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Xing Zhou,1,* Quan Lu,2,* Qiu Wang,2,* Wenxin Chu,2 Jianhao Huang,2 Jinming Yu,2 Yuechou Nong,2 Wensheng Lu2,* 1Pharmacy Department, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, People’s Republic of China; 2Department of Endocrinology and Metabolism, National Key Endocrine Clinical Construction Specialty, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wensheng Lu; Yuechou Nong, Department of Endocrinology and Metabolism, National Key Endocrine Clinical Construction Specialty, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, No. 6, Taoyuan Road, Nanning, Guangxi, 530021, People’s Republic of China, Email Lwswxqz@163.com; wslu@gxams.org.cn; yuechou_gx@163.comBackground: Mitochondrial calcium uptake-induced mitophagy may play an essential role in myocardial ischemia/reperfusion (MI/R) injury. Diltiazem hydrochloride (DIL), a traditional calcium channel blocker, can alleviate MI/R injury by blocking calcium overload. However, whether the protective mechanism of DIL involves mitophagy remains elusive. This study aimed to clarify the underlying molecular mechanism by which DIL ameliorates MI/R injury by downregulating mitophagy in vivo and in vitro.Methods: Thirty rats were randomized into three groups: the sham, MI/R, and MI/R+DIL (1 mg/kg) groups (n = 10/per group). MI/R injury was induced by ligating the left anterior descending (LAD) artery for 30 min followed by 60 min of reperfusion in vivo. H9C2 cells were selected to establish an oxygen-glucose deprivation/recovery (OGD/R) model to simulate MI/R injury in vitro. The potential mechanism by which DIL alleviates MI/R injury was analyzed based on tissue morphology, mitophagy-related gene transcription, and protein expression.Results: According to histological and immunohistochemical evaluations, DIL significantly alleviated myocardial damage in vivo. Moreover, DIL significantly increased cell viability, attenuated OGD/R-induced apoptosis, and inhibited mitochondrial autophagy in vitro. Mechanistically, DIL attenuated mitochondrial autophagy through the upregulation of dual-specificity protein phosphatase 1 (DUSP1) and the downregulation of c-Jun N-terminal kinase (JNK) and Bcl2 interacting protein 3-like (BNIP3L, also known as NIX) expression.Conclusion: Diltiazem hydrochloride protects against myocardial ischemia/reperfusion injury in a BNIP3L/NIX-mediated mitophagy manner in vivo and in vitro.Keywords: diltiazem hydrochloride, calcium channel blockers, myocardial infarction, myocardial ischemia/reperfusion injury, mitophagy

Wenbin Lu,1,&ast; Xinning Chang,1,&ast; Wei Wu,2– 5 Peipei Jin,1 Shengwei Lin,1 Lize Xiong,2– 5 Xiya Yu2– 5 1Faculty of Anesthesiology, Changhai Hospital, Naval Medical University/Second Military Medical University, PLA, Shanghai, People’s Republic of China; 2Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 3Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 4Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 5Clinical Research Centre for Anesthesiology and Perioperative Medicine, Tongji University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lize Xiong; Xiya Yu, Email mzkxlz@126.com; lizexiong@tongji.edu.cn; yuxiyash@163.comObjective: To explore the effect of scalp nerve block (SNB) combined with intercostal nerve block (ICNB) on quality of recovery (QoR) after deep brain stimulation (DBS) in patients with Parkinson’s disease (PD).Methods: We conducted a prospective randomized controlled trial in which 88 patients with PD were randomly assigned to undergo SNB combined with ICNB (SNB group) or not (control group) before surgery. The primary outcome was the 15-item QoR (QoR-15) score 24 h after surgery. The secondary outcomes included QoR-15 scores at 72 h and 1 month after surgery, pain-related events, recovery events in post-anesthesia care unit (PACU), duration of anesthesia and surgery, and nerve block-related adverse events.Results: The QoR-15 score at 24 h after surgery was significantly higher in SNB group than Control group: 122.0 ± 7.6 vs 113.5 ± 11.3 (P = 0.006). SNB combined with ICNB improved QoR-15 scores at 72 h (P = 0.004) but not at 1 month after surgery (P = 0.230). The SNB group was positively related to QoR-15 scores 24 h after surgery (β = 8.92; 95% CI = 4.52~13.32) after adjusting for confounding variables. The numeric rating scale pain scores at PACU discharge and at 24 h, intraoperative opioid consumption, rescue analgesic use, and the incidence of postoperative nausea and vomiting (PONV) in SNB group were significantly lower than Control group (P < 0.05).Conclusion: Preoperative SNB combined with ICNB improved QoR and analgesia after surgery, and reduced intraoperative opioid consumption and the incidence of PONV in patients with PD who underwent DBS.Keywords: deep brain stimulation, intercostal nerve block, Parkinson’s disease, quality of recovery, scalp nerve block

Weilin Lu,1,&ast; Kaiming Li,2,&ast; Haisi Wu,2,&ast; Jinyu Li,2 Yan Ding,2 Xiaolin Li,1 Zhipeng Liu,3 Huae Xu,2 Yinxing Zhu3,4 1The First Affiliated Hospital with Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing, People’s Republic of China; 3Taizhou Affiliated Hospital of Nanjing University of Chinese Medicine, Taizhou, People’s Republic of China; 4Taizhou People’s Hospital affiliated to Nanjing Medical University, Taizhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huae Xu; Yinxing Zhu, Email xuhuae@njmu.edu.cn; zhuyinxing@njmu.edu.cnBackground: The causal relationship of breast cancer (BC) with cardiovascular disease (CVD) and the underlying mediating pathways remains elusive. Our study endeavors to investigate the causal association between BC and CVD, with a focus on identifying potential metabolic mediators and elucidating their mediation effects in this causality.Methods: In this study, we conducted two-sample Mendelian randomization (MR) to estimate the causal effect of BC (overall BC, ER+ BC, ER- BC) from the Breast Cancer Association Consortium (BCAC) on CVD including coronary heart disease (CHD), hypertensive heart disease (HHD), ischaemic heart disease (IHD), and heart failure (HF) from the FinnGen consortium. Then, we used two-step MR to evaluate 18 metabolic mediators of the association and calculate the mediated proportions.Results: Genetically predicted ER+ BC was causally associated with an increased risk of CVD including CHD (OR = 1.034, 95% CI: 1.004– 1.065, p = 0.026), HHD (OR = 1.061, 95% CI: 1.002– 1.124, p = 0.041), IHD (OR = 1.034, 95% CI: 1.007– 1.062, p=0.013), and HF (OR = 1.055, 95% CI: 1.013– 1.099, p = 0.010), while no causality was observed for overall BC and ER- BC. Furthermore, high-density lipoprotein cholesterol (HDL-C) was identified as a mediator of the association between ER+BC and CVD, including CHD (with 15.2% proportion)) and IHD (with 15.5% proportion), respectively.Conclusion: This study elucidates the potential causal impact of ER+ BC on subsequent risk of CVD, including CHD, HHD, IHD, and HF. We also outline the metabolic mediator HDL-C as a priority target for preventive measures to reduce excessive risk of CVD among patients diagnosed with ER+BC.Keywords: breast cancer, cardiovascular disease, ER status, Mendelian randomization, metabolic mediators, HDL-C

