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Haiming Yan,1– 3,&ast; Suling Chen,1,2,&ast; Xinrui Gao,1,2,&ast; Yuanhui Jiang,1,2 Guangyu Liang,1,2 Jie Peng,1,2 Shaohang Cai1,2 1Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2State Key Laboratory of Organ Failure Research; Key Laboratory of Infectious Diseases Research in South China, Ministry of Education; Guangdong Provincial Key Laboratory of Viral Hepatitis Research; Guangdong Provincial Clinical Research Center for Viral Hepatitis; Guangdong Institute of Hepatology, Guangzhou, People’s Republic of China; 3Department of Infectious Diseases, The First People’s Hospital of Foshan, Foshan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Peng; Shaohang Cai, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China, Email pjie138@163.com; shaohangcai@foxmail.comBackground: Metabolic disorders and immunosenescence increase the risk of complications in people living with HIV (PLWH), affecting mortality and quality of life. However, their relationship remains unclear.Methods: Participants were grouped by median TyG index, and logistic regression identified baseline independent factors of a high TyG index at Week 24. The association of the TyG index for hepatic steatosis was determined using ROC curves. We also explored correlations between the TyG index and aging markers, including CD4/CD8 ratio and CD8+ T cells and evaluated health-related quality of life (HRQoL).Results: A total of 203 PLWH were included in the study. We observed that PLWH in high TyG group tended to be older (P< 0.001), have greater body weight (P< 0.001), higher ALT levels (P=0.021), and increased low-density lipoprotein levels (P=0.001). ROC analysis revealed that TyG index was closely associated with hepatic steatosis at Week 52 (AUC=0.743) and Week 104 (AUC=0.728). Moreover, a higher TyG index was positively correlated with CD8+ T cell counts, while patients in the high TyG group had lower CD4/CD8 ratios at Week 52 and Week 104. Poorer mental health was observed in patients with CD8+ T cell counts ≥ 1000 and a high TyG index. Multivariate analysis further identified baseline older age (OR=1.108, P=0.002), elevated cholesterol (OR=3.407, P< 0.001), and low HDL (OR=0.003, P< 0.001) as factors associated with a high TyG index at Week 24.Conclusion: The TyG index is closely linked to metabolic disorders and immunosenescence in PLWH. It offers a basis for personalized treatment strategies, improving physical and mental health and reducing complication risks.Keywords: HIV/AIDS, triglyceride-glucose index, metabolic disorders, immunosenescence, hepatic steatosis

Fangyuan Lai,1,&ast; Xiuqiong Huang,2,&ast; Jiao Peng,3 Nannan He,4 Zhongqiang Cao,1 Yuhui Wu,4 Wei Li,5 Zebin Chen,1 Xuejuan Li1 1Department of Pharmacy, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China; 2Department of Pharmacy, The First People’s Hospital of Zhaoqing, Zhaoqing, People’s Republic of China; 3Department of Pharmacy, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China; 4Department of Pediatric Intensive Care Unit, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China; 5Department of Pharmacy, The Third People’s Hospital of Shenzhen, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuejuan Li, Department of Pharmacy, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China, Email xuejuanli@126.comObjective: The first-line treatment for severe Pneumocystis carinii pneumonia (PCP) is trimethoprim-sulfamethoxazole (TMP/SMZ). Here, we report a case involving 6-month-old child with a PCP infection, highlighting the role of clinical pharmacists in providing individualized pharmaceutical care and guidance through the process of therapeutic drug monitoring (TDM).Methods: The clinical pharmacist monitored the concentration of TMP/SMZ in the serum, urine and sputum of a 6-month-old child with PCP infection. To improve the serum levels of TMP/SMZ, the dose of TMP/SMZ was increased, while infusions of other medications were reduced to decrease the rate of drug excretion. Additionally, the patient received other supportive medications to enhance clinical therapeutic efficacy.Results: Clinical pharmacists observed that, despite administration of a sufficient dose of TMP/SMZ, plasma concentration of TMP/SMZ remained below the therapeutic window, while urine concentrations were extremely high. This phenomenon was attributed to Augmented Renal Clearance (ARC), often seen in critically ill patients and associated with increased renal clearance. Throughout treatment, the concentrations of SMZ remained below the minimum effective concentration, while the concentrations of TMP fell within the effective target range. However, sufficient therapeutic effects were ultimately achieved and observed in the patient, likely due to improved drug distribution in lung tissue (sputum) and the patient’s recovering immune functions. Finally, thanks to individualized pharmaceutical care from clinical pharmacists and the combined efforts of clinicians, the patient was discharged after 58 days of hospitalization.Conclusion: Throughout treatment, the clinical pharmacist played a vital role in optimizing the treatment plan based on the serum, urine and sputum concentrations of TMP/SMZ and providing pharmaceutical care to ensure a safe, rational and effective medications in children. Individualized dose adjustments, particularly high-dose TMP/SMZ guided by TDM, can significantly enhance the management of PCP in pediatric patients and support clinical pharmacists in delivering individualized pharmaceutical care.Keywords: Pneumocystis carinii pneumonia, trimethoprim/sulfamethoxazole, therapeutic drug monitoring, plasma drug concentration

Jia Zhang,1 Zhijian Wang,1 Yushan Jiang,1 Dan Zhang,2 Wanyan Den,3 Danni Wang,1 Jiayi Peng,1 Jiajun Li,4,&ast; Wenxiang Huang1,&ast; 1Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Emergency and Critical Care, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Pathogenic Biology, College of Basic Medicine, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 4Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenxiang Huang, Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China, Email wenxiang_huang@163.comAbstract: Streptococcus pyogenes, also known as Group A Streptococcus (GAS), can cause severe invasive diseases with high fatality rates. We report a case of necrotizing fasciitis and myositis complicated by Streptococcal Toxic Shock-Like Syndrome (STSS) caused by the invasive emm 22/ST46 strain of Streptococcus pyogenes in China. A previously healthy 57-year-old Chinese Canadian man presented with right calf pain and ulceration following a hike in the Gobi Desert, which progressed to unconsciousness and severe infection. Despite initial treatment, his condition deteriorated, leading to his transfer to our intensive care unit. Metagenomic Next-Generation Sequencing identified Streptococcus pyogenes, and antimicrobial susceptibility testing revealed resistance to erythromycin, tetracycline, and clindamycin. Despite broad-spectrum antimicrobial therapy, debridement, and supportive measures, the patient’s condition necessitated amputation of the right lower limb. He recovered and was discharged from the hospital on Day 43. Whole-genome sequencing of the isolate identified 15 multiple virulence factors. Phylogenetic analysis revealed that the closest relative of the isolate was a strain identified in China. This case underscores the importance of early recognition and treatment of invasive GAS infections to prevent severe outcomes, and we should pay attention to invasive emm 22/ST46 GAS infections in China.Keywords: group A Streptococcus, streptococcal toxic shock-like syndrome, amputation, superantigens, metagenomic next-generation sequencing

Youqian Li,1,2 Wei Zhong,1,2 Zhidong Liu,1,2 Changjing Huang,1,2 Junyin Peng,1,2 Hanlin Li1,2 1Center for Cardiovascular Diseases, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 2Guangdong Provincial Engineering and Technology Research Center for Molecular Diagnostics of Cardiovascular Diseases, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of ChinaCorrespondence: Youqian Li, Center for Cardiovascular Diseases, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, No. 63 Huangtang Road, Meijiang District, Meizhou, People’s Republic of China, Email d_yoyo@163.comBackground: Aldehyde dehydrogenase 2 (ALDH2) is a key catalytic enzyme involved in the aldehyde metabolism that plays an important role in the occurrence and development of acute myocardial infarction (AMI). However, the relationship of ALDH2 polymorphism and susceptibility to AMI may differ among different regions and populations, and it has not yet been reported in Hakka population. The purpose of the present study was to investigate it in this population.Methods: Four hundred and nineteen AMI patients and 636 individuals without AMI were included in the present study. The ALDH2 rs671 polymorphism was genotyped using polymerase chain reaction (PCR)-microarray. Differences in ALDH2 rs671 genotypes and alleles between patients and controls were compared, and the relationship between ALDH2 rs671 genotypes and AMI risk was analyzed.Results: Patients with AMI had a lower frequency of ALDH2 rs671 G/G genotype (43.2% vs 52.7%, p=0.003), and a higher G/A genotype (45.6% vs 38.5%, p=0.025) than controls. And AMI patients had a lower frequency of ALDH2 rs671 G allele (66.0% vs 71.9%), and a higher A allele (34.0% vs 28.1%) (p=0.004) than controls. Logistic regression analysis showed that overweight (body mass index (BMI)≥ 24.0 kg/m2 vs BMI 18.5– 23.9 kg/m2: odds ratio (OR) 2.046, 95% confidence interval (CI): 1.520– 2.754, p< 0.001), history of hypertension (yes vs no: OR 3.464, 95% CI: 2.515– 4.770, p< 0.001), ALDH2 rs671 G/A genotype (G/A vs G/G: OR 1.476, 95% CI: 1.102– 1.976, p=0.009), and A/A genotype (A/A vs G/G: OR 1.656, 95% CI: 1.027– 2.668, p=0.038) maybe the independent risk factors for AMI.Conclusion: Overweight (BMI≥ 24.0 kg/m2), a history of hypertension, and ALDH2 rs671 G/A or A/A genotypes increased the risk of developing AMI in Hakka population.Keywords: aldehyde dehydrogenase 2, acute myocardial infarction, polymorphism, Hakka

Siyu Pan,1 Yixiao Wang,1 Yuchen Zhang,1 Xiaoyu Ma,1 Jingfeng Peng,1 Fangfang Li,1,2 Wenhao Qian,1,2 Jing Zong1,2 1Institute of Cardiovascular Diseases, Xuzhou Medical University, Xuzhou, People’s Republic of China; 2Department of Cardiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of ChinaCorrespondence: Jing Zong, Department of Cardiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China, Tel +8618205000580, Email xyfyzongjing@126.comObjective: To investigate the Levels of Nucleotide-binding, leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) and Adiponectin (APN) and their relationship with the severity of coronary artery disease in patients with Unstable Angina (UA) and Type 2 Diabetes (T2D).Methods: Two hundred and thirty-one patients with UA were diagnosed by CAG in the Department of Cardiology of the Affiliated Hospital of Xuzhou Medical University from July 2022 to May 2023 were included, and 74 healthy subjects were included as the control group. The levels of NLRP3 and APN in each group were detected by ELISA and the Gensini score in each patient according to the results of CAG. The correlations between NLRP3, APN, and Gensini score were analyzed. According to whether complicated with T2D or not, we further analyze the effect of NLRP3 and APN levels of patients with UA and T2D on the severity of coronary artery stenosis.Results: The levels of NLRP3 in UA with T2D group were the highest, followed by simple UA group, and the lowest in the control group, and the level of APN was the opposite. Spearman Correlation analysis showed that the level of NLRP3 was positively correlated with Gensini score (ρ1=0.688, P

Jianlan Peng,1 Shiying Li,2 Huihui Ti1,3 1School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China; 3Guangdong Province Precise Medicine and Big Data Engineering Technology Research Center for Traditional Chinese Medicine, Guangzhou, People’s Republic of ChinaCorrespondence: Huihui Ti; Shiying Li, Email tihuihui@126.com; lisy-sci@gzhmu.edu.cnAbstract: Low immunogenicity of tumors poses a challenge in the development of effective tumor immunotherapy. However, emerging evidence suggests that certain therapeutic approaches, such as chemotherapy, radiotherapy, and phototherapy, can induce varying degrees of immunogenic cell death (ICD). This ICD phenomenon leads to the release of tumor antigens and the maturation of dendritic cells (DCs), thereby enhancing tumor immunogenicity and promoting immune responses. However, the use of a single conventional ICD inducer often fails to achieve in situ tumor ablation and establish long-term anti-tumor immune responses. Furthermore, the induction of ICD induction varies among different approaches, and the distribution of the therapeutic agent within the body influences the level of ICD and the occurrence of toxic side effects. To address these challenges and further boost tumor immunity, researchers have explored nanosystems as inducers of ICD in combination with tumor immunotherapy. This review examines the mechanisms of ICD and different induction methods, with a specific focus on the relationship between ICD and tumor immunity. The aim is to explore the research advancements utilizing various nanomaterials to enhance the body’s anti-tumor effects by inducing ICD. This paper aims to contribute to the development and clinical application of nanomaterial-based ICD inducers in the field of cancer immunotherapy by providing important theoretical guidance and practical references.Keywords: tumor immunotherapy, immunogenicity, ICD, DAMPs, nanosystems

Kaibo Hu,1,2,&ast; Yanghuan Ou,1,&ast; Leyang Xiao,1,2,&ast; Ruonan Gu,1,2 Fei He,1,2 Jie Peng,1,2 Yuan Shu,1,2 Ting Li,1,2 Liang Hao1 1Department of Orthopedics, Second Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China; 2The Second Clinical Medical College, Nanchang University, Nanchang, 330006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liang Hao, Tel +86 136 0700 8562, Email ndefy07018@ncu.edu.cnBackground: Osteoarthritis (OA) is a major cause of human disability. Despite receiving treatment, patients with the middle and late stage of OA have poor survival outcomes. Therefore, within the framework of predictive, preventive, and personalized medicine (PPPM/3PM), early personalized diagnosis of OA is particularly prominent. PPPM aims to accurately identify disease by integrating multiple omic techniques; however, the efficiency of currently available methods and biomarkers in predicting and diagnosing OA should be improved. Disulfidptosis, a novel programmed cell death mechanism and appeared in particular metabolic status, plays a mysterious characteristic in the occurrence and development of OA, which warrants further investigation.Methods: In this study, we integrated three public datasets from the Gene Expression Omnibus (GEO) database, including 26 OA samples and 20 normal samples. Via a series of bioinformatic analysis and machine learning, we identified the diagnostic biomarkers and several subtypes of OA. Moreover, the expression of these biomarkers were verified in our in-house cohort and the single cell dataset.Results: Three significant regulators of disulfidptosis (NCKAP1, OXSM, and SLC3A2) were identified through differential expression analysis and machine learning. And a nomogram constructed based on these three regulators exhibited ideal efficiency in predicting early- and late-stage OA. Furthermore, based on the expression of three regulators, we identified two disulfidptosis-related subtypes of OA with different infiltration of immune cells and personalized expression level of immune checkpoints. Notably, the expression of the three regulators was demonstrated in a single-cell RNA profile and verified in the synovial tissue in our in-house cohort including 6 OA patients and 6 normal people. Finally, an efficient disulfidptosis-mediated diagnostic model was constructed for OA, with the AUC value of 97.6923% in the training set and 93.3333% and 100% in two validation sets.Conclusion: Overall, with regard to PPPM, this study provided novel insights into the role of disulfidptosis regulators in the personalized diagnosis and treatment of OA.Keywords: osteoarthritis, disulfidptosis, perspective of predictive, preventive and personalized medicine, immune microenvironment, diagnostic model

