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Jin Cheng,1,* Honglei Ju,1,* Guixiang Wang,2,* 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*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

Jiahua Cheng,1,* Wujuan Li,1,* Lanlin Wang,1,* Yu Gao,1 Yueran Ma,1 Min Zhou,1 Tian Yang,1 Changwu Yue,1,2 Long Yan,3 Yuhong Lyu1,2 1Yan’an Key Laboratory of Microbial Drug Innovation and Transformation, School of Basic Medicine, Yan’an University, Yan’an, Shaanxi, People’s Republic of China; 2Shaanxi Engineering and Technological Research Center for Conversation and Utilization of Regional Biological Resources, Yan’an University, Yan’an, Shaanxi, People’s Republic of China; 3Medical Imaging Center, Yan’an Traditional Chinese Medicine Hospital, Yan’an, Shaanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Long Yan; Yuhong Lyu, Email yanlong840212@163.com; yuhonglyu@126.comPurpose: To explore the protective effects and mechanisms of Jiawei Qifuyin on APP/PS1 mice, a model for Alzheimer’s disease (AD).Methods: Network pharmacology tools were used to predict anti-AD targets and signaling pathways affected by Jiawei Qifuyin. In vitro studies assessed antioxidant and oxygen radical scavenging abilities, immune cell proliferation, and inflammatory cytokine levels in lipopolysaccharide-induced BV2 microglial cells. Cognitive ability in APP/PS1 mice was evaluated using the Morris Water Maze test. mRNA expression of neuroinflammatory factors, changes in intestinal microbiota, and short-chain fatty acid content were analyzed post-treatment.Results: Network pharmacology predicted that Jiawei Qifuyin affects AKT1, TNF-α, and AGE/RAGE pathways. It showed concentration-dependent antioxidant effects and modulated immune cell proliferation. IL-2, IL-6, and TNF-α levels in LPS-induced BV2 cells were significantly reduced. Treated animals exhibited improved cognitive performance, decreased brain amyloid-beta levels, and downregulated expression of IL-1β, IL-6, RAGE, and NF-κB. Significant changes in intestinal microbiota composition and SCFA content were observed.Conclusion: Jiawei Qifuyin may enhance immunity and improve cognitive impairment in APP/PS1 mice through regulation of inflammatory factors, gut microbiota, and the gut-brain axis.Keywords: Alzheimer’s disease, Jiawei Qifuyin, neuroinflammation, intestinal microbiota, short chain fatty acid

Peijie Zhou,&ast; Shangshang Yu,&ast; Xuan Wang,&ast; Xiaofei Zhang, Dongyan Guo, Chongbo Zhao, Jiangxue Cheng, Jing Wang, Jing Sun Department of Pharmaceutics, College of Pharmacy, The Key Laboratory of Basic and New Drug Research of Traditional Chinese Medicine, Shaanxi Provincial Engineering Technology Research Center for Traditional Chinese Medicine Decoction Pieces, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Sun, Email ph.175@163.comBackground: Cerebral ischaemia-reperfusion injury (CIRI) could worsen the inflammatory response and oxidative stress in brain tissue. According to previous studies, ferulic acid methyl ester (FAME), as the extract with the strongest comprehensive activity in the traditional Chinese medicine Huang Hua oil dot herb, has significant anti-oxidative stress and neuroprotective functions, and can effectively alleviate CIRI, but its mechanism of action is still unclear.Methods: Firstly, the pharmacological effects of FAME were investigated by in vitro oxidative stress and inflammatory experiments. Secondly, evaluate the therapeutic effects of FAME in the treatment of CIRI by brain histopathological staining and cerebral infarct area by replicating the in vivo MACO model. Thirdly, RNA-Seq and network pharmacology were utilized to predict the possible targets and mechanisms of FAME for CIRI at the molecular level. Finally, the expression of key target proteins, as well as the key regulatory relationships were verified by molecular docking visualization, Western Blotting and immunohistochemistry.Results: The results of in vitro experiments concluded that FAME could significantly reduce the content of TNF-α, IL-1β and ROS, inhibiting COX-2 and iNOS protein expression in cells(p< 0.01). FAME was demonstrated to have anti-oxidative stress and anti-inflammatory effects. The results of in vivo experiments showed that after the administration of FAME, the area of cerebral infarction in rats with CIRI was reduced, the content of Bcl-2 and VEGF was increased(p< 0.05). Network pharmacology and RNA-Seq showed that the alleviation of CIRI by FAME may be through PI3K-AKT and HIF-1 signaling pathway. Enhanced expression of HIF-1α, VEGF, p-PI3K, p-AKT proteins in the brain tissues of rats in the FAME group was verified by molecular docking and Western Blotting.Conclusion: FAME possesses significant anti-inflammatory and anti-oxidative stress activities and alleviates CIRI through the PI3K/HIF-1α/VEGF signaling pathway. Keywords: ferulic acid methyl ester, cerebral ischemia-reperfusion injury, WGCNA, RNA-Seq, network pharmacology, molecular docking techniques

Abstract Background Epimedin A (EA) has been shown to suppress extensive osteoclastogenesis and bone resorption, but the effects of EA remain incompletely understood. The aim of our study was to investigate the effects of EA on osteoclastogenesis and bone resorption to explore the corresponding signalling pathways. Methods Rats were randomly assigned to the sham operation or ovariectomy group, and alendronate was used for the positive control group. The therapeutic effect of EA on osteoporosis was systematically analysed by measuring bone mineral density and bone biomechanical properties. In vitro, RAW264.7 cells were treated with receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) to induce osteoclast differentiation. Cell viability assays, tartrate-resistant acid phosphatase (TRAP) staining, and immunofluorescence were used to elucidate the effects of EA on osteoclastogenesis. In addition, the expression of bone differentiation-related proteins or genes was evaluated using Western blot analysis or quantitative polymerase chain reaction (PCR), respectively. Results After 3 months of oral EA intervention, ovariectomized rats exhibited increased bone density, relative bone volume, trabecular thickness, and trabecular number, as well as reduced trabecular separation. EA dose-dependently normalized bone density and trabecular microarchitecture in the ovariectomized rats. Additionally, EA inhibited the expression of TRAP and NFATc1 in the ovariectomized rats. Moreover, the in vitro results indicated that EA inhibits osteoclast differentiation by suppressing the TRAF6/PI3K/AKT/NF-κB pathway. Further studies revealed that the effect on osteoclast differentiation, which was originally inhibited by EA, was reversed when the TRAF6 gene was overexpressed. Conclusions The findings indicated that EA can negatively regulate osteoclastogenesis by inhibiting the TRAF6/PI3K/AKT/NF-κB axis and that ameliorating ovariectomy-induced osteoporosis in rats with EA may be a promising potential therapeutic strategy for the treatment of osteoporosis.

Dan Zhang, Bingtao Zhai, Jing Sun, Jiangxue Cheng, Xiaofei Zhang, Dongyan Guo State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, and Shaanxi University of Chinese Medicine, Xi’an, 712046, People’s Republic of ChinaCorrespondence: Dongyan Guo, Email 2051080@sntcm.edu.cnAbstract: Dried toad skin (TS) and toad venom (TV) are the dried skin of the Bufo bufo gargarizans Cantor and the Bufo melanostictus Schneider, which remove the internal organs and the white secretions of the skin and retroauricular glands. Since 2005, cinobufacini preparations have been approved by the State Food and Drug Administration for use as adjuvant therapies in the treatment of various advanced cancers. Meanwhile, bufalenolides has been identified as the main component of TS/TV, exhibiting antitumor activity, inducing apoptosis of cancer cells and inhibiting cancer cell proliferation or metastasis through a variety of signaling pathways. However, clinical agents frequently face limitations such as inherent toxicity at high concentrations and insufficient tumor targeting. Additionally, the development and utilization of these active ingredients are hindered by poor water solubility, low bioavailability, and rapid clearance from the bloodstream. To address these challenges, the design of a targeted drug delivery system (TDDS) aims to enhance drug bioavailability, improve targeting within the body, increase drug efficacy, and reduce adverse reactions. This article reviews the TDDS for TS/TV, and their active components, including passive, active, and stimuli-responsive TDDS, to provide a reference for advancing their clinical development and use.Keywords: dried toad skin, toad venom, targeted drug delivery system, passive targeted, active targeted, stimuli-responsive targeted

Jianping Cheng,1 Chanjuan Fan,1 Zhen Li,1 Zhaojing Dong,2 Xiaolin Zhao,1 Yong Cai,1 Haiou Ding,3 Yan Dou,4 Xiaomei Zhang4 1Department of Gastroenterology and Oncology, Civil Aviation General Hospital, Beijing, People’s Republic of China; 2Department of Medical Record, Civil Aviation General Hospital, Beijing, People’s Republic of China; 3Department of Pharmacy, Civil Aviation General Hospital, Beijing, People’s Republic of China; 4Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Jianping Cheng, Department of Gastroenterology and Oncology, Civil Aviation General Hospital, Beijing, 100123, People’s Republic of China, Tel +86 10 85762244, Email cjpczy2004@163.com Xiaomei Zhang, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, 100112, People’s Republic of China, Email zhangxiaomeinew@163.comBackground and Objectives: The success rate of Helicobacter pylori (H. pylori) eradication in China is declining. The aim of this study was to evaluate eradication outcomes in clinical practice and identifies factors contributing to treatment failure.Methods: A retrospective review was conducted on patients treated for H. pylori infection with 14-day bismuth-containing quadruple therapy at a Beijing medical center from January 2020 to December 2023. We analyzed demographic and clinical data, eradication rates across regimens, and performed multivariate analysis to pinpoint predictors of failure.Results: Out of 3340 participants, 2273 (68.1%) achieved eradication. Amoxicillin-based combinations (69.2%) outperformed other antibiotic regimens (58.9%, p < 0.001), with amoxicillin plus doxycycline reaching a 71.4% success rate. Esomeprazole-based regimens were more effective (73.6%) than other PPI regimens (65.2%, p = 0.001), notably, a rabeprazole, amoxicillin, doxycycline, and bismuth combination had an 80.0% success rate. Age, gender, and smoking and drinking were significant eradication failure predictors.Conclusion: In real-world settings, 14-day amoxicillin and esomeprazole-based quadruple regimens have been demonstrated to be more effective than other regimens. Age, gender, and lifestyle habits are identified as independent risk factors for eradication failure.Registration: This study was registered in the Chinese Clinical Trial Registry on 08/01/2024 (clinical trial registration number: ChiCTR2400079647).Keywords: Helicobacter pylori, quadruple therapy, antibiotics, proton pump inhibitor, retrospective study

Jie Cheng,1,&ast; Ya Liu,2,&ast; Guangli Zhang,3 Liping Tan,1 Zhengxiu Luo3 1Department of Emergency, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Big Data Engineering Center, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, People’s Republic of China; 2Department of Pediatrics, Chongqing Youyoubaobei Women and Children’s Hospital, Chongqing, 401147, People’s Republic of China; 3Department of Respiratory Medicine, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Big Data Engineering Center, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhengxiu Luo, Email luozhengxiu816@hospital.cqmu.edu.cnObjective: Mycoplasma pneumoniae (MP) is highly resistant to macrolides in China. However, macrolides still exhibit clinical effectiveness in some macrolide-resistant patients. We tend to explore azithromycin effectiveness in Mycoplasma pneumoniae pneumonia (MPP) children with A2063/2064G mutation.Methods: This retrospective observational cohort study was conducted at the Children’s Hospital of the Chongqing Medical University. Children with macrolide-resistant mutations (A2063/2064G) diagnosed as MPP were retrospectively enrolled. Receiver operating characteristic (ROC) curves and logistic regression analysis were used to evaluate and identify independent risk factors for treatment failure (progress to refractory Mycoplasma pneumoniae pneumonia [RMPP]) in macrolide-unresponsive Mycoplasma pneumoniae pneumonia (MUMPP) children with the A2063/2064G mutation.Results: One hundred fifty-five children were retrospectively enrolled. More than 20% (36/155, 23.23%) of patients experienced defervescence within 3 days of azithromycin treatment. RMPP was diagnosed in 54 patients (54/155, 34.84%) and the incidence of RMPP during hospitalization was 22.72 per 1000 person-days. Logistic regression analysis showed that lactate dehydrogenase (LDH) ≥ 399 (U/L) was an independent risk factor for RMPP (odds ratio [OR] 4.66, 95% confidence interval [CI] 1.31– 17.10, P=0.017). During the year followed, RMPP patients had a significantly higher incidence of bronchiolitis obliterans and bronchiectasis than non-RMPP patients (16.67% vs 1.98%, P=0.001; 9.26% vs 0.00%, P=0.005, respectively).Conclusion: Azithromycin was effective in children with MPP with the A2063/2064G mutation. For MUMPP children with A2063/2064G mutation, children with LDH ≥ 399 (U/L) had significant higher risk for progression to RMPP, and should consider to be treated with alternative antibiotics (eg tetracyclines, and fluoroquinolones).Keywords: azithromycin effectiveness, A2063/2064G mutation, mycoplasma pneumoniae pneumonia, children