Zhiyang Wu,1,&ast; Wenjun Lu,2,&ast; Xin Zhang,1 Qiaoying Xia,2 Han Zuo,2 Xi Guo,1 Yu Liu,1 Fan Zhang,3 Xin Zhang,4 Luyao Zhang2 1Department of Critical Care Medicine, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, People’s Republic of China; 2Department of Pathology and Pathophysiology, School of Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 3Department of Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, People’s Republic of China; 4Department of General Surgery, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Luyao Zhang, Department of Pathology and Pathophysiology, School of Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China, Email zhangluyao@njucm.edu.cn Xin Zhang, Department of General Surgery, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, People’s Republic of China, Email 514557061@qq.comPurpose: Protectin D1 (PD1), a biologically active molecule derived from docosahexaenoic acid (DHA), plays a major role in the body’s endogenous lipid-mediated inflammatory response. The study aims to explore the relationship between PD1, inflammatory response and the severity of acute pancreatitis (AP).Patients and Methods: Sixty consecutive AP patients within 72h of disease onset were enrolled as the study group, a further thirty healthy people were enrolled as the control group. General demographics collected at the time of enrollment. Serum PD1, Citrullinated Histone 3 (CitH3), myeloperoxidase-Deoxyribonucleic acid (MPO-DNA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) level were measured in AP patients on enrollment day 0, day 1, day 3 and day 7. Meanwhile, the Acute Physiology and Chronic Health evaluation II (APACHE II) scores, Sequential Organ Failure Assessment (SOFA) scores were also evaluated on day 0, day 1, day 3 and day 7.Results: AP was severe in 29 patients (48.3%), moderately severe acute pancreatitis (MSAP) was found in 9 patients (15%), and mild acute pancreatitis (MAP) was found in 22 patients (36.7%). The level of PD1, CitH3 and MPO-DNA were statistically significantly higher in AP patients than in the healthy population. Serum PD1, CitH3 and MPO-DNA concentration increased with AP severity. In AP patients, PD1 has a strong linear association with TNF-α, CitH3 and MPO-DNA. The AUC for SAP predicted by PD1 was 0.938. The calculated cut-off point for prognosis SAP is 7.94 pg/mL. The AUC for infected pancreatic necrosis (IPN) predicted by PD1 was 0.836 and the cut-off point was 8.65 pg/mL. The AUC for organ failure (OF) predicted by PD1 was 0.719 and the cut-off point was 7.94 pg/mL.Conclusion: PD1 is associated with both the presence of AP and the severity of pancreatitis.Keywords: PD1, acute pancreatitis, CitH3, MPO-DNA, infected pancreatic necrosis, organ failure

Yan Jiang,1,&ast; Baolin Luo,2,&ast; Wen Lu,1 Yaqin Chen,1 Yanchun Peng,2 Liangwan Chen,3,4 Yanjuan Lin2,3 1School of Nursing, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 2Department of Nursing, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China; 3Department of Cardiovascular Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China; 4Fujian Provincial Special Reserve Talents Laboratory, Fuzhou, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liangwan Chen, Department of Cardiovascular Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China, Email fjxhlwc@163.com Yanjuan Lin, Department of Nursing, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China, Email fjxhyjl@163.comPurpose: The Aggregate Index of Systemic Inflammation (AISI) has emerged as a novel marker for inflammation and prognosis, but its role in patients with acute myocardial infarction has not been studied. Therefore, this study aimed to investigate the impact of different AISI levels on the clinical outcomes of patients with acute myocardial infarction.Patients and Methods: This study was a retrospective study, including 1044 patients with acute myocardial infarction (AMI) who were treated at the Fujian Medical University Affiliated Union Hospital, China from May 2017 to December 2022. The patients were divided into high and low AISI groups based on the median value (Q1 Group, ≤ 416.15, n=522; Q2 Group, ≥ 416.16, n=522), and the differences in baseline characteristics and clinical outcomes between the two groups were analyzed. The primary outcome included major adverse cardiovascular and cerebrovascular events (MACCEs), while the secondary outcomes included contrast-induced nephropathy (CIN) risk and all-cause rehospitalization rate.Results: The findings of the single-factor analysis suggest that a significant association between high AISI levels and the occurrence of MACCEs in AMI patients. After adjusting for confounding factors, the results indicated that compared to Q1, patients in the Q2 group had a higher risk of all-cause mortality [adjusted odds ratio (aOR) 4.64; 95% CI 1.37– 15.72; p=0.032], new-onset atrial fibrillation (aOR 1.75; 95% CI 1.02– 3.00; p=0.047), and CIN (aOR 1.75; 95% CI 1.02– 3.01; p=0.043), with all differences being statistically significant.Conclusion: In the population of AMI patients, an elevated AISI level is significantly associated with an increased risk of cardiovascular death and can serve as an early marker for adverse prognosis.Keywords: acute myocardial infarction, inflammation index, clinical outcomes, MACCEs

