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Yaonan Hong,1,2,* Qi Liu,1,2,* Chuanao Xin,1,2,* Huijin Hu,1,2 Zhenchao Zhuang,1– 3 Hangping Ge,1,2,4 Yingying Shen,1,2,4 Yuechao Zhao,1,2,4 Yuhong Zhou,1,2,4 Baodong Ye,1,2,4 Dijiong Wu1,2,4,5 1Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, People’s Republic of China; 2The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Clinical Laboratory, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 4National Traditional Chinese Medicine Clinical Research Base (Hematology), Hangzhou, Zhejiang, People’s Republic of China; 5Department of Oncology and Hematology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Zhejiang Chinese Medicine University, Wenzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dijiong Wu, Department of Hematology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, Zhejiang, 310006, People’s Republic of China, Tel +86-571-86620325, Email wudijiong@zcmu.edu.cnBackground: Limited data were available to understand the significance of ferroptosis in leukemia prognosis, regardless of the genomic background.Methods: RNA-seq data from 151 AML patients were analyzed from The Cancer Genome Atlas (TCGA) database, along with 70 healthy samples from the Genotype-Tissue Expression (GTEx) database. Ferroptosis-related genes (FRGs) features were constructed by multivariate COX regression analysis and risk scores were calculated for each sample and a novel prediction model was identified. The validation was carried out using data from 35 AML patients and 13 healthy controls in our cohort. Drug sensitivity analysis was conducted on various chemotherapeutic drugs.Results: A signature of 10 FRGs was identified, as prognostic predictors for AML, and the risk scores were calculated to constructed the prognostic features of FRGs. Significantly lower overall survival was observed in the high-risk group. The predictive ability of these features for AML prognosis was confirmed using Cox regression analysis, ROC curves, and DCA. The prediction model performed well in our clinical practices, and had its potential superiority when comparing to classical NCCN risk stratification. Multiple chemotherapy drugs, including paclitaxel, dactinomycin, cisplatin, etc. had a lower IC50 in FRGs high-risk group than low-risk group.Conclusion: The AML prognosis model based on FRGs accurately predicts AML prognosis and drug sensitivity, and the drugs identified worthy further investigation.Keywords: ferroptosis, prediction model, TCGA, acute myeloid leukemia, drug sensitivity

Mingqi Yang,1,2 Lian Bai,3 Yunju Ma,1,2 Xuanqi Cao,1,2 Qingya Cui,1,2 Depei Wu,1,2 Xiaowen Tang1,2 1National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People’s Republic of China; 3Canglang Hospital of Suzhou, Suzhou, People’s Republic of ChinaCorrespondence: Xiaowen Tang; Depei Wu, Department of Hematology, The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Suzhou, People’s Republic of China, Tel +8613913538266 ; +8613951102021, Email xwtang1020@163.com; drwudepei@163.comAbstract: Acute promyelocytic leukemia (APL) is characterized by a reciprocal translocation t (15;17) (q24;q21), which leads to the fusion of PML and RARα genes known as PML-RARα fusion. A few cases of potentially hereditary leukemia-related genes in APL have been reported, but no instances of familial aggregation of APL have been documented. Here, we describe a family in whom two members successively affected by APL。The potential familial association observed in these two cases of APL highlights the need for further investigation and more definitive genetic lineage tracing in order to understand the genetic basis of this disease.Keywords: familial, acute promyelocytic leukemia, APL differentiation syndrome, hereditary predisposition, germline mutation

Chuanyun Tang,1,* Kexun Zhou,2,* Di Wu,1,* Hong Zhu2 1The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of China; 2Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong Zhu, Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, No. 37, GuoXue Xiang, Chengdu, 610041, People’s Republic of China, Tel/Fax +86-28-85423262, Email zhuhong938@wchscu.cnAbstract: Cardiovascular disease (CVD) is a major global health issue with high mortality and morbidity rates. With the advances in nanotechnology, nanoparticles are receiving increasing attention in diagnosing and treating CVD. Previous studies have explored the use of nanoparticles in noninvasive diagnostic technologies, such as magnetic resonance imaging and computed tomography. Nanoparticles have been extensively studied as drug carriers and prognostic factors, demonstrating synergistic efficacy. This review summarized the current applications of nanoparticles in CVD and discussed their opportunities and challenges for further exploration.Keywords: nanoparticles, cardiovascular disease, diagnosis, therapy, nanoparticle functionalization

Xiawan Yang,1– 3,* Yingying Shen,1– 3,* Tonglin Hu,1– 3 Hangchao Li,1– 3 Yun Zhang,1– 3 Yiping Shen,1– 3 Dijiong Wu1– 4 1Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, People’s Republic of China; 2The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 3National Traditional Chinese Medicine Clinical Research Base (Hematology), Hangzhou, Zhejiang, People’s Republic of China; 4Department of Oncology and Hematology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Zhejiang Chinese Medicine University, Wenzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dijiong Wu; Yiping Shen, Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Youdian Road No. 54, Hangzhou, 310006, Zhejiang, People’s Republic of China, Tel +86-0571-86620325, Email wudijiong@zcmu.edu.cn; shenyp_@126.comBackground: Perianal infection has a high incidence and mortality rate in patients with acute myeloid leukemia (AML). Sometimes there is a lack of effective anti-infective treatment regimens.Case Presentation: A 58-year-old male diagnosed with AML presented with secondary perianal infection and septic shock upon admission. Although multiple pathogen cultivation and antibiotic sensitivity tests indicated the presence of sensitive strains, the corresponding antibiotics were ineffective. As a last resort, carrimycin was introduced, ultimately controlling the infection and leading to disease remission.Conclusion: Carrimycin is a complementary treatment option when conventional antibiotic therapy fails. It operates through multiple mechanisms beyond its antibiotic properties and warrants further investigation.Keywords: carrimycin, perianal infection, acute myeloid leukemia, immunomodulatory

Junqi Liao,1,&ast; Yuan Zhu,1,2,&ast; Aimei Zhang,1 Dan Wu,1 Xiaohui Yan,1 Qiuhua He,1 Fantao Song,1 Jingyi Chen,1 Yunze Li,1 Li Li,1 Zhaoyao Chen,1 Wenlei Li,1 Qin Yang,2 Zhuyuan Fang,3 Minghua Wu1 1Department of Neurology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210029, People’s Republic of China; 2Department of Medicine, Physiology and Biophysics, UC Irvine Diabetes Center, University of California Irvine (UCI), Irvine, CA, USA; 3Department of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Minghua Wu, Department of Neurology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, 155 Hanzhong Road, Nanjing, 210029, People’s Republic of China, Email yfy0069@njucm.edu.cn Zhuyuan Fang, Department of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, 155 Hanzhong Road, Nanjing, 210029, People’s Republic of China, Email fangzhuyuan@njucm.edu.cnBackground: The relationship between insulin resistance-related indices and the outcomes of acute ischemic stroke (AIS) is still unclear. This study aimed to explore the association between the Apo B/Apo A-1 ratio and the Prognostic Nutritional Index (PNI) with the 90-day outcomes of AIS.Methods: A total of 2011 AIS patients with a 3-month follow-up were enrolled in the present study from January 2017 to July 2021. Multivariate logistic regression modeling was performed to analyze the relationship between Apo B/Apo A-1 ratio, PNI, and AIS poor outcomes. The mediating effect between the three was analyzed using the Bootstrap method with PNI as the mediating variable.Results: Among the 2011 included AIS patients, 20.3% had a poor outcome. Patients were categorized according to quartiles of Apo B/Apo A-1 ratio and PNI. Multivariate logistic regression revealed that the fourth Apo B/Apo A-1 ratio quartile had poorer outcomes than the first quartile (OR 1.75,95%CL 1.21– 2.53, P=0.003), and the fourth PNI quartile exhibited a lower risk of poor outcomes than the first quartile (OR 0.40, 95%CL 0.27– 0.61, P< 0.001). PNI displayed a significant partially mediating effect (21.4%) between the Apo B/Apo A-1 ratio and poor AIS outcomes.Conclusion: The Apo B/Apo A-1 ratio is a risk factor for poor AIS outcomes, whereas PNI acts as a protective factor. The association between the ApoB/ApoA-1 ratio and poor AIS outcomes was partially mediated by PNI.Keywords: insulin resistance, Apo B/Apo A-1 ratio, prognostic nutritional index, acute ischemic stroke, outcomes

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

Yukai Hao,1 Baoling Zhao,1 Dongchao Wu,1 Xuejun Ge,1 Jianmin Han2 1Department of Endodontics, Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, People’s Republic of China; 2Central Laboratory, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing, 100081, People’s Republic of ChinaCorrespondence: Xuejun Ge, The Department of Endodontics, Shanxi Medical University School and Hospital ofStomatology, 63 Xinjian South Road, Yingze District, Taiyuan, 030001, People’s Republic of China, Tel +8613834568537, Email gxj19722003@163.com Jianmin Han, Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguan Cun South Street, Beijing, 100081, People’s Republic of China, Tel +8613810459668, Email hanjianmin@bjmu.edu.cnIntroduction: Recombinant humanized collagen, as a novel biomaterial, exhibits multiple excellent biological functions, such as inhibition of inflammation, promotion of cell proliferation and vascular proliferation, and promotion of tissue healing. However, there is a lack of conclusive evidence regarding the specific role of recombinant humanized collagen type 17 (rhCol 17) in oral ulcer healing. This study explored whether rhCol 17 could promote the proliferation of human gingival fibroblasts (HGFs) and inhibit its inflammation, and whether it could promote the healing of oral ulcers in rats by inhibiting inflammation and accelerating tissue healing.Methods: At the cellular level, we investigated the effect of rhCol 17 on the proliferation of (HGFs) by CCK8; HGFs were mixed with lipopolysaccharide (LPS) to investigate the effect of rhCol 17 on HGFs in an inflammatory state. Eighteen adult male Sprague-Dawley rats were randomly distributed into three groups: blank control group, carbomer group (carbomer sprayed only), and rhCol 17 group (carbomer containing rhCol 17 sprayed), 1 time/day. The samples were collected at D3 and D5. At completion, histological staining and PCR were carried out to study its effect on the healing of oral ulcers in rats.Results: Through cellular experiments, we found that rhCol 17 possesses good biocompatibility and anti-inflammatory properties, and can effectively promote the proliferation and migration of HGFs, as well as significantly reduce the inflammation level of the cells. The animal experimental results showed that rhCol 17 could significantly reduce the inflammation level, promote collagen deposition and angiogenesis at the ulcer site, thus effectively accelerating the healing of oral ulcers in rats.Conclusion: In summary, the collagen sprays containing rhCol 17 have excellent anti-inflammatory effects and could accelerate tissue healing and are expected to provide a new effective treatment for patients with recurrent oral ulcers.Keywords: oral ulcer, inflammation, wound healing, recombinant humanized collagen

Meng Zhang,1,2 Qi Yuan,1 Peiwen Wang,1 Fan Zhang,1 Dan Wu,1 He Bai,1 Jieting Liu,1 Haifeng Liu,1 Xiaohuan Yuan1 1College of Life Science, Mudanjiang Medical University, Mudanjiang, People’s Republic of China; 2The First Hospital of Qiqihar, Qiqihar, People’s Republic of ChinaCorrespondence: Xiaohuan Yuan, College of Life Science, Mudanjiang Medical University, No. 3 Tongxiang Road, Mudanjiang, 157011, People’s Republic of China, Tel/Fax +86-453-6984401, Email yuanxiaohuan@mdjmu.edu.cnPurpose: Nanovesicles (NVs) derived from bone mesenchymal stem cells (BMSCs) as drug delivery systems are considered an effective therapeutic strategy for diabetes. However, its mechanism of action remains unclear. Here, we evaluated the efficacy and molecular mechanism of BMSC-derived NVs carrying the curcumin analog H8 (H8-BMSCs-NVs) on hepatic glucose and lipid metabolism in type 2 diabetes (T2D).Subjects and Methods: Mouse BMSCs were isolated by collagenase digestion and H8-BMSCs-NVs were prepared by microvesicle extrusion. The effects of H8-BMSCs-NVs on hepatic glucose and lipid metabolism were observed in a T2D mouse model and a HepG2 cell insulin resistance model. To evaluate changes in potential signaling pathways, the PI3K/AKT/AMPK signaling pathway and expression levels of G6P and PEPCK were assessed by Western blotting.Results: H8-BMSCs-NVs effectively improved lipid accumulation in liver tissues and restored liver dysfunction in T2D mice. Meanwhile, H8-BMSCs-NVs effectively inhibited intracellular lipid accumulation in the insulin resistance models of HepG2 cells. Mechanistic studies showed that H8-BMSCs-NVs activated the PI3K/AKT/AMPK signaling pathway and decreased the expression levels of G6P and PEPCK.Conclusion: These findings demonstrate that H8-BMSCs-NVs improved hepatic glucose and lipid metabolism in T2D mice by activating the PI3K/AKT/AMPK signaling pathway, which provides novel evidence suggesting the potential of H8-BMSCs-NVs in the clinically treatment of T2D patients.Keywords: bone mesenchymal stem cell, nanovesicles, curcumin analogue H8, type 2 diabetes

