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Hongling Du,1– 3 Shunjie Zhang,1 Kezhu Yuan,4 Zhirui Yang,5 Mingquan Wu4 1Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Pharmacy, Sichuan Public Health Clinical Center, Chengdu, Sichuan, People’s Republic of China; 3State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 4Department of Pharmacy, Sichuan Orthopedic Hospital, Chengdu, Sichuan, People’s Republic of China; 5Department of Nuclear Medicine, Chengdu Second People’s Hospital, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Mingquan Wu, Department of Pharmacy, Sichuan Orthopedic Hospital, Chengdu, Sichuan, People’s Republic of China, Email 18782976939@163.comBackground: Rehmanniae Radix (RR) has received attention for its antithrombotic effect. However, few studies have independently explored the bioactive components responsible for its antithrombotic bioactivity and the potential mechanism. We aimed to reveal the antithrombotic mechanisms of RR by using metabolomics integrated with network pharmacology.Methods: A thrombosis model was established by intraperitoneal injection of type I carrageenan in rats, and antithrombotic function was evaluated at different doses of RR. Metabolomics was used to identify the differential metabolites in the serum. Network pharmacology was then applied to identify the potential targets for the antithrombotic activity of the RR. An integrated network of metabolomics and network pharmacology was constructed using Cytoscape. Finally, key targets were verified using molecular docking.Results: RR at 5.4 g/kg significantly alleviated the thrombosis. Thirteen potentially significant metabolites were involved in the therapeutic effects of RR against thrombosis, most of which were regulated for recovery after RR treatment. An integrated analysis of metabolomics and network pharmacology showed that the antithrombosis effect of RR was closely associated with the regulation of PLA2G2A, PTGS1, ALOX5, and CYP2C9. Molecular docking showed high affinity between the key targets and components of RR. We speculated that the components of RR, such as catalpol, ferulic acid methyl ester, and methyl 4-hydroxycinnamate, might act on key proteins, including PLA2G2A, PTGS1, and ALOX5, to exert antithrombosis effects.Conclusion: This study confirmed the antithrombotic effect of high-dose RR, revealed the antithrombotic mechanism and potential material basis, and laid the foundation for the antithrombotic clinical application of RR. Furthermore, it provides a successful case reference for screening natural herbal components and exploring their potential pharmacological mechanisms.Keywords: Rehmanniae radix, antithrombotic effects, metabolomics, network pharmacology

Sining Zeng,1,2,* Min Wu,1,* Ling Xu,1 Zining Guo,1 Shufan Chen,1 Keyu Ling,1 Haihan Li,1 Xiaoli Yu,1 Xiaoping Zhu1 1Department of Nursing, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China; 2School of Nursing, Soochow University, Suzhou, 215031, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoping Zhu, Department of Nursing, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China, Tel +86-021-66300588, Fax +86-021-66307542, Email xiaopingzhu0424@163.comBackground and Objectives: While extensive research has examined the rehabilitation challenges faced by stroke survivors, there is limited literature addressing the difficulties encountered by older adult stroke survivors and their caregivers in accessing rehabilitation and long-term care within the Chinese community. This study aimed to investigate the specific challenges related to access, quality, and coordination of rehabilitation and long-term care experienced by older adult stroke survivors and their caregivers within the Chinese community.Methods: A qualitative phenomenological design was employed to explore the lived experiences of stroke survivors and their caregivers within the Chinese community. A purposive sampling method was used to recruit participants from June to August 2023. Participants engaged in face-to-face semi-structured interviews. The data were analyzed using an inductive thematic analysis approach to identify and understand key themes and sub-themes.Results: The study involved 38 participants, consisting of 21 older adult stroke survivors (13 males, 8 females) and 17 family caregivers (7 males, 10 females), recruited from five Chinese community health service stations. The analysis identified four distinct themes and 11 sub-themes that encapsulated the challenges faced by participants. These themes include (1) Difficulties in accessing medical services (insufficient medical resources, lack of rehabilitation resources, and time-consuming processes), (2) Challenges in daily life (inconvenience in daily mobility, inadequate financial support, and difficulties in applying for home care services), (3) Psychosocial stress (loneliness, powerlessness, and worry about burdening others), (4) Insufficient information (lack of awareness of available community services, and limited public health education activities).Conclusion: Older adult stroke survivors and their caregivers in Chinese communities face significant challenges. To improve their well-being and quality of life, it is crucial to address these challenges through enhanced access to healthcare, better support for daily living, and more effective information dissemination. Meeting these needs requires a coordinated effort from healthcare providers, community stakeholders, and policymakers to develop and implement effective, long-term care solutions.Keywords: stroke, survivors, caregivers, community, qualitative research

Ziyan Zhong,1,* Jian Liu,2,* Yan Luo,1 Mei Wu,1 Feng Qiu,1 Hongqing Zhao,1 Yang Liu,1 Yajing Wang,3 Hongping Long,2 Lei Zhao,4 Yuhong Wang,1 Yuanshan Han,2 Pan Meng1 1Science & Technology Innovation Center, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China; 2The First Hospital, Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People’s Republic of China; 3Office of Science & Technology, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China; 4School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuanshan Han, The First Hospital, Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People’s Republic of China, Email 121983755@qq.com Pan Meng, Science & Technology Innovation Center, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China, Email 004181@hnucm.edu.cnBackground: Depression, a leading cause of disability worldwide, is characterized by dysfunction of immature neurons, resulting in dysregulated calcium homeostasis and impaired structural plasticity. Jujuboside A (JuA), a biologically active compound derived from Semen Ziziphi Spinosae, has demonstrated anti-anxiety and anti-insomnia properties. Recent studies suggest that JuA may be a promising antidepressant, but its underlying mechanisms remain unclear.Methods: Sprague-Dawley rats were subjected to chronic unpredictable mild stress (CUMS) to induce a depression model. JuA (12.5 mg/kg, 25 mg/kg, 50 mg/kg) was administered orally for 4 weeks. Emotional and cognitive function were assessed. Monoamine neurotransmitter levels were measured using enzyme-linked immunosorbent assay (ELISA). The number of immature neurons and calcium homeostasis were evaluated by immunofluorescence. Western blotting and immunofluorescence were employed to detect the expression of Sonic hedgehog (Shh) signaling proteins. Additionally, lentiviral vector expressing Shh shRNA (LV-Shh-RNAi) were infused intracerebrally to investigate the role of Shh in JuA’s antidepressant effects.Results: JuA significantly ameliorated depressive-like behavior and cognitive dysfunction in CUMS rats, increased monoamine neurotransmitter levels in serum and hippocampal tissue, reduced the number of BrdU/DCX (bromodeoxyuridine/doublecortin)-positive immature neurons, and attenuated calcium ion (Ca2+) concentration and Ca2+/calmodulin-dependent protein kinase II (CaMKII) levels in immature neurons. JuA also markedly elevated synaptic density and prominence complexity, upregulated Shh, Gli family zinc finger 1 and 2 (Gli1/2), synaptophysin (Syn) and postsynaptic density protein-95 (PSD-95) expression in the ventral dentate gyrus (vDG). However, knockdown of Shh in the vDG counteracted JuA’s therapeutic effects.Conclusion: These findings collectively suggest that JuA improves depressive-like behavior in CUMS rats by modulating calcium homeostasis and synaptic structural plasticity in immature neurons through the Shh signaling pathway.Keywords: Jujuboside A, Sonic hedgehog, Immature neuron, Calcium homeostasis, Depression

Jiong Li,1 Dongqin Lei,1 Yanbing Cao,2,3 Fuli Xin,2,3 Zhenxi Zhang,1 Xiaolong Liu,2,3 Ming Wu,2,3 Cuiping Yao1 1Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Biomedical Photonics and Sensing, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, 710049, People’s Republic of China; 2The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, People’s Republic of China; 3Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, People’s Republic of ChinaCorrespondence: Ming Wu, Mengchao Hepatobiliary Hospital of Fujian Medical University, 312 Xi Hong Road, Fuzhou, 350025, People’s Republic of China, Email wmmj0419@163.com Cuiping Yao, School of Life Science and Technology, Xi’an Jiaotong University, 28 Xian Ning West Road, Xi’an, 710049, People’s Republic of China, Email zsycp@xjtu.edu.cnIntroduction: Photodynamic therapy (PDT) has attracted increasing attention in the clinical treatment of epidermal and luminal tumors. However, the PDT efficacy in practice is severely impeded by tumor hypoxia and the adverse factors associated with hydrophobic photosensitizers (PSs), including low delivery capacity, poor photoactivity and limited ROS diffusion. In this study, Pt nanozymes decorated two-dimensional (2D) porphyrin metal-organic framework (MOF) nanosheets (PMOF@HA) were fabricated and investigated to conquer the obstacles of PDT against hypoxic tumors.Materials and Methods: PMOF@HA was synthesized by the coordination of transition metal iron (Zr4+) and PS (TCPP), in situ generation of Pt nanozyme and surface modification with hyaluronic acid (HA). The abilities of hypoxic relief and ROS generation were evaluated by detecting the changes of O2 and 1O2 concentration. The cellular uptake was investigated using flow cytometry and confocal laser scanning microscopy. The SMMC-7721 cells and the subcutaneous tumor-bearing mice were used to demonstrate the PDT efficacy of PMOF@HA in vitro and in vivo, respectively.Results: Benefiting from the 2D structure and inherent properties of MOF materials, the prepared PMOF@HA could not only serve as nano-PS with high PS loading but also ensure the rational distance between PS molecules to avoid aggregation-induced quenching, enhance the photosensitive activity and promote the rapid diffusion of generated radical oxide species (ROS). Meanwhile, Pt nanozymes with catalase-like activity effectively catalyzed intratumoral overproduced H2O2 into O2 to alleviate tumor hypoxia. Additionally, PMOF@HA, with the help of externally coated HA, significantly improved the stability and increased the cell uptake by CD44 overexpressed tumor cells to strengthen O2 self-supply and PDT efficacy.Conclusion: This study provided a new strategy of integrating 2D porphyrin MOF nanosheets with nanozymes to conquer the obstacles of PDT against hypoxic tumors.Keywords: 2D porphyrin MOF, hypoxic relief, Pt nanozyme, photodynamic therapy

Dongdong Chen,1,2,* Surong Qian,3,* Wenjun Qian,3 Miao Wu,3 Xinlong Wang,3 Haitao Shen,1 Xianming Long,4 Ming Ye,1 Yan Gong,3 Gang Chen1 1Department of Neurosurgery& Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, People’s Republic of China; 2Department of Neurosurgery, The Affiliated Hospital of Jiang Nan University, Wuxi, Jiangsu, 214000, People’s Republic of China; 3Department of Rehabilitation Medicine, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital Rehabilitation Medical Center, Gusu School, Suzhou, Jiangsu, 215000, People’s Republic of China; 4Department of Rheumatology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan Gong; Ming Ye, Email gongyan200605@126.com; yeming@suda.edu.cnBackground: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique that shows promise for the treatment of Parkinson’s disease (PD). However, there is still limited understanding of the optimal stimulation frequencies and whether rTMS can alleviate PD symptoms by regulating the CaMKII-CREB-BMAL1 pathway.Methods: A PD mouse model was induced intraperitoneally with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and treated with 1 Hz, 5 Hz, and 10 Hz rTMS. The neurological function, survival of dopaminergic neurons, and protein levels of Tyrosine hydroxylase (TH), α-synuclein(α-syn), and brain-derived neurotrophic factor (BDNF) in the striatum were measured to determine the optimal stimulation frequencies of rTMS treatment in PD mice. The levels of melatonin, cortisol, and the circadian rhythm of Brain and muscle ARNT-like 1 (BMAL1) in PD model mice were detected after optimal frequency rTMS treatment. Additionally, KN-93 and Bmal1siRNA interventions were used to verify that rTMS could alleviate PD symptoms by regulating the CaMKII-CREB-BMAL1 pathway.Results: Administration of 10 Hz rTMS significantly improved neurological function, increased the protein levels of TH and BDNF, and inhibited abnormal aggregation of a-syn. Furthermore, administration of 10 Hz rTMS regulated the secretion profile of cortisol and melatonin and reversed the circadian arrhythmia of BMAL1 expression. After the KN-93 intervention, the MPTP+rTMS+KN-93 group exhibited decreased levels of P- Ca2+/calmodulin-dependent protein kinase II (CaMKII)/CaMKII, P-cAMP-response-element-binding protein (CREB)/CREB, BMALI, and TH. After Bmal1siRNA intervention, the protein levels of BMAL1 and TH were significantly reduced in the MPTP+10 Hz+ Bmal1siRNA group. At the same time, there were no significant changes in the proportions of P-CaMKIIα/CaMKIIα and P-CREB/CREB expression levels. Finally, immunohistochemical analysis showed that the number of TH-positive neurons was high in the MPTP+10 Hz group, but decreased significantly after KN-93 and Bmal1siRNA interventions.Conclusion: Treatment with 10 Hz rTMS alleviated MPTP-induced PD symptoms by regulating the CaMKII-CREB-BMAL1 pathway. This study provides a comprehensive perspective of the therapeutic mechanisms of rTMS in PD.Keywords: Parkinson’s disease, transcranial magnetic stimulation, brain and muscle ARNT-like 1, Ca2+/calmodulin-dependent protein kinase II, cAMP-response-element-binding protein

Meng Wu,1,* Shuang Wu,1,* Rui Guo2 1Department of Pharmacy, the First Hospital of China Medical University, Shenyang, 110001, People’s Republic of China; 2Department of Critical Care Medicine, the First Hospital of China Medical University, Shenyang, 110001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rui Guo, Email 18840047020@163.comBackground: Breast cancer is the leading cause of cancer-related deaths among women worldwide. Identifying robust biomarkers for predicting outcomes is essential for improving patient care and reducing fatalities. ZMAT3, a zinc finger protein with potential carcinogenic properties, has been associated with various cancers. However, its role in breast cancer prognosis remains unclear.Methods: We investigated the expression level of ZMAT3 in breast cancer tissues and its association with clinical outcomes through bioinformatics analysis and experimental validation. We examined the correlation between ZMAT3 expression and immune characteristics. ZMAT3 mRNA expression data from The Cancer Genome Atlas (TCGA) were analysed in relation to overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI) in patients with breast cancer. Immunohistochemistry (IHC) was performed on breast cancer tissues to assess ZMAT3 protein levels, with findings validated using qPCR and cell experiments.Results: ZMAT3 mRNA levels were significantly upregulated in breast cancer samples compared to normal tissues. High ZMAT3 expression was significantly correlated with the poor OS, DSS and PFI. A significant positive correlation was observed between high ZMAT3 mRNA levels and the abundance of tumour-infiltrating lymphocytes (TILs), especially CD8+T cells and regulatory T cells (Tregs). Multivariate Cox regression analysis identified ZMAT3 as an independent prognostic factor for breast cancer. IHC staining confirmed increased ZMAT3 protein expression in breast cancer tissues, which was further validated by qPCR and cell function tests.Conclusion: Our findings suggest that ZMAT3 is a prognostic biomarker linked to immune invasion in breast cancer. Elevated ZMAT3 expression correlates with adverse clinical outcomes, indicating its potential role in disease progression.Keywords: breast cancer, cancer prognosis, immunotherapy, bioinformatics, ZMAT3

