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Ruixi Li,1 Lulu Liu,1 Yong Liu,1 Jiang Tang,1 Jinsong Li2 1Yueyang Guangji Hospital, Yueyang, Hunan, People’s Republic of China; 2Department of Spine Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Jinsong Li, Department of Spine Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China, Tel +86-731-88618826, Fax +86-731-88618526, Email jinsongli_csu@163.comIntroduction: Protocadherin 9 (PCDH9), a member of the cadherin superfamily of transmembrane proteins, plays a role in cell adhesion and neural development. Recent studies suggest that PCDH9 may function as a tumor suppressor in certain cancers, though its specific role in breast cancer remains unclear.Methods: UALCAN database to retrieve information on PCDH9 expression in breast cancer tissues compared with that in normal tissues. The biological effects of PCDH9 in breast cancer cells were analyzed using the DepMap database. Stable knockdown or overexpression of PCDH9 in breast cancer cell lines and subsequently assessed tumor cell proliferation and migration. Synthetic lethal screening was conducted for breast cancer cells with low PCDH9 expression or deficiency.Results: In this study, we observed significant downregulation of PCDH9 in breast cancer tissues, with its expression negatively correlated with progression-free survival. Further investigations revealed that decreased PCDH9 expression promotes breast cancer cell proliferation and migration, while overexpression of PCDH9 has the opposite effect. Subsequently, we identified the TAS-102, an approved drug for metastatic colorectal cancer, exhibited selective cytotoxicity against breast cancer cells with low PCDH9 expression.Conclusion and discussion: In summary, our study identified PCDH9 as a tumor suppressor in breast cancer and highlighted TAS-102 as a potential therapeutic option for tumors with low PCDH9 expression or deficiency. The specific interaction between TAS-102 and PCDH9 warrants further exploration, providing deeper insights into its mode of action in treating PCDH9-deficient breast cancer.Keywords: breast cancer, PCDH9, synthetic lethality, TAS-102

Jie Jia,1,* Tao Sun,1,* Jiamin Tang,1 Kaidi Sun,1 Zhengnan Meng,1 Hailong Zhu,2 Xianhong Huang1 1Department of Health Policy and Management, School of Public Health, Hangzhou Normal University, Hangzhou, 311121, People’s Republic of China; 2Department of Sociology, School of Public Administration, Hangzhou Normal University, Hangzhou, 311121, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xianhong Huang, Department of Health Policy and Management, School of Public Health, Hangzhou Normal University, Hangzhou, 311121, People’s Republic of China, Tel/Fax +86-571-2886-5627, Email hxh974291@163.comPurpose: Healthcare professionals’ participation is crucial for the efficient implementation of multidisciplinary team (MDT) collaboration models. We identified the key factors influencing healthcare professionals’ preference to participate in MDTs in tertiary hospitals.Methods: To clarify the attributes and levels of the discrete choice experiment (DCE), we conducted a targeted literature review and conducted in-depth interviews with MDT service providers. Following this, a DCE was designed to evaluate healthcare professionals’ preferences for MDT participation, and the influence of factors such as salary subsidies, leadership attention, patient participation, quality assessment, working intensity, and case complexity. A conditional logit model estimated the utility of each attribute. Willingness-to-pay estimates were derived by taking the negative ratio of the coefficients of non-economic and economic attributes. A series of policy simulation analyses were conducted.Results: Two hundred healthcare professionals completed the questionnaire, with 180 valid responses used for analysis. All attributes were statistically significant. Leadership attention and working intensity were the primary factors influencing staff willingness to participate in MDTs, followed by quality assessment and salary subsidies. Significant preference differences were observed between respondents; compared with mid-level staff, senior-level healthcare professionals believed patient engagement would be more helpful in boosting participation. The policy simulation showed that changing leadership attention from “neglect” to “emphasis” would increase the probability of staff choosing to participate in MDTs from 24.4% to 66.98%.Conclusion: Leadership attention was the primary concern for healthcare professionals in MDTs. To effectively motivate staff participation in MDTs, policymakers should adopt a holistic approach that considers work motivation and individual backgrounds, including competitive salary packages and a positive work environment. They should concurrently introduce MDT case complexity measurement tools to optimize resource allocation. Addressing staff members’ unique needs and career aspirations by creating targeted training programs, pathways for advancement, and personalized career development plans are also crucial.Keywords: multidisciplinary medical services, participation motivation, health services research, discrete choice experiment

Ying Pan,1 Mengjie Zhao,1 Tiantian Song,2 Jia Tang,2 Ming Kuang,2 Hongying Liu,2,* Shao Zhong3,* 1Department of General Practice, Kunshan Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu, People’s Republic of China; 2Hangzhou Kang Ming Information Technology Co., Ltd, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Endocrinology, Gusu School, Nanjing Medical University, The First People’s Hospital of Kunshan, Kunshan, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shao Zhong, Department of Endocrinology, Gusu School, Nanjing Medical University, the First People’s Hospital of Kunshan, Kunshan, 215300, People’s Republic of China, Tel +86 13328056828, Email drzhong@163.com Hongying Liu, Hangzhou Kang Ming Information Technology Co., Ltd, Hangzhou, 310000, People’s Republic of China, Tel +86 02164045531, Email hongyingliu@91jkys.comAbstract: Insulin resistance (IR) is the major mechanism in the pathogenesis of type 2 diabetes mellitus (T2DM). Early identification of IR is of great significance for preventing the onset of T2DM and delaying the progression of the disease. Previous studies have shown that triglyceride-glucose (TyG) index can be used as an effective surrogate marker for IR. There is a significant correlation between TyG index and T2DM and its common complications. In addition, the predictive efficacy of TyG index is better than that of other IR surrogate indicators. TyG index may not only become an important marker to identify people at high risk of T2DM and its complications, but is also expected to become a strong predictor of the prognosis of these diseases. However, there are still some challenges in the widespread application of TyG index in clinical practice. In the future, more high-quality studies are needed to clarify the assessment methods of TyG index for the prognosis of T2DM and its complications. Further investigations of the relationship between TyG index and T2DM and its complications will be expected to provide new ideas and methods for the prevention and treatment of T2DM and its complications.Keywords: triglyceride-glucose index, type 2 diabetes mellitus, complication, insulin resistance

Lijuan Liang,1,* Ming Jia,2,3,* Min Zhao,4,* Yiping Deng,5,* Jun Tang,5 Xinghui He,2 Yilin Liu,2 Kexin Yan,2 Xin Yu,6 Hong Yang,7 Chunhong Li,2 Yao Li,2,8 Tao Li4 1Department of Pharmacy, Hejiang County People’s Hospital, Luzhou, Sichuan, People’s Republic of China; 2Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 3Nanchong Institute for Food and Drug Control, Nanchong, Sichuan, People’s Republic of China; 4Key Laboratory of Medical Electrophysiology of Ministry of Education, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 5Analysis and Testing Center, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 6Chinese Pharmacy Laboratory, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 7Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 8Science and Technology department, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yao Li; Tao Li, Email lnetyao@163.com; leta49@swmu.edu.cnAbstract: As a pivotal transition metal oxide, manganese dioxide (MnO2) has garnered significant attention owing to its abundant reserves, diverse crystal structures and exceptional performance. Nanosizing MnO2 results in smaller particle sizes, larger specific surface areas, optimized material characteristics, and expanded application possibilities. With the burgeoning research efforts in this field, MnO2 has emerged as a promising nanomaterial for tumor diagnosis and therapy. The distinctive properties of MnO2 in regulating the tumor microenvironment (TME) have attracted considerable interest, leading to a rapid growth in research on MnO2-based nanomaterials for tumor diagnosis and treatment. Additionally, MnO2 nanomaterials are also gradually showing up in the regulation of chronic inflammatory diseases. In this review, we mainly summarized the recent advancements in various MnO2 nanomaterials for tumor diagnosis and therapy. Furthermore, we discuss the current challenges and future directions in the development of MnO2 nanomaterials, while also envisaging their potential for clinical translation.Keywords: manganese dioxide nanoparticles, tumors, inflammation, biomedicine, research progress

PingPing Jiang,1,* JingTao Tang,2,* Min Zhang,3 Dan Wang1 1Department of Anesthesia, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 2Department of Anesthesia, The Second People’s hospital of Neijiang, Neijiang, Sichuan, People’s Republic of China; 3Department of Clinical Medicine, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: PingPing Jiang, Department of Anesthesia, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, People’s Republic of China, Tel +86 15881496034, Email 307174907@qq.comPurpose: This study aimed to observe the effect of bilateral transverse abdominis plane (TAP) block on the MACBAR of sevoflurane in gynecological patients with laparoscopic pneumoperitoneal stimulation.Patients and Methods: Fifty patients who underwent laparoscopic surgery were randomly assigned to either the control group (n= 25) or the TAP block group (n= 25). Patients in the TAP block group were subjected to a bilateral transversal abdominal muscle plane block with 0.33% ropivacaine (20 mL on each side) guided by ultrasound. The control group received an equal volume of normal saline. The MACBAR of sevoflurane in each group was determined using a sequential allocation technique.Results: The MACBAR of sevoflurane in the TAP block group was significantly lower than that in the control group (4.20% [95% confidence interval {CI}, 4.02%– 4.38%] vs 5.03% [95% CI, 4.89%– 5.18%]).Conclusion: Bilateral TAP block can reduce the MACBAR of sevoflurane in gynecological patients with pneumoperitoneum stimulation.Trial Registration Number: ChiCTR2100046517. The trial is publicly available and registered at www.chictr.org.cn on May 18, 2021.Keywords: Transverse abdominis plane block, Adrenergic response, Minimum alveolar concentration, Pneumoperitoneum stimulation, Sevoflurane

Liming Qin,1,2,&ast; Moqin Qiu,3,&ast; Jingmei Tang,2 Shuyan Liu,4 Qiuling Lin,5 Qiongguang Huang,2 Xiaoxia Wei,5 Qiuping Wen,1 Peiqin Chen,6 Zihan Zhou,7 Ji Cao,7 Xiumei Liang,8 Qian Guo,9 Cunli Nong,9 Yizhen Gong,5 Yuying Wei,1 Yanji Jiang,10 Hongping Yu,1,2,11– 13 Yingchun Liu1 1Department of Experimental Research, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 2School of Public Health, Guangxi Medical University, Nanning, People’s Republic of China; 3Department of Respiratory Oncology, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 4Key Laboratory of Biological Molecular Medicine Research, Education Department of Guangxi Zhuang Autonomous Region, Guangxi Medical University, Nanning, People’s Republic of China; 5Department of Clinical Research, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 6Editorial Department of Chinese Journal of Oncology Prevention and Treatment, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 7Department of Cancer Prevention and Control, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 8Department of Disease Process Management, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 9Liuzhou Worker’s Hospital, Liuzhou, People’s Republic of China; 10Department of Scientific Research, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 11Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Ministry of Education, Guangxi Medical University, Nanning, People’s Republic of China; 12Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning, People’s Republic of China; 13Key Cultivated Laboratory of Cancer Molecular Medicine of Guangxi Health Commission, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingchun Liu; Hongping Yu, Department of Experimental Research, Guangxi Medical University Cancer Hospital, 71&num; Hedi Road, Qingxiu District, Nanning, People’s Republic of China, Tel +86-15877191237 ; +86-771-5330850, Fax +86-771-5312000, Email liuyingchun@stu.gxmu.edu.cn; yuhongping@stu.gxmu.edu.cnPurpose: P53 is a suppressor gene closely related to carcinogenesis. However, the associations between genetic variants in the p53 signaling pathway and prognosis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remain unknown. The current study aims to analyze associations between the single nucleotide polymorphisms (SNPs) in p53 pathway-related genes and survival of patients with HBV-HCC.Methods: We evaluated the associations between 4698 SNPs in 70 genes of the p53 pathway and overall survival (OS) of 866 patients in additive genetic models by using Cox proportional hazards regression analysis. Stepwise multivariable Cox regression analysis was conducted to determine the independent effects of identified SNPs in single-locus analyses. The expression of quantitative trait loci (eQTL) was also analyzed using data from GTEx and 1000 Genomes Project, and functional prediction of SNPs was performed by using RegulomeDB v2.2, 3DSNP v2.0, HaploReg v4.2 and VannoPortal.Results: We found that two novel SNPs of CD82 rs7925603 A > G and PMAIP1 rs4396625 A > T, were significantly and independently associated with OS [adjusted hazards ratios (HRs) and 95% confidence intervals (CI) were 1.27 (1.10– 1.48) and 0.77 (0.66– 0.91), respectively; P = 0.001 and = 0.002, respectively] and that the combined risk genotypes of these SNPs showed a significant association with OS in patients with HBV-HCC (Ptrend < 0.001). Further eQTL analysis in the GTEx dataset showed that the rs7925603 G allele was associated with lower CD82 mRNA expression levels, while the rs4396625 T allele was associated with higher PMAIP1 mRNA expression levels in whole blood cells.Conclusion: We identified two observed survival-associated SNPs in CD82 and PMAIP1 in the p53 pathway, which influenced HBV-HCC survival possibly through a mechanism of altering mRNA expression. Large studies are warranted to validate our findings.Keywords: hepatocellular carcinoma, hepatitis B virus, p53 signaling pathway, genetic variants, survival

Xiaobing Li,1 De Wu,2 Jing Tang,3 Yuebing Wu3 1Department of Thoracic Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Pathology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Department of Lymphoma, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Yuebing Wu, Department of Lymphoma, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, 116&num; South Zhuodaoquan Road, Hongshan District, Wuhan, 430079, People’s Republic of China, Tel/Fax +86-27-87670351, Email wuyuebing0328@126.comBackground: Existing research data indicates that albumin-bound paclitaxel (nab-ptx), anlotinib, and PD-1/L1 inhibitors have individually shown efficacy in second-line and subsequent treatments for advanced non-small cell lung cancer (NSCLC). This study seeks to investigate the potential of an optimized treatment regimen in this context by combining these three drugs and evaluating both efficacy and safety outcomes.Patients and Methods: Between January 2020 and January 2022, we collected data from pre-treated advanced NSCLC patients who received a combination therapy of nab-ptx, anlotinib, and PD-1/L1 inhibitors as a second-line or later treatment. The primary endpoints for the study included the objective response rate (ORR), progression-free survival (PFS), disease control rate (DCR) and overall survival (OS), while adverse events (AEs) were also recorded.Results: Our findings revealed that the ORR of this regimen in pretreated NSCLC patients was 35.71%, with mean PFS of 5.0 months and mean OS of 10.0 months. Further analysis suggested correlations between the efficacy of the regimen and factors such as PD-L1 expression levels, the occurrence of certain types of adverse events, and the status of NK cell activity. Additionally, the tolerable toxicity profile of this regimen indicates its potential applicability in the treatment of pretreated advanced NSCLC.Conclusion: Our study displayed that triple-drug combination of nab-ptx, anlotinib and PD-1/L1 inhibitors showed promising efficiency and tolerated cytotoxicity in the 2nd or above line treatment of advanced NSCLC, indicating the potential of such regimen as an important option for second-line treatment of advanced NSCLC. However, due to limitations in patient numbers, its actual clinical value awaits further research confirmation.Keywords: nab-ptx, anlotinib, PD-1/L1, NSCLC, triple drug combination

