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Bo-Ran Deng,1,&ast; Yang Zhang,2,&ast; Zi-Feng Xie,3,&ast; Ding-Ding Wang,4,&ast; Tao Zeng,1 Dong-Bo Zhang,3 Li Huang,1 Qi-Yan Wang,1 Tu Shen,3 Qiao-Ling Wu3 1Surgical Anesthesia Center, Zigong Hospital of TCM, Zigong, 643000, People’s Republic of China; 2Department of Anesthesia, Da’an District Maternal and Child Health Hospital, Zigong, 643000, People’s Republic of China; 3Department of Anesthesia, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121000, People’s Republic of China; 4Department of Anesthesia, EYE & ENT Hospital of Fudan University, Shanghai, 200031, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tu Shen; Qiao-Ling Wu, Department of Anesthesia, the First Affiliated Hospital of Jinzhou Medical University, No. 40, Section 3, Songpo Road, Linghe District, Jinzhou, 121000, People’s Republic of China, Email shentu2011@sina.com; wqiaoling2013@sina.comPurpose: The debate continues over the differential impact of remimazolam vs propofol on hemodynamic stability. This study aims to elucidate the effects of a combination of remimazolam and esketamine vs propofol and esketamine on hemodynamic parameters in elderly patients undergoing painless colonoscopies.Patients and Methods: We conducted a randomized controlled trial involving 754 patients, divided equally between two treatment groups. The remimazolam-esketamine group (RE group) received 0.15 mg/kg of remimazolam and 0.3 mg/kg of esketamine. Conversely, the propofol-esketamine group (PE group) was administered 1.5 mg/kg of propofol with 0.3 mg/kg of esketamine. Primary outcomes focused on the incidence of hypotension. Secondary outcomes assessed were other hemodynamic adverse events, intraoperative blood pressure and heart rate fluctuations, usage of vasoactive agents, sedation efficacy, and additional adverse reactions.Results: Hypotension occurred significantly less frequently in the RE group (9.78%, 95% confidence interval[CI]: 6.67– 12.87%) compared to the PE group (23.57%, 95% CI: 21.22– 30.52%), P< 0.001. The RE group also showed lower incidences of sinus tachycardia, sinus bradycardia, and required less support from vasoactive agents (P< 0.001). Additionally, the RE group experienced smaller fluctuations in blood pressure and heart rate (P< 0.05). Both groups achieved a 100% sedation success rate. Notably, the RE group had a longer induction period but a quicker recovery time (P< 0.001), and lower rates of respiratory depression (P=0.006) and injection pain (P< 0.001).Conclusion: Remimazolam combined with esketamine offers superior hemodynamic stability and significantly reduces adverse event rates compared to propofol plus esketamine in elderly patients undergoing painless colonoscopies, while maintaining effective sedation.Keywords: remimazolam, esketamine, colonoscopy, elderly patients, hemodynamic effects

Jinbao Shi, Aliang Xu, Liuying Huang, Shaojie Liu, Binxuan Wu, Zuhong Zhang Department of Nephrology, Ningde Hospital of Traditional Chinese Medicine, Ningde, Fujian, People’s Republic of ChinaCorrespondence: Jinbao Shi, Department of Nephrology, Ningde Hospital of Traditional Chinese Medicine, No. 16 Donghu Road, Ningde, Fujian, People’s Republic of China, Email shijinbao00721@aliyun.comBackground: Chronic kidney disease (CKD) involves complex immune dysregulation and altered gene expression profiles. This study investigates immune cell infiltration, differential gene expression, and pathway enrichment in CKD patients to identify key diagnostic biomarkers through machine learning methods.Methods: We assessed immune cell infiltration and immune microenvironment scores using the xCell algorithm. Differentially expressed genes (DEGs) were identified using the limma package. Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) were performed to evaluate pathway enrichment. Machine learning techniques (LASSO and Random Forest) pinpointed diagnostic genes. A nomogram model was constructed and validated for diagnostic prediction. Spearman correlation explored associations between key genes and immune cell recruitment.Results: The CKD group exhibited significantly altered immune cell infiltration and increased immune microenvironment scores compared to the normal group. We identified 2335 DEGs, including 124 differentially expressed immune-related genes. GSEA highlighted significant enrichment of inflammatory and immune pathways in the high immune score (HIS) subgroup, while GSVA indicated upregulation of immune responses and metabolic processes in HIS. Machine learning identified four key diagnostic genes: RGS1, IL4I1, NR4A3, and SOCS3. Validation in an independent dataset (GSE96804) and clinical samples confirmed their diagnostic potential. The nomogram model integrating these genes demonstrated high predictive accuracy. Spearman correlation revealed positive associations between the key genes and various immune cells, indicating their roles in immune modulation and CKD pathogenesis.Conclusion: This study provides a comprehensive analysis of immune alterations and gene expression profiles in CKD. The identified diagnostic genes and the constructed nomogram model offer potent tools for CKD diagnosis. The immunomodulatory roles of RGS1, IL4I1, NR4A3, and SOCS3 warrant further investigation as potential therapeutic targets in CKD.Keywords: chronic kidney disease, diagnostic biomarkers, immune microenvironment, GSEA, GSVA, machine learning

Liudan Huang,1 Xuexin Chen,2 Yuhua Zhang1 1Department of Pediatrics, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 2Department of Neonatology, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of ChinaCorrespondence: Liudan Huang, Department of pediatrics, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China, Email 15917932267@163.comBackground: Neonatal respiratory distress syndrome (NRDS) is common in preterm infants. Prognostic nutritional index (PNI)((albumin (g/L)+(5×total lymphocyte count (109/L)) is a comprehensive indicator of nutritional and immune levels, and associated with several diseases. The relationship between PNI and the risk of NRDS in newborns of different gestational ages remains unclear.Methods: A total of 2722 preterm infants were included in this retrospective study. PNI level and clinical records of these neonates (adverse pregnancy and birth history, amniotic fluid contamination, nuchal cord, placental abnormality, mode of delivery, gender and birth weight of neonates, Apgar scores) were collected. The clinical features of the infants with and without NRDS were compared. Logistic regression analysis was used to evaluate the relationship between PNI and NRDS in newborns with different gestational ages.Results: There were 1226 neonates with NRDS and 1496 without NRDS. The differences in the proportions of placenta abnormality, cesarean section, and small for gestational age (SGA) among infants with 34– 37 weeks, 28+1-33+6 weeks, and ≤ 28 weeks gestational age were statistically significant. Logistic analysis showed that cesarean section (odds ratio (OR): 1.550, 95% confidence interval (CI): 1.197– 2.007, p=0.001), and low PNI (OR: 1.417, 95% CI: 1.110– 1.808, p=0.005) were associated with NRDS in infants born at 34– 37 weeks gestational. Adverse pregnancy and birth history (OR: 1.507, 95% CI: 1.124– 2.019, p=0.006), SGA (OR: 1.994, 95% CI: 1.455– 2.733, p< 0.001), and low PNI (OR: 1.626, 95% CI: 1.230– 2.149, p=0.001) were associated with NRDS in infants with 28+1-33+6 weeks gestational age. Low PNI (OR: 5.512, 95% CI: 1.555– 19.536, p=0.008) was associated with NRDS in infants with ≤ 28 weeks gestational age.Conclusion: The risk factors for NRDS in preterm infants with different gestational ages were different. But the low PNI level is associated with an increased risk of NRDS in preterm infants with all different gestational ages.Keywords: neonatal respiratory distress syndrome, preterm infants, risk factors, prognostic nutritional index

Shanying Liao,1 Chao Liu,2 Beibei Wang,1 Linlin Huang,1 Zhongwen Zheng,1 Jin Kang3 1Department of Gastroenterology and Hepatology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510080, People’s Republic of China; 2Department of Pathology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510080, People’s Republic of China; 3Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510080, People’s Republic of ChinaCorrespondence: Shanying Liao, Department of Gastroenterology and Hepatology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510080, People’s Republic of China, Email liaoshanying@gdph.org.cnObjective: This study was designed to investigate the clinical, pathological, endoscopic, and imaging characteristics of gastrointestinal metastasis in patients with lung cancer.Methods: The clinical data of 20 patients with primary lung cancer with gastrointestinal metastasis.Results: This study included sixteen men and four women, ranging in age from 31 to 75 years. The time interval from the diagnosis of lung cancer to the detection of gastrointestinal metastasis ranged from 13 to 142 months. The most common sites of metastasis were the small intestine (eight cases), colon (four cases), and upper gastrointestinal tract (eight cases). The major symptoms included obstruction, perforation, abdominal pain, abdominal distension, anorexia, and anemia. The predominant pathological type was poorly differentiated adenocarcinoma (seventeen cases). A single ulcer was mostly seen on endoscopy, and some cases showed a slight depression of the intestinal wall. The CT and PET-CT scan revealed bowel wall thickening, intraluminal polypoid masses, and intestinal perforation.Conclusion: Gastrointestinal metastasis of lung cancer is mainly observed in the small intestine, colon, and stomach, and is often detected when severe complications such as gastrointestinal obstruction and perforation occurred. Regular evaluation of gastrointestinal conditions during lung cancer diagnosis and treatment is recommended to improve the diagnostic accuracy and prevent misdiagnosis.Keywords: lung cancer, gastrointestinal tract, metastasis, endoscopic biopsy

Lizhen Huang,1,&ast; Yanjun Jin,2,&ast; Ching-Wen Chien,3 Qinyi Xu,3 Yen-Ching Chuang,4– 6 Tao-Hsin Tung6,7 1School of Economics and Management, Fuzhou University, Fuzhou, Fujian, 350108, People’s Republic of China; 2Department of Urology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Zhejiang, 317000 People’s Republic of China; 3Institute for Hospital Management, Tsing Hua University, Shenzhen Campus, Shenzhen, People’s Republic of China; 4Business College, Taizhou University, Taizhou, Zhejiang, 318000, People’s Republic of China; 5Institute of Public Health & Emergency Management, Taizhou University, Taizhou, Zhejiang, 318000, People’s Republic of China; 6Key Laboratory of Evidence-Based Radiology of Taizhou, Linhai, Zhejiang, 317000, People’s Republic of China; 7Evidence-based Medicine Center, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Zhejiang, 317000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yen-Ching Chuang; Tao-Hsin Tung, Email yenching.chuang@gmail.com; ch2876@gmail.comBackground: Improving overall and individual health literacy is a major focus of national initiatives in China and similar initiatives globally. However, few studies have examined the identification and improvement of individual health literacy levels, especially among patients.Purpose: To develop an interpretable method with decision rules to assess the health literacy levels of male patients and identify key factors influencing health literacy levels.Methods: Using a convenience sampling method, we conducted on-site surveys with 212 male patients of a hospital in China from July 2020 to September 2020. The questionnaire was developed by the Ministry of Health of the People’s Republic of China. A total of 206 of the completed surveys were ultimately included for analyses in this study. The rough set theory was used to identify conditional attributes (ie, key factors) and decision attributes (ie, levels of health literacy) and to establish decision rules between them. These rules specifically describe how different combinations of conditional attributes can affect health literacy levels among men.Results: Basic knowledge, concepts, and health skills are important in identifying whether male patients have health literacy. Health skills, scientific health concepts, healthy lifestyles and behaviors, infectious disease prevention and control literacy, basic medical literacy, and health information literacy can be identified as cognitive behaviors with varying degrees of health literacy among patients.Conclusion: This model can effectively identify the key factors and decision rules for male patients’ health literacy. Simultaneously, it can be applied to clinical nursing practice, making it easier for hospitals to guide male patients to improve their health literacy.Keywords: health literacy, male patients, key factors, decision rules, rough set theory, RST

Jianqun Yin,&ast; Jiawei Chen,&ast; Ting Wang, Huiming Sun, Yongdong Yan, Canhong Zhu, Li Huang, Zhengrong Chen Respiratory Department, Children’s Hospital of Soochow University, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhengrong Chen; Li Huang, Respiratory Department, Children’s Hospital of Soochow University, No. 303 Jingde Road, Gusu District, Suzhou City, Jiangsu Province, People’s Republic of China, Tel +86-13771721180 ; +86-18962183510, Email chenzhengrong@suda.edu.cn; huanglilcy@163.comObjective: To investigate the significance of VISTA in bronchial asthma and its impact on the disease.Methods: Human peripheral blood of asthma children was gathered. The expression concentrations of VISTA, IL-4, IL-6, CD25, CD40L, and PD-L2 in peripheral blood plasma were detected by ELISA. We established the mouse model of asthma and intervened with agonistic anti-VISTA mAb (4C11) and VISTA fusion protein. ELISA, flow cytometry, and Western blotting were performed to detect the expression levels of Th1, Th2, and Th17 cell subsets and related characteristic cytokines, as well as the protein levels of MAPKs, NF-κB, and TRAF6 in lung tissues. In addition, the infiltration of eosinophils and inflammatory cells, airway mucus secretion, and VISTA protein expression in lung histopathological sections of different groups of mice were analyzed.Results: The concentration of VISTA in human asthma group decreased significantly (p < 0.05); A positive correlation was observed between VISTA and CD40L. The intervention of 4C11 mAb and fusion protein respectively during the induction period increase the differentiation of Th1 cells and the secretion of IFN-γ, and inhibit the differentiation of Th2 and Th17 cells, as well as the secretion of IL-4, IL-5, IL-13 and IL-17, partially reduce the pathological changes of asthma in mouse lungs and correct the progress of asthma. The MAPK, NF-κB, and TRAF6 protein levels were the middle range in the 4C11 mAb and fusion protein groups (p < 0.05).Conclusion: The findings suggest VISTA may play a negative regulatory role in the occurrence and development of bronchial asthma.Keywords: VISTA, bronchial asthma, Th2 cells, cytokines, anti-VISTA mAb, VISTA fusion protein

