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Huabin Wang,1– 4 Rui Zhang,1,3,4 Jing Xu,1,3,4 Min Zhang,1,3,4 Xueyun Ren,1,3,4 Yuhui Wu5 1Department of Pediatrics, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, People’s Republic of China; 2Postdoctoral Mobile Station, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 3Jining Key Laboratory for Prevention and Treatment of Severe Infection in Children, Affiliated Hospital of Jining Medical University, Jining, People’s Republic of China; 4Shandong Provincial Key Medical and Health Discipline of Pediatric Internal Medicine, Affiliated Hospital of Jining Medical University, Jining, People’s Republic of China; 5Department of Pediatric Intensive Care Unit, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of ChinaCorrespondence: Xueyun Ren; Yuhui Wu, Email renxueyun2006@163.com; wyuhoo@163.comObjective: Identifying high-risk children with poor prognoses during the early stages of sepsis and providing timely and appropriate interventions are imperative. The objective of this study was to develop a prognostic prediction model for pediatric sepsis utilizing the neutrophil to lymphocyte and platelet ratio (NLPR).Methods: A multivariable logistic regression analysis was conducted to investigate the association between the NLPR and in-hospital mortality among septic children upon admission. To minimize the potential confounding factors that could introduce bias, a propensity score matching analysis was employed. Subsequently, a nomogram prediction model was developed to assess the risk of in-hospital mortality in septic children, incorporating the NLPR as a key factor. The performance of this prediction model was then evaluated.Results: A total of 230 septic children were enrolled in the study. Multivariate logistic regression analysis revealed that the NLPR was an independent risk factor for in-hospital mortality, with an odds ratio of 8.31 (95% CI 3.69– 18.68). The finding remained consistent after propensity score matching analysis. A nomogram prediction model was developed that incorporates the NLPR, arterial blood lactate level, and Pediatric Critical Illness Score (PCIS). Among the various models, this nomogram exhibited the highest area under the curve (AUC) value of 0.831. The calibration curve demonstrated good agreement between the predicted and observed outcomes. Decision curve analysis indicated that the prediction model outperformed the PCIS. Internal validation of the model yielded an AUC value of 0.824 and a kappa value of 0.420, indicating its reliability and accuracy.Conclusion: The NLPR serves as an independent risk factor for in-hospital mortality among septic children. The nomogram prognostic prediction model could effectively guide clinicians in accurately predicting the prognosis of septic children, thus enabling timely and effective treatment interventions.Keywords: pediatric sepsis, NLPR, prognosis, clinical prediction model

Yijia Guo,1– 3,&ast; Ruyun Zhang,4,&ast; Xinling Gan,5 Erli Wang,6 Shuihua Lu,7 Hui Jiang,3 Hongfei Duan,8 Zhengzhou Yuan,9 Weimin Li,2,3,10 Yong Liu1 1Department of Neurology, Chengdu Medical College, The First Affiliated Hospital, Chengdu, People’s Republic of China; 2Beijing Municipal Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, People’s Republic of China; 3Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Department of Emergency, Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China; 5Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 6Department of Radiology, The First People’s Hospital of Longquanyi District, Chengdu, People’s Republic of China; 7National Clinical Research Center for Infectious Diseases, Guangdong Provincial Clinical Research Center for Tuberculosis, Shenzhen Third People’s Hospital, Southern University of Science and Technology, Shenzhen, People’s Republic of China; 8Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People’s Republic of China; 9Department of Neurology, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 10National Tuberculosis Clinical Laboratory of China, Beijing Key Laboratory in Drug Resistance Tuberculosis Research, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People’s Republic of China&ast;These authors contributed equally to this work as first authorsCorrespondence: Yong Liu, Chengdu Medical College, The First Affiliated Hospital, No. 278, Middle Section, Baoguang Avenue, Xindu District, Chengdu, 610500, People’s Republic of China, Email 410578100@qq.comBackground: The predictors associated with clinical outcomes in patients with tuberculous meningitis (TBM) remain unclear. We aimed to analyse the relationship between systemic inflammation and clinical outcomes, as well as to explore whether systemic inflammation level influences the effectiveness of dexamethasone on treatment.Methods: Between January 2011 and December 2021, TBM patients admitted to five hospitals were observed consecutively. Baseline and post-treatment systemic inflammation levels were calculated using the neutrophil-lymphocyte-ratio (NLR). Generalized linear mixed models were employed to identify predictors of clinical outcomes. Propensity score matching and subgroup analyses were conducted to evaluate the effect of dexamethasone on treatment outcomes across different NLR levels.Results: A total of 1203 TBM patients were included in the study. During the follow-up, 144 (13.6%) participants experienced early neurological deterioration within 7 days after admission, and 345 (28.67%) exhibited poor functional outcome at the 12-month follow-up. Multivariate analysis revealed that post-treatment NLR was significantly associated with early neurological deterioration (OR=1.25; 95% CI, 1.14– 1.33; P< 0.001), and poor outcome (OR=1.34; 95% CI, 1.26– 1.45; P< 0.001). After propensity score matching, dexamethasone treatment was not associated with early neurological deterioration (OR=0.83; 95% CI, 0.42– 1.66; P=0.610) or poor outcome (OR=1.22; 95% CI, 0.49– 2.11; P=0.490) in the highest quartile of post-treatment NLR. The effect of dexamethasone on treatment outcomes did not significantly vary with disease severity stratification.Conclusion: Elevated systemic inflammation is an independent risk factor for neurological outcome in TBM patients. Further studies are required to investigate systemic inflammation in more severely affected population to better predict the outcomes following anti-inflammatory therapies.Keywords: tuberculous meningitis, systemic inflammation, neurological outcome

Yujia Huang,1,2,&ast; Yinan Li,2,&ast; Tong Su,3 Hao Wang,2 Shuyu Xu,2 Jingzhou Xu,2 Siqi Zheng,4 Jing Du,2 Yajing Wang,2 Ruike Zhang,2 Yao Meng,2 Xin Guo,2 Lei Xiao,2 Yunxiang Tang3 1Psychology Department, The Second Naval Hospital of Southern Theater Command, Sanya, People’s Republic of China; 2Department of Medical Psychology, Faculty of Psychology, Naval Medical University, Shanghai, People’s Republic of China; 3Faculty of Psychology, Naval Medical University, Shanghai, People’s Republic of China; 4Department of Psychology, TongJi University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Xiao; Yunxiang Tang, Email xiaolei0237@163.com; tangyun7633@sina.comObjective: To investigate the effects of sleep quality, sleep deprivation, and napping on facial emotion recognition (FER) accuracy and speed.Methods: This research included a cross-sectional study (102 qualified participants) and a randomized controlled study (26 in the napping group and 24 in the control group). The stimuli for the FER task were obtained from the Chinese Facial Affective Picture System (CFAPS). Four facial expressions (fearful, disgusted, sad, and angry) were used. The Pittsburgh Sleep Quality Index (PSQI), Self-Rating Anxiety Scale, and Self-Rating Depression Scale were used to measure participants’ sleep quality and psychological conditions. In Study 1, FER ability was compared between good and poor sleepers. In Study 2, all participants were sleep-deprived for one night, and completed the FER task before and after sleep deprivation. After different interventions (ie, napping for one hour, or walking around for ten minutes), the participants completed the third FER task.Results: Study 1: Poor sleepers were able to recognize sad expressions more accurately compared with good sleepers. Study 2: 30-h sleep deprivation had no significant effect on the accuracy (ACC). Napping after sleep deprivation improved the FER ACC of upper-face expressions and marginally significantly improved the FER ACC of disgusted expressions.Conclusion: Better sleep quality was linked to lower FER accuracy, particularly in recognizing sad expressions, while no significant differences in recognition speed were observed. Additionally, 30 hours of sleep deprivation did not affect FER accuracy, but napping after sleep deprivation improved accuracy for upper-face and marginally for disgusted expressions.Keywords: facial emotion recognition, sleep quality, facial features, facial emotion, sleep deprivation, sleep loss

Fanlingzi Shen,1,2,&ast; Yu Song,3,&ast; Yan Qiang,1,&ast; Xiangjin Gao,1 Siyuan Li,2 Rui Zhang,1 Zhongzhi Gao,1 Bin Li,1 Wencheng Jiang,4 Ruiping Wang1,2 1Clinical Research Center, Shanghai Skin Diseases Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Department of Dermatology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Department of Traditional Chinese Medicine, Shanghai Skin Diseases Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wencheng Jiang, Department of Traditional Chinese Medicine, Shanghai Skin Diseases Hospital, Medical School, Tongji University, 1278 Baode Road, Shanghai, 200443, People’s Republic of China, Email drjiangwencheng@163.com Ruiping Wang, Clinical Research & Innovation Transformation Center, Shanghai Skin Diseases Hospital, Medical School, Tongji University, 1278 Baode Road, Shanghai, 200443, People’s Republic of China, Email w19830901@126.comPurpose: Tobacco smoking and alcohol drinking are positively associated with psoriasis prevalence and disease severity. Researches focusing on the influence of smoking and drinking on the treatment efficacy of psoriasis are still limited, especially their interaction effect. This study aims to explore the interactive effects of smoking and drinking on the treatment efficacy in psoriasis patients.Patients and Methods: From 2021 to 2022, we recruited 560 patients with psoriasis from Shanghai Skin Diseases Hospital. Demographic and clinical features as well as treatment efficacy were collected through questionnaire interview and physical examination during patient’s hospital visit at week 0, week 4 and week 8. Logistic regression model was used to explore the influence of smoking and drinking on the treatment efficacy in psoriasis patients, and multiplicative and additive interaction models were used to verify the interaction effect of smoking and drinking on the treatment efficacy.Results: The prevalence of smoking and drinking among psoriasis patients was respectively 43.8% and 25.4%, and 19.6% of them with both smoking and drinking. Logistic regression analysis showed that patients with smoking (OR=7.78, 95% CI: 5.26~11.49) and drinking (OR=5.21, 95% CI: 3.29~8.27) had higher risk of experiencing the failure to achieve PASI75 at week 8, even with the adjustment of confounders. Moreover, multiplicative as well as additive model showed that tobacco smoking interacted with alcohol drinking which influenced the treatment efficacy more severely (OR=12.74, 95% CI: 7.16~22.67). The proportion of PASI75 achievement in female patients (OR=19.54) and patients with methotrexate (OR=28.31) and biologics (OR=21.61) were more likely being affected by smoking and drinking.Conclusion: Tobacco smoking and alcohol drinking could increase the failure of PASI75 achievement in patients with psoriasis, individually and interactively. We recommend that dermatologists should educate patients to pay attention to the negative effects of smoking and drinking, encourage them to quit, and thus improve the treatment efficacy.Keywords: psoriasis, tobacco smoking, alcohol drinking, interaction, additive model, multiplicative model

Mengyue Sun,1 Yuanyuan Liu,2 Shan Tang,2 Yiming Li,2 Ridong Zhang,2 Li Mao2 1Department of Geratology, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huaian, Jiangsu, 223300, People’s Republic of China; 2Department of Endocrinology, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huaian, Jiangsu, 223300, People’s Republic of ChinaCorrespondence: Li Mao, Email maoli_mail@126.comAim: This study investigated differences in gut flora between osteoporosis (OP) patients and healthy individuals using 16S rDNA sequencing. The correlation between differential flora abundance and bone mineral density (BMD) was analyzed, and key flora and potential mechanisms associated with OP were explored.Methods: Forty-three OP patients and twenty-four healthy volunteers were recruited. Gender, age, height, weight, and BMD data were collected. DNA from fecal samples was extracted for 16S rDNA sequencing. The Kruskal–Wallis test assessed differences in gut flora composition, while LEfSe analysis identified significant flora. Spearman correlation analysis examined the relationship between differential flora and BMD, and PICRUSt predicted pathways involved in OP.Results: Significant differences in microbial composition were found between the two groups. Klebsiella, Escherichia-Shigella, and Akkermansia were biomarkers in OP patients, with Faecalibacterium in the healthy group. Akkermansia abundance negatively correlated with lumbar BMD, while Klebsiella and Escherichia-Shigella negatively correlated with femoral neck and hip BMD. Faecalibacterium showed a positive correlation with BMD. Functional predictions indicated differences in metabolism-related pathways between the groups.Conclusion: Gut flora differed significantly between OP patients and healthy individuals. Akkermansia, Klebsiella, and Escherichia-Shigella could serve as diagnostic biomarkers for OP, highlighting the potential of gut flora in OP diagnosis and treatment.Keywords: osteoporosis, intestinal flora, 16S rDNA

