nodule type, tumor lung interface, air bronchogram or vacuolar signs, and abnormal vascular changes was established with good predictive efficacy for solitary nodular IMA.Keywords: invasive mucinous adenocarcinoma of the lung, influencing factors, risk score modeling

Yonghui Hu,1,2,&ast; Wangna Tang,1,2,&ast; Wenjie Liu,1,2 Zhibo Hu,1,2 Congqing Pan1,2 1NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, People’s Republic of China; 2Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University, Tianjin, 300134, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Congqing Pan, NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, People’s Republic of China, Email profpancq@163.comBackground: Epithelial–mesenchymal transition (EMT) plays an important role in interstitial matrix deposition and renal fibrosis in diabetic kidney disease (DKD). It has been verified that Astragaloside IV (AS-IV) is beneficial for ameliorating DKD. However, the underlying mechanisms of AS-IV on regulating EMT in DKD are yet to be established. Accumulated evidence has suggested that C-X3-C motif ligand 1 (CX3CL1) plays a significant role in the progression of EMT.Purpose: We aimed to investigate whether AS-IV could alleviate EMT by regulating CX3CL1 in DKD and reveal its underlying mechanisms.Methods: For the in vivo study, mice were divided into the following five groups (n=10): db/m+vehicle, db/db+vehicle, db/db+AS-IV-L (10mg/kg/d), db/db+AS-IV-M (20mg/kg/d), db/db+AS-IV-H (40mg/kg/d). After 12 weeks of treatment, the renal injuries were assessed based on the related parameters of urine, blood and histopathological examination. Immunohistochemistry and Western blotting were used to detect relative proteins levels. Then in HK-2 cells, the molecular mechanism of AS-IV attenuating the EMT in mice with DKD through the CX3CL1-RAF/MEK/ERK pathway was studied.Results: In the present study, we found that AS-IV reduced urinary protein levels and improved renal pathological damage in DKD mice. Moreover, AS-IV ameliorated the renal tubular EMT induced by hyperglycemia or high glucose (HG), and decreased the expression of CX3CL1 and inhibited the activation of the RAF/MEK/ERK pathway in vivo and in vitro. In HK-2 cells, downregulation of CX3CL1 suppressed the stimulation of the RAF/MEK/ERK pathway and EMT induced by HG. However, CX3CL1 overexpression eliminated the benefits of AS-IV on the RAF/MEK/ERK pathway and EMT.Conclusion: In summary, we indicated that AS-IV alleviates renal tubular EMT through the CX3CL1-RAF/MEK/ERK signaling pathway, indicating that CX3CL1 could be a potential therapeutic target of AS-IV in DKD.Keywords: Astragaloside IV, epithelial–mesenchymal transition, CX3CL1, diabetic kidney disease, renal fibrosis

Yan Lan, Chensheng Pan, Xiuli Qiu, Jinfeng Miao, Wenzhe Sun, Guo Li, Xin Zhao, Zhou Zhu, Suiqiang Zhu Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Zhou Zhu; Suiqiang Zhu, Tel +86-18171081029 ; +86-13035101141, Email zhouzhu@hust.edu.cn; zhusuiqiang@163.comPurpose: Previous studies have shown that persistent post-stroke depression (PSD) was associated with unfavorable prognosis. The aim of this multicenter prospective study was to investigate the predictors associated with persistent PSD, develop a nomogram and validate its clinical usefulness by decision curve analysis (DCA).Patients and Methods: A total of 875 acute ischemic stroke patients from four hospitals were consecutively recruited and completed 1-year follow-ups. Sociodemographic indicators, vascular risk factors, clinical information, serum biochemical indicators and cytokines were collected on admission. The functional outcome was assessed at 1 year after stroke. Persistent depression was defined as having a presentation of depression at each follow-up points and the depressive symptoms occurring persistently since the diagnosis of depression.Results: There were 513 patients who experienced PSD during the 1-year follow-up, the cumulative incidence of PSD within 1 year was 58.6%. Persistent PSD was recorded in 289 patients, of which 59 (20.4%) result in unfavorable outcomes. The risk factors of persistent PSD in 1 year after stroke were the Hamilton Depression Scale-17 items (HAMD-17) score at admission, serum direct bilirubin and free serum thyroxine (FT4) level and activated partial thromboplastin time (APTT). Nomogram conducted based on these factors has a C-index (± standard deviation) of 0.655 ± 0.039, and the DCA demonstrated that the nomogram had a favorable clinical utility.Conclusion: We found that persistent depression after stroke in the first-year time course after stroke was associated with HAMD-17 score at admission, lower serum direct bilirubin and FT4 level, and APTT. A nomogram was developed with advisable clinical usefulness in our study.Keywords: persistent post-stroke depression, nomogram, decision curve analysis