Shiyu Hu,1,2,&ast; Wenyu Chen,2,&ast; Xiaoli Tan,2,&ast; Ye Zhang,1,2 Jiaye Wang,1,2 Lifang Huang,3 Jianwen Duan4 1Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Respiratory Medicine, The Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of China; 3Health Management Center, The Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of China; 4Department of Hepatobiliary Surgery, Quzhou People’s Hospital, Quzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lifang Huang, Health Management Center, The Affiliated Hospital of Jiaxing University, No. 1882, Zhonghuan South Road, Nanhu District, Jiaxing, Zhejiang, 314001, People’s Republic of China, Email jxhuanglifang@126.com Jianwen Duan, Department of Hepatobiliary Surgery, Quzhou People’s Hospital, No. 2, Zhongloudi, Quzhou, Zhejiang, 324000, People’s Republic of China, Email 695377686@qq.comPurpose: The purpose of this study is to develop and validate a clinical prediction model for diagnosing Metabolic Syndrome (MetS) based on indicators associated with its occurrence.Patients and Methods: This study included a total of 26,637 individuals who underwent health examinations at the Jiaxing First Hospital Health Examination Center from January 19, 2022, to December 31, 2022. They were randomly divided into training (n = 18645) and validation (n = 7992) sets in a 7:3 ratio. Firstly, the Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithm was employed for variable selection. Subsequently, a multifactor Logistic regression analysis was conducted to establish the predictive model, accompanied by nomograms. Thirdly, model validation was performed using Receiver Operating Characteristic (ROC) curves, Harrell’s concordance index (C-index), calibration plots, and Decision Curve Analysis (DCA), followed by internal validation.Results: In this study, six predictive indicators were selected, including Body Mass Index, Triglycerides, Blood Pressure, High-Density Lipoprotein Cholesterol, Low-Density Lipoprotein Cholesterol, and Fasting Blood Glucose. The model demonstrated excellent predictive performance, with an AUC of 0.978 (0.976– 0.980) for the training set and 0.977 (0.974– 0.980) for the validation set in the nomogram. Calibration curves indicated that the model possessed good calibration ability (Training set: Emax 0.081, Eavg 0.005, P = 0.580; Validation set: Emax 0.062, Eavg 0.007, P = 0.829). Furthermore, decision curve analysis suggested that applying the nomogram for diagnosis is more beneficial when the threshold probability of MetS is less than 89%, compared to either treating-all or treating-none at all.Conclusion: We developed and validated a nomogram based on MetS risk factors, which can effectively predict the occurrence of MetS. The proposed nomogram demonstrates significant discriminative ability and clinical applicability. It can be utilized to identify variables and risk factors for diagnosing MetS at an early stage.Keywords: metabolic syndrome, risk factors, nomogram, prediction

Nargiza Nuralieva,1,2 Ming Chang,1,2 Lei Huang,1,2 Sanjayan TS3 1School of Psychology, Shaanxi Normal University, Xi’an, Shaanxi, 710062, People’s Republic of China; 2Shaanxi Provincial Key Laboratory of Behavioral and Cognitive Neuroscience, Xi’an, Shaanxi, 710062, People’s Republic of China; 3School of Education, Goa University, Goa, IndiaCorrespondence: Ming Chang, Email changming@snnu.edu.cnAbstract: Depression and anxiety are pervasive mental health issues, affecting millions globally and often accompanied by cognitive impairments with significant repercussions in daily life and professions, particularly in safety-critical roles like community-living pilots. This exploration assesses Neurocognitive Remediation Therapy (NRT) as an innovative solution for addressing cognitive deficits linked to depression and anxiety in these pilots. Theoretical underpinnings of NRT draw from cognitive rehabilitation, neuropsychology, and neuroplasticity principles. Depression and anxiety often manifest as cognitive deficits, impacting attention, memory, executive functions, and decision-making. NRT interventions aim to address these impairments by enhancing cognitive flexibility, attentional control, and memory through training exercises and cognitive restructuring, empowering individuals to regain cognitive functionality and adaptability. Empirical evidence supports NRT’s efficacy in enhancing cognitive functioning, showing significant improvements in attention, memory, and executive functions. This review focuses on NRT’s potential to improve cognition in community pilots, demonstrating its effectiveness in reducing cognitive deficits and enhancing job performance, even in high-pressure environments like aviation. The practical implications of NRT for pilots are profound. Tailored programs can address specific cognitive challenges, such as maintaining vigilance and decision-making under stress. Integrating NRT into training regimens enhances skill sets and mental resilience, contributing to safety and success. Additionally, NRT positively impacts emotional well-being, reducing stress and improving overall quality of life. In Conclusion, NRT emerges as a promising intervention for enhancing cognitive functioning in community-living pilots with depression and anxiety. Evidence suggests its potential to improve performance, job satisfaction, and overall well-being. Further research and implementation are crucial to fully realize its benefits and ensure pilots’ safety and success.Keywords: community, cognitive, neurocognitive remediation therapy, depression

Lili Huang,1,&ast; Yesong Liu,2,&ast; Tingting Geng,1,&ast; Nannan Zhang,2 Liang Sun,1 Shouling Wu,3 Xiang Gao1 1Department of Nutrition and Food Hygiene, School of Public Health, Institute of Nutrition, Fudan University, Shanghai, People’s Republic of China; 2Department of Neurology, Kailuan General Hospital, Tangshan, People’s Republic of China; 3Department of Cardiology, Kailuan General Hospital, Tangshan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiang Gao, Department of Nutrition and Food Hygiene, School of Public Health, Institute of Nutrition, Fudan University, 130 Dongan Road, Shanghai, 200032, People’s Republic of China, Email xiang_gao@fudan.edu.cn Shouling Wu, Department of Cardiology, Kailuan General Hospital, 57 Xinhua East Road, Tangshan, 063000, People’s Republic of China, Tel +86 315 3025655, Fax +86 315 3725312, Email drwusl@163.comBackground: Sleep complaints were reported to be associated with stroke, however, the evidence on the association between healthy sleep pattern and stroke risk in Chinese is limited.Objective: The aim of this study was to investigate the association between healthy sleep pattern and stroke in Chinese, and the influence of metabolic diseases on the association.Methods: A total of 11,851 participants from the Kailuan study in China without stroke at baseline were included. We calculated a healthy sleep score according to four sleep factors, and defined the low-risk groups as follows: no insomnia, no excessive daytime sleepiness, no frequent snoring, and sleep 7– 8h/d. Each low-risk sleep factor was assigned a score of 1. Cox proportional hazard models were used to assess the association between healthy sleep score and stroke. Mediation analysis was used to estimate the role of metabolic diseases (obesity, diabetes, and hypertension) in the healthy sleep score-stroke association.Results: During a mean follow-up period of 7.7 years, 504 cases of stroke were identified. A higher healthy sleep score was associated with a lower risk of stroke in a dose-response manner (P-trend=0.03). The adjusted hazard ratio (HR) for participants with a healthy sleep score of 4 versus ≤ 2 was 0.75 (95% confidence interval [CI]: 0.56, 0.96). In addition, obesity, diabetes, and hypertension collectively explained 21.9% (95% CI: 17.2, 26.5) of the association between healthy sleep score and stroke.Conclusion: Adherence to healthy sleep pattern was associated with a lower risk of stroke, and the favorable association was partially mediated by metabolic diseases.Keywords: healthy sleep pattern, metabolic disease, stroke, mediation

Ziwei Jiang,&ast; Lianglong Chen,&ast; Lei Huang, Shengxiang Yu, Jiabao Lin, Mengyao Li, Yanbin Gao, Lei Yang Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Yang, Department of Burns, Nanfang Hospital, Southern Medical University, Jingxi Street, Baiyun District, Guangzhou, 510515, People’s Republic of China, Tel +86-20-6164-1841, Email yuanyang@smu.edu.cnAbstract: Endogenous stem cell homing refers to the transport of endogenous mesenchymal stem cells (MSCs) to damaged tissue. The paradigm of using well-designed biomaterials to induce resident stem cells to home in to the injured site while coordinating their behavior and function to promote tissue regeneration is known as endogenous regenerative medicine (ERM). ERM is a promising new avenue in regenerative therapy research, and it involves the mobilizing of endogenous stem cells for homing as the principal means through which to achieve it. Comprehending how mesenchymal stem cells home in and grasp the influencing factors of mesenchymal stem cell homing is essential for the understanding and design of tissue engineering. This review summarizes the process of MSC homing, the factors influencing the homing process, analyses endogenous stem cell homing studies of interest in the field of skin tissue repair, explores the integration of endogenous homing promotion strategies with cellular therapies and details tissue engineering strategies that can be used to modulate endogenous homing of stem cells. In addition to providing more systematic theories and ideas for improved materials for endogenous tissue repair, this review provides new perspectives to explore the complex process of tissue remodeling to enhance the rational design of biomaterial scaffolds and guide tissue regeneration strategies.Keywords: endogenous stem cell homing, in situ tissue regeneration, biomimetic design, wound healing, bioactive materials

Shengfeng Wang,1,&ast; Ruxue Fang,1,&ast; Lei Huang,1,&ast; Liping Zhou,1,2 Haibo Liu,3 Meiling Cai,4 Abubakar Sha’aban,5 Chunxiang Yu,1 Mohammed Ahmed Akkaif3 1Rehabilitation Department of Chinese Medicine, The Fourth People’s Hospital of Kunshan, Kunshan City, Jiangsu Province, People’s Republic of China; 2Department of Community Health, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, Pulau Pinang, Malaysia; 3Department of Cardiology, QingPu Branch of Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 4Department of Obstetrics and Gynecology, Qingpu Branch, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 5Health and Care Research Wales Evidence Centre, Cardiff University, Heath Park, Cardiff, UK&ast;These authors contributed equally to this workCorrespondence: Mohammed Ahmed Akkaif, Department of Cardiology, QingPu Branch of Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China, Email akkaif@fudan.edu.cn Chunxiang Yu, Rehabilitation Department of Chinese medicine, The Fourth People’s Hospital of Kunshan, Kunshan City, Jiangsu Province, People’s Republic of China, Email yuchunxiang868@gmail.comAbstract: Cardiovascular diseases (CVDs) are increasingly prevalent in clinical settings. With the continuous improvement of people’s living standards, the gradual acceleration of the pace of life, and the deterioration of the living environment in recent years, the incidence of CVDs is increasing annually. The prevalence of CVDs among individuals aged 50 and above is notably elevated, posing a significant risk to patients’ well-being and lives. At this juncture, numerous clinical treatment choices are available for managing CVDs, with traditional Chinese medicine (TCM) therapy standing out as a practical, safe, and reliable option. Over the recent years, there has been growing acknowledgement among both medical professionals and patients. With the expanding integration of TCM in the treatment of various clinical conditions, the use of TCM in managing CVDs has gained significant attention within the medical community, potentially emerging as an efficacious approach for addressing cardiovascular diseases. This article conducts a comprehensive review of the TCM approach, particularly acupuncture, as a supplementary treatment for CVDs, highlighting its ability to effectively lower blood pressure, decrease coronary artery events, mitigate arrhythmias, and enhance cardiac function when used alongside conventional medication. The review underscores the promise of acupuncture in enhancing cardiovascular health, although variations in research methodologies necessitate standardized applications.Keywords: cardiovascular diseases, traditional Chinese medicine, acupuncture, clinical treatment

