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Xiyan Yu,1,* Difei Wu,2,* Fangzhou Li,3 Wei Qiao,4 Xujiao Chen3 1The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Geriatrics, the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, People’s Republic of China; 4The First Department of Health Care, China-Japan Friendship Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xujiao Chen, Department of Geriatrics, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, 310003, People’s Republic of China, Email lily197459@163.com Wei Qiao, The First Department of Health Care, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China, Email viviqiao601@sina.comBackground: Cardiovascular disease (CVD) has become the leading cause of death worldwide. High muscle mass can reduce the incidence and mortality of CVD. In recent years, increasing attention has been given to the relationship between intrinsic capacity (IC) and CVD. This study aims to explore the relationship between the decline of IC, muscle strength, and muscle quality in older patients with CVD, providing a new method and basis for early recognition of IC decline in the older adults.Methods: This cross-sectional study included 475 older individuals from communities in Zhejiang. General data were collected, and a comprehensive geriatric assessment (CGA) was conducted. Participants with CVD were divided into three groups: IC retention, IC impairment, and IC significantly impaired. Bioelectrical impedance analysis (BIA) measurements were completed. Student’s t-test or non-parametric tests (Mann–Whitney) were used to analyze the correlation between IC and muscle-related indicators. The best cutoff values were obtained using ROC curve analysis.Results: Compared to non-CVD patients, CVD patients were older, more educated, and had higher rates of polypharmacy and comorbidity. IC decreased more significantly in CVD patients. Age (P=0.001), Fried (P=0.024), and GDS-5 (P=0.002) increased with the severity of IC decline. ADL (P=0.002), MMSE (P=0.000), MNA-SF (P=0.000), SARC-Calf (P=0.026), waist circumference (P=0.037), and muscle quality (P=0.010) decreased with the decline in IC. When IC decreased, the cutoff values for hand grip strength, waist circumference, and muscle quality were 25.45 kg, 72.55 cm, and 3.05, respectively. When IC decreased significantly, the cutoff values were 17.15 kg, 71.55 cm, and 2.28, respectively.Conclusion: The results of this study showed that in patients with CVD, the hand grip strength and muscle quality of patients with IC injury were lower than those of patients with IC retention.Keywords: CVD, intrinsic capacity, muscle quality more...

Dan Wu,1 Fang Li,2 Feifei Yang,3 Jun Liu4 1Department of Dermatology, Peking University First Hospital Ningxia Women and Children’s Hospital (Ningxia Hui Autonomous Region Maternal and Child Health Hospital), Yinchuan City, Ningxia Hui Autonomous Region, 750011, People’s Republic of China; 2Department of Pathology, Peking University First Hospital Ningxia Women and Children’s Hospital (Ningxia Hui Autonomous Region Maternal and Child Health Hospital), Yinchuan City, Ningxia Hui Autonomous Region, 750011, People’s Republic of China; 3Department of Dermatology, Tongzhou Maternal & Child Health Hospital of Beijing, Beijing City, 101101, People’s Republic of China; 4Department of Critical Care Medicine, the First People’s Hospital of Yinchuan, Yinchuan City, Ningxia Hui Autonomous Region, 750001, People’s Republic of ChinaCorrespondence: Jun Liu, Department of Critical Care Medicine, the First People’s Hospital of Yinchuan, No. 2 Liqun West Street, Xingqing District, Yinchuan City, Ningxia Hui Autonomous Region, 750001, People’s Republic of China, Email JunLiunnu@outlook.comBackground: Numerous lines of evidence suggest that neuropeptide Y (NPY) is critically involved in the modulation of neuropathic pain. Postherpetic neuralgia (PHN) is characterized by prolonged duration, severe pain, and significant treatment resistance, substantially impairing patients’ quality of life. This study aims to evaluate the potential of plasma NPY levels in patients with PHN as a predictive biomarker for the development of this condition.Methods: Between February 2022 and December 2023, 182 patients with herpes zoster (HZ) were recruited. Thirty-eight volunteers with no history of HZ were also recruited as controls. Clinical factors, NPY, brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF) were assessed within 3 days of healing. Logistic regression analysis was used to predict the development of PHN.Results: NPY levels were lower and BDNF and NGF were higher in HZ patients than those in controls. Only NPY levels were lower in patients with PHN (n = 59) compared with those without PHN (n = 123). Age, acute pain severity, and rash area were independent predictors of PHN, as were NPY levels. The area under the curve (AUC) to predict the development of PHN based on the combination of NPY levels and clinical factors was 0.873 (95% CI: 0.805 to 0.940), and the AUC was 0.804 based on only clinical factors (AUC: 0.804, 95% CI: 0.728 to 0.881).Conclusion: Low plasma NPY levels are a predictor of developing PHN in patients with HZ. Combining clinical predictors with NPY levels may improve predictive accuracy.Keywords: neuropeptide Y, herpes zoster, postherpetic neuralgia, sensory neurons more...