Xundi Bao,1 Shuo Liang,1 Jun Li,1 Qian Ye,1 Dandan Wu,1 Shu Wang,2 Yue Li,1 Yunsheng Ding,1 Jie Liu3 1Clinical Laboratory, Anhui Provincial Chest Hospital (Provincial Institute of Tuberculosis Control), Hefei, Anhui, People’s Republic of China; 2Department of Science and Education, Anhui Provincial Chest Hospital (Provincial Institute of Tuberculosis Control), Hefei, Anhui, People’s Republic of China; 3Tuberculosis Control Institute, Anhui Provincial Chest Hospital (Provincial Institute of Tuberculosis Control), Hefei, Anhui, People’s Republic of ChinaCorrespondence: Xundi Bao, Clinical laboratory, Anhui Provincial Chest Hospital (Provincial Institute of Tuberculosis Control), No. 397, Jixi Road, Shushan District, Hefei, Anhui, People’s Republic of China, Tel +86-13866774716, Email baoxundi@163.comObjective: To preliminarily assess the prevalence and control effect of tuberculosis and drug-resistant tuberculosis (TB) in Anhui province, and analyze the trends in the changing drug resistance spectrum of Mycobacterium tuberculosis (Mtb) isolated in Anhui province from 2016 to 2022.Methods: From 2016 to 2022, a total of 2336 culture-positive tuberculosis strains were collected from four drug resistance monitoring sites. Patient demographic information was collected and drug susceptibility testing was conducted.Results: Among the 2336 Mycobacterium tuberculosis complex strains, 1788 (76.54%) were from male patients and 548 (23.46%) were from female patients. The majority were of Han ethnicity, from rural areas, and employed in agriculture, with 12.54% (285/2273) having diabetes. A total of 1893 (81.04%) strains were sensitive to all six anti-TB drugs tested, and 443 (18.96%) strains were resistant to at least one or more anti-TB drugs. The drug resistance rate for patients undergoing initial treatment was 16.80% (348/2071), and 35.85% (95/265) for those receiving retreatment. Among the six anti-TB drugs, the resistance rates from highest to lowest were: INH (10.55%, 236/2336), SM (8.18%, 183/2336), OFX (6.53%, 146/2336), RFP (5.95%, 133/2336), EMB (2.37%, 53/2336), KM (1.97%, 44/2336). Significant differences were observed in MDR strains across different ages, types, with or without diabetes, and geographical sources (χ 2=14.895,76.534,6.032,5.109, all P< 0.05).Conclusion: The tuberculosis prevention and control measures have controlled the drug resistance rate of Mycobacterium tuberculosis to a certain extent. However, there are still statistical differences in drug resistance rates among TB patients with different categories, age groups, regions, and diabetic diseases. Early detection and prompt treatment of patients with drug-resistant TB remain critical to controlling the spread of this disease.Keywords: tuberculosis, mycobacterium, drug resistance, surveillance, population distribution, characteristic analysis

Xiaojuan Wu,1,2,&ast; Daoyan Wu,1,2,&ast; Guzhen Cui,1 Khui Hung Lee,3 Tingxiu Yang,1,2 Zhengrong Zhang,1,2 Qi Liu,4 Jinbao Zhang,1 Eng Guan Chua,3 Zhenghong Chen1,2 1Key Laboratory of Microbiology and Parasitology of Education Department of Guizhou & Joint Laboratory of Helicobacter Pylori and Intestinal Microecology of Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, People’s Republic of China; 2Key Laboratory of Endemic and Ethnic Diseases of Ministry of Education, Guizhou Medical University, Guiyang, People’s Republic of China; 3Helicobacter Research Laboratory, the Marshall Centre for Infectious Disease Research and Training, School of Biomedical Sciences, University of Western Australia, Perth, Western Australia, Australia; 4Department of Gastroenterology, Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhenghong Chen, Department of Microbiology, School of Basic Medical Science, Guizhou Medical University, Guiyang, People’s Republic of China, Tel + 86-13985006815, Email chenzhenghong@gmc.edu.cnBackground: Persistent infections caused by Helicobacter pylori (H. pylori), which are resistant to antibiotic treatment, pose a growing global public health concern. Biofilm formation is known to be associated with persistent infections due to its role in enhancing antimicrobial resistance and the tolerance of many pathogenic bacteria.Objective: This study aims to evaluate the biofilm formation of clinical isolates of H. pylori and its impact on antibiotic eradication.Methods: The thickness, morphology, and structure of biofilms derived from nine H. pylori strains were examined using confocal laser scanning microscopy, scanning electron microscopy, and transmission electron microscopy. Subsequently, the susceptibility of both planktonic and biofilm bacteria was assessed through the determination of minimum inhibitory concentration and minimum biofilm eradication concentration for amoxicillin, clarithromycin, levofloxacin, and tetracycline.Results: The results revealed varying biofilm thicknesses and densities among the strains, characterised by the presence of numerous filaments intertwining and connecting bacterial cells. Additionally, several cases exhibited susceptibility based on MIC measurements but resistance according to MBEC measurements, with MBEC indicating a higher resistance rate. Pearson Correlation analysis demonstrated a positive correlation between biofilm thickness and MBEC results (0 < r < 1), notably significant for amoxicillin (r = 0.801, P = 0.009) and tetracycline (r = 0.696, P = 0.037).Conclusion: Different strains of H. pylori exhibit variations in their capacity to release outer membrane vesicles (OMVs) and form biofilms. Biofilm formation can influence the effectiveness of amoxicillin and tetracycline in eradicating susceptible bacterial strains.Keywords: Helicobacter pylori, antibiotic resistance, biofilm formation, biofilm-specific resistance

Longfei Fan,1 Zhongqiang Qin,1 Di Wu,1 Yunchuan Yang,2 Yigang Zhang,2 Bo Xie,1 Jingyu Qian,1 Jianzhu Wei,1 Zhaoying Wang,1 Peipei Yang,1 Zhen Qian,1 Mu Yuan,1 Ziyi Zhu,1 Yulin Tan,1 Yi Tan2 1Department of Interventional Radiology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, 233000, People’s Republic of China; 2Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, 233000, People’s Republic of ChinaCorrespondence: Yi Tan, Email doctortanyi2007@126.comPurpose: To study the relationship between LARS1 expression and immune infiltration and prognosis in hepatocellular carcinoma (HCC).Patients and Methods: The clinical characteristics together with LARS1 expression levels were obtained from the TCGA database. Immunohistochemistry confirmed LARS1 expression levels in paraneoplastic and tumor tissues. To investigate LARS1-related downstream molecules, a network of protein-protein interactions (PPIs) and the Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) were built. Furthermore, gene set enrichment analysis (GSEA) was used to analyze the pathways associated with LARS1 expression, whereas Single-sample GSEA (ssGSEA) was applied to perform an association study between immune infiltration and LARS1 gene expression. The TISCH Database and the TISIDB database were used to compare the difference of LARS1 expression in hepatocellular carcinoma and immunomodulators.Results: In comparison to that in normal tissues, the LARS1 expression level was elevated in tumor tissues. LARS1 expression exhibited substantial correlation with AFP, Histologic grade, pathologic stage, Residual tumor, and Vascular invasion in HCC. Higher LARS1 expression in HCC was linked to lower progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS). According to the GO/KEGG study, the important biological process (neutral lipid metabolic process), cellular component (triglyceride-rich plasma lipoprotein), molecular functions (lipase inhibitor activity), and KEGG pathway (cholesterol metabolism) could be a probable function mechanism in promoting HCC. Various pathways as per GSEA revealed that they were enriched in samples with elevated LARS1 expression. The expression level of LARS1 in malignant tumor cells after immunotherapy was significantly higher than that before immunotherapy. LARS1 was also remarkably linked to the infiltration level and the immunomodulators.Conclusion: LARS1 can be used as a biomarker of HCC, which is associated to immune infiltration of HCC.Keywords: hepatocellular carcinoma, leucyl-tRNA synthetase 1, bioinformatics analysis, biomarker, the cancer genome atlas

Chuihao Kong,1,2,&ast; Kaidi Wang,1,2,&ast; Lei Sun,1,3 Hongsu Zhao,1,2 Tongsheng Wang,1 Wuxi Zhou,1 Deling Wu,1,2 Fengqing Xu1,2 1School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, People’s Republic of China; 2Anhui Province Key Laboratory of New Manufacturing Technology for Traditional Chinese Medicine Decoction Pieces, Hefei, 230012, People’s Republic of China; 3Zhejiang CONBA Pharmaceutical Co. LTD, Hangzhou, 310052, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wuxi Zhou; Fengqing Xu, School of Pharmacy, Anhui University of Chinese Medicine, 350 Longzihu Road, Xinzhan District, Hefei, 230012, People’s Republic of China, Email zhouwuxi@ahtcm.edu.cn; xufengqing@ahtcm.edu.cnBackground: Mangiferin (MA), a bioactive C-glucosyl xanthone with a wide range of interesting therapeutic properties, has recently attracted considerable attention. However, its application in biomedicine is limited by poor solubility and bioavailability. Carbon dots (CDs), novel nanomaterials, have immense promise as carriers for improving the biopharmaceutical properties of active components because of their outstanding characteristics.Methods: In this study, a novel water-soluble carbon dot (MC-CDs) was prepared for the first time from an aqueous extract of Moutan Cortex Carbonisata, and characterized by various spectroscopies, zeta potential and high-resolution transmission electron microscopy (HRTEM). The toxicity effect was investigated using the CCK-8 assay in vitro. In addition, the potential of MC-CDs as carriers for improving the pharmacokinetic parameters was evaluated in vivo.Results: The results indicated that MC-CDs with a uniform spherical particle size of 1– 5 nm were successfully prepared, which significantly increased the solubility of MA in water. The MC-CDs exhibited low toxicity in HT-22 cells. Most importantly, the MC-CDs effectively affected the pharmacokinetic parameters of MA in normal rats. UPLC-MS analysis indicated that the area under the maximum blood concentration of MA from mangiferin-MC-CDs (MA-MC-CDs) was 1.6-fold higher than that from the MA suspension liquid (MA control) after oral administration at a dose of 20 mg/kg.Conclusion: Moutan Cortex-derived novel CDs exhibited superior performance in improving the solubility and bioavailability of MA. This study not only opens new possibilities for the future clinical application of MA but also provides evidence for the development of green biological carbon dots as a drug delivery system to improve the biopharmaceutical properties of insoluble drugs. Keywords: Moutan Cortex, carbon dots, mangiferin, solubility, bioavailability

Yingying Shen,1,2,&ast; Junmin Cao,3,&ast; Tonglin Hu,1,2 Xiawan Yang,1,2 Yuechao Zhao,1,2 Yiping Shen,1,2 Baodong Ye,1,2 Yunsong Yu,4 Dijiong Wu1,2 1Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, People’s Republic of China; 2National Traditional Chinese Medicine Clinical Research Base (Hematology), Hangzhou, Zhejiang, People’s Republic of China; 3Department of Clinical Laboratory, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, People’s Republic of China; 4Department of Infectious Diseases, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dijiong Wu, Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, 310006, People’s Republic of China, Tel +86-0571-86620325, Email wudijiong@zcmu.edu.cn Yunsong Yu, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang, 310024, People’s Republic of China, Tel +8613805790432, Email yvys119@zju.edu.cnBackground: Carbapenem-resistant P. aeruginosa (CRPA) is a common hospital-acquired bacterium. It exhibits high resistance to many antibiotics, including ceftazidime/avibactam and cefteolozane/tazobactam. The presence of carbapenem-resistant genes and co-existence Klebsiella pneumoniae carbapenemase (KPC) and metallo-β-lactamases (MBLs) further inactivated all β-lactams. Understanding the resistance genes of CRPA can help in uncovering the resistance mechanism and guiding anti-infective treatment. Herein, we reported a case of perianal infection with hypervirulent ST463 Pseudomonas aeruginosa.Case Presentation: The case is a 32-year-old acute myeloid leukemia (AML) patient with fever and septic shock during hematopoietic stem cell transplantation (HSCT), and the pathogen was finally identified as a highly virulent sequence type 463 (ST463) P. aeruginosa harboring carbapenem-resistant genes blaAFM-1 and blaKPC-2, which was detected in the bloodstream and originated from a perianal infection. The strain was resistant to ceftazidime/avibactam but successfully treated with polymyxin B, surgical debridement, and granulocyte engraftment after HSCT. The AML was cured during the 19-month follow-up.Conclusion: This case emphasizes the importance of metagenomic next-generation sequencing (mNGS) and whole-genome sequencing (WGS) in identifying microbes with rare resistant genes, and managing CRPA, especially in immunocompromised patients. Polymyxin B may be the least resistant option.Keywords: carbapenem-resistant pseudomonas aeruginosa, blaAFM, blaKPC, ST463

Xian Li,1,&ast; Hong Lai,2,&ast; Peng Wang,3 Shuai Feng,4 Xuexin Feng,4 Chao Kong,3 Dewei Wu,5 Chunlin Yin,5 Jianghua Shen,6 Suying Yan,6 Rui Han,7 Jia Liu,7 Xiaoyi Ren,8 Ying Li,8 Lu Tang,9 Dong Xue,9 Ying Zhao,9 Hao Huang,10 Xiaoying Li,10 Yanhong Zhang,10 Xue Wang,11 Chunxiu Wang,12 Ping Jin,13 Shibao Lu,3 Tianlong Wang,4 Guoguang Zhao,14 Chaodong Wang1 On behalf of the APPLE-MDT Research Team, Xuanwu Hospital, Capital Medical University and National Clinical Research Center for Geriatric Diseases1Department of Neurology & Neurobiology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, 100053, People’s Republic of China; 2Department of Neurology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, People’s Republic of China; 3Department of Orthopedic Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 4Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 5Department of Cardiology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 6Department of Pharmacy, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 7Department of Gerontology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 8Department of Nutrition, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 9Department of Oral Medicine, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 10Department of Medical Administration, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 11Department of Medical Library, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 12Center for Evidence-Based Medicine, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 13Center for Medical Information, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 14Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, 100053, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chaodong Wang, Department of Neurology, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, No. 45 Changchun Street, Beijing, 100053, People’s Republic of China, Tel/Fax +86-10-8319-8677, Email cdongwang@xwhosp.orgPurpose: We aimed to identify the risk factors for postoperative cognitive decline (POCD) by evaluating the outcomes from preoperative comprehensive geriatric assessment (CGA) and intraoperative anesthetic interventions.Patients and Methods: Data used in the study were obtained from the Aged Patient Perioperative Longitudinal Evaluation–Multidisciplinary Trial (APPLE-MDT) cohort recruited from the Department of Orthopedics in Xuanwu Hospital, Capital Medical University between March, 2019 and June, 2022. All patients accepted preoperative CGA by the multidisciplinary team using 13 common scales across 15 domains reflecting the multi-organ functions. The variables included demographic data, scales in CGA, comorbidities, laboratory tests and intraoperative anesthetic data. Cognitive function was assessed by Montreal Cognitive Assessment scale within 48 hours after admission and after surgery. Dropping of ≥ 1 point between the preoperative and postoperative scale was defined as POCD.Results: We enrolled 119 patients. The median age was 80.00 years [IQR, 77.00, 82.00] and 68 patients (57.1%) were female. Forty-two patients (35.3%) developed POCD. Three cognitive domains including calculation (P = 0.046), recall (P = 0.047) and attention (P = 0.007) were significantly worsened after surgery. Univariate analysis showed that disability of instrumental activity of daily living, incidence rate of postoperative respiratory failure (PRF) ≥ 4.2%, STOP-Bang scale score, Caprini risk scale score and Sufentanil for maintenance of anesthesia were different between the POCD and non-POCD patients. In the multivariable logistic regression analysis, PRF ≥ 4.2% (odds ratio [OR] = 2.343; 95% confidence interval [CI]: 1.028– 5.551; P = 0.046) and Sufentanil for maintenance of anesthesia (OR = 0.260; 95% CI: 0.057– 0.859; P = 0.044) was independently associated with POCD as risk and protective factors, respectively.Conclusion: Our study suggests that POCD is frequent among older patients undergoing elective orthopedic surgery, in which decline of calculation, recall and attention was predominant. Preoperative comprehensive geriatric assessments are important to identify the high-risk individuals of POCD.Keywords: cognitive dysfunction, postoperative cognitive complications, orthopedic surgery, comprehensive geriatric assessment, risk factors