Yanli Guo,1,&ast; Dinggui Huang,2,&ast; Jingxia Sun,3,&ast; Zhenwei Zhai,3,&ast; Hewei Xiao,4,&ast; Weiguang Hao,5 Qiu Wang,3 Jianhao Huang,3 Miaomiao Jin,1 Wensheng Lu3,&ast; 1Department of Endocrinology, Heji Affiliated Hospital of Changzhi Medical College, Changzhi, Shanxi, 046011, People’s Republic of China; 2Project Fund Supervision Center, Health Commission of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China; 3Department of Endocrinology and Metabolism, Guangxi Academy of Medical Sciences, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China; 4Scientific Research Cooperation Department, Guangxi Academy of Medical Sciences, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China; 5Department of Endocrinology, Tongde Hospital, Yuncheng, Shanxi, 044000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wensheng Lu, Department of Endocrinology and Metabolism, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, No. 6, Taoyuan Road, Nanning, Guangxi, 530021, People’s Republic of China, Email Lwswxqz@163.comAim: This study aimed to assess the efficacy of antithyroid drugs (ATDs) and radioactive iodine-131 (RAI) therapies in reducing the risk of major adverse cardiovascular events (MACEs) and all-cause mortality in patients with hyperthyroidism complicated with type 2 diabetes mellitus (T2DM).Methods: Between January 2013 and December 2021, 540 subjects were included in the analysis. All participants were followed up for 9 years, with a median of 54 months (2451 person-years). The subjects were categorized into two groups: the ATDs group (n = 414) and the RAI group (n = 126). According to the free triiodothyronine (FT3) tertiles, the patients receiving RAI were further grouped as follows: low-level (≤ 4.70 pmol/L, n = 42), moderate-level (4.70– 12.98 pmol/L, n = 42), and high-level (≥ 12.98 pmol/L, n = 42). The efficacy of ATDs and RAI therapies in reducing the risk of MACEs and all-cause mortality was assessed.Results: Of the 540 participants, 163 experienced MACEs (30.19%), 25 (15.34%) of whom died. Multivariate Cox regression analyses revealed that RAI was associated with a 38.5% lower risk of MACEs (P = 0.016) and a 77.1% lower risk of all-cause mortality (P = 0.046). Stratified analyses indicated that RAI had a protective effect on MACEs in patients aged ≥ 60 years (P = 0.001, P for interaction = 0.031) and patients with a duration of diabetes mellitus ≥ 6 years (P = 0.013, P for interaction = 0.002). Kaplan‒Meier analysis revealed a lower cumulative incidence of MACEs and all-cause mortality in the RAI group (log-rank, all P < 0.05). Moreover, the ROC curve suggested an optimal FT3 cut-off value of 5.4 pmol/mL for MACE (P < 0.001).Conclusion: Our findings suggested that RAI therapy effectively reduced the risk of MACEs and all-cause mortality in elderly patients with hyperthyroidism combined with T2DM.Keywords: hyperthyroidism, type 2 diabetes mellitus, radioactive iodine-131, major adverse cardiovascular events, all-cause mortality

Hua Liu,1,&ast; Wenxi Wu,1,&ast; Min Xu,2 Xiaoyang Ling,2 Wei Lu,2 Feng Cheng,1 Jian Wang2 1Department of Neurosurgery, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, 215300, People’s Republic of China; 2Department of Neurosurgery, Kunshan Hospital of Traditional Chinese Medicine, Kunshan Affiliated Hospital of Nanjing University of Chinese Medicine, Kunshan, 215300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Cheng, Department of Neurosurgery, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, 215300, People’s Republic of China, Email chengf1215@163.com Jian Wang, Department of Neurosurgery, Kunshan Hospital of Traditional Chinese Medicine, Kunshan Affiliated Hospital of Nanjing University of Chinese Medicine, Kunshan, 215300, People’s Republic of China, Email wj458381670@126.comBackground and Aim: Traumatic brain injury (TBI) is a severe public health problem in elderly patients, and frailty is associated with higher mortality rates in older patients. This study aims to assess the prognostic value of frailty in patients with TBI.Methods: Clinical data from 348 TBI patients treated at Affiliated Kunshan Hospital of Jiangsu University and Kunshan Hospital of Traditional Chinese Medicine between December 2018 and December 2020 were retrospectively collected. Univariate and multivariate logistic regression analyses were used to determine risk factors affecting in-hospital mortality, and receiver operating characteristic (ROC) curves were plotted to assess the discriminatory power of the frailty index. Frailty was assessed using the FRAIL scale, where FRAIL stands for Fatigue, Resistance, Ambulation, Illness, and Loss of weight, with each item scored as 0 or 1.Results: Using the FRIAL questionnaire, 122 patients had low frailty and 226 had high frailty. Multivariate logistic regression analysis showed that high frailty was a risk factor for in-hospital mortality in TBI patients (P< 0.001, OR=2.012 [1.788– 2.412]). The proportion of infections occurring in the two groups was statistically different (P=0.015), with severely infected TBI patients being more likely to develop complications. The ROC curve showed an area under the curve for the FRAIL score of 0.845 [0.752– 0.938].Conclusion: Frailty is an important risk factor for in-hospital mortality in elderly TBI patients, and more attention should be paid to patients with high levels of frailty. Clinicians should consider the degree of frailty when assessing TBI and making treatment decisions.Keywords: frailty, traumatic brain injury, in-hospital mortality, prognosis

Xueya Xu,&ast; Weili Lu,&ast; Hua Zhang, Xiaoying Wang, Caixia Huang, Qiuping Huang, Wen Xu, Wei Xu Pharmacy College, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoying Wang; Wei Xu, Pharmacy College, Fujian University of Traditional Chinese Medicine, 1 Qiuyang Road, Fuzhou, 350122, People’s Republic of China, Email 2003032@fjtcm.edu.cn; 2000017@fjtcm.edu.cnBackground: The combination of nanoplatform-based chemotherapy and photodynamic therapy (PDT) is a promising way to treat cancer. Celastrol (Cela) exhibits highly effective anti-hepatoma activity with low water solubility, poor bioavailability, non-tumor targeting, and toxic side effects. The combination of Cela-based chemotherapy and PDT via hepatoma-targeting and reactive oxygen species (ROS)-responsive polymeric micelles (PMs) could solve the application problem of Cela and further enhance antitumor efficacy.Methods: In this study, Cela and photosensitizer chlorin e6 (Ce6) co-loaded glycyrrhetinic acid-modified carboxymethyl chitosan-thioketal-rhein (GCTR) PMs (Cela/Ce6/GCTR PMs) were prepared and characterized. The safety, ROS-sensitive drug release, and intracellular ROS production were evaluated. Furthermore, the in vitro anti-hepatoma effect and cellular uptaken in HepG2 and BEL-7402 cells, and in vivo pharmacokinetic, tissue distribution, and antitumor efficacy of Cela/Ce6/GCTR PMs in H22 tumor-bearing mice were then investigated.Results: Cela/Ce6/GCTR PMs were successfully prepared with nanometer-scale particle size, favorable drug loading capacity, and encapsulation efficiency. Cela/Ce6/GCTR PMs exhibited a strong safety profile and better hemocompatibility, exhibiting less damage to normal tissues. Compared with Cela-loaded GCTR PMs, the ROS-responsiveness of Cela/Ce6/GCTR PMs was increased, and the release of Cela was accelerated after combination with PDT. Cela/Ce6/GCTR PMs can efficiently target liver tumor cells by uptake and have a high cell-killing effect in response to ROS. The combination of GCTR PM-based chemotherapy and PDT resulted in increased bioavailability of Cela and Ce6, improved liver tumor targeting, and better anti-hepatoma effects in vivo.Conclusion: Hepatoma-targeting and ROS-responsive GCTR PMs co-loaded with Cela and Ce6 combined with PDT exhibited improved primary hepatic carcinoma therapeutic effects with lower toxicity to normal tissues, overcoming the limitations of monotherapy and providing new strategies for tumor treatment. Keywords: ROS-responsive polymeric micelles, photodynamic therapy, hepatoma-targeting, celastrol, combination anti-hepatoma therapy