Li Zhang,1,2 Zimu Yu,3 Yunfeng Zhang,1 Hengyu Wang,4,5 Juntao Cheng,6 Chao Shi1 1Department of Oncology, Gaoxin Branch Of The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, People’s Republic of China; 2First School of Clinical Medicine, Jiangxi Medical College, Nanchang University, Nanchang, 330031, People’s Republic of China; 3Medical College of Zhengzhou University, Zhengzhou University, Zhengzhou, 450001, People’s Republic of China; 4Queen Mary College, Nanchang University, Nanchang, 330031, People’s Republic of China; 5School of Biological and Biomedical Sciences, Queen Mary University of London, London, UK; 6Peking University First Hospital, Peking University, Beijing, 100034, People’s Republic of ChinaCorrespondence: Chao Shi, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Donghu District, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel +86 151 7049 8679, Email ndyfy4540@ncu.edu.cnPurpose: Although brain metastasis (BM) from gastric cancer (GC) is relatively uncommon, its incidence has been increasing owing to advancements in treatment modalities. Unfortunately, patients diagnosed with BM from gastric cancer have poor life expectancy. Our study aims to establish a predictive model for brain metastasis in advanced gastric cancer patients, thus enabling the timely diagnosis of brain metastasis.Patients and Methods: The clinicopathological features of a cohort which included 40 GC patients with brain metastasis, 32 of whom from the First Affiliated Hospital of Nanchang University, 2 from Gaoxin Branch of the First Affiliated Hospital of Nanchang University, remaining 6 from Anyang District Hospital, and 80 non-metastatic advanced GC patients from the First Affiliated Hospital of Nanchang University between 2018 and 2022. Data were retrospectively analyzed.Results: Age, tumor size, differentiation, lymph node grade, tumor location, Lauren classification, liver metastasis, carbohydrate antigen 199 (CA199), lactate dehydrogenase (LDH), and human epidermal growth factor receptor 2 (Her-2) were associated with BM. A nomogram integrated with nine risk factors (tumor size, differentiation, lymph node grade, tumor location, Lauren classification, liver metastasis, CA-199, LDH, and Her-2) showed good performance (Area Under Curve 0.95, 95% CI: 0.91– 0.98).Conclusion: We developed and validated a nomogram that achieved individualized prediction of the possibility of BM from GC. This model enables personalized imaging review schedules for timely brain metastasis detection in advanced gastric cancer patients.Keywords: brain metastasis, gastric cancer, nomogram, risk factors

Junjie Cheng,1,&ast; Yuan Yuan,1,&ast; Jinmeng Li,1 Ruoying Zhang,1 Xudong Fan,1 Zhirou Xu,2 Huirong Lin,3 Xinjun Cai,1 Mingfeng Zheng4 1Department of Pharmacy, Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, People’s Republic of China; 2Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, People’s Republic of China; 3Department of Pharmacy, Taizhou Cancer Hospital, Taizhou, People’s Republic of China; 4Department of Orthopaedics, Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingfeng Zheng; Xinjun Cai, Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, Zhejiang Province, 310003, People’s Republic of China, Email zmfyxz3@163.com; zjtcmcxj@zcmu.edu.cnPurpose: Previous studies have indicated that the development of severe adverse events is associated with linezolid peak concentration (Cmax), but the factors affecting linezolid Cmax and evidences on therapeutic drug monitoring to anticipate toxicity in drug-resistant tuberculosis (DR-TB) patients have not been clarified clearly. This study aimed to explore the factors influencing linezolid Cmax and investigate the association between linezolid concentration and hematological toxicity.Patients and Methods: This study included patients with drug-resistant tuberculosis treated with linezolid from January 2022 to September 2023. We analyzed the factors affecting linezolid Cmax using chi-squared and binary logistic regression. The diagnostic utility of linezolid Cmax in predicting hematological toxicity was evaluated using receiver operating characteristic (ROC) analysis.Results: A total of 76 patients were enrolled in the study. 63.20% met the standard rates for linezolid Cmax. Age (P=0.036), weight (P=0.0016), and creatinine clearance (P=0.0223) significantly correlated with the Cmax. Hematological toxicity was observed in 46.05% (35/76) of patients, characterized by thrombocytopenia (31.58%, 24/76), anemia (6.58%, 5/76), and leukopenia (21.05%, 16/76). ROC curve analysis confirmed the predictive value of linezolid Cmax for thrombocytopenia with an area under curve of 0.728.Conclusion: Suboptimal linezolid Cmax was prevalent among patients with DR-TB, with age, weight, and renal function emerging as influential factors. Elevated linezolid Cmax increases the risk of thrombocytopenia. Meticulous monitoring of linezolid Cmax is imperative during anti-DR-TB therapy to tailor treatment and mitigate hematological toxicity.Keywords: linezolid, therapeutic drug monitoring, influencing factors, hematological toxicity

Shuang Xiao,1 Anthony Androulakis,2 William D Skelton,3 Irene L Quan,4 Jinlian Cheng,1 Yan Wang,1 Xueqi Zhu,1 Haiqun Zhang5 1Office of Drug Clinical Trial Institution, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 2School of Public Health, University of South Carolina, Columbia, SC, USA; 3D.AC, The Acupuncture Clinic, Columbia, SC, USA; 4Northwestern University Feinberg School of Medicine, Chicago, IL, USA; 5Trauma Orthopaedics, Beijing Fengsheng Special Hospital of Traditional Medical Traumatology and Orthopaedics, Beijing, People’s Republic of ChinaCorrespondence: Jinlian Cheng, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, 23 Art Museum Back Street, Dongcheng District, Beijing, People’s Republic of China, Tel +86-010-87906813, Email cjltitan@126.comAim: The aim of this study is to assess the willingness, motivation, satisfaction levels, and expectations of participants engaged in clinical trials, while also exploring factors that influence compliance from the participants’ standpoint. Furthermore, this research aims to enhance the understanding of all stakeholders involved in clinical trials about the needs of participants and to offer evidence-based and pragmatic recommendations for effectively managing clinical trial participants.Methods: An electronic questionnaire covers various aspects of Traditional Chinese Medicine (TCM) clinical trials. The distribution of the electronic questionnaire was facilitated through WeChat groups, WeChat Moments, and individual interactions. Count data was expressed in terms of frequency (or rate), and subsequent analysis was conducted utilizing the standard chi-squared test. A p value≤ 0.05 was considered significant. By drawing a Pareto chart, the priority of factors influencing participants’ willingness to participate in clinical trials was systematically assessed.Results: 88 participants answered the questionnaire. A decline in education level corresponded to a decreasing comprehension of participants’ grasp of “clinical trial” and “clinical trial participant” (p< 0.05). The primary reason for participants’ reservations about joining clinical trials stems from their inadequate comprehension of clinical trial details. The key factors contributing to participants’ reluctance to engage in clinical trials encompass aspects of trial design, the operational procedures, insufficient understanding of clinical trial particulars, concerns about potential harm to their bodies and opposition from family members. Importantly, these areas of participants’ hesitation and unwillingness to partake in clinical trials mirror the factors participants’ dissatisfaction contributing to.Conclusion: We found four factors significantly influencing participants’ willingness to engage and their overall satisfaction: the participant’s profile, trial design, trial institution setup, and the qualifications of the researchers. Derived from these critical factors, this paper presents a series of constructive measures.Keywords: clinical trial, traditional Chinese medicine, compliance, satisfaction, participants

Yingxiu Liang,1 Xiaohong Hou,1 Haoying Chen,1 Ruqing Yang,1 Ruina Wang,1 Ruotong Mao,1 Junzhao Zhao,1 Hui Chen,2 Jing Cheng1 1Reproductive Center, Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325088, People’s Republic of China; 2School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, New South Wales, 2007, AustraliaCorrespondence: Jing Cheng, Reproductive Center, Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, No. 306 Hualongqiao Road, Lucheng District, Wenzhou, Zhejiang Province, 325088, People’s Republic of China, Tel +86 13780193700, Fax +86 57788002304, Email jingchengdoc_gyn@hotmail.com Hui Chen, Faculty of Science, University of Technology Sydney, No. 15 of Broadway, Ultimo, New South Wales, 2007, Australia, Tel/Fax +61 295141328, Email chenhuimind@sina.comObjective: Additive human menopausal gonadotropin (HMG)/recombinant luteinizing hormone (r-LH) to follicle-stimulating hormone (FSH) can improve pregnancy outcomes in patients with poor ovarian response during assisted reproductive procedures. However, their effects on patients with normal ovarian response during such procedures are unclear, which formed the aim of this study.Methods: This retrospective study enrolled 456 infertile women who underwent in vitro fertilization or intracytoplasmic sperm injection treatment. Group 1 received FSH; Group 2 received FSH+HMG/r-LH; Group 3 received FSH+HMG+r-LH.Results: The age and Body Mass Index were significantly greater in Group III. The endometrial thickness was greater in Groups II and III, suggesting better endometrial receptivity. Better pregnancy and birth outcomes were seen in Group 3. In sub-cohorts of women older than 32 years old or with overweight/obesity, pregnancy and birth outcomes were also much better in Group 3, albeit without statistical significance.Conclusion: The addition of both HMG and r-LH to FSH may improve the chance of infertile women with normal ovarian responses to have more success in having live birth babies, specifically in those over 32 years of age or with overweight/obese patients who typically face challenges in conceiving and sustaining a pregnancy.Keywords: in vitro fertilization, intracytoplasmic sperm injection, live birth rate, cumulative live birth rate

Xichen Wan,1– 3 Tong Lin,1– 3 Yunzhen Luo,4 Jiaxu Hong,1– 3,5 Jingyi Cheng,1– 3,&ast; Keqing Zhao6,&ast; 1Department of Ophthalmology and Visual Science, Eye & ENT Hospital, Fudan University, Shanghai, People’s Republic of China; 2NHC Key Laboratory of Myopia and Related Eye Diseases, Shanghai, People’s Republic of China; 3Key laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, People’s Republic of China; 4Department of Otolaryngology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, People’s Republic of China; 5Department of Ophthalmology, The Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China; 6Department of Otolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Keqing Zhao, Department of Otolaryngology, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai, 200031, People’s Republic of China, Email rhinoresearch@163.com Jingyi Cheng, Department of Ophthalmology and Visual Science, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai, 200031, People’s Republic of China, Email tippicjy@126.comPurpose: To evaluate the effect of vidian neurectomy (VN) on the ocular surface and the possibility of dry eye in the treatment of allergic rhinitis.Methods: Twelve participants were recruited in this prospective study. Prior to and after 1 and 6 months of VN, an ocular surface disease index (OSDI) questionnaire was obtained, and the Schirmer’s tear test (STT), break-up time (BUT), corneal fluorescence staining (CFS) score, and Keratograph 5M were used to evaluate the ocular surface condition.Results: Two patients (16.67%) met the dry eye diagnosis criteria one month after surgery; however, their symptoms were relieved after to 3– 4 months and none of them met the diagnostic criteria for dry eye after six months. Compared with the baseline values, the STT was significantly reduced (P=0.002), while the tear meniscus height (TMH) (P=0.262), break-up time (BUT) (P=0.916), first keratographic tear film break-up time (NK-BUTfirst) (P=0.791), and average keratographic break-up time (NK-BUTave) (P=0.970) did not change significantly 6 months after surgery. The degree of STT decreased from baseline to 6-month and was related to the basic STT (ρ= 0.837, P=0.001) and sex (ρ= − 0.584, P= 0.026) but not to age, OSDI score, BUT, NK-BUTfirst, NK-BUTave or CFS (all P> 0.05). Among these factors, STT at baseline was confirmed to be a predictor of a decline in tear secretion after surgery (B = 0.731, P< 0.001).Conclusion: In this 6-month prospective pilot study, decreased tearing was observed after VN, but this decrease did not increase the possibility of dry eyes.Keywords: vidian neurectomy, ocular surface, dry eye

Chao Zuo,1 Yi Liu,1 Ziqiang Wang,2 Jing Cheng,1 Dongli Yang,1 Huasong Gong,1 Yu Wang,3 Yongchao Qiao1 1Department of Clinical Laboratory, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, People’s Republic of China; 2Research Center of Clinical Laboratory Science, Bengbu Medical College, Bengbu, Anhui, People’s Republic of China; 3Department of Geriatrics, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, People’s Republic of ChinaCorrespondence: Yongchao Qiao, Department of Clinical Laboratory, Affiliated Hospital of Guilin Medical University, Le Qun Road 15, Guilin, Guangxi, 541001, People’s Republic of China, Email qiaoyc@glmc.edu.cn Yu Wang, Department of Geriatrics, Affiliated Hospital of Guilin Medical University, Le Qun Road 15, Guilin, Guangxi, 541001, People’s Republic of China, Tel +86 773 2822730, Email wangyu101101@163.comIntroduction: This study aimed to investigate the association of Nicotinamide phosphoribosyl transferase (NAMPT) rs61330082 polymorphism with co-morbid hypertension (HTN) and the progression of hypertension in Chinese patients with type 2 diabetes mellitus (T2DM).Methods: A total of 453 T2DM patients were genotyped for the polymorphism of rs61330082 using SNP-scan high-throughput technology. These patients were divided into T2DM group (261 patients) and T2DM combined with hypertension group (T2MH, 192 patients). The T2MH group was further categorized into Grade I, Grade II, and Grade III based on the results of the Hypertension Grade Score. Peripheral blood plasma urea, plasma creatinine, renin-angiotensin system (RAS) indexes, and lipid biochemistry indexes were measured in patients and analyzed in relation to NAMTP polymorphisms.Results: We found that the presence of the NAMPT rs61330082-AA genotype was associated with a significantly increased risk of developing higher-grade hypertension in patients with T2MH. In addition, the A allele of the NAMPT rs61330082 gene displayed more associated in developing a higher grade of hypertension compared to the G allele. Also, the level of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) increased with hypertension grade in the NAMPT rs61330082-GG genotype.Conclusion: NAMPT rs61330082 polymorphism was significantly associated with the progression of hypertension grade in T2MH patients and also affected plasma creatinine and LDL-c levels.Keywords: NAMPT, polymorphism, T2DM, hypertension classification

Introduction. With the development of the Internet, the popularity of online novels, especially in China, prompts the declining interest in reading paper books. The potential impact of online novels on adolescents has become a matter of public concern. Most studies examine the role of online novels in students’ learning process, as well as the impact on young people’s communication and social interaction. However, so far, the impact of online novels on adolescents’ values and psychology has been understudied despite their critical importance in shaping young peopleʼs identity. Therefore, the purpose of this study is to determine the influence of online novels on the values and psychology of Chinese secondary school learners. Materials and Methods. To address this challenge, a survey was conducted among students attending Yifu Educational Institution in Nanning, China. Questionnaires developed through the Question Star app were distributed through relevant user groups on social media platforms including WeChat and Tencent QQ. Results. As a result, positive (increased general knowledge and literacy, the opportunity to spend free time productively) and negative (impact on learning and physical health, decreased literary abilities, promotion of tendencies harmful for society) characteristics of the influence of online novels on adolescents were identified. Practical recommendations were formulated aimed at counteracting negative impact of online novels on adolescents such as the need to strengthen the ideological and moral education of students, the necessity to develop national cultural superiority and pride of modern youth, as well as to introduce young people to useful bibliography. Discussion and Conclusion. The results obtained will make a significant contribution to such fields as psychology, sociology and education. Also, the results of the study will serve as a basis for the development of new approaches to combat the negative impact of Internet novels on the values of adolescents. The results of the study may be useful for specialists of educational institutions and all those who care about the upbringing of the younger generation.