Xin Guo,1,&ast; Ying Xu,1,&ast; Yao Meng,1,2,&ast; Hao Lian,1,&ast; Jingwen He,1 Ruike Zhang,1 Jingzhou Xu,1 Hao Wang,1 Shuyu Xu,1 Wenpeng Cai,1 Lei Xiao,1 Tong Su,3 Yunxiang Tang3 1Department of Medical Psychology, Faculty of Psychology, Naval Medical University, Shanghai, People’s Republic of China; 2Department of Diving and Hyperbaric Medical Research, Naval Special Medical Center, Naval Medical University, Shanghai, People’s Republic of China; 3Faculty of Psychology, Naval Medical University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunxiang Tang, Email tangyun7633@sina.comBackground: Napping deprivation in habitual nappers leads to cognitive impairment. The ameliorative effect of acute aerobic exercise has been demonstrated for this post-cognitive impairment. However, it is still unclear which intensity of aerobic exercise is the most effective and how long this improvement can be sustained.Methods: Fifty-eight healthy adults with a chronic napping habit were randomly assigned to four intervention groups after undergoing nap deprivation: a sedentary control group, a low-intensity exercise group (50– 59% maximum heart rate, HRmax), a moderate-intensity exercise group (60– 69% HRmax), and a high-intensity exercise group (70– 79% HRmax). Working memory (N-back task), vigilance (Psychomotor Vigilance Task, PVT), and response inhibitory capacity (Go/NoGo task) were measured.Results: Regression analyses showed a quadratic trend between exercise intensity and working memory reaction time and accuracy (F =3.297– 5.769, p < 0.05, R2 =10.7– 18.9%). The effects of exercise were optimal at low-intensity. There was a significant quadratic trend between exercise intensity and PVT lapse (F =4.314, p =0.042, R² =7.2%). The effect of exercise increased with higher intensity. Prolonged observation found that the effect of low-intensity exercise on working memory was maintained for 2 hours.Conclusion: The effect of low-intensity exercise might be underestimated. Low-intensity exercise significantly improved working memory performance, and the effects could be maintained throughout the afternoon. In contrast, the effects of high-intensity exercise were unlikely to be maintained and might even have negative effects. Future researchers can broaden the categories of participants to enhance the external validity and collect diverse physiological indicators to explore related physiological mechanisms.Keywords: exercise intensity, executive function, habitual nappers, nap deprivation, working memory

Juncai Lv,1,&ast; Weiwei Yan,1,&ast; Ran Zhang,1 Xi Chen,1,2 Ziyuan Ren,1,2 Dawei Chen,1 Jinming Yu1 1Department of Radiation Oncology and Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 2Cheeloo College of Medicine, Shandong University Cancer Center, Jinan, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinming Yu; Dawei Chen, Department of Radiation Oncology and Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China, Tel +86-531-8798-4777, Fax +86-531-8798-4079, Email sdyujinming@163.com; dave0505@yeah.netPurpose: There exists a dearth of research concerning non-small cell lung cancer (NSCLC) patients experiencing overall progressive disease concomitant with shrinking lesions after immunotherapy. This is a special type of mixed response. We aim to evaluate the clinical characteristics and treatment options of these patients during immunotherapy.Patients and Methods: We categorized patients into two groups: Progressive Disease with Mixed Responses (PDMR) (n = 31) and Progressive Disease with None Mixed Responses (PDNMR) (n = 144), depending on whether at least one target lesion had shrunk by ≥ 30% at the point of overall progression. Computed tomography scans and magnetic resonance imaging were utilized to evaluate the clinicopathological significance of these patients, and a multivariate analysis was conducted to scrutinize the clinical characteristics and prognosis-influencing factors in these patients.Results: Patients in the PDMR group had worse staging and a greater proportion of previous radiotherapy. The median overall survival (mOS 22 vs 36.4 months; P = 0.019) and median progression-free survival (mPFS 5.83 vs 9.03 months; P = 0.031) of the PDMR group were shorter than PDNMR group. Longer subsequent OS with continued immunotherapy after PDMR compared with patients who do not continue with immunization after PDMR (mOS 23.9 vs 6.5 months; P = 0.024).Conclusion: PDMR was primarily observed in stage IV patients and previously irradiated patients. OS and PFS were inferior in patients with PDMR compared to patients with PDNMR. The continuation of immunotherapy in PDMR patients could extend their survival.Keywords: non-small cell lung cancer, immunotherapy, mixed response, progression

Ran Zhang,1,2 Ya-Jie Lei,1,2 Sheng-Yue Wen,1,2 Jian Pang,1,2 Yue-Long Cao,1,2 Min Zhang,1,2 Hong-Sheng Zhan,1,2 Xun Lin,3 Bo Chen1,2 1Shi’s Center of Orthopedics and Traumatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Institute of Orthopedics and Traumatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Bo Chen; Xun Lin, Tel +86-21-20256519, Email cbm818@shutcm.edu.cn; linxund@163.comPurpose: To prove more accurately that Chinese herbal bath therapy may be a safe, effective, simple alternative treatment modality for knee OA, we designed a randomized, double-blind, placebo-controlled trial to explore the effectiveness of SSBD for the relief of pain, daily activities, and quality of life in patients with knee OA.Patients and Methods: A single-center, 52-week, randomized controlled trial of SSBD versus placebo is being performed. A total of 200 patients with symptomatic knee OA will be randomly allocated to the SSBD treatment or placebo intervention group for 4 weeks. The two groups of patients are allowed to steam and bathe their knees once every other day, using one packet of SSBD each time, for 30 minutes, 3 times a week, for a total of 4 weeks. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale at 4 weeks is the primary outcome measure, and the secondary outcomes include WOMAC stiffness and function scores, the Lysholm knee scale score, quality of life, the Brief Pain Inventory score, the Patient’s Global Impressions of Improvement Scale score and the Clinical Global Impressions of Severity scale score. The safety of the herbal medications will also be evaluated.Conclusion: We will discuss whether SSBD has greater advantages in terms of efficacy, safety, and patient overall perception than does placebo control in middle-aged and elderly patients with knee OA. The findings may provide new and valuable information about the efficacy and safety of Chinese herbal bath therapy in the treatment of knee osteoarthritis.Keywords: balneotherapy, traditional Chinese medicine, complementary and integrative medicine, randomized placebo-controlled trial, knee osteoarthritis

Junshuang Guo,1,2 Ruike Zhang,1 Ruirui Dong,1 Fan Yang,1 Yating Wang,1 Wang Miao1 1Neuro-Intensive Care Unit of the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of China; 2Department of Immunology, School of Basic Medical Science, Central South University, Changsha City, Hunan Province, People’s Republic of ChinaCorrespondence: Wang Miao, Neuro-Intensive Care Unit of the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, 450000, People’s Republic of China, Email miaowang7211@126.comBackground: Machine learning (ML) is increasingly used in medical predictive modeling, but there are no studies applying ML to predict prognosis in Guillain-Barré syndrome (GBS).Materials and Methods: The medical records of 223 patients with GBS were analyzed to construct predictive models that affect patient prognosis. Least Absolute Shrinkage and Selection Operator (LASSO) was used to filter the variables. Decision Trees (DT), Random Forest (RF), Extreme Gradient Boosting (XGBoost), k-nearest Neighbour (KNN), Naive Bayes (NB), Neural Network (NN). Light Gradient Boosting Machine (LGBM) and Logistic Regression (LR) were used to construct predictive models. Clinical data from 55 GBS patients were used to validate the model. SHapley additive explanation (SHAP) analysis was used to explain the model. Single sample gene set enrichment analysis (ssGSEA) was used for immune cell infiltration analysis.Results: The AUCs (area under the curves) of the 8 ML algorithms including DT, RF, XGBoost, KNN, NB, NN, LGBM and LR were as follows: 0.75, 0.896 0.874, 0.666, 0.742, 0.765, 0.869 and 0.744. The accuracy of XGBoost (0.852) was the highest, followed by LGBM (0.803) and RF (0.758), with F1 index of 0.832, 0.794, and 0.667, respectively. The results of the validation set data analysis showed AUCs of 0.839, 0.919, and 0.733 for RF, XGBoost, and LGBM, respectively. SHAP analysis showed that the SHAP values of blood neutrophil/lymphocyte ratio (NLR), age, mechanical ventilation, hyporeflexia and abnormal glossopharyngeal vagus nerve were 0.821, 0.645, 0.517, 0.401 and 0.109, respectively.Conclusion: The combination of NLR, age, mechanical ventilation, hyporeflexia and abnormal glossopharyngeal vagus used to predict short-term prognosis in patients with GBS has a good predictive value.Keywords: Guillain-Barré syndrome, machine learning, prognosis, SHAP

Rongrong Zhang,1,&ast; Wenjun Xu,1,&ast; Hongquan Wei,1,&ast; Boshi Li,1 Yaoxing Wang,1 Xueqing He,1 Jun Cao,1 Xinyu He,1 Mingxiang Xu,1,2 Wenjie Lu,1 Youzhi Xu1 1College of Basic Medicine, Anhui Medical University, Hefei, 230032, People’s Republic of China; 2Center for Scientific Research, Anhui Medical University, Hefei, 230032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Youzhi Xu; Wenjie Lu, Email xuyouzhi@ahmu.edu.cn; wenjie63136@163.comPurpose: Currently, there is still no clear treatment for polycystic ovary syndrome (PCOS). YJKL has better therapeutic effects and lower toxic side effects for PCOS type infertility. This study aims to clarify the potential mechanism of YJKL Decoction in the treatment of PCOS based on network pharmacology and experiments verification.Patients and Methods: Network pharmacology and experimental validation approach were used to investigate the bioactive ingredients, critical targets and potential mechanisms of YJKL Decoction against PCOS. Firstly, we use network pharmacology methods to collect core targets, and then validate their effects on diseases through experiments.Results: Five core targets were screened, Threonine kinase 1 (AKT1), Cellular tumor antigen p53 (TP53), Tumor necrosis factor (TNF), Albumin (ALB) and Vascular endothelial growthfactor A (VEGFA). KEGG analysis showed that YJKL treatment for PCOS mainly include AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway and HIF-1 signaling pathway. The molecular docking results showed that compounds have higher affinity with targets. Finally, experimental results had shown that YJKL Decoction had an better therapeutic effects in the treatment of PCOS.Conclusion: Based on a systematic network pharmacology approach and experimental verification, our results comprehensively illustrated the active ingredients, potential targets, and molecular mechanism of YJKL for application to PCOS and helps to illustrate mechanism of action on a comprehensive level.Keywords: traditional Chinese Medicine, YJKL, polycystic ovary syndrome, PCOS, molecular docking, experimental validation

Yawen Mo,1,&ast; Wenjuan Zhang,1,&ast; Xiangcheng Tang,1 Rui Zhang,2 Yinghuan Wang,1 Lingling Zheng3 1Department of Strabismus and Amblyopia, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, People’s Republic of China; 2Department of Anesthesia, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, People’s Republic of China; 3Department of Nursing Administration, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lingling Zheng, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 7 Jinsui Road, Guangzhou, People’s Republic of China, Email zhenglingling@gzzoc.comPurpose: Strabismus surgery is most commonly performed on children under general anesthesia. However, few studies have focused on the postoperative discomfort in children after strabismus surgery. This study aimed to evaluate postoperative discomfort and the associated risk factors in children who underwent strabismus surgery under general anesthesia.Patients and Methods: A single-center prospective observational study including 300 children who underwent strabismus surgery after general anesthesia was conducted. Patients’ characteristics, preoperative anxiety, surgical and anesthesia data, discomfort within 24 hours after postanesthesia care unit were recorded. The primary outcome was the incidence of postoperative discomfort.Results: Approximately 51.33% of the children complained of at least one of the following types of postoperative discomfort: postoperative nausea and vomiting (PONV) (23.00%), headache (4.33%), dizziness (20.33%) and emergence agitation (EA) (5.33%). Multivariate analysis indicated that history of motion sickness (P< 0.001, odds ratio [OR]=3.72), and surgery in the dominant eye (P=0.010, OR=2.00) were independent predictors of postoperative discomfort; age was an independent predictor of EA (P< 0.001, OR=0.36); prism diopter≥ 40 was an independent predictor of headache (P=0.005, OR=5.53); age (P=0.020, OR=1.12) and history of motion sickness (P=0.001, OR=2.80) were independent predictors of dizziness; history of motion sickness (P=0.001, OR=2.63) and surgery of inferior oblique anterior transposition (IOAT) (P=0.004, OR=3.10) were independent predictors of PONV.Conclusion: The most frequent postoperative symptoms in children after undergoing strabismus surgery under general anesthesia are PONV, dizziness, EA, and headache. Younger age, larger angle of strabismus, history of motion sickness, surgery on the dominant eye, and surgery of IOAT may be additional risk factors for postoperative discomfort.Keywords: strabismus surgery, discomfort, postoperative nausea, vomiting, general anesthesia

