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Chao Wu,&ast; Chunxia He,&ast; Haimeng Wang, Wenming Wang, Hongzhong Jin Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongzhong Jin, Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy Medical Science and Peking Union Medical College, No. 1 Shuai Fu Yuan Street, Beijing, 100730, People’s Republic of China, Fax +86-10-6915-1502, Email jinhongzhong@263.netPurpose: This prospective observational study investigated whether interleukin (IL)-17A inhibitors could reduce serum uric acid (SUA) levels in psoriatic patients with hyperuricemia. It also explored the risk factors for hyperuricemia in psoriatic patients and the effectiveness of IL-17A inhibitors for the skin lesions of psoriatic patients with hyperuricemia.Methods: Patients aged ≥ 18 years with moderate to severe plaque psoriasis along with concomitant hyperuricemia (defined as an SUA level > 416 μmol/L in men and > 357 μmol/L in women) at baseline were treated with either secukinumab or ixekizumab. SUA levels were longitudinally assessed over 1 year. We evaluated the changes in SUA level and factors associated with SUA changes. Binary logistic regression was conducted to identify risk factors for hyperuricemia in psoriatic patients. Additionally, we examined effectiveness of IL-17A inhibitors for patients with psoriasis and hyperuricemia including Psoriasis Area Severity Index (PASI) 75, 90, and 100 response rates at 1 year.Results: Our study included 196 individuals diagnosed with psoriasis and hyperuricemia. The mean SUA levels were 481± 68 μmol/L at baseline and 442± 78 μmol/L after 1 year of treatment with IL-17A inhibitors (p< 0.001). Subgroup analysis revealed a consistent and significant decrease in SUA levels across different genders, age groups (30– 39, 40– 49, ≥ 50 years), BMI categories, baseline PASI scores, PASI improvement rates, and among patients treated with different IL-17A inhibitors. Patients aged ≥ 50 years and with a BMI < 24 exhibited a higher SUA reduction rate. Male gender, age under 40 years, obesity, hypertension, hypertriglyceridemia, and a PASI score of ≥ 20 were independent risk factors for hyperuricemia in patients with psoriasis. The PASI 75, 90, and 100 response rates in psoriatic patients with hyperuricemia were 88.3%, 60.2%, and 28.6%, respectively, after 1 year of treatment with IL-17A inhibitors.Conclusion: Our findings suggest that SUA levels decrease significantly under IL-17A inhibitors treatment in psoriatic patients with hyperuricemia. Patients aged ≥ 50 years and with a BMI < 24 had greater benefits. This study provides a theoretical basis for the selection of biologics to treat psoriatic patients with hyperuricemia.Keywords: psoriasis, uric acid, hyperuricemia, IL-17A inhibitor

Jin Cheng,1,&ast; Honglei Ju,1,&ast; Guixiang Wang,2,&ast; Chiyi He,1 Wei Wang1 1Department of Gastroenterology, Yijishan Hospital of Wannan Medical College, Wuhu, People’s Republic of China; 2Department of Gastroenterology, The Second Affiliated Hospital of Wannan Medical College, Wuhu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Wang, Department of Gastroenterology, Yijishan Hospital of Wannan Medical College, No. 2, Zheshan West Road, Wuhu, Anhui Prov, 241000, People’s Republic of China, Email wwwy@wnmc.edu.cnBackground: The Systemic Inflammation Response Index (SIRI) has demonstrated predictive capabilities for clinical outcomes in various diseases. However, its prognostic utility in decompensated liver cirrhosis (DLC) remains underexplored. This study aimed to investigate the association between SIRI and the risk of short-term (3 and 6 months) all-cause mortality in DLC patients.Methods: A total of 926 eligible patients with DLC from diverse etiologies was included in this study. In the initial cohort, the predictive accuracy of SIRI was evaluated using receiver operating characteristic (ROC) curve analysis. Patients were categorized into high- and low-SIRI groups based on the Youden index. Multivariable logistic regression analysis was employed to evaluate the independent association between SIRI and all-cause mortality. Restricted cubic spline (RCS) analysis was utilized to visualize the relationship between the continuous variable SIRI and mortality risk. These findings were validated in a validation cohort.Results: The initial cohort had mortality rates of 8.8% and 11.6% at 3 and 6 months, respectively. The SIRI level was significantly higher in the deceased group compared to the survival group. At both time points, SIRI was an independent indicator of all-cause mortality. RCS analysis demonstrated the risk of the risk of increased with an increase in SIRI value. The Validation cohort validated the independent association between higher SIRI levels and lower short-term all-cause mortality.Conclusion: This study’s findings underscore the prognostic value of SIRI in DLC patients, indicating that higher SIRI levels are significantly associated with short-term adverse outcomes.Keywords: decompensated liver cirrhosis, systemic inflammation response index, prognosis, all-cause mortality

Ye Yang,1,&ast; Lin Wang,1,&ast; Zhiyang Zeng,2 Chunmeng He,1 Yanqiu Wang,1 Ying Huang1 1Department of Gastroenterology, Children’s Hospital of Fudan University/National Children’s Medical Center, Shanghai, 201102, People’s Republic of China; 2Department of Central Laboratory, Fengxian Central Hospital Affiliated to Southern Medical University, Shanghai, 201499, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Huang, Department of Gastroenterology, Children’s Hospital of Fudan University/National Children’s Medical Center, No. 399 Wanyuan Road, Minhang District, Shanghai, 201102, People’s Republic of China, Tel +86-21-64931727, Email yhuang815@163.comPurpose: Spleen tyrosine kinase (Syk) is a widely-expressed cytoplasmic non-receptor tyrosine kinase involved in regulating various signaling pathways and plays an important role in chronic inflammation and autoimmune diseases. Gain-of-function SYK variants have been implicated in pediatric inflammatory bowel diseases. This study aimed to investigate the effects of gain-of-function SYK variants on the susceptibility to experimental colitis and macrophage function.Methods: Colitis was induced using dextran sodium sulfate and dinitrobenzene sulfonic acid in mice harboring a gain-of-function variant in SYK (SykS544Y). Intestinal inflammation was assessed via disease activity index, histological analysis, and Western blotting. The frequencies of macrophages, phagocytosis, and reactive oxygen species (ROS) production in bone marrow-derived macrophages (BMDM) were measured via flow cytometry. Chemokines and BMDM chemotaxis were analyzed using real-time quantitative reverse transcription polymerase chain reaction and Transwell assays. The expression of nucleotide-binding domain leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome-related proteins were detected using immunohistochemistry, enzyme-linked immunoassay and Western blotting.Results: SykS544Y mice exhibited increased susceptibility to experimental colitis, and macrophage infiltration in colon tissues significantly increased. We observed increased expression of macrophage chemokines in colon tissues and enhanced chemotaxis in SykS544Y BMDM. Additionally, we detected increased levels of fluorescent microspheres and 2.7-dichloride-hydro fluorescein diacetate-labeled ROS in SykS544Y BMDM. Moreover, enhanced levels of NLRP3 inflammasome-related proteins were observed in the colon tissues and BMDM from SykS544Y mice.Conclusion: Gain-of-function variant in SYK may contribute to the pathogenesis of pediatric inflammatory bowel diseases by promoting macrophage migration, phagocytosis, ROS production and activation of NLRP3 inflammasomes.Keywords: inflammatory bowel disease, SYK, gain-of-function variant, macrophage

Zuo Wang,1,2,&ast; Siqi Guo,3,&ast; Chong He,2,4,&ast; Lingling Chen,5 Jinxia Wang,2 Wenbo Xiu,2 Gao Zhang,2 Yang Chen,2 An Li,2 Xiong Zhu,6 Xiao Xiao,2 Ling Yu,3 Fang Lu2,4,7 1Department of Clinical Laboratory, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 3Department of Ophthalmology, Daping Hospital, Army Medical Center, Army Medical University, Chongqing, People’s Republic of China; 4Medico-Engineering Cooperation on Applied Medicine Research Center, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 5Department of Immunology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, People’s Republic of China; 6Department of Prenatal Diagnosis, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 7Health Management Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Yu; Fang Lu, Email oculistlingyu@hotmail.com; lufangfang@126.comObjective: Evidence suggests that dysbiosis of the gut microbiota plays a pivotal role in the development of glaucoma. This dysbiosis is commonly associated with chronic intestinal inflammation and increased intestinal permeability. However, the understanding of intestinal inflammation and permeability in glaucoma remains insufficient. This study aims to investigate the potential relationship between fecal inflammation and permeability markers and glaucoma.Methods: We recruited 114 glaucoma patients and 75 healthy controls. Levels of fecal lactoferrin (Lf) and alpha-1 antitrypsin (AAT) were quantified using enzyme linked immunosorbent assay (ELISA) to compare both biomarkers between groups and across different severity grades of glaucoma. Logistic regression analysis was used to assess the association between these fecal biomarkers and glaucoma. The severity of glaucoma was assessed based on the mean deviation (MD) in the visual field.Results: In this study, we observed elevated levels of fecal Lf and AAT in glaucoma patients. The proportion of glaucoma patients with abnormal fecal Lf levels (≥ 7.25 μg/g) was significantly higher than that of the controls (p = 0.012). A positive correlation was noted between fecal Lf and AAT (rho = 0.20, p = 0.006). After adjusting for age and sex, multivariable logistic regression analysis indicated that both fecal Lf (OR = 1.11, 95% CI: 1.01– 1.21, p = 0.026) and AAT (OR = 1.01, 95% CI: 1.01– 1.02, p < 0.001) positively correlated with glaucoma. These biomarkers might reflect glaucoma severity, with significant differences in fecal Lf levels observed between moderate and severe stages, but not in the early stage. Furthermore, increasing levels of fecal AAT correlated with greater severity of glaucomatous injury and a larger vertical cup-to-disc ratio (VCDR) (p < 0.05).Conclusion: This study suggests an increase in intestinal inflammation and permeability in glaucoma, further indicating the importance of the ‘gut-retina axis’ in the pathogenesis of the disease and potentially offering new therapeutic avenues.Keywords: fecal lactoferrin, fecal alpha-1 antitrypsin, glaucoma, intestinal inflammation, intestinal permeability, intestinal barrier

Sifan Ji,1,2,&ast; Hang Qi,1,2,&ast; Li Yan,1,2,&ast; Duo Zhang,1,2 Yang Wang,1,2 HaLiSai MuDanLiFu,1,2 Chuqing He,1,2 Wei Xia,1,2 Qian Zhu,1,2 Yan Liang,1,2 Jian Zhang1,2 1Department of Obstetrics and Gynecology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Zhang, Department of Obstetrics and Gynecology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China, Tel +86 18017316017, Email zhangjian_ipmch@sjtu.edu.cnIntroduction: Endometriosis (EM) is an estrogen-dependent benign gynecologic disease affecting approximately 10% of reproductive-age women with a high recurrence rate, but lacks reliable biomarkers. No previous studies have investigated the possible use of extracellular vesicle (EV)-associated micro RNAs (miRNAs) from menstrual blood (MB) as candidate diagnostic or prognostic markers of EM.Methods: Specimens were obtained from endometriosis and non-endometriosis patients at the International Peace Maternity and Child Health Hospital in Shanghai. Microarray was used to screen differentially expressed miRNAs among peritoneal fluid (PF), fallopian tube fluid (FF), and MB. Dual-luciferase reporter gene assay was carried out to verify the relationship between miR-4443 and ACSS2. Cell proliferation and Transwell invasion assays were performed in vitro after intervention on miR-4443 and ACSS2 in hEM15A human endometrial stromal cells and primary human endometrial stromal cells (hESCs). Spearman correlation analysis, receiver operating characteristic (ROC) curve analysis, and survival analysis were applied to clinical data, including severity of symptoms and relapse of EM among EM patients.Results: EV-associated miR-4443 was abundant in MB of endometriosis patients. ACSS2 knockdown and miR-4443 overexpression promoted cell proliferation and migration via the PI3K/AKT pathway. miR-4443 levels in MB-EVs were positively correlated with the degree of dyspareunia (r=0.64; P< 0.0001) and dysmenorrhea (r=0.42; P< 0.01) in the endometriosis group. ROC curve analyses showed an area under the curve (AUC) of 0.741 (95% CI 0.624– 0.858; P< 0.05) for miR-4443 and an AUC of 0.929 (95% CI 0.880– 0.978; P< 0.05) for the combination of miR-4443 and dysmenorrhea.Conclusion: MB-derived EV-associated miR-4443 might participate in endometriosis development, thus providing a new candidate biomarker for the noninvasive prediction of endometriosis recurrence. Keywords: endometriosis, menstrual blood, biomarker, extracellular vesicles, miR-4443

Chengxue He,1,2,&ast; YanHui Guo,3,&ast; Nina Zhou,2,&ast; Zhen Wang,4,&ast; Teli Liu,2 Xiaoxia Xu,2 Feng Wang,2 Hua Zhu,2 Zhi Yang,1,2 Xianteng Yang,1,5 Lei Xia2 1Medical College, Guizhou University, Guiyang, GuiZhou Province, People’s Republic of China; 2Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China; 3Department of Radiology, Peking University Third Hospital, Beijing, People’s Republic of China; 4Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Hepato-Pancreato-Biliary Surgery, Sarcoma Center, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China; 5Department of Orthopedics, Guizhou Provincial People’s Hospital, Guiyang, GuiZhou Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Xia; Zhi Yang, Tel +86 010-88197852 ; +86 010-88196196, Email xialei9012288@126.com; pekyz@163.comBackground: In recent years, PD-L1 has been primarily utilized as an immune checkpoint marker in cancer immunotherapy. However, due to tumor heterogeneity, the response rate to such therapies often falls short of expectations. In addition to its role in immunotherapy, PD-L1 serves as a specific target on the surface of tumor cells for targeted diagnostic and therapeutic interventions. There is an absence of a fully developed PD-L1-targeted diagnostic and therapeutic probe for clinical use, which constrains the exploration and clinical exploitation of this target.Methods and Results: In this study, we engineered a PD-L1-targeted probe with multimodal imaging and dual therapeutic functionalities utilizing organic melanin nanoparticles. Functionalization with the WL12-SH peptide endowed the nanoprobe with specific targeting capabilities. Subsequent radiolabeling with 89Zr (half-life: 100.8 hours) and chelation of Mn2+ ions afforded the probe the capacity for simultaneous PET and MRI imaging modalities. Cellular uptake assays revealed pronounced specificity, with -positive cells exhibiting significantly higher uptake than -negative counterparts (p < 0.05). Dual-modal PET/MRI imaging delineated rapid and sustained accumulation at the neoplastic site, yielding tumor-to-non-tumor (T/NT) signal ratios at 24 hours post-injection of 16.67± 3.45 for PET and 6.63± 0.64 for MRI, respectively. We conjugated the therapeutic radionuclide 131I (half-life: 8.02 days) to the construct and combined low-dose radiotherapy and photothermal treatment (PTT), culminating in superior antitumor efficacy while preserving a high safety profile. The tumors in the cohort receiving the dual-modality therapy exhibited significantly reduced volume and weight compared to those in the control and monotherapy groups.Conclusion: We developed and applied a novel -targeted multimodal theranostic nanoprobe, characterized by its high specificity and superior imaging capabilities as demonstrated in PET/MRI modalities. Furthermore, this nanoprobe facilitates potent therapeutic efficacy at lower radionuclide doses when used in conjunction with PTT. Keywords: theranostics, PET/MRI, melanin nanoparticles, photothermal therapy

