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Fengyi Yang,1,2,* Qiaoyan Dong,3,* Zhuo Chen,1,2,* Benjian Gao,1,2,* Dongning Zheng,1,2 Rui Wang,1,2 Shu Qin,1,2 Fangyi Peng,1,2 Ming Luo,1,2 Jin Yang,1,2 Mengmei Nie,4 Bo Li,1,2 Xiaoli Yang1,2 1Department of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Academician (Expert) Workstation of Sichuan Province, Metabolic Hepatobiliary and Pancreatic Diseases Key Laboratory of Luzhou City, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 3Luzhou Senior High School, Luzhou, 646000, People’s Republic of China; 4Department of Urological Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bo Li; Xiaoli Yang, Email liboer2002@126.com; 344920646@qq.comPurpose: The efficacy of systemic therapy for hepatocellular carcinoma (HCC) is limited mainly by the complex tumor defense mechanism and the severe toxic side-effects of drugs. The efficacy of apatinib (Apa), a key liver cancer treatment, is unsatisfactory due to inadequate targeting and is accompanied by notable side-effects. Leveraging nanomaterials to enhance its targeting represents a crucial strategy for improving the effectiveness of liver cancer therapy.Patients and Methods: A metal polyphenol network-coated apatinib-loaded metal-organic framework-based multifunctional drug-delivery system (MIL-100@Apa@MPN) was prepared by using metal-organic frameworks (MOFs) as carriers. The nanoparticles (NPs) were subsequently characterized using techniques such as X-ray diffraction (XRD), transmission electron microscopy (TEM), zeta potential measurements, and particle size analysis. In vitro experiments were conducted to observe the drug release kinetics and cytotoxic effects of MIL-100@Apa@MPN on HepG2 cells. The in vivo anti-tumor efficacy of MIL-100@Apa@MPN was evaluated using the H22 tumor-bearing mouse model.Results: The formulated MIL-100@Apa@MPN demonstrates remarkable thermal stability and possesses a uniform structure, with measured drug-loading (DL) and encapsulation efficiency (EE) rates of 28.33% and 85.01%, respectively. In vitro studies demonstrated that HepG2 cells efficiently uptake coumarin-6-loaded NPs, and a significant increase in cumulative drug release was observed under lower pH conditions (pH 5.0), leading to the release of approximately 73.72% of Apa. In HepG2 cells, MIL-100@Apa@MPN exhibited more significant antiproliferative activity compared to free Apa. In vivo, MIL-100@Apa@MPN significantly inhibited tumor growth, attenuated side-effects, and enhanced therapeutic effects in H22 tumor-bearing mice compared to other groups.Conclusion: We have successfully constructed a MOF delivery system with excellent safety, sustained-release capability, pH-targeting, and improved anti-tumor efficacy, highlighting its potential as a therapeutic approach for the treatment of HCC.Keywords: metal-organic frameworks nanoparticles, apatinib, drug-targeting delivery, ferroptosis therapy, hepatocellular carcinoma

Shuo Qin, Michael WL Chee Centre for Sleep and Cognition, National University of Singapore, SingaporeCorrespondence: Michael WL Chee, Centre for Sleep and Cognition, National University of Singapore, Singapore, Email michael.chee@nus.edu.sgAbstract: The regularity of sleep/wake patterns across multiple days is emerging as an important determinant of health. However, the association between sleep regularity and health outcomes in the aging population is not well understood. The current systematic review identified 22 publications that examined the relationship between sleep regularity and selected health outcomes: cardiovascular risk, cognitive impairment, and mortality. All studies were published after 2010, reflecting a growing research interest in daily sleep regularity. Low sleep regularity was consistently associated with higher cardiovascular risk and elevated risk of all-cause mortality. Results on cognitive impairment are mixed, with inconsistency likely attributed to small sample sizes and differences in sleep regularity assessment. Overall, regularity in sleep carries important information about health and should be included in future studies that collect daily sleep measures. Gaps in literature and methodological shortcomings are discussed.Keywords: sleep regularity, Aging, cardiovascular health, cognitive impairment, mortality

Jun Mei Teng,1 Shuiqing Qin,2 Danyu Lu,1 Yefa Gu,3 Shi Jie Tang,3 Qiong Yan,1 Jiawei Yao,1 Chao Zhang1 1Laboratory Department, The Fifth People’s Hospital of Nanning, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Department of Science and Education, The Fifth People’s Hospital of Nanning, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China; 3Department of Psychiatry, The Fifth People’s Hospital of Nanning, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of ChinaCorrespondence: Danyu Lu, Laboratory Department, The Fifth People’s Hospital of Nanning, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China, Tel +86 13457087740, Email 297459717@qq.comPurpose: To investigate the CYP2C19 genotype distribution and allelic frequency among the Zhuang and Han schizophrenic populations in Guangxi, examine the correlation between CYP2C19 genetic variants and standardized blood levels of Valproic Acid (VPA) in schizophrenic patients, and evaluate the effects of age, gender, and Body Mass Index (BMI) on standardized VPA blood concentrations.Patients and Methods: Between February and December 2022, 192 Zhuang and Han schizophrenia patients treated with VPA were studied. Steady-state VPA concentrations were determined using homogeneous enzyme immunoassays, and CYP2C19 *1, *2, and *3 loci via q-PCR. CYP2C19 genotype distributions between Zhuang and Han groups in Nanning were compared using chi-square tests and contrasted with other ethnicities. Non-parametric tests analyzed VPA variations, identifying critical factors through multivariate stepwise regression.Results: The study identified five CYP2C19 genotypes at the *2 and *3 loci, with the *3/*3 genotype absent in both cohorts. The CYP2C19 distribution in Guangxi Zhuang and Han mirrors, yet diverges significantly from Hui and Kazakh groups. Among 192 subjects, VPA blood levels remained consistent across metabolic types and ages 18– 60 but varied significantly by gender. Multivariate analysis revealed gender and BMI as significant factors, overshadowing CYP2C19 genotype and age.Conclusion: In Guangxi, CYP2C19 genetic variants in Zhuang and Han schizophrenia patients demonstrate statistically indistinguishable allelic and metabolic distributions. Gender and BMI can influence standardized VPA blood concentrations in schizophrenia patients. However, in our study cohort, the CYP2C19 genotype and age are not the primary determinants of standardized VPA blood levels.Keywords: CYP2C19 gene, valproic acid, blood drug concentration, Zhuang Chinese, Han Chinese

Jiasheng Deng,1,* Le Qin,2,* Sulang Qin,3,* Ruisheng Wu,1 Guidong Huang,1 Yibin Fang,4 Lanlan Huang,4 Zhipin Zhou4 1School of Pharmacy, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530200, People’s Republic of China; 2Department of Pharmacy, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, 533000, People’s Republic of China; 3School of Graduate Studies, Youjiang Medical University for Nationalities, Baise, Guangxi, 533000, People’s Republic of China; 4Department of Pharmacy, Liuzhou People’s Hospital, Liuzhou, Guangxi, 545006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhipin Zhou, Department of Pharmacy, Liuzhou People’s Hospital, 8 Wenchang Road, Cheng Zhong District, Liuzhou, Guangxi, People’s Republic of China, Tel +86 − 18776921947, Email gxzhouzhipin@126.comAbstract: Pyroptosis is a novel pro-inflammatory mode of programmed cell death that differs from ferroptosis, necrosis, and apoptosis in terms of its onset and regulatory mechanisms. Pyroptosis is dependent on cysteine aspartate protein hydrolase (caspase)-mediated activation of GSDMD, NLRP3, and the release of pro-inflammatory cytokines, interleukin-1 (IL-1β), and interleukin-18 (IL-18), ultimately leading to cell death. Non-coding RNA (ncRNA) is a type of RNA that does not encode proteins in gene transcription but plays an important regulatory role in other post-transcriptional links. NcRNA mediates pyroptosis by regulating various related pyroptosis factors, which we termed the pyroptosis signaling pathway. Previous researches have manifested that pyroptosis is closely related to the development of liver diseases, and is essential for liver injury, alcoholic fatty liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), liver fibrosis, and liver cancer. In this review, we attempt to address the role of the ncRNA-mediated pyroptosis pathway in the above liver diseases and their pathogenesis in recent years, and briefly outline that TCM (Traditional Chinese Medicine) intervene in liver diseases by modulating ncRNA-mediated pyroptosis, which will provide a strategy to find new therapeutic targets for the prevention and treatment of liver diseases in the future.Keywords: non-coding RNA, pyroptosis, liver diseases, inflammasomes, gasdermin, traditional Chinese medicine