Suling Chen,1,&ast; Yuanhui Jiang,1,&ast; Xiaoli Lin,1,&ast; Hongjie Chen,1 Xiaoxuan Wu,2 Zhe Qian,3 Xuwen Xu,1 Huiqun Zhong,1 Jie Peng,1 Shaohang Cai1 1Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Communicable and Endemic Disease Control and Prevention, Haizhu District Center for Disease Control and Prevention, Guangzhou, People’s Republic of China; 3Second Department of Elderly Respiratory, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial Geriatrics Institute, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huiqun Zhong; Jie Peng, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China, Email lovely870821@163.com; pjie138@163.comPurpose: This study aims to investigate the relationship between estimated pulse wave velocity (ePWV) and metabolic syndrome (MetS) in people living with HIV (PLWH), proposing a novel and convenient predictor for early detection of MetS in PLWH.Patients and Methods: A total of 485 PLWH were enrolled. These participants were categorized into two groups based on the estimated pulse wave velocity (ePWV) level. Demographic and clinical data were collected to investigate the correlation between ePWV and MetS.Results: The cohort of 485 PLWH was categorized into high-ePWV and low-ePWV groups based on ePWV cutoff value of 10 m/s. We observed significant differences in components of MetS including triglycerides (TG, P < 0.05), HDL cholesterol (HDL-C, P < 0.01), systolic blood pressure (SBP, P < 0.001), diastolic blood pressure (DBP, P < 0.05), and fasting plasma glucose (FPG, P < 0.001) between the two groups. Furthermore, we employed receiver operating characteristic (ROC) curves to demonstrate the effectiveness of ePWV as a predictive indicator for MetS in PLWH (AUC = 0.739, P

Zhiming Mo,1 Jiayi Yuan,1 Xuelian Guan,1 Jianhong Peng2 1Department of Pharmaceutical Center, Dongguan Traditional Chinese Medicine Hospital, Dongguan, 523000, People’s Republic of China; 2Department of Internal Medicine, Dongguan Traditional Chinese Medicine Hospital, Dongguan, 523000, People’s Republic of ChinaCorrespondence: Jianhong Peng, Department of Internal Medicine, Dongguan Traditional Chinese Medicine Hospital, No. 3, Dongcheng Section, Songshan Lake Avenue, Dongcheng District, Dongguan, Guangdong Province, 523000, People’s Republic of China, Tel +86 0769-22245614, Email pengjhzyy@outlook.comAbstract: Curcumin, derived from Curcuma longa (turmeric), exhibits significant potential in dermatology, addressing conditions like atopic dermatitis, psoriasis, chronic wounds, skin cancer, and infections through its anti-inflammatory, antioxidant, anticancer, and antimicrobial properties. This review synthesizes evidence on curcumin’s mechanisms, including modulation of immune responses and promotion of wound healing, showcasing its efficacy in reducing inflammation, cytokine levels, and enhancing skin barrier functions. Studies highlight curcumin’s ability to selectively target tumor cells, suggesting a multifaceted approach to cancer therapy with minimal side effects. Despite promising therapeutic benefits, challenges remain in bioavailability, potency, and targeted delivery, underscoring the need for further research to optimize dosages, delivery methods, and assess long-term safety. The integration of curcumin into dermatological practice requires a balanced consideration of evidence-based efficacy and safety. Curcumin’s comprehensive utility in dermatology, coupled with the necessity for advanced scientific exploration, emphasizes the importance of combining traditional knowledge with contemporary research to improve patient care in dermatology. This approach could significantly enhance outcomes for individuals with skin-related conditions, marking curcumin as a versatile and promising agent in the field.Keywords: curcumin, atopic dermatitis, psoriasis, chronic wounds, skin cancer

Shuting Wu, Guichan Liao, Jingchun Mao, Haiming Yan, Juanjuan Chen, Jie Peng Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Jie Peng, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China, Tel +8613802515784, Fax +86 20 87719653, Email Pjie138@163.comPurpose: The purpose of the study was to explore the potential risk factors of mortality in patients with severe pneumonia during the omicron pandemic in South China in 2022.Methods: Clinical data was collected from patients hospitalized with omicron COVID-19. Then, patients were categorized into the non-survival and survival groups. A comprehensive analysis was conducted to analyze the factors associated with negative outcome in individuals suffering from severe omicron COVID-19.Results: In this study, 155 severe COVID-19 patients were included, comprising 55 non-survivors and 100 survivors. Non-survivors, in comparison to survivors, exhibited elevated levels of various biomarkers including neutrophil count, hypersensitive troponin T, urea, creatinine, C-reactive protein, procalcitonin, interleukin-6, plasma D-dimer, and derived neutrophil-to-lymphocyte ratio (dNLR) (P < 0.05). They also displayed reduced lymphocyte count, platelet count, and albumin levels (P < 0.05) and were more prone to developing comorbidities, including shock, acute cardiac and renal injury, acute respiratory distress syndrome, coagulation disorders, and secondary infections. Platelet count (PLT) < 100 × 10^/L, interleukin-6 (IL-6) > 100 pg/mL, and dNLR > 5.0 independently contributed to the risk of death in patients suffering from severe COVID-19.Conclusion: PLT, IL-6, and dNRL independently contributed to the risk of mortality in patients with severe pneumonia during the 2022 omicron pandemic in South China.Keywords: COVID-19, omicron, severe infection, dNLR, risk factors

Yi Tang,1,&ast; Zhengqi Hu,2,&ast; Zhibin Liu,2 Siling Peng,2 Tiancheng Liu,2 Yaoyuan Xiao,2 Jianqiang Peng,1 Hongwei Pan,1 Zhaofen Zheng,1 Jin He1 1Department of Cardiology, Hunan Provincial People’s Hospital, the First Affiliated Hospital of Hunan Normal University, Clinical Medicine Research Center of Heart Failure of Hunan Province, Hunan Normal University, Changsha, People’s Republic of China; 2Department of Cardiology, Hunan Provincial People’s Hospital, the First Affiliated Hospital of Hunan Normal University, Changsha, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jin He, Email 394929734@qq.comPurpose: The levels of human epididymis protein 4 (HE4) is associated not only with the prognosis of patients with acute heart failure (AHF), but also with chronic kidney disease (CKD). Our study aims to understand the prediction value of HE4 on prognosis in patients with AHF combined with CKD.Patients and Methods: This study prospectively enrolled patients diagnosed with AHF combined with CKD at the Department of Cardiology of Hunan Provincial People’s Hospital from March 2019 to December 2022. Serum levels of HE4 were measured using a chemiluminescence microparticle immunoassay. The endpoint events included heart failure readmission and cardiovascular death.Results: A total of 130 patients with AHF combined with CKD were included in the stud. The median age is 73 years (interquartile range: 65– 79 years). Among the patients, 94 experienced the endpoint events. The multivariable Cox analysis reveals that LnHE4 (HR=2.280, 95% CI 1.300– 3.998, P = 0.004) and age (HR=1.024, 95% CI 1.003– 1.045, P = 0.025) are independent predictors of the endpoint events. The Kaplan-Meier survival curve demonstrates that patients with HE4 levels> 276.15 pmol/L has a significantly higher incidence of endpoint events compared to those with HE4 levels≤ 276.15 pmol/L (Log rank test: χ 2=19.689, P < 0.001). After adjusting for age and gender, the HR is 2.520 (95% CI: 1.626– 3.906, P < 0.001).Conclusion: HE4 is an independent predictor of heart failure readmission and cardiovascular death in patients with AHF combined with CKD.Keywords: Human epididymis protein 4, Acute heart failure, Chronic kidney disease, Prognosis

Xingqiang Wang,1,2,&ast; Xianna Yang,3,&ast; Shiqi Wang,3,&ast; Xiaofang Tian,1 Jianmei Yin,3 Nian Liu,3 Pengtao Di,1 Jipeng Qi,3 Ya Li,3 Jimin Chen,3,4 Yang Wu,1 Jingjin Wu,1,2 Weiqing Zhao,5 Jiangyun Peng,1,2 Ling Zhang,1,2 Lingli Gu1 1Department of Rheumatology, The No. 1 Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan, 650021, People’s Republic of China; 2Yunnan Provincial Clinical Medicine Research Center of Rheumatism in TCM, Yunnan Provincial Hospital of Traditional Chinese Medicine, Kunming, Yunnan, 650021, People’s Republic of China; 3The First School of Clinical Medicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, 650021, People’s Republic of China; 4Department of Integrative Internal Medicine, The Lijiang Hospital of Traditional Chinese Medicine, Lijiang, Yunnan, 674100, People’s Republic of China; 5Department of Rheumatology and Immunology, The First People’s Hospital of Yunnan Province and The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, 650034, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Zhang; Lingli Gu, Email zebaiyuan@126.com; guyuxin82@126.comAbstract: Glucocorticoids (GC) are crucial in the treatment of rheumatoid arthritis (RA), but discontinuing GC effectively in RA patients poses a significant challenge for rheumatologists. In this two-stage, single-center, non-randomized controlled trial, we investigated the benefits of combining Chinese traditional herbal treatment with csDMARDs to aid GC discontinuation in terms of GC tapering, disease control, and safety. A total of 231 participants were enrolled, of which 150 eligible subjects were included in the first phase and allocated to three groups (control group, treatment group 1, and treatment group 2) based on their willingness to take traditional Chinese medicine and syndrome differentiation, in a 1:1:1 ratio. All groups received basic treatment consisting of methotrexate tablets (10 mg, qw), leflunomide (10 mg, qd), and stratified GC bridging therapy and tapering regimen (The intervention regimen was developed based on rigorous adherence to available evidence). Treatment group 1 received basic treatment combined with Juanbi Granule, while treatment group 2 received basic treatment combined with Yupingfeng Guizhi Decoction Granule. Efficacy was evaluated after a 12-week follow-up, with slightly adjustments to the treatment group based on efficacy and change of syndrome, followed by continued observation until 24 weeks to complete the study. The efficacy evaluation and data analysis were conducted in a blinded manner, including group label concealment, data cleaning, confounder and control regimen analysis, and outcome analysis. This project has received ethical approval from the Ethics Committee of Yunnan Provincial Hospital of Traditional Chinese Medicine (YLZ [2022] Ethical Review No. (006)-01) and has been registered with the China Clinical Trials Registry (Registration number: ChiCTR2300067676, Registered 17 January 2023, https://www.chictr.org.cn/showproj.html?proj=184908). This trial was the first to evaluate the clinical efficacy of combining Chinese herbal medicines with standard Western medicines to facilitate the discontinuation of glucocorticoid (GC) therapy in patients with rheumatoid arthritis (RA).Keywords: rheumatoid arthritis, glucocorticoids tapering, clinical trial, traditional Chinese medicine, Yupingfeng Guizhi Decoction, Juanbi Decoction

Yifang Huang,1,2 Jiahuan Peng,2 Weibing Wang,1 Xueying Zheng,2,&ast; Guoyou Qin,1,2 Huilin Xu3,&ast; 1Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, People’s Republic of China; 2Department of Biostatistics, National Health Commission Key Laboratory of Health Technology Assessment, Ministry of Education Key Laboratory of Public Health Safety, School of Public Health, Fudan University, Shanghai, People’s Republic of China; 3Shanghai Minhang Center for Disease Control and Prevention, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xueying Zheng, Department of Biostatistics, National Health Commission Key Laboratory of Health Technology Assessment, Ministry of Education Key Laboratory of Public Health Safety, School of Public Health, Fudan University, 138 Yi Xue Yuan Road, Shanghai, 200032, People’s Republic of China, Email xyzheng@fudan.edu.cn Huilin Xu, Shanghai Minhang Center for Disease Control and Prevention, 965 Zhong Yi Road, Shanghai, 201101, People’s Republic of China, Email iamxuhuilin@163.comPurpose: The association between body mass index (BMI) and all-cause mortality may vary among hypertensive patients of different ages. This study aimed to investigate the age-dependent association between BMI and all-cause mortality among patients with hypertension.Patients and Methods: A total of 212,394 participants with hypertension aged 20– 85 years from Minhang Hypertension Standardization Management System in Shanghai of China were included. Follow-up began at the time when individuals were first recorded and ended at death, loss to follow-up, or December 31, 2018, whichever came first. Additive Cox proportional hazards models with thin plate smoothing functions and conventional Cox proportional hazards models were adopted to examine the relationship between BMI, age, and mortality. The joint effect of BMI and age on mortality was assessed using a bivariate response model.Results: We found that the BMI–mortality relationship followed a U-shaped pattern, with a trough at 26– 27 kg/m2. Compared with normal weight, underweight was associated with a 50% increased risk of premature mortality (hazard ratio 1.50, 95% confidence interval 1.43 to 1.57). Whereas among those aged 45– 59 and 60– 85 years, overweight was associated with 13% (0.87, 0.80 to 0.94) and 18% (0.82, 0.80 to 0.84) reduction in risk of death, respectively. Bivariate response model indicated a significant interaction between BMI and age (P < 0.05). Among younger and older patients, we found a descending trend for mortality risk, with BMI increasing at different age levels, whereas a reverse J-shaped relation pattern was observed among middle-aged patients.Conclusion: The impact of BMI on all-cause mortality in hypertensive patients varies with age, and moderate weight gain may benefit longevity in middle-aged and older patients.Keywords: body mass index, age, all-cause mortality, hypertension, generalized additive model