Chunxia Yin,1,&ast; Taohua Lan,2,3,&ast; Yunshan Wu,4,5 Jing Cai,1 Haoxiang Li,1 Xiaolan Kuang,1 Lin Jiao,1 Xiaomin Ou,1 Hua Yang,2 Bo Liu,3– 5 Weihui Lu2,6,7 1The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Department of Cardiology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China; 3State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 4Guangzhou Key Laboratory of Chirality Research on Active Components of Traditional Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China; 5Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 6State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 7Chinese Medicine Guangdong Laboratory, Guangdong Hengqin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weihui Lu, Bo Liu, The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Email weihui.lu@gzucm.edu.cn; doctliu@gzucm.edu.cnPurpose: This study was designed to evaluate the effect and mechanism of the Qushi Huatan (QSHT) decoction against coronary heart disease (CHD) through network pharmacology and experimental verification.Methods: In the present study, the active ingredients of the QSHT decoction were identified by ultra performance liquid chromatography/tandem mass spectrometry (UPLC/MS), then the potential ingredients and coronary heart disease targets were predicted using the SwissTarget Prediction database and the database of Genecards and OMIM database, respectively. A herb-compound-target network was constructed using Cytoscape. GO and KEGG enrichment analysis were performed using the ClusterProfiler data package of R software. Molecular docking was used to predict the core targets of QSHT against CHD. In addition, we used a myocardial infarction (MI) and high-fat diet ApoE−/− mice model to investigate the cardioprotective effects of QSHT. Western blotting and immunochemistry were used to verify the core targets and the signaling pathway.Results: A total of 68 active ingredients were found in the QSHT decoction. Network pharmacology indicated 28 targets and 147 signal pathways, including AKT1, HIF-1α, GSK-3β, TLR4 and NF-κB, those key targets were also verified by molecular docking. The results of GO and KEGG enrichment analysis showed that the targets of QSHT against CHD were largely associated with inflammatory and oxidative stress, and AKT/HIF-1α and TLR4/NF-κB pathways might be key functional pathways. In vivo, QSHT significantly improved cardiac function and attenuated fibrosis and inflammation. Furthermore, QSHT could significantly inhibit the expression of HIF-1α, TLR4, phosphorylation of AKT1, GSK-3β and NF-κB after MI in ApoE−/− mice.Conclusion: Based on network pharmacology, molecular docking and experimental verification, this study demonstrated that QSHT could improve cardiac function and attenuate cardiac fibrosis by regulating TLR4/NF-κB and AKT/HIF-1α signaling pathway in post- MI and high-fat diet ApoE−/− mice.Keywords: network pharmacology, molecular docking, Qushi Huatan decoction, coronary heart disease

Wei Lu,&ast; Zhenyu Yang,&ast; Mengjie Wang, Ye Zhang, Zuoliang Qi, Xiaonan Yang Department of Hemangioma and Vascular Malformation, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100144, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaonan Yang, Department of Hemangioma and Vascular Malformation, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100144, People’s Republic of China, Email yxnan@aliyun.comIntroduction: Infantile Hemangioma (IH) is a prevalent benign vascular tumor affecting approximately 5– 10% of infants. Its underlying pathogenesis remains enigmatic, and current therapeutic approaches show limited effectiveness. Our study aimed to discover potential IH-associated therapeutics through a transcriptomic, computational drug repurposing methodology.Methods: Utilizing the IH-specific dataset GSE127487 from the Gene Expression Omnibus, we identified differentially expressed genes (DEGs) and conducted weighted gene coexpression network analysis (WGCNA). Subsequently, a protein-protein interaction (PPI) network was constructed to obtain the top 100 hub genes. Drug candidates were sourced from the Connectivity Map (CMap) and Comparative Toxicogenomics Database (CTD).Results: Our analysis revealed 1203 DEGs and a significant module of 1780 mRNAs strongly correlated with IH. These genes were primarily enriched in the PI3K/AKT/MTOR, RAS/MAPK, and CGMP/PKG signaling pathway. After creating a PPI network of overlapping genes, we filtered out the top 100 hub genes. Ultimately, 44 non-toxic drugs were identified through the CMap and CTD databases. Twelve molecular-targeting agents (belinostat, chir 99021, dasatinib, entinostat, panobinostat, sirolimus, sorafenib, sunitinib, thalidomide, U 0126, vorinostat, and wortmannin) may be potential candidates for IH therapy. Moreover, in vitro experiments demonstrated that entinostat, sorafenib, dasatinib, and sirolimus restricted the proliferation and migration and initiated apoptosis in HemEC cells, thereby underscoring their potential therapeutic value.Conclusion: Our investigation revealed that the pathogenic mechanism underlying IH might be closely associated with the PI3K/AKT/MTOR, RAS/MAPK, and CGMP/PKG signaling pathways. Furthermore, we identified twelve molecular-targeting agents among the predicted drugs that show promise as therapeutic candidates for IH.Plain Language Summary: Transcriptomic analysis used to discover potential therapeutics for Infantile Hemangioma (IH).Key IH-related pathways: PI3K/AKT/MTOR, RAS/MAPK, and CGMP/PKG signaling identified.Identified 44 non-toxic drugs as potential IH therapies via CMap and CTD.Twelve molecular agents show potential as IH therapy candidates.In vitro studies confirmed entinostat, sorafenib, dasatinib, and sirolimus inhibit HemEC cell proliferation and induce apoptosis. Keywords: infantile hemangioma, entinostat, sirolimus, hub gene, transcriptome, bioinformatics

