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Hao Huang,1 Zhiping Long,2 Ying Deng,3 Zhicong Huang,3 Zhonghua Lv,4 Qian Sun,4 Hui Liu,4 Hongsheng Liang,5 Fulan Hu6 1Department of Preventive Medicine, Zhuhai Campus of Zunyi Medical University, Zhuhai, Guangdong, People’s Republic of China; 2Department of Epidemiology, Public Health School of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 3Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, People’s Republic of China; 4Department of Neurosurgery, Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 5Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 6Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Medical School, Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Fulan Hu, Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Medical School, Shenzhen, Guangdong, People’s Republic of China, Email hufu1525@163.com Hao Huang, Department of Preventive Medicine, Zhuhai Campus of Zunyi Medical University, Zhuhai, Guangdong, People’s Republic of China, Email hhxiaowo@163.comPurpose: Mitochondrial metabolism is essential for energy production and the survival of brain cells, particularly in astrocytes. Cuproptosis is a newly identified form of programmed cell death that occurs due to the disruption of mitochondrial metabolism caused by excessive copper toxicity. However, the relationship between cuproptosis-related genes (CRGs) in the tumor microenvironment (TME) and the prognosis of gliomas remains unclear.Patients and Methods: In this study, we utilized 32,293 cells obtained from three in-house single-cell RNA sequencing (scRNA-seq) datasets, along with 6,148 cells acquired from the Chinese Glioma Genome Atlas (CGGA) involving 14 glioma patients, to identify and validate the TME of gliomas.Results: Based on an analysis of 32,293 single cells, we investigated intra-tumor heterogeneity, intercellular communication, and astrocyte differentiation trajectories in gliomas. Our findings revealed that the TGFβ signaling pathway exhibited a higher relative strength in astrocyte subpopulations. Additionally, we identified a novel three-gene signature (CDKN2A, SOX2, and MPC1) was identified for prognostic prediction. Furthermore, glioma patients with a high-risk score demonstrated poorer overall survival (OS) compared to those with a low-risk score in both training and testing datasets (Ptraining set < 0.001; Ptest set = 0.037).Conclusion: Our study revealed the prognostic value of the CRGs in astrocytes exhibiting tumor immunosuppressive characteristics in glioma. We established a novel three-gene prognostic model that offers new insights into the prognosis and treatment strategies for gliomas. Keywords: scRNA-seq, gliomas, astrocyte, cuproptosis, prognosis

Zhuohua Zhang,1,2 Yan Liu,2 Da Huang,2 Zhaohe Huang1,3,4 1Department of Cardiology, First Affiliated Hospital of Jinan University, Guangzhou, 510630, People’s Republic of China; 2Department of Cardiology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, People’s Republic of China; 3Affiliated Southwest Hospital, Youjiang Medical University for Nationalities, Baise, 533000, People’s Republic of China; 4Graduate School, Youjiang Medical University for Nationalities, Baise, 533000, People’s Republic of ChinaCorrespondence: Zhaohe Huang, Department of Cardiology, First Affiliated Hospital of Jinan University, Guangzhou, 510630, People’s Republic of China, Tel +86 13977691455, Fax +86 776-2853272, Email bshuangzhaohe@163.comPurpose: Myocardial ischemia-reperfusion injury (MIRI) is characterized by inflammation and ferroptosis, but the precise mechanisms remain unknown. This study used single-cell transcriptomics technology to investigate the changes in various cell subtypes during MIRI and the regulatory network of ferroptosis-related genes and immune infiltration.Methods: Datasets GSE146285, GSE83472, GSE61592, and GSE160516 were obtained from Gene Expression Omnibus. Each cell subtype in the tissue samples was documented. The Seurat package was used for data preprocessing, standardization, and clustering. Cellphonedb was used to investigate the ligand-receptor interactions between cells. The hdWGCNA analysis was used to create a gene co-expression network. GSVA and GSEA were combined to perform functional enrichment and pathway analysis on the gene set. Furthermore, characteristic genes of the disease were identified using Lasso regression and SVM algorithms. Immune cell infiltration analysis was also performed. MIRI rat models were created, and samples were taken for RT-qPCR and Western blot validation.Results: The proportion of MIRI samples in the C2, C6, and C11 subtypes was significantly higher than that of control samples. Three genes associated with ferroptosis (CD44, Cfl1, and Zfp36) were identified as MIRI core genes. The expression of these core genes was significantly correlated with mast cells and monocyte immune infiltrating cells. The experimental validation confirmed the upregulation of Cd44 and Zfp36 expression levels in MIRI, consistent with current study trends.Conclusion: This study used single-cell transcriptomics technology to investigate the molecular mechanisms underpinning MIRI. Numerous important cell subtypes, gene regulatory networks, and disease-associated immune infiltration were also discovered. These findings provide new information and potential therapeutic targets for MIRI diagnosis and treatment.Keywords: myocardial ischemia-reperfusion injury, ferroptosis, immune cell infiltration, single-cell transcriptome sequencing, WGCNA

Weixiong Chen,1,2,&ast; Jianqiang Liang,3,&ast; Shuang He,1,4,5 Qingsong Liang,1,4,5 Wenting Tian,6 Aobo Lu,1 Demin Li,1 Zhicheng Huang,1 Guanyi Wu1,4,5 1College of Basic Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530299, People’s Republic of China; 2School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, People’s Republic of China; 3Department of Dermatology, the First People’s Hospital of Yulin, Yulin, Guangxi, 537000, People’s Republic of China; 4Key Laboratory for Complementary and Alternative Medicine Experimental Animal Models of Guangxi, Nanning, Guangxi, 530299, People’s Republic of China; 5Guangxi Key Laboratory of Translational Medicine for Treating High-Incidence Infectious Diseases with Integrative Medicine, Nanning, Guangxi, 530299, People’s Republic of China; 6College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530299, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guanyi Wu, College of Basic Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530299, People’s Republic of China, Email wugy@gxtcmu.edu.cnPurpose: Psoriasis is an immune-related disorder characterized by silver scales, epidermis thickness, and itching. She-Chuang-Si-Wu-Tang (SSWT), a traditional Chinese medicine decoction, has been used clinically for 400 years. Although it benefits psoriasis treatment, the mechanism of action is still unclear. This study explores SSWT’s molecular mechanism in treating psoriasis through network pharmacology analysis and experiments.Methods: We identified relevant SSWT and psoriasis targets using network pharmacology and conducted SSWT quality control with high-performance liquid chromatography (HPLC). A mouse model of psoriasis was established using imiquimod (IMQ), with the drug administered continuously for seven days, spanning an eight-day period. During the experiment, we observed spontaneous scratching behaviors and assessed the Psoriasis Area and Severity Index (PASI) scores. At the conclusion of the experiment, we examined skin tissue pathology under an optical microscope and measured epidermal thickness. Additionally, we used enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) to measure interleukin (IL)-23, IL-17A, IL-17F, and interferon (IFN)-γ levels in the mice’s serum and their mRNA expression in the skin. Western blot analysis was conducted to assess protein levels related to signaling pathways.Results: Results indicate that SSWT may target IL-17 signaling pathways and T helper (Th) 17 cell differentiation, as predicted by network pharmacology. SSWT significantly improved the PASI and Baker scores, reduced epidermal thickness, and decreased spontaneous scratching in IMQ-induced mice. Additionally, SSWT treatment significantly lowered the concentrations of inflammatory factors in the serum and skin lesions, as well as mRNA expression levels, compared to the IMQ group. Furthermore, SSWT significantly inhibited the phosphorylation of both the signal transducer and activator of transcription 3 (STAT3) and mitogen-activated protein kinase (MAPK) pathways.Conclusion: In summary, this study unveiled the potential anti-psoriatic mechanism of SSWT, offering new evidence for its clinical application. Keywords: She-Chuang-Si-Wu-Tang, psoriasis, inflammation, itch, STAT3, MAPK

Fuzhen Yuan,1 Zhenhua Huang,1,2 Dingye Yao,1,2 Junsheng Sun1,2 1Department of General Practice, Longgang District Central Hospital of Shenzhen, Shenzhen, 5181116, People’s Republic of China; 2Shenzhen Clinical College of Medicine, Guangzhou University of Chinese Medicine, Shenzhen, 5181116, People’s Republic of ChinaCorrespondence: Junsheng Sun, Department of General Practice, Longgang District Central Hospital of Shenzhen, No. 6082, Longgang Avenue, Longgang District, Shenzhen, Guangdong Province, 518100, People’s Republic of China, Tel +86-15338897372, Email junshengsun@126.comAbstract: Vitamin B12 is essential for various bodily functions, and its deficiency may cause hematological manifestations. We report a case of a previously healthy 65-year-old female who was admitted to our hospital with reduced sense of taste and painful tongue. The serum level of vitamin B12 was decreased. However, her complete blood count did not show any evidence of macrocytosis, instead, her mean corpuscular volume was low. Gene sequencing indicated an β-thalassemia minor and that probably masked the megaloblastic features of vitamin B12 deficiency.Keywords: pernicious anemia, autoimmune gastritis, thalassemia, glossitis

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

Jiaqiong Lin,1,2 Yan Lin,3 Xiaoyong Li,4 Fei He,5 Qinyuan Gao,3 Yuanjun Wang,3 Zena Huang,3 Fu Xiong5,6 1Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, People’s Republic of China; 2Dongguan Maternal and Child Health Care Hospital, Postdoctoral Innovation Practice Base of Southern Medical University, Dongguan, People’s Republic of China; 3Yunkang School of Medicine and Health, Nanfang College, Guangzhou, People’s Republic of China; 4General Surgery Department; Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 5Department of Medical Genetics/Experimental Education/Administration Center, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 6Department of Fetal Medicine and Prenatal Diagnosis, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Fu Xiong, Department of Medical Genetics/Experimental Education/Administration Center, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, People’s Republic of China, Email xiongfu@smu.edu.cn Zena Huang, Yunkang School of Medicine and Health, Nanfang College, Guangzhou, 510970, People’s Republic of China, Email 506647168@qq.comBackground: Diabetic kidney disease (DKD) is an intricate complication of diabetes with limited treatment options. Anoikis, a programmed cell death activated by loss of cell anchorage to the extracellular matrix, participated in various physiological and pathological processes. Our study aimed to elucidate the role of anoikis-related genes in DKD pathogenesis.Methods: Differentially expressed genes (DEGs) associated with anoikis in DKD were identified. Weighted gene co-expression network analysis (WGCNA) was conducted to identify DKD-correlated modules and assess their functional implications. A diagnostic model for DKD was developed using LASSO regression and Gene set variation analysis (GSVA) was performed for enrichment analysis. Experimental validation was employed to validate the significance of selected genes in the progression of DKD.Results: We identified 10 anoikis-related DEGs involved in key signaling pathways impacting DKD progression. WGCNA highlighted the yellow module’s significant enrichment in immune response and regulatory pathways. Correlation analysis further revealed the association between immune infiltration and anoikis-related DEGs. Our LASSO regression-based diagnostic model demonstrated a well-predictive efficacy with seven identified genes. GSVA indicated that gene function in the high-risk group was primarily associated with immune regulation. Further experimental validation using diabetic mouse models and data analysis in the single-cell dataset confirmed the significance of PYCARD and SFN in DKD progression. High glucose stimulation in RAW264.7 and TCMK-1 cells showed significantly increased expression levels of both Pycard and Sfn. Co-expression analysis demonstrated distinct functions of PYCARD and SFN, with KEGG pathway analysis showing significant enrichment in immune regulation and cell proliferation pathway.Conclusion: In conclusion, our study provides valuable insights into the molecular mechanisms involved in DKD pathogenesis, specifically highlighting the role of anoikis-related genes in modulating immune infiltration. These findings suggest that targeting these genes may hold promise for future diagnostic and therapeutic approaches in DKD management.Keywords: diabetic kidney disease, anoikis, immune infiltration, biomarker, PYCARD, SFN

Yanhong Liu,1 Qi Wang,1 Chuanlei Zheng,1,2 Zhengchun Huang,3 Jian Li,3 Ming Hao,1 Minghua Dong,1,2 Xiaoting Luo,2,4 Qingfeng Wu1,2 1School of Public Health & Healthcare Management, Gannan Medical University, Ganzhou, People’s Republic of China; 2Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, People’s Republic of China; 3School of Basic Medicine Sciences, Gannan Medical University, Ganzhou, People’s Republic of China; 4School of General Practice Medicine, Gannan Medical University, Ganzhou, People’s Republic of ChinaCorrespondence: Qingfeng Wu, Gannan Medical University, Rongjiang New District College Park, Ganzhou, Jiangxi, 341000, People’s Republic of China, Tel +86-797-8169713, Fax +86-797-8169600, Email wuqf2006@gmu.edu.cnPurpose: The prevalence of diabetes in China is increasing, influenced by economic and genetic factors, with varying rates across regions. The Hakka population in Ganzhou city has unique exposures compared to surrounding districts, while limited research reported the epidemiological characteristics of type 2 diabetes mellitus (T2DM) in this population. This study aims to investigate the prevalence and influencing factors of T2DM among the population, thereby establishing a robust foundation for disease prevention and control measures.Patients and Methods: In 2017, a multistage random sampling method selected 3028 individuals from Ganzhou City’s permanent resident population. Physical examinations, blood tests, and questionnaire surveys were conducted for data collection, with binary logistic regression analysis used to examine factors affecting T2DM prevalence.Results: A total of 2978 valid samples were included in this study. The average age of the surveyed population was 52.83± 7.88 years, comprising 966 males and 2012 females. The prevalence rates of T2DM were 11.8% and 12.9% in males and females, respectively, while the standardized prevalence rate was recorded as 9.1%. Logistic regression analysis revealed that age (Odds Ratio[OR]=1.05, 95% Confidence Interval [CI]:1.03– 1.06), hypertension (OR=2.22, 95% CI:1.71– 2.93), family history of diabetes (OR= 3.54, 95% CI: 2.58– 4.85), overweight (OR=1.73, 95% CI: 1.20– 2.48), high total cholesterol (OR=1.17, 95% CI:1.09– 1.27), elevated low-density lipoprotein cholesterol (OR=1.19, 95% CI:1.00– 1.40) and serum insulin (OR=1.05, 95% CI:1.03– 1.06) were identified as significant risk factors for T2DM, Conversely, a higher level of high-density lipoprotein cholesterol (OR=0.55, 95% CI:0.36– 0.84) was found to be inversely related to T2DM development.Conclusion: The prevalence of T2DM in Ganzhou city has significantly increased. The effective implementation of comprehensive management strategies aimed at addressing hypertension, overweight, dyslipidemia, and abnormal serum insulin level is essential for promoting overall well-being and efficiently controlling the prevalence of T2DM.Keywords: type 2 diabetes mellitus, cross-sectional studies, epidemiology, influence factors