Shangren Qin,1 Xiaoyan Ni,2 Ye Ding3 1School of Public Health, Hangzhou Normal University, Hangzhou, Zhejiang, People’s Republic of China; 2Cangqian Street Community Health Service Center, Hangzhou, Zhejiang, People’s Republic of China; 3School of Public Health, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Ye Ding, School of Public Health, Hangzhou Medical College, 8 Yikang Street, Hangzhou, 311399, People’s Republic of China, Tel +86-571-87692813, Email dingye729@126.comconvenienBackground: There have been few studies concerning delayed medical attention among middle-aged and older adults, and in-depth analyses of delay duration and symptoms have been lacking.Methods: In this cross-sectional study exploiting a face-to-face questionnaire survey, we investigated delays in seeing a doctor among ≥ 45-year-old people in Zhejiang, China over the past year, and analyzed relevant influencing factors through logistics regression.Results: A total of 1034 people aged ≥ 45 years were enrolled, whose overall occurrence of delay in seeing a doctor was 28.24% (23.00% for older adults aged ≥ 60 years). Factors like the presence of 2 chronic diseases, intense social loneliness, and more health care needs contributed to the occurrence of delay in seeing a doctor (OR (95% CI) = 2.102 (1.252– 3.529); OR (95% CI) = 1.030 (1.002– 1.059); OR (95% CI) = 1.049 (1.002– 1.099). Contrastively, factors like convenient access to medical care and good self-reported health status inhibited such occurrence OR (95% CI) = 0.321 (0.199– 0.519); OR (95% CI) = 0.369 (0.183– 0.745). The foremost reason was wanting to wait and see if the problem would get better on its own (117, 40.07%). Respiratory system disease (14.90%), dental problems (13.82%), and cardiac disease (13.61%) constituted the top 3 types of diseases whose treatments were delayed. Additionally, for the majority of older adults, the delay duration was 1– 2 weeks (99, 33.90%), and the economic burden was the cause of the longest delay in seeing a doctor among middle-aged and older adults.Conclusion: To alleviate the problem of delay in seeing a doctor among middle-aged and older adults, their families and society should enhance care for them and reduce their sense of social loneliness. Emphasis should be placed by the government on helping middle-aged and older adults with financial difficulties so that their medical convenience can be improved.Keywords: middle-aged, older adults, delaying doctor visits, China, cross-sectional study

Xiaofeng Zhang,1,&ast; Jiaqi Zhang,1,&ast; Yongzhi Cai,1 Yue Li,1 Shiyun Qin,1 Jingtao Li,1 Decai Zeng,1 Tongtong Huang,1 Liu Liu Huang,2 Yanfen Zhong,1 Lihui Wei,1 Ji Wu1 1Department of Ultrasonic Medicine, the First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Cardiothoracic Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ji Wu, Email gxnnwuji@163.comBackground: Rheumatic mitral stenosis(RMS) may leads to left ventricular remodeling (LVR), which can persist even after valve surgery. Identifying markers for early structure and function in patients with rheumatic heart disease who are at risk for adverse LVR after surgery can help determine the optimal timing of intervention. This study aimed to investigate whether preoperative parameters of global left ventricular long-axis strain (LVGLS) and mechanical discretization (MD) could predict postoperative adverse LVR.Methods: A total of 109 adult patients with RMS and 50 healthy controls were enrolled in this study. Baseline clinical features, conventional echocardiography results, LVGLS, and MD were compared between the two groups. Pre- and post-surgery echocardiography measurements were collected, and adverse LVR was defined as a> 15% increase in left ventricular end-diastolic volume or > 10% decrease in left ventricular ejection fraction. Binary regression analysis was used to determine independent predictors of poor left ventricular remodeling.Results: The variables associated with adverse LVR in this study were LVGLS (P< 0.001, odds ratio: 1.996, 95% CI: 1.394– 2.856) and MD (P=0.011, odds ratio: 1.031, 95% CI: 1.007– 1.055). The poorly reconstructed group had lower absolute values of LVGLS and higher MD than the healthy control group and the non-poorly reconstructed group. A LVGLS cutoff of − 15.0% was the best predictor for patients with poorly reconstructed LVR (sensitivity: 75.7%; specificity: 100.0%; AUC: 0.93), and a MD cutoff of 63.8ms was the best predictor (sensitivity: 63.8%; specificity: 98.6%; AUC: 0.88).Conclusion: Speckle tracking echocardiography has potential value for predicting the progression of adverse LVR and for identifying non-responders among patients with RMS undergoing surgery.Keywords: rheumatic mitral stenosis, left ventricular remodeling, left ventricular global longitudinal strain, mechanical dispersion, speckle tracking echocardiography

Yuqin Feng,1,2 Si Qin,3 Huarun Li,3 Yemei Yang,1 Yushi Zheng,1 Hongsheng Liu,4 Wei Yin Yap,1,5 Xianyi Zhou,1 Ju Wen2,3 1Department of Dermatology, the Third Affiliated Hospital of Southern Medical University, Guangzhou, 510630, People’s Republic of China; 2The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510280, People’s Republic of China; 3Department of Dermatology, Guangdong Second Provincial General Hospital, Guangzhou, 510317, People’s Republic of China; 4Guangdong Huace Life Medicine Research Center, Guangzhou, 511450, People’s Republic of China; 5School of International Education of Southern Medical University, Guangzhou, 510515, People’s Republic of ChinaCorrespondence: Xianyi Zhou; Ju Wen, Email zxy1962@163.com; wenju3139@163.comBackground: Hydrogel dressings have been used as a crucial method to keep the wound wet and hasten the healing process. Due to safety concerns regarding the gel components, low mechanical adhesiveness, and unsatisfactory anti-inflammatory capacity qualities for practical uses in vivo, leading to the clinical translation of wound dressings is still difficult.Methods: A type of composite hydrogel (acrylamide/polyethylene glycol diacrylate/tannic acid, ie, AM/PEGDA/TA) by double bond crosslinking, Schiff base, and hydrogen bond interaction is proposed. The mechanical characteristics, adhesiveness, and biocompatibility of the hydrogel system were all thoroughly examined. Additionally, a full-thickness cutaneous wound model was employed to assess the in vivo wound healing capacity of resulting hydrogel dressings.Results: Benefiting the mechanism of multiple crosslinking, the designed composite hydrogels showed significant mechanical strength, outstanding adhesive capability, and good cytocompatibility. Moreover, the hydrogel system also had excellent shape adaptability, and they can be perfectly integrated into the irregularly shaped wounds through a fast in situ forming approach. Additional in vivo tests supported the findings that the full-thickness wound treated with the composite hydrogels showed quicker epithelial tissue regeneration, fewer inflammatory cells, more collagen deposition, and greater levels of platelet endothelial cell adhesion molecule (CD31) expression.Conclusion: These above results might offer a practical and affordable product or method of skin wound therapy in a medical context.Keywords: hydrogel dressing, tannins, multiple-crosslinking, anti-inflammatory, full-thickness wound healing