Yanyan Wang,1 He Wang,2 Wenzhe Sun,1 Jinfeng Miao,1 Wenwen Liang,1 Xiuli Qiu,1 Yan Lan,1 Chensheng Pan,1 Guo Li,1 Xin Zhao,1 Zhou Zhu,1 Suiqiang Zhu1 1Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China; 2Department of Medical Affairs, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of ChinaCorrespondence: Zhou Zhu; Suiqiang Zhu, Tel +86 18171081029 ; +86 13035101141, Fax +86 27-83663337, Email zhouzhu@hust.edu.cn; zhusuiqiang@163.comBackground: Post-stroke depression (PSD) is the most common neuropsychiatric complication after stroke, seriously affecting the quality of survivors’ life. As one of the important causes of PSD, neuroendocrine mechanism has been widely studied in recent years. The main objective of this study was to investigate the relationship between adrenocorticotropic hormone (ACTH) on admission and PSD at 3 months.Methods: This is a hospital-based prospective cohort study, which was conducted at three independent hospitals (Tongji Hospital, Wuhan First Hospital and Wuhan Central Hospital) between August 2018 and June 2019. A total of 768 ischemic stroke patients were finally eligible for analysis and categorized into equal tertiles according to the distribution of ACTH and the number of patients. The χ2-test, Mann–Whitney U-test and Kruskal–Wallis test were used to check for statistical significance. And restricted cubic spline (RCS) regression model was used to explore the non-linear relationship between continuous ACTH levels and PSD at 3 months.Results: The optimal cut-off points of ACTH were as follows: (T1) 0.32– 20.55 pg/mL, (T2) 20.56– 39.79 pg/mL, (T3) 39.80– 143.40 pg/mL. A total of 305 patients (39.7%) were diagnosed as PSD at 3 months follow-up. Significant differences were found between the PSD and non-PSD groups in ACTH concentration (P = 0.001). After adjustment for all conventional confounders, the odds ratios of PSD were 1.735 (95% CI = 1.176– 2.560, P = 0.005) for the highest tertile of ACTH and 1.496 (95% CI = 1.019– 2.194, P = 0.040) for the middle tertile of ACTH, as compared with the lowest tertile. In multiple-adjusted RCS regression, continuous ACTH showed saturation effect relation with PSD risk after 31.02 pg/mL (P for nonlinear = 0.0143).Conclusion: Higher ACTH level on admission is a significant and independent biomarker to predict the development of PSD at 3 months follow-up. Besides, saturation effect was revealed even if the underlying mechanism is unclear. For stroke patients, doctors should pay attention to the baseline ACTH for screening high-risk PSD in clinical practice.Keywords: neuroendocrinology, HPA axis, adrenocorticotropic hormone, post-stroke depression, restricted cubic spline, saturation effect