Xuan Zhong,1,&ast; Nongping Feng,2,&ast; Binfa Ouyang,1 Dan Zhao,1 Lin Lei,3 Ji Peng,3 Xiaolin Peng1 1Department of Oncology, Injury and Nutrition, Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen, Guangdong Province, People’s Republic of China; 2Department of Non-Communicable Disease Prevention and Control, Shenzhen Longgang Center for Chronic Disease Control, Shenzhen, Guangdong Province, People’s Republic of China; 3Department of Cancer Prevention and Control, Shenzhen Center for Chronic Disease Control, Shenzhen, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaolin Peng, Department of Oncology, Injury and Nutrition, Shenzhen Nanshan Center for Chronic Disease Control, No. 7, Huaming Road, Nanshan District, Shenzhen, Guangdong Province, People’s Republic of China, Tel +86-0755-26640203, Email 25731738@qq.comAim: The rising incidence and death rate of colorectal cancer (CRC) have posed a severe danger to the lives and health of residents. Individuals at high risk of CRC are drawing growing attention as the majority of the population impacted by CRC. Hence, it is imperative to examine the detection rates and modifiable factors affecting the populations at high risk for CRC in Shenzhen.Methods: The multi-stage stratified cluster sampling method was used to select residents aged 45– 74 years old from September 2020 to December 2021. The community-based CRC screening was attended by a total of 30,921 residents from urban and suburb regions. The association between modifiable risk factors and the detection rate of high-risk groups was analyzed using multinomial logistic regression with the inverse probability treatment weighting (IPTW) based on the propensity score.Results: The cross-sectional analysis included 24,613 people after excluding 6308 people who had missing or invalid fecal occult blood test (FOBT) results. The detection rate for high-risk groups during CRC screening was 28.50%. Higher rate of high-risk groups was detected among those who were male, aged 60 or above, college or above, other marital status, and living in urban (P < 0.05). Demographic characteristics after IPTW showed a weak correlation coefficient with the detection rate of CRC high-risk both in high-risk and general-risk groups (SMD < 0.1), suggesting a balanced group of participants. The results of logistic regression with IPTW indicated that smoking, drinking, obesity, lack of exercise, vegetable or fruit eating infrequently, red meat, processed meat, cereal food and their clustering status were more inclined to be risk indicators of CRC (P < 0.05).Conclusion: The detection rate for high-risk CRC groups was comparatively high in Shenzhen. The distribution characteristics of lifestyle and dietary risk factors of high-risk groups should be given consideration when adopting individualized intervention measures and comprehensive prevention and control strategies.Keywords: modifiable risk factors, colorectal cancer, high-risk group, propensity score method

ABSTRACT Intestinal digestibility can be affected by the interaction between host and gut microbiota, which could influence feed efficiency in poultry. In this study, the performance of 1480 10-week-old Wannan Yellow chickens was recorded for 6 weeks, and the feed conversion ratio (FCR) was calculated. Thirteen 16-week-old chickens (7 in the high and 6 in the low FCR group) were selected for carcass performance, ileum structure, and microbiota composition analysis. The results showed that ileum weight and length were significantly higher (p

Mengying Yao,1– 3,&ast; Dawei Lian,1– 3,&ast; Meizhu Wu,1– 3 Yuting Zhou,1– 3 Yi Fang,1– 4 Siyu Zhang,1– 3 Wenqiang Zhang,1– 3 Yanyan Yang,1– 4 Renfeng Li,1– 3 Hong Chen,1– 3 Youqin Chen,5 Aling Shen,1– 4 Jun Peng1– 3 1Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China; 2Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China; 3Fujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, Fujian, People’s Republic of China; 4Innovation and Transformation Center, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China; 5Department of Pediatrics, Case Western Reserve University School of Medicine, Rainbow Babies and Children’s Hospital, Cleveland, OH, USA&ast;These authors contributed equally to this workCorrespondence: Aling Shen; Jun Peng, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, People’s Republic of China, Tel +86 18050286255 ; +86 15806070011, Email saling86@hotmail.com; pjunlab@hotmail.comPurpose: This study aimed to investigate the molecular mechanisms of isoliensinine, a kind of bibenzyl isoquinoline alkaloid which isolated from a TCM named Lotus Plumule (Nelumbo nucifera Gaertn), in treating renal interstitial fibrosis (RIF) by using RNA sequencing, KEGG analysis and in vivo experimental approaches.Methods: Spontaneous hypertension rats (SHRs) were randomly assigned into five groups, consisting of SHR, SHR+Isoliensinine-L (2.5 mg/kg/day), SHR+Isoliensinine-M (5 mg/kg/day), SHR+Isoliensinine-H (10 mg/kg/day), and SHR+Valsartan (10 mg/kg/day) groups (n = 6 for each group). A control group of Wistar Kyoto rats (n = 6) was also included. Rats were treated intragastrically with isoliensinine, valsartan, or double-distilled water of equal volume for 10 weeks. To examine the therapeutic impact on hypertensive renal injury, fibrosis, and its underlying mechanisms, multiple techniques were employed, including hematoxylin and eosin staining, Masson trichrome staining, RNA sequencing, gene ontology (GO) function and pathway enrichment analysis and immunohistochemistry.Results: Resultantly, the use of isoliensinine at different concentrations or valsartan showed significant improvement in renal pathological injury in SHRs. RNA sequencing and KEGG analysis uncovered 583 differentially expressed transcripts and pathways enriched in collagen formation and ECM–receptor interaction after treatment with isoliensinine. There was also a reduction in the increase of collagen and upregulation of collagen I & III, TGF-β 1, p-Smad2, and p-Smad3 in the renal tissue of SHRs. Thus, isoliensinine ameliorated renal injury and collagen deposition in hypertensive rats, and inhibiting the activation of the TGF-β 1/Smad2/3 pathway might be one of the underlying mechanisms.Conclusion: This study showed that treatment with isoliensinine effectively reduced the renal injury and fibrosis in SHRs. In addition, isoliensinine inhibited the TGF-β 1/Smad2/3 signaling in-vivo. These findings provided strong evidence for the therapeutic benefits of isoliensinine in combating renal injury and fibrosis.Graphical Abstract: Keywords: isoliensinine, RNA sequencing, hypertension, renal injury, TGF-β 1/Smad2/3 pathway, collagen deposition

Peng J, Chen W, Chen J, Yuan Y, Zhang J, He Y. Cancer Manag Res. 2018;10:1163-1175. We, the Editor and Publisher of the journal Cancer Management and Research, have retracted the following article. Following publication of the article, concerns were raised about the duplication of images from Figure 3 with images from an unrelated article. Specifically, Images for Figure 3C and 3D have been duplicated with images for Figure 2c, 2d and 2h from Cao Q, Liu F, Ji K, et al. MicroRNA-381 inhibits the metastasis of gastric cancer by targeting TMEM16A expression. J Exp Clin Cancer Res. 2017;36:29. https://doi.org/10.1186/s13046-017-0499-z. The authors responded to our queries but were unable to provide a satisfactory explanation for the duplicated images or provide satisfactory data for the study. As verifying the validity of published work is core to the integrity of the scholarly record, the Publisher and Editor requested to retract the article and the authors agree with this decision. The authors wish to apologize for any inconvenience caused to the journal and readers. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Jialun Peng,1,&ast; Qilong Zhai,1,&ast; Jinzheng Li,1 Xingyu Chen,1 Hongyu Wu,1 Tao Zhong,1 Gangyi Tang,2 Dajun Yu,2 Lixian He,2 Jinxu Li2 1Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China; 2Department of General Surgery, Wushan County People’s Hospital of Chongqing, Chongqing, 404700, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinzheng Li; Gangyi Tang, Tel +86 138 9600 6584 ; +86 159 2387 3984, Fax +86 023 6369 3000, Email 303234@hospital.cqmu.edu.cn; 604267374@qq.comAbstract: Liver abscesses caused by Clostridium perfringens are rare but rapidly fatal. In only a few days, patients progress from liver abscess to sepsis, intravascular hemolysis, multiple organ failure, and even death. These abscesses often occur in patients after trauma or surgery or in those with immunodeficiency. Because patients only show non-specific symptoms such as fever and abdominal pain in the early stage, they can easily be misdiagnosed and miss the therapeutic window, resulting in a poor prognosis. The diagnosis of Clostridium perfringens liver abscess mainly depends on computed tomography (CT), needle aspiration, and/or blood culture. After diagnosis, treatments such as antibiotic therapy, surgical abscess drainage, blood transfusion as needed, and correction of metabolic disturbances must be immediately administered to prevent severe complications. Here, we present two cases of liver abscess due to Clostridium perfringens infection. Both patients initially presented only with fever, abdominal pain, and jaundice, symptoms that were easily confused with cholangitis caused by cholelithiasis. The patients then progressed rapidly and, despite receiving antimicrobial and multimodal sepsis treatment, both eventually died of multiple organ dysfunction syndrome. Clinicians should be on high alert for Clostridium perfringens liver abscesses disguised as biliary disease. Early diagnosis and treatment with the appropriate antibiotics and surgery are fundamental for the survival of the affected patients.Keywords: intravascular hemolysis, biliary diseases, diagnosis, treatment

Yan Jia,1,&ast; Ya Liu,1,&ast; Yilin Huang,1,&ast; Jie Wang,1 Hanyue Wang,1 Shu Tan,2 Yuxin Shi,1 Qingxia Wang,3 Jie Peng1 1Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Emergency, Loudi Central Hospital, Loudi, Hunan, People’s Republic of China; 3Gastrointestinal Endoscopy Center, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Peng, Department of Gastroenterology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, People’s Republic of China, Tel/Fax +86-731-89753722, Email pengjie2014@csu.edu.cn Qingxia Wang, Gastrointestinal Endoscopy Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, People’s Republic of China, Tel/Fax +86-15874189639, Email 1772509440@qq.comObjective: Infection is a common complication of acute pancreatitis (AP). Klebsiella pneumoniae (KP) is one of the most common pathogens associated with nosocomial infections. Our study focuses on investigating the clinical characteristics and risk factors for death of Klebsiella pneumoniae infections in AP patients, further to quantify the prognosis of the patients, and provide evidence for guiding antibiotic use and improving prognosis.Methods: The data of epidemiology, clinical manifestations and drug resistance rate with K. pneumoniae infections in AP patients from January 1, 2012 to August 30, 2022 were retrospectively collected. Logistic regression model and Cox regression model were, respectively, used to determine the risk factors for carbapenem-resistant Klebsiella pneumoniae (CRKP) acquisition and death. The nomogram prediction model was built by RMS software package to predict the 90-day survival rate.Results: One hundred and twenty-six AP patients combined with K. pneumoniae infections, with a mortality rate of 34.9%. The most common infection sites were pancreas and peri-pancreas (54.8%), followed by lung (20.6%) and blood stream (18.3%). The resistance rate of K. pneumoniae to commonly used antibiotics in clinical practice was high, especially CRKP, which was only sensitive to sulfamethoxazole-trimethoprim (SMZ-TMP) and tigecycline (TGC) (resistance rates were 37.57% and 17.57%, respectively). Independent risk factors for CPKP acquisition were male (OR = 1.655, 95% CI 0.642– 4.265, P = 0.017) and PICC/CVC implantation (OR = 3.157, 95% CI 1.223– 8.147, P = 0.021). Independent risk factors for mortality included carbapenem resistance (HR = 2.556, 95% CI 1.011– 6.462, P = 0.047), hemorrhage (HR = 2.392, 95% CI 1.104– 5.182, P = 0.027), septic shock (HR = 3.022, 95% CI 1.312– 6.959, P = 0.009), age > 60 years (HR = 2.977, 95% CI 1.303– 6.799, P = 0.01), creatinine > 177μmol/L (HR = 2.815, 95% CI 1.075– 7.369, P = 0.035).Conclusion: K. pneumoniae infection has become a serious threat for AP patients, which recommends us more attention and active new strategies seeking.Keywords: Klebsiella pneumoniae, carbapenems, drug resistance, acute pancreatitis, mortality, risk factors, nomogram

Jianmin Li,1,2,&ast; Wenyi Zhang,1,2,&ast; Shuang Liu,1,2,&ast; Fan Yang,2 Yupeng Zhou,2 Lin Cao,1,2 Yiming Li,1,2 Yunfei Guo,1,2 Xiang Qi,1,2 Guoping Xu,1 Jing Peng,1 Yang Zhao1,2 1Department of Radiology, The Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China; 2Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Zhao; Jing Peng, Department of Radiology, The Second Hospital of Tianjin Medical University, Tianjin, 300211, People’s Republic of China, Email yang.zhao@tmu.edu.cn; jing.peng@tmu.edu.cnPurpose: BSA-biomineralized Gd nanoparticles (Gd@BSA NPs) have been recognized as promising nanoscale MR contrast agents. The aim of this study was to carry out a preclinical evaluation of these NPs in a middle-sized animal model (rabbits).Methods: New Zealand white rabbits were treated intravenously with Gd@BSA NPs (0.02 mmol Gd/kg) via a clinically-used high-pressure injector, with commercial Gd-diethylene triamine pentaacetate (Gd-DTPA)-injected group as control. Then MR angiography was performed according to the standard clinical protocol with a 3.0-T MR scanner. The SNR and CNR of the main arteries and branches were monitored. Pharmacokinetics and bioclearance were continuously evaluated in blood, urine, and feces. Gd deposition in vital organs was measured by ICP‒MS. Weight monitoring, HE staining, and blood biochemical analysis were also performed to comprehensively estimate systemic toxicity.Results: The ultrasmall Gd@BSA NPs (< 6 nm) exhibited high stability and T1 relaxivity. Compared to Gd-DTPA, Gd@BSA NPs demonstrated superior vascular system imaging performance at ultralow doses, especially of the cardiac artery and other main branches, and exhibited a significantly higher SNR and CNR. Notably, the Gd@BSA NPs showed a shorter half-life in blood, less retention in organs, and improved biocompatibility.Conclusion: The preclinical evaluations here demonstrated that Gd@BSA NPs are promising and advantageous MR CA candidates that can be used at a low dose with excellent MR imaging performance, thus suggesting its further clinical trials and applications.Keywords: preclinical evaluation, ultralow dose, high-pressure injector, MR angiography