Yan Fang,1,2 Huali Liu,1,2 Yuan Li,1,2 Ji Cheng,1 Xia Wang,1 Bing Shen,3 Hongbo Chen,1,2 Qunhua Wang4 1Department of Obstetrics and Gynaecology, Maternal and Child Health Hospital Affiliated to Anhui Medical University, Hefei, People’s Republic of China; 2The Fifth Clinical College of Anhui Medical University, Hefei, People’s Republic of China; 3School of Basic Medicine, Anhui Medical University, Hefei, People’s Republic of China; 4Department of Obstetrics and Gynaecology, the First Affiliated Hospital of USTC, Hefei, People’s Republic of ChinaCorrespondence: Hongbo Chen, Maternal and Child Health Hospital Affiliated to Anhui Medical University, No. 15 Yimin Street, Luyang District, Hefei City, Anhui Province, People’s Republic of China, Email chenhongbo@ahmu.edu.cn Qunhua Wang, Department of Obstetrics and Gynaecology, the First Affiliated Hospital of USTC, Hefei, People’s Republic of China, Email wqh971234@163.comPurpose: To investigate the risk factors associated with preeclampsia in hyperglycemic pregnancies and develop a predictive model based on routine pregnancy care.Patients and Methods: The retrospective collection of clinical data was performed on 951 pregnant women with hyperglycemia, including those diagnosed with diabetes in pregnancy (DIP) and gestational diabetes mellitus (GDM), who delivered after 34 weeks of gestation at the Maternal and Child Health Hospital Affiliated to Anhui Medical University between January 2017 and December 2019. Observation indicators included liver and kidney function factors testing at 24– 29+6 weeks gestation, maternal age, and basal blood pressure. The indicators were screened univariately, and the “rms” package in R language was applied to explore the factors associated with PE in HIP pregnancy by stepwise regression. Multivariable logistic regression analysis was used to develop the prediction model. Based on the above results, a nomogram was constructed to predict the risk of PE occurrence in pregnant women with HIP. Then, the model was evaluated from three aspects: discrimination, calibration, and clinical utility. The internal validation was performed using the bootstrap procedure.Results: Multivariate logistic regression analysis showed that cystatin C, uric acid, glutamyl aminotransferase, blood urea nitrogen, and basal systolic blood pressure as predictors of PE in pregnancy with HIP. The predictive model yielded an area under curve (AUC) value of 0.8031 (95% CI: 0.7383– 0.8679), with an optimal threshold of 0.0805, at which point the sensitivity was 0.8307 and specificity of 0.6604. Hosmer–Lemeshow test values were P = 0.3736, Brier score value was 0.0461. After 1000 Bootstrap re-samplings for internal validation, the AUC was 0.7886, the Brier score was 0.0478 and the predicted probability of the calibration curve was similar to the actual probability. A nomogram was constructed based on the above to visualize the model.Conclusion: This study developed a model for predicting PE in pregnant women with HIP, achieving high predictive performance of PE risk through the information of routine pregnancy care.Keywords: hyperglycemia in pregnancy, preeclampsia, prediction model, nomogram, internal validation

Peng Lai,1,2 Shirui Cheng,1,2 Xingyao Chen,1 Fangdong Cheng,3– 5 Jun Cheng,3– 5 Ming Xin,3,4,6 Deliang Zhu,3,4,6 Zhengjie Li,1,2 Xi Wu,1 Fang Zeng1,2 1Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 2Acupuncture & Brain Research Center, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 3Geriatric Diseases Institute of Chengdu, Chengdu Fifth People’s Hospital (The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), Chengdu, Sichuan, People’s Republic of China; 4Cancer Prevention and Treatment Institute of Chengdu, Chengdu Fifth People’s Hospital (The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), Chengdu, Sichuan, People’s Republic of China; 5Department of Orthopedic, Chengdu Fifth People’s Hospital (The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), Chengdu, Sichuan, People’s Republic of China; 6Department of Rehabilitation, Chengdu Fifth People’s Hospital (The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Fang Zeng; Xi Wu, Email zengfang@cdutcm.edu.cn; wuxi@cdutcm.edu.cnIntroduction: Acupuncture is effective for patients with chronic low back pain (CLBP), which can relieve pain intensity and regulate negative emotional states such as pain-related anxiety and depression. Previous studies mainly discuss the analgesic mechanism of acupuncture treatment of CLBP, but there are multiple dimensions to pain, including sensation, emotion and cognition. Therefore, this study aims to investigate the central mechanism of acupuncture for CLBP from the perspective of emotional regulation by functional magnetic resonance imaging (fMRI).Methods and Analysis: A total of 72 patients with CLBP will be recruited in the study and randomly assigned to the verum acupuncture group or the sham acupuncture group. The trail will last for 18 weeks including a 2-week baseline, a 4-week treatment and a 12-week for follow-up period. The primary outcomes are the visual analog scale (VAS) and the Japanese Orthopaedic Association Scores (JOA) score. The secondary outcomes are the 12-item short form health survey (SF-12), the state trait anxiety inventory (STAI), the self-rating anxiety scale (SAS) and self-rating depression scale (SDS). The VAS, JOA, STAI SAS and SDS will be collected at baseline, week 2, week 4, and after follow-up. The SF-12 will be evaluated at baseline, week 2 and week 4. Functional magnetic resonance imaging (MRI) data will be collected at baseline and the end of treatment. Emotion-related brain regions will be chosen as regions of interest (ROIs). The gray matter volume (GMV), amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), functional connectivity (FC), and large-scale functional brain network based on these ROIs will be analyzed within and between the two groups.Discussion: This study will verify the emotional regulation of acupuncture and explore the mechanism of acupuncture for emotion regulation in patients with CLBP.Trial Registration Number: https://www.chictr.org.cn/showproj.html?proj=195486, identifier: ChiCTR2300070557.Keywords: acupuncture, chronic low back pain, emotion regulation, functional magnetic resonance imaging

Jun Cheng,&ast; Jinjin Pan,&ast; Dongmei Zhao, Xuejiao Ma, Qiulin Sun, Jiabin Li Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiabin Li, Tel/Fax +86-551-62922281, Email lijiabin@163.comAbstract: The global prevalence of hepatitis C virus (HCV) infection is approximately 3%, with a post-infection chronicity rate of up to 50%– 85%. HCV reactivation can occur when anti-HCV positive individuals receive antineoplastic therapy. In this study, we report a case of an anti-HCV positive patient with negative HCV RNA after 12 weeks of direct antiviral therapy. Two months later, sorafenib was used to treat hepatocellular carcinoma, and HCV reactivation occurred after 8 months of the treatment. HCV RNA was negative after 12 weeks of antiviral treatment with Sofosbuvir-velpatasvir. We also discussed the mechanism of HCV reactivation caused by sorafenib and the antiviral treatment regimen after HCV reactivation with the relevant literature.Keywords: hepatocellular carcinoma, sorafenib, HCV-RNA, anti-HCV therapy, reactivation

Jie Cheng,1 Ya Liu,2 Shaojun Li,1 Kaibin Pu,1 Lin Yang,1 Liping Tan1 1Department of Emergency, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, People’s Republic of China; 2Department of Pediatrics, Chongqing Youyoubaobei Women and Children’s Hospital, Chongqing, 401147, People’s Republic of ChinaCorrespondence: Liping Tan, Tel +86-23-63630194, Email tanlp0825@hotmail.comObjective: Third-generation cephalosporin-resistant (3GC-R) bloodstream infection (BSI) is associated with poor prognosis. We investigated the incidence of and risk factors for 3GC-R Escherichia coli (E. coli) BSI in children.Methods: Patients with E. coli BSIs who were hospitalized at the Children’s Hospital of Chongqing Medical University were retrospectively enrolled. Univariate and multivariate logistic regression analyses were used to identify the independent risk factors for 3GC-R BSI.Results: Two hundred fifty-two children with E. coli BSIs were enrolled. The mortality rate was 11.51% (29/252). The infection rate of 3GC-R E. coli was 48.81% (123/252), and the incidence of E. coli BSI during hospitalization was 18.58 per 1000 person-days. Approximately half (47.22%, 119/252) of the children were infected with extended-spectrum beta-lactamases (ESBLs) produced by E. coli. More than one-third (37.30%, 94/252) of the children were unnecessarily administrated carbapenems. According to our logistic regression analysis, a history of carbapenem administration, an elevated Pediatric Sequential Organ Failure Assessment (pSOFA) score ≥ 2, and antimicrobial agent administration before blood culture were independently associated with 3GC-R BSI (odds ratio [OR] 2.05, 95% confidence interval [CI] 1.08– 3.94, P=0.029; OR 2.00, 95% CI 1.10– 3.71, P=0.025, OR 1.86, 95% CI 1.02– 3.42, P=0.044, respectively).Conclusion: In this study, the incidence of 3GC-R E. coli BSI among children was retrospectively evaluated. Patients with a history of carbapenem administration, an elevated pSOFA score ≥ 2 and who were administrated antimicrobial agents before blood culture had an increased risk of 3GC-R E. coli BSI.Keywords: third-generation cephalosporin-resistant, inappropriate use of carbapenems, Escherichia coli, bloodstream infection, children

Hao Yang,1– 3,&ast; Guanglin Lei,2,&ast; Zhuoya Deng,1 Fang Sun,1 Yuying Tian,1 Jinxia Cheng,1 Hongyu Yu,1 Cong Li,1 Changqing Bai,4 Shaogeng Zhang,2 Guangwen An,5 Penghui Yang1 1Faculty of Hepato-Pancreato-Biliary Surgery, Institute of Hepatobiliary Surgery, the First Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Department of Hepatological Surgery, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Department of Surgery, Taian City Central Hospital, Taian, People’s Republic of China; 4Department of Respiratory, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Guangdong, People’s Republic of China; 5Department of Pharmacy, No. 984 Hospital of the PLA, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Penghui Yang; Guangwen An, Email ypenghuiamms@hotmail.com; anchen337722@163.comBackground: Oncolytic virus (OV) therapy has emerged as a promising novel form of immunotherapy. Moreover, an increasing number of studies have shown that the therapeutic efficacy of OV can be further improved by arming OVs with immune-stimulating molecules.Methods: In this study, we used reverse genetics to produce a novel influenza A virus, termed IAV-OX40L, which contained the immune-stimulating molecule OX40L gene in the influenza virus nonstructural (NS1) protein gene. The oncolytic effect of IAV-OX40L was explored on hepatocellular carcinoma (HCC)HCC cells in vitro and in vivo.Results: Hemagglutination titers of the IAV-OX40L virus were stably 27– 28 in specific-pathogen-free chicken embryos. The morphology and size distribution of IAV-OX40L are similar to those of the wild-type influenza. Expression of OX40L protein was confirmed by Western blot and immunofluorescence. MTS assays showed that the cytotoxicity of IAV-OX40L was higher in HCC cells (HepG2 and Huh7) than in normal liver cells (MIHA) in a time- and dose-dependent manner in vitro. We found that intratumoral injection of IAV-OX40L reduced tumor growth and increased the survival rate of mice compared with PR8-treated controls in vivo. In addition, the pathological results showed that IAV-OX40L selectively destroyed tumor tissues without harming liver and lung tissues. CD4+ and CD8+ T cells of the IAV-OX40L group were significantly increased in the splenic lymphocytes of mice. Further validation confirmed that IAV-OX40L enhanced the immune response mainly by activating Th1-dominant immune cells, releasing interferon-γ and interleukin-2.Conclusion: Taken together, our findings demonstrate the novel chimeric influenza OV could provide a potential therapeutic strategy for combating HCC and improve the effectiveness of virotherapy for cancer therapy.Keywords: OVs, OX40L, IAV, HCC