Xu Zhang,1,&ast; Xue Zhou,2,&ast; Wenhao Zhai,1,&ast; Jing Cui,1 Ziyi Pan,1 Liuyi Du,1 Linlin Wen,1 Rongrong Ye,1 Boya Zhang,1 Lei Huang,1 Daowei Li,1 Chungang Wang,2 Hongchen Sun1 1Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, Changchun, 130021, People’s Republic of China; 2Department of Chemistry, Northeast Normal University, Changchun, 130024, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Daowei Li; Lei Huang, Email jluldw@jlu.edu.cn; huanglei17@mails.jlu.edu.cnBackground: Vital pulp therapy (VPT) is considered a conservative treatment for preserving pulp viability in caries and trauma-induced pulpitis. However, Mineral trioxide aggregate (MTA) as the most frequently used repair material, exhibits limited efficacy under inflammatory conditions. This study introduces an innovative nanocomposite hydrogel, tailored to simultaneously target anti-inflammation and dentin mineralization, aiming to efficiently preserve vital pulp tissue.Methods: The L-(CaP-ZnP)/SA nanocomposite hydrogel was designed by combining L-Arginine modified calcium phosphate/zinc phosphate nanoparticles (L-(CaP-ZnP) NPs) with sodium alginate (SA), and was characterized with TEM, SEM, FTIR, EDX, ICP–AES, and Zeta potential. In vitro, we evaluated the cytotoxicity and anti-inflammatory properties. Human dental pulp stem cells (hDPSCs) were cultured with lipopolysaccharide (LPS) to induce an inflammatory response, and the cell odontogenic differentiation was measured and possible signaling pathways were explored by alkaline phosphatase (ALP)/alizarin red S (ARS) staining, qRT-PCR, immunofluorescence staining, and Western blotting, respectively. In vivo, a pulpitis model was utilized to explore the potential of the L-(CaP-ZnP)/SA nanocomposite hydrogel in controlling pulp inflammation and enhancing dentin mineralization by Hematoxylin and eosin (HE) staining and immunohistochemistry staining.Results: In vitro experiments revealed that the nanocomposite hydrogel was synthesized successfully and presented desirable biocompatibility. Under inflammatory conditions, compared to MTA, the L-(CaP-ZnP)/SA nanocomposite hydrogel demonstrated superior anti-inflammatory and pro-odontogenesis effects. Furthermore, the nanocomposite hydrogel significantly augmented p38 phosphorylation, implicating the involvement of the p38 signaling pathway in pulp repair. Significantly, in a rat pulpitis model, the L-(CaP-ZnP)/SA nanocomposite hydrogel downregulated inflammatory markers while upregulating mineralization-related markers, thereby stimulating the formation of robust reparative dentin.Conclusion: The L-(CaP-ZnP)/SA nanocomposite hydrogel with good biocompatibility efficiently promoted inflammation resolution and enhanced dentin mineralization by activating p38 signal pathway, as a pulp-capping material, offering a promising and advanced solution for treatment of pulpitis. Keywords: nanocomposite hydrogel, vital pulp therapy, pulpitis, p38 signaling pathway

Xiamin Pu,1 Houqiang Huang,2 Xiaolei Zhao,3 Feng Liu,1 Yebo Leng,4 Ya Deng,5 Lingyi Huang,5 Xingchen Zhou,5 Fen Xu,1 Yongli Huang,6 Shengmin Guo2 1Department of Cardiovascular Medicine, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Department of Nursing, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 3Department of Hematology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 4Department of Orthopedics, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 5School of Nursing, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 6Department of Outpatient, The Affiliated Hospital, Southwest Medical University, Luzhou, People’s Republic of ChinaCorrespondence: Shengmin Guo, Department of Nursing, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China, Tel +86-13980255653, Email 2930773281@qq.comBackground: A global public health problem, frailty is closely associated with poor prognosis after percutaneous coronary intervention (PCI) in older patients with acute myocardial infarction (AMI). Although exercise intervention is the most commonly used method to reverse and alleviate frailty, its application is restricted in patients with acute myocardial infarction following PCI due to cardiovascular instability and autonomic imbalance. Consequently, there is a need for a new practical intervention to address frailty syndrome in these patients.Purpose: This study aimed to investigate the effect of neuromuscular electrical stimulation in frail older AMI patients post-PCI.Patients and Methods: A single-blind, randomized controlled trial was carried out in the Department of Cardiovascular Medicine from March to October 2023. A total of 100 eligible participants were randomly divided into two groups: experimental (n = 50) and control (n = 50) groups, respectively. Both groups received usual care. The experimental group underwent neuromuscular electrical stimulation (NMES) on bilateral quadriceps and gastrocnemius muscles for 30 minutes daily from day 1 to day 7 after surgery. The primary outcomes measured included the frailty score, lower limb muscle strength, and lower limb muscle quality. Secondary outcomes included the activities of daily living score, inflammatory markers, and length of hospital stay. All participants were included in an intention-to-treat analysis after the study ended.Results: The frailty scores of the two groups exhibited a gradual decrease over time, and the scores of the experimental group were lower than those of the control group at 4 and 7 days after surgery (P< 0.001). Concurrently, the lower limb muscle strength showed an increasing trend over the time in the experimental group and a decreasing trend in the control group, and the scores of the experimental group surpassed those of the control group (p< 0.001). Moreover, a statistical difference was observed in the lower limb muscle mass across the groups after 7 days postoperatively compared with baseline on both sides (p< 0.05).Conclusion: Neuromuscular electrical stimulation has the potential to enhance lower limb function and alleviate frailty in elderly patients with acute myocardial infarction after PCI. These findings introduce a novel intervention approach for frailty management in the elderly population.Keywords: acute myocardial infarction, older, frailty, neuromuscular electrical stimulation, PCI

Lu Huang, Yujing Fu, Jinghong Cao, Jianjun Zhai Department of Obstetrics and Gynecology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, People’s Republic of ChinaCorrespondence: Jianjun Zhai, Department of Obstetrics and Gynecology, Beijing Tongren Hospital, Capital Medical University, NO.1 of Dongjiaominxiang Street, Dongcheng District, Beijing, 100730, People’s Republic of China, Email jianjunzhai0504@163.comObjective: As a common endocrine and metabolic disorder, polycystic ovary syndrome (PCOS) is mostly associated with an obese phenotype. The present research focuses on the clinical significance of miR-379 in obesity-PCOS and attempts to elucidate its potential mechanisms.Methods: Healthy individuals (n = 46), obesity-PCOS (n = 92), and non-obesity PCOS (n = 31) subjects were enrolled. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to examine the level of serum miR-379. The receiver operating characteristic (ROC) curve and logistic regressions were applied to reveal the diagnostic significance. Dual luciferase reporters were performed to validate the targeting relationships. And cell count kit (CCK-8) assay was used to detect cell proliferation.Results: Serum miR-379 was highly expressed in PCOS patients (P < 0.05), in especially obesity-PCOS patients. Higher miR-379 was associated with greater body mass index (BMI), higher bioavailable testosterone (bT), and greater insulin resistance (IR). Additionally, miR-379 was an independent risk factor for the development of obesity-PCOS. The sensitivity of miR-379 in identifying patients with obesity-PCOS from healthy or non-obesity-PCSO patients was 81.52% and 72.83%, and the specificity was 86.96% and 80.65%. Semaphorin 3 A (SEMA3A) was identified as a target of miR-379 and was reduced in the patients with obesity PCOS (P < 0.05). Inhibition of miR-375 reduced KGN proliferation, but this reduction was partially restored by silencing of SEMA3A (P < 0.05).Conclusion: Elevated miR-379 assists the diagnosis of obesity-PCOS and regulates the proliferation of KGN by targeting SEMA3A engaged in disease development.Keywords: obesity, PCOS, miR-379, diagnostic, SEMA3A

Liuyi Huang,&ast; Xi Li,&ast; Wei Zhou, Haiqing Zhu, Yuehong Lao, Xiaoxia Huang, Zhenjia Deng, Yuting Tang, Jian Wang Department of Clinical Laboratory, the First Affiliated Hospital of Guangxi Medical University, Key Laboratory of Clinical Laboratory Medicine of Guangxi Department of Education, Nanning, Guangxi, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Wang, Department of Clinical Laboratory, the First Affiliated Hospital of Guangxi Medical University, Key Laboratory of Clinical Laboratory Medicine of Guangxi Department of Education, No. 6 Shuangyong Road, Nanning, Guangxi, 530021, People’s Republic of China, Email wangjian0771@163.comObjective: There are no studies examining the role of the neutrophil-to-lymphocyte ratio (NLR), the C-reactive protein-to-albumin ratio (CAR), the systemic inflammatory index (SII), and the systemic inflammatory response index (SIRI) in anti-synthetase syndrome (ASS). We aim to compare NLR, CAR, SII, and SIRI in ASS and dermatomyositis/polymyositis (DM/PM), as well as to examine potential correlations between NLR, CAR, SII, and SIRI and clinical features and laboratory parameters in ASS.Methods: Retrospective collection of data from 111 patients with ASS and 175 patients with DM/PM. A Spearman rank correlation analysis was utilized to analyze the correlation between NLR, CAR, SII, and SIRI and inflammatory indexes. Receiver operating characteristic (ROC) curves were used to assess the diagnostic value. Univariate logistic regression analysis was performed to assess risk factors for interstitial lung disease (ILD).Results: Compared with DM/PM, NLR, CAR, SII, and SIRI were significantly greater in ASS patients (p < 0.05). NLR, CAR, SII, and SIRI were correlated with albumin, lactic dehydrogenase (LDH), C-reactive protein (CRP), ferritin, white blood cell (WBC), platelets, and myositis disease activity assessment visual analog scales (MYOACT) score (p < 0.05). The ROC curves analysis showed that NLR, SII, and SIRI were all highly predictive of the occurrence of ASS. Comparisons based on clinical characteristics showed elevated levels of NLR, CAR, SII, and SIRI in ASS patients with ILD, fever, and infection (p < 0.05). Univariate logistic regression analysis revealed that NLR, CAR, and SII were significant risk factors for ASS-ILD (p < 0.05).Conclusion: The levels of NLR, CAR, SII, and SIRI were higher in ASS than in DM/PM and correlated with disease activity and specific clinical features. NLR, CAR, SII, and SIRI may be an aid in differentiating ASS from DM/PM and maybe promising biomarkers for ASS.Keywords: the neutrophil-to-lymphocyte ratio, the C-reactive protein-to-albumin ratio, the systemic immune inflammation index, the systemic inflammation response index, anti-synthase syndrome

Yinyu Zhao,1,2 Nan Guo,1,3 Yidan Zhu,1,2 Jingyuan Shang,4 Jiali Chen,1,3 Xingxian Luo,1 Yi Liu,1 Xiaohong Zhang,1 Lin Huang1 1Department of Pharmacy, Peking University People’s Hospital, Beijing, People’s Republic of China; 2School of Pharmaceutical Sciences, Peking University, Beijing, People’s Republic of China; 3School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China; 4Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pharmacy, Peking University Cancer Hospital and Institute, Beijing, People’s Republic of ChinaCorrespondence: Xiaohong Zhang; Lin Huang, Department of Pharmacy, Peking University People’s Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, People’s Republic of China, Email zhangxiaohong@pkuph.edu.cn; huanglin@pkuph.edu.cnAbstract: Several population pharmacokinetic (PPK) models of B cell lymphoma-2 (BCL-2) venetoclax (VEN) have been developed and published to characterize the influencing factors of pharmacokinetics in hematologic malignancies. This review described PPK models of VEN examining the magnitude and types of covariate effects in PK parameters, as well as identified areas that require further investigation in order to facilitate their use. Currently, there are six analyses on PPK models of VEN summarized in this review. Most analyses described the pharmacokinetics of VEN with a two-compartment model and all covariates are categorical. The median estimated apparent clearance (CL/F) was 446 L/Day and apparent volume of distribution of the central compartment (V2/F) was 114.5 L. The median IIV of CL/F reported was 39.5% and V2/F was 46.7%. Most commonly, CYP3A inhibitors, OATP1B3 inhibitors and rituximab co-administration were found to be significant covariates on CL/F. In addition, sex and population were influential covariates on V2/F. A detailed description of the characteristics of PPK models of VEN is provided in this review, as well as the effects of covariates on the PK parameters. For future development of the VEN PPK model, CYP3A inhibitors, rituximab co-administration, OATP1B1 transporter inhibitors, sex, population, and food might be considered. Further research and comprehensive investigations should be undertaken to explore reference ranges for therapeutic drug monitoring, define the potential role of patients with cerebrospinal fluid complications, and assess new or potential covariates. These endeavors will facilitate the development of personalized VEN therapy.Keywords: venetoclax, BCL-2 inhibitor, population pharmacokinetics, PPK model, systematic review

Si Liu, Dan Yang, Wen Li, Qiuping Chen, Danni Lu, Liang Xiong, Junjie Wu, Hui Ao, Lihua Huang State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of ChinaCorrespondence: Lihua Huang; Hui Ao, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China, Email huanglihua@cdutcm.edu.cn; aohui2005@126.comPurpose: Polygala tenuifolia Willd. (PT), a traditional Chinese medicinal plant extensively employed in managing Alzheimer’s disease, exhibits notable gastrointestinal side effects as highlighted by prior investigations. In contrast, Magnolia officinalis Rehd. et Wils (MO), a traditional remedy for gastrointestinal ailments, shows promising potential for ameliorating this adverse effect of PT. The objective of this study is to examine the underlying mechanism of MO in alleviating the side effects of PT.Methods: Hematoxylin-eosin (H&E) staining was used to observe the structural damage of zebrafish intestine, and enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory factors and oxidative stress. The integrity of the intestinal tight junctions was examined using transmission electron microscope (TEM). Moreover, the expression of intestinal barrier genes and PI3K/AKT/NF-κB signaling pathway-related genes was determined through quantitative real-time PCR. The changes in intestinal microbial composition were analyzed using 16S rRNA and metagenomic techniques.Results: MO effectively ameliorated intestinal pathological damage and barrier gene expression, and significantly alleviated intestinal injury by reducing the expression of inflammatory cytokines IL-1β, IL-6, TNF-α, and inhibiting the activation of PI3K/AKT/NF-κB pathway. Furthermore, MO could significantly increase the relative abundance of beneficial microorganisms (Lactobacillus, Blautia and Saccharomyces cerevisiae), and reduce the relative abundance of pathogenic bacteria (Plesiomonas and Aeromonas).Conclusion: MO alleviated PT-induced intestinal injury, and its mechanism may be related to the inhibition of PI3K/AKT/NF-κB pathway activation and regulation of intestinal flora.Keywords: polygala tenuifolia, PI3K/AKT/NF-κB, gut microbiota, inflammation, intestinal injury