Fei Cai,1,2,&ast; Di Wu,3,&ast; Junling Liu,1 Shuxi Song,1 Jingyu Li,1 Zhendong Zheng,1 Long Xu1 1Department of Oncology, General Hospital of Northern Theater Command, Shenyang, Liaoning, People’s Republic of China; 2Beifang Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China; 3Department of Diagnostic Radiology, General Hospital of Northern Theater Command, Shenyang, Liaoning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhendong Zheng; Long Xu, Department of Oncology, General Hospital of Northern Theater Command, Shenyang, Liaoning, 110000, People’s Republic of China, Email gcp_zzd@sina.com; doctorxul@163.comObjective: Cystic brain metastases (BMs) are rare in small cell lung cancer (SCLC), and there are limited data on the treatment and prognosis of cystic BMs. Whole brain radiotherapy has been the mainstay for BMs since several years. Immune checkpoint inhibitors in extensive stage small cell lung cancer (ES-SCLC) have been shown to be suitable for patients who experienced better overall survival and progress-free survival and have been approved as the first-line treatment for ES-SCLC. In this report, we described two ES-SCLC patients developed cystic BMs after immunotherapy, after which the patients continued to treat the primary lesion with immune checkpoint inhibitors and the cystic BMs with radiotherapy.Case Description: Two male patients were diagnosed with ES-SCLC at the first admission and were subsequently treated with immunotherapy plus platinum therapy, during which cystic BMs developed. One patient received whole brain radiotherapy and the other received whole brain radiotherapy and Gamma knife radiosurgery (GKRS). Immunotherapy was continued after the brain lesions were controlled. It has been 33 months since the first patient was diagnosed and is now in stable condition. The other patient achieved an overall survival of 30 months.Conclusion: This report describes two patients with cystic brain metastases in ES-SCLC. Whole brain radiotherapy has a good effect on local control of cystic brain metastases in small cell lung cancer and can significantly improve the symptoms of patients. At the same time, we treat immunotherapy as the first-line treatment, and then perform cross-immunotherapy after disease progression, combined with anti-vascular targeting drugs. The patient did not develop severe iRAEs.Keywords: ES-SCLC, immunotherapy, cystic BMs, cross-line immunotherapy

Qiong Ge,1,&ast; Zhewen Zhang,2,&ast; Zhiming Cao,2 Dan Wu,3 Changping Xu,1 Jianbiao Yao,3 Jian Gao,1 Yan Feng1 1Key Laboratory of Public Health Detection and Etiological Research of Zhejiang Province, Department of Microbiology, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang, 310051, People’s Republic of China; 2College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China; 3Zhejiang Provincial Key Laboratory of Traditional Chinese Medicine Pharmaceutical Technology, Zhejiang Conba Pharmaceutical Co., Ltd, Hangzhou, Zhejiang, 310057, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Feng, Key Laboratory of Public Health Detection and Etiological Research of Zhejiang Province, Department of Microbiology, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang, 310051, People’s Republic of China, Tel/Fax +86-571-87115204, Email yfeng@cdc.zj.cnPurpose: This study aims to investigate the in vitro antiviral effects of the aqueous solution of Changyanning (CYN) tablets on Enterovirus 71 (EV71), and to analyze its active components.Methods: The in vitro anti-EV71 effects of CYN solution and its herbal ingredients were assessed by testing the relative viral RNA (vRNA) expression level and the cell viability rates. Material basis analysis was performed using HPLC-Q-TOF-MS/MS detection. Potential targets and active components were identified by network pharmacology and molecular docking. The screened components were verified by in vitro antiviral experiments.Results: CYN solution exerted anti-EV71 activities as the vRNA is markedly reduced after treatment, with a half maximal inhibitory concentration (IC50) of 996.85 μg/mL. Of its five herbal ingredients, aqueous extract of Mosla chinensis (AEMC) and leaves of Liquidambar formosana Hance (AELLF) significantly inhibited the intracellular replication of EV71, and the IC50 was tested as 202.57 μg/mL and 174.77 μg/mL, respectively. Based on HPLC-Q-TOF-MS/MS results, as well as the comparison with the material basis of CYN solution, a total of 44 components were identified from AEMC and AELLF. Through network pharmacology, AKT1, ALB, and SRC were identified as core targets. Molecular docking performed between core targets and the components indicated that 21 components may have anti-EV71 effects. Of these, nine were selected for in vitro pharmacodynamic verification, and only rosmarinic acid manifested in vitro anti-EV71 activity, with an IC50 of 11.90 μg/mL. Moreover, rosmarinic acid can stably bind with three core targets by forming hydrogen bonds.Conclusion: CYN solution has inhibitory effects on EV71 replication in vitro, and its active component was identified as rosmarinic acid. Our study provides a new approach for screening and confirmation of the effective components in Chinese herbal preparation.Keywords: antiviral effects, material basis analysis, component-target-pathway-disease network, protein–protein interaction network, core targets, rosmarinic acid

Yuanyuan Xie,1,&ast; Shifang Li,1,&ast; Dinan Wu,2 Yining Wang,2 Jiepeng Chen,3 Lili Duan,3 Shuzhuang Li,4 Yuyuan Li2 1The First Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China; 2Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, People’s Republic of China; 3Sungen Bioscience Co., Ltd, Guangdong, People’s Republic of China; 4College of Basic Medical Science, Dalian Medical University, Dalian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuyuan Li; Shuzhuang Li, Tel +86 411 86118983, Email liyuyuan831221@163.com; shuzhuangli@126.comAbstract: Vitamin K (VK) comprises a group of substances with chlorophyll quinone bioactivity and exists in nature in the form of VK1 and VK2. As its initial recognition originated from the ability to promote blood coagulation, it is known as the coagulation vitamin. However, based on extensive research, VK has shown potential for the prevention and treatment of various diseases. Studies demonstrating the beneficial effects of VK on immunity, antioxidant capacity, intestinal microbiota regulation, epithelial development, and bone protection have drawn growing interest in recent years. This review article focuses on the mechanism of action of VK and its potential preventive and therapeutic effects on infections (eg, asthma, COVID-19), inflammation (eg, in type 2 diabetes mellitus, Alzheimer’s disease, Parkinson’s disease, cancer, aging, atherosclerosis) and autoimmune disorders (eg, inflammatory bowel disease, type 1 diabetes mellitus, multiple sclerosis, rheumatoid arthritis). In addition, VK-dependent proteins (VKDPs) are another crucial mechanism by which VK exerts anti-inflammatory and immunomodulatory effects. This review explores the potential role of VK in preventing aging, combating neurological abnormalities, and treating diseases such as cancer and diabetes. Although current research appoints VK as a therapeutic tool for practical clinical applications in infections, inflammation, and autoimmune diseases, future research is necessary to elucidate the mechanism of action in more detail and overcome current limitations.Keywords: vitamin K, VK-dependent proteins, infection, inflammation, auto-immune disease

Jiawei Lu,1 Kai Guo,1 Elaine Zhiqing Liu,2 Corben Braun,3 Yufeng Huang,1 Desheng Wu1 1Department of Spine Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Center for Asian Health, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA; 3Department of Orthopedic Surgery, McKay Labs, University of Pennsylvania, Philadelphia, PA, USACorrespondence: Desheng Wu, Email 1300116@tongji.edu.cnPurpose: Lumbar disc herniation, often treated with surgical decompression when conservative measures fail, presents challenges due to prolonged prone positioning in surgeries. This retrospective study evaluates the benefits of preoperative adaptive training to mitigate post-surgical physiological changes.Patients and Methods: A review of medical records from June 2021 to March 2023 identified 170 patients unresponsive to conservative treatments. Grouped into adaptive training and control groups based on historical data, the former had undergone exercises to prepare for surgery and postoperative changes. Vital signs and VAS scores were extracted from patient records to assess training impact.Results: The adaptive training group demonstrated stabilized vital signs intraoperatively, with a notable improvement in surgical exposure compared to the control group. However, there were no significant differences in operative time or blood loss between the groups. Additionally, postoperative VAS scores showed no significant improvement in the adaptive training group at follow-up intervals of 14 days, 1 month, and 3 months post-operation, compared to the control group.Conclusion: Our study reveals that preoperative adaptive training stabilizes intraoperative blood pressure fluctuations in lumbar disc herniation surgeries. However, this stabilization does not significantly impact long-term postoperative pain management. This highlights the need for further research to explore comprehensive strategies that effectively combine preoperative training with postoperative care.Keywords: lumbar surgery, preoperative education, adaptive training, retrospective analysis

Xiaomei Jiang,1,&ast; Xiaohong Jiang,2,&ast; Dongjie Wu,1 Wanzhu Xie,3 Xiong Liu,1 Jintao Zheng4 1Department of Dermatology, Liuzhou Traditional Chinese Medicine Hospital, Liuzhou, 545001, People’s Republic of China; 2Department of Pharmacy, Shantou University Medical College, Shantou, 515041, People’s Republic of China; 3Department of Rehabilitation, Liuzhou Worker’s Hospital, Liuzhou, 545001, People’s Republic of China; 4Department of Biotechnology and Food Engineering, Guangdong Technology Israel Institute of Technology, Shantou, 515063, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jintao Zheng, Department of Biotechnology and Food Engineering, Guangdong Technology Israel Institute of Technology, Shantou, 515063, People’s Republic of China, Tel +86 156 2584 9047, Email jintao.zheng@gtiit.edu.cnBackground: Radiotherapy is a widely used clinical tool for tumor treatment but can cause systemic toxicity if excessive radiation is administered. Although numerous nanoparticles have been developed as radiosensitizers to reduce the required dose of X-ray irradiation, they often have limitations, such as passive reliance on radiation-induced apoptosis in tumors, and little consider the unique tumor microenvironment that contributes radiotherapy resistance.Methods: In this study, we developed and characterized a novel self-assembled nanoparticle containing dysprosium ion and manganese ion (Dy/Mn-P). We systematically investigated the potential of Dy/Mn-P nanoparticles (NPs) as a reactive oxygen species (ROS) amplifier and radiosensitizer to enhance radiation therapy and modulate the tumor microenvironment at the cellular level. Additionally, we evaluated the effect of Dy/Mn-P on the stimulator of interferon genes (STING), an innate immune signaling pathway.Results: Physicochemical analysis demonstrated the prepared Dy/Mn-P NPs exhibited excellent dispersibility and stability, and degraded rapidly at lower pH values. Furthermore, Dy/Mn-P was internalized by cells and exhibited selective toxicity towards tumor cells compared to normal cells. Our findings also revealed that Dy/Mn-P NPs improved the tumor microenvironment and significantly increased ROS generation under ionizing radiation, resulting in a ~70% increase in ROS levels compared to radiation therapy alone. This enhanced ROS generation inhibited ~92% of cell clone formation and greatly contributed to cytoplasmic DNA exposure. Subsequently, the activation of the STING pathway was observed, leading to the secretion of pro-inflammatory immune factors and maturation of dendritic cells (DCs).Conclusion: Our study demonstrates that Dy/Mn-P NPs can potentiate tumor radiotherapy by improving the tumor microenvironment and increasing endogenous ROS levels within the tumor. Furthermore, Dy/Mn-P can amplify the activation of the STING pathway during radiotherapy, thereby triggering an anti-tumor immune response. This novel approach has the potential to expand the application of radiotherapy in tumor treatment.Keywords: radiotherapy, Dy/Mn-P NPs, ROS, tumor microenvironment, STING pathway

Cheng Peng, Yilin Xu, Jing Wu, Donghai Wu, Lili Zhou, Xinhua Xia School of Pharmacy, Hunan University of Chinese Medicine, Changsha, People’s Republic of ChinaCorrespondence: Xinhua Xia; Lili Zhou, Email xiaxinhua001@hnucm.edu.cn; 004683@hnucm.edu.cnAbstract: The tumor microenvironment (TME) plays an important role in various stages of tumor generation, metastasis, and evasion of immune monitoring and treatment. TME targeted therapy is based on TME components, related pathways or active molecules as therapeutic targets. Therefore, TME targeted therapy based on environmental differences between TME and normal cells has been widely studied. Biomimetic nanocarriers with low clearance, low immunogenicity, and high targeting have enormous potential in tumor treatment. This review introduces the composition and characteristics of TME, including cancer‑associated fibroblasts (CAFs), extracellular matrix (ECM), tumor blood vessels, non-tumor cells, and the latest research progress of biomimetic nanoparticles (NPs) based on TME. It also discusses the opportunities and challenges of clinical transformation of biomimetic nanoparticles.Keywords: nanoparticles, biomimetic delivery system, tumor therapy, cell membrane-coating