Dan Yang, Jing Ning, Xiaomin Liao, Haixing Jiang, Shanyu Qin Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of ChinaCorrespondence: Shanyu Qin, Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, No. 6. Shuangyong Road, Nanning, Guangxi, 53000, People’s Republic of China, Tel +86 139 7711 0511, Email qinshanyu@gxmu.edu.cnPurpose: Endoscopic ultrasound-guided fine-needle injection (EUS-FNI) offers a promising minimally invasive approach for locally targeted management of advanced pancreatic cancer. However, the efficacy is limited due to the rapid plasma clearance of chemotherapeutic agents. Injectable hydrogels can form drug release depots, which provide a feasible solution for optimizing targeted chemotherapy through EUS-FNI.Methods: A drug delivery system was developed, consisting of gemcitabine (GEM) and thermo-sensitive hydrogel (PLGA-PEG-PLGA, PPP). The injectability, gel formation ability, biocompatibility and sustained drug delivery properties of PPP hydrogel were verified in vitro and in vivo. The effects of GEM/PPP hydrogel on cell proliferation, invasion, metastasis, and apoptosis were explored through co-culturing with PANC-1 cells. The therapeutic effects of GEM/PPP hydrogel on xenograft mice were compared with those of GEM, ethanol and polidocanol using the precisely targeted EUS-FNI technology. Tumor sections were examined by H&E, Ki-67, and TUNEL staining.Results: GEM/PPP hydrogel exhibited excellent injectability, biocompatibility, and the capability of sustained drug delivery for up to 7 days by forming a gel triggered by body temperature. It demonstrated the best therapeutic effects, significantly reducing proliferation, invasion and migration of PANC-1 cells while promoting apoptosis. After precise injection using EUS-FNI technology, GEM/PPP hydrogel resulted in a reduction of tumor weight by up to 75.96% and extending the survival period by 14.4 days with negligible adverse effects. Pathological examination revealed no systemic toxicity and significant apoptosis and minimal proliferation as well.Conclusion: The combination of GEM/PPP hydrogel and EUS-FNI technology provides an optimal approach of precise chemotherapy for pancreatic cancer, builds a bridge for clinical translation of basic research, and brings great hope for innovation of minimally invasive treatment modalities. The first-hand EUS image data obtained in this study also serves as a crucial reference for future clinical trials.Keywords: drug delivery systems, thermo-sensitive hydrogel, endoscopic ultrasound-guided fine needle injection, pancreatic cancer, translational medical research

Mingyang Gao,1,&ast; Yanan Li,1,&ast; Jiaxu Yu,1 Wei Li,1 Shiji Qin,2 Yahui Zhang,3 Lian Zhu,4 Zhiyong Hou,4 Qiujun Wang1 1Department of Anesthesiology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, People’s Republic of China; 2Department of Foot and Ankle Surgery, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 3Department of Nursing, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 4Department of Orthopaedics, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiujun Wang, Department of Anesthesiology, Third Hospital of Hebei Medical University, No. 139, Ziqiang Road, Shijiazhuang City, Hebei, People’s Republic of China, Tel/Fax +86-311-8860-2072, Email wangqiujunsy@163.comPurpose: A single-injection nerve block provides excellent analgesia in a short time, but rebound pain after the nerve block disappears has attracted researchers’ attention. The aim of this study is to evaluate the effect of intravenous dexamethasone on rebound pain after adductor canal block (ACB) and popliteal sciatic nerve block in patients with ankle fracture.Methods: We recruited 130 patients with ankle fractures scheduled for open reduction and internal fixation (ORIF), each of whom received ACB and popliteal sciatic nerve block. Patients were divided into two groups: C (ropivacaine only) and IV (ropivacaine with intravenous dexamethasone). The primary outcome was the incidence of rebound pain. Secondary outcomes included the following: pain scores at 6 h (T1), 12 h (T2), 18 h (T3), 24 h (T4), and 48 h (T5) after operation; duration of the nerve block; number of presses of the analgesia pump and rescue analgesic consumption in the three-day postoperative period; quality of recovery scale (QoR-15 score); postoperative sleep quality; satisfaction of patients; and levels of serum inflammatory markers (IL-1β, IL-6, and TNF-α) six hours after surgery.Results: Compared with group C, the incidence of rebound pain in group IV was significantly reduced, and the duration of nerve block was extended by approximately nine hours (P< 0.05). Moreover, patients in group IV had significantly lower pain scores at T2-T4, lower levels of serum inflammatory markers (IL-1β, IL-6, and TNF-α), higher QoR-15 score two days after the operation, and satisfactory sleep quality the night after surgery (P< 0.05).Conclusion: Intravenous dexamethasone can reduce the rebound pain after adductor block and sciatic popliteal nerve block in patients with ankle fracture surgery, prolong the duration of nerve block, and improve the quality of early postoperative recovery.Keywords: dexamethasone, nerve block, postoperative analgesia, ankle fracture, rebound pain

Rui Song,1,2,&ast; Hanghang Ni,1,&ast; Juntao Huang,1,&ast; Chenglei Yang,1 Shangdong Qin,1,3 Huaning Wei,1 Jiefu Luo,1 Yuxiang Huang,1 Bangde Xiang1– 3 1Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 2Key Laboratory of Early Prevention and Treatment for Regional High-Frequency Tumors, Ministry of Education, Nanning, People’s Republic of China; 3Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bangde Xiang, Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, 71 Hedi Road, Qingxiu District, Nanning, Guangxi, 530021, People’s Republic of China, Tel +86-7715301253, Email xiangbangde@gxmu.edu.cnPurpose: The study aimed to investigate the ability of inflammation-immunity-nutrition score (IINS) and inflammatory burden index (IBI), individually or in combination, to predict prognosis of hepatocellular carcinoma (HCC) patients after hepatectomy.Methods: A total of 701 patients who underwent HCC resection at Guangxi Medical University Cancer Hospital were enrolled in the study. An IINS ranging from 0 to 3 was defined based on preoperative C-reactive protein (CRP), lymphocyte count, and serum albumin level, while an IBI was based on CRP and neutrophil-to-lymphocyte ratio. The prognostic value of IINS and IBI was assessed using univariate and multivariate Cox regression and Kaplan–Meier survival curves. The concordance index and calibration curve were used for internal validation of models. Decision curve analysis, net reclassification index and integrated discrimination improvement were used to compare the predictive performance of the models with traditional staging systems.Results: IINS and IBI were able to predict poor prognosis in HCC patients after hepatectomy, and a nomogram based on the IINS predicted survival at 1, 3, and 5 years better than other models or traditional staging systems.Conclusion: IINS may be accurate predictors of survival in HCC patients after hepatectomy, with potentially greater prognostic value than conventional markers.Keywords: hepatocellular carcinoma, inflammation-immunity-nutrition score, inflammatory burden index, prognosis, hepatectomy

Yunxu Tian,1 Yanbin Zhu,1,2 Kexin Zhang,1 Miao Tian,1 Shuhui Qin,2 Xiuting Li1 1Department of Orthopaedic Surgery, The 3rd Hospital of Hebei Medical University, Shijiazhuang, 050051, Hebei, People’s Republic of China; 2Hebei Bone Research Institute, Key Laboratory of Biomechanics of Hebei Province, Shijiazhuang, 050051, Hebei, People’s Republic of ChinaCorrespondence: Yanbin Zhu; Xiuting Li, Department of Orthopaedic Surgery, The 3rd Hospital of Hebei Medical University, Shijiazhuang, 050051, Hebei, People’s Republic of China, Email zhuyanbin111@126.com; lixiuting2021@126.comBackground: Pneumonia is a devastating complication following geriatric hip fracture surgery, and preoperative hypoalbuminemia may be a potentially modifiable factor leading to improved outcome. This study aimed to quantify the relationship between preoperative hypoalbuminemia and postoperative pneumonia.Methods: We retrospectively reviewed the medical records of elderly patients (≥ 60 years) who underwent surgeries for hip fracture in a tertiary referral center between 2016 and 2020. According to the preoperative serum albumin level, they were divided into two groups: < 35 g/ L and ≥ 35 g/ L. To reduce potential confounding, propensity score matching (PSM) in a 1:1 ratio was performed, with the caliper value set as 0.002; and further conditional logistic regression analysis was used to control the other potential confounders to determine the association strength.Results: Among 3,147 eligible patients included, PSM yielded 1,318 matched patients, with 659 in each respective group, suggesting significantly improved balance in most variables (standardized mean deviation improvement range, 20.7% to 99.1%), except for basophil count. The conditional logistic regression analysis, adjusted for PS and other intra- or post-operative variables, showed 6.18-fold (relative ratio, 6.18; 95% CI, 3.15– 11.98; P< 0.001) increased risk of postoperative pneumonia associated with preoperative hypoalbuminemia.Conclusion: Preoperative hypoalbuminemia was identified to be independently and highly associated with development of postoperative pneumonia in elderly patients undergoing hip fracture surgeries. However, whether the patients who had such condition may benefit from preoperative targeted nutritional support needs to be clarified by more prospective studies.Keywords: hip fracture, geriatric population, hypoalbuminemia, pneumonia