Liqiong Ding,1,&ast; Fengnan Xu,1,&ast; Binhua Luo,1,&ast; Liyuan Cheng,1 Lingping Huang,2 Yanlong Jia,3 Jieqiong Ding1 1Xianning Medical College, Hubei University of Science and Technology, Xianning, Hubei Province, People’s Republic of China; 2Department of Medical Ultrasound, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning, Hubei Province, People’s Republic of China; 3Department of Radiology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanlong Jia, Department of Radiology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei Province, 441021, People’s Republic of China, Tel +86 13669006180, Email yanlongjia@163.com Jieqiong Ding, Xianning Medical College, Hubei University of Science and Technology, Xianning, Hubei Province, 437100, People’s Republic of China, Tel +86 13797244300, Email djq197911@163.comBackground: Medical imaging modalities, such as magnetic resonance imaging (MRI), ultrasound, and fluorescence imaging, have gained widespread acceptance in clinical practice for tumor diagnosis. Each imaging modality has its own unique principles, advantages, and limitations, thus necessitating a multimodal approach for a comprehensive disease understanding of the disease process. To enhance diagnostic precision, physicians frequently integrate data from multiple imaging modalities, driving research advancements in multimodal imaging technology research.Methods: In this study, hematoporphyrin-poly (lactic acid) (HP-PLLA) polymer was prepared via ring-opening polymerization and thoroughly characterized using FT-IR, 1H-NMR, XRD, and TGA. HP-PLLA based nanoparticles encapsulating perfluoropentane (PFP) and salicylic acid were prepared via emulsion-solvent evaporation. Zeta potential and mean diameter were assessed using DLS and TEM. Biocompatibility was evaluated via cell migration, hemolysis, and cytotoxicity assays. Ultrasonic imaging was performed with a dedicated apparatus, while CEST MRI was conducted using a 7.0 T animal scanner.Results: We designed and prepared a novel dual-mode nanoimaging probe SA/PFP@HP-PLLA NPs. PFP enhanced US imaging, while salicylic acid bolstered CEST imaging. With an average size of 74.43 ± 1.12 nm, a polydispersity index of 0.175 ± 0.015, and a surface zeta potential of − 64.1 ± 2.11 mV. These NPs exhibit excellent biocompatibility and stability. Both in vitro and in vivo experiments confirmed the SA/PFP@HP-PLLA NP’s ability to improve tumor characterization and diagnostic precision.Conclusion: The SA/PFP@HP-PLLA NPs demonstrate promising dual-modality imaging capabilities, indicating their potential for preclinical and clinical use as a contrast agent.Keywords: contrast agent, perfluoropentane, salicylic acid, ultrasound imaging, chemical exchange saturation transfer

Yan Chen,&ast; Xiaohuan Huang,&ast; Hongfei Chen, Junru Tong, Lingling Huang, Junyou Su, Li Deng Department of Obstetrics, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Deng; Junyou Su, Email dengli@gxmu.edu.cn; sujunyou@sr.gxmu.edu.cnBackground: Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome characterized by excessive activation of NK cells and cytotoxic T lymphocytes, subsequently leading to macrophage activation and increased cytokine production. Misdiagnosis due to nonspecific clinical presentations and inadequate understanding of the disease can significantly jeopardize the safety of both the mother and the infant. We report a case of pregnancy combined with HLH and conduct a literature review to provide insights into the diagnosis and treatment of pregnancy-related HLH.Case Presentation: We discussed a case of a pregnant woman with persistent postpartum fever, serum ferritin, and elevated liver function, who failed to respond to repeated anti-infective therapy and was diagnosed with HLH after multidisciplinary diagnostic treatment. We gave dexamethasone treatment, and the patient’s temperature and blood cells quickly returned to normal. Finally, exome sequencing revealed heterozygous variation in UNC13D gene, so we considered this case as pregnancy combined with primary HLH (pHLH).Conclusion: We report the case of HLH diagnosed during pregnancy and show that early diagnosis and timely intervention can prevent rapid disease progression, reduce maternal mortality rates, and improve survival rates. Additionally, molecular genetic testing can confirm pathogenic gene mutations, providing essential genetic counseling for patients with pHLH who plan to conceive a healthy child.Keywords: hemophagocytic lymphohistiocytosis, hemophagocytic syndrome, pregnancy, case report

Lining Huang,1 Zhaoxiang Wang,1 Ying Pan,1 Kaixin Zhou,2 Shao Zhong1 1Gusu School, Nanjing Medical University, the First People’s Hospital of Kunshan, Kunshan, 215300, People’s Republic of China; 2Guangzhou Laboratory, Guangzhou, 510005, People’s Republic of ChinaCorrespondence: Shao Zhong, Department of Endocrinology, Gusu School, Nanjing Medical University, the First People’s Hospital of Kunshan, Kunshan, 215300, People’s Republic of China, Tel +86 13328056828, Email drzhong@163.comObjective: Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by insulin resistance and progressively impaired insulin secretion resulting in dynamic fluctuations in glucose levels.High blood urea nitrogen (BUN) levels have been linked to decreased insulin sensitivity, suppressed insulin synthesis and increased risk of incident diabetes mellitus in humans as well as insulin use in patients with T2DM.This study characterize the association between BUN levels and short-term and long-term glycemic variability(GV) in the elderly patients with T2DM who were hospitalized.Methods: A total of 927 elderly patients with T2DM were included in the study. The short-term GV was quantified using parameters such as standard deviation (SD), coefficient of variation (CV), time in range (TIR), and mean amplitude of glycemic excursions (MAGE), based on multi-point fingertip blood glucose monitoring. The long-term GV was quantified using parameters such as SD, CV, variation independent of the mean (VIM), and average successive variability (ARV), based on fasting blood glucose(FPG). The relationship between BUN levels and short-term and long-term GV in elderly T2DM who were hospitalized was explored using methods such as Spearman correlation coefficient, linear regression analysis, logistic regression analysis, and interaction tests.Results: In elderly patients with T2DM were hospitalized, there is a significant correlation between BUN levels and both short-term and long-term GV. BUN is negatively correlated with the GV parameter TIR (r=− 0.12, P=0.000), and positively correlated with SD (r=0.12, P=0.000), CV (r=0.07, P=0.026), MAGE (r=0.11, P=0.001), FPG-SD (r=0.08, P=0.013), and FPG-CV (r=0.08, P=0.014).Furthermore, the association remains consistent across different age, gender, BMI, and haemoglobin A1c (HbA1c) subgroups (P interaction > 0.05).Conclusion: In elderly patients with T2DM were hospitalized, BUN levels were positively associated with GV.Therefore, monitoring BUN levels were beneficial in assessing the degree of GV.Keywords: diabetes mellitus, glycemic variability, vascular lesions of diabetes mellitus, glycemic variability parameters

Kang Zhao,1,&ast; Hanfei Zhu,1,&ast; Lidong Huang,1,&ast; Ningli Yang,2 Saleh Mohammed Alhaj Othman,1 Wenbing Shi,1 Hongxia Hua,2 Hui Liang,2 Qin Xu1 1School of Nursing, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qin Xu, School of Nursing, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, Jiangsu, 211166, People’s Republic of China, Tel +86 13601587208, Email qinxu@njmu.edu.cn Hui Liang, Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Gulou District, Nanjing, Jiangsu, 210029, People’s Republic of China, Tel +86 13951601358, Email lianghui@jsph.org.cnBackground: Diet and physical activity (PA) are pivotal behaviors for managing energy balance post-bariatric surgery. Given the need for dual behavioral management, understanding the interplay of cognitive factors influencing these behaviors is crucial. This study applied the compensatory carry-over action model (CCAM) to explore the impact of cognitive factors on behaviors and their subsequent effects on subjective health outcomes.Methods: This cross-sectional study was conducted among patients at the third month after bariatric surgery in China. Data on diet and PA status, behavioral cognitive factors (intention, self-efficacy, compensatory belief, transfer cognition), and subjective health outcomes (perceived stress, well-being, quality of life) were collected. Structural equation model (SEM) was employed to test hypotheses in CCAM and assess mediation relationships.Results: Analysis of data from 239 patients revealed the following: (1) Among antecedent cognitive factors, only compensatory belief significantly influenced diet (P< 0.001). (2) Intention and self-efficacy directly correlated with their respective behaviors, while compensatory belief affected intention, and transfer cognition impacted self-efficacy (P< 0.05), aligning with CCAM hypotheses. (3) PA demonstrated significant influence only on perceived stress (P=0.004), whereas diet significantly affected all subjective health outcomes (P< 0.05). (4) Mediation analysis indicated intention partially mediated the relationship between compensatory belief and diet and fully mediated the relationship between compensatory belief and PA. Self-efficacy completely mediated the relationship between transfer cognition and diet and PA.Conclusion: Transfer cognition’s carry-over effect did not directly influence behaviors among antecedent cognitions. Interventions should primarily target improving diet by mitigating compensatory belief. Moreover, diet exhibited a more pronounced impact on overall health compared to PA. Consequently, prioritizing dietary intervention over PA intervention is warranted based on the analysis of CCAM and the aim of promoting joint behaviors post-bariatric surgery.Keywords: bariatric surgery, compensatory carry-over action model, diet, physical activity, cognitive factors

Qingrong Ouyang, Lei Xu, Yunwei Zhang, Luwen Huang, Linlin Li, Ming Yu Department of Neurology, Suining Central Hospital, Suining, 629000, People’s Republic of ChinaCorrespondence: Ming Yu, Tel +86 18008258574, Email ym1376@sns120.comBackground: Cognitive impairment, a prevalent non-motor symptom in advanced Parkinson’s disease (PD), has been associated with hyperhomocysteinemia, an important risk factor for PD progression and cognitive decline in PD. However, evidence regarding the association between homocysteine (Hcy) and cognitive function during early PD remains insufficient. Therefore, this study aims to examine the correlation between Hcy levels and cognitive function in the early stage of PD.Methods: The study included 218 individuals in the early stages of PD who were consecutively admitted to the Suining Central Hospital Neurology Department. All the individuals completed the Parkinson’s Disease Cognitive Rating Scale (PD-CDR). The Unified Parkinson’s Disease Rating Scale part III (UPDRS-III) was employed for measuring the severity of motor symptoms, while the Hoehn-Yahr scale was used to measure the clinical symptom stage. Fasting venous blood samples were also drawn to measure the Hcy concentration, red blood cell folate, and vitamin B12.Results: In this cross-sectional study, 47 (21.5%) patients with PD showed cognitive dysfunction. The serum Hcy levels were significantly higher in the cognitive impairment PD (PDCI) group compared with the cognitive normal PD group (P< 0.001). The Generalized Additive Model (GAM) analysis revealed a nonlinear relationship between Hcy and the risk of PDCI. Multiple logistic regression analyses demonstrated a positive relationship between elevated Hcy and the risk of PDCI in the fully adjusted model ([OR]:3.1, 95% CI, 1.1– 8.5, P=0.028). Segmented linear regression analysis showed that when Hcy levels were above 17.7 umol/l, the risk of PDCI increased by 1.6 times for every 1 unit elevated in Hcy (95% CI:1.1– 2.2, P=0.008).Conclusion: This study revealed a nonlinear positive correlation between the risk of PDCI and elevated serum Hcy levels in early PD patients, suggesting hyperhomocysteinemia as one of the treatable factors for cognitive impairment in the early stages of PD.Keywords: homocysteine, early Parkinson’s disease, cognitive impairment, relationship

Ling Lv,1 Xin Zhang,1 Yajun Liu,1 Xutong Zhu,2 Ruihan Pan,1 Lifa Huang1 1Department of Neurosurgery, the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, People’s Republic of China; 2The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Lifa Huang, Department of Neurosurgery, the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), No. 54 Youdian Road, Hangzhou, 310006, People’s Republic of China, Tel/Fax +86-57186620251, Email jazzle@163.comPurpose: Dysregulated liquid-liquid phase separation (LLPS) instigates tumorigenesis through biomolecular condensate dysfunction. However, the association between LLPS-associated genes and glioma remains underexplored.Patients and Methods: Differentially expressed genes (DEGs) of glioma were obtained from the GSE50161 dataset, including 34 glioma and 13 normal samples. We analyzed differentially expressed LLPS-related genes in glioma from public databases. These genes informed refined molecular subtyping on the TCGA-glioma dataset. CIBERSORT assessed immune cell infiltration across three subclusters. A prognostic model was devised using univariate and lasso Cox regressions on intersecting genes. Prognostic gene expression was validated in glioma cells via RT-qPCR.Results: A total of 673 differentially expressed LLPS-associated genes were identified in glioma. Three distinct molecular subtypes (C1, C2, and C3) of glioma were obtained with a marked variance in the expression of immune checkpoint genes PD1 and PDL1. Differences in immune cell infiltration were observed across subtypes. In addition, a tri-gene prognostic signature (TAGLN2, NTNG2, and IGF2BP2) was derived with significant survival differences between high and low-risk groups. The prognostic model displayed impressive AUC values for 1, 3, and 5-year survival in both training and validation sets. Further analysis highlighted a notable correlation between the three prognostic genes and immune cells in glioma samples. Furthermore, we found the upregulation of TAGLN2 and IGF2BP2 and the downregulation of NTNG2 in glioma tumors and cells.Conclusion: This study innovatively uncovers the significant role of LLPS-related genes in glioma tumor grading and prognosis. The constructed tri-gene prognostic model holds promise for enhancing personalized prognosis assessments and optimizing immunotherapy strategies for glioma patients.Keywords: liquid-liquid phase separation, glioma, prognostic model, molecular subtype, immune cell infiltration