Xiaobo Wang,1 Zongyao Chen,1 Jianing Tang,2,3 Jing Cao2,4– 6 1Department of General Surgery, the Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 2National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 3Department of Liver Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 4Multidisciplinary Breast Cancer Center, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 5Clinical Research Center for Breast Cancer in Hunan Province, Changsha, Hunan, People’s Republic of China; 6NHC Key Laboratory of Carcinogenesis (Central South University), Cancer Research Institute and School of Basic Medicine, Central South University, Changsha, People’s Republic of ChinaCorrespondence: Jing Cao, Email Jing.cao@csu.edu.cn; Jianing Tang, Email tangjn@csu.edu.cnBackground: Breast cancer is the leading cause of cancer-related death in women. Necroptosis, a form of programmed necrotic cell death, occurs in many solid tumors, including breast cancer, and influences anti-tumor immunity. The role of necroptosis in managing breast cancer recurrence remains unclear.Methods: Gene expression profiles and clinical data of breast cancer patients were obtained from the GEO (GSE20685, GSE21653, GSE25055) and TCGA databases. Data analysis and visualization were performed using R. Unsupervised Consensus Clustering and LASSO-COX regression stratified breast cancer patients. GO, KEGG, GSVA, ESTIMATE, and ROC analyses were used to investigate necroptotic signatures. In vitro and in vivo experiments validated necroptosis’s role in breast cancer immunity.Results: The potential function of necroptotic signature in immunity was first indicated with GO analysis in BRCA cohort. Next, two prognostic models based on the necroptotic profiles both suggested a link between low-risk group with a particular necroptotic immune signature. And a variety of immune cells and immune pathways were shown to be positively associated with a patient’s risk score. As an altered immune checkpoint pattern was observed after regulating necroptotic genes, where TIM-3 and LAGLS9 elevated significantly in low-risk group, further validation in vitro and in vivo demonstrated that manipulating a subset of necroptotic gene set could sensitize tumor response to the co-blockade immunotherapy of anti-TIM-3 and anti-PD-1.Conclusion: We demonstrated two strategies to stratify breast cancer patients based on their necroptotic profiles and showed that necroptotic signature could assign patients with different tumor immune microenvironment patterns and different recurrence-related prognosis. A subset of necroptotic gene set, composed of TLR3, RIPK3, NLRP3, CASP1, ALDH2 and EZH2, was identified as a biomarker set for predicting immunotherapy-response and recurrence-related prognosis. Targeting necroptosis could helpfacilitate the development of novel breast cancer treatments and tailor personalized medical treatment.Keywords: breast cancer, recurrence, necroptosis, tumor immune microenvironment

Sha-Sha Tao,1– 3,&ast; Fan Cao,4,&ast; Ruo-Di Zhang,1,2,&ast; Shu-Zhen Xu,1,2 Xiao-Xiao Li,1,2 Jian Tang,1,2 Xiao-Ke Yang,5 Hai-Feng Pan1,2 1Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, Anhui, People’s Republic of China; 3Experimental Teaching Center for Preventive Medicine, School of Public Health, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 4Department of Ophthalmology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 5Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hai-Feng Pan, Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, People’s Republic of China, Email panhaifeng1982@sina.com; panhaifeng@ahmu.edu.cnBackground: Cytokines act a vital role in autoimmune neuroinflammatory diseases (ANDs) with undetermined causal relationships. Mendelian randomization (MR) analysis was performed to estimate the causal effects of circulating levels of cytokines on the risk of ANDs.Methods: The causal relationship between 34 circulating cytokines and 4 kinds of ANDs, including multiple sclerosis (MS), neuromyelitis optica (NOM), chronic inflammatory demyelinating polyneuropathy (CIDP) and myasthenia gravis (MG) were explored using four methods of MR analysis. MR-PRESSO, MR-Egger regression methods and Cochran’s Q statistic were utilized to identify the instrumental variables (IVs) with potential pleiotropy and heterogeneity. The Bonferroni correction was used for multiple group comparisons. P-value less than 3.68E-04 (0.05/ (34&ast;4)) was considered statistically significant.Results: Negative causal effects of circulating levels of interleukin (IL)-8 (OR = 0.648, 95% CI: 0.494-0.851, P = 0.002) on risk of MS, chemokine (C–C Motif) ligand (CCL)-5 (OR = 0.295, 95% CI: 0.103-0.841, P = 0.022) and stem cell growth factor-beta (SCGF-β) (OR = 0.745, 95% CI: 0.565-0.984, P = 0.038) on risk of CIDP, as well as positive causal effects of circulating levels of IL-2 receptor α (IL-2Rα) (OR = 1.216, 95% CI: 1.120-1.320, P = 3.20E-06) and chemokine C-X-C motif ligand (CXCL)-10 (OR = 1.404, 95% CI: 1.094-1.803, P = 0.008) on MS were observed. Nevertheless, only IL-2Rα still had a causal effect on MS after Bonferroni correction.Conclusion: The results identify a genetically predicted causal effect of IL-2Rα, IL-8 and CXCL-10 on MS, CCL-5 and SCGF-β on CIDP.Keywords: cytokines, autoimmune neuroinflammatory diseases, ANDs, causal relationship, Mendelian randomization

Xianmin Zhu,1 Shuang Dong,1 Jing Tang,1 Rong Xie,1 Huijing Wu,1 Jun Guan,2 Sheng Hu1 1Department of Medical Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Hematology, Wuhan NO.1 Hospital, Wuhan, People’s Republic of ChinaCorrespondence: Sheng Hu, Department of Medical Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, 116 South Road, Wuhan, 430079, People’s Republic of China, Email ehusmn@163.comAbstract: In recent years, there have been limited reports on the efficacy of later-line anti-programmed cell death − 1 (PD-1) therapy in achieving prolonged and complete remission in patients with hepatocellular carcinoma (HCC). Tislelizumab, a humanized anti-PD-1 monoclonal IgG4 antibody, has shown promising results in the treatment of HCC. This report highlights the case of a patient with HCC who experienced the development of lung metastatic lesions following HCC resection and chemotherapy, but achieved a prolonged complete response (CR) after receiving tislelizumab treatment. In April 2017, a 56-year-old male diagnosed with primary HCC underwent hepatectomy and hepatic arterial infusion pump placement. Following the surgery, the patient received adjuvant hepatic arterial infusion chemotherapy (HAIC) with 4 cycles of cisplatin+5-fluorouracil (PF) regimen starting in June 2017. In May 2018, lung metastatic lesions were detected, and the patient underwent 4 cycles of oxaliplatin+leucovorin+5-fluorouracil (FOLFOX) chemotherapy. However, the disease progressed in August 2018, leading to the administration of arsenic trioxide treatment. Despite this, further progression was observed in October 2018, prompting the patient’s enrollment in a clinical trial for tislelizumab therapy. Initially, the patient achieved a partial response (PR) to tislelizumab, which was followed by a CR that lasted for almost 4 years. Unfortunately, tislelizumab treatment had to be discontinued due to immune-related adverse events (AE). Subsequently, the patient received lenvatinib and maintained a CR until July 2023. Tislelizumab monotherapy, when used as a third-line treatment, has demonstrated remarkable efficacy in facilitating patients with advanced HCC to attain a durable CR.Keywords: hepatocellular carcinoma, complete response, immune checkpoint inhibitor, tislelizumab, chemotherapy failure, metastasis

Jianing Tang,1,2,&ast; Yuexin Luo,1,2,&ast; Qirui Wang,1,2 Juntao Wu,1,2 Yulong Wei1 1Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2First Clinic School, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yulong Wei, Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, People’s Republic of China, Email yulongwei_HUST@163.comAbstract: As a major cause of low back pain, intervertebral disc degeneration is an increasingly prevalent chronic disease worldwide that leads to huge annual financial losses. The intervertebral disc consists of the inner nucleus pulposus, outer annulus fibrosus, and sandwiched cartilage endplates. All these factors collectively participate in maintaining the structure and physiological functions of the disc. During the unavoidable degeneration stage, the degenerated discs are surrounded by a harsh microenvironment characterized by acidic, oxidative, inflammatory, and chaotic cytokine expression. Loss of stem cell markers, imbalance of the extracellular matrix, increase in inflammation, sensory hyperinnervation, and vascularization have been considered as the reasons for the progression of intervertebral disc degeneration. The current treatment approaches include conservative therapy and surgery, both of which have drawbacks. Novel stimuli-responsive delivery systems are more promising future therapeutic options than traditional treatments. By combining bioactive agents with specially designed hydrogels, scaffolds, microspheres, and nanoparticles, novel stimuli-responsive delivery systems can realize the targeted and sustained release of drugs, which can both reduce systematic adverse effects and maximize therapeutic efficacy. Trigger factors are categorized into internal (pH, reactive oxygen species, enzymes, etc.) and external stimuli (photo, ultrasound, magnetic, etc.) based on their intrinsic properties. This review systematically summarizes novel stimuli-responsive delivery systems for intervertebral disc degeneration, shedding new light on intervertebral disc therapy.Keywords: stimulus response, delivery system, intervertebral disc degeneration, biomaterial

Jiao Zhang,1,2 Yi Yin,3,4 Jiliang Tang,5 Yingrong Zhang,1,2 Yanan Tian,1,2 Fengkai Sun1,2,6 1Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 2Department of Gastroenterology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 3Department of Paediatrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 4Department of Paediatrics, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 5Emergency Department, Rizhao Central Hospital, Rizhao, People’s Republic of China; 6College of Acupuncture and Massage, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of ChinaCorrespondence: Fengkai Sun, Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jingwu Road 324&num;, Jinan, 250021, People’s Republic of China, Tel +86-531-68776902, Fax +86-531-68776072, Email sunfengkai2016@126.com; sunfengkai@sdfmu.edu.cnBackground: Effective biomarkers are needed to predict the efficacy of immune checkpoint inhibitors (ICIs) therapy in hepatocellular carcinoma (HCC). We evaluated the early changes in serum interleukin-8 (IL-8) levels as a biomarker of response to ICIs in patients with unresectable HCC.Methods: Eighty patients who received ICIs therapy alone or in combination with other treatments for unresectable HCC were included. Serum was collected at baseline and 2– 4 weeks after the first dose. Serum IL-8 levels were measured using by ELISA.Results: In the progressive disease (PD) group, serum IL-8 levels increased significantly before the second dose of ICIs therapy compared with baseline levels (P < 0.001). Early changes in serum IL-8 levels were significantly associated with the response to ICIs therapy (P < 0.001). A cutoff value of 8.1% increase over the baseline most effectively predicted the response to ICIs. Increases in serum IL-8 levels > 8.1% indicated the uselessness of ICIs immunotherapy in patients with unresectable HCC. Patients with increases in serum IL-8 levels > 8.1% had significantly shorter overall survival (OS) and progression-free survival (PFS) than those with increases in serum IL-8 levels ≤ 8.1% (P < 0.001). Increases in serum IL-8 levels > 8.1% were independent prognosticators of worse OS (P = 0.003) and PFS (P < 0.001).Conclusion: Early changes in serum IL-8 levels, measured only 2– 4 weeks after starting therapy, could predict the response to ICIs therapy, as well as OS and PFS of patients with unresectable HCC. Increases in serum IL-8 levels > 8.1% indicated the uselessness of ICIs immunotherapy and predicted worse OS and PFS.Keywords: interleukin-8, immune checkpoint inhibitor, response, serum biomarker, hepatocellular carcinoma

Boyong Wang,1,&ast; Qiaojie Wang,1,&ast; Mingzhang Li,1 Jinlong Yu,1 Feng Jiang,1 Yujie Hu,1 Geyong Guo,1 Xiaohua Chen,2 Jin Tang,3 Pei Han,1 Hao Shen1 1Department of Orthopedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, People’s Republic of China; 2Department of Infectious Diseases, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, People’s Republic of China; 3Clinical Laboratory, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Shen, Department of Orthopedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, People’s Republic of China, Email shenhao7212@sina.comObjective: The diagnosis of tubercular orthopedic implant-associated infection (TB-IAI) is challenging. This study evaluated the value of metagenomic next-generation sequencing (mNGS) for the diagnosis of TB-IAI and developed a standardized diagnostic procedure for TB-IAI.Methods: The records of all patients with TB-IAI diagnosed and treated at our institution between December 2018 and September 2022 were retrospectively reviewed. Patient demographic characteristics, medical history, laboratory test, microbial culture, histopathology, and mNGS results, and time to diagnosis were recorded. The diagnostic efficiency of mNGS for TB-IAI was assessed by comparing the results and diagnostic time with that of other diagnostic modalities.Results: Ten patients were included in the analysis, including eight with prosthetic joint infections and two with fracture-related infections. The mNGS positivity rate was 100% (10/10), which was higher than that of TB-antibody (11%, 1/9), real-time quantitative polymerase chain reaction (22%, 2/9), T-SPOT.TB (25%, 2/8), purified protein derivative (50%, 4/8), microbial culture (50%, 5/10), and histopathology (20%, 2/10). mNGS shortened the time to diagnosis of TB-IAI. A standardized diagnostic procedure for TB-IAI was developed based on the findings.Conclusion: mNGS is useful for the diagnosis of TB-IAI. mNGS is recommended in cases where it is difficult to identify a pathogen using routine diagnostic tests. The standardized diagnostic procedure might improve TB-IAI diagnosis.Importance: TB-IAI is a rare infection, which occurs after orthopedic surgery and hard to diagnose microbiologically. mNGS is a new detection technique not yet discussed in current literature as a means for TB-IAI diagnostics. Here we describe a cohort of patients with TB-IAI diagnosed by mNGS show high efficiency of mNGS for detection of this pathology and present a clinical algorithm supplementing conventional methods for TB-IAI assessment.Keywords: metagenomic next-generation sequencing, implant-associated infection, Mycobacterium tuberculosis complex, orthopedic infection, diagnosis