Hui Gao,1 Xi Cheng,1 Xu Zuo,2 Zhaolan Huang2 1Department of General Practice, Tianyou Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei Province 430000, People’s Republic of China; 2Department of Respiratory and Digestive, Geriatric Hospital Affiliated with Wuhan University of Science and Technology, Wuhan, Hubei Province, 430000, People’s Republic of ChinaCorrespondence: Zhaolan Huang, Department of Respiratory and Digestive, Geriatric Hospital Affiliated with Wuhan University of Science and Technology, No. 2, Huangjiahu West Road, Hongshan District, Wuhan, Hubei Province, 430000, People’s Republic of China, Tel +86-19819051958, Email 45477428@qq.comBackground: Chronic Obstructive Pulmonary Disease (COPD) progression in the elderly is notably influenced by nutritional, immune, and inflammatory status. This study aimed to investigate the impact of adequate energy supply on these indicators in COPD patients.Methods: COPD patients meeting specific criteria were recruited and categorized into energy-adequate and energy-deficient groups based on their energy supply. Comparable demographic factors such as age, gender, smoking and drinking history, COPD duration, inhaled drug classification, and home oxygen therapy application were observed. Notable differences were found in BMI and inhaled drug use between the two groups.Results: The energy-adequate group exhibited significant improvements in various health indicators, including lymphocyte count, hemoglobin, CRP, total cholesterol, prealbumin, albumin, PNI, SII, SIRI, CAR, and CONUT scores in the secondary auxiliary examination. These positive changes suggest a notable enhancement in nutritional, immune, and inflammatory status.Conclusion: This research highlights the substantial benefits of adequate energy supply in elderly COPD patients. The observed improvements in nutritional, immune, and inflammatory markers underscore the importance of addressing energy needs to positively influence disease-related outcomes in this population. These findings have implications for developing targeted interventions to optimize the well-being of elderly individuals with COPD.Keywords: elderly, chronic obstructive pulmonary disease, energy supply, nutritional status, immune function, inflammatory response

Jian Cui,1 Yunliang Sun,2 Haifeng Jing,3 Qiang Chen,1 Zhihao Huang,1 Xin Qi,1 Hao Cui1 1Department of Big Data and Fundamental Sciences, Shandong Institute of Petroleum and Chemical Technology, Dongying, Shandong, 257061, People’s Republic of China; 2Department of Respiratory and Sleep Medicine, Bin Zhou Medical University Hospital, Binzhou, Shandong, 256600, People’s Republic of China; 3College of Software and Microelectronics, Peking University, Beijing, 100000, People’s Republic of ChinaCorrespondence: Jian Cui, Department of Big Data and Fundamental Sciences, Shandong Institute of Petroleum and Chemical Technology, 271 Bei Er Lu, Dongying City, Shandong Province, 257061, People’s Republic of China, Tel +86-15066073763, Email jian.cui@sdipct.edu.cnPurpose: Sleep structure is crucial in sleep research, characterized by its dynamic nature and temporal progression. Traditional 30-second epochs falter in capturing the intricate subtleties of various micro-sleep states. This paper introduces an innovative artificial neural network model to generate continuous sleep depth value (SDV), utilizing a novel multi-feature fusion approach with EEG data, seamlessly integrating temporal consistency.Methods: The study involved 50 normal and 100 obstructive sleep apnea–hypopnea syndrome (OSAHS) participants. After segmenting the sleep data into 3-second intervals, a diverse array of 38 feature values were meticulously extracted, including power, spectrum entropy, frequency band duration and so on. The ensemble random forest model calculated the timing fitness value for all the features, from which the top 7 time-correlated features were selected to create detailed sleep sample values ranging from 0 to 1. Subsequently, an artificial neural network (ANN) model was trained to delineate sleep continuity details, unravel concealed patterns, and far surpassed the traditional 5-stage categorization (W, N1, N2, N3, and REM).Results: The SDV changes from wakeful stage (mean 0.7021, standard deviation 0.2702) to stage N3 (mean 0.0396, standard deviation 0.0969). During the arousal epochs, the SDV increases from the range (0.1 to 0.3) to the range around 0.7, and decreases below 0.3. When in the deep sleep (≤ 0.1), the probability of arousal of normal individuals is less than 10%, while the average arousal probability of OSA patients is close to 30%.Conclusion: A sleep continuity model is proposed based on multi-feature fusion, which generates SDV ranging from 0 to 1 (representing deep sleep to wakefulness). It can capture the nuances of the traditional five stages and subtle differences in microstates of sleep, considered as a complement or even an alternative to traditional sleep analysis.Keywords: sleep depth value, sleep continuity, EEG features, timing fitness, ANN model

Ziwei Huang,1 Shanli Zhang,1 Zehui Qin,1 Gaoxiang Ai,1 Minhua Li,1 Shiting Gong,1 Yuhong Liu,1 Huifang Zeng,2 Jiannan Chen,1 Ziren Su,1 Zhengquan Lai3 1School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 2The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 3Department of Pharmacy, Shenzhen University General Hospital/Shenzhen University Clinical Medical Academy, Shenzhen University, Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Zhengquan Lai, Department of Pharmacy, Shenzhen University General Hospital/Shenzhen University Clinical Medical Academy, Shenzhen University, Shenzhen, Guangdong, People’s Republic of China, Email cruise0303@163.com Ziren Su, School of pharmaceutical sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China, Email suziren@gzucm.edu.cnPropose: Oxyberberine (OBB), one of the main metabolites of berberine derived from intestinal and erythrocyte metabolism, exhibits appreciable anti-hyperuricemic activity. However, the low water solubility and poor plasma concentration–effect relationship of OBB hamper its development and utilization. Therefore, an OBB-hydroxypropyl-β-cyclodextrin (HP-β-CD) supersaturated drug delivery system (SDDS) was prepared and characterized in this work.Methods: OBB-HP-β-CD SDDS was prepared using the ultrasonic-solvent evaporation method and characterized. Additionally, the in vitro and in vivo release experiments were conducted to assess the release kinetics of OBB-HP-β-CD SDDS. Subsequently, the therapeutic efficacy of OBB-HP-β-CD SDDS on hyperuricemia (HUA) was investigated by means of histopathological examination and evaluation of relevant biomarkers.Results: The results of FT-IR, DSC, PXRD, NMR and molecular modeling showed that the crystallized form of OBB was transformed into an amorphous OBB-HP-β-CD complex. Dynamic light scattering indicated that this system was relatively stable and maintained by formation of nanoaggregates with an average diameter of 23 nm. The dissolution rate of OBB-HP-β-CD SDDS was about 5 times higher than that of OBB raw material. Furthermore, the AUC0-t of OBB-HP-β-CD SDDS (10.882 μg/mL&ast;h) was significantly higher than that of the raw OBB counterpart (0.701 μg/mL&ast;h). The oral relative bioavailability of OBB-HP-β-CD SDDS was also enhanced by 16 times compared to that of the raw material. Finally, in vivo pharmacodynamic assay showed the anti-hyperuricemic potency of OBB-HP-β-CD SDDS was approximately 5– 10 times higher than that of OBB raw material.Conclusion: Based on our findings above, OBB-HP-β-CD SDDS proved to be an excellent drug delivery system for increasing the solubility, dissolution, bioavailability, and anti-hyperuricemic potency of OBB. Keywords: oxyberberine, cyclodextrin, supersaturated drug delivery systems, pharmacokinetics, hyperuricemia

Yongchao Li,1,&ast; Jinfeng Gao,2,&ast; Shuhua Liu,1 Shijian Chen,3 Xiaoyue Wei,3 Yalun Guan,1 Xuejiao Li,1 Yunfeng Li,1 Zhongqiang Huang,1 Ge Li,1 Yuhong Zhao,3 Pinghua Liu,4 Yu Zhang1 1Guangdong Provincial Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring Institute, Guangzhou, 510663, People’s Republic of China; 2Guangdong Quality Supervision and Testing Station for Medical and Health Care Appliances, Institute of Biological and Medical Engineering, Guangdong Academy of Sciences, Guangzhou, 510632, People’s Republic of China; 3School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, People’s Republic of China; 4Department of Chemistry, Boston University, Boston, MA, 02215, USA&ast;These authors contributed equally to this workCorrespondence: Yu Zhang; Pinghua Liu, Email zhangyugzh@hotmail.com; pinghua@bu.eduBackground: Ergothioneine (EGT) is an antioxidant, which could be detected in human tissues, and human skin cells could utilize EGT and play an anti-oxidative role in keratinocytes. And in this study we are going to elucidate whether EGT could protect the skin from photoaging by Ultraviolet (UV) exposure in mice and its molecule pathway.Methods: Histological analysis was performed for evaluating the skin structure change. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were measured with biological assay for evaluating oxidative and antioxidative ability of skin exposed to UV light. And the level of marker molecules in mouse skin were detected by hydroxyproline (Hyp) assay, immunohistochemical analysis, Western blot, and quantitative real-time PCR (qRT-PCR). The markers of skin aging and cell death were tested by cell culture and treatment, Western blot and qRT-PCR.Results: EGT decreased the levels of inflammatory factors induced by UV exposure in mouse skin. MDA and SOD activity detection showed that EGT decreased MDA levels, increased SOD activity, and upregulated PI3K/Akt/Nrf2 signals in mouse skin exposed to UV, which further activated Nrf2 in the nucleus and enhanced the expression of Nrf2 target genes. In the cell model, we revealed that EGT could inhibit the increase in senescence-associated β-galactosidase-positive cells and p16 and γ-H2A.X positive cells induced by etoposide and activate PI3K/Akt/Nrf2 signaling. Moreover, a PI3K inhibitor blocked EGT protection against etoposide-induced cell death.Conclusion: The study showed EGT may play an important protective role against cell damage or death through the PI3K/Akt/Nrf2 signaling pathway in skin.Keywords: ergothioneine, skin aging, PI3K/Akt, Nrf2

Lini Chen,&ast; Weiyong Qin,&ast; Jiangdong Wu, Guilin Zhao, Xiaoqing Jiang, Minghui Li, Zijin Huang,&ast; Xueke Du&ast; Department of Anesthesiology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zijin Huang; Xueke Du, Department of Anesthesiology, the Second Affiliated Hospital of Guangxi Medical University, No. 166 of Daxue East Road, Nanning, Guangxi, 530007, People’s Republic of China, Tel +86-13768114848 ; Tel +86-17307711159, Email batistuta921@163.com; duxueke@gxmu.edu.cnPurpose: This study aims to evaluate the effect of remimazolam on induction and maintenance of general anesthesia in kidney transplant patients.Methods: 120 patients undergoing kidney transplant were divided into two groups: Propofol group (Group P) and Remimazolam group (Group R). Anesthesia induction: remimazolam had injected IV at a dose of 0.15– 0.35 mg/kg in Group R, while propofol had injected IV at a dose of 2.0– 2.5 mg/kg in Group P. Anesthesia maintenance: remimazolam was injected IV at a dose of 0.3– 1.0 mg·kg− 1·h− 1 and propofol was injected IV at a dose of 1– 12 mg·kg− 1·h− 1 in Group R, propofol was injected IV at a dose of 3– 12 mg·kg− 1·h− 1 in Group P. All patients have the same remaining anesthesia durgs.Results: Compared with Group P, in Group R the time of disappearance of the eyelash reflex and the time to drop to 60 in BIS was longer (P < 0.05), the time of awakening was shorted (P < 0.05), the MAP of T6 was fluctuated less (P < 0.05), the incidence of hypotension and injection pain during induction was reduced (P < 0.001), the incidence of intraoperative bradycardia during operation was reduced (P < 0.05), the dosages of sedatives drug during maintenance was reduced (P < 0.05). There was no statistically significant difference in postoperative renal function between the two groups of patients (P > 0.05).Conclusion: Remimazolam can be safely and effectively used for the induction and maintenance of general anesthesia in kidney transplant patients.Keywords: remimazolam, propofol, general anesthesia, kidney transplant

Zhaowei Huang,1,2,&ast; Changming Chen,3,&ast; Linlin Tan,4 Yi Ling,3 Wukai Ma,3 Jinan Zhang1,2 1Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Endocrinology & Rheumatology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, People’s Republic of China; 3Department of Rheumatology & Immunology, The Second Affiliated Hospital of Guizhou University of Chinese Medicine, Guiyang, Guizhou, People’s Republic of China; 4Department of Internal Medicine, Jinshazhou Hospital Affiliated to Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinan Zhang, Email zhangjinan@hotmail.comBackground: Rheumatoid arthritis (RA) is a common autoimmune disease with the main symptoms being joint swelling and pain. In severe cases, joint deformity or even complete loss of function occurs. Technetium methylene diphosphonate (99Tc-MDP) is widely used for RA treatment in China, but there are no studies on the effects of 99Tc-MDP on intestinal flora.Objective: To explore the effects of 99Tc-MDP treatment on the composition and function of the intestinal flora and to provide new information on the mechanism of 99Tc-MDP in RA treatment.Methods: Stool samples from RA patients before and after 99Tc-MDP treatment were collected to form two groups (Before and After). Total genomic DNA of the samples was extracted for 16S rRNA gene sequencing. The altered composition of the intestinal flora, the key target bacteria regulated by 99Tc-MDP, and the pathways of action of 99 Tc-MDP were analyzed by bioinformatics.Results: A total of 64 fresh stool samples were collected from 32 RA patients. Compared to the Before group, the After group showed increased Bacteroidetes abundance and decreased Firmicutes abundance. At the genus level, Prevotella increased whereas Escherichia decreased. Both α and β diversity analyses showed that 99Tc-MDP treatment did not affect gut microbial diversity in RA patients. LEfSe analyses and random forest analyses showed Bacteroidetes, Prevotella, Enterococcus, Escherichia and Ruminococcaceae were the main 99Tc-MDP regulating bacteria. Functional enrichment analysis revealed that the functional differences in gut flora of the two groups centered on Metabolism and Genetic Information Processing.Conclusion: This study revealed differences in the composition of the gut microbiota in RA patients before and after 99Tc-MDP treatment. The therapeutic effect of 99Tc MDP is mainly achieved through Bacteroidetes, Prevotella, and Enterococcus. Regulating metabolism and genetic information processing of gut flora may be the mechanism of 99Tc-MDP in treating RA.Keywords: rheumatoid arthritis, 99Tc-MDP, gut microbiota, 16S rRNA, bioinformatics

