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Bi Lin,1 Chaohao Huang2 1Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Hepatological Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of ChinaCorrespondence: Chaohao Huang, Department of Hepatological Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China, Email kirbylin2010@sina.comPurpose: Acute pancreatitis (AP) is a common digestive disorder characterized by high morbidity and mortality. This study aims to uncover differentially expressed long noncoding RNAs (lncRNAs) and mRNAs, as well as related pathways, in the early stage of acute pancreatitis (AP), with a focus on the role of Neat1 in AP and severe acute pancreatitis (SAP).Methods: In this study, we performed high-throughput RNA sequencing on pancreatic tissue samples from three normal mice and three mice with cerulein-induced AP to describe and analyze the expression profiles of long non-coding RNAs (lncRNAs) and mRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted on the differentially expressed mRNAs to identify enriched pathways and biological processes. An lncRNA-miRNA-mRNA interaction network was constructed to elucidate potential regulatory mechanisms. Furthermore, we utilized Neat1 knockout mice to investigate the role of Neat1 in the pathogenesis of cerulein-AP and L-arginine-severe acute pancreatitis (SAP).Results: Our results revealed that 261 lncRNAs and 1522 mRNAs were differentially expressed in the cerulein-AP group compared to the control group. GO and KEGG analyses of the differentially expressed mRNAs indicated that the functions of the corresponding genes are enriched in cellular metabolism, intercellular structure, and positive regulation of inflammation, which are closely related to the central events in the pathogenesis of AP. A ceRNA network involving 5 lncRNAs, 226 mRNAs, and 61 miRNAs were constructed. Neat1 was identified to have the potential therapeutic effects in AP. Neat1 knockout in mice inhibited pyroptosis in both the AP/SAP mouse models.Conclusion: We found that lncRNAs, particularly Neat1, play a significant role in the pathogenesis of AP. This finding may provide new insights into further exploring the pathogenesis of SAP and could lead to the identification of new targets for the treatment of AP and SAP.Keywords: acute pancreatitis, lncRNA, ceRNA, NEAT1, pyroptosis

Xueya Xu,* Weili Lu,* Hua Zhang, Xiaoying Wang, Caixia Huang, Qiuping Huang, Wen Xu, Wei Xu Pharmacy College, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoying Wang; Wei Xu, Pharmacy College, Fujian University of Traditional Chinese Medicine, 1 Qiuyang Road, Fuzhou, 350122, People’s Republic of China, Email 2003032@fjtcm.edu.cn; 2000017@fjtcm.edu.cnBackground: The combination of nanoplatform-based chemotherapy and photodynamic therapy (PDT) is a promising way to treat cancer. Celastrol (Cela) exhibits highly effective anti-hepatoma activity with low water solubility, poor bioavailability, non-tumor targeting, and toxic side effects. The combination of Cela-based chemotherapy and PDT via hepatoma-targeting and reactive oxygen species (ROS)-responsive polymeric micelles (PMs) could solve the application problem of Cela and further enhance antitumor efficacy.Methods: In this study, Cela and photosensitizer chlorin e6 (Ce6) co-loaded glycyrrhetinic acid-modified carboxymethyl chitosan-thioketal-rhein (GCTR) PMs (Cela/Ce6/GCTR PMs) were prepared and characterized. The safety, ROS-sensitive drug release, and intracellular ROS production were evaluated. Furthermore, the in vitro anti-hepatoma effect and cellular uptaken in HepG2 and BEL-7402 cells, and in vivo pharmacokinetic, tissue distribution, and antitumor efficacy of Cela/Ce6/GCTR PMs in H22 tumor-bearing mice were then investigated.Results: Cela/Ce6/GCTR PMs were successfully prepared with nanometer-scale particle size, favorable drug loading capacity, and encapsulation efficiency. Cela/Ce6/GCTR PMs exhibited a strong safety profile and better hemocompatibility, exhibiting less damage to normal tissues. Compared with Cela-loaded GCTR PMs, the ROS-responsiveness of Cela/Ce6/GCTR PMs was increased, and the release of Cela was accelerated after combination with PDT. Cela/Ce6/GCTR PMs can efficiently target liver tumor cells by uptake and have a high cell-killing effect in response to ROS. The combination of GCTR PM-based chemotherapy and PDT resulted in increased bioavailability of Cela and Ce6, improved liver tumor targeting, and better anti-hepatoma effects in vivo.Conclusion: Hepatoma-targeting and ROS-responsive GCTR PMs co-loaded with Cela and Ce6 combined with PDT exhibited improved primary hepatic carcinoma therapeutic effects with lower toxicity to normal tissues, overcoming the limitations of monotherapy and providing new strategies for tumor treatment. Keywords: ROS-responsive polymeric micelles, photodynamic therapy, hepatoma-targeting, celastrol, combination anti-hepatoma therapy

Min He, Huinan Wu, Guanrong Lin, Yongqin Wang, Longling Shi, Chaoling Huang, Qingyun Xu, Zhenxing Li, Shanbo Huang, Yanni Chen, Na Li Department of Endocrinology, Shishi General Hospital, Shishi, Fujian, 362700, People’s Republic of ChinaCorrespondence: Min He, Department of Endocrinology, Shishi General Hospital, No. 2156 Shijin Road, Shishi, Fujian, 362700, People’s Republic of China, Tel +8613506048712, Email heminhem463@163.comObjective: This study proposes a region-wide blood glucose management system to solve the problem of blood glucose management in patients with diabetes.Methods: A professional team of doctors, nurses and dietitians jointly developed a region-wide blood glucose management system. The system operates through a collaborative approach where each team member utilises their specialised role, such as data monitoring, algorithm development or patient support, to contribute to a comprehensive blood glucose management network. This integration ensures accurate glucose tracking, personalised feedback and timely adjustments to treatment plans. The system allows the patient to have a good treatment plan, giving comprehensive medical guidance, and the physician team is responsible for the patient’s health status.Results: The region-wide blood glucose management system increased the overall blood glucose monitoring rate of patients and reduced the hospitalisation time (from 11.27 days to 9.52 days) and hospitalisation costs (from 12,173.8 yuan to 9502.4 yuan). At the same time, the system effectively counted the incidence and occurrence time of hyperglycaemia and hypoglycaemia adverse events, which can provide a reference for clinical prevention of adverse events.Conclusion: A region-wide blood glucose management system can improve medical efficiency, save medical resources and provide a strong guarantee for the health of patients with diabetes. Compared with the traditional diabetes management mode, the region-wide blood glucose management system is more systematic and standardised, meaning it can better meet the needs of patients with diabetes.Keywords: diabetic, glucose management, professional team, guarantee for the health, improve medical efficiency

Chunrong Huang,1,2,* Yulian Gao,1,2,* Hongxia Lin,1– 3,* Qinmei Fan,4,* Ling Chen,1,2 Yun Feng1,2 1Department of Respiratory and Critical Care Medicine, Ruijin Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 2Institute of Respiratory Diseases, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, 610000, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, The First People’s hospital of Jin Zhong, JinZhong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ling Chen; Yun Feng, Email co840608@hotmail.com; fy01057@163.comBackground: To evaluate the clinical features of patients with Acinetobacter baumannii bloodstream infection (BSI).Methods: Totally 200 inpatients with Acinetobacter baumannii BSI were included, clinical features of Acinetobacter baumannii BSI inpatients between 90-day survival and 90-day mortality groups, between 30-day survival and 30-day mortality groups, between patients infected with multidrug-resistant (MDR group) and sensitive Acinetobacter baumannii (sensitive group) were analyzed. The prognostic factors of 90-day mortality were analyzed by univariate logistic regression and multivariate logistic regression. The survival curve in bloodstream infectious patients with multidrug-resistant (MDR group) and sensitive Acinetobacter baumannii (sensitive group) was analyzed by Kaplan–Meier analysis.Results: The 90-day mortality patients had significantly higher carbapenem-resistant bacterial infection and critical care unit (ICU) admission. The 90-day and 30-day mortality groups showed higher C-reactive protein (CRP) and serum creatinine (Scr) levels and lower red blood cells (RBC) and albumin (ALB) levels than their survival counterparts, respectively. Critical surgery, ICU admission and delayed antibiotic treatment were independently prognostic risk predictors for 90-day mortality in Acinetobacter baumannii BSI patients, while critical surgery and diabetes were independently prognostic risk predictors for 90-day mortality in carbapenem-resistant Acinetobacter baumannii BSI patients. Compared with sensitive group, MDR group showed significantly longer ICU and whole hospital stay, lower levels of lymphocytes, RBC, hemoglobin, lactate dehydrogenase and ALB, higher frequency of infection originating from the skin and skin structure. Moreover, patients in the MDR group had a significantly worse overall survival than the sensitive group.Conclusion: We identified the prognostic factors of Acinetobacter baumannii BSI and carbapenem-resistant Acinetobacter baumannii BSI patients. Critical surgery, ICU admission, delayed antibiotic treatment or diabetes were significantly associated with the mortality of those patients. Moreover, aggressive measures to control MDR Acinetobacter baumannii could lead to improved outcomes. Keywords: Acinetobacter baumannii, bloodstream infection, mortality, prognostic predictors, multidrug-resistance

Youqian Li,1,2 Wei Zhong,1,2 Zhidong Liu,1,2 Changjing Huang,1,2 Junyin Peng,1,2 Hanlin Li1,2 1Center for Cardiovascular Diseases, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 2Guangdong Provincial Engineering and Technology Research Center for Molecular Diagnostics of Cardiovascular Diseases, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of ChinaCorrespondence: Youqian Li, Center for Cardiovascular Diseases, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, No. 63 Huangtang Road, Meijiang District, Meizhou, People’s Republic of China, Email d_yoyo@163.comBackground: Aldehyde dehydrogenase 2 (ALDH2) is a key catalytic enzyme involved in the aldehyde metabolism that plays an important role in the occurrence and development of acute myocardial infarction (AMI). However, the relationship of ALDH2 polymorphism and susceptibility to AMI may differ among different regions and populations, and it has not yet been reported in Hakka population. The purpose of the present study was to investigate it in this population.Methods: Four hundred and nineteen AMI patients and 636 individuals without AMI were included in the present study. The ALDH2 rs671 polymorphism was genotyped using polymerase chain reaction (PCR)-microarray. Differences in ALDH2 rs671 genotypes and alleles between patients and controls were compared, and the relationship between ALDH2 rs671 genotypes and AMI risk was analyzed.Results: Patients with AMI had a lower frequency of ALDH2 rs671 G/G genotype (43.2% vs 52.7%, p=0.003), and a higher G/A genotype (45.6% vs 38.5%, p=0.025) than controls. And AMI patients had a lower frequency of ALDH2 rs671 G allele (66.0% vs 71.9%), and a higher A allele (34.0% vs 28.1%) (p=0.004) than controls. Logistic regression analysis showed that overweight (body mass index (BMI)≥ 24.0 kg/m2 vs BMI 18.5– 23.9 kg/m2: odds ratio (OR) 2.046, 95% confidence interval (CI): 1.520– 2.754, p< 0.001), history of hypertension (yes vs no: OR 3.464, 95% CI: 2.515– 4.770, p< 0.001), ALDH2 rs671 G/A genotype (G/A vs G/G: OR 1.476, 95% CI: 1.102– 1.976, p=0.009), and A/A genotype (A/A vs G/G: OR 1.656, 95% CI: 1.027– 2.668, p=0.038) maybe the independent risk factors for AMI.Conclusion: Overweight (BMI≥ 24.0 kg/m2), a history of hypertension, and ALDH2 rs671 G/A or A/A genotypes increased the risk of developing AMI in Hakka population.Keywords: aldehyde dehydrogenase 2, acute myocardial infarction, polymorphism, Hakka

Wanlan Fu,1 Yunxiang Cao,2 Jian Liu,2 Chuanbing Huang,2 Kaiyan Shu,1 Nanfei Zhu1 1First Clinical Medical College, Anhui University of Chinese Medicine, Hefei, Anhui, 230012, People’s Republic of China; 2Department of Rheumatology, First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, 230031, People’s Republic of ChinaCorrespondence: Yunxiang Cao, Department of Rheumatology, First Affiliated Hospital of Anhui University of Chinese Medicine, 117 Meishan Road, Shushan District, Hefei, Anhui, 230031, People’s Republic of China, Tel +86-13514984395 ; +0551-62838591, Email cyx800805@163.comPurpose: This study probed the mechanism of action of Xinfeng Capsule (XFC) in myocardial injury in rats with adjuvant arthritis (AA) via the growth arrest-specific transcript 5 (GAS5)/microRNA-21 (miR-21)/Toll-like receptor 4 (TLR4) axis.Methods: Rats were injected with Freund’s complete adjuvant to establish a rat model of AA. Then, some modeled rats were given normal saline or drugs only, and some modeled rats were injected with adeno-associated viruses or necrosulfonamide (NSA; a pyroptosis inhibitor) before drug administration. Toe swelling and arthritis index (AI) were calculated. Pathological and morphological changes in synovial and myocardial tissues were analyzed with hematoxylin-eosin staining, and pyroptotic vesicles and the ultrastructural changes of myocardial tissues were observed with transmission electron microscopy. The serum levels of interleukin (IL)-1β, IL-18, IL-6, and tumor necrosis factor (TNF)-α were detected, and lactate dehydrogenase (LDH) release was measured in myocardial tissues, accompanied by the examination of GAS5, miR-21, TLR4, nuclear factor-kB (NF-κB) p65, nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), Caspase-1, and Gasdermin D (GSDMD) expression in myocardial tissues.Results: After AA modeling, rats presented with significantly increased toe swelling and AI scores, synovial and myocardial tissue damage, elevated pyroptotic vesicles, and markedly enhanced serum levels of IL-1β, IL-18, IL-6, and TNF-α, accompanied by significantly diminished GAS5 expression, substantially augmented miR-21, TLR4, NF-κB p65, NLRP3, Caspase-1, and GSDMD expression, greatly increased LDH release in myocardial tissues. XFC treatment significantly declined toe swelling, AI scores, synovial and myocardial tissue damage, and the serum levels of IL-1β, IL-18, IL-6, and TNF-α in AA rats. Additionally, XFC treatment markedly elevated GAS5 expression and substantially lowered LDH release and miR-21, TLR4, NF-κB p65, NLRP3, Caspase-1, and GSDMD expression in myocardial tissues of AA rats. Moreover, the above effects of XFC in AA rats were further promoted by GAS5 overexpression or NSA treatment.Conclusion: XFC alleviated myocardial injury in AA rats by regulating the GAS5/miR-21/TLR4 axis and inhibiting pyroptosis and pro-inflammatory cytokine secretion.Keywords: adjuvant arthritis, myocardial injury, GAS5/miR-21/TLR4 axis, pyroptosis, Xinfeng Capsule