Bin Zheng,1– 3,&ast; Fei Pan,1– 3,&ast; Minfei Shi,1– 3 Cuiping He,1– 3 Beibei He,1– 3 Rongrong Wang,1– 3 Guolian Ren,1– 3 Shuang Yang,4 Shuqiu Zhang1– 3 1School of Pharmacy, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China; 2Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China; 3Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China; 4School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shuang Yang, School of Basic Medical Sciences, Shanxi Medical University, No. 56, Xinjian South Road, Taiyuan, 030001, People’s Republic of China, Email yangshuangzz@126.com Shuqiu Zhang, School of Pharmacy, Shanxi Medical University, No. 56, Xinjian South Road, Taiyuan, 030001, People’s Republic of China, Email shuqiu.zhang@sxmu.edu.cnPurpose: Reducing the first-pass hepatic effect via intestinal lymphatic transport is an effective way to increase the oral absorption of drugs. 2-Monoacylglycerol (2-MAG) as a primary digestive product of dietary lipids triglyceride, can be assembled in chylomicrons and then transported from the intestine into the lymphatic system. Herein, we propose a biomimetic strategy and report a 2-MAG mimetic nanocarrier to target the intestinal lymphatic system via the lipid absorption pathway and improve oral bioavailability.Methods: The 2-MAG mimetic liposomes were designed by covalently bonding serinol (SER) on the surface of liposomes named SER-LPs to simulate the structure of 2-MAG. Dihydroartemisinin (DHA) was chosen as the model drug because of its disadvantages such as poor solubility and high first-pass effect. The endocytosis and exocytosis mechanisms were investigated in Caco-2 cells and Caco-2 cell monolayers. The capacity of intestinal lymphatic transport was evaluated by ex vivo biodistribution and in vivo pharmacokinetic experiments.Results: DHA loaded SER-LPs (SER-LPs-DHA) had a particle size of 70 nm and a desirable entrapment efficiency of 93%. SER-LPs showed sustained release for DHA in the simulated gastrointestinal environment. In vitro cell studies demonstrated that the cellular uptake of SER-LPs primarily relied on the caveolae- rather than clathrin-mediated endocytosis pathway and preferred to integrate into the chylomicron assembly process through the endoplasmic reticulum/Golgi apparatus route. After oral administration, SER-LPs efficiently promoted drug accumulation in mesenteric lymphatic nodes. The oral bioavailability of DHA from SER-LPs was 10.40-fold and 1.17-fold larger than that of free DHA and unmodified liposomes at the same dose, respectively.Conclusion: SER-LPs improved oral bioavailability through efficient intestinal lymphatic transport. These findings of the current study provide a good alternative strategy for oral delivery of drugs with high first-pass hepatic metabolism. Keywords: intestinal lymphatic transport, biomimetic liposomes, first-pass hepatic metabolism, oral delivery, dihydroartemisinin

Di Zhang,1,&ast; Yu Guan,1,&ast; Xiuxiu Zhou,1 Mingzi Zhang,2 Yu Pu,1 Pengchen Gu,2 Yi Xia,1 Yang Lu,2 Jia Chen,2 Wenting Tu,1 Kunyao Huang,2 Jixin Hou,2 Hua Yang,2 Chicheng Fu,2 Qu Fang,2 Chuan He,2 Shiyuan Liu,1 Li Fan1 1Department of Radiology, Second Affiliated Hospital, Naval Medical University, Shanghai, People’s Republic of China; 2Scientific Research Department, Shanghai Aitrox Technology Corporation Limited, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Fan; Shiyuan Liu, Department of Radiology, Second Affiliated Hospital, Naval Medical University, 415 Fengyang Road, Shanghai, 200003, People’s Republic of China, Tel +13564684699 ; +13761304518, Fax +86 21 63587668, Email czyxfl@smmu.edu.cn; radiology_cz@163.comPurpose: To develop a novel method for calculating small airway resistance using computational fluid dynamics (CFD) based on CT data and evaluate its value to identify COPD.Patients and Methods: 24 subjects who underwent chest CT scans and pulmonary function tests between August 2020 and December 2020 were enrolled retrospectively. Subjects were divided into three groups: normal (10), high-risk (6), and COPD (8). The airway from the trachea down to the sixth generation of bronchioles was reconstructed by a 3D slicer. The small airway resistance (RSA) and RSA as a percentage of total airway resistance (RSA%) were calculated by CFD combined with airway resistance and FEV1 measured by pulmonary function test. A correlation analysis was conducted between RSA and pulmonary function parameters, including FEV1/FVC, FEV1% predicted, MEF50% predicted, MEF75% predicted and MMEF75/25% predicted.Results: The RSA and RSA% were significantly different among the three groups (p< 0.05) and related to FEV1/FVC (r = − 0.70, p < 0.001; r = − 0.67, p < 0.001), FEV1% predicted (r = − 0.60, p = 0.002; r = − 0.57, p = 0.004), MEF50% predicted (r = − 0.64, p = 0.001; r = − 0.64, p = 0.001), MEF75% predicted (r = − 0.71, p < 0.001; r = − 0.60, p = 0.002) and MMEF 75/25% predicted (r = − 0.64, p = 0.001; r = − 0.64, p = 0.001).Conclusion: Airway CFD is a valuable method for estimating the small airway resistance, where the derived RSA will aid in the early diagnosis of COPD.Keywords: COPD, small airway disease, CT, fluid dynamics

Ke Li,1,2,&ast; Lupeng Qiu,1,2,&ast; Yang Zhao,3,&ast; Xiaohui Sun,1,2 Jiakang Shao,1 Chang He,1,2 Boyu Qin,4 Shunchang Jiao4 1Medical School of Chinese PLA, Beijing, 100853, People’s Republic of China; 2Department of Oncology, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 3Department of Vascular Intervention, Special Medical Center for Strategic Support Forces, Beijing, 100101, People’s Republic of China; 4Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shunchang Jiao; Boyu Qin, Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, 8 Dongdajie Street, Fengtai District, Beijing, 100071, People’s Republic of China, Email jiaosc@vip.sina.com; qpm2017@126.comPurpose: This study aims to investigate the process of small cell lung cancer (SCLC) patients from achieving optimal efficacy to experiencing disease progression until death. It examines the predictive value of the treatment response on progression free survival (PFS) and overall survival (OS) of SCLC patients.Patients and Methods: We conducted a retrospective analysis on 136 SCLC patients diagnosed from 1992 to 2018. Important prognostic factors were identified to construct nomogram models. The predictive performance of the models was evaluated using the receiver operating characteristic curves and calibration curves. Survival differences between groups were compared using Kaplan–Meier survival curves. Subsequently, an independent cohort consisting of 106 SCLC patients diagnosed from 2014 to 2021 was used for validation.Results: We constructed two nomograms to predict first-line PFS (PFS1) and OS of SCLC. The area under the receiver operating characteristic curves for the PFS1 nomogram predicting PFS at 3-, 6-, and 12-months were 0.919 (95% CI: 0.867– 0.970), 0.908 (95% CI: 0.860– 0.956) and 0.878 (95% CI: 0.798– 0.958), and for the OS nomogram predicting OS at 6-, 12-, and 24-months were 0.814 (95% CI: 0.736– 0.892), 0.819 (95% CI: 0.749– 0.889) and 0.809 (95% CI: 0.678– 0.941), indicating those two models with a high discriminative ability. The calibration curves demonstrated the models had a high degree of consistency between predicted and observed values. According to the risk scores, patients were divided into high-risk and low-risk groups, showing a significant difference in survival rate. And these findings were validated in another independent validation cohort.Conclusion: Based on the patients’ treatment response after standardized treatment, we developed and validated two nomogram models to predict PFS1 and OS of SCLC. The models demonstrated good accuracy, reliability and clinical applicability by validating in an independent cohort.Keywords: small cell lung cancer, treatment response, patient prognosis, nomogram prognostic model

Yu Huang,1,&ast; Shuyang Wu,1,&ast; Jingjing Li,1,2 Chenglin He,1 Yanfen Cheng,3 Nan Li,1 Yitao Wang,1,4 Yihan Wu,1 Jinming Zhang1 1State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Department of Rehabilitation Sciences, Faculty of Health and Social Sciences, Hong Kong Polytechnic University, Hong Kong, SAR, People’s Republic of China; 3Chengdu University, Chengdu, People’s Republic of China; 4Macau Center for Research and Development in Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinming Zhang; Yihan Wu, State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China, Email cdutcmzjm@126.com; yihanwuone@126.comBackground: Chemo-photodynamic combination therapy has demonstrated significant potential in the treatment of cancer. Triptolide (TPL), a naturally derived anticancer agent, when combined with the photosensitizer Chlorin e6 (Ce6), has shown to provide enhanced anti-tumor benefits. However, the development of stimuli-responsive nanovehicles for the co-delivery of TPL and Ce6 could further enhance the efficacy of this combination therapy.Methods: In this study, we synthesized a pH/ROS dual-responsive mPEG-TK-PBAE copolymer, which contains a pH-sensitive PBAE moiety and a ROS-sensitive thioketal (TK) linkage. Through a self-assembly process, TPL and Ce6 were successfully co-loaded into mPEG-TK-PBAE nanoparticles, hereafter referred to as TPL/Ce6 NPs. We evaluated the pH- and ROS-sensitive drug release and particle size changes. Furthermore, we investigated both the in vitro suppression of cellular proliferation and induction of apoptosis in HepG2 cells, as well as the in vivo anti-tumor efficacy of TPL/Ce6 NPs in H22 xenograft nude mice.Results: The mPEG-TK-PBAE copolymer was synthesized through a one-pot Michael-addition reaction and successfully co-encapsulated both TPL and Ce6 by self-assembly. Upon exposure to acid pH values and high ROS levels, the payloads in TPL/Ce6 NPs were rapidly released. Notably, the abundant ROS generated by the released Ce6 under laser irradiation further accelerated the degradation of the nanosystem, thereby amplifying the tumor microenvironment-responsive drug release and enhancing anticancer efficacy. Consequently, TPL/Ce6 NPs significantly increased PDT-induced oxidative stress and augmented TPL-induced apoptosis in HepG2 cells, leading to synergistic anticancer effects in vitro. Moreover, administering TPL/Ce6 NPs (containing 0.3 mg/kg of TPL and 4 mg/kg of Ce6) seven times, accompanied by 650 nm laser irradiation, efficiently inhibited tumor growth in H22 tumor-bearing mice, while exhibiting lower systemic toxicity.Conclusion: Overall, we have developed a tumor microenvironment-responsive nanosystem for the co-delivery of TPL and Ce6, demonstrating amplified synergistic effects of chemo-photodynamic therapy (chemo-PDT) for hepatocellular carcinoma (HCC) treatment.Keywords: triptolide, PDT, ROS, Ce6, pH responsive, hepatic carcinoma

Nanxing Huang, Yunqiu Che, Xiaju Hu, Jiajia Liu, Chaozhu He School of Nursing, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of ChinaCorrespondence: Chaozhu He, School of Nursing, Jiangxi Medical College, Nanchang University, 461 Bayi Street, Nanchang, People’s Republic of China, Tel +86 13803523962, Email 1250896898@qq.comAim: To evaluate the existing level of emergency capabilities among shared nurses and analyze the factors influencing these capabilities.Methods: An descriptive cross-sectional survey was conducted from September to October 2023, a purposive sampling method was employed to select 340 shared nurses as the subjects for investigation in Nanchang and Ganzhou cities of Jiangxi Province, as well as Wenzhou city in Zhejiang Province. A self - designed questionnaire on the emergency capabilities of shared nurses was utilized for data collection.Results: This investigation encompassed the collection of 340 valid questionnaires, assessing the overall emergency response proficiency of shared nurses. The cumulative score amounted to (170.81± 24.62), averaging (4.27± 0.62). It is noteworthy that the dimension scoring the highest was preparedness (4.33± 0.68), whereas the recovery capability dimension received the lowest score (4.17± 0.75). Through multiple linear regression analysis, it was determined that marital status, participation in emergency capability training, and experience in home nursing services significantly influenced the emergency capabilities of shared nurses (P< 0.05).Conclusion: Shared nurses in China demonstrate a moderately high level of emergency response capability. The marital status, participation in emergency capacity training, and on-site nursing service experience are pivotal factors influencing the emergency capabilities of shared nurses. Nursing administrators should prioritize the development of emergency capacity training and team building for shared nurses, establishing a scientifically standardized mechanism for training, assessment, and management. The implementation of performance evaluation mechanisms for shared nurses is crucial to enhance professional awareness within the workforce.Keywords: shared nurses, internet + nursing services, emergency capability, cross-sectional study, influencing factors analysis