Enhao Huang,1,2,&ast; Huadao Li,2,3,&ast; Hanghang Han,1,2,&ast; Lianshan Guo,4 Yubing Liang,3 Zijin Huang,1 Ke Qin,5 Xueke Du1 1Department of Anesthesiology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530007, People’s Republic of China; 2Key Laboratory for Basic Science and Prevention of Perioperative Organ Dysfunction, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China; 3Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China; 4Department of Emergency, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530007, People’s Republic of China; 5Guilin People’s Hospital, Guilin, Guangxi Zhuang Autonomous Region, 541100, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ke Qin; Xueke Du, Email qinke303@163.com; duxueke@gxmu.edu.cnPurpose: The primary objective of this study was to develop an innovative nanomedicine-based therapeutic strategy to alleviate Postoperative Neurocognitive Disorder (PND) in patients undergoing surgery.Patients and Methods: To achieve this goal, polydopamine-coated Kaempferol-loaded Metal-Organic Framework nanoparticles (pDA/KAE@ZIF-8) were synthesized and evaluated. The study involved encapsulating Kaempferol (KAE) within ZIF-8 nanoparticles, followed by coating with polydopamine (PDA) to enhance biocompatibility and targeted delivery. The characterization of these nanoparticles (NPs) was conducted using various techniques including Scanning Electron Microscopy, Fourier-Transform Infrared Spectroscopy, X-ray Diffraction, and Ultraviolet-Visible spectroscopy. The efficacy of pDA/KAE@ZIF-8 NPs was tested in both in vitro and in vivo models, specifically focusing on their ability to penetrate the blood-brain barrier and protect neuronal cells against oxidative stress.Results: The study found that pDA/KAE@ZIF-8 NPs efficiently penetrated the blood-brain barrier and were significantly taken up by neuronal cells. These nanoparticles demonstrated remarkable Reactive Oxygen Species (ROS) scavenging capabilities and stability under physiological conditions. In vitro studies showed that pDA/KAE@ZIF-8 NPs provided protection to HT-22 neuronal cells against H2O2-induced oxidative stress, reduced the levels of pro-inflammatory cytokines, and decreased apoptosis rates. In a PND mouse model, the treatment with pDA/KAE@ZIF-8 NPs significantly improved cognitive functions, surpassing the effects of KAE alone. This improvement was substantiated through behavioral tests and a noted reduction in hippocampal inflammation.Conclusion: The findings from this study underscore the potential of pDA/KAE@ZIF-8 NPs as an effective nanotherapeutic agent for PND. This approach offers a novel direction in the postoperative care of elderly patients, with the potential to transform the therapeutic landscape for neurocognitive disorders following surgery. The application of nanotechnology in this context opens new avenues for more effective and targeted treatments, thereby improving the quality of life for patients suffering from PND.Keywords: nanomedicine, reactive oxygen species, blood-brain barrier

Yujie Xie,1 Fanglin Shao,1 Yuxiu Ji,1 Dechao Feng,1,2 Ling Wang,3 Zonghai Huang,3 Shengjian Wu,1 Fuhua Sun,1 Hong Jiang,4 Akira Miyamoto,5 Haiming Wang,6 Chi Zhang1 1Rehabilitation Medicine Department, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3School of Information and Communication Engineering, University of Electronic Science and Technology, Chengdu, Sichuan, People’s Republic of China; 4Rehabilitation Medicine Department, Xichong County People’s hospital, Nanchong, Sichuan, People’s Republic of China; 5Faculty of Rehabilitation, Nishikyushu University, Kansaitama, Japan; 6Department of Rehabilitation Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Haiming Wang, Department of Rehabilitation Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China, Tel +868950771, Fax +86 830 8950771, Email wanghaiming866@163.com Chi Zhang, Rehabilitation Medicine Department, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China, Email chizhang_swmu@126.comPurpose: To provide a comprehensive analysis of associated genes with osteoarthritis (OA). Here, we reported a network analysis of OA progression by using a Steiner minimal tree algorithm.Methods: We collected the OA-related genes through screening the publications in MEDLINE. We performed functional analysis to analyze the associated biochemical pathways of the OA-related genes. Pathway crosstalk analysis was constructed to explore interactions of the enriched pathways. Steiner minimal tree algorithm was used to analyze molecular pathway networks. The average clustering coefficient was compared with the corresponding values of the Osteoarthritis-specific network. The new finding RNA was compared with former single-cell RNA-seq analysis results.Results: A gene set with 177 members reported to be significantly associated with Osteoarthritis was collected from 187 studies. Functional enrichment analysis revealed a specific related-OA gene including skeletal system development, cytokine-mediated signaling pathway, inflammatory response, cartilage development, and extracellular matrix organization. We performed a pathway crosstalk analysis among the 72 significantly enriched pathways. A total of 151 of the 177 genes in the Osteoarthritis gene set were included in the human interactome network. There were 31 genes in the former single-cell RNA-seq analysis results. The CLU, ENO1, SRRM1, UBC, HMGB1, NR3C1, NOTCH2NL, and CBX5 have significantly increased expression in seven molecularly defined populations of OA cartilage.Conclusion: The Steiner tree-based approach finds new biological molecules associated with OA genes.Keywords: network analysis, Steiner minimal tree, osteoarthritis, bioinformatics, osteoarthritis genes

Yan Lv, Zheren Huang, Yan Ma Department of Obstetrics and Gynecology, the Third Affiliated Hospital of Soochow University, Changzhou, 213003, People’s Republic of ChinaCorrespondence: Yan Ma, Department of Obstetrics and Gynecology, the Third Affiliated Hospital of Soochow University, Changzhou, 213003, People’s Republic of China, Tel +86-0-13813693377, Email mayan19820117@126.comBackground: We aimed to investigate the association between maternal neutrophil ratio and histological chorioamnionitis (HCA) risk in pregnant women with premature rupture of membranes (PROM) in late pregnancy.Methods: A retrospective analysis was conducted on 95 cases of women with PROM in their late pregnancy between March 2018 and August 2021. These women were divided into two groups based on the presence of HCA. General clinical data and laboratory indicators were compared between the two groups. A generalized additive model was used for curve fitting, and a segmented regression model was used to explain further the non-linear relationship between neutrophil ratio and HCA risk.Results: After adjusting for confounding factors, the curve fitting showed a “U”-shaped curve relationship between the neutrophil ratio and the risk of HCA. When the neutrophil ratio was < 76.3%, the risk of HCA exhibited a decreasing trend, but the difference was not statistically significant (adjusted OR = 0.884, 95% CI: 0.781– 1.001, P = 0.053). However, when the neutrophil ratio was > 76.3%, the HCA risk was significantly increased (adjusted OR = 1.339, 95% CI: 1.067– 1.680, P = 0.012). Furthermore, we equally divided the neutrophil ratio into three groups. The risk of HCA was significantly increased in the low-ratio group (OR = 4.292, 95% CI: 1.247– 14.706, P = 0.021) compared with the middle-ratio group, which was used as the reference group. Similarly, the HCA risk of the high-ratio group (OR = 13.145, 95% CI: 1.796– 96.233, P = 0.011) was also significantly enhanced. However, there was no significant difference in HCA risk between the high-ratio and low-ratio groups (OR = 1.182, 95% CI: 0.357– 3.909, P = 0.784).Conclusion: There was a significant “U”-shaped relationship between maternal neutrophil ratio and HCA risk in women with PROM in late pregnancy.Keywords: premature rupture of membranes, late pregnancy, neutrophil ratio, histological chorioamnionitis, non-linear relationship

Zhuo Huang, Yusheng Zhi, Haiyan Cao, Zhuan Bian,&ast; Miao He&ast; State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhuan Bian; Miao He, State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, People’s Republic of China, Email bianzhuan@whu.edu.cn; hemiao@whu.edu.cnPurpose: Exosomes are important “messengers” in cell-cell interactions, but their potential effects on palatal fusion are still unknown. This study aimed to explore the role and mechanism of exosomes derived from palatal mesenchymal cells in epithelial-mesenchymal communication during palatogenesis.Methods: The expression of exosome marker CD63 and CD81 in palatal cells during palatogenesis was detected by immunofluorescence staining. After being purified from the supernatant of human embryonic palatal mesenchymal (HEPM) cells, exosomes (HEPM-EXO) were characterized by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and Western blot. HEPM-EXO were co-cultured with human immortalized oral epithelial cells (HIOEC). The effects of HEPM-EXO on the cell proliferation, migration, apoptosis and epithelial-mesenchymal transition (EMT) of HIOEC were evaluated. The proteins encapsulated in HEPM-EXO were analyzed by proteomic analysis.Results: The extensive expression of CD63 and CD81 in palatal epithelial and mesenchymal cells were continuously detected during E12.5~E14.5, suggesting that exosomes were involved in the process of palatal fusion. The expression of CD63 was also observed in the acellular basement membrane between the palatal epithelium and the mesenchyme in vivo, and HEPM-EXO could be internalized by HIOEC in vitro, suggesting that exosomes are potent to diffuse through the cellular tissue boundary to mediate palatal cell-cell communication. Exposure of HEPM-EXO to HIOEC substantially inhibited the proliferation and stimulated the migration of HIOEC, but had no significant effect on cell apoptosis and EMT. Proteomic analysis revealed the basic characteristics of the proteins in HEPM-EXO and that exosomal THBS1 may potentially regulate the cell behaviors of HIOEC, which needs further verification. Gene ontology (GO) analysis uncovered that the proteins highly expressed in HEPM-EXO are closely related to wound healing, implying a promising therapeutic opportunity of HEPM-EXO in tissue injury treatment with future studies.Conclusion: HEPM-EXO mediated cell-cell communication by regulating cell proliferation and migration of oral epithelial cells during palatogenesis.Keywords: epithelial-mesenchymal interactions, extracellular vesicles, palatogenesis, proteomics, wound healing

Lingling Zhu,1,2 Qiang Zhou,1,2 Ziyue Huang,3 Yuan Yang,4,5 Ying Yang,6 Yao Du,6 Yuqian Zhao,2 Xiaoping Yu,7 Tingyuan Li,2 Wen Chen5 1College of Public Health, Chengdu Medical College, Chengdu, Sichuan, 610500, People’s Republic of China; 2Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, Sichuan, 610041, People’s Republic of China; 3Mianyang Maternal and Child Health Care Hospital, Mianyang, Sichuan, 621000, People’s Republic of China; 4School of Public Health, Xiamen University, Xiamen, Fujian, 361102, People’s Republic of China; 5Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China; 6Yanting County Maternal and Child Health Hospital, Mianyang, Sichuan, 621600, People’s Republic of China; 7School of Preclinical Medicine, Chengdu University, Chengdu, Sichuan, 610106, People’s Republic of ChinaCorrespondence: Xiaoping Yu, School of Preclinical Medicine, Chengdu University, Chengdu, Sichuan, 610106, People’s Republic of China, Tel +86 13981909673, Email yuxiaoping@cdu.edu.cn Tingyuan Li, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86 28 85420667, Email ltyuan008@126.comBackground: This study aimed to explore the current knowledge level of breast cancer among rural women in Southwest China and analyze the influencing factors of breast cancer cognition.Methods: From May to November 2022, 1468 rural women were invited to participate in this study. Demographic information and the Chinese version of the Breast Cancer Awareness Measure (C-BCAM) were collected through one-on-one investigations. The data were analyzed using descriptive statistics, chi-square tests, and multiple regression analysis in SPSS 26.0.Results: The study included a total of 1468 rural women with a median age of 54.0 (IQR, 47.0, 60.0).The average score of breast cancer in the study population was 73.0 (IQR, 66.0, 82.0). Among women in Southwest China, the awareness rates of knowledge on breast cancer symptoms, barriers to seeking medical help, and risk factors were 68.8%, 98.4%, and 62.1%, respectively. The awareness rate was found to increase with higher education levels (P< 0.001) and decrease with increasing age (P< 0.001). Multivariate logistic regression analysis identified three variables that might influence breast cancer awareness: education level, contraceptive measures, and history of breast disease (all P< 0.05). Specifically, history of breast disease (Odds ratio (OR) = 1.907, 95% CI = 1.128 ~ 3.223), middle school education (OR = 2.155, 95% CI = 1.585 ~ 2.928), and junior college education and above (OR = 5.536, 95% CI = 1.898 ~ 16.148) were positive factors for women’s breast cancer awareness. Conversely, the use of intrauterine devices (OR = 0.523, 95% CI = 0.384 ~ 0.712) was found to be a negative factor for women’s breast cancer awareness.Conclusion: This study highlights the insufficient awareness of breast cancer among women in rural area of Southwest China. It emphasizes the necessity of health education to improve female breast cancer awareness.Keywords: China, breast cancer, awareness, screening, rural women

Jia Huang,1 Wenjun Li,2 Yecheng Sun,1,&ast; Zhutang Huang,1,&ast; Rong Cong,1,&ast; Chen Yu,1,&ast; Hongyan Tao2 1The Second Clinical Medical School, Lanzhou University, Lanzhou, Gansu, 730000, People’s Republic of China; 2Department of Respiratory, The Second Hospital of Lanzhou University, Lanzhou, Gansu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongyan Tao, Department of Respiratory, The Second Hospital of Lanzhou University, Lanzhou, Gansu, People’s Republic of China, Email 1165463182@qq.comAbstract: Preserved Ratio Impaired Spirometry (PRISm) manifests notable epidemiological disparities across the globe, with its prevalence and influential factors showcasing pronounced diversities among various geographical territories and demographics. The prevalence of PRISm fluctuates considerably among regions such as Latin America, the United States, and Asian nations, potentially correlating with a myriad of determinants, including socioeconomic status, environmental factors, and lifestyle modalities. Concurrently, the link between PRISm and health risks and other disorders, especially its distinction and interrelation with chronic obstructive pulmonary disease (COPD), has become a pivotal subject of scientific enquiry. Radiographic anomalies, such as perturbations in the pulmonary parenchyma and structural alterations, are posited as salient characteristics of PRISm. Furthermore, PRISm unveils intricate associations with multiple comorbidities, inclusive of hypertension and type 2 diabetes, thereby amplifying the intricacy in comprehending and managing this condition. In this review, we aim to holistically elucidate the epidemiological peculiarities of PRISm, its potential aetiological contributors, its nexus with COPD, and its association with radiographic aberrations and other comorbidities. An integrative understanding of these dimensions will provide pivotal insights for the formulation of more precise and personalised preventative and therapeutic strategies.Keywords: PRISm, pulmonary function, epidemiology, comorbid associations