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

Boyan Liu,1– 3,&ast; Yunbo Xie,2,4,&ast; Jun Chen,4 Junli Xue,1– 3 Xiaoyi Zhang,2 Min Zhao,2 Xiubin Jia,2 Yiwei Wang,4 Shucun Qin1,2 1The Second Affiliated Hospital of Shandong First Medical University, Tai’an, 271000, People’s Republic of China; 2Taishan Institute for Hydrogen Biomedicine, Shandong First Medical University and Shandong Academy of Medical Sciences, Tai’an, 271000, People’s Republic of China; 3College of Basic Medical Sciences, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, People’s Republic of China; 4Department of General Practice, The Affiliated Hospital of Chengde Medical University, Chengde, 067000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shucun QinThe Second Affiliated Hospital of Shandong First Medical University, Tai’an, 271000, People’s Republic of ChinaTel/Fax +86 538 6222986Email scqin@sdfmu.edu.cnYiwei WangDepartment of General Practice, The Affiliated Hospital of Chengde Medical University, Chengde, 067000, People’s Republic of ChinaTel/Fax +86 314 2279511Email chengdewyw@126.comBackground: Molecular hydrogen (H2) has been recognized as an effective antioxidant with no or little side effects. While it is known that oxidative stress is closely associated with aging, the beneficial effect of H2 on oxidative stress-related aging is still unclear. In this study, a mouse model of D-galactose-induced aging was employed to investigate the protective effects of H2.Methods: The mice were administrated of H2 via different routes (4% H2 inhalation, H2-rich water drinking, and H2-rich saline injection), the aging-related biomarkers in plasma and the oxidative stress in different tissues were measured.Results: The results showed that H2 improved aging-related biomarkers, ie, total antioxidant capacity, advanced glycation end products, tumor necrosis factor-α, free fatty acids, and alanine aminotransferase in plasma. Furthermore, H2 alleviated oxidative stress in the liver, brain, and heart by reducing the levels of lipid peroxidation and malondialdehyde and increasing the activity of superoxide dismutase. In addition, it seems that 4% H2 inhalation was the most effective regarding the amount of H2 taken up and in reducing the markers of oxidative stress in some of the tissues; however, the other routes of administration resulted in the same efficacy in most indicators.Conclusion: H2 can prevent oxidative stress in D-galactose-induced aging mice when administered by different routes.Keywords: molecular hydrogen, administration routes, oxidative stress, aging, D-galactose

Shengmei Qin,1,&ast; Lan Huang,1,&ast; Jie Zhou,1 Hao Wang,1 Qi Li,1 Hengjing Wu,2 Jing Wu1 1School of Nursing, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Clinical Center for Intelligent Rehabilitation Research, Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Medicine, Tongji University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Wu; Hengjing Wu Tel +8613817556859Email jingwuclose@126.com; whjdata@126.comPurpose: To investigate the prevalence and related risk factors associated with coronary heart disease (CHD) among middle-aged and elderly patients with vision impairment (VI).Patients and Methods: The study was conducted with 1355 visually impaired adults over 45 years old, recruited from a Rehabilitation Hospital in China. Visual impairment is diagnosed by a doctor according to guidelines. Data were analyzed using multiple correspondence and logistic regression analysis. This research represents an important step towards the development of empirically based practical suggestions for decision-makers and health professionals that support visually impaired middle-aged and elderly people to participate in physical exercise and weight management when needed.Results: Of the 1335 middle-aged and elderly adults (mean age ± SD, 63.56 ± 7.74 years; 45.6% male) with VI, a total of 154 (11.5%) developed CHD. In all people with VI, age (OR 1.47; 95% CI 1.16– 2.02), hypertension (OR 2.14; 95% CI 1.46– 3.14), diabetes (OR 3.79; 95% CI 2.29– 6.27), blindness (OR 1.68; 95% CI 1.16– 2.43), moderate activity (OR 0.86; 95% CI 0.69– 0.98), and HR < 60 beats/min (OR 1.43; 95% CI 1.08– 2.48) are significantly related to CHD. Statistical analysis based on age grouping indicated that fasting plasma glucose, hypertension, diabetes, blindness, heart rate (< 60 beats/min), and moderate activity were shown to have a strong association with development of CHD in age group < 65 years (p < 0.05).Conclusion: Compared with historical data, poorer vision degree, resting heart rate below 60 beats a minute and low physical activity level are emerging as new and increasing threats to CHD in middle-aged and elderly VI population. Interventions to enhance physical functioning and risk screening may be effective in the prevention of CHD in VI population.Keywords: coronary heart disease, vision disability, prevalence, risk factors, physical activity

Shaomei Tang,1 Xiaoliang Huang,2 Haixing Jiang,1 Shanyu Qin1 1Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of ChinaCorrespondence: Shanyu QinDepartment of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of ChinaEmail qsy0511@163.comBackground: Pancreatic adenocarcinoma (PAAD) is an extremely malignant cancer. Immunotherapy is a promising avenue to increase the survival time of patients with PAAD.Methods: RNA sequencing and clinical data for PAAD were downloaded from the TCGA database. The ssGSEA method and weighted gene co-expression network analysis were used to calculate the relative abundance of tumor-infiltrating immune cells and identify the related modules. Least absolute shrinkage and selection operator (LASSO) and Cox regression analyses were used to construct a prognostic model. MCPcounter and EPIC were also used to assess immune cell components using gene expression profiles.Results: The B cells closely related module was identified, and five genes, including ARID5A, CLEC2B, MICAL1, MZB1, and RAPGEF1, were ultimately selected to establish a prognostic signature to calculate the risk scores of PAAD patients. Kaplan–Meier curves showed worse survival in the high-risk patients (p < 0.05), and the area under the receiver operating characteristic (ROC) curves of risk score for 1-year and 3-year survival were 0.78 and 0.80, respectively, based on the training set. Similar results were verified using the validated and combined sets. Interestingly, the low-risk group presented significantly elevated immune and stromal scores, proportion of B cells, and associations between these five genes and B cells were identified using multiple methods including ssGSEA, MCPcounter, and EPIC.Conclusion: This is the first attempt to study a B cells-related prognostic signature, which is instrumental in the exploration of novel prognostic biomarkers in PAAD.Keywords: B cells, prognostic signature, WGCNA, ssGSEA, pancreatic adenocarcinoma