Yujun He,1,2,&ast; Furui Miao,2,&ast; Cai He,1 Yushan Fan,2 Fangzhi Zhang,2 Pu Yang,3 Miaodong Wang,3 Jiujie He2 1Nancheng Branch Hospital, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Guangxi University of Chinese Medicine, Nanning City, People’s Republic of China; 2Faculty of Acupuncture, Moxibustion and Tui Na, Guangxi University of Chinese Medicine, Nanning City, People’s Republic of China; 3Graduate School of Guangxi University of Traditional Chinese Medicine, Guangxi University of Chinese Medicine, Nanning City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Cai He, Nancheng Branch Hospital, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Guangxi University of Chinese Medicine, No. 356 Nanmian Street, Xixiangtang District, Nanning City, 530011, People’s Republic of China, Email 578485231@qq.com Yushan Fan, Faculty of acupuncture, moxibustion and tui Na, Guangxi University of Chinese Medicine, 179 Mingxiu East Road, Xi Xiang Tang District, Nanning City, 530001, People’s Republic of China, Email doctorfanyushan@163.comBackground: Carpal tunnel syndrome (CTS) is the most prevalent upper limb compressive neuropathy. A considerable number of clinical trials and meta-analyses have provided evidence supporting the effectiveness of acupuncture in treating CTS. Nevertheless, the ideal choice of acupoints remains ambiguous.Objective: A data mining analysis was conducted with the objective of determining the most effective acupoint combinations and selection for CTS.Methods: A search was conducted across seven Chinese and English electronic bibliographic databases spanning from their inception to March 2023. Selected were clinical trials that evaluated the efficacy of acupuncture therapy for CTS, with or without randomised controlled methods. Data extraction mainly included acupoint prescriptions. Information such as first author, study design and study setting were also extracted. The principal outcomes comprised the clinical manifestations linked to CTS. Statistical descriptions were generated using Excel 2019. The analysis of association rules was conducted using SPSS Modeler 18.0. Using SPSS Statistics 26.0, exploratory factor analysis and cluster analysis were conducted.Results: 142 trials (including 86 RCTs and 56 non RCTs) were identified, and 193 groups of effective prescriptions involving 68 acupoints were extracted. The most frequently used acupoints were Da-ling (PC7), Nei-guan (PC6), He-gu (LI4), Wai-guan (TE5), and Yang-xi (LI5). The most frequently used meridians were the pericardial meridian and the large intestine meridian. The majority of special acupoints used were Five-shu points and Yuan-source points, with acupoints on the upper limbs being the most frequently used. The core acupoint groups were analyzed and 11 groups of association rules, 8 factors, and 5 effective cluster groups were obtained.Conclusion: The evidence-based acupoint selection and combinations of acupuncture therapy for carpal tunnel syndrome were provided by the findings of this study.Keywords: acupuncture, carpal tunnel syndrome, data mining, descriptive statistics, association rule analysis, exploratory factor analysis, cluster analysis

Lei Feng,1,&ast; Ning Zhang,1,&ast; Lan Luo,1,&ast; Jie Liu,1,&ast; Yong Yao,1,&ast; Ming-Sheng Gao,1,&ast; Jin Pan,1,&ast; Cai He2 1The Division of Gastroenterology and Hepatology, Suining Central Hospital, Suining City, Sichuan Province, People’s Republic of China; 2The Division of Gastroenterology and Hepatology, Yibin Second People’s Hospital, Yibin City, Sichuan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Feng, The Division of Gastroenterology and Hepatology, Suining Central Hospital, Suining City, Sichuan Province, People’s Republic of China, Tel +8618008258982, Email fenglei822@163.comBackground: Several studies suggest that Proteasome 26S Subunit, ATPase (PSMC) family genes are of great importance in tumor progression and spreading, but the study for systematic evaluation of the function of PSMC genes in hepatocellular carcinoma (HCC) is currently lacking.Methods: The functions of PSMC genes in HCC were analyzed using multiple online databases, including the TCGA database, GEO database, HPA database, cBioPortal database, DAVID, and KEGG pathway. Experiments were later conducted to verify PSMC expression.Results: High levels of PSMC gene expression were detected in HCC tissues and PSMCs exhibited potentially powerful abilities in diagnosing HCC patients. All PSMC proteins are expressed to varying degrees in HCC tissues and high expression of the PSMC genes lead to poor prognosis in patients with HCC. Moreover, DNA methylation involves the regulation of the expression of PSMC2 and PSMC5 in HCC, and the levels of methylation of PSMC2 or PSMC5 correlate positively with patient overall survival in HCC patients. The copy number alteration and mutation of PSMC genes were observed and related to the expression of PSMCs in HCC. Functional enrichment analysis showed that many highly co-expressed genes of PSMCs had a potential role in tumor progression and metastasis, which merited further in-depth study. Functional network analysis also suggests that the primary biological function of PSMC genes is the regulation of protein homeostasis and energy metabolism in HCC. Moreover, the expression levels of PSMCs are related to immune cell infiltrates and immunomodulatory factors in HCC.Conclusion: Our study indicates that PSMC genes are the potential target for precision immunotherapy and novel prognostic biomarkers for HCC.Keywords: Proteasome 26s Subunit, ATPase, PSMC, hepatocellular carcinoma, prognostic biomarkers, therapeutic targets

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

Rong Yin, Shasha Xu, Jing Zhu, Haiou Zhu, Chao He Department of Hepatobiliary Center Ward II, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Rong Yin, Department of Hepatobiliary Center Ward II, The First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing, 210029, People’s Republic of China, Email y13851709399@163.comBackground: Hilar cholangiocarcinoma (HCCA) is a common malignant tumor of the biliary system. Factors such as limited physical function, intractability, and high mortality caused by the tumor lead to negative emotions, such as anxiety and depression in patients. In this study, we investigated the risk factors for negative emotions in patients undergoing radical resection of HCCA during the perioperative period and its effect on prognosis to provide strategies for alleviating the negative emotional disorders of patients and improving prognosis.Methods: From September 2016 to August 2021, we retrospectively examined 205 patients with HCCA who underwent radical resection in our hospital. The incidence of negative emotions and the clinical parameters of patients were compared using Chi-square tests and t-tests. The independent risk factors for unfavorable feelings in patients during the perioperative period were determined using binary logistic regression. The key variables influencing the postoperative survival status of HCCA patients were identified using the log-rank univariate analysis and Cox proportional risk regression analysis.Results: The results of the binary logistic regression analysis showed that perioperative negative emotions were independently influenced by family monthly income (OR = 0.069), medical insurance (OR = 0.089), family care (OR = 0.013), sleep quality (OR = 0.071), TNF-α (OR = 5.851), and bile leakage (OR = 29.412) (P < 0.05). The age of the patient (OR = 2.003), preoperative CA19– 9 (OR = 2.038), lymph node metastases (OR = 2.327), and negative mood (OR = 3.054) were independent risk variables that affected the survival status of patients, as determined by the results of Cox regression analysis (P < 0.05).Conclusion: In this study, we found that anxiety and depression in patients undergoing radical operation of HCCA are related to family monthly income, medical insurance, sleep quality, family care, TNF-α, and bile leakage; also, negative emotions have adverse effects on prognosis.Keywords: hilar cholangiocarcinoma, radical resection, depression, anxiety, risk factors, prognosis

Chen He,1– 3,&ast; Huiyan Ding,4,&ast; Lubo Li,5 Jing Chen,6 Xiaofei Mo,1– 3 Yinan Ding,4 Wenjing Chen,4 Qiusha Tang,4 Yuetao Wang1– 3 1Department of Nuclear Medicine, the Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, People’s Republic of China; 2Institute of Clinical Translation of Nuclear Medicine and Molecular Imaging, Soochow University, Changzhou, Jiangsu Province, People’s Republic of China; 3Changzhou Clinical Medical Center, Changzhou, Jiangsu, People’s Republic of China; 4Medical School of Southeast University, Nanjing, People’s Republic of China; 5The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, People’s Republic of China; 6Taikang Xianlin Drum Tower Hospital, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiusha Tang; Yuetao Wang, Email panyixi-tqs@163.com; yuetao-w@163.comBackground: Radiation therapy (RT) is commonly used to treat glioblastoma, but its immunomodulatory effect on tumors, through mechanisms such as immunogenic cell death (ICD), is relatively weak. Gold nanoparticles (AuNPs) have been suggested as potential radio-sensitizers, but it is unclear if they can enhance radiation-induced ICD. This study aimed to investigate the potential of AuNPs to improve the effectiveness of radiation-induced ICD.Methods: G422 cells were treated with a combination of AuNPs and RT to induce cell death. Various assays were conducted to assess cell death, surface expression of CRT, and release of HMGB1 and ATP. In vitro co-culture experiments with bone marrow-derived dendritic cells (BMDCs) were performed to analyze the immunogenicity of dying cancer cells. Flow cytometry was used to measure the maturation rate of BMDCs. An in vivo mouse tumor prophylactic vaccination model was employed to assess immunogenicity.Results: The study findings presented here confirm that the combination of radiotherapy (RT) with AuNPs can induce a stronger ICD effect on glioblastoma cells compared to using RT alone. Specifically, treatment with AuNPs combined with RT resulted in the emission of crucial damage-associated molecular patterns (DAMPs) such as CRT, HMGB1 (479.41± 165.34pg/mL vs 216.04± 178.16 pg/mL, &ast;P< 0.05) and ATP (The release of ATP in the AuNPs + RT group was 1.2 times higher than in the RT group, &ast;P< 0.05). The proportion of BMDC maturation rate was higher in the group treated with AuNPs and RT compared to the group treated with RT alone. (32.53± 0.52% vs 25.03± 0.28%,&ast;&ast;&ast;P < 0.001). In the tumor vaccine experiment, dying tumor cells treated with AuNPs and RT effectively inhibited tumor growth in mice when exposed to living tumor cells.Conclusion: These results indicate that AuNPs have the ability to enhance RT-induced ICD.Keywords: Immunogenic cell death, Gold nanoparticles, Radiation therapy, Glioblastoma

Chunxiang He,1,2 Ze Li,1,2 Miao Yang,1,2 Wenjing Yu,1,2 Rongsiqing Luo,1,2 Jinyong Zhou,1,2 Jiawei He,1,2 Qi Chen,1,2 Zhenyan Song,1,2 Shaowu Cheng1,2 1School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of China; 2Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Zhenyan Song; Shaowu Cheng, Tel +86 073188458257, Email songzhenyan2013@hnucm.edu.cn; scheng@hnucm.edu.cnAbstract: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by complex pathophysiological features. Amyloid plaques resulting from extracellular amyloid deposition and neurofibrillary tangles formed by intracellular hyperphosphorylated tau accumulation serve as primary neuropathological criteria for AD diagnosis. The activation of microglia has been closely associated with these pathological manifestations. Non-coding RNA (ncRNA), a versatile molecule involved in various cellular functions such as genetic information storage and transport, as well as catalysis of biochemical reactions, plays a crucial role in microglial activation. This review aims to investigate the regulatory role of ncRNAs in protein expression by directly targeting genes, proteins, and interactions. Furthermore, it explores the ability of ncRNAs to modulate inflammatory pathways, influence the expression of inflammatory factors, and regulate microglia activation, all of which contribute to neuroinflammation and AD. However, there are still significant controversies surrounding microglial activation and polarization. The categorization into M1 and M2 phenotypes may oversimplify the intricate and multifaceted regulatory processes in microglial response to neuroinflammation. Limited research has been conducted on the role of ncRNAs in regulating microglial activation and inducing distinct polarization states in the context of neuroinflammation. Moreover, the regulatory mechanisms through which ncRNAs govern microglial function continue to be refined. The current understanding of ncRNA regulatory pathways involved in microglial activation remains incomplete and may be influenced by spatial, temporal, and tissue-specific factors. Therefore, further in-depth investigations are warranted. In conclusion, there are ongoing debates and uncertainties regarding the activation and polarization of microglial cells, particularly concerning the categorization into M1 and M2 phenotypes. The study of ncRNA regulation in microglial activation and polarization, as well as its mechanisms, is still in its early stages and requires further investigation. However, this review offers new insights and opportunities for therapeutic approaches in AD. The development of ncRNA-based drugs may hold promise as a new direction in AD treatment.Keywords: Alzheimer’s disease, non-coding RNA, neuroinflammation, microglia activation, miRNA, circRNA, lncRNA

Weiling Zhou,1 Qian Gao,1 Lianjing Wang,2 Weijing Li,2 Cuiying He,2 Yanting Li,3 Lei Feng,1 Wei Liu,2 Lihong Liu,2 Yuan Wang1 1Department of Endocrine and Metabolic Diseases, The Fourth Hospital of Hebei Medical University, Shijiazhuang, HeBei Province, 050000, People’s Republic of China; 2Department of Hematology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, HeBei Province, 050000, People’s Republic of China; 3Department of Glandular Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, HeBei Province, 050000, People’s Republic of ChinaCorrespondence: Lihong Liu, Department of Hematology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, HeBei Province, 050000, People’s Republic of China, Email liulihong111222@163.com Yuan Wang, Department of Endocrine and Metabolic Diseases, The Fourth Hospital of Hebei Medical University, Shijiazhuang, HeBei Province, 050000, People’s Republic of China, Email wyuan1111122222@163.comBackground: Diffuse large B-cell lymphoma (DLBCL) involving the breast, spleen, and bone in a male patient with hepatitis B virus (HBV) infection is extremely rare in clinical practice.Case Presentation: We report a case of DLBCL involving the breast, spleen, and bone (triple expression of Bcl-2+, Bcl-6+, and 70% positive C-mcy) in a male patient with HBV admitted to our hospital. The patient was treated with EPOCH× 4, lenalidomide+EPOCH× 2 chemotherapy, intermittent methotrexate intrathecal injections to prevent central invasion, and autologous stem cell transplantation (ASCT). The patient is currently in complete remission, and the follow-up time was 43 months.Conclusion: A patient with DLBCL involving the breast, spleen, and bone can be treated with a combination of multiple regimens. If the patient’s economic conditions permit it, ASCT can be considered.Keywords: breast, viral hepatitis B, diffuse large B-cell lymphoma, triple expression, autologous stem cell transplantation