Zhiwei Wu, Changhao Huang Department of Organ Transplantation, XiangYa Hospital of Central South University, Changsha, People’s Republic of ChinaCorrespondence: Changhao Huang, Email Chhuang@csu.edu.cnPurpose: Mannose receptor C-type 1 (MRC1) is an endocytic lectin receptor primarily expressed in macrophages, dendritic cells, and some endothelial cells. However, the role of MRC1 in cancers remains unclear.Methods: We analyzed MRC1 expression using The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Cancer Cell Line Encyclopedia (CCLE), and single-cell datasets. We systematically explored the prognostic implications and diagnostic value of MRC1. Immune-related indicators, including immune cells, immune scores, and immune checkpoint molecules, were used to estimate their correlation with MRC1 expression. Finally, we explored its potential ties to immunotherapy success markers such as tumor mutation burden and DNA repair genes.Results: MRC1 showed both pro- and anti-tumor leanings depending on the cancer types. High levels correlated with poorer outcomes in six cancers but improved prognosis in some cancers like glioblastoma multiforme. This trend extended to the immune arena, where MRC1 intertwined with diverse immune parameters, suggesting its influence on affecting the tumor’s immunological landscape. Intriguingly, its expression positively associated with factors favoring immunotherapy efficacy while negatively correlating with some potential barriers. Single-cell analysis pinpointed a specific link between MRC1 and DNA damage/repair pathways in breast cancer.Conclusion: Our study provides a comprehensive landscape of MRC1 levels and diverse regulatory patterns in different cancers, deepening the understanding of MRC1’s roles in tumorigenesis and immunity.Keywords: MRC1, biomarker, immunotherapy, single-cell, pan-cancer analysis

Xin Zheng,&ast; Qiaoqing Zhang,&ast; Weijuan Su, Wei Liu, Caoxin Huang, Xiulin Shi, Xuejun Li Department of Endocrinology and Diabetes, Xiamen Diabetes Institute, Fujian Province Key Laboratory of Translational Research for Diabetes, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiulin Shi; Caoxin Huang, Email shixiulin2002@163.com; cxhuang@xmu.edu.cnPurpose: Nutrient intake for pregnant women with gestational diabetes mellitus (GDM) is important to ensure satisfactory birth outcomes. This study aims to explore the dietary profiles of patients with GDM, compare the results with the Chinese dietary guidelines or Dietary Reference Intakes (DRIs) from China and investigate the relationship between maternal dietary intake and pregnancy outcomes.Patients and Methods: A total of 221 patients with GDM in the second trimester were included in the cohort. Dietary intake data were collected using a 24-hour recall method for three consecutive days. The pregnancy outcomes of these participants were subsequently monitored. Both univariate logistic regression and multivariate logistic regression analyses were conducted to explore the associations between dietary intake variables or general characteristics variables and adverse pregnancy outcomes.Results: Participants with adverse pregnancy outcomes showed a lower intake of iodine and vitamin D, a lower percentage of dietary energy intake from carbohydrates and a higher percentage of dietary energy intake from fats, compared to participants without adverse pregnancy outcomes. The gestational weight gain and family history of diabetes were associated with an increased risk of adverse pregnancy outcomes. Conversely, regular exercise, the intake of iodine and Vitamin D, and the percentage of dietary energy intake from carbohydrates were associated with a decreased risk.Conclusion: The daily diet of pregnant women with GDM in China did not meet the dietary guidelines or DRIs. The low intake of Vitamin D and iodine, the low dietary carbohydrate ratio, family history of diabetes, lack of exercise, and high gestational weight gain were associated with increased risk of adverse pregnancy outcomes in pregnant women with GDM.Keywords: gestational diabetes, nutrient intake, dietary reference intakes, pregnancy outcomes, adverse pregnancy outcome

Tsung-Lung Lu,1 Chienhsiu Huang2 1Department of Nursing, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Dalin Town, Chiayi County, Taiwan; 2Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Dalin Town, Chiayi County, TaiwanCorrespondence: Chienhsiu Huang, Department of Internal medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Dalin Town, Chiayi County, Taiwan, Email hgssport@yahoo.com.twBackground: In recent years, Delftia acidovorans has gained attention for its rare occurrence in patient infections. The literature consists mostly of case reports, necessitating further research to comprehensively understand risk factors, clinical characteristics, and management strategies.Methods: We conducted a retrospective cohort study involving patients diagnosed with Delftia acidovorans infection at a tertiary teaching hospital between January 2014 and December 2022. The data included demographic details, comorbidities, bacterial cultures, antibiotic susceptibility, and treatment outcomes.Results: There were 26 patients diagnosed with Delftia acidovorans infection who were predominantly older with multiple comorbidities. Approximately 76.9% of Delftia acidovorans infection patients had polymicrobial infections. Twenty-one patients had received antibiotics within three months before they developed the Delftia acidovorans infection, and these antibiotics were primarily third-generation cephalosporins, glycopeptides and fluoroquinolones. Antibiotic susceptibility testing showed resistance to aminoglycosides and susceptibility to imipenem, meropenem, ceftazidime, and piperacillin/tazobactam. Treatment outcome showed a mortality rate of 11.5%, mainly in patients with malignancy and advanced age.Conclusion: Delftia acidovorans infections predominantly affect older patients with multiple comorbidities. In terms of antibiotic therapy, carbapenems, cephalosporins, and piperacillin/tazobactam with antipseudomonal activity could all be considered.Keywords: Delftia acidovorans, antibiotic susceptibility, mortality rate

Yi Zhang,1,&ast; Xinrui Wang,1,&ast; Chong Huang,2 Hui Yang,1 Chunguo Jiang,3 Xiaojia Yu,1 Jun Hong,2 Yi Zhang,1 Yushu Wang,1 Rui Zhao,1 Zhuoling An,1 Zhaohui Tong3 1Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2School of Pharmaceutical Sciences, Capital Medical University, Beijing, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhuoling An, Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel +00-86-010-85231362, Email anzhuoling@163.com Zhaohui Tong, Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel +00-86-010-85231464, Email tongzhaohuicy@sina.comObjective: The efficacy of nirmatrelvir–ritonavir for hospitalized patients with COVID-19 has not been fully established.Methods: We conducted a retrospective analysis of hospitalized COVID– 19 patients with high risk for disease progression at Beijing Chaoyang Hospital from October 15, 2022, to March 31, 2023. Patients ≥ 18 years old who were hospitalized with COVID-19 within 5 days of symptom onset were included. Baseline data were obtained from the routine electronic health record database of the hospital information system. Outcomes were monitored at 28 days via electronic medical record reviews or telephone interviews.Results: We identified 1120 patients hospitalized with COVID-19 during the study period. After exclusions, 167 nirmatrelvir–ritonavir users and 132 controls were included. 28-day all-cause mortality rate was 12.0% (20/167) in the nirmatrelvir–ritonavir group, versus 22.7% (30/132) in the control group (unadjusted log-rank p = 0.010; HR = 0.49, 95% confidence interval [CI] = 0.28– 0.86, IPTW-adjusted HR = 0.58, 95% CI = 0.40– 0.86). The 28-day disease progression rates did not differ between the two groups (unadjusted HR = 0.59, 95% CI = 0.34– 1.02, IPTW-adjusted HR = 0.73, 95% CI = 0.50– 1.06). Nirmatrelvir–ritonavir significantly reduced all-cause mortality and disease progression within 28 days among patients aged ≥ 65 years without ≥ 2 vaccine doses.Conclusion: We found significantly reduced all-cause mortality in the nirmatrelvir–ritonavir group, particularly in elderly patients who were incompletely vaccinated. Future randomized controlled studies are needed to validate our findings.Keywords: nirmatrelvir–ritonavir, COVID-19, hospitalized

Yanxia He,1,&ast; Zhumei Luo,1,&ast; Haoqing Chen,2,3,&ast; Liqing Ping,2,3 Cheng Huang,2,3 Yan Gao,2,3 Huiqiang Huang2,3 1Department of Oncology, The Third People’s Hospital of Chengdu, Sichuan, People’s Republic of China; 2State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 3Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huiqiang Huang; Yan Gao, Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China, Email huanghqsysucc@163.com; gaoyan@sysucc.org.cnBackground: Systemic inflammation, immunity, and nutritional status are closely related to patients’ outcomes in several kinds of cancers. This study aimed to establish a new nomogram based on inflammation-immunity-nutrition score (IINS) to predict the prognosis of extranodal natural killer/T-cell lymphoma (ENKTL) patients.Methods: The clinical data of 435 patients with ENTKL were retrospectively reviewed and randomly assigned to training cohort (n=305) and validation cohort (n=131) at a ratio of 7:3. Cox regression analysis was employed to identify independent prognostic factors and develop a nomogram in the training cohort. Harrell’s concordance index (C-index), calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) curve were employed to assess the performance of the nomogram and compare it with traditional prognostic systems (PINK, IPI, KPI). Internal validation was performed using 1000 bootstrap resamples in the validation cohort. Kaplan-Meier survival analyses were conducted to compare the overall survival (OS) of patients in different risk groups.Results: In the training cohort, in addition to several classic parameters, IINS was identified as an independent prognostic factor significantly associated with the OS of patients. The nomogram established based on the independent prognostic indicators showed superior survival prediction efficacy, with C-index of 0.733 in the training cohort and 0.759 in the validation cohort compared to the PINK (0.636 and 0.737), IPI (0.81 and 0.707), and KPI (0.693 and 0.639) systems. Furthermore, compared with PINK, IPI, and IPI systems, the nomogram showed relatively superior calibration curves and more powerful prognostic discrimination ability in predicting the OS of patients. DCA curves revealed some advantages in terms of clinical applicability of the nomogram compared to the PINK, IPI, and IPI systems.Conclusion: Compared with traditional prognostic systems, the nomogram showed promising prospects for risk stratification in ENKTL patient prognosis, providing new insights into the personalized treatment.Keywords: inflammation-immunity-nutrition score, extranodal natural killer/T-cell lymphoma, nomogram, prognosis, overall survival

Chenjun Huang,1,&ast; Xiao Xiao,1,&ast; Lin Tong,2,&ast; Zhiyuan Gao,1 Jun Ji,2 Lin Zhou,3 Ya Li,4 Lijuan Liu,5 Huijuan Feng,5 Meng Fang,2 Chunfang Gao1,2 1Department of Clinical Laboratory Medicine Center, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, People’s Republic of China; 2Department of Laboratory Medicine, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, People’s Republic of China; 3Department of Laboratory Medicine, Shanghai Changzheng Hospital, Shanghai, 200003, People’s Republic of China; 4Department of Laboratory Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, People’s Republic of China; 5Department of Laboratory Medicine, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunfang Gao, Department of Clinical Laboratory Medicine Center, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, People’s Republic of China, Tel +86-21-65161782-1210, Email gaocf1115@163.com; gaocf1115@shutcm.edu.cnPurpose: Early detection of hepatocellular carcinoma (HCC) through surveillance could reduce this cancer-associated mortality. We aimed to develop and validate algorithms using panel serum biomarkers to identify HCC in a real-world multi-center study in China.Patients and Methods: A total of 10,359 eligible subjects, including HCCs and benign liver diseases (BLDs), were recruited from six Chinese medical centers. The three nomograms were built using logistic regression and their sensitivities and specificities were carefully assessed in training and validation cohorts. HCC patients after surgical resection were followed to determine the prognostic values of these algorithms. Prospective surveillance performance was assessed in a cohort of chronic hepatitis B patients during 144 weeks follow-up.Results: Independent risk factors such as alpha-fetoprotein (AFP), lens cuinaris agglutinin-reactive fraction of AFP (AFP-L3), des-gamma-carboxy prothrombin (DCP), albumin (ALB), and total bilirubin (TBIL) obtained from train cohort were used to construct three nomograms (LAD, C-GALAD, and TAGALAD) using logistic regression. In the training and two validation cohorts, their AUCs were all over 0.900, and the higher AUCs appeared in TAGALAD and C-GALAD. Furthermore, the three nomograms could effectively stratify HCC into two groups with different survival and recurrence outcomes in follow-up validation. Notably, TAGALAD could predict HCC up to 48 weeks (AUC: 0.984) and 24 weeks (AUC: 0.900) before clinical diagnosis.Conclusion: The proposed nomograms generated from real-world Chinese populations are effective and easy-to use for HCC surveillance, diagnosis, as well as prognostic evaluation in various clinical scenarios based on data feasibility.Keywords: hepatocellular carcinoma, real-world data, diagnostic, prognosis, algorithm

Yi Jiang,1,&ast; Xiaoming Liao,1,&ast; Wei Tang,2 Chunyu Huang,3 You Pan,2 Shipeng Ning2 1Department of Breast Surgery, Guangxi Medical University Cancer Hospital, Nanning, 530000, People’s Republic of China; 2Department of Breast Surgery, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530000, People’s Republic of China; 3Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan, 430072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shipeng Ning, Email nspdoctor@sr.gxmu.edu.cnIntroduction: The presence of cancer stem cells (CSCs) significantly limits the therapeutic efficacy of radiotherapy (RT). Efficient elimination of potential CSCs is crucial for enhancing the effectiveness of RT.Methods: In this study, we developed a biomimetic hybrid nano-system (PMC) composed of MnCO3 as the inner core and platelet membrane (PM) as the outer shell. By exploiting the specific recognition properties of membrane surface proteins, PMC enables precise targeting of CSCs. Sonodynamic therapy (SDT) was employed using manganese carbonate nanoparticles (MnCO3 NPs), which generate abundant reactive oxygen species (ROS) upon ultrasound (US) irradiation, thereby impairing CSC self-renewal capacity and eradicating CSCs. Subsequent RT effectively eliminates common tumor cells.Results: Both in vitro cell experiments and in vivo animal studies demonstrate that SDT mediated by PMC synergistically enhances RT to selectively combat CSCs while inhibiting tumor growth without noticeable side effects.Discussion: Our findings offer novel insights for enhancing the efficacy and safety profiles of RT.Keywords: cancer stem cells clearance, radiosensitization, platelet membrane, sonodynamic therapy, manganese carbonate nanoparticles