Chang Su,1– 3 Zeyu Wang,4 Zhen Qin,1– 3 Yan Lv,1– 3 Yachen Hou,1– 3 Ge Zhang,1– 3 Mengdie Cheng,1– 3 Xinyue Cui,1– 3 Zhiyu Liu,1– 3 Pengchong Du,1– 3 Tianding Liu,1– 3 Peiyu Yuan,1– 3 Junnan Tang,1– 3 Jinying Zhang1– 3 1Department of Cardiology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Key Laboratory of Cardiac Injury and Repair of Henan Province, Zhengzhou, Henan, People’s Republic of China; 3Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan, People’s Republic of China; 4Department of Cardiology, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Junnan Tang; Jinying Zhang, Department of Cardiology, First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jianshe Road, Zhengzhou, Henan, 450052, People’s Republic of China, Tel +86 15890696166 ; +86 13503830283, Email fcctangjn@zzu.edu.cn; jyzhang@zzu.edu.cnBackground: The triglyceride-glucose (TYG) index is a novel and reliable marker reflecting insulin resistance. Its predictive ability for cardiovascular disease onset and prognosis has been confirmed. However, for advanced chronic heart failure (acHF) patients, the prognostic value of TYG is challenged due to the often accompanying renal dysfunction (RD). Therefore, this study focuses on patients with aHF accompanied by RD to investigate the predictive value of the TYG index for their prognosis.Methods and Results: 717 acHF with RD patients were included. The acHF diagnosis was based on the 2021 ESC criteria for acHF. RD was defined as the eGFR < 90 mL/(min/1.73 m2). Patients were divided into two groups based on their TYG index values. The primary endpoint was major adverse cardiovascular events (MACEs), and the secondary endpoints is all-cause mortality (ACM). The follow-up duration was 21.58 (17.98– 25.39) months. The optimal cutoff values for predicting MACEs and ACM were determined using ROC curves. Hazard factors for MACEs and ACM were revealed through univariate and multivariate COX regression analyses. According to the univariate COX regression analysis, high TyG index was identified as a risk factor for MACEs (hazard ratio = 5.198; 95% confidence interval [CI], 3.702– 7.298; P < 0.001) and ACM (hazard ratio = 4.461; 95% CI, 2.962– 6.718; P < 0.001). The multivariate COX regression analysis showed that patients in the high TyG group experienced 440.2% MACEs risk increase (95% CI, 3.771– 7.739; P < 0.001) and 406.2% ACM risk increase (95% CI, 3.268– 7.839; P < 0.001). Kaplan-Meier survival analysis revealed that patients with high TyG index levels had an elevated risk of experiencing MACEs and ACM within 30 months.Conclusion: This study found that patients with high TYG index had an increased risk of MACEs and ACM, and the TYG index can serve as an independent predictor for prognosis.Keywords: TyG index, advanced chronic heart failure, renal dysfunction, prognosis factor

Wanqi Gong,1 Jiamei Tang,1 Yang Chen,2 Jing Ma3 1School of Journalism and Communication, Guangdong University of Foreign Studies, Guangzhou, People’s Republic of China; 2Health Science Center, Jinan University, Guangzhou, People’s Republic of China; 3The First Affiliated Hospital of Guangzhou Medical University, Department of Gynecology and Obstetrics, Guangzhou, People’s Republic of ChinaCorrespondence: Jiamei Tang, School of Journalism and Communication, Guangdong University of Foreign Studies, No. 1689 Bai Yun Avenue, Guangzhou, 510420, People’s Republic of China, Tel +86 20 39328095, Email tangjiamei@gdufs.edu.cnPurpose: Clinical nursing in obstetrics and gynecology is a technically demanding job. Doctors and nurses have different professional backgrounds and work priorities, and there are differences in communication modes, which can easily lead to poor communication between medical staff and their patients. Therefore this study aims to examine the different communication roles and emphases of obstetrician and gynecologists, nurses and midwives in different sections of SEGUE framework, and further navigate the effectiveness and differences of offline and online provider-patient communication.Participants and Methods: This study employs in-depth interviews to address the research questions. A total of 24 health care providers, including 8 doctors, 5 midwives and 11 nurses, were interviewed face-to-face or by telephone.Results: Doctors pay more attention to the “giving information” stage, while nurses pay more attention to “set the stage” and “elicit information” steps. Midwives and nurses spend more time with patients before and after labor. In addition to information giving, they also accommodate the “understand the patient’s perspective” and “end the encounter” steps. Nurses and midwives would attach greater importance to “understanding of patients’ perspective”. Online medical consultation is more convenient for patients, which can be used as a follow-up complement to offline medical consultation.Conclusion: The health care providers of different types in obstetrics and gynecology communicate collaboratively with patients, highlighting the equally important role of midwives and nurses when communicating with patients. Nurses focus on “set the stage” and “elicit information” stage. Midwife is another important information source and medical care provider, especially for pregnant women in stable conditions. Nutrition clinic of midwife could be recommended for hospitals in second- and third-tier cities, which could help to alleviate obstetricians’ workload. The provision of an online collaborative consultation could be beneficial supplement after face-to-face doctor-patient communication.Keywords: SEGUE framework, physician-patient communication, obstetrician and gynecologist, online health consultation, midwife

Ying Chen,1,2,&ast; Wen-Xia Li,1,2,&ast; Jia-Hua Wu,1,2 Geng-Hang Chen,2 Chun-Min Yang,1,2 Hai Lu,1,2 Xi Wang,3 Shu-Sen Wang,4 Heng Huang,5 Li Cai,6 Li Zhao,7 Rou-Jun Peng,8 Ying Lin,9 Jun Tang,3 Jian Zeng,10 Le-Hong Zhang,11 Yong-Li Ke,12 Xian-Ming Wang,13 Xin-Mei Liu,14 An-Qin Zhang,15 Fei Xu,4 Xi-Wen Bi,4 Jia-Jia Huang,4 Ji-Bin Li,16 Dan-Mei Pang,17 Cong Xue,4 Yan-Xia Shi,4 Zhen-Yu He,18 Huan-Xin Lin,18 Xin An,4 Wen Xia,4 Ye Cao,16 Ying Guo,16 Ruo-Xi Hong,4 Kui-Kui Jiang,4 Yong-Yi Zhong,4 Ge Zhang,19 Piyawan Tienchaiananda,20 Masahiro Oikawa,21 Zhong-Yu Yuan,4 Qian-Jun Chen22,23 1Department of Breast Surgery, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, People’s Republic of China; 2Department of Breast Surgery, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 3Department of Breast Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 4Department of Medical Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 5Department of Breast Oncology, Lianjiang People’s Hospital, Lianjiang, People’s Republic of China; 6Department of Medical Oncology, The Affiliated Tumour Hospital of Harbin Medical University, Harbin, People’s Republic of China; 7Department of Breast Oncology, Guangzhou First People Hospital, Guangzhou, People’s Republic of China; 8Department of Integrated Therapy in Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 9Department of Breast Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 10Department of Breast Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 11Department of Breast Oncology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 12Department of Breast Oncology, General Hospital of PLA Guangzhou Military Area, Guangzhou, People’s Republic of China; 13Department of Breast Oncology, Shenzhen Second People’s Hospital, Shenzhen, People’s Republic of China; 14Department of Breast Oncology, Haikou People’s Hospital, Haikou, People’s Republic of China; 15Department of Breast Oncology, Maternal and Child Health Care Hospital of Guangdong Province, Guangzhou, People’s Republic of China; 16Department of Good Clinical Practice, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 17Department of Medical Oncology, Foshan First People’s Hospital, Foshan, People’s Republic of China; 18Department of Radiotherapy, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 19Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases (TMBJ), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong; 20Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Rangsit University, Rajavithi Hospital, Bangkok, Thailand; 21The Department of Breast Surgery, New-wa-kai Oikawa Hospital, Fukuoka, Japan; 22State Key Laboratory of Traditional Chinese Medicine Syndrome/Departments of Gynecologic Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 23State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qian-Jun Chen, 55N, Neihuanxi Road, Guangzhou, Guangdong, 510006, People’s Republic of China, Tel +86 1868883505, Email cqj55@163.com Zhong-Yu Yuan, 651 Dongfeng Road, Guangzhou, Guangdong, 510060, People’s Republic of China, Tel +86 13798027658, Email yuanzhy@sysucc.org.cnPurpose: Results from studies of extended capecitabine after the standard adjuvant chemotherapy in early stage triple-negative breast cancer (TNBC) were inconsistent, and only low-dose capecitabine from the SYSUCC-001 trial improved disease-free survival (DFS). Adjustment of the conventional adjuvant chemotherapy doses affect the prognosis and may affect the efficacy of subsequent treatments. This study investigated whether the survival benefit of the SYSUCC-001 trial was affected by dose adjustment of the standard adjuvant chemotherapy or not.Patients and Methods: We reviewed the adjuvant chemotherapy regimens before the extended capecitabine in the SYSUCC-001 trial. Patients were classified into “consistent” (standard acceptable dose) and “inconsistent” (doses lower than acceptable dose) dose based on the minimum acceptable dose range in the landmark clinical trials. Cox proportional hazards model was used to investigate the impact of dose on the survival outcomes.Results: All 434 patients in SYSUCC-001 trial were enrolled in this study. Most of patients administered the anthracycline-taxane regimen accounted for 88.94%. Among patients in the “inconsistent” dose, 60.8% and 47% received lower doses of anthracycline and taxane separately. In the observation group, the “inconsistent” dose of anthracycline and taxane did not affect DFS compared with the “consistent” dose. Moreover, in the capecitabine group, the “inconsistent” anthracycline dose did not affect DFS compared with the “consistent” dose. However, patients with “consistent” taxane doses benefited significantly from extended capecitabine (P=0.014). The sufficient dose of adjuvant taxane had a positive effect of extended capecitabine (hazard ratio [HR] 2.04; 95% confidence interval [CI] 1.02 to 4.06).Conclusion: This study found the dose reduction of adjuvant taxane might negatively impact the efficacy of capecitabine. Therefore, the reduction of anthracycline dose over paclitaxel should be given priority during conventional adjuvant chemotherapy, if patients need dose reduction and plan for extended capecitabine.Keywords: adjuvant chemotherapy, capecitabine, SYSUCC-001, triple-negative breast cancer, TNBC

Tao Wen,1,&ast; Xuan Liu,2,&ast; Tao Pang,1,&ast; Mingming Li,1 Guangyang Jiao,3 Xiangcheng Fan,1 Jigui Tang,4 Ci’an Zhang,4 Zhipeng Wang,1 Xiaoqiang Yue,4,&ast; Wansheng Chen,1,3,5 Feng Zhang1,5 1Department of Pharmacy, Changzheng Hospital, Naval Medical University, Shanghai, People’s Republic of China; 2Oncology-Department, Shanghai Guanghua Hospital of Integrative Medicine, Shanghai, People’s Republic of China; 3The SATCM Key Laboratory for New Resources & Quality Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Department of Traditional Chinese Medicine, Changzheng Hospital, Naval Medical University, Shanghai, People’s Republic of China; 5Shanghai Key Laboratory for Pharmaceutical Metabolite Research, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Zhang; Wansheng Chen, Changzheng Hospital, Naval Medical University, No. 415, Fengyang Road, Shanghai, 200003, People’s Republic of China, Email fengzhang@smmu.edu.cn; chenwansheng@smmu.edu.cnPurpose: The aim of this study was to verify the effectiveness and explore the mechanism of Chaihu-Guizhi-Ganjiang decoction (CGGD) in the treatment of chronic non-atrophic gastritis (CNAG) with gallbladder heat and spleen cold syndrome (GHSC) by metabolomics based on UHPLC-Q-TOF/MS.Patients and Methods: An observational controlled before-after study was conducted to verify the effectiveness of CGGD in the treatment of CNAG with GHSC from January to June 2023, enrolling 27 patients, who took CGGD for 28 days. 30 healthy volunteers were enrolled as the controls. The efficacy was evaluated by comparing the traditional Chinese medicine (TCM) syndrome and CNAG scores, and clinical parameters before and after treatment. The plasma levels of hormones related to gastrointestinal function were collected by ELISA. The mechanisms of CGGD in the treatment of CNAG with GHSC were explored using a metabolomic approach based on UHPLC-Q-TOF/MS.Results: Patients treated with CGGD experienced a statistically significant improvement in TCM syndrome and CNAG scores (p < 0.01). CGGD treatment evoked the concentration alteration of 15 biomarkers, which were enriched in the glycerophospholipid metabolism, and branched-chain amino acids biosynthesis pathways. Moreover, CGGD treatment attenuated the abnormalities of the gastrointestinal hormone levels and significantly increased the pepsinogen level.Conclusion: It was the first time that this clinical trial presented detailed data on the clinical parameters that demonstrated the effectiveness of CGGD in the treatment of CNAG with GHSC patients. This study also provided supportive evidence that CNAG with GHSC patients were associated with disturbed branched-chain amino acid metabolism and glycerophospholipid levels, suggesting that CNAG treatment based on TCM syndrome scores was reasonable and also provided a potential pharmacological mechanism of action of CGGD. Keywords: traditional Chinese medicine, chronic gastritis, metabolomics, branched-chain amino acid, glycerophospholipid