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

Tong Chen,1– 4 Yu Liu,2,3 Shiquan Wu,2 Siyu Long,2 Ling Feng,4,5 Wenqian Lu,6 Wenya Chen,2 Guoai Hong,2 Li Zhou,2 Fang Wang,2 Yuechan Luo,2 Hequn Zou,2,4,6 Weihua Liu7 1Department of Nephrology, Chongqing Key Laboratory of Prevention and Treatment of Kidney Disease, Chongqing Clinical Research Center of Kidney and Urology Diseases, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, 400037, People’s Republic of China; 2South China Hospital of Shenzhen University, Shenzhen, 518116, People’s Republic of China; 3Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National Regional Key Technology Engineering Laboratory for Medical Ultrasound School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, 518060, People’s Republic of China; 4Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 5Department of Nephrology, Shenzhen Hospital, Southern Medical University, Shenzhen, People’s Republic of China; 6School of Medicine, The Chinese University of Hong Kong, Shenzhen, People’s Republic of China; 7Department Nephrology of Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fujian, 350001, People’s Republic of ChinaCorrespondence: Weihua Liu, Department Nephrology of Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fujian, 350001, People’s Republic of China, Email lwh10280465@163.com Hequn Zou, School of Medicine, The Chinese University of Hong Kong, Shenzhen, People’s Republic of China, Email zouhequn@cuhk.edu.cnBackground: Obesity and insulin resistance (IR) are positively associated with chronic kidney disease (CKD). Previous studies have identified triglyceride-glucose index (TyG) as a valuable surrogate of insulin resistance. Recently, new indicators combining TyG and simple anthropometric indices have emerged, The objective of this study was to assess the diagnostic accuracy of TyG and newly TyG related indicators in detecting CKD and explore which indices were superior in associating with CKD in Chinese population.Methods: Correlation test, logistic regression analysis, and receiver operating characteristic (ROC) analyses were used to evaluate the optimal cut-off and value of TyG, TyG-body mass index (TyG-BMI), TyG-waist circumference (TyG-WC), TyG-waist to height ratio (TyG-WHtR) for predicting CKD.Results: TyG-WHtR, TyG-WC, and TyG-BMI correlated with several risk factors for CKD. After adjusting for confounders, TyG-WHtR and TyG-WC remained significantly associated with CKD, while TyG-BMI did not. The highest quartiles of TyG-WHtR and TyG-WC had 1.95- and 1.91-fold increased risk of CKD than the lowest quartiles (P< 0.05). TyG-WHtR had the largest AUC (0.687) for CKD detection, followed by TyG-WC (0.669), TyG (0.652), and TyG-BMI (0.648). A united model that involved TyG-WHtR and other risk variables had higher predictive performance (AUC=0.791) than a single TyG related indicator. However, TyG had the highest OR (2.713, 95% CI, 1.446– 5.090) for reduced eGFR in the fully adjusted model. A united model that involved TyG and WHtR separately had stronger predictive ability (AUC: 0.794) than the model that involved TyG-WHtR individually (AUC:0.791).Conclusion: This study found that TyG-WHtR had a better diagnostic value in the diagnosis of CKD, compared to other TyG related indicators, but none of the TyG related indicators showed a stronger association with CKD than TyG. Further research and more refined algorithms are needed to verify these new indicators.Keywords: chronic kidney disease, insulin resistance, obesity, TyG related indicators

Haishui Sun,1,&ast; Xiao Wang,2,3,&ast; Zhaoyang Guo,4,&ast; Zhenrong Hu,5 Yuanchen Yin,4 Shuhan Duan,6 Wenwen Jia,2 Wei Lu,2,3 Jingzhou Hu1,7 1Department of Oral and Maxillofacial - Head and Neck Oncology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, People’s Republic of China; 2Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, People’s Republic of China; 3Shanghai Key Laboratory of D&A for Metal Functional Materials, School of Materials Science and Engineering, Tongji University, Shanghai, People’s Republic of China; 4School of Stomatology, Weifang Medical University, Weifang, Shandong Province, People’s Republic of China; 5Department of Stomatology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 6Shanghai Key Laboratory of Stomatology, Department of Oral Surgery, Shanghai Ninth People’s Hospital, College of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Research Institute of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 7Department of Oral and Maxillofacial Surgery, Zhang Zhiyuan Academician Workstation, Hainan Western Central Hospital, Shanghai Ninth People’s Hospital, Danzhou, Hainan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingzhou Hu; Wei Lu, Email huyayi@shsmu.edu.cn; weilu@tongji.edu.cnIntroduction: Traditional surgical resection, radiotherapy, and chemotherapy have been the treatment options for patients with head and neck squamous cell carcinoma (HNSCC) over the past few decades. Nevertheless, the five-year survival rate for patients has remained essentially unchanged, and research into treatments has been relatively stagnant. The combined application of photothermal therapy (PTT) and immunotherapy for treating HNSCC has considerable potential.Methods: Live-dead cell staining and CCK-8 assays proved that Fe3O4 nanoparticles are biocompatible in vitro. In vitro, cellular experiments utilized flow cytometry and immunofluorescence staining to verify the effect of Fe3O4 nanoparticles on the polarisation of tumor-associated macrophages. In vivo, animal experiments were conducted to assess the inhibitory effect of Fe3O4 nanoparticles on tumor proliferation under the photothermal effect in conjunction with BMS-1. Tumour tissue sections were stained to observe the effects of apoptosis and the inhibition of tumor cell proliferation. The histological damage to animal organs was analyzed by hematoxylin and eosin (H&E) staining.Results: The stable photothermal properties of Fe3O4 nanoparticles were validated by in vitro cellular and in vivo animal experiments. Fe3O4 photothermal action not only directly triggered immunogenic cell death (ICD) and enhanced the immunogenicity of the tumor microenvironment but also regulated the expression of tumor-associated macrophages (TAMs), up-regulating CD86 and down-regulating CD206 to inhibit tumor growth. The PD-1/PD-L1 inhibitor promoted tumor suppression, and reduced tumor recurrence and metastasis. In vivo studies demonstrated that the photothermal action exhibited a synergistic effect when combined with immunotherapy, resulting in significant suppression of primary tumors and an extension of survival.Conclusion: In this study, we applied Fe3O4 photothermolysis in a biomedical context, combining photothermolysis with immunotherapy, exploring a novel pathway for treating HNSCC and providing a new strategy for effectively treating HNSCC.Keywords: photothermal therapy, immunotherapy, tumor-associated macrophages, head and neck squamous cell carcinoma

Wensheng Lu,1 JianFeng Wang,2 YuanJing Zhang,1 Ruixue Chang,1 Jun Zhao3 1Department of Dermatology, The No. 1 Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui, People’s Republic of China; 2Department of Dermatology, The No. 1 Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui, People’s Republic of China; 3Department of Dermatology, The Lu’an Hospital Affiliated to Anhui Medical University, Lu’an, Anhui, People’s Republic of ChinaCorrespondence: Wensheng Lu; Jun Zhao, Email 492051693@qq.com; 13085092159@163.comIntroduction: This study observed the effectiveness of ustekinumab and reactivation risk of concurrent latent tuberculosis infection (LTBI) and inactive hepatitis B virus (HBV) infection in Chinese mainland psoriasis patients on ustekinumab treatment.Methods: This retrospective, multicenter, observational study was conducted in three centers in China. Adult patients with moderate to severe plaque psoriasis were treated with ustekinumab for 28 weeks. The effectiveness endpoint included 75% and 90% improvement in Psoriasis Area Severity Index (PASI75/90) response rate, percentage of PASI improvement, change of absolute PASI score and body surface area involvement (BSA) score, absolute PASI ≤ 1/3 and Physicians’ Global Assessment (PGA)=0/1, as well as Dermatology life quality index (DLQI)=0/1 response rate at week 4, 16 and 28. Screening of tuberculosis and hepatitis were performed at baseline and week 28.Results: A total of 82 patients were enrolled between March 2021 and May 2023 and the number of patients combined with LTBI and inactive HBV infection was 20 and 21 respectively. The PASI75 and PASI90 response rate at week 28 was 95.1% and 81.7% respectively. The mean PASI score decreased from 14.93 ± 12.07 at baseline to 0.78 ± 1.86 at week 28, and the mean BSA score decreased from 21% ± 18% at baseline to 1% ± 2% at week 28 (both P< 0.001 compared with baseline). DLQI 0/1 response rate at week 28 was 73.2%. No reactivation of LTBI and inactive HBV infection and also no new-onset tuberculosis and hepatitis B occurred in patients without LTBI and inactive HBV infection at baseline.Conclusion: Ustekinumab demonstrated great effectiveness in Chinese plaque psoriasis patients and good safety in psoriasis concurrent with LTBI and inactive HBV infection under the real-world setting.Keywords: ustekinumab, plaque psoriasis, real-world effectiveness, LTBI, inactive HBV infection