Lanlang Zhang,1 Lixia Huang,2 Shanshan Liu,3 Xiaofeng Sun4 1Department of Haemodialysis, Fuyong People’s Hospital of Baoan District, Shenzhen, Guangdong Province, 518103, People’s Republic of China; 2Department of Gastrology, Fuyong People’s Hospital of Baoan District, Shenzhen, Guangdong Province, 518103, People’s Republic of China; 3Nursing Department, Fuyong People’s Hospital of Baoan District, Shenzhen, Guangdong Province, 518103, People’s Republic of China; 4Department of Ultrasound, Shenzhen Baoan Women’s and Children’s Hospital, Shenzhen, Guangdong Province, 518000, People’s Republic of ChinaCorrespondence: Xiaofeng Sun, Department of Ultrasound, Shenzhen Baoan Women’s and Children’s Hospital, Shenzhen, Guangdong Province, 518000, People’s Republic of China, Tel +86-13723457417, Email 350787457@qq.comAbstract: This study aimed to optimize bowel preparation efficacy for colonoscopy in elderly constipation patients. A 71-year-old patient with chronic constipation and a history of poor bowel preparation. To address these challenges, we implemented a personalized strategy combining of PEG administration and walking exercise. The PEG was administered according to a protocol, with intermittent exercise breaks of 10 minute. Bowel cleanliness was assessed using the Boston Bowel Preparation Scale (BBPS). Adverse reactions and tolerance were closely monitored throughout the intervention. The patient’s BBPS score improved from 3 to 8 post-intervention. The exercise intervention was well-tolerated (rating I), and mild nausea was observed only after the first PEG dose. No severe adverse reactions occurred. Subsequent Follow-up revealed symptom relief. The personalized approach combining (PEG and exercise intervention) successfully improved bowel preparation quality in the elderly constipation patient undergoing colonoscopy. This approach considers age-related changes in gastrointestinal function and activity level, offering an effective strategy to improve patient tolerance and reduce adverse reactions during bowel preparation. The findings underscore the importance of tailoring interventions for elderly constipation patients to optimize the colonoscopy experience.Keywords: compound polyethylene glycol electrolyte powder, exercise intervention plan, bowel preparation, colonoscopy, elderly, constipation

Jiasheng Deng,1,&ast; Le Qin,2,&ast; Sulang Qin,3,&ast; Ruisheng Wu,1 Guidong Huang,1 Yibin Fang,4 Lanlan Huang,4 Zhipin Zhou4 1School of Pharmacy, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530200, People’s Republic of China; 2Department of Pharmacy, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, 533000, People’s Republic of China; 3School of Graduate Studies, Youjiang Medical University for Nationalities, Baise, Guangxi, 533000, People’s Republic of China; 4Department of Pharmacy, Liuzhou People’s Hospital, Liuzhou, Guangxi, 545006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhipin Zhou, Department of Pharmacy, Liuzhou People’s Hospital, 8 Wenchang Road, Cheng Zhong District, Liuzhou, Guangxi, People’s Republic of China, Tel +86 − 18776921947, Email gxzhouzhipin@126.comAbstract: Pyroptosis is a novel pro-inflammatory mode of programmed cell death that differs from ferroptosis, necrosis, and apoptosis in terms of its onset and regulatory mechanisms. Pyroptosis is dependent on cysteine aspartate protein hydrolase (caspase)-mediated activation of GSDMD, NLRP3, and the release of pro-inflammatory cytokines, interleukin-1 (IL-1β), and interleukin-18 (IL-18), ultimately leading to cell death. Non-coding RNA (ncRNA) is a type of RNA that does not encode proteins in gene transcription but plays an important regulatory role in other post-transcriptional links. NcRNA mediates pyroptosis by regulating various related pyroptosis factors, which we termed the pyroptosis signaling pathway. Previous researches have manifested that pyroptosis is closely related to the development of liver diseases, and is essential for liver injury, alcoholic fatty liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), liver fibrosis, and liver cancer. In this review, we attempt to address the role of the ncRNA-mediated pyroptosis pathway in the above liver diseases and their pathogenesis in recent years, and briefly outline that TCM (Traditional Chinese Medicine) intervene in liver diseases by modulating ncRNA-mediated pyroptosis, which will provide a strategy to find new therapeutic targets for the prevention and treatment of liver diseases in the future.Keywords: non-coding RNA, pyroptosis, liver diseases, inflammasomes, gasdermin, traditional Chinese medicine

Jincheng Ma,1– 3,&ast; Jiansong Lin,4,&ast; Xite Lin,1– 3 Yuan Ren,1– 3 Dabin Liu,5 Shuting Tang,1– 3 Leyi Huang,1– 3 Shuxia Xu,4 Xiaodan Mao,1– 3 Pengming Sun1– 3,5 1Laboratory of Gynecologic Oncology, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 2Key Laboratory of Women and Children’s Critical Diseases Research, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 3Fujian Clinical Research Center for Gynecological Oncology, Fujian Maternity and Child Health Hospital (Fujian Obstetrics and Gynecology Hospital), Fuzhou, Fujian Province, People’s Republic of China; 4Department of Pathology, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 5Department of Gynecology, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaodan Mao; PengMing Sun, Email maodan1985@fjmu.edu.cn; sunfemy@hotmail.comObjective: This study introduced a novel subtype classification method for endometrial cancer (EC) with mismatch repair deficiency (MMRd) by employing immune status and prognosis as the foundational criteria. The goal was to enhance treatment guidance through precise subtype delineation.Methods: Study Cohort: This study encompassed a cohort of 119 patients diagnosed with MMRd-EC between 2015 and 2022. Analyses using t-tests and Mann–Whitney U-tests were performed to assess prognostic markers and peripheral blood immune cell profiles in patients with MutS deficiency (MutS-d) versus those with MutL deficiency (MutL-d). Logistic regression analysis was used to identify independent risk factors. Bioinformatics Analysis: An online database was used to assess the prognostic implications, immune cell infiltration, and immune checkpoint involvement associated with the deficiency of MutS versus MutL in EC.Results: Patients with MutL-d exhibited heightened risk factors, including elevated cancer grade and increased myometrial invasion, leading to poorer prognosis and shorter overall survival and progression-free survival. Regarding systemic immune status, patients with MutL-d demonstrated decreased peripheral blood lymphocyte percentage, lymphocyte count, and CD8+ T cell percentage. For local immunity, the infiltration of natural killer cells, CD8+ T cells, and cytotoxic T lymphocytes in the tumor tissue was reduced in patients with MutL-d. Additionally, patients with MutL-d exhibited lower expression of immune checkpoint markers. The composition of immune subtypes and survival outcomes also indicate that patients with MutL-d have a poorer immune status and prognosis than the patients with MutS-d.Conclusion: Patients with MMRd-EC can be subclassified according to MutS or MutL deficiency. Patients with MutS-d exhibited better immune status, prognosis, and immunotherapy benefits than those with MutL-d. These results can help guide patients to a more precise treatment.Keywords: endometrial cancer, mismatch repair-deficiency, immune, molecular classification, MutL, MutS

Meilan Xian,1,2,&ast; Jiaoyuan Xu,1,3,&ast; Yamei Zheng,4 Lei Zhang,4 Jie Zhao,4 Jie Chen,1 Siguang Li,1 Lingsang Lin,1 Yi Zhong,4 Zehua Yang,4 Tian Xie,4 Linhui Huang,4 Yipeng Ding1,4 1Department of General Practice, Hainan Affiliated Hospital of Hainan Medical University, Hainan General Hospital, Haikou, Hainan, 570311, People’s Republic of China; 2Department of General Diseases, Hainan Chengmei Hospital, Haikou, Hainan, 570300, People’s Republic of China; 3Department of General Clinic, Longbo Health Hospital, Lingao County, Hainan, 571800, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570311, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yipeng Ding; Linhui Huang, Department of General Practice, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Hainan General Hospital, No. 19, Xiuhua Road, Xiuying District, Haikou, Hainan, 570311, People’s Republic of China, Email ypding@yeah.net; rochelle-11@163.comBackground: Chronic obstructive pulmonary disease (COPD) is a common respiratory disorder in pulmonology. Chuanbeimu (CBM) is a traditional Chinese medicinal herb for treating COPD and has been widely utilized in clinical practice. However, the mechanism of CBM in the treatment of COPD remains incompletely understood. This study aims to investigate the underlying therapeutic mechanism of CBM for COPD using network pharmacology and experimental approaches.Methods: Active ingredients and their targets were obtained from the Traditional Chinese Medicine Systems Pharmacology database. COPD-associated targets were retrieved from the GeneCards database. The common targets for CBM and COPD were identified through Venn diagram analysis. Protein-protein interaction (PPI) networks and disease-herb-ingredient-target networks were constructed. Subsequently, the results of the network pharmacology were validated by molecular docking and in vitro experiments.Results: Seven active ingredients and 32 potential targets for CBM were identified as closely associated with COPD. The results of the disease-herb-ingredient-target network and PPI network showed that peimisine emerged as the core ingredient, and SRC, ADRB2, MMP2, and NOS3 were the potential targets for CBM in treating COPD. Molecular docking analysis confirmed that peimisine exhibited high binding affinity with SRC, ADRB2, MMP2, and NOS3. In vitro experiments demonstrated that peimisine significantly upregulated the expression of ADRB2 and NOS3 and downregulated the expression of SRC and MMP2.Conclusion: These findings indicate that CBM may modulate the expression of SRC, ADRB2, MMP2, and NOS3, thereby exerting a protective effect against COPD.Keywords: chuanbeimu, molecular docking, network pharmacology, experiment verification, chronic obstructive pulmonary disease

Xue-hua Xu,1,&ast; Jie-rong Cai,2,&ast; Hui-feng Fan,1,&ast; Ting-ting Shi,1 Di-yuan Yang,1 Li Huang,3 Dong-wei Zhang,1 Gen Lu1 1Department of Respiratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Pediatrics, Guangzhou Panyu District Central Hospital, Guangdong, Guangdong, People’s Republic of China; 3Pediatric Intensive Care Unit, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gen Lu, Department of Respiratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, 510120, People’s Republic of China, Tel +86 20 38076135, Fax +86 20 38076626, Email lugen5663330@sina.comPurpose: Plastic bronchitis (PB), a rare complication of respiratory infection characterized by the formation of casts in the tracheobronchial tree, can lead to airway obstruction and severe condition. Adenovirus is one of the common pathogens of PB caused by infection. This study aimed to evaluate the clinical features and risk factors for PB in children with severe adenovirus pneumonia.Methods: A retrospective study of children with severe adenovirus pneumonia with bronchoscopy results at Guangzhou Women and Children’s Hospital between January 2018 and January 2020 was performed. Based on bronchoscopy, we divided children with severe adenovirus pneumonia into two groups: PB and non-PB. Binary logistic regression analysis was used to identify independent risk factors for PB in patients with severe adenovirus pneumonia after univariate analysis.Results: Our study examined 156 patients with severe adenovirus pneumonia with bronchoscopy results in hospital. Among them, 18 developed PB and 138 did not. On multivariate analysis, the independent risk factors of PB in children with severe adenovirus pneumonia were history of allergies (OR 10.147, 95% CI 1.727– 59.612; P=0.010), diminished breath sounds (OR 12.856, 95% CI 3.259– 50.713; P=0.001), and increased proportion of neutrophils (> 70%; OR 8.074, 95% CI 1.991– 32.735; P=0.003).Conclusion: Children with severe adenovirus pneumonia with a history of allergies, diminished breath sounds, and increased the proportion of neutrophils > 70% may show higher risk of PB.Keywords: plastic bronchitis, severe adenovirus pneumonia, risk factors, children