Yichun Zhang, Jun Peng, Wenjun Sun, Haipeng Zhang, Guang Yang Department of Pharmacy, Hebei Yanda Hospital, Langfang City, Hebei Province, People’s Republic of ChinaCorrespondence: Yichun Zhang, Department of Pharmacy, Hebei Yanda Hospital, Yanjiao Simhuilan West Road, Sanhe City, Langfang City, Hebei Province, 065200, People’s Republic of China, Tel +86-316-3306055, Email yi2022chun@163.comObjective: Home pharmaceutical care delivers individualised, whole-process and continuous pharmaceutical services and health education. This study aims to explore the feasibility of home pharmaceutical services as a combination of medical and nursing care.Methods: Patient information was collected from 1 October 2020 to 30 September 2021 and was analysed and evaluated. We then developed a family medication plan and investigated its effectiveness and any issues encountered during the implementation process.Results: A total of 102 patients received services, and 100% of the patients were satisfied with these. Moreover, using home pharmaceutical care saved approximately USD1,359.64 (RMB9,360.45) in outpatient costs and USD41,077.76 (RMB282,700) in inpatient costs, and the number of hospitalisations was reduced by 16%.Conclusion: It is beneficial to make home pharmaceutical services available as a combination of medical and nursing care. Pharmacists can help patients solve medication-related problems and reduce the number of hospitalisations and medical costs through standardised service models while ensuring safe, effective, economical and rational drug use for patients.Keywords: medical care, nursing, home care, home pharmacist, standard services

We propose a method based on the Hilbert–Huang transform (HHT) to recover the high-energy waveform of low-frequency quasiperiodic oscillations (QPOs). Based on the method, we successfully obtain the modulation of the phase-folded light curve above 170 keV using the QPO phase reconstructed at lower energies in MAXI J1535–571 with Insight-HXMT observations. A comprehensive simulation study is conducted to demonstrate that such modulation indeed originates from the QPO. Thus, the highest energies turn out to significantly exceed the upper limit of ∼100 keV for QPOs reported previously using the Fourier method, marking the first opportunity to study QPO properties above 100 keV in this source. Detailed analyses of these high-energy QPO profiles reveal different QPO properties between the 30–100 and 100–200 keV energy ranges: the phase lag remains relatively stable, and the amplitude slightly increases below ∼100 keV, whereas above this threshold, soft phase lags and a decrease in amplitude are observed. Given the reports of a hard-tail detection in broad spectroscopy, we propose that the newly discovered QPO properties above 100 keV are dominated by the hard-tail component, possibly stemming from a relativistic jet. Our findings also indicate a strong correlation between the QPOs originating from the jet and corona, supporting the scenario of jet–corona coupling precession. We emphasize that our proposed HHT-based method can serve as an efficient manner in expanding the high-energy band for studying QPOs, thereby enhancing our understanding of their origin.

Jian Peng,1– 3,&ast; Yue Wang,3,&ast; Zhaoyin Wu,3 Chengju Mao,3 Lu Li,1,2 Huijun Cao,4 Zhilang Qiu,3 Guo Guo,3,5 Guiyou Liang,4,5 Feng Shen1,2 1Department of Intensive Care Unit, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550009, People’s Republic of China; 2Guizhou Institute of Precision Medicine, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550009, People’s Republic of China; 3Key Laboratory of Infectious Immune and Antibody Engineering of Guizhou Province, Cellular Immunotherapy Engineering Research Center of Guizhou Province, School of Biology and Engineering/School of Basic Medical Sciences, Guizhou Medical University, Guiyang, Guizhou, 550025, People’s Republic of China; 4Department of Cardiac Surgery, the affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550009, People’s Republic of China; 5Translational Medicine Research Center, Guizhou Medical University, Guiyang, Guizhou, 550025, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Shen; Guiyou Liang, Email doctorshenfeng@163.com; guiyou515@163.comIntroduction: Acinetobacter baumannii has become a major difficulty in the treatment of bacteria-associated infection. The previously reported antimicrobial peptide Cec4 exhibited good and stable activity against A. baumannii in vitro, but the mechanisms and effects in vivo are elusive.Methods: The effects of Cec4 on bacterial membrane permeability, membrane potential and bacterial reactive oxygen species were measured. The cell membrane localization of antimicrobial peptides was studied by fluorescence labelling. The ability of bacteria to develop resistance to antimicrobial peptides was studied by continuous induction, and transcriptome difference was analysed. The in vivo toxicity of Cec4 against nematodes and mice was studied, and the in vivo therapeutic potential of Cec4 against A. baumannii was assessed.Results: Cec4 effectively cleared multidrug-resistant A. baumannii by altering bacterial cell membrane permeability, changing bacterial cell membrane polarity, and increasing bacterial intracellular reactive oxygen species. Cec4 affected the expression of the secretion system, outer membrane, and efflux pump genes of A. baumannii. In addition, the bacteria did not acquire stable drug-resistant ability. Cec4 at 1.024 mg/mL did not affect the proliferation of HeLa and HepG2 cells, and Cec4 at 45 mg/kg had little effect on the mortality of Caenorhabditis elegans, even the liver and kidney tissues of mouse. Most importantly, Cec4 could effectively improve the survival rates and reduce the bacterial load of various tissues in the mouse model of infection.Conclusion: In conclusion, Cec4 can damage the cell membrane of bacteria, and the bacteria is not easy to produce resistance to Cec4. Besides, Cec4 has good potential for the treatment of multidrug-resistant A. baumannii infections.Keywords: antimicrobial peptide, A. baumannii, sepsis, skin infection, drug safety

Jing Peng,1,* Jiaming Su,2,* Lei Song,1 Qiuyi Lv,1 Ying Gao,1 Jingling Chang,1 Hua Zhang,1 Yihuai Zou,1 Xing Chen3 1Department of Encephalopathy, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Department of Nephrology, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Department of Brain Function Examination, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xing Chen, Department of brain function examination, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, No. 05 Haiyuncang Road, Beijing, People’s Republic of China, Tel +86 18610044016, Email yeahchency@sina.comObjective: Limb numbness is a frequent symptom of post-stroke somatosensory dysfunction, which may be alleviated by non-invasive therapy such as acupuncture. However, the precise mechanism via acupuncture remains unknown. The goal of this study was to investigate how the amplitude of low-frequency fluctuations (ALFF) and functional connectivity (FC) changed between stroke patients with limb numbness and healthy people, as well as how acupuncture might work.Methods: 24 stroke sequelae patients with unilateral limb numbness and 14 matched healthy controls were enrolled in the study. The patients with limb numbness received acupuncture therapy three days a week for four weeks. We mainly assessed the clinical outcomes via the visual analogue scale (VAS). In addition, fMRI data from patients with unilateral limb numbness at baseline and after treatment (4th week) were collected, as well as data from healthy controls at baseline.Results: Compared with the healthy subjects, the patient group demonstrated significantly decreased ALFF in several brain regions, mainly associated with the sensorimotor network (SMN) and default mode network (DMN), including left superior frontal gyrus (SFG), right temporal fusiform cortex (TFC), right middle frontal gyrus (MFG), bilateral middle temporal gyrus (MTG), right putamen (PUT), right precentral gyrus (preCG), right planum polare (PP), and left supplementary motor area (SMA). These regions were chosen as the seeds for investigating the FC alteration induced by acupuncture. Several sensorimotor-related brain regions were activated by acupuncture, and the FC of the left supramarginal gyrus (SMG) with right MTG, as well as brain-stem, cerebellum vermis 9 with right MFG showed enhancement following acupuncture in the patient group, which had a significant correlation with clinical outcomes.Conclusion: Acupuncture treatment may be used to stimulate brain areas associated with somatosensory processing and to strengthen the FC of sensorimotor and cognitive brain networks in order to achieve therapeutic effect.Keywords: acupuncture, stroke, somatosensory dysfunction, functional magnetic resonance imaging, amplitude of low-frequency fluctuation, functional connectivity

Hongzhou Liu,&ast; Ying Xu,&ast; Jie Peng School of Clinical Medicine, The First Affiliated Hospital of Chengdu Medical College, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Peng, Email pengjieo85@163.comBackground: GST genes were reported to be involved in susceptibility to mental disorder. The results between deletions of GST genes and schizophrenia were inconclusive and confusing. Therefore, we performed this updated meta-analysis to outline the association using a new method for quality assessment.Methods: Sixteen reported studies were selected, and the overall OR and 95% CI were calculated and analyzed by Review Manager 5.4 and STATE 12. The Newcastle-Ottawa Quality Assessment Scale (NOS) for case–control studies was rewritten to evaluate the quality of published studies, as there was no “Exposure” in these studies and other factors should be suggested to assess the quality.Results: There was no significant association between deletions of GST genes and SZ risk (p > 0.05 in Random model). We also failed to find a significant relation between null genotypes and SZ risk in East Asian population. Based on further analysis of PCR methods, GSTM1 null was weakly associated with SZ risk in 8 studies using multiplex PCR (OR = 1.17, 95% CI = 1.00– 1.37, p = 0.05), but GSTT1 null was a protective factor for SZ risk (OR = 0.73, 95% CI = 0.56– 0.94, p = 0.02). When stratified by rewritten NOS stars and deductions, GSTM1 null was significantly associated with SZ risk in 9 studies with high quality (OR = 1.24, 95% CI = 1.08– 1.43, p = 0.002), and in 10 studies with no deductions (OR = 1.20, 95% CI = 1.05– 1.38, p = 0.007).Conclusion: GSTM1 null genotype may be a genetic risk factor for SZ in studies using multiplex PCR and high-quality studies. However, GSTT1 null might be a protective factor. Besides, we provided a new method for quality assessment and it was useful and should be promoted in further analysis.Keywords: glutathione S-transferase T1, GSTM1, polymorphism, schizophrenia, meta-analysis

Yingying Wei,1,&ast; Jiahuan Peng,2,&ast; Han Li,1 Mengtian Wei,1 Hao Peng,1 Kai Wang,1 Yongfu Yu,2 Qizhi He3 1Clinical and Translational Research Center, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Department of Biostatistics, School of Public Health, Fudan University, Shanghai, People’s Republic of China; 3Department of Pathology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qizhi He, Department of Pathology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, No. 2699, West Gaoke Road, Pudong District, Shanghai, 201204, People’s Republic of China, Fax +86-2120261141, Email qizhihe2013@163.comPurpose: Infants with macrosomia are more likely to be born to mothers with gestational diabetes mellitus (GDM). This study aimed to investigate the associations between maternal blood glucose levels and fetal weight, placental weight, and risk of macrosomia in mothers with GDM.Patients and Methods: This retrospective study included 3211 singletons of mothers with GDM at the Shanghai First Maternity and Infant Hospital between January 2017 and December 2019. All women underwent an oral glucose tolerance test (OGTT) during the 24– 28 weeks gestation period. Data on fetal and placental parameters were collected at delivery. Multiple linear regression models were used to evaluate the associations of maternal blood glucose levels with fetal weight and placental weight, while multiple logistic regression model was used to estimate the association between maternal blood glucose levels and the risk of macrosomia.Results: The prevalence of GDM in our study was 7%. Fasting plasma glucose (FPG) was positively correlated with fetal weight (r2=0.0329, P< 0.001), and macrosomia risk (odds ratio [OR], 2.42; 95% confidence interval [CI], 1.93– 3.04; P< 0.001). After adjusting for gestational age, the result remained significant (OR, 2.67; 95% CI, 2.11– 3.38; P< 0.001). In contrast, there was no significant relationship between 1-h plasma glucose (1hPG) or 2-h plasma glucose (2hPG) and fetal weight (P=0.18, P=0.46). Additionally, 1hPG or 2hPG was not strongly associated with macrosomia risk (OR, 0.95; 95% CI, 0.85– 1.05; P=0.32 vs OR, 0.94; 95% CI, 0.85– 1.05; P=0.28). Maternal blood glucose levels did not affect placental weight. The associations were similar in women carrying male and female fetuses.Conclusion: Maternal fasting plasma glucose levels were strongly associated with increased birth weight and macrosomia risk. Our findings suggest that fasting plasma glucose may predict birth weight.Keywords: gestational diabetes mellitus, blood glucose levels, weight, macrosomia