Min Jiang,1,&ast; Hui Zhang,2,&ast; Wenjun Lu,3 Xuedan Qiu,1 Chenyao Lin,1 Rongqing Zhao,1 Qingcao Li,1 Qiaoping Wu1 1Clinical Laboratory, The Affiliated LiHuiLi Hospital of Ningbo University, Ningbo, Zhejiang Province, People’s Republic of China; 2Clinical Laboratory, Ninghai County Chengguan Hospital, Ningbo, Zhejiang Province, People’s Republic of China; 3Intensive Care Units, The Affiliated LiHuiLi Hospital of Ningbo University, Ningbo, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingcao Li; Qiaoping Wu, The Affiliated LiHuiLi Hospital of Ningbo University, 1111 Jiangnan Road, Ningbo, Zhejiang Province, 315040, People’s Republic of China, Tel +86-574-55835786, Fax +86-574-55835781, Email lqc_lab@163.com; lhlyywqp@163.comBackground: Klebsiella pneumoniae (KP) is a common nosocomial pathogen. Capsules are an important component of KP’s virulence, among which the K1, K2, K5, K20, K54, and K57 serotypes are predominant and exhibit varying degrees of virulence.Methods: The capsule and virulence genes of 150 carbapenem-resistant Klebsiella pneumoniae (CRKP) and 213 carbapenem-sensitive Klebsiella pneumoniae (CSKP) isolates were examined by polymerase chain reaction (PCR). The isolates were tested for hypermucoviscosity by string tests. Phylogenetic relationships between KP isolates were analyzed using multilocus sequence typing (MLST) and a Galleria mellonella infection model confirmed the differences in virulence.Results: A total of 111 of 363 isolates of KP were detected, the highest detected serotypes were K1, K5, and K2, and CSKP was detected more frequently than CRKP. There was a greater prevalence of K1 and K2 serotypes in CSKP, while in CRKP, K5 serotypes were more prevalent. K1 isolates had the highest detection rates for hypermucoviscosity Klebsiella pneumoniae (hmKP) and hypervirulent Klebsiella pneumoniae (hvKP), and carried the most virulence genes. K54 isolates had the lowest detection rate of hmKP while K5 isolates had the lowest detection rate of hvKP and carried the fewest virulence genes. MLST results for serotypes K1, K20, and K57 showed significant homogeneity, while those for serotypes K2, K5, and K54 showed diversity. The Galleria mellonella infection model showed that the K1 serotype was the most virulent and the K54 serotype was the weakest.Conclusion: CSKP isolates were detected more frequently than CRKP isolates for capsular serotype detection. K1 isolates had the most virulence gene and strongest virulence, K5 isolates carried the fewest virulence genes, and K54 isolates had the weakest virulence. Furthermore, significant homogeneity was observed among K1, K20, and K57 isolates.Keywords: Klebsiella pneumoniae, capsular serotypes, virulence, MLST

Xi Wang,1 Xinxin Liu,1 Yaoyao Guo,1,2 Tingting Gong,1 Wenmin Lu,1,3 Meihua Han,1 Yifei Guo,1 Xiangtao Wang1 1Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2College of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, People’s Republic of China; 3College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, People’s Republic of ChinaCorrespondence: Xiangtao Wang, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 151, Malianwa North Road, Haidian District, Beijing, 100193, People’s Republic of China, Tel +86-10-57833266, Email xtaowang@163.comBackground: Breast cancer is a heterogeneous disease globally accounting for approximately 1 million new cases annually. Chemotherapy remains the main therapeutic option, but the antitumor efficacy needs to be improved.Methods: Two multifunctional nanoparticles were developed in this paper using oleic acid and mPEG2k-PCL2k as the drug carriers. Squamocin (Squ) was employed as a chemotherapeutic agent. Resiquimod (R848) or ginsenoside Rh2 was co-encapsulated in the nanoparticles to remold the immunosuppressive tumor microenvironment, and IR780 was coloaded as a photosensitizer to realize photothermal therapy.Results: The obtained Squ-R848-IR780 nanoparticles and Squ-Rh2-IR780 nanoparticles were uniformly spherical and approximately (162.200 ± 2.800) nm and (157.300 ± 1.1590) nm, respectively, in average diameter, with good encapsulation efficiency (above 85% for each drug), excellent stability in various physiological media and high photothermal conversion efficiency (24.10% and 22.58%, respectively). After intravenous administration, both nanoparticles quickly accumulated in the tumor and effectively enhanced the local temperature of the tumor to over 45 °C when irradiated by an 808 nm laser. At a low dose of 0.1 mg/kg, Squ nanoparticles treatment alone displayed a tumor inhibition rate of 55.28%, pulmonary metastasis inhibition rate of 59.47% and a mean survival time of 38 days, which were all higher than those of PTX injection (8 mg/kg) (43.64%, 25 days and 37.25%), indicating that Squ was a potent and effective antitumor agent. Both multifunctional nanoparticles, Squ-Rh2-IR780 nanoparticles and Squ-R848-IR780 nanoparticles, demonstrated even better therapeutic efficacy, with tumor inhibition rates of 90.02% and 97.28%, pulmonary metastasis inhibition rates of 95.42% and 98.09, and mean survival times of 46 days and 52 days, respectively.Conclusion: The multifunctional nanoparticles coloaded with squamocin, R848 and IR 780 achieved extraordinary therapeutic efficacy and excellent antimetastasis activity and are thus promising in the future treatment of breast tumors and probably other tumors.Keywords: breast cancer, multifunctional nanoparticle, antitumor efficacy, antimetastasis, combined therapy