Chao Huang,1,&ast; Jixiang Pei,1,&ast; Daisong Li,1 Tao Liu,2 Zhaoqing Li,1 Guoliang Zhang,1 Ruolan Chen,1 Xiaojian Xu,1 Bing Li,3,4 Zhexun Lian,1 Xian-Ming Chu1,5 1Department of Cardiology, the Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266100, People’s Republic of China; 2The Affiliated Qingdao Central Hospital of Qingdao University, The Second Affiliated Hospital of Medical College of Qingdao University, Qingdao, Shandong, 266042, People’s Republic of China; 3Department of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, 266000, People’s Republic of China; 4Department of Dermatology, The Affiliated Haici Hospital of Qingdao University, Qingdao, 266033, People’s Republic of China; 5The Affiliated Cardiovascular Hospital of Qingdao University, Qingdao, 266071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhexun Lian; Xian-Ming Chu, Tel +86-532-82913257, Email lianzx566@163.com; chuxianming@qdu.edu.cnPurpose: Doxorubicin-induced cardiotoxicity (DIC) is a severe side reaction in cancer chemotherapy that greatly impacts the well-being of cancer patients. Currently, there is still an insufficiency of effective and reliable biomarkers in the field of clinical practice for the early detection of DIC. This study aimed to determine and validate the potential diagnostic and predictive values of critical signatures in DIC.Methods: We obtained high-throughput sequencing data from the GEO database and performed data analysis and visualization using R software, GO, KEGG and Cytoscape. Machine learning methods and weighted gene coexpression network (WGCNA) were used to identify key genes for diagnostic model construction. Receiver operating characteristic (ROC) analysis and a nomogram were used to assess their diagnostic values. A multiregulatory network was built to reveal the possible regulatory relationships of critical signatures. Cell-type identification by estimating relative subsets of RNA transcript (CIBERSORT) analysis was used to investigate differential immune cell infiltration. Additionally, a cell and animal model were constructed to investigate the relationship between the identified genes and DIC.Results: Among the 3713 differentially expressed genes, three key genes (CSGALNACT1, ZNF296 and FANCB) were identified. A nomogram and ROC curves based on three key genes showed excellent diagnostic predictive performance. The regulatory network analysis showed that the TFs CREB1, EP300, FLI1, FOXA1, MAX, and MAZ modulated three key genes. An analysis of immune cell infiltration indicated that many immune cells (activated NK cells, M0 macrophages, activated dendritic cells and neutrophils) might be related to the progression of DIC. Furthermore, there may be various degrees of correlation between the three critical signatures and immune cells. RT‒qPCR demonstrated that the mRNA expression of CSGALNACT1 and ZNF296 was significantly upregulated, while FANCB was significantly downregulated in DOX-treated cardiomyocytes in vitro and in vivo.Conclusion: Our study suggested that the differential expression of CSGALNACT1, ZNF296 and FANCB is associated with cardiotoxicity and is also involved in immune cell infiltration in DIC. They might be potential biomarkers for the early occurrence of DIC.Keywords: doxorubicin, cardiotoxicity, biomarker, machine learning, immune infiltration

Ying Qin,1 Jingwen Zhao,1 Yong Yang,1 Yanjing Liu,1 Hui Xiang,2 Jingfeng Tong,3 Chengchen Huang3 1Department of Psychiatry, the Second People’s Hospital of Guizhou Province, Guiyang, 550004, People’s Republic of China; 2Department of Psychology, Guizhou Provincial People’s Hospital, Guiyang, 550002, People’s Republic of China; 3Shanghai Conlight Medical Laboratory, Co, Ltd, Shanghai, 200032, People’s Republic of ChinaCorrespondence: Chengchen Huang, Shanghai Conlight Medical Laboratory Co, Ltd, Shanghai, People’s Republic of China, Email huangcc@kangliyixue.comPurpose: We investigate the association of HTR1A rs10042486 and rs6295 with efficacy and plasma concentrations of atypical antipsychotics in the treatment of male patients with schizophrenia.Patients and Methods: A total of 140 male patients diagnosed with schizophrenia who were treated with any single atypical antipsychotic between May 2020 and May 2022 were retrospectively included. Clinical symptoms were assessed using Positive and Negative Syndrome Scale (PANSS). All SNPs were typed using Agena Bioscience MassARRAY DNA mass spectrometry. Plasma concentrations of antipsychotics at week 3, 6 and 12 after treatment commence were analyzed using mass spectrometry.Results: For efficacy of atypical antipsychotics, we observed no significant difference between HTR1A rs10042486, rs6295 and positive symptom improvement, where the patients with heterozygous mutant at the rs10042486 and rs6295 locus were superior to those with wild-type or homozygous mutant genotypes on negative symptom improvement, especially at 12 weeks of follow-up when the difference between genotypes at the rs6295 locus have statistical significance (P = 0.037). For plasma concentration, we found that quetiapine plasma concentrations were significantly lower in patients with mutation-heterozygous types than in wild-type and homozygous mutation genotypes at week 6. In contrast, higher plasma concentrations were found for mutant heterozygous than wild genotypes in the risperidone monotherapy analysis, and the difference among genotypes at the rs6295 locus was statistically significant at 6 weeks of follow-up.Conclusion: The assessment of the correlation of genetic polymorphisms of HTR1A rs6295 and rs10042486 in male patients with schizophrenia with the monitoring of therapeutic drug concentrations and therapeutic efficacy provides a constructive foundation for the clinical individualization of antipsychotics, such as quetiapine and risperidone, which is important in selecting the dose of the medication and improving the improvement of negative symptoms.Keywords: schizophrenia, HTR1A, polymorphism, plasma concentration, atypical antipsychotics, asian male patients

Xuliang Guo, Lefei Han, Wenyu Chen, Huixin He, Weijin Zhang, Chaoqi Huang, Xiu Wang School of Pharmacy, Bengbu Medical College, Bengbu, Anhui, People’s Republic of ChinaCorrespondence: Xiu Wang; Xuliang Guo, Department of Pharmacy, Bengbu Medical College, No. 2600 Donghai Road, Bengbu, People’s Republic of China, Email bbwx1016@163.com; 2021001@bbmc.edu.cnIntroduction: Combination therapy provides better outcomes than a single therapy and becomes an efficient strategy for cancer treatment. In this study, we designed a hypoxia- and singlet oxygen-responsive polymeric micelles which contain azo and nitroimidazole groups for enhanced cellular uptake, repaid cargo release, and codelivery of photosensitizer Ce6 and hypoxia-activated prodrug tirapazamine TPZ (DHM-Ce6@TPZ), which could be used for combining Ce6-mediated photodynamic therapy (PDT) and PDT-activated chemotherapy to enhance the therapy effect of cancer.Methods: The hypoxia- and singlet oxygen-responsive polymeric micelles DHM-Ce6@TPZ were prepared by film hydration method. The morphology, physicochemical properties, stimuli responsiveness, in vitro singlet oxygen production, cellular uptake, and cell viability were evaluated. In addition, the in vivo therapeutic effects of the micelles were verified using a tumor xenograft mice model.Results: The resulting dual-responsive micelles not only increased the concentration of intracellular photosensitizer and TPZ, but also facilitated photosensitizer and TPZ release for enhanced integration of photodynamic and chemotherapy therapy. As a photosensitizer, Ce6 induced PDT by generating toxic singlet reactive oxygen species (ROS), resulting in a hypoxic tumor environment to activate the prodrug TPZ to achieve efficient chemotherapy, thereby evoking a synergistic photodynamic and chemotherapy therapeutic effect. The cascade synergistic therapeutic effect of DHM-Ce6@TPZ was effectively evaluated both in vitro and in vivo to inhibit tumor growth in a breast cancer mice model.Conclusion: The designed multifunctional micellar nano platform could be a convenient and powerful vehicle for the efficient co-delivery of photosensitizers and chemical drugs for enhanced synergistic photodynamic and chemotherapy therapeutic effect of cancer.Keywords: photodynamic therapy, hypoxia-responsive, singlet oxygen-responsive, combination therapy

Yan-jiao Zhang,1 Chao Huang,2 Xiu-guang Zu,1 Jin-ming Liu,1 Yong-jun Li1 1Department of Cardiology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, People’s Republic of China; 2Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, People’s Republic of ChinaCorrespondence: Yong-jun Li, Department of Cardiology, The Second Hospital of Hebei Medical University, Heping West Road No. 215, Shijiazhuang, 050000, People’s Republic of China, Tel +86 15803210938, Email liyongjunbgr@126.comObjective: Immunogenic cell death (ICD) is part of the immune system’s response to coronary artery disease (CAD). In this study, we bioinformatically evaluated the diagnostic and therapeutic utility of immunogenic cell death-related genes (IRGs) and their relationship with immune infiltration features in CAD.Methods: We acquired the CAD-related datasets GSE12288, GSE71226, and GSE120521 from the Gene Expression Omnibus (GEO) database and the IRGs from the GeneCards database. After identifying the immune cell death-related differentially expressed genes (IRDEGs), we developed a risk model and detected immune subtypes in CAD. IRDEGs were identified using least absolute shrinkage and selection operator (LASSO) analysis. Using a nomogram, we confirmed that both the LASSO model and ICD signature genes had good diagnostic performance.Results: There was a high degree of coincidence and immune representativeness between two CAD groups based on characteristic genes and hub genes. Hub genes were associated with the interaction of neuroactive ligands with receptors and cell adhesion receptors. The two groups differed in terms of adipogenesis, allograft rejection, and apoptosis, as well as the ICD signature and hub gene expression levels. The two CAD-ICD subtypes differed in terms of immune infiltration.Conclusion: Quantitative real-time PCR (qRT-PCR) correlated CAD with the expression of OAS3, ITGAV, and PIBF1. The ICD signature genes are candidate biomarkers and reference standards for immune grouping in CAD and can be beneficial in precise immune-targeted therapy.Keywords: bioinformatics, gene signature, immune infiltration, hub genes, immune grouping, immune-targeted therapy

Jingwen Jiang,1– 3,&ast; Na Kong,1– 3,&ast; Qingqing Shi,1– 3,&ast; Yuan Yan,1– 3 Xiaoyue Shen,1– 3 Jie Mei,1– 3 Haixiang Sun,1– 3 Chenyang Huang1– 3 1Center for Reproductive Medicine and Obstetrics and Gynecology, Drum Tower Clinic Medical College of Nanjing Medical University, Nanjing, 210008, People’s Republic of China; 2Reproductive Medicine Center, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, People’s Republic of China; 3Center for Molecular Reproductive Medicine, Nanjing University, Nanjing, 210008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haixiang Sun; Chenyang Huang, Center for Reproductive Medicine and Obstetrics and Gynecology, Drum Tower Clinic Medical College of Nanjing Medical University, Nanjing, 210008, People’s Republic of China, Tel +8625-8310-6666-70261, Fax +8625-8310-7188, Email stevensunz@163.com; dianshui19901562@126.comBackground: Previous studies suggested higher serum progesterone (P) levels were strongly associated with a lower clinical pregnancy rate (CPR) for in vitro fertilization-embryo transfer (IVF-ET). However, the effect of increased serum P levels on the day of human chorionic gonadotropin (hCG) administration on clinical outcomes in short-acting gonadotropin-releasing hormone agonist (GnRHa) downregulated IVF-ET cycles remains unclear.Methods: We conducted a retrospective cohort study from January 2017 to December 2021, which included a total of 1664 patients receiving their first short-acting GnRHa IVF-ET cycles at our reproductive medicine centre of Nanjing Drum Tower Hospital. The smooth curve fitting and interaction analysis were employed to analyse the association between the CPR and the serum P levels with different embryo types (cleavage-stage embryo or blastocyst). In addition, total cycles were grouped according to different P levels on the trigger day of hCG administration for further analysis.Results: The CPR of patients with increased serum P level (higher than 1.5 ng/mL) on the hCG day did not decrease. A smoothing curve fitting showed that the CPR did not change obviously with the increase in serum P levels. Subgroup analysis of different types of embryos transferred showed that no correlation was observed between the CPR and serum P levels on the day of hCG administration in cleavage-stage embryo transfer cycles. However, the CPR of patients receiving blastocyst transfer showed a downward trend with the increase in serum P levels. At the same time, an interaction analysis also confirmed that the CPR of blastocyst transfer was more likely to be affected by elevated serum P levels on the hCG day.Conclusion: In the luteal phase short-acting GnRHa downregulated IVF-ET cycles, the elevated serum P levels on the hCG day did not affect the CPR of cleavage-stage embryo transfer but reduced the CPR of blastocyst transfer.Keywords: short-acting GnRHa, elevated progesterone level, hCG trigger day, clinical pregnancy rate, blastocyst transfer

Chuangjia Huang,1,2,&ast; Yu Zhang,3,&ast; Jianfen Su,1,2,&ast; Xiaoling Guan,1,2 Sheng Chen,1,2 Xiaowei Xu,1,2 Xiaohua Deng,1,2 Lingmin Zhang,1,2 Jionghua Huang1 1Department of Cardiology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, People’s Republic of China; 2Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, People’s Republic of China; 3Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jionghua Huang; Lingmin Zhang, Email mdhjh2014@126.com; zhanglm@gzhmu.edu.cnBackground: High-level low-density lipoprotein cholesterol (LDL-C) plays a vital role in the development of atherosclerotic cardiovascular disease. Low-density lipoprotein receptors (LDLRs) are scavengers that bind to LDL-C in the liver. LDLR proteins are regulated by proprotein convertase subtilisin/kexin type 9 (PCSK9), which mediates the degradation of LDLR and adjusts the level of the plasma LDL-C. The low expression of PCSK9 leads to the up-regulation of liver LDLRs and the reduction of plasma LDL-C. Hepatocytes are attractive targets for small interfering RNA (siRNA) delivery to silence Pcsk9 gene, due to their significant role in LDL-C regulation.Methods: Here, a type of liver-specific ionizable lipid nanoparticles is developed for efficient siRNA delivery. This type of nanoparticles shows high stability, enabling efficient cargo delivery specifically to hepatocytes, and a membrane-active polymer that reversibly masks activity until an acidic environment is reached.Results: Significantly, the siPcsk9 (siRNA targeting to Pcsk9)-loaded nanoparticles (GLP) could silence 90% of the Pcsk9 mRNA in vitro. In vivo study showed that the improved accumulation of GLP in the liver increased LDLR level by 3.35-fold and decreased plasma LDL-C by 35%.Conclusion: GLP has shown a powerful effect on reducing LDL-C, thus providing a potential therapy for atherosclerotic cardiovascular disease. Keywords: ionizable lipid nanoparticles, bad cholesterol, PCSK9, small interfering RNA, liver-specific delivery