Jun Feng, Liya Zhang, Jihong Tang, Bingbing Zhang, Xiao Xiao, Xiaoyan Shi Department of Neurology, Children’s Hospital of Soochow University, Suzhou, Jiangsu, 215025, People’s Republic of ChinaCorrespondence: Liya Zhang; Jihong Tang, Email zhliyasz@163.com; tjhsuzhou@163.comObjective: To evaluate the efficacy and safety of lacosamide (LCM) monotherapy in the treatment of self-limited epilepsy with centrotemporal spikes (SeLECTS).Methods: In this study, 89 children with SeLECTS who were treated with LCM monotherapy in the Children’s Hospital Affiliated to Soochow University from June 2019 to June 2021 were included. Clinical seizures and spike wave index (SWI) on video EEG during slow-wave sleep were evaluated before and after treatment. The role of LCM monotherapy in improving SWI, controlling clinical seizures and improving cognition was analyzed, and corresponding adverse reactions were documented.Results: There were 52 males and 37 females in this group, with an average age of 7.6 ± 2.1 years. The total effective rate was 93.83% and at 18 months of treatment, the cumulative control rate was 85.19%, the retention rate was 91.01% and the effective rate in terms of EEG spike index was 72.92%, all of which showed a high rate; there was no statistically significant difference in intelligence quotient before and after treatment (P > 0.05). In addition, it was found in the study that the earlier the age of onset, the less obvious the improvement in SWI after LCM treatment; the lower the baseline seizure frequency, the more significant the improvement in SWI after LCM treatment.Conclusion: LCM monotherapy had curative effect and adverse reactions for SeLECTS, with no negative impact on cognition. These significant findings indicate that LCM is likely to become a widely prescribed ASM for the treatment of SeLECTS. Meanwhile, the onset age and baseline seizure frequency had certain value in judging prognosis and predicting curative effect.Keywords: lacosamide, epilepsy, self-limited epilepsy with centrotemporal spikes, efficacy, safety

Chunmei Yang,1,2 Tingwan Du,1 Yueying Zhao,1 Youhui Qian,1 Jiashi Tang,1 Xiaohong Li,2,&ast; Ling Ma1,3,&ast; 1Department of Nutrition and Food Hygiene, School of Public Health, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Health Management Center, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 3Environmental Health Effects and Risk Assessment Key Laboratory of Luzhou, School of Public Health, Southwest Medical University, Luzhou, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaohong Li; Ling Ma, Email 1848922774@qq.com; xjml@swmu.edu.cnPurpose: To construct and validate a precise and personalized predictive model for non-alcoholic fatty liver disease (NAFLD) to enhance NAFLD screening and healthcare administration.Patients and Methods: A total of 730 participants’ clinical information and outcome measurements were gathered and randomly divided into training and validation sets in a ratio of 3:7. Using the least absolute shrinkage and selection operator (LASSO) regression and multiple logistic regression, a nomogram was established to select risk predictor variables. The NAFLD prediction model was validated through the receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis (DCA).Results: After random grouping, the cohort comprised 517 in the training set and 213 in the validation set. The prediction model employed nine of the 20 selected variables, namely gender, hypertension, waist circumference, body mass index, blood platelet, triglycerides, high-density lipoprotein cholesterol, plasma glucose, and alanine aminotransferase. ROC curve analysis yielded an area under the curve values of 0.877 (95% Confidence Interval [CI]: 0.848– 0.907) for the training set and 0.871 (95% CI: 0.825– 0.917) for the validation set. Optimal critical values were determined as 0.472 (0.786, 0.825) in the training set and 0.457 (0.743, 0.839) in the validation set. Calibration curves for both sets showed proximity to the ideal diagonal, with P-values of 0.972 and 0.370 for the training and validation sets, respectively (P > 0.05). DCA indicated favorable clinical applicability of the model.Conclusion: We constructed a nomogram model that could complement traditional NAFLD detection methods, aiding in individualized risk assessment for NAFLD.Keywords: non-alcoholic fatty liver disease, nomogram, prediction model, LASSO

Zhijian Wu,1– 3 Xiaotian Jin,1 Ilyas Tudahun,1 Shangjie Wu,2,3 Mingxian Chen,1 Jianjun Tang1 1Department of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, Changsha, 410011, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 3Hunan Centre for Evidence-Based Medicine, Changsha, 410011, People’s Republic of ChinaCorrespondence: Jianjun Tang; Mingxian Chen, Department of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, No. 139 Middle Renmin Road, Furong District, Changsha, Hunan, 410011, People’s Republic of China, Fax + 86 731 85533525, Email tom200210@csu.edu.cn; xymingxianchen@csu.edu.cnBackground and Aims: Whether IMH can directly cause persistent myocardial necrosis after reperfusion therapy in STEMI patients is still unclear. We conducted a prospective study to compare the cardiovascular parameters in patients with STEMI with and without IMH to explore the potential correlations between IMH and poor outcomes.Methods and Results: We prospectively enrolled 65 consecutive patients with newly diagnosed STEMI admitted to the CCU of the Second Xiangya Hospital of Central South University between April 2019 and November 2021, all of whom underwent primary PCI. Of these, 38 (58.5%) and 27 (41.5%) patients were in the IMH-absent and IMH-present groups, respectively. At a mean time of 5– 7 days after reperfusion therapy, the volume of MI measured using LGE sequence was larger in STEMI patients with IMH than in patients without IMH (34.2 ± 12.7 cm3 vs 21.1 ± 13.1 cm3, P< 0.001). HsTNT levels were significantly higher in the IMH-present group than in the IMH-absent [2500.0 (1681.5– 4307.0) pg/mL vs 1710.0 (203.0– 3363.5) pg/mL, P=0.021] group during hospitalization. The LVEF measured using CMR in the IMH-present group was lower than that in the IMH-absent group (30.7 ± 9.8% vs 42.3 ± 11.0%, P < 0.001). The rate of MACE at 12 months in IMH-present group was significantly higher than in the IMH-absent group (9/27 VS 2/38, P = 0.012).Conclusion: IMH can lead to further expansion of MI volumes in patients with STEMI, resulting in lower LVEF and higher MACE rate in the post-discharge follow-up.Keywords: myocardial infarction, cardiac magnetic resonance, intramyocardial hemorrhage, infarction volume, outcome

Yunhong Ren,1,&ast; Yinhao Guo,2,&ast; Jing Tang,2 Ling He,1 Meiling Li,1 Xuemei Huang,1 Qin Lu,1 Baoxia Sun,1 Haixia Feng,1 Huan Liu,1 Juan Du,1 Jun Li1 1Mianyang Key Laboratory of Anesthesia and Neuroregulation, Department of Anesthesiology, Mianyang Central Hospital, Mianyang, Sichuan, 621000, People’s Republic of China; 2Department of Anesthesiology, North Sichuan Medical College, Nanchong, Sichuan, 637000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Li; Juan Du, Mianyang Key Laboratory of Anesthesia and Neuroregulation, Department of Anesthesiology, Mianyang Central Hospital, Mianyang, Sichuan, People’s Republic of China, Email lj89199@163.com; 1151941061@qq.comPurpose: This study aimed to investigate the effects of different psychological personalities and pain catastrophizing levels on postoperative analgesia in patients undergoing cesarean section.Patients and Methods: Puerperas who underwent cesarean section at our hospital between January and August 2023 were recruited into the study and assessed using the Eysenck Personality Questionnaire-Revised Short Scale (EPQRSC) and Pain Catastrophizing Scale (PCS). Data on the numerical pain intensity at rest and during activity 24 h after surgery, number and dosage of analgesia pumps, and satisfaction with analgesia were recorded. According to the numerical pain score during activity 24 h post-operation, the patients were divided into the analgesia incomplete group (≥ 4) and control group (< 4). Univariate analysis, Spearman correlation analysis, and binary logistic regression analysis were used to evaluate the influence of personality characteristics and PCS on postoperative analgesia.Results: A total of 778 women were included in the study. The incidence of inadequate analgesia was 89.8%. The satisfaction rate of analgesia was 66.8%. Univariate analysis showed that extraversion; neuroticism; PCS; numbers of previous cesarean delivery; ASA; analgesic satisfaction; and 24-h analgesia pump compressions and dosage were associated with postoperative analgesia after cesarean section (P< 0.05). Using binary logistic regression analysis, the first cesarean section (odds ratio [OR]=0.056, 95% confidence interval [CI]=1.913– 19.174), the number of 24-h analgesic pump compressions (OR=8.464, 95% CI=0.356– 0.604), extraversion (OR=0.667, 95% CI=0.513– 0.866), neuroticism (OR=1.427, 95% CI=1.104– 1.844), and PCS (OR=7.718, 95% CI=0.657– 0.783) were factors affecting postoperative analgesia.Conclusion: The incidence of inadequate analgesia after a cesarean section was high (89.8% on the first day after surgery). Formulating accurate analgesia programs for women undergoing cesarean section with extraversion, neuroticism personality characteristics, and pain catastrophizing behaviors is necessary for improving their postoperative analgesia effects and satisfaction and promoting postpartum comfort.Keywords: aftercare, anesthetics, breast feeding, fear, personal satisfaction, postpartum depression

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

Pingping Yao,1 Yuying Jia,1 Xuewei Kan,1 Jiaqi Chen,1 Jinliang Xu,1 Huichao Xu,1 Shuyang Shao,1 Bing Ni,2 Jun Tang1 1Department of Dermatology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230000, People’s Republic of China; 2Department of Pathophysiology, Third Military Medical University, Chongqing, 400038, People’s Republic of ChinaCorrespondence: Bing Ni; Jun Tang, Email nibing@tmmu.edu.cn; tangjun0212@ustc.edu.cnBackground: Psoriasis is a common chronic, recurrent, and inflammatory skin disease. Identifying novel and potential biomarkers is valuable in the treatment and diagnosis of psoriasis. The goal of this study was to identify novel key biomarkers of psoriasis and analyze the potential underlying mechanisms.Methods: Psoriasis-related datasets were downloaded from the Gene Expression Omnibus database to screen differential genes in the datasets. Functional and pathway enrichment analyses were performed on the differentially expressed genes (DEGs). Candidate biomarkers for psoriasis were identified from the GSE30999 and GSE6710 datasets using four machine learning algorithms, namely, random forest (RF), least absolute shrinkage and selection operator (LASSO) logistic regression, weighted gene co-expression network analysis (WGCNA), and support vector machine recursive feature elimination (SVM-RFE), and were validated using the GSE41662 dataset. Next, we used CIBERSORT and single-cell RNA analysis to explore the relationship between ADAM23 and immune cells. Finally, we validated the expression of the identified biomarkers expressions in human and mouse experiments.Results: A total of 709 overlapping DEGs were identified, including 426 upregulated and 283 downregulated genes. Enhanced by enrichment analysis, the differentially expressed genes (DEGs) were spatially arranged in relation to immune cell involvement, immune-activating processes, and inflammatory signals. Based on the enrichment analysis, the DEGs were mapped to immune cell involvement, immune-activating processes, and inflammatory signals. Four machine learning strategies and single-cell RNA sequencing analysis showed that ADAM23, a disintegrin and metalloprotease, may be a unique, critical biomarker with high diagnostic accuracy for psoriasis. Based on CIBERSORT analysis, ADAM23 was found to be associated with a variety of immune cells, such as macrophages and mast cells, and it was upregulated in the macrophages of psoriatic lesions in patients and mice.Conclusion: ADAM23 may be a potential biomarker in the diagnosis of psoriasis and may contribute to the pathogenesis by regulating immunological activity in psoriatic lesions.Keywords: psoriasis, machine learning, differential gene analysis, CIBERSORT, ADAM23

Yuteng Ma,1 Zhe Wang,2 Jian Sun,1 Jingtong Tang,1 Jianping Zhou,1 Ming Dong1 1Department of Gastrointestinal Surgery, First Hospital of China Medical University, Shenyang, 110001, People’s Republic of China; 2Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, 110001, People’s Republic of ChinaCorrespondence: Ming Dong, Email dongming@cmu.edu.cnPurpose: Colon cancer is one of the leading causes of death worldwide, and screening of effective molecular markers for the diagnosis is prioritised for prevention and treatment. This study aimed to investigate the diagnostic and predictive potential of genes related to the lipid metabolism pathway, regulated by a protein called sterol-regulatory element-binding transcription Factor 2 (SREBF2), for colon cancer and patient outcomes.Methods: We used machine-learning algorithms to identify key genes associated with SREBF2 in colon cancer based on a public database. A nomogram was created to assess the diagnostic value of these genes and validated in the Cancer Genome Atlas. We also analysed the relationship between these genes and the immune microenvironment of colon tumours, as well as the correlation between gene expression and clinicopathological characteristics and prognosis in the China Medical University (CMU) clinical cohort.Results: Three genes, 7-dehydrocholesterol reductase (DHCR7), hydroxysteroid 11-beta dehydrogenase 2 (HSD11B2), and Ral guanine nucleotide dissociation stimulator-like 1 (RGL1), were identified as hub genes related to SREBF2 and colon cancer. Using the TCGA dataset, receiver operating characteristic curve analysis showed the area under the curve values of 0.943, 0.976, and 0.868 for DHCR7, HSD11B2, and RGL1, respectively. In the CMU cohort, SREBF2 and DHCR7 expression levels were correlated with TNM stage and tumour invasion depth (P < 0.05), and high DHCR7 expression was related to poor prognosis of colon cancer (P < 0.05). Furthermore, DHCR7 gene expression was positively correlated with the abundance of M0 and M1 macrophages and inversely correlated with the abundance of M2 macrophages, suggesting that the immune microenvironment may play a role in colon cancer surveillance. There was a correlation between SREBF2 and DHCR7 expression across cancers in the TCGA database.Conclusion: This study highlights the potential of DHCR7 as a diagnostic marker and therapeutic target for colon cancer.Keywords: colon cancer, sterol-regulatory element-binding transcription Factor 2, SREBF2, 7-dehydrocholesterol reductase, DHCR7, diagnosis, machine learning

Zixuan Wang,1 Yuanchen Lu,1 Li Li,2 Xiaoting Wu,2 Junliang Liu,2 Jie Tang,3 Wei Wang,3 Lili Lu2 1First Medical College, Xuzhou Medical University, Xuzhou, People’s Republic of China; 2Department of Gastroenterology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China; 3School of Public Health, Xuzhou Medical University, Xuzhou, People’s Republic of ChinaCorrespondence: Wei Wang, School of Public Health, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China, Tel +86-15152118260, Email weiwang90@163.com Lili Lu, Department of Gastroenterology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China, Tel +86-15905204534, Email lulili1990@163.comPurpose: Anxiety, as an important public health issue, may frequently trouble the chronic GI patients with severe symptoms. In this study, we aimed to investigate the relationship between the severity of GI symptoms and anxiety symptoms and further examine whether this relationship was mediated through illness perception.Patients and Methods: A total of 295 patients with chronic GI disease from the affiliated hospital of Xuzhou Medical University were enrolled in this cross-sectional study. They were interviewed with self-reported questionnaires containing demographic variables, clinical variables, and several self-rating scales. Multivariable linear regression models were established to explore the relationship between the severity of GI symptoms and anxiety symptoms. Finally, we performed the mediation analysis to test the mediating effect of illness perception.Results: After adjustments for key demographic and clinical covariates, the severity of GI symptoms was positively associated with anxiety symptoms (β=0.214, 95% CI: 0.009– 0.028, P < 0.001). Additionally, the results of the mediation analysis suggested that illness perception partially mediated the association between the severity of GI symptoms and anxiety symptoms with a mediating ratio of 25.3%.Conclusion: Our findings indicated that chronic GI patients with more severe GI symptoms were more likely to have anxiety symptoms and this effect is partially mediated by illness perception. Therefore, illness perception is recommended to be integrated into the routine assessment of chronic GI patients, and perception-based interventions may be beneficial in relieving anxiety symptoms among patients with severe chronic GI diseases.Keywords: illness perception, anxiety symptoms, severity of GI symptoms, chronic GI diseases, mediating effect