Chunlei Tan,1 Jinling Xu,2 Shiyuan Zhang,1 Shuqiang Liu,1 Xiaotian Yang,1 Danping Wu,1 Boqian Yu,1 Yuanxi Huang1 1Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, People’s Republic of China; 2Endoscope Department, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, People’s Republic of ChinaCorrespondence: Yuanxi Huang, Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, People’s Republic of China, Tel/Fax +86-0451-86298053, Email rxwk@163.comPurpose: The current investigation is to assess FOXP3 expression in breast cancer patients and evaluate the predictive significance of FOXP3.Patients and Methods: A cohort of 313 cases between January 2015 and November 2015 were enrolled this research. Immunohistochemistry (IHC) assay was utilized to detect the expression levels of FOXP3 in primary breast carcinoma specimens. These patients were separated into two groups by semiquantitative scoring approach. Chi-square test and Fisher’s exact test were conducted to investigate the correlations between FOXP3 expression in tumors and clinicopathological variables. Kaplan–Meier method and Log rank test were utilized to generate survival curves for disease-free survival (DFS) and overall survival (OS). The independent factors were examined using Cox regression analysis. Nomogram models were created for assessing DFS and OS rates.Results: Depending on the levels of FOXP3 expression in tumors, these patients were categorized into two groups: low FOXP3 expression (174 cases) and high FOXP3 expression (139 cases). The patients exhibiting low levels of FOXP3 expression in tumors demonstrated a longer survival duration contrasted with those with high expression (DFS: 88.75 vs 65.87 months, χ2=36.1100, P< 0.0001; OS: 89.70 vs 78.37 months, χ2=32.4900, P< 0.0001). Multivariate analysis revealed that FOXP3 was a significant prognostic factor [DFS: hazard ratio (HR): 2.822, 95% CI: 1.595– 4.992, P< 0.0001; OS: HR: 3.232, 95% CI: 1.812– 5.763, P< 0.0001]. The good predictive clinical utility of FOXP3-based nomograms within the threshold probability range for different survival rates was demonstrated by calibration curve and decision curve analyses.Conclusion: FOXP3 expression serves as a crucial prognostic indicator in breast cancer patients, and may aid preoperative evaluation in clinical practice.Keywords: breast cancer, FOXP3, chemotherapy, radiotherapy, survival more...

Xiaolan Guo,1 Dansen Wu,1 Xiaoping Chen,2 Jing Lin,1 Jialong Chen,1 Liming Wang,1 Songjing Shi,1 Huobao Yang,1 Ziyi Liu,3 Donghuang Hong1,4 1Department of Critical Care Medicine, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, People’s Republic of China; 2Computer Science and Mathematics, Fujian University of Technology, Fuzhou, Fujian, People’s Republic of China; 3Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Fujian Provincial Key Laboratory of Critical Care Medicine, Fuzhou, Fujian, People’s Republic of ChinaCorrespondence: Ziyi Liu, Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, No. 160, Pujian Road, Pudong District, Shanghai, 200127, People’s Republic of China, Email liu-ziyi@sjtu.edu.cn Donghuang Hong, Department of Critical Care Medicine, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, No. 134, Dongjie Street, Gulou District, Fuzhou, Fujian, 350001, People’s Republic of China, Email hongdh2003@fjmu.edu.cnPurpose: The objective of this study was to identify the risk factors associated with Carbapenem-resistant Enterobacteriaceae (CRE) colonization in intensive care unit (ICU) patients and to develop a predictive risk model for CRE colonization.Patients and Methods: In this study, 121 ICU patients from Fujian Provincial Hospital were enrolled between January 2021 and July 2022. Based on bacterial culture results from rectal and throat swabs, patients were categorized into two groups: CRE-colonized (n = 18) and non-CRE-colonized (n = 103). To address class imbalance, Synthetic Minority Over-sampling Technique (SMOTE) was applied. Statistical analyses including T-tests, Chi-square tests, and Mann–Whitney U-tests were employed to compare differences between the groups. Feature selection was performed using Lasso regression and Random Forest algorithms. A Logistic regression model was then developed to predict CRE colonization risk, and the results were presented in a nomogram.Results: After applying SMOTE, the dataset included 198 CRE-colonized patients and 180 non-CRE-colonized patients, ensuring balanced groups. The two groups were comparable in most clinical characteristics except for diabetes, previous emergency department admission, and abdominal infection. Eight independent risk factors for CRE colonization were identified through Random Forest, Lasso regression, and Logistic regression, including Acute Physiology and Chronic Health Evaluation (APACHE) II score > 16, length of hospital stay > 31 days, female gender, previous carbapenem antibiotic exposure, skin infection, multi-site infection, immunosuppressant exposure, and tracheal intubation. The risk prediction model for CRE colonization demonstrated high accuracy (87.83%), recall rate (89.9%), precision (85.6%), and an AUC value of 0.877. Patients were categorized into low-risk (0– 90 points), medium-risk (91– 160 points), and high-risk (161– 381 points) groups, with corresponding CRE colonization rates of 1.82%, 7.14%, and 58.33%, respectively.Conclusion: This study identified independent risk factors for CRE colonization and developed a predictive model for assessing the risk of CRE colonization.Keywords: carbapenem-resistant Enterobacteriaceae, intensive care unit, colonization, risk factors, risk prediction model more...