Chen Pan,1 Honghong Wang,2 Minzhen Chen,3 Yu Cai,1 Peihuan Li,4 Changgen Xiao,5 Qiuping Tang,1 Deborah Koniak-Griffin6 1Department of Clinical Psychology, The Third Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 2Department of Fundamental Nursing, Xiangya School of Nursing, Central South University, Changsha, People’s Republic of China; 3Department of AIDS, The First Hospital of Changsha, Changsha, People’s Republic of China; 4College of Resources of Environment, Hunan Agricultural University, Changsha, People’s Republic of China; 5Department of Applied Psychology, Hunan University of Chinese Medicine, Changsha, People’s Republic of China; 6School of Nursing, University of California Los Angeles, Los Angeles, CA, USACorrespondence: Qiuping Tang, Department of Clinical Psychology, The Third Xiangya Hospital of Central South University, Changsha, People’s Republic of China, Tel +86 731 88618567, Email tt96@sina.comBackground/Purpose: Nurses engaged in the care of people living with HIV (PLWH) are commonly exposed to workplace stress. This study aimed to explore the stress experiences and coping strategies among nurses taking care of PLWH in China.Methods: Nurses were recruited from the AIDS department of a public, general, third-grade class-A hospital, which has the largest HIV care department in the Hunan Province of China. Thirty-three nurses working in the AIDS Department were recruited in this qualitative study. Eight nurses participated in a focus group and 25 nurses underwent in-depth individual interviews aimed at characterizing the nurse’s feelings and struggles with stress during caregiving for PLWH. The interviews were audio-recorded, transcribed verbatim, anonymized, and imported into NVivo 8.0 software. The data were coded and subjected to thematic analysis.Results: Concerns about occupational exposure, heavy workload, mental health problems and risk behaviors of patients, and discrimination towards nurses caring for PLWH were the four main sources of stress. The negative impact of stress included problems with emotion regulation, somatic health and sleep, and work performance. Some participants also reported a positive impact of work stress on their mental health. Using personality strengths, problem-solving, help-seeking, concealing and avoiding/suppression were common coping strategies employed by nurses caring for PLWH.Conclusion: Our findings help characterize the stress experienced by nurses caring for PLWH in the Chinese cultural context, and may inform specific interventions to help manage stress and promote mental health of nurses.Keywords: HIV, nurses, stress, job burnout, coping

Yao Yao,&ast; Yumeng Jia,&ast; Yan Wen, Bolun Cheng, Shiqiang Cheng, Li Liu, Xuena Yang, Peilin Meng, Yujing Chen, Chun’e Li, Jingxi Zhang, Zhen Zhang, Chuyu Pan, Huijie Zhang, Cuiyan Wu, Xi Wang, Yujie Ning, Sen Wang, Feng Zhang Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng ZhangKey Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of ChinaEmail fzhxjtu@mail.xjtu.edu.cnPurpose: Most previous genetic studies of sleep behaviors were conducted individually, without comprehensive consideration of the complexity of various sleep behaviors. Our aim is to identify the genetic architecture and potential biomarker of the sleep health score, which more powerfully represents overall sleep traits.Patients and Methods: We conducted a genome-wide association study (GWAS) of sleep health score (overall assessment of sleep duration, snoring, insomnia, chronotype, and daytime dozing) using 336,463 participants from the UK Biobank. Proteome-wide association study (PWAS) and transcriptome-wide association study (TWAS) were then performed to identify candidate genes at the protein and mRNA level, respectively. We finally used linkage disequilibrium score regression (LDSC) to estimate the genetic correlations between sleep health score and other functionally relevance traits.Results: GWAS identified multiple variants near known candidate genes associated with sleep health score, such as MEIS1, FBXL13, MED20 and SMAD5. HDHD2 (PPWAS = 0.0146) and GFAP (PPWAS = 0.0236) were identified associated with sleep health score by PWAS. TWAS identified ORC4 (PTWAS = 0.0212) and ZNF732 (PTWAS = 0.0349) considering mRNA expression level. LDSC found significant genetic correlations of sleep health score with 3 sleep behaviors (including insomnia, snoring, dozing), 4 psychiatry disorders (major depressive disorder, attention deficit/hyperactivity disorder, schizophrenia, autism spectrum disorder), and 9 plasma protein (such as Stabilin-1, Stromelysin-2, Cytochrome c) (all LDSC PLDSC < 0.05).Conclusion: Our results advance the comprehensive understanding of the aetiology and genetic architecture of the sleep health score, refine the understanding of the relationship of sleep health score with other traits and diseases, and may serve as potential targets for future mechanistic studies of sleep phenotype.Keywords: sleep, sleep health score, genome-wide association study, genetics, complex-traits