Hui Li,1,* Shukui Qin,1,* Ying Liu,2 Zhendong Chen,3 Zhenggang Ren,4 Jianping Xiong,5 Zhiqiang Meng,6 Xiao Zhang,7 Linna Wang,7 Xiaojing Zhang,7 Jianjun Zou7 1Department of Medical Oncology Center, Bayi Affiliated Hospital, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2Department of Oncology, Cancer Hospital of Henan Province, Zhengzhou, People’s Republic of China; 3Department of Clinical Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 4Department of Clinical Oncology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 5Department of Clinical Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 6Minimally Invasive Treatment Center, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 7Jiangsu Hengrui Medicine Co., Ltd, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shukui QinDepartment of Medical Oncology Center, Bayi Affiliated Hospital, Nanjing University of Chinese Medicine, No. 34, 34 Biao, Yanggongjing Street, Nanjing, 210002, People’s Republic of ChinaTel + 86-25-80864541Email qinsk@csco.org.cnBackground: Immune checkpoint inhibitors and chemotherapy can synergistically increase efficacy in a variety of malignancies. We conducted this phase Ib/II study to assess the safety and efficacy of anti-PD-1 antibody camrelizumab in combination with FOLFOX4 for treatment-naive advanced hepatocellular carcinoma (aHCC).Methods: This open-label, multicenter phase Ib/II study (NCT03092895) enrolled patients with aHCC and without prior systemic treatment for treatment with camrelizumab (3 mg/kg) and FOLFOX4 every two weeks. First, six patients were enrolled, followed by an additional 28 patients after dose-limiting toxicity cases were determined to be < 33% of patients. The primary endpoint was tolerability and safety of treatment.Results: A total of 34 aHCC patients were enrolled and received study treatment. No dose-limiting toxicity were observed in the first six patients enrolled. Twenty-nine (85.3%) of the total 34 patients had grade ≥ 3 treatment-related adverse events (TRAEs), with the most common ones being decreased neutrophil count (55.9%) and decreased white blood cell count (38.2%). No TRAEs-related deaths occurred. The objective response and disease control rate were 29.4% (95% CI, 15.1– 47.5) and 79.4% (95% CI, 62.1– 91.3), respectively. The median duration of response, progression-free survival, and overall survival was 6.9 months (range, 3.3– 11.5), 7.4 months (95% CI, 3.9– 9.2), and 11.7 months (95% CI, 8.2– 22.0), respectively.Conclusion: Camrelizumab combined with FOLFOX4 for first-line treatment of patients with aHCC showed good safety and tolerability, with promising preliminary antitumor activity.Keywords: PD-1 monoclonal antibody, camrelizumab, FOLFOX4 regimen, hepatocellular carcinoma, combination therapy

Wei Li,1 Yinan Gong,1 Jingyi Liu,1 Yongming Guo,1– 3 Huiling Tang,1 Siru Qin,1 Yadan Zhao,1 Songtao Wang,1 Zhifang Xu,1– 3 Bo Chen1– 3 1Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 2School of Acupuncture & Moxibustion and Tuina, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, People’s Republic of China; 3National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300381, People’s Republic of ChinaCorrespondence: Zhifang XuSchool of Acupuncture & Moxibustion and Tuina, Tianjin University of Traditional Chinese Medicine, No. 10 Poyang Lake Road, Tuanbo New Town, Jinghai District, Tianjin, 301617, People’s Republic of ChinaTel +86-22-5959-6290Fax +86-22-2748-5189Email xuzhifangmsn@hotmail.comBo ChenSchool of Acupuncture & Moxibustion and Tuina, Tianjin University of Traditional Chinese Medicine, No. 10 Poyang Lake Road, Tuanbo New Town, Jinghai District, Tianjin, 301617, People’s Republic of ChinaTel +86-22-5959-6290Fax +86-22-2748-5189Email tjutcmchenbo@163.comAbstract: Chronic low back pain (CLBP), lasting > 3 months, is the end result of multiple pathogenic factors. Unfortunately, little is known about CLBP pathogenesis, which limits its advancements in clinical therapy and disease management. This paper summarizes the known pathological axes of CLBP, involving both peripheral and central systems. In particular, this paper details injurious nerve stimulation, inflammation-induced peripheral pathway, and central sensitization. Lumbar components, such as intervertebral disc (IVD), facet joints, muscles, fascia, ligaments, and joint capsules, contain pain receptors called nociceptors. Degeneration of the aforementioned lumbar components activates inflammatory pathways, which can directly damage nerves, lower nociceptor threshold to fire action potentials (AP), and cause pain. Additionally, damaged lumbar IVDs and endplates can also lead to the pathologic invasion of nerve growth and innervation, followed by the compression of herniated IVDs on nerve roots, thereby causing traumatic neuropathic pain. The central mechanism of CLBP involves alteration of the sensory processing of the brain and malfunction of the descending pain modulatory system, which facilitates pain amplification in the center nervous system (CNS). Lastly, abnormalities in the brain biochemical metabolism, activation of glial cells, and subsequent inflammation also play important roles in CLBP development. Taken together, inflammation plays an important role in both peripheral and central sensitization of CLBP. Due to the heterogeneity of CLBP, its pathological mechanism remains complex and difficult to understand. Therefore, it is a worthy field for future research into the subcomponents of CLBP pathogenesis, in order to distinguish the specific form of the disease, identify its origins, and develop corresponding highly effective comprehensive therapy against CLBP.Keywords: chronic low back pain, inflammation, degeneration, nerve innervation, central sensitization

Shuyi Qin,1,2,* Xinjuan Yu,1,2,* Qianli Ma,3,* Li Lin,4 Qinghai Li,1,2 Hong Liu,1,2 Lei Zhang,5 Shuguang Leng,6 Wei Han1,2 1Department of Pulmonary and Critical Care Medicine, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, Shandong, People’s Republic of China; 2Respiratory Disease Key Laboratory of Qingdao, Qingdao Municipal Hospital, Qingdao, Shandong, People’s Republic of China; 3Department of Radiology, Qingdao Municipal Hospital, Qingdao, Shandong, People’s Republic of China; 4Department of Pulmonary Medicine, Shandong Provincial Chest Hospital, Jinan, Shandong, People’s Republic of China; 5Department of Hospital Infection, Qingdao Municipal Hospital, Qingdao, Shandong, People’s Republic of China; 6Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM, USA*These authors contributed equally to this workCorrespondence: Wei HanDepartment of Pulmonary and Critical Care Medicine, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No. 5 Donghaizhong Road, Qingdao, Shandong, People’s Republic of ChinaTel +86 532 85937579Email hanw@qdu.edu.cnShuguang LengDepartment of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM, USATel +1 505 3489465Email sleng@salud.unm.eduPurpose: To explore a practical marker for quantitatively analyzing the small airway remodeling in COPD by HRCT.Patients and Methods: Twenty-four patients with COPD (GOLD I, n = 7; GOLD II, n = 8; GOLD III+IV, n = 9) and 14 healthy controls (7 normal pulmonary function; 7 small-airway disease (SAD)) were enrolled in the study as five groups, GOLD I, GOLD II, GOLD III+IV, normal and SAD. All subjects underwent HRCT and spirometry. With ISP 9.0, whole emphysema index (EI) and the airway parameters, including wall area (WA), lumen area (LA), airway area (AA) of the 3rd, 5th and 9th generations of bronchi, were measured successively. The ratio of LA/AA and WA/AA in the 3rd, 5th and 9th generations of bronchi were calculated and compared among groups.Results: For the five groups, EI was increased only in GOLD III+IV group (P < 0.05), while the ratio of LA/AA (9-LA/AA) and WA/AA (9-WA/AA) in 9th generation of bronchi have significantly changed since SAD group (P < 0.05). There were significant correlation between FEV1generations of bronchi (r3 = 0.429, r5 = 0.583, r9 = 0.592, respectively, P < 0.05); FEV1% and WA/AA (r3 = – 0.428, r5 = – 0.532, r9 = – 0.570, respectively, P < 0.05); as well as MMEF% and LA/AA (r3 = 0.421, r5 = 0.566, r9 = 0.610, respectively, P < 0.05); MMEF% and WA/AA (r3 = – 0.421, r5 = – 0.529, r9 = – 0.593, respectively, P < 0.05).Conclusion: Small airway remodeling has occurred in the early stage of COPD, while emphysema in the late stage of COPD. The 9-LA/AA and 9-WA/AA are accurate and practical markers for small airway remodeling of COPD.Keywords: COPD, high-resolution CT, emphysema index, pulmonary function test