Yaonan Hong,1,2,&ast; Qi Liu,1,2,&ast; Chuanao Xin,1,2,&ast; 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&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 +86-571-86620325, 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 more...

Yanye Tu,1 Hui Gao,1 Rongqing Zhao,1 Jiliang Yan,1 Diyu Wu2 1Clinical Laboratory of Ningbo Medical Centre Lihuili Hospital, Ningbo University, Ningbo, Zhejiang Province, People’s Republic of China; 2School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, People’s Republic of ChinaCorrespondence: Hui Gao, Email gaoh711@126.comObjective: This study aims to investigate the association between antimicrobial resistance genes and virulence factors in ST11 and non-ST11 types of CR-KP in bloodstream infections in the intensive care unit, providing a theoretical basis for infection control and clinical diagnosis and treatment.Methods: From January 2021 to June 2023, samples of Klebsiella pneumoniae from bloodstream infections were collected at our hospital, focusing on those resistant to carbapenems. The resistance genes, housekeeping genes, and virulence genes were identified through PCR and analyzed using the GrapeTree software to perform MLST-based minimum spanning tree typing.Results: Among the 85 CR-KP cases, 61.18% were of the ST11 type, predominantly of the KL64 capsular type; non-ST11 types were mainly ST15, accounting for 25.88%, predominantly of the KL5 capsular type. The carriage rates of virulence genes such as rmpA2, entB, silS, kpn, iucA, peg-344, and terB were significantly higher in the ST11 group than in the non-ST11 group. The primary carbapenemase identified was class A enzyme blaKPC-2, with a higher carriage rate in the ST11 group. Drug susceptibility tests showed that the resistance rates for cefepime, ertapenem, nitrofurantoin, amikacin, and gentamicin were also higher in the ST11 group, consistent with the resistance genotype findings.Conclusion: The study reveals that ST11 type CR-KP in intensive care unit bloodstream infections exhibits stronger resistance and higher virulence compared to non-ST11 types, posing significant challenges to clinical treatment. Thus, strict control over the use of carbapenem antibiotics is essential to prevent the spread of resistant plasmids.Keywords: intensive care unit, bloodstream infections, ST11 CR-KP, Non-ST11 CR-KP, resistance genes, virulence genes more...