Wei Wu,1– 4,&ast; Wenbin Lu,5,&ast; Dongmei Hong,1– 4 Xiya Yu,1– 4 Lize Xiong1– 4 1Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Shanghai, 200434, People’s Republic of China; 2Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200434, People’s Republic of China; 3Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200434, People’s Republic of China; 4Clinical Research Centre for Anesthesiology and Perioperative Medicine, Tongji University, Shanghai, 200434, People’s Republic of China; 5Faculty of Anesthesiology, Changhai Hospital, Naval Medical University/Second Military Medical University, PLA, Shanghai, 200433, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiya Yu; Lize Xiong, Tel +86-21-55603999 ; +86-21-55603002, Fax +86-21-56660851, Email yuxiyash@163.com; mzkxlz@126.com; lizexiong@tongji.edu.cnBackground: The hemoglobin-albumin-lymphocyte-platelet (HALP) index is a novel biomarker reflecting systemic inflammation and nutritional status which are important for coronavirus disease 2019 (COVID-19) mortality. However, the association between HALP and mortality in patients with COVID-19 has yet to be investigated.Methods: A cohort of COVID-19 Omicron BA.2 infected patients admitted to the Shanghai Fourth People’s Hospital, School of Medicine, Tongji University from April 12, 2022 to June 17, 2022 was retrospectively analyzed. Laboratory examinations on hospital admission, including hemoglobin, albumin, and lymphocyte and platelet, were collected. The association between baseline HALP and in-hospital poor overall survival (OS) was assessed using Kaplan–Meier curves, Cox regression models, interaction, and stratified analyses.Results: A total of 2147 patients with COVID-19 Omicron BA.2 infection were included in the final analyses, and mortality in the hospital was 2.65%. Multivariate analysis indicated that low HALP index was independently associated with in-hospital mortality of COVID-19 patients [hazard ratio (HR) = 2.08; 95% confidence interval (CI) = 1.17– 3.73]. Subgroup analysis demonstrated that low HALP index was an independent risk factor for in-hospital mortality in COVID-19 patients with age ≥ 70 (HR = 2.22, CI = 1.18– 4.15) and severe cases (HR = 2.09, CI = 1.13– 3.86).Conclusion: HALP index is independently related to in-hospital poor OS for COVID-19 Omicron BA.2 infected patients, especially for age ≥ 70 and severe cases. HALP index on hospital admission is a useful candidate biomarker for identifying high risk of mortality in COVID-19 Omicron BA.2 infected patients.Keywords: biomarkers, COVID-19, hemoglobin-albumin-lymphocyte-platelet index, mortality, Omicron BA.2

Xiuxian Huang,1,&ast; Zhengming Li,1,&ast; Zhenwei Zhai,1,&ast; Qiu Wang,1 Rongyan Wei,1 Jiacheng Mo,2 Jianhao Huang,1 Wensheng Lu1,&ast; 1Department of Endocrinology and Metabolism of Guangxi Academy of Medical Sciences, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China; 2Information Network Center of Guangxi Academy of Medical Sciences, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wensheng Lu, Email lwswxqz@163.comAim: Metabolic dysfunction-related fatty liver disease (MAFLD) is closely related to metabolic disorders. However, the relationship between MAFLD and the prognosis in diabetic foot ulcers (DFUs) remains unclear. This study aimed to explore the association between MAFLD and the risk of major adverse cardiac and cerebral events (MACCEs) in patients with DFUs.Methods: 889 inpatients with DFUs (PEDIS/TEXAS mild and above) were included in this study from 2013 to 2023. All participants were placed into non-MAFLD (n = 643) and MAFLD (n = 246) groups and followed up every 6 months for 10.9 years with a median of 63 months through in-person outpatient interviews and family fixed-line telephone visits. The association between MAFLD and the risk of MACCEs was evaluated through Multivariate Cox regression analyses, Stratified analyses and Kaplan-Meier survival analyses.Results: Of the 889 subjects, 214 (24.07%) experienced MACCEs. Multivariate Cox regression analysis showed that MAFLD was independently associated with MACCEs (P < 0.001), of which with non-fatal myocardial infarction (P = 0.04), non-fatal stroke (P = 0.047), coronary artery revascularization (P = 0.002), heart failure (P = 0.029), and all-cause mortality (P = 0.021), respectively. The stratified analysis revealed that compared with non-MAFLD (HR=1), DFUs with MAFLD had a 2.64-fold increased risk for MACCEs (P < 0.001; P for interaction = 0.001) in peripheral arterial disease (PAD) subgroup. Kaplan-Meier analysis evidenced that the MAFLD group had a higher cumulative incidence of MACCEs (log-rank, all P < 0.05).Conclusion: MAFLD is a high-risk factor for MACCEs in patients with DFUs. The findings will remind clinicians to pay more attention to MAFLD in patients with DFUs, especially in patients with DFUs combined with PAD as early as possible in clinical practice and adopt timely effective intervention strategies to prevent the occurrence of MACCEs to improve the clinical prognosis in patients with DFUs.Keywords: diabetic foot ulcers, peripheral arterial disease, metabolic dysfunction-associated fatty liver disease, major adverse cardiac and cerebral events

Yan Teng, Mingyang Ren, Xianhong Yang, Wei Lu, Xiaohua Tao Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou, 310014, People’s Republic of ChinaCorrespondence: Xiaohua Tao, Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China, Tel +86-13505811700, Email taoxiaohua@hmc.edu.cnBackground: Mucous membrane pemphigoid (MMP), a rare autoimmune vesiculous and erosive disorder, may affect multiple mucous membranes, with the oral cavity being the most commonly affected site. Its treatment depends on the site(s) of mucosal involvement and disease severity.Patients and Methods: A 62-year-old female patient with MMP that predominantly involved the oral cavity strongly rejected systemic corticosteroid or immunosuppressive agents and was successfully treated with abrocitinib, a highly selective JAK-1 inhibitor with a good safety profile.Results: The case demonstrated good efficacy and safety profile of abrocitinib for the treatment of MMP with predominant oral involvement.Conclusion: Abrocitinib is a promising agent for the treatment of MMP with oral involvement.Keywords: abrocitinib, mucous membrane pemphigoid, JAK inhibitor