Li Huang,1– 3,&ast; Jingyang Tang,1– 3,&ast; Gang Tian,1– 3 Hualin Tao,1– 3 Zhaoyinqian Li1– 3 1Department of Laboratory Medicine, the Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 2Sichuan Province Engineering Technology Research Center of Molecular Diagnosis of Clinical Diseases, Luzhou, People’s Republic of China; 3Molecular Diagnosis of Clinical Diseases Key Laboratory of Luzhou, Luzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhaoyinqian Li, Department of Laboratory Medicine, the Affiliated Hospital of Southwest Medical University, No. 25, Taiping Street, Jiangyang District, Luzhou, Sichuan, 646000, People’s Republic of China, Tel/Fax +86 08303165731, Email lizhaoyinqian@swmu.edu.cnPurpose: Acinetobacter baumannii has evolved to become a major pathogen of nosocomial infections, resulting in increased morbidity and mortality. This study aimed to investigate the risk factors, outcomes, and predictions of extensively drug-resistant (XDR)-A. baumannii nosocomial infections in patients with nervous system diseases (NSDs).Methods: A retrospective study of patients infected with XDR-A. baumannii admitted to the Affiliated Hospital of Southwest Medical University (Luzhou, China) from January 2021 to December 2022 was conducted. Three multivariate regression models were used to assess the risk factors and predictive value for specific diagnostic and prognostic subgroups.Results: A total of 190 patients were included, of which 84 were diagnosed with NSDs and 80% of those were due to stroke. The overall rates of all-cause mortality for XDR-A. baumannii nosocomial infections and those in NSDs were 38.9% and 40.5%, respectively. Firstly, hypertension, indwelling gastric tube, tracheotomy, deep puncture, bladder irrigation, and pulmonary infections were independent risk factors for XDR-A. baumannii nosocomial infections in patients with NSDs. Moreover, pulmonary infections, the aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio, and the neutrophil-to-lymphocyte ratio (NLR) were significantly associated with increased mortality rates in patients with nosocomial infections caused by XDR-A. baumannii. Thirdly, NLR and cardiovascular diseases accounted for a high risk of mortality for XDR-A. baumannii nosocomial infections in patients with NSDs. The area under the curves of results from each multivariate regression model were 0.827, 0.811, and 0.853, respectively.Conclusion: This study reveals the risk factors of XDR-A. baumannii nosocomial infections in patients with NSDs, and proves their reliable predictive value. Early recognition of patients at high risk, sterilizing medical tools, and regular blood monitoring are all critical aspects for minimizing the nosocomial spread and mortality of A. baumannii infections.Keywords: risk factors, mortality, prediction, extensively drug-resistant Acinetobacter baumannii, nosocomial infection, nervous system diseases

Zhaoyinqian Li,1– 3,&ast; Tingting Li,1– 4,&ast; Jingyang Tang,1– 3 Li Huang,1– 3 Yinhuan Ding,1– 3 Zhangrui Zeng,1– 3 Jinbo Liu1– 3 1Department of Laboratory Medicine, the Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 2Sichuan Province Engineering Technology Research Center of Molecular Diagnosis of Clinical Diseases, Luzhou, People’s Republic of China; 3Molecular Diagnosis of Clinical Diseases Key Laboratory of Luzhou, Luzhou, People’s Republic of China; 4Department of Laboratory Medicine, West China Fourth Hospital, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinbo Liu, Department of Laboratory Medicine, the Affiliated Hospital of Southwest Medical University, No. 25, Taiping Street, Jiangyang District, Luzhou, Sichuan, 646000, People’s Republic of China, Tel/Fax +86 08303165730, Email liujb7203@swmu.edu.cnIntroduction: The prevalence of diabetic foot ulcers (DFUs) is increasing, leading to a huge financial burden and human suffering. Furthermore, antibiotic resistance is an urgent problem in the realm of clinical practice. Antimicrobial peptides are an effective and feasible strategy for combating infections caused by drug-resistant bacteria. Therefore, we investigated the in vitro antimicrobial ability of the lipopeptide surfactin, either alone or in combination with conventional antibiotics, against the standard and clinical strains of Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), isolated from patients with DFUs.Methods: The minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of surfactin on the selected strains were evaluated by a microbroth dilution technique. The growth curves of the selected strains with and without surfactin were measured, and transmission electron microscopy was used to observe the structure of surfactin-treated bacterial cells. The biofilm inhibitory abilities of surfactin were assessed by crystal violet staining. The antimicrobial interactions between surfactin and conventional antibiotics were established using a checkerboard assay, as well as determining the mutant prevention concentration. The inhibitory effect of surfactin on penicillinase was tested by iodometry.Results: The MIC and MBC values of surfactin ranged from 512 to 1024 μg/mL and 1024 to 2048 μg/mL, respectively. Moreover, surfactin significantly prevented the S. aureus biofilm formation and displayed limited toxicity on human red blood cells. The synergies between surfactin and ampicillin, oxacillin, and tetracycline against S. aureus were revealed. In vitro resistance was not readily produced by surfactin. The action of surfactin may be by disrupting bacterial cell membranes and inhibiting penicillinase.Conclusion: Surfactin appears to be a potential option for the treatment of DFUs infected with MRSA, as it is capable of improving antimicrobial activities and can be used alone or in combination with conventional antibiotics to prevent or postpone the emergence of resistance.Keywords: surfactin, antimicrobial peptides, diabetic foot ulcers, methicillin-resistant Staphylococcus aureus, synergistic effect

Yu Mao,1 Yuan Xie,1 Jiani Tang,1 Yujing Shen,2 Yang Liu,1 Bing Sun1 1Department of Cardiology, Tongji Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Department of Echocardiography, Tongji Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Bing Sun, Department of Cardiology, Tongji Hospital, Tongji University School of Medicine, No. 389, Xincun Road, Putuo District, Shanghai, 200065, People’s Republic of China, Tel +86 21-66111048, Email woowoocncn@163.comPurpose: The purpose of this study was to assess the left ventricular function effects of permanent left bundle branch pacing (LBBP) versus traditional right ventricular pacing (RVP).Patients and Methods: Consecutive patients receiving pacemaker implantation were included and divided into left bundle branch block (LBBB) group and right ventricular pacing (RVP) group. Baseline characteristics were collected, and they received 1-year follow-up. Electrocardiogram (ECG) characteristics and pacing parameters were assessed before and after implantation. Cardiac function parameters such as left ventricular ejection fraction (LVEF) and tricuspid regurgitation (TR) were recorded and compared.Results: Of 78 patients included, 45 patients received LBBP (mean age, 72.7 ± 12.2 years; male, 55.6%) and 33 patients underwent RVP (mean age 72.9 ± 11.8 years; male, 63.6%). The pacing parameters were satisfactory during the implantation and remained stable during mid-term follow-up. During the follow-up period, LBBP patients had a greater decrease in LVEDD and LVESD. The TR in the LBBP group was significantly improved as compared to the RVP group (P=0.016).Conclusion: Permanent LBBP achieves favorable cardiac hemodynamic effects with good stability and safety. LBBP may reduce severe TR at 1-year follow-up, and LBBP may be an option for patients with severe TR.Keywords: left bundle branch pacing, electrical synchrony, mechanical synchrony, left ventricular function, tricuspid regurgitation

Yan Zhou,1,2,&ast; Zekun Zhou,3,&ast; Xiaojuan Wu,2 Zefeng Wang,2 Wangdan Qi,1 Jing Yang,1 Liming Qing,3 Juyu Tang,3 Le Deng1 1State Key Laboratory of Developmental Biology of Freshwater Fish, Department of Microbiology, College of Life Science, Hunan Normal University, Changsha, Hunan, People’s Republic of China; 2State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Hunan University, Key Laboratory for Bio-Nanotechnology and Molecule Engineering of Hunan Province, Changsha, Hunan, People’s Republic of China; 3Department of Orthopedics, Hand and Microsurgery, Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Le Deng, State Key Laboratory of Developmental Biology of Freshwater Fish, Department of Microbiology, College of Life Science, Hunan Normal University, Changsha, Hunan, People’s Republic of China, Email dengle@hunnu.edu.cn Juyu Tang, Department of Orthopedics, Hand and Microsurgery, Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China, Email tangjuyu@csu.edu.cnPurpose: We aimed to develop an oxidative-stress-activated palladium-copper nanozyme to reduce bacterial’s heat sensitivity by down-regulating heat shock proteins to overcome the shortcomings of conventional photothermal antimicrobial therapy and achieve mild photothermal bactericidal efficacy.Methods: We first synthesized palladium-copper nanozymes (PC-NPs) by hydration and used transmission electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy to demonstrate their successful preparation. Their photothermal therapy (PTT) and chemo-dynamic therapy (CDT) activities were then determined by a series of photothermal performance tests and peroxidase-like performance tests, and the destruction of heat shock proteins by reactive oxygen species (ROS) was verified at the protein level by Western Blotting tests, providing a basis for the effective bacteria-killing by the mild-temperature photothermal treatment subsequently applied. We also validated this promising programmed and controlled antimicrobial treatment with palladium-copper nanozymes by in vivo/in vitro antimicrobial assays. A hemolysis assay, MTT cytotoxicity test and histopathological analysis were also performed to assess the in vivo safety of PC-NPs.Results: In the micro-acidic environment of bacterial infection, PC-NPs showed peroxidase-like activity that broke down the H2O2 at the wound into hydroxyl radicals and down-regulated bacterial heat shock proteins. The application of PC-NPs increased bacteria’s sensitivity to subsequent photothermal treatment, enabling the elimination of bacteria via mild photothermal treatment.Conclusion: The programmed synergistic catalytic enhancement of CDT and mild photothermal therapy achieves the most efficient killing of bacteria and their biofilms, which brings future thinking in the relationship between heat shock proteins and oxidative stress damage in bacteria.Keywords: nanozyme, mild-temperature photothermal therapy, DnaK, reactive oxygen species, ROS, antibiofilm

Jinrong Tang,1 Sheng Li,1 Manli Zhang,1 Fengzhi Li,1 Ying Tang,2 Fangfang Yang3 1Department of Clinical Laboratory, Mianyang Hospital of Traditional Chinese Medicine/Mianyang Hospital Affiliated to Chengdu University of Traditional Chinese Medicine, Mianyang, Sichuan, 621000, People’s Republic of China; 2Youxian District Center for Disease Control and Prevention of Mianyang City, Mianyang, Sichuan, 621000, People’s Republic of China; 3Department of Clinical Laboratory, The Third Hospital of Mianyang (Sichuan Mental Health Center), Mianyang, Sichuan, 621000, People’s Republic of ChinaCorrespondence: Fangfang Yang, Department of Clinical Laboratory, The Third Hospital of Mianyang (Sichuan Mental Health Center), Mianyang, Sichuan, 621000, People’s Republic of China, Tel +86-19817592909, Email yhge2159@163.comAbstract: Non-O1, non-O139 Vibrio cholerae (NOVC) can cause cholera-like diarrhea, but it rarely causes extraintestinal infection, so it is easily overlooked. In this report, we present a case of NOVC detected through blood culture in a 58-year-old male patient with cirrhosis, resulting in severe infection. The patient had been diagnosed with cirrhosis seven years prior and was admitted to the hospital due to abdominal distension and gastrointestinal bleeding. Gram-negative bacilli were isolated from blood cultures and identified as V. cholerae using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and average nucleotide identity (ANI). Moreover, the serum agglutination test showed that the strain was non-O1/non-O139. Further whole genome sequencing and analysis of the strain showed that the strain mainly carried virulence genes tox R, RTX, hly A, T3SS/T6SS, but no resistant genes such as sulII, dfrA1, strB were detected. It provides information for the study of the pathogenic mechanism and drug resistance mechanism of V. cholerae. The patient had severe symptoms and a poor prognosis, indicating that although the NOVC strain infected in this patient had few virulence genes, it was not weak in pathogenicity. It may be caused by the effect of some virulence genes, which should be paid attention to.Keywords: non-O1/non-O139 Vibrio cholerae, whole genome analysis, cirrhosis, virulence factors