Yuxia Fang,1 Yilu Zhao,2 Lei Qin,1 Ziyue Song,1 Ruzhi Zhang1 1Department of Dermatology and STD, The Second Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, 241001, People’s Republic of China; 2Department of Dermatology, The First Affiliated Hospital of Bengbu Medical University, Bengbu Medical University, Bengbu, Anhui, People’s Republic of ChinaCorrespondence: Ruzhi Zhang, Department of Dermatology and STD, The Second Affiliated Hospital of Wannan Medical College, 10 Kangfu Road, Wuhu, Anhui, 241001, People’s Republic of China, Tel +8618761161826, Email zhangruzhi628@163.comBackground: Intramuscular (IM) injection of penicillin G Benzathine (PGB) is widely recognized as the primary treatment for patients at all stages of syphilis. However, the discomfort and induration associated with PGB injections are often a challenge for patients. While lidocaine is already known to reduce injection pain and is standard practice in some countries, the added value of combining lidocaine with the z-track technique has not been thoroughly investigated. This study aims to observe the use of combining lidocaine with the Z-track technique in the treatment of syphilis, and to explore less painful methods of administering IM PGB for the treatment of syphilis in adult patients.Methods: 32 syphilis patients requiring penicillin treatment were injected with 1.2 million units of penicillin on both sides of the buttocks. The left side was injected using the traditional method with 0.9% saline as the solvent (control Group), while the right side was injected using a “z” injection method with 0.2% lidocaine as the solvent (experimental Group). The success rate of the single injection, the intensity and duration of the post-injection pain and the induration reaction were observed and recorded.Results: There was no statistically significant difference in single injection success rate and immediate post injection pain score between the two sides (P> 0.05). However, the right side had a lower pain score at 30 minutes post injection and fewer induration reactions, showing a statistically significant difference between the two sides (P< 0.05). Chi-squared analysis showed that age, gender and BMI had no significant effect on pain scores 30 minutes after injection in either the control or intervention groups. (P> 0.05).Conclusion: The lidocaine + Z-track penicillin method can reduce delayed pain and induration reactions in patients with syphilis, and provides an additional approach to improving patient comfort beyond the standard use of lidocaine alone. This method merits clinical promotion.Keywords: syphilis, penicillin G benzathine, PGB, intramuscular injection

Yishan Duan,1,&ast; Jing Ren,2,&ast; Jing Wang,3,&ast; Suyan Wang,4 Rui Zhang,1 Huohuo Zhang,1 Jinrui Hu,1 Wen Deng,1 Weimin Li,1,3,4 Bojiang Chen1,3 1Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan Province, 610041, People’s Republic of China; 2The Integrated Care Management Center, West China Hospital of Sichuan University, Chengdu, Chengdu, Sichuan Province, 610041, People’s Republic of China; 3Precision Medicine Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, 610041, People’s Republic of China; 4Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan Province, 610041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bojiang Chen; Weimin Li, Email cjhcbj@outlook.com; weimin003@163.comPurpose: Early empiric antibiotics were prescribed to numerous patients during the Coronavirus disease 2019 (COVID-19) pandemic. However, the potential impact of empiric antibiotic therapy on the clinical outcomes of patients hospitalized with COVID-19 is yet unknown.Methods: In this retrospective cohort study, early antibiotics use cohort was defined as control group, which was compared with no antibiotic use and delayed antibiotic use cohorts for all-cause mortality during hospitalization. The 1:2 propensity score matched patient populations were further developed to adjust confounding factors. Survival curves were compared between different cohorts using a Log rank test to assess the early antibiotic effectiveness.Results: We included a total of 1472 COVID-19 hospitalized patients, of whom 87.4% (1287 patients) received early antibiotic prescriptions. In propensity-score-matched datasets, our analysis comprised 139 patients with non-antibiotic use (with 278 matched controls) and 27 patients with deferred-antibiotic use (with 54 matched controls). Patients with older ages, multiple comorbidities, severe and critical COVID-19 subtypes, higher serum infection indicators, and inflammatory indicators at admission were more likely to receive early antibiotic prescriptions. After adjusting confounding factors likely to influence the prognosis, there is no significant difference in all-cause mortality (HR=1.000(0.246– 4.060), p = 1.000) and ICU admission (HR=0.436(0.093– 2.04), p = 0.293), need for mechanical ventilation (HR=0.723(0.296– 1.763), p = 0.476) and tracheal intubation (HR=1.338(0.221– 8.103), p = 0.751) were observed between early antibiotics use cohort and non-antibiotic use cohort.Conclusion: Early antibiotics were frequently prescribed to patients in more severe disease condition at admission. However, early antibiotic treatment failed to demonstrate better clinical outcomes in hospitalized patients with COVID-19 in the propensity-score-matched cohorts.Keywords: Coronavirus disease 2019, COVID-19, early antibiotics use, bacterial co-infections, clinical outcomes

Li Lin,1,* Zeyu Huang,2,* Bangsheng Xi,3,* Xiaoming Qin,1 Kongchao Yang,1 Ruzhi Zhang1 1Department of Dermatology, The Second Affiliated Hospital of Wannan Medical College, Wuhu, People’s Republic of China; 2Department of Dermatology, The Third Affiliated Hospital of Soochow University, Changzhou, People’s Republic of China; 3Department of Clinical Laboratory, The First Affiliated Hospital of Wannan Medical college, Wuhu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ruzhi Zhang, Email zhangruzhi628@163.comAbstract: Cutaneous squamous cell carcinoma (SCC) is a common non-melanoma skin cancer (NMSC). Although most cutaneous SCC in people with lighter skin pigmentation as a result of sun damage, patients with underlying conditions such as skin ulcers and chronic inflammation-including conditions such as lupus vulgaris (LV) and chronic discoid lupus erythematosus—are also predisposed to developing SCC. Here we report a case of secondary SCC diagnosed in a 54-year-old patient with 20 years of lupus vulgaris without prior formal systemic treatment, a rarity in clinical practice. Two months ago, the patient developed papules on the right cheek that ulcerated and discharged purulent fluid. Laboratory tests revealed a positive TSPOT result and histopathological examination confirmed granulomatous lesions, supporting the diagnosis of SLE. However, a tissue biopsy unexpectedly revealed a moderately differentiated SCC of the keratinizing type. In this case, we performed surgical excision of the lesion followed by cosmetic closure and adjuvant photodynamic therapy (PDT). Concurrently, the patient underwent systemic anti-tuberculosis treatment. At 6 months post-treatment, no tumour recurrence was observed and the rash associated with lupus erythematosus had also resolved. The patient was satisfied with the treatment outcome.Keywords: lupus vulgaris, squamous cell carcinoma, surgical excision, photodynamic therapy

Zhongbiao Nie,1 Cuilv Liang,2 Zhihong Li,1 Xinqiang Han,3 Ran Zhang4 1Department of Pharmacy, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, People’s Republic of China; 2Department of Pharmacy, Second Affiliated Hospital, Fujian Medical University, Quanzhou, 362000, People’s Republic of China; 3Department of General, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, People’s Republic of China; 4Department of Nephrology, Affiliated Hospital of Shanxi University of Chinese Medicine, Taiyuan, 030024, People’s Republic of ChinaCorrespondence: Ran Zhang, Department of Nephrology, Affiliated Hospital of Shanxi University of Traditional Chinese Medicine, Taiyuan, 030024, People’s Republic of China, Tel +86-13633516515, Email 115462888@qq.comPurpose: This study comprehensively describes and evaluates the correlation between gabapentinoids and all types of delirium.Methods: We used AERSMine to select all adverse reaction data from 2004 Q1 to the 2022 Q4 in the FDA Adverse Event Reporting System (FAERS) database, and delirium events reported by gabapentinoids drugs were included in this study. Collected and analyzed the clinical details of these reports. We have developed four models. Among the four models, reporting odds ratio (ROR) and proportional reporting ratio (PRR) were used to evaluate the potential association between and delirium. We undertook a subgroup analysis for the age and sex cohorts.Results: A total of 2950 reports of gabapentinoids-related delirium was collected. Excluding cases with a history of delirium (Model 2), opioid drugs (Model 3), and other adverse events related to gabapentinoids drugs (Model 4), pain cases with gabapentin drugs as the main suspected drug were selected. In model 1, the reporting rates of delirium at the delirium and delirium tremens levels were higher in the gabapentinoids group than in the non-gabapentinoids group (ROR 1.09(1.05,1.13); ROR 1.54(1.16,2.04)). In model 2.3 the delira and the delirium level were higher in the gabapentinoids group (ROR 1.42(1.29,1.56), ROR 1.44(1.31,1.59); ROR 1.43(1.30,1.58), ROR 1.46(1.33,1.61)). There is no difference in delirium levels in Model 4. Delirium levels were higher in the gabapentinoids group than in the non-gabapentinoids group in ≥ 65 years old. The delirium and deliria levels were higher in the male group than in the female group.Conclusion: The delirium adverse reactions of the gabapentinoids group were significantly higher than those of non-gabapentinoids group in the first three models. However, with the removal of confounding factors, there was no significant difference in this type of adverse reaction in Model 4. In elderly and male patients, the incidence of delirium with gabapentinoids was significantly increased.Keywords: gabapentinoids, delirium, adverse reactions, FAERS, pharmacovigilance

Jiangpei Shi,1,&ast; Rongguang Zhang,1,&ast; Yu Wang,1 Yingwei Sun,1 Xiaoyan Gu,1 Yu An,1 Xinyu Chai,1 Xiaoyu Wang,2 Zhi Wang,1 Yaqi Lyu,1 Teng Guo,1 Nianping Feng,1 Ying Liu1 1School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nianping Feng; Ying Liu, Email npfeng@shutcm.edu.cn; debbyly@shutcm.edu.cnBackground: Metastasis is a complex process involving multiple factors and stages, in which tumor cells and the tumor microenvironment (TME) play significant roles. A combination of orally bioavailable therapeutic agents that target both tumor cells and TME is conducive to prevent or impede the progression of metastasis, especially when undetectable. However, sequentially overcoming intestinal barriers, ensuring biodistribution in tumors and metastatic tissues, and enhancing therapeutic effects required for efficient therapy remain challenging.Methods: Inspired by the unique chemical features of natural herbs, we propose an oral herb–nanoparticle hybrid system (HNS) formed through the self-binding of Platycodon grandiflorum–Curcuma zedoaria (HG), a herb pair/group used in clinical practice to treat breast cancer metastasis, to lipid–polymer nanoparticles (LPNs) loaded with silibinin. The molecular structure responsible for HG association with LPNs was assessed using surface-enhanced Raman spectroscopy for HNS surface chemistry characterization. Moreover, the molecular class of HG was identified using UPLC–Orbitrap–MS/MS to further confirm the surface binding. Mucus diffusion and in vivo biodistribution were evaluated using in vitro multiple-particle tracking and environment-responsive fluorescence probe in 4T1 tumor-bearing mice, respectively. The alleviation of breast cancer metastasis was assessed in 4T1 tumor-bearing mice, and the underlying mechanism was investigated.Results: The HNS reduced particle–mucus interactions by altering hydrophilicity and surface characteristics compared to LPNs. The epithelium transportation of HNS and absorption through Peyer’s patch in mice were improved, promoting their biodistribution in the lung and tumor tissues. Furthermore, the HNS alleviated lung metastasis by inducing cell apoptosis and regulating the expression of MMP-9 and TGF-β 1, which altered the TME in 4T1 tumor-bearing mice.Conclusion: HNS provides an appealing system with multi-component binding of herbal medicine to facilitate both oral nanoparticle delivery efficiency and the alleviation of lung metastasis. This strategy may potentially help improve treatment for patients with breast cancer.Keywords: herb–nanoparticle hybrid system, intestinal biological barrier, tumor microenvironment, breast cancer lung metastasis

Yunyan Zheng,1,&ast; Weiwei Shi,1,2,&ast; Huiying Wang,1 Ruzhi Zhang3 1Department of Dermatology, The Third Affiliated Hospital of Soochow University, Changzhou, People’s Republic of China; 2Department of Dermatology, Affiliated Hospital 2 of Nantong University, Nantong, People’s Republic of China; 3Department of Dermatology, The Second Affiliated Hospital of Wannan Medical College, Wuhu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ruzhi Zhang, Department of Dermatology, The Second Affiliated Hospital of Wannan Medical College, 10 Kangfu Road, Wuhu, 241000, People’s Republic of China, Email zhangruzhi628@163.comPurpose: This study aimed to improve the understanding of sporotrichosis by analyzing the epidemiological characteristics, clinical manifestations, mycological features, and pathological characteristics of the disease in eastern China.Methods: Clinical data of 49 patients diagnosed with cutaneous sporotrichosis in dermatology clinics over a 20-year period were collected and analyzed retrospectively. The analysis included patient demographics, occupations, clinical types, lesion sites, misdiagnosis rates, laboratory investigations, treatment and outcomes.Results: The study included 22 male and 27 female patients, with a mean age of 52.4 years. Farmers (42.86%) and manual workers (28.57%) had a higher risk of infection. The most common clinical types were lymphocutaneous (30.61%) and fixed (69.39%), predominantly affecting the face and upper limbs. Misdiagnosis as other infectious skin diseases occurred in 35 patients (71.43%). Fungal culture and histopathological examination were important diagnostic tools. Treatment with oral itraconazole for three months led to relief and regression of the skin lesions in most patients, although a few experienced recurrences.Conclusion: Cutaneous sporotrichosis mainly affects individuals working in agriculture and manual labour, with lymphocutaneous and fixed types being the predominant clinical manifestations. The high misdiagnosis rate emphasizes the importance of early recognition, accurate diagnosis and standardized treatment for the prognosis and cure of sporotrichosis. Fungal culture and histopathological examination are essential for diagnosis, and oral itraconazole is an effective treatment option.Keywords: sporotrichosis, cutaneous form, clinical analysis, epidemiology, misdiagnosis