Huamei Wei,1,&ast; Xianjian Wu,2,&ast; Lizheng Huang,3,&ast; Chen Long,3 Qi Lu,3 Zheng Huang,3 Yanyan Huang,3 Wenchuan Li,2 Jian Pu2 1Department of Pathology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, People’s Republic of China; 2Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, People’s Republic of China; 3Graduate College of Youjiang Medical University for Nationalities, Baise, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Pu, Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18 Zhongshan Two Road, Baise, Guangxi, 533000, People’s Republic of China, Email Pujianym@163.comObjective: Tumor-associated macrophages play a crucial role in the development of hepatocellular carcinoma (HCC). Our study aimed to investigate the relationship between long coding RNA (lncRNA) maternally expressed gene 3 (MEG3), RNA-binding protein human antigen R (HuR), and messenger RNA C–C motif chemokine 5 (CCL5) in the modulation of M1 and M2 macrophage polarization in HCC.Methods: To induce M1 or M2 polarization, LPS/IFNγ- or IL4/IL13 were used to treat bone marrow derived macrophages (BMDMs). The localization of MEG3 in M1 and M2 macrophages was assessed using fluorescence in situ hybridization assay. Expression levels of MEG3, HuR, CCL5, M1, and M2 markers were measured by RT-qPCR or immunofluorescence staining. Flow cytometry was performed to determine the proportion of F4/80+CD206+ and F4/80+CD68+ cells. RNA pulldown assay was performed to detect the binding of lncRNA MEG3 and HuR. The impacts of HuR on CCL5 stability and activity of CCL5 promoter were evaluated using actinomycin D treatment and luciferase reporter assay. Cell migration, invasiveness, and angiogenesis were assessed using transwell migration and invasion assays and a tube formation assay. A mixture of Huh-7 cells and macrophages were injected into nude mice to explore the effect of MEG3 on tumorigenesis.Results: MEG3 promoted M1-like polarization while dampening M2-like polarization of BMDMs. MEG3 bound to HuR in M1 and M2 macrophages. HuR downregulated CCL5 by inhibiting CCL5 transcription in macrophages. In addition, overexpression of MEG3 suppressed cell metastasis, invasion, and angiogenesis by obstructing macrophage M2 polarization. MEG3 inhibited tumorigenesis in HCC via promotion of M1-like polarization and inhibition of M2-like polarization. Rescue experiments showed that depletion of CCL5 in M2 macrophages reversed MEG3-induced suppressive effect on cell migration, invasion, and tube formation.Conclusion: MEG3 suppresses HCC progression by promoting M1-like while inhibiting M2-like macrophage polarization via binding to HuR and thus upregulating CCL5.Keywords: hepatocellular carcinoma, maternally expressed gene 3, macrophage polarization, human antigen R, C-C motif chemokine 5

Zhisheng Huang,1,2 Zuowang Cheng,3 Xia Deng,4 Ying Yang,5 Na Sun,5 Peibin Hou,5 Ruyue Fan,5 Shuai Liu6,7 1Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, National Regional Center for Respiratory Medicine, Jiangxi Hospital of China-Japan Friendship Hospital, Nanchang, Jiangxi, People’s Republic of China; 3Department of Clinical Laboratory, Zhangqiu District People’s Hospital Affiliated to Jining Medical University, Jinan, Shandong, People’s Republic of China; 4School of Public Health, Shandong Second Medical University, Weifang, Shandong, People’s Republic of China; 5Shandong Center for Disease Control and Prevention, Jinan, Shandong, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 7Shandong Key Laboratory of Infectious Respiratory Disease, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Shuai Liu; Ruyue Fan, Email liushuai_sam@163.com; fanruyue2022@163.comBackground: Coronavirus disease 2019 (COVID-19) is a respiratory infectious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The objective of this study is to identify reliable and accurate biomarkers for the early stratification of disease severity, a crucial aspect that is currently lacking for the impending phases of the next COVID-19 pandemic.Methods: In this study, we identified important module and hub genes related to clinical severe COVID-19 using differentially expressed genes (DEGs) screening combing weighted gene co-expression network analysis (WGCNA) in dataset GSE213313. We further screened and confirmed these hub genes in another two new independent datasets (GSE172114 and GSE157103). In order to evaluate these key genes’ stability and robustness for diagnosing or predicting the progression of illness, we used RT-PCR validation of selected genes in blood samples obtained from hospitalized COVID-19 patients.Results: A total of 968 and 52 DEGs were identified between COVID-19 patients and normal people, critical and non-critical patients, respectively. Then, using WGCNA, 10 modules were constructed. Among them, the blue module positively associated with clinic disease severity of COVID-19. From overlapped section between DEGs and blue module, 12 intersected common differential genes were obtained. Subsequently, these hub genes were validated in another two new independent datasets as well and 9 genes that overlapped showed a highly correlation with disease severity. Finally, the mRNA expression levels of these hub genes were tested in blood samples from COVID-19 patients. In severe cases, there was increased expression of MCEMP1, ANXA3, CD177, and SCN9A. In particular, MCEMP1 increased with disease severity, which suggested an unfavorable development and a frustrating prognosis.Conclusion: Using comprehensive bioinformatical analysis and the validation of clinical samples, we identified four major candidate genes, MCEMP1, ANXA3, CD177, and SCN9A, which are essential for diagnosis or development of COVID-19.Keywords: COVID-19, differentially expressed genes, WGCNA, hub genes, neutrophil

Baojun Guo,1,2 Hui Gan,1 Mingshan Xue,1,3 Zhifeng Huang,1 Zhiwei Lin,1 Shiyun Li,1 Peiyan Zheng,1 Baoqing Sun1 1Department of Clinical Laboratory of the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, 510120, People’s Republic of China; 2School of Medicine, Henan University, Kaifeng, 475004, People’s Republic of China; 3Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, 510060, People’s Republic of ChinaCorrespondence: Baoqing Sun; Peiyan Zheng, Email sunbaoqing@vip.163.com; gdmcslxx@126.comBackground: This study analyzed the burden of chronic obstructive pulmonary disease (COPD) in China, the United States, and India from 1990 to 2019 and projected the trends for the next decade.Methods: This study utilized the GBD 2019 to compare the age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), age-standardized disability-adjusted life years (DALYs) rate, and the proportion attributed to different risk factors in China, the United States, and India. Joinpoint models and autoregressive integrated moving average (ARIMA) models were employed to capture the changing trends in disease burden and forecast outcomes.Results: From 1990 to 2019, China’s age-standardized COPD incidence and mortality rates decreased by 29% and 70%, respectively. In the same period, India’s rates decreased by 8% and 33%, while the United States saw an increase of 9% in COPD incidence and a 22% rise in mortality rates. Smoking and ambient particulate matter pollution are the two most significant risk factors for COPD, while household air pollution from solid fuels and low temperatures are the least impactful factors in the United States and India, respectively. The proportion of risk from household air pollution from solid fuels is higher in India than in China and the United States. Predictions for 2030 suggest that the age-standardized DALY rates, ASIR, and ASMR in the United States and India are expected to remain stable or decrease, while China’s age-standardized incidence rate is projected to rise.Conclusion: Over the past three decades, the incidence of COPD has been decreasing in China and India, while showing a slight increase in the United States. Smoking and ambient particulate matter pollution are the primary risk factors for men and women, respectively. The risk of household air pollution from solid fuels in India needs attention.Keywords: COPD, global burden of disease, risk factors, DALYs

Bo-Lun Zhang,1 Jia Liu,2 Guanghao Diao,2 Jianping Chang,1 Junshuai Xue,1 Zhen Huang,1 Hong Zhao,1 Lingxiang Yu,2 Jianqiang Cai1 1Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Hepatobiliary Surgery, the Fifth Medical Center of the PLA General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Jianqiang Cai, Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, People’s Republic of China, Tel +86-10-87787100, Fax +86-10-67709698, Email caijianqiang@cicams.ac.cnPurpose: We developed a nomogram based on the liver function, nutrition, inflammation, and immunity (LFNII) score to predict recurrence-free survival (RFS) post-resection in patients with hepatocellular carcinoma (HCC) exhibiting alpha-fetoprotein (AFP) negativity (AFP ≤ 20 ng/mL).Patients and Methods: Clinical data of 661 patients diagnosed with alpha-fetoprotein-negative hepatocellular carcinoma (AFP-NHCC) who underwent surgical resection at two medical centers between 2012 and 2021 were collected. A total of 462 and 199 patients served as the training and validation sets, respectively. Pre-operative blood markers were collected and analyzed for LFNII. The LFNII score was formulated using the least absolute shrinkage and selection operator Cox regression model. A nomogram model was developed using the training set to incorporate other relevant clinicopathological indicators and predict postoperative recurrence. Model discrimination was assessed using the receiver operating characteristic curve, calibration was evaluated using a calibration curve, and clinical applicability was assessed using clinical decision curve analysis. A comparison with liver cancer staging was performed using the nomogram model. Finally, a cohort study was conducted to validate our findings.Results: We derived the LFNII scores from nine indicators. Elevated LFNII scores correlated with unfavorable clinicopathological features. The LFNII score area under the curve revealed superior predictive efficacy at 1-, 2-, and 5-year RFS intervals, with values of 0.675, 0.658, and 0.633, respectively. Multivariate Cox analysis revealed that a high LFNII score independently increased RFS risk in patients with AFP-NHCC. The C-index of the LFNII-nomogram model was 0.686 (95% confidence interval [CI], 0.651– 0.721). The nomogram model’s clinical application value surpassed that of standard HCC staging systems.Conclusion: The LFNII score-derived nomogram effectively predicted the RFS of patients with AFP-NHCC after curative resection.Keywords: hepatocellular carcinoma, alpha-fetoprotein-negative, immunity, inflammation, nutrition, recurrence-free survival

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

Zhaohui Liu, Yi Jin, Lingfei Wang, Zeqing Huang Department of Anesthesiology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning, People’s Republic of ChinaCorrespondence: Zeqing Huang, Department of Anesthesiology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, No. 44 Xiaoheyan Road, Dadong District, Shenyang, Liaoning, 110042, People’s Republic of China, Tel +86 18900917545, Email huangzeqing1973@163.comPurpose: This study was conducted to assess whether ciprofol vs propofol could affect the incidence of postoperative delirium (POD) in elderly patients with lung cancer after thoracoscopic surgery.Patients and Methods: In this study, a total of 84 elderly patients undergoing thoracoscopic surgery for lung cancer were recruited and randomized into two groups to receive anesthesia with either ciprofol or propofol. The primary outcome was the incidence of POD within three days after surgery. Secondary outcomes included the Confusion Assessment Method (CAM) score, intraoperative indicators related to mean arterial pressure (MAP), and cerebral tissue oxygen saturation (SctO2). Moreover, MAP- and SctO2-related indicators associated with POD were analyzed.Results: The incidence of POD was 7.1% and 16.7%, respectively, in the ciprofol group and the propofol group (risk ratio [RR], 0.37; 95% confidence interval [CI], 0.07 to 2.03; risk difference [RD], − 9.6%; 95% CI, − 23.3% to 4.1%; p = 0.178). Compared with those in the propofol group, patients in the ciprofol group had lower CAM scores three days after surgery (13 (12, 15) vs 15 (14, 17); 12 (11, 13) vs 14 (13, 16); 12 (11, 12) vs 13 (12, 14), p< 0.05). Besides, patients in the ciprofol group exhibited higher mean and minimum MAP (88.63 ± 6.7 vs 85 ± 8.3; 69.81 ± 9.59 vs 64.9 ± 9.43, p< 0.05) and SctO2 (77.26 ± 3.96 vs 75.3 ± 4.49, 71.69 ± 4.51 vs 68.77 ± 6.46, p< 0.05) and percentage of time for blood pressure stabilization (0.6 ± 0.14 vs 0.45 ± 0.14, p< 0.05) than those in the propofol group. Furthermore, MAP and SctO2-related indicators were validated to correlate with POD.Conclusion: Anesthesia with ciprofol did not increase the incidence of POD compared with propofol. The results demonstrated that ciprofol could improve intraoperative MAP and SctO2 levels and diminish postoperative CAM scores.Keywords: ciprofol, postoperative delirium, thoracoscopic surgery, cerebral tissue oxygen saturation

Zhanlin Liao,1,&ast; Liangzhi Huang,1,&ast; Jun Chen,2 Ting Chen,1 Dezhi Kong,1 Qifeng Wei,1 Qiao Chen,1 Bin Deng,1 Yanyan Li,1 Shuai Zhong,1 Zugui Huang1 1Department of Endocrine, Affiliated Nanping First Hospital of Fujian Medical University, Nanping, Fujian, 353006, People’s Republic of China; 2Department of Ophthalmology, Affiliated Nanping First Hospital of Fujian Medical University, Nanping, Fujian, 353006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zugui Huang, Department of Endocrine, Affiliated Nanping First Hospital of Fujian Medical University, No. 317 Zhongshan Road, Nanping, Fujian, 353006, People’s Republic of China, Email 15159969783@163.comBackground: Type 2 diabetes (T2DM) combined nonalcoholic fatty liver disease (NAFLD) are characterized by metabolic disruptions. Liraglutide has been proved to be effective in T2DM. If LRG could regulate NAFLD combined T2DM has not been reported.Methods: Intraperitoneal injection of 1% streptozotocin (STZ) plus high-sugar and high-fat diet was used to induce NAFLD combined T2DM animal model. Palmitic acid (200 μmol/L) and glucose (25 mmol/L) incubation were used to induce cell model. The cell apoptosis, mRNA and protein expression were measured through flow cytometry, PCR, and Western blotting, respectively.Results: Liraglutide significantly improved the liver injury of NAFLD combined T2DM rats, but Com-C reversed the effect of liraglutide. The decreased AMPK/mTOR signaling pathway in the NAFLD combined T2DM animals was greatly activated by liraglutide. Com-C reversed the protection effects of liraglutide on palmitic acid+glucose induced cell damage.Conclusion: Liraglutide could greatly alleviate the damage caused by NAFLD+T2DM and palmitic acid+glucose. The protection effects of liraglutide were greatly inhibited by suppressing AMPK/mTOR signaling pathway. This research might provide a novel therapeutic strategy for the prevention and treatment of NAFLD combined T2DM disease.Keywords: type 2 diabetes, nonalcoholic fatty liver disease, liraglutide, AMPK/mTOR, autophagy