Jiawei Cai,1– 3,&ast; Chao He,4,&ast; Jiaheng Xu,1– 3,&ast; Qiu He,1– 3 Jinye Su,1– 3 Zanyi Wu,1– 3 Yawen Xu1– 3 1Department of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, People’s Republic of China; 2Department of Neurosurgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, People’s Republic of China; 3Fujian Provincial Institutes of Brain Disorders and Brain Sciences, First Affiliated Hospital, Fujian Medical University, Fuzhou, People’s Republic of China; 4Department of Neurosurgery, Zhuji Affiliated Hospital of Wenzhou Medical University, Zhuji, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yawen Xu; Zanyi Wu, Department of Neurosurgery, The First Affiliated Hospital, Fujian Medical University, No. 20 Chazhong Road, Taijiang District, Fuzhou, Fujian, 350005, People’s Republic of China, Email xuyawen121314@163.com; kirby98@126.comObjective: To identify whether intracranial hematoma (ICH) evacuation improves the prognosis of patients with ruptured anterior communicating artery (AcomA) aneurysms concomitant with small ICHs (≥ 10 mL and < 25 mL).Methods: Data on patients diagnosed with small ICHs secondary to ruptured AcomA aneurysms who underwent surgery in our department between January 2010 and February 2018 was retrospectively analyzed. The patients were divided into two groups based on whether the hematoma was evacuated. The modified Rankin Scale (mRS) was used to assess prognosis six months after onset.Results: The study recruited 58 patients, 19 of whom underwent aneurysm clipping and ICH evacuation. While 33 patients underwent aneurysm clipping, 6 patients underwent coiling embolism without ICH evacuation. The average ICH volume was 15.27± 4.07 mL. In the hematoma-evacuated group, 13 (68.4%) patients had unfavorable outcomes (mRS scores of 4 to 6). In the non-evacuated hematoma group, 13 (33.3%) patients had unfavorable outcomes (P = 0.001), postoperative infarction occurred in 11 (57.9%) patients in the hematoma evacuation group and 9 (23.1%) patients in the other group (P = 0.009).Conclusion: ICH evacuation was associated with unfavorable outcomes and postoperative infarction in ruptured AcomA aneurysms with concomitant small hematomas (< 25 mL). Aneurysm clipping or coiling without ICH evacuation may be a safe and effective choice; however, further investigation is needed.Keywords: AcomA aneurysms, intracranial hematoma, infarction, prognosis, ICH evacuation

Dong Jia, Xueying Yuan, Chaoqun He, Faping Tu Department of Anesthesiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, People’s Republic of ChinaCorrespondence: Faping Tu, Department of Anesthesiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, People’s Republic of China, Tel +86-13808270833, Email tfpnc@163.comPurpose: Sufentanil has been widely used to inhibit the hemodynamic responses caused by tracheal intubation. Using intravenous lidocaine may reduce the dose of sufentanil and better maintain the hemodynamics. This study aimed to determine the effects of intravenous lidocaine on the median effective concentration (EC50) of sufentanil for endotracheal intubation in obese patients.Patients and Methods: This is a randomized, double-blind, up-and-down sequential allocation study. Fifty obese patients undergoing bariatric surgery were randomly allocated in a 1:1 ratio into the lidocaine group and the saline group. Anesthesia was induced using a target-controlled infusion of propofol and sufentanil. The effect-site concentration (Ce) of propofol was 3.5 μg/mL. The Ce of sufentanil for the first patient was 0.4 ng/mL, and the sufentanil dose for the next patient was determined according to the responses of the previous patient, using Dixon’s up-and-down sequential method with an interval of 0.05 ng/mL. When the target concentration of propofol and sufentanil was reached, lidocaine 1.5 mg/kg or the same volume of normal saline was infused over 3 min. Tracheal intubation was performed 3 min after the end of the lidocaine or normal saline infusion. Probit regression was used to calculate the EC50 and 95% confidence interval (CI) of sufentanil.Results: Thirty-eight patients completed this study. The EC50 of sufentanil was 0.36 ng/mL (95% CI: 0.31– 0.41 ng/mL) in the lidocaine group, which was significantly lower than 0.50 ng/mL (95% CI: 0.43– 0.62 ng/mL) in the saline group. In addition, compared with saline group, the dosage of sufentanil in lidocaine group decreased significantly during the test. The hemodynamics of the two groups were stable during the study period.Conclusion: Intravenous lidocaine 1.5 mg/kg decreased the EC50 of sufentanil required for tracheal intubation in obese patients undergoing bariatric surgery.Keywords: lidocaine, median effective concentration, sufentanil, obesity

Jilin Yang,1,&ast; Lingyi Li,2,&ast; Xiaolin Zhu,1 Chen He,1 Ting Li,1 Jiahong Qin,1 Yijie Wang1 1Department of Critical Care Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 2Department of Medical, Hangzhou Matridx Biotechnology Company, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yijie Wang, Tel +13888126379, Email 81543505@qq.comBackground: Surface pathogens in the ICU pose a global public health threat, especially to elderly patients who are immunocompromised. To detect these pathogens, unbiased methods such as metagenomic next-generation sequencing (mNGS) are increasingly utilized for environmental microbiological surveillance.Methods: In a six-month study from January to July 2022, we investigated microbial communities in Chinese geriatric ICUs by regularly monitoring multiple surfaces at three-month intervals. Using mNGS sequencing, we analyzed microorganisms present at eight specific locations within the ICU. Additionally, we compared pathogen profiles and drug resistance genes between patient cultures and environmental samples collected during the same period.Results: The microbial composition remained relatively stable over time, but significant differences in alpha diversities were observed among various surfaces such as floors, hands, pumps, trolleys, and ventilator inlets/outlets. Surfaces with high contact frequency for healthcare workers, including workstations, ventilator panels, trolleys, pumps, and beds, harbored pathogenic microorganisms such as Acinetobacter baumannii, Cutibacterium acnes, Staphylococcus haemolyticus, Pseudomonas aeruginosa, and Enterococcus faecium. Acinetobacter baumannii, particularly the carbapenem-resistant strain (CRAB), was the most frequently identified pathogen in geriatric ICU patients regardless of testing method used. The mNGS approach enabled detection of viruses, fungi, and parasites that are challenging to culture. Additionally, an abundance of drug resistance genes was found in almost all environmental samples.Conclusion: The microbial composition and abundance in the ICU remained relatively constant over time. The floor exhibited the highest microbial diversity and abundance in the ICU environment. Drug-resistant genes in the ICU environment may migrate between patients. Overall, mNGS is an emerging and powerful tool for microbiological monitoring of the hospital environment.Keywords: geriatric intensive care unit, environmental microorganisms, mNGS, infection and prevention and control, hospital-acquired infections

Yujun He,1 Furui Miao,1 Yushan Fan,1 Fangzhi Zhang,1 Pu Yang,2 Xinyi Zhao,3 Miaodong Wang,2 Cai He,1 Jiujie He1 1Faculty of Acupuncture, Moxibustion and Tui Na of Guangxi University of Chinese Medicine, Nanning, 530001, People’s Republic of China; 2Graduate School of Guangxi University of Traditional Chinese Medicine, Nanning, 530200, People’s Republic of China; 3Guangxi Zhuang Yao Medicine Center of Engineering and Technology, Guangxi University of Chinese Medicine, Nanning, 530200, People’s Republic of ChinaCorrespondence: Furui Miao; Yushan Fan, Faculty of Acupuncture, Moxibustion and Tui Na, Guangxi University of Chinese Medicine, 179 Mingxiu East Road, Xi Xiang Tang District, Nanning, Guangxi, 530001, People’s Republic of China, Email snowymiao@163.com; doctorfanyushan@163.comBackground: Piriformis syndrome (PS) is a common disease that is difficult to clinically treat, which seriously affects people’s health and living quality. Multiple clinical studies have demonstrated that acupuncture therapy is an effective treatment for PS, but the optimal method of various acupuncture methods has remained unknown. The aim of this study protocol is to compare the efficacy and the safety of different acupuncture methods for PS.Methods: We will search seven electronic bibliographic databases (PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, Chinese Biomedical Literature Database, and Chongqing VIP Database) from inception to June 2023. Randomized controlled trials (RCTs) will be selected for assessing the effectiveness of acupuncture therapy on PS. Primary outcome measure for this study is pain intensity, and the secondary outcomes are clinical symptoms and signs, physical activity, effective rate, and adverse events. Study selection, data extraction, and risk of bias assessment will be independently completed by at least two reviewers. Then, standard pairwise meta-analysis and network meta-analysis will be conducted using Revman 5.3, Stata V.15.1 and OpenBUGS V.3.2.3. The heterogeneity will be explored by subgroup, meta-regression, and sensitivity analysis, if applicable. Finally, Grading of Recommendations, Assessment, Development and Evaluation (GRADE) pro system will be used to evaluate the quality of evidence.Results: Our systematic review and network meta-analysis will identify the best acupuncture treatment method for PS patients.Conclusion: The results of our review will help decision-makers make educated choices regarding evidence-based acupuncture management options for PS.Prospero Registration Number: No. CRD42022335028.Keywords: piriformis syndrome, systematic review, network meta-analysis, protocol

Yujun He,1 Furui Miao,1 Yushan Fan,1 Fangzhi Zhang,1 Pu Yang,2 Xinyi Zhao,3 Miaodong Wang,2 Cai He,1 Jiujie He1 1Faculty of Acupuncture, Moxibustion and Tui Na, Guangxi University of Chinese Medicine, Nanning, People’s Republic of China; 2Graduate School, Guangxi University of Chinese Medicine, Nanning, People’s Republic of China; 3Guangxi Zhuang Yao Medicine Center of Engineering and Technology, Guangxi University of Chinese Medicine, Nanning, People’s Republic of ChinaCorrespondence: Yushan Fan, Faculty of Acupuncture, Moxibustion and Tui Na, Guangxi University of Chinese Medicine, 179 Mingxiu East Road, Xi Xiang Tang District, Nanning, People’s Republic of China, Email doctorfanyushan@163.comBackground: Carpal tunnel syndrome (CTS), as the most common compression neuropathy in the upper limb, can lead to upper limb dysfunction in patients. The effectiveness of acupuncture in treating CTS has been validated based on numerous clinical trials and meta-analyses, but questions remain, such as how to select the best acupoints. Our purpose is to conduct the first data mining analysis to identify the most effective acupoint selection and combinations for treating CTS.Methods: We will search 7 electronic bibliographic databases (PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, Chinese Biomedical Literature Database and Chongqing VIP Database) from inception to March 2023. Clinical trials assessing the effectiveness of acupuncture therapy on the management of CTS will be selected. Reviews, protocols, animal trials, case reports, systematic reviews, and meta-analyses will be excluded. The primary outcome measure will be clinical result associated with CTS. Descriptive statistics will be performed in Excel 2019. Association rule analysis will be performed in SPSS Modeler 18.0. Exploratory factor analysis and cluster analysis will be performed in SPSS Statistics 26.0.Results: This study will investigate the most effective acupoint selection and combinations for patients with CTS.Conclusion: Our findings will provide evidence for the effectiveness and potential treatment prescriptions of acupoint application for patients with CTS, helping clinicians and patients make a more informed decision together.Keywords: acupuncture, carpal tunnel syndrome, data mining, descriptive statistics, association rule analysis, exploratory factor analysis, cluster analysis

Xijing Huang,1,&ast; Yan Pan,1,&ast; Ya Liu,1,&ast; Zhou Zhou,1 Yinghui Zhang,1 Caiping Gao,1 Chong He1,2 1Department of Gastroenterology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chong He, Email herrickhoo@163.comBackground: Ulcerative colitis (UC) is a chronic relapsing remitting form of inflammatory bowel disease (IBD). Current disease monitoring includes evaluation of symptoms, fecal calprotectin, and colonoscopy. Due to limited availability of the latter two modalities in China, we sought a readily available, inexpensive, disease monitoring laboratory assessment. We recently identified a novel serological index (the neutrophil-to-bilirubin ratio, NBR) for monitoring disease activity in Crohn’s disease. However, the clinical significance has not been evaluated in UC. Here, we aimed to verify the hypothesis that NBR might be useful in monitoring clinical and endoscopic activity in patients with UC.Methods: To test our hypothesis, we conducted a single-center, retrospective study including a total of 188 patients with UC and 145 non-IBD controls. NBR was calculated to determine its practical value in monitoring disease activity (including clinical and endoscopic activity). Disease activity of UC was determined by the partial Mayo score and the Mayo endoscopic score (MES) system.Results: NBR was significantly higher in patients with UC than that in controls (12.10, IQR: 9.85– 16.69 versus 5.06, IQR: 3.94– 6.55; p < 0.001) and showed positive correlations with clinical and endoscopic disease activity in UC. Additionally, NBR was significantly lower in patients with endoscopic mucosal healing (MH) than that in those without endoscopic MH (8.81, IQR: 6.67– 11.67 versus 13.51, IQR: 11.04– 18.71; p < 0.001). Serial evaluation of NBR in a subset of patients demonstrated that NBR was significantly decreased during the MH stage compared with that during the endoscopically active stage.Conclusion: Our study suggests that NBR may be a promising candidate for assessing disease activity in UC, with potential for widespread clinical use and significant clinical implications.Keywords: ulcerative colitis, bilirubin, neutrophil-to-bilirubin ratio, mucosal healing

Pei Hu, Wei Wang, Chiyi He Department of Gastroenterology, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, People’s Republic of ChinaCorrespondence: Wei Wang, Department of Gastroenterology, Yijishan Hospital of Wannan Medical College, No. 2, Zheshan West Road, Wuhu, Anhui, 241000, People’s Republic of China, Tel +86-0553-5739316, Email wwwy@wnmc.edu.cnPurpose: Various hematological indicators have been reported to predict lymph node metastasis (LNM) in gastric cancer (GC) patients, but the relationship between FLR and LNM has not been studied. Therefore, the aim of this study was to evaluate the role of preoperative fibrinogen-to-lymphocyte ratio (FLR) in predicting LNM in patients with clinically node-negative (cN0) advanced gastric cancer (AGC).Patients and Methods: We retrospectively reviewed 571 eligible patients with primary AGC adenocarcinoma who underwent radical gastrectomy (discovery cohort). Patients were divided into high and low FLR groups according to the optimal cutoff value determined by Youden index. FLR is an independent predictor of LNM determined by logistic regression and validated in the validation cohort of 207 patients. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of FLR for LNM. The nonlinear relationship between FLR and LNM risk was assessed using restricted cubic spline. Sensitivity analyses were performed according to FLR quartiles to further assess the robustness of the results. The nomogram was built based on FLR and clinicopathological characteristics, and was evaluated by calibration curves, ROC curve analysis and decision curve analysis.Results: In the discovery cohort, the area under the curve (AUC) value for FLR to predict LNM was 0.592. There is a linear relationship between the FLR value and the risk of LNM, and the risk of LNM increased with FLR value. High FLR level is an independent risk factor for LNM, and the results of sensitivity analysis robust this finding. The nomogram for individual risk assessment performed well. Furthermore, we verified the FLR was an independent predictor of LNM in the validation cohort.Conclusion: FLR was an independent predictor of LNM in patients with cN0 AGC.Keywords: advanced gastric cancer, clinically node-negative, lymph node metastasis, fibrinogen-to-lymphocyte ratio, nomogram