Junjie Peng,&ast; Min Wang,&ast; Yanqiu Wu,&ast; Yongchun Shen, Lei Chen Department of Respiratory and Critical Care Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Chen; Yongchun Shen, Department of Respiratory and Critical Care Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, People’s Republic of China, Email lchens@126.com; shen_yongchun@126.comBackground: Some clinical indicators have been reported to be useful in differentiating asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) from pure asthma/COPD, but the results were inconsistent. This study aims to evaluate the diagnostic value of these indicators for ACO.Methods: Databases of PubMed, EMBASE, Ovid and Web of Science were retrieved. Pooled standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated in random-effects models.Results: 48 eligible studies were included. The pooled results indicated, compared with pure asthma, ACO patients had lower levels of forced expiratory volume in the first second (FEV1)% predicted (pred) (SMD=− 1.09, 95% CI − 1.3 to − 0.87), diffusion lung capacity for carbon monoxide (DLCO)% pred (SMD=− 0.83, 95% CI − 1.24 to − 0.42), fractional exhaled nitric oxide (FeNO) (SMD=− 0.23, 95% CI − 0.36 to − 0.11), and higher levels of induced sputum neutrophil (SMD = 0.51, 95% CI 0.21 to 0.81), circulating YKL-40 (SMD = 0.96, 95% CI 0.27 to 1.64). However, relative to COPD alone, ACO patients had higher levels of FEV1% pred (SMD = 0.15, 95% CI 0.05 to 0.26), DLCO% pred (SMD = 0.38, 95% CI 0.16 to 0.6), FeNO (SMD = 0.59, 95% CI 0.40 to 0.78), serum total immunoglobulin (Ig)E (SMD = 0.42, 95% CI 0.1 to 0.75), blood eosinophil (SMD = 0.44, 95% CI 0.29 to 0.59), induced sputum eosinophil (SMD = 0.62, 95% CI 0.42 to 0.83), and lower levels of induced sputum neutrophil (SMD=− 0.48, 95% CI − 0.7 to − 0.27), circulating YKL-40 (SMD=− 1.09, 95% CI − 1.92 to − 0.26).Conclusion: Compared with pure asthma/COPD, ACO patients have different levels of FEV1% pred, DLCO% pred, FeNO, serum total IgE, blood eosinophil, induced sputum eosinophil/neutrophil, and circulating YKL-40, which could be helpful to establish a clinical diagnosis of ACO.Keywords: asthma, asthma-COPD overlap, COPD, indicators, meta-analysis

Ping Li,1,&ast; Junjie Peng,1,&ast; Guangxi Chen,1,2,&ast; Fangying Chen,1,3 Yongchun Shen,1 Lin Liu,4 Lei Chen1 1Laboratory of Pulmonary Diseases and Department of Respiratory and Critical Care Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, People’s Republic of China; 2Department of Sleep Medicine, Jiujiang First People’s Hospital, Jiujiang, People’s Republic of China; 3Department of Tuberculosis, the Third People’s Hospital of Tibet Autonomous Region, Lhasa, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, 363 Hospital, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Chen, Department of Respiratory and Critical Care Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, People’s Republic of China, Email lchens@126.com Lin Liu, Department of Respiratory and Critical Care Medicine, 363 Hospital, Chengdu, People’s Republic of China, Email lliniu@126.comPurpose: DNA methylation, a major epigenetic modification, has been documented to play an important role in chronic obstructive pulmonary disease (COPD). In this study, we aimed to profile the DNA methylation patterns in a mouse model of airway inflammation induced by cigarette smoke (CS), a foremost risk factor of COPD.Material and Methods: To establish a model of airway inflammation, wild-type mice were exposed to mainstream CS or room air for 2 hours twice daily, 6 days per week for consecutive 4 weeks. Lung tissues of the mice were collected for genome-wide DNA methylation analysis by liquid hybridization capture-based bisulfite sequencing, which were used for intersection analysis with gene expression by cDNA microarray to identify candidate methylated genes. Then, functional enrichment analyses with protein–protein interaction (PPI) network regarding these genes were conducted to explore the potential mechanisms.Results: After 4-week CS exposure, the level of DNA methylation accompanied by a subacute airway inflammation was markedly enhanced, and 2002 differentially methylated genes (DMGs) were annotated, including 565 DMGs contained methylations in gene promoters, which were used for intersection with the differentially expressed genes. Then, 135 candidate methylated genes were further selected by the intersection, among which 58 genes with functional methylated modification were finally identified. Further analyses revealed candidate methylated genes were significantly enriched in a complicated network of signals and processes, including interleukins, toll-like receptors, T-cells differentiation, oxidative stress, mast cells activation, stem cells proliferation, etc., as well as the 58 functional methylated genes were partially located at key positions in PPI network, especially CXCL1, DDX58 and JAK3.Conclusion: This study suggests CS exposure significantly enhances DNA methylated level, and the potential functional methylated genes are closely related to complicated inflammatory-immune responses, which may provide some new experimental evidence in understanding the epigenetic mechanisms of CS-induced airway inflammation in COPD.Keywords: chronic obstructive pulmonary disease, airway inflammation, cigarette smoke, DNA methylation, liquid hybridization capture-based bisulfite sequencing

HM Adnan Hameed1– 4&ast;, Cuiting Fang1– 4&ast;, Zhiyong Liu,1– 3 Yanan Ju,1– 3 Xingli Han,1– 4 Yamin Gao,1– 4 Shuai Wang,1– 3,5 Gift Chiwala,1– 4 Yaoju Tan,6 Ping Guan,6 Jinxing Hu,6 Xiaoli Xiong,1– 3 Jiacong Peng,3,7 Yongping Lin,3,7 Muzammal Hussain,4 Nanshan Zhong,3,7,8 Dmitry A Maslov,9 Gregory M Cook,10,11 Jianxiong Liu,6 Tianyu Zhang1– 4 1State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Guangzhou, People’s Republic of China; 2China-New Zealand Joint Laboratory of Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Guangzhou, People’s Republic of China; 3Guangdong-Hong Kong-Macau Joint Laboratory of Respiratory Infectious Diseases, Guangzhou, People’s Republic of China; 4University of Chinese Academy of Sciences (UCAS), Beijing, People’s Republic of China; 5National Clinical Research Center for Infectious Diseases, Guangdong Provincial Clinical Research Center for Tuberculosis, Shenzhen Third People’s Hospital, Shenzhen, People’s Republic of China; 6State Key Laboratory of Respiratory Disease, Guangzhou Chest Hospital, Guangzhou, People’s Republic of China; 7State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 8Guangzhou National Laboratory, Guangzhou, People’s Republic of China; 9Laboratory of Bacterial Genetics, Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia; 10Department of Microbiology and Immunology, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand; 11Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland, New Zealand&ast;These authors contributed equally to this workCorrespondence: Tianyu Zhang, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Room A207, 190 Kaiyuan Ave, Science Park, Huangpu District, Guangzhou, 510530, People’s Republic of China, Tel +86-2032015270, Email zhang_tianyu@gibh.ac.cn Jianxiong Liu, Guangzhou Chest Hospital, 62 Hengzhigang Road, Yuexiu District, Guangzhou, People’s Republic of China, Tel +86-2083595977, Email ljxer64@qq.comObjective: Rifampicin (RIF)-resistance, a surrogate marker for multidrug-resistant tuberculosis (TB), is mediated by mutations in the rpoB gene. We aimed to investigate the prevalence of mutations pattern in the entire rpoB gene of Mycobacterium tuberculosis clinical isolates and their association with resistance level to RIF.Methods: Among 465 clinical isolates collected from the Guangzhou Chest Hospital, drug-susceptibility of 175 confirmed Mtb strains was performed via the proportion method and Bactec MGIT 960 system. GeneXpert MTB/RIF and sanger sequencing facilitated in genetic characterization, whereas the MICs of RIF were determined by Alamar blue assay.Results: We found 150/175 (85.71%) RIF-resistant strains (MIC: 4 to > 64 μg/mL) of which 57 were MDR and 81 pre-XDR TB. Genetic analysis identified 17 types of mutations 146/150 (97.33%) within RRDR (codons 426– 452) of rpoB, mainly at L430 (P), D435 (V, E, G, N), H445 (N, D, Y, R, L), S450 (L, F) and L452 (P). D435V 12/146 (8.2%), H445N 16/146 (10.9%), and S450L 70/146 (47.94%) were the most frequently encountered mutations. Mutations Q432K, M434V, and N437D are rarely identified in RRDR. Deletions at (1284– 1289 CCAGCT), (1295– 1303 AATTCATGG), and insertion at (1300– 1302 TTC) were detected within RRDR of three RIFR strains for the first time. We detected 47 types of mutations and insertions/deletions (indels) outside the RRDR. Four RIFR strains were detected with only novel mutations/indels outside the RRDR. Two of the four had (K274Q + C897 del + I491M) and (A286V + L494P), respectively. The other two had (G1687del + P454L) and (TT1835-6 ins + I491L) individually. Compared with phenotypic characterization, diagnostic sensitivities of GeneXpert MTB/RIF and sequencing analysis were 95.33% (143/150), and 100% (150/150) respectively.Conclusion: Our findings underscore the key role of RRDR mutations and the contribution of non-RRDR mutations in rapid molecular diagnosis of RIFR clinical isolates. Such insights will support early detection of disease and recommend the appropriate anti-TB regimens in high-burden settings.Keywords: rifampicin-resistance, Mycobacterium tuberculosis, rpoB, GeneXpert MTB/RIF, resistance-determining region

Zhuoxi Wu,1,&ast; Mi Yang,1,&ast; Peng Zhao,1,2 Feng Zou,1 Jing Peng,1 Qiangting Deng,3 Guangyou Duan,4,&ast; Hong Li1,&ast; 1Department of Anesthesiology, Second Affiliated Hospital of Army Medical University, People’s Liberation Army of China, Chongqing, People’s Republic of China; 2Department of Anesthesiology, Chinese People’s Liberation Army of China (PLA) No. 964 Hospital, Changchun, People’s Republic of China; 3Editorial Office of Journal of Third Military Medical University, Army Medical University, People’s Liberation Army of China, Chongqing, People’s Republic of China; 4Department of Anesthesiology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Li; Guangyou Duan, Email lh78553@163.com; dgy1986anesthesia@126.comBackground: Our previous study found that a long-term diet incorporating spicy foods can reduce the human basal pain threshold. Capsaicin is the pungent ingredient in chili peppers. Transient receptor potential vanilloid type1 is the capsaicin receptor expressed in the oral cavity and is the primary sensory neuron of the “pain” pathway. Few studies have examined the association between long-term spicy diet and chronic postsurgical pain (CPSP). Women who underwent elective cesarean section (eCS) have consistent characteristics of CPSP. This study aimed to investigate the relationship between a long-term spicy diet and the incidence of CPSP after eCS.Methods: Participants were divided into a low frequency group (LF, numerical rating scale (NRS)< 5) for spicy food consumption and a high frequency group (HF, NRS≥ 5) by receiver operator characteristic analysis. The primary outcome was the incidence of CPSP three months after eCS. Propensity score matching (PSM) analysis was performed between the two frequency groups. Stepwise logistic regression analysis was then performed.Results: Of the 1029 enrolled patients, data from 982 were analyzed 3 months after eCS. After PSM, the incidence of CPSP in the HF group (30.1% [108/359]) was higher than that in the LF group (19.8% [71/359]; P = 0.001). Compared with the LF group, the risk of CPSP in the HF group increased 1.61 times by 3 months (95% CI 1.18– 2.20, P = 0.003). PSM results found that 1 year, the incidence of CPSP in the HF group (15.2% [56/369]) was higher than that in the LF group (8.1% [30/369], P = 0.003).Conclusion: With an NRS≥ 5 as a boundary, women who consumed spicy food ≥ 2 days/week were more likely to have CPSP than those who consumed spicy food < 2 days/week.Keywords: long-term spicy diet, chronic postsurgical pain, capsaicin, TRPV1, cesarean section

Fei Gao,&ast; Cheng Li,&ast; Jiahui Peng, Wei Lu, Wei Zhu, Jian Zhou, Jingyi Lu, Xiaojing Ma Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingyi Lu; Xiaojing Ma, Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 600 Yishan Road, Shanghai, 200233, People’s Republic of China, Tel +86-21-64369181, Fax +86-21-64368031, Email lujingy1@126.com; maxiaojing@sjtu.edu.cnAim: Dickkopf-1 (DKK-1) is a major inhibitor of Wingless protein signaling pathway, which is involved in glucose metabolism and cardiovascular diseases. The aim of the study was to investigate the changes of serum DKK-1 levels after hypoglycemic treatments and the relationship between DKK-1 and clinical parameters.Materials and Methods: The study was a sub-study of a previously published clinical trial (the effect of Acarbose on glycemic variability in patients with type 2 diabetes mellitus using premixed insulin compared to metformin). All subjects underwent anthropometric and biochemical assessments at baseline and endpoint. Serum DKK-1 levels of 92 subjects were measured at baseline and after 12-week hypoglycemic treatment.Results: DKK-1 levels were significantly decreased after hypoglycemic treatment for 12 weeks (P < 0.001). ΔDKK-1 levels were not correlated with improvement of metabolic parameters (all P > 0.05) but were negatively correlated with baseline DKK-1 levels (r = − 0.263, P = 0.011). Spearman correlation showed that baseline DKK-1 levels were positively related to baseline total cholesterol (r = 0.226, P = 0.030) and low-density lipoprotein cholesterol (LDL-C) (r = 0.277, P = 0.007). Compared with the higher baseline DKK-1 group (≥ 3700 pg/mL), subjects in the lower baseline DKK-1 group (< 3700 pg/mL) had significantly lower baseline glycated hemoglobin A1c levels (P = 0.008) and LDL-C levels (P = 0.048). Systolic and diastolic pressure were decreased more significantly in the lower baseline DKK-1 group than that in the higher baseline DKK-1 group (both P < 0.05).Conclusion: Serum DKK-1 levels were decreased after hypoglycemic treatments. Patients with lower baseline DKK-1 levels were featured by more favorable cardiometabolic factors.Keywords: cardiovascular risk factor, dickkopf-1, hypoglycemic treatment, type 2 diabetes mellitus