Xinyu Dai,1,&ast; Rui Zhang,2,&ast; Nan Deng,1 Le Tang,3 Bangshu Zhao1 1Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Neurosurgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 3Department of Psychiatry, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bangshu Zhao, Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China, Tel +8615823079815, Email Bangshuzhao@hospital.cqmu.edu.cnAbstract: The prevalence of severe mental disorders has been rising annually. Electroconvulsive therapy (ECT) is considered a valuable treatment option in psychiatry for conditions such as schizophrenia and medication-resistant depression, especially when other treatments have proven insufficient. ECT rapidly improves patients’ mood, alleviates symptoms, and demonstrates significant therapeutic effects. Currently, the form of ECT used in clinical practice is modified electroconvulsive therapy (mECT), which is administered under general anesthesia. Accumulative evidence has confirmed that different anesthetic drugs, anesthetic-ECT time interval, anesthetic depth, and airway management can impact the outcomes of ECT. Therefore, this review aims to summarize the current impact of anesthesia factors on ECT, providing reference for clinical anesthesia during ECT procedures.Keywords: mental disorders, ECT, anesthesia factors

Ruijie Zhang,1,&ast; Xinran Dong,2,&ast; Lu Zhang,1,&ast; Xinao Lin,1 Xuefeng Wang,1 Yan Xu,3 Chuyan Wu,4 Feng Jiang,1 Jimei Wang1 1Department of Neonatology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, People’s Republic of China; 2Center for Molecular Medicine, Children’s Hospital of Fudan University, Shanghai, People’s Republic of China; 3Department of Neurology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, People’s Republic of China; 4Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jimei Wang; Feng Jiang, Department of Neonatology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, People’s Republic of China, Email wjm821920@163.com; dxyjiang@163.comBackground: Neonatal sleep is pivotal for their growth and development, yet manual interpretation of raw images is time-consuming and labor-intensive. Quantitative Electroencephalography (QEEG) presents significant advantages in terms of objectivity and convenience for investigating neonatal sleep patterns. However, research on the sleep patterns of healthy neonates remains scarce. This study aims to identify QEEG markers that distinguish between different neonatal sleep cycles and analyze QEEG alterations across various sleep stages in relation to postmenstrual age.Methods: From September 2023 to February 2024, full-term neonates admitted to the neonatology department at the Obstetrics and Gynecology Hospital of Fudan University were enrolled in this study. Electroencephalographic (EEG) recordings were obtained from neonates aged 37– 42 weeks, within 1– 7 days post-birth. The ROC curve was employed to evaluate QEEG features related to amplitude, range EEG (rEEG), spectral density, and connectivity across different sleep stages. Furthermore, regression analyses were performed to investigate the association between these QEEG characteristics and postmenstrual age.Results: The alpha frequency band’s spectral_diff_F3 emerged as the most potent discriminator between active sleep (AS) and quiet sleep (QS). In distinguishing AS from wakefulness (W), the theta frequency’s spectral_diff_C4 was the most effective, whereas the delta frequency’s spectral_diff_P4 excelled in differentiating QS from W. During AS and QS phases, there was a notable increase in entropy within the delta frequency band across all monitored brain regions and in the spectral relative power within the theta frequency band, correlating with postmenstrual age (PMA).Conclusion: Spectral difference showcases the highest discriminative capability across awake and various sleep states. The observed patterns of neonatal QEEG alterations in relation to PMA are consistent with the maturation of neonatal sleep, offering insights into the prediction and evaluation of brain development outcomes.Keywords: quantitative EEG, neonates, sleep, postmenstrual age

Xiaoqing Ma,&ast; Ruoying Zhang,&ast; Xinjun Cai, Yuying Lang, Huaichong Wang, Jinmeng Li Department of Pharmacy, Hangzhou Red Cross Hospital, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinmeng Li, Department of Pharmacy, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang Province, 310000, People’s Republic of China, Email jinmeng608@163.comAbstract: As a new generation of oxazolidinone antibacterial drugs, contezolid has been shown to have comparable or even stronger activity than linezolid and has a low risk of adverse reactions such as bone marrow suppression toxicity. However, there are currently very few clinical reports and pharmacokinetic data of contezolid on the anti-tuberculosis therapy. Therefore, we report a case study of the pharmacokinetic study of contezolid in elderly patients with renal insufficiency and tuberculosis. The patient’s condition improved after receiving an anti-tuberculosis regimen containing contezolid, with significant absorption of pleural effusion and lung plaques and nodules reduced. During the treatment, the patients’ platelet and white blood cell levels fluctuated within normal ranges, but hemoglobin levels significantly decreased and did not recover after discontinuation of contezolid. The trough concentration of contezolid and the concentration at 2, 4, 6, and 10 h after administration were 1.27μg/mL, 3.88μg/mL, 6.32μg/mL, 8.99μg/mL, and 3.14μg/mL, respectively. The plasma concentrations of bedaquiline and cycloserine during the treatment were also monitored. This study demonstrated the efficacy and safety of contezolid in the treatment of multidrug-resistant tuberculosis and analyzed its pharmacokinetic changes in elderly patients with renal insufficiency, providing a reference for the clinical use of contezolid.Keywords: contezolid, tuberculosis, plasma concentration, efficacy, safety

Wenze Han,1,2 Ran Zhang,1,2 Shuzhi Liu,1,2 Tong Zhang,1,2 Xuemin Yao,1,2 Yuxin Cao,1,2 Jiadi Li,1,2 Xiaoming Liu,1,2 Bing Li1,2 1Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, 030001, People’s Republic of China; 2Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, People’s Republic of ChinaCorrespondence: Xiaoming Liu; Bing Li, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, 030001, People’s Republic of China, Email lxming0912@163.com; libing1975vip@163.comAbstract: Whiskers are nanoscale, high-strength fibrous crystals with a wide range of potential applications in dentistry owing to their unique mechanical, thermal, electrical, and biological properties. They possess high strength, a high modulus of elasticity and good biocompatibility. Hence, adding these crystals to dental composites as reinforcement can considerably improve the mechanical properties and durability of restorations. Additionally, whiskers are involved in inducing the value-added differentiation of osteoblasts, odontogenic osteocytes, and pulp stem cells, and promoting the regeneration of alveolar bone, periodontal tissue, and pulp tissue. They can also enhance the mucosal barrier function, inhibit the proliferation of tumor cells, control inflammation, and aid in cancer prevention. This review comprehensively summarizes the classification, properties, growth mechanisms and preparation methods of whiskers and focuses on their application in dentistry. Due to their unique physicochemical properties, excellent biological properties, and nanoscale characteristics, whiskers show great potential for application in bone, periodontal, and pulp tissue regeneration. Additionally, they can be used to prevent and treat oral cancer and improve medical devices, thus making them a promising new material in dentistry.Keywords: whiskers, dentistry, growth mechanism, biomaterials

Fengxing Huang,1,2,&ast; Youwei Wang,1,2,&ast; Yu Shao,1,2,&ast; Runan Zhang,1,2 Mengting Li,1,2 Lan Liu,1,2,&ast; Qiu Zhao1,2,&ast; 1Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People’s Republic of China; 2Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Wuhan, 430071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lan Liu; Qiu Zhao, Email lliugi@whu.edu.cn; qiuzhao@whu.edu.cnIntroduction: Immune cell interactions and metabolic changes are crucial in determining the tumor microenvironment and affecting various clinical outcomes. However, the clinical significance of metabolism evolution of immune cell evolution in colorectal cancer (CRC) remains unexplored.Methods: Single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing data were acquired from TCGA and GEO datasets. For the analysis of macrophage differentiation trajectories, we employed the R packages Seurat and Monocle. Consensus clustering was further applied to identify the molecular classification. Immunohistochemical results from AOM and AOM/DSS models were used to validate macrophage expression. Subsequently, GSEA, ESTIMATE scores, prognosis, clinical characteristics, mutational burden, immune cell infiltration, and the variance in gene expression among different clusters were compared. We constructed a prognostic model and nomograms based on metabolic gene signatures identified through the MEGENA framework.Results: We found two heterogeneous groups of M2 macrophages with various clinical outcomes through the evolutionary process. The prognosis of Cluster 2 was poorer. Further investigation showed that Cluster 2 constituted a metabolically active group while Cluster 1 was comparatively metabolically inert. Metabolic variations in M2 macrophages during tumor development are related to tumor prognosis. Additionally, Cluster 2 showed the most pronounced genomic instability and had highly elevated metabolic pathways, notably those associated with the ECM. We identified eight metabolic genes (PRELP, NOTCH3, CNOT6, ASRGL1, SRSF1, PSMD4, RPL31, and CNOT7) to build a predictive model validated in CRC datasets. Then, a nomogram based on the M2 risk score improved predictive performance. Furthermore, our study demonstrated that immune checkpoint inhibitor therapy may benefit patients with low-risk.Discussion: Our research reveals underlying relationships between metabolic phenotypes and immunological profiles and suggests a unique M2 classification technique for CRC. The identified gene signatures may be key factors linking immunity and tumor metabolism, warranting further investigations. Keywords: CRC, macrophages, metabolic classification, tumor immunity, prognosis model

Yucheng Hu,1 Rong Zhang,2 Junjie Li,1 Huan Wang,3 Meiya Wang,3 Qiuyi Ren,1 Yueqi Fang,1 Li Tian1 1Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 2Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 3Chengdu university of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Li Tian, Hospital of Chengdu university of Traditional Chinese Medicine, No. 41, 12 Qiaolu, Qingyang District, Chengdu, Sichuan, People’s Republic of China, Email 18980880129@qq.comhaAbstract: Allergic rhinitis is a chronic non-infectious inflammation of the nasal mucosa mediated by specific IgE. Recently, the human microbiome has drawn broad interest as a potential new target for treating this condition. This paper succinctly summarizes the main findings of 17 eligible studies published by February 2024, involving 1044 allergic rhinitis patients and 954 healthy controls from 5 countries. These studies examine differences in the human microbiome across important mucosal interfaces, including the nasal and intestinal areas, between patients and controls. Overall, findings suggest variations in the gut microbiota between allergic rhinitis patients and healthy individuals, although the specific bacterial taxa that significantly changed were not always consistent across studies. Due to the limited scope of existing research and patient coverage, the relationship between the nasal microbiome and allergic rhinitis remains inconclusive. The article discusses the potential immune-regulating role of the gut microbiome in allergic rhinitis. Further well-designed clinical trials with large-scale recruitment of allergic rhinitis patients are encouraged.Keywords: allergic rhinitis, microbiota dysbiosis, nasal microbiome, short-chain fatty acids, immunomodulation

Yuan Zhuang,1,2 Ru Zhang,3,4 Miaomiao Li,3,4 Yaru Zou,1 Shui Jiang,1 Yanan Zhang,1 Shiguo Liu,3,4 Bo Yu1 1Dermatological Department, The Affiliated Hospital of QingdaoUniversity, Qingdao, People’s Republic of China; 2dermatological department, Women and Children’s hospital, Qingdao University, Qingdao, People’s Republic of China; 3Medical Genetic Department, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 4Prenatal Diagnosis Center, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of ChinaCorrespondence: Bo Yu, Dermatological department, The Affiliated Hospital of QingdaoUniversity, Qingdao, People’s Republic of China, Email yubo@qduhospital.cn Shiguo Liu, Medical Genetic Department, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China, Email liushiguo@qdu.edu.cnIntroduction: Hypohidrotic ectodermal dysplasia (HED) is a genetic disorder that influences structures of ectodermal origin, such as teeth, hair, and sweat glands. Compared with autosomal recessive and dominant modes of inheritance, the X-linked HED (XLHED) characterized by Hypodontia/Oligodontia teeth, Absent/sparse hair, Anhidrosis/hypohidrosis, and characteristic facial features, is the most frequent and its primary cause is the mutation of ectodysplasin A (EDA) gene. This research aimed to expound the clinical and molecular features of a Chinese male with XLHED and to summarize and compare several previous findings.Methods: Genomic DNA was obtained from the peripheral blood of the proband and his family members, then Sanger sequencing was used to perform a mutational analysis of EDA. Real-time quantitative PCR and Western blotting were used to detect EDA expression. The transcriptional activity of NF-κB was detected using a luciferase assay.Results: The probandwith XLHED was identified a novel EDA mutation, c.1119G>C(p.M373I), that affected the molecular analysis of transmembrane protein exon8 mutations, inherited from the mother. He showed a severe multiple-tooth loss, with over 20 permanent teeth missing and sparse hair and eyebrows, dry, thin, and itching skin. Furthermore, his sweating function was abnormal to a certain extent.Discussion: The functional study showed that this novel mutant led to a significant decrease in the EDA expression level and transcriptional activity of NF-κB. Our findings extend the range of EDA mutations in XLHED patients, which provides the basis and idea for further exploring the pathogenesis of XLHED.Keywords: EDA, X-linked hypohidrotic ectodermal dysplasia, gene mutation