Peng Guo,1,&ast; Chi Huang,2,&ast; Qin Yang,1 Guofeng Zhong,1 Junbo Zhang,1 Mengyu Qiu,1 Rui Zeng,3 Kaijun Gou,3 Chen Zhang,1 Yan Qu1 1State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China; 2Department of Pharmacy, Jiang’an Hospital of Traditional Chinese Medicine, Yibin, 644200, People’s Republic of China; 3Institute of Tibetan Plateau, Southwest Minzu University, Chengdu, 610225, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Qu; Chen Zhang, State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, People’s Republic of China, Email quyan028@126.com; chenzhang_1990@126.comAbstract: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic joint inflammation, eventually leading to severe disability and premature death. At present, the treatment of RA is mainly to reduce inflammation, swelling, and pain. Commonly used drugs are non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, and disease-modifying anti-rheumatic drugs (DMARDs). These drugs lack specificity and require long-term, high-dose administration, which can cause serious adverse effects. In addition, the oral, intravenous, and intra-articular injections will reduce patient compliance, resulting in high cost and low bioavailability. Due to these limitations, microneedles (MNs) have emerged as a new strategy to efficiently localize the drugs in inflamed joints for the treatment of RA. MNs can overcome the cuticle barrier of the skin without stimulating nerves and blood vessels. Which can increase patient compliance, improve bioavailability, and avoid systemic circulation. This review summarizes and evaluates the application of MNs in RA, especially dissolving MNs (DMNs). We encourage the use of MNs to treat RA, by describing the general properties of MNs, materials, preparation technology, drug release mechanism, and advantages. Furthermore, we discussed the biological safety, development prospects, and future challenges of MNs, hoping to provide a new strategy for the treatment of RA. Keywords: rheumatoid arthritis, dissolving microneedles, transdermal delivery system, degradability, biosafety

Cheng Huang,1 Peiming Zhang,2 Yu Dong,1 Ruchun Chang,2 Jinxiong Lao,2,3 Ziyong Li,2,3 Danchun Lan2 1Acupuncture and Rehabilitation Clinical School of Medicine, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Department of Acupuncture and Moxibustion, Foshan Hospital of Traditional Chinese Medicine, Foshan, People’s Republic of China; 3The Eighth Clinical School of Medicine, Guangzhou University of Chinese Medicine, Foshan, People’s Republic of ChinaCorrespondence: Danchun Lan, Email Danchun2013@aliyun.comObjective: To systematically evaluate the efficacy of acupuncture in the treatment of schizophrenia.Methods: We searched China National Knowledge Infrastructure (CNKI), Wanfang Database, Chongqing VIP Chinese Science and Technology Periodical Database (VIP), China Biology Medicine Database (CBM), PubMed, Embase, Web of Science, Cochrane Library for relevant literature on the acupuncture treatment of schizophrenia published from database inception to May 17, 2023. The evaluation criteria included total effective rate, incidence of adverse reactions, TESS scale, PANSS scale, BPRS scale, SANA scale, SAPS scale. Two researchers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. The RevMan 5.4 software was used for meta-analysis, risk of bias (ROB) evaluation tool was used to evaluate the risk of bias of the studies, and the GRADE evaluation tool was used to evaluate the quality of evidence. The study was registered on PROSPERO, CRD42023416438.Results: A total of 38 RCTs involving 3143 patients were included in the meta-analysis. The results showed that acupuncture can improve the total effective rate [OR=3.43 (95% CI: 2.71, 4.35), moderate credibility], reduce the incidence of adverse reactions [OR=0.45 (95% CI: 0.32, 0.63), moderate credibility], reduce the TESS score (side effect scale) [MD=− 1.83 (95% CI: − 2.94, − 0.71), very low credibility]. Acupuncture also reduced the PANSS total score [MD=− 5.75 (95% CI: − 8.08, − 3.42), very low credibility], SANA score [MD=− 2.66 (95% CI: − 6.84, 1.51), very low credibility], SAPS score [MD=− 1.26 (95% CI: − 2.55, − 0.02), very low credibility], and BPRS score [MD=− 7.02 (95% CI: − 10.59, − 3.46), very low credibility].Conclusion: Existing evidence indicates that acupuncture as an adjunctive therapy can improve the total effective rate of SZ patients, reduce the incidence of adverse reactions, improve clinical symptoms, and alleviate depression and anxiety in SZ patients. However, more high-quality clinical research evidence is still needed to support these findings.Keywords: acupuncture, meta-analysis, schizophrenia

Chumei Huang,1,2,&ast; Jiahui Chen,1,&ast; Xiaoxia Zhan,2,&ast; Laisheng Li,2 Shu An,2 Guijun Cai,1 Nan Yu1,3 1Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Laboratory Medicine, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China; 3Department of Medical Laboratory, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nan Yu, Email yunanzhujiang@163.comBackground: Neonatal sepsis (NS) is an important cause of mortality and morbidity in newborn infants. However, early diagnosis of proven sepsis (culture-positive sepsis) is difficult. We aimed to define the best combination of biomarkers to diagnose the onset of neonatal sepsis, distinguish culture-positive neonatal sepsis and predict the time of confirmation of neonatal sepsis.Methods: This retrospective cohort study was conducted from January 2016 to December 2020. Clinical characteristics and laboratory results were collected from the electronic medical records. Hematology profiles and biochemical indices were obtained upon hospital admission. Multivariate logistic regression analysis was used to evaluate the risk factors and construct a nomogram. The performance of the nomogram was evaluated by receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Multivariable linear regression was used to identify the association between admission-to-diagnosis interval (ADI) and correlated variables.Results: Overall, 148 infants with neonatal sepsis (67 culture positive sepsis and 81 culture negative sepsis) and 150 controls were included. C-reactive protein (CRP) (p< 0.001), platelets (PLT) (p=0.011), urea nitrogen (BUN) (p=0.001) and conjugated bilirubin (BC) (p=0.007) were independent risk factors for neonatal sepsis. The diagnostic nomogram based on CRP, PLT, BUN and BC showed excellent diagnostic accuracy for neonatal sepsis (AUC=0.928). The nomogram based on red blood cell distribution width (RDW) and mean platelet volume (MPV) was efficient in distinguishing proven neonatal sepsis from clinical sepsis, with an AUC of 0.700 in the training group and 0.689 in the validation group. Decision curve analysis (DCA) showed that the nomogram had good clinical utility. Multivariable analysis revealed gestational age, CRP, and MPV were significantly associated with admission-to-diagnosis interval in culture-positive sepsis (p < 0.001).Conclusion: Different combinations biomarkers were performant to diagnose the onset of neonatal sepsis, distinguish culture-positive neonatal sepsis, predict the time of confirmation, and aid in individual therapy.Keywords: neonatal sepsis, nomogram, laboratory serum biomarkers

Meiyan Sun,1,2,&ast; Xiaoyong Zhao,2,&ast; Xingyue Li,2 Chunling Wang,2 Lili Lin,3 Kaifang Wang,2 Yingui Sun,2 Wei Ye,3 Haiyan Li,3 Ye Zhang,1 Chaolu Huang2,4 1Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, People’s Republic of China; 2Department of Anesthesiology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong Province, 261053, People’s Republic of China; 3The First Clinical Medical College, Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 4Department of Clinical Medicine, Qiandongnan Ethnic Vocational and Technical College, Kaili, 556000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ye Zhang, Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, People’s Republic of China, Email zhangy@ahmu.edu.cn Chaolu Huang, Department of Clinical Medicine, Qiandongnan Ethnic Vocational and Technical College, Kaili, 556000, People’s Republic of China, Email huangzhaolu2020@163.comObjective: Diabetes mellitus (DM) implicates oxidative stress, apoptosis, and inflammation, all of which may contribute liver injury. Aerobic exercise is assured to positively regulate metabolism in the liver. This project was designed to investigate whether and how aerobic exercise improves DM-induced liver injury.Methods: Seven-week-old male db/db mice and age-matched m/m mice were randomly divided into a rest control group or a group that received 12 weeks of aerobic exercise by treadmill training (10 m/min). Haematoxylin and eosin (HE) staining, electron microscopy, Oil Red O staining and TUNEL assays were used to evaluate the histopathological changes in mouse liver. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TRIG), cholesterol (CHOL) were analyzed by serum biochemical analysis. Interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), and tissue levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were analyzed via ELISA. Nuclear factor E2-associated factor-2 (Nrf2), nuclear factor κB (NF-κB) and JAK2/STAT3 pathway-related proteins were measured by immunofluorescence, Western blotting and q-PCR. F4/80 expression in liver tissues was assessed by immunohistochemistry.Results: In diabetic mice, exercise training significantly decreased the levels of serum TRIG, CHOL, IL-6, TNF-α, ALT and AST; prevented weight gain, hyperglycaemia, and impaired glucose and insulin tolerance. Morphologically, exercise mitigated the diabetes-induced increase in liver tissue microvesicles, inflammatory cells, F4/80 (macrophage marker) levels, and TUNEL-positive cells. In addition, exercise reduced the apoptosis index, which is consistent with the results for caspase-3 and Bax. Additionally, exercise significantly increased SOD activity, decreased MDA levels, activated Nrf2 and decreased the expression of NF-kB, phosphorylated JAK2 and STAT3 proteins in the livers of diabetic mice.Conclusion: This study demonstrated that aerobic exercise reversed liver dysfunction in db/db mice with T2DM by reducing oxidative stress, apoptosis and inflammation, possibly by enhancing Nrf2 expression and inhibiting the JAK2/STAT3 cascade response.Keywords: db/db mice, aerobic exercise, inflammation, apoptosis, Nrf2, JAK2/STAT3

Lili Cheng,1 Chuanbing Huang,2 Ming Li,2 Shuangshuang Shang,2 Junjie Chen,1 Zhongfu Tang1 1The First Clinical Medical College, Anhui University of Traditional Chinese Medicine, Hefei, Anhui Province, 230038, People’s Republic of China; 2Department of Rheumatology and Immunology, First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui Province, 230038, People’s Republic of ChinaCorrespondence: Chuanbing Huang, Department of Rheumatology and Immunology, First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui Province, 230038, People’s Republic of China, Tel +86-15156986428, Email Chuanbinh@163.comPurpose: This study aims to explore the effect and underlying mechanism of Chonggu Granules (CGG) in knee osteoarthritis (KOA) in rats.Methods: A papain-induced KOA model was established in rats. The pathological alterations of extracellular matrix in rat cartilage tissues were observed through hematoxylin and eosin (H&E) staining, followed by Mankin score for quantitative scoring. The ultrastructure of cartilage extracellular matrix was examined under a transmission electron microscopy (TEM). ELISA was used to measure the levels of IL-6, TNF-α, and IL-1β in rat serum. Immunofluorescence was performed for assessing the levels of MMP-3, MMP-13, and Col2al in rat cartilage. Western blot was used to identify the protein expressions of wnt1, GSK-3β, β-catenin, and Aggrecan in rat cartilage. The mRNA relative expressions of miR-148a-3p, wnt1, β-catenin, and GSK-3β in rat cartilage were detected by RT-PCR. Luciferase reporter gene was used to detect the target genes of miR-148a-3p.Results: CGG significantly improved articular cartilage tissue and extracellular matrix metabolism compared to the model group as indicated by H&E, Mankin score, and TEM data. Moreover, low, medium, and high doses of CGG reduced the levels of IL-6, TNF-α, IL-1β, MMP-3, and MMP-13 in serum to varying degrees but increased the levels of Col2al and Aggrecan. Mechanistically, CGG targeted wnt1 by increasing the expression of miR-148a-3p in a dose-dependent manner, thereby downregulating the mRNA and protein expressions of β-catenin in cartilage tissue and upregulating the mRNA and protein expressions of GSK-3β.Conclusion: CGG may control the miR-148a-3p/wnt/β-catenin signaling pathway to decrease the levels of its downstream target genes MMP-13 and MMP-3, increase the expressions of Col2al and Aggrecan, and downregulate the contents of inflammatory cytokines IL-6, TNF-α, and IL-1β, thereby improving the metabolism of cartilage extracellular matrix and alleviating the degeneration of articular cartilage in KOA.Keywords: knee osteoarthritis, cartilage extracellular matrix metabolism, chonggu granules, miR-148a-3p, Wnt/β-catenin signaling pathway