Xue Yang,1,* Man Wu,2,* Tangzhiming Li,3,* Jie Yu,4 Tian Fu,5 Guoping Li,6 Huanwen Xiong,7 Gang Liao,8 Sensen Zhang,9 Shaofeng Li,10 Zhonghua Zeng,11 Chun Chen,12 Benhui Liang,13,14 Zhiguo Zhou,15 Ming Lu16 1Shenzhen Institute of Respiratory Diseases, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Shanghai Public Health Clinical Center Affiliated to Fudan University, Shanghai, People’s Republic of China; 3Department of Cardiology, Shenzhen Cardiovascular Minimally Invasive Medical Engineering Technology Research and Development Center, Shenzhen People’s Hospital (The Second Clinical Medical College, The First Affiliated Hospital, Southern University of Science and Technology, Jinan University), Shenzhen, Guangdong, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, Jining No 1. People’s Hospital, Jining, Shandong, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Tongde Hospital of Zhejiang Hangzhou, Zhejiang, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, Gaoxin Branch of The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 8Department of Respiratory and Critical Care Medicine, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, Guangdong, People’s Republic of China; 9Department of Respiratory Medicine, The Third Central Hospital of Tianjin, Tianjin, People’s Republic of China; 10Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, People’s Republic of China; 11Department of Respiratory and Critical Care Medicine, The First People’s Hospital of Fuzhou, Jiangxi, People’s Republic of China; 12Cancer Center, Department of Pulmonary and Critical Care Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, People’s Republic of China; 13Department of Cardiology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 14Department of Structural Heart Disease, National Center for Cardiovascular Disease, China & State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Health Commission Key Laboratory of Cardiovascular Regeneration Medicine, National Clinical Research Center for Cardiovascular Diseases, Beijing, People’s Republic of China; 15Department of Pulmonary and Critical Care Medicine, The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, People’s Republic of China; 16Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhiguo Zhou, Department of Pulmonary and Critical Care Medicine, The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, People’s Republic of China, Email zhouzhiguo1217@163.com Ming Lu, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China, Email 602032934@qq.comIntroduction: C. psittaci pneumonia has atypical clinical manifestations and is often ignored by clinicians. This study analyzed the clinical characteristics, explored the risk factors for composite outcome and established a prediction model for early prediction of composite outcome among C. psittaci pneumonia patients.Methods: A multicenter, retrospective, observational cohort study was conducted in ten Chinese tertiary hospitals. Patients diagnosed with C. psittaci pneumonia were included, and their clinical data were collected and analyzed. The composite outcome of C. psittaci pneumonia included death during hospitalization, ICU admission, and mechanical ventilation. Univariate and multivariable logistic regression analyses were conducted to determine the significant variables. A ten-fold cross-validation was performed to internally validate the model. The model performance was evaluated using various methods, including receiver operating characteristics (ROC), C-index, sensitivity, specificity, positive/negative predictive value (PPV/NPV), decision curve analysis (DCA), and clinical impact curve analysis (CICA).Results: In total, 83 patients comprised training cohorts and 36 patients comprised validation cohorts. CURB-65 was used to establish predictive Model 1. Multivariate logistic regression analysis identified three independent prognostic factors, including serum albumin, CURB-65, and white blood cells. These factors were employed to construct model 2. Model 2 had acceptable discrimination (AUC of 0.898 and 0.825 for the training and validation sets, respectively) and robust internal validity. The specificity, sensitivity, NPV, and PPV for predicting composite outcome in the nomogram model were 91.7%, 84.5%, 50.0%, and 98.4% in the training sets, and 100.0%, 64.7%, 14.2%, and 100.0% in the validation sets. DCA and CICA showed that the nomogram model was clinically practical.Conclusion: This study constructs a refined nomogram model for predicting the composite outcome in C. psittaci pneumonia patients. This nomogram model enables early and accurate C. psittaci pneumonia patients’ evaluation, which may improve clinical outcomes.Keywords: Chlamydia psittaci pneumonia, nomogram, prediction model, composite outcome

Menghan Yu,1 Xiaoshu Fu,1 Yanli Zhu,2 Miao Li,3 Min Wu,1 Entong Zhou,1 Hanwen Dong,1 Likun Wang,1 Ruoxi Wang,4 Fang Liu,2 Chunlai Jiang,1 Xiangwei Kong,5 Weiheng Su1,6 1National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, People’s Republic of China; 2People’s Hospital of Jiangyuan District, Baishan, Jilin Province, People’s Republic of China; 3Department of Neurosurgery, China-Japan Union Hospital, Jilin University, Changchun, People’s Republic of China; 4School of Public Health, Capital Medical University, Beijing, People’s Republic of China; 5Changchun University of Science and Technology, Changchun, People’s Republic of China; 6Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, School of Life Sciences, Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Weiheng Su, National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, People’s Republic of China, Email suweiheng@jlu.edu.cn Xiangwei Kong, Changchun University of Science and Technology, Changchun, People’s Republic of China, Email tenbpro@163.comPurpose: Tick-borne encephalitis virus (TBEV) infections result in severe central nervous system diseases in humans across Asia and Europe. In China, cases of tick-borne encephalitis are primarily caused by the Far East subtype of TBEV, which exhibits a distinct disease course compared to other extensively studied subtypes. However, there is limited knowledge regarding the nucleic acid and serological diagnostic characteristics of patients infected with the TBEV in China, which is the focus of investigation in the present study.Methods: This study established a TaqMan qPCR approach to detect TBEV RNA in the serum with optimal specificity, sensitivity, and precision. Using TaqMan qPCR and ELISA assay for TBEV IgM detection, serum samples from 63 hospitalized patients bitten by ticks in Northeast China were investigated for diagnostic characteristics.Results: Twenty-five patients were positive for viral RNA; nineteen patients were positive for IgM, and nine were positive for both viral RNA and IgM. Through comparative analysis, TBEV RNA copies were negatively correlated with the virus incubation period. IgM levels were positively correlated with the clinical symptom scores of patients. The severity of clinical symptoms and the length after the tick bite could be used to predict the IgM occurrence. Furthermore, IgM levels and viral RNA copies were not correlated in double-positive patients.Conclusion: Both nucleic acid and serological detection methods exhibited distinct windows for detecting TBEV infection, with some overlap, and were associated with specific correlated factors. This study provided novel insights into the diagnosis and course of TBEV-induced tick-borne encephalitis in China.Keywords: tick-borne encephalitis, TBE, tick-borne encephalitis virus, TBEV, TaqMan qPCR, IgM

Xi Wu, Qin Li, Mingxing Wu, Haobo Huang, Zhe Liu, He Huang, Lei Wang Department of Cardiology, Xiangtan Central Hospital, Xiangtan, Hunan, 411100, People’s Republic of ChinaCorrespondence: Lei Wang, Department of Cardiology, Xiangtan Central Hospital, Xiangtan, Hunan, 411100, People’s Republic of China, Email heartwl@126.comObjective: The research was carried out to determine and compare the efficiency of completely transradial access (cTRA) and transfemoral access (TFA) in retrograde chronic total occlusion (CTO) percutaneous coronary intervention (PCI).Background: The cases of retrograde chronic total occlusion (CTO) percutaneous coronary intervention usually need the dual access. The transradial method is now used more frequently in CTO PCI, and improves the safety of CTO PCI.Methods: This retrospective, observational study was carried out in a single center. Participants were patients who underwent dual-access retrograde CTO PCI from January 2017 to October 2023, categorized into two groups: cTRA (biradial access) and TFA (bifemoral, or combined radial and femoral access). All patients in the cTRA group received conventional radial access. All punctures of the femoral artery were performed without fluoroscopic or ultrasound guidance. None of the patients in the TFA group accepted any arterial closure devices. Clinical, angiographic and procedural characteristics and the occurrence of in-hospital major adverse cardiovascular events (MACE) of the cTRA and TFA procedures were recorded.Results: This research involved 187 CTO PCI procedures with dual access, of which 88 were done using cTRA and the rest (99) were carried out through TFA. The J-CTO (Multicenter Chronic Total Occlusion Registry of Japan) score was lower in the cTRA group than TFA group (2.1± 0.6 vs 3.0± 0.8; P < 0.001). The technical success (84.1% vs 82.8%; P= 0.817), procedural success (80.7% vs 79.8%; P= 0.906) and in-hospital MACE rates (5.7% vs 4.0%; P= 0.510) were the same for both groups. For a J-CTO score of 3 or higher, technical success rate was significantly lower in the cTRA group than the TFA group (58.1% vs 74.2%; P < 0.001).Conclusion: In the retrograde CTO PCI, the percentages of success and in-hospital MACE were similar for both cTRA and TFA. Meanwhile, cTRA may be used for simpler lesions (J-CTO score < 3) as compared to TFA.Keywords: transradial approach, transfemoral approach, chronic total occlusion, retrograde, percutaneous coronary intervention

Xiujing Lu,&ast; Xi Lan,&ast; Xiaoqian Fu, Jing Li, Min Wu, Lu Xiao, Yachang Zeng Department of Obstetrics and Gynecology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yachang Zeng, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China, Email zengyachang@163.comPurpose: Preeclampsia (PE) is a serious complication of obstetrics and represents a significant challenge in terms of understanding its underlying mechanism. It has been shown that a number of disorders involve dysregulation of the CBP/p300-interacting transactivator with glutamic acid/aspartic acid-rich carboxyl-terminal domain 2 (CITED2). However, the relationship between PE and CITED2 is still mostly unclear. This work aimed to confirm the hub genes linked to PE and explore the roles of CITED2 in trophoblast using experimental and bioinformatic methods.Methods: To determine the hub genes, bioinformatics research was performed on two datasets from the Gene Expression Omnibus (GEO) public database. Immune infiltration analysis and enrichment analysis were also used to identify the related pathways and immune cells. PCR and WB were then used to validate the mRNA and protein levels of CITED2 in the PE samples. Finally, the expression of CITED2 was knocked down using siRNA to investigate the function of CITED2 in trophoblast development in vitro.Results: The study’s findings showed that the NOTCH signaling pathways, glycolysis, and hypoxia were the main areas of enrichment for the six PE-related genes that were tested. The results of immune infiltration suggest that activated NK cells and regulatory T cells may play an important role in this process. CITED2 was significantly upregulated in the PE placenta. In functional tests, the knockdown of CITED2 may enhance apoptosis while suppressing migration, invasion, and proliferation of cells.Conclusion: This study offers important proof that CITED2 influences trophoblast cell function and may one day be a therapeutic target for PE.Keywords: preeclampsia, CITED2, placenta, cell function, bioinformatics

Junqi Liao,1,&ast; Yuan Zhu,1,2,&ast; Aimei Zhang,1 Dan Wu,1 Xiaohui Yan,1 Qiuhua He,1 Fantao Song,1 Jingyi Chen,1 Yunze Li,1 Li Li,1 Zhaoyao Chen,1 Wenlei Li,1 Qin Yang,2 Zhuyuan Fang,3 Minghua Wu1 1Department of Neurology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210029, People’s Republic of China; 2Department of Medicine, Physiology and Biophysics, UC Irvine Diabetes Center, University of California Irvine (UCI), Irvine, CA, USA; 3Department of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Minghua Wu, Department of Neurology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, 155 Hanzhong Road, Nanjing, 210029, People’s Republic of China, Email yfy0069@njucm.edu.cn Zhuyuan Fang, Department of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, 155 Hanzhong Road, Nanjing, 210029, People’s Republic of China, Email fangzhuyuan@njucm.edu.cnBackground: The relationship between insulin resistance-related indices and the outcomes of acute ischemic stroke (AIS) is still unclear. This study aimed to explore the association between the Apo B/Apo A-1 ratio and the Prognostic Nutritional Index (PNI) with the 90-day outcomes of AIS.Methods: A total of 2011 AIS patients with a 3-month follow-up were enrolled in the present study from January 2017 to July 2021. Multivariate logistic regression modeling was performed to analyze the relationship between Apo B/Apo A-1 ratio, PNI, and AIS poor outcomes. The mediating effect between the three was analyzed using the Bootstrap method with PNI as the mediating variable.Results: Among the 2011 included AIS patients, 20.3% had a poor outcome. Patients were categorized according to quartiles of Apo B/Apo A-1 ratio and PNI. Multivariate logistic regression revealed that the fourth Apo B/Apo A-1 ratio quartile had poorer outcomes than the first quartile (OR 1.75,95%CL 1.21– 2.53, P=0.003), and the fourth PNI quartile exhibited a lower risk of poor outcomes than the first quartile (OR 0.40, 95%CL 0.27– 0.61, P< 0.001). PNI displayed a significant partially mediating effect (21.4%) between the Apo B/Apo A-1 ratio and poor AIS outcomes.Conclusion: The Apo B/Apo A-1 ratio is a risk factor for poor AIS outcomes, whereas PNI acts as a protective factor. The association between the ApoB/ApoA-1 ratio and poor AIS outcomes was partially mediated by PNI.Keywords: insulin resistance, Apo B/Apo A-1 ratio, prognostic nutritional index, acute ischemic stroke, outcomes