Chunqing Wang, Xiaoyao Jiang, Di Wu, Mengjun Ge, Li Deng Department of General Practice, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of ChinaCorrespondence: Chunqing Wang, Department of General Practice, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of China, Email yamail@126.comObjective: Discussing the relationship between geriatric nutritional risk index (GNRI) and platelet-to-lymphocyte ratio (PLR) on stroke-associated pneumonia (SAP) in acute ischemic stroke (AIS) patients, developing and validating a web-based dynamic nomogram.Methods: A total of 996 AIS patients admitted to the Department of General Medicine and Neurology at Xuzhou Medical University Affiliated Hospital were collected. They were divided into Non-SAP group and SAP group based on the occurrence of SAP. The data was randomly divided into training set and validation set in a ratio of 7:3. LASSO regression and multivariable logistic regression analysis were used to screen for independent risk factors and develop a dynamic nomogram. Area under the receiver operating characteristic curve (AUC-ROC), calibration curve, and decision curve analysis (DCA) curve were used to validate the model’s discriminative ability, calibration, and clinical value, respectively.Results: Among AIS patients, a total of 221 cases (22.19%) developed SAP. Age, NIHSS score, comorbid atrial fibrillation, dysphagia, PLR, and GNRI were identified as independent factors influencing the occurrence of SAP in AIS patients. A web-based dynamic nomogram was developed based on these six variables. The training set showed an AUC-ROC of 0.864 (95% CI: 0.828– 0.892), while the validation set showed an AUC-ROC of 0.825 (95% CI: 0.772– 0.882), indicating good predictive ability and discrimination of the model. The calibration curve demonstrated good calibration of the model, and the DCA curve showed its clinical value. This model can be accessed and utilized by anyone on the website (https://moonlittledoctor.shinyapps.io/ANADPG/).Conclusion: PLR and GNRI are independent factors influencing the occurrence of SAP in AIS patients, and a dynamic nomogram was constructed to predict the risk of SAP in AIS patients. It can guide clinical decision-making and improve patient prognosis.Keywords: GNRI, PLR, dynamic nomogram, acute ischemic stroke, stroke-associated pneumonia

Qiangjian Mao,1,&ast; Biao Huang,1,&ast; Daocheng Zhu,1 Yuqing Wang,2 Shiqi Xu,2 Desheng Wu,1 Guomin Huang,1 Ziru Li,1 Zhenhai Chi,1 Rixin Chen1 1The Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, People’s Republic of China; 2Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhenhai Chi; Rixin Chen, The Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, People’s Republic of China, Email 348916661@qq.com; chenrixin321@163.comBackground: Acupuncture therapy has been widely used in the treatment of musculoskeletal pain (MP) in many countries around the world. However, there are no bibliometric studies on acupuncture therapy for MP. Therefore, the aim of this study was to analyze the current status, frontiers and hot spots in the use of acupuncture therapy for the treatment of MP.Methods: Literature on acupuncture therapy for MP was extracted from the Web of Science Core Collection database from 2003 to 2022. CiteSpace 6.2.R4 (64-bit) software was used to analyze the number and centrality of journals, countries, institutions, authors, references and keywords, and the functions of co-occurrence and clustering were applied to draw a visual knowledge map.Results: Over the past 20 years, the annual journal publications have been on a steady upward trend, with 438 articles published in 143 journals, including Acupuncture in Medicine Journal published the most (28, 6.39%), JAMA-Journal of the American Medical Association was the journal with the highest impact factor (IF = 120.7003), USA dominated with the most publications (140, 31.96%) among 44 countries, and among 196 research organizations Kyung Hee University was the most prolific (19, 4.34%) and Ha, In-Hyuk was the most published author (9, 2.05%). “Acupuncture” is the most popular and highly sought after keywords. “Low back pain” is the keyword with the highest centrality.Conclusion: This article provides the current situation of the use of acupuncture therapy in the treatment of MP in the past 20 years, and statistical analysis reveals that “low back pain”, “knit osteoporosis” and “break cancer” are new research diseases related to acupuncture therapy for MP, and “myobasic trigger point” is a new research direction of acupuncture therapy for MP. Therefore, this study helps researchers grasp the research hotspots and provide certain references for in-depth research and future topic selection.Keywords: musculoskeletal pain, acupuncture therapy, bibliometrics, CiteSpace

Meirong Zhu,1,2 Tongyu Jin,1 Ding Wu,3 Shanchao Zhang,4,&ast; Aihua Wang1,4,&ast; 1Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, People’s Republic of China; 2Department of Critical Medicine, Jinan Central Hospital, Jinan, People’s Republic of China; 3Vascular Surgery, Jinan Central Hospital, Jinan, People’s Republic of China; 4Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong First Medical University, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Aihua Wang, Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, People’s Republic of China, Tel +8613791120819, Email wangah_0052@sina.com Shanchao Zhang, Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong First Medical University, Jinan, People’s Republic of China, Tel +8618678295562, Email zhangshanchao2012@163.comPurpose: Atherosclerosis (AS) is the most common cause of cardiovascular and cerebrovascular diseases. However, the mechanisms underlying atherosclerotic plaque progression remain unclear. This study aimed to investigate the genes associated with the development of atherosclerosis in the aorta of ApoE−/− male mice, which could serve as novel biomarkers and therapeutic targets in interventions to halt plaque progression.Methods: Eight-week-old ApoE−/− mice were fed a normal purified laboratory diet or a Western Diet (WD) for 6 or 22 weeks. High-throughput sequencing technology was used to analyze the transcriptomes of the aortas of four groups of mice that were exposed to different dietary conditions. We retrieved and downloaded the human Arteriosclerosis Disease Chip dataset GSE100927 from the Gene Expression Omnibus (GEO) database and selected 29 cases of carotid atherosclerotic lesions and 12 cases of normal carotid tissues as the experimental and control groups, respectively, to further verify our dataset. In addition, we used quantitative reverse transcription polymerase chain reaction (QT-PCR) to verify the expression levels of the core genes in an atherosclerosis mouse model.Results: There were 265 differentially expressed genes (DEGs) between the ApoE−/− Male mice AS22W group and Sham22W group. In addition to the well-known activation of inflammation and immune response, t the autophagy-lysosome system is also an important factor that affects the development of atherosclerosis. We identified five core genes (Atp6ap2, Atp6v0b, Atp6v0d2, Atp6v1a, and Atp6v1d) in the protein-protein interaction (PPI) network that were closely related to autophagosomes. Hub genes were highly expressed in the carotid atherosclerosis group in the GSE100927 dataset (P < 0.001). QT-PCR showed that the RNA level of Atp6v0d2 increased significantly during the development of atherosclerotic plaque in ApoE−/− male mice.Conclusion: Five core genes which affect the development of aortic atherosclerosis through the autophagy-lysosome system, especially Atp6v0d2, were screened and identified using bioinformatic techniques.Keywords: molecular mechanism, bioinformatics, core gene, lysosome, aortic plaque development

Dandan Wu,1,&ast; Junxiao Cong,1,&ast; Jiali Wei,1 Jing Hu,1 Wenhao Sun,1 Wei Ran,2 Chenghui Liao,1 Housheng Zheng,1 Liang Ye1 1Department of Immunology, International Cancer Center, Shenzhen University Health Science Center, Shenzhen, People’s Republic of China; 2State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liang Ye, Department of Immunology, International Cancer Center, Shenzhen University Health Science Center, Shenzhen, 518055, People’s Republic of China, Tel +86-0755-26631420, Fax +86-0755-86671943, Email liangyeszu@163.comBackground: The emergence of the coronavirus disease 2019 (COVID-19) pandemic and the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern (VOCs) requires the continuous development of safe, effective, and affordable prevention and therapeutics. Nanobodies have demonstrated antiviral activity against a variety of viruses, providing a new candidate for the prevention and treatment of SARS-CoV-2 and its variants.Methods: SARS-CoV-2 glycoprotein spike 1 subunit (S1) was selected as the target antigen for nanobody screening of a naïve phage display library. We obtained a nanobody, named Nb-H6, and then determined its affinity, inhibition, and stability by ELISA, Competitive ELISA, and Biolayer Interferometry (BLI). Infection assays of authentic and pseudotyped SARS-CoV-2 were performed to evaluate the neutralization of Nb-H6. The structure and mechanism of action were investigated by AlphaFold, docking, and residue mutation assays.Results: We isolated and characterized a nanobody, Nb-H6, which exhibits a broad affinity for S1 and the receptor binding domain (RBD) of SARS-CoV-2, or Alpha (B.1.1.7), Delta (B.1.617.2), Lambda (C.37), and Omicron (BA.2 and BA.5), and blocks receptor angiotensin-converting enzyme 2 (ACE2) binding. Moreover, Nb-H6 can retain its binding capability after pH or thermal treatment and effectively neutralize both pseudotyped and authentic SARS-CoV-2, as well as VOC Alpha (B.1.1.7), Delta (B.1.617.2), and Omicron (BA.2 and BA.5) pseudoviruses. We also confirmed that Nb-H6 binds two distinct amino acid residues of the RBD, preventing SARS-CoV-2 from interacting with the host receptor.Conclusion: Our study highlights a novel nanobody, Nb-H6, that may be useful therapeutically in SARS-CoV-2 and VOC outbreaks and pandemics. These findings also provide a molecular foundation for further studies into how nanobodies neutralize SARS-CoV-2 and variants and imply potential therapeutic targets for the treatment of COVID-19.Keywords: COVID-19, antiviral medication, single-domain antibody, neutralizing antibody, bio-screening

Linghang Zhou, Jin Tan, Yuzhe Dai, Keke Zhu, Yanbo Xiao, Dan Wu, Zongkang Wang, Yisi Tan, Yijie Qin Department of Stomatology, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People’s Republic of ChinaCorrespondence: Jin Tan, Department of Stomatology, The First Affiliated Hospital of Hunan University of Chinese Medicine, 95 Shaoshan Middle Road, Changsha, Hunan, People’s Republic of China, Email 310176@hnucm.edu.cnPurpose: Arecoline is one of the main toxic components of arecoline to cause oral mucosal lesions or canceration, which seriously affects the survival and life quality of patients. This study analyzed the mechanism of Jiawei Danxuan Koukang (JDK) in alleviating arecoline induced oral mucosal lesions, to provide new insights for the treatment of oral submucosal fibrosis (OSF) or cancerosis.Methods: Metabolomics was applied to analyze the composition of JDK and serum metabolites. The active ingredients of JDK were analyzed by the combined ultra-high performance liquid chromatography and mass spectrometry. The target network of JDK, metabolites and OSF was analyzed by network pharmacology, and molecular docking. Oral mucosal lesions and fibrosis were analyzed by HE and Masson staining. Cell differentiation, proliferation and apoptosis were detected. The expressions of α-SMA, Collagen I, Vimentin, Snail, E-cadherin, AR and NOTCH1 were detected by Western blot.Results: Arecoline induced the gradual atrophy and thinning of rat oral mucosal, collagen accumulation, the increase expressions of fibrosis-related proteins and Th17/Treg ratio. JDK inhibited arecoline-induced oral mucosal lesions and inflammatory infiltration. Arecoline induced changes of serum metabolites in Aminoacyl-tRNA biosynthesis, Alanine, aspartate and glutamate metabolism and Arginine biosynthesis pathways, which were reversed by M-JDK. Quercetin and AR were the active ingredients and key targets of JDK, metabolites and OSF interaction. Arecoline promoted the expression of AR protein, and the proliferation of oral fibroblasts. Quercetin inhibited the effect of arecoline on oral fibroblasts, but was reversed by AR overexpression. Arecoline induced NOTCH1 expression in CAL27 and SCC-25 cells, and promoted cell proliferation, but was reversed by M-JDK or quercetin.Conclusion: JDK improved the arecoline-induced OSF and serum metabolite functional pathway. Quercetin targeted AR protein to improve arecoline-induced OSF. JDK and quercetin inhibited arecoline-induced NOTCH1 protein expression in CAL27 and SCC-25 cells to play an anti-oral cancer role.Graphical Abstract: Keywords: oral submucous fibrosis, Jiawei Danxuan Koukang, arecoline, pharmacology, metabolomics

Guanlin Huang,&ast; Xiaoping Zhou,&ast; Zhenyu Zhang,&ast; Wentao Lai, Qi Zhong, Daxing Wu, Xinyun Ye Department of Neurosurgery, Ganzhou People’s Hospital, Ganzhou, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinyun Ye, Department of Neurosurgery, Ganzhou People’s Hospital, Ganzhou, Jiangxi, 341000, People’s Republic of China, Email yexinyun1270@163.comBackground: Brain abscesses are a rare but serious complication of focal intracerebral infection.Case Description: We present a patient of acute subdural abscess with brain abscess in the left temporal lobe. After craniotomy, combined with the Third Next Generation Sequencing and Gene Diagnosis (TNGS & GD) of abscess, we prescribed sensitive antibiotics; the patient recovers well and the abscess did not recur.Conclusion: For patients with acute subdural abscess, combined craniotomy and the TNGS & GD of abscess could achieve good results.Keywords: intracerebral infection, brain abscess, acute subdural abscess, craniotomy, the Third Next Generation Sequencing and Gene Diagnosis, TNGS & GD