Zhihao Wang,1 Kidane Siele Embaye,1 Qing Yang,2 Lingzhi Qin,1 Chao Zhang,1 Liwei Liu,1 Xiaoqian Zhan,1 Fengdi Zhang,3 Xi Wang,1 Shenghui Qin1 1Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Department of Pharmacy, Hiser Medical Center of Qingdao, Qingdao, 266033, People’s Republic of China; 3Department of Pathology, Wuhan Third Hospital, Wuhan, 430030, People’s Republic of ChinaCorrespondence: Shenghui QinInstitute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of ChinaTel +86-15102744765Fax + 86-027-87541509Email 2015tj0147@hust.edu.cnPurpose: Given that metabolic reprogramming has been recognized as an essential hallmark of cancer cells, this study sought to investigate the potential prognostic values of metabolism-related genes (MRGs) for the diagnosis and treatment of hepatocellular carcinoma (HCC).Methods: In total, 2752 metabolism-related gene sequencing data of HCC samples with clinical information were obtained from the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). One hundred and seventy-eight the differentially expressed MRGs were identified from the ICGC cohort and TCGA cohort. Then, univariate Cox regression analysis was performed to identify these genes that were related to overall survival (OS). A novel metabolism-related prognostic signature was developed using the least absolute shrinkage and selection operator (Lasso) and multivariate Cox regression analyses in the ICGC dataset. The Broad Institute’s Connectivity Map (CMap) was used in predicting which compounds on the basis of the prognostic MRGs. Furthermore, the signature was validated in the TCGA dataset. Finally, the expression levels of hub genes were validated in HCC cell lines by Western blotting (WB) and quantitative real-time PCR (qRT-PCR).Results: We found that 17 MRGs were most significantly associated with OS in HCC. Then, the Lasso and multivariate Cox regression analyses were applied to construct the novel metabolism-relevant prognostic signature, which consisted of six MRGs. The prognostic value of this prognostic model was further successfully validated in the TCGA dataset. Further analysis indicated that this particular signature could be an independent prognostic indicator after adjusting to other clinical factors. Six MRGs (FLVCR1, MOGAT2, SLC5A11, RRM2, COX7B2, and SCN4A) showed high prognostic performance in predicting HCC outcomes. Candidate drugs that aimed at hub ERGs were identified. Finally, hub genes were chosen for validation and the protein, mRNA expression of FLVCR1, SLC5A11, and RRM2 were significantly increased in human HCC cell lines compared to normal human hepatic cell lines, which were in agreement with the results of differential expression analysis.Conclusion: Our data provided evidence that the metabolism-related signature could serve as a reliable prognostic and predictive tool for OS in patients with HCC.Keywords: hepatocellular carcinoma, metabolism-related genes, prognostic signature, biomarker

Ying Dai, Shaoyun Qin, Huaqin Pan, Tianyu Chen, Dachen Bian Department of Respiratory and Critical Care Medicine, Taizhou People’s Hospital, Taizhou, People’s Republic of ChinaCorrespondence: Ying DaiDepartment of Respiratory and Critical Care Medicine, Taizhou People’s Hospital, No. 366, Taihu Road, Taizhou 225300, Jiangsu, People’s Republic of ChinaEmail 444680223@qq.comBackground: Comorbid congestive heart failure (CHF) was associated with worse prognosis in patients with chronic obstructive pulmonary disease (COPD), while few studies specially investigated critically ill patients. This study investigated the associations between comorbid COPD with or without CHF and prognosis of patients admitted to intensive care units (ICU).Methods: We conducted a retrospective cohort study in the Medical Information Mart for Intensive Care III database. Adult ICU patients were included and categorized as patients without COPD and CHF, patients with COPD but without CHF, patients with CHF but without COPD, and patients with both COPD and CHF. The study outcomes were 28-day mortality and 90-day mortality after ICU admission. Kaplan–Meier curves were plotted to estimate the survival distributions between groups and multivariable Cox regression analyses were employed to evaluate the associations between comorbid COPD and/or CHF and the study outcomes.Results: A total of 29,589 patients were included with 20,507 patients without COPD and CHF, 1575 patients with COPD, 6190 patients with CHF, and 1317 patients with both COPD and CHF. The highest 28-day mortality rate and 90-day mortality rate were found in patients with both COPD and CHF (15.95% and 25.74%, respectively), while patients with COPD and patients with CHF had similar mortality rates, also observed in Kaplan–Meier curves. Compared with patients without COPD or CHF, comorbid COPD or CHF both significantly increased the risk of 28-day mortality and 90-day mortality, but comorbid COPD and CHF together was associated with the highest risk of mortality (hazard ratio 1.55 (95% confidence interval (CI) 1.33– 1.80) and 1.25 (95% CI 1.16– 1.35) for 28-day mortality and 90-day mortality, respectively), while no significant interaction between COPD and CHF was found.Conclusion: ICU patients with comorbid COPD or CHF both experienced greater mortalities, while these two risk factors seemed to play an independent role.Keywords: chronic obstructive pulmonary disease, comorbidity, heart failure, mortality, critical care

Sina Qin,* Meng-hua Chen,* Wei Fang, Xiao-feng Tan, Lu Xie, Ye-gui Yang, Tao Qin, Nuo LiIntensive Care Unit, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China*These authors contributed equally to this workBackground: Various and opposite roles of epigallocatechin gallate (EGCG) have been reported in different studies. We aimed to investigate how EGCG affects the cerebral injury in a cardiac arrest/cardiopulmonary resuscitation (CA/CPR) model of rat.Methods: The rats which were subjected to CA/CPR randomly received low dose of EGCG (3 mg/kg, Low-EGCG group, n=16), high dose of EGCG (9 mg/kg, High-EGCG group, n=16) and equal volume of 0.9% saline solution (NS group, n=16) at the first minute after return of spontaneous circulation (ROSC). The rats underwent anesthesia and intubation were defined as Sham group (n=16). Twenty-four hours after ROSC, neural defect score (NDS), ROS fluorescence intensity, degree of mitochondrial permeability transition pore (mPTP) opening, ATP contents and mitochondrial ATP synthase expression were evaluated in the four groups. The expression of extracellular signal-regulated kinase (ERK) activity and cleaved-caspase 3 were also detected by Western blot.Results: CA/CPR induced severe ischemia-reperfusion injury (IRI), resulted in mitochondrial dysfunction and upregulated phosphorylation of ERK. EGCG dose-dependently alleviated the IRI after CA/CPR, inhibited ERK activity and restored mitochondrial function and, as indicated by improved NDS, reduced ROS level, decreased mPTP opening, elevated ATP content, increased ATPase expression and downregulated cleaved-caspase 3 level.Conclusion: EGCG alleviated global cerebral IRI by restoring mitochondrial dysfunction and ERK modulation in a rat CA/CPR model, which might make it a potential candidate agent against IRI after CA/CPR in the future. Further study is needed to determine whether higher dosage of EGCG might aggravate cerebral IRI post-CA/CPR.Keywords: EGCG, CA/CPR, ischemia-reperfusion injury, mitochondrial permeability transition pore, ATP, ERK

Lijuan Xu,1,* Ping Wang,2,* Jing Cheng,2 Shangshang Qin,2,3 Weihong Xie1 1The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450001, China; 2School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, China; 3Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou, Henan 450001, China *These authors contributed equally to this work Background and purpose: The spread of the plasmid-mediated, colistin-resistance gene mcr-1 into New Delhi metallo-β-lactamase (NDM)-producing bacterial isolates can cause untreatable infections. In this study, we conducted a molecular characterization of a novel, conjugative, bla NDM-5-positive IncFII plasmid (pNDM-EC16-50) together with an mcr-1-bearing IncI2 plasmid in a single Escherichia coli ST167 clinical isolate EC16-50.Methods and results: EC16-50, which belongs to the E. coli strain ST167 and phylogroup A, was identified to co-produce NDM-5 and MCR-1. S1-PFGE and Southern blotting showed that blaNDM-5 and mcr-1 genes were located on ~95 kb and ~65 kb plasmids, respectively. A conjugation assay revealed that both blaNDM-5- and mcr-1-bearing plasmids were self-transmissible. Comparative plasmid analysis suggested that blaNDM-5-harboring F2:A-:B-plasmid might have evolved from the well-reported NDM-carrying pMC-NDM-like plasmid via recombination with a locally emerged pSJ_94 plasmid, whereas the mcr-1-carrying IncI2 plasmid was similar to previously reported mcr-1-bearing plasmids in China.Conclusion and impact: This study represents the first report of the NDM-5 carrying IncFII- but not IncX3-type plasmid in an MCR-1-producing E. coli isolate. More striking was the dissemination of mcr-1 in a successful epidemic NDM-5-producing E. coli clone ST167, which could facilitate the spread of colistin resistance in carbapenemase-producing E. coli isolates. Keywords: Escherichia coli, ST167, MCR-1, IncFII plasmid, NDM-5