Zongfeng Zhao,1,&ast; Jie Cheng,2,&ast; Wanqun Sun,1 Jian Zhu,3 Sheng Lu,3 Yanyan Feng,4 Zhendong Song,5 Yali Yang,6 Xiujuan Wu3 1Department of Scientific Research, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Urology, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, People’s Republic of China; 3Department of Dermatology, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, People’s Republic of China; 4Chengdu Second People’s Hospital, Chengdu, Sichuan Province, People’s Republic of China; 5WLSA Shanghai Academy, Shanghai, People’s Republic of China; 6Department of Dermatology, Shanghai Ninth Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yali Yang, Department of Dermatology, Shanghai Ninth Hospital affiliated to Shanghai Jiao Tong University, School of Medicine, No. 639, Manufacturing Bureau Road, Huangpu District, Shanghai, 200011, People’s Republic of China, Email ky7812@126.com Xiujuan Wu, Department of Dermatology, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, No. 966, Huaihai Middle Road, Xuhui District, Shanghai, 200031, People’s Republic of China, Email xjwuxj@sina.comPurpose: Psoriasis is an incurable chronic inflammatory skin disease. The exact function and regulatory mechanism of non-coding RNA upregulation in psoriasis remains to be elucidated. The aim of this study was to analyse the role of the lncRNA-miRNA-mRNA network of psoriasis and LINC01176 in the pathogenesis of psoriasis.Patients and Methods: We performed miRNA, lncRNA, and mRNA sequencing analysis in pretreatment and treatment psoriatic tissues and normal tissues, constructed an lncRNA-miRNA-mRNA coexpression network and screened mRNA-associated pathways using bioinformatics analysis. We further validated the regulatory role of LINC01176-miR-218-5p on the proliferation and inflammation of the psoriatic model by dual-luciferase reporter assay, cell transfection, CCK-8 method, TUNEL staining and animal model construction method. An lncRNA-miRNA-mRNA coexpression network was successfully constructed by RNA-seq data analysis.Results: We obtained the relationship between LINC01176, miR-218-5p and IL36-G. Analysis of the apoptotic and proliferative capacity of the transfected cells showed that miR-218-5p up-regulation significantly inhibited cell proliferation and promoted apoptosis. A mouse model of psoriasis was successfully established. Phenotypic observations revealed that keratin-forming cells in mice coated with LINC01176-shRNA emulsifier were significantly lower than those in the model group and close to those in the normal group. HE and immunohistochemical experiments were performed, and the results showed the role and mechanism of action of LINC01176-shRNA. Suppression of LINC01176 significantly inhibited the expression of IL-36G in psoriatic tissues. LINC01176 showed a targeting and positive correlation with IL36-G expression.Conclusion: Our study shows that LINC01176 promotes the proliferation and invasion of keratinocytes and inhibits apoptosis by targeting miR-218-5p, which acts as a repressor of the psoriasis-associated IL-36G. The shRNA-LINC01176 emulsion showed potential treatment capability in alleviating symptoms of psoriasis.Keywords: psoriasis, LINC01176, IL-36G, inflammation

Lin Sheng,1– 4,&ast; Yumeng Wei,1,3,&ast; Chao Pi,1,3,&ast; Ju Cheng,3,4 Zhilian Su,1– 4 Yuanyuan Wang,1,5 Tao Chen,1– 4 Jie Wen,1– 4 Yuxun Wei,1– 4 Jingwen Ma,1– 4 Jia Tang,1– 4 Huiyang Liu,1– 4 Zerong Liu,6,7 Hongping Shen,8 Ying Zuo,9 Wenwu Zheng,10 Ling Zhao2– 4 1Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, People’s Republic of China; 2Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 3Key Laboratory of Medical Electrophysiology, Ministry of Education, Development Planning Department of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 4Central Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 5Department of Clinical Pharmacy, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 6Central Nervous System Drug Key Laboratory of Sichuan Province, Sichuan Credit Pharmaceutical CO., Ltd. Luxian County, Luzhou City, People’s Republic of China; 7Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400030, People’s Republic of China; 8Clinical Trial Center, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 9Department of Comprehensive Medicine, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 10Department of cardiology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenwu Zheng, Department of Cardiology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China, Tel/Fax +86 830 3165311, Email zhengwenwu888@163.com Ling Zhao, Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, No. 182, Chunhui Road, Longmatan District, Luzhou, Sichuan, 646000, People’s Republic of China, Tel/Fax +86 830 3160093, Email zhaoling@swmu.edu.cnPurpose: The early stage of this study verified that a turmeric extract (TUR) including 59% curcumin (CU), 22% demethoxycurcumin (DMC), and 18% bisdemethoxycurcumin (BDMC), could enhance the stability of CU and had greater antidepressant potential in vitro. The objective of the study was to develop a nano-delivery system containing TUR (TUR-NE) to improve the pharmacokinetic behavior of TUR and enhance its antidepressant effect.Methods: The antidepressant potential of TUR was explored using ABTS, oxidative stress-induced cell injury, and a high-throughput screening model. TUR-NE was fabricated, optimized and characterized. The pharmacokinetic behaviors of TUR-NE were evaluated following oral administration to normal rats. The antidepressant effect of TUR-NE was assessed within chronic unpredictable mild stress model (CUMS) mice. The behavioral and biochemical indexes of mice were conducted.Results: The results depicted that TUR had 3.18 and 1.62 times higher antioxidant capacity than ascorbic acid and CU, respectively. The inhibition effect of TUR on ASP+ transport was significantly enhanced compared with fluoxetine and CU. TUR-NE displayed a particle size of 116.0 ± 0.31 nm, polydispersity index value of 0.121 ± 0.007, an encapsulation rate of 98.45%, and good release and stability in cold storage. The results of pharmacokinetics indicated the AUC(0-t) of TUR-NE was 8.436 and 4.495 times higher than that of CU and TUR, while the Cmax was 9.012 and 5.452 times higher than that of CU and TUR, respectively. The pharmacodynamic study confirmed that the superior antidepressant effect of TUR-NE by significantly improving the depressant-like behaviors and elevating the content of 5-hydroxytryptamine in plasma and brain in CUMS mice. TUR-NE showed good safety with repeated administration.Conclusion: TUR-NE, which had small and uniform particle size, enhanced the bioavailability and antidepressant effect of TUR. It could be a promising novel oral preparation against depression.Keywords: turmeric extract, curcuminoids, nanoemulsion, stability, antidepressant effect, 5-hydroxytryptamine

Jin Cheng,1,2 Wei Wang2 1Department of Medicine, Wuhan University of Science and Technology, Wuhan, 430000, People’s Republic of China; 2Department of Gastroenterology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, People’s Republic of ChinaCorrespondence: Wei Wang, Department of Gastroenterology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, No. 136, Jingzhou Street, Xiangyang, Hubei, 441021, People’s Republic of China, Tel +8613972088242, Email 32857107@qq.comBackground: Evidence for an association between dietary acid load (DAL) and non-alcoholic fatty liver disease (NAFLD) is scarce and controversial. We aimed to address whether an association exists between DAL and NAFLD/advanced liver fibrosis (AHF) among US adults in a nationally representative study.Methods: This was a cross-sectional study. We included adult participants from the National Health and Nutrition Examination Survey 1999– 2018. Potential renal acid load (PRAL) and estimated net endogenous acid production (NEAP) was calculated from the literature and NAFLD/AHF was diagnosed by noninvasive markers. We comprehensively explored these relationships using multivariate adjusted regression models, restricted cubic spline, stratification analysis, and sensitivity analysis.Results: We enrolled a total of 18,855 participants. All DAL metrics were positively and nonlinearly associated with NAFLD (all p-values < 0.0001), whereas NEAPF and NEAPR may be associated with AHF. In the stratified analysis, we found that the correlation between DAL and NAFLD exists in all ages and genders, but the effect of DAL seems to be more obvious in middle-aged, elderly and women. Similarly, we found that the effect of DAL on AHF was more significant in 45– 60-year-olds and women. Sensitivity analyses revealed stability of all results.Conclusion: DAL including PRAL and NEAP were positively associated with NAFLD in a large nationally representative cross-sectional study. NEAPF and NEAPR may be associated with increased odds of AHF. Adjustment for diet-dependent DAL requires age- and sex-specific strategies. Future prospective studies are needed to validate our findings.Keywords: nonalcoholic fatty liver disease, NHANES, liver fibrosis, dietary acid load, nutrient

Yunbo Yan,1 Linqian Yu,1 Binyang Chen,1 Chang’an Cao,1 Hairong Zhao,1,2 Qiang Wang,1 De Xie,1 Yuemei Xi,1 Chenggui Zhang,2 Jidong Cheng1,3 1Department of Internal Medicine, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of China; 2Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, Dali University, Dali, People’s Republic of China; 3Xiamen Key Laboratory of Translational Medicine for Nucleic Acid Metabolism and Regulation, Xiamen, People’s Republic of ChinaCorrespondence: Jidong Cheng; Chenggui Zhang, Email jidongcheng36@hotmail.com; chenggui_zcg@hotmail.comBackground: Gouty arthritis is characterized by the accumulation of monosodium urate crystals (MSU) in the synovial joints and surrounding tissues. Mastoparan M (Mast-M) is a biologically active peptide composed of 14 amino acids, extracted from wasp venom. This study aims to assess the impact of Mast-M on in vitro and in vivo gouty arthritis induced by lipolyaccharide (LPS) plus MSU crystal stimulation.Methods: PMA-differentiated THP-1 macrophages were pre-treated with Mast-M or left untreated, followed by stimulation with LPS and MSU crystals. Cell lysates were collected to assess the expression of the NLRP3 inflammasome, inflammatory signaling pathways, and oxidative stress. Furthermore, to evaluate the in vivo anti-inflammatory effect of Mast-M, an experimental acute gouty arthritis mouse model was established through intra-articular injection of MSU crystals.Results: Mast-M treatment demonstrated significant inhibition of the phosphorylation of MAPKs/NF-κB signaling pathways and reduction in oxidative stress expression in LPS and MSU-induced THP-1 macrophages. This resulted in the suppression of downstream NLRP3 inflammasome activation and IL-1β release. In vivo, Mast-M effectively attenuated the inflammation induced by MSU in mice with gouty arthritis. Specifically, Mast-M reduced swelling in the paws, inhibited the infiltration of neutrophils and macrophages into periarticular tissue, and decreased the activation of the NLRP3 inflammasome and IL-1β production.Conclusion: Mast-M significantly improves gouty arthritis, and its potential mechanism may be achieved by inhibiting the MAPK/NF-κB pathway and alleviating oxidative stress, thus suppressing the activation of NLRP3 inflammasomes.Keywords: Mastoparan M, NLRP3, MAPKs, NF-κB, oxidative stress, gout

Junning Cheng,&ast; Yuewen Lao,&ast; Xiangping Chen, Xiaoting Qiao, Weijing Sui, Xiaoyan Gong, Yiyu Zhuang Nursing Department, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yiyu Zhuang, Nursing Department, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, People’s Republic of China, Tel +8613588708076, Email zhuangyy@zju.edu.cnPurpose: To develop a dynamic nomogram of subsyndromal delirium (SSD) in intensive care unit (ICU) patients and internally validate its efficacy in predicting SSD.Patients and Methods: Patients who met the inclusion and exclusion criteria in the ICU of a tertiary hospital in Zhejiang from September 2021 to June 2022 were selected as the research objects. The patient data were randomly divided into the training set and validation set according to the ratio of 7:3. The least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression were used to screen the predictors of SSD, and R software was used to construct a dynamic nomogram. Receiver operating characteristic (ROC) curve, calibration band and decision curve were used to evaluate the discrimination, calibration and clinical effectiveness of the model.Results: A total of 1000 eligible patients were included, including 700 in the training set and 300 in the validation set. Age, drinking history, C reactive protein level, APACHE II, indwelling urinary catheter, mechanical ventilation, cerebrovascular disease, respiratory failure, constraint, dexmedetomidine, and propofol were predictors of SSD in ICU patients. The ROC curve values of the training set was 0.902 (95% confidence interval: 0.879– 0.925), the best cutoff value was 0.264, the specificity was 78.4%, and the sensitivity was 88.0%. The ROC curve values of the validation set was 0.888 (95% confidence interval: 0.850– 0.930), the best cutoff value was 0.543, the specificity was 94.9%, and the sensitivity was 70.9%. The calibration band showed good calibration in the training and validation set. Decision curve analysis showed that the net benefit in the model was significantly high.Conclusion: The dynamic nomogram has good predictive performance, so it is a precise and effective tool for medical staff to predict and manage SSD in the early stage.Keywords: subsyndromal delirium, intensive care unit, nomogram, prediction model, LASSO

Xiaorong Xu,&ast; Jing Cheng,&ast; Yeping Zhang, Xin Wang, Mulei Chen, Lin Xu, Wenshu Zhao Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital Affiliated to Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenshu Zhao; Lin Xu, Email zhaowenshu1965@126.com; xul853@126.comBackground: The efficacy of chronic heart failure (CHF) checklist management in reducing adverse outcomes of heart failure patients is still uncertain. This study explores whether CHF checklist management is more useful than usual care in reducing adverse health outcomes in the medium- and long-term among CHF patients.Methods: In our prospective study, 132 patients with CHF were randomly assigned to CHF management group and usual care group by random number method. Patients in CHF management group were conducted through CHF checklist by cardiologists and general practitioner. Patients assigned to usual care were treated by non-stationary medical group without checklist. All groups were followed up for 18 months.Results: There was no significant difference in overall mortality rate between management group and control group during 18 months (12.3% [8/65] vs. 11.7% [7/60], P = 0. 912]). The re-hospitalization rate of heart failure in management group (18.5% [12/65]) was significantly lower than that in usual care group (38.3% [23/60]) after 18 months of follow-up (P = 0.013). Median NT-proBNP level (632.3 ng/l vs. 1678 ng/l, p = 0.004) was lower in management group than that in usual care group. Cardiac ultrasonography was performed at 18 months between the management and usual care group. LVEDD (55.88± 7.11 mm vs. 60.92± 8.06 mm) and LVESD (43.25± 8.42mm vs. 48.41± 9.02mm) were decreased (P< 0.01). LVEF was increased (45.36± 10.64% vs. 39.96 ± 10.15%, P< 0.01). The utilization rate of ACEI/ARB/ARNI, β-blocker were high in management group.Conclusion: CHF checklist management by cardiologists and general practitioners can significantly reduce the re-hospitalization and improve cardiac function. CHF management through heart failure checklist may improve prognosis in patients with CHF in the medium- and long-term.Keywords: chronic heart failure, heart failure management, heart failure checklist, prognosis, re-hospitalization rate, CHF