Yanni Tan,1,&ast; Yameng Li,2,&ast; Xiuxian Huang,3,&ast; Zhenwei Zhai,3,&ast; Qiu Wang,3,&ast; Yanli Guo,4 Junjun Li,5 Wensheng Lu3,&ast; 1Department of Endocrinology and Respiratory of the Third People’s Hospital of Nanning, Nanning, Guangxi, 530003, People’s Republic of China; 2Medical Department of Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China; 3Department of Endocrinology and Metabolism of Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China; 4Yuncheng Vocational and Technical University, Yuncheng, Shanxi, 044000, People’s Republic of China; 5Hospital Dean’s Office of Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wensheng Lu, Department of Endocrinology and Metabolism, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, No. 6, Taoyuan Road, Nanning, Guangxi, 530021, People’s Republic of China, Email Lwswxqz@163.com Junjun Li, Hospital Dean’s Office of Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, No. 6, Taoyuan Road, Nanning, Guangxi, 530021, People’s Republic of China, Email lijunjun6225@163.comObjective: To explore the relationship between red blood cell distribution width to albumin (RDW/ALB) ratio (RAR) and the risk of rehospitalization and rehospitalization all-cause mortality in middle-aged and elderly survivors with sepsis based on an ambispective longitudinal cohort from the Intensive Care Unit (ICU).Methods: Between 2017 and 2022, 455 adults who survived the first-episode severe sepsis without recurrence for at least 3 months were included in this study. All participants were followed up every 4 weeks for 12 months. According to the tertiles of RAR, participants were divided into three groups: low-level (≤ 0.36, n = 152), moderate-level (0.37– 0.44, n = 152), and high-level (≥ 0.45, n = 151). The relationship between RAR and the risk of rehospitalization and rehospitalization all-cause mortality was evaluated.Results: Out of 455 participants, 156 experienced rehospitalization (34.3%), of which 44 (28.2%) died. Receiver operating characteristic (ROC) analysis showed that the RAR cut-off values for rehospitalization and rehospitalization all-cause mortality were 0.4251 and 0.4743, respectively. Multivariate Cox regression analysis indicated that the RAR was positively associated with rehospitalization (P = 0.011) and all-cause mortality (P = 0.006). Compared with the low-level, the high-level RAR presented a higher dose-dependent rehospitalization risk (P = 0.02) and rehospitalization all-cause mortality (P = 0.044). The stratified analysis displayed that compared to the low-level, with the RAR increasing by 1.0, the risk for rehospitalization increased 3.602-fold in aged < 65 patients (P = 0.002) and 1.721-fold in female patients (P = 0.014). Kaplan–Meier survival analysis implied a significant positive association between the RAR and the cumulative incidence of rehospitalization and rehospitalization all-cause mortality (log-rank, all P < 0.001).Conclusion: RAR has a reliable predictive value for the risk of rehospitalization and rehospitalization all-cause mortality in patients with sepsis. Consequently, monitoring RAR for at least 1 year after surviving sepsis in female patients aged < 65 in clinical practice is critical.Keywords: sepsis, red blood cell distribution width, albumin, rehospitalization, rehospitalization all-cause mortality

Pan Lei,1,2 Wanying Shen,2 Huijuan Tang,2 Li You,2 Guoyi Chen,2 Yijun Tang,1 Wei Lu3 1Hubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of Medicine, Shiyan, People’s Republic of China; 2Hubei Hongshan Laboratory, College of Biomedicine and Health, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, People’s Republic of China; 3Department of Pharmacy, Taihe Hospital, Hubei University of Medicine, Shiyan, People’s Republic of ChinaCorrespondence: Yijun Tang, Hubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of Medicine, Shiyan, People’s Republic of China, Email tyj_799@taihehospital.com Wei Lu, Department of Pharmacy, Taihe Hospital, Hubei University of Medicine, Shiyan, People’s Republic of China, Email luwei0903@taihehospital.comPurpose: Adagrasib is a selective and reversible inhibitor of KRAS G12C, which significantly delays the progression of solid tumors. However, the absorption, distribution, metabolism, and excretion of adagrasib in vivo are unclear. This study explores the absorption and distribution of adagrasib in vivo.Methods: An ultra-high performance liquid chromatography-tandem quadrupole mass spectrometry (UPLC-MS/MS) method was established for the determination of adagrasib in the rat plasma and tissue. Sprague-Dawley rats were intravenous administrated (5 mg/kg) and oral administrated (30 mg/kg) with adagrasib, and the plasma concentration of adagrasib was determined. After single oral administration of adagrasib (30 mg/kg), the heart, liver, spleen, lung, kidney, intestine, and pancreas were excised. The organs were homogenized with saline solution, and the concentration of adagrasib in tissues was determined.Results: The intra- and inter-day accuracy were from 84.90% to 113.47%, and the precision was within ± 15%. The matrix effect and recovery were within ± 15%. The maximum plasma concentration (Cmax) of adagrasib was 677.45 ± 58.72 ng/mL. The elimination half-life time (t1/2) was 3.50 ± 0.21 h after oral administration and 2.08 ± 0.54 h after intravenous administration. The oral bioavailability was 50.72%. The highest concentrations of adagrasib in liver was 5047.80 ± 676.48 ng/g at 2 h after administration, and it was still detectable at 24 hours after administration.Conclusion: Adagrasib was slowly absorbed and cleared rapidly, and it was also widely distributed in vivo. This study provides a potential reference for adagrasib in clinical studies.Keywords: adagrasib, UPLC-MS/MS, pharmacokinetics, tissue distribution

Tong Chen,1– 3 Shiquan Wu,1 Ling Feng,4 SiYu Long,1 Yu Liu,1,2 WenQian Lu,5 Wenya Chen,1 Guoai Hong,1 Li Zhou,1 Fang Wang,1 Yuechan Luo,1 Hequn Zou1,3,5 1Department of Nephrology, South China Hospital of Shenzhen University, Shenzhen, People’s Republic of China; 2Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National Regional Key Technology Engineering Laboratory for Medical Ultrasound School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, People’s Republic of China; 3Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 4Department of Nephrology, Shenzhen Hospital, Southern Medical University, Shenzhen, People’s Republic of China; 5Department of Medicine, The Chinese University of Hong Kong, Shenzhen, People’s Republic of ChinaCorrespondence: Hequn Zou, School of Medicine, The Chinese University of Hong Kong, Shenzhen, People’s Republic of China, Email zouhequn@cuhk.edu.cnBackground: The annual prevalence of metabolic syndrome (MetS) is increasing. Therefore, early screening and recognition of MetS are critical. This study aimed to evaluate the association between high-density lipoprotein (HDL) subclasses and MetS and to examine whether they could serve as early indicators in a Chinese community-based population with normal high-density lipoprotein cholesterol (HDL-C) levels.Methods: We used microfluidic chip technology to measure HDL subclasses in 463 people with normal HDL levels in 2018. We assessed how HDL subclasses correlated with and predicted insulin resistance (IR) and metabolic syndrome (MetS), evaluated by homeostatic model insulin resistance index (HOMA-IR) and the 2009 International Diabetes Federation (IDF), the American Heart Association (AHA), and the National Heart, Lung, and Blood Institute (NHLBI) criteria, respectively. We used correlation tests and ROC curves for the analysis.Results: The results indicate that there was a negative association between HDL2b% and the risk of IR and MetS in both sexes. Subjects in the highest quartile of HDL2b% had a significantly lower prevalence of IR and MetS than those in the lowest quartile (P< 0.01). Correlation analysis between HDL2b% and metabolic risk factors showed that HDL2b% had a stronger association with these factors than HDL-C did in both sexes. ROC curve analysis also showed that HDL2b% had significant diagnostic value for IR and MetS compared to other lipid indicators.Conclusion: This study showed that MetS alters the distribution of HDL subclasses even when HDL-C levels are within the normal range. HDL-2b% has better diagnostic value for IR and MetS than HDL-C alone and may be a useful marker for early screening.Keywords: HDL subclass, insulin resistance, metabolic syndrome, normal HDL-C population