Beibei Luo, Wenbo Xu, Dan Ye, Xuejing Bai, Mengna Wu, Chunting Zhang, Rui Shi Clinical Laboratory, People’s Hospital of Yuxi City, the Sixth Affiliated Hospital of Kunming Medical University, Yuxi City, Yunnan Province, 653100, People’s Republic of ChinaCorrespondence: Wenbo Xu, Clinical Laboratory, People’s Hospital of Yuxi City, the Sixth Affiliated Hospital of Kunming Medical University, 21 Nieer Road, Yuxi City, Yunnan Province, 653100, People’s Republic of China, Email xwb103196@sina.comIntroduction: Dyslipidemia commonly complicates type 2 diabetes mellitus, yet the relationship between glycosylated hemoglobin and blood lipid levels remains uncertain.Methods: This retrospective cross-sectional study included 27,158 participants from the People’s Hospital of Yuxi. Statistical comparisons for continuous variables utilized analysis of variance (ANOVA), while chi-square analysis was employed for categorical variables. Boxplots assessed the concentration, dispersion, and deviation of total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL-C), and high-density lipoprotein (HDL-C) distribution. A linear regression analysis examined the association between HbA1c and lipid profile, complemented by a fitting curve to visualize trends.Results: Participants who developed diabetes exhibited higher age and elevated Body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), TC, TG, LDL-C, and FPG levels compared to those without diabetes (p < 0.001). Linear regression analysis demonstrated significant associations between HbA1c values and TC, TG, LDL-C, and HDL-C (p < 0.001). The plotted curve indicated that as TC, TG, and LDL levels increased, HbA1c levels rose, while HDL levels decreased.Conclusion: HbA1c was positively correlated with TC, TG, LDL-C, and negatively correlated with HDL-C in the population in the central Yunnan Plateau.Keywords: dyslipidemia, HbA1c, lipid profile

Min Wang,1,&ast; Lin Yang,1,&ast; Suhan Zhang,2 Meng Wu,1 Zhenfeng Sun,3 Liu Shen,1 Xiaowei Xu,1 Liangkun Ma,2 Jiao Li1 1Institute of Medical Information/Library, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100020, People’s Republic of China; 2Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China; 3Daxing District Maternal and Child Health Hospital, Beijing, 102699, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiao Li, Institute of Medical Information & Library Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100020, People’s Republic of China, Tel +8618618461596, Email li.jiao@imicams.ac.cnBackground: Maternity health management has always been the area of concern and considering, and considering its complexity and multidisciplinary, it is necessary to provide effective training for healthcare workers.Purpose: To evaluate the impact of a multidisciplinary experiential training model on the knowledge, attitude, and practice of healthcare workers in maternity health management.Patients and Methods: We conducted a novel educational model, Multidisciplinary Maternity Health Experiential Training based on Knowledge, Attitude and Practice (MMHET), which combined theoretical knowledge, practical skills, and human-centred humanistic care, offering a comprehensive offline education program supported by online teaching materials structured around knowledge graphs. Pre- and post-test surveys were used to assess the changes in participants’ knowledge, attitudes, and practices.Results: From May to July 2023, a total of 322 participants attended the course, and only a small percentage had participated in experiential training. For all topics, the vast majority of participants endorsed the course, and the attitude content had the highest percentage of participants who said they agreed. Among the groups with different years of working life, the highest percentage of participants in the > 20 years group strongly endorsed the course.Conclusion: The preliminary findings indicate that the MMHET model is well-received and feasible, demonstrating its potential to enhance maternity health management education.Keywords: continuing education, pregnancy health, assessment, healthcare, medical education

Boyu Zhang,1,&ast; Yajun Bi,2,&ast; Kang Wang,1,&ast; Xingjun Guo,3 Zeming Liu,1 Jia Li,1 Min Wu1 1Department of Plastic and Cosmetic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Department of Pediatrics, Dalian Municipal Women and Children’s Medical Center (Group), Dalian Medical University, Dalian, Liaoning Province, 116011, People’s Republic of China; 3Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jia Li; Min Wu, Department of Plastic and Cosmetic Surgery, Tongji Hospital, Tongji Medical College 1095 Jiefang Avenue, Wuhan, Hubei, People’s Republic of China, Tel +86 18846818658 ; +86 13554254796, Email 4338311@qq.com; wumin@hust.edu.cnAbstract: Wound healing is a sophisticated and orderly process of cellular interactions in which the body restores tissue architecture and functionality following injury. Healing of chronic diabetic wounds is difficult due to impaired blood circulation, a reduced immune response, and disrupted cellular repair mechanisms, which are often associated with diabetes. Stem cell-derived extracellular vesicles (SC-EVs) hold the regenerative potential, encapsulating a diverse cargo of proteins, RNAs, and cytokines, presenting a safe, bioactivity, and less ethical issues than other treatments. SC-EVs orchestrate multiple regenerative processes by modulating cellular communication, increasing angiogenesis, and promoting the recruitment and differentiation of progenitor cells, thereby potentiating the reparative milieu for diabetic wound healing. Therefore, this review investigated the effects and mechanisms of EVs from various stem cells in diabetic wound healing, as well as their limitations and challenges. Continued exploration of SC-EVs has the potential to revolutionize diabetic wound care. Keywords: diabetes, wound healing, stem cells, EVs, ncRNAs, regeneration

Ling Zhang,1,2 Ronghua Liu,1,2 Shuangmei Ye,1,2 Mingfu Wu,1,2 Rong Liu1,2 1Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of ChinaCorrespondence: Mingfu Wu; Rong Liu, Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Anv, Wuhan, Hubei, 430030, People’s Republic of China, Email wu_mingfu@tjh.tjmu.edu.cn; liurongdoctor@tjh.tjmu.edu.cnPurpose: To recommend the classification of unilateral genital tract obstruction with ipsilateral renal anomaly (UGTOIRA) syndrome into five types based on the site of obstruction, and to analyze the clinical manifestations and precise diagnosis of the syndrome.Methods: The data, including demographic characteristics, symptoms, and precise diagnoses from 59 patients over the last decade, were retrospectively analyzed. Data analysis was conducted using the statistical software package SPSS 26.0.Results: All 59 patients diagnosed with UGTOIRA syndrome were classified into five types based on the site of obstruction: Type I (vaginal obstruction) (45, 76.3%), Type II (cervicovaginal obstruction) (7, 11.9%), Type III (cervical obstruction) (3, 5.1%), Type IV (unilateral partial cervical aplasia) (3, 5.1%), and Type V (Unilateral isthmus atresia) (1, 1.7%). Of these cases, there were 34 cases (57.6%) with communication and 25 cases (42.4%) without communication between the left and right genital tracts. The chief complaints included dysmenorrhea alone in 28 cases (47.5%), dysmenorrhea accompanied by blood dripping after menstruation in 12 cases (20.3%), blood dripping after menstruation alone in 14 cases (23.7%), purulent vaginal secretions in one case (1.7%), vaginal pain in one case (1.7%), irregular menstruation in one case (l.7%), and infertility in two cases (3.4%). The precise diagnostic criteria include the affected side, abnormalities in the kidney and ureter, the site of obstruction, the location of blood accumulation, the size of the ipsilateral genital tract, whether there is communication and its site, the type based on the site of obstruction, and the presence and type of complications.Conclusion: This classification of UGTOIRA syndrome encompasses the anatomical features of all cases reported in our study. Only by fully understanding the anatomical characteristics of this syndrome and identifying its clinical manifestations can clinicians make precise diagnoses as early as possible and provide individualized management.Keywords: uterine malformation, cervical malformation, vaginal malformation, classification, clinical manifestation, diagnosis

Jiayang Li,1,2,&ast; Wenqi Wu,3,&ast; Meilin Wu,4 Zhitao Zhou,4 Jiajie Wang,1 Mingjie Qiu,4 Li Xu,4 Jianan Ren,1,2 Xiuwen Wu1,2 1School of Medicine, Southeast University, Nanjing, People’s Republic of China; 2Research Institute of General Surgery, Jinling Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 3School of Medicine, Nanjing University, Nanjing, People’s Republic of China; 4Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiuwen Wu; Jianan Ren, Research Institute of General Surgery, Jinling Hospital, School of Medicine, Southeast University, 305 East Zhongshan Road, Nanjing, 210002, People’s Republic of China, Email wuxiuwen@nju.edu.cn; jiananr@nju.edu.cnPurpose: Klebsiella pneumoniae carbapenemase (KPC) and New Delhi metallo-β-lactamase (NDM) co-producing carbapenem-resistant Klebsiella pneumoniae (KPC-NDM-CRKP) isolates have been increasingly reported worldwide but have not yet been systematically studied. Thus, we have conducted a study to compare the risk factors, molecular characteristics, and mortality involved in clinical bloodstream infections (BSIs) caused by KPC-NDM-CRKP and KPC-CRKP strains.Methods: A retrospective study was conducted on 231 patients with BSIs caused by CRKP at Jinling Hospital in China from January 2020 to December 2022. Antimicrobial susceptibility testing, carbapenemase genes detection and whole-genome sequencing were performed subsequently.Results: Overall, 231 patients were included in this study: 25 patients with KPC-NDM-CRKP BSIs and 206 patients with KPC-CRKP BSIs. Multivariate analysis implicated ICU-acquired BSI, surgery within 30 days, and longer stay of hospitalization prior to CRKP isolation as independent risk factors for KPC-NDM-CRKP BSIs. The 30-day mortality rate of the KPC-NDM-CRKP BSIs group was 56% (14/25) compared with 32.5% (67/206) in the KPC-CRKP BSIs control group (P = 0.02). The ICU-acquired BSIs, APACHE II score at BSI onset, and BSIs caused by KPC-NDM-CRKP were independent predictors for 30-day mortality in patients with CRKP bacteremia. The most prevalent ST in KPC-NDM-CRKP isolates was ST11 (23/25, 92%), followed by ST15 (2/25, 8%).Conclusion: In patients with CRKP BSIs, KPC-NDM-CRKP was associated with an excess of mortality. The likelihood that KPC-NDM-CRKP will become the next “superbug” highlights the significance of epidemiologic surveillance and clinical awareness of this pathogen.Keywords: KPC and NDM co-producing carbapenem-resistant Klebsiella pneumoniae, Bloodstream infections, risk factors, molecular characteristics, mortality

Min Wu,1,2,&ast; Sining Zeng,3,&ast; Yi Zhang,1,2,&ast; Yanru Liu,1,2 Bingbing Li,1,2 Xuemei Yi,1,2 Yuling Shi,1,2 Xiaoping Zhu3 1Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, 200443, People’s Republic of China; 2Institute of Psoriasis, Tongji University School of Medicine, Shanghai, 200443, People’s Republic of China; 3Nursing Department, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoping Zhu, Nursing Department, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, 301 Yanchang Middle Road, Jing’an District, Shanghai, People’s Republic of China, Tel +86-021-66300588, Fax +86-021-66307542, Email xiaopingzhu0424@163.com Yuling Shi, Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, 1278 Baode Road, Jing’an District, Shanghai, People’s Republic of China, Tel +86-021-36803020, Fax +86-021-36803021, Email shiyuling1973@tongji.edu.cnBackground: Psoriasis is a chronic autoimmune inflammatory skin condition characterized by erythema, papules, and scales. It imposes a heavy psychological and social strain on both patients and their families. Surprisingly, there’s limited research delving into the disease burden and coping strategies of spouses contending with psoriasis.Objective: The objective is to explore the disease burden faced and coping strategies utilized by spouses of individuals living with psoriasis. This exploration aims to offer insights crucial for devising mental health support and intervention strategies.Methods: The research methodology employed in this study was phenomenological, a qualitative approach. A total of fifteen spouses of patients with psoriasis were selected using an objective sampling method for in-depth, semi-structured interviews. Thematic analysis was then applied to the recorded interview data to derive meaningful themes.Results: This study has identified and analyzed three core themes concerning the disease burden and coping strategies of spouses of patients with psoriasis: Overwhelming disease burden; Lack of support system; Coping strategies (Problem - centered coping strategies: Proactive acquisition of disease knowledge; Active confrontation of illness - related issues; Behavioral habit alteration; and Emotional - centered coping strategies: Active acceptance and normalization; Passive acceptance and internalized stigma; Avoidance of disease - related problems).Conclusion: This study adds valuable insights into comprehending the disease burden encountered by spouses of patients with psoriasis and sheds light on the coping strategies they employ. Healthcare providers should proactively recognize and address the burden experienced by spouses early on. Establishing a robust support network is crucial, and promoting adaptive coping strategies can significantly aid spouses in effectively navigating and managing the complexities associated with psoriasis.Keywords: psoriasis, spouse, disease burden, coping strategies, qualitative research

Traidit Thianthanyakij,1,2,&ast; Yinghui Zhou,1,&ast; Mengyi Wu,3,&ast; Yuting Zhang,4 Jui-Ming Lin,1 Yan Huang,4 Yuou Sha,1 Jiayi Wang,1 Sirapath Peter Kong,2 Jinran Lin,1 Qingmei Liu,1 Wenyu Wu1,5,6 1Department of Dermatology, Huashan Hospital, Fudan University, Shanghai Institute of Dermatology, Shanghai, 200040, People’s Republic of China; 2Faculty of Medicine, Thammasat University (Rangsit Campus), Pathumthani, 12120, Thailand; 3Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China; 4State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, 200433, People’s Republic of China; 5Department of Dermatology, Jing’an District Central Hospital, Shanghai, 200040, People’s Republic of China; 6Academy for Engineering and Technology, Fudan University, Shanghai, 200433, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingmei Liu; Wenyu Wu, Email liuqing.mei@163.com; wenyu_wu@fudan.edu.cnBackground: Existing research links oxidative stress and inflammation to hair loss. Salvianolic acid B (SAB) is known for its anti-oxidative, anti-inflammatory, and other beneficial pharmacological properties.Objective: To assess the efficacy of SAB in modulating hair growth.Methods: In vivo experiments were conducted using C57BL/6 mice to evaluate the effects of SAB on hair and skin parameters. The study involved ex vivo analysis of human hair follicles (HFs) for hair shaft length and hair growth cycle assessment. In vitro, human dermal papilla cells (hDPCs) were cultured with SAB, and their proliferation, protection against H2O2-induced oxidative damage, and gene/protein expression alterations were examined using various analytical techniques, including Real-Time Cell Analysis (RTCA), DCFH-DA Assay, RNA-seq, and KEGG pathway analysis.Results: SAB treatment in mice significantly improved hair growth and vascularization by day 21. In human HFs, SAB extended hair shaft length and delayed the transition to the catagen phase. SAB-treated hDPCs showed a notable decrease in the expression of oxidation-antioxidation-related genes and proteins, including reduced phosphorylation levels of ERK and p38.Conclusion: The study indicates that SAB promotes hDPC proliferation and offers protection against oxidative stress, highlighting its potential as a therapeutic agent for enhancing hair growth and treating hair loss.Keywords: salvianolic acid B, hair growth, hair cycle, hair follicle, dermal papilla cells