Dong Wu,1,&ast; Bingyu Long,1,&ast; Bangxiao Huang,1,&ast; Xiaomei Zhong,1 Xiaoer Chen,1 Xiaoping Shen,1 Qiu Huang,1 Wenchao Zhang,1 Jiayuan Wu,2 Min Chen,1 Dongming Li,1 Bin Wu,1 Dong Lv,3 Dan Huang,1 Xuanna Zhao1 1Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, People’s Republic of China; 2Department of Clinical Research, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, People’s Republic of China; 3Department of Psychiatry, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuanna Zhao; Dan Huang, Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, No. 57, South of Renmin Road, Zhanjiang, Guangdong, 524013, People’s Republic of China, Email 792665234@qq.com; 287538250@qq.comBackground: Education and living environment are related to mental health. But the independent and combined effects of them on mental health among patients with chronic obstructive pulmonary disease (COPD) are uncertain.Methods: The independent and combined effects of education and living environment on mental health were assessed by binary logistic regression in 1064 COPD patients. Additive interaction was assessed with the relative excess risk ratio (RERI), attribution percentage (AP), and synergy index (SI).Results: Our results shown that low education level and urban living environment were independently associated with higher risks for anxiety (odds ratio [OR]: 1.56, 95% confidence interval [CI] 1.06– 2.29 and OR:2.15, 95% CI 1.51– 2.05) or depression (OR:1.62, 95% CI 1.17– 2.27 and OR: 2.01, 95% CI 1.46– 2.75) among COPD patients. The combination effect of them was also associated with higher risks for anxiety (OR: 7.90, 95% CI 3.83– 16.29, P < 0.001) or depression (OR: 11.79, 95% CI 5.77– 24.10, P < 0.001) among these patients. Furthermore, we observed strong synergistic additive interactions between them for anxiety (SI: 11.57, 95% CI 1.41– 95.27; RERI: 6.31, 95% CI 1.60– 11.01; AP: 0.8, 95% CI 0.66– 0.94) and depression (SI: 31.31, 95% CI 1.59– 617.04; RERI: 10.44, 95% CI 2.66– 18.23; AP: 0.89, 95% CI 0.8– 0.97).Conclusion: Low education levels and living in urban areas had an independent and synergistic effects on mental health among COPD patients.Keywords: anxiety, China, COPD, depression, education, living environment more...

Taoying Lu,1– 3 Mingyue Fan,1 Jianxiong Cai,4 Aolin Liu,1 Qianwen Xie,2,3 Xiaowen Zhou,1 Bei Chang,1 Lingjia Yin,2,3,5 Guli Jiang,6 Bin Sun,7 Wenyi Tang,7 Darong Wu4 1The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Outcome Assessment Research Team in Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 3Outcome Assessment Research Team in Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China; 4State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 5Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden; 6Department of Scientific Research, Guangzhou Cadre Health Management Center, Guangzhou, People’s Republic of China; 7Department of Traditional Chinese Medicine, Guangzhou Cadre Health Management Center, Guangzhou, People’s Republic of ChinaCorrespondence: Darong Wu, 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, Email darongwu@gzucm.edu.cnBackground: Dampness syndrome is a basic syndrome of many major and chronic diseases. Early screening and identification of dampness syndrome are important. The Dampness Syndrome Scale of Chinese Medicine (DSSCM) was developed to measure the occurrence and severity of dampness syndrome. The measurement characteristics of the DSSCM should be further validated. The objective of this study is to evaluate the reliability and validity of the DSSCM based on a cross-sectional survey.Methods: The development of DSSCM was based on the traditional Chinese medicine (TCM) theory, expert consensus and clinical investigations. Participants were recruited from Guangdong Provincial Hospital of Chinese Medicine and Guangzhou Cadre Health Management Center in Guangdong Province, China. All participants completed the baseline questionnaire and DSSCM. The reliability of the DSSCM was evaluated by internal consistency reliability and test–retest reliability. The factor structure was tested with confirmatory factor analysis (CFA), while discriminant validity was evaluated by calculating the difference between the total score of the DSSCM and its four dimensions for participants with or without dampness syndrome. We used a clinician’s diagnosis of dampness syndrome as a criterion to evaluate the criterion validity. Multivariate regression analysis was used to analyze the associations among gender, age, height, and weight and dampness syndrome.Results: A total of 880 participants were enrolled for psychometric validation and 869 participants were included in the final analyses after exclusion. The mean age of the participants was 42.62± 12.86 years. The Cronbach’s alpha coefficients for the four dimensions of the DSSCM were 0.809, 0.891, 0.816 and 0.780. The ICCs for the four dimensions of the DSSCM were 0.806, 0.674, 0.780 and 0.760. For validity, the results showed that the DSSCM had good content validity, discriminant validity and criterion validity. For the CFA, the root mean square error of approximation (RMSEA) was 0.091; the standardized root mean square residual (SRMR) was 0.074; the comparative fit index (CFI) was 0.766; and the Tucker–Lewis index (TLI) was 0.745. Weight was found to be associated with the total scores of the DSSCM and its three dimensions.Conclusion: The DSSCM has good reliability and validity to support its use as a tool for assessing the severity of dampness syndrome. This study provides empirical evidence for future updates to the DSSCM.Keywords: dampness syndrome, dampness syndrome scale of Chinese medicine, reliability, validity more...