Shanlian Hu,1 Depei Wu,2 Jing Wu,3 Yabing Zhang,4 Mette Bøgelund,5 Johannes Pöhlmann,6 Richard F Pollock6 1School of Public Health, Fudan University, Shanghai, People’s Republic of China; 2First Affiliated Hospital of Soochow University, Soochow University, Suzhou, People’s Republic of China; 3School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, People’s Republic of China; 4Shanghai Institute of Technology, Shanghai, People’s Republic of China; 5Incentive Partners ApS, Holte, Denmark; 6Covalence Research Ltd, Harpenden, United KingdomCorrespondence: Richard F Pollock, Covalence Research Ltd, Rivers Lodge, West Common, Harpenden, AL5 2JD, United Kingdom, Tel +44 20 8638 6525, Email pollock@covalence-research.comPurpose: Treatment process attributes can affect health state utilities associated with therapy. For intravenous iron, used to treat iron deficiency and iron deficiency anemia, research into process attributes is still lacking. This study estimated utilities associated with process attributes for intravenous iron infusions.Methods: An online survey including seven health state vignettes and time trade-off tasks was administered to participants, who were not patients living with iron deficiency or iron deficiency anemia, from a Chinese online panel. Vignettes used an identical description of iron deficiency and iron deficiency anemia but differed in the annual number of infusions, infusion duration, and infusion-associated risk of hypophosphatemic osteomalacia. Disutilities and their rate of change as the number of infusions increased were examined using a power model.Results: The survey was completed by 1091 participants. The highest utilities were observed for one annual infusion of 15– 30 minutes or 30– 60 minutes, without risk of hypophosphatemic osteomalacia (0.754 and 0.746, respectively). In comparison, more infusions and infusions with a risk of hypophosphatemic osteomalacia were associated with lower utilities. Utility continued to decrease, but at a diminishing rate, as the annual number of infusions increased, with utility decrements of 0.006 and 0.002, respectively, when going from zero to one and from four to five infusions per year. All marginal disutilities were small (values < 0.01).Conclusion: This study suggested that treatment attributes of intravenous iron infusions affect health state utilities. Using intravenous iron formulations that allow for fewer and shorter infusions without the risk of hypophosphatemic osteomalacia can reduce the number of visits required and increase patients’ quality of life.Plain Language Summary: A lack of iron in the body can be treated successfully using intravenous infusions of iron, but it is not yet known how different intravenous iron formulations affect patients’ quality of life.Intravenous iron formulations differ in how often and for how long (per infusion) they need to be administered; for example, while one available intravenous iron formulation allows most iron deficits to be corrected in a single visit, others can require several visits. Formulations also seem to differ in the risk of complications relating to low phosphate and bone softening.This study presented descriptions of treatment options, differing in the number and duration of infusions as well as in risk, to more than 1000 Chinese respondents. Based on their answers, the differences between intravenous iron administration regimes could be valued and linked to quality of life. Intravenous iron treatment with fewer, shorter infusions and without risk of bone softening was found to come with a better quality of life. Each additional infusion reduced quality of life, but less so if treatment already involved several infusions. These findings can help patients and physicians to make clinical decisions that focus not only on efficacy and safety but also on the quality of life.Keywords: China, disutility, health-related quality of life, intravenous iron, iron deficiency, time trade-off

Haiyan He,1,&ast; Hang Ma,1,&ast; Zhuo Chen,2 Jingliang Chen,1 Dandan Wu,1 Xuedong Lv,1 Jie Zhu1 1Department of Respiratory Medicine, The Second Affiliated Hospital of Nantong University, Nantong First People’s Hospital, Nantong, Jiangsu, 226001, People’s Republic of China; 2Department of Invasive Technology, The Second Affiliated Hospital of Nantong University, Nantong First People’s Hospital, Nantong, Jiangsu, 226001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuedong Lv; Jie Zhu, The Second Affiliated Hospital of Nantong University, Nantong First People’s Hospital, 6 North Road Hai’er Xiang, Nantong, 226001, Jiangsu, People’s Republic of China, Email xuedonglv@126.com; zhujie123123@126.comPurpose: Chromosomal abnormalities represent genomic signatures linked to cancer prognosis and responses to chemotherapy, immunotherapy, and drug resistance. This study aimed to investigate the impact of chromosome copy number variants (CNVs) on the efficacy of tyrosine kinase inhibitors (TKIs) in EGFR-mutated non-small cell lung cancer (NSCLC) patients, as well as its prognostic implications for progression-free survival (PFS) and overall survival (OS) in EGFR wild-type patients.Methods: A total of 110 patients with advanced NSCLC were enrolled in this study and categorized into EGFR-mutated and wild-type groups. Utilizing next-generation sequencing (NGS) technology, we assessed 24 genes and chromosome CNVs associated with lung cancer pathways in patients’ tissue samples.Results: Within the EGFR-mutated group, patients with a gain in Chr 1p13.3-p13.1 exhibited poor TKI responses, a high relapse rate, and shortened PFS (P = 0.002). Conversely, EGFR-mutated patients with a gain in 14q31.1-q31.3 demonstrated favorable TKI responses and relatively extended PFS (P = 0.005). Among EGFR wild-type patients, the presence of 7q31.1-q31.31 CNV emerged as an independent factor influencing both PFS and OS (P = 0.013, P = 0.004). Notably, patients with a gain in 7q31.1-q31.31 exhibited prolonged PFS and OS. Additionally, independent prognostic significance for OS in EGFR wild-type patients was observed for CNVs in 9q21.31-q22.2 and 11p11.11-q12.1 regions (P = 0.001). Patients with gains in these regions experienced extended OS, while losses were predictive of poorer outcomes.Conclusion: Our results suggested that chromosomal copy number variation is a practical indicator for predicting the response of EGFR-targeted therapy and prognosis for NSCLC patients.Keywords: copy number variations, non-small cell lung cancer, EGFR-TKI response, prognosis

Yifan Lu,1,2,&ast; Ying Cui,1,3,&ast; Ying Zhu,1,4,&ast; Edward S Lu,1 Rebecca Zeng,1 Itika Garg,1 Raviv Katz,1 Rongrong Le,1,5 Jay C Wang,1 Demetrios G Vavvas,1,2 Deeba Husain,1,2 Joan W Miller,1,2 David Wu,1,2 John B Miller1,2 1Harvard Retinal Imaging Lab, Massachusetts Eye and Ear, Boston, MA, USA; 2Department of Ophthalmology, Harvard Medical School, Boston, MA, USA; 3Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China; 4Eye Center of Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 5Wenzhou Medical University Affiliated Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: John B Miller, Retina Service, Mass, Eye and Ear Infirmary, Harvard Medical School, 243 Charles St, Boston, MA, 02114, USA, Tel +1 (617) 573-3750, Fax +1 (617) 573-3698, Email john_miller@meei.harvard.eduPurpose: Retinal artery occlusion (RAO) is an ophthalmic emergency that can lead to poor visual outcomes and is associated with an increased risk of stroke and cardiovascular events. Wide-field swept-source OCT-A (WF SS-OCTA) can provide quick and non-invasive angiographic information with a wide field of view. Here, we looked for associations between OCT-A vascular imaging metrics and vision in RAO patients.Methods: Patients with diagnoses of central (CRAO) or branched retinal artery occlusion (BRAO) were included. 6mm × 6mm Angio and 15mm × 15mm AngioPlex Montage OCT-A images were obtained for both eyes in each patient using Zeiss Plex Elite 9000 WF SS-OCTA device. Each 6mm × 6mm image was divided into nine Early Treatment Diabetic Retinopathy Study (ETDRS) subfields. Non-perfusion area (NPA) was manually measured using 15mm × 15mm images. A linear regression model was utilized to identify correlation between imaging metrics and vision. P-values less than 0.05 were considered as statistically significant.Results: Twenty-five subjects were included. For RAO eyes, there was a statistically significant inverse correlation between retinal thickness as well as superficial capillary plexus (SCP) vessel density (VD) and vision. An inverse correlation was found between deep capillary plexus (DCP) VD and vision without statistical significance. There was a positive correlation between choroidal thickness as well as choroidal volume and vision without statistical significance. No significant correlation was found between the metrics and vision in contralateral eyes. For NPA and vision, no significant correlation was identified.Conclusion: This is the first study to investigate the utility of WF SS-OCTA in RAO and to demonstrate correlations between retinal vascular imaging metrics and visual outcomes. The results of this study provide a basis to understand the structural changes involved in vision in RAO and may guide management of RAO and prevention of cerebral stroke and cardiovascular accidents.Keywords: WF SS-OCTA, RAO, BRAO, CRAO, ETDRS, ARI network

Dehai Wu,1,&ast; Guanqun Liao,2,&ast; Yuanfei Yao,3,&ast; Lining Huang,4 Bowen Dong,5 Yong Ma,6 Guangchao Yang6 1Department of Hepatic Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 2Department of Hepatobiliary Surgery, Foshan Hospital Affiliated to Southern Medical University, Foshan, People’s Republic of China; 3Key Laboratory of Tumor Immunology in Heilongjiang, Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, People’s Republic of China; 4Department of Hepatobiliary Surgery, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, People’s Republic of China; 5Department of Biochemistry & Molecular Biology, Harbin Medical University, Harbin, People’s Republic of China; 6Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Department of Hepatic Minimal Invasive Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guangchao Yang; Yong Ma, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Department of Hepatic Minimal Invasive Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People’s Republic of China, Tel +86 13796000181 ; +86 13836006500, Email guangchaoyang@hrbmu.edu.com; doctormy80@163.comBackground: The aim of this study is to explore the role of acetyl-CoA acyltransferase 2 (ACAA2) in the progression of hepatocellular carcinoma (HCC).Methods: Bulk RNA data and single-cell RNA data were acquired from The Cancer Genome Atlas and Gene Expression Omnibus. Both in vitro and in vivo studies were used to determine the effect of ACAA2 on the progression of HCC, and RNA sequencing analysis was performed to explore the mechanism.Results: We found downregulation of ACAA2 was involved in the malignant progression of HCC. The patient with low ACAA2 level had an immunosuppressive microenvironment in the HCC and predicted to have a poor prognosis. Decreased ACAA2 facilitated HCC proliferation and metastasis by activating the nuclear factor-κB (NFκB) signaling pathway. And increased CXCL1 induced by NFκB signaling pathway might be responsible for low level of ACAA2 related immunosuppressive microenvironment. Furthermore, the expression of ACAA2 was also detected in immune cells. The expression of ACAA2 in CD4+TCF7+T, CD4+FOXP3+T, CD8+GZMK+T, and CD8+KLRD1+T cells was inversely correlated with the composition of CD8+PDCD1+T cells in HCC. This effect might be due to the CCL5-CCRs and HLA-E-KLRCs ligand-receptor networks.Conclusion: In a conclusion, downregulated ACAA2 promoted the progression of hepatocellular carcinoma and might be participated in the formation of immunosuppressive microenvironment. ACAA2 could be served as a favorable indicator for the prognosis of HCC and an ideal biomarker for immunotherapy.Keywords: hepatocellular carcinoma, acetyl-CoA acyltransferase 2, immunotherapy, nuclear factor-κB signaling pathway, biomarker

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

Min Gao,1,2,&ast; Yongwen Li,3,&ast; Hua Huang,4,&ast; Yaguang Fan,3 Ruifeng Shi,4 Lianchun Su,5 Chen Chen,3 Xuanguang Li,4 Guangsheng Zhu,4 Di Wu,4 Peijun Cao,4 Hongyu Liu,3 Jun Chen,3– 5 Shirong Kang1 1Department of Thoracic Surgery, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot, 010010, People’s Republic of China; 2Inner Mongolia Medical University, Hohhot, 010010, People’s Republic of China; 3Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 4Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, 300052, People’s Republic of China; 5Department of Thoracic Surgery, First Affiliated Hospital of Shihezi University School of Medicine, Shihezi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Chen; Shirong Kang, Email huntercj2004@qq.com; bssbzzk2013@163.comBackground: Genetic susceptibilities play a large role in the pathogenesis of lung cancer (LC). The polycomb repressive complex 2 (PRC2) is a conserved chromatin-associated complex that represses gene expression and is crucial for proper organismal development and gene expression patterns. Despite PRC2 dysregulation has been observed in various human cancers, the relationship between PRC2 genes variants and lung cancer risk remains largely unexplored.Methods: To investigate the association between single nucleotide polymorphisms (SNPs) in PRC2 genes and the risk of developing LC, we genotyped blood genomic DNA from 270 LC patients and 452 healthy individuals of Chinese Han ethnicity using the TaqMan™ genotyping technique.Results: We found that rs17171119T>G(adjusted odds ratio (OR) = 0.662, 95% CI: 0.467– 0.938, P < 0.05), rs10898459 T>C(adjusted OR = 0.615, 95% CI: 0.4– 0.947, P < 0.05), and rs1136258 C>T(adjusted OR = 0.273, 95% CI: 0.186– 0.401, P < 0.001) were significantly associated with a reduced risk of LC. Stratified analysis revealed a protective effect of rs17171119 in both male and female patients, specifically those with lung adenocarcinoma (LUAD). Additionally, rs1391221 showed a protective effect in both the LUAD and lung squamous cell carcinoma (LUSC) groups, while rs1136258 exhibited a protective effect in both females and males, as well as in both LUAD and LUSC groups. Furthermore, analysis of The Cancer Genome Atlas (TCGA) dataset revealed expression levels of EED and RBBP4 in both LUAD and LUSC.Conclusion: This study provides evidence that allelic variants in EZH2, EED, and RBBP4 may act as protective factors against LC development and could serve as genetic markers associated with susceptibility to LC.Keywords: the polycomb repressive complex 2, single nucleotide polymorphism, lung cancer