Luyang Gao,&ast; Sicheng Zhang,&ast; Zhihui Zhao, Qing Zhao, Tao Yang, Qixian Zeng, Yi Zhang, Xin Li, Zhihua Huang, Anqi Duan, Qin Luo, Zhihong Liu Center for Respiratory and Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, National Clinical Research Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhihong Liu; Qin Luo, Center for Respiratory and Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, National Clinical Research Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Xicheng District, Beijing, 100037, People’s Republic of China, Tel/Fax +86-010-88396589, Email zhihongliufuwai@163.com; luoqin2009@163.comIntroduction: Mounting evidence indicates a possible connection between the systemic inflammatory response index (SIRI) and the prognosis of heart failure, but its role in idiopathic pulmonary arterial hypertension (IPAH) is not well understood. This study aimed to investigate the relationship between SIRI and variables such as functional ability, echocardiography results, hemodynamic measurements, and long-term outcomes in patients with IPAH.Methods: The study included 426 consecutive IPAH patients who underwent right heart catheterization at Fuwai Hospital from January 2013 to December 2020. SIRI was calculated using composite inflammation indicators from routine blood tests. The main outcome measure was clinical deterioration. Spearman correlation coefficients were used to assess associations between SIRI and indicators of IPAH severity. Receiver operating characteristic (ROC) curve analysis was conducted to determine the optimal SIRI threshold and predictive ability. Kaplan-Meier analysis and Cox proportional hazard models were used to examine the relationship between SIRI and clinical deterioration.Results: SIRI showed positive associations with indicators such as N-terminal pro-brain natriuretic peptide, right ventricular end-diastolic diameter, pericardial effusion, mean pulmonary arterial pressure, and pulmonary vascular resistance. Conversely, SIRI had inverse relationships with 6-minute walking distance and left ventricular end-diastolic diameter. Kaplan-Meier curves revealed a significantly higher rate of clinical deterioration in individuals with SIRI > 0.741 compared to those with SIRI ≤ 0.741 (P < 0.001). Adjusted Cox analysis showed SIRI remained an independent predictor of clinical worsening (hazard ratio 1.366, 95% confidence interval 1.073– 1.738, P = 0.011). ROC analysis demonstrated SIRI provided additional predictive value beyond the risk assessment score of the European Society of Cardiology/European Respiratory Society.Discussion: In summary, SIRI could predict the severity and prognosis of IPAH independently. It was associated with various indicators of IPAH severity and was a significant predictor of clinical deterioration. SIRI also offered additional predictive value beyond existing risk assessment scores.Keywords: prognosis, pulmonary arterial hypertension, risk factor, systemic inflammatory response index

Xinshui Wang,1 Zheren Huang,2 Yan Ma2 1Department of Endocrinology, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, People’s Republic of China; 2Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, People’s Republic of ChinaCorrespondence: Yan Ma, Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, People’s Republic of China, Tel +86-0-13813693377, Email mayan19820117@126.comBackground: This study aimed to develop and validate a model to predict histologic chorioamnionitis (HCA) risk in late preterm and term premature rupture of membranes (PROM) patients using clinical and laboratory parameters.Methods: We conducted a retrospective study on 116 late preterm and term PROM cases, divided into a training (n=81) and a validation set (n=35). A multivariable logistic regression model was developed using the training set. Performance was assessed via the area under the receiver operating characteristic curve (AUC) and net reclassification index (NRI). Decision curve analysis (DCA) evaluated the model’s clinical utility. Additionally, nomograms and a web version of the model were developed.Results: In the training set, the combined model constructed using maternal BMI, gravidity, amniotic fluid characteristics, and prenatal white blood cell (WBC) count showed significantly higher AUC than WBC alone (0.859 vs 0.710, P=0.010), with improved accuracy and sensitivity. In the validation set, the AUC of the combined model remained higher than that of WBC, but the difference was not statistically significant (0.728 vs 0.584, P=0.173). NRI analysis indicated that the combined model improved the correct classification of HCA by 25.0% (P=0.012) compared to that of WBC alone. DCA demonstrated that the combined model had a higher net benefit than WBC in most cases. The nomograms and web version of the model provided convenient tools for clinicians to predict the risk of HCA.Conclusion: This study successfully developed and validated a clinically feasible multivariable model to predict the risk of HCA in women with late preterm and term PROM.Keywords: histologic chorioamnionitis, laboratory indicators, late pregnancy, predictive model, premature rupture of membranes

Zibin Cui,1,&ast; Xiangdong Liu,2,&ast; Zehua Feng,2 Zhengzong Huang3 1School of Management, Guangdong University of Technology, Guangzhou, People’s Republic of China; 2School of Law, Guangdong University of Technology, Guangzhou, People’s Republic of China; 3School of Marxism, Shenzhen Technology University, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zehua Feng; Zhengzong Huang, Email zehuafeng@gdut.edu.cn; huangzhengzong@sztu.edu.cnBackground: Blockchain is expected to mitigate consumers’ risk-aversion and quality uncertainty about generic drugs in medicine supply chains. This study investigates the effect of blockchain adoption for disclosing the quality information of generic drugs that compete with original drugs in the market and proposes legal measures accordingly.Methods: We employ a game-theoretic model to analyze a medicine supply chain including a generic drug manufacturer, an original drug manufacturer, and a retailer. We examine when should the supply chain members adopt blockchain for generic drugs and how blockchain affects the medicine supply chain.Results: Our results show that the quality information of generic drugs determines how blockchain adoption affects the price and sales quantity of generic and original drugs. Moreover, we observe that the generic drugs manufacturer and the retailer decide to adopt blockchain only if consumers’ risk-aversion degree is sufficiently low. Also, a low risk-aversion degree can lead to higher whole supply chain’s profitability with blockchain adoption, and generate a win-win-win situation of blockchain adoption for the consumers, the generic drug manufacturer, and the retailer.Conclusion: To mitigate consumers’ risk aversion, the law should safeguard consumer rights. Blockchain adoption can benefit the medicine supply chain and consumers under certain conditions. However, it also requires the coordination of supply chain members’ benefits and the disclosure of quality information.Keywords: generic drug, medicine supply chain, risk aversion, quality uncertainty, blockchain adoption

Huang Z, Liang H, Chen L. Onco Targets Ther. 2020;13:2193–2202. We, the Editor and Publisher of the journal OncoTargets and Therapy 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”.

Jiaqiong Lin,1 Xiaoyong Li,2 Yan Lin,3 Zena Huang,3 Fei He,4 Fu Xiong4,5 1Dongguan Maternal and Child Health Care Hospital, Postdoctoral Innovation Practice Base of Southern Medical University, Dongguan, People’s Republic of China; 2General Surgery Department; Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 3Yunkang School of Medicine and Health, Nanfang College, Guangzhou, People’s Republic of China; 4Department of Medical Genetics/Experimental Education/Administration Center, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 5Department of Fetal Medicine and Prenatal Diagnosis, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Fu Xiong, Department of Medical Genetics/Experimental Education/Administration Center, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, People’s Republic of China, Email xiongfu@smu.edu.cnBackground: Diabetic nephropathy (DN) is one of the primary causes of end-stage renal disease, yet effective therapeutic targets remain elusive. This study aims to identify novel diagnostic biomarkers and potential therapeutic candidates for DN.Methods: Differentially expressed genes (DEGs) in GSE96804 and GSE142025 were identified and functional enrichment analysis was performed. Diagnostic biomarkers were selected using machine learning algorithms and evaluated by Receiver Operating Characteristic analysis. c-Fos expression was validated in an established DN mouse model. Immune infiltration levels were assessed with Single-Sample Gene Set Enrichment Analysis. Co-expression analysis revealed regulatory relationships involving FOS. cMAP predicted potential therapeutic candidates. Transcriptome sequencing and experiments in RAW264.7 cells was performed to investigate molecular mechanisms of emetine.Results: In both datasets, we identified 44 upregulated and 74 downregulated DEGs involved in focal adhesion, ECM-receptor interaction, and the PI3K-Akt signaling pathway. FOS emerged as a robust diagnostic marker with decreased expression in DN patients and DN mouse. Co-expression analysis revealed potential regulatory mechanisms of FOS, implicating the MAPK signaling pathway, regulation of cell proliferation and apoptotic signaling pathways. Immune dysregulation was observed in DN patients. Notably, emetine was identified as a potential therapeutic candidate. Transcriptome sequencing and experimental validation demonstrated emetine suppressed M1 macrophage polarization by inhibiting the activation of NF-κB signaling pathway, as well as reducing the expression of Il-18 and Ccl5.Conclusion: In conclusion, our study identified FOS as a promising diagnostic biomarker and emetine as a potential therapeutic candidate for DN. These findings enhance our understanding of DN pathogenesis and present novel prospects for therapeutic strategies.Keywords: diabetic nephropathy, diagnostic markers, FOS, emetine, immune infiltration, inflammation

Yifan Sun,1 Zixuan Huang,2 Xuezheng Gao,1 Limin Chen,3 Jun Wang,1,3 Zhenhe Zhou,1,3 Hongliang Zhou4 1Department of Psychiatry, The Affiliated Wuxi Mental Health Center of Nanjing Medical University, Wuxi City, 214151, People’s Republic of China; 2Department of Music and Wellbeing, School of Music, University of Leeds, Leeds City, UK; 3Department of Psychiatry, The Affiliated Mental Health Center of Jiangnan University, Wuxi City, 214151, People’s Republic of China; 4Department of Psychology, The Affiliated Hospital of Jiangnan University, Wuxi City, 214151, People’s Republic of ChinaCorrespondence: Jun Wang, Department of Clinical Psychology, The Affiliated Wuxi Mental Health Center of Nanjing Medical University, Wuxi City, 214151, People’s Republic of China, Tel +86 13358119628, Fax +86 51083219366, Email woodfish2@126.com; Zhenhe Zhou, Department of Psychiatry, The Affiliated Wuxi Mental Health Center of Nanjing Medical University, Wuxi City, 214151, People’s Republic of China, Tel +86 13358118986, Fax +86 51083219366, Email zhouzh@njmu.edu.cnPurpose: Anhedonia, a core symptom of major depressive disorder (MDD), is explored in this study, focusing on the neural underpinnings through the examination of two event-related potential (ERP) components: feedback-related negativity (FRN) and stimulus-preceding negativity (SPN).Patients and Methods: This cross-sectional study was conducted in China from March 2022 to March 2023. It involved 35 MDD patients and 31 healthy controls (HC) participating in a modified 2-door task with simultaneous EEG recordings. Depression severity and anhedonia were assessed using the Hamilton Depression Scale (HAMD) and the Temporal Experience of Pleasure Scale (TEPS-CV), respectively. FRN and SPN metrics, along with correlations with each other and clinical assessments, were examined.Results: In comparison to the HC group, the MDD group exhibited significantly lower scores in TEPS-CV (t = 2.854, p = 0.006) and its subscales (t = − 3.596, p = 0.001 and t = 2.434, p = 0.018, respectively), along with consistently reduced amplitudes of FRN (F 1.64= 4.726, p = 0.033) and SPN (F 1.64= 4.195, p = 0.045) across all conditions. Limited correlations were observed between ERP metrics and clinical indicators, except for positive correlations between FRN amplitudes (loss minus win) and HAMD scores (r = 0.392, p = 0.020), and SPN amplitudes after losing (SPN-L) and TEPS-CV consumption subscale scores (r = 0.357, p = 0.035). Notably, while the HC group displayed no significant FRN-SPN correlations, the MDD group exhibited positive FRN-SPN correlations under distinct conditions (r = 0.376, p = 0.026 and r = 0.355, p = 0.037, respectively).Conclusion: Our data reveal subjective and objective anhedonia in both consumption and anticipation, suggesting a shared impairment in reward feedback processing and anticipatory neural mechanisms in individuals with MDD. These findings deepen our understanding of anhedonia’s neural foundations and may guide targeted interventions for this core symptom.Keywords: major depressive disorder, anhedonia, event-related potential, reward processing, feedback-related negativity, stimulus-preceding negativity