Weiquan Du,1 Zhaoyuan Fan,1 Diankun Li,2 Mingshuang Wu1 1School of Sociology and Population Studies, Nanjing University of Posts and Telecommunications, Nanjing, People’s Republic of China; 2School of Economics, Nanjing University of Posts and Telecommunications, Nanjing, People’s Republic of ChinaCorrespondence: Weiquan Du, School of Sociology and Population Studies, Nanjing University of Posts and Telecommunications, No. 9, Wenyuan Road, Nanjing City, 210023, People’s Republic of China, Tel +86 13451870628, Email duwq@njupt.edu.cnPurpose: This study focuses on how Internet use behavior affects adolescents’ mental health and whether self-education expectations and parental support mediate the relationship between Internet use behavior and adolescents’ mental health.Methods: The data for this paper came from the results of the student questionnaire of the 2018 Programme for International Student Assessment (PISA 2018), which was a structured questionnaire that asked students about their family situation, school life, studies, internet use, and mental health, among other things. A sample of 336,600 children in grades 7– 13 was selected for this study. The data were analyzed using STATA version 16 and the theoretical framework was tested using a mediated effects model.Results: The results of the study showed that Internet use behavior made a positive contribution to mental health and the mediating effects of self-education expectations and parental support on the relationship between Internet use behavior and adolescent mental health were all significant.Conclusion: It is recommended that appropriate policies should be formulated to help adolescents use the Internet rationally, and the positive effects of parental support and self-education expectations should be utilized.Keywords: adolescent, mental health, internet use, self-education expectations, parental support

Tianrui Zhang,1,&ast; Sha Fu,1,&ast; Xiaofeng Cao,2 Yangjingyi Xia,1 Manyan Hu,1 Qinghua Feng,1 Yujun Cong,1 Yuan Zhu,1 Xiaogang Tang,1 Minghua Wu1 1Department of Neurology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210029, People’s Republic of China; 2Department of Neurology, Jiangyan Hospital of Chinese Medicine, Taizhou, Jiangsu, 225500, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Minghua Wu; Xiaogang Tang, Department of Neurology, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Road, Nanjing, 210029, People’s Republic of China, Tel +8613951786719, Email yfy0069@njucm.edu.cn; zhongyiTXG@163.comPurpose: According to many previous studies, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR) and hypersensitive C-reactive protein (CRP) are commonly used as important indicators to assess the prognosis of intravenous thrombolysis in AIS patients. Based on this, we used two novel biomarkers C-NLR (CRP/neutrophil-to-lymphocyte ratio) and C-LMR (CRP×lymphocyte-to-monocyte ratio) to investigate their correlation with 90-day outcomes in AIS patients after intravenous thrombolysis.Patients and Methods: A total of 204 AIS patients who received intravenous thrombolysis at the Stroke Center of Jiangsu Province Hospital of Chinese Medicine from January 2021 to December 2022 were retrospectively included. All patients were followed up 90 days after thrombolysis to assess their prognosis. Patients with a modified Rankin scale score (mRS) of 3– 6 were included in the unfavorable outcome group, and those with a score of 0– 2 were included in the favorable outcome group. Logistic regression analysis, receiver operating characteristic (ROC) curve, and Kaplan–Meier survival curve were used to investigate the association between C-NLR, C-LMR, and 90-day prognosis in AIS patients treated with early intravenous thrombolysis.Results: C-NLR (OR=1.586, 95% CI=1.098~2.291, P=0.014) and C-LMR (OR=1.099, 95% CI=1.025~1.179, P=0.008) were independent risk factors for 90-day prognosis of AIS patients treated with early intravenous thrombolysis. The higher C-NLR and C-LMR were associated with unfavorable prognosis.Conclusion: C-NLR and C-LMR can be used as biomarkers to predict prognosis of AIS patients treated with early intravenous thrombolysis.Keywords: modified rankin scale, reperfusion therapy, inflammatory reaction, cerebral vascular disease, clinical prognosis

Aiming Lv,1,2 Bian Ba Zhuo Ma,3 De Qiong,2 Da Wa Zhuo Ma,2 Pu Bu Zhuo Ma,3 Donghua Yao,4 Da Zhen,2 Chunxiu Tang,2 Bian Ba Zhuo Ma,2 Youzhi Lu,2 Long Cai,2 Yutong Zhang,2 Jinyu Yin,2 Tong Ding,2 Lang Ji Qu Zhen,2 Da Wa Cang,5 Meng Wu,5 Yulan Chen,5 Ye Li1 1Department of Obstetrics and Gynecology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Department of Obstetrics and Gynecology, Women and Children’s Hospital of Tibet Autonomous Region, Lhasa City, TB, People’s Republic of China; 3Department of Obstetrics and Gynecology, Lhasa People’s Hospital, Lhasa, TB, 850000, People’s Republic of China; 4Department of Obstetrics and Gynecology, Nyingchi People’s Hospital, Nyingchi City, TB, People’s Republic of China; 5Department of Obstetrics and Gynecology, Tibet University Medical School, Lhasa City, TB, People’s Republic of ChinaCorrespondence: Ye Li, Department of Obstetrics and Gynecology, Beijing Hospital, National center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, China, No. 1 DaHua Road, Dong Dan, Beijing, 100730, People’s Republic of China, Tel +86 13611118475, Fax +86 10 85136220, Email liyewtfy@126.comPurpose: To explore the effect of coronavirus disease 2019 (COVID-19) infection on neonates in plateau regions.Methods: Cases of newborns born to pregnant women infected with COVID-19 who received prenatal care or treatment at the Women and Children’s Hospital of the Tibet Autonomous Region and the Lhasa People’s Hospital between January 2020 and December 2022 (infected group) and newborns born to healthy pregnant women (non-infected group) who were included by age, underlying disease and length of hospital stay were retrospectively collected. According to the inclusion and exclusion criteria, 381 patients in the infected group and 314 patients in the non-infected group were included in the study.Results: The results of multivariate analysis showed that admission to the neonatal intensive care unit (OR = 3.342, 95% CI = 1.564– 6.764), shortness of breath (OR = 2.853, 95% CI = 1.789– 3.154), irregular breathing (OR = 2.465, 95% CI = 1.879– 4.112) and neonatal jaundice (OR = 2.324, 95% CI = 1.989– 2.445) were the factors influencing the low Apgar scores of neonates in the infected group (all P < 0.05).Conclusion: Neonates born to pregnant women infected with COVID-19 had lower Apgar scores and higher incidences of complications, such as shortness of breath, groaning, irregular breathing and neonatal jaundice, than newborns born to pregnant women not infected with COVID-19.Keywords: COVID-19, pregnant women, newborn

Li Chen,1,2,&ast; Qiang Liu,2,&ast; Chunlei Tan,3,&ast; Tiangen Wu,4,&ast; Meng Wu,5 Xiaosheng Tan,5 Jinwen Liu,1 Jing Wang2 1Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China; 2Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China; 3Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, People’s Republic of China; 4Department of Hepatobiliary&Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China; 5Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; Key Laboratory of Organ Transplantation, Ministry of Education; NHC Key Laboratory of Organ Transplantation; Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, Hubei, 430030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Wang, Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China, Email wangjing@cicams.ac.cn Jinwen Liu, Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China, Email Liujinwen@tjh.tjmu.edu.cnObjective: The current study is conducted to investigate the potential prognostic value of the age-male-albumin-bilirubin-platelets (aMAP) score in breast cancer patients with liver metastasis after surgery.Methods: This is a retrospective study of 178 breast cancer patients who developed liver metastasis after surgery. These patients were treated and followed up from 2000 to 2018 at our hospital. The aMAP risk score was estimated in accordance with the following formula: . The optimal cutoff value of the aMAP was evaluated via X-tile. Kaplan-Meier, Log-rank and Cox proportional hazards regression models were applied to determine the clinical influence of the aMAP score on the survival outcomes. The nomogram models were established by multivariate analyses. The calibration curves and decision curve analysis were applied to evaluate the estimated performance of the nomogram models.Results: A total of 178 breast cancer patients were divided into low aMAP score group (< 47.6) and high aMAP score group (≥ 47.6) via X-tile plots. The aMAP score was a potential prognostic factor in multivariate analysis. The median disease free survival (p=0.0013) and overall survival (p=0.0003) in low aMAP score group were longer than in high aMAP score group. The nomograms were constructed to predict the DFS with a C-index of 0.722 (95% CI, 0.673– 0.771), and the OS with a C-index of 0.708 (95% CI, 0.661– 0.755). The aMAP-based nomograms had good predictive performance.Conclusion: The aMAP score is a potential prognostic factor in breast cancer with liver metastasis after surgery. The aMAP score-based nomograms were conducive to discriminate patients at high risks of liver metastasis and develop adjuvant treatment and prevention strategies.Keywords: breast cancer, aMAP score, liver metastasis, albumin, prognosis

Mengying Wu,1 Jia Kang,1 Jia Tao,1 Yanwen Yang,2 Gang Li,1 Wei Jia1,3 1Medical Experimental Center, General Hospital of Ningxia Medical University, Yinchuan, People’s Republic of China; 2Department of Neurology, General Hospital of Ningxia Medical University, Yinchuan, People’s Republic of China; 3Ningxia Key Laboratory of Clinical and Pathogenic Microbiology, General Hospital of Ningxia Medical University, Yinchuan, People’s Republic of ChinaCorrespondence: Wei Jia, Medical Experimental Center, General Hospital of Ningxia Medical University, Yinchuan, 750001, People’s Republic of China, Tel +86 951-6744013, Email Jiawei220803@163.comPurpose: To understand the detection rate and distribution characteristics of Linezolid-nonsusceptible Enterococcus (LNSE) and analyze the molecular typing and main drug resistance mechanisms of LNSE, providing a theoretical basis for the precision prevention and control of LNSE hospital infections.Methods: A total of 40 LNSE strains isolated from clinical specimens between January 1, 2012, and December 31, 2022, were collected. The LNSE isolates identified by instrument detection were confirmed using a microbroth dilution method. The WHONET 5.0 software was used for statistical analysis of LNSE detection rate, and the LNSE judgment was based on the 2022 CLSI criteria. PCR methods were used to detect 23S rRNA, cfr, optrA, and L3, L4 ribosomal RNA sites for linezolid resistance genes, and gene sequencing was used to verify the amplified PCR products. Multiple locus sequence typing (MLST) was performed to analyze the homology of LNSE strains.Results: A total of 6924 Enterococcus isolates were separated and identified from January 1, 2012, to December 31, 2022, of which 40 were LNSE strains (26 Enterococcus faecalis, 14 Enterococcus faecium), with a detection rate of 0.58% (40/6924). Among them, 28 Linezolid-intermediated Enterococcus(LIE) were detected, accounting for 0.4% (28/6924), and 12 Linezolid-resistant Enterococcus(LRE) were detected, with a detection rate of 0.17% (12/6924). Among the LNSE strains, 23 were resistant to genes. The 40 LNSE strains could be divided into 20 different ST types, with ST16 being the main type, accounting for 12.5% (5/40).Conclusion: The detection of LNSE strains was dominated by Enterococcus faecalis, and the main resistance mechanism of LRE strains was carrying the optrA gene, with 23S rRNA gene mutations also contributing to resistance. New resistance gene phenotypes (optrA +/23S rRNA+) emerged. Most LRE cases were sporadic, and clonal dissemination was observed in some strains.Keywords: linezolid-nonsusceptible Enterococcus, PCR, MLST, ST16, optrA

Mei Wu,1,2,&ast; Jingui Zhao,1,2,&ast; Zhongqiang Liu,1,2 Haiyang Zhang1,2 1Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haiyang Zhang, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China, Tel + 86 15756273633, Fax + 86 15756273633, Email icudoc@163.comBackground: Clinically, Carbapenem-resistant Pseudomonas aeruginosa (CRPA) meningitis is extremely difficult to cure and has a high mortality rate. Intrathecal injection of polymyxins B is suggested to be an effective anti-infective means to treat intracranial infection with CRPA. However, due to the potential drug toxicity of polymyxin B in children, this regimen has rarely been reported in pediatrics.Case Description: A 5-year-old male patient diagnosed with Epstein-Barr virus-induced hemophagocytic syndrome (HPS) exhibited persistent fever for over a month despite antibacterial and chemotherapy regimens. During hospitalization, the patient presented with unconsciousness, nystagmus, and myasthenia. Cerebrospinal fluid (CSF) analysis indicated elevated leukocyte counts and protein levels. Sputum and blood cultures, as well as metagenomic next-generation sequencing (mNGS) of CSF, identified CRPA. Intravenous and intrathecal polymyxin B administration resulted in temperature normalization and amelioration of consciousness disturbances and nystagmus. Subsequent CSF analysis yielded normal results, while polymyxin B treatment exhibited no nephrotoxicity or neurotoxicity.Conclusion: Intrathecal injection of polymyxin B in children with meningitis caused by CRPA is an effective treatment without remarkable adverse events.Keywords: polymyxin B, intrathecal injection, carbapenem resistant, Pseudomonas aeruginosa, meningitis

Fengbo Liu,1 Yue Xi,2 Ning Li,3 Ming Wu4 1School of Physical Education, Zhengzhou University of Light Industry, Zhengzhou, Henan Province, People’s Republic of China; 2College of Physical Education and Health, East China Normal University, Shanghai, People’s Republic of China; 3School of Physical Education, Putian University, Putian, Fujian Province, People’s Republic of China; 4Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of ChinaCorrespondence: Fengbo Liu, School of Physical Education, Zhengzhou University of Light Industry, Zhengzhou, Henan Province, People’s Republic of China, Email lfbzzuli@126.comObjective: To explore the impact of brief mindfulness training on college students’ mobile phone addiction and the mediating effect of the sense of meaning in life between them.Methods: This study has employed the mixed experimental design of 2 (experimental conditions) × 2 (time points), randomly assigned 44 college students into a mindfulness training group and a control group (22 college students in each group), and selected the Freiburg Mindfulness Inventory (FMI), Mobile Phone Addiction Tendency Scale (MPATS), and Chinese Meaning in Life Questionnaire (C-MLQ) to conduct separate tests before and after mindfulness training.Results: The results show that: (1) in the pretest, the differences between the mindfulness training group and the control group in the level of mindfulness, the level of mobile phone addiction, and the sense of meaning in life are not statistically significant; (2) in the posttest, compared with those of the control group, both the FMI score (p=0.013) and the C-MLQ score (p< 0.001) of the mindfulness training group improve significantly, while the MPATS score (p=0.008) of the mindfulness training group declines significantly; and (3) the Bootstrap analysis of the mediating effect shows that after the change in C-MLQ (95% CI [0.537, 11.630]) enters the equation, the direct effect of mindfulness training is not significant (95% CI [− 3.254, 5.861]).Conclusion: The results of this study reveal the impact and mechanism of brief mindfulness training on college students’ mobile phone addiction, and provide an empirical basis for intervening on mobile phone addiction.Keywords: brief mindfulness, mobile phone addiction, sense of meaning in life, mediating effect