Ying Lu,1,&ast; Weiqi Wang,1,&ast; Zijie Tang,1 Linan Chen,1 Min Zhang,2 Qiu Zhang,3 Lei Wu,4 Jun Jiang,5 Xiaolong Zhang,5 Chuan He,1 Hao Peng1,5,6 1Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou, People’s Republic of China; 2Department of Central Office, Suzhou National New and Hi-tech Industrial Development Zone Center for Disease Control and Prevention, Suzhou, People’s Republic of China; 3Department of Chronic Disease, Gusu Center for Disease Control and Prevention, Suzhou, People’s Republic of China; 4Department of Maternal and Child Health, Suzhou Industrial Park Center for Disease Control and Prevention, Suzhou, People’s Republic of China; 5Department of Tuberculosis Control, Suzhou Center for Disease Control and Prevention, Suzhou, People’s Republic of China; 6Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Peng; Chuan He, Department of Epidemiology, School of Public Health, Medical College of Soochow University, 199 Renai Road, Industrial Park District, Suzhou, 215123, People’s Republic of China, Tel +86 512 6588 0079, Email penghao@suda.edu.cn; hechuan@suda.edu.cnObjective: Rapid identification is critical for ischemic stroke due to the very narrow therapeutic time window. The objective of this study was to construct a diagnostic model for the rapid identification of ischemic stroke.Methods: A mixture population constituted of patients with ischemic stroke (n = 481), patients with hemorrhagic stroke (n = 116), and healthy individuals from communities (n = 2498) were randomly resampled into training (n = 1547, mean age: 55 years, 44% males) and testing (n = 1548, mean age: 54 years, 43% males) samples. Serum corin was assayed using commercial ELISA kits. Potential risk factors including age, sex, education level, cigarette smoking, alcohol consumption, obesity, blood pressure, lipids, glucose, and medical history were obtained as candidate predictors. The diagnostic model of ischemic stroke was developed using a backward stepwise logistic regression model in the training sample and validated in the testing sample.Results: The final diagnostic model included age, sex, cigarette smoking, family history of stroke, history of hypertension, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, fasting glucose, and serum corin. The diagnostic model exhibited good discrimination in both training (AUC: 0.910, 95% CI: 0.884– 0.936) and testing (AUC: 0.907, 95% CI: 0.881– 0.934) samples. Calibration curves showed good concordance between the observed and predicted probability of ischemic stroke in both samples (all P> 0.05).Conclusion: We developed a simple diagnostic model with routinely available variables to assist rapid identification of ischemic stroke. The effectiveness and efficiency of this model warranted further investigation.Keywords: ischemic stroke, serum corin, biomarker, prediction model

Yimin Han1 &ast;, Boya Wang2 &ast;, Han Gao,3 Chengwei He,3 Rongxuan Hua,4 Chen Liang,4 Sitian Zhang,4 Ying Wang,5 Shuzi Xin,3 Jingdong Xu3 1Department of Oral Medicine, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, People’s Republic of China; 2Undergraduate Student of 2018 Eight Program of Clinical Medicine, Peking University People’s Hospital, Beijing, 100083, People’s Republic of China; 3Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, People’s Republic of China; 4Department of Clinical Medicine, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, People’s Republic of China; 5Department of Dermatology, Beijing Tong Ren Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingdong Xu, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, No. 10, Xitoutiao, Youanmenwai, Fengtai District, Beijing, 100069, People’s Republic of China, Tel/Fax +86 10-8391-1469, Email xujingdong@163.comAbstract: The gut microbiota is the most abundant and diverse microbiota in the human body and the vagus nerve is the most widely distributed and complex nerve in the body, both of them are essential in maintaining homeostasis. The most important phenomenon is how they coordinate to regulate functions, which has attracted the great attention of scientists. The academic literature on the correlation with a host of intestinal diseases and even systemic diseases has revealed the bidirectional communication between the gut microbiota and the brain, which can be carried out via multiple patterns. In the review, firstly, we have a general overview of the gut microbiota and the gut microbiota-brain axis. Secondly, according to the distribution characteristics of the vagus nerve, we analyzed and summarized its function in the intestinal tract. At the same time, we have summarized the underlying mechanism of some behavior changes such as depressive and anxiety-like behaviors and related neurodegenerative diseases caused by the vagus nerve and intestinal microecological environment disorders, and then we also analyzed inconsistency of the experimental evidence in order to propose novel strategies for the clinical practice.Keywords: gut microbiota-brain axis, gut microbiota, brain, vagus nerve, behavior, neurodegenerative diseases

Lin Li,&ast; Pengwei Liu,&ast; Xiaoping Niu, Chiyi He Departments of Gastroenterology, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoping Niu; Chiyi He, Departments of Gastroenterology, Yijishan Hospital of Wannan Medical College, Wuhu, 241001, People’s Republic of China, Email 47440311@qq.com; hechiyi11@163.comIntroduction: Recently, the extraintestinal manifestations of Crohn’s disease (CD) have attracted more and more attention, among which interstitial lung disease (ILD) is a rare extraintestinal manifestation. Clinical presentation is polymorphic and pathogenesis remains unclear. The purpose of this article is to elaborate on these rare extraintestinal manifestations of CD, and the importance of short-term chest computed tomography (CT) for differential diagnosis is emphasized.Case Presentation: A 27-year-old male patient, who is a student, presented with chief complaints of “loose stools for 4 months, intermittent low-grade fever for 1 month”. The next day, he developed a high fever with a body temperature of 39.8°C. A chest CT scan revealed multiple patellar ground glass shadows which suggested ILD. In the time of Corona virus disease (COVID-19), novel coronavirus pneumonia was first suspected according to the patient’s history and symptoms, but laboratory examinations did not confirm. Colonoscopy showed multiple ulcers between the sigmoid colon to the terminal ileum, and pathology found epithelioid granuloma in submucosa. Moreover, a total gastrointestinal CT angiography showed that segmental leaping thickening of the bowel. Based on the above results, we ultimately made a diagnosis of CD. After using systemic steroid therapy, his fever was quickly relieved, and a follow-up chest CT showed that multiple patellar ground glass shadows were almost completely absorbed. Then, infliximab was used, and a repeat colonoscopy showed that intestinal ulcers were significantly improved.Conclusion: ILD is a rare extraintestinal manifestation of CD and reveals the excellent response to systemic steroid therapy. Manifestations of pulmonary disease associated with IBD are polymorphic; therefore; clinicians should be more vigilant regarding IBD-related ILD, especially when infectious causes have been excluded in the time of COVID-19. For those with ILD related to IBD, a short-term follow-up CT would be crucial.Keywords: Crohn’s disease, interstitial lung disease, steroid, infliximab

Can Feng,1,&ast; Shihui Hong,1,&ast; Rong Fan,1,&ast; Xinjie Shi,2 Zhao Ma,3 Changgui Li,4 Chenghao Liu,5 Cong He,6 Min Fan,1 Ruiping Wang7,8 1Department of Cardiology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, People’s Republic of China; 2Department of Neurology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, People’s Republic of China; 3Department of Acupuncture and Moxibustion, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, People’s Republic of China; 4Department of Hematology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, People’s Republic of China; 5Department of Endocrinology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, People’s Republic of China; 6Department of Gastroenterology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, People’s Republic of China; 7Clinical Research Center, Shanghai Skin Diseases Hospital, Tongji University, Shanghai, People’s Republic of China; 8School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Fan; Ruiping Wang, Email fanminyueyang@outlook.com; w19830901@126.comBackground: An epidemic of the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in March 2022, and over 600,000 cases were confirmed until early May 2022 in Shanghai, China. Data on Omicron infections are available in other countries, but the clinical features of patients in the Chinese population, especially in Shanghai, are still lacking. We collected data from a subset of asymptomatic and mildly ill patients to learn about the age and sex disparity of Omicron infection based on changes in cycle threshold values.Methods: The basic information of 325 patients who were consecutively admitted to the Shanghai Geriatrics Center was collected through medical records, and patients were tested for viral nucleic acid carriage using nasal swab samples during hospitalization. SAS 9.4 was used for data analysis, and a p value < 0.05% was considered statistically significant.Results: Among the 325 included patients, 58.8% were males, with a mean age of 47.2 years and 13.6 days of hospitalization on average. The average number of nucleic acid tests among female patients was 4.7, which was higher than that among male patients (4.1). The median value of the slope for cycle threshold (Ct) changes in the nucleic acid detection (NAD) test was 1.4. Logistic regression indicated that the proportion of slope for Ct changes > 1.5 was slightly higher among male patients than among female patients (odds ratio (OR) = 1.06, 95% confidence interval (CI): 0.68– 1.66), and patients aged < 45 years and 45– 59 years had a higher proportion of slope for Ct changes > 1.5 than patients aged ≥ 60 years. Ct values were more variable in the early stages of infection and stabilized in the later stages of infection.Conclusion: Among patients with mild illness or asymptomatic infection, the Ct value is a good, timely, and cost-effective method to reflect the recovery progress of patients. The slope of Ct changes was steeper among younger patients and male patients, which indicates faster disease recovery.Keywords: COVID-19, SARS-CoV-2, cycle threshold, Omicron, RT‒PCR, nucleic acid tests

Mingqiang Gong,1,2,&ast; Yunxia Shen,2,&ast; Wenbin Liang,2 Zhen Zhang,3 Chunxue He,4 Mingwu Lou,2 ZiYu Xu2 1Department of Acupuncture and Moxibustion, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, People’s Republic of China; 2Department of Radiology, Longgang Central Hospital, Shenzhen, People’s Republic of China; 3Department of Radiology, The Third People’s Hospital of Longgang District, Shenzhen, People’s Republic of China; 4Department of Radiology, Shenzhen Clinical Medicine College, Guangzhou University of Chinese Medicine, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingwu Lou; ZiYu Xu, Department of Radiology, Longgang Central Hospital, No. 6082, Longgang Avenue, Longgang District, Shenzhen, 518000, People’s Republic of China, Tel +86 13808854650 ; +86 13824321925, Email mingwulou@sina.com; xuziyu82@163.comPurpose: Methamphetamine use may cause severe neurotoxicity and cognitive impairment, leading to addiction, overdose, and high rates of relapse. However, few studies have systematically focused on functional impairments detected by neuroimaging in methamphetamine abstainers (MAs) during short-term abstinence. This study aimed to investigate effective connectivity, resting-state networks, and internetwork functional connectivity in MA brains to improve clinical treatment.Methods: Twenty MAs and 27 age- and education-matched healthy controls underwent resting-state functional magnetic resonance imaging. The amplitude of low-frequency fluctuations and Granger causality were analyzed to investigate disrupted brain regions and effective connectivity, respectively. Independent component analysis and functional network connectivity were used to identify resting-state networks and internetwork functional connectivity, respectively.Results: Compared with healthy controls, MAs demonstrated abnormal amplitudes of low-frequency fluctuations in the bilateral precuneus, left posterior cingulate cortex (PCC), left middle frontal gyrus (MFG), left superior parietal lobule, left supplementary motor area (SMA), and left inferior parietal lobule (IPL). Moreover, MAs showed decreased effective connectivity from the left PCC to the left precuneus, increased effective connectivity from the left precuneus to the left MFG and from the right precuneus to the left SMA, and altered functional connectivity within the default mode network (DMN), frontoparietal network, sensorimotor network, ventral attention network, cerebellar network, and visual network. Importantly, hyperconnectivity between the DMN and ventral attention network and hypoconnectivity between the DMN and cerebellar network as well as the DMN and frontoparietal network were demonstrated in MAs.Conclusion: Our study implies that in short-term methamphetamine abstinence, disruptions to the DMN and executive network may a play key role, providing new insights for early rehabilitation.Keywords: methamphetamine, abstinence, network, Granger causality analysis, independent component analysis

Weiling Zhou,1 Weijing Li,2 Cuiying He,2 Ruijuan Ma,2 Qian Gao,1 Yuan Wang,1 Lei Feng,1 Lihong Liu2 1Department of Endocrine and Metabolic Diseases, The Fourth Hospital of Hebei Medical University (Hebei Tumor Hospital), Shijiazhuang, People’s Republic of China; 2Department of Hematology, The Fourth Hospital of Hebei Medical University (Hebei Tumor Hospital), Shijiazhuang, People’s Republic of ChinaCorrespondence: Lihong Liu, Department of Hematology, The Fourth Hospital of Hebei Medical University (Hebei Tumor Hospital), Shijiazhuang, People’s Republic of China, Tel +86 13831177920, Email liulihong111222@163.comPurpose: To explore the effects of primary and secondary hyperglycemia and the application of the hypoglycemic drug metformin on the prognosis of patients with diffuse large B-cell lymphoma (DLBCL).Methods: We performed a retrospective analysis of 1767 DLBCL patients.Cox regression method was used for analysis to evaluate the prognostic factors, and the Kaplan-Meier method was used to draw a survival curve to analyze the effect of hyperglycemia and the hypoglycemic drug metformin on the progression-free survival (PFS) and overall survival (OS) of DLBCL patients.Results: Our study showed that patients with hyperglycemia tend to have higher age (age> 60 years), high body mass index (BMI)(≥ 24kg/m2), late Ann Arbor stage (III–IV), high international prognostic index (IPI) (3– 5 score), high lactic dehydrogenase (LDH) level (> 250U/L), bulky disease and comorbidity. Hyperglycemia affects the survival time of the DLBCL population (PFS: adjusted HR 1.41, 95% CI: 1.16– 1.70, P < 0.001, OS: adjusted HR 1.33, 95% CI:1.09– 1.61, P=0.004).Compared with the non-hyperglycemia group, the secondary hyperglycemia increase affects the prognosis of the DLBCL population (P< 0.001). Compared with the secondary hyperglycemia group, the primary hyperglycemia group has a poor prognosis (P< 0.05). For patients with DLBCL and hyperglycemia (732 patients in total), the use of metformin can improve their PFS and OS (PFS: adjusted HR 0.69, 95% CI: 0.49– 0.96, P=0.028, OS: adjusted HR 0.68, 95% CI: 0.49– 0.95, P=0.024).Conclusion: Hyperglycemia and secondary hyperglycemia are related to the poor prognosis of DLBCL population.For patients with DLBCL combined with hyperglycemia, the application of metformin can improve survival rate.Keywords: hyperglycemia, diffuse large B-cell lymphoma, metformin, recrudescence, death, prognosis