Xin Qiao,1– 3,&ast; Jie Tang,1– 3,&ast; Lei Dou,1– 3 Shiyao Yang,1,3,4 Yuting Sun,1,3,4 Hongchen Mao,1– 3 Deqin Yang1– 3 1Department of Endodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, 401147, People’s Republic of China; 2Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, 401147, People’s Republic of China; 3Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 401147, People’s Republic of China; 4Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, 401147, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Deqin Yang, Department of Endodontics, Stomatological Hospital of Chongqing Medical University, No. 426, Songshi North Road, Yubei District, Chongqing, People’s Republic of China, Tel +86-23-8886-0060, Email yangdeqin@hospital.cqmu.edu.cnPurpose: Dental pulp stem cell-derived exosomes (DPSC-EXO), which have biological characteristics similar to those of metrocytes, have been found to be closely associated with tissue regeneration. Periodontitis is an immune inflammation and tissue destructive disease caused by plaque, resulting in alveolar bone loss and periodontal epithelial destruction. It is not clear whether DPSC-EXO can be used as an effective therapy for periodontal regeneration. The purpose of this study was not only to verify the effect of DPSC-EXO on reducing periodontitis and promoting periodontal tissue regeneration, but also to reveal the possible mechanism.Methods: DPSC-EXO was isolated by ultracentrifugation. Then it characterized by transmission electron microscope (TEM), nanoparticle tracking analysis (NTA) and Western Blot. In vitro, periodontal ligament stem cells (PDLSCs) were treated with DPSC-EXO, the abilities of cell proliferation, migration and osteogenic potential were evaluated. Furthermore, we detected the expression of IL-1β, TNF-αand key proteins in the IL-6/JAK2/STAT3 signaling pathway after simulating the inflammatory environment by LPS. In addition, the effect of DPSC-EXO on the polarization phenotype of macrophages was detected. In vivo, the experimental periodontitis in rats was established and treated with DPSC-EXO or PBS. After 4 weeks, the maxillae were collected and detected by micro-CT and histological staining.Results: DPSC-EXO promoted the proliferation, migration and osteogenesis of PDLSCs in vitro. DPSC-EXO also regulated inflammation by inhibiting the IL-6/JAK2/STAT3 signaling pathway during acute inflammatory stress. In addition, the results showed that DPSC-EXO could polarize macrophages from the M1 phenotype to the M2 phenotype. In vivo, we found that DPSC-EXO could effectively reduce alveolar bone loss and promote the healing of the periodontal epithelium in rats with experimental periodontitis.Conclusion: DPSC-EXO plays an important role in inhibiting periodontitis and promoting tissue regeneration. This study provides a promising acellular therapy for periodontitis.Keywords: exosome, anti-inflammatory, osteogenesis, periodontitis, macrophages, IL-6/JAK2/STAT3 signaling pathway

Shaodan Zhou,1 Yishuang Wen,1 Chao Liu,1 Jian Zhong,1 Manli Liang,1 Yu Wu,2 Sirao Lv,1 Zhuowei Gong,1 Dayuan Lao,1 Taiyan Li,1 Ting Lu,1 Jingqun Tang,1 Xuean Mo,1 Wen Huang1 1Department of Neurology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2University of Pittsburgh School of Medicine, Pittsburgh, PA, USACorrespondence: Wen Huang, Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi, 530021, People’s Republic of China, Tel +86-771-5356504, Fax +86-771-5350031, Email hwen1229@163.comPurpose: With the adjustment of prevention strategies in December 2022, coronavirus disease 2019 (COVID-19) became widely prevalent in China. This study is aimed to describe the clinical characteristics of myasthenia gravis (MG) patients with COVID-19 and identify risk factors of exacerbation in MG patients with COVID-19 in Guangxi.Patients and Methods: A total of 489 MG patients and 587 control subjects in Guangxi during the COVID-19 pandemic were enrolled in this case–control study. After contacting the participants, the clinical data of MG patients and the control group were analyzed. The clinical characteristics of MG patients with COVID-19 were described. Multivariable logistic regression analysis was used for discovering independent risk factors of MG exacerbation in the patients with MG and COVID-19.Results: A total of 311 (75.30%) MG patients and 428 (72.91%) control subjects were infected with COVID-19, and 64.31% of MG patients with COVID-19 were women. The median age at the time of interview was 41 (IQR: 28, 54) years old, and median onset age was 36 (IQR: 24, 51), both of which were lower than those in MG patients without COVID-19. MG duration was 24 (IQR: 9, 72) months. About 44.69% of patients were generalized MG (GMG). About 11.90% of MG patients with COVID-19 showed severe COVID-19 symptoms and the duration of symptomatic COVID-19 was 9.57 ± 6.79 days, higher than those in the control group. About 35.69% MG patients with immunosuppressive drugs were infected with COVID-19, which is higher than those in the non-infected MG patients (21.57%). A total of 120 (38.59%) MG patients with COVID-19 had comorbidities. About 21 (20.19%) of the 104 MG patients without vaccination showed severe COVID-19 symptoms. Multivariable logistic regression analysis showed that baseline MG activities of daily living profile (MG-ADL, OR 1.280, 95% CI: 1.010– 1.621, p = 0.041), duration of COVID-19 (OR 1.158, 95% CI: 1.100– 1.220, p < 0.001), GMG (OR 2.331, 95% CI: 1.228, 4.426, p = 0.010), and lack of COVID vaccination (OR 2.075, 95% CI: 1.152, 3.738, p = 0.015) were independent factors of exacerbation in MG patients with COVID-19.Conclusion: MG patients with immunosuppressive drugs, younger onset, longer MG duration, or comorbidities are more susceptible to COVID-19. The baseline MG-ADL, duration of symptomatic COVID-19, GMG, and lack of COVID-19 vaccination are independent risk factors of exacerbation in MG patients with COVID-19.Keywords: myasthenia gravis, COVID-19, exacerbation, vaccination, clinical characteristics

Jia Tang, Tiantian Song, Ming Kuang, Yiping Feng, Guangrong Liu, Hongying Liu Hangzhou Kang Ming Information Technology Co., Ltd, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Hongying Liu, Hangzhou Kang Ming Information Technology Co., Ltd, 401 Building 4, Haichuang Park (across from Taobao City) 998 Wenyi West Road, Yuhang District, Hangzhou, Zhejiang Province, 310000, People’s Republic of China, Tel +86 021 64045531, Email hongyingliu@91jkys.comAbstract: The COVID-19 pandemic is a huge public health crisis in the 21st century. In addition to the acute symptoms, a considerable proportion of patients worldwide have suffered from post-COVID-19 syndrome, commonly known as Long COVID. The impact of Long COVID on individual and public health burden cannot be ignored. According to recent researches, Long COVID has been affecting multiple organ systems throughout the body, with respiratory, mental, nervous and digestive symptoms often seen in Chinese population. Clinical studies have proved that symptoms were alleviated by a variety of treatments, such as physical therapy, rehabilitation training, psychological support, behavioral cognitive therapy, stem cell therapy, etc. Based on the current clinical evidence, it is recommended to strengthen the scientific research on Long COVID and actively carry out early monitoring and intervention in the future, so as to effectively prevent the long-term disease burden and economic pressure.Keywords: Long COVID, post-COVID conditions, China, clinical characteristics, management strategies

Xiaokang Cheng,1,2,&ast; Yuxuan Wu,1,&ast; Bin Chen,2 Jiagang Tang1 1Department of Orthopedics, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, People’s Republic of China; 2Department of Orthopedics, The Affiliated Hospital of Chengde Medical University, Chengde, 067000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiagang Tang, Email tangjiaguang2013@163.comPurpose: The purpose of this research was to compare the efficacy of unilateral biportal endoscopic decompression (UBE) and percutaneous transforaminal endoscopic decompression (PTED) in the treatment of elderly patients with single-level lumbar lateral recess stenosis (LRS).Materials and Methods: Data from January 2020 to March 2022 were analyzed. Thirty-eight patients in the PTED group and thirty-nine patients in the UBE group completed the minimum 12-month follow-up. The demographic data and perioperative outcomes were reviewed. Clinical outcomes were evaluated using the VAS for back and leg pain, the Oswestry Disability Index (ODI), and the modified MacNab criteria.Results: Both groups of patients completed surgery and a one-year follow-up. There was no significant difference between the two groups in demographics data. UBE has the advantage in operative duration and X-ray time; as far as incision length, blood loss, and drainage volume are concerned, PTED is advantageous. Under the modified MacNab criteria, UBE exhibited a good-to-excellent rate similar to that of PTED (84.6% vs 81.6%, P> 0.05). There were no significant differences at any point in time between UBE and PTED with respect to ODI, VAS, or back pain scores (P> 0.05). UBE and PTED did not differ significantly in terms of complications.Conclusion: Both PTED and UBE achieved favorable outcomes in single-level LRS. For operative time and X-ray times, UBE is more advantageous, while PTED offers better estimates of blood loss, incision length, and drainage volume.Keywords: lateral recess stenosis, unilateral biportal endoscopic decompression, percutaneous transforaminal endoscopic decompression, endoscopic, minimally invasive surgery

Jian Tang,1 Hong Yuan,2 Yun Long Wu,1 Shui Fu,3 Xiao Yong Pan4 1Department of Intensive Care, First People’s Hospital of Linping District, Hangzhou, Zhejiang Province, People’s Republic of China; 2Department of Cardiology, First People’s Hospital of Linping District, Hangzhou, Zhejiang Province, People’s Republic of China; 3Clinical Laboratory Department, First People’s Hospital of Linping District, Hangzhou, Zhejiang Province, People’s Republic of China; 4Clinical Laboratory Department, The People’s Hospital of Cangnan Zhejiang, Wenzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Xiao Yong Pan, Clinical Laboratory Department, The People’s Hospital of Cangnan Zhejiang, Wenzhou, Zhejiang Province, People’s Republic of China, Email pxy01234567892023@163.comObjective: To explore the serial measurement of heparin-binding protein and D-dimer in the prediction of 28-day mortality and efficacy evaluation of critically-ill patients with sepsis.Methods: We recruited a total of 51 patients with sepsis in the ICU of our hospital. They were divided into a survival group or a death group according to their prognosis 28 days after treatment. The HBP and D-dimer levels in these patients were determined on the 1st (24h), 3rd, and 5th days. Besides, the sequential organ failure assessment (SOFA) score of these patients was recorded at admission. The patients in both groups were subjected to comparison regarding HBP and D-dimer levels and SOFA scores within 24h of admission. Additionally, a correlation between the levels of HBP and D-dimer and the SOFA score was statistically measured, while the predictive effectiveness of these factors for the prognosis of patients with sepsis was also determined. Moreover, the dynamic changes in HBP and D-dimer during the treatment of both groups were analyzed.Results: The HBP and D-dimer levels and the SOFA scores in the survival group were considerably lower than those in the death group, and the differences were statistically significant (P< 0.05). Additionally, the levels of HBP and D-dimer in sepsis patients were positively correlated with the SOFA score (P< 0.05). The area under the curve (AUC) of HBP, D-dimer, and their combination in predicting the prognosis of patients with sepsis was 0.824, 0.771, and 0.830, respectively. Besides, the sensitivity and specificity of their combination in predicting the prognosis of patients with sepsis were 68.42% and 92.31%, respectively. The HBP and D-dimer levels presented a downward trend in the survival group during treatment, while they exhibited an upward trend in the death group.Conclusion: HBP and D-dimer realize high predictive effectiveness for the prognosis of patients with sepsis, while the combined use of these two factors achieves superior effectiveness. Thus, they can be applied to the prediction of 28-day mortality and efficacy evaluation of sepsis patients.Keywords: sepsis, heparin-binding protein, HBP, D-dimer, sequential organ failure assessment score, SOFA, prognosis

Yuting Liu,1,&ast; Jie Tang,1,&ast; Xiaolan Qiu,1,&ast; Lucy A Teng,2 Mukesh K Sriwastva,2 Xuedong Han,1 Zhi Li,1 Minmin Liu,1 Shuangyue Liu,1 Dongzhu Da,1 Zhi Li,1 Linlin Zhen,1 Yi Ren1 1Department of Breast and Thyroid Surgery, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huai’an, Jiangsu, People’s Republic of China; 2Brown Cancer Center, Department of Microbiology & Immunology, University of Louisville, Louisville, KY, USA&ast;These authors contributed equally to this workCorrespondence: Yi Ren; Linlin Zhen, Department of Breast and Thyroid Surgery, The Affiliated Huai’an No. 1 People’s Hospital, Nanjing Medical University, Huai’an, Jiangsu, People’s Republic of China, Email only_renyi@163.com; simu1027@sina.comBackground: Recent therapeutic approaches have improved survival rate for women with breast cancer, but the survival rate for metastatic breast cancer is still low. Exosomes released by various cells are involved in all steps of breast cancer development.Methods: We established the multimodal imaging report expression in breast cancer cells with lentivirus vectors pGluc and pBirA to investigate the secreted exosomes. Comparative microRNA (miRNA) analysis was performed with miRNA qPCR array in mice with breast cancer lung metastasis. The co-immunoprecipitation and chromatin immunoprecipitation assays were used to identify the mechanism of miRNA sorting to exosomes. The potential therapeutic strategy using an anti-sorting antibody was used to investigate breast cancer lung metastasis.Results: We identified 26 high- and 32 low-expression level miRNAs in exosomes from metastasis compared to those from primary tumors and normal tissues. The tumor suppressors, including miR-200c and let-7a, were reduced in tumor tissues and metastasis but increased in the respective exosomes compared to normal tissues. Furthermore, the Ras-related protein (Rab1A) facilitated miR-200c sorting to exosomes circumventing the influence of tumor suppressor miR-200c on tumor cells, while the metastatic exosome cargo miR-200c inhibited F4/80+ macrophage immune response. Administration of anti-Rab1A antibody significantly repressed the trafficking of miR-200c to exosomes and breast cancer lung metastasis.Conclusion: Our study has identified a novel molecular mechanism for breast cancer lung metastasis mediated by exosome cargo miRNAs and provided a new therapeutic strategy for cancer immunotherapy.Graphical Abstract: Keywords: extracellular vehicles, exosomes, breast cancer lung metastasis, miR-200c, Rab1A, miRNA sorting

Hao Zhang,1 Yingping Deng,1 Zeshi Li,2 Jing Tang1 1Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2West China Clinical Medical College, Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Jing Tang, Email tangjing0802@163.comAbstract: The SMILE lenticule is a complete corneal stroma that is removed from SMILE surgery. Since the increasing number of SMILE surgeries, a large number of SMILE lenticules have been produced, so the reuse and preservation of the stromal lens has become a research hotspot. Due to the rapid development of the preservation and clinical reuse of SMILE lenticules, there have been many related studies in recent years, so we updated it on this basis. We searched PubMed, Web of Science, Embase, Elsevier Science, CNKI, WANFANG Data and other databases for all articles published on the preservation and clinical reuse of SMILE lenticules, screened useful articles, selected relevant articles published in the last five years as the main body for summary, and then reached a conclusion. The existing preservation methods of SMILE lenticule include Moist chamber storage at low temperature, cryopreservation technique dehydrating agent and corneal storage medium, which have their own advantages and disadvantages. Presently, smile lenticules can be used for the treatment of corneal ulcers and perforations, corneal tissue defects, hyperopia, presbyopia and keratectasia, which have been proven to be relatively effective and safe. More research on smile lenticule reuse needs to be carried out to confirm its long-term efficacy.Keywords: SMILE lenticule, refractive surgery, preservation, clinical reuse