Runing Zhou,1 Xiyu Sun,2 Mingyue Guo,1 Huimin Zhang,1 Xuanfu Chen,1 Meixu Wu,1 Haozheng Liang,1 Xiaoyin Bai,1 Gechong Ruan,1 Hong Yang1 1Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China; 2Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of ChinaCorrespondence: Hong Yang, Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, 100730, People’s Republic of China, Tel +86-10-69155014, Email yangh@pumch.cnAim: The diagnosis of inflammatory bowel disease (IBD) worldwide is complicated and results in diagnostic delay. However, the diagnostic interval of IBD and the factors associated with diagnostic delay in patients in China have not been determined.Methods: We retrospectively analyzed clinical data of hospitalized IBD patients in Peking Union Medical College Hospital from January 1998 to January 2018. Patients were divided into non-delayed and delayed groups according to their diagnostic interval.Results: A total of 516 and 848 patients were confirmed to have Crohn’s disease (CD) and ulcerative colitis (UC), respectively. The median diagnostic intervals were 6 and 20 months in patients with UC and CD, respectively (P< 0.05). A decreasing trend in the diagnostic interval for IBD was observed over time, from 9 months to 1 month in UC patients and from 30 months to 3 months in CD patients. The longest diagnostic interval was 29.5 months in CD patients with first symptoms at the age of 51– 60 years and 12.5 months in UC patients at the age of 41– 50 years. In patients with CD, intestinal obstruction (OR=2.71), comorbid diabetes (OR=4.42), and appendectomy history (OR=2.18) were risk factors for diagnostic delay, whereas having fever as the first symptom may reduce its risk (OR=0.39). In patients with UC, the misdiagnosis of chronic enteritis (OR=2.10) was a risk factor for diagnostic delay.Conclusion: The diagnostic interval for IBD has decreased over the years. Some clinical manifestations, such as initial symptoms and age at symptom onset, may help to shorten this interval. Diseases such as tuberculosis and infectious enteritis should be considered during differentiation.Keywords: inflammatory bowel disease, diagnostic delay, China

Mingjuan Wu,&ast; Xin Xie,&ast; Qianying Jiang Department of Gynaecology, Wuxi Maternal and Child Health Hospital, Wuxi School of Medicine, Jiangnan University, Wuxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qianying Jiang, Department of Gynaecology, Wuxi Maternal and Child Health Hospital, Wuxi School of Medicine, Jiangnan University, No. 48, Huaishu Road, Wuxi, 214002, People’s Republic of China, Email jqy1727@163.comBackground: Ovarian cysts are common diseases among women. They might affect reproductive function in severe cases, and thus, patients with ovarian cysts often have negative emotions.Purpose: In this study, we elucidated the risk factors for negative emotions in patients with ovarian cysts during the perioperative period and their impact on prognosis.Methods: From August 2019 to August 2021, we retrospectively included 330 female patients with pathologically diagnosed benign ovarian cysts as potential participants in this study. Based on the established inclusion and exclusion criteria, 308 patients were finally included. We performed the t-test and Chi-squared test to analyze the relationship between the negative emotions of the patients and prognosis. Binary logistic regression and linear regression were used to assess independent risk factors for negative patient mood and prognosis.Based on SAS and SDS scores, patients with anxiety and/or depression are considered to combined negative emotions.Results: In total, 47 patients (15.3%) had negative emotions during the perioperative period. The results of the binary logistic regression analysis showed that the menstrual status (OR = 3.099, P = 0.028), intraoperative blood loss (OR = 1.043, P = 0.029), recurrence (OR = 3.691, P = 0.047), and several other factors were independent risk factors for negative emotions. The results of the linear regression analysis showed that the presence of combined negative affect (P = 0.000), recurrence (P = 0.010), postoperative IL-2 (P = 0.035), and several other factors were independent risk factors for patient prognosis.Conclusion: In clinical work, identifying the independent risk factors for negative emotions and enhancing their behavioral awareness and self-efficacy is necessary to improve their quality of life after surgery. Meanwhile, we will continue our exploration of the causes of negative emotions in patients in the future.Keywords: benign ovarian cyst, negative emotions, prognosis, anxiety, depression

Xi Wu, Mingxing Wu, Haobo Huang, Lei Wang, Zhe Liu, Jie Cai, He Huang Department of Cardiology, Xiangtan Central Hospital, Xiangtan, Hunan, 411100, People’s Republic of ChinaCorrespondence: He Huang, Department of Cardiology, Xiangtan Central Hospital, Xiangtan, Hunan, 411100, People’s Republic of China, Email 1764200045@e.gzhu.edu.cnPurpose: The prognostic implications of calcified versus non-calcified tissue protrusions (TPs) following stent implantation remain undetermined. This study aimed to evaluate the differential clinical outcomes associated with calcified and non-calcified TP morphologies.Patients and Methods: Employing intravascular ultrasound (IVUS), we identified calcified TPs as calcium fragment extrusions permeating the stent struts, while non-calcified TPs were characterized as plaque and/or thrombus extensions through the stent into the arterial lumen. The primary endpoint encompassed target lesion failure (TLF), comprising cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization (TLR), or stent thrombosis, assessed in patients with a follow-up period exceeding one year.Results: Of 1033 patients subjected to pre- and post-intervention IVUS, 62 exhibited calcified TPs (6.0%), and 279 presented non-calcified TPs (27.0%), forming the basis of this analysis. Multivariable linear regression indicated calcified nodules as a significant predictor of calcified TP [Odds Ratio (OR) 2.47; 95% Confidence Interval (CI) 2.33 to 2.62; P < 0.001], with ST-segment elevation myocardial infarction emerging as an inverse correlate [OR 0.82; 95% CI 0.73 to 0.93; P = 0.004]. Two-year data revealed a higher incidence of TLF in patients with calcified TPs versus their non-calcified counterparts (11.3% vs 2.2%, P < 0.001), and a marked increase in clinically driven TLR (9.7% vs 1.4%, P < 0.001). Calcified TPs were independently correlated with increased TLF risk in the adjusted model [Hazard Ratio (HR) 2.47; 95% CI 1.17 to 5.16; P = 0.027].Conclusion: After drug-eluting stent implantation, IVUS-identified calcified TPs correlate with adverse clinical outcomes compared to non-calcified TP formations.Keywords: percutaneous coronary intervention, intravascular ultrasound, tissue protrusion, prognosis

Honghao Yu,&ast; Yiping Wu,&ast; Boyu Zhang, Mingchen Xiong, Yi Yi, Qi Zhang, Min Wu Department of Plastic and Cosmetic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qi Zhang; Min Wu, Tel +86 15951072198 ; +86 13554254796, Email zhangqi06172@163.com; wumin@hust.edu.cnBackground: Skin wound is a widespread health problem and brings extraordinary burdens to patients. Exosomes derived from adipose-derived stem cells (ADSC-Exos) are considered promising strategies for repairing skin wounds. E2F1 is a member of the E2F family of transcription factors involved in cell growth and apoptosis. E2F1 deficiency in mice enhances wound healing by improving collagen deposition and angiogenesis. Additionally, E2F1 can regulate the transcription and paracrine activity of multiple miRNAs, which will inevitably reshape the paracrine expression profile of ADSC-Exos. This study aimed to investigate the impact of transcription factor E2F1 deficiency on the functions of ADSC-Exos in promoting wound healing.Methods: First, we obtained ADSCs from subcutaneous adipose tissues of WT and E2F1–/– C57BL/6 mice and separated their exosomes, denoted as ADSCWT-Exos and ADSCE2F1-/--Exos. The wound healing effects of ADSCWT-Exos and ADSCE2F1-/--Exos in full-thickness skin wound models were investigated by wound images, H&E staining, and immunohistochemical staining. For the in vitro study, the abilities of ADSCWT-Exos and ADSCE2F1-/--Exos to promote cell activities, collagen formation, and angiogenesis were evaluated. The potential mechanism by which ADSCE2F1-/--Exos promote wound healing was determined by miRNA sequencing, ChIP‒qPCR, and dual-luciferase assays.Results: ADSCE2F1-/--Exos accelerated wound healing by promoting collagen formation and angiogenesis. As a result, compared with the lower wound healing rate of 30.5% within 7 days in the control group and 42.3% in the ADSCWT-Exo group, ADSCE2F1-/--Exos significantly increased the wound healing rate to 72.5%. In vitro, ADSCE2F1-/--Exos activated the function of fibroblasts and vascular endothelial cells. The loss of E2F1 promoted miR-130b-5p expression in ADSCE2F1-/--Exos through transcriptional regulation. MiRNA high-throughput sequencing identified 12 differently expressed miRNAs between ADSCE2F1-/- and ADSCWT. ADSCE2F1-/--Exos enhanced fibroblast activities via the miR-130b-5p/TGFBR3 axis and TGF-β activation.Conclusion: Our results indicated that ADSCE2F1-/--Exos effectively promoted wound healing by regulating the miR-130b-5p/TGFBR3 axis, thus providing a novel strategy of gene-engineered stem cell exosomes for accelerating wound healing. Keywords: wound healing, adipose-derived stem cells, exosome, E2F1, miR-130b-5p

Jingbo Li,1,&ast; Kun Zhou,2,3,&ast; Meng Wu,3,&ast; Rongzheng Zhang,3 Xi Jin,3 Han Qiao,3 Jiaqi Li,3 Xinyang Cao,3 Shuyun Zhang,3 Guanglu Dong4 1Department of Anesthesiology Research Institute, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 2Department of Clinical Laboratory, Beidahuang Industry Group General Hospital, Harbin, People’s Republic of China; 3Scientific Research Center, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 4Department of Tumor Radiotherapy, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guanglu Dong, Department of Tumor Radiotherapy, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China, Tel +1 380 450 3001, Email DGL64@163.com Shuyun Zhang, Scientific Research Center, the Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China, Tel +1 321 450 1198, Email 13214501198@163.comPurpose: Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer-related deaths, posing a significant threat to people in diverse regions. T-cell exhaustion (Tex) can hinder the efficacy of immunotherapy in patients with HCC, and the transcription factors that regulate Tex in HCC have not yet been fully elucidated.Patients and Methods: We used the single sample gene set enrichment analysis (ssGSEA) method to define the transcription factor pathway that regulates Tex and employed LASSO regression analysis to establish Tex related genes (TEXRS). To predict differences in immunotherapy efficacy between the two groups, we used the immunophenotype score and submap algorithm. RT-qPCR was used to detect the expression levels of the model genes in 21 pairs of HCC tissues. Finally, we assessed the cell communication strength and identified ligand receptors using the “CellChat” R package.Results: Nine Tex transcription factors were identified as regulators of the HCC immune microenvironment, with Tex scores affecting patient survival. Patients with a high Tex Risk Score (TEXRS) had significantly worse overall survival compared to patients with low TEXRS. After adjusting for confounding factors, TEXRS remained an independent prognostic factor. Importantly, TEXRS performed well in multiple independent external validation cohorts. Various algorithms have shown that patients in the low-TEXRS group might benefit more from immunotherapy. Finally, RT-qPCR analysis of 21 HCC samples showed that C7, CD5L, and SDS were significantly downregulated in HCC tissues, consistent with the bioinformatics analysis results.Conclusion: TEXRS proved to be a valuable predictor of immunotherapy and transcatheter arterial chemoembolization efficacy in patients with HCC. This holds promise for enhancing the prognosis and treatment outcomes of patients with HCC.Keywords: T-cell exhaustion, transcription factors, single-cell RNA sequencing, immune microenvironment, immunotherapy

Yongkang Liu,1 Cuiping Yuan,1 Xiao Chen,1 Xiaokun Fang,1 Jingru Hao,1 Maodong Zhou,1 Xin Sun,1 Minghua Wu,2 Zhongqiu Wang1 1Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China; 2Department of Encephalopathy Center, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of ChinaCorrespondence: Zhongqiu Wang, Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China, Tel/Fax +86 25-86618472, Email zhqwang2012@126.com Minghua Wu, Department of Encephalopathy Center, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China, Tel/Fax +86 25-86618472, Email yfy0069@njucm.edu.cnPurpose: White matter hyperintensities (WMH) are the common marker of cerebral small vessel disease (CSVD). Dyslipidemia plays a notable role in the pathogenesis of CSVD. However, the relationship between dyslipidemia and WMH is poorly elucidated. This study aims to investigate the association between serum lipid fractions and WMH in patients with acute ischemic stroke (AIS).Patients and Methods: A total of 901 patients with AIS were included in this study. The burden of WMH, including deep white matter hyperintensities (DWMH), periventricular white matter hyperintensities (PVWMH), and total WMH load, were evaluated on magnetic resonance imaging (MRI) by the Fazekas scale. All the WMH burden were set as dichotomous variables. Serum levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) were collected. The association of serum lipid fractions with WMH burden was analyzed using univariate and multivariate logistic regression models.Results: The average age of the participants was 67.6± 11.6 years, and 584 cases (64.8%) were male. About 33.5% (n = 302) patients were smoker, and 23.5% (n = 212) patients had a history of alcohol consumption. The proportion of previous diabetes, ischemic cardiomyopathy and hypertension was 39.0% (n = 351), 21.2% (n = 191) and 75.9% (n = 684), respectively. The average of serum HDL-c, TC, TG, LDL-c levels for all participants were 1.26 ± 0.28 mmol/l, 4.54 ± 1.06 mmol/l, 1.67 ± 1.09 mmol/l, 3.08 ± 0.94 mmol/l. There were no statistical associations between HDL-c, TG, TC, LDL-c and each type of WMH burden (P > 0.05) in multivariate logistic regression analysis. Similar findings were found in subgroup analysis based on gender classification.Conclusion: Serum lipid levels were not associated with the presence of any type of WMH in patients with AIS.Keywords: white matter hyperintensities, HDL-c, triglyceride, total cholesterol, LDL-c, acute ischemic stroke