Guizhen Zhang,1,&ast; Xuejian Li,1,&ast; Chunyun Huang,1 Yuanyuan Jiang,1 Jian Su,1 Ying Hu2 1Guangxi Scientific Research Center of Traditional Chinese Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi, People’s Republic of China; 2Faculty of Pharmacy, Guangxi University of Chinese Medicine, Nanning, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Su, Guangxi Key Laboratory of Zhuang and Yao Ethnic Medicine, Guangxi Scientific Research Center of Traditional Chinese Medicine, Guangxi University of Chinese Medicine, 13 Wuhe Avenue, Nanning, Guangxi, 530200, People’s Republic of China, Tel +86-0771-3946492, Fax +86-0771-3946492, Email sujian5000@hotmail.com Ying Hu, Department of Pharmacology, Faculty of Pharmacy, Guangxi University of Chinese Medicine, 13 Wuhe Avenue, Nanning, Guangxi, 530200, People’s Republic of China, Tel +86-0771-3946492, Fax +86-0771-3946492, Email huying5000@hotmail.comPurpose: The aim of this study was to develop a liposome gel containing levo-tetrahydropalmatine (l-THP) and evaluate its transdermal properties.Methods: A L16 (43) orthogonal experiment was conducted to optimize the preparation of l-THP liposomes and assess their characterization and stability in a gel. The transdermal features were analyzed through in vivo and in vitro experiments on rats and Strat-M® membrane, respectively. The metabolism of l-THP in liver and skin S9 fractions was also studied.Results: The optimization of the orthogonal experiment revealed that the ideal mass ratio of phosphatidylcholine, cholesterol, and l-THP during preparation was 10:1:3. The resulting liposome exhibited a particle size of 68 nm, a PDI of 0.27, a drug loading of 4.33%, an encapsulation of 18.79%, and a zeta potential of − 41.27 mV. Both the l-THP and its liposome-gel formulation were found to be stable for a duration of 45 days at 4 °C and 30 °C. During the in vivo transdermal study, the maximum concentration (Cmax) of l-THP from the liposome gel was 0.16 μg/mL, and the time to reach this maximum concentration (tmax) was 1.2 hours. The relative bioavailability of l-THP in the liposome gel was 233.8% compared to the emulsion. The concentration of l-THP (prepared in PBS) decreased at a rate of 0.0067 μg/mL/min in the liver S9 fraction and 0.0027 μg/mL/min in the skin S9 fraction, however, this difference was not observed when l-THP was encapsulated in liposomes. l-THP passed through the Strat-M® membrane at a rate of 0.0032 mg/cm2/h and 0.002 mg/cm2/h for the emulsion and liposome gel, respectively.Conclusion: The optimal process for the preparation of l-THP liposomes was obtained. Compared to the emulsion, the liposomes provided greater bioavailability when used transdermally. The liposomes also provided greater stability for l-THP during storage.Graphical Abstract: Keywords: liposome, transdermal property, l-tetrahydropalmatine, S9 fraction, orthogonal experiment, stability

Tianyou Chen,1,&ast; Chong Liu,1 Zide Zhang,2 Tuo Liang,2 Jichong Zhu,1 Chenxing Zhou,1 Shaofeng Wu,1 Yuanlin Yao,1,&ast; Chengqian Huang,1 Bin Zhang,1 Sitan Feng,1 Zequn Wang,1 Shengsheng Huang,1 Xuhua Sun,1 Liyi Chen,1 Xinli Zhan1 1Department of Spine and Osteopathy Ward, the First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Spine Ward, Liuzhou People’s Hospital, Liuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinli Zhan, Department of Spine and Osteopathy Ward, the First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China, Email zhanxinli@stu.gxmu.edu.cnObjective: The objective of this study was to utilize machine learning techniques to analyze perioperative factors and identify blood glucose levels that can predict the occurrence of surgical site infection following posterior lumbar spinal surgery.Methods: A total of 4019 patients receiving lumbar internal fixation surgery from an institute were enrolled between June 2012 and February 2021. First, the filtered data were randomized into the test and verification groups. Second, in the test group, specific variables were screened using logistic regression analysis, Lasso regression analysis, support vector machine, and random forest. Specific variables obtained using the four methods were intersected, and a dynamic model was constructed. ROC and calibration curves were constructed to assess model performance. Finally, internal model performance was verified in the verification group using ROC and calibration curves.Results: The data from 4019 patients were collected. In total, 1327 eligible cases were selected. By combining logistic regression analysis with three machine learning algorithms, this study identified four predictors associated with SSI, namely Modic changes, sebum thickness, hemoglobin, and glucose. Using this information, a prediction model was developed and visually represented. Then, we constructed ROC and calibration curves using the test group; the area under the ROC curve was 0.988. Further, calibration curve analysis revealed favorable consistency of nomogram-predicted values compared with real measurements. The C-index of our model was 0.986 (95% CI 0.981– 0.994). Finally, we used the validation group to validate the model internally; the AUC was 0.987. Calibration curve analysis revealed favorable consistency of nomogram-predicted values compared with real measurements. The C-index was 0.982 (95% CI 0.974– 0.999).Conclusion: Logistic regression analysis and machine learning were employed to select four risk factors: Modic changes, sebum thickness, hemoglobin, and glucose. Then, a dynamic prediction model was constructed to help clinicians simplify the monitoring and prevention of SSI.Keywords: surgical site infection, lumbar spine surgery, machine learning, blood glucose, dynamic prediction model

Chang Huang,1,2,&ast; Zhutian Zhang,1,2,&ast; Jifeng Gu,3,&ast; Dan Li,1,2 Shunxiang Gao,1,2 Rong Zhang,1,2 Rong Shi,4 Jianguo Sun1,2 1Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, 200031, People’s Republic of China; 2NHC Key Laboratory of Myopia, Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, 200031, People’s Republic of China; 3Department of Pharmacy, Eye & ENT Hospital, Shanghai Key Laboratory of Bioactive Small Molecules, Fudan University, Shanghai, 200031, People’s Republic of China; 4Science and Technology Experimental Center, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianguo Sun, Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, People’s Republic of China, Email jgsun@fudan.edu.cn Rong Shi, Science and Technology Experimental Center, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China, Email rongshi56@126.comPurpose: Autoimmune uveitis is a kind of sight-threatening ocular and systemic disorders. Recent treatments on autoimmune uveitis still remain many limitations due to extreme complexity and undetermined pathogenesis. In this study, a novel dual-drug nanocomposite formulation is developed to treat experimental autoimmune uveitis by a combined and sustained therapy method.Methods: The dual-drug nanocomposite formulation is constructed by integrating berberine (BBR)-loaded mesoporous silica nanoparticles (MSNs) into dexamethasone (DEX)-loaded thermogel (BBR@MSN-DEX@Gel). The BBR@MSN-DEX@Gel is characterized by transmission electron microscopy, dynamic light scattering, Fourier transform infrared spectrometer and rheometer. The in vitro drug release profile, cytotoxicity and anti-inflammation effectiveness of BBR@MSN-DEX@Gel on lipopolysaccharide-stimulated human conjunctival epithelial cells are investigated. After the in vivo drug release profile and biosafety of the dual-drug nanocomposite formulation are confirmed, its treatment effectiveness is fully assessed based on the induced experimental autoimmune uveitis (EAU) Lewis rat’s model.Results: The dual-drug nanocomposite formulation has good injectability and thermosensitivity, suitable for administration by an intravitreal injection. The BBR@MSN-DEX@Gel has been found to sustainably release both drugs for up to 4 weeks. The carrier materials have minimal in vitro cytotoxicity and high in vivo biosafety. BBR@MSN-DEX@Gel presents obviously anti-inflammatory effectiveness in vitro. After administration of BBR@MSN-DEX@Gel into Lewis rat’s eye with EAU by an intravitreal injection, the nanocomposite formulation significantly suppresses inflammatory reaction of autoimmune uveitis via a dual-drug combined and sustained therapy method, compared with the equivalent dose of single-component formulations.Conclusion: BBR@MSN-DEX@Gel serves as a promising dual-drug nanocomposite formulation for future treatment of autoimmune uveitis.Keywords: nanocomposite formulation, combined and sustained therapy, dexamethasone, berberine, experimental autoimmune uveitis

Shuo Zhang,1,&ast; Yishu Wang,1,&ast; Shuai Zhang,1 Chengqi Huang,1 Qiyang Ding,2 Ji Xia,2 Daocheng Wu,1 Wei Gao2 1The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, 710049, People’s Republic of China; 2Department of Anesthesiology & Center for Brain Science & Center for Translational Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710049, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Daocheng Wu, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, 710049, People’s Republic of China, Tel/Fax +86-29-82663941, Email wudaocheng@mail.xjtu.edu.cn Wei Gao, Department of Anesthesiology & Center for Brain Science & Center for Translational Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710049, People’s Republic of China, Tel +86 15209225834, Email gaowei2906@xjtufh.edu.cnAbstract: Anesthetics, which include both local and general varieties, are a unique class of drugs widely utilized in clinical surgery to alleviate pain and promote relaxation in patients. Although numerous anesthetics and their traditional formulations are available in the market, only a select few exhibit excellent anesthetic properties that meet clinical requirements. The main challenges are the potential toxic and adverse effects of anesthetics, as well as the presence of the blood-brain barrier (BBB), which makes it difficult for most general anesthetics to effectively penetrate to the brain. Loading anesthetics onto nanocarriers as anesthetic nanomedicines might address these challenges and improve anesthesia effectiveness, reduce toxic and adverse effects, while significantly enhance the efficiency of general anesthetics passing through the BBB. Consequently, anesthetic nanomedicines play a crucial role in the field of anesthesia. Despite their significance, research on anesthetic nanomedicines is still in its infancy, especially when compared to other types of nanomedicines in terms of depth and breadth. Although local anesthetic nanomedicines have received considerable attention and essentially meet clinical needs, there are few reported instances of nanomedicines for general anesthetics. Given the extensive usage of anesthetics and the many of them need for improved performance, emerging anesthetic nanomedicines face both unparalleled opportunities and considerable challenges in terms of theory and technology. Thus, a comprehensive summary with systematic analyses of anesthetic nanomedicines is urgently required. This review provides a comprehensive summary of the classification, properties, and research status of anesthetic nanomedicines, along with an exploration of their opportunities and challenges. In addition, future research directions and development prospects are discussed. It is hoped that researchers from diverse disciplines will collaborate to study anesthetic nanomedicines and develop them as a valuable anesthetic dosage form for clinical surgery.Keywords: anesthesia, nanocarriers, blood-brain barrier, drugs

Chunqi Huang,1 Zhou Yin,1 Yeqing Yang,1 Nan Mo,2,3 Hui Yang,3,4 Ying Wang3,5,6 1Department of Laboratory Medicine, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Xinhua Hospital of Zhejiang Province, Hangzhou, Zhejiang, 310053, People’s Republic of China; 2School of Fourth Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China; 3Department of Clinical Research Center, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310053, People’s Republic of China; 4School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, People’s Republic of China; 5Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou, Zhejiang, 310053, People’s Republic of China; 6Luqiao Second People’s Hospital, Taizhou, Zhejiang, 317200, People’s Republic of ChinaCorrespondence: Ying Wang, Department of Clinical Research Center, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310014, People’s Republic of China, Tel +86 18367124548, Email nancywangying@163.comPurpose: Ibuprofen is the first of the nonsteroidal anti-inflammatory drug (NSAID) to be used in the clinic. Our aim was to explore the pharmacokinetics (PK), bioequivalence, food effect, and safety of oral ibuprofen sustained-release capsules by two sponsors in healthy volunteers (HVs).Methods: Two separate randomized, open-label, single-dose, crossover-design studies were conducted: a fasting study (n = 24) and a fed study (n = 24). In each study, HVs were 1:1 divided into two groups (T-R and R-T) and received 0.3-g/capsule ibuprofen with a 3-day washout. The plasma was collected for up to 24 hours at the time point after dosing on Day 1/Day 4. The plasma concentrations of ibuprofen were measured using an HPLC-MS/MS method, and PK parameters were determined by noncompartmental methods.Results: Forty-eight healthy volunteers were enrolled. In fasting subjects, the maximum plasma concentration (Cmax, mean ± SD) was 14.86± 3.19 μg/mL at 5.0 (4.0, 7.0) hours (median [min, max]) for sponsor T, and 13.88± 2.60 μg/mL at 4.5 (3.0, 8.0) hours for sponsor R. In fed subjects, Cmax was 21.31± 4.08 μg/mL at 5.6 (4.3, 10.0) hours for sponsor T, and 19.77± 3.36 μg/mL at 6.0 (2.0, 8.0) hours for sponsor R. All 90% confidence intervals (CIs) for Cmax, AUC0-t, and AUC0-∞ were within the bioequivalence bounds (80– 125%) both fasting and fed studies.Conclusion: Ibuprofen is well tolerated and has a favorable safety profile. In both fasting and fed study, there were no serious AEs, or AEs leading to withdrawal. Bioequivalence is achieved under fasting and fed conditions, supporting the demonstration of biosimilarity.Keywords: ibuprofen, bioequivalence, pharmacokinetics, safety, HVs

Chaoyi Huang,1,2 Xinchao Miao,1,2 Jiang Li,1,2 Jieyi Liang,1,2 Junxi Xu,1,2 Zhe Wu1,2 1Department of Prosthodontics, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, People’s Republic of ChinaCorrespondence: Zhe Wu, Department of Prosthodontics, Affiliated Stomatology Hospital of Guangzhou Medical University, No. 39, Huangsha Road, Guangzhou, People’s Republic of China, Tel +86 020 8850 1980, Fax +86 020 8850 1980, Email zhewudentist@gzhmu.edu.cnIntroduction: Improving the biological sealing around dental abutments could promote the long-term success of implants. Although titanium abutments have a wide range of clinical applications, they incur esthetic risks due to their color, especially in the esthetic zone. Currently, zirconia has been applied as an esthetic alternative material for implant abutments; however, zirconia is purported to be an inert biomaterial. How to improve the biological activities of zirconia has thus become a popular research topic. In this study, we presented a novel self-glazed zirconia (SZ) surface with nanotopography fabricated by additive 3D gel deposition and investigated its soft tissue integration capability compared to that of clinically used titanium and polished conventional zirconia surfaces.Materials and Methods: Three groups of disc samples were prepared for in vitro study and the three groups of abutment samples were prepared for in vivo study. The surface topography, roughness, wettability and chemical composition of the samples were examined. Moreover, we analyzed the effect of the three groups of samples on protein adsorption and on the biological behavior of human gingival keratinocytes (HGKs) and human gingival fibroblasts (HGFs). Furthermore, we conducted an in vivo study in which the bilateral mandibular anterior teeth of rabbits were extracted and replaced with implants and corresponding abutments.Results: The surface of SZ showed a unique nanotopography with nm range roughness and a greater ability to absorb protein. The promoted expression of adhesion molecules in both HGKs and HGFs was observed on the SZ surface compared to the surfaces of Ti and PCZ, while the cell viability and proliferation of HGKs and the number of HGFs adhesion were not significant among all groups. In vivo results showed that the SZ abutment formed strong biological sealing at the abutment–soft tissue interface and exhibited markedly more hemidesmosomes when observed with a transmission electron microscope.Conclusion: These results demonstrated that the novel SZ surface with nanotopography promoted soft tissue integration, suggesting its promising application as a zirconia surface for the dental abutment.Keywords: dental abutment, self-glazed zirconia, nanotopography, adhesion molecule, soft tissue integration, 3D gel deposition