Junzi Chen,&ast; Yumin Xiang,&ast; Rong Bao, Yuyi Zheng, Yingxi Fang, Jiajia Feng, Di Wu, Xiaojie Chen Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, School of Pharmaceutical Sciences, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, 310053, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaojie Chen; Di Wu, Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, School of Pharmaceutical Sciences, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, People’s Republic of China, Email chenxiaojie0902@163.com; wudichem@zju.edu.cnIntroduction: Breast cancer ranks among the most prevalent cancers in women, characterized by significant morbidity, disability, and mortality. Presently, chemotherapy is the principal clinical approach for treating breast cancer; however, it is constrained by limited targeting capability and an inadequate therapeutic index. Photothermal therapy, as a non-invasive approach, offers the potential to be combined with chemotherapy to improve tumor cellular uptake and tissue penetration. In this research, a mesoporous polydopamine-coated gold nanorod nanoplatform, encapsulating doxorubicin (Au@mPDA@DOX), was developed.Methods: This nanoplatform was constructed by surface coating mesoporous polydopamine (mPDA) onto gold nanorods, and doxorubicin (DOX) was encapsulated in Au@mPDA owing to π-π stacking between mPDA and DOX. The dynamic diameter, zeta potential, absorbance, photothermal conversion ability, and drug release behavior were determined. The cellular uptake, cytotoxicity, deep penetration, and anti-tumor effects were subsequently investigated in 4T1 cells. After that, fluorescence imaging, photothermal imaging and pharmacodynamics studies were utilized to evaluate the anti-tumor effects in tumor-bearing mice model.Results: This nanoplatform exhibited high drug loading capacity, excellent photothermal conversion and, importantly, pH/photothermal dual-responsive drug release behavior. The in vitro results revealed enhanced photothermal-facilitated cellular uptake, drug release and tumor penetration of Au@mPDA@DOX under near-infrared irradiation. In vivo studies confirmed that, compared with monotherapy with either chemotherapy or photothermal therapy, the anti-tumor effects of Au@mPDA@DOX are synergistically improved.Conclusion: Together with good biosafety and biocompatibility, the Au@mPDA@DOX nanoplatform provides an alternative method for safe and synergistic treatment of breast cancer. Keywords: breast cancer, synergistic therapy, polydopamine, gold nanorod, chemotherapy more...

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 more...

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 more...

Xiawan Yang,1– 3,&ast; Yingying Shen,1– 3,&ast; 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&ast;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 more...

Chuanyun Tang,1,&ast; Kexun Zhou,2,&ast; Di Wu,1,&ast; 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&ast;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 more...

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 more...

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 more...

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 more...

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 more...

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 more...

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 more...

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 more...

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 more...

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 more...

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 more...

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 more...

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 more...

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 more...

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 more...

The ultra-low thermal expansion coefficient α makes the Fe-Ni Invar alloys useful in various applications. Their low strength and low Curie temperature Tc are, however, limiting factors. Interestingly, some Fe-based bulk metallic glasses (BMGs), with inherent high strength, exhibit the clear Invar effect. In particular, the (Fe71.2B24Y4.8)96Nb4 BMG has the lowest α among Fe-based BMGs, but it unfortunately also has the lowest Tc. In this work, silicon was added into this alloy with the aim to elevate Tc while maintaining a low α. It was found that when silicon partially substituted boron, Tc did not increase significantly but α did, which is not ideal. On the other hand, when silicon partially substituted yttrium and niobium and especially niobium, Tc increased significantly while α did not, which is close to the ideal scenario. When 3% of niobium was substituted by silicon, Tc reached the maximum value of 296 °C while α remained a low value of 7.4 × 10−6/°C. Comparing to the Fe-Ni Invar alloy, although this BMG has an inferior α, it has much higher Tc (+115 °C) and strength (∼9 times), presenting a potential for application as a new Invar material with moderate (low) thermal expansion, high operating temperature, and high strength. [ABSTRACT FROM AUTHOR] more...

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 more...

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 more...

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 more...

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 more...

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 more...