The concept of injecting supercritical CO2 (sCO2) into a geothermal reservoir was computationally investigated to assess its performance in terms of the benefit of using CO2 captured from fossil power plants for geothermal heat mining. A coupled wellbore-reservoir system was simulated considering the flow of pure sCO2 in an injection well, the interaction of sCO2 and water in a permeable reservoir, and the flow of the two-phase mixture of sCO2 and water in a production well. Results of simulations indicate that this CO2 application is capable of providing a good source of renewable energy. It was found that for a reservoir with a 0.08 km3 volume, about 8-9 MWth could be extracted in a steady state fashion for a 30-year lifetime operation. This is approximately equivalent to 100 MWth/km3. A sensitivity analysis provided information on the impact of certain parameters on the performance of the integrated system. The injection flowrate, the distance between the production and injection wellbores and the penetrating depth of the production wellbore into the reservoir have a first order impact on the pressure management of the reservoir. Additionally, CO2 injection temperature has a large effect on the thermosiphon characteristics of the system.

Guo Li,1 Jinfeng Miao,1 Chensheng Pan,1 Ping Jing,2 Guohua Chen,3 Junhua Mei,3 Wenzhe Sun,1 Yan Lan,1 Xin Zhao,1 Xiuli Qiu,1 Yanyan Wang,1 Zhou Zhu,1 Suiqiang Zhu,1 Lifei Lian1 1Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China; 2Department of Neurology, Wuhan Central Hospital, Wuhan, Hubei, 430014, People’s Republic of China; 3Department of Neurology, Wuhan First Hospital, Wuhan, Hubei, 430022, People’s Republic of ChinaCorrespondence: Lifei Lian Tel +86-151 7150 7263Email 47009189@qq.comPurpose: Post-stroke depression (PSD) is one of the most common and severe psychological sequelae after stroke, negatively affecting the patient’s functional outcome and quality of life. Rapidly measurable biomarkers to predict PSD are pivotal for the optimized care and allocation of healthcare resources. Lactic dehydrogenase (LDH) levels are increased in patients with central nervous system (CNS) disorders such as cerebral infarction and hypoxic–ischemic encephalopathy, which may be related to the occurrence of PSD in acute ischemic stroke (AIS) patients. This study aimed to investigate whether LDH levels on admission are associated with PSD at discharge.Patients and Methods: A multicenter prospective cohort study was conducted, including all consecutive AIS patients within 7 days after symptom onset from May 2018 to October 2019. According to the distribution of LDH and the number of patients, patients were divided into equal tertiles. PSD was evaluated by DSM-V criteria and the 17-item Hamilton Rating Scale for Depression (HRSD-17) at discharge.Results: A total of 518 AIS patients were included. The optimal cut-off points of LDH were: lowest tertile (T1) 102– 159/L, middle tertile (T2) 160– 189 U/L, and upper tertile (T3) 190– 520 U/L. A total of 249 patients (48.07%) were diagnosed with PSD at discharge. After adjusting for potential confounding factors, the odds ratio of T3 PSD was 1.698 (95% CI, 1.070– 2.694, P=0.025), compared with T1.Conclusion: In summary, LDH serum levels on admission are associated with PSD at discharge. Clinicians should pay more attention to the baseline LDH level in screening for PSD at discharge.Keywords: post-stroke depression, lactic dehydrogenase, screen, cohort study