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

Kang Ge,1,2 Yilu Zhao,2,3 Xiao Liu,4 Ruzhi Zhang5 1Jiaxing Key Discipline of Medicine --Dermatology and Venereology, The Affiliated Hospital of Jiaxing University, The First Hospital of Jiaxing, Jiaxing, Zhejiang, People’s Republic of China; 2Department of Dermatology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, People’s Republic of China; 3Department of Dermatology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, People’s Republic of China; 4School of Materials Science and Engineering, Changzhou University, Changzhou, Jiangsu, People’s Republic of China; 5Department of Dermatology and STD, The Second Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, People’s Republic of ChinaCorrespondence: Ruzhi Zhang, Department of Dermatology and STD, The Second Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, 241001, People’s Republic of China, Tel +8618761161826, Email zhangruzhi628@163.comObjective: ALA-PDT (5-aminolevulinic acid photodynamic therapy) is a central modality in the treatment of skin diseases. Increasing the bioavailability of ALA remains a critical issue. With this in mind, our study explores a novel route of ALA delivery by loading acrylic nanoparticles (ANPs).Methods: ALA-ANPs were synthesized by emulsion polymerisation and characterised by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). The effects of ALA-ANPs on HaCaT cell line were evaluated, including characteristics, morphological changes, protoporphyrin IX (PpIX) fluorescence kinetics, reactive oxygen species (ROS) levels, mitochondrial membrane potential and ki67 expression in these cells.Results: The ANPs had uniform sizes, smooth surfaces and excellent light transmittance, with diameters of 150– 200 nm. In contrast, the ALA - ANPs had uneven surfaces and poor light transmittance, with diameters of 220– 250 nm. During 12 hours of co-incubation of HaCaT cells with ALA, the intracellular accumulation of PpIX increased over time. Notably, after 6 hours of incubation, PpIX levels induced by 1.81 mg/mL ALA-ANPs exceeded those induced by 1.0 mM ALA (p < 0.01). CCK-8 results showed a positive correlation between PDT-induced inhibition of HaCaT cell proliferation and ALA concentration when ALA concentration remained below 2.0 mM. Compared to the 1.0 mM ALA group, the 1.81 mg/mL ALA-ANPs group showed decreased mitochondrial membrane potential, ki67 immunofluorescence intensity and cell proliferation. In contrast, ROS levels were significantly increased in the 1.81 mg/mL ALA-ANPs group (p < 0.01).Conclusion: Loading ANPs provide improved stability and potency for ALA. The ALA-ANPs-PDT approach has superior inhibitory effects on HaCaT proliferation in vitro.Keywords: 5-aminophenolvalic acid, ALA, acrylate nanoporous, photodynamic therapy

Hui Xu,1 Ruixue Zhang,1 Xiaoxue Zhang,1 Yueguang Cheng,2 Liping Lv,3 Lianjun Lin1 1Department of Geriatrics, Peking University First Hospital, Beijing, People’s Republic of China; 2Department of Emergency, Beijing Jingmei Group General Hospital, Beijing, People’s Republic of China; 3Department of Interventional Pulmonology, Anhui Chest Hospital, Hefei, People’s Republic of ChinaCorrespondence: Lianjun Lin, Department of Geriatrics, Peking University First Hospital, Xishiku Avenue 8, Xicheng District, Beijing, 100034, People’s Republic of China, Tel +8613671246076, Fax +86-10-83572981, Email 06474@pkufh.comPurpose: Aspiration pneumonia (AP) challenges public health globally. The primary aim of this study was to ascertain the microbiological profile characteristics of patients with AP evaluated by combined detection methods, including conventional microbiological tests (CMTs), chips for complicated infection detection (CCID), and metagenomic next-generation sequencing (mNGS).Patients and Methods: From June 2021 to March 2022, a total of thirty-nine patients with AP or community-acquired pneumonia with aspiration risk factors (AspRF-CAP) from 3 hospitals were included. Respiratory specimens, including bronchoalveolar lavage fluid (BALF), sputum, and tracheal aspirate, were collected for microorganism detection.Results: Patients with AP were more inclined to be older, to have a shorter duration from illness onset to admission, to have a higher prevalence of different underlying diseases, particularly diabetes mellitus, chronic heart disease, and cerebrovascular disease, and to have a higher CURB-65 score (all P < 0.05). A total of 213 and 31 strains of microorganisms were detected in patients with AP and AspRF-CAP, respectively. The most common pathogens in AP were Corynebacterium striatum (17/213, 7.98%), Pseudomonas aeruginosa (15/213, 7.04%), Klebsiella pneumoniae (15/213, 7.04%), and Candida albicans (14/213, 6.57%). Besides, the most common pathogens in AspRF-CAP were Candida albicans (5/31, 16.13%), Pseudomonas aeruginosa (3/31, 9.68%) and Klebsiella pneumoniae (3/31, 9.68%). Moreover, Klebsiella pneumoniae (7/67, 10.45%) and Candida glabrata (5/67, 7.46%) were the most common pathogens among the 9 non-survived patients with AP.Conclusion: The prevalent pathogens detected in cases of AP were Corynebacterium striatum, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Candida albicans. Early combined detection methods for patients with AP enhance the positive detection rate of pathogens and potentially expedites the initiation of appropriate antibiotic therapeutic strategies.Keywords: aspiration, pneumonia, microbiology, metagenomic next-generation sequencing, chips, combined detection

Yuwei Ma,1,2,&ast; Tao Jiang,1,2,&ast; Rong Zhang,1 Fei Liu,3 Shilong Song,1,2 Huijun Zhang,4 Jingwen Huang,1 Zelai He1,2 1The First Affiliated Hospital of Bengbu Medical University & Tumor Hospital Affiliated to Bengbu Medical University, Bengbu, 233004, People’s Republic of China; 2Department of Radiation Oncology, the First Affiliated Hospital of Bengbu Medical University & Tumor Hospital Affiliated to Bengbu Medical University, Bengbu, 233004, People’s Republic of China; 3Anhui Province Key Laboratory of Clinical and Preclinical Research in Respiratory Disease, Molecular Diagnosis Center, Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Bengbu Medical University, Bengbu, 233004, People’s Republic of China; 4Department of Cardiothoracic Surgery, Huashan Hospital of Fudan University, Shanghai, 200040, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zelai He; Jingwen Huang, Email hezelai@alumni.sjtu.edu.cn; he.ze.lai@163.com; byyfyhjw@163.comIntroduction: Lung cancer’s high incidence and dismal prognosis with traditional treatments like surgery and radiotherapy necessitate innovative approaches. Despite advancements in nanotherapy, the limitations of single-treatment modalities and significant side effects persist. To tackle lung cancer effectively, we devised a temperature-sensitive hydrogel-based local injection system with near-infrared triggered drug release. Utilizing 2D MXene nanosheets as carriers loaded with R837 and cisplatin (DDP), encapsulated within a temperature-sensitive hydrogel-forming PEG-MXene@DDP@R837@SHDS (MDR@SHDS), we administered in situ injections of MDR@SHDS into tumor tissues combined with photothermal therapy (PTT). The immune adjuvant R837 enhances dendritic cell (DC) maturation and tumor cell phagocytosis, while PTT induces tumor cell apoptosis and necrosis by converting light energy into heat energy.Methods: Material characterization employed transmission electron microscopy, X-ray photoelectron spectroscopy, phase transition temperature, and near-infrared thermography. In vitro experiments assessed Lewis cell proliferation and apoptosis using CCK-8, Edu, and TUNEL assays. In vivo experiments on C57 mouse Lewis transplant tumors evaluated the photothermal effect via near-infrared thermography and assessed DC maturation and CD4+/CD8+ T cell ratios using flow cytometry. The in vivo anti-tumor efficacy of MDR@SHDS was confirmed by tumor growth curve recording and HE and TUNEL staining of tumor sections.Results: The hydrogel exhibited excellent temperature sensitivity, controlled release properties, and high biocompatibility. In vitro experiments revealed that MDR@SHDS combined with PTT had a greater inhibitory effect on tumor cell proliferation compared to MDR@SHD alone. Combining local immunotherapy, chemotherapy, and PTT yielded superior anti-tumor effects than individual treatments.Conclusion: MDR@SHDS, with its simplicity, biocompatibility, and enhanced anti-tumor effects in combination with PTT, presents a promising therapeutic approach for lung cancer treatment, offering potential clinical utility.Keywords: 2D Mxene, drug delivery system, hydrogel, lung cancer

Meiling He,1 Chunfeng Liang,1 Yadan Pang,1 Mengjie Jiang,1 Meiying Long,2 Zhongqiang Yao,3 Xiaoting Wang,1 Ruijun Zhang,1 Qiaoyuan Wu,1 Shixiong Liang,1 Jianxu Li1 1Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, 530021, People’s Republic of China; 2School of Public Health, Guangxi Medical University, Nanning, 530021, People’s Republic of China; 3Department of General Affairs, Guangxi Medical University Cancer Hospital, Nanning, 530021, People’s Republic of ChinaCorrespondence: Shixiong Liang; Jianxu Li, Tel +86 13917716605 ; +86 18878732921, Email shixliang@sina.com; lijianxu1236@163.comPurpose: The combination of radiotherapy and monoclonal antibody against programmed cell death 1 (anti-PD1) showed preliminary efficacy in hepatocellular carcinoma (HCC). This study aimed to identify the prognostic factors and construct a nomogram to predict the overall survival (OS) of patients with advanced HCC after treatment with intensity-modulated radiotherapy (IMRT) plus anti-PD1.Patients and Methods: The OS and progression-free survival (PFS) of 102 patients with BCLC stage C HCC was analyzed using the Kaplan-Meier method. Potential independent prognostic factors were determined using univariate and multivariate Cox regression analyses. A nomogram was established to predict prognosis whose accuracy and reliability was verified by a calibration curve and area under the receiver operating characteristic curve (AUROC).Results: The median PFS and OS rates of the 102 patients with advanced HCC were 9.9 months and 14.3 months, respectively. Ninety-three patients were evaluated for efficacy, including five (5.38%) with complete response and 48 (51.61%) with partial response, with an overall response rate of 56.99%. Grade 3 and 4 adverse reactions (AEs) were observed in 32.35% of patients; no grade 5 AEs occurred. Multivariate Cox analysis revealed albumin and alpha-fetoprotein levels, neutrophil counts 3– 4 weeks after IMRT initiation, and platelet-to-lymphocyte ratio 3– 4 weeks after IMRT initiation to be independent prognostic factors. The nomogram model constructed using these factors had good consistency and accuracy with 1– 3 years AUROC of 78.7, 78.6, and 93.5, respectively.Conclusion: IMRT plus anti-PD1 showed promising efficacy and controllable adverse reactions in treating advanced HCC. The nomogram model demonstrated good reliability and clinical applicability.Plain Language Summary: The combination of radiotherapy and monoclonal antibody against programmed cell death 1 (anti‑PD1) showed preliminary efficacy and manageable safety in HCC. We retrospectively evaluated the efficacy and safety of 102 patients with advanced HCC treated with intensity-modulated radiotherapy (IMRT) plus anti-PD1. The study shows that the combination showed promising efficacy with a median PFS and OS of 9.9 months and 14.3 months, respectively. The adverse reactions were controllable. The novel nomogram model established based on independent prognostic factors including albumin, alpha-fetoprotein, neutrophils count 3– 4 weeks after IMRT initiation and platelet-to-lymphocyte ratio 3– 4 weeks after IMRT initiation demonstrated good reliability.Keywords: hepatocellular carcinoma, advanced, intensity-modulated radiotherapy, antibody against programmed cell death 1, nomogram

Zhiping Qi,1 Su Pan,1 Xiaoyu Yang,1 Renfeng Zhang,1 Cheng Qin,1 Hongye Yan,1 Longchuan Zhu,1 Weijian Kong2 1Department of Orthopedic Surgery, The Second Hospital of Jilin University, Changchun, 130041, People’s Republic of China; 2Department of Nuclear Medicine, The Second Hospital of Jilin University, Changchun, 130041, People’s Republic of ChinaCorrespondence: Weijian Kong; Longchuan Zhu, Email kongweijian0613@sina.com; zhulongchuan0504@163.comPurpose: Spinal cord injury (SCI) is an incurable and disabling event that is accompanied by complex inflammation-related pathological processes, such as the production of excessive reactive oxygen species (ROS) by infiltrating inflammatory immune cells and their release into the extracellular microenvironment, resulting in extensive apoptosis of endogenous neural stem cells. In this study, we noticed the neuroregeneration-promoting effect as well as the ability of the innovative treatment method of FTY720-CDs@GelMA paired with NSCs to increase motor function recovery in a rat spinal cord injury model.Methods: Carbon dots (CDs) and fingolimod (FTY720) were added to a hydrogel created by chemical cross-linking GelMA (FTY720-CDs@GelMA). The basic properties of FTY720-CDs@GelMA hydrogels were investigated using TEM, SEM, XPS, and FTIR. The swelling and degradation rates of FTY720-CDs@GelMA hydrogels were measured, and each group’s ability to scavenge reactive oxygen species was investigated. The in vitro biocompatibility of FTY720-CDs@GelMA hydrogels was assessed using neural stem cells. The regeneration of the spinal cord and recovery of motor function in rats were studied following co-treatment of spinal cord injury using FTY720-CDs@GelMA hydrogel in combination with NSCs, utilising rats with spinal cord injuries as a model. Histological and immunofluorescence labelling were used to determine the regeneration of axons and neurons. The recovery of motor function in rats was assessed using the BBB score.Results: The hydrogel boosted neurogenesis and axonal regeneration by eliminating excess ROS and restoring the regenerative environment. The hydrogel efficiently contained brain stem cells and demonstrated strong neuroprotective effects in vivo by lowering endogenous ROS generation and mitigating ROS-mediated oxidative stress. In a follow-up investigation, we discovered that FTY720-CDs@GelMA hydrogel could dramatically boost NSC proliferation while also promoting neuronal regeneration and synaptic formation, hence lowering cavity area.Conclusion: Our findings suggest that the innovative treatment of FTY720-CDs@GelMA paired with NSCs can effectively improve functional recovery in SCI patients, making it a promising therapeutic alternative for SCI.Keywords: spinal cord injury, carbon dots, FTY720, neural stem cells, hydrogel, GelMA, nerve damage repair