Huadong Chen,1 Xing’e Xu,1 Jiren Peng,2 Xuan Ge,3 Jing’an Zhang,1 Qianqian Dong,1 Xiunan Jiang,1 Piaopiao Li1 1Department of Pharmacy, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, People’s Republic of China; 2Department of Vasculocardiology, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, People’s Republic of China; 3Health Management Center, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, People’s Republic of ChinaCorrespondence: Huadong Chen, Department of Pharmacy, Affiliated Dongyang Hospital of Wenzhou Medical University, 60th Wuning West Road, Dongyang, People’s Republic of China, Email chuadong666@163.comIntroduction: Adherence to warfarin is associated with improved outcome in patients with atrial fibrillation (AF), but the adherence status of patients in rural areas of China is not known.Methods: A questionnaire-based study evaluating warfarin adherence of rural residents with AF was carried out in Dongyang, China. Potentially eligible patients were screened and contacted by telephone, and their demographic characteristics were collected. Illness perception was assessed using the Brief Illness Perception Questionnaire (BIPQ), and warfarin adherence was assessed using a Chinese-version adherence scale. Univariate and multivariate analyses were conducted to identify factors associated with unsatisfactory adherence.Results: A total of 201 patients (male, n=99; mean age, 70.3± 8.12 years) were included, among whom 95 (47.3%) patients showed good adherence and 63 (31.3%) poor adherence. Number of co-dispensed drugs (multivariate analysis: odds ratio [OR]=3.64, 95% confidence interval [CI] 1.35– 9.81, p=0.011) and BIPQ score (OR=1.25, 95% CI 1.17– 1.33, p< 0.001) were identified as factors associated with good adherence.Conclusion: Medical adherence to warfarin needs to improve in rural patients with AF. Efforts that can reduce the number of co-dispensed drugs and increase illness perception may improve warfarin adherence. This study may benefit future management of warfarin administration to rural patients with AF.Keywords: adherence, warfarin, illness perception, polypharmacy, rural

Huajing Yang,1,&ast; Zihui Wang,1,&ast; Shan Xiao,1 Cuiqiong Dai,1 Xiang Wen,1 Fan Wu,1,2 Jieqi Peng,1 Heshan Tian,1 Yumin Zhou,1,2 Pixin Ran1,2 1National Center for Respiratory Medicine, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Guangzhou Laboratory, Bio-Island, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pixin Ran; Yumin Zhou, National Center for Respiratory Medicine, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China, Tel +86 2083205187, Fax +86 20-81340482, Email pxran@gzhmu.edu.cn; zhouyumin410@126.comBackground: The effect of serum uric acid (SUA) levels on lung function in chronic obstructive pulmonary disease (COPD) people remained unclear. We aimed to investigate the association between SUA and lung function.Methods: A cross-sectional study was performed to measure the SUA levels and lung function in 2797 consecutive eligible individuals. Of these, individuals in our study were divided into two groups, the COPD group (n=1387) and the non-COPD group (n=1410). The diagnosis of COPD is defined as post-bronchodilator first second of forced expiratory volume (FEV1)/forced vital capacity (FVC) ratio of less than 0.70. Multivariable adjustment linear models were applied to estimate the effect of SUA levels on FEV1% predicted, FVC% predicted, and FEV1/FVC stratified by COPD status.Results: After multivariable adjustment, each 1 mg/dL increase of SUA was significantly associated with a decrease in FEV1% predicted (− 1.63%, 95% confidence interval [CI] − 2.37 to − 0.90), FVC % predicted (− 0.89%, 95% CI − 1.55 to − 0.24), and FEV1/FVC (− 0.70%, 95% CI − 1.10 to − 0.30). In the COPD group, each 1 mg/dL increase of SUA was significantly associated with decreases in FEV1% predicted (− 1.87%, 95% CI − 2.91 to − 0.84), FVC% predicted (− 1.35%, 95% CI − 2.35 to − 0.34), and FEV1/FVC (− 0.63%, 95% CI − 1.18 to − 0.08). However, no significant association between lung function and SUA was found among people without COPD.Conclusion: High SUA levels were associated with lower lung function, especially in COPD patients. However, no statistically significant effect of SUA on lung function was found in people without COPD.Keyword: serum uric acid, lung function, COPD, non-COPD

Guichan Liao, Ziying Liu, Muye Xia, Hongjie Chen, Houji Wu, Bing Li, Tao Yu, Shaohang Cai, Xiaoyong Zhang, Jie Peng State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Jie Peng, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China, Tel +86 20 6278 7428, Fax +86 20 8771 9653, Email pjie138@163.comPurpose: The immunoinhibitory receptor, programmed death 1 (PD-1), plays a critical role in immune suppression during chronic viral infection. The significance of circulating soluble PD-1 (sPD-1) in patients with chronic hepatitis B who have discontinued long-term nucleos(t)ide analog (NA) treatment remains unknown.Patients and Methods: A prospective cohort study was conducted using serial blood samples from chronic hepatitis B patients who discontinued long-term NA treatment. The current analysis included 115 non-cirrhotic patients with HBV DNA negative and HBsAg positive at the moment of NA discontinuation. Levels of sPD-1 were measured in all available samples using sandwich enzyme-linked immunoassay.Results: Sixty-two patients experienced a clinical relapse and 14 occurred HBsAg loss, with 8-year cumulative rates of 56.6% and 23.4%, respectively. Time-dependent receiver operating characteristic curve analysis for sPD-1 derived 156 pg/mL, which is equivalent to the detectable threshold, as an optimal cut-off value for predicting 8-year clinical relapse. Patients with detectable sPD-1 at end of treatment (EOT) had a significant lower incidence of clinical relapse (48% vs 67%, hazard ratio [HR] 0.454, p = 0.006), but a remarkable higher probability of HBsAg loss (33.7% vs 2.4%, HR 9.17, p = 0.038), compared to those who with undetectable sPD-1, respectively.Conclusion: EOT sPD-1 levels predicted clinical relapse and HBsAg loss after treatment discontinuation and may help to guide a finite NA treatment plan for patients with chronic hepatitis B virus infection.Keywords: chronic hepatitis B, discontinuation, programmed cell death 1 protein, nucleos(t)ide analogs

Fan Lai,1,&ast; Xin Li,1,&ast; Qi Wang,1,&ast; Yingjuan Luo,1 Xin Wang,1 Xiuhua Huang,1 Jiajia Zhang,1 Jieru Peng,1 Qin Wang,1 Li Fan,1 Wen Li,1 Junrong Huo,1 Tianjiao Liu,1 Yalan Li,2 Yonghong Lin,1 Xiao Yang1 1Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 2The Fourth People’s Hospital of Chengdu, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao Yang; Yonghong Lin, Chengdu Women’s and Children’s Central Hospital, 1617 Riyue Avenue, Qingyang District, Chengdu, 611731, Sichuan, People’s Republic of China, Tel +86 13882288881 ; +86 13808031895, Email yangxiaocwcch@aliyun.com; linyonghongcwcch@aliyun.comPurpose: Fever is one of the most typical clinical symptoms of coronavirus disease 2019 (COVID-19), and non-contact infrared thermometers (NCITs) are commonly used to screen for fever. However, there is a lack of authoritative data to define a “fever” when an NCIT is used and previous studies have shown that NCIT readings fluctuate widely depending on ambient temperatures and the body surface site screened. The aim of this study was to establish cut-off points for normal temperatures of different body sites (neck, forehead, temples, and wrist) and investigate the accuracy of NCITs at various ambient temperatures to improve the standardization and accuracy of fever screening.Patients and Methods: A prospective investigation was conducted among 904 participants in the outpatient and emergency departments of Chengdu Women’s and Children’s Central Hospital. Body temperature was measured using NCITs and mercury axillary thermometers. A receiver operating characteristic curve was used to determine the accuracy of body temperature detection at the four body surface sites. Data on participant characteristics were also collected.Results: Among the four surface sites, the neck temperature detection group had the highest accuracy. When the neck temperature was 37.35°C as the optimum fever diagnostic threshold, the sensitivity was 0.866. The optimum fever diagnostic thresholds for forehead, temporal, and wrist temperature were 36.65°C, 36.65°C, and 36.75°C, respectively. Moreover, triple neck temperature detection had the highest sensitivity, up to 0.998, whereas the sensitivity of triple wrist temperature detections was 0.949. Notably, the accuracy of NCITs significantly reduced when the temperature was lower than 18°C.Conclusion: Neck temperature had the highest accuracy among the four NCIT temperature measurement sites, with an optimum fever diagnostic threshold of 37.35°C. Considering the findings reported in our study, we recommend triple neck temperature detection with NCITs as the fever screening standard for COVID-19.Keywords: COVID-19, epidemiology, fever, infrared rays, mass screening

Junnan Peng,* Rui Tang,* Di Qi, Qian Yu, Hao Hu, Wen Tang, Jing He, Daoxin Wang Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Daoxin Wang; Jing He, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Chongqing Medical University, No. 76 Linjiang Road, Yuzhong District, Chongqing, 400010, People’s Republic of China, Email wangdaoxin0163@163.com; miss_hejing@126.comBackground: Eosinophils play an essential role in the pathogenesis of acute respiratory distress syndrome (ARDS). We aimed to assess the association between the baseline blood eosinophils, eosinophil changes during the first week in the intensive care unit (ICU) and short-term patient outcomes.Methods: All patients meeting the Berlin definition of ARDS from the Medical Information Mart for Intensive Care IV database were retrospectively analyzed. We used logistic regression, Kaplan–Meier survival and random forest analysis to determine the association between the baseline eosinophils and short-term mortality. Then the trends in eosinophils over time were compared between the survivors and non-survivors using a generalized additive mixed model (GAMM), which is a common approach used for analysis of repeated measurement data. Area under the receiver-operating characteristic curve (AUC) was used to evaluate the predictive value.Results: A total of 1685 patients were included, and the 30-day mortality was 25.1%. Kaplan–Meier analysis showed that patients with high baseline eosinophils (> 0.3%) had lower 30-day mortality (p < 0.001). Random forest model selected the baseline eosinophils as an important factor associated with 30-day mortality. Multivariable logistic regression analysis identified high baseline eosinophils as an independent factor for 30-day mortality (OR 0.743, 95% CI 0.568– 0.970). The GAMM result showed that the levels of eosinophils were increased in both survival and non-survival groups, and the between-group differences increased over time, with an average of 0.154 daily after adjusting for confounders. The AUC of changes in eosinophils within the first week was significantly higher than that of baseline eosinophils.Conclusion: There is a negative association between the baseline eosinophils and short-term mortality in ARDS patients, and the differences in eosinophils increased over time between the survivors and non-survivors. Higher increase in eosinophils is associated with decreased short-term mortality, and dynamic monitoring of eosinophils could better predict the survival of ARDS patients.Keywords: ARDS, eosinophils, 30-day mortality, generalized additive mixed model, change

Chaowen He, Dongxuan Huang, Fan Yang, Dongsheng Huang, Yahui Cao, Jianfeng Peng, Xiaohua Luo Department of Pulmonary and Critical Care Medicine, Shenzhen Longhua District Central Hospital, Shenzhen, 518110, Guangdong, People’s Republic of ChinaCorrespondence: Chaowen He, Department of Pulmonary and Critical Care Medicine, Shenzhen Longhua District Central Hospital, No. 187 Guanlan Avenue, Longhua District, Shenzhen, 518110, Guangdong, People’s Republic of China, Tel +86-18123964996, Email chaowh0331@163.comBackground: This study aims to investigate the expression and clinical value of long non-coding RNA (lncRNA) HEIH in peripheral blood of patients with non-small cell lung cancer (NSCLC).Methods: Healthy subjects (N=70), patients with lung squamous cell carcinoma (LUSC, N=70) and patients with lung adenocarcinoma (LUAD, N=80) were included. LncRNA HEIH expression in peripheral blood of included subjects was detected using RT-qPCR. According to the median expression of lncRNA HEIH, LUSC and LUAD patients were allocated into lncRNA HEIH high/low expression groups. The correlation between lncRNA HEIH and clinical indicators of patients was analyzed; Logistic multifactor regression was used to analyze the independent risk factors influencing lncRNA HEIH level. Receiver-operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of lncRNA HEIH and carcinoembryonic antigen (CEA) in LUSC/LUAD patients. MedCalc-Comparison of ROC curves was used to compare the area under ROC curve. The cumulative survival rates of lncRNA HEIH high/low expression group were analyzed by Kaplan–Meier curve. COX multivariate analysis was used to assess the independent factors affecting prognosis of NSCLC.Results: LncRNA HEIH in peripheral blood of LUSC/LUAD patients was higher than that in healthy controls, with no evident difference between LUSC and LUAD groups. In LUSC/LUAD patients, TNM stage, lymph node metastasis, distal metastasis, and CEA were independent risk factors affecting lncRNA HEIH; patients with high lncRNA HEIH expression had larger pack-years and tumor size, higher CEA level and tumor stage, and higher risk of lymph node metastasis and distal metastasis. LncRNA HEIH had higher diagnostic efficiency than CEA in NSCLC patients. High expression of lncRNA HEIH predicted poor prognosis in patients with NSCLC and was an independent risk factor for prognosis of NSCLC.Conclusion: High expression of lncRNA HEIH is helpful in the diagnosis of NSCLC and predicts poor prognosis.Keywords: non-small cell lung cancer, long non-coding RNA HEIH, prognosis, carcinoembryonic antigen, lung squamous cell carcinoma, lung adenocarcinoma, peripheral blood