Bei Wen,1 Yinbing Pan,2 Jianguo Cheng,3,4 Li Xu,1 Jijun Xu3,5 1Department of Anesthesiology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China; 2Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People’s Republic of China; 3Department of Pain Management, Cleveland Clinic, Cleveland, OH, 44195, USA; 4Department of Neuroscience, Cleveland Clinic, Cleveland, OH, 44195, USA; 5Department of Inflammation and Immunity; Cleveland Clinic, Cleveland, OH, 44195, USACorrespondence: Li Xu; Jijun Xu, Email pumchxuli@163.com; xuj3@ccf.orgAbstract: Complex Regional Pain Syndrome (CRPS) is an excess and/or prolonged pain and inflammation condition that follows an injury to a limb. The pathogenesis of CRPS is multifaceted that remains incompletely understood. Neuroinflammation is an inflammatory response in the peripheral and central nervous systems. Dysregulated neuroinflammation plays a crucial role in the initiation and maintenance of pain and nociceptive neuronal sensitization, which may contribute to the transition from acute to chronic pain and the perpetuation of chronic pain in CRPS. The key features of neuroinflammation encompass infiltration and activation of inflammatory cells and the production of inflammatory mediators in both the central and peripheral nervous systems. This article reviews the role of neuroinflammation in the onset and progression of CRPS from six perspectives: neurogenic inflammation, neuropeptides, glial cells, immune cells, cytokines, and keratinocytes. The objective is to provide insights that can inform future research and development of therapeutic targets for CRPS.Keywords: complex regional pain syndrome, neuroinflammation, neurogenic inflammation, glial cells, keratinocytes

Ya-Ming Xie,1 Wenfeng Lu,2 Jian Cheng,1 Mugen Dai,3 Si-Yu Liu,4 Dong-Dong Wang,1 Tian-Wei Fu,1 Tai-Wei Ye,1 Jun-Wei Liu,1 Cheng-Wu Zhang,1 Dong-Sheng Huang,1 Lei Liang1 1Department of Hepatobiliary & Pancreatic Surgery and Minimally Invasive Surgery, General Surgery, Cancer Center, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, People’s Republic of China; 3Department of Gastroenterology, The Fifth Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China; 4Department of Laboratory Medicine, The Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research of Zhejiang Province, Zhejiang University Lishui Hospital, Lishui, Zhejiang, People’s Republic of ChinaCorrespondence: Lei Liang; Dong-Sheng Huang, Department of Hepatobiliary & Pancreatic Surgery and Minimally Invasive Surgery, General Surgery, Cancer Center, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China, Email liangl1992@hotmail.com; huangdshz88@hotmail.comBackground: Nutritional and inflammatory status has been reported to be associated with the prognosis of hepatocellular carcinoma (HCC), but many studies did not include all biomarkers simultaneously. The present study aimed to determine the impact of Naples prognostic score (NPS) on the long-term survival in patients undergoing hepatectomy for HCC.Methods: Patients with HCC after curative resection were eligible. Then, all patients were stratified into three groups according to the NPS. Clinical features and survival outcomes were compared among the three groups. Independent prognostic factors were determined by COX analysis. The time dependent receiver operating characteristic (ROC) curves were used to compare prognostic performance with other immunonutrition scoring systems.Results: A total of 476 patients were enrolled eventually. Baseline characteristics showed that patients with higher NPS had a higher proportion of poor liver function and advanced tumor features. Accordingly, Kaplan-Meier survival curves showed that patients with higher NPS had a lower rate of overall survival (OS) and recurrence-free survival (RFS). Multivariable COX analysis demonstrated that NPS was an independent risk factor of OS (NPS group 2 vs 1: HR=1.958, 95% CI: 1.038– 3.369, p = 0.038; NPS group 3 vs 1: HR=2.608, 95% CI: 1.358– 5.008, p=0.004, respectively) and RFS (NPS group 2 vs 1: HR=2.014, 95% CI: 1.299-2-3.124, p=0.002; NPS group 3 vs 1: HR=2.002, 95% CI: 1.262– 3.175, p=0.003, respectively). The time-dependent ROC curve showed that NPS was superior to other models in prognostic performance and discriminatory power for long-term survival (median AUC 0.675, 95% CI: 0.586– 0.712, P < 0.05).Conclusion: The NPS is a simple tool strongly associated with long-term survival in patients undergoing curative hepatectomy for HCC.Keywords: hepatocellular carcinoma, Naples prognostic score, nutritional indicator, inflammatory indicator, prognostic performance

Ye J, Li R, Cheng J, et al. Int J Nanomedicine. 2022;17:6047–6064. The authors have advised that there is an error in Figure 9 on page 6060 of the published paper. Due to an error that occurred inadvertently at the time of figure assembly, figure part D is incorrect. Although it does not affect the conclusion that AmB nanoformulations can significantly promote macrophage proliferation when incubated with high concentrations, it is an obvious mistake. The correct Figure 9 is as follows. Figure 9 Continued. Figure 9 In vitro cytotoxicity of AmB injection, AmB-CSC, and AmB-Lipo in murine RAW264.7 macrophages. The murine RAW264.7 macrophages were treated with AmB injection (A), AmB-CSC (C), and AmB-Lipo (E) at AmB concentrations of 0.1–50 µg/mL for 24 h and the cell viability was determined using CCK-8 kits. Each value represents the mean ± SEM (n = 6). ***p < 0.001 compared with the control (Ctrl) group. The cell morphology of RAW264.7 macrophages after incubation with AmB injection (B), AmB-CSC (D), and AmB-Lipo (F) was observed by Cell Imaging Multimode Reader (Cytation 5, BioTek).Abbreviations: AmB, amphotericin B; AmB-CSC, AmB cholesteryl sulfate complex; AmB-Lipo, AmB liposome; SEM, standard error of the mean. The authors apologise for this error.

Chunkun Yang,1,&ast; Jiawen Cheng,1,&ast; Qinwei Zhu,2 Qingquan Pan,2 Kui Ji,2 Jun Li1 1Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Department of Emergency, Weifang Hospital of Traditional Chinese Medicine, Weifang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Li, Email gamyylj@163.comAbstract: Cardiovascular disease (CVD) is one of the leading causes of death in the world. Paeonol(Pae) is a phenolic component extracted from peony bark, peony root and Xu Changqing. Studies have shown that Pae can protect cardiomyocytes by inhibiting oxidative stress, promoting mitochondrial fusion, regulating mitochondrial autophagy and inhibiting inflammation. In addition, Pae improves ventricular remodeling by inhibiting myocardial apoptosis, hypertrophy and fibrosis. Pae also has a good protective effect on blood vessels by inhibiting vascular inflammation, reducing the expression of adhesion molecules, inhibiting vascular proliferation, and inhibiting oxidative stress and endoplasmic reticulum stress(ERS). Pae also has the effect of anti-endothelial cell senescence, promoting thrombus recanalization and vasodilating. In conclusion, the molecular targets of Pae are very complex, and the relationship between different targets and signaling pathways cannot be clearly explained, which requires us to use systems biology methods to further study specific molecular targets of Pae. It has to be mentioned that the bioavailability of Pae is poor, and some nanotechnology-assisted drug delivery systems improve the therapeutic effect of Pae. We reviewed the protective mechanism of paeonol on the cardiovascular system, hoping to provide help for drug development in the treatment of CVD.Keywords: paeonol, oxidative stress, inflammation, mitochondrial fusion, adhesion, autophagy

Zehui Qin,1 Minhua Li,1,2 Juanjuan Cheng,1,2 Ziwei Huang,1,2 Gaoxiang Ai,1,2 Chang Qu,3 Youliang Xie,1 Yucui Li,1 Huijun Liao,4 Jianhui Xie,5– 7 Ziren Su1,2 1School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, People’s Republic of China; 2Dongguan Institute of Guangzhou University of Chinese Medicine, Dongguan, 523808, People’s Republic of China; 3College of Forestry and Landscape Architecture, South China Agricultural University, Guangzhou, 510006, People’s Republic of China; 4Department of Clinical Pharmacy and Pharmaceutical Services, Huazhong University of Science and Technology Union Shenzhen Hospital (the 6th affiliated Hospital of Shenzhen University), Shenzhen, People’s Republic of China; 5The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 6State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 7Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, People’s Republic of ChinaCorrespondence: Ziren Su, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR China, Dongguan Institute of Guangzhou University of Chinese Medicine, Dongguan, 523808, People’s Republic of China, Email suziren@gzucm.edu.cn Huijun Liao, Department of Clinical Pharmacy and Pharmaceutical Services, Huazhong University of Science and Technology Union Shenzhen Hospital (the 6th affiliated hospital of Shenzhen University), Shenzhen, People’s Republic of China, Email liaohuijun1016@163.comPropose: Berberine (BBR) is extensively studied as an outstanding anti-hyperuricemia drug. However, the clinical application of BBR was limited due to its poor absorption and low bioavailability. Therefore, there is an urgent necessity to find a novel drug formulation to address the issues of BBR in clinical application.Methods: Herein, we conducted the solubility, characterization experiments to verify whether BBR and sodium taurocholate (STC) self-assembled nanoparticles (STC@BBR-SANPs) could form. Furthermore, we proceeded the release experiment in vitro and in vivo to investigate the drug release effect. Finally, we explored the therapeutic effect of STC@BBR-SANPs on hyperuricemia (HUA) through morphological observation of organs and measurement of related indicators.Results: The solubility, particle size, scanning electron microscopy (SEM), and stability studies showed that the stable STC@BBR-SANPs could be formed in the BBR-STC system at ratio of 1:4. Meanwhile, the tissue distribution experiments revealed that the STC@BBR-SANPs could accelerate the absorption and distribution of BBR. In addition, the pharmacology study demonstrated that both BBR and STC@BBR-SANPs exhibited favorable anti-HUA effects and nephroprotective effects, while STC@BBR-SANPs showed better therapeutic action than that of BBR.Conclusion: This work indicated that STC@BBR-SANPs can be self-assembly formed, and exerts excellent uric acid-lowering effect. STC@BBR-SANPs can help to solve the problems of poor solubility and low absorption rate of BBR in clinical use, and provide a new perspective for the future development of BBR.Graphical Abstract: Keywords: berberine, sodium taurocholate, intermolecular interactions, self-assembled, nanoparticles, hyperuricemia

Yuxun Wei,1– 4,&ast; Yumeng Wei,1– 4,&ast; Lin Sheng,1– 4 Jingwen Ma,1– 4 Zhilian Su,1– 4 Jie Wen,1– 4 Lanmei Li,5 Qiang Jia,2,6 Huiyang Liu,1– 4 Hui Si,2,4 Linjin Xiong,1– 4 Jinglin Chen,1– 4 Ju Cheng,3,4 Ying Zuo,2,7 Hongru Yang,8 Ling Zhao2– 4 1Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, People’s Republic of China; 2Key Laboratory of Medical Electrophysiology, Ministry of Education, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University; Luzhou, Sichuan, People’s Republic of China; 3Central Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 4Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 5Nanchong Key Laboratory of Individualized Drug Therapy, Department of Pharmacy, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 6Ethics Committee Office, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 7Department of Comprehensive Medicine, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 8Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Zhao, Key Laboratory of Medical Electrophysiology, Ministry of Education, Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China, Tel/Fax +86 830 3160093, Email zhaoling-998@163.com Hongru Yang, Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China, Tel/Fax +86 830 8585668, Email yanghongru801@126.comPurpose: The present study aimed to construct a co-loading platform encapsulating curcumin and paclitaxel at ratios of 2:1– 80:1 (w/w) designated “CU-PTX-LNP” and explored the synergistic effects of CU-PTX at different composite proportions on liver cancer cells using the combination index (CI) method.Methods: The CU lipid nanoplatform (CU-LNP) formulation was optimized via single-factor and orthogonal experiments. Various concentrations of PTX were added to the optimal formulation of CU-LNP to generate CU-PTX-LNP and the nanoplatform characterized via differential scanning calorimetry (DSC), transmission electron microscope (TEM), X-ray diffraction (XRD), zeta potential, polydispersity index (PDI), and size analyses. The cumulative release, stability, and cytotoxicity of CU-PTX-LNP in LO2, HepG2, and SMMC-7221 cells were assessed in vitro, followed by safety investigation and pharmacokinetic studies in vivo. The anti-tumor activity of CU-PTX-LNP was also evaluated using nude mice.Results: CU-PTX-LNP formulations containing CU:PTX at a range of proportions (2:1– 80:1; w/w) appeared as uniformly dispersed nanosized spherical particles with high entrapment efficiency (EE> 90%), sustained release and long-lasting stability. Data from in vitro cytotoxicity assays showed a decrease in the IC50 value of PTX of CU-PTX-LNP (by 5.47– 332.7 times in HepG2 and 4.29– 143.21 times in SMMC-7221 cells) compared to free PTX. In vivo, CU-PTX-LNP displayed excellent biosafety, significant anti-tumor benefits and enhanced pharmacokinetic behavior with longer mean residence time (MRT(0-t); CU: 4.31-fold, PTX: 4.61-fold) and half-life (t1/2z; CU: 1.83-fold, PTX: 2.28-fold) relative to free drugs.Conclusion: The newly designed CU-PTX-LNP platform may serve as a viable technological support system for the successful production of CU-PTX composite preparations.Keywords: curcumin, paclitaxel, lipid nano platform, synergistic effect