Xiaoling Liu, Ermei Zhong, Jinzhi Li, Chunxia Huang, Weixin Liu, Liping Zeng, Ge Song, Ronghua Jiang, Yu Liu NHC Key Laboratory of Male Reproduction and Genetics, Guangdong Provincial Reproductive Science Institute (Guangdong Provincial Fertility Hospital), Guangzhou, 510600, People’s Republic of ChinaCorrespondence: Ge Song, NHC Key Laboratory of Male Reproduction and Genetics, Guangdong Provincial Reproductive Science Institute (Guangdong Provincial Fertility Hospital), No. 17 Mei Dong Road, Guangzhou, 510600, People’s Republic of China, Tel/Fax +86-020-87301316, Email gzdhmjyd@163.comBackground: This study aimed to explore the current situation of anxiety and depression on day of transfer in couples receiving in vitro fertilization and embryo transfer (IVF-ET) with donor sperm and analyze its influencing factors.Methods: This study selected 187 IVF-ET administered couples who received donor sperm from our Hospital from August 2021 to July 2022. On the day of IVF-ET with donor sperm transplantation, patients were investigated with general data questionnaire, self-rating anxiety scale (SAS) and self-rating depression scale (SDS) to analyze their anxiety and depression scores and their influencing factors.Results: Scores of anxiety and depression on the day of transplantation in patients receiving IVF-ET with donor sperm were 43.98± 6.80 and 46.03± 10.61 respectively, which were higher compared to levels of Chinese health norm (P< 0.05). The anxiety score of patients’ spouses was 41.23± 6.69 and depression score was 44.23± 11.65, which were higher compared to levels of Chinese health norm (P< 0.05). Score of anxiety and depression of women was significantly higher compared to those of their spouse (P< 0.05). Anxiety and depression scores of women in non-pregnant group were significantly higher compared to those in pregnant group (P< 0.05). Regression analysis showed that education level and annual family income were influencing factors of anxiety and depression scores of IVF-ET with donor sperm couples on the day of transfer, and number of eggs taken and transfer times were influencing factors of depression scores of IVF-ET with donor sperm patients on the day of transfer.Conclusion: Psychological state of couples receiving IVF-ET with donor sperm was significantly affected, especially in female side. Medical staff should focus on patients with low education level, low family income, and more times of transfer and egg retrieval, and take targeted intervention measures to keep them in good psychological state, which is conducive to improving pregnancy outcome.Keywords: in vitro fertilization and embryo transfer with donor sperm, day of transfer, anxiety, depression, psychological state

Yue Zhang,&ast; Peng Chen,&ast; Wang Zhang, Chenkai Huang,&ast; Xuan Zhu&ast; Department of Gastroenterology, Jiangxi Province and Jiangxi Clinical Research Center for Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuan Zhu; Chenkai Huang, Department of Gastroenterology, Jiangxi Province and Jiangxi Clinical Research Center for Gastroenterology, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China, Email waiyongtg@163.com; hckroy@163.comBackground: Acute decompensated cirrhosis (AD) is related to high medical costs and high mortality. We recently proposed a new score model to predict the outcome of AD patients and compared it with the common score model (CTP, MELD and CLIF-C AD score) in the training and validation sets.Materials and Methods: A total of 703 patients with AD were enrolled from The First Affiliated Hospital of Nanchang University between December 2018 and May 2021. These patients were randomly assigned to the training set (n=528) and validation set (n=175). Risk factors affecting prognosis were identified by Cox regression analysis and then used to establish a new score model. The prognostic value was determined by the area under the receiver operating characteristic curve (AUROC).Results: A total of 192 (36.3%) patients in the training cohort and 51 (29.1%) patients in the validation cohort died over the course of 6 months. A new score model was developed with predictors including age, bilirubin, INR, WBC, albumin, ALT and BUN. The new prognostic score (0.022×Age + 0.003×TBil + 0.397×INR + 0.023×WBC- 0.07×albumin + 0.001×ALT + 0.038×BUN) for long-term mortality was superior to three other scores based on both training and internal validation studies.Conclusion: This new score model appears to be a valid tool for assessing the long-term survival of AD patients, improving the prognostic value compared with the CTP, MELD and CLIF-C AD scores.Keywords: new score, prognosis, CTP score, MELD score, CLIF-C AD score

Tianyu Yu,&ast; Jiangnan Dong,&ast; Qi Qi,&ast; Qiang Lv, Jun Li, Chaojun Huang, Xiaoyan Cai Department of General Surgery, Gongli Hospital of Shanghai Pudong New Area, Shanghai, 200135, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoyan Cai, Department of General Surgery, Gongli Hospital of Shanghai Pudong New Area, Shanghai, 200135, People’s Republic of China, Tel/Fax +86-21-58858730, Email cxy6429@163.comPurpose: The Omicron variant of SARS-CoV-2 has emerged as a significant global concern, characterized by its rapid transmission and resistance to existing treatments and vaccines. However, the specific hematological and biochemical factors that may impact the clearance of Omicron variant infection remain unclear. The present study aimed to identify easily accessible laboratory markers that are associated with prolonged virus shedding in non-severe patients with COVID-19 caused by the Omicron variant.Patients and Methods: A retrospective cohort study was conducted on 882 non-severe COVID-19 patients who were diagnosed with the Omicron variant in Shanghai between March and June 2022. The least absolute shrinkage and selection operator regression model was used for feature selection and dimensional reduction, and multivariate logistic regression analysis was performed to construct a nomogram for predicting the risk of prolonged SARS-CoV-2 RNA positivity lasting for more than 7 days. The receiver operating characteristic (ROC) curve and calibration curves were used to assess predictive discrimination and accuracy, with bootstrap validation.Results: Patients were randomly divided into derivation (70%, n = 618) and validation (30%, n = 264) cohorts. Optimal independent markers for prolonged viral shedding time (VST) over 7 days were identified as Age, C-reactive protein (CRP), platelet count, leukocyte count, lymphocyte count, and eosinophil count. These factors were subsequently incorporated into the nomogram utilizing bootstrap validation. The area under the curve (AUC) in the derivation (0.761) and validation (0.756) cohorts indicated good discriminative ability. The calibration curve showed good agreement between the nomogram-predicted and actual patients with VST over 7 days.Conclusion: Our study confirmed six factors associated with delayed VST in non-severe SARS-CoV-2 Omicron infection and constructed a Nomogram which may assist non-severely affected patients to better estimate the appropriate length of self-isolation and optimize their self-management strategies.Keywords: SARS-CoV-2, COVID-19, Omicron, viral shedding time, nomogram

Xin Liu,1 Lili An,2 Yonghui Zhou,1 Wei Peng,1 Cong Huang1 1College of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang City, People’s Republic of China; 2Dermatology Department, the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang City, People’s Republic of ChinaCorrespondence: Xin Liu, College of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang City, People’s Republic of China, Tel +8618886056643, Email 1046977102@qq.comPurpose: Staphylococcus epidermidis has become one of the most common causes of septicemia. Meanwhile, S. epidermidis has acquired resistance to many antibiotics. Among these, methicillin-resistant S. epidermidis (MRSE) were frequently isolated. Similar to methicillin resistant Staphylococcus aureus (MRSA), they also exhibited multi-resistance, which presented a danger to human health. Patrinia scabiosaefolia as traditional Chinese medicine had strong antibacterial activity against MRSE. However, the mechanism of P. scabiosaefolia against MRSE is not clear.Methods: Here, the morphology of cell wall and cell membrane, production of β-lactamase and PBP2, energy metabolism, antioxidant system were systematically studied.Results: The data showed that P. scabiosaefolia damaged the cell wall and membrane. In addition, β-lactamase, energy metabolism and antioxidant system were involved in mechanisms of P. scabiosaefolia against MRSE.Conclusion: These observations provided new understanding of P. scabiosaefolia against MRSE to control MRSE infections.Keywords: methicillin-resistantStaphylococcus epidermidis, Patrinia scabiosifolia, β-lactamase, energy metabolism, antioxidant system

Guo P, Huang C, Yang Q, et al. Int J Nanomedicine. 2023;18:7759-7784. The authors have advised the correspondence section on page 7759 is incorrect. The correct correspondence address is as follows. Correspondence: Yan Qu, State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, People’s Republic of China, Email quyan028@126.com The authors apologize for this error.

Tsung-Lung Lu,1 Yiling Chuang,1 Chienhsiu Huang2 1Department of Nursing, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi County, Taiwan; 2Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi County, TaiwanCorrespondence: Chienhsiu Huang, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, NO. 2, Min-Sheng Road, Dalin Town, Chiayi County, Taiwan, Email hgssport@yahoo.com.tw; dm550671@tzi.com.twBackground: The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is 2 to 3 times more contagious than the Delta variant and poses a new challenge in containing transmission in community and health care settings. Transmission in hospitals can cause nosocomial outbreak infections and affect patients and health care workers. This study describes a coronavirus disease 2019 (COVID-19) outbreak in a medical ward. The purpose of the investigation was to determine the transmission source of the outbreak, as well as the measures implemented to prevent and control it.Methods: A cluster of SARS-CoV-2 infections that affected health care workers, inpatients, and caregivers was thoroughly researched in a medical ward. There were several strict outbreak measures implemented in our hospital, and these measures controlled the nosocomial COVID-19 outbreak in this study.Results: Seven cases of SARS-CoV-2 infection were diagnosed within 2 days in the medical ward. The infection control team declared a nosocomial outbreak of the COVID-19 Omicron variant. Several strict outbreak measures were implemented as follows: 1. The medical ward was closed and cleaning and disinfection were performed. 2. All patients and caregivers with negative test results were transferred to a spare COVID-19 isolation ward. 3. Relatives’ visits were not allowed, and no new patient was admitted during the outbreak period. 4. Health care workers were retrained on wearing personal protective equipment and enhanced techniques and practices of hand hygiene, social distancing, and self-monitoring of fever and respiratory symptoms.Conclusion: This outbreak occurred in a non-COVID-19 ward during the COVID-19 Omicron variant phase of the pandemic. Our strict outbreak measures halted and contained the nosocomial COVID-19 outbreak in 10 days. Future studies are needed to establish a standard policy of COVID-19 outbreak measure implementation.Keywords: SARS-CoV-2, COVID-19, nosocomial outbreak, medical ward, Omicron variant

Chenlu Huang,1,&ast; Weixia Li,2,&ast; Chong Chen,2,&ast; Wei Xu,1 Ling Fei,1 Shuai Tao,3 Qiankun Hu,1 Xudong Xie,1 Xiongyue Cao,1 Xiao-Yu Zhang,1,4 Liang Chen,1 Qiang Li,1 Yuxian Huang1 1Department of Liver Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai, People’s Republic of China; 2Department of Infectious Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai, People’s Republic of China; 3Research Unit, Shanghai Public Health Clinical Center, Fudan University, Shanghai, People’s Republic of China; 4Section of Education, Shanghai Public Health Clinical Center, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuxian Huang; Qiang Li, Email yxhuang@fudan.edu.cn; liqiang66601@163.comAim: The early prognosis evaluation of acute-on-chronic liver failure (ACLF) is important to decrease its mortality. We aimed to develop a new score to accurately predict the outcome of patients with ACLF.Methods: A derivation set of 408 patients with hepatitis B virus-related ACLF (HBV-ACLF) based on the Asian Pacific Association for the Study of the Liver criteria is used to develop a prognostic score that was validated in 209 patients with HBV-ACLF and 195 patients with non-HBV-ACLF.Results: Seven factors were significantly related to the 28-day mortality and constituted a new score (CHINAT-CD4 = 0.320 × ln (creatinine) + 0.668 × hepatic encephalopathy score + 0.745 × ln (international normalized ratio) + 0.476 × ln (neutrophil) + 0.251 × ln (aspartate aminotransferase) + 0.411 × ln (total bilirubin) - 0.605 × ln (CD4+ T cells count)). The C-indices of the new score for the 28-/90-day mortality (0.810/0.806) outperformed those of the other seven scores (p≤ 0.05). The results were confirmed in a validation set (0.798/793 for HBV-ACLF; 0.790/0.788 for non-HBV-ACLF). The novel score based on CD4+ T cell count showed high predictive performance for the 28-/90-day mortality of ACLF.Conclusion: The novel score based on CD4+ T cell count can accurately predict the 28-/90-day mortality for patients with ACLF.Keywords: liver failure, chronic liver disease, prognostic score, risk stratification, inflammatory markers

Mingjie Lu,1,&ast; Ling Gong,1,&ast; Chengyan Huang,1 Meng Ye,2 Hongping Wang,3 Yi Liu,3 Daishun Liu3 1Department of Respiratory Medicine, The Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi), Zunyi, Guizhou, 563000, People’s Republic of China; 2Scientific Research Center, The Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi), Zunyi, Guizhou, 563000, People’s Republic of China; 3Zunyi Medical University, Zunyi, Guizhou, 563000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Daishun Liu, Zunyi Medical University, No. 6 Xuefu West Road, Xinpu New District, Zunyi, Guizhou, 563000, People’s Republic of China, Email ldslwtg@126.comObjective: This study was conducted to retrospectively analyze the clinical characteristics of CTD-ILD patients to provide strategies for clinical management.Methods: This study collected and analyzed the clinical data and relevant examination results of 161 patients diagnosed with CTD-ILD between 01 January 2018 and 01 January 2021.Results: A total of 161 CTD-ILD patients, 74.53% were females and 25.47% were males, 32.92% were elderly and 67.08% were non-elderly. The main clinical symptoms of CTD-ILD patients were cough (44.72%), decreased activity tolerance (40.37%). RA-ILD was the most common one in the non-elderly and the elderly CTD-ILD patients (48.15% and 50.94%, respectively). Compared with non-elderly, elderly patients with CTD-ILD had a longer duration of CTD (p=0.04). However, fatigue (p=0.005), activity tolerance (p=0.029), the incidence of pulmonary diffusion dysfunction (p=0.047), and systemic immunoinflammatory index (SII, p=0.014) (platelet × NLR) were all decreased. The standard deviation of red blood cell distribution width (RDW) (p=0.024) and immunoglobulin (IgA) (p=0.033) was significantly increased. The smoking index was significantly higher in men than in women with CTD-ILD (p=0.000), but symptoms of reduced activity tolerance were less pronounced than in women (p< 0.05). Elderly CTD-ILD patients (p=0.003) and women from non-elderly patients were prone to lower hemoglobin (p=0.000). Among the elderly, the lymphocyte ratio was more significantly elevated in female CTD-ILD patients than in males (p=0.018). In contrast, neutrophil to lymphocyte ratio (NLR) and SII were lower in female (p=0.038) than in male CTD-ILD patients (p=0.043).Conclusion: CTD-ILD mainly affects non-elderly and women. Age may not be involved with decreased activity tolerance and increased lung function impairment in CTD-ILD patients. However, the elderly patients with CTD-ILD, especially the elderly female patients with low inflammation levels and high immune disorders, have a poor prognosis.Keywords: CTD-ILD, rheumatoid arthritis, pulmonary functions, clinical characteristics