Fang Gao,1,&ast; Xialin Zhang,2,&ast; Xiaolan Wang,2 Junyan Zhang,3 Fang Wang,1 Yan Zhou,4 Jing Wang,1 Xuewen Li,5 Ruijuan Zhang2 1Department of Prevention Care in Healthcare, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of Hematology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 3Department of Clinical Epidemiology and Evidence-Based Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 4Department of Laboratory, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 5Department of Cardiology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ruijuan Zhang; Xuewen Li, Email 13593169668@163.com; xuewenli1010@126.comPurpose: To determine the current status of vitamin D status and the associated factors for its deficiency among Chinese hospital staff.Methods: The physical examination data of 2509 hospital staff members was analyzed alongside that of 1507 patients who visited the hospital during the corresponding period of the examination. Serum concentration of 25-hydroxyvitamin D (25(OH)D) were measured in the participants. The hospital staff also completed surveys about general information, laboratory examination, and occupational characteristics.Results: The median vitamin D status (serum 25(OH)D concentration) of the participants was 9.0 ng/mL, ranging from 6.5 to 44.7 ng/mL, and the prevalence of deficiency (< 12.3 ng/mL) was 81.47% (2044/2509). The multivariable logistic regression revealed that nurses (OR = 1.54, 95% CI 1.09– 2.19, p = 0.015), BMI below 18 (OR = 2.39, 95% CI 1.02– 5.58, p = 0.045) associated with higher prevalence of vitamin D deficiency. In the contrast, age above 30 (OR = 0.69, 95% CI 0.53– 0.91, p = 0.009) and a high level of uric acid (OR = 0.56, 95% CI 0.41– 0.78, p = 0.001) associated with lower prevalence of vitamin D deficiency. The prevalence of vitamin D deficiency was higher among the hospital staff (81.47%) compared to the patients who visited the hospital during the same time period (65.69%). A substantial disparity was observed in the propensity score matching dataset (69.14% vs 79.94%, p < 0.001).Conclusion: Hospital staff are a high-risk group for vitamin D deficiency. Paying attention to vitamin D status and supplementation of this vitamin are pertinent aspects of hospital staff health care. Outdoor activities, vitamin D supplementation, and foods rich in vitamin D should be advocated.Keywords: vitamin D deficiency, 25-hydroxyvitamin D, hospital staff, cross-sectional

Rui Zhang,1,2 Zhengyao Yang,3 Xiaoyong Shen,3 Lu Xia,4 Yun Cheng5 1Department of Nursing, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China; 2School of Nursing, Fudan University, Shanghai, 200030, People’s Republic of China; 3Department of Chest Surgery, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China; 4Day Surgery Unit, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China; 5School of Medicine, The Chinese University of Hong Kong, Shenzhen, 518172, People’s Republic of ChinaCorrespondence: Lu Xia, Day Surgery Unit, Huadong Hospital Affiliated to Fudan University, No. 221 of Yanan West Road, Jingan District, Shanghai, 200040, People’s Republic of China, Tel +86 21-62483180-530401, Email yihaibeilu@126.com Yun Cheng, School of Medicine, The Chinese University of Hong Kong, Shenzhen, 518172, People’s Republic of China, Tel +86 755-23519000, Email cloud2011930@qq.comObjective: To identify latent classes of preoperative physical dysfunction in elderly patients with early lung cancer. To analyze the differences in demographic characteristics between different classes.Methods: We invited elderly patients with early lung cancer who were scheduled for surgery at Shanghai Elderly Characteristic Hospital to participate in the study using a convenience sampling method. We took latent class analysis to divide elderly patients with early lung cancer into latent classes based on preoperative physical dysfunction features. Furthermore, we used single-factor analysis and multinomial logistic regression to investigate the influence variables of each latent class.Results: The characteristics of preoperative physical dysfunction in elderly patients with early lung cancer can be divided into “Anxiety/depression emotion-poor sleep group” “Frailty of physical function group” “Pulmonary hypofunction-low activity tolerance group”. The distribution of age, chronic disease history, COPD history, smoking history and perceived social support level of elderly patients with early lung cancer in different potential categories were not the same, and the differences were statistically significant (P< 0.05). The elderly lung cancer patients with chronic disease history and age ≥ 75 years were more likely to be classified as “frailty of physical function group”. The elderly lung cancer patients with COPD and smoking history were more likely to be classified into “pulmonary hypofunction-low activity tolerance group”. Elderly lung cancer patients with moderate or low degree of perceived social support were more prone to be grouped into “anxiety/depression emotion-poor sleep group”.Conclusion: The variety of preoperative physical dysfunction seen in elderly patients with early lung cancer can be categorized into three latent classes. Medical professionals should create strategies for intervention for multiple patient populations with the goal of further enhancing their general state of life.Keywords: elderly, lung neoplasm, preoperative physical dysfunction, latent class analysis, influence factors

Ruonan Zhang, Yiying Xiong, Linyi Zhang, Lin Liu Department of Hematology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Lin Liu, Email liulin@cqmu.edu.cnPurpose: To investigate the clinical characteristics, etiology, and risk factors of bacterial bloodstream infection (BSI) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. This study also aimed to provide a clinical basis for early identification of high-risk patients and optimization of empirical antimicrobial treatment.Patients and Methods: This is a retrospective study of clinical data during agranulocytosis from 331 patients with hematological malignancies who underwent allo-HSCT at our institute between January 2016 and December 2022. The incidence, distribution and drug resistance patterns, and the risk factors of BSI were analyzed.Results: Among the 331 HSCT patients, 250 had febrile neutropenia and 45 cases were found to have BSI. The incidence of BSI in patients with agranulocytosis fever was 18% (45/250). A total of 48 pathogens were isolated during BSI episodes, gram-negative bacteria (GNB) accounted for 70.8% (34/48), gram-positive bacteria (GPB) for 29.2% (14/48). Multivariate analysis revealed that ≥grade 2 acute graft-versus-host disease (aGVHD) and previous BSI within 6 months before HSCT were independently associated with an increased occurrence of BSI. Coagulase-negative staphylococci (CoNS) and Escherichia coli were the most commonly isolated GPB and GNB, respectively. A total of 32 GNB were tested for drug susceptibility, the detection rate of carbapenem-resistant Enterobacteriaceae (CRE) was 12.5% (4/32), and extended-spectrum β-lactamase (ESBL) accounted for 56.3% (18/32).Conclusion: BSIs are still a common and severe complication after allo-HSCT. In our center, BSIs in allo-HSCT patients are dominated by gram-negative bacteria and the resistance rate to carbapenem drugs is high. Risk factors for BSI during agranulocytosis were previous BSI within 6 months before HSCT and ≥grade 2 aGVHD.Keywords: allogeneic hematopoietic stem cell transplantation, bloodstream infection, pathogenic bacteria, antibiotic resistance patterns, risk factors

Xumei Wu,1,2 Feifei Yang,3 Ruina Zhang1 1Department of Dermatology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Dermatology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of China; 3Department of Dermatology, Tongzhou Maternal & Child Health Hospital of Beijing, Beijing, People’s Republic of ChinaCorrespondence: Ruina Zhang, Department of Dermatology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People’s Republic of China, Tel +8613811708671, Email zrn1780@126.comObjective: To outline the clinical manifestations observed in patients with scabies misdiagnosed as generalized eczema, analyse the factors contributing to these misdiagnoses and explore potential reasons for the resurgence of scabies.Patients and Methods: A retrospective analysis was performed to investigate the patients with scabies misdiagnosed as generalized eczema.Results: We included 23 patients, with twelve (52.17%) being male and eleven (47.83%) female. The illness duration ranged from 0.5 to 7 months. Among all patients, 12 (52.17%) were residents of nursing homes, 5 (21.74%) were staff members of these facilities, 4 (17.39%) were caregivers of long-term hospitalized relatives, 1 (4.35%) was a construction worker, and 1 (4.35%) had a history of tourism. The rash predominantly affected the trunk and extremities, 12 patients (52.17%) are each involved the perineum and fingers webbings. The presentations included erythema, papules, and nodules. The main complaint of all patients was nocturnal itch. Under direct microscopy, 5 patients (21.74%) tested positive for scabies mites, and 3 (13.04%) showed histopathological features consistent with scabies. All patients were initially misdiagnosed with generalized eczema.Conclusion: Over half of all patients diagnosed with scabies either resided or worked in long-term care facilities. The lack of awareness of scabies among medical staff in long-term care facilities readily led to frequent misdiagnosis. Comprehensive measures should be implemented urgently to strengthen disease management.Keywords: scabies, long-term care facilities, elderly, misdiagnose, pruritus

Rui Zhang,1,&ast; Zhengwei Gui,2,&ast; Jianguo Zhao,1 Lu Zhao2 1Department of Thyroid and Breast Surgery, Wuhan No. 1 Hospital, Wuhan, 430030, People’s Republic of China; 2Department of Thyroid and Breast Surgery, Tongji Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lu Zhao, Department of Thyroid and Breast Surgery, Tongji Hospital affiliated with Tongji Medical College of Huazhong University of Science and Technology, No. 1095 of Jiefang Avenue, Wuhan, 430030, People’s Republic of China, Email luzhao268@outlook.comPurpose: B-cell lymphoma 9 (BCL9), a key transcription co-activator of the Wnt pathway, contributed to tumor progression and metastasis in various tumors, whereas, the role of BCL9 in papillary thyroid cancer (PTC) has not been investigated.Methods: We acquired PTC gene expression data from The Cancer Genome Atlas (TCGA) database. Fifty-nine PTC tissues were applied to validate the clinical significance of BCL9. Cell experiments were applied to investigate the role of BCL9. Bioinformatics analysis was employed to investigate the biological functions of BCL9.Results: We found that BCL9 was higher expressed (P < 0.05) and an independent risk factor for lymph node metastasis (OR = 3.770, P = 0.025), as well as associated with poorer progression-free survival (PFS) (P = 0.049) in PTC. BCL9 knockdown inhibited proliferation and invasion of PTC cells. BCL9 was positively associated with the key genes of Wnt/β-catenin and MAPK pathway by co-expression analysis. GO, KEGG and GSEA analysis showed BCL9 might participated in PPAR, cAMP, and focal adhesion pathway. CIBERSORT analysis found BCL9 was negatively associated with CD8+ T cells and NK cell infiltration and positively with PD-L1 expression.Conclusion: Therefore, BCL9 was associated with lymph node metastasis and shorter PFS of PTC, due to promotion of PTC cell proliferation and invasion, activation of Wnt/β-catenin and MAPK pathway, inhibition of CD8+ T and NK cell infiltration, and promotion of PD-L1 expression.Keywords: BCL9, papillary thyroid cancer, lymph node metastasis, tumor immune microenvironment, tumor-infiltrating immune cells

Rui Zhang,1,2,&ast; Yingying Ge,3,&ast; Lu Xia,4 Yun Cheng5 1Department of Nursing, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China; 2Department of Nursing, Fudan University, Shanghai, 200433, People’s Republic of China; 3Yijiangmen Community Health Service Center, Nanjing, 210009, People’s Republic of China; 4Day Surgery Unit, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China; 5School of Medicine, The Chinese University of Hong Kong, Shenzhen, 518172, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lu Xia, Day Surgery Unit, Huadong Hospital Affiliated to Fudan University, 221 of Yanan West Road, Jingan District, Shanghai, 200040, People’s Republic of China, Tel +86 21-62483180-530401, Email yihaibeilu@126.com Yun Cheng, School of Medicine, The Chinese University of Hong Kong, Shenzhen, 518172, People’s Republic of China, Tel +86 755-23516157, Email cloud2011930@qq.comBackgrounds: With the advent of the big data era, hospital information systems and mobile care systems, among others, generate massive amounts of medical data. Data mining, as a powerful information processing technology, can discover non-obvious information by processing large-scale data and analyzing them in multiple dimensions. How to find the effective information hidden in the database and apply it to nursing clinical practice has received more and more attention from nursing researchers.Aim: To look over the articles on data mining in nursing, compiled research status, identified hotspots, highlighted research trends, and offer recommendations for how data mining technology might be used in the nursing area going forward.Methods: Data mining in nursing publications published between 2002 and 2023 were taken from the Web of Science Core Collection. CiteSpace was utilized for reviewing the number of articles, countries/regions, institutions, journals, authors, and keywords.Results: According to the findings, the pace of data mining in nursing progress is not encouraging. Nursing data mining research is dominated by the United States and China. However, no consistent core group of writers or organizations has emerged in the field of nursing data mining. Studies on data mining in nursing have been increasingly gradually conducted in the 21st century, but the overall number is not large. Institution of Columbia University, journal of Cin-computers Informatics Nursing, author Diana J Wilkie, Muhammad Kamran Lodhi, Yingwei Yao are most influential in nursing data mining research. Nursing data mining researchers are currently focusing on electronic health records, text mining, machine learning, and natural language processing. Future research themes in data mining in nursing most include nursing informatics and clinical care quality enhancement.Conclusion: Research data shows that data mining gives more perspectives for the growth of the nursing discipline and encourages the discipline’s development, but it also introduces a slew of new issues that need researchers to address.Keywords: data mining, nursing, bibliometric analysis, global trends, hotspots