Qian Huang,1,&ast; Xing Chen,1,2,&ast; Hui Yan Shen,1 Jia Mou Zhou,1 He Qiao Zhang,1 Li Wang,1 Ren Chen,1 Jing Cheng,1 Yan Zhang,1 Dong Mei Zhang,1 Gui Mei Chen1 1School of Health Service Management, Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 2School of Public Health, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gui Mei Chen; Dong Mei Zhang, Email chengm@ahmu.edu.cn; zdmd@sina.comPurpose: We aimed to analyze the relationship between handgrip strength/relative handgrip strength among older Han adults with type 2 diabetes mellitus (T2DM) by gender to determine the optimal cut-off value of grip strength for older adults.Methods: A multi-stage sampling method was used to conduct a questionnaire survey and physical examination of 6128 older adults in Anhui Province. Chi-squares tests, t-tests, analysis of variance, and logistic regression analysis were used to analyze the association between handgrip strength/relative handgrip strength and T2DM between the sexes. The decision tree model (CRT) was used to explore the predictive value of handgrip strength /relative handgrip strength on T2DM.Results: There was an association between handgrip strength and T2DM (P = 0.006, OR = 0.985, 95% CI = 0.975, 0.996), which was found in females (P = 0.013, OR = 0.978, 95% CI = 0.961, 0.995) but not in males (P = 0.125, OR = 0.989, 95% CI = 0.976, 1.003). Relative handgrip strength was also correlated with T2DM (P = 0.014, OR = 0.730, 95% CI = 0.568, 0.939), which was found in females (P = 0.003, OR = 0.534, 95% CI = 0.352, 0.809) but not in males (P = 0.432, OR = 0.879, 95% CI = 0.638, 1.212). The incidence of T2DM in elderly females with hypertension who were uneducated and with a handgrip strength of < 17.350 kg was 24.3% (115 cases), whereas that in elderly females with hypertension and a relative handgrip strength of < 0.240 was 29.0% (127 cases).Conclusion: According to our results, handgrip strength and relative handgrip strength were associated with T2DM. People with hypertension had a higher risk of T2DM in women with a handgrip strength of ≤ 17.350kg and a relative grip strength of ≤ 0.240. Further research is needed to validate the effectiveness of this cut-off for implementing interventions and avoiding risks.Keywords: diabetes mellitus, handgrip strength, gender, older adult

Drug-induced nephrotoxicity is a leading cause of drug attrition, partly due to the limited relevance of pre-clinical models of the proximal tubule. Culturing proximal tubule epithelial cells (PTECs) under fluid flow to mimic physiological shear stress has been shown to improve select phenotypes, but existing flow systems are expensive and difficult to implement by non-experts in microfluidics. Here, we designed and fabricated an accessible and modular flow system for culturing PTECs under physiological shear stress, which induced native-like cuboidal morphology, downregulated pathways associated with hypoxia, stress, and injury, and upregulated xenobiotic metabolism pathways. We also compared the expression profiles of shear-dependent genes in our in vitro PTEC tissues to that of ex vivo proximal tubules and observed stronger clustering between ex vivo proximal tubules and PTECs under physiological shear stress relative to PTECs under negligible shear stress. Together, these data illustrate the utility of our user-friendly flow system and highlight the role of shear stress in promoting native-like morphological and transcriptomic phenotypes in PTECs in vitro, which is critical for developing more relevant pre-clinical models of the proximal tubule for drug screening or disease modeling.

Fan Hu,1,2,* Meng-Lu Lin,1,2,* Juan-Li Mou,1,2,* Jia-Hui Feng,1,2 Kai Huang,1,2 Yao-Jia Lao,1,2 Jie Cheng,1,2 Jun Lin1,2 1Department of Gastroenterology/Hepatology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 2The Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun Lin, Email linjun64@126.comBackground: Carbapenem resistant Klebsiella pneumoniae (CRKP) is an independent risk factor for nosocomial infection which poses a serious threat to human health. How to prevent and suppress CRKP infection and explore its drug resistance mechanisms have become a huge challenge and possesses immediate significance.Methods: A total of 45 CRKP strains isolated from hospitalized patients in Zhongnan Hospital of Wuhan University were collected from August 2018-December 2020. The strain’s identification and antimicrobial susceptibility tests were performed using the VITEK 2 automated identification instrument. Single molecule DNA sequencing of 45 CRKP isolates was performed by the third generation high-throughput sequencing technology.Results: The results were analyzed by multi locus sequence typing (MLST) and phylogenetic analysis. Antimicrobial susceptibility showed that 45 CRKP isolates were multi-drug resistant strains, and the resistance rates to common antibiotics were as high as 68%. Whole genome sequencing results showed that the CRKP strains carried multiple drug resistance genes and virulence factors. MLST analysis found two different sequence types (ST), of which 44 were ST11 and 1 was ST1049.Conclusion: Through whole genome sequencing (WGS), we found multiple drug-resistant genes and virulence factors, and there was obvious dominant microbiota. The source was mainly related to nosocomial infection. The ST11-KPC Klebsiella pneumoniae was the main type, which was consistent with the most common type in China. We identified several dominant microbiotas which may serve as a target in the clinical prevention and treatment of severe bacterial infections. Our finding may have a role for guiding clinical antibiotic choosing.Keywords: Klebsiella pneumoniae, carbapenemases, whole-genome sequencing, resistance genes, virulence factor

Minhua Li,1,&ast; Zehui Qin,1,&ast; Qiuxia Yu,2 Ziwei Huang,3 Juanjuan Cheng,1 Linjiang Zhong,1 Yuhong Liu,1 Jianhui Xie,4– 6 Yucui Li,1 Jiannan Chen,1 Ruoting Zhan,1 Ziren Su1 1School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, People’s Republic of China; 2The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, 510120, People’s Republic of China; 3The First Affiliated Hospital of Chinese Medicine Guangzhou University of Chinese Medicine, Guangzhou, 510120, People’s Republic of China; 4The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, People’s Republic of China; 5State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, People’s Republic of China; 6Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, 510120, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ruoting Zhan; Ziren Su, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, no. 232, Waihuandong Road, Guangzhou Higher Education Mega Center, Guangzhou, 510006, People’s Republic of China, Email zhanrt@gzucm.edu.cn; suziren@gzucm.edu.cnBackground: Berberine (BBR) is the primary active component of Phellodendri Chinensis Cortex (PCC), which has been traditionally used to treat inflammatory diseases. However, the discrepancy between its low bioavailability and significant therapeutic effect remains obscure. The purpose of this study was to explore the previously unsolved enigma of the low bioavailability of BBR and its appreciable anti-inflammatory effect to reveal the action mechanism of BBR and PCC.Methods: The quantitative analysis of BBR and its metabolite oxyberberine (OBB) in blood and tissues was performed using high-performance liquid chromatography to investigate the conversion and distribution of BBR/OBB mediated by erythrocytes. Routine blood tests and immunohistochemical staining were used to explore the potential relationship between the amounts of monocyte/macrophage and the drug concentration in erythrocytes and tissues (liver, heart, spleen, lung, kidney, intestine, muscle, brain and pancreas). To comparatively explore the anti-inflammatory effects of BBR and OBB, the acetic acid-induced vascular permeability mice model and lipopolysaccharide-induced RAW 264.7 macrophages were employed.Results: Nearly 92% of BBR existed in the erythrocytes in rats. The partition coefficient of BBR between plasma and erythrocytes (Kp/b) decreased with time. OBB was found to be the oxidative metabolite of BBR in erythrocytes. Proportion of BBR/OBB in erythrocytes changed from 9.38% to 16.30% and from 13.50% to 46.24%, respectively. There was a significant relationship between the BBR/OBB concentration in blood and monocyte depletion after a single administration of BBR. BBR/OBB was transported via erythrocytes to various tissues (liver, kidney, spleen, lung, and heart, etc), with the liver achieving the highest concentration. OBB exhibited similar anti-inflammatory effect in vitro and in vivo as BBR with much smaller dosage.Conclusion: BBR was prodominantly found in erythrocytes, which was critically participated in the biodistribution, pharmacokinetics, metabolism and target delivery of BBR and its metabolite. The anti-inflammatory activity of BBR and PCC was intimately associated with the metabolism into the active congener OBB and the targeted delivery to monocytes/macrophages mediated by the erythrocytes.Graphical Abstract: Keywords: erythrocytes, Phellodendri Chinensis Cortex, transformation, berberine, anti-inflammation

Jun Ye,1,2 Renjie Li,1,2 Jialing Cheng,1,2 Dongdong Liu,1,2 Yanfang Yang,1,2 Hongliang Wang,1,2 Xiaoyan Xu,1,2 Lin Li,1,2 Panpan Ma,3 Yuling Liu1,2 1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 3Beijing Union Second Pharmaceutical Factory, Beijing, People’s Republic of ChinaCorrespondence: Yuling Liu, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Xiannongtan Street, Beijing, 100050, People’s Republic of China, Tel +86 10-89285188, Fax +86 10-89285190, Email ylliu@imm.ac.cnBackground: Amphotericin B (AmB) nanoformulations have been widely used for the treatment of invasive fungal infections in clinical practice, all of which are lyophilized solid dosage forms that improve storage stability. The colloidal stability of reconstituted lyophilized nanoparticles in an injection medium is a critical quality attribute that directly affects their safety and efficacy during clinical use.Methods: In the present study, the colloidal stability of commercial AmB nanoformulations, including AmB cholesteryl sulfate complex (AmB-CSC) and AmB liposome (AmB-Lipo), was evaluated using the dynamic (DLS) and static multiple light scattering (SMLS) techniques.Results: Compared to the DLS technique, the SMLS technique allows for a more objective and accurate evaluation of the colloidal stability of AmB nanoformulations. The results obtained using the SMLS technique demonstrated that AmB-CSC and AmB-Lipo exhibited excellent colloidal stability in both sterile water and 5% dextrose injection. The disk-like structure of the AmB-CSC nanoparticles more readily adsorbed serum proteins to form protein corona compared to the spherical structure of AmB-Lipo after incubation with serum. Additionally, AmB-CSC and AmB-Lipo can significantly reduce the in vitro cytotoxicity and in vivo nephrotoxicity of AmB, which may be attributed to the good colloidal stability and the improved pharmacokinetic profiles of AmB nanoformulations.Conclusion: To the best of our knowledge, this study is the first to compare the colloidal stability of commercial AmB nanoformulations. These findings will provide useful information not only to inform the clinical use of available AmB nanoformulations but also for improving the design and conduct of translational research on novel AmB nanomedicines.Keywords: nano-drug delivery systems, colloidal stability, amphotericin B, dynamic light scattering, static multiple light scattering

Bowen Chen,1,2,&ast; Linzhi Zhang,2,3,&ast; Jiamin Cheng,2,&ast; Tong Wu,2 Jin Lei,2,4 Xu Yang,5 Rongling Zhang,6 Rifaat Safadi,7 Yinyin Li,2 Tongguo Si,3 Yinying Lu1,2,8,9 1Peking University 302 Clinical Medical School, Beijing, People’s Republic of China; 2Senior Department of Hepatology, the 5th Medical Center of the PLA General Hospital, Beijing, People’s Republic of China; 3Tianjin Medical University Cancer Institute and Hospital, Tianjin, People’s Republic of China; 4Guizhou Medical University, Guiyang, People’s Republic of China; 5Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 6Department of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 7Liver Unit, Hadassah-Hebrew University Hospital, Jerusalem, Israel; 8Center for Synthetic & System Biology, Tsinghua University, Beijing, People’s Republic of China; 9Guangdong Key Laboratory of Epigenetics, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yinying Lu, Peking University 302 Clinical Medical School, No. 100, Middle Road of the West 4th Ring, Beijing, 100039, People’s Republic of China, Email luyinying1973@163.com Tongguo Si, Tianjin Medical University Cancer Institute and Hospital, Tiyuan North Huanhu West Road, Hexi District, Tianjin, 300060, People’s Republic of China, Email sitg77@163.comPurpose: This study aimed to investigate the incidence rate and risk factors for hepatic encephalopathy (HE) among unresectable hepatocellular carcinoma (uHCC) patients with liver cirrhosis who received sorafenib or lenvatinib treatment.Patients and Methods: uHCC patients with cirrhosis who received first-line sorafenib or lenvatinib treatment between September 2014 and February 2021 were continually reviewed in our single-center retrospective study. The Hepatic Encephalopathy Scoring Algorithm was used to evaluate the occurrence and grade of HE during treatment, and logistic regression models were used to further explore the risk factors for HE.Results: A total of 454 eligible patients were enrolled in our study, with 214 and 240 patients in the sorafenib and lenvatinib groups, respectively. At time of data cut-off (2021– 12), the incidence of HE in sorafenib group (4.2%, 95% CI:2– 7%) was significantly lower than that in lenvatinib group (11.3%,95% CI:7– 15%) (p = 0.006), with alcoholic cirrhosis [OR: 5.857 (95% CI: 1.519– 22.591)], Child-Pugh > 7 [OR: 3.023 (95% CI: 1.135– 8.053)], blood ammonia ≥ 38.65 μmol/L [OR: 4.693 (95% CI: 1.782– 12.358)], total bile acid ≥ 29.5 μmol/L [OR: 11.047 (95% CI: 4.414– 27.650)] and duration of treatment ≥ 5.6 months [OR: 4.350 (95% CI: 1.701– 11.126)] to be risk factors for the occurrence of HE during first-line systemic therapy.Conclusion: In our study, for off-label uHCC patients (Child-Pugh > 7) with alcoholic cirrhosis, hyperammonemia, hypercholesterolemia, and estimated longer duration of treatment, the application of lenvatinib has to be cautious, which needs to be confirmed in future clinical trials.Keywords: hepatic encephalopathy, hepatocellular carcinoma, liver cirrhosis, sorafenib, lenvatinib