Shucheng Liu,1 Yilin Wang,2 Bin Gao,2 Jun Peng2 1Department of Urology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang City, Hunan Province, People’s Republic of China; 2Department of Neurology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang City, Hunan Province, People’s Republic of ChinaCorrespondence: Jun PengDepartment of Neurology, The First Affiliated Hospital, Hengyang Medical School, University of South China, No. 69 Chuanshan Road, Hengyang City, Hunan Province, People’s Republic of China, Tel +86 19958919270, Fax +86 734-8578774, Email pengjun278@163.comPurpose: To establish and validate a nomogram model for predicting stress-related gastrointestinal bleeding in critically ill patients with primary intracerebral hemorrhage.Patients and Methods: From January 2018 to March 2021, we conducted a hospital-based study by screening eligible patients with acute intracerebral hemorrhage. Univariate and multivariate logistic regression analyses were performed to determine the predictors for stress-related gastrointestinal bleeding in patients with primary intracerebral hemorrhage. The nomogram was constructed on the basis of multivariate logistic model and was internally validated by bootstrap resampling. The discriminative performance of the nomogram was evaluated using the calibration and concordance index (C-index), which was equal to the area under the curve of receiver-operating characteristics. Hosmer-Lemeshow test was performed to check the model’s goodness of fit. A decision curve analysis was used to assess its clinical utility.Results: A total of 410 patients were enrolled in this study. Stress-related gastrointestinal bleeding occurred in 115 patients (28.0%). Multivariate analysis demonstrated that gastric pH at admission [odds ratio (OR): 0.52, 95% confidence interval (CI): 0.41– 0.66, P < 0.001], ICH volume (OR: 1.03, 95% CI: 1.02– 1.05, P < 0.001) and sepsis (OR: 2.56, 95% CI: 1.54– 4.25, P < 0.001) were independent predictors for stress-related gastrointestinal bleeding in critically ill patients with ICH. The nomogram including gastric pH at admission, ICH volume and sepsis presented good discrimination with C-index of 0.770 (95% CI: 0.716 to 0.822), which was confirmed to be 0.764 through bootstrapping validation. The calibration plot showed good agreement between the predicted and observed outcomes. The Hosmer–Lemeshow test showed a goodness-of-fit (Chi-Square = 8.085, DF = 8, P = 0.425). Decision curve analysis demonstrated that the nomogram was clinically beneficial.Conclusion: The proposed nomogram based on gastric pH at admission, ICH volume and sepsis can accurately predict the risk of stress-related gastrointestinal bleeding in critically ill patients with primary intracerebral hemorrhage.Keywords: nomogram, stress-related gastrointestinal bleeding, intracerebral hemorrhage, prediction, decision curve analysis

Jiao Peng,1– 3,&ast; Xi Li,4,&ast; Lin Zheng,3,5 Lifang Duan,1 Zhengxian Gao,2,5 Die Hu,1 Jie Li,6 Xiaofeng Li,6 Xiangchun Shen,5 Haitao Xiao2 1Department of Pharmacy, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China; 2School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, People’s Republic of China; 3Engineering Research Center for the Development and Application of Ethnic Medicine and TCM, Ministry of Education, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, People’s Republic of China; 4Department of Gastroenterology, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China; 5School of Pharmacy, State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, People’s Republic of China; 6Department of Laboratory Medicine, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haitao Xiao, School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, 518060, People’s Republic of China, Email xhaitao@szu.edu.cn Xiangchun Shen, School of Pharmacy, Guizhou Medical University, Guizhou, 550004, People’s Republic of China, Email shenxiangchun@126.comPurpose: GLP-1 based therapy represents a new treatment option for inflammatory bowel disease. Ban-Lan-Gen (BLG) granule, a known anti-viral TCM formulation, exhibits potential anti-inflammatory activities in treating various kinds of inflammation. However, its anti-inflammatory effect on colitis and the underlying mechanisms remain unknown.Methods: Dextran sulfate sodium (DSS)-induced chronic relapsing colitis in mice was established. The disease activity index, histological sign of damage, and levels of proinflammatory cytokines were performed to assess the protective effects of BLG. Serum GLP-1 level and colonic Gcg, GPR41 and GRP43 expression, the community compositions of gut microbiota, the levels of SCFAs in the feces and GLP-1 release from primary murine colon epithelial cells were performed to characterize the effects of BLG on gut microbiota and gut SCFA derived-GLP-1 production.Results: BLG treatment significantly alleviated body weight loss, DAI, colon shortening, colon tissue damage, and pro-inflammatory cytokine levels of TNF-α, IL-1β and IL-6 in the colon tissues. Moreover, BLG treatment could observably restore colonic Gcg, GPR41 and GRP43 expression and serum GLP-1 level of colitic mice, as well as correct the alteration of gut microbiota in colitic mice by increasing the abundances of SCFA-producing bacteria, eg, Akkermansia and Prevotellaceae_UCG-001, and decreasing the abundances of bacteria, eg, Eubacterium_xylanophilum_group, Ruminococcaceae_UCG-014, Intestinimonas, and Oscillibacter. Furthermore, BLG treatment could markedly increase the levels of SCFAs in feces of colitic mice. In parallel, ex vivo assay also showed that and the extract of feces from BLG-treatment mice could greatly stimulate the secretion of GLP-1 from primary murine colon epithelial cells.Conclusion: These findings suggest that the anti-colitis effects of BLG are achieved at least partly by regulating gut microbiota and restoring gut SCFA derived-GLP-1 production, and BLG has the potential to be developed as a promising agent for the treatment of chronic relapsing colitis.Keywords: colitis, Ban-Lan-Gen granule, gut microbiota, short-chain fatty acids, GLP-1

Yunqing Sun,&ast; Zhuohong Li,&ast; Guichan Liao, Muye Xia, Xuwen Xu, Shaohang Cai, Jie Peng Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Peng; Shaohang Cai Email pjie138@163.com; shaohangcai@foxmail.comBackground and Aim: The long‐term outcomes of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV‐ACLF) remain not well known. This study aimed to investigate whether aMAP score can predict re-hospitalization, hepatocellular carcinoma (HCC) occurrence and long-term mortality in patients with HBV-ACLF.Methods: A total of 82 patients diagnosed with HBV-ACLF and survived over 6 months were enrolled. The median follow-up period was 105 (75.9, 134.1) months. The Cox proportional hazards or logistic regression analysis was used to determine independent risk factors. Cumulative incidence of HCC and survival rate were evaluated using Kaplan–Meier analysis.Results: Multivariate analysis identified that the aMAP risk score was an independent predictor of re-hospitalization (odds ratio [OR] = 1.112, 95% confidence interval [CI]: 1.021– 1.211, p = 0.015), hepatocellular carcinoma occurrence (hazards ratio [HR] = 2.277, 95% CI: 1.014– 5.114, p = 0.046) and mortality (HR = 1.366, 95% CI: 1.040– 1.794, p = 0.025). High-risk aMAP scores were associated with higher risk of HCC occurrence and mortality.Conclusion: A higher aMAP score was an independent risk predictor of re-hospitalization, HCC occurrence and mortality, respectively, in HBV-ACLF patients who survived over 6 months, which can be applicable for early risk stratification and clinical decision.Keywords: acute-on-chronic liver failure, chronic hepatitis B virus infection, re-hospitalization, hepatocellular carcinoma, mortality, prognosis

Xiangyuan Qiu,1 Xinying Li,1 Yuanliang Yan,2 Yuan Cai,3 Qiuju Liang,2 Bi Peng,3 Zhijie Xu,3– 5 Muzhang Xiao,6 Fada Xia,1 Jinwu Peng3,4 1Department of Thyroid Surgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People’s Republic of China; 2Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People’s Republic of China; 3Department of Pathology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People’s Republic of China; 4Department of Pathology, Xiangya Changde Hospital, Changde, 415000, Hunan, People’s Republic of China; 5National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People’s Republic of China; 6Department of Burn and Plastic Surgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People’s Republic of ChinaCorrespondence: Muzhang XiaoDepartment of Burn and Plastic Surgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People’s Republic of ChinaEmail xmzsir@sina.comFada XiaDepartment of Thyroid Surgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People’s Republic of ChinaEmail xiafada@csu.edu.cnBackground: N6-methyladenosine (m6A) is most common internal RNA modification in eukaryotic cells. Existing evidence shows that m6A is closely related to pathogenesis and progression in breast cancer (BRCA). Therefore, it is critical to investigate the key role of m6A target genes in BRCA.Methods: M6A target genes in BRCA are acquired using RMVar online database. The differentially expressed genes (DEGs) from three microarray datasets (GSE5764, GSE22358, GSE9014) is processed by GEO2R. Oncomine, GEPIA, UALCAN and TNMplot were applied to validate the expression of DST. Survival analyses were performed via DRUGSURV and Kaplan–Meier Plotter database. Univariable survival and multivariate Cox analysis were completed to assess the prognostic value of DST and receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic value of DST. We also investigated the correlation between DST and cancer immune infiltration via using CIBERSORT, TIMER and TISIDB.Results: DST and COL11A1 were significantly expressed in both DEGs and m6A target genes set. COL11A1 show no significance on the patients’ survival. However, high expression of DST was related to the favorable prognosis. Multivariate analysis revealed that the DST dysregulation is an independent prognostic factor and ROC indicated that the great diagnostic value of DST with AUC of 0.948. Subsequently, immunological analyses showed that DST was significantly associated with various immune infiltration cells, including NK cells, T helper cells and Mast cells. Furthermore, DST was also related with multiple immune checkpoints and chemokines, including LAG3, LMTK3 CD24, CXCL12, KDR and CX3CR1. These results indicated the potential roles of DST in the development of BRCA via altering the immune response.Conclusion: DST can influence the development and progression of BRCA by altering the immune microenvironment.Keywords: breast cancer, DST, N6-methyladenosine, immune microenvironment, immune infiltration

Longbing Yang,1 Zhuqing Tian,1 Luoxiong Zhou,1,2 Lijuan Zhu,1 Chaoqin Sun,1 Mingjiao Huang,1 Jian Peng,1,3 Guo Guo1,3,4 1School of Basic Medical Sciences, The Key and Characteristic Laboratory of Modern Pathogen Biology, Guizhou Medical University, Guiyang, 550025, People’s Republic of China; 2School of Public Health, Guizhou Medical University, Guiyang, 550025, People’s Republic of China; 3Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, 550025, People’s Republic of China; 4Translational Medicine Research Center, Guizhou Medical University, Guiyang, 550025, People’s Republic of ChinaCorrespondence: Guo GuoBuilding Wuben, School of Basic Medical Sciences, Guizhou Medical University, College Town, Gui’an New District, Guiyang, 550025, People’s Republic of China, Tel/fax +86 851 882 59268, Email guoguojsc@163.comBackground: Cryptococcus neoformans is a common human fungal pathogen in immunocompromised people, as well as a prevalent cause of meningitis in HIV-infected individuals. With the emergence of clinical fungal resistance and the shortage of antifungal drugs, it is urgent to discover novel antifungal agents. AMP-17, a novel antimicrobial peptide from Musca domestica, has antifungal activity against C. neoformans. However, its antifungal and anti-biofilm activities remain unclear. Thus, this study aimed to evaluate the antifungal activity of AMP-17 against planktonic cells and biofilms of C. neoformans.Methods: The minimum inhibitory concentration (MIC), the biofilm inhibitory and eradicating concentration (BIC and BEC) were determined by the broth microdilution assay or the 2, 3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction assay, respectively. The inhibitory and killing activities of AMP-17 against C. neoformans were investigated through the time-inhibition/killing kinetic curves. The potential antifungal mechanism of AMP-17 was detected by flow cytometry, scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). The efficiency of AMP-17 against biofilm formation or preformed biofilm was evaluated by crystal violet staining and XTT reduction assays. The morphology of pre-biofilms was tested by optical microscopy (OM) and CLSM.Results: AMP-17 exhibited in vitro antifungal activity against C. neoformans planktonic cells and biofilms, with MICs of 4∼ 16 μg/ml, BIC80 and BEC80 of 16∼ 32 μg/ml, 64∼ 128 μg/ml, respectively. In addition, the 2× and 4× MIC of AMP-17 exhibited similar inhibition levels compared to the 2× and 4× MIC of the clinical drugs FLC and AMB in C. neoformans growth. Moreover, the time-kill results showed that AMP-17 (8× MIC) did not significantly eliminate colony forming units (CFU) after 6 h of treatment; however, there was 2.9-log reduction in CFU of C. neoformans. Furthermore, increasing of the permeability of the fungal cell membrane was observed with the treatment of AMP-17, since the vast change as fungal leakage and cell membrane disruption. However, the DNA binding assay of AMP-17 indicated that the peptide did not target DNA. Besides, AMP-17 was superior in inhibiting and eradicating biofilms of C. neoformans compared with FLC.Conclusion: AMP-17 exhibited potential in vitro antifungal activity against the planktonic cells and biofilms of C. neoformans, and it may disrupt fungal cell membranes through multi-target interactions, which provides a promising therapeutic strategy and experimental basis for Cryptococcus-associated infections.Keywords: antimicrobial peptides, AMP-17, Cryptococcus neoformans, antifungal mechanism, anti-biofilm

Sheng Hu, Wenxiong Zhang, Qiang Guo, Jiayue Ye, Deyuan Zhang, Yang Zhang, Weibiao Zeng, Dongliang Yu, Jinhua Peng, Yiping Wei, Jianjun Xu Department of Thoracic Surgery, The Second Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, People’s Republic of ChinaCorrespondence: Yiping Wei; Jianjun XuThe Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of ChinaTel +86 13687919322; +86 13907913526Email weiyip2000@hotmail.com; xujianjun3526@163.comBackground: On April 15, 2021, the Surveillance, Epidemiology, and End Results (SEER) database released the latest lung cancer follow-up data. We selected 922,317 lung cancer patients diagnosed from 2000 to 2017 for survival analysis to provide updated data for lung cancer researchers.Research Question: This study explored the latest trends of survival time in terms of gender, race, nationality, age, income, address, histological type and primary site.Study Design and Methods: The SEER database covers 27.8% of the US population. We used life table, Kaplan–Meier, log-rank, Breslow and Tarone-Ware tests to calculate survival rate, time, and curve and to compare differences in survival distribution. We performed univariate and multivariate Cox proportional hazards analyses.Results: The median survival time of all lung cancer patients diagnosed in 2017 increased by 41.72% compared to 2000. Median survival time of female patients diagnosed in 2017 increased by 70.94% compared to 2000. Median survival time of those diagnosed in 2017 for different primary sites was as follows: right middle lobe was the longest, then left lower lobe, right upper lobe, right lower lobe, and left upper lobe. Lung cancer patients older than 75 years had a significantly shorter median survival time. Patients living in metropolitan areas of 250,000 to 1 million had a longer median survival time. Median survival time in the adenocarcinoma group was significantly greater than other patients. Median survival of Asian and other races diagnosed in 2017 was 97.87% higher than those diagnosed in 2000. Survival rate of lung cancer increased gradually with the year of diagnosis.Interpretation: The rapid improvement of the prognosis of female and young lung cancer patients contributes to the improvement of the overall prognosis. Primary lung cancer in the right middle lobe has the best prognosis.Keywords: Cox regression analysis, Kaplan Meier survival analysis, lung cancer, prognosis, SEER