Xueying Zhang,1– 3,* Chen He,1– 3,* Peijun Ju,4,* Qingrong Xia,1– 3 Jianliang Gao,1– 3 Loufeng Zhang,1– 3 Xuequan Chen,1– 3 Hui Yuan,1– 3 Hua Gao,1– 3 Yang Zhang,1– 3 Junwei Yan,1– 3 Wen Xie,1– 3,* Cuizhen Zhu1– 3,* 1Affiliated Psychological Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Clinical Center for Psychiatry and Mental Health, Hefei Fourth People’s Hospital, Hefei, People’s Republic of China; 3Anhui Mental Health Center, Hefei, People’s Republic of China; 4Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Psychotic Disorders, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wen Xie; Cuizhen Zhu, Affiliated Psychological Hospital of Anhui Medical University, No. 316 Huangshan Road, Shushan District, Hefei, Anhui, People’s Republic of China, Tel +86 13339102285 ; +86 13705535258, Fax +86 055163616000, Email xiewen0808@sina.com; zhucuizhen88@126.comPurpose: The study aimed to clarify the cognitive impairments of schizophrenia with metabolic syndrome while evaluating their potential as risk factors.Patients and Methods: We recruited 153 participants and divided them into three groups according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria and the guideline standards for the prevention and treatment of dyslipidemia in Chinese adults in 2007 for metabolic syndrome, as follows: healthy control group (n = 47); nonmetabolic syndrome group (n = 58); and metabolic syndrome group (n = 48). Psychotic symptoms were evaluated using the Positive and Negative Syndrome Scale. Cognitive function and automatic thinking were estimated using the Montreal Cognitive Assessment Scale, Verbal Fluency Test, and Automatic Thoughts Questionnaire. Serum biochemical parameters were measured by automatic biochemistry analyzer.Results: One-way ANOVA analysis revealed that differential cognition impairments in schizophrenia patients compared to controls. Furthermore, results of multiple comparisons showed that more serious barriers in orientation, language fluency, and negative automatic thinking existed in the metabolic syndrome group than in the healthy and non-metabolic syndrome groups. Spearman correlation and stepwise linear regression analyses showed that psychopathological symptoms, high waist circumference, and high triglyceride were the predictive factors for negative automatic thoughts, orientation, and language fluency. Those results collectively revealed that high waist circumference, high triglyceride and negative automatic thinking had validity and effectiveness in predicting the cognitive function impairments of the metabolic syndrome group.Conclusion: The present findings strongly supported the notion that aberrant parameters of high waist circumference, high triglyceride and high negative automatic thoughts had validity and effectiveness predictive role for cognitive impairments in the schizophrenics with metabolic syndrome. The schizophrenia patients with metabolic syndrome should receive regular monitoring and adequate treatment for metabolic and psychological risk factors.Keywords: second-generation antipsychotics, negative symptoms, diet, Montreal Cognitive Assessment Scale, Verbal Fluency Test

Taoli Sun,1 Wenjuan Quan,1 Sha Peng,1 Dongmei Yang,2 Jiaqin Liu,3 Chaoping He,1 Yu Chen,2 Bo Hu,2 Qinhui Tuo2,4 1School of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, People’s Republic of China; 2School of Medicine, Hunan University of Chinese Medicine, Changsha, 410208, People’s Republic of China; 3Department of Pharmacy, the Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 4The First hospital of Hunan University of Chinese Medicine, Changsha, 410007, People’s Republic of ChinaCorrespondence: Qinhui Tuo, School of Medicine, Hunan University of Chinese Medicine, Changsha, 410208, People’s Republic of China, Tel +86-18874089105, Email qhtuo@aliyun.comBackground: Huo Luo Xiao Ling Dan (HLXLD), a famous Traditional Chinese Medicine (TCM) classical formula, possesses anti-atherosclerosis (AS) activity. However, the underlying molecular mechanisms remain obscure.Aim: The network pharmacology approach, molecular docking strategy, and in vitro validation experiment were performed to explore the potential active compounds, key targets, main signaling pathways, and underlying molecular mechanisms of HLXLD in treating AS.Methods: Several public databases were used to search for active components and targets of HLXLD, as well as AS-related targets. Crucial bioactive ingredients, potential targets, and signaling pathways were acquired through bioinformatics analysis. Subsequently, the molecular docking strategy and molecular dynamics simulation were carried out to predict the affinity and stability of active compounds and key targets. In vitro cell experiment was performed to verify the findings from bioinformatics analysis.Results: A total of 108 candidate compounds and 321 predicted target genes were screened. Bioinformatics analysis suggested that quercetin, dihydrotanshinone I, pelargonidin, luteolin, guggulsterone, and β-sitosterol may be the main ingredients. STAT3, HSP90AA1, TP53, and AKT1 could be the key targets. MAPK signaling pathway might play an important role in HLXLD against AS. Molecular docking and molecular dynamics simulation results suggested that the active compounds bound well and stably to their targets. Cell experiments showed that the intracellular accumulation of lipid and increased secretory of TNF-α, IL-1β, and MCP-1 in ox-LDL treated RAW264.7 cells, which can be significantly suppressed by pretreating with dihydrotanshinone I. The up-regulation of STAT3, ERK, JNK, and p38 phosphorylation induced by ox-LDL can be inhibited by pretreating with dihydrotanshinone I.Conclusion: Our findings comprehensively demonstrated the active compounds, key targets, main signaling pathways, and underlying molecular mechanisms of HLXLD in treating AS. These findings would provide a scientific basis for the study of the complex mechanisms underlying disease and drug action.Keywords: Huo Luo Xiao Ling Dan, atherosclerosis, network pharmacology, molecular docking, molecular dynamics simulation, dihydrotanshinone I, STAT3, MAPK signaling pathway

Yue Li,&ast; Dalei Zhou,&ast; Qing Liu, Weijie Zhu, Zulu Ye, Caiyun He Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Caiyun He; Zulu Ye, Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, No. 651, Dongfeng Road, Yuexiu District, Guangzhou, 510060, People’s Republic of China, Tel +86-18665593050 ; +86-15017590433, Fax +20-87340921, Email hecy@sysucc.org.cn; yezl@sysucc.org.cnPurpose: Fat mass and obesity-associated protein (FTO) and AlkB homolog 1 (ALKBH1) are m6A demethylases that have been demonstrated to be associated with the overall survival of patients with gastric cancer (GC). This study investigates the influence of genetic variants of FTO and ALKBH1 on susceptibility to GC.Patients and Methods: Potentially functional single nucleotide polymorphisms (SNPs) of FTO and ALKBH1 were genotyped in 419 patients with GC and 569 healthy controls by Kompetitive allele-specific PCR.Results: The AG and AG/AA variants of FTO rs2287142 were significantly associated with a decreased GC risk (for AG/AA vs GG: adjusted OR = 0.73, p = 0.020). The GA and GA/GG variants of ALKBH1 rs1076496 were closely correlated with an increased risk of GC in people aged ≥ 55 years (for GA/GG vs AA: adjusted OR = 1.51, p = 0.041) but showed a decreasing tendency of risk of GC in people aged < 55 years (adjusted OR = 0.85, p = 0.444). FTO rs2287142 and ALKBH1 rs1076496 conformed to the principle of a dominant model. FTO haplotype rs1421091-rs1421092-rs2287142-rs9939609 CTAT was closely associated with a lower risk of total GC (adjusted OR = 0.62, p = 0.023), while CTGA was linked with an increased risk of intestinal GC (adjusted OR = 2.51, p = 0.005). ALKBH1 rs1048147-rs1076496-rs11159286 CAC haplotype was significantly associated with a decreased risk of GC in people aged ≥ 55 years (adjusted OR = 0.41, p = 0.008). The FTO rs2287142-rs9939609 AG/AA-TT combination was associated with a decreased risk of GC only in the presence of rs1421091 TC/TT (adjusted OR = 0.70, p = 0.047), demonstrating that these FTO SNPs might have a cooperative effect on susceptibility to GC.Conclusion: FTO and ALKBH1 SNPs may have predictive value in evaluating susceptibility to GC with differing age or Lauren classification.Keywords: FTO, ALKBH1, gastric cancer, susceptibility, Lauren classification

Chunxue He,1,2,&ast; Mingqiang Gong,3,4,&ast; Gengxiao Li,1,2 Yunxia Shen,2 Longyin Han,5 Bin Han,6 Mingwu Lou2 1Shenzhen Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, People’s Republic of China; 2Department of Radiology, Longgang District Central Hospital of Shenzhen, Shenzhen, People’s Republic of China; 3The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, People’s Republic of China; 4Department of Acupuncture, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, People’s Republic of China; 5Department of Neurology, Beijing Longfu Hospital, Beijing, People’s Republic of China; 6Department of Rehabilitation Medicine, Longgang District Central Hospital of Shenzhen, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Han; Mingwu Lou, Tel +86 13928488998 ; +86 13808854650, Email hhbb08@163.com; mingwulou@sina.comPurpose: To investigate white matter alterations in post-stroke cognitive impairment (PSCI) patients at the subacute stage employing diffusion kurtosis and tensor imaging.Methods: Thirty PSCI patients at the subacute phase and 30 healthy controls (HC) underwent diffusion kurtosis imaging (DKI) scans and neuropsychological assessments. Based on the tract-based spatial statistics and atlas-based ROI analysis, fractional anisotropy (FA), mean diffusivity (MD), mean kurtosis (MK), kurtosis fractional anisotropy (KFA), axial kurtosis (AK), and radial kurtosis (RK) were compared in specific white matter fiber bundles between the groups (with family-wise error correction). Adjusting for age and gender, a partial correlation was conducted between neurocognitive assessments and DKI metrics in the PSCI group.Results: In comparison with the HC, PSCI patients significantly showed decreased MK, RK, and FA and increased MD values in the genu of corpus callosum, anterior limb internal capsule, and left superior corona radiata. In addition, DKI detected more white matter region changes in MK (31/48), KFA (40/48), and RK (25/48) than DTI with FA (28/48) and MD (21/48), which primarily consisted of the right cingulum, right superior longitudinal fasciculus, and left posterior limb of internal capsule. In the left anterior limb of internal capsule, MK and RK values were significantly negatively correlated with TMT-B (r = − 0.435 and − 0.414, P < 0.05), and KFA values (r = − 0.385, P < 0.05) of corpus callosum negatively associated with TMT-B.Conclusion: Combing DTI, DKI, and neuropsychological tests, we found extensive damaged white matter microstructure and poor execution performance in subacute PSCI patients. DKI could detect more subtle white matter changes than DTI metrics. Our findings provide added information for exploring the mechanisms of PSCI and conducting cognitive rehabilitation in the subacute stage.Keywords: diffusion kurtosis imaging, diffusion tensor imaging, subacute ischemic stroke, cognitive impairment

Zhoumeng Lin,1– 4,&ast; Wei-Chun Chou,1– 4,&ast; Yi-Hsien Cheng,3,4 Chunla He,5 Nancy A Monteiro-Riviere,6,7 Jim E Riviere7,8 1Department of Environmental and Global Health, College of Public Health and Health Professions, University of Florida, Gainesville, FL, USA; 2Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL, USA; 3Institute of Computational Comparative Medicine, Kansas State University, Manhattan, KS, USA; 4Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA; 5Department of Biostatistics, College of Public Health and Health Professions, University of Florida, Gainesville, FL, USA; 6Nanotechnology Innovation Center of Kansas State, Kansas State University, Manhattan, KS, USA; 7Center for Chemical Toxicology Research and Pharmacokinetics, North Carolina State University, Raleigh, NC, USA; 8 1Data Consortium, Kansas State University, Olathe, KS, USA&ast;These authors contributed equally to this workCorrespondence: Zhoumeng Lin, Department of Environmental and Global Health, College of Public Health and Health Professions, University of Florida, 1225 Center Dr., Gainesville, FL, 32610, USA, Tel +1 352-273-6160, Email linzhoumeng@ufl.eduBackground: Low delivery efficiency of nanoparticles (NPs) to the tumor is a critical barrier in the field of cancer nanomedicine. Strategies on how to improve NP tumor delivery efficiency remain to be determined.Methods: This study analyzed the roles of NP physicochemical properties, tumor models, and cancer types in NP tumor delivery efficiency using multiple machine learning and artificial intelligence methods, using data from a recently published Nano-Tumor Database that contains 376 datasets generated from a physiologically based pharmacokinetic (PBPK) model.Results: The deep neural network model adequately predicted the delivery efficiency of different NPs to different tumors and it outperformed all other machine learning methods; including random forest, support vector machine, linear regression, and bagged model methods. The adjusted determination coefficients (R2) in the full training dataset were 0.92, 0.77, 0.77 and 0.76 for the maximum delivery efficiency (DEmax), delivery efficiency at 24 h (DE24), at 168 h (DE168), and at the last sampling time (DETlast). The corresponding R2 values in the test dataset were 0.70, 0.46, 0.33 and 0.63, respectively. Also, this study showed that cancer type was an important determinant for the deep neural network model in predicting the tumor delivery efficiency across all endpoints (19– 29%). Among all physicochemical properties, the Zeta potential and core material played a greater role than other properties, such as the type, shape, and targeting strategy.Conclusion: This study provides a quantitative model to improve the design of cancer nanomedicine with greater tumor delivery efficiency. These results help to improve our understanding of the causes of low NP tumor delivery efficiency. This study demonstrates the feasibility of integrating artificial intelligence with PBPK modeling approaches to study cancer nanomedicine.Graphical Abstract: Keywords: artificial intelligence, machine learning, physiologically based pharmacokinetic modeling, nanomedicine, drug delivery, nanotechnology