Mingjuan Liu,1– 3 Meiyi Tong,1,2 Jia Zhou,1,2 Yining Lan,1,2 Mengyin Wu,1,2 Hanlin Zhang,1,2 Ling Leng,2 Heyi Zheng,1,2 Yanfeng Li,4 Mingli Li,5 Jun Li1,2 1Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, People’s Republic of China; 2State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, People’s Republic of China; 3 4+4 M.D. Program, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, People’s Republic of China; 4Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, People’s Republic of China; 5Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, People’s Republic of ChinaCorrespondence: Mingli Li; Jun Li, Email limingli@pumch.cn; lijun35@hotmail.comPurpose: General paresis is a common type of neurosyphilis featuring progressive cognitive deterioration. The lack of a golden standard of diagnosis and its nonspecific clinical manifestations resulted in a high rate of misdiagnoses. This study aims to investigate the clinical, laboratory and radiological presentations of general paresis and enrich its knowledge for timely diagnoses.Patients and methods: The study collected hospitalized patients admitted for general paresis from September 2002 to November 2022. Their socio-demographical and medical status, clinical presentations, cognitive assessments, laboratory and radiographical manifestations and treatment information were collected retrospectively.Results: A total of 20 males and 5 females were included. Patients’ ages ranged from 30 to 66 years (average 50.3 years). The average and median time for diagnosing general paresis was 14.1 months and 10.0 months respectively. The most frequent initial symptom is memory deterioration (68.0%). Impaired calculative ability and memory deterioration were the most frequent cognitive anomalies, as found in 50% and 45.4% of subjects during examination. The mean and median scores of MoCA was 16.7 and 17 respectively. Serological tests revealed positive TPPA for all patients and a median RPR titer at 1:64 positive. All CSF samples with TPPA and FTA-ABS results reported positivity. The MRI manifestations of general paresis include patchy or speckled hyperintensities (70.8%) and cerebral atrophy (45.8%). The most common lesioned sites in MRI were the ventricular and paraventricular area (50.0%) and temporal lobes (45.8%). For treatment, penicillin-based anti-syphilitic plans were adopted in 17 patients (68.0%).Conclusion: The clinical features and radiological alternations of general paresis patients often exhibited diverse and nonspecific alternations. However, some specific clinical manifestations and auxiliary examinations can provide meaningful clues for the identification and differential diagnosis of this disease.Keywords: neurosyphilis, general paresis, syphilis, neuropsychiatric symptoms

Jian Liu,1,2 Minglan Wu,1,2 Jiejing Kai,1,2 Meihua Lin,1,2 Yunliang Zheng,1,2 Yiya Jiang,1,2 Qian Huang,1,2 You Zhai,1,2 Yunqing Qiu2,3 1Department of Clinical Pharmacy, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 2Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, Hangzhou, Zhejiang Province, People’s Republic of China; 3State Key Laboratory for Diagnosis and Treatment of Infectious Disease, the First Affiliated Hospital, Zhejiang University, School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Yunqing Qiu, Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, Hangzhou, Zhejiang Province, 310003, People’s Republic of China, Tel/Fax +86 571 87236606, Email qiuyq@zju.edu.cnPurpose: Tenofovir amibufenamide (TMF) is a novel nucleotide reverse transcriptase inhibitor. The aim of this study was to investigate the effect of food on the single-dose pharmacokinetic properties of TMF.Patients and Methods: In this open-label, randomized, crossover study, after an overnight fast, eligible subjects received a single 25 mg dose of TMF tablet, either under fasted conditions or following consumption of a high-fat, high-calorie meal, followed by a two-week washout period. Blood samples were collected until 144 h after administration. TMF and its metabolite, tenofovir (TFV), were analyzed using validated liquid chromatography-tandem mass spectrometry methods. The geometric mean ratio (GMR) and the corresponding 90% confidence interval (CI) values of AUC0–t, AUC0–∞, and Cmax were acquired for analysis. The absence of an effect of food was indicated if the 90% CI values were within the predefined equivalence limits of 80%– 125%. Safety and tolerability were also assessed.Results: For TMF, adjusted GMR (90% CI) values for the fed versus fasted states were 150.28% (125.36%– 180.16%), 158.24% (130.42%– 192.00%), and 57.65% (45.68%– 72.76%) for AUC0–t, AUC0–∞, and Cmax, respectively. For TFV, the GMR (90% CI) of Cmax was 82.00% (74.30%– 90.49%) after administration under fed conditions, slightly outside the bioequivalence boundary of 80%– 125%, while the corresponding values for AUC0–t and AUC0–∞ were within range. The absorption of TMF was delayed by food, with median Tmax values of 0.33 and 1.00 h in fasted and fed conditions, respectively. The adverse events observed in subjects were all mild.Conclusion: Our results demonstrated that TMF tablets were well-tolerated in healthy volunteers. When TMF tablets were taken with food, Tmax was delayed and exposures of TMF and TFV were higher than under fasted conditions. The modest changes observed are not considered clinically relevant, so TMF can be taken with or without food.Plain Language Summary: Tenofovir amibufenamide (TMF) is the first innovative, oral anti-hepatitis B drug to be developed in China. To better understand the effect of food on TMF bioavailability, 25 mg of TMF was given with or without food randomly to twenty healthy volunteers. Plasma samples were collected up to 144 h after dosing to measure the concentrations of TMF and its metabolite, tenofovir (TFV).The rate of drug absorption was measured by determining the maximum plasma concentration of drug (Cmax) and the time to Cmax (Tmax). The amount of drug absorbed was measured using the area under the plasma concentration-time curve (AUC). When subjects were fed, the AUC values for TMF and TFV were higher than when they fasted. The Cmax values for TMF and TFV under fed conditions were lower compared with fasted conditions. The Tmax of TMF was delayed when subjects were fed compared with fasted. The modest changes observed are not considered clinically relevant. The adverse events (AEs) occurring in volunteers were all mild. Our findings suggested that TMF can be taken with or without food.Graphical Abstract: Keywords: tenofovir amibufenamide, food, pharmacokinetics, safety

Mingshuang Wu,&ast; Chenxi Pan,&ast; Yi He, Bo Yang Department of Urology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi He; Bo Yang, The Second Affiliated Hospital of Dalian Medical University, 467, Zhongshan Road, Shahekou District, Dalian, 116044, People’s Republic of China, Tel/Fax +86 411 84671291, Email heyi_gzr@163.com; yangbo20160101@163.comPurpose: The goal of this study was to assess the prognostic impact of the lower urinary tract symptoms (LUTS) in advanced prostate cancer (PCa) patients before progression to castration-resistant prostate cancer (CRPC).Methods: A retrospective analysis of the follow-up data for 152 CRPC patients was performed. Severe LUTS symptom was defined as an International Prostate Symptoms Score (IPSS) ≥ 20 at baseline. Cox regression analysis was conducted to assess CRPC prognostic factors. Nomogram model was created and assessed using the concordance index (C-index), calibration curves, receiver operating characteristic (ROC) curves, and decision curve analyses (DCA).Results: The median CRPC free survival of patients with severe LUTS was 20.5 months, significantly longer than that (7.5 months) of less symptomatic patients. Furthermore, severe LUTS, the hemoglobin, albumin, lymphocyte, and platelet (HALP) score, and Gleason sum were determined to be independent prognostic markers and combined to establish a nomogram, which performed well in the customized prediction of CRPC progression at 6th, 12th, 18th and 24th month. The C-index (0.794 and 0.816 for the training and validation cohorts, respectively), calibration curve, and ROC curve all validated the prediction accuracy. DCA curve showed that it could be effective in helping doctors make judgments. The Nomogram-related risk score separated the patients into two groups with notable progression differences.Conclusion: Severe LUTS was significantly associated with decreased risk for rapid progression to CRPC. The developed nomogram could help identify patients who are at a high risk of rapid CRPC progression and provide tailored follow-up and therapeutic advice.Keywords: LUTS, HALP, castration-resistant prostate cancer, nomogram

Mengjun Wu,1 Chan Dai,2 Fanfan Zeng3 1Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 3Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of ChinaCorrespondence: Fanfan Zeng, Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China, Email zengfanfan@126.comAbstract: Psoriasis is a common inflammatory skin disease characterized by abnormal proliferation of epidermal keratinocytes and massive infiltration of inflammatory cells. Many kinds of cells, including keratinocytes, T lymphocytes, dendritic cells, neutrophils, and macrophages, are reported to play critical roles in the pathogenesis and progression of psoriasis. However, to date, the role of each kind of cell in the pathogenesis and development of psoriasis has not been systematically reviewed. In addition, although antibodies developed targeting cytokines (e.g. IL-23, IL-17A, and TNF-α) released by these cells have shown promising results in the treatment of psoriasis patients, these targeted antibodies still do not cure psoriasis and only provide short-term relief of symptoms. Furthermore, long-term use of these antibodies has been reported to have adverse physical and psychological effects on psoriasis patients. Therefore, gaining a deeper understanding of the cellular and molecular pathogenesis of psoriasis and providing new thoughts on the development of psoriasis therapeutic drugs is of great necessity. In this review, we summarize the roles of various cells involved in psoriasis, aiming to provide new insights into the pathogenesis and development of psoriasis at the cellular level and hoping to provide new ideas for exploring new and effective psoriasis treatments.Keywords: psoriasis, cellular pathogenesis, keratinocytes, immune cells

Mingjuan Liu,1– 3 Jia Zhou,1,2 Yining Lan,1,2 Hanlin Zhang,1,2 Mengyin Wu,1,2 Xinyi Zhang,4 Ling Leng,1,2 Xia Mi,5 Jun Li1,2 1Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 3 4+4 M.D. Program, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 4Departments of Internal Medicine and Cellular & Molecular Physiology, Yale School of Medicine, New Haven, CT, USA; 5Department of Dermatology, Strategic Support Force Medical Center, Beijing, People’s Republic of ChinaCorrespondence: Xia Mi; Jun Li, Tel +86-69156699, Email mixia501@163.com; lijun35@hotmail.comAbstract: The COVID-19 pandemic has profoundly changed our lives. While healthcare resources were redistributed and mobilized to focus on dealing with the COVID-19 crisis, there have been unmet medical needs of patients with other diseases such as syphilis, weaving an integral but neglected component of the pandemic story. In different countries, the epidemiology of newly reported syphilis underwent diverse changes during the COVID-19 pandemic. Asymptomatic cases experienced the largest decline in number. From the perspective of transmission, on one hand, the implementation of lockdown measures led to a higher degree of abstinence and sex distancing in many countries, thereby reducing the transmission of syphilis. On the other hand, vertical transmission was reported to have increased significantly during COVID-19. Meanwhile, the volume of STI clinic capacity declined, and STI staff were redeployed to facilitate the contact tracing of COVID-19. As a result, many STI centers converted traditional in-person clinical services to telemedicine and self-testing. However, syphilis testing and clinical treatment cannot fully adapt to this conversion. In syphilis diagnosis, COVID-19 infection and vaccination were reported to cause false positivity in syphilis serological tests. Diverse cutaneous manifestations of COVID-19 could resemble the skin lesions in syphilis patients, requiring differential diagnosis from clinicians. As for the post-pandemic years, consequent to service interruptions and diagnosis delays, a surge in the number of confirmed cases of syphilis is expected. The COVID-19 pandemic has also been a meaningful lesson for the control and prevention of infectious diseases. The experience in combating COVID-19 has underscored the importance of maintaining a robust and well-supported medical system for the provision of sexual health services and better healthcare equality even during eras of crisis, not least for syphilis patients.Keywords: COVID-19, syphilis, sexual behavior, STD prevention

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

Xi Wu,&ast; Mingxing Wu,&ast; Haobo Huang,&ast; Zhe Liu, Jie Cai, Qizhou Zhang, He Huang Department of Cardiology, Xiangtan Central Hospital, Xiangtan, Hunan, 411100, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: He Huang, Department of Cardiology, Xiangtan Central Hospital, Xiangtan, Hunan, 411100, People’s Republic of China, Email 1764200045@e.gzhu.edu.cnPurpose: This research aimed to evaluate the procedural and in-hospital clinical outcomes of percutaneous coronary intervention (PCI) for ostial or stumpless chronic total occlusion (CTO) utilizing both the antegrade-only and retrograde approaches.Methods: A comprehensive retrospective examination was conducted on the procedural and in-hospital clinical outcomes of 89 consecutive patients subjected to ostial or stumpless CTO PCI at our institution between April 2015 and October 2022.Results: The antegrade-only technique demonstrated a superior technical success rate (92.0% vs 71.9%, p = 0.041) and procedural success rate (92.0% vs 68.8%, p = 0.022) in comparison to the retrograde approach (RA). The RA group presented a notably elevated Japanese-CTO (J-CTO) score relative to the antegrade-only approach group (2.45± 0.73 vs 1.64± 0.70, p < 0.001). The antegrade-only approach group manifested an increased frequency of microchannels at the proximal stump relative to the RA group (56.0% vs 10.9%, p < 0.001). In-hospital major adverse cardiac events (MACE) and in-hospital myocardial infarction (MI) were observed more prevalently in the RA group (18.8% vs 0, p = 0.003; 15.6% vs 0, p = 0.008; respectively). A J-CTO score below 2 and the manifestation of microchannels at the proximal stump were identified as predictors for successful antegrade-only approach PCI for ostial or stumpless CTO (OR: 2.79 [95% CI: 1.92– 5.03, P =0.003]; OR: 2.89 [95% CI: 1.32– 6.03, P =0.001]; respectively).Conclusion: Relative to RA PCI for ostial or stumpless CTO, the antegrade-only approach is utilized for less complex CTO lesions and is associated with a diminished probability of in-hospital MACE.Keywords: chronic total occlusion, percutaneous coronary intervention, intravascular ultrasound