Xu Zhou,1,2,&ast; Aolin Tang,2,3,&ast; Chengjie Xiong,2,&ast; Guoquan Zhang,2 Liangliang Huang,1,2 Feng Xu1,2 1The First School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 2Department of Orthopaedics, General Hospital of Central Theater Command, Wuhan, 430070, People’s Republic of China; 3Department of Orthopaedics, Minda Hospital of Hubei Minzu University, Enshi, 445000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liangliang Huang; Feng Xu, Department of Orthopaedics, General Hospital of Central Theater Command, Wuhan, 430070, People’s Republic of China, Email hll666789@163.com; fengxu1969@163.comBackground: Treating peripheral nerve injuries (PNI) with defects remains challenging in clinical practice. The commercial conduits have shown suboptimal nerve regeneration and functional recovery due to their basic tubular design without electroactive and oriented topographical cues.Purpose: To develop a new scaffold with oriented microstructure and electroactive Graphene oxide (GO) and investigate its’ therapeutic effect on nerve regeneration in vitro and in vivo.Methods: This study employed a straightforward approach to co-spin PCL and GO, yielding an oriented hybrid nanofibrous scaffold known as the O-GO/PCL scaffold. The physical and chemical properties of nanofibrous scaffold were tested by scanning electron microscopy (SEM), transmission electron microscope (TEM), tensile test and so on. Primary Schwann cells (SCs) and dorsal root ganglia (DRG) were used to investigate the impact of the newly developed scaffolds on the biological behavior of neural cells in vitro. Transcriptome sequencing (mRNA-seq) was employed to probe the underlying mechanisms of the synergistic effect of electroactive GO and longitudinal topographic guidance on nerve regeneration. Furthermore, the developed O-GO/PCL scaffold was utilized to bridge a 10-mm sciatic nerve defect in rat, aiming to investigate its therapeutic potential for peripheral nerve regeneration in vivo.Results and discussion: The SEM and TEM revealed that the newly developed O-GO/PCL scaffold showed longitudinally oriented microstructure and GO particles were homogenously and uniformly distributed inside the nanofibers. Primary SCs were utilized to assess the biocompatibility of the GO-based scaffold, revealing that negligible cytotoxicity when GO concentration does not exceed 0.5%. In vitro analysis of nerve regeneration demonstrated that axons in the O-GO/PCL group exhibited an average length of 1054.88 ± 161.32 μm, significant longer than those in the other groups (P < 0.05). Moreover, mRNA sequencing results suggested that the O-GO/PCL scaffold could enhance nerve regeneration by upregulating genes associated with neural regeneration, encompassing ion transport, axon guidance and cell–cell interactions. Most importantly, we employed the O-GO/PCL scaffold to repair a 10-mm sciatic nerve defect in rat, resulting in augmented nerve regeneration, myelination, and functional recovery.Conclusion: The O-GO/PCL scaffold with oriented microstructure and electroactive GO represents a promising heral nerve reconstruction. Keywords: nanofibers, topographical guidance, electroactive, graphene oxide, nerve regeneration

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

Jiahui Ma,1– 4,&ast; Xue Yang,5,&ast; Zhiming Liu,1– 4 Hao Fu,1– 4 Sizhou Fan,1– 4 Kai Wang,1– 4 Yan Li,1– 4 Lvzhen Huang,1– 4 Mingwei Zhao1– 4 1Department of Ophthalmology, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Eye Diseases and Optometry Institute, Peking University People’s Hospital, Beijing, People’s Republic of China; 3Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, People’s Republic of China; 4College of Optometry, Peking University Health Science Center, Beijing, People’s Republic of China; 5Department of Ophthalmology, Peking University International Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kai Wang; Yan Li, Email wang_kai@bjmu.edu.cn; 13801153660@163.comPurpose: To investigate the impact of vergence dysfunction on myopia progression in children with Defocus incorporated multiple segments (DIMS) spectacle lenses.Patients and Methods: We retrospectively enrolled children prescribed DIMS spectacle lenses to slow myopic progression. Baseline vergence dysfunction was determined according to phoria at distance and near. Axial length (AL) measurement and cycloplegic subjective refraction were performed before fitting the lenses and at six-month and one-year follow-ups. The six-month and one-year AL and spherical equivalent (SE) change from baseline were calculated and compared in subgroups stratified with the type of vergence dysfunction.Results: Two hundred and ninety-two myopic children were included. Significant AL elongation and SE progression were observed at six months and one year (P < 0.05 for all comparisons). Multiple regression demonstrated that AL elongation at six months (P < 0.001) and one year (P < 0.001) was negatively correlated with age, and SE progression at six months was associated with age (P = 0.002). The AL elongation at six months in children with convergence excess was significantly greater than in normal myopic subjects (P = 0.011) and subjects with convergence insufficiency (P = 0.008), divergence excess (P = 0.007), divergence insufficiency (P = 0.024) and basic esophoria (P = 0.048) at six months.Conclusion: The present research demonstrated that vergence dysfunction influences myopia progression for myopic children with DIMS, and the children with convergence excess suffer from the greatest myopia progression among different types of vergence dysfunction.Keywords: myopia, vergence dysfunction, defocus spectacles, axial length

Li Wang,1,2,&ast; Ching Sin Siau,2,&ast; Nizam Baharom,3 Mohd Izzuddin Hairol,2 Lixin Huang,4 Lei Hum Wee2,5– 7 1Ya’an Polytechnic College, Ya’an, Sichuan, 625000, People’s Republic of China; 2Center for Community Health Studies (ReaCH), Faculty of Health Sciences, Universiti Kebangsaan Malaysia (UKM), Kuala Lumpur, 50300, Malaysia; 3Primer Healthcare Department, Faculty of Medicine and Health Sciences, Universiti Sains Islam Malaysia (USIM), Nilai, Negeri Sembilan, 71800, Malaysia; 4Chengdu Sport University, Chengdu, Sichuan, 610000, People’s Republic of China; 5School of Medicine, Faculty of Health & Medical Sciences, Taylor’s University, Subang Jaya, Selangor, 47500, Malaysia; 6Non-Communicable Diseases and Public Health Research Group, Faculty of Health and Medical Sciences, Taylor’s University, Subang Jaya, 47500, Malaysia; 7Digital Health and Innovations Impact Lab, Taylor’s University, Subang Jaya, 47500, Malaysia&ast;These authors contributed equally to this workCorrespondence: Ching Sin Siau, Klinik Psikologi Kesihatan, Block G, Jalan Raja Muda Abdul Aziz, Kuala Lumpur, 50300, Malaysia, Email chingsin.siau@ukm.edu.myPurpose: E-cigarettes (ECs) are gaining popularity among young people. This study aimed to assess university student vapers’ search frequency and source credibility of commonly used media in China, and their association with daily EC users’ motivation to quit EC use.Participants and Methods: This was a cross-sectional study involving an online quantitative survey in six universities in Chengdu, China. Participants answered questions on their EC use patterns, motivation to quit EC, use frequency and source credibility of media use. Hierarchical linear regression analyses were performed to determine the association between media search frequency and source credibility concerning EC health information with the motivation to quit EC.Results: There were a total of 325 participants (Mean age = 20.43, SD = 1.333). Video platforms and social media were ranked frequently used by the participants and were deemed to be more trustworthy. Perceived trustworthiness of online media was the most influential predictor of motivation to quit EC. Those who reported a higher frequency of accessing video platforms and medical health applications recorded higher motivation to quit EC use. Source credibility of news portals were associated higher motivation to quit EC. The association between higher nicotine dependence and lower motivation to quit EC was attenuated when media source credibility and trustworthiness of online media were added into the fully adjusted regression models.Conclusion: There is an association between media use frequency and source credibility to search for EC health information and motivation to quit vaping. More studies could be conducted to examine the effects of media use content on perceptions towards vaping and their motivation to quit vaping.Keywords: vaping, media search, health information, motivation to quit, college students

Mingzheng Yao,1 Dan Liang,2 Xiuli Zeng,1 Xiaomei Xie,1 Jiali Gao,1 Li’an Huang1 1Department of Neurology, The First Affiliated Hospital, Jinan University, Guangzhou, People’s Republic of China; 2Department of Neurology, The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Foshan, People’s Republic of ChinaCorrespondence: Li’an Huang, Department of Neurology, The First Affiliated Hospital, Jinan University, Guangzhou, People’s Republic of China, Email huanglian1306@126.comPurpose: Galectin-3 is a key regulator of microglial proliferation and activation and may have dual and time-dependent effects on ischemic stroke. This study aimed to prospectively investigate the dynamic changes in Galectin-3 levels in patients with acute ischemic stroke receiving endovascular therapy and its clinical significance.Patients and Methods: A total of 105 patients with acute ischemic stroke who underwent endovascular therapy were prospectively enrolled. Plasma Galectin-3 was quantitatively detected by an enzyme-linked immunosorbent assay before the operation and at 1 day, 3 days and 7 days after the operation. A linear mixed-effect model, Pearson correlation analysis and receiver operating characteristic (ROC) curve analysis were used to evaluate the dynamic changes in the plasma Galectin-3 concentration and its relationship with clinical outcomes.Results: Increases in plasma Galectin-3 levels at 1 day and 3 days after surgery were associated with early neurological deterioration and death (both P < 0.05). Increased Galectin-3 levels before surgery and at 1 day and 3 days after surgery were associated with poor prognosis (P < 0.05). Pearson correlation analysis revealed that Galectin-3 levels before surgery (r =0.318, P =0.002), at 1 day (r =0.318, P =0.001), 3 days (r =0.429, P < 0.001) and 7 days after surgery (r =0.340, P =0.001) were positively correlated with NIHSS scores. The ROC curve results showed that Galectin-3 concentration had a certain predictive value for death at 1 day (AUC=0.707, P=0.013), 3 days (AUC=0.708, P=0.016) and 7 days after the operation (AUC=0.708, P=0.016), but this predictive value was lower than that of the NIHSS score.Conclusion: In acute ischemic stroke patients receiving endovascular therapy, an increase in the plasma Galectin-3 levels were associated with death, poor prognosis, and early neurological deterioration. Galectin-3 levels were significantly correlated with the NIHSS score and had a certain predictive value for death.Plain Language Summary: Galectin-3 is a key regulator of microglial proliferation and activation and may have dual and time-dependent effects on ischemic stroke. However, relevant clinical studies are less at present. In this study, we found that an increase in the plasma Galectin-3 levels had significant values in death, poor prognosis, and early neurological deterioration in acute ischemic stroke patients receiving endovascular therapy at various times.Keywords: ischemic stroke, Galectin-3, endovascular therapy, inflammation, dynamic change, outcome

Dianming Li,1,&ast; Weiman Shi,1,&ast; Changfeng Hu,1,2 Chengping Wen,1,2 Lin Huang,1,2 Qiao Wang1,2 1College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou City, People’s Republic of China; 2Key Laboratory of Chinese Medicine Rheumatology of Zhejiang Province, Hangzhou City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lin Huang; Qiao Wang, College of Basic Medical Sciences, Key Laboratory of Chinese medicine rheumatology of Zhejiang Province, Zhejiang Chinese Medical University, Hangzhou City, Zhejiang Province, People’s Republic of China, Tel +86 571-86613587, Email huanglin@zcmu.edu.cn; wangqiao0309@163.comBackground: Gouty arthritis (GA) is a common inflammatory disease caused by deposition of monosodium urate (MSU) crystals in diarthrodial joints. GA attacks commonly involved in joint with red, swollen, heat and pain, and often happened in unilateral foot-first metatarsophalangeal. Accumulated studies have proved that lipids play critical roles in biological processes and lipids biomarkers can substitute for the diagnosis of various diseases.Methods: Herein, shotgun lipidomics was used to quantitatively analyze serum lipidomes of a gouty model which was induced by injecting MSU crystals and feeding high-fat diet with/without treatment with allopurinol. Meanwhile, ELISA kit was used to detect mouse serum levels of inflammatory cytokines (eg, tumor necrosis factor-α, interleukin 1 beta) and HE staining was used to observe the infiltration of inflammatory cells in the foot pad.Results: A total of 9 types of serum lipids were detected in lipidomics by shotguns, and the result of NMDS’ analysis demonstrated significant differences in lipids profiles between the control and model group. It is worth noting that lipid abnormality in GA (such as Ceramide (Cer), sphingomyelin (SM), 4-hydroxyalkenals (HNE), phosphatidylinositol (PI), ethanolamine glycerophospholipid (PE), etc.) is related with phospholipid and energy metabolism, and allopurinol treatment could correct the aberrant metabolism of lipid to some extent.Conclusion: Our results indicated that various aberrant lipid metabolisms were present in the established gouty model, and allopurinol treatment could relief this aberrant metabolism of lipids to some degree.Keywords: gouty arthritis, lipidomics, autoimmune reaction, glycerophospholipid metabolism, sphingolipid metabolism, inflammation

Li Zeng,1 Yongqiang Shu,1,2 Wei Xie,3 Yaping Zeng,4 Kunyao Li,5 Ting Long,1 Ling Huang,1 Xiang Liu,1 Haijun Li,1,2 Dechang Peng1,2 1Department of Radiology, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of China; 2Department of PET, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of China; 3Department of Radiology, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of China; 4Department of Radiology, Jiangxi Provincial People’s Hospital, Nanchang, People’s Republic of China; 5Department of Radiology, Yongchuan Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Dechang Peng; Haijun Li, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 17, Yongwai Zheng Street, Donghu District, Nanchang, Jiangxi Province, 330006, People’s Republic of China, Tel +86 79186427565, Email pengdcdoctor@163.com; haijunli1990@163.comPurpose: Previous studies demonstrated that there was abnormal functional connectivity (FC) in the amygdala subregions in obstructive sleep apnea (OSA), which was associated with cognitive function. However, it is not clear whether these abnormalities can be improved after continuous positive airway pressure (CPAP) treatment. Therefore, the aim of this research was to investigate the changes in FC of amygdala subregions with other brain regions after 6 months of CPAP treatment (post-CPAP) in patients with OSA.Patients and Methods: Fifteen OSA patients underwent Magnetic Resonance Imaging prior to CPAP treatment (pre-CPAP) and following CPAP treatment. The amygdala was divided into six subregions, including bilateral dorsal amygdala (DA), medial amygdala (MA) and ventral amygdala (VA). The FC was calculated by using the amygdala subregions as seeds. A paired sample T-test was employed to assess alterations in the amygdala subregions FC of pre-CPAP and post-CPAP OSA patients, and correlation analysis was then conducted to evaluate the association between the changed FC and clinical assessment.Results: Compared to pre-CPAP OSA patients, post-CPAP OSA patients displayed an enhanced FC between the left DA and the right posterior cingulate cortex (PCC), whereas the FC between the left MA and the right postcentral gyrus, and between the right MA and the left middle frontal gyrus, decreased. Moreover, significant correlation between the FC value of left DA-right PCC and Hamilton Anxiety Inventory scores was found in pre-CPAP OSA patients.Conclusion: Altered FC between the amygdala subregions and other brain regions in OSA patients induced by CPAP treatment was related to cognitive, emotional, and sensorimotor function. Our study found altered FC between amygdala subregions and cognitive and motor-related brain regions in post-CPAP OSA patients, providing potential neuroimaging indicators for CPAP treatment.Keywords: obstructive sleep apnea, amygdala, functional connectivity, treatment, emotion