Yihong Wang,&ast; Manyi Li,&ast; Chen Pan,&ast; Haiping Huang, Xiaoqing Hu, Jisheng Liu Department of Otolaryngology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jisheng LiuDepartment of Otolaryngology, The First Affiliated Hospital of Suzhou University, 188 Shizi Street, Suzhou, 215000, Jiangsu Province, People’s Republic of ChinaTel +86-13506216162Email ljswwq@sina.comPurpose: Hsa_circ_0007637 was discovered to be differentially expressed in nasopharyngeal carcinoma (NPC). However, the exact function and mechanism of Hsa_circ_0007637 on NPC have not been studied. This study firstly researched the function and mechanism of Hsa_circ_0007637 on NPC progression.Methods: Hsa_circ_0007637, miR-636 and TPD52 expressions in 80 NPC patients were detected by quantitative real-time polymerase chain reaction. Hsa_circ_0007637 effect on NPC cell proliferation, apopticosis, invasion and migration was investigated by cell counting kit-8 assay, flow cytometry, transwell experiment and wound healing assay accordingly. Dual-luciferase reporter gene assay, RNA immunoprecipitation experiment and RNA fluorescence in situ hybridization experiment were performed to identify the binding between Hsa_circ_0007637 and miR-636. Dual-luciferase reporter gene assay and RNA pull down assay were conducted to verify the binding between miR-636 and TPD52. TPD52 protein expression in NPC cells was determined by Western blot. In vivo study was performed using nude mice. Immunohistochemistry was performed to assess TPD52 and Ki67 expression in tissues.Results: Hsa_circ_0007637 was overexpressed in NPC tissues and cells. High Hsa_circ_0007637 expression predicted a poor outcome for NPC patients. Hsa_circ_0007637 knockdown decreased proliferation, invasion, migration and increased apoptosis of NPC cells (P < 0.01). Hsa_circ_0007637 could enhance TPD52 expression via sponging miR-636. miR-636 overexpression or TPD52 knockdown weakened the promoting effect of Hsa_circ_0007637 on NPC cells malignant phenotype (P < 0.01). Hsa_circ_0007637 knockdown suppressed NPC cells growth in vivo (P < 0.01).Conclusion: Hsa_circ_0007637 facilitates NPC progression by sponging miR-636/TPD52 axis.Keywords: NPC, Hsa_circ_0007637, miR-636/TPD52, proliferation, apoptosis

Lemeng Zhang, Yongzhong Luo, Tianli Cheng, Jianhua Chen, Hua Yang, Xiaoping Wen, Zhou Jiang, Haitao Li, Changqie Pan Thoracic Medicine Department 1, Hunan Cancer Hospital, Changsha, Hunan Province, 410013, People’s Republic of ChinaCorrespondence: Yongzhong Luo Tel/Fax +86-731-89762220Email luoyongzhong@hnca.org.cnPurpose: The prognostic value of an N6-methyladenosine (m6A) methylation-related immune gene signature for lung adenocarcinoma (LUAD) was investigated.Patients and Methods: Gene expression and clinical phenotype data of LUAD patients were downloaded from The Cancer Genome Atlas database. A list of immune-related genes was retrieved from the InnateDB database. Correlation analysis, survival analysis, and univariate and multivariate Cox regression analyses were performed. After allocating patients into a high-risk or a low-risk group, the corresponding survival rates, immune microenvironment, expression of immune checkpoint genes, and modulation of Kyoto Encyclopedia of Genes and Genomes pathways were examined. Finally, the expression levels of prognostic biomarkers were assessed in the GSE126044 dataset.Results: Seven m6A-related immune prognostic genes were identified. High expression of PSMD10P1, DIDO1, ABCA5, and CIITA was associated with high survival rates, while that of PRC1, ZWILCH, and ANLN was associated with low survival rates. The high- and low-risk groups showed significant differences in terms of the abundance of six tumor-infiltrating immune cell types and expression of 12 immune checkpoint genes. The risk group acted as an independent prognostic factor (hazard ratio = 0.398, 95% confidence interval = 0.217– 0.729, P = 0.003). Finally, the developed nomogram could predict most efficiently the 1-, 2-, and 3-year survival probability of LUAD patients with a C-index of 0.833.Conclusion: A seven-gene risk signature, associated with the immune microenvironment in LUAD, showed independent prognostic value.Keywords: lung adenocarcinoma, N6-methyladenosine methylation, immune-related genes, immune microenvironment, prognostic signature