Yuan Li,1,2,&ast; Miaoting Wu,1,&ast; Xiaohuan Hu,1,&ast; Gaihe Chen,1,&ast; Xiaojuan Yao,1 Xin Zhou,3 Jiejie Lu1 1Department of Cosmetic Dermatology, The Fifth People’s Hospital of Hainan Province, Haikou, Hainan, People’s Republic of China; 2Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 3Medical Administration Department, The Fifth People’s Hospital of Hainan Province, Haikou, Hainan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiejie Lu, Department of Cosmetic Dermatology, The Fifth People’s Hospital of Hainan Province, No. 8 Longhua Road, Longhua District, Haikou, Hainan, 570100, People’s Republic of China, Email lujiejie677@163.com Xin Zhou, Medical Administration Department, The Fifth People’s Hospital of Hainan Province, No. 8 Longhua Road, Longhua District, Haikou, Hainan, 570100, People’s Republic of China, Email zx5575759@126.comAbstract: Eosinophilic pustular folliculitis (EPF) is a rare skin disease for which the gold standard of diagnosis relies on the invasive examination of pathological tissue sections. However, due to its invasive nature, many patients tend to refuse this diagnostic test. In such situations, reflectance confocal microscopy (RCM) can be a valuable diagnosis tool. Reflectance confocal microscopy (RCM) can accurately identify the specific structures for biopsy and provide objective imaging data to evaluate clinical symptoms following treatment. Therefore, we present a case report demonstrating the utility of RCM in diagnosing and assessing the treatment of the rare disease EPF for reference.Keywords: eosinophilic pustular folliculitis, minocycline, reflectance confocal microscopy, non-invasive detection

Mingshuang Wu,1 Yi He,1 Chenxi Pan2 1Department of Urology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 2Department of Breast Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of ChinaCorrespondence: Yi He; Chenxi Pan, The Second Affiliated Hospital of Dalian Medical University, 467, Zhongshan Road, Shahekou District, Dalian, 116044, People’s Republic of China, Tel/Fax +86 411 84671291, Email heyi_gzr@163.com; PCX980205@outlook.comPurpose: Serum lipids were reported to be the prognostic factors of various cancers, but their prognostic value in small cell lung cancer (SCLC) patients remains unclear. This study investigated the relationship between lipid profiles and clinical outcomes in extensive-stage (ES) SCLC by establishing a predictive risk classification model.Patients and Methods: We retrospectively analyzed the prognostic values of pretreatment serum lipids and their derivatives in patients with a confirmed diagnosis ES-SCLC. Independent factors of progression-free survival (PFS) were determined by univariate and multivariate cox analysis. Then, prognostic nomograms were established, of which predictive performance was evaluated by concordance index (C-index), calibration curves, receiver operating characteristic (ROC) curves, and decision curve analyses (DCA).Results: A total of 158 patients was included in this study. Four optimal PFS-related factors, total cholesterol (TC) ≥ 5.30, high-density lipoprotein cholesterol (HDL-C) > 1.30, triglycerides (TG)/HDL-C > 2.18, and ki67 expression > 70%, were included to construct the predictive nomogram. The C-indexes in training and validation sets were 0.758 and 0.792, respectively. ROC curves, calibration plots, and DCA all suggested favorable discrimination and predictive ability. Besides, the nomogram also performed better predictive ability than ki67 expression. Nomogram-related risk score divided the patients into two groups with significant progression disparities.Conclusion: The promising prognostic nomogram based on lipid parameters could help clinicians to conveniently and accurately evaluate the prognosis of ES-SCLC patients and identify high-risk groups, so as to formulate individualized therapeutic regimens and follow-up strategies in time.Keywords: small cell lung cancer, serum lipid, ki67, chemotherapy, nomogram

Shuang Xu,1 Yi Fu,2 Dan Xu,1 Shuang Han,1 Mingzhi Wu,3 Xinrong Ju,1 Meng Liu,1 De-Sheng Huang,4,5 Peng Guan4,6 1Library of China Medical University, Shenyang, Liaoning, People’s Republic of China; 2School of Health Management, China Medical University, Shenyang, Liaoning, People’s Republic of China; 3Library of Shenyang Pharmaceutical University, Shenyang, Liaoning, People’s Republic of China; 4Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, Shenyang, Liaoning, People’s Republic of China; 5Department of Intelligent Computing, School of Intelligent Medicine, China Medical University, Shenyang, Liaoning, People’s Republic of China; 6Department of Epidemiology, School of Public Health, China Medical University, Shenyang, Liaoning, People’s Republic of ChinaCorrespondence: De-Sheng Huang; Peng Guan, China Medical University, Shenyang, Liaoning, 110122, People’s Republic of China, Email dshuang@cmu.edu.cn; pguan@cmu.edu.cnBackground: Before the COVID-19 pandemic, tuberculosis is the leading cause of death from a single infectious agent worldwide for the past 30 years. Progress in the control of tuberculosis has been undermined by the emergence of multidrug-resistant tuberculosis. The aim of the study is to reveal the trends of research on medications for multidrug-resistant pulmonary tuberculosis (MDR-PTB) through a novel method of bibliometrics that co-occurs specific semantic Medical Subject Headings (MeSH).Methods: PubMed was used to identify the original publications related to medications for MDR-PTB. An R package for text mining of PubMed, pubMR, was adopted to extract data and construct the co-occurrence matrix-specific semantic types. Biclustering analysis of high-frequency MeSH term co-occurrence matrix was performed by gCLUTO. Scientific knowledge maps were constructed by VOSviewer to create overlay visualization and density visualization. Burst detection was performed by CiteSpace to identify the future research hotspots.Results: Two hundred and eight substances (chemical, drug, protein) and 147 diseases related to MDR-PTB were extracted to form a specific semantic co-occurrence matrix. MeSH terms with frequency greater than or equal to six were selected to construct high-frequency co-occurrence matrix (42 × 20) of specific semantic types contains 42 substances and 20 diseases. Biclustering analysis divided the medications for MDR-PTB into five clusters and reflected the characteristics of drug composition. The overlay map indicated the average age gradients of 42 high-frequency drugs. Fifteen top keywords and 37 top terms with the strongest citation bursts were detected.Conclusion: This study evaluated the literatures related to MDR-PTB drug therapy, providing a co-occurrence matrix model based on the specific semantic types and a new attempt for text knowledge mining. Compared with the macro knowledge structure or hot spot analysis, this method may have a wider scope of application and a more in-depth degree of analysis.Keywords: multidrug-resistant tuberculosis, pulmonary tuberculosis, medication trends, specific semantic types, MeSH tree, pubMR

Zhigang Liu,1,&ast; Jiahui Liang,1,&ast; Hangzhan Hu,1,&ast; Mengli Wu,1,&ast; Jingjing Ma,1 Ziwei Ma,1 Jianing Ji,1 Hengyi Chen,2 Xiaoquan Li,1 Zhizeng Wang,1,2 Yang Luo2,3 1Joint National Laboratory for Antibody Drug Engineering, Clinical Laboratory of the First Affiliated Hospital, School of Medicine, Henan University, Kaifeng, 475004, People’s Republic of China; 2Center of Smart Laboratory and Molecular Medicine, Jiangjin Hospital, School of Medicine, Chongqing University, Chongqing, 400044, People’s Republic of China; 3College of Life Science and Laboratory Medicine, Kunming Medical University, Kunming, 650500, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhizeng Wang, Joint National Laboratory for Antibody Drug Engineering, Clinical Laboratory of the First Affiliated Hospital, School of Medicine, Henan University, Kaifeng, 475004, People’s Republic of China, Tel +86 15093628687, Email wzhzeng@126.com Yang Luo, Center of Smart Laboratory and Molecular Medicine, Jiangjin Hospital, School of Medicine, Chongqing University, Chongqing, 400044, People’s Republic of China, Tel +86 13594088001, Email luoy@cqu.edu.cnIntroduction: Neutralizing antibodies (NAbs) are essential for preventing reinfection with SARS-CoV-2 and the recurrence of COVID-19; nonetheless, the formation of NAbs following vaccination and infection remains enigmatic due to the lack of a practical and effective NAb assay in routine laboratory settings. In this study, we developed a convenient lateral flow assay for the rapid and precise measurement of serum NAb levels within 20 minutes.Methods: Receptor-binding domain-fragment crystallizable (RBD-Fc) and angiotensin-converting enzyme 2-histidine tag (ACE2-His) were expressed by the eukaryotic expression systems of Spodoptera frugiperda clone 9 and human embryonic kidney 293T, respectively. Then, colloidal gold was synthesized and conjugated with ACE2. After optimizing various operating parameters, an NAb lateral flow assay was constructed. Subsequently, its detection limit, specificity, and stability were systematically evaluated, and clinical samples were analyzed to validate its clinical feasibility.Results: RBD-Fc and ACE2-His were obtained with 94.01% and 90.05% purity, respectively. The synthesized colloidal gold had a uniform distribution with an average diameter of 24.15 ± 2.56 nm. With a detection limit of 2 μg/mL, the proposed assay demonstrated a sensitivity of 97.80% and a specificity of 100% in 684 uninfected clinical samples. By evaluating 356 specimens from infected individuals, we observed that the overall concordance rate between the proposed assay and conventional enzyme-linked immunosorbent assay was 95.22%, and we noticed that 16.57% (59/356) of individuals still did not produce NAbs after infection (both by ELISA and the proposed assay). All the above tests by this assay can obtain results within 20 minutes by the naked eye without any additional instruments or equipment.Conclusion: The proposed assay can expediently and reliably detect anti-SARS-CoV-2 NAbs after infection, and the results provide valuable data to facilitate effective prevention and control of SARS-CoV-2.Clinical trial registration: Serum and blood samples were used under approval from the Biomedical Research Ethics Subcommittee of Henan University, and the clinical trial registration number was HUSOM-2022-052. We confirm that this study complies with the Declaration of Helsinki.Keywords: clinical detection, colloidal gold, neutralizing antibody, point-of-care test, SARS-CoV-2

Shaopeng Chen,1,2,&ast; Mindan Wu,3,&ast; Zhilin Xiong,1,&ast; Jiewen Huang,1 Yingying Lv,1 Yuyan Li,4 Minjuan Zeng,5 Tianwen Lai1 1Institute of Respiratory Diseases, The First Dongguan Affiliated Hospital of Guangdong Medical University, Dongguan, People’s Republic of China; 2Blood Donation Service Department, Zhanjiang Blood Center, Zhanjiang, People’s Republic of China; 3Department of Pulmonary and Critical Care Medicine, Shantou Central Hospital, Shantou, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, Dongguan Hospital of Southern Medical University, Dongguan, People’s Republic of China; 5Laboratory Animal Center, Guangdong Medical University, Zhanjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tianwen Lai; Minjuan Zeng, Email laitianwen2011@163.com; mjzeng@gdmu.edu.cnPurpose: Particulate matter (PM2.5) is a common risk factor for airway inflammation. Alveolar macrophages play a critical role in airway inflammation. Sirtuin 6 (SIRT6) is a class Ill histone deacetylase that exerts an anti-inflammatory effect in airway diseases. However, the role of SIRT6 on PM2.5-induced airway inflammation in macrophages remains unclear. We aimed to determine whether SIRT6 protects against PM2.5-induced airway inflammation in macrophages.Methods: The effect of SIRT6 on PM2.5-induced airway inflammation was assessed by using THP1 cells or bone marrow-derived macrophages (BMDMs) exposed to PM2.5 in vitro and myeloid cell-specific SIRT6 conditional knockout mice (Sirt6fl/fl-LysMCre) in vivo.Results: PM2.5 increased SIRT6 expression in THP1 cells, but SIRT6 gene silencing decreased PM2.5 induced inflammatory cytokines in THP1 cells. Moreover, the expression of SIRT6 and inflammatory cytokines was also decreased in BMDMs with myeloid-specific deletion of SIRT6 after stimulation of PM2.5. In vivo, Sirt6fl/fl-LysMCre mice substantially decreased airway inflammation in response to PM2.5 exposure.Conclusion: Our results revealed that SIRT6 promotes the PM2.5-induced airway inflammation in macrophages and indicated that inhibition of SIRT6 in macrophages may represent therapeutic strategy for airway disorders induced by airborne particulate pollution.Keywords: particulate matter, SIRT6, macrophage, lung inflammation

Diya Jhuti,1,2 Gohar Zakaryan,1 Hussein El-Kechen,3 Nadia Rehman,3 Mark Youssef,4 Cristian Garcia,4 Vaibhav Arora,1 Babalwa Zani,5 Alvin Leenus,6 Michael Wu,7 Oluwatoni Makanjuola,8 Lawrence Mbuagbaw3,9– 11 1Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada; 2Department of Health, Behavior, and Society, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; 3Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada; 4Faculty of Medicine, University of Toronto, Toronto, ON, Canada; 5Public Health Research Unit, AB Consulting, Cape Town, South Africa; 6Faculty of Law, University of Ottawa, Ottawa, ON, Canada; 7Michael DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada; 8Faculty of Science, McMaster University, Hamilton, ON, Canada; 9Biostatistics Unit, Father Sean O’Sullivan Research Centre, Hamilton, ON, Canada; 10Centre for Development of Best Practices in Health, Yaoundé Central Hospital, Yaoundé, Cameroon; 11Department of Global Health, Stellenbosch University, Cape Town, South AfricaCorrespondence: Lawrence Mbuagbaw, Biostatistics Unit/FSORC, 50 Charlton Avenue East, St Joseph’s Healthcare—Hamilton, 3rd Floor Martha Wing, Room H321, Hamilton, ON, L8N 4A6, Canada, Tel +1-905-522-1155 ext 35929, Fax +1-905-528-7386, Email mbuagblc@mcmaster.caIntroduction: Engagement in the HIV care cascade is required for people living with HIV (PLWH) to achieve an undetectable viral load. However, varying definitions of engagement exist, contributing to heterogeneity in research regarding how many individuals are actively participating and benefitting from care. A standardized definition is needed to enhance comparability and pooling of data from engagement studies.Objectives: The objective of this paper was to describe the various definitions for engagement used in HIV clinical trials.Methods: Articles were retrieved from CASCADE, a database of 298 clinical trials conducted to improve the HIV care cascade (https://hivcarecascade.com/), curated by income level, vulnerable population, who delivered the intervention, the setting in which it was delivered, the intervention type, and the level of pragmatism of the intervention. Studies with engagement listed as an outcome were selected from this database.Results: 13 studies were eligible, of which five did not provide an explicit definition for engagement. The remaining studies used one or more of the following: appointment adherence (n=6), laboratory testing (n=2), adherence to antiretroviral therapy (n=2), time specification (n=5), intervention adherence (n=5), and quality of interaction (n=1).Conclusion: This paper highlights the existing diversity in definitions for engagement in the HIV care cascade and categorize these definitions into appointment adherence, laboratory testing, adherence to antiretroviral therapy, time specification, intervention adherence, and quality of interaction. We recommend consensus on how to describe and measure engagement.Keywords: HIV, engagement, antiretroviral therapy, adherence, retention, cascade