Chen Huang,1,&ast; Chunbin Li,2,3,&ast; Jiaxuan Cai,1,4,&ast; Jie Chen,1 Baobei Wang,1 Mengxia Li,1 Wei Zhou,5 Jianguo Wang,3 Pengfei Zhang,2 Jian V Zhang1 1Center for Energy Metabolism and Reproduction, Shenzhen Key Laboratory of Metabolic Health, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People’s Republic of China; 2Guangdong Key Laboratory of Nanomedicine, CAS Key Laboratory of Health Informatics, Shenzhen Bioactive Materials Engineering Laboratory for Medicine, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People’s Republic of China; 3College of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot, People’s Republic of China; 4Shenzhen College of Advanced Technology, University of Chinese Academy of Sciences, Shenzhen, People’s Republic of China; 5Gynecology Department, Huazhong University of Science and Technology Union, Shenzhen Hospital, Shenzhen, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian V Zhang; Pengfei Zhang, Shenzhen Institute of Advance Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, 518055, People’s Republic of China, Tel +86 0755-86392591, Fax +86 0755-86585222, Email jian.zhang@siat.ac.cn; pf.zhang@siat.ac.cnIntroduction: Lack of highly expressed tumor target and ligands limits application of nano-medicine against triple-negative breast cancer (TNBC). Previous study reported that placenta-derived oncofetal chondroitin sulfate glycosaminoglycan chain (CSA) expressed on 90% of stage I–III invasive ductal breast carcinomas. Our study found the CSA anchor protein VAR2CSA derived small peptide plCSA had strong binding activity with TNBC cell lines and tumor tissue. Here, we combined the AIEgens TBZ-DPNA and therapy drug paclitaxel (PTX) to fabricate near-infrared fluorescence-guided nanodrug (plCSA-NP) to investigate its targeting and anti-tumor effect on TNBC.Methods: We synthesized and purified TBZ-DPNA with one step, measured optical properties and photoluminescence (PL) spectra. We prepared nanodrug plCSA-NP by encapsulating TBZ-DPNA and PTX and conjugating them with peptide plCSA. We evaluated plCSA-NP targeting activity by examining AIEdots fluorescence signal on TNBC cell lines and subcutaneous and lung metastatic mouse model. We assessed PTX delivery effect by cytotoxicity assay on TNBC line and tumor growth of subcutaneous and lung metastatic mouse models.Results: PL spectra and TEM imaging results showed plCSA-NP had maximum emission feature at 718 nm and nearly monodispersed nanosphere with an average diameter of 70 nm. In vitro studies showed plCSA-NPs had high affinity and cytotoxicity with TNBC cell lines. In vivo subcutaneous and lung metastasis mouse studies showed plCSA-NPs accumulated on TNBC tumor tissue, and significantly prevented TNBC subcutaneous and lung metastasis tumor growth.Conclusion: In conclusion, we provide solid evidence for chondroitin sulfate targeting peptide plCSA guided nanodrug, exhibit good targeting efficiency and therapeutic effect against TNBC primary and lung metastatic tumor growth.Keywords: triple-negative breast cancer, lung metastasis, chemotherapy, aggregation-induced emission, drug delivery system, plCSA

Dong Xu,1 Xu Zhu,2 Junyu Huo,2 Xupin Xie,1 Changpin Huang,1 Xin Fang,1 Ting Yin3 1Department of Vascular Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Cardiology, Jiangsu Province Hospital and Nanjing Medical University, First Affiliated Hospital, Nanjing, Jiangsu, People’s Republic of China; 3Intensive Care Unit, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Ting Yin, Intensive Care Unit, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310000, People’s Republic of China, Tel +86 13777879077, Fax +86 56005600, Email ameliyt@163.com Xin Fang, Department of Vascular, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310000, People’s Republic of China, Tel +86 13867478324, Fax +86 56005600, Email fangxin324@hotmail.comPurpose: Peripheral arterial disease (PAD) presenting with underlying hypertension (HTN) poses a higher risk of bilateral lower limb amputation than PAD patients without HTN. While the role of HTN management of PAD patients has received limited attention. We analyzed the clinical characteristics of PAD in adults with HTN and explored risk factors for PAD to construct a nomogram for evaluating critical limb ischemia (CLI) and lesion severity.Methods Patients and Methods: Between January 2014 and December 2019, we retrospectively evaluated 1886 patients with peripheral artery disease with coexisting HTN. Patients were randomly divided into training (n = 1320, 70%) and validation cohorts (n = 566, 30%), and according to the subjective experience of PAD [Fontaine classification (I–II vs III–IV)], patients were further classified into intermittent claudication (IC) and CLI groups. LASSO regression and multivariate Cox proportional hazard analyses were used to construct a nomogram using variables defined in the training cohort, which was validated in the validation cohort. The evaluation of the predictive discriminative, accuracy and clinical application are further analyzed.Results: In the training cohort, optimal independent factors included age, male sex, body mass index, diabetes mellitus, heart rate, triglyceride, and uric acid (AM-BDHTU), which were included in the nomogram predicting the CLI risk (all P < 0.05). The C-index values for CLI risk in PAD with HTN patients were 0.729 (95% CI: 0.704– 0.807) and 0.728 (95% CI: 0.652– 0.744) in the training and validation sets, respectively. Calibration curves indicated good consistency between predicted and actual outcomes. DCA confirmed the clinical utility of the diagnostic model.Conclusion: The AM-BDHTU nomogram, constructed and validated using simple to obtain clinical variables, when combined with the Fontaine classification, effectively predicts the risk of CLI among PAD patients with HTN.Keywords: peripheral arterial disease, hypertension, vascular-related complications, LASSO regression, nomogram, predictive diagnosis

Christina Huang,1,* Sarah Gold,1,* Rakan Radi,1 Seth Amos,1 Howa Yeung1,2 1Department of Dermatology, Emory University School of Medicine, Atlanta, GA, USA; 2Clinical Resource Hub, Veterans Affairs Southeast Network Veterans Integrated Service Network 7, Decatur, GA, USA*These authors contributed equally to this workCorrespondence: Howa Yeung, Department of Dermatology, Emory University School of Medicine, 1525 Clifton Road NE Suite 100, Atlanta, GA, 30322, USA, Tel +1 (404) 727-9838, Fax +1 (404) 727-5878, Email howa.yeung@emory.eduAbstract: Transgender adolescents seek gender-affirming medical care to address gender identity and incongruence. Improved understanding of the dermatologic impact of gender-affirming medical care such as pubertal suppression, hormone therapy, and surgeries can enhance patient outcome. Pubertal suppression treats dysphoria associated with development of secondary sex characteristics, including androgen-driven acne. Gender-affirming hormone therapy influences acne and hair development in transgender adolescents. Dermatologists can help manage skin effects associated with chest binding and gender-affirming hormone therapy and surgery. Provision of patient-centered gender-affirming care in dermatologic and multidisciplinary settings is essential to improve skin and overall outcomes of gender-affirming therapy.Keywords: gender-affirming care, testosterone, estrogen, acne, anti-androgen

Danyang Li,1 Tong Wang,2 Qianli Ma,3 Lu Zhou,1 Yanqing Le,1 Yafei Rao,1 Liang Jin,1 Yuqiang Pei,1 Yaning Cheng,4 Chen Huang,5 Xiaoyan Gai,1 Yongchang Sun1 1Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 2Department of Thoracic Surgery, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 3Department of Thoracic Surgery, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China; 4School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, People’s Republic of China; 5Center of Basic Medical Research, Peking University Third Hospital, Beijing, 100191, People’s Republic of ChinaCorrespondence: Xiaoyan Gai; Yongchang Sun, Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, No. 49 North Garden Road, Haidian District, Beijing, 100191, People’s Republic of China, Email gxy81wfl79@163.com; suny@bjmu.edu.cnBackground: It has been reported that a disintegrin and metalloproteinase 9 (ADAM9) is involved in the pathogenesis of cigarette smoke (CS)-associated chronic obstructive pulmonary disease (COPD). But how CS exposure leads to upregulation of ADAM9 remains unknown.Methods: Patients who underwent lobectomy for a solitary pulmonary nodule were enrolled and divided into three groups: non-smokers with normal lung function, smokers without COPD and smoker patients with COPD. Immunoreactivity of interleukin (IL)-17A and ADAM9 in small airways and alveolar walls was measured by immunohistochemistry. Wild-type and Il17a−/− C57BL/6 mice were exposed to CS for six months, and ADAM9 expression in the airway epithelia was measured by immunoreactivity. In addition, the protein and mRNA expression levels of IL-17A and ADAM9 were assessed in CS extract (CSE) and/or IL-17A-treated human bronchial epithelial (HBE) cells.Results: The immunoreactivity of ADAM9 was increased in the airway epithelia and alveolar walls of patients with COPD compared to that of the controls. The expression of IL-17A was also upregulated in airway epithelial cells of patients with COPD and correlated positively with the level of ADAM9. The results from the animal model showed that Il17a−/− mice were protected from emphysema induced by CS exposure, together with a reduced level of ADAM9 expression in the airway epithelia, suggesting a possible link between ADAM9 and IL-17A. Consistently, our in vitro cell model showed that CSE stimulated the expression of ADAM9 and IL-17A in HBE cells in a dose- and time-dependent manner. Recombinant IL-17A induced ADAM9 upregulation in HBE cells and had a synergistic effect with CSE, whereas blocking IL-17A inhibited CSE-induced ADAM9 expression. Further analysis revealed that IL-17A induced c-Jun N-terminal kinase (JNK) phosphorylation, thereby increasing ADAM9 expression.Conclusion: Our results revealed a novel role of IL-17A in CS-related COPD, where IL-17A contributes to ADAM9 expression by activating JNK signaling.Keywords: chronic obstructive pulmonary disease, a disintegrin and metalloproteinase 9, interleukin-17A, airway epithelium

Jinyan Lin,&ast; Yu Zhang,&ast; Chongxi Bao, Huasong Lu, Yun Zhong, Chuanfeng Huang, Qiuping Huang, Dezhen Wang, Jing Luo, Ke Wang, Jinliang Kong Pulmonary and Critical Care Medicine Ward, Guangxi Medical University First Affiliated Hospital, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinliang Kong; Ke Wang, Pulmonary and Critical Care Medicine Ward, Guangxi Medical University First Affiliated Hospital, No. 6 Shuangyong Road, Nanning, 530021, People’s Republic of China, Email kjl071@126.com; 497256113@qq.comBackground: Streptococcus constellatus, a commensal, plays an important role in purulent infections. It has been reported as aggressive pathogen causing pleural empyema. But the role of S. constellatus in empyema has not been taken seriously. There are no studies about clinical characteristics of empyema caused by S. constellatus domestically and abroad. This study aimed to explore the clinical features and management of empyema caused by S. constellatus.Methods: A retrospective review of 9 patients diagnosed with empyema caused by S. constellatus in a hospital between January 2010 and August 2021 was performed.Results: S. constellatus empyema were mostly seen in old males (66.7%) with comorbid diseases. The high-risk factors include diabetes mellitus, oral infection, and oral surgery. All were unilateral encapsulated empyema (right-side, 55.6%), diagnosed with pneumonia (bilateral pneumonia, 88.9%; ipsilateral lung abscess, 44.4%). 33.3% of patients had S. constellatus and anaerobes co-isolated. S. constellatus were sensitive to penicillin G, linezolid, levofloxacin, vancomycin, ceftriaxone, and chloramphenicol, resistant to erythromycin, tetracycline, and clindamycin. 33.3% of the patients needed ventilator support. The primary treatment to S. constellatus empyema was timely pus drainage, intravenous antibiotics, and enough nutrition support, intrapleural fibrinolytics and surgery (VAST recommended first) in necessity.Conclusion: S. constellatus may cause pneumonia and lung abscess first and then spread to cause empyema mainly in old males with comorbid diseases. S. constellatus often co-isolated with anaerobes in empyema. Antibiotics should cover simultaneously both S. constellatus and anaerobes.Keywords: S. constellatus, empyema, clinical features, anaerobes