Zenghua Deng,1,2,&ast; Kanghua Huang,3,&ast; Dongfang Liu,1 Nan Luo,1,2 Tingting Liu,1 Long Han,1 Dexiao Du,1 Dongbo Lian,1,2 Zhaohui Zhong,4 Jirun Peng1,2 1Department of Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of China; 2Ninth School of Clinical Medicine, Peking University, Beijing, 100038, People’s Republic of China; 3Department of Radiation Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, People’s Republic of China; 4Department of General Surgery, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jirun Peng; Zhaohui Zhong Email pengjr@medmail.com.cn; pengjr@bjsjth.cn; zhongzhaohui@pkuph.edu.cnBackground: Hepatocellular carcinoma (HCC) is the most common subtype of primary liver cancer, which causes ∼ 800,000 deaths annually world-wide. Immune checkpoint inhibitor (ICI) has reformed cancer therapy and achieved unprecedented results in various malignancies, including HCC. However, the response rate of immunotherapy is very low in HCC. Considereing the complicated and unique immune status in liver, we hypothesize that critical molecules will affect prognosis and correlate with immune context in the tumor microenvironment of HCC.Methods: Using Kaplan–Meier plotter, GEPIA2 and Integrative Molecular Database of Hepatocellular Carcinoma (HCCDB), survival genes and their prognostic value were estimated in HCC. Based on Tumor Immune Estimation Resource (TIMER), association between survival genes and immune infiltration was examined in HCC. FunRich and STRING were used to analyze gene ontology and protein–protein interaction (PPI) Network, qRT-PCR was used to measure mRNA level of candidates; and a Cell Counting Kit-8 was used to measure proliferation of HCC cell line.Results: Using multiple databases, we identified 36 key prognostic genes highly expressed in HCC and associated with poor survival of patients. Meanwhile, the 36 gene signatures correlated with immune infiltration in HCC. Moreover, these genes were significantly associated with exhausted T cells and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in HCC. Among the 36 key genes, SKA3, SGOL2, SPINDOC, TEDC2, TMCO3 and NUP205 were highly expressed in tumor samples compared with adjacent normal tissues in our HCC cohort (n=22). Additionally, proliferation of SMMC7721 cell line was inhibited when it interfered with SiRNA of each gene.Conclusion: The 36 genes may serve as potential prognostic biomarkers and molecular targets to ameliorate tumor immune microenvironment (TIME) in HCC and therefore represent a novel avenue for individualized immunotherapy in HCC.Keywords: HCC, prognosis, immune infiltrates, exhausted T cell, MDSC

Junmu Peng,1,2,&ast; Jie Qin,1,&ast; Tianji Huang,1 Xiaoji Luo,1 Weiyang Zhong,1 Zhengxue Quan1 1Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Department of Orthopedic Surgery, The Ninth People’s Hospital of Chongqing, Chongqing, 400799, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weiyang Zhong Email 492467112@qq.comBackground: A retrospective study aimed to introduce a new method for improving the diffusion degree of bone cement and to observe its clinical efficacy in percutaneous vertebroplasty treating osteoporotic vertebral compression fractures (OVCFs).Methods: From January 2019 to March 2020, a total of 83 patients were enrolled and reviewed. The patients were divided into two groups according to the operation method. The clinical and radiographic parameters were recorded and compared between these two groups. Those who received percutaneous vertebroplasty with haemorrhage aspiration were recorded as group A (n=42). In group A, the haemorrhage in the vertebral fracture was aspirated compared with conventional percutaneous vertebroplasty. Patients who underwent conventional percutaneous vertebroplasty were classified as group B (n=41).Results: Visual analogue scale (VAS) values and Oswestry Disability Index (ODI) scores showed no significant difference between the two groups preoperatively, postoperatively or at the final follow-up (FU) (P> 0.05). The intraoperative VAS score (bone cement injection) in group A was significantly lower than that in group B (3.83± 0.79 vs 5.44± 1.32, P < 0.01). The local kyphotic angle (LKA) (final follow-up), LKA loss, fractured vertebral anterior height loss (FVAHL) and anterior vertebral height loss ratio (AVHLR) were significantly lower in group A than in group B. The anterior vertebral height ratio (AVHR) at the final FU in group A was higher than that in group B (P=0.013). The distribution of bone cement was significantly different (P=0.034). By analysing the distribution pattern of bone cement, it was found that the values of LKA loss, FVAHL and AVHLR were superior in the type A bone cement distribution to those in types B and C.Conclusion: Compared with traditional surgical methods, bone haemorrhage aspiration could improve the diffusion degree of bone cement and reduce the height loss and deformity of injured vertebrae. This method provides a feasible new scheme for improving the dispersion of bone cement.Keywords: osteoporotic vertebral compression fractures, percutaneous vertebroplasty, bone cement distribution, fracture haemorrhage aspiration

Bang Li,1,2,&ast; Yan Liu,1,2,&ast; Jiao Peng,3 Chao Sun,2 Weiqing Rang1 1Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, Hunan, People’s Republic of China; 2School of Public Health, Wuhan University, Wuhan, Hubei, People’s Republic of China; 3Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weiqing RangHunan Key Laboratory of Typical Environmental Pollotion and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, The 28th of Changsheng Road, Hengyang, Hunan, People’s Republic of ChinaEmail rwqktz2018@126.comPurpose: To explore the esophageal cancer (EC) incidence and mortality trends and risk factors in China during 2005– 2015.Materials and Methods: The data were stratified by area (urban, rural), gender (male, female), and age groups (0 ∼, 5 ∼, …, 85 ∼). The age-standardized incidence rate (ASIR) and mortality rate (ASMR), age-specific incidence and mortality were calculated to describe the trends, which were analyzed by Joinpoint software, negative binomial regression model, and age-period-cohort model.Results: Trends in EC ASIR decreased markedly during 2010– 2015 (APC=− 6.14%, P< 0.05), and the average annual percent change (AAPC) value was − 8.07% (95% confidence interval (CI): − 9.98∼− 6.12) for rural areas during 2005– 2015. The ASMR was on a fast-downward trend after 2011 (APC=− 6.67%, P< 0.05), with AAPC values of − 1.34% (95% CI: − 2.56∼− 0.19) for males, − 3.39% (95% CI: − 5.65, − 1.07) for females, and − 9.67% (95% CI: − 10.56∼− 8.77) for rural areas during 2005– 2015. The age-specific incidence and mortality increased with age. The risk of EC for males was 3.1675 times higher than females (P< 0.001), and for urban areas, it was 0.58 times larger than rural (P< 0.001). The age and period effects presented an increasing trend, with a decreasing trend for the cohort effects in incidence and mortality risk. Later birth cohorts presented lower risks than previous birth cohorts.Conclusion: ASIR and ASMR in China are higher in males than females, and higher in rural than urban areas, which have decreased during 2005– 2015, especially in rural areas. The incidence increased with age up to the peak age group of 75. Area, gender, and age were independent risk factors for EC incidence.Keywords: esophageal cancer, junction regression, negative binomial regression model, age-period-cohort analyses

Lulu Zhang,1,2,&ast; Chi Zhang,1,2,&ast; Yaling Zeng,3,&ast; Yamei Li,1,2 Shuhong Huang,3 Feng Wang,3 Junping Peng1,2 1NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3Shenzhen Center for Chronic Disease Control, Shenzhen, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng WangShenzhen Center for Chronic Disease Control, No. 2021, Buxin Road, Luohu District, Shenzhen, Guangdong, People’s Republic of ChinaTel/Fax +86-10-25504463Email biowangfeng@163.comJunping PengNHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College; Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences, No. 6, Rongjing Eastern Street, BDA, Beijing, People’s Republic of ChinaTel/Fax +86-10-67878493Email pengjp@hotmail.comAbstract: We here described a ceftriaxone-resistant Neisseria gonorrhoeae FC428 clone (YL201) with moderate-level resistance to azithromycin in Shenzhen, South China in 2020. The NG-STAR type of YL201 is ST2238, containing a mosaic penA-60.001 allele, which is a typical characteristic of FC428 clone. YL201 harbours four copies of the 23S rRNA C2611T mutation, conferring moderate-level resistance to azithromycin. The MLST type is ST1600, identical with two N. gonorrhoeae FC428 clones identified in Hangzhou. Genome-wide phylogeny analysis demonstrates that YL201 is clustered with other FC428 clones from Hangzhou (South-east China) and Chengdu (South-west China). Isolates within this cluster have relatively higher MIC for ceftriaxone and display closely related MLST STs (ST1600 and ST7363) but are different from the ST of typical FC428 clone (ST1903). As ST1600 and ST7363 are common STs in Shenzhen, the further spread of FC428 clones may increase the severity of gonococcal resistance. In summary, identifying a multidrug-resistant (MDR) N. gonorrhoeae isolate in Shenzhen showed FC428 clones have undergone further transmission in China and presented more extensive and concerning antimicrobial resistance (AMR) characteristics during the spread.Keywords: Neisseria gonorrhoeae, ceftriaxone, azithromycin, phylogeny, antimicrobial resistance

Qiqing Gao,&ast; Yao Cheng,&ast; Zhuohong Li, Qingyun Tang, Rong Qiu, Shaohang Cai, Xuwen Xu, Jie Peng, Hongyan Xie Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Peng; Hongyan XieDepartment of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of ChinaTel +86 20 62787428Fax +86 20 87719653Email pjie138@163.com; 492577598@qq.comBackground: Malnutrition is one of the most critical factors affecting patients’ risk of infection and length of stay, and it may affect the prognosis of patients with sepsis. There have been no studies that have applied nutritional risk screening tools to stratify patients with sepsis according to prognosis.Methods: We retrospectively analyzed the clinical data of 425 adult sepsis inpatients who were grouped based on nutritional risk screening (NRS) score, including a nutrition score, disease severity score, and age score. Prognostic factors were analyzed using univariate and multivariate regression analyses.Results: Of the enrolled patients, 174 had an NRS score of ≥ 3; these patients were older and had a longer hospitalization time but lower body mass index (BMI), albumin (ALB) than others. Univariate Cox regression analysis showed that age, ALB, C-reactive protein (CRP), and NRS score were significantly (P< 0.05) associated with in-hospital mortality. Multivariate analysis showed that age (hazard ratio [HR]=1.020, 95% confidence interval [CI]: 1.005– 1.036; P=0.008) and ALB (HR=0.924, 95% CI: 0.885– 0.966; P< 0.001) were independent risk factors for sepsis-related mortality. The Kaplan–Meier analysis revealed that the cumulative in-hospital mortality of sepsis patients with an NRS score of ≥ 3 was significantly higher than that of patients with an NRS score of < 3 (P=0.022).Conclusion: NRS scores can effectively risk stratify sepsis patients. Patients with high NRS scores should be monitored more closely to halt further disease progression.Keywords: sepsis, malnutrition, NRS, risk stratification, prognostic assessment

Hong Zhu,&ast; Jiarui Peng,&ast; Wei Li Department of Endocrinology, The Third People’s Hospital of Yunnan Province, Kunming, 650011, Yunnan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei LiDepartment of Endocrinology, The Third People’s Hospital of Yunnan Province, No. 292, Beijing Road, Guandu District, Kunming, 650011, Yunnan, People’s Republic of ChinaTel/Fax +86-871-63194278Email Liwei813_2@126.comObjective: Diabetic nephropathy (DN) represents the most common diabetic complication that may lead to end-stage renal disease. This work focused on the effect of FOXA1 on the DN development and the molecular mechanism.Methods: A mouse model of DN was induced by high-fat diets and streptozotocin. The concentrations of blood glucose and urinary protein in mice, and the pathological changes in mouse kidney tissues were determined. A podocyte cell line MPC-5 was treated with high glucose (HG) to mimic a DN-like condition in vitro. FOXA1 and SATB1 were overexpressed in HG-treated MPC-5 cells and in DN mice to explore their effects on cell proliferation and apoptosis, and on pathological changes in mouse kidney tissues. The binding relationship between FOXA1 and STAB1 was predicted and validated. Activation of the Wnt/β-catenin pathway was detected.Results: FOXA1 was poorly expressed in the kidney tissues of DN mice. Overexpression of FOXA1 reduced the concentrations of fasting blood glucose and 24-h urinary protein in mice. It also suppressed the accumulation of glomerular mesangial matrix and hyperplasia of glomerular basement membrane, and reduced collagen deposition and interstitial fibrosis in mouse kidney. Also, FOXA1 reduced HG-induced apoptosis of MPC-5 cells. FOXA1 bound to the promoter region of SATB1 for transcription suppression. Overexpression of SATB1 activated the Wnt/β-catenin pathway and blocked the protective roles of FOXA1 in DN mice and in HG-treated MPC-5 cells.Conclusion: This study demonstrated that FOXA1 transcriptionally suppresses SATB1 expression and inactivates the Wnt/β-catenin signaling pathway, thereby inhibiting podocyte apoptosis and DN progression.Keywords: diabetic nephropathy, FOXA1, SATB1, Wnt/β-catenin, MPC-5