Mengdi Xie,1,&ast; Kang Yuan,2,&ast; Xinyi Zhu,2,&ast; Jingjing Chen,3 Xiaohao Zhang,4 Yi Xie,2 Min Wu,1 Zhaojun Wang,2 Rui Liu,2 Xinfeng Liu1,2,5 1Department of Neurology, Jinling Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Neurology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, People’s Republic of China; 3Department of Neurology, Changhai Hospital, Navy Medical University, Shanghai, People’s Republic of China; 4Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 5Stroke Center & Department of Neurology, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinfeng Liu, Department of Neurology, Jinling Hospital, Nanjing Medical University, No. 305 East Zhongshan Road, Nanjing, Jiangsu Province, 210000, People’s Republic of China, Tel +86 2584801861, Fax +86 2584805169, Email xfliu2@vip.163.com Rui Liu, Department of Neurology, Affiliated Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210000, Jiangsu Province, People’s Republic of China, Tel +86 2584801861, Fax +86 2584805169, Email liurui8616@163.comBackground: Systemic immune inflammation has been investigated as a prognostic marker of different diseases. This study is designed to assess the association of systemic immune-inflammation index (SII) with long-term mortality of stroke-associated pneumonia (SAP) patients.Methods: Patients aged ≥ 18 years with SAP were selected from the Nanjing Stroke Registry Program in China. We retrospectively evaluated systemic immune-inflammation response with SII and pneumonia severity with the pneumonia severity index and the confusion, uremia, elevated respiratory rate, hypotension, and aged 65 years or older score. To explore the correlation between SII and mortality in SAP patients, multivariable Cox regressions and competing risk regressions were conducted. Mediation analysis was also performed to assess the role of pneumonia severity.Results: Among 611 patients in the SAP population, death occurred in 164 patients (26.8%) during the median follow-up of 3.0 (1.2– 4.6) years. In multivariate analysis, higher SII scores could predict increased mortality in patients with SAP (adjusted hazard ratio 2.061; 95% confidence interval, 1.256– 3.383; P = 0.004), and the association was mediated by pneumonia severity. Moreover, adding SII to traditional models improved their predictive ability for mortality.Conclusion: Our study displayed that SII was characterized in SAP patients with different prognoses. Elevated SII scores increased the risk of mortality. Further research is required for the clinical practice of the index among SAP patients.Keywords: systemic immune-inflammation index, stroke-associated pneumonia, mortality, China

Xuezhu Wang,1,&ast; Xu Yang,2,&ast; Jingnan Wang,1 Chengyan Dong,3 Jie Ding,1 Meiqi Wu,1 Yanyu Wang,2 Haiyan Ding,4 Hui Zhang,4 Xinting Sang,2 Haitao Zhao,2 Li Huo1 1Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Center for Rare Diseases Research, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3GE Healthcare China, Beijing, People’s Republic of China; 4Department of Biomedical Engineering, Tsinghua University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Huo; Haitao Zhao, &num;1 Shuaifuyuan, Dongcheng District, Beijing, People’s Republic of China, Tel +86 13910801986; +86 13901246374, Email huoli@pumch.cn; zhaoht@pumch.cnPurpose: The combination of PD-1/PD-L1 inhibitors and molecular targeted agents showed promising efficacy for unresectable hepatocellular carcinoma (uHCC). This study aimed to investigate the prognostic value of metabolic parameters from 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) in patients with uHCC underwent the combined therapies.Patients and Methods: Patients with uHCC treated with a combination of immunotherapy and targeted therapy who underwent baseline 18F-FDG PET/CT between July 2018 and December 2021 were recruited retrospectively. The metabolic tumor volume (MTV), total lesion glycolysis (TLG), maximum standardized uptake values (SUVmax), and clinical and biological parameters were recorded. A multivariate prediction model was developed for overall survival (OS) using these parameters together with clinical prognostic factors.Results: Seventy-seven patients were finally included. The median OS was 16.8 months. We found that a high MTV (≥ 39.65 cm3 as the median value) was significantly associated with OS (P< 0.05). In multivariate analyses for OS, a high MTV, high Eastern Cooperative Oncology Group performance status (ECOG-PS, ≥ 1), Child-Pugh (B-C) grade, and the presence of bone metastasis were significantly associated with poor OS (HR 1.371, HR 3.73, HR 15.384, and HR 2.994, all P< 0.05, respectively). A multivariate prognostic model including MTV and prognostic factors, such as ECOG-PS, Child-Pugh grade, and bone metastasis, further improved the identification of different OS subgroups.Conclusion: High MTV is an adverse prognostic factor in patients with uHCC treated with a combination of immunotherapy and molecular targeted agents. Integrating PET/CT parameters with clinical prognostic factors could help to personalize immunotherapy.Graphical Abstract: Keywords: unresectable hepatocellular carcinoma, PD-1 inhibitor, PD-L1 inhibitor, PET/CT, metabolic tumor volume, prognostic model

Xudong Dong,1,2,&ast; Ailing Ding,2,&ast; Hong Hu,1 Fanping Xu,1 Lingyan Liu,1 Min Wu1,3 1The Obstetrical Department of the First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650500, People’s Republic of China; 2Faculty of Life Science and Technology, Kunming University of Science & Technology, Kunming, 650500, People’s Republic of China; 3Yunnan Provincial Key Laboratory of Carbon Sequestration and Pollution Control in Soils, Faculty of Environmental Science & Engineering, Kunming University of Science & Technology, Kunming, 650500, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Wu, Email minwupp@163.comPurpose: As two of the most severe and common medical disorders during pregnancy, gestational diabetes mellitus (GDM) and hypertensive disorder complicating pregnancy (HDCP) cause adverse effects on placental barrier function and thus may lead to a high risk of intrauterine exposure to toxic metals from mother to fetus. This study investigates the impact of the placental barrier on the transfer of cadmium (Cd) from mother to fetus and the relationship between pregnancy complications.Methods: A total of 107 pairs of samples were collected in Kunming, China; 29 were from healthy pregnant women, and 78 were from patients with pregnancy complications. Cd was measured in each mother’s placenta and maternal and umbilical cord blood. The expressions of MT and Cd-MT complex in blood and placental tissue samples were determined by enzyme-linked immunosorbent assay (ELISA).Results: The cesarean section rate in the whole pathological group (60.7%) was higher than that in the normal group (20.7%), and the ratio of the effective barrier (ratio of maternal blood to umbilical cord blood> 1) in the pathological group (74%) was lower than that in the normal group (79%). In addition, the proportion of practical placental barriers in women aged 20– 25 years was 83.3%, 76.3% in women aged 26– 30 years, 74.3% in women aged 31– 35 years, 70% in women aged 36– 40 years, and 71% in women aged 40– 45 years. The Cd content in the placenta of the three pathological groups was significantly higher than that in maternal and umbilical cord blood (P< 0.05), and the distribution of Cd was the same as that in the normal group. However, there was no significant difference between maternal and umbilical cord blood Cd concentrations in the pathological group. The Cd concentration in the normal group’s maternal blood was significantly higher than that in cord blood (P< 0.05). In addition, the expression levels of both metallothionein (MT) and Cd-MT complex in placenta is much higher than in maternal and umbilical blood, and which in normal group are significantly higher than those in pathological group.Conclusion: Both mothers and fetuses are at increased health risk for pregnancy disorders when maternal age, BMI, or body weight increases. Increased maternal age increases the likelihood of Cd transfer from the mother to the fetus. Pregnancy complications may induce lower expression of MT, thus reducing the Cd-MT complex in the placenta, weakening the placental barrier, and increasing the risk of Cd transfer and exposure to the fetus.Keywords: gestational diabetes mellitus, gestational hypertension, maternal blood, placenta barrier, pregnancy complication

Low-grade polymetallic chalcopyrite ore has a high lead and iron content and a low softening point, which is difficult to treat using conventional pyrometallurgical and hydrometallurgical processes. In order to investigate the suitable methodology for efficient utilization, it was pelletized with CaO for oxidation roasting in the present work. By controlling the Po2 and Pso2 in the gas phase, the metal sulfide in the ore was converted into easily soluble metal oxide, the thermal analysis of the roasting process was carried out and the acid leaching of the extracted calcine at atmospheric pressure was investigated. The results show that by pelletizing with CaO and then roasting at 800 ℃ for 1 h, chalcopyrite is converted into CuO, which can be easily dissolved, galena and pyrite are converted into PbO2 and Fe2O3, respectively, and sulfur reacts with CaO and turns into CaSO4, which can fix the sulfur in the calcine. The copper leaching rate of calcine can reach 98.60 wt.% under atmospheric pressure in the H2SO4-H2O system. CaO can increase the softening point of raw materials, improve the roasting effect, promote the phase transformation of chalcopyrite in the oxidation process, and convert sulfur into CaSO4 to fix sulfur, effectively avoiding SO2 pollution to the environment.

Mingfen Wu,1 Xiaohan Xu,2 Rongsheng Zhao,2 Xiangrong Bai,3 Bin Zhu,1 Zhigang Zhao1 1Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 2Department of Pharmacy, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 3Department of Pharmacy, Xuanwu Hospital Capital Medical University, Beijing, 100053, People’s Republic of ChinaCorrespondence: Zhigang Zhao; Bin Zhu, Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Fengtai District, Beijing, 100070, People’s Republic of China, Tel +8601059978036 ; +8601059975444, Fax +8601059976856, Email 1022zzg@sina.com; zbtcm@163.comPurpose: Medication adherence plays an important role in glycemic control in type 2 diabetes mellitus (T2DM) self-management. To analyze the factors influencing medication adherence in T2DM patients and the effect of pharmacist-led interventions, we conducted a study in Beijing, China.Patients and Methods: T2DM patients with hypoglycemic drugs for at least 6 months were enrolled. A pharmacist-led survey was conducted followed by individualized interventions for those non-adherent patients monthly within 3 months. FPG, HbA1c, and 2hPG were measured as the comprehensive glycemic control. Medication adherence was determined according to the patient’s self-reported compliance with prescribed medication during the last 3 months.Results: A total of 763 T2DM patients were included. The average age was 63.26± 11.89 years, with 363 males. After pharmacist intervention, the patients with good adherence increased from 34.21% to 39.06%, while poor adherence decreased from 32.5% to 24.5% (p < 0.001). The average adherence score was a significant increase (p < 0.001) from 27.846± 4.185 to 29.831± 7.065. Furthermore, our study demonstrated that pharmacist-led interventions significantly increased glycemic control (FPG from 42.33% to 53.60%, p < 0.001; 2hPG from 41.68% to 48.75%, p = 0.005; HbA1c from 24.12% to 29.23%, p = 0.024). The results found that body mass index (OR 0.643, 95% CI 0.437– 0.945), use of medications empirically (occasionally (OR=3.066, 95% CI 2.069– 4.543); often (OR=2.984, 95% CI 1.107– 8.044)), following the doctor’s advice to visit (OR 2.129, 95% CI 1.079– 4.202) and lifestyle compliance (OR 2.835, 95% CI 1.094– 7.346) were the independent risk factors of non-adherence (p < 0.05), the area under the ROC curve was 0.716.Conclusion: Self-reported medication adherence and glycemic control in T2DM patients were poor which can be improved by pharmacist-led interventions. Interventions should focus on empirical medication behavior, non-adherence to lifestyle, and failure to follow the doctor’s advice. The recall bias with self-reported results needs further objective data to verify.Keywords: T2DM, medication adherence, glycemic control, current status, risk factor, pharmacist-led interventions

Min Wu,1 Shuo Feng,1 Meng Qian,2 Song Wang,3 Kaiguang Zhang1 1Department of Gastroenterology, Affiliated Provincial Hospital, Anhui Medical University, Anhui, People’s Republic of China; 2Graduate School of Bengbu Medical College, Anhui, People’s Republic of China; 3Department of Gastroenterology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Anhui, People’s Republic of ChinaCorrespondence: Kaiguang Zhang, Department of Gastroenterology, Affiliated Provincial Hospital, Anhui Medical University, Anhui, People’s Republic of China, Email zhangkaiguang@ustc.edu.cn Song Wang, Department of Gastroenterology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Anhui, People’s Republic of China, Email drwangsong@163.comPurpose: Helicobacter pylori (H. pylori) infection is a high-risk factor for gastric cancer (GC). The main aim of this study was to evaluate the effect of H. pylori on gastritis staging systems and the value of H. pylori combined with gastritis staging systems in predicting GC risk.Patients and Methods: This study enrolled 609 patients with gastric atrophy (GA) and 527 patients with gastric intestinal metaplasia (GIM), who were graded by the OLGA and OLGIM staging systems, respectively. Each individual underwent serum pepsinogen (PG) test, H. pylori detection and questionnaire investigation. We did a real-world retrospective follow-up survey for them in April 2022.Results: Compared with H. pylori-negative patients, H. pylori-positive patients had higher serum PGs/gastrin-17 (G-17) levels and lower PGR levels, regardless of OLGA/OLGIM stages I–II or III–IV. Furthermore, eight patients with atrophic gastritis who progressed to GC were previously in OLGA stages III–IV and OLGIM stages II–IV. The average duration of this process was 2.19± 1.03 years. Logistic regression analysis indicated that PGI and H. pylori infection were independent risk factors of individuals with OLGA stages III–IV. Age and PGR were independent risk factors of patients with OLGIM stages III–IV. PGI and PGR had good clinical diagnostic values for OLGA stages III–IV and OLGIM stages III–IV, respectively.Conclusion: Patients with OLGA/OLGIM stages III–IV should undergo endoscopic surveillance regardless of H. pylori infection. H. pylori-positive patients with OLGIM stage II also have a high risk of GC. H. pylori combined with PGI and PGR is helpful to evaluate the severity of chronic gastritis.Keywords: atrophy, metaplasia, Helicobacter pylori, gastric cancer, risk factors