Bowen Chen1,2 &ast;, Jin Lei1,3 &ast;, Haitao Zhao,4 Jinghui Dong,5 Zhen Zeng,1 Yinyin Li,1 Lingxiang Yu,1 Lin Zhou,6 Aiying Jia,5 Yinying Lu,1– 3 Jiamin Cheng1 1Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, People’s Republic of China; 2Peking University 302 Clinical Medical School, Beijing, People’s Republic of China; 3Guizhou Medical University Clinical Medical School, Guiyang, People’s Republic of China; 4Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 5Radiology Department, The Fifth Medical Center of PLA General Hospital, Beijing, People’s Republic of China; 6Department of Oncology, The Fifth Medical Center of PLA General Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiamin Cheng; Yinying Lu, Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, No. 100, Middle Road of the West 4th Ring, Beijing, 100039, People’s Republic of China, Tel +86-10-66933294 ; +86-10-66933380, Email chengjiamin300@163.com; luyinying1973@163.comPurpose: To explore the efficacy and safety of sorafenib- or lenvatinib-based combination therapy with PD-1 inhibitors in elderly patients aged ≥ 75 years with unresectable hepatocellular carcinoma (uHCC).Patients and Methods: Systemic therapy-naïve uHCC patients who received first-line sorafenib- or lenvatinib-based combination therapy with PD-1 inhibitors were continually reviewed. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) in accordance with the Response Evaluation Criteria in Solid Tumors version 1.1. Adverse events (AEs) and immune-related AEs (irAEs) were also evaluated. Groups and subgroups were separated at the ages of 65 and 75 years and compared with 1:1 matching.Results: Total 169 eligible patients were enrolled, including 24 aged ≥ 75 years. Median progression-free survival (PFS) and overall survival (OS) in these 24 elderly patients were 4.6 (95% CI: 2.6– 6.6) months, and 17.0 (95% CI: 11.2– 22.8) months, with 3-, 6-, 12-month OS rate at 82.90%, 73.70%, and 57.50%. Age ≥ 75 years was confirmed to be a risk factor influencing PFS among patients aged ≥ 65 years. Adverse events (AEs) were recorded in all these 24 elderly patients, with seven patients experiencing immune-mediated AEs (irAEs). Nearly 30% of elderly patients stopped treatment due to AEs (16% of these due to irAEs). No statistical differences were found in all efficacy endpoints at the cutoff age of 65 years.Conclusion: For patients aged ≥ 75 years, application of PD-1 inhibitors in combination with sorafenib or lenvatinib is promising, but this has to be done with caution and needs to be confirmed by future prospective studies.Keywords: hepatocellular carcinoma, elderly, PD-1 inhibitors, efficacy, safety

Shan Huang,1 Bingtao Zhai,1 Yu Fan,2 Jing Sun,1 Jiangxue Cheng,1 Junbo Zou,1 Xiaofei Zhang,1 Yajun Shi,1 Dongyan Guo1 1Shaanxi Province Key Laboratory of New Drugs and Chinese Medicine Foundation Research, College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, 712046, People’s Republic of China; 2School of Basic Medicine, Shaanxi University of Chinese Medicine, Xianyang, 712046, People’s Republic of ChinaCorrespondence: Dongyan Guo, Tel +86-029-38185180, Email xmc2051080@163.comBackground: Ulcerative colitis (UC) is one of the intractable diseases recognized by the World Health Organization, and paeonol has been proven to have therapeutic effects. However, the low solubility of paeonol limits its clinical application. To prepare and optimize paeonol liposome, study its absorption mechanism and the anti-inflammatory activity in vitro and in vivo, in order to provide experimental basis for the further development of paeonol into an anti-inflammatory drug in the future.Methods: Paeonol loaded liposomes were prepared and optimized by thin film dispersion-ultrasonic method. The absorption mechanism of paeonol-loaded liposomes was studied by pharmacokinetics, in situ single-pass intestinal perfusion and Caco-2 cell monolayer model, the anti-inflammatory activity was studied in a mouse ulcerative model.Results: Box-Behnken response surface methodology permits to screen the best formulations. The structural and morphological characterization showed that paeonol was entrapped inside the bilayer in liposomes. Pharmacokinetic studies found that the AUC0-t of Pae-Lips was 2.78 times than that of paeonol suspension, indicating that Pae-Lips significantly improved the absorption of paeonol. In situ single intestinal perfusion and Caco-2 monolayer cell model results showed that paeonol was passively transported and absorbed, and was the substrate of P-gp, MRP2 and BCRP, and the Papp value of Pae-Lips was significantly higher than that of paeonol. In vitro and in vivo anti-inflammatory experiments showed that compared with paeonol, Pae-Lips exhibited excellent anti-inflammatory activity.Conclusion: In this study, Pae-Lips were successfully prepared to improve the oral absorption of paeonol. Absorption may involve passive diffusion and efflux transporters. Moreover, Pae-Lips have excellent anti-inflammatory activity in vitro and in vivo, which preliminarily clarifies the feasibility of further development of Pae-Lips into oral anti-inflammatory drugs.Keywords: paeonol liposomes, intestinal absorption, Caco-2 monolayer cell model, absorption mechanism, anti-inflammatory activity

Kidney macrophages are comprised of both monocyte-derived and tissue resident populations; however, the heterogeneity of kidney macrophages and factors that regulate their heterogeneity are poorly understood. Herein, we performed single cell RNA sequencing (scRNAseq), fate mapping, and parabiosis to define the cellular heterogeneity of kidney macrophages in healthy mice. Our data indicate that healthy mouse kidneys contain four major subsets of monocytes and two major subsets of kidney resident macrophages (KRM) including a population with enriched Ccr2 expression, suggesting monocyte origin. Surprisingly, fate mapping data using the newly developed Ms4a3Cre Rosa Stopf/f TdT model indicate that less than 50% of Ccr2+ KRM are derived from Ly6chi monocytes. Instead, we find that Ccr2 expression in KRM reflects their spatial distribution as this cell population is almost exclusively found in the kidney cortex. We also identified Cx3cr1 as a gene that governs cortex specific accumulation of Ccr2+ KRM and show that loss of Ccr2+ KRM reduces the severity of cystic kidney disease in a mouse model where cysts are mainly localized to the kidney cortex. Collectively, our data indicate that Cx3cr1 regulates KRM heterogeneity and niche-specific disease progression.

Zhaokang Bao,1,&ast; Jiale Cheng,1,&ast; Jiahao Zhu,2,&ast; Shengjun Ji,3 Ke Gu,2 Yutian Zhao,2 Shiyou Yu,1 You Meng1 1Department of Oncology Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, People’s Republic of China; 2Department of Radiotherapy and Oncology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, People’s Republic of China; 3Department of Radiotherapy and Oncology, The affiliated Suzhou Hospital of Nanjing Medical University, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: You Meng, Department of Oncology Surgery, The affiliated Suzhou Hospital of Nanjing Medical University, Gusu School, Nanjing Medical University, 16 West Baita Road, Suzhou, Jiangsu, People’s Republic of China, Email drmengyou@163.comObjective: We used bioinformatics analysis to identify potential biomarker genes and their relationship with breast cancer (BC).Materials and Methods: We used a weighted gene co-expression network analysis (WGCNA) to create a co-expression network based on the top 25% genes in the GSE24124, GSE33926, and GSE86166 datasets obtained from the Gene Expression Omnibus. We used the DAVID online platform to perform GO and KEGG pathway enrichment analyses and the Cytoscape CytoHubba plug-in to screen the potential genes. Then, we related the genes to prognostic values in BC using the Oncomine, GEPIA, and Kaplan–Meier Plotter databases. Findings were validated by immunohistochemical (IHC) staining in the Human Protein Atlas and the TCGA-BRCA cohort. LinkedOmics identified the interactive expressions of hub genes. We used UALCAN to evaluate the methylation levels of these hub genes. MethSurv and SurvivalMeth were used to assess the multilevel prognostic value. Finally, we assessed hub gene association with immune cell infiltration using TIMER.Results: The mRNA levels of MKI67, UBE2C, GTSE1, CCNA2, and MND1 were significantly upregulated in BC, whereas ESR1, THSD4, TFF1, AGR2, and FOXA1 were significantly downregulated. The DNA methylation signature analysis showed a better prognosis in the low-risk group. Further subgroup analyses revealed that MND1 might serve as an independent risk factor for unfavorable BC prognosis. Additionally, MND1 expression levels positively correlate with the immune infiltration statuses of CD4+ T cells, CD8+ T cells, B cells, neutrophils, dendritic cells, and macrophages.Conclusion: Our results indicate that the ten hub genes may be involved in BC’s carcinogenesis, development, or metastasis, and MND1 may be a potential biomarker and therapeutic target for BC.Keywords: breast neoplasms, immunohistochemistry, polymerase chain reaction, biomarker

Pingping Zhao,1 Junxin Yan,1 Binjing Pan,1 Jingfang Liu,1,2 Songbo Fu,1,2 Jianguo Cheng,1,2 Liting Wang,1,2 Gaojing Jing,1,2 Qiong Li1,2 1The First Clinical Medical College, Lanzhou University, Lanzhou, Gansu, People’s Republic of China; 2Department of Endocrinology, The First Hospital of Lanzhou University, Lanzhou, Gansu, People’s Republic of ChinaCorrespondence: Jingfang Liu, Department of Endocrinology, the First Hospital of Lanzhou University, Lanzhou, Gansu, 730000, People’s Republic of China, Tel +86 931-8356242, Email ljf824168@126.comObjective: To explore the relationship between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2DM).Methods: A total of 1168 patients with T2DM were divided into the non-CKD and CKD groups, and the difference in the prevalence of NAFLD was compared. The differences in serum creatinine (SCr) and urine albumin-to-creatinine ratio (UACR) levels were compared between the non-NAFLD and NAFLD groups. Patients with T2DM were divided into three groups according to their UACR levels (UACR < 30 mg/g [U1 group]; UACR ≤ 30 mg/g to < 300 mg/g [U2 group]; and UACR ≥ 300 mg/g [U3 group]) or estimated glomerular filtration rate (eGFR) levels (≥ 90 mL/min [G1 group]; eGFR ≤ 60 mL/min to < 90 mL/min [G2 group]; and eGFR < 60 mL/min (G3 group]). The difference in the prevalence and risks of NAFLD in the different UACR or eGFR level groups was analyzed.Results: The prevalence of NAFLD in the CKD group was higher than that in the non-CKD group (63.5% vs 50.5%, p < 0.001). The SCr and UACR levels in the NAFLD group were higher than those in the non-NAFLD group (both p< 0.05). The prevalence of NAFLD in the U3 group (75.6%) was higher than that in the U1 (50.5%, p < 0.05) and U2 (60.1%, p < 0.05) groups, and the prevalence of NAFLD in the U2 group (60.1%) was higher than that in the U1 group (50.5%, p < 0.05). The risk of NAFLD in the U3 group was higher than that in the U2 group (odds ratio [OR] = 3.032 and 1.473). Despite adjusting the parameters further, the NAFLD risk in the U3 group remained higher than that in the U2 group (OR = 1.660 and 2.342).Conclusion: The risk of NAFLD in patients with T2DM is closely related to CKD.Keywords: type 2 diabetes, non-alcoholic fatty liver disease, chronic kidney disease

Jian Shen,1 Bimeng Zhang,2 Jianjie Chen,3 Jiazheng Cheng,1 Jiali Wang,1 Xianhui Zheng,1 Yu Lan,1 Xiaowen Zhang1 1Department of Pediatrics, Shuguang Hospital Affiliated to Shanghai Traditional Chinese Medical University, Shanghai, 201203, People’s Republic of China; 2Department of Acupuncture and Moxibustion, Shanghai General Hospital (The First People’s Hospital Affiliated to Shanghai Jiaotong University), Shanghai, 200080, People’s Republic of China; 3Department of Internal Medicine, Shuguang Hospital Affiliated to Shanghai Traditional Chinese Medical University, Shanghai, 201203, People’s Republic of ChinaCorrespondence: Jian Shen Department of Pediatrics, Shuguang Hospital Affiliated to Shanghai Traditional Chinese Medical University, Shanghai, 201203, People’s Republic of China Tel +86-21-53821650 Email shenjian_78@shutcm.edu.cnObjective: Irritable bowel syndrome (IBS) is characterized by abdominal pain, bloating, and stool irregularity. However, its pathophysiological mechanisms, which trigger intestinal motility disorders and diarrhea leading to diarrhea-predominant IBS (D-IBS), remain largely unknown.Methods: In the present study, we established a D-IBS rat model by mother–infant separation combined with restraint stress. Then we exposed the modelled rats to suberoylanilide hydroxamic acid (SAHA) treatment, followed by determination of their visceral sensitivity. Toluidine blue staining served to reveal the effects of SAHA treatment on mast cells of D-IBS model rats. Then we measured the expression of serotonin (5-hydroxytryptamine; 5-HT) and its receptors by ELISA.Results: Construction of short hairpin RNA (sh)-serotonin transporter (SERT) lentivirus vectors verified the regulation of the 5-HT signaling pathway by phosphorylated (p)-STAT/SERT. SAHA treatment of D-IBS model rats reduced the fecal water content, electromyography integral change rate, abdominal withdrawal reflex score, and number of mast cells, as well as the expression of 5-HT type 3A (5-HT3AR), 3B receptor (5-HT3BR), and 4 receptor (5-HT4R) receptors. The treatment also elevated the expression of signal transducer and activator for transcription 3 (STAT3) and SERT. Activation of p-STAT3 may reverse the inhibitory effect of SAHA on the elevated visceral sensitivity of D-IBS model rats. Moreover, SAHA promoted the transcription of SERT through repression of the p-STAT3/5-HT signaling, thereby inhibiting the visceral sensitivity of D-IBS model rats.Conclusion: This study highlights that SAHA treatment can alleviate D-IBS through regulation of the p-STAT3/SERT/5-HT signaling pathway.Keywords: diarrhea type irritable bowel syndrome, SAHA, p-STAT3, SERT, 5-HT