Zeyu Huang,1 Mingyan Chen,1 Yang Peng,1 Ruzhi Zhang2 1Department of Dermatology, The Third Affiliated Hospital of Soochow University, Changzhou, People’s Republic of China; 2Department of Dermatology, The Second Affiliated Hospital of Wannan Medical College, Wuhu, People’s Republic of ChinaCorrespondence: Ruzhi Zhang, Department of Dermatology, The Second Affiliated Hospital of Wannan Medical college, No. 10 Rehabilitation Road, Jinghu District, Wuhu, 241101, People’s Republic of China, Tel +86 18761161826, Email zhangruzhi628@163.comAbstract: Tinea capitis, a common cutaneous fungal infection, shows an increasing prevalence with the increasing number of pets. We present tinea capitis in a 4-year-old girl presenting without typical symptoms such as alopecia or hair breakage. After a comprehensive evaluation including dermoscopy, Wood’s light, direct KOH fluorescent staining, scanning electron microscopy, fungal culture and mass spectrometry analysis, a diagnosis of tinea capitis infected Microsporum canis carried by domestic cats was made. We preliminarily explored the two modes of hair erosion by tinea capitis fungi and analyzed the possibility of the feature in this case. This case highlights the importance of accurate diagnosis and appropriate therapeutic intervention in cases of paediatric tinea capitis, particularly in households with resident pets.Keywords: dermoscopy, microsporum canis, scanning electron microscopy, mass spectrometry, tinea capitis

Huiying Wang,1 Ruzhi Zhang2 1Department of Dermatology, The Third Affiliated Hospital of Soochow University, Changzhou, People’s Republic of China; 2Department of Dermatology, The Second Affiliated Hospital of Wannan Medical College, Wuhu, People’s Republic of ChinaCorrespondence: Ruzhi Zhang, Department of Dermatology, The Second Affiliated Hospital of Wannan Medical College, Wuhu, 241000, People’s Republic of China, Tel +8618761161826, Email zhangruzhi628@163.comAbstract: A 43-year-old male was diagnosed with vitiligo and had been treated with topical nitrogen mustard at the age of 13. Following two years of treatment, eruptive cherry angiomas developed and presented as widely distributed red papules throughout his trunk and proximal limbs. Ceasing the use of nitrogen mustard slowed the emergence of lesions. This case highlights the potential adverse effects associated with nitrogen mustard treatment in individuals with susceptibility, as it may lead to the onset of eruptive cherry angiomas.Keywords: eruptive cherry angiomas, nitrogen mustard, vitiligo

Zhao K, Zhang R, Li T, Xiong Z. Cancer Manag Res. 2019;11:3861–3868. We, the Editor and Publisher of the journal Cancer Management and Research have retracted the published article. Following publication, concerns were raised regarding the use of non-verifiable cell lines described in the article. The concerns related specifically to the use of cell lines which were found to be either contaminated, wrongly identified, improperly indexed, unavailable through external cell line repositories, and/or lacking publications describing their establishment. Overall, these concerns raised doubts about the validity of the findings described in the article. The corresponding author did not respond to our queries and was unable to provide information relating to the use of these cell lines or provide original data relating to the study. As verifying the validity of published work is core to the integrity of the scholarly record, the Publisher and Editor requested to retract the article and the corresponding author was notified of 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”.

Understanding reaction kinetics can provide valuable information for the design and optimization of a reaction process. In this study, the reduction degree and carbonitriding ratio of TiO2 in the CH4-H2-N2 system were investigated to understand the kinetics of carbonitriding reduction. The experimental results revealed the following important findings. The reduction degree of TiO2 increased significantly within the temperature range of 1000°C to 1200°C. At the same time, the duration of complete carbonitride time decreased with increasing temperature. However, it was found that excessively high temperatures (1200°C) had a detrimental effect on the degree of reduction. Consequently, the optimal reduction temperature was set at 1100°C, in order to achieve a balance between reduction degree and reaction time. The process of carbonitride reduction of TiO2 in the CH4-H2-N2 system corresponded to the unreacted nuclear model, where the process was mainly controlled by chemical reactions. A calculated apparent activation energy of 99.35 kJ/mol was obtained for the carbonitriding reduction process. The identification of the optimal reduction temperature and the dominant role of chemical reactions provide valuable insights for the design and optimization of carbonitriding processes with titanium compounds.

Changyou Luo,1,&ast; Ruiqing Zhang,2,&ast; Ji Liu,1,&ast; Xingyue He,1 Shengzhou Li,1 Chuanjiang Ran,1 Songbo Ma,3 Yan Shen1 1Department of Pharmaceutics, China Pharmaceutical University, Nanjing, 211100, People’s Republic of China; 2Children’s Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Oral and Maxillofacial Surgery, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou, Jiangsu, 225300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Shen; Songbo Ma, Email shenyan@cpu.edu.cn; masongbo1978@163.comPurpose: Rapid detection and diagnosis of diseases facilitate timely and effective treatment of cardiovascular diseases (CVD). The establishment of a one-step rapid detection method provides a new method for the initial screening and disease risk assessment of patients with cardiovascular diseases in primary medical units.Methods: Hollow gold nanoparticles (HGNPs) were synthesized using a cobalt template method followed by use as signal amplification probes for ultra-sensitive quantitative detection of serum C-reactive protein (CRP). To induce the localized surface plasmon resonance (LSPR) and improve protein labeling efficiency, we developed a sensitive detection mode by coating polyvinylpyrrolidone (PVP-K30) on the HGNPs, resulting in a significant improvement in detection performance.Results: Compared to traditional colloidal GNP-based LFTA, PVP-coated HGNPs exhibit a lower visual detection limit of 1 ng/mL, which a 25-fold decrement compare to using GNPs as the antibody-labeled probe, and the detection limit could be reduced to 0.14 ng/mL under the quantitative instrument.Conclusion: The one-step method based on HGNP immunochromatographic strips modified with PVP established in this study can be used for the detection of CRP and hs-CRP in biological samples. The performance of the immunochromatographic technique designed in this study was evaluated from the perspective of synthetic markers, and the application conditions of this strip were screened, verifying its high specificity, indicating that it has high sensitivity and strong detection limit compared to colloidal gold. The sensitivity of the hollow gold immunochromatographic test strip in this article has been increased by about 25 times, providing a new method for rapid detection of CVD in clinical diagnosis.Keywords: C-reactive protein, lateral flow immunoassay, hollow gold nanoparticles, in vitro diagnostics, polyvinylpyrrolidone

Sachula,&ast; Zhenjie Yang,&ast; Tianyuan Yu, Jinping Chen, Runlong Zhang, Yingqi Zhang, Jiayue Liu, Hanyu Zhang, Jiawei Sun School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tianyuan Yu, School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, People’s Republic of China, Tel +8618210220868, Email yutianyuan@sina.comPurpose: This study aimed to investigate changes in metabolomic expression in the spinal dorsal horn (SDH) and thalamus during a Tuina session, aiming to elucidate the mechanism of immediate analgesia.Methods: The rats were randomly divided into three groups: the Sham group, the Model group, and the Tuina group. A minor chronic constriction injury (minor CCI) model was established in both the Model group and the Tuina group. The therapeutic effect of Tuina was determined using the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) tests. Differential metabolites of the SDH and thalamus were detected using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Bioinformatic analysis was performed using CV, PCA, Venn, and KEGG.Results: The therapeutic effect of MWT and TWL after instant Tuina intervention was significant. The therapeutic effect of Tuina instant was significantly better compared to the Model group. In the Veen analysis, it was found that Tuina instantly regulates 10 differential metabolites in the SDH and 5 differential metabolites in the thalamus. In the KEGG enrichment analysis, we found that differential metabolites were enriched in 43 pathways in the thalamus and 70 pathways in the SDH.Conclusion: Tuina therapy may have analgesic effects by metabolizing neurotransmitters such as 2-Picolinic Acid, 5-Hydroxy-Tryptophan Glutathione Betaine-aldehyde-chloride Leucine Lysine Methionine Sarcosine Succinic Acid Histidine Acetylcholine and 5-Hydroxyindoleacetic Acid through the cAMP pathway. It also affects pathways of neurodegeneration-multiple diseases, butanoate metabolism, tyrosine metabolism. Keywords: neuropathic pain, tuina, neurotransmitters, thalamus, spinal dorsal horn, LC-MS

Kui Zhang,1,&ast; Yan Liu,2,&ast; Zhenrui Zhao,1 Xuewen Shi,1 Ruihao Zhang,1 Yixiang He,1 Huaibin Zhang,1 Wenji Wang3 1The First Clinical Medical College of Lanzhou University, Lanzhou, People’s Republic of China; 2Department of Gynecology, First Affiliated Hospital of Xi ‘an Medical College, Xi’ an, People’s Republic of China; 3Department of Orthopedics, the First Hospital of Lanzhou University, Lanzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenji Wang, The First Hospital of Lanzhou University, Lanzhou, 730000, People’s Republic of China, Tel +8613893221698, Email ldyyjzwwj@outlook.comBackground: Polyvinyl alcohol/Chitosan hydrogel is often employed as a carrier because it is non-toxic, biodegradable, and has a three-dimensional network structure. Meanwhile, Magnesium-doped nano-hydroxyapatite(Mg-nHA) demonstrated high characterization to promote the osteogenic differentiation of bone marrow derived mesenchymal stem cell(BMSCs). Therefore, in order to develop a porous hydrogel scaffold for the application of bone tissue engineering, an appropriate-type Mg-nHA hydrogel scaffold was developed and evaluated.Methods: A composite hydrogel containing magnesium-doped nano-hydroxyapatite (Mg-nHA/PVA/CS) was developed using a magnetic stirring-ion exchange method and cyclic freeze-thaw method design, with polyvinyl alcohol and chitosan as the main components. Fourier transform infrared spectra (FTIR), electron energy dispersive spectroscopy (EDS), X-ray photoelectron spectrometer (XPS) and scanning electron microscopy (SEM) were employed to analyze the chemical structure, porosity, and elemental composition of each hydrogels. The equilibrium swelling degree, moisture content, pH change, potential for biomineralization, biocompatibility, the osteogenic potential and magnesium ion release rate of the composite hydrogel were also evaluated.Results: SEM analysis revealed a well-defined 3D spatial structure of micropores in the synthesised hydrogel. FTIR analysis showed that doping nanoparticles had little effect on the hydrogel’s structure and both the 5% Mg-nHA/PVA/CS and 10% Mg-nHA/PVA/CS groups promoted amide bond formation. EDS observation indicated that the new material exhibited favourable biomineralization ability, with optimal performance seen in the 5% Mg-nHA/PVA/CS group. The composite hydrogel not only displayed favourable water content, enhanced biocompatibility, and porosity (similar to human cancellous bone), but also maintained an equilibrium swelling degree and released magnesium ions that created an alkaline environment around it. Additionally, it facilitated the proliferation of bone marrow mesenchymal stem cells and their osteogenic differentiation.Conclusion: The Mg-nHA/PVA/CS hydrogel demonstrates significant potential for application in the field of bone repair, making it an excellent composite material for bone tissue engineering. Keywords: magnesium-doped nano-hydroxyapatite, polyvinyl alcohol, chitosan, hydrogel, physical crosslinking

Runmin Zhang, Muzhe Li, Huiyun Li, Xun Ran, Fengtian Jin, Qingshan Tan, Zhiwei Chen Department of Orthopaedics, The First Affiliated Hospital of University of South China, Hengyang, People’s Republic of ChinaCorrespondence: Zhiwei Chen, Department of Orthopaedics, The First Affiliated Hospital of University of South China, 69| Chuanshan Road, Hengyang, Hunan, People’s Republic of China, Tel +86-13973409923, Email CZW9915@sina.comAbstract: Inflammation is a common feature of many inflammatory diseases and tumors, and plays a decisive role in their development. Exosomes are extracellular vesicles unleashed by assorted types of cells, and it is widely known that exosomes of different immune cell sources play different functions. Exosome production has recently been reported for immune cells comprising macrophages, T cells, B cells, and dendritic cells (DCs). Immune cell-derived exosomes are involved in a variety of inflammatory responses.Herein, we summarize and review the role of macrophages, T cells, B cells, and dendritic cells (DC) in inflammatory diseases, with a focus on the role of immune cell-derived exosomes in osteoarthritis, rheumatoid arthritis, and the inflammatory tumor microenvironment (TME).These findings are expected to be important for developing new treatments for inflammatory diseases and ameliorating tumor-related inflammation. Keywords: inflammatory diseases, immune cell-derived exosomes, osteoarthritis, rheumatoid arthritis, inflammatory tumor microenvironment