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

Chaoe Zhou,1,&ast; Jun Li,2,&ast; Fude Zhou,3 Lei Huang,4 Xinmin Liu,1 Haichao Li5 1Department of Geriatrics, Peking University First Hospital, Beijing, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Beijing Tsinghua Changgung Hospital, Beijing, People’s Republic of China; 3Renal Division, Department of Medicine, Peking University First Hospital, Beijing, People’s Republic of China; 4Department of Clinical Laboratory, Peking University First Hospital, Beijing, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, Peking University First Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinmin Liu, Department of Geriatrics, Peking University First Hospital, Tel +86-10-8357-2128, Beijing, 100034, People’s Republic of China, Email lxm2128@163.com Haichao Li, Department of Respiratory and Critical Care Medicine, Peking University First Hospital, Tel +86-10-8357-2128, Beijing, 100034, People’s Republic of China, Email lhch91767@sina.comAbstract: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an acute, rare and potentially fatal drug reaction. To date, limited studies have reported secondary Pneumocystis jirovecii pneumonia (PJP) infection during the treatment of DRESS syndrome. A 53-year-old man was admitted to the hospital due to a persistent fever lasting for 5 days. He had a medical history of hypertension, psoriasis, urticaria, and had recently been treated with carbamazepine for nerve spasm two weeks ago. After admission, the patient presented with a high fever accompanied by chills, abdominal pain, bilateral upper limb muscle pain, and generalized lymph nodes enlargement. Laboratory tests revealed elevated eosinophils and atypical lymphocytes. Subsequently, the patient developed multiple internal organ complications, including oliguria, elevated serum creatinine, liver enzymes, and cardiac troponin I. Based on diagnostic criteria, the patient was diagnosed with DRESS syndrome. To manage the DRESS syndrome, the patient was successively or simultaneously prescribed methylprednisolone, cyclosporin and intravenous immunoglobulin, resulting in an improvement of the condition. However, during the treatment, the patient was infected with Pneumocystis jirovecii. Despite targeted therapy with trimethoprim/sulfamethoxazole, primaquine and clindamycin successively, no remission was observed. Chest CT scans exhibited multiple exudations in both lungs, indicative of interstitial pneumonia. Unfortunately, the patient’s oxygenation progressively declined, leading to his untimely demise. This rare case further highlights the need for clinicians to be aware of the risk of Pneumocystis jirovecii infection in DRESS syndrome patients treated with long-term and high-dose glucocorticoid therapy.Keywords: DRESS syndrome, Pneumocystis jirovecii pneumonia, carbamazepine, glucocorticoid therapy, case report

Yun Zhao,1,&ast; Lijun Zhao,1,&ast; Zhaohuang Wang,1 Shuhui Cui,1 Chenchen Ren,2 Li Yang,2 Yang Bai,2 Yuanhang Zhu,2 Jingyan Xie,3 Yujuan Li,3 Xiaoqing Wu,3 Jing Feng,3 Shanqing Man,4 Longmei Huang,4 Xiaoqi Li,4 Xiaotian Yu,4 Jianliu Wang1 1Department of Obstetrics and Gynecology, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, National Clinical Research Center for Obstetrics and Gynecology, Zhengzhou Key Laboratory of Cervical Disease, Zhengzhou Key Laboratory of Endometrial Disease Prevention and Treatment, Zhengzhou, Henan, People’s Republic of China; 3Department of Obstetrics and Gynecology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 4Hangzhou New Horizon Health Technology Co. Ltd, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianliu Wang, Department of Obstetrics and Gynecology, Peking University People’s Hospital, 11 Xizhimen South Street, Xicheng District, Beijing, 100044, People’s Republic of China, Tel +8618901086568, Email wangjianliu1203@163.comObjective: The objective of this study is to assess the clinical performance of a urine-based high-risk human papillomavirus (hrHPV) test for the detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+).Methods: Between September and December 2021, women aged 20 to 65 years referred to colposcopy clinic were prospectively recruited at three clinical centers in China. Paired urine and cervical specimens from all enrolled women were obtained for hrHPV DNA fluorescence quantitative PCR test. The results of liquid-based cytology (LBC), colposcopy and diagnostic biopsies were collected. We evaluated the sensitivity and specificity for CIN and assessed the agreement/kappa value.Results: A total of 732 women (median age, 40 years) with valid results were included in the study, and 130 (17.8%) women were histologically confirmed as CIN2+. The sensitivity of urine and cervical test for CIN2+ and CIN3+ were 87.69% and 85.45%, respectively. The specificity of urine test performed better than cervical test in women with

Xiaojuan Wang,1,&ast; Lingling Huang,1,&ast; Wenbin Guo,2,&ast; Langlang Tang,1 Aiyu Wu,3 Peng Wu,4 Xiance Zhao,4 Qi Lin,1 Lian Yu3 1Department of Radiology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, Fujian, 364000, People’s Republic of China; 2Department of Pathology, Pingtan Comprehensive Experimental Area Hospital, Fuzhou, Fujian, 350400, People’s Republic of China; 3Department of Rheumatology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, Fujian, 364000, People’s Republic of China; 4Philips Healthcare, Shanghai, 200000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qi Lin, Department of Radiology, Longyan First Affiliated Hospital of Fujian Medical University, No. 105, Jiu Yi North Road, Xin Luo District, Longyan City, 364000, People’s Republic of China, Tel + 86 13950881931, Email linqii8m@126.com Lian Yu, Department of Rheumatology, Longyan First Affiliated Hospital of Fujian Medical University, No. 105, Jiu Yi North Road, Xin Luo District, Longyan City, 364000, People’s Republic of China, Email yulianian@126.comPurpose: The purpose of this study was to observe cerebral microstructure and microcirculation features, as well as changes in white matter (WM) and gray matter (GM) among patients with non-neuropsychiatric systemic lupus erythematosus (non-NPSLE).Methods: We compared 36 female patients with non-NPSLE and 20 age- and gender-matched healthy controls (HCs) who underwent 3.0T MRI imaging with diffusion kurtosis imaging (DKI) and 3D pseudo-continuous Arterial Spin Labeling (pCASL). Mean kurtosis (MK), mean kurtosis tensor (MKT), and cerebral blood flow (CBF) values were obtained from 25 brain regions, including WM and GM. We analyzed the correlation between imaging indicators and clinical data.Results: When compared with HCs, patients with non-NPSLE had reduced MK and MKT values in regional WM, deep GM, and the left frontal lobe cortical GM, and increased CBF in the right parietal lobe WM and right semioval center (SOC). The MK and MKT values were weakly correlated with CBF in some regions, including WM and GM. Complement 3 (C3) and Complement 4 (C4) showed a weak positive correlation with MK and MKT in some regions, including WM and deep GM, while platelet (PLT) was positively correlated with MKT in the left frontal lobe WM; dsDNA antibody was correlated negatively with MK in the right occipital lobe WM; and erythrocyte sedimentation rate (ESR) was correlated negatively with CBF in the left SOC.Conclusion: Our findings revealed the presence of brain microstructural and microvascular abnormalities in non-NPSLE patients, indicating microstructural damage in the cortical GM, which was less commonly reported. We found DKI and pCASL useful in detecting early brain lesions, and MK was a more sensitive and beneficial indicator.Keywords: arterial spin labeling, cerebral blood flow, diffusion kurtosis imaging, gray matter, systemic lupus erythematosus, white matter

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

Katerina L Byanova,1,&ast; Rebecca Abelman,2,&ast; Crystal M North,3 Stephanie A Christenson,1 Laurence Huang1,2 1Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA; 2Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA; 3Division of Pulmonary and Critical Care Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA&ast;These authors contributed equally to this workCorrespondence: Laurence Huang, HIV, Infectious Diseases, and Global Medicine Division, Room 2807, UCSF Pride Hall, 2540 23rd Street, San Francisco, CA, 94110, USA, Tel +1 (415) 476-4082, Extension 406, Fax +1 (415) 476-6953, Email laurence.huang@ucsf.eduAbstract: Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder characterized by airflow limitation and persistent respiratory symptoms. People with HIV (PWH) are particularly vulnerable to COPD development; PWH have demonstrated both higher rates of COPD and an earlier and more rapid decline in lung function than their seronegative counterparts, even after accounting for differences in cigarette smoking. Factors contributing to this HIV-associated difference include chronic immune activation and inflammation, accelerated aging, a predilection for pulmonary infections, alterations in the lung microbiome, and the interplay between HIV and inhalational toxins. In this review, we discuss what is known about the epidemiology and pathobiology of COPD among PWH and outline screening, diagnostic, prevention, and treatment strategies.Keywords: HIV, COPD, tuberculosis, air pollution, immune activation, smoking, pulmonary infections

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

Xiulin Huo,1,2 Peiying Huang,1 Hexuan Di,3 Tianxiao Ma,3 Sufang Jiang,1 Jie Yao,4 Lining Huang1 1Department of Anesthesiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Anesthesiology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 3Department of Orthopaedic Surgery, The Key Laboratory of Orthopedic Biomechanics of Hebei Province, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 4Department of Anesthesiology, The First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei, People’s Republic of ChinaCorrespondence: Lining Huang, Department of Anesthesiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China, Email 15803213730@163.comPurpose: Postamputation neuropathic pain is a common disease in patients with malignant tumor amputation, seriously affecting amputees’ quality of life and mental health. The objective of this study was to identify independent risk factors for phantom limb pain in patients with tumor amputation and to construct a risk prediction model.Methods: Patients who underwent amputation due to malignant tumors from 2013 to 2023 were retrospectively analyzed and divided into phantom limb pain group and non-phantom limb pain group. To determine which preoperative factors would affect the occurrence of phantom limb pain, we searched for candidate factors by univariate analysis and used multivariate logistic regression analysis to identify independent factors and construct a predictive model. The receiver operating characteristic curve (ROC) was drawn to further evaluate the accuracy of the prediction model in evaluating the phantom limb pain after amputation of bone and soft tissue tumors.Results: Multivariate analysis showed that age (OR, 1.054; 95% CI, 1.027 to 1.080), preoperative pain (OR, 5.773; 95% CI, 2.362 to 14.104), number of surgeries (OR, 3.425; 95% CI, 1.505 to 7.795), amputation site (OR, 5.848; 95% CI, 1.837 to 18.620), amputation level (OR, 8.031; 95% CI, 2.491 to 25.888) were independent risk factors for phantom limb pain for bone and soft tissue tumors. The the area under the curve (AUC) of this model was 0.834.Conclusion: Risk factors for postoperative phantom limb pain were the site of amputation, proximal amputation, preoperative pain, multiple amputations, and older age. These factors will help surgeons to individualize and stratify phantom limb pain and help patients with risk counseling. In particular, an informed clinical decision targeting those modifiable factors can be considered when needed.Keywords: neuropathic pain, phantom limb pain, bone and soft tissue tumors, amputation, risk factors, prediction model

Tingxuan Huang, Youjia Wu, Lingyi Huang, Renyi Lin, Zhenyue Li, Xiaoxiao Wang, Pingping Wu, Liying Huang School of Pharmacy, Fujian Medical University, Fuzhou, Fujian, People’s Republic of ChinaCorrespondence: Liying Huang; Pingping Wu, School of Pharmacy, Fujian Medical University, Xuefu North Road University Town, Fuzhou, Fujian, 350122, People’s Republic of China, Tel +8613860635139 ; +8615980271679, Fax +86059422862016, Email fjmuhly88@sina.com; 631763708@qq.comPurpose: Compound Anoectochilus roxburghii (Wall.) Lindl oral liquid (CAROL) is often as a hepatoprotective agent. The present study aimed to elucidate the protective mechanism of CAROL against alcoholic liver injury in rats by untargeted metabolomics combined with multivariate statistical analysis.Methods: An alcoholic liver disease model was established in sprague-dawley (SD) rats by gavage of alcohol, and CAROL treatment was administered. The hepatoprotective effect of CAROL was evaluated by examining liver tissues changes and detecting biochemical index activities and cytokines in serum and liver homogenates. The metabolites in serum samples were examined using ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC–QTOF/MS) and multivariate statistical analysis to screen for differentially expressed metabolites and Kyoto Encyclopedia of Genes and Genomes (KEGG) to assess potential metabolic pathways.Results: CAROL has the potential to downregulate inflammation levels and alleviate oxidative stress. The differential metabolites are mainly engaged in riboflavin metabolism, arginine and proline metabolism, phenylalanine, tyrosine and tryptophan biosynthesis metabolism, phenylalanine metabolism, pyrimidine metabolism, and vitamin B6 metabolism to achieve hepatoprotective effects.Conclusion: CAROL may exhibit beneficial hepatoprotective effects by reducing inflammation, mitigating oxidative stress, and modulating metabolites and their metabolic pathways.This study has important implications for advancing the clinical application of CAROL. Keywords: compound Anoectochilus roxburghii (Wall.) Lindl. oral liquid, alcoholic liver injury, untargeted metabolomics, UHPLC–QTOF/MS, metabolic pathway analysis