Yurong Xiong,1,2,&ast; Yun Yu,1,2,&ast; Jianduan Cheng,3 Wei Zhou,2,4 Huihui Bao,1,2,4 Xiaoshu Cheng1,2,4 1Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Jiangxi Provincial Cardiovascular Disease Clinical Medical Research Center, Nanchang, Jiangxi, People’s Republic of China; 3Wuyuan Chinese Medicine Hospital, Shangrao, Jiangxi, People’s Republic of China; 4Center for Prevention and Treatment of Cardiovascular Diseases, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huihui Bao; Xiaoshu Cheng, Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel +8613870092915 ; +8613607089128, Fax +86-0791-86262262, Email huihui_bao77@126.com; xiaoshumenfan126@163.comObjective: This study aimed to assess the associations of sleep duration, midday napping and the risk of atrial fibrillation (AF) in patients with hypertension.Methods: We conducted a cross-sectional study enrolling 11,524 hypertensive participates from the Chinese Hypertension Registry Study. Information on sleep duration and midday napping were obtained by a self-administered questionnaire. Multivariate logistic regression analyses were performed to estimate odds ratio (OR) and 95% confidence intervals (CIs) for the risk of AF.Results: Compared with sleeping 6 to ≤ 8 hours/night, those reporting shorter sleep duration (≤ 5 hours/night) had a greater risk of AF (OR 1.95; 95% CI 1.28– 2.95) in the fully adjusted model, while longer sleep (≥ 9 hours/night) was not significantly associated with the risk of AF. Compared with nonhabitual nappers, nappers had a higher risk of AF (OR 1.28; 95% CI 1.03– 1.60) in the fully adjusted model. Moreover, we observed significant joint effects of sleeping ≤ 5 hours/night and nap (OR 2.13; 95% CI 1.09– 4.14) on the risk of AF after adjusting for confounding factors.Conclusion: Short sleep duration and midday napping were independently and jointly associated with higher risks of AF in patients with hypertension.Keywords: sleep medicine, midday napping, atrial fibrillation, hypertension

Xiaowu Zhong,1– 3,&ast; Lihua Yao,1,2,&ast; Lei Xu,3,&ast; Qiang Ma,1,2 Guangcheng Huang,1,2 Miyuan Yang,2 Chuanli Gao,2 Jibing Cheng,1,2 Xi Zhou,2 Qinrong Li,2 Xiaolan Guo1– 3 1Department of Clinical Laboratory, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, People’s Republic of China; 2Department of Laboratory Medicine, North Sichuan Medical College, Nanchong, 637000, People’s Republic of China; 3Translational Medicine Research Center, North Sichuan Medical College, Nanchong, 637000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaolan Guo, Department of Clinical Laboratory, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, People’s Republic of China, Tel +86-817-2282059, Fax +86-817-2282059, Email alan5200@hotmail.comBackground: Lung adenocarcinoma (LUAD) is the most common dangerous malignant tumor and the leading cause of global cancer incidence and mortality. The Solute Carrier 1A (SLC1A) family play a significant part in cellular biological process, inflammation, and immunity. Specific functions of the SLC1A family in lung cancer are still not systematically described.Objective: This study aimed to explore the best biological understanding of SLC1A family in lung cancer.Methods: To study the expression and role of the SLC1A family in lung cancer, researchers used a variety of bioinformatics databases and tools.Results: Aberrant expression of SLC1A family genes were demonstrated and analyzed the association with gender, tumor grade, cancer stages, and nodal metastasis status. The ectopic expression of SLC1A family genes has prognostic value for LUAD patients. Immune infiltration revealed a significant correlation between SLC1A family genes expression in LUAD. SLC1A family genes were involved in manifold biological processes and have different levels of DNA methylation and genetic alteration.Conclusions: These findings suggested that members of the SLC1A family could be a potential target for the development of LUAD therapeutics as well as a reliable indicator of LUAD prognostic value.Graphical Abstract: Keywords: lung adenocarcinoma, SLC1A family, expression, prognosis, bioinformatics analysis

Yee Huang, Li Nan, Chenwen Xiao, Jie Dong, Ke Li, Jvfen Cheng, Quanan Ji, Qiang Wei, Guolian Bao, Yan Liu Institute of Animal Husbandry and Veterinary Medicine, Zhejiang Academy of Agricultural Science, Hangzhou, 310021, People’s Republic of ChinaCorrespondence: Guolian Bao; Yan Liu, Institute of Animal Husbandry and Veterinary Medicine, Zhejiang Academy of Agricultural Science, Hangzhou, 310021, People’s Republic of China, Email baoguolian@163.com; 35792191@qq.comPurpose: Outer membrane vesicles (OMVs) are spherical nano-sized proteolipids secreted by numerous pathogenic Gram-negative bacteria. Due to the immunostimulatory properties and protective efficacy, OMVs have received increasing attention as a candidate for the vaccine to prevent and treat bacterial infections. However, the immune response remains elusive due to the low structural stability and poor size homogeneity of the vesicles. In this study, OMVs were used to coat self-assembled glycyrrhizic acid nanoparticles (GANs) and obtain a stable OMV vaccine. The immunoprotective effects and anti-infection efficacy were evaluated in vivo and in vitro.Methods: The OMVs were prepared by ultrafiltration method and fused with GAN through mechanical extrusion. The characteristics, including morphology, hydrodynamic size, zeta potential, and stability were evaluated. The in vitro immunological function of GAN-OMV on the macrophages and in vivo immune efficacy and anti-infection effect were examined and compared.Results: The results showed that the GAN-OMV were homogenous with a size of 130 nm and a stable core-shell structure. Micropinocytosis-dependent and clathrin-mediated endocytotic pathways effectively internalized the GAN-OMV into the macrophages and promoted cell proliferation, cytokine secretion, and M1 polarization. Furthermore, subcutaneous GAN-OMV vaccination contributed to significantly higher Borderella bronchiseptica (Bb)-specific antibody production and lymphocyte proliferation. The splenic lymphocytes of mice immunized with GAN-OMVs displayed a higher ratio of CD4+/CD8+ T cells and CD19+ B cells and produced significantly higher levels of Th1/Th2/Th17 cytokines. GAN-OMV also effectively prevented Bb reinfection.Conclusion: In this study, GAN-OMV was developed successfully to stimulate Th1/Th2/Th17 immune responses against Bb and provide a promising strategy for novel vaccine development against the microbial pathogen.Keywords: outer membrane vesicles, glycyrrhizic acid nanoparticle, macrophage, protective immune response, anti-bacterial infection

Huan Li,1,2 Bingtao Zhai,1,2 Jing Sun,1,2 Yu Fan,3 Junbo Zou,1,2 Jiangxue Cheng,1,2 Xiaofei Zhang,1,2 Yajun Shi,1,2 Dongyan Guo1,2 1State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi University of Chinese Medicine, Xi’an, 712046, People’s Republic of China; 2The Key Laboratory of Basic and New Drug Research of Traditional Chinese Medicine, Shaanxi University of Chinese Medicine, Xi’an, 712046, People’s Republic of China; 3College of Basic Medicine, Shaanxi University of Chinese Medicine, Xi’an, 712046, People’s Republic of ChinaCorrespondence: Dongyan GuoState Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi University of Chinese Medicine, Xi’an, 712046, People’s Republic of ChinaTel +86 29-3818-5180Email xmc2051080@163.comPurpose: Aralia taibaiensis, a medicinal food plant, and total saponins from its root bark extract inhibit α-glucosidase activity, which is associated with type 2 diabetes; however, the inhibitory mechanism is unknown. Furthermore, a green extraction technique superior to conventional hot reflux extraction (HRE) is needed for the rapid and easy extraction of A. taibaiensis total saponins (TSAT) to exploit and utilize this resource. Our aim was to develop a green extraction method for obtaining TSAT and to investigate the mechanism by which TSAT inhibits α-glucosidase.Materials and Methods: In this study, the ultrasound-assisted extraction (UAE) process was optimized using a Box–Behnken design, and the extraction mechanism was investigated using scanning electron microscopy (SEM). High-performance liquid chromatography (HPLC) was used for qualitative and quantitative analyses of TSAT. In vitro glycosylation assays, enzyme kinetics, fluorescence spectroscopy measurements, atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FT-IR) and molecular docking techniques were used to investigate the mechanism by which the A. taibaiensis active ingredients inhibit α-glucosidase.Results: The optimal parameters for the extraction yield were obtained as an ethanol concentration of 73%, ultrasound time of 34 min, ultrasound temperature of 61 °C and solid–liquid ratio of 16 g/mL, which were better than HRE. The SEM analysis showed that UAE effectively disrupted plant cells, thus increasing the TSAT yield. In vitro α-glucosidase inhibition experiments showed that both TSAT and its active ingredient, araloside A, inhibited α-glucosidase activity by binding to α-glucosidase, thereby changing the conformation and microenvironment of α-glucosidase to subsequently inhibit enzyme activity.Conclusion: The optimal extraction conditions identified here established a basis for future scale-up of ultrasound extraction parameters with the potential for obtaining maximum yields. In vitro enzyme inhibition experiments investigated the mechanism of the TSAT interaction with α-glucosidase and further explored whether araloside A may be the main contributor to the good inhibition of α-glucosidase activity by TSAT.Keywords: Aralia taibaiensis total saponins, ultrasound-assisted extraction, Box–Behnken design, α-glucosidase, inhibitory mechanism

Wang Liu,1,&ast; Yu Zeng,1,&ast; Yanda Li,2,&ast; Nanhong Li,3 Min Peng,1 Junfen Cheng,1 Binbin Tian,4 Mingdi Chen5 1Department of Respiration, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, People’s Republic of China; 2Department of Internal Medicine, Central People’s Hospital of Zhanjiang, Zhanjiang, Guangdong, People’s Republic of China; 3Department of Pathology and Pathophysiology, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 4Department of Critical Care Medicine, Central People’s Hospital of Zhanjiang, Zhanjiang, Guangdong, People’s Republic of China; 5Department of Critical Care Medicine, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingdi Chen; Binbin Tian Email 724877563@qq.com; 1169855063@qq.comBackground: In December 2019, coronavirus disease 2019 (COVID-19) caused by a novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2; previously known as 2019-nCoV) emerged in Wuhan, China, and caused many infections and deaths. At present, there are no specific drugs for the etiology and treatment of COVID-19. A combination of traditional Chinese and western medicine is proposed to treat COVID-19, in which Huang Lian Jie Du decoction (HLJDD) is recommended for the treatment of COVID-19 in many provinces in China and has been widely used in the clinic. This study explored the potential targets of HLJDD in the treatment of COVID-19 based on network pharmacology.Methods: First, the chemical composition and targets of HLJDD and COVID-19-related targets were obtained through the TCMSP, UniProt, GeneCards and OMIM databases. Second, HLJDD target and HLJDD-COVID-19 target networks were constructed via the STRING database and Cytoscape software. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the HLJDD-COVID-19 targets was applied via the DAVID database.Results: Our study identified a total of 67 active ingredients of HLJDD and 204 targets of HLJDD. A total of 502 COVID-19-related targets were obtained, of which 47 were intersecting targets of HLJDD and COVID-19. A total of 179 GO terms and 77 KEGG terms, including the TNF signaling pathway, NF-κB signaling pathway and HIF-1 signaling pathway, were identified.Conclusion: The present study explored the potential targets and signaling pathways of HLJDD during the treatment of COVID-19, which may provide a basis for the research and development of drugs for the treatment of COVID-19.Keywords: Huang Lian Jie Du decoction, coronavirus disease 2019, COVID-19, SARS-CoV-2, network pharmacology, traditional Chinese medicine

Jie Cheng,1,&ast; Siyang Wang,2,&ast; Jingying Jia,3 Qian Chen,3 Yunxiao Song,4 Junsheng Li1 1Department of Urinary Surgery, Shanghai Xuhui Central Hospital, Shanghai, People’s Republic of China; 2Department of Geratology, Shanghai Xuhui Central Hospital, Shanghai, People’s Republic of China; 3Department of Central Laboratory, Shanghai Xuhui Central Hospital, Shanghai, People’s Republic of China; 4Department of Clinical Laboratory, Shanghai Xuhui Central Hospital, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junsheng LiDepartment of Urinary Surgery, Shanghai Xuhui Central Hospital, No. 966 Huaihai Road, Shanghai, 200031, People’s Republic of ChinaTel +86-21 31270810Email lijunshengdy@163.comPurpose: Red cell distribution width (RDW), an inflammation biomarker, has been linked to poor outcomes in patients with different types of cancers. The present study aimed to investigate the relationship between pre-/post-treatment 3-month RDW levels and changes in RDW with 3-year prognosis of prostate cancer.Patients and Methods: A total of 348 patients with prostate cancer were recruited between June 1, 2012 and June 1, 2017 and were followed up for at least 3 years. RDW was measured with the Mindray BC-6800Plus automatic blood counting system at pre- and post-treatment 3-month. Demographic and clinical information of the participants were also collected. The overall survival (OS) and cancer-specific survival (CSS) were analyzed using the Kaplan–Meier method. Cox regression and competing risk regression analyses were performed.Results: During the follow-up period, 51 (14.66%) deaths occurred. The levels of pre- and post-treatment RDW levels were significantly higher in the death group than in the survival group (p< 0.001). In the death group, the level of RDW continued to rise in most subjects, and the mean level of RDW was significantly higher at post-treatment than pre-treatment, contrary to the results observed in the survival group. Multivariate Cox regression analysis revealed that high pre-treatment RDW, high post-treatment RDW, and persistently higher RDW were independently associated with OS and CSS (p< 0.001). Similar results were observed in the competing risk regression analysis. Kaplan–Meier analysis revealed that patients with higher pre-treatment RDW levels, higher post-treatment RDW levels, and persistently higher RDW levels had poorer 3-year OS and CSS rates (p< 0.05).Conclusion: The levels of and changes in RDW before and after treatment were associated with the 3-year prognosis of prostate cancer, suggesting that RDW might be an efficient prognostic predictor in patients with prostate cancer.Keywords: red cell distribution width, prostate cancer, prognostic, overall survival, cohort study