Xiaobin Gu,1 Xianshu Gao,1 Ming Cui,1 Mu Xie,1 Mingwei Ma,1 Shangbin Qin,1 Xiaoying Li,1 Xin Qi,1 Yun Bai,1 Dian Wang2 1Department of Radiation Oncology, Peking University First Hospital, Peking University, Beijing, People’s Republic of China; 2Department of Radiation Oncology, Rush University Medical Center, Chicago, IL, USA Objective: This study was aimed to compare survival outcomes in high-risk prostate cancer (PCa) patients receiving external beam radiotherapy (EBRT) or radical prostatectomy (RP). Materials and methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify PCa patients with high-risk features who received RP alone or EBRT alone from 2004 to 2008. Propensity-score matching (PSM) was performed. Kaplan–Meier survival analysis was used to compare cancer-specific survival (CSS) and overall survival (OS). Multivariate Cox regression analysis was used to identify independent prognostic factors. Results: A total of 24,293 patients were identified, 14,460 patients receiving RP and 9833 patients receiving EBRT. Through PSM, 3828 patients were identified in each group. The mean CSS was 128.6 and 126.7 months for RP and EBRT groups, respectively (P20 ng/mL were significant risk factors for both CSS and OS. Conclusion: This study suggested that survival outcomes might be better with RP than EBRT in high-risk PCa patients aged

Jia Li,1,2* Shuhui Qin,1,2* Yongqian Li,1,2 Yong Shen1,2 1Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Peoples Republic of China; 2The Key Laboratory of Orthopedic Biomechanics of Hebei Province, The Third Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China *These authors contributed equally to this work Background: The purpose of the research was to evaluate cervical sagittal parameters on magnetic resonance imaging (MRI) in patients with Modic changes and its impact on axial neck pain. Methods: This study consisted of 266 consecutive asymptomatic or symptomatic patients with Modic changes, whose average age was 50.9±12.6 years from January 2015 to December 2016. Cervical sagittal parameters included sagittal alignment of the cervical spine (SACS), T1 slope, thoracic inlet angle (TIA), and neck tilt (NT). The Modic changes group was compared with an asymptomatic control group of 338 age- and gender-matched adults. Results: In the Modic changes group, T1 slope was significantly higher (25.8º±6.3º) compared with that in the control group (22.5º±6.8º) (P=0.000). However, there was no significant difference of the NT, TIA, and SACS between the two groups. Patients in the Modic changes group were more likely to have experienced historical axial neck pain compared with the control group (P=0.000). With regard to the disc degeneration, it indicated that the disc in the Modic changes group had more severe disc degeneration (P=0.032). Conclusion: T1 slope in the Modic changes group was significantly higher compared to that of the control group. The findings suggested that a higher T1 slope with broken compensation of cervical sagittal mechanism may be associated with the development of Modic changes in the cervical spine. Keywords: Modic changes, T1 slope, axial neck pain, cervical spine

Tian-yu Chen,1,2,* Zhong-min Zhang,1,2,* Xiao-chen Zheng,1,2 Liang Wang,1,2 Min-jun Huang,1,2 Si Qin,3 Jian Chen,1,2 Ping-lin Lai,4 Cheng-liang Yang,1,2 Jia Liu,1,2 Yi-fan Dai,5 Da-di Jin,1,2 Xiao-chun Bai1,2,4 1Department of Orthopaedic, the Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, People's Republic of China; 2Academy of Orthopaedics, Guangdong Province, Guangzhou, Guangdong, People's Republic of China; 3Department of Dermatology and STD, Guangdong No.2 Provincial People's Hospital, Guangzhou, Guangdong, People's Republic of China; 4Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, Guangdong, People's Republic of China; 5Center of Metabolic Disease Research, Nanjing Medical University, Jiangsu, People's Republic of China *These authors contributed equally to this work Aim: To investigate the effect of endogenous n-3 polyunsaturated fatty acids (PUFAs) on bone marrow adipogenesis under osteoporosis conditions. Methods: A mouse osteoporosis model overexpressing the FAT1 gene from Caenorhabditis elegans and converting n-6 PUFAs to n-3 PUFAs endogenously was used. Results: The mice presented significantly lower bone marrow adiposity (adipocyte volume/tissue volume, mean adipocyte number) but increased the bone parameters (bone mineral density, bone mineral content, bone volume/total volume) in the distal femoral metaphysis. Conclusion: Endogenous n-3 PUFAs protect bone marrow adipogenesis, which provides a novel drug target. Keywords: antiosteoporosis, n-3 PUFAs, bone marrow, adipogenesis

Objective: The aim of the present subgroup analysis of the FRESCO trial is to determine the efficacy and hepatotoxicity of fruquintinib in Chinese patients with metastatic CRC with liver metastasis (CRLM) who were receiving third-line or posterior-line therapy., Methods: Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier method. Hazard ratio (HR) was estimated through Cox proportional hazards model. Hepatotoxicity was coded using the standardized MedDRA queries of hepatic failure, fibrosis, cirrhosis, and other liver injury-related conditions and graded using the Common Terminology Criteria Adverse Events grades. The efficacy of fruquintinib in patients with CRLM was evaluated in various subgroups., Results: A total of 287 (69.0%) patients with metastatic CRC had liver metastasis (LM, fruquintinib: 185 and placebo: 102). Median OS in patients with CRLM was significantly prolonged with fruquintinib compared with placebo (8.61 months vs 5.98 months; HR=0.59, 95% CI, 0.45-0.77, P<0.001). In patients with CRLM, the incremental median PFS for patients in the fruquintinib-treated group was significantly higher than in the placebo group (median PFS: 3.71 vs.1.84 months; HR=0.22, 95% CI: 0.17-0.30; P<0.001). Compared with placebo, significant improvements in OS were observed with fruquintinib in LM patients regardless of lung metastasis, prior target therapy, and K-RAS status. In patients with CRLM, treatment-emergent hepatotoxicities of any grade occurred in 7 (3.8%) patients in the fruquintinib group vs 2 (2.0%) in the placebo group., Conclusion: Fruquintinib demonstrated a statistically significant increase in OS and PFS as compared with placebo in Chinese patients with CRLM. The hepatotoxicity of fruquintinib was less reported, and comparable with placebo in patients with CRLM., Clinicaltrialsgov Identifier: NCT02314819., Competing Interests: Ning Wang, Bin Zhang, and Qiang Zhang are employees of Eli Lilly and Company. Weiguo Su and Xiaojun Guo are employees of Hutchison MediPharma Limited. Dr Lin Shen reports non-financial support from Lilly, non-financial support from HMPL, during the conduct of the study; grants from Beijing Xiantong Biomedical Technology, grants from Qilu Pharmaceutical, grants from ZaiLab Pharmaceutical, grants from Beihai Kangcheng (Beijing) Medical Technology, grants from Jacobio Pharmaceuticals; received consulting fees from MSD, Merck, Mingji Biopharmaceutical, Haichuang pharmaceutical, Harbour Biomed, and BI; also received fees for speakers Bureaus from Hutchison Whampoa, Hengrui, ZaiLab, CSTONE pharmaceutical; and a member of Advisory Board of Rongchang Pharmaceutical, ZaiLab, CSTONE Pharmaceutical, BMS, outside the submitted work. The other authors have nothing to disclose., (© 2021 Qin et al.)