Wei L, Chen Z, Cheng N, et al. Onco Targets Ther. 2020;13:2459–2468 At the author’s request, we, the Editors and Publisher of OncoTargets and Therapy, have retracted the following article. Following publication of the article, the authors raised concerns regarding the duplication of images from Figures 2, 3 and 4 with images from other unrelated articles. Specifically, Images for Figure 2C have been duplicated with images for Figure 2G from Huang L, Jian Z, Gao Y, et al. RPN2 promotes metastasis of hepatocellular carcinoma cell and inhibits autophagy via STAT3 and NF-κB pathways. Aging (Albany NY). 2019;11:6674–6690. https://doi.org/10.18632/aging.102167; Figure 3C from Cai C, Min S, Yan B, et al. MiR-27a promotes the autophagy and apoptosis of IL-1β treated-articular chondrocytes in osteoarthritis through PI3K/AKT/mTOR signaling. Aging (Albany NY). 2019; 11:6371–6384. https://doi.org/10.18632/aging.102194 (RETRACTED) and Figure 3E from Song Z, Wang H, Zong F, Zhu C, Tao Y. MicroRNA-506 regulates apoptosis in retinoblastoma cells by targeting sirtuin 1. Cancer Manag Res. 2019;11:8419–8429. https://doi.org/10.2147/CMAR.S211122. Images for Figure 3A have been duplicated with images for Figures 4A and 6E from Liu X, Zhang P, Li Y, Zhao N, Han H. The AMPK‑mTOR axis requires increased MALAT1 expression for promoting granulosa cell proliferation in endometriosis. Experimental and Therapeutic Medicine. 2021;21:21. https://doi.org/10.3892/etm.2020.9453 Figure 5A from Cai et al (2019); Figures 5A and 5B from Li M, Meng X, Li M. MiR-126 promotes esophageal squamous cell carcinoma via inhibition of apoptosis and autophagy. Aging (Albany NY). 2020;12:12107–12118. https://doi.org/10.18632/aging.103379; Figure 6A from Kumari S, Mehta SL, Li PA. Glutamate Induces Mitochondrial Dynamic Imbalance and Autophagy Activation: Preventive Effects of Selenium. PLoS ONE. 2012;7(6):e39382. https://doi.org/10.1371/journal.pone.0039382 and Figure 6G from Huang L et al (2019). Images for Figures 3B and 4B have been duplicated with images for Figures 3c and 3d from Zhou J, Zhang Y, Han Z, et al. RETRACTED ARTICLE: miR-506 contributes to malignancy of cutaneous squamous cell carcinoma via targeting of P65 and LAMC1. Cell Cycle. 2019;18(3):333–345, DOI: 10.1080/15384101.2019.1568747; Figures 2A, 4C and 4F from Ouyang L, Yi L, Li J, et al. SIRT6 overexpression induces apoptosis of nasopharyngeal carcinoma by inhibiting NF-κB signaling. Onco Targets Ther. 2018;11:7613–7624. https://doi.org/10.2147/OTT.S179866 and Figures 6a and 6b from Zhong R, Li S, Fang K, Yang L, Wang L. microRNA-1225 inhibit apoptosis of pancreatic cancer cells via targeting JAK1. Cell Cycle. 2019;18(9):990–1000, DOI: 10.1080/15384101.2019.1608127. The authors were cooperative and explained that after becoming aware of the concerns, they evaluated the study and were unable to explain the image duplication, provide original data or verify the validity of the reported findings. As verifying the validity of published work is core to the integrity of the scholarly record, the authors found it necessary to retract the article and we, the Editors and Publisher, agree with this decision. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Peixv Chen,1,2,&ast; Yiting Li,1,2,&ast; Di Wu,1,2 Fang Liu,1 Chao Cao1 1Department of Respiratory and Critical Care Medicine, Key Laboratory of Respiratory Disease of Ningbo, First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315000, People’s Republic of China; 2Medical College of Ningbo University, Ningbo, Zhejiang, 315000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chao Cao, Department of Respiratory and Critical Care Medicine, Key Laboratory of Respiratory Disease of Ningbo, First Affiliated Hospital of Ningbo University, 59 Liuting Road, Ningbo, Zhejiang, 315000, People’s Republic of China, Email caocdoctor@163.comBackground: Many studies have shown that active smoking leads to an increasing incidence of chronic obstructive pulmonary disease (COPD). However, studies interested in the effects of secondhand smoke exposure (SHS exposure) on COPD were less or underappreciated.Methods: A systematic review and meta-analysis was conducted to investigate the association between SHS exposure and the risk of COPD. Three databases (PubMed, Embase and Web of Science) were searched to obtain data. After assessing the study quality, stratified analyses were performed according to the region, gender, and duration of exposure. Cochran’s Q and I2 were utilized for heterogeneity assessment. To assess publication bias, we used a funnel plot and Egger’s test.Results: A total of 15 studies (6 cross-sectional studies, 6 case-control studies, and 3 cohort studies) with 25,592 participants were involved in this meta-analysis. This study showed that SHS exposure was associated with an increased risk of COPD (odds ratio (OR): 2.25, 95% CI: 1.40– 3.62, I2 = 98%, p < 0.01 for heterogeneity based on a random-effects analysis model), especially in those with a longer time exposure of more than 5 years was 4.38 (95% CI: 1.28– 15.00, I2 = 89%, p < 0.01 for heterogeneity based on a random-effects analysis model). In addition, SHS exposure also increases the risk of COPD in women (odds ratio (OR): 2.02, 95% CI: 1.52– 2.67, I2 = 0%, p = 0.89 for heterogeneity based on a random-effects analysis model).Conclusion: The findings suggest that SHS exposure is associated with the risk of COPD, especially for individuals with a long time exposed.Trial Registry: Prospero CRD42022329421.Keywords: COPD, secondhand smoke exposure, systemic review, meta-analysis

Jianhua Zeng,1,2,&ast; Shilang Xiong,3,&ast; Jingyu Zhou,4 Peng Wei,4 Kai Guo,1 Feng Wang,1 Min Ouyang,4 Zhisheng Long,5 Aihua Yao,6 Jingtang Li,7 Long Xiong,4 Desheng Wu1 1Department of Spine Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200092, China; 2Department of Spine Surgery, People’s Hospital of Ganxian District, Ganzhou, Jiangxi, 341100, China; 3Department of Orthopedics, the First Affiliated Hospital of Nanchang University, Artificial Joints Engineering and Technology Research Center of Jiangxi Province, Nanchang, Jiangxi, 330006, China; 4Department of Orthopedics, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China; 5Department of Spine Surgery, Jiangxi Provincial People’s Hospital the First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, 330006, China; 6School of Materials Science and Engineering, Tongji University, Shanghai, 201804, China; 7Department of Traumatology, Jiangxi provincial People’s Hospital the First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, 330006, China&ast;These authors contributed equally to this workCorrespondence: Desheng Wu; Long Xiong, Email 1300116@tongji.edu.cn; ncxionglong2@126.comIntroduction: Bone tissue engineering is a promising method to treat bone defects. However, the current methods of preparing composite materials that mimic the complex structure and biological activity of natural bone are challenging for recruitment of bone marrow mesenchymal stem cells (BMSCs), which affects the application of these materials in situ bone regeneration. Hollow hydroxyapatite microspheres (HHMs) possess a natural porous bone structure, good adsorption, and slow release of chemokines, but have low ability to recruit BMSCs and induce osteogenesis. In this study, The HHM/chitosan (CS) and recombinant human C-X-C motif chemokine ligand 13 (rhCXCL13)-HHM/CS biomimetic scaffolds that optimize bone regeneration and investigated their mechanism of BMSC recruitment and osteogenesis through cell and animal experiments and transcriptomic sequencing.Methods: Evaluate the physical characteristics of the HHM/CS and rhCXCL13-HHM/CS biomimetic scaffolds through Scanning Electron Microscopy (SEM), X-Ray Diffraction (XRD), and the cumulative release curve of rhCXCL13. Transwell migration experiments and co-culture with BMSCs were conducted to study the recruitment ability and osteogenic differentiation of the scaffolds. Transcriptomic sequencing was performed to analyze the osteogenic differentiation mechanism. The osteogenesis and bone healing performance were evaluated using a rabbit radial defect model.Results: SEM demonstrated that the rhCXCL13-HHM/CS scaffold comprised hydroxyapatite microspheres in a porous three-dimensional network. The rhCXCL13 showed excellent sustained release capability. The rhCXCL13-HHM/CS scaffold could recruit BMSCs and induce bone regeneration. Transcriptome sequencing and experimental results showed that the osteogenesis mechanism of rhCXCL13-HHM/CS was through the PI3K-AKT pathway. In vivo, the rhCXCL13-HHM/CS scaffold significantly promoted osteogenesis and angiogenesis at 12 weeks after surgery.Conclusion: The rhCXCL13-HHM/CS scaffold demonstrates excellent potential for BMSC recruitment, osteogenesis, vascularized tissue-engineered bone reconstruction, and drug delivery, providing a theoretical basis for material osteogenesis mechanism study and promising clinical applications for treating large bone defects.Keywords: bone regeneration, rhCXCL13-HHM/CS scaffold, recruit BMSCs, transcriptome sequencing, bone repair

Yong Zhou,1,&ast; Lei Yang,1,&ast; Yifu Lyu,1,&ast; Di Wu,1 Ying Zhu,1 Jingjing Li,1 Dabo Jiang,1 Xiaofei Xin,1 Lifang Yin1– 4 1Department of Pharmaceutics, China Pharmaceutical University, Nanjing, People’s Republic of China; 2NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, China, Nanjing, People’s Republic of China; 3Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Nanjing, People’s Republic of China; 4State Key Laboratory of Natural Medicine, China Pharmaceutical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lifang Yin; Xiaofei Xin, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, People’s Republic of China, Tel +86 (025)83271018, Email lifangyin@cpu.edu.cn; xxin@cpu.edu.cnPurpose: Oxidative stress, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and adenosine signaling are factors associated with psoriatic inflammation. Topical delivery of methotrexate (MTX) has become an option to overcome the side effects caused by systemic therapy in psoriasis, leading to the suppression of NF-κB activation through boosting adenosine release. However, thickened psoriatic skin is the primary restriction against local drug delivery.Methods: In this study, a ROS responsive MTX prodrug (MTX-TK-HA) was synthesized with the feature of CD44 mediated active targeting to hyperproliferative keratinocytes. MTX prodrug and PLA-mPEG were formulated by nano-precipitation method to develop the MTX-TK-HA/PLA-mPEG nanoassemblies. To achieve painless transdermal delivery, a dissolving microneedle was applied for direct loading of these nanoassemblies by micromolding technique. The particle size, zeta potential, ROS-responsiveness, permeability, and mechanical strength of nanoassemblies and microneedle arrays were determined, respectively. Then, MTT assay, immunoblot analysis, ELISA assay, flow cytometry, and histological staining were utilized to thoroughly evaluate the efficacy of nanoassemblies-loaded microneedles in an imiquimod-induced psoriatic mouse model.Results: Nanoassemblies-loaded microneedle arrays were capable of significantly penetrating imiquimod-induced psoriatic epidermis in mice. The efficient topical delivery of these nanoassemblies was achieved by potent mechanical strength and hyaluronic acid as the dissolvable matrix for microneedle arrays. CD44-mediated endocytosis enabled the intracellular uptake of nanoassemblies in keratinocytes, and methotrexate was released from MTX-TK-HA with ROS stimuli, followed by suppressing the proliferation of epidermal cells via NF-κB pathway blockade.Conclusion: In a psoriatic mouse model, nanoassemblies loaded microneedle arrays relieve inflammatory skin disorders via regulation of adenosine and NF-κB signaling. Our study offered a rational design for the transdermal delivery of hydrophobic agents and defined an effective therapeutic option for psoriasis treatment.Keywords: psoriasis, ROS-responsiveness, microneedle, topical delivery, methotrexate

Long Feng,1,&ast; Di Wu,2,&ast; Ping Ping,3,&ast; Jieqiong Lin,4,&ast; Yali Zhao,5 Yao Yao,6,7 Pei Zhang,8 Shihui Fu2,9 1Department of Anesthesiology, Hainan Hospital of Chinese People’s Liberation Army General Hospital, Sanya, People’s Republic of China; 2Department of Cardiology, Hainan Hospital of Chinese People’s Liberation Army General Hospital, Sanya, People’s Republic of China; 3General Station for Drug and Instrument Supervision and Control, Joint Logistic Support Force of Chinese People’s Liberation Army, Beijing, People’s Republic of China; 4Department of Pathology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, People’s Republic of China; 5Central Laboratory, Hainan Hospital of Chinese People’s Liberation Army General Hospital, Sanya, People’s Republic of China; 6Center for the Study of Aging and Human Development and Geriatrics Division, Medical School of Duke University, Durham, NC, USA; 7Center for Healthy Aging and Development Studies, National School of Development, Peking University, Beijing, People’s Republic of China; 8School of Life Science, Beijing Institute of Technology, Beijing, People’s Republic of China; 9Department of Geriatric Cardiology, Chinese People’s Liberation Army General Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shihui Fu, Department of Cardiology, Hainan Hospital of Chinese People’s Liberation Army General Hospital, Sanya, People’s Republic of China, Email xiaoxiao0915@126.com Yali Zhao, Central Laboratory, Hainan Hospital of Chinese People’s Liberation Army General Hospital, Sanya, People’s Republic of China, Email zhaoyl301@163.comPurpose: Age related cognitive function (ARCF) is of increasing concern in an aging population. Few studies have examined the relationships between ARCF and antibody expression or blood pressure, particularly in older populations. Large sample sizes are needed to elucidate these relationships to inform better strategies for identification and prevention of cognitive decline. The present study was designed to investigate these relationships in Chinese oldest-old and centenarian adults.Patients and Methods: A household survey was performed that included 436 centenarians and 520 oldest-old adults (80– 99 years) residing in 16 cities and counties of Hainan province, China. ARCF was assessed using the mini-mental state examination.Results: The median age of participants in this study was 92 years, with a range of 80 to 116 years. Females accounted for 68.5% (655) of the participant pool. Multivariate linear regression analysis showed that age [Exp(B): − 0.220, 95% confidence interval (CI): − 0.270–-0.169], female gender [Exp(B): − 3.459, 95% CI:-4.458–-2.460], Han ethnicity [Exp(B): − 1.732, 95% CI: − 2.693–-0.772], serum creatinine [Exp(B): − 0.019, 95% CI: − 0.037–-0.001], immunoglobulin light chain KAP [Exp(B): − 0.008, 95% CI: − 0.015– 0.000], and anti-ribonucleoprotein antibody [Exp(B): − 6.393, 95% CI: − 10.898–-1.887] were negatively associated with ARCF (P < 0.05). Coronary artery disease [Exp(B): 1.957, 95% CI: 0.170– 3.744] and diastolic pressure [Exp(B): 0.041, 95% CI: 0.002– 0.079] were positively associated with ARCF (P < 0.05).Conclusion: ARCF was positively associated with diastolic pressure and negatively associated with antibody expression in Chinese oldest-old and centenarian adults.Keywords: age related cognitive function, antibody expression, centenarian, diastolic pressure, oldest-old