Chaowen He, Dongxuan Huang, Fan Yang, Dongsheng Huang, Yahui Cao, Jianfeng Peng, Xiaohua Luo Department of Pulmonary and Critical Care Medicine, Shenzhen Longhua District Central Hospital, Shenzhen, 518110, Guangdong, People’s Republic of ChinaCorrespondence: Chaowen He, Department of Pulmonary and Critical Care Medicine, Shenzhen Longhua District Central Hospital, No. 187 Guanlan Avenue, Longhua District, Shenzhen, 518110, Guangdong, People’s Republic of China, Tel +86-18123964996, Email chaowh0331@163.comBackground: This study aims to investigate the expression and clinical value of long non-coding RNA (lncRNA) HEIH in peripheral blood of patients with non-small cell lung cancer (NSCLC).Methods: Healthy subjects (N=70), patients with lung squamous cell carcinoma (LUSC, N=70) and patients with lung adenocarcinoma (LUAD, N=80) were included. LncRNA HEIH expression in peripheral blood of included subjects was detected using RT-qPCR. According to the median expression of lncRNA HEIH, LUSC and LUAD patients were allocated into lncRNA HEIH high/low expression groups. The correlation between lncRNA HEIH and clinical indicators of patients was analyzed; Logistic multifactor regression was used to analyze the independent risk factors influencing lncRNA HEIH level. Receiver-operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of lncRNA HEIH and carcinoembryonic antigen (CEA) in LUSC/LUAD patients. MedCalc-Comparison of ROC curves was used to compare the area under ROC curve. The cumulative survival rates of lncRNA HEIH high/low expression group were analyzed by Kaplan–Meier curve. COX multivariate analysis was used to assess the independent factors affecting prognosis of NSCLC.Results: LncRNA HEIH in peripheral blood of LUSC/LUAD patients was higher than that in healthy controls, with no evident difference between LUSC and LUAD groups. In LUSC/LUAD patients, TNM stage, lymph node metastasis, distal metastasis, and CEA were independent risk factors affecting lncRNA HEIH; patients with high lncRNA HEIH expression had larger pack-years and tumor size, higher CEA level and tumor stage, and higher risk of lymph node metastasis and distal metastasis. LncRNA HEIH had higher diagnostic efficiency than CEA in NSCLC patients. High expression of lncRNA HEIH predicted poor prognosis in patients with NSCLC and was an independent risk factor for prognosis of NSCLC.Conclusion: High expression of lncRNA HEIH is helpful in the diagnosis of NSCLC and predicts poor prognosis.Keywords: non-small cell lung cancer, long non-coding RNA HEIH, prognosis, carcinoembryonic antigen, lung squamous cell carcinoma, lung adenocarcinoma, peripheral blood

Donglan Yuan,1,&ast; Ting Guo,2,&ast; DanDan Zhu,1 Hongshan Ge,1 Yinling Zhao,1 Aihua Huang,1 Xiaosu Wang,1 Xiuhong Cao,3 CuiQin He,1 Hua Qian,1 Hong Yu4 1Department of Obstetrics and Gynecology, Taizhou People’s Hospital Affiliated to YangZhou University, Taizhou, Jiangsu, 225300, People’s Republic of China; 2Center for Molecular Medicine, Taizhou People’s Hospital Affiliated to YangZhou University, Taizhou, Jiangsu, 225300, People’s Republic of China; 3Department of Operation, Taizhou People’s Hospital Affiliated to YangZhou University, Taizhou, Jiangsu, 225300, People’s Republic of China; 4Department of Pathology, Taizhou People’s Hospital Affiliated to YangZhou University, Taizhou, Jiangsu, 225300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hua QianDepartment of Obstetrics and Gynecology, Taizhou People’s Hospital Affiliated to YangZhou University, 399 Hailing Road, Hailing District, Taizhou, Jiangsu, 225300, People’s Republic of ChinaEmail qianhuayx333@126.comHong YuDepartment of Pathology, Taizhou People’s Hospital Affiliated to YangZhou University, 399 Hailing Road, Hailing District, Taizhou, Jiangsu, 225300, People’s Republic of ChinaEmail Yuhongyuhong1234@126.comBackground: Ovarian cancer is a life-threatening disease with a high mortality rate in women. Our previous work presented that long non-coding RNA (lncRNA) activated by transforming growth factor beta (TGF-β) (lncRNA ATB) played a role of oncogene in ovarian cancer. However, whether exosomal lncRNA ATB from ovarian cancer cells could regulate the tumorigenesis of ovarian cancer remains unclear.Methods: RT-qPCR assay was performed to evaluate the level of lncRNA ATB in cancer cells (SKOV3 and A2780). In addition, ovarian cancer cells-secreted exosomes were collected with ultracentrifugation. CCK8 assay was performed to detect the viability of ovarian cells and HUVECs. Meanwhile, Western blot was performed to detect the expression of mechanism related protein and tube formation assay was used to observe the angiogenesis of HUVECs. Finally, xenograft mice model was used to verify the role of ovarian cancer cell-derived exosomes in vivo.Results: Ovarian cancer cells-derived exosomes promoted the viability, angiogenesis and migration of HUVECs; however, knockdown of lncRNA ATB in HUVECs reversed these phenomena. In addition, exosomal lncRNA ATB promoted the tumorigenesis of ovarian cancer via regulating miR-204-3p/TGFβR2 axis. Furthermore, ovarian cancer cells-secreted exosomal lncRNA ATB increased tumor growth in vivo.Conclusion: Exosomal lncRNA ATB derived from ovarian cancer cells could improve tumor microenvironment via regulating miR-204-3p/TGFβR2 axis. Thus, this study might provide new knowledge for the treatment of ovarian cancer.Keywords: ovarian cancer, exosome, lncRNA ATB, TGFβR2, tumor microenvironment

Yuliang Wang,1– 3 Linna Peng,1– 3 Hongyan Lu,1– 3 Zhanhao Zhang,1– 3 Shishi Xing,1– 3 Dandan Li,1– 3 Chunjuan He,1– 3 Tianbo Jin,1– 3 Li Wang1– 3 1Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, 712082, Shaanxi, People’s Republic of China; 2Engineering Research Center of Tibetan Medicine Detection Technology, Ministry of Education, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, 712082, People’s Republic of China; 3Key Laboratory of High Altitude Hypoxia Environment and Life Health, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, 712082, People’s Republic of ChinaCorrespondence: Li Wang Tel +86-15706028826Email wangli_xzmd@163.comBackground: We aimed to enrich the pharmacogenomic information of a Blang population (BP) from Yunnan Province in China.Methods: We genotyped 55 very important pharmacogene (VIP) variants from the PharmGKB database and compared their genotype distribution (GD) in a BP with that of 26 populations by the χ2 test. The minor allele frequency (MAF) distribution of seven significantly different single-nucleotide polymorphisms (SNPs) was conducted to compare the difference between the BP and 26 other populations.Results: Compared with the GD of 55 loci in the BP, among 26 studied populations, GWD, YRI, GIH, ESN, MSL, TSI, PJL, ACB, FIN and IBS were the top-10 populations, which showed a significantly different GD > 35 loci. CHB, JPT, CDX, CHS, and KHV populations had a significantly different GD < 20 loci. A GD difference of 27– 34 loci was found between the BP and 11 populations (LWK, CEU, ITU, STU, PUR, CLM, GBR, ASW, BEB, MXL and PEL). The GD of five loci (rs750155 (SULT1A1), rs4291 (ACE), rs1051298 (SLC19A1), rs1131596 (SLC19A1) and rs1051296 (SLC19A1)) were the most significantly different in the BP as compared with that of the other 26 populations. The genotype frequency of rs1800764 (ACE) and rs1065852 (CYP2D6) was different in all populations except for PEL and LWK, respectively. MAFs of rs1065852 (CYP2D6) and rs750155 (SULT1A1) showed the largest fluctuation between the BP and SAS, EUR, AFR and AMR populations.Conclusion: Our data can provide theoretical guidance for safe and efficacious personalized drug use in the Blang population.Keywords: Blang population, single-nucleotide polymorphism, SNP, very important pharmacogene, genotype distribution, pharmacogenomics, personalized drug use

Yudong Ning,1 Hong Yang,2 Sheng Qin,2 Bangrong Cao,3 Zuxian Zhong,4 Chuanshi He,5 Guiquan Zhu6 1Department of Head and Neck Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2Department of Pathology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 3Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 4Department of Head and Neck Radiotherapy, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 5Sichuan Key Laboratory of Radiation Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610041, People’s Republic of China; 6Department of Head and Neck Oncology, West China Hospital of Stomatology, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, 610041, People’s Republic of ChinaCorrespondence: Guiquan ZhuDepartment of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Renmin South Road, Chengdu, Sichuan, 610041, People’s Republic of ChinaEmail zhugq@scu.edu.cnObjective: We aimed to identify new prognostic factors of oral squamous cell carcinoma (OSCC) among platelet-related parameters, establish a survival prediction model to predict the survival status of OSCC patients, and analyze the therapeutic effect of neoadjuvant chemotherapy on OSCC patients on the basis of real-world data.Materials and Methods: The real-world data of patients with OSCC confirmed by pathologic examination at Cancer Hospital from January 2011 to January 2015 and May 2017 to January 2020 were collected. We analyzed clinicopathologic factors using a Cox regression analysis, the Kaplan-Meier method, and propensity score matching (PSM).Results: The multivariate Cox regression analysis of not only validated the traditional prognostic factors such as tumor site, neural invasion, poor differentiation, and tumor-node-metastasis (TNM) stage but also identified a new prognostic factor, preoperative mean platelet volume (MPV) for overall survival (OS, HR, 0.47; 95% CI: 0.25– 0.89, P = 0.020). A nomogram was created to predict the probability of 3-year and 5-year OS. We found that neoadjuvant chemotherapy improved OS in patients with OSCC.Conclusion: Preoperative MPV, being associated with female, neoadjuvant chemotherapy, and advanced stage (Stage III and IV), may be a new prognostic factor for OS of patients with OSCC. The nomograms provided useful prediction for OS in OSCC patients. Neoadjuvant chemotherapy may improve the OS of patients with OSCC.Keywords: oral squamous cell carcinoma, overall survival, nomogram, mean platelet volume, neoadjuvant chemotherapy, induction chemotherapy

Kelun Wu,1– 3 Chuan He,1– 3 Yue Wu,1– 3 Xiaojie Zhou,1– 3 Pan Liu,1– 3 Wei Tang,1,3 Mei Yu,1,2 Weidong Tian1– 3 1State Key Laboratory of Oral Disease & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Oral Regenerative Medicine, West China School of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 2Engineering Research Center of Oral Translational Medicine, Ministry of Education, West China School of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 3Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610065, Sichuan, People’s Republic of ChinaCorrespondence: Mei YuState Key Laboratory of Oral Disease & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Oral Regenerative Medicine, West China School of Stomatology, Sichuan University, Chengdu, People’s Republic of ChinaEmail yumei925@hotmail.comWei TangDepartment of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of ChinaTel/Fax +86-28-85503499Email mydrtw@vip.sina.comPurpose: Small extracellular vesicles (sEV) play an irreplaceable role in cell–cell communication. However, sEV in solution aggregate with each other during preservation, leading to impairment of the structures, contents, and functions of sEV. Therefore, there is a need to develop an optimal preservation method that combines high recovery rate, low cost, convenience, and easy-transportation in one. In this study, a new preservation strategy different from the cryopreservation or lyophilization was developed by reducing sEV particles aggregation.Methods: The sEV were encapsulated in thermoresponsive gelatin methacryloyl (GelMA) hydrogels at 4°C to reduce particles aggregation during the reversible cross-linking process. The sEV movement was visualized in different mediums and particles’ number, size, structure and protein of 28 days preserved sEV were compared to fresh sEV. Human umbilical vein endothelial cells (HUVEC) and rat adipose-derived stromal stem cells (rASC) were isolated and cultured with fresh and preserved sEV to test the cellular response. A mice subcutaneous model was adopted to detect controlled release and angiogenesis ability of preserved sEV.Results: Through particles tracks visualization, GelMA hydrogels significantly decreased the sEV movement. After 28 days preservation in GelMA at 4°C, the particles number, size, structure and protein of sEV were similar to fresh sEV. In vitro, preserved sEV had the same ability to promote cell proliferation, migration and angiogenesis as fresh sEV. In vivo, preserved sEV-GelMA could artificially regulate the absorptivity of GelMA hydrogels and controlled released sEV for therapeutic application, and preserved sEV encapsulated in GelMA significantly promoted angiogenesis in mice.Conclusion: Our results demonstrated that sEV encapsulated in GelMA could be a novel strategy for long-term preservation of sEV for therapeutic application.Keywords: small extracellular vesicles, particle track visualization, preservation, controlled release, aggregation, gelatin methacryloyl hydrogel

Chen He,1 Huiyan Ding,1 Jing Chen,1 Yinan Ding,1 Rui Yang,2 Chunmei Hu,3 Yanli An,1 Dongfang Liu,1 Peidang Liu,1 Qiusha Tang,1 Zhiyuan Zhang4 1Medical School of Southeast University, Nanjing, People’s Republic of China; 2Research Institute for Reproductive Health and Genetic Diseases, The Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University, Wuxi, People’s Republic of China; 3Department of Tuberculosis, The Second Affiliated Hospital of Southeast University (The Second Hospital of Nanjing), Nanjing, People’s Republic of China; 4Department of Neurosurgery, Nanjing Jinling Hospital, Nanjing University, Nanjing, People’s Republic of ChinaCorrespondence: Qiusha TangMedical School of Southeast University, 87 Dingjiaqiao Road, Nanjing, People’s Republic of ChinaEmail panyixi-tqs@163.comZhiyuan ZhangDepartment of Neurosurgery, Nanjing Jinling Hospital, Nanjing University, Nanjing, People’s Republic of ChinaEmail zzy8896@163.comBackground: Inducing the immunogenic cell death of tumour cells can mediate the occurrence of antitumour immune responses and make the therapeutic effect more significant. Therefore, the development of treatments that can induce ICD to destroy tumour cells most effectively is promising. Previously, a new type of pH-sensitive polymersome was designed for the treatment of glioblastoma which represents a promising nanoplatform for future translational research in glioblastoma therapy. In this study, the aim of this work was to analyse whether chemoradiotherapy of the novel pH-sensitive cargo-loaded polymersomes can induce ICD.Methods: Cell death in U87-MG and G422 cells was induced by Au-DOX@PO-ANG, and cell death was analysed by CCK-8 and flow cytometry. The release of CRT was determined by using laser scanning confocal microscopy and flow cytometry. ELISA kits were used to detect the release of HMGB1 and ATP. The dying cancer cells treated with different treatments were cocultured with bone-marrow-derived dendritic cells (BMDCs), and then flow cytometry was used to determine the maturation rate of BMDCs (CD11c+CD86+CD80+) to analyse the in vitro immunogenicity. Tumour vaccination experiments were used to evaluate the ability of Au-DOX@PO-ANG to induce ICD in vivo.Results: We determined the optimal treatment strategy to evaluate the ability of chemotherapy combined with radiotherapy to induce ICD and dying cancer cells induced by Au-DOX@PO-ANG+RT could induce calreticulin eversion to the cell membrane, promote the release of HMGB1 and ATP, and induce the maturation of BMDCs. Using dying cancer cells induced by Au-DOX@PO-ANG+RT, we demonstrate the efficient vaccination potential of ICD in vivo.Conclusion: These results identify Au-DOX@PO-ANG as a novel immunogenic cell death inducer in vitro and in vivo that could be effectively combined with RT in cancer therapy.Keywords: immunogenic cell death, ICD, glioblastoma, radiotherapy, polymersomes, nanodrug delivery system