Shuying Rao,1 Chuanzhi Xu,2 Chonghua Wan,1 Zhiwen Huang,3 Xingping Huang,4 Shu Chen1 1Research Center for Quality of Life and Applied Psychology, School of Humanities and Management, Guangdong Medical University, Dongguan, People’s Republic of China; 2Department of Statistics, School of Public Health, Kunming Medical University, Kunming, People’s Republic of China; 3Cardiovascular Department, the Affiliated Hospital of Guangdong Medical University, Zhanjiang, People’s Republic of China; 4Department of Research and Teaching, Dongguan Eighth’ Hospital, Dongguan, People’s Republic of ChinaCorrespondence: Chonghua Wan, Tel/Fax +86-0769-22896255, Email wanchh@hotmail.comPurpose: Coronary heart disease (CHD) is difficult to cure, so more attention should be paid to improving patients’ health-related quality of life (HRQoL). This paper focuses on identifying factors that affect HRQoL.Patients and Methods: Overall, 189 in-patients with coronary heart disease were investigated at the Affiliated Hospital of Guangdong Medical University between 2015 and 2016. The scale Quality of Life Instruments for Chronic Diseases-Coronary heart disease (QLICD-CHD V2.0) was used to evaluate HRQoL and collect demographic information. Medical records were applied to collect patients’ clinical indicators. A simple correlation analysis, Student’s t-test, and a one-way analysis of variance were first performed to filter factors that might associate with HRQoL, and multiple linear regression was applied to finally identify related factors.Results: Findings from multiple linear regression showed that the total score was related to family economy, treatment, indirect bilirubin, and albumin with regression coefficient B=5.209, − 6.615, 0.378, and 0.548, respectively. The physical functions were related to treatment, albumin, globular proteins, chloride, and red blood cell count with B=− 9.031, 1.000, 0.612, 1.320, and 5.161, respectively. The psychological function was in association with family economy, clinical course, serum phosphorus, and percentage of lymphocyte population with B=7.487, 6.411, − 16.458, and 0.090, respectively. The social function was associated with family economy, blood urea nitrogen, serum creatinine, and platelet distribution width with B=7.391, 1.331, − 0.060, and − 0.929, respectively. The special module was in association with treatment, indirect bilirubin, and serum calcium with B=− 7.791, 0.414, and 23.017, respectively.Conclusion: Clinical indicators including albumin, globular proteins, chloride, red blood cell count, serum phosphorus, percentage of lymphocyte population, blood urea nitrogen, serum creatinine, platelet distribution width, indirect bilirubin, and serum calcium, as well as socio-demographic factors including the family economy, clinical course, and treatment, may affect coronary heart disease patients’ HRQoL.Keywords: quality of life, coronary heart disease, socio-demographic factors, clinical indicators, scale

Huamei Wei,1,&ast; Lizheng Huang,2,&ast; Qi Lu,2,&ast; Zheng Huang,2 Yanyan Huang,2 Zuoming Xu,3 Wenchuan Li,3 Jian Pu3,4 1Department of Pathology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, People’s Republic of China; 2Graduate College of Youjiang Medical University for Nationalities, Baise, People’s Republic of China; 3Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, People’s Republic of China; 4Guangxi Clinical Medical Research Center of Hepatobiliary Disease, Baise, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Pu, Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18 Zhongshan Two Road, Baise, 533000, People’s Republic of China, Email jian_pu@126.comPurpose: N6-methyladenosine (m6A) modification plays an important role in regulating RNA maturation, stability, and translation. Thus, m6A modification is involved in various pathophysiological processes including hepatocellular carcinoma (HCC). However, the direct contribution of m6A modifications to RNA function in HCC remains unclear. Here, we identified LEAWBIH (long non-coding RNA epigenetically activating Wnt/β-catenin signalling in HCC) as an m6A-modified long non-coding RNA (lncRNA) and investigated the effects of m6A on the function of LEAWBIH in HCC.Methods: Quantitative polymerase chain reaction was performed to measure the gene expression in tissues and cells. The level of m6A modification was detected using a methylated RNA immunoprecipitation assay and single-base elongation- and ligation-based qPCR amplification method. Cell proliferation was evaluated using the Glo cell viability and CCK-8 assays. Cell migration and invasion were evaluated using Transwell migration and invasion assays. The mechanisms of m6A modified LEAWBIH were investigated using chromatin isolation by RNA purification, chromatin immunoprecipitation, and dual-luciferase reporter assays.Results: LEAWBIH was highly expressed and correlated with poor survival in HCC patients. LEAWBIH was identified as a m6A-modified transcript. m6A modification increased LEAWBIH transcript stability. The m6A modification level of LEAWBIH was increased in HCC, and a high m6A modification level of LEAWBIH predicted poor survival. LEAWBIH promotes HCC cell proliferation, migration, and invasion in an m6A modification-dependent manner. Mechanistic investigations revealed that m6A-modified LEAWBIH activated Wnt/β-catenin signaling. m6A-modified LEAWBIH binds to the m6A reader YTHDC1, which further interacts with and recruits H3K9me2 demethylase KDM3B to CTNNB1 promoter, leading to H3K9me2 demethylation and CTNNB1 transcription activation. Functional rescue assays showed that blocking Wnt/β-catenin signaling abolished the role of LEAWBIH in HCC.Conclusion: m6A-modified LEAWBIH exerts oncogenic effects in HCC by epigenetically activating Wnt/β-catenin signaling, highlighting m6A-modified LEAWBIH as a promising therapeutic target for HCC.Keywords: hepatocellular carcinoma, N6-methyladenosine, histone methylation, Wnt/β-catenin signaling

Lingyan Qin,&ast; Qingwei Ma,&ast; Chunrong Zhang, Zuojie Lu, Luchao Liu, Zhihu Huang Department of Clinical Laboratory, Minzu Hospital of Guangxi Zhuang Autonomous Region, Affiliated Minzu Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhihu Huang, Department of Clinical Laboratory, Minzu Hospital of Guangxi Zhuang Autonomous Region, Affiliated Minzu Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530001, People’s Republic of China, Tel +86-0771-3112210, Fax +86-0771-863112210, Email hoftiger@126.comPurpose: This paper aims to study the relationship between lipoprotein-associated phospholipase A2 (Lp-PLA2) and GDM (gestational diabetes mellitus) by detecting Lp-PLA2 level and its gene polymorphism.Patients and Methods: From January to June 2022, 82 GDM patients treated in our hospital were included as an experimental group, and 89 healthy pregnant women during the same period were selected as the control group. Lp-PLA2 concentration and TG, TC, HDL-C, and LDL-C levels were tested with specialized instruments in clinical laboratories. The PLA2G7 gene polymorphisms (rs1805017, rs1805018, and rs76863441) were detected by fluorescent probe method and sequencing.Results: Lp-PLA2 concentration was significantly higher in GDM group than control group (P< 0.05). Among three polymorphism loci of PLA2G7 gene (rs1805017, rs1805018, and rs76863441) the significant associations were only found in GT genotype of rs76863441 loci (P< 0.05).Conclusion: Pregnant women with high levels of Lp-PLA2 concentration are more likely to develop GDM, especially those with PLA2G7 rs76863441 polymorphism. Lp-PLA2 concentration and PLA2G7 rs1805017 polymorphism may be a novel marker for GDM diagnosis and prediction.Keywords: gestational diabetes mellitus, PLA2G7, Lp-PLA2, gene polymorphism

Zhihua Huang,&ast; Anqi Duan,&ast; Zhihui Zhao, Qing Zhao, Yi Zhang, Xin Li, Sicheng Zhang, Luyang Gao, Chenhong An, Qin Luo, Zhihong Liu Center for Respiratory and Pulmonary Vascular Diseases, Department of Cardiology, Fuwai Hospital, National Clinical Research Center for Cardiovascular Diseases, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qin Luo; Zhihong Liu, Center for Respiratory and Pulmonary Vascular Diseases, Department of Cardiology, Fuwai Hospital, National Clinical Research Center for Cardiovascular Diseases, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Xicheng District, Beijing, 100037, People’s Republic of China, Tel +86 010 8832859, Email luoqin2009@163.com; zhihongliufuwai@163.comPurpose: Acute pulmonary embolism (PE) poses a life-threatening risk with high mortality rates. While the coexistence of PE and obstructive sleep apnea (OSA) is gaining recognition, its influence on PE severity and prognosis remains uncertain. This study aims to investigate the associations between OSA and disease severity, as well as outcomes, in patients with acute PE.Patients and Methods: We conducted a retrospective cohort study on patients diagnosed with acute PE who had undergone previous cardiorespiratory polygraphy. OSA severity was assessed using the apnea-hypopnea index (AHI) derived from cardiorespiratory polygraphy. The severity of acute PE was evaluated using the simplified Pulmonary Embolism Severity Index (sPESI) score. Logistic regression analysis was performed to investigate the associations between AHI and the risk of belonging to the sPESI≥ 1 group. Cox regression analysis was used to examine the relationship between AHI and long-term adverse events, defined as a composite of all-cause mortality and non-fatal cardiovascular events.Results: Among 145 acute PE patients (mean age 62.2 years, 49.7% male), 94 (64.8%) had OSA. Patients with OSA had a significantly higher proportion of sPESI≥ 1 (89.4% vs 68.6%, p=0.002) than non-OSA patients. Each unit increase in AHI was associated with a 15% increased risk of severe PE (sPESI≥ 1) (odds ratio: 1.15, 95% CI 1.05– 1.26, p=0.002) after adjusting for confounders. During a median follow-up of 15.2 months, 27 (18.6%) patients experienced adverse events. Increased AHI independently predicted a higher risk of adverse events (hazard ratio: 1.03, 95% CI: 1.00– 1.05, p=0.026), even after adjusting for potential confounders. AHI ≥ 8 events/h was associated with a significantly higher adjusted hazard ratio of 2.56 (95% CI: 1.15– 5.72, p=0.022) for adverse events compared to AHI < 8 events.Conclusion: OSA is common in acute PE patients and is linked to increased disease severity and adverse outcomes. Implementing routine OSA screening and management may aid risk stratification and improve outcomes in acute PE patients.Keywords: sleep apnea, pulmonary embolism, outcomes, prognosis, cardiovascular

Lin Chen,1,&ast; Qi Zhang,2,&ast; Zheng Huang,1,&ast; Weiwei Da,1 Shuang Liu,1 Chunchun Xue,1 Chao Ding,1 Deta Chen,1 Tianyou Fan,1 Qi Shi,1 Xiaofeng Li1 1Department of Orthopedics, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Traditional Chinese Medicine, Xuhui District Tianping Street Community Health Center, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaofeng Li, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 274 Middle Zhijiang Road, Shanghai, 200071, People’s Republic of China, Tel +86-13816504131, Email lixiaofeng0409@163.comPurpose: Non-specific chronic neck pain (NSCNP) is an increasingly common musculoskeletal disease and an important issue in the global healthcare system. Some studies have shown that the combination of manual therapy and exercise is effective in treating NSCNP but still with several limitations. Traditional Chinese manual therapy (tuina) is a Chinese manual therapy that consists of soft tissue manipulation and spinal manipulation. This study aims to design a randomized controlled trial to assess the effect of a tuina combined with specific therapeutic neck exercise modified protocol for NSCNP patients.Patients and Methods: This is a study protocol for a randomized, participant-, assessor- and analyst-blinded controlled trial. Eighty-eight eligible NSCNP patients will be randomly allocated into tuina combined with specific therapeutic neck exercise group (TSTE group) and tuina combined with sham therapeutic neck exercise group (TS group) in a ratio of 1:1. All participants will receive 8 treatment sessions applied in 4 weeks and then be followed up for another 12 weeks. Clinical data will be collected at baseline, during treatment phase (at the 2- and 4-week) and at the 8-, 12-, 16-week follow-ups. The primary outcome is the changes in neck pain intensity (visual analogue scale). The secondary outcomes include neck disability (Neck Disability Index), cervical range of motion (ROM), neck muscle endurance, cervical muscle cross-sectional area, cervical curvature and analgesic consumption. Adverse events will be collected and recorded throughout the study.Conclusion: We will discuss whether our tuina combined with specific therapeutic neck exercise modified protocol is more effective at improving pericervical muscle endurance, ROM, cervical muscle cross-sectional area and cervical curvature than tuina alone, thereby decreases neck pain and disability in individuals with NSCNP more effectively.Trial Registration: Chinese Clinical Trials Registry, ChiCTR2300067903. Registered on 31 January 2023.Keywords: manual therapy, non-specific neck pain, specific therapeutic exercise, randomized controlled trial

Chuan Tan,1,&ast; Yanyan Huang,2,&ast; Zheng Huang,2,&ast; Yuanjia Ning,2 Lizheng Huang,2 Xianjian Wu,1 Yuan Lu,1 Huamei Wei,3 Jian Pu1 1Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, People’s Republic of China; 2Graduate College of Youjiang Medical University for Nationalities, Baise, People’s Republic of China; 3Department of Pathology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Pu, Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18 Zhongshan Two Road, Baise, Guangxi, People’s Republic of China, Email jian_pu@126.comPurpose: N6-methyladenosine (m6A) modification has shown critical roles in regulating mRNA fate. Non-coding RNAs also have important roles in various diseases, including hepatocellular carcinoma (HCC). However, the potential influences of m6A modification on non-coding RNAs are still unclear. In this study, we identified a novel m6A-modified ATP8B1-AS1 and aimed to investigate the effects of m6A on the expression and role of ATP8B1-AS1 in HCC.Methods: qPCR was performed to measure the expression of related genes. The correlation between gene expression and prognosis was analyzed using public database. m6A modification level was measured using MeRIP and single-base elongation- and ligation-based qPCR amplification method. The roles of ATP8B1-AS1 in HCC were investigated using in vitro and in vivo functional assays. The mechanisms underlying the roles of ATP8B1-AS1 were investigated by ChIRP and ChIP assays.Results: ATP8B1-AS1 is highly expressed in HCC tissues and cell lines. High expression of ATP8B1-AS1 is correlated with poor overall survival of HCC patients. ATP8B1-AS1 is m6A modified and the 792 site of ATP8B1-AS1 is identified as an m6A modification site. m6A modification increases the stability of ATP8B1-AS1 transcript. m6A modification level of ATP8B1-AS1 is increased in HCC tissues and cell lines, and correlated with poor overall survival of HCC patients. ATP8B1-AS1 promotes HCC cell proliferation, migration, and invasion, which were abolished by the mutation of m6A-modified 792 site. Mechanistic investigation revealed that m6A-modified ATP8B1-AS1 interacts with and recruits m6A reader YTHDC1 and histone demethylase KDM3B to MYC promoter region, leading to the reduction of H3K9me2 level at MYC promoter region and activation of MYC transcription. Functional rescue assays showed that depletion of MYC largely abolished the oncogenic roles of ATP8B1-AS1.Conclusion: m6A modification level of ATP8B1-AS1 is increased and correlated with poor prognosis in HCC. m6A-modified ATP8B1-AS1 exerts oncogenic roles in HCC via epigenetically activating MYC expression.Keywords: hepatocellular carcinoma, N6-methyladenosine, noncoding RNA, histone methylation, MYC signaling