Zhangdi Xu,1– 3,&ast; Bihui Pan,1– 3,&ast; Yue Li,1– 3 Yi Xia,1– 3 Jinhua Liang,1– 3 Yilin Kong,1– 3 Xinyu Zhang,1– 3 Jing Tang,1– 3 Li Wang,1– 3 Jianyong Li,1– 3 Wei Xu,1– 3,&ast; Jiazhu Wu1– 3,&ast; 1Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, People’s Republic of China; 2Key Laboratory of Hematology of Nanjing Medical University, Nanjing, People’s Republic of China; 3Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiazhu Wu; Wei Xu, Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, People’s Republic of China, Tel +86-25-83781120, Fax +86-25-83781120, Email wujiazhu09@sina.com; xuwei10000@hotmail.comBackground: Chronic lymphocytic leukemia (CLL) is a subtype of B-cell malignancy with high heterogeneity. Ferroptosis is a novel cell death induced by iron and lipid peroxidation and exhibits prognostic value in many cancers. Emerging studies on long non-coding RNAs (lncRNAs) and ferroptosis reveal the unique value in tumorigenesis. However, the prognostic value of ferroptosis-related lncRNAs (FRLs) remains unclear in CLL.Aim: We aimed to construct a FRLs risk model to predict prognosis and improve prognostic stratification for clinical practice.Methods: RNA-sequencing data and clinical characteristics of CLL patients were downloaded from the GEO database. Based on ferroptosis-related genes from FerrDb database, differentially expressed FRLs with prognostic significance were identified and used to generate the risk model. The capability of the risk model was assessed and evaluated. GO and KEGG analyses were performed to confirm biological roles and potential pathways.Results: A novel ferroptosis-related lncRNAs prognostic score (FPS) model containing six FRLs (PRKCQ, TRG.AS1, LNC00467, LNC01096, PCAT6 and SBF2.AS1) was identified. Patients in the training and validation cohort were evenly divided into high- and low-risk groups. Our results indicated that patients in the high-risk group had worse survival than those in the low-risk group. Functional enrichment analyses showed that the differently expressed genes (DEGs) between the two groups were enriched in the chemokine signaling pathway, hematopoietic cell lineage, T cell differentiation, TCR pathway and NF-κB pathway. Moreover, significant differences in immune cell infiltration were also observed. Surprisingly, FPS was proved to be an independent prognostic indicator for OS.Conclusion: We established and evaluated a novel prognostic risk model with 6 FRLs that could predict prognosis accurately and describe the distinct immune infiltration in CLL.Keywords: chronic lymphocytic leukemia, ferroptosis, long non-coding RNAs, prognosis, immune infiltration

Yueyan Li,1 Chen Zhang,2 Xuan Huang,1 Jing Tang1 1Department of Pharmacy, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, People’s Republic of China; 2Institute of Reproduction and Development, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Jing Tang, Department of Pharmacy, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, People’s Republic of China, Tel +86 21 33180593, Fax +86 21 33180593, Email 1817@fckyy.org.cnPurpose: Antimicrobial agents are frequently prescribed during pregnancy. This study aims to explore the association between antimicrobial exposure and pregnancy outcomes.Patients and Methods: A multi-center retrospective cohort study of pregnant patients (n=370) was conducted in 22 tertiary hospitals in China. Adverse pregnancy outcomes and admission of neonate to neonatal intensive care unit (NICU) were considered as outcomes. The effect of antimicrobial exposure on pregnancy outcomes was assessed using a multivariate logistic regression model.Results: Use of first-generation cephalosporins during pregnancy was associated with a significantly higher risk of adverse pregnancy outcomes (odds ratio [OR]: 3.64 [95% confidence interval, CI: 1.43– 9.24], P = 0.007) and admission of neonate to the NICU (OR: 3.41, 95% CI: 1.37– 8.53, P=0.009) compared with use of third-generation cephalosporins, after adjusting for gestational age of exposure to antimicrobial agents, cesarean section, and antimicrobial dose. Similarly, a higher risk of adverse pregnancy outcomes (OR: 14.76, 95% CI: 4.43– 49.11) and neonatal NICU admission (OR: 11.74, 95% CI: 3.59– 38.35) were observed among women with first-generation cephalosporins use compared with mothers with no antimicrobial use.Conclusion: Both first- and third-generation cephalosporins use was associated with an increased risk of adverse pregnancy and neonatal outcomes. In addition, first-generation cephalosporins were associated with an increased risk of those pregnant and neonatal outcomes, when compared with third-generation cephalosporins. We should require to determine the indications and contraindications for use of cephalosporins during pregnancy.Keywords: maternal infections, antimicrobial agents, adverse pregnancy outcomes, NICU, cephalosporin

Hui Liu,1 Dongyan Wang,1 Jingnan Tang,1 Linlin Yu,2 Shanshan Su1 1Department of Nephrology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 2Department of Science and Technology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Shanshan Su, Department of Nephrology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China, Email sushan8223@163.comObjective: We investigate the relationship between the changes of serum 25-hydroxyvitamin D3 (25(OH)D3) and vasohibin-1 (VASH-1) and renal function injury in patients with type 2 diabetic nephropathy.Methods: In this study, 143 patients with diabetic nephropathy (DN) were selected as DN group, and 80 patients with type 2 diabetes mellitus were selected as T2DM group. The serum 25 (OH) D3, VASH-1, blood glucose index, inflammation index and renal function index were compared between the two groups. According to the urinary microalbumin/creatinine ratio (UACR), the DN group was divided into microalbuminuria group (UACR range≥ 30.0mg/g and < 300.0mg/g) and macroalbuminuria group (UACR≥ 300.0mg/g) for stratified comparison. The correlation between 25-hydroxyvitamin D3, VASH-1 and inflammation index and renal function index was analyzed by simple linear correlation analysis.Results: The level of 25 (OH) D3 in DN group was significantly lower than that in T2DM group (P< 0.05). The levels of VASH-1, CysC, BUN, Scr, 24h urine protein, serum CRP, TGF-β 1, TNF-α and IL-6 in DN group were higher than those in T2DM group (P< 0.05). The level of 25 (OH) D3 in DN patients with massive proteinuria was significantly lower than that in DN patients with microalbuminuria. The level of VASH-1 in DN patients with massive proteinuria was higher than that in DN patients with microalbuminuria (P< 0.05). There was a negative correlation between 25 (OH) D3 and CysC, BUN, Scr, 24h urine protein, CRP, TGF-β 1, TNF-α, IL-6 in patients with DN (P< 0.05). VASH-1 was positively correlated with Scr, 24h urinary protein, CRP, TGF-β 1, TNF-α and IL-6 in patients with DN (P< 0.05).Conclusion: The level of serum 25 (OH) D3 in DN patients was considerably decreased, and the level of VASH-1 was increased, which was related to the degree of renal function injury and inflammatory response.Keywords: 25 hydroxyvitamin D3, angiogenesis inhibitor protein 1, type 2 diabetes, diabetic nephropathy, renal function damage, inflammation indicators

Jialei Zhu,&ast; Jing Jin,&ast; Jing Tang Department of Pharmacy, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Tang, Department of Pharmacy, Obstetrics and Gynecology Hospital of Fudan University, 128 Shenyang Road, Yangpu District, Shanghai, 200090, People’s Republic of China, Tel +86-21-33189900, Email 1817@fckyy.org.cnAbstract: Previous studies have demonstrated that oxytocin was a viable therapy option for postpartum depression. However, the role remains controversial. To evaluate the efficacy of oxytocin on women postpartum depression, we searched PubMed, Web of Science, Cochrane Library, and EmBase for literatures from inception of the database to April 18th, 2022. Randomized controlled trials (RCTs) that investigated the effects of oxytocin on postpartum depression were selected for this study. Six RCTs (195 women) were gathered. The effects of oxytocin were roughly divided into emotion and cognition. The modulation of oxytocin to women’s emotion was demonstrated in four of the trials. The results were conflicting: One trial showed that oxytocin alleviated the depressive mood; two trials showed that oxytocin had no effect (but reduce negative thoughts in healthy mothers, or decrease the narcissistic trait); another trial showed that oxytocin aggravated depression. Women’s cognition was shown to be regulated by oxytocin in four of the trials. In general, oxytocin enhanced postpartum depressive women’s perception of their relationship with the infants. This systematic review showed that the effect of oxytocin on postpartum depression is still uncertain. We partly support that exogenous oxytocin might improve the cognition of women with postpartum depression to their infants, while the effect on emotion is still controversial. Further RCTs with larger samples and more diversified evaluation criteria are needed to better reveal its efficacy on postpartum depression.Keywords: oxytocin, postpartum depression, postnatal depression, systematic review, randomized controlled trial

Yueyan Li, Jialei Zhu, Jing Tang Department of Pharmacy, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200090, People’s Republic of ChinaCorrespondence: Jing Tang, Department of Pharmacy, Obstetrics and Gynecology hospital of Fudan University, 128 Shenyang Road, Yangpu District, Shanghai, 200090, People’s Republic of China, Tel/Fax +86 21 33180593, Email 1817@fckyy.org.cnBackground: Traditional medicine is a common treatment option for endometrioid-related symptoms. In the past few decades, Guixiong Xiaoyi formula has been widely used as a traditional medicine for the treatment of endometriosis.Purpose: This study aimed to prepare compound Angelica Ligusticum wallichii granule (CALG) by modern technological methods and to study its pharmacodynamics and mechanisms of treating endometriosis.Methods: The ingredients of CALG were determined by UPLC-Q-TOF/MS. Target prediction of compounds and diseases was performed using databases, and the mechanisms of CALG were predicted by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes and verified by molecular docking. Furthermore, a rat model of endometriosis was established to study the effects of CALG on endometriosis in vivo.Results: CALG with good specificity, durability, and stability was obtained following a detailed preparation process and quality control standard. Using network systems pharmacology, 109 chemical compositions and 104 core targets were identified for the treatment of endometriosis. The composition-target-channel-disease network topology analysis of the top 15 chemical compositions of CALG showed that the beneficial effect of CALG on endometriosis was attributed to phenolic compounds. In addition, CALG treatment reduced the volume of ectopic uterine lesions, promoted apoptosis, inhibited the secretion of inflammatory cytokines, and increased HIF-1 expression in rats with endometriosis.Conclusion: CALG induces apoptosis and inhibits inflammation and is a promising drug for the treatment of endometriosis.Graphical Abstract: Keywords: endometriosis, Angelica Ligusticum wallichii granule, network systems pharmacology, molecular docking, traditional Chinese medicine

Yujia Liu,1,2,&ast; Jingyun Tang,3,&ast; Yongchang Sun1 1Department of Respiratory and Critical Medicine, Peking University Third Hospital, Beijing, People’s Republic of China; 2Department of Respiratory and Critical Medicine, Peking University International Hospital, Beijing, People’s Republic of China; 3Blood Research Laboratory, Chengdu Blood Center, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongchang Sun, Department of Respiratory and Critical Medicine, Peking University Third Hospital, 49 North Garden Road, Haidian District Beijing, People’s Republic of China, Tel +86-010-82265020, Email suny@bjmu.edu.cnBackground: Both COPD and interstitial lung abnormalities (ILAs) are conditions associated with smoking and age. The impact of coexistent ILAs on the manifestations and outcomes of COPD or emphysema awaits evaluation.Methods: We searched PubMed and Embase using Medical Subject Headings terms in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Results: Eleven studies were included in the review. The sample size of the studies ranged from 30 to 9579. ILAs were reported in 6.5% to 25.7% of the patients with COPD/emphysema, higher than that reported in the general populations. COPD/emphysema patients with ILAs were older, mostly male, and had a higher smoking index than those without ILAs. Hospital admission and mortality were increased in COPD patients with ILAs compared to those without ILAs, whereas the frequency of COPD exacerbations was discrepant in 2 of the studies. The FEV1 and FEV1% predicted tended to be higher in the group with ILAs, but not significantly in most of the studies.Conclusion: ILAs were more frequent in subjects with COPD/emphysema than in the general population. ILAs may have a negative impact on hospital admission and mortality of COPD/emphysema. The impact of ILAs on lung functions and exacerbations of COPD/emphysema was discrepant in these studies. Further prospective studies are warranted to provide high-quality evidence of the association and interaction between COPD/emphysema and ILAs.Keywords: COPD, emphysema, interstitial lung abnormalities, review

Hui Li,1 Mingquan Huang,2 Yonglian Yang,3 Jun Tang,3 Yunli Ye1 1School of Public Health, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2Department of Breast Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 3School of Basic Medical Science, Southwest Medical University, Luzhou, Sichuan, People’s Republic of ChinaCorrespondence: Yunli Ye, Southwest Medical University, No. 1 Section 1, Xianglin Road, Longmatan District, Luzhou, Sichuan, People’s Republic of China, Tel/Fax +86 0813 3161797, Email yunliye072@swmu.edu.cnPurpose: To understand the practices and willingness of Chinese women to undergo opportunistic screening for breast cancer (BC) and cervical cancer (CC).Patients and Methods: From July to August 2021, a cross-sectional study of 1446 women from six cities in Sichuan Province, China, was conducted. A questionnaire was used to investigate practices, willingness, and barriers to opportunistic screening for BC and CC. Furthermore, potential factors for opportunistic screening willingness were analyzed using the chi-squared test and logistic regression.Results: During their lifetime, 312 (21.6%) and 388 (26.8%) women had undergone opportunistic screening for BC and CC, respectively. There were 1069 (73.9%) women willing to accept physician-recommended screening during a medical visit, while 835 (57.7%) were willing to have a voluntary screening at a healthcare institution. The main barriers to reluctance to participate in physician-recommended and voluntary screenings were “no symptoms; hence, no need for screening” and “unwillingness or difficulty in paying screening cost”. Ethnic minorities, lower education levels, and menopause were inversely associated, whereas awareness of the screening methods and eligibility for screening were positively associated with physician-recommended and voluntary screenings (P < 0.05). Furthermore, awareness of “two-cancers” screening was positively associated with physician-recommended screening (P < 0.05).Conclusion: BC and CC opportunistic screening rates in Sichuan Province were low. The willingness to undergo physician-recommended screening was high, while that towards individual initiative screening was low. Public health education should be strengthened to increase cancer prevention awareness and knowledge of cancer screening, especially for women with low education, ethnic minorities, and post-menopause, for whom tailored interventions are suggested. In addition, novel ways of sharing screening costs need to be explored.Keywords: physician-recommended screening, voluntary screening, “two-cancers” screening, behavior, willingness