Background: The fat mass and obesity-associated protein (FTO) was identified as a critical demethylase involved in regulating cellular mRNA stability by removing N6-methyladenosine (m6A) residues from mRNA. Emerging evidence has revealed that FTO is deeply implicated in lung cancer. However, knowledge of the function of FTO in lung adenocarcinoma (LUAC) is limited., Methods: FTO and FTO R96Q (R96Q), an FTO missense mutant lacking demethylase activity, were ectopically overexpressed, and FTO was knocked down via siRNA in A549 and H1299 cells. The relationships between FTO with cell characteristics and mRNA m6A levels were explored. Furthermore, RNA sequencing was performed on A549 cells., Results: FTO overexpression enhanced the proliferation, migration, and invasion ability of A549 and H1299 cells, decreased mRNA m6A levels. Interestingly, overexpression of R96Q, blunted the effects of FTO overexpression on cell proliferation and invasion. Through RNA sequencing analysis of A549 cells overexpressing FTO or R96Q and control A594 cells, 45 genes were identified as affected by m6A mRNA demethylation. Most of these genes were related to lung cancer, such as laminin γ2, thrombospondin 1, nerve growth factor inducible, integrin alpha11, and proprotein convertase subtilisin/kexin type 9. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses suggested that these genes are fundamental to cancer development processes, such as cell migration and extracellular matrix organization., Conclusion: Our research shows that FTO facilitates LUAC cell progression by activating cell migration through m6A demethylation; however, further research on the mechanism underlying FTO activity in LUAC is necessary., Competing Interests: The authors declare that they have no competing interests., (© 2020 Ding et al.)

Background and Purpose: The spread of the plasmid-mediated, colistin-resistance gene mcr-1 into New Delhi metallo-β-lactamase (NDM)-producing bacterial isolates can cause untreatable infections. In this study, we conducted a molecular characterization of a novel, conjugative, bla NDM-5 -positive IncFII plasmid (pNDM-EC16-50) together with an mcr-1 -bearing IncI2 plasmid in a single Escherichia coli ST167 clinical isolate EC16-50., Methods and Results: EC16-50, which belongs to the E. coli strain ST167 and phylogroup A, was identified to co-produce NDM-5 and MCR-1. S1-PFGE and Southern blotting showed that bla NDM-5 and mcr-1 genes were located oñ95 kb and ~65 kb plasmids, respectively. A conjugation assay revealed that both bla NDM-5 - and mcr-1 -bearing plasmids were self-transmissible. Comparative plasmid analysis suggested that bla NDM-5 -harboring F2:A-:B-plasmid might have evolved from the well-reported NDM-carrying pMC-NDM-like plasmid via recombination with a locally emerged pSJ&#95;94 plasmid, whereas the mcr-1 -carrying IncI2 plasmid was similar to previously reported mcr-1 -bearing plasmids in China., Conclusion and Impact: This study represents the first report of the NDM-5 carrying Inc-FII- but not IncX3-type plasmid in an MCR-1-producing E. coli isolate. More striking was the dissemination of mcr-1 in a successful epidemic NDM-5-producing E. coli clone ST167, which could facilitate the spread of colistin resistance in carbapenemase-producing E. coli isolates., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Purpose: The incidence of subthreshold depression (StD) in adolescents is growing rapidly, which in turn is known to impair functioning and increase the risk of major depression. It is therefore important to provide effective intervention to prevent the transition from StD to major depression. As a traditional Chinese mind-body exercise, Tai Chi Chuan (TCC) may be an available selection. Researchers have shown the effectiveness of mindfulness-based therapy on depression; however, for the StD youth, there have been no studies to investigate whether mindfulness-based Tai Chi Chuan (MTCC) can be recommended as an effective exercise for improving their psychological state. The aim of present study was to evaluate the effect of MTCC on psychological outcomes of StD adolescents including the depression levels and mindfulness state in a randomized controlled trial (RCT)., Patients and Methods: An RCT was carried out. A sample of 64 participants who meet the inclusion criteria agreed to be arranged randomly to either the MTCC group (n=32) or the control group (n=32). Participants of the MTCC group received an 8-week, 2 days per week, 90-minute MTCC intervention for each session. Usual physical curriculum was administered to the participants in the control group. The effectiveness of MTCC training was measured by blinded evaluators through validated scales, which included depressive symptoms, stress, and mindfulness level before and after the intervention., Results: Significant improvements in psychological health were observed from MTCC groups. After 8-week intervention, superior outcomes were also observed for MTCC when compared with control group for decrease in depression ( F =59.482, P <0.001) and stress level ( F =59.482, P <0.001) and increase in mindfulness ( F =59.482, P <0.001)., Conclusion: The findings of this preliminary study indicated the effects of the MTCC intervention on depression level among StD youngsters. This study provides preliminary evidence that MTCC is suitable for Chinese adolescents and is effective in decreasing depression level., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Introduction: Methylsulfonic apatinib (hereinafter referred to as Apatinib) is a small-molecule angiogenesis inhibitor highly and selectively targeted to vascular endothelial growth factor receptor-2. At present, a series of basic and clinical studies have confirmed that Apatinib mono-therapy can inhibit the growth of different carcinomas. Our experiment aimed to determine whether there is a synergistic effect between the combination of the traditional cytotoxic chemotherapy drugs paclitaxel (TAX), oxaliplatin (L-OHP), 5-fluorouracil (5-FU), and Apatinib., Materials and Methods: We evaluated the combined effect using cytological experiments and a fluorescence imaging xenograft model. In vitro, the inhibition of cell proliferation increased notably when Apatinib was combined with TAX, L-OHP, and 5-FU. Then, for the mechanistic research, we selected the optimal dose of drugs that also had a synergistic effect. Apatinib combined with the aforementioned drugs, especially the combination of Apatinib and 5-FU, decreased the invasion and migration ability of the cells and increased the apoptosis ratio; expression of the anti-apoptotic protein Bcl-2 significantly decreased, and expression of the pro-apoptotic protein Bax increased. In vivo, when Apatinib was combined with TAX, L-OHP, and 5-FU, the volume of the xenograft model was significantly inhibited, the strength of the green fluorescence was weakened and the microvessel density decreased., Results: The combination of Apatinib with TAX and 5-FU was synergistic (coefficient of drug interaction <1); the combination effect of Apatinib and L-OHP was only additive, with a shorter associated survival time., Conclusion: The combination of Apatinib and classical chemotherapy drugs may be an optimal choice for gastric cancer treatment., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

The aim of this study was to observe the efficacy and safety of apatinib combined with toptecan therapy in the multiline treatment of platinum-resistant recurrent ovarian cancer patients. The clinical records of three patients with platinum-resistant recurrent ovarian cancer treated with apatinib combined with toptecan therapy were analyzed and followed up for 3 months, and the related literatures were reviewed. The three patients achieved partial response and the tumor marker CA125 levels decreased significantly as an outcome of the treatment. Major adverse reactions were hypertension, hand-foot skin reaction, and anemia, which were manageable with medication. Apatinib combined with toptecan multiline therapy in the treatment of platinum-resistant recurrent ovarian cancer patients is effective, and the adverse effects are tolerated. Large-scale studies should be conducted to further determine the efficacy and safety of this treatment protocol., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. The etiology of AMD remains poorly understood and no treatment is currently available for the atrophic form of AMD. Atrophic AMD has been proposed to involve abnormalities of the retinal pigment epithelium (RPE), which lies beneath the photoreceptor cells and normally provides critical metabolic support to these light-sensing cells. Cumulative oxidative stress and local inflammation are thought to represent pathological processes involved in the etiology of atrophic AMD. Studies of tissue culture and animal models reveal that oxidative stress-induced injury to the RPE results in a chronic inflammatory response, drusen formation, and RPE atrophy. RPE degeneration in turn causes a progressive degeneration of photoreceptors, leading to the irreversible loss of vision. This review describes some of the potential major molecular and cellular events contributing to RPE death and inflammatory responses. In addition, potential target areas for therapeutic intervention will be discussed and new experimental therapeutic strategies for atrophic AMD will be presented.