Ziran Wang,1,&ast; Lingjun Kong,1,&ast; Rui Zhang,1 Xiaobo Yang,2 Zhe Cao,3 Tengda Xu,4 Han Zhang,1 Yaling Dou1 1Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3Hunan Light of Life Biotechnology Co., Ltd., Ningxiang, Hunan, People’s Republic of China; 4Department of Health Management, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yaling Dou, Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China, Email douyl@pumch.cnObjective: To evaluate the diagnostic performance of aldo-keto reductase family 1 member B10 (AKR1B10) in a Beijing cohort with hepatocellular carcinoma (HCC).Methods: This study included 521 subjects who visited Peking Union Medical College Hospital from June 2017 to May 2023, including 109 cases of HCC, 165 cases of healthy controls, 106 cases of benign liver diseases, and 141 cases of other cancers. Serum AKR1B10 levels were measured and compared across various groups. Diagnostic performances of serum AKR1B10 and other tumor markers were assessed using receiver operator characteristic (ROC) curves. In addition, a subset of HCC patients who underwent surgical resection were recruited for clinical follow-up study.Results: We found that serum AKR1B10 expression was higher in patients with HCC relative to other control groups. The association between serum AKR1B10 and clinical features of HCC was not observed. Serum AKR1B10 showed a high diagnostic performance for HCC, and when combined with AFP, the diagnostic effectiveness was significantly improved. Specifically, serum AKR1B10 showed superior diagnostic effectiveness for AFP-negative HCC. The clinical follow-up study indicated a gradual decrease in serum AKR1B10 after surgery.Conclusion: Our study demonstrated that serum AKR1B10 is a promising biomarker for HCC, and when used in combination with AFP can significantly improve the detection rate of HCC.Keywords: AKR1B10, AFP, hepatocellular carcinoma, diagnostic performance

Huajian Zhao,1 Ruifen Zhang,2 Yi Chen1 1School of Communication, Soochow University, Suzhou, Jiangsu Province, 215127, People’s Republic of China; 2School of Public Health, Soochow University, Suzhou, Jiangsu Province, 215127, People’s Republic of ChinaCorrespondence: Yi Chen, School of Communication, Soochow University, Suzhou, Jiangsu Province, 215127, People’s Republic of China, Email chenyisuda@suda.edu.cnPurpose: The use of traditional Chinese medicine (TCM) for disease prevention and healthcare has been strongly supported by the Chinese government in recent years, but public perception of TCM remains controversial or resistant, especially in preventing and treating COVID-19. It is therefore crucial to understand the factors that influence public attitudes.Methods: By applying a measure of attitudes towards TCM in epidemic prevention, this study conducted a nationwide survey (n=1192) on the relationships between attitudes towards TCM for the control of COVID-19 and trust, perceptions of risk, scientific literacy, policy endorsement, and cultural values.Results: The results of the study showed surprisingly that scientific literacy and risk perception did not dominate the Chinese public’s attitudes towards TCM for the control of COVID-19. Meanwhile, egalitarianism, policy endorsement, trust in scientist and healthcare personnel played a positive role. Moreover, egalitarianism positively regulates the relationship between trust in scientist and attitudes towards TCM epidemic prevention and control, while collectivism negatively regulates the relationship of the preceding variables.Conclusion: All these findings suggest that attitudes towards the use of TCM are not based on rational cognition and logical reasoning, but are mainly influenced by emotional and cultural factors. This study will help researchers and practitioners understand the importance of cultural values, trust, policy endorsement, and attitudes towards TCM epidemic prevention and control to TCM’s use in healthcare.Keywords: TCM, cultural values, policy endorsement, COVID-19

Xiaohui Bian,1– 3,&ast; Jining He,1– 3,&ast; Rui Zhang,1– 3 Sheng Yuan,1– 3 Kefei Dou1– 4 1Cardiometabolic Medicine Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3State Key Laboratory of Cardiovascular Disease, Beijing, People’s Republic of China; 4National Clinical Research Center for Cardiovascular Diseases, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kefei Dou, Cardiometabolic Medicine Center, National Clinical Research Center for Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, A 167 Beilishi Road, Xicheng District, Beijing, 100037, People’s Republic of China, Tel +86-13801032912, Fax +86-10-6831-3012, Email drdoukefei@126.comBackground: Chronic low-grade inflammation is the common mechanism of both atherosclerosis and type 2 diabetes mellitus (T2DM), and systemic immune-inflammation index (SII) has been emerged as a novel and simple inflammatory biomarker. However, the association between SII and glycemic metabolism and their synergetic effect on the prognosis of coronary artery disease (CAD) patients remains unclear.Methods: A total of 8602 patients hospitalized for percutaneous coronary intervention (PCI) were included. The primary endpoint was major adverse cardiovascular events (MACE), including all-cause death, myocardial infarction (MI), and target vessel revascularization. According to the optimal cut-off value of SII for MACEs, patients were grouped into higher levels of SII (SII-H) and lower levels of SII (SII-L) and further divided by the concomitance of T2DM into four groups: SII-H/T2DM, SII-H/Non-T2DM, SII-L/T2DM, SII-L/Non-T2DM.Results: During a median 2.4-year follow-up, 522 MACEs occurred. The optimal cut-off value of SII for MACEs was 502.5. A 1-unit increase of SII (transformed by natural logarithm) was associated with a 29% increase of MACE risks in the T2DM cohort [adjusted hazard ratio (HR): 1.29, 95% confidence interval (CI): 1.03 to 1.61, P = 0.024], while had no effect in the non-T2DM cohort (HR: 1.03, 95% CI: 0.80 to 1.34, P = 0.800). Compared to those in SII-H/T2DM group, patients in SII-H/Non-T2DM, SII-L/T2DM, SII-L/Non-T2DM had significantly decreased risk of MACEs [adjusted HR: 0.77, 95% CI: 0.61 to 0.98, P = 0.036; adjusted HR: 0.66, 95% CI: 0.50 to 0.87, P = 0.003; adjusted HR: 0.58, 95% CI: 0.45 to 0.74, P < 0.001; respectively]. Multivariable Cox regression analysis also indicated the highest risk in T2DM patients with higher levels of SII than others (P for trend < 0.001).Conclusion: In this large-scale real-world study, diabetic patients with elevated SII levels were associated with worse clinical outcomes after PCI.Keywords: systemic immune-inflammation index, type 2 diabetes mellitus, coronary artery disease, percutaneous coronary intervention

Yilu Zhao,1,2,&ast; Kang Ge,3,&ast; Ruzhi Zhang4 1Department of Dermatology, the First Affiliated Hospital of Bengbu Medical University, Bengbu Medical University, Bengbu, Anhui, People’s Republic of China; 2Department of Dermatology, the Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, People’s Republic of China; 3Department of Dermatology, the Affiliated Hospital of Jiaxing University, the First Hospital of Jiaxing, Jiaxing, Zhejiang, People’s Republic of China; 4Department of Dermatology and STD, the Second Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ruzhi Zhang, Department of Dermatology and STD, the Second Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, 241001, People’s Republic of China, Tel +8618761161826, Email zhangruzhi628@163.comObjective: To identify potential diagnostic markers for vitiligo and determine the significance of immune cell infiltration in pathology.Methods: Three publicly available gene expression profiles (GSE53146, GSE75819 and GSE65127 datasets) from human vitiligo and control samples were downloaded from the GEO database. Differentially expressed genes (DEGs) were screened between 20 vitiligo and 20 control samples. Logical regression of the selection operator (LASSO) model and support vector machine recursive feature elimination (SVM-RFE) analysis were performed to identify candidate biomarkers. The area under the receiver operating characteristic curve (AUC) value was obtained and was used to evaluate the discriminatory ability. The expression level and diagnostic value of the biomarkers in vitiligo were further validated in the GSE65127 dataset (10 vitiligo patients and 10 healthy controls). Finally, the immune cell infiltration of vitiligo was evaluated by CIBERSORT, and the correlation between biomarkers and infiltrating immune cells was analyzed. The compositional patterns of the 22 types of immune cell fractions in vitiligo were estimated from the pooled cohorts using CIBERSORT. In addition, we established a mouse model of vitiligo with monobenzone and validated the screened biomarkers.Results: A total of 23 associated DEGs were identified, including 9 up-regulated and 14 down-regulated genes. Subsequently, 17 genes meeting prognostic criteria and 2 common genes (DCT and KIF1A) were obtained by SVM and Venn diagram screening. Immunodifferential analysis showed that microenvironment of vitiligo patients was altered. Finally, the different expression was verified by polymerase chain reaction (PCR).Conclusion: Biomarkers associated with vitiligo can be screened by comprehensive strategies, and immune cell infiltration plays a key role in the development of vitiligo.Keywords: vitiligo, predictive biomarker, Lasso-SVM algorithms

Cheng Qin, Zhiping Qi, Su Pan, Peng Xia, Weijian Kong, Bin Sun, Haorui Du, Renfeng Zhang, Longchuan Zhu, Dinghai Zhou, Xiaoyu Yang Department of Orthopedic Surgery, the Second Hospital of Jilin University, Changchun, 130041, People’s Republic of ChinaCorrespondence: Xiaoyu Yang, Department of Orthopedic Surgery, the Second Hospital of Jilin University, Changchun, TX, 130041, People’s Republic of China, Email yangxiaoy@jlu.edu.cnAbstract: Spinal cord injury (SCI) treatment represents a major challenge in clinical practice. In recent years, the rapid development of neural tissue engineering technology has provided a new therapeutic approach for spinal cord injury repair. Implanting functionalized electroconductive hydrogels (ECH) in the injury area has been shown to promote axonal regeneration and facilitate the generation of neuronal circuits by reshaping the microenvironment of SCI. ECH not only facilitate intercellular electrical signaling but, when combined with electrical stimulation, enable the transmission of electrical signals to electroactive tissue and activate bioelectric signaling pathways, thereby promoting neural tissue repair. Therefore, the implantation of ECH into damaged tissues can effectively restore physiological functions related to electrical conduction. This article focuses on the dynamic pathophysiological changes in the SCI microenvironment and discusses the mechanisms of electrical stimulation/signal in the process of SCI repair. By examining electrical activity during nerve repair, we provide insights into the mechanisms behind electrical stimulation and signaling during SCI repair. We classify conductive biomaterials, and offer an overview of the current applications and research progress of conductive hydrogels in spinal cord repair and regeneration, aiming to provide a reference for future explorations and developments in spinal cord regeneration strategies. Keywords: neural tissue engineering, electrical stimulation, electrical signal, conductive biomaterials, spinal cord injury microenvironment

Xiangjin Gao,1,2,&ast; Xiuqi Zhang,1,&ast; Le Kuai,3,&ast; Qing Yang,4 Huan Li,4 Rui Zhang,1 Bin Li,1 Ruiping Wang1,2 1Clinical Research Center, Shanghai Skin Diseases Hospital, Medical School of Tongji University, Shanghai, People’s Republic of China; 2School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Obstetrics and Gynecology Department, Songjiang Maternal and Child Health-Care Hospital, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ruiping Wang, Clinical Research Center, Shanghai Skin Diseases Hospital, Medical School of Tongji University, 1278 Baode Road, Jing’an District, Shanghai, 200443, People’s Republic of China, Tel +86-189 1879 1651, Fax +86-21-3680 3000, Email w19830901@126.comObjective: This study was based on a gestational diabetes mellitus (GDM) cohort in Shanghai to examine the association between physical exercise and plasma glucose control among GDM women with and determine what the effects of pre-pregnancy body mass index (BMI).Methods: In this study, GDM was diagnosed if the plasma glucose values at any of the following time points reached the diagnostic threshold: fasting blood glucose (5.1 mmol/L), 1-hour blood glucose (10.0 mmol/L), and 2-hour blood glucose (8.5 mmol/L) by 75 g oral glucose tolerance test (OGTT). Information on GDM women was extracted from the hospital’s health records and prenatal examination forms and was obtained through face-to-face interviews after delivery. A restricted cubic spline curve with four knots was used to flexibly model the relationship between the duration of moderate-intensity physical exercise and the percentage of abnormal plasma glucose among GDM patients with different BMI values. In this study, a P-value less than 0.05 (two-tailed) was considered as statistical significance.Results: Among 1139 GDM women with GDM, the median percentage of abnormal plasma glucose (PG) was 40.0% (interquartile range (IQR): 20.0– 66.7%), and the difference between overweight-obese group and underweight-normal group was statistically significant (50.0% vs 40.0%, P < 0.001). In this study, engaging in more physical exercise during pregnancy contributed to a higher prevalence of satisfactory glycemic control, and women with BMI < 25 kg/m2 should engage in no less than 90 minutes of moderate-intensity physical activity per day to achieve satisfactory glycemic control (prevalence of abnormal PG < 35%). However, over 120 minutes of daily moderate-intensity physical activity is required for GDM women with a BMI ≥ 25 kg/m2 to achieve satisfactory glycemic control.Conclusion: Overweight or obese women with GDM have a higher risk of poor glycemic control and require a longer duration of physical exercise to achieve the same level of blood glucose control.Keywords: gestational diabetes mellitus, plasma glucose control, physical exercise, overweight and obesity