Lin Gao,1 Qindi Liu,2 Weiwei Zhang,1 Hong Sun,1 Zhiming Kuang,1 Guangping Zhang,1 Zhenfei Huang1 1Department of Intensive Care Unit, Ganzhou People’s Hospital, Ganzhou City, Jiangxi Province, 341000, People’s Republic of China; 2Department of Respiratory and Critical Medicine, Ganzhou Fifth People’s Hospital, Ganzhou City, Jiangxi Province, 341000, People’s Republic of ChinaCorrespondence: Zhenfei Huang, Department of Intensive Care Unit, Ganzhou People’s Hospital, No. 17, Hongqi Avenue, Zhanggong District, Ganzhou City, Jiangxi Province, 341000, People’s Republic of China, Email H13507977932@163.comIntroduction: Severe pneumonia progresses rapidly, so early assessment of the severity and prognosis is crucial for reducing mortality rates.Objective: We explore the role of serum microRNA-24 (miR-24) and microRNA-223 (miR-223) in the prognosis of severe pneumonia.Methods: There were a total of 96 patients with general pneumonia, 94 patients with severe pneumonia, and 93 healthy people, who were enrolled in this study. The levels of serum miR-24 and miR-223 were detected by real-time fluorescent quantitative PCR in all groups.Results: The serum miR-223 level in the severe group was higher than that in the common group and the control group, and the miR-24 level was lower than that in the common group and the control group (P< 0.05). The serum miR-223 levels and APACHEII scores in the death group were higher than those in the survival group on the first, third, and seventh day after admission, while the miR-24 levels were lower than those in the survival group (P< 0.05). The proportion of patients with mechanical ventilation in the death group was higher than that in the survival group (P< 0.05). The level of serum miR-24 was negatively correlated with APACHEII score and mechanical ventilation in patients who died of severe pneumonia (P< 0.05), and miR-223 was positively correlated with APACHEII score and mechanical ventilation (P< 0.05). The AUC predicted by serum miR-24, miR-223, and APACHEII scores alone and jointly were 0.867, 0.839, 0.791, and 0.952, respectively. MiR-24 and miR-223 are protective and independent risk factors for mortality in severe pneumonia patients, respectively (P< 0.05). MiR-24 was a protective factor affecting the death of patients with severe pneumonia, and miR-223 was an independent risk factor affecting the death of patients with severe pneumonia (P< 0.05).Conclusion: The combination of serum miR-24 and miR-223 levels on the first day after admission and APACHEII score can effectively predict prognosis.Keywords: severe pneumonia, micro RNA-24, micro RNA-223, prognosis

Zheng Huang,&ast; Ning Liu,&ast; Shenghong Hu, Xia Ju, Siqi Xu, Shengbin Wang Department of Anesthesiology, Bengbu Medical College, Anqing Municipal Hospital, Anqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Siqi Xu; Shengbin Wang, Email errtg555@163.com; shbw1965@126.comPurpose: This study evaluated the effect of a combined infusion of dexmedetomidine and esketamine on the quality of recovery in patients undergoing modified radical mastectomy.Methods: A total of 135 patients were randomly divided into three groups: dexmedetomidine group (group D) received dexmedetomidine (0.5 μg/kg loading, 0.4 μg/kg/h infusion), dexmedetomidine plus low-dose esketamine group (group DE1) received dexmedetomidine (0.5 μg/kg loading, 0.4 μg/kg/h infusion) and esketamine (0.5 mg/kg loading, 2 μg/kg/min infusion), dexmedetomidine plus high-dose esketamine group (group DE2) received dexmedetomidine (0.5 μg/kg loading, 0.4 μg/kg/h infusion) and esketamine (0.5 mg/kg loading, 4 μg/kg/min infusion). The primary outcome was the overall quality of recovery-15 (QoR-15) scores at 1 day after surgery. The secondary endpoints were total QoR-15 scores at 3 days after surgery, propofol and remifentanil requirement, awaking and extubation time, postoperative visual analogue scale (VAS) pain scores, rescue analgesic, nausea and vomiting, bradycardia, excessive sedation, nightmares, and agitation.Results: The overall QoR-15 scores were much higher in groups DE1 and DE2 than in groups D 1 and D 3 days after surgery (P < 0.05). VAS pain scores at 6, 12, 24 h postoperatively, propofol and remifentanil requirements were significantly lower in groups DE1 and DE2 than in group D (P < 0.05). Compared with group D, awaking time, extubation time, and post-anesthesia care unit (PACU) stay were significantly prolonged in groups DE1 and DE2 (P < 0.05) and were much longer in group DE2 than in group DE1 (P < 0.05). The proportion of postoperative rescue analgesics and bradycardia was higher and the incidence of excessive sedation was lower in group D than in groups DE1 and DE2 (P < 0.05).Conclusion: Dexmedetomidine plus esketamine partly improved postoperative recovery quality and decreased the incidence of bradycardia but prolonged awaking time, extubation time, and PACU stay, especially dexmedetomidine plus 4 μg/kg/min esketamine.Keywords: dexmedetomidine, esketamine, quality of recovery, modified radical mastectomy

Zu-Fei Wu,1,&ast; Wen-Tao Su,2,3,&ast; Shi Chen,4 Bai-Da Xu,2 Gang-Jun Zong,2,3 Cun-Ming Fang,1 Zheng Huang,1 Xue-Jun Hu,1 Gang-Yong Wu,2,3 Xiao-Lin Ma1 1Department of Cardiology, Xuancheng People’s Hospital, Xuanchen, Anhui, 242000, People’s Republic of China; 2Department of Cardiology, the 904th Hospital of the PLA Joint Logistics Support Force, Wuxi, Jiangsu, 214044, People’s Republic of China; 3Department of Cardiology, Wuxi Clinical College of Anhui Medical University, Wuxi, Jiangsu, 214044, People’s Republic of China; 4Department of Cardiology, Wuxi No.5 People’s Hospital, Wuxi, Jiangsu, 214044, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gang-Yong Wu, Department of Cardiology, the 904th Hospital of the PLA Joint Logistics Support Force, Wuxi, Jiangsu, 214044, People’s Republic of China, Email wuwangyi520@sina.comObjective: To investigate the correlation between serum parathyroid hormone (PTH) levels and in-hospital major adverse cardiovascular events (MACE) in patients with acute ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PCI), and establish a risk prediction model based on parameters such as PTH for in-hospital MACE.Methods: This observational retrospective study consecutively enrolled 340 patients who underwent primary PCI for STEMI between January 2016 and December 2020, divided into a MACE group (n=92) and a control group (n=248). The least absolute shrinkage and selection operator (LASSO) and logistic regression analyses were used to determine the risk factors for MACE after primary PCI. The rms package in R-studio statistical software was used to construct a nomogram, to detect the line chart C-index, and to draw a calibration curve. The decision curve analysis (DCA) method was used to evaluate the clinical application value and net benefit.Results: Correlation analysis revealed that PTH level positively correlated with the occurrence of in-hospital MACE. Receiver operating characteristic curve analyses revealed that PTH had a good predictive value for in-hospital MACE. Multivariate logistic regression analysis indicated that Killip class II–IV, and FBG were independently associated with in-hospital MACE after primary PCI. A nomogram model was constructed using the above parameters. The model C-index was 0.894 and the calibration curve indicated that the model was well calibrated. The DCA curve suggested that the nomogram model was better than TIMI score model in terms of net clinical benefit.Conclusion: Serum PTH levels in patients with STEMI are associated with in-hospital MACE after primary PCI, and the nomogram risk prediction model based on PTH demonstrated good predictive ability with obvious clinical practical value.Keywords: parathyroid hormone, acute ST-segment elevation myocardial infarction, percutaneous coronary intervention, nomograms

Xuezheng Gao,1 Zixuan Huang,2 Jiangjuan Li,3 Zhenhe Zhou,1,3 Hongliang Zhou4 1Department of Psychiatry, The Affiliated Wuxi Mental Health Center of Nanjing Medical University, Wuxi City, 214151, People’s Republic of China; 2Department of Music and Wellbeing, School of Music, University of Leeds, Leeds City, UK; 3Department of Psychiatry, The Affiliated Mental Health Center of Jiangnan University, Wuxi City, 214151, People’s Republic of China; 4Department of Psychology, The Affiliated Hospital of Jiangnan University, Wuxi City, 214151, People’s Republic of ChinaCorrespondence: Zhenhe Zhou, Department of Psychiatry, The Affiliated Wuxi Mental Health Center of Nanjing Medical University, Wuxi City, 214151, People’s Republic of China, Tel +86-13358118986, Fax +86-510-83219366, Email zhouzh@njmu.edu.cn Hongliang Zhou, Department of Psychology, The Affiliated Hospital of Jiangnan University, Wuxi City, 214151, People’s Republic of China, Tel +86-18341654302, Fax +86-510-85808820, Email Hongliangzh2022@hotmail.comPurpose: Patients with schizophrenia show deficits in facial emotion recognition and emotional intensity assessment, and also exhibit structural and functional irregularities in specific brain regions. In this study, we aimed to examine differences in active brain regions involved in processing the Emotion Intensity Recognition Task (EIRT), which can serve as an indicator of emotion recognition and ability to perceive intensity, between patients with schizophrenia and healthy controls (HCs). The purpose of this study was to investigate dysfunctional brain regions and investigate the role of the amygdala in social cognition deficits in patients with schizophrenia by focusing on alterations in amygdala activity linked to facial emotion recognition.Participants and Methods: Twenty-two patients who met a diagnostic criteria for schizophrenia according to DSM-IV and 27 HCs participated in an MRI scan while completing the EIRT. Behavioral and MRI data were collected and analyzed.Results: Behavioral results showed that patients with schizophrenia made significantly more errors in recognizing surprise, happiness, sadness, fear, and neutral expressions, and patients with schizophrenia exhibited significantly slower response times in recognizing happy facial expressions. Imaging results showed that schizophrenia patients found hypoactivation in several inferior parietal and temporal regions, in the cerebrum and anterior cingulate; and decreased amygdala activation in individuals with schizophrenia was associated with impaired recognition of fear in facial expressions.Conclusion: Facial emotion processing deficits are emotion-specific (surprise, happiness, sadness, fear, and neutral expressions) in schizophrenia. Hypoactivation in several inferior parietal and temporal regions, in the cerebrum and anterior cingulate, was thought to contribute to symptom formation in schizophrenia. Reduction in amygdala activation in schizophrenia patients was associated with impairment of the fear-emotional process.Keywords: schizophrenia, social cognition, functional magnetic resonance imaging, emotion, facial affect recognition, amygdala

Zeling Huang,&ast; Binjie Lu,&ast; Xianda Zhang,&ast; Jiangping Wang, Xuefeng Cai, Yujiang Liu, Jianxiong Mo, Yuwei Li, Bo Xu, Xiaofeng Shen Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, Jiangsu, 215008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo Xu; Xiaofeng Shen, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, Jiangsu, 215008, People’s Republic of China, Tel +86 18359146790, Email xubo12080@163.com; 29240818@qq.comPurpose: The aim of this study was to investigate the effect of Zhiqiao Gancao decoction (ZQGCD) on hyperalgesia in lumbar disc herniation (LDH) and its mechanism.Methods: The potential mechanism of ZQGCD’s therapeutic effect on LDH was investigated through network pharmacology, which involved screening the targets of eight components that were absorbed into the bloodstream. The effects of CCR2 inhibitors and ZQGCD-containing serum on the excitability of the CCL2/CCR2 signaling pathway and dorsal root ganglion neurons (DRGn) were investigated in vitro. The effects of CCR2 inhibitors and ZQGCD on the expression of the CCL2/CCR2 signaling pathway and ASIC3 in the rat intervertebral disc and dorsal root ganglion (DRG), the degree of disc degeneration, the threshold of foot retreat, and the latency of foot retreat in LDH rats were examined in vivo. The binding affinities and interaction modes between CCR2 and the components absorbed into the blood were analyzed using the AutodockVina 1.2.2 software.Results: Network pharmacology revealed that ZQGCD could treat LDH through a mechanism involving the chemokine signaling pathway. It was observed that the CCR2 inhibitor and ZQGCD-containing serum downregulated CCR2 and ASIC3 expression and decreased cell excitability in DRGn. The CCL2/CCR2 signaling pathway was activated in the degenerated intervertebral disc and DRG of LDH rats, increased the expression of ASIC3, and decreased the mechanical allodynia domain and thermal hyperalgesia domain. However, a CCR2 inhibitor or ZQGCD could ameliorate the above changes in LDH rats. The target proteins, CCL2 and CCR2, exhibited a robust affinity for the eight components that were absorbed into the bloodstream.Conclusion: The CCL2/CCR2 pathway was activated in the intervertebral disc and DRG of LDH rats. This was accompanied by upregulation of ASIC3 expression, increased excitability of DRGn, and the occurrence of hyperalgesia. ZQGCD improves hyperalgesia in LDH rats by inhibiting the CCL2/CCR2 pathway and downregulating ASIC3 expression.Keywords: lumbar disc herniation, dorsal root ganglion neurons, hyperalgesia, traditional Chinese medicine, molecular docking

Zehui Qin,1 Minhua Li,1,2 Juanjuan Cheng,1,2 Ziwei Huang,1,2 Gaoxiang Ai,1,2 Chang Qu,3 Youliang Xie,1 Yucui Li,1 Huijun Liao,4 Jianhui Xie,5– 7 Ziren Su1,2 1School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, People’s Republic of China; 2Dongguan Institute of Guangzhou University of Chinese Medicine, Dongguan, 523808, People’s Republic of China; 3College of Forestry and Landscape Architecture, South China Agricultural University, Guangzhou, 510006, People’s Republic of China; 4Department of Clinical Pharmacy and Pharmaceutical Services, Huazhong University of Science and Technology Union Shenzhen Hospital (the 6th affiliated Hospital of Shenzhen University), Shenzhen, People’s Republic of China; 5The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 6State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 7Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, People’s Republic of ChinaCorrespondence: Ziren Su, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR China, Dongguan Institute of Guangzhou University of Chinese Medicine, Dongguan, 523808, People’s Republic of China, Email suziren@gzucm.edu.cn Huijun Liao, Department of Clinical Pharmacy and Pharmaceutical Services, Huazhong University of Science and Technology Union Shenzhen Hospital (the 6th affiliated hospital of Shenzhen University), Shenzhen, People’s Republic of China, Email liaohuijun1016@163.comPropose: Berberine (BBR) is extensively studied as an outstanding anti-hyperuricemia drug. However, the clinical application of BBR was limited due to its poor absorption and low bioavailability. Therefore, there is an urgent necessity to find a novel drug formulation to address the issues of BBR in clinical application.Methods: Herein, we conducted the solubility, characterization experiments to verify whether BBR and sodium taurocholate (STC) self-assembled nanoparticles (STC@BBR-SANPs) could form. Furthermore, we proceeded the release experiment in vitro and in vivo to investigate the drug release effect. Finally, we explored the therapeutic effect of STC@BBR-SANPs on hyperuricemia (HUA) through morphological observation of organs and measurement of related indicators.Results: The solubility, particle size, scanning electron microscopy (SEM), and stability studies showed that the stable STC@BBR-SANPs could be formed in the BBR-STC system at ratio of 1:4. Meanwhile, the tissue distribution experiments revealed that the STC@BBR-SANPs could accelerate the absorption and distribution of BBR. In addition, the pharmacology study demonstrated that both BBR and STC@BBR-SANPs exhibited favorable anti-HUA effects and nephroprotective effects, while STC@BBR-SANPs showed better therapeutic action than that of BBR.Conclusion: This work indicated that STC@BBR-SANPs can be self-assembly formed, and exerts excellent uric acid-lowering effect. STC@BBR-SANPs can help to solve the problems of poor solubility and low absorption rate of BBR in clinical use, and provide a new perspective for the future development of BBR.Graphical Abstract: Keywords: berberine, sodium taurocholate, intermolecular interactions, self-assembled, nanoparticles, hyperuricemia