Linli Xing,1,&ast; Yiyi Chen,2– 4,&ast; Xia Ling,2– 5 Dandan Wu,6 Lu Sun,2– 4 Jingrong Lin,7 Yan Chen2– 4 1Office of Nutrition and Diet, Xixi Hospital of Hangzhou, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 3Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of China; 4Regional Medical Center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 5Department of Laboratory Medicine, Blood Center of Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of China; 6Department of Infectious Diseases, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 7Department of Respiratory Medicine, the Affiliated People’s Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Chen, Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, People’s Republic of China, Tel +86-571-8600-6142, Email chenyan@zju.edu.cn Jingrong Lin, Department of Respiratory Medicine, The Affiliated People’s Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China, Email 44964808@qq.comAbstract: The detection of novel livestock-associated methicillin-resistant Staphylococcus aureus (MRSA) is important in both clinics and livestock. In this study, we report a MRSA-infected patient who was associated with livestock as a butcher, from whom we collected two MRSA strains FJ0318 and FJ0322. To further understand the correlation between these MRSA isolates and livestock, whole-genome sequencing and comparative genomic analyses were performed for these two isolates. Phylogenetic analysis revealed that these two strains were homologous. Multilocus sequence typing showed that these two strains belong to ST7, which is a common lineage in retail meat and meat products in China. The genetic islands in FJ0318 and FJ0322 were different from those in other common clones, such as ST59, ST8, and ST5. A mosaic plasmid with a sequence identical to that of the plasmid pE2 from livestock was found in strain FJ0318. Additionally, a novel prophage island was identified on the chromosome. Furthermore, the sequence of the island was similar to that of phage SP6 identified in livestock. ST7 may originate from livestock and be transmitted to communities, causing invasive infections.Keywords: MRSA, ST7, whole genome analysis, livestock

Xiao Zhao,1– 3,&ast; Ying Wang,1– 4,&ast; Tingting Zhu,1– 3 Huili Wu,1– 3 Diya Leng,1– 3 Zhiguo Qin,5 Yan Li,6 Daming Wu1– 3 1Department of Endodontics, the Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Jiangsu Province Key Laboratory of Oral Diseases, Nanjing, People’s Republic of China; 3Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, People’s Republic of China; 4Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, People’s Republic of China; 5Nanjing Medical University, the First Clinical Medical College, Jiangsu Province Hospital, Nanjing, People’s Republic of China; 6State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Daming Wu, Department of Endodontics, the Affiliated Stomatological Hospital of Nanjing Medical University, Jiangsu Province Key Laboratory of Oral Diseases, Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, 1 Shanghai Road, Nanjing, 210029, People’s Republic of China, Tel +086 025-69593056, Fax +086 025-86516414, Email wdming@njmu.edu.cnBackground: Mesoporous calcium-silicate nanoparticles (MCSNs) are advanced biomaterials that have been used to control drug delivery for many years. Ultrasmall Prussian blue nanoparticles (UPBNPs) showed high peroxidase and catalase-like activities. This study evaluated the antibacterial and antibiofilm properties, mechanism and cytotoxicity of UPBNPs-MCSNs composites synthesized by both as precursors.Methods: UPBNPs-MCSNs were prepared and characterized. The antibacterial effect of UPBNPs-MCSNs was evaluated by the MTT assay and CFU counting method, and their biosafety was tested by CCK8. Then explore the antibacterial mechanism, including TEM observation of bacterial morphology, and detection of bacterial ROS, LPO and GSH levels. The antibiofilm activity of UPBNPs-MCSNs was tested by E. faecalis biofilm model in human roots. The roots were pretreated with materials and cultured with E. faecalis, and the survival of E. faecalis on the root canal wall was observed by SEM and CLSM.Results: The results showed that UPBNPs-MCSNs had potent antibacterial and antibiofilm activities. They can aggregate on the dentin surface and significantly inhibit E. faecalis adhesion and colonization. Their antibacterial activity is as effective as NaClO and calcium hydroxide (CH), can significantly prolong the time of bacterial colonization than CH, but have lower cytotoxicity to normal cells. We found that UPBNPs-MCSNs trigger a like classic ferroptosis pathway in bacteria. UPBNPs-MCSNs can induce bacteria to produce ROS and LPO, and reduce GSH level. Moreover, we observed that the metal ions chelator and the antioxidant could block their antibacterial activity.Conclusion: These results reveal that UPBNPS-MCSNs have high antibacterial and antibiofilm, and can mediate the bacterial redox pathway ROS/GSH like the classical pathway of ferroptosis, providing a theoretical basis for them to develop into a safe and effective novel root canal disinfectant.Keywords: antibacterial activity, root canal disinfectant, mesoporous materials, reactive oxygen species, Prussian blue

Dehua Wu1 &ast;, Baojuan Ye1 &ast;, Chunyan Tang,2,3 Jingjing Xue,2,3 Qiang Yang,1 Fei Xia1 1School of Psychology, School of Education, Center of Mental Health Education and Research, Jiangxi Normal University, Nanchang, People’s Republic of China; 2Health Education and Counseling Center, Nanchang Medical College, Nanchang, People’s Republic of China; 3Health Education and Counseling Center, Jiangxi Health Vocational College, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunyan Tang, Nanchang Medical College/Jiangxi Health Vocational College, No. 689 Huiren Avenue, Xiaolan Economic Development Zone, Nanchang, Jiangxi Province, Email tangchunyan@ncmc.edu.cnBackgrounds and Aims: Self-compassion is important for authentic-durable happiness, particularly during the COVID-19 pandemic. To better understand the potential complexity of effects, this study sought to explore (a) the mediating role of meaning of life in the association between self-compassion and authentic-durable happiness and (b) the moderating role of COVID-19 burnout in the relationship between self-compassion and meaning of life.Methods: We conducted a cross-sectional online survey study in China from February 1 to 14, 2021. Online survey questionnaire technique and convenience sampling method were used for data collection. Participants anonymously completed the measures of self-compassion scale short form, COVID-19 burnout scale, meaning in life questionnaire, and subjective authentic-durable happiness scale. The data were examined utilizing Pearson’s r correlations and moderated mediation analysis.Results: This study included 1165 Chinese college students (Mage = 19.68 years, SD = 1.37). Self-compassion (M = 3.39, SD = 0.49) was significantly positively associated with authentic-durable happiness (M = 3.82, SD = 0.66) (r = 0.45, p < 0.001), and mediation analyses indicated that meaning of life (M = 4.65, SD = 0.86) partially mediated this association (indirect effect = 0.103, SE = 0.016, 95% CI = [0.073, 0.135]). Moderated mediation analysis further revealed that COVID-19 burnout (M = 1.87, SD = 0.72) buffered the relation between self-compassion and meaning of life (β = − 0.05, p < 0.033).Discussion and Conclusion: Findings of this study shed light on a correlation between self-compassion and authentic-durable happiness. In addition, this study underlines the importance of intervening in COVID-19 burnout among college students and enhancing the meaning of life in order to promote and safeguard authentic-durable happiness in the setting of COVID-19.Keywords: coronavirus, students, self-compassion, meaning of life, happiness, psychological burnout

Wen Bao,1,&ast; Deqing Wu,1,&ast; Wei Han,1 Rui Kong,1 Nan Wang,1 Jie Lu2 1Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, 200072, People’s Republic of China; 2Department of Gastroenterology, Gongli Hospital, School of Medicine, Shanghai University, Shanghai, 200135, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Lu, Email kennisren@hotmail.comBackground: Extracorporeal shock wave lithotripsy (ESWL) and endoscopic retrograde cholangiopancreatography (ERCP) are the main treatments for chronic calcific pancreatitis (CCP). However, clinical outcomes remain unclear for patients underwent different interventional therapies based on these two techniques.Methods: A total of 125 patients with CCP who underwent ESWL, ERCP or a combined treatment at two medical centers from January 2019 to January 2020 were considered. Patients were divided into four groups according to intervention types (ESWL-alone, ERCP-alone, ESWL-ERCP and ERCP-ESWL). A retrospective survey with a follow-up for 2 years was conducted. The main outcome measures were postoperative complications, abdominal pain and re-intervention during the follow-up. Possible prognostic factors were evaluated by multivariate analysis.Results: Patients in ESWL-ERCP group had the highest complete pain relief rate (49.28%), the lowest pain frequency (1 time/year) and intensity (VAS-score, 1.84± 1.93) during the follow-up, which were statistically significant compared with the other three groups. ESWL-ERCP group also had the lowest postoperative complication rate (6%), while the highest complication rate (16%) was observed in ESWL-alone group. Both ESWL-alone and ESWL-ERCP group had significant lower frequencies of re-interventions (0.44 ± 0.73, 0.57± 0.98, respectively) after the initial treatments. An analysis of treatment-based prognostic factors found significant interactions between age, course of CCP, max pancreatic duct stone diameter, calcium, glycosylated hemoglobin (HbA1c) and triglyceride.Conclusion: ESWL-ERCP was considered as the most effective interventional therapy for CCP with a better safety in a two-year follow-up. Prognostic factors may help to determine the patients who benefit by this technique.Keywords: chronic calcific pancreatitis, ESWL, ERCP, follow-up

Dan Wu,1 Tingzhong Yang,2 Fabian Herold,3 Daniel L Hall,4,5 Notger Mueller,3 Albert Yeung,4,6 Arthur F Kramer,7,8 Tianyou Guo,1 Liye Zou1 1Body-Brian-Mind Laboratory, School of Psychology/The Shenzhen Humanities & Social Sciences Key Research Bases of the Center for Mental Health, Shenzhen University, Shenzhen, 518060, People’s Republic of China; 2Women’s Hospital/Center for Tobacco Control Research, Zhejiang University School of Medicine, Hangzhou, 310058, People’s Republic of China; 3Research Group Degenerative and Chronic Diseases, Movement, Faculty of Health Sciences Brandenburg, University of Potsdam, Potsdam, 14476, Germany; 4Department of Psychiatry, Harvard Medical School, Boston, MA, 02115, USA; 5Mongan Institute, Massachusetts General Hospital, Boston, MA, 02114, USA; 6Depression Clinical and Research Program, Massachusetts General Hospital, Boston, MA, 02114, USA; 7Beckman Institute, University of Illinois, Urbana, IL, 61801, USA; 8Center for Cognitive & Brain Health, Northeastern University, Boston, MA, 02115, USACorrespondence: Tianyou Guo, Body-Brian-Mind Laboratory, School of Psychology/The Shenzhen Humanities & Social Sciences Key Research Bases of the Center for Mental Health, Shenzhen University, Shenzhen, Guangdong, 518060, People’s Republic of China, Email gtyou168@126.comPurpose: The objectives of this study were to examine the psychometric properties of the Uncertainty Stress Scale (USS) and to compare the usefulness of two versions of the scale (USS-4 and USS-10) among a large community-based sample of Chinese adults.Participants and Methods: The Uncertainty Stress Scale was validated in 904 community residents (mean age: 32.71 ± 10.99; male: 41.7%) through an online survey conducted in February 2020. Psychometric properties of reliability (Cronbach’s alpha), construct validity (confirmatory factor analysis), and criterion validity (correlation and ROC curve analyses) were evaluated using established benchmarks. To validate the USS, we used the Chinese version of the Perceived Stress Scale (CPSS). In addition, sensitivity, specificity, and suitable cutoff values of the two versions of USS were determined.Results: Both versions of the USS had high internal consistency (USS-10: 0.941; USS-4: 0.851). Confirmatory factor analyses supported a one-factor structure for both measures. Both USS-4 and USS-10 scores were significantly positively correlated with CPSS scores, indicating acceptable criterion validity.Conclusion: The findings of the current study confirmed that the psychometric properties of two Chinese versions of USS are acceptable. Furthermore, the 4-item USS was as effective as the 10-item USS for the measurement of uncertainty stress in our community-based sample of Chinese adults suggesting that the USS-4 is a time-efficient alternative to the USS-10 which can be used when the circumstances require a time-efficient instrument (eg, in epidemiological studies with a large test battery).Keywords: Validation, Uncertainty Stress Scale, Community-based Sample

Jia Xu,1,2,&ast; Jiahui Yu,1,3,&ast; Wei Jiao,3 Guangxing Chen,1 Lijuan Liu,1 Mingying Zhang,1 Danbin Wu1 1Department of Rheumatology, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Department of Gynecology, Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, People’s Republic of China; 3First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Danbin Wu, Department of Rheumatology, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China, Email danbinwu@126.comBackground: Recently, research on rheumatoid arthritis (RA) has made rapid progress and grown rapidly. It is a challenge to comprehensively understand RA research and hotspots. The aim of this study was to explore the current status and research trends of RA through bibliometric analysis and to provide directions for future development.Methods: Publications on RA from 2011 to 2020 were retrieved from the Web of Science Core Collection database (WoSCC). VOSviewer, CiteSpace and online bibliometric platform were used to analyze publication characteristics, including countries, institutions, journals, authors, core references, and keywords.Results: A total of 17,037 publications were included. The publications steadily increased over the 10 years. The United States (3648 publications), with the largest proportion of publications and citations, was the largest contributor. Karolinska Institutet (508) and Annals of the Rheumatoid Disease (763) were the most active institution and journal, respectively. Emery P (193) and Tanaka Y (193) were the most prolific authors, and Smolen JS ranked first among the cited authors. The most cited reference focused on recommendations for the management of RA with synthetic and biological disease-modifying antirheumatic drugs. A co-occurrence network analysis revealed four highly connected clusters of keywords in RA research, including etiology, pathology, prognosis, biomarkers and treatment of RA.Conclusion: The present study shows a systematic and comprehensive overview of the RA-related research in the past 10 years. Clinical trials on the long-term efficiency and safety of JAK inhibitors and other novel targeted drugs may be the potential research directions for future study in this field.Keywords: rheumatoid arthritis, bibliometric analysis, pain, publications, research trends