Ziyuan Shen,1,&ast; Fei Wang,2,&ast; Chenlu He,1,&ast; Dashan Li,3 Shanlin Nie,3 Zhenzhen Bian,3 Mingkang Yao,4 Yuhao Xue,5 Ying Wang,6 Weiying Gu,2 Taigang Zhu,7 Yuye Shi,5 Hao Zhang,4 Shuiping Huang,1,8 Yuqing Miao,9 Wei Sang3 On behalf of the Huaihai Lymphoma Working Group1Department of Epidemiology and Biostatistics, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 2Department of Hematology, The First People’s Hospital of Changzhou, Changzhou, Jiangsu, People’s Republic of China; 3Department of Hematology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 4Department of Hematology, Affiliated Hospital of Jining Medical University, Jining, Shandong, People’s Republic of China; 5Department of Hematology, The First People’s Hospital of Huaian, Huaian, Jiangsu, People’s Republic of China; 6Department of Personnel, Suqian First Hospital, Suqian, Jiangsu, People’s Republic of China; 7Department of Hematology, The General Hospital of Wanbei Coal-Electric Group, Suzhou, People’s Republic of China; 8Center for Medical Statistics and Data Analysis, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 9Department of Hematology, Yancheng First People’s Hospital, Yancheng, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei SangDepartment of Hematology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of ChinaTel +8613645207648Email xyfylbl515@xzhmu.edu.cnYuqing MiaoDepartment of Hematology, Yancheng First People’s Hospital, Yancheng, Jiangsu, People’s Republic of ChinaTel +8613851342032Email miaomiaomyq@163.comIntroduction: Immunonutritional status is associated with the survival of DLBCL. This multicenter retrospective study aimed to explore the prognostic value of Prognostic Nutrition Index (PNI) in DLBCL patients by using propensity score matched analysis (PSM).Methods: A total of 990 DLBCL cases were recruited from 5 centers of Huaihai Lymphoma Working Group (HHLWG). A 1:1 PSM analysis was performed using the nearest-neighbor method, with a caliper size of 0.02. Cox regression analysis was used to examine factors associated with survival.Results: The median age at diagnosis was 62 years and 52.5% were males, with the 3-y overall survival of 65.1%. According to the MaxStat analysis, 44 was the optimal cut-off point of PNI. After PSM analysis, a total of 282 patients in PNI < 44 group could be propensity matched to PNI ≥ 44 patients, creating a group of 564 patients. Multivariable analysis revealed that PNI, age, central nervous system involvement and International Prognostic Index (IPI) were independent prognostic factors for DLBCL. Kaplan–Meier analysis indicated that patients with low PNI in Ann Arbor Stage (III/VI), ECOG (< 2), IPI (LR+LIR), GCB, and BCL-2 negative groups had a poor prognosis.Discussion: PNI could accurately stratify the prognosis of DLBCL after PSM analysis.Keywords: diffuse large B-cell lymphoma, prognostic nutrition index, propensity score matched, prognosis

Chaobin He,1,&ast; Shuxin Sun,2,&ast; Yu Zhang,3,&ast; Shengping Li1 1Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 2Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong Province, People’s Republic of China; 3State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, 510060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shengping Li Email lishengp@mail.sysu.edu.cnBackground: Irreversible electroporation (IRE) is shown to not only improve the prognosis of patients with locally advanced pancreatic cancer (LAPC) but also activate the immune system. Considering the immune-activating function of IRE, IRE may enhance the effect of immune checkpoint inhibitors in the treatment of LAPC. We aimed to compare the effect and safety of IRE combined with toripalimab versus IRE alone for LAPC.Methods: We retrospectively collected data from LAPC patients treated with IRE plus toripalimab (240mg, 7 days after IRE) or IRE alone at Sun Yat‑sen University Cancer Center. Overall and progression-free survival and treatment-related adverse events were evaluated and compared.Results: From August 2015 to June 2020, a total of 85 patients were collected and analyzed in this study: 70 in the IRE group and 15 in the IRE plus toripalimab group. The IRE plus toripalimab group showed longer OS [44.33 months (95% CI 17.39– 71.27) versus 23.37 months (95% CI 21.20– 25.54), P=0.010] and PFS [27.5 months (95% CI not reached) versus 10.6 months (95% CI 7.79– 13.42), P=0.036], compared with IRE group. There were no treatment-related deaths in all patients of this study. Although pancreatic fistula, biliary fistula, abscess, vomiting and gastroparesis were a little more common in IRE plus toripalimab group, no significant differences in the rates of all adverse events between these two groups were observed.Conclusion: IRE plus toripalimab had acceptable toxic effects and might improve survival in LAPC compared with IRE alone.Keywords: locally advanced pancreatic cancer, irreversible electroporation, toripalimab, efficacy, prognosis

Ling Yu,1,&ast; Yang Chen,2,&ast; Xiang Xu,2 Qiwei Dong,2,3 Wenbo Xiu,2 Qinyuan Chen,2 Jinxia Wang,2 Chong He,2,3 Jian Ye,1 Fang Lu2,3 1Department of Ophthalmology, Daping Hospital, Army Medical Center, Army Medical University, Chongqing, People’s Republic of China; 2Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 3Medico-Engineering Cooperation on Applied Medicine Research Center, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fang LuClinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, 32 The First Ring Road West 2, Chengdu, Sichuan, 610072, People’s Republic of ChinaTel/Fax +86-028-87394201Email lufangfang@126.comJian YeDepartment of Ophthalmology, Daping Hospital, Army Medical Center, Army Medical University, No. 10, Changjiang Branch, Daping, Yuzhong District, Chongqing, 400042, People’s Republic of ChinaTel/Fax +86-023-68811229Email yejian1979@163.comBackground: Glaucoma is a group of retinal neurodegenerative diseases causing irreversible visual impairment. The pathogenesis of this disease is complicated. Studies have shown that the immune system is involved in the neurodegenerative process of glaucoma. There are continuous evidences that autoantibodies play a crucial role in the pathogenesis of glaucoma. However, focuses on B cells, the antibody-producing cells in glaucoma are surprisingly limited.Methods: Fresh peripheral blood samples were collected from 44 glaucoma patients (38 with primary angle-closure glaucoma (PACG) and 6 with (primary open-angle glaucoma POAG)) and 36 age-matched healthy donors (HD). Density gradient centrifugation was performed to obtain peripheral blood mononuclear cells (PBMC). Flow cytometry was performed to determine B cell phenotypes. The severity of glaucoma was determined based on the mean deviation (MD) of visual field.Results: In this study, we demonstrated that total B cells was significantly increased in glaucoma patients compared to HD. Next, we checked changes of different B cell subsets in glaucoma. Glaucoma patients were found to have a significant increase in the frequencies of antibody-secreting cells (ASC)/plasmablasts, naïve, and CD19+ CD27− IgD− double negative (DN) subpopulations, but a decrease in the CD27+ IgD+ unswitched memory compartment. Notably, we found that the increment of CD27− IgD− DN B cells was significantly magnified according to the clinical severity.Conclusion: We demonstrate, for the first time, that peripheral B cell subsets are altered and unveil the correlation of a newly identified pro-inflammatory CD27− IgD− DN subset with clinical features of glaucoma, suggesting that these B cell subsets could serve as potential biomarkers to monitor the disease progression of glaucoma patients.Keywords: glaucoma, B cells, CD27− IgD− double negative B cells, retinal neurodegeneration

Chunjuan He,1 Linna Peng,1 Shishi Xing,1 Dandan Li,1 Li Wang,1 Tianbo Jin1,2 1Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, 712082, People’s Republic of China; 2Key Laboratory for Basic Life Science Research of Tibet Autonomous Region, Xizang Minzu University, Xianyang, Shaanxi, 712082, People’s Republic of ChinaCorrespondence: Tianbo JinKey Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, #6, Wenhui East Road, Xianyang, 712082, Shaanxi, People’s Republic of ChinaTel/Fax +86-29-88895902Email jintianbo@gmail.comBackground: Genetic variation influences drug reaction or adverse prognosis. The purpose of this research was to genotype very important pharmacogenetic (VIP) variants in the Tibetan population.Methods and Materials: Blood samples from 200 Tibetans were randomly collected and 59 VIP variants were genotyped, and then compared our data to 26 other populations in the 1000 project to further analyze and identify significant difference.Results: The results showed that on comparing with most of the 26 populations from the 1000 project, rs4291 (ACE), rs1051296 (SLC19A1) and rs1065852 (CYP2D6) significantly differed in the Tibetan population. Furthermore, three significant loci were related to drug response. In addition, the allele frequency of Tibetans least differed from that of East Asian populations, and most differed from that of Americans.Conclusion: Three significant loci of variation ACE rs4291, SLC19A1 rs1051296 and CYP2D6 rs1065852 were associated with drug response. This result will contribute to improving the information of the Tibetan in the pharmacogenomics database, and providing a theoretical basis for clinical individualised drug use in Tibetans.Keywords: the Tibetan population, pharmacogenomics, VIP variants

Qingsong Wang,1 Xiu-ling Zhou,2 Guang-hai Mei,3 Jiantao Wang,1 Zhongyu Yu,1 Yue Hu,1 Xinyu Guo,1 Hanyu Zhang,1 Xiaodie Xu,4 Chengfeng He,4 Jingchun Guo,4 Yinghong Tao,5 Houguang Zhou1 1Department of Geriatrics, Huashan Hospital, National Clinical Research Center for Aging and Medicine, Fudan University, Shanghai, 200040, People’s Republic of China; 2Department of Ultrasonics, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China; 3Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China; 4National Key Laboratory of Medical Neurobiology, Institute of Brain Science, Fudan University, Shanghai, 200030, People’s Republic of China; 5Department of Medical Examination Center, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of ChinaCorrespondence: Houguang ZhouDepartment of Geriatrics of Huashan Hospital, National Clinical Research Center for Aging and Medicine, Fudan University, No. 24 Ward, Building 6, No.12 Middle WuLuMuQi Road, JingAn District, Shanghai, 200040, People’s Republic of ChinaTel +86-21-52887246Email zhouhouguang@huashan.org.cnYinghong TaoDepartment of Medical Examination Center of Huashan Hospital, Fudan University, Building 4, No. 12 Middle WuLuMuQi Road, JingAn District, Shanghai, 200040, People’s Republic of ChinaTel +86-21-52889087Email taoyinghong@huashan.org.cnAim: Metabolic inflammation syndrome (MIS) can lead to a series of complications, but its exact inflammatory mechanism is still unclear. The aim of this study was to explore the correlation between heparanase (HPA) and MIS, and the close relationship between HPA and other chronic low-grade inflammation index, such as C-reactive protein (CRP) and interleukin-6 (IL-6).Methods: A total of 105 patients with MIS in the physical examination population of Huashan Hospital affiliated to Fudan University from May to June 2018 were selected as the MIS group, and 52 patients who were relatively healthy during the same period were used as the control group. The basic clinical data of the selected candidates were collected, the levels of serum HPA, CRP and IL-6 were measured by ELISA, and the levels of blood glucose and blood lipids were also detected.Results: Compared with the control group, the levels of HPA, CRP, IL-6, FBG, HbA1C, and TG of MIS group were all significantly elevated (all P< 0.05), and HDL-C levels were considerably reduced (P< 0.05). Correlation analysis showed that there was a noticeably positive correlation between serum HPA level and CRP, IL-6 levels (P< 0.05).Conclusion: Higher HPA levels might play a certain role in the occurrence and development of MIS. There was a certain close correlation between serum HPA level and CRP and IL-6 levels, and which indicated that HPA was involved in the chronic low-grade inflammatory reaction process of MIS.Keywords: metabolic inflammatory syndrome, MIS, heparanase, HPA, C-reactive protein, CRP, interleukin-6, IL-6, chronic low-grade inflammation, CLGI

Xiaoli Liu,1,* Linna Peng,1,* Dandan Li,1 Chunjuan He,1 Shishi Xing,1 Yuhe Wang,2 Yongjun He1 1Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, 712082, People’s Republic of China; 2Department of Clinical Laboratory, The Affiliated Hospital of Xizang Minzu University, Xianyang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yongjun HeKey Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, #6 East Wenhui Road, Xianyang, 712082, Shaanxi, People’s Republic of ChinaTel +86-18691008772Email 545139647@qq.comBackground: Rheumatoid arthritis (RA), an autoimmune systemic inflammatory disease, largely resulted from genetic factor. Our purpose was to explore the association for IL1R1 and IL1R2 genetic variants with RA susceptibility in the Chinese Han population.Patients and Methods: A total of 508 RA patients and 494 controls were involved in this case–control study; single-nucleotide polymorphisms (SNPs) genotyping was identified by the Agena MassARRAY platform. The relationship between polymorphisms and RA susceptibility was calculated using the Pearson’s Chi-square test with odds ratios and 95% confidence intervals (CIs) in multiple genetic models. The Pearson’s Chi-square test and Student’s t-test were used for sample basic characteristic analysis. And linkage disequilibrium (LD) analysis and haplotype analysis were performed by logistic regression analysis.Results: The result from this study showed that rs2072472 (IL1R2) was an increased risk factor of RA (adjusted OR = 1.41, p = 0.011). Stratified analysis indicated SNPs rs10490571, rs956730, rs3917318 of IL1R1, and SNPs rs4851527, rs719250, rs3218896, rs3218977, rs2072472 of IL1R2 had impacts on RA risk after stratification based on gender and average age (54 years). Finally, haplotype analysis revealed that Ars3218977Ars2072472 haplotype in IL1R2 was related to a decreased RA risk (adjusted OR = 0.79; 95% CI = 0.65– 0.94; p = 0.010). Yet, rs3917225(IL1R1) and rs11674595(IL1R2) were not significant in RA association analysis.Conclusion: We determined SNPs (rs3917318, rs956730, rs1049057) of IL1R1 and SNPs (rs3218977, rs719250, rs4851527, rs3218896, rs2072472) of IL1R2 were correlated with the RA susceptibility in the Chinese Han population.Keywords: rheumatoid arthritis, RA, IL1R1/IL1R2, single-nucleotide polymorphism, SNP, susceptibility