Ling Lu,1 Yan Ma,2 Jie Deng,1 Jiaqiong Xie,1 Chaolin Huang1 1Department of Gynaecology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, People’s Republic of China; 2Department of Obstetrics, The First Affiliated Hospital of Chengdu Medical College, Chengdu, People’s Republic of ChinaCorrespondence: Chaolin Huang; Jiaqiong Xie, Department of Gynaecology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, People’s Republic of China, Email huang.chaolin@qq.com; 475105126@qq.comObjective: This study aimed to investigate ATG7 levels in pregnant women with and without gestational diabetes mellitus (GDM) and explore the potential associations between ATG7 levels and GDM.Methods: This was a cross-sectional study conducted in a large tertiary hospital in Chengdu, China. The ATG7 levels in pregnant women at between 24 and 28 weeks of gestation with (n=84) and without GDM (n=649) were measured by using an ELISA kit. Glucose, HbA1c, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were measured by an automatic biochemistry analyser. The homeostasis model assessment of insulin resistance (HOMA-IR) and insulin secretion (HOMA-β) were calculated according to published formulas. The associations of ATG7 levels with laboratory parameters, GDM, and insulin resistance were evaluated using correlation analysis or a regression model.Results: The ATG7 levels were significantly lower in pregnant women with GDM than in those without GDM. The correlation analyses found that ATG7 levels correlated positively with HOMA-β but correlated negatively with HOMA-IR, oral glucose tolerance test (OGTT) glucose levels, TGs, and LDL-C. There were no significant correlations between ATG7 levels and HbA1c, HDL-C, or TC. After adjusting for potential confounders, lower ATG7 levels were shown to be associated with a higher risk of GDM. Furthermore, multiple linear regression analyses showed that ATG7 levels were negatively associated with insulin resistance.Conclusion: ATG7 levels are significantly lower in pregnant women with GDM than in those without GDM, and lower ATG7 levels are associated with a higher risk of GDM. ATG7 levels were negatively associated with insulin resistance. Autophagy deficiency, which is caused by lower ATG7 levels, may be the underlying mechanism that mediates insulin resistance in the development of GDM.Keywords: ATG7, autophagy, cross-sectional study, gestational diabetes mellitus, insulin resistance

Zhiyun Shen,1,* Yaping Zhang,2,* Chun Yang,3 Jie Liu,3 Chenxu Huang,1 Xian Zhang,1 Yuxia Zhang,1 Ying Lin1 1Department of Nursing, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Emergency, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Network Center, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuxia Zhang; Ying Lin, Department of Nursing, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China, Tel +86 21-64041990, Email zhang.yuxia@zs-hospital.sh.cn; lin.ying@zs-hospital.sh.cnBackground: For a long time, fluid balance monitoring has been one of the most difficult problems in the management of patients with heart failure (HF). There is considerable interest in technology-facilitated fluid balance monitoring. However, little is known about patient acceptance and the use of mobile technology for fluid balance monitoring.Objective: The aim of this study was to develop a mobile app for technology-facilitated fluid balance monitoring and to determine its usability.Methods: A mixed-methods study was conducted in a tertiary hospital in Shanghai, China. A mobile app named I-Self-Care was developed through a best practice implementation project. Patients and nurses both completed the System Usability Scale (SUS, 0– 100) and participated in semistructured interviews.Results: I-Self-Care includes patients’ daily fluid intake and output (I&O), symptoms, hospitalization, and diuretic records. It can automatically calculate food water content and perform real-time analysis of I&O. The average SUS scores were 81.74 (SD 5.44) among 36 patients and 80.80 (SD 13.26) among 28 nurses (scale 0– 100, with 100 being the best usability), which means that I-Self-Care has high usability for both patients and nurses. Semistructured interviews about the usability of the app were conducted with 17 participants. During the interviews, the patients expressed the high ease of use of I-Self-Care, their expectations for a continuously updated database, and improved self-management behaviour. The nurses thought that family support and repeated operation demonstrations were needed for patients to use the app. The nurses also expressed the convenience of this app for nursing work and the information security of patients.Conclusion: With participant feedback, we confirmed the usability of I-Self-Care for fluid balance monitoring in patients with HF. Continuously updated databases, family support, repeated operation demonstrations, and information security are important for HF patients to use I-Self-Care.Keywords: fluid balance monitoring, intake and output, mobile applications, telemedicine, heart failure

Lili Fang,1– 3,&ast; Minxue Liu,4,&ast; Chunlan Huang,5,&ast; Xiaobo Ma,1– 3 Yanqing Zheng,1– 3 Wenjuan Wu,6 Jian Guo,6,&ast; Jiangshan Huang,1– 3 Heping Xu1– 3 1Department of Laboratory Medicine, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, People’s Republic of China; 2Xiamen Key Laboratory of Genetic Testing, Xiamen, Fujian, People’s Republic of China; 3School of Public Health, Xiamen University, Xiamen, Fujian, People’s Republic of China; 4The Maternal & Child Health Hospital, The Children’s Hospital, The Obstetrics & Gynecology Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, People’s Republic of China; 5Department of Clinical Laboratory, Liuzhou People’s Hospital, Liuzhou, Guangxi, People’s Republic of China; 6Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Heping Xu; Jiangshan, Hung Department of Laboratory Medicine, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, People’s Republic of China, Email xmsunxhp@163.com; 13600918159@163.comIntroduction: Talaromyces marneffei is a life-threatening pathogen that causes systemic talaromycosis in immunocompromised and acquired immunodeficiency syndrome (AIDS) patients. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) as a tool to cluster T. marneffei isolates is rarely reported and the data on antifungal susceptibility of T. marneffei isolated in the southern region of China, especially in Fujian, is hardly found.Methods: MALDI-TOF MS was used to cluster 135 T. marneffei isolates, and the minimum inhibitory concentration (MIC) values of amphotericin B, itraconazole, posaconazole, voriconazole, fluconazole, anidulafungin, micafungin, caspofungin and 5-fluorocytosine with Sensititre YeastOne™ YO10 assay were measured during January 2017 to October 2020 in Fujian and Guangxi.Results: MALDI-TOF MS correctly identified 100% of the T. marneffei isolates. Hierarchical clustering of MALDI-TOF peak profiles identified four different clusters. MICs for itraconazole, posaconazole, voriconazole and amphotericin B were as follows: ≤ 0.015– 0.03 μg/mL, ≤ 0.008– 0.03 μg/mL, ≤ 0.008– 0.06 μg/mL, ≤ 0.12– 1 μg/mL, respectively. MICs for echinocandins and fluconazole were comparatively high.Conclusion: Since only simple sample preparation is required and since results are available in a short period of time, MALDI-TOF MS can be considered as a method for identification and clustering of T. marneffei. Itraconazole, posaconazole, voriconazole and amphotericin B can be used to treat T. marneffei infected patients due to the low MICs.Keywords: Talaromyces marneffei, MALDI-TOF, antifungal susceptibility, HIV-infected, non-HIV-infected

Chienhsiu Huang Department of Internal Medicine, Division of Chest Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi County, TaiwanCorrespondence: Chienhsiu Huang, Department of Internal medicine, Division of Chest medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi County, Taiwan, Tel +886-9-21552418, Email hgssport@yahoo.com.tw; dm550671@tzuchi.com.twBackground: The gender differences in patients requiring prolonged mechanical ventilation are not understood. We investigated the effects of gender differences in terms of age, causes of respiratory failure, discharge status, successful weaning, mortality rate and long-term survival outcomes in patients receiving prolonged mechanical ventilation.Methods: We conducted a six-year retrospective study of patients requiring prolonged mechanical ventilation. Survival curves for all patients requiring prolonged mechanical ventilation and those who were very old (aged ≥ 80 years) were compared based on gender.Results: Among the 574 patients enrolled. There was no statistically significant difference between male and female patients regarding successful weaning, ventilator dependence, or in-hospital mortality. We gathered long-term follow-up data on 296 patients, including 70 very old male patients and 41 very old female patients. The 6-month, 3-year, and 5-year mortality rates for the 189 male patients were 75.1%, 85.2%, and 89.9%, respectively; the corresponding rates for the 107 female patients were 66.4%, 86.0%, and 88.8%, respectively. There was no statistically significant difference between two groups regarding mortality rates. The five-year survival curve of male patients was similar to that of female patients. The 6-month, 1-year, and 5-year mortality rates for the 70 very old male patients were 90.0%, 95.7%, and 97.1%, respectively; the corresponding rates for the 41 very old female patients were 63.4%, 90.2%, and 95.1%, respectively. There was a statistically significant difference between very old male and very old female patients in the 6-month mortality rate and the five-year survival curve.Conclusion: There were no gender differences in weaning status, ventilator dependence, in-hospital mortality, or survival outcomes among patients requiring prolonged mechanical ventilation. Among very old patients requiring prolonged mechanical ventilation, the risk of death was 34% lower in very old female patients than in very old male patients for a period of five years.Keywords: prolonged mechanical ventilation, respiratory care center, gender medicine, long-term survival

Houren Zhou,1 Hui Liu,2 Yue Zhang,3 Ying Xin,3 Chi Huang,3 Mingzhong Li,4 Xiaoyun Zhao,2 Pingtian Ding,2 Zhijun Liu3 1Ultrasound Department, The Second Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China; 2School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China; 3Ultrasound Department, Shengjing Hospital, China Medical University, Shenyang, People’s Republic of China; 4School of Pharmacy, De Montfort University, Leicester, LE1 9BH, UKCorrespondence: Zhijun Liu, Ultrasound Department, Shengjing Hospital, China Medical University, 36 Sanhao Street, Shenyang, Liaoning Province, 110004, People’s Republic of China, Email liuzj1@sj-hospital.orgObjective: Gastric cancer is one of the most lethal malignancies in the world. However, the current research on the diagnosis and treatment of nano-ultrasound contrast agents in the field of tumor is mostly focused on breast cancer, ovarian cancer, prostate cancer, liver cancer, etc. Due to the interference of gas in the stomach, there is no report on the treatment of gastric cancer. Herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) therapy system is the most mature tumor suicide gene in cancer treatment. At the same time, in order to improve its safety and efficiency, we designed a gastric tumor targeted ultrasound-triggered phase-transition nano ultrasound contrast agent PFH/AGM-CBA/HSV-TK/Liposome (PAHL)-Affibody complex.Methods: In our study, guanidinylated SS-PAAs polymer poly(agmatine/N, N′-cystamine-bis-acrylamide) (AGM-CBA) was used as a nuclear localization vector of suicide gene to form a polyplex, perfluorohexane (PFH) was used as ultrasound contrast agent, liposomes were used to encapsulate perfluorohexane droplets and the polyplexes of AGM-CBA/HSV-TK, and affibody molecules were conjugated to the prepared PAHL in order to obtain a specific targeting affinity to human epidermal growth factor receptor type 2 (ErbB2) at gastric cancer cells. With the aid of ultrasound targeted microbubble destruction technology and the nuclear localization effect of AGM-CBA vector, the transfection efficiency of the suicide gene in gastric cancer cells was significantly increased, leading to significant apoptosis of gastric cancer cells.Results: It was shown that PAHL-Affibody complex was nearly spherical with an average diameter of 560 ± 28.9 nm, having higher and specific affinity to ErbB2 (+) gastric cells. In vitro experiments further confirmed that PAHL could target gastric cancer cells expressing ErbB2. In a contrast-enhanced ultrasound scanning study, the prepared ultrasound-triggered phase-change nano-ultrasound contrast agent, PAHL, showed improved ultrasound enhancement effects. With the application of the low-frequency ultrasound, the gene transfection efficiency of PAHL was significantly improved, thereby inducing significant apoptosis in gastric cancer cells.Conclusion: This study constructs PFH/AGM-CBA/HSV-TK/Liposome-Affibody nano ultrasound contrast agent, which provides new ideas for the treatment strategy of ErbB2-positive gastric cancer and provides some preliminary experimental basis for its inhibitory effect.Keywords: Herpes simplex virus thymidine kinase/ganciclovir, poly (agmatine/N, N′-cystamine-bis-acrylamide), ErbB2 targeting, gene transfection, low-frequency ultrasound

Qiang Gong,1 Haruki Momma,1 Yufei Cui,1,2 Cong Huang,3 Kaijun Niu,4 Ryoichi Nagatomi1,5 1Department of Medicine and Science in Sports and Exercise, Tohoku University Graduate School of Medicine, Sendai, Japan; 2Institute of Exercise Epidemiology and Department of Physical Education, Huaiyin Institute of Technology, Huaian, People’s Republic of China; 3Department of Physical Education, Zhejiang University, Hangzhou, People’s Republic of China; 4Department of Epidemiology, School of Public Health, Tianjin Medical University, Tianjin, People’s Republic of China; 5Division of Biomedical Engineering for Health & Welfare, Tohoku University Graduate School of Biomedical Engineering, Sendai, JapanCorrespondence: Ryoichi Nagatomi, Division of Biomedical Engineering for Health & Welfare, Tohoku University Graduate School of Biomedical Engineering, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan, Tel/Fax + 81-22-717-8586, Email nagatomi@med.tohoku.ac.jpPurpose: Vegetable intake is an important part of our everyday diet and is associated with many positive health outcomes. Although previous studies have investigated the association between vegetable consumption and depressive symptoms among various populations, no study has examined this association in the adult working population. The present study investigated whether the frequency of consumption of a specific type of vegetable is associated with the prevalence of depressive symptoms in Japanese adult workers.Participants and Methods: The final participants consisted of 1724 Japanese adults, and a cross-sectional study was conducted to analyze the results. The frequency of vegetable consumption and depressive symptoms was evaluated using a brief-type self-administered diet history questionnaire and the Zung Self-Rating Depression Scale (SDS), respectively. The association between the variables was examined using Poisson regression analysis. Age-stratified analysis was performed, and SDS cut-off values of 45 and 50 were used to perform a sensitivity analysis.Results: After adjustment for covariates, including age, body mass index, sociodemographic and lifestyle-related variables, health condition, C-reactive protein, and other dietary variables, an inverse association was found between tomato product consumption and the prevalence of depressive symptoms among men (P for trend < 0.01); however, no significant association was found for other vegetable types. For women, there was no association between the frequency of consumption of any of the vegetable types and the prevalence of depressive symptoms. The results were confirmed by the age-stratified analysis for both genders.Conclusion: Consumption of tomato products may help alleviate depressive symptoms, regardless of differences in dietary culture among men.Keywords: vegetables, depression, Japan, adults, workers, tomato products

Wu X, Xu Q, Chen P, et al. Cancer Manag Res. 2019;11:8125–8133. We, the Editor and Publisher of Cancer Management and Therapy are retracting the published article. Concerns were raised following the authors request to correct images in Figure 5. It was found some of the images had been duplicated. Specifically, Images from Figure 5A, shRNA-SMYD3-3, and 5B, Control, shRNA-NC and shRNA-SMYD3-3 have regions of overlap and duplication. When approached for an explanation, the authors were cooperative but were unable to adequately address the concerns raised and could not provide sufficient supporting information. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The authors listed in this publication have been informed and agree with this decision. We have been informed in our decision-making by our editorial policies and the COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.