Lijuan Liu,1,2,&ast; Wenzhuo Huang,1,2,&ast; Zhuoer Huang,1,3 Jiaxin Liu,1,3 Xiaoyuan Zheng,1 Jing Tang,1,2 Ying Wu,1 Xiaohui Wang,1 Yongzhen Liao,4 Li Cong1 1School of Medicine, Hunan Normal University, Changsha, People’s Republic of China; 2Teaching and Research Section of Clinical Nursing, Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 3Xiangya School of Nursing, Central South University, Changsha, People’s Republic of China; 4Shunde Polytechnic, Foshan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Cong, School of Medicine, Hunan Normal University, Changsha, People’s Republic of China, Tel/Fax +86-0731-88912446, Email congli@hunnu.edu.cnBackground: Oral anticoagulant is a necessary long-term treatment after mechanical valve replacement (MVR), and medication adherence has a great impact on patients with MVR. Although family caregiver burden is negatively correlated with medication adherence, little is known about the underlying mechanism.Purpose: To test whether family caregiver burden influences medication adherence through post-traumatic growth or medication literacy in patients with MVR.Patients and Methods: A total of 206 patients after MVR were included in this cross-sectional study from July 2021 to December 2021. Data regarding medication adherence, family caregiver burden, post-traumatic growth, and medication literacy were collected by questionnaires. Data were analyzed through SPSS, and pathway analysis was conducted by using AMOS, based on the bootstrapping method.Results: Post-traumatic growth was positively associated with medication adherence (r = 0.284, P < 0.05). Post-traumatic growth independently mediated the association of family caregiver burden on medication adherence [β = 0.32, 95% confidence intervals: (− 0.016, − 0.008)]. The mediated effect value for post-traumatic growth was 0.07, accounting for 24.14% of the total effect. The model’s fit indices were adequate.Conclusion: The mediating effect of post-traumatic growth between family caregiver burden and medication adherence existed in patients with MVR. Interventions considering post-traumatic growth may be useful to increase medication adherence and improve patient rehabilitation.Keywords: medication adherence, family caregiver burden, post-traumatic growth, medication literacy, mediation analyses, mechanical valve replacement

Cunqing Kong,1,&ast; Banghao Xu,2,&ast; Guanhua Qiu,1 Meng Wei,2 Mengqi Zhang,3 Shengxian Bao,1 Jiali Tang,1 Lequn Li,2 JunJie Liu1 1Department of Ultrasound, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China; 2Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China; 3Department of Interventional Therapy Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: JunJie Liu, Department of ultrasound, Affiliated Tumor Hospital of Guangxi Medical University, 71 Hedi Road, Nanning, 530021, People’s Republic of China, Email liujunjie@gxmu.edu.cn Lequn Li, Department of hepatobiliary surgery, Affiliated Tumor Hospital of Guangxi Medical University, 71 Hedi Road, Nanning, 530021, People’s Republic of China, Email li_lequn@263.netIntroduction: Photoimmunotherapy is a breakthrough treatment for malignant tumors. Its uniqueness is that it uses antibody mediated targeted delivery to achieve high tumor specificity and uses laser-activated biophysical mechanism to accurately induce the rapid death of cancer cells and avoid damaging the surrounding normal tissues.Methods: In this paper, an iron-based micelle was designed to encapsulate the photothermal agent indocyanine green (ICG) and a cyclic tripeptide of arginine-glycine-aspartic acid (cRGD) as targeted multifunctional ICG@SANPs-cRGD nanoparticles for combined photothermal/photodynamic/immune therapy of breast cancer.Results: The experimental results show that ICG@SANPs-cRGD nanoparticles have good biocompatibility and photothermal conversion ability. Photothermal therapy (PTT) and photodynamic therapy (PDT) based on ICG@SANPs-cRGD can not only inhibit the proliferation, invasion and migration of tumor cells, but also directly kill tumor cells by inducing apoptosis or necrosis. Dual-mode fluorescence light (FL) and magnetic resonance imaging (MRI) imaging in mice confirmed the selective accumulation at tumor sites and imaging ability of ICG@SANPs-cRGD. PTT/PDT combined with Anti-PD-L1 immunotherapy based on ICG@SANPs-cRGD mediated the immunogenic cell death (ICD) of tumor cells by regulating the expression of immune-related indicators and activated the body’s immune response mechanism, which enhanced the immunotherapy effect of immune checkpoint block (ICB). PTT/PDT combined with Anti-PD-L1 therapy not only prevented the progression of the primary tumor but also inhibited the distant metastasis of the tumor.Discussion: This study explores the biomedical application of PTT/PDT combined with Anti-PD-L1 based on ICG@SANPs-cRGD nanomaterials for breast cancer treatment and demonstrates the potential of ICG@SANPs-cRGD as a multifunctional therapeutic platform for future cancer therapy.Keywords: photodynamic therapy, photothermal therapy, immune checkpoint blocking, immune enhancement effect

Zhongbin Zhang,1,2,&ast; Jinqing Chen,1,&ast; Linghui Zou,1,&ast; Jing Tang,1 Jiaxin Zheng,1 Meijiao Luo,1 Gang Wang,1 Dan Liang,1,2 Yuyang Li,1 Ben Chen,1 Hongjun Yan,1 Wenya Ding1– 3 1Guangxi University of Chinese Medicine, Nanning, People’s Republic of China; 2Key Laboratory of Common Technology of Chinese Medicine Preparations, Guangxi University of Chinese Medicine, Nanning, People’s Republic of China; 3College of Veterinary Medicine, Northeast Agricultural University, Harbin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenya Ding, Guangxi University of Chinese Medicine, Nanning, People’s Republic of China, Tel +86-15045630868, Email DingWenYa666@163.comBackground and Purpose: Infections caused by Staphylococcus aureus (S. aureus) colonization in medical implants are resistant to antibiotics due to the formation of bacterial biofilm internal. Baicalein (BA) has been confirmed as an inhibitor of bacterial biofilm with less pronounced effects owing to its poor solubility and absorption. Studies have found that β-cyclodextrin-grafted chitosan (CD-CS) can improve drug efficiency as a drug carrier. Therefore, this research aims to prepare BA-loaded CD-CS nanoparticles (CD-CS-BA-NPs) for S. aureus biofilm elimination enhancement.Methods: CD-CS-BA-NPs were prepared via the ultrasonic method. The NPs were characterized using the X-ray diffraction (XRD), Thermo gravimetric analyzer (TGA), Transmission electron microscopy (TEM) and Malvern Instrument. The minimum inhibitory concentration (MIC) of the NPs were investigated. The biofilm models in vivo and in vitro were constructed to assess the S. aureus biofilm elimination ability of the NPs. The Confocal laser method (CLSM) and the Live/Dead kit were employed to explore the mechanism of the NPs in promoting biofilm elimination.Results: CD-CS-BA-NPs have an average particle size of 424.5 ± 5.16 nm, a PDI of 0.2 ± 0.02, and a Zeta potential of 46.13 ± 1.62 mV. TEM images revealed that the NPs were spherical with uniform distribution. XRD and TGA analysis verified the formation and the thermal stability of the NPs. The NPs with a MIC of 12.5 ug/mL exhibited a better elimination effect on S. aureus biofilm both in vivo and in vitro. The mechanism study demonstrated that the NPs may permeate into the biofilm more easily, thereby improving the biofilm elimination effect of BA.Conclusion: CD-CS-BA-NPs were successfully prepared with enhanced elimination of S. aureus biofilm, which may serve as a reference for future development of anti-biofilm agents.Graphical Abstract: Keywords: baicalein, β-cyclodextrin-grafted chitosan, nanoparticles, Staphylococcus aureus, biofilm elimination

Lixiang Wang, Yingping Deng, Ke Ma, Hongbo Yin, Chengshu Sun, Jing Tang Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of ChinaCorrespondence: Jing Tang, Department of Ophthalmology, West China Hospital of Sichuan University, No.37, Guoxue Alley, Sichuan, People’s Republic of China, Tel +86 18980603835, Email tangjing0802@163.comBackground: Corneal crosslinking is widely applied to enhance corneal biomechanical properties and delay the progression of keratoconus. The surgical procedure and application of ultraviolet A irradiation (UVA) during corneal crosslinking have been recognized to induce the reactivation of simplex herpes virus (HSV) but are rarely reported and poorly analyzed.Case Presentation: We report the first case series of herpetic keratitis in 4 keratoconus patients undertaking corneal crosslinking, who were all clinically diagnosed at routine follow-up visits 3 days to 1 month after the surgery. Different from the typical new onset of secondary herpetic keratitis that mainly presents with epithelial lesions and severe eye pain, these patients all presented with stromal infiltrates and were generally asymptomatic except for vision blurring in 2 patients. All patients responded well to antiviral therapy, topical steroids, and epithelial nourishment medication, leaving corneal macula or nebula at the last follow-up visit.Conclusion: Close follow-up is essential and the most effective way to diagnose herpetic keratitis after corneal crosslinking due to the lack of subjective symptoms. The prophylactic use of antiviral therapy on asymptomatic patients is controversial and should be evaluated based on long-term prognosis.Keywords: simplex herpes virus, herpetic keratitis, keratoconus, corneal crosslinking, prophylactic antiviral therapy

Yingna Chen,1 Jieya Lu,2 Zhihao Xie,1 Jialing Tang,1 Xuejiao Lian,1 Xiuwen Li1 1School of Pharmacy, School of Medicine, Changzhou University, Changzhou, Jiangsu, People’s Republic of China; 2Department of Nephrology, Yixing Hospital of Traditional Chinese Medicine, Yixing, Jiangsu, People’s Republic of ChinaCorrespondence: Yingna Chen, School of Pharmacy, School of Medicine, Changzhou University, No. 21, Lake Gehu Road, Wujin District, Changzhou, Jiangsu, People’s Republic of China, Tel +86-13813661630, Email chenyingna@cczu.edu.cn Jieya Lu, Department of Nephrology, Yixing Hospital of Traditional Chinese Medicine, 128 Yangquan East Road, Yicheng Street, Yixing, Jiangsu, People’s Republic of China, Tel +86-15906153777, Email ljy7011645@sina.comBackground: Tumor microenvironment has attracted more and more attention in oncology. Alisol B23 acetate (AB23A) inhibits the proliferation of tumor cells including non-small cell lung cancer (NSCLC) cells. However, whether AB23A plays a role in the tumor microenvironment of NSCLC still remains obscure.Methods: After THP-1 cells were polarized to M0 type by PMA, M0 macrophages were differentiated into M1 by LPS and IFNγ, and were differentiated into M2 by IL-4 and IL-13. The differentiation of THP-1 cells was detected by flow cytometry. After AB23A was given to macrophage RT-qPCR and ELISA detected the expressions of IL-6, IL-1β, IL-10 and TGF-β. Western blot and RT-qPCR detected the expressions of CD11b and CD18 at both mRNA and protein levels. Lung cancer cell A549 cells were induced by above related macrophage culture medium. Cell proliferation was detected by CCK-8. Tunel, wound healing and Transwell detected the apoptotic, migration and invasion capabilities. Next, M0 and M1-type macrophages were cultured in the cell culture medium of conventional A549 cells, to which AB23A was added. Subsequently, cell differentiation and inflammatory response were measured. Finally, the expression of CD18 in A549 cells was knocked down to construct NSCLC tumor-bearing mice and AB23A was applied for intragastric administration. Immunohistochemistry detected the polarization of macrophages in tumor tissues. Western blot detected the expressions of CD11b, CD18, invasion-, migration- and apoptosis-related proteins.Results: AB23A promoted the polarization of macrophages towards M1, thus promoting the apoptosis and inhibiting the invasion and migration of A549 cells. The tumor cell culture medium induced M0 macrophages to M2, while AB23A reversed this effect. AB23A targeted CD11b/CD18 and improved the polarization of macrophages, thereby affecting tumor invasion, migration and apoptosis.Conclusion: AB23A affected the polarization of tumor-associated macrophages through the targeted regulation of CD11b/CD18, thus inhibiting the development of lung cancer.Keywords: Alisol B23 acetate, lung cancer, CD11b/CD18, tumor microenvironment

Tingting Li,&ast; Zhaoyinqian Li,&ast; Li Huang, Jingyang Tang, Zixuan Ding, Zhangrui Zeng, Yao Liu, Jinbo Liu Department of Laboratory Medicine, the Affiliated Hospital of Southwest Medical University, Lu Zhou, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinbo Liu, Department of Laboratory Medicine, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China, Tel +86 08303165730, Email liujb7203@swmu.edu.cnObjective: Diabetic foot ulcers (DFUs) and ESKAPE pathogens have attracted attention globally, but the role of ESKAPE pathogens in diabetic foot infection is not well described. The purpose of this study was to evaluate the clinical features, antimicrobial resistance, and risk factors for ESKAPE infection in patients with DFUs.Methods: A retrospective study was conducted on 180 patients with diabetic foot infection admitted to The Affiliated Hospital of Southwest Medical University (Luzhou, China), from January 2017 to April 2021. Antimicrobial susceptibilities of all isolates were determined. Multivariate logistic regression analysis was performed to analyze the independent risk factors for ESKAPE infection, multidrug-resistant (MDR)-ESKAPE infection, MDR-pathogen infection, and severe group in patients with DFUs.Results: A total of 206 isolates were collected, of which 42.2% were ESKAPE pathogens. The independent risk factors for ESKAPE infection were cigarette smoking (OR = 1.958; 95% CI, 1.015– 3.777) and peripheral vascular disease (OR = 2.096; 95% CI, 1.100– 3.992), while alcohol consumption (OR = 2.172; 95% CI, 1.104– 4.272) was the independent risk factor for MDR-pathogen infection. Additionally, the independent risk factors for severe DFU group were invasive treatment (OR = 326.642; 95% CI, 76.644– 1392.08), the duration of systemic antibiotic treatment (OR = 0.918; 95% CI, 0.849– 0.992), and length of hospital stay (OR = 1.145; 95% CI, 1.043– 1.256). No independent risk factors for MDR-ESKAPE infection were found.Conclusion: Our data established the microbiological features of ESKAPE pathogens and clinical manifestations of diabetic foot infection, and provide support for monitoring and management of ESKAPE infection in patients with DFUs in southwest China.Keywords: diabetic foot ulcers, ESKAPE pathogens, infection, antimicrobial resistance, risk factors