Yuelong Liang,1,&ast; Zhengze Huang,1,&ast; Xuqiu Shen,1,&ast; Yiyin Zhang,1 Yihan Chai,1 Kexin Jiang,1 Qi Chen,2 Feng Zhao3 1Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of General Surgery, Hangzhou Fuyang Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Clinical Laboratory, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuelong Liang; Feng Zhao, Email yuelongliang@zju.edu.cn; fengzhao3901@zju.edu.cnBackground: Antimicrobial peptides (AMPs) can act on the bacterial cell membrane to play an antibacterial role in types of drug-resistant bacteria. Therefore, AMPs have attracted more and more attention in the treatment of drug-resistant bacteria.Methods: Bibliometric analysis was employed to sort out the development and trends in the research of AMPs in the treatment of drug-resistant bacteria and map the knowledge structure for scholars.Results: Since 2010, the publications and citations in this field have exploded, indicating a growing global interest in the field of AMPs for the treatment of drug-resistant bacteria. And as major countries in this field, China and the USA had conducted very in-depth exchanges and cooperation, which had injected a steady stream of impetus into this field. Both old and new scholars have made efforts, and related fields have developed rapidly, especially in the synthesis and improvement of novel AMPs. In recent years, research directions in the field of AMPs for the treatment of drug-resistant bacteria gradually focused on the practical application, optimization of drug delivery mode, optimization of synthesis mode, screening of new AMPs and other fields, indicating that the relevant research results of AMPs for the treatment of drug-resistant bacteria had entered the actual clinical stage, with higher practical significance.Conclusion: The research history, global research status, future research hotspots, and trends of the research of AMPs in the treatment of drug-resistant bacteria were discussed in depth in this study, which can provide research references and inspiration for researchers inside and outside the related field.Keywords: antimicrobial peptides, AMP, drug-resistant bacteria, bibliometric

Qing Wei,1,&ast; Guoman Liu,1,&ast; Zihua Huang,1,&ast; Yanyan Huang,1 Lizheng Huang,1 Zheng Huang,1 Xianjian Wu,2 Huamei Wei,3 Jian Pu2 1Graduate College of Youjiang Medical University for Nationalities, Baise, Guangxi, 533099, People’s Republic of China; 2Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, 533000, People’s Republic of China; 3Department of Pathology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, 533000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Pu, Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18 Zhongshan two Road, Baise, Guangxi, 533000, People’s Republic of China, Tel +86 776-2836646, Email Pujianym@163.comBackground: Hepatocellular carcinoma (HCC) is the predominant histological type of primary liver cancer, which ranks sixth among the most common human tumors. Tumor-associated macrophages (TAMs) are an important component of tumor microenvironment (TME) and the M2 macrophage polarization substantially contributes to tumor growth and metastasis. Long non-coding RNA (lncRNA) MEG3 was reported to restrain HCC development. However, whether MEG3 regulates macrophage phenotypic polarization in HCC remains unclear.Methods: Bone marrow derived macrophages (BMDMs) were treated with LPS/IFNγ and IL4/IL13 to induce the M1 and M2 macrophage polarization, respectively. M2-polarized BMDMs were simultaneously transfected with adenovirus vector overexpressing MEG3 (Adv-MEG3). Subsequently, M2-polarized BMDMs were cultured for 24 h with serum-free medium, the supernatants of which were harvested as conditioned medium (CM). HCC cell line Huh7 was cultured with CM for 24 h. F4/80+CD68+ and F4/80+CD206+ cell percentages in M1-and M2-polarized BMDMs were calculated using flow cytometry. Huh7 cell migration, invasion and angiogenesis were determined via Transwell assay and tube formation experiment. Nude mice were implanted with Huh7 cells and Adv-MEG3-transfected M2-polarizd BMDMs, and tumor growth and M2 macrophage polarization markers were assessed. The binding between miR-145-5p and MEG3 or disabled-2 (DAB2) was verified by luciferase reporter assay.Results: MEG3 presented lower expression in HCC tissues than in normal controls, and low expression of MEG3 was correlated to poorer prognosis of HCC patients. MEG3 expression was enhanced during LPS/IFNγ-induced M1 polarization, but was reduced during IL4/IL13-induced M2 polarization. MEG3 overexpression inhibited the expression of M2 polarization markers in both M2-polarized BMDMs and mice. Mechanically, MEG3 bound with miR-145-5p to regulate DAB2 expression. Overexpressing MEG3 suppressed M2 polarization-induced HCC cell metastasis and angiogenesis by upregulating DAB2 and inhibited in vivo tumor growth.Conclusion: LncRNA MEG3 curbs HCC development by repressing M2 macrophage polarization via miR-145-5p/DAB2 axis.Keywords: hepatocellular carcinoma, tumor microenvironment, macrophage polarization, MEG3, miR-145-5p, DAB2, metastasis

Chen Y, Deng Y, Chen L, Huang Z, Yan Y, Huang Z. J Inflamm Res. 2023;16:1077–1089. We, the Editors and Publisher of Journal of Inflammation Research, have retracted the following article. Following publication of the article, concerns were raised about the duplication of images from Figure 5D with images from another unrelated article. Specifically, The images for Figure 5D, have been duplicated with the images for Figure 4G from Wang M, Li Q, Yu S, et al. Coronin 3 Promotes the Development of Oncogenic Properties in Glioma Through the Wnt/β-Catenin Signaling Pathway. Onco Targets Ther. 2020;13:6661–6673. https://doi.org/10.2147/OTT.S257001. The authors did not respond to our queries and were unable to provide an explanation for the duplicated images or provide data for the study. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article and the authors were notified of this. 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”.

Ruoyang Lin,1 Renpin Chen,1 Lechi Ye,2 Zhiming Huang,1 Xianfan Lin,1 Tanzhou Chen1 1Department of Gastroenterology and Hepatology, the First Affiliated Hospital of Wenzhou, Medical University, Wenzhou, People’s Republic of China; 2Department of Colorectal and Anal Surgery, the First Affiliated Hospital of Wenzhou, Medical University, Wenzhou, People’s Republic of ChinaCorrespondence: Tanzhou Chen, Tel +8613706661269, Email cctzz@163.comBackground: Researches showed RNA methylation genes can affect the prognosis of tumors. Thus, the study aimed to comprehensively analyze the effects of RNA methylation regulatory genes in prognosis and treatment of colorectal cancer (CRC).Methods: Prognostic signature associated with CRCs were constructed by differential expression analysis, Cox and Least Absolute Shrinkage and Selection Operator (LASSO) analyses. Receiver operating characteristic (ROC) and Kaplan–Meier survival analyses were used to validate the reliability of the developed model. Gene Ontology (GO), Gene set variation analysis (GSVA), and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed for functional annotation. Finally, normal and cancerous tissue were collected to validate gene by quantitative real-time PCR (qRT-PCR).Results: A prognostic risk model based on leucine rich pentatricopeptide repeat containing (LRPPRC) and ubiquitin-like with PHD and ring finger domains 2 (UHRF2) was constructed and relevant to the overall survival (OS) of CRC. Functional enrichment analysis revealed that collagen fibrous tissue, ion channel complex and other pathways were significantly enriched, which might help explain the underlying molecular mechanisms. There were significant differences in ImmuneScore, StromalScore, ESTIMATEScore between high- and low-risk groups (p < 0.05). Ultimately, qRT-PCR validation showed that a significant upregulation in the expression of LRPPRC and UHRF2 in cancerous tissue, which verified the effectiveness of our signature.Conclusion: In conclusion, 2 prognostic genes (LRPPRC and UHRF2) related to RNA methylation were identified by bioinformatics analysis, which might supply a new insight into the treatment and evaluation of CRC.Keywords: colorectal cancer, prognosis, RNA methylation regulatory genes, tumor microenvironment, immunotherapy

Yun Wang,1 Zhongfeng Huang,2 Huijuan Chen,3 Ye Yuan,2 Edward B McNeil,4 Xiaolong Lu,5 Aihua Zhang1 1Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 2Department of Tuberculosis, Guiyang Public Health Clinical Center, Guiyang, Guizhou, People’s Republic of China; 3Department of Tuberculosis Prevention and Control, Guizhou Center for Disease Prevention and Control, Guiyang, Guizhou, People’s Republic of China; 4Department of Infectious Diseases, School of Public Health and Primary Care, Chinese University of Hong Kong, Hong Kong, People’s Republic of China; 5School of Medicine and Health Management, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of ChinaCorrespondence: Aihua Zhang, Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China, Tel +86 851 88416187, Fax +86 851 88416187, Email 97349238@qq.comPurpose: We aimed to assess the household financial burden due to multidrug-resistant tuberculosis (MDR-TB) treatment and its predictors, examine its association with patient mobility, and test their impact on patient loss to follow-up (LTFU).Methods: A cross-sectional study combining follow-up data collection was conducted at the largest designated MDR-TB hospital in Guizhou. Data were collected from medical records and questionnaires. Household financial burden was measured by the incidence of 2 indicators: catastrophic total costs (CTC) and catastrophic health expenditure (CHE). Mobility was classified as mover or non-mover after the patient’s address was verified twice. A multivariate logistic regression model was used to identify associations between variables. Model I and Model II were separated by CHE and CTC.Results: Out of 180 households, the incidence of CHE and CTC was 51.7% and 80.6%, respectively. Families with low income and patients who were primary income earners were significantly associated with catastrophic costs. 42.8% of patients were movers. Patients from households with CHE (ORadj=2.2, 95% CI: 1.1– 4.1) or with CTC (ORadj=2.6, 95% CI: 1.1– 6.3) were more likely to move. Finding a job against financial difficulty (58.4%) was the top reason for movers. 20.0% of patients experienced LTFU. Patients from households with catastrophic payments (CHE: ORadj=4.1, 95% CI 1.6– 10.5 in Model I; CTC: ORadj=4.8, 95% CI 1.0– 22.9 in Model II), patients who were movers (ORadj=6.1, 95% CI 2.5– 14.8 in Model I; ORadj=7.4, 95% CI 3.0– 18.7 in Model II) and primary income earners (ORadj=2.5, 95% CI: 1.0– 5.9 in Model I; ORadj=2.7, 95% CI 1.1– 6.6 in Model II) had an increased risk of LTFU.Conclusion: There is a significant association between household financial burden due to MDR-TB treatment and patient mobility in Guizhou. They impact patients’ treatment adherence and cause LTFU. Being a primary breadwinner increases the risk for catastrophic household payments and LTFU.Keywords: household catastrophic costs, migration, loss to follow-up, Guizhou, MDR-TB

Zhifeng Huang,1,&ast; Hui Gan,1,&ast; Yiyun Huang,2,&ast; Huiqing Zhu,1 Tingting Liu,1 Tong Chen,1 Runpei Lin,1 Manrong Xie,2 Baoqing Sun1 1Department of Laboratory, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Helong Street Community Health Service Center, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Baoqing Sun; Manrong Xie, Department of Clinical Laboratory, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510180, People’s Republic of China, Tel +86 18816781502, Email sunbaoqing@vip.163.com; Xmr20041103@163.comPurpose: To investigate the lifestyle and stress of mothers during pregnancy to analyze the risk factors for the disease in early childhood.Patients and Methods: A cross-sectional survey was conducted from January 2022 to June 2022 in a sub-district in Guangzhou, China. A total of 3437 valid questionnaires were eventually collected. The questionnaire consisted of 56 questions in three sections included questions on child’s birth conditions and early life environment, questions on mother’s lifestyle during pregnancy, and questions about father.Results: 49.75% of the children were likely to have allergic diseases (suspected allergy group). There were more boys in the suspected allergy group (58% vs 50%), and the percentage of children born at first birth was also higher in the suspected allergy group (61% vs 51%). 67% to 69% of children had suspicious allergies when one parent claimed an allergy, and 80.1% when both parents reported an allergy. The results of the multifactorial logistic model showed that male had 1.49 (1.28 to 1.73) times the risk of allergic diseases than female, and preterm births increased the risk of allergic diseases by 1.53 (1.13– 2.07) times compared to full-term births. Both unplanned pregnancies and pregnancy complications increased the risk of allergic diseases in children before school age [1.34 (1.15– 1.55) and 1.82 (1.46– 2.26)]. Among pregnant women who reported regular passive smoking, the risk of the disease was increased 2.43 (1.71 to 3.50) times in preschool children. Reported allergies in all family members were significant risk factors for allergic diseases in children, especially mother [2.88 (2.41~3.46)]. In the prenatal period, maternal negative emotions are more common in children with suspected allergies.Conclusion: Nearly half of the children in the region suffer from allergic diseases. Sex, birth order and full-term delivery all contributed to early childhood allergy. Family history of allergy, especially maternal, was the most important risk factor, and the number of family members with allergy was significantly associated with the allergy in children. Maternal effects are also reflected in prenatal conditions such as unplanned pregnancy, smoke exposure, pregnancy complications, and prenatal stress.Keywords: cross-sectional, heritability, risk factor, questionnaire, allergic rhinitis