Youfeng Guo, Haihong Zhao, Jiawei Lu, Haowei Xu, Tao Hu, Desheng Wu Department of Spine Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200092, People’s Republic of ChinaCorrespondence: Desheng Wu; Tao Hu, Email wds980331@163.com; dr_hutao@tongji.edu.cnObjective: This study was designed to determine whether lymphocyte to monocyte ratio (LMR) correlated with the intervertebral disc degeneration (IDD) severity and the postoperative spinal fusion rate in patients with lumbar disc disease.Methods: 303 patients undergoing posterior lumbar decompression and fusion were retrospectively analyzed. An examination of the blood count was performed before surgery. The cumulative grade was calculated by summing the pfirrmann grades of all lumbar discs. Grouping was based on the 50th percentile of cumulative grade and spinal fusion. The relationship between LMR and IDD severity and spinal fusion was explored using correlation analyses and logistic regression models. The receiver operating characteristic (ROC) curve was performed to measure model discrimination, and Hosmer-Lemeshow (H-L) test was used to measure calibration. Meanwhile, the ROC curve evaluated the discrimination ability of LMR in predicting severe degeneration and fusion failure.Results: LMR was significantly lower in the severe degeneration group (cumulative grade > 18) than in the mild to moderate degeneration group (cumulative grade ≤ 18). Furthermore, the LMR of the fusion group was significantly higher than that of the non-fusion group. The multivariate binary logistic models revealed that LMR was an independently influencing factor of the severe degeneration and fusion failure (OR: 0.793, 95% CI: 0.638– 0.987, p = 0.038; OR: 0.371, 95% CI: 0.258– 0.532, p < 0.001). The models showed excellent discrimination and calibration. The area under the curve (AUC) of severe degeneration and fusion failure identified by LMR were 0.635 and 0.643, respectively, and the corresponding cut-off values were 3.16 and 3.90.Conclusion: LMR is significantly associated with the risk of severe disc degeneration and spinal fusion failure.Keywords: intervertebral disc degeneration, spinal fusion, lymphocyte to monocyte ratio, prognostic factor

Edward H Hu,1 Therese Buie,2 Rishma J Jensen,2 David Wu,3 Ravinder D Pamnani4 1Wolfe Eye Clinic, Marshalltown, IA, USA; 2Illinois Eye Center, Peoria, IL, USA; 3University of Illinois at Chicago, Chicago, IL, USA; 4Byers Center for Biodesign, Stanford University, Stanford, CA, USACorrespondence: Edward H Hu, Wolfe Eye Clinic, 309 East Church Street, Marshalltown, IA, USA, Tel +641 754-6200, Email ehu@wolfeclinic.comPurpose: To determine the effect of a microinterventional lens prefragmentation wire loop device (miLOOP®; Carl Zeiss Meditec AG, Oberkochen, Germany), on adverse events (AEs), cumulative dispersed energy (CDE), and vision outcomes when used before phacoemulsification of high-grade mature cataracts.Setting: Three ambulatory surgical centers in the Peoria, IL region.Design: Retrospective comparative consecutive case series; single-surgeon.Methods: Patient outcomes were compared before and after introduction of miLOOP-assisted lens fragmentation prior to phacoemulsification during cataract surgeries performed 2016‒2020. The primary outcome was intraoperative AE rate/type. Secondary outcomes included ultrasound cumulative dispersed energy (CDE) administered during phacoemulsification, postoperative AEs, and best-corrected visual acuity (BCVA).Results: Data from 765 subjects (mean age 72.9 years; 1025 eyes) comprised 524 conventional lens disassembly (Control) eyes and 501 Device eyes. One hundred percent of the cataracts in both groups were advanced WHO Grade 3+ nuclei. Significantly fewer intraoperative AEs occurred in the Device group versus Controls (2.2% and 6.3% of eyes, respectively; p=0.0011). Postoperative AE rates were comparable between groups (Controls=2.9%, Device=3.5%). Mean CDE from ultrasound was significantly reduced by 21% when the microfilament loop device was used for nuclear disassembly (9.6± 5.2 CDE units) versus Controls (11.6± 6.4 CDE units; p< 0.0001). Median postoperative BCVA was 20/25 Snellen (0.091 logMAR) in both groups. More than 70% of both Control and Device eyes had postoperative BCVA better than 20/30 Snellen.Conclusion: Microinterventional lens fragmentation was associated with lower ultrasound energy use and improved intraoperative safety than traditional unassisted surgery of advanced high-grade cataracts, while maintaining similarly acceptable postoperative complication rates and BCVA functional outcomes.Keywords: lens disassembly, phacoemulsification cataract surgery, cumulative dispersed energy, safety, microinterventional surgery, adverse events

Taoying Lu,1– 3 Jingwen Yan,4 Jianfang Chang,5 Jianxiong Cai,1– 3 Lingjia Yin,1,3,6 Jiamin Yuan,1,7 Li Huang,1,7 Yingshuai Li,8 Minghua Bai,9 Kit-Tai Hau,5 Darong Wu,1– 3 Zhimin Yang1,7 1State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 3Program for Outcome Assessment in TCM, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China; 4The Second Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 5Department of Education Psychology, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China; 6Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden; 7Health Construction Administration Center, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China; 8National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 9School of Traditional Chinese Medicine/National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of ChinaCorrespondence: Darong Wu; Zhimin Yang, State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, 111 Dade Road, Guangzhou, 510120, People’s Republic of China, Tel +86 13808869436 ; +86 13822296363, Email darongwu@gzucm.edu.cn; yangyo@vip.tom.comBackground: Body constitution is a fundamental concept in traditional Chinese medicine (TCM) for clinical diagnosis, treatment of illness, and community-based health promotion. Clinical assessment of patients’ body constitutions, however, has never been easy and consistent, even by well-trained clinicians and TCM practitioners. Therefore, questionnaires such as the popular Constitution in Chinese Medicine Questionnaire (CCMQ) can be an appealing and convenient assessment alternative. The present research borrowed advanced methodologies for questionnaire development in psychology and other social sciences to examine the performance of the CCMQ in terms of (i) the strength of relations of each item with its designated constitution, (ii) the reliabilities of each constitution, and (iii) the overall 9-constitution structure. This research provided empirical evidence to support the use of the CCMQ and proposed directions for refinement in future revisions of the CCMQ or similar measures.Methods: A total of 1571 volunteers from three villages in southern China participated in the CCMQ survey. The item characteristics, reliabilities, interconstitution correlations, and confirmatory factor analysis of the 9-body-constitution structure were examined.Results: The results generally supported the appropriateness of the clinical observations (the questionnaire items) and the CCMQ 9-constitution classification structure. Nevertheless, some relatively weaker items, item pairs with similar meanings, and highly overlapping constitutions were identified for future CCMQ revisions.Conclusion: The CCMQ measured the 9 constitutions efficiently and with reasonably good reliability and construct validity. Given the various challenges to assessing TCM body constitutions even by experienced clinicians, the CCMQ provides an appealing alternative to measure the Chinese body constitutions of healthy participants in large-scale research or community health promotion programs. The present study also demonstrated how advanced methodologies in social sciences can help validate and refine the CCMQ and similar complementary medicine measures.Keywords: Chinese constitution, body constitution, CCMQ, Constitution in Chinese Medicine Questionnaire, reliability, construct validity

Yan Zhang, Danrong Wu, Ruoqiu Wang, Min Luo, Dong Wang, Kaiyue Wang, Yi Ai, Li Zheng, Qiao Zhang, Lixin Shi Department of Endocrinology and Metabolism, Guiqian International General Hospital, Guiyang, People’s Republic of ChinaCorrespondence: Qiao Zhang; Lixin Shi, Department of Endocrinology and Metabolism, Guiqian International General Hospital, Guiyang, People’s Republic of China, Tel/Fax +86 851-86277666, Email endocrine_zq@126.com; slx1962@medmail.com.cnAbstract: Ectopic pituitary adenoma (EPA) is a pituitary adenoma unrelated to the intrasellar component and is an extremely rare disease. EPA resembles typical pituitary adenomas in morphology, immunohistochemistry, and hormonal activity, and it may present with specific or non-specific endocrine manifestations. Here, we report a rare case of ectopic adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma in the clival region. Only three patients with ACTH-secreting pituitary adenomas occurring in the clivus have been previously reported, and the present case was diagnosed as a clivus-ectopic ACTH-secreting pituitary macroadenoma. Thus, in addition to the more common organs, such as the lung, thymus, and pancreas, in the diagnosis of ectopic ACTH syndrome, special attention should be paid to the extremely rare ectopic ACTH-secreting pituitary adenoma of the clivus region.Keywords: ectopic pituitary adenoma, Cushing’s syndrome, clivus, adrenocorticotropic hormone, endocrine

Qi Han,1 Feifan Meng,1 Ming Chen,1 Xiangjun Lu,1 Deyuan Zhao,1 Dongze Wu,1 Tingting Wang,2 Rujie Qin1 1Department of Orthopedics, The First People’s Hospital of Lianyungang Affiliated to Xuzhou Medical University, Lianyungang, Jiangsu, People’s Republic of China; 2Department of Dermatology, The First People’s Hospital of Lianyungang Affiliated to Xuzhou Medical University, Lianyungang, Jiangsu, People’s Republic of ChinaCorrespondence: Rujie Qin, Department of Orthopedics, The First People’s Hospital of Lianyungang Affiliated to Xuzhou Medical University, No. 6 East Zhenhua Road, Haizhou, Lianyungang, Jiangsu, 222061, People’s Republic of China, Email gkdrqlyg@sina.comObjective: To evaluate the early clinical effect of percutaneous endoscopic transforaminal lumbar interbody fusion (PE-TLIF) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) surgery in the treatment of middle-aged and elderly patients with single-level lumbar disc herniation accompanied by lumbar instability.Methods: From January 2019 to June 2020, a total of 82 consecutive patients were categorised into PE-TLIF group and MIS-TLIF group based on different surgical methods. The visual analog scale (VAS), Oswestry disability index (ODI), Japanese Orthopaedic Association (JOA) score, perioperative objective serological index, operation time, intraoperative blood loss, time to back to work or normal life, and Modified MacNab score were used as the evaluation indexes. The differences between the two groups were analyzed and the clinical effects were compared.Results: The VAS back pain of PE-TLIF group was decreased compared to that of MIS-TLIF group in the postoperative 1 week and 1 month. The operative time in PE-TLIF group was obviously longer than that in MIS-TLIF group. The hospital stay was significantly shorter in PE-TLIF group than that in MIS-TLIF group. More intraoperative blood loss and postoperative drainage were recorded in MIS-TLIF group. Compared with MIS-TLIF, PE-TLIF surgery was associated with a shorter time to ambulation after surgery and a shorter time to back to work or normal life. Significant statistical differences were observed in IL-6, CRP, and CK on postoperative 3 days between the two groups.Conclusion: For middle-aged and elderly patients, PE-TLIF and MIS-TLIF surgery both have obvious clinical efficacy and safety. However, with less intraoperative blood loss, shorter recovery time and less injury to the patients, people undergoing PE-TLIF surgery can return to work or normal life faster. It is speculated that PE-TLIF has a higher incidence of complications and recurrence rate than that MIS-TLIF. PE-TLIF may be a better choice for middle-aged and elderly patients with single-level lumbar disc herniation.Keywords: lumbar disc herniation, minimally invasive surgery, percutaneous endoscopic transforaminal lumbar interbody fusion, minimally invasive transforaminal lumbar interbody fusion, middle-aged and elderly

Guanlin Huang, Wentao Lai, Daxing Wu, Qianliang Huang, Qi Zhong, Xinyun Ye Department of Neurosurgery, Ganzhou People’s Hospital, Ganzhou, Jiangxi, 341000, People’s Republic of ChinaCorrespondence: Xinyun Ye, Department of Neurosurgery, Ganzhou People’s Hospital, Ganzhou, Jiangxi, 341000, People’s Republic of China, Email yexinyun1270@163.comAbstract: Objective: To explore the treatment scheme for intracranial infection with Acinetobacter baumannii. Methods: We retrospective analyzed two cases of patients of intracranial infection with Acinetobacter baumannii. Results: The intracranial infection was controlled effectively by the scheme to intravenous“tigecycline + cefperazone-sulbactam”combined with intrathecal tigecycline injection, the two patients recover well with 21 months’ follow-up. Conclusions: Tigecycline-based drug scheme combined with intrathecal tigecycline injection can achieve the effect of controlling intracranial infection. Lumbar cisterna drainage tube plays a major role in controlling intracranial infection.Keywords: multidrug resistant Acinetobacter baumannii, intracranial infection, tigecycline

Yiguan Qian,&ast; Yang Li,&ast; Ke Chen,&ast; Ning Liu, Xi Hong, Di Wu, Zheng Xu, Liuhua Zhou, Luwei Xu, Ruipeng Jia, Yu-Zheng Ge Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ruipeng Jia; Yu-Zheng Ge, Department of Urology, Nanjing First Hospital, Nanjing Medical University Nanjing, Jiangsu, People’s Republic of China, Tel +86-15850675660, Email ruipengj@163.com; geyuzheng@njmu.edu.cnBackground: Polo-like kinase 1 (PLK1) belongs to polo-like kinases family and affects cell cycles. However, the role of PLK1 in some malignant tumors remains unclear.Methods: To obtain a comprehensive view of PLK1 expression patterns, public databases including The Cancer Genome Atlas, Cancer Cell Line Encyclopedia, the Genotype-Tissue Expression, and human cell landscape databases were employed. The correlation of PLK1 expression with prognosis, immune infiltrations, immune checkpoint genes, tumor mutational burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), and DNA methylation was examined. Besides, we validated the results of clear cell renal cell carcinoma (ccRCC) in two cohorts, with quantitative real-time PCR, Western blot, and loss-of-function experiments.Results: By mining public datasets, we discovered that PLK1 expression in tumor tissues and cancer cell lines displayed heterogeneity compared to normal controls across different cancers. Besides, high expression of PLK1 results in shorter survival time in 15 cancer types, especially in ccRCC. PLK1 expression showed strong association with immune cell infiltration and immune checkpoint genes across cancer types. Moreover, we identified a strong association between PLK1 expression and TMB, MSI MMR, and DNA methylation. PLK1 was validated to be highly expressed in ccRCC tissues and promote ccRCC cell proliferation, migration, invasion, and cell cycle. Mechanistically, PLK1 could regulate forkhead box protein M1 and target cell cycle-associated genes to participate in cell cycle control.Conclusion: PLK1 has important prognostic value and is associated with tumor immunity across cancer types including ccRCC.Keywords: PLK1, pan-cancer analysis, ccRCC, biomarker, tumor immunity