Jia Xu,1,&ast; Chengjia Luo,1,&ast; Liang Huang,2 Xi Xiao,3 Ling Liu,1 Zhiling Yang1 1Department of Clinical Pharmacy, Hunan Provincial People’s Hospital (The First-Affiliated Hospital of Hunan Normal University), Changsha, 410016, People’s Republic of China; 2Department of Rehabilitation, Hunan Provincial People’s Hospital (The First-Affiliated Hospital of Hunan Normal University), Changsha, 410016, People’s Republic of China; 3Department of Clinical Laboratory, Hunan Provincial People’s Hospital (The First-Affiliated Hospital of Hunan Normal University), Changsha, 410016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiling Yang, Tel +86 0737-84762738, Email pharma8888@sina.comBackground: Ceftazidime-avibactam (CAZ-AVI) is a new cephalosporin/β-lactamase inhibitor combination that received clinical approval in China in 2019. This study aims to investigate the efficacy and safety of CAZ-AVI in the treatment of Klebsiella pneumoniae (KP) infection in a hospital, and differences in efficacy among various infection sites and between monotherapy and combination therapy, providing valuable insights for its further application.Methods: Patients who used CAZ-AVI between January 2019 and April 2023 were identified through the hospital information system. Demographic information, details of the infection site, KP strain’s drug sensitivity report, treatment duration, combination therapies, adverse drug reactions (ADR), and 28-day survival were recorded. Clinical and microbiological efficacies were analyzed using SPSS 23.0 software to compare different infection sites and combination therapies.Results: The overall effective clinical response (CR) rate of CAZ-AVI against KP infection was 62.13%, with a favorable microbial response (MR) rate was 65.68% and a 28-day survival rate was 63.91%. No significant difference occurred in effective CR and 28-day survival rate among different infection sites (P = 0.709 and 0.862, respectively). The favorable MR rate for abdominal infections was slightly lower than that for other sites of infection (P = 0.021). No significant differences in effective CR, favorable MR, and 28-day survival between monotherapy and combination therapy were present (P values were 0.649, 0.123, and 0.280, respectively). The incidence of ADR was 1.78%, including increased creatinine, elevated transaminase, hematuria, and thrombocytopenia.Conclusion: CAZ-AVI demonstrates good clinical efficacy and safety in the treatment of KP infections. The clinical efficacy of CAZ-AVI was similar across different infection sites, and combination therapy did not show an advantage over monotherapy. Further studies are warranted. It should be noted that CAZ-AVI may induce thrombocytopenia and hematuria.Keywords: ceftazidime-avibactam, Klebsiella pneumoniae, carbapenem-resistant Enterobacteriaceae, urethral hemorrhage, thrombocytopenia, combination therapy

Zhiwei Chen,1,&ast; Chuling Zhu,2,&ast; Lingna Huang,1,&ast; Yuanjie Qi,1 Xiaoyao Guo,1 Li Xie,1 Hua Li1 1Department of Gynecologic, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China; 2Department of Women’s health Department, QuanZhou Women and Children’s Hospital, Quanzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hua Li, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, 18 Daoshan Road, Fuzhou, Fujian, 350001, People’s Republic of China, Tel +86-18005016206, Email fjsfylihua@163.com Li Xie, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, 18 Daoshan Road, Fuzhou, Fujian, 350001, People’s Republic of China, Tel +86-13635281861, Email 309381162@qq.comObjective: Excessive pain will have adverse effects on the mother and fetus. Labor epidural analgesia greatly reduces the pain, which is widely carried out abroad. Labor epidural anesthesia-associated fever (LEAF) is the biggest problem for labor epidural anesthesia. This study aimed to evaluate the clinical value of serum magnesium levels to predict the LEAF.Methods: Overall 528 singleton term-pregnant women who underwent labor epidural anesthesia in Fujian Provincial Maternity and Children’s Health Hospital, affiliated hospital of Fujian Medical University from January 2019 to June 2019, were analyzed retrospectively. The serum magnesium level was detected using venous blood samples. The relationship between the serum magnesium level and LEAF was interpreted, and the optimal cut-off values of the serum magnesium level to predict LEAF were calculated.Results: Overall, 65 (12.30%) participants had LEAF. And a higher rate of the bulging membrane, gestational hypertension, neonatal intensive care unit (NICU) admission, and the different mode of delivery was significantly associated with LEAF. Also, the serum magnesium level demonstrated higher significantly in presence of LEAF than absence (P< 0.05). What is more, it indicated that the area under the receiver operating characteristic curve (AUC) for the serum magnesium level was 0.825, and an optimal cut-off of the serum magnesium level was 0.855 mg/dl. Furthermore, it demonstrated that the serum magnesium level had the highest OR (OR= 7.49; 95% CI (4.58– 14.35)) (P< 0.001). The bulging membrane is an independent risk factor presence of LEAF (OR = 1.55; 95% CI (1.01– 2.43)) (P=0.038).Conclusion: This study demonstrated that the baseline of serum magnesium can provide a suitable biomarker to predict LEAF. It can help to provide a useful target for LEAF treatment and enhance surveillance before fever.Keywords: serum magnesium level, labor epidural anesthesia associated fever, inflammation, risk, therapy

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

Songkun Gao,1,2,&ast; Lei Huang,1– 3,&ast; Tong Wang,1,2 Jiandong Wang1,2 1Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, 100026, People’s Republic of China; 2Gynecologic Oncology Department, Beijing Maternal and Child Health Care Hospital, Beijing, 100026, People’s Republic of China; 3Gynecology department, Yanqing Maternal and Child Health Care Hospital, Beijing, 102199, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tong Wang; Jiandong Wang, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Qihelou Street, Dongcheng District, Beijing, 100006, People’s Republic of China, Email fcyywt@ccmu.edu.cn; wangjiandongxy@ccmu.edu.cnPurpose: Investigation of HPV infection treatment in women undergoing cervical cold-knife conization for advanced cervical intraepithelial neoplasia.Patients and Methods: A retrospective analysis was conducted on patients who underwent cervical cold-knife conization for cervical intraepithelial neoplasia grade II–III at Beijing Obstetrics and Gynecology Hospital from January 2017 to December 2018. The HPV infection status of the patients at 6 months, 1 year, and 2 years after surgery was collected. We use chi square analysis and binary logistic regression to evaluate various factors such as age, number of pregnancies, number of cesarean sections, number of vaginal deliveries, HPV type, size of surgical specimens (diameter and height), and the influence of specimen edge on HPV infection.Results: A total of 334 patients were included in the analysis. The patients are mainly infected with HPV 16/58/52. Age is a influencing factor for HPV recovery 12 months after CKC surgery (P=0.002). Based on the diagnosis of HPV one year after CKC, the recovery rate of HPV58 patients is significantly lower than HPV16. Age is a influencing factor for the recovery of HPV infection (P< 0.05).Conclusion: The treatment of HPV infection by CKC is related to the patient’s age and HPV subtype but not to number of pregnancies, number of pregnancies, number of vaginal deliveries, size of surgical specimens, and marginal conditions. The rate of HPV negative conversion is relatively high 24 months after the patient does not undergo surgery, but there is currently a lack of data on cervical lesions that match HPV results.Keywords: cold-knife conization, HPV infection, recovery rate, high-grade cervical intraepithelial neoplasia

Yuyi Chen,1 Xuemei Zhao,1 Lin Liang,1 Pengchao Tian,1 Jiayu Feng,1 Liyan Huang,1 Boping Huang,1 Yihang Wu,1 Jing Wang,1 Jingyuan Guan,1 Xinqing Li,1 Jian Zhang,1,2 Yuhui Zhang1 1Heart Failure Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2Key Laboratory of Clinical Research for Cardiovascular Medications, National Health Committee, Beijing, People’s Republic of ChinaCorrespondence: Yuhui Zhang, Heart Failure Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China, Tel +8615901314243, Email yuhuizhangjoy@163.com Jian Zhang, Heart Failure Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China, Tel +8613911102015, Email fwzhangjian62@126.comObjective: To identify biomarkers with independent prognostic value and investigate the prognostic value of multiple biomarkers in combination in patients hospitalized with heart failure.Methods: A total of 884 consecutive patients hospitalized with heart failure from 2015 to 2017 were enrolled. Twelve biomarkers were measured on admission, and the relationships between biomarkers and outcomes were assessed.Results: During the median follow-up of 913 days, 291 patients (32.9%) suffered from primary endpoint events. Soluble suppression of tumorigenicity-2 (sST2) (per log [unit] increase, adjusted HR [95% CI]: 1.39 [1.13,1.72], P = 0.002) and big endothelin-1 (big ET-1) (per log [unit] increase, adjusted HR [95% CI]: 1.56 [1.23,1.97], P < 0.001) remained independent predictors of primary endpoint event after adjusting for other predictors including N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT). Both sST2 (C-statistic: 0.810 vs 0.801, P = 0.005, and 0.832 vs 0.826, P = 0.024, respectively) and big ET-1 (C-statistic: 0.829 vs 0.801, P = 0.001, and 0.843 vs 0.826, P < 0.001, respectively) significantly improved the predictive value for primary endpoint event at 1 year and 3 years. However, only big ET-1 (C-statistic: 0.852 vs 0.846, P = 0.014) significantly improved the predictive value at 3 months when added to clinical predictors and known biomarkers. According to the number of elevated biomarkers (including NT-proBNP, hs-cTnT, sST2, and big ET-1), patients with three or more elevated biomarkers had a higher risk of primary endpoint event compared to those with two elevated biomarkers (P = 0.001), as well as in patients with two elevated biomarkers compared to those with one elevated biomarker (P = 0.004). However, the risk of primary endpoint event was comparable between patients with one elevated biomarker and those with no elevated biomarker (P = 0.582).Conclusion: Multiple biomarkers in combination could provide a better prognostic value than a single biomarker. sST2 and big ET-1 could act as alternatives of multi-biomarkers strategies for prognosis evaluation beyond NT-proBNP and hs-cTnT in patients hospitalized with heart failure.Keywords: heart failure, prognostic value, multiple biomarkers, sST2, big ET-1

Yu Zhou,1,&ast; Huoying Cai,1,&ast; Lin Huang,1,&ast; Mingshan Wang,1 Ruiming Liu,2 Siwen Wang,1 Yuansen Qin,1 Chen Yao,1 Zuojun Hu1 1Division of Vascular Surgery, National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Disease, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Laboratory of Department of Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zuojun Hu; Chen Yao, Email huzuojun@mail.sysu.edu.cn; yaochen@mail.sysu.edu.cnBackground: Arteriosclerosis obliterans (ASO) is the leading cause of nontraumatic lower-extremity amputations. Multiple researches have suggested that circular RNAs (circRNAs) played vital regulatory functions in cancer and cardiovascular disease. Nevertheless, the underlying effect and pathological mechanism of circRNAs in the formation and progression of ASO are still indistinct.Methods and Results: This study used microarray analysis to investigate the expression portrait of circRNAs in normal lower extremity arteries and ASO arteries. Bioinformatics analysis was conducted using the KEGG database to study the enrichment of differentially expressed circRNAs (DE circRNAs) and predict their functions. The accuracy of microarray assay was verified by evaluating expression of the top 5 upregulated and 5 downregulated circRNAs (raw density of normal group ≥ 200) using RT-qPCR. A circRNA-miRNA-mRNA interaction network was further predicted using software. Compared to the normal lower extremity group, the ASO arteries with HE and EVG staining presented hyperplastic fibrous membrane and luminal stenosis. A total of 12,735 circRNAs were identified, including 1196 DE circRNAs with 276 upregulated and 920 downregulated in ASO group based on |log2(FC)| > 1 and padj < 0.05. Among selected 10 circRNAs, RT-qPCR confirmed that hsa_circ_0003266, hsa_circ_0118936 and hsa_circ_0067161 were upregulated while hsa_circ_0091934 and hsa_circ_0092022 were downregulated in ASO group (p < 0.05). GO analysis presented that the DE circRNAs were primarily enriched in protein binding, intracellular part and organelle organization. KEGG pathway analysis indicated that MAPK signaling pathway, human T-cell leukemia virus 1 infection, proteoglycans in cancer were associated with the DE circRNAs. The circRNA-miRNA-mRNA interactive network revealed that both mRNAs and miRNAs linked to circRNAs played an indispensable role in ASO.Conclusion: This study described the expression portrait of circRNAs in human ASO arteries, and revealed the molecular background for further investigations of the circRNA regulatory mechanism in the formation and progression of ASO.Keywords: arteriosclerosis obliterans, circular RNA, gene ontology analysis, pathway analysis, circRNA-miRNA-mRNA interaction network