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

Mincong Wang,1,&ast; Yue Meng,1,&ast; Huifeng Zhu,1 Yong Hu,1 Chang-Peng Xu,2 Xiaomin Chao,1 Wenqiang Li,3 Chengguo Li,1 Chenglong Pan1 1Department of Joint Surgery, The Fifth Affiliated Hospital of Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Orthopaedics, Guangdong Second Provincial General Hospital, Guangzhou, People’s Republic of China; 3Engineering Technology Research Center for Sports Assistive Devices of Guangdong, Guangzhou Sport University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chenglong Pan; Chengguo Li Email pclgjwk@163.com; 356846516@qq.comIntroduction: Viola betonicifolia is a rich source of numerous secondary metabolites, such as alkaloids, flavonoids, tannins, phenolic compounds, saponins, triterpenoids, and so on, that are biologically active towards different potential biomedical applications. To broaden the potential use of Viola betonicifolia in the realm of bionanotechnology, we investigated the plant’s ability to synthesize gold nanoparticles (Au NPs) in a green and efficient manner for the very first time.Methods: The gold nanoparticles (VB-Au NPs) were synthesized using the leaves extract of Viola betonicifolia, in which plant’s secondary metabolites function as both reducing and capping agents. The VB-Au NPs were successfully characterized with spectroscopic techniques. The antimicrobial properties of the VB-Au NPs were further explored against bacterial and mycological species. Additionally, their antioxidant, cytotoxic, and cytobiocompatibility properties were examined in vitro against linoleic acid peroxidation, MCF-7 cancer cells, and human mesenchymal stem cells (hMSCs), respectively.Results: Results demonstrated that VB-Au NPs presented excellent antibacterial, antifungal, and biofilm inhibition performance against all the tested microbial species compared to plant leaves extract and commercially purchased chemically synthesized gold NPs (CH-Au NPs). Moreover, they also exhibited significant antioxidant potential, comparable to the external standard. The VB-Au NPs displayed good cytobiocompatibility with hMSCs and demonstrated excellent cytotoxic potential against MCF-7 cancer cells compared to CH-Au NPs. The current work presents a green method for synthesizing VB-Au NPs with enhanced antioxidant, antimicrobial, cytotoxic and biofilm inhibition efficacy compared to CH-Au NPs might be attributed to the synergistic effect of the nanoparticle’s physical properties and the adsorbed biologically active phytomolecules from the plant leaves extract on their surface.Conclusion: Thus, our study establishes a novel ecologically acceptable route for nanomaterials’ fabrication with increased and/or extra medicinal functions derived from their herbal origins.Keywords: Viola betonicifolia, gold NPs, antimicrobial, biofilm inhibition, antioxidant

Chunyang Pan, Yi Zhao, Haojie Xie, Yongyan Zhou, Ranran Duan, Yanfei Li, Yanjie Jia, Tao Peng Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of ChinaCorrespondence: Tao PengDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Erqi District, Zhengzhou, Henan Province, People’s Republic of ChinaTel +861 367 366 5072Email zdyfy0420@163.comPurpose: To describe and compare the clinical features of patients with first-episode neuromyelitis optica spectrum disorder (NMOSD) in a normal complement C4 group and a low complement C4 group, and explore the mechanism by which low complement C4 affects the clinical features of patients with NMOSD.Patients and Methods: We retrospectively analyzed clinical data of 169 aquaporin-4 (AQP4) antibody positive patients with NMOSD from the First Affiliated Hospital of Zhengzhou University from December 2013 to March 2021. Prior to treatment, the blood was drawn for detection, and the patients underwent a 3.0 Tesla MRI examination. A low complement C4 level was defined as a serum complement C4 level < 0.14 g/L. Depending on whether the complement C4 level was reduced, it was divided into the normal complement C4 group and low complement C4 group. The basic demographics, clinical manifestations, laboratory examinations, and imaging findings of the two groups were compared.Results: Among the 169 AQP4 antibody positive patients, 54 were low-complement C4 patients and 115 were normal. There were no significant differences in the demographics, clinical manifestations, treatment options, or admission Expanded Disability Status Scale (EDSS) score between two groups (P > 0.05). The median of discharged EDSS was the same (4 vs 4), but the difference between the two was statistically significant (P = 0.019). Compared with the normal complement C4 group, the blood uric acid level (225 vs 179; P = 0.001) and the C3 level (1.06 vs 0.87, P = 0.000) of the low complement C4 group were significantly lower. The incidence of brainstem lesions in patients with low complement C4 was higher (53.7% vs 33%, P = 0.01).Conclusion: The treatment effect of the first-episode AQP4 antibody positive NMOSD low complement C4 group was poor, the blood-brain barrier was more severely damaged, and the disease changes were likely to involve the brainstem.Keywords: blood-brain barrier, brainstem, humoral immunity, optic neuritis