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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

Ying Lv, Wenqing Li, Wei Liao, Haibo Jiang, Yuwei Liu, Jiansheng Cao, Wenfei Lu, Yufei Feng Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Ministry of Education, Harbin, 150040, People’s Republic of ChinaCorrespondence: Yufei Feng, 150040, Tel +86-18503653988, Email fuf-002@163.comAbstract: Natural products have proven to have significant curative effects and are increasingly considered as potential candidates for clinical prevention, diagnosis, and treatment. Compared with synthetic drugs, natural products not only have diverse structures but also exhibit a range of biological activities against different disease states and molecular targets, making them attractive for development in the field of medicine. Despite advancements in the use of natural products for clinical purposes, there remain obstacles that hinder their full potential. These challenges include issues such as limited solubility and stability when administered orally, as well as short durations of effectiveness. To address these concerns, nano-drug delivery systems have emerged as a promising solution to overcome the barriers faced in the clinical application of natural products. These systems offer notable advantages, such as a large specific surface area, enhanced targeting capabilities, and the ability to achieve sustained and controlled release. Extensive in vitro and in vivo studies have provided further evidence supporting the efficacy and safety of nanoparticle-based systems in delivering natural products in preclinical disease models. This review describes the limitations of natural product applications and the current status of natural products combined with nanotechnology. The latest advances in nano-drug delivery systems for delivery of natural products are considered from three aspects: connecting targeting warheads, self-assembly, and co-delivery. Finally, the challenges faced in the clinical translation of nano-drugs are discussed. Keywords: natural products, nanotechnology, drug delivery, targeting

Jia Hao,1 Weijian Lu,2 Wanqi Gong,3 Xiaoxi Chen4 1School of English for International Business, Guangdong University of Foreign Studies, Guangzhou, People’s Republic of China; 2School of Business and Economics, Maastricht University, Maastricht, Netherlands; 3School of Journalism and Communication, Guangdong University of Foreign Studies, Guangzhou, People’s Republic of China; 4School of Management, Jinan University, Guangzhou, People’s Republic of ChinaCorrespondence: Wanqi Gong, School of Journalism and Communication, Guangdong University of Foreign Studies, No. 1689 Bai Yun Avenue, Guangzhou, 510420, People’s Republic of China, Tel +86 20 39328095, Email yunkigong@gmail.comPurpose: Inspiration is a psychological construct that has been relatively understudied in times of difficulty. This study aims to investigate the mediating effect of inspiration on the relationship between emotions and coping strategies in the context of adversity and to testify the effect in Chinese as well as the International societies.Participants and Methods: Using the snowball sampling method, two survey studies were conducted among 523 Chinese and 503 international participants during and soon after the local Covid-19 outbreak to testify how positive and negative emotions contributed to various coping strategies and whether the experience of inspiration mediated these relations. Structural equation modeling (SEM) was used to analyze the data.Results: Positive emotions had a higher impact on problem-solving and seeking social support coping strategies, whereas negative emotions had a higher impact on avoidance coping strategy. Both positive and negative emotions had positive relationships with inspiration, but positive emotions had a higher impact than negative ones. The indirect effects of emotions on problem-solving and social support coping strategies through inspiration were significantly positive, while the avoidance coping strategy was not influenced by the experience of inspiration.Conclusion: The results suggest that being inspired in both positive and negative emotions is positively related to approach coping strategies in adverse situations such as COVID-19, with the effect patterns slightly differing between Chinese participants and their Western counterparts. This study highlights the importance of inspiration experience as a motivational state that can help individuals bring newly acquired ideas into fruition, especially during times of difficulty. By understanding the role of inspiration in the context of adversity, public health systems can better assist individuals in different societies to cope with the challenges they face.Keywords: COVID-19, coping, inspiration, emotions

Wenbin Lu,&ast; Shengwei Lin,&ast; Cheng Wang, Peipei Jin, Jinjun Bian Faculty 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: Peipei Jin; Jinjun Bian, Faculty of Anesthesiology, Changhai Hospital, Naval Medical University, 168, Changhai Road, Shanghai, 200433, People’s Republic of China, Tel/Fax +86-021-31161886 ; +86-021-31161841, Email kingpei89@163.com; jinjunbicu@163.comPurpose: To explore the relationship between the systemic inflammation response index (SIRI) and postoperative delirium (POD) in older patients with hip arthroplasty surgery.Patients and Methods: Older patients who underwent elective hip arthroplasty surgery were included in this retrospective study. SIRI, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were collected from blood routine examination at admission. Binary logistic regression analysis was performed to evaluate the association between SIRI levels and POD was analyzed.Results: Ultimately, 116 older patients who met the inclusion criteria were assessed. Thirty-four (29%) of 116 patients diagnosed with POD were defined as the POD group, and the rest consisted of the Non-POD group. Compared with non-POD patients, POD patients showed significantly higher levels of SIRI (P < 0.001) and NLR (P = 0.002) at admission. There was no significance in the levels of PLR between two groups. SIRI was independently associated with the occurrence of POD in multivariate logistic regression analysis [odds ratio (OR) = 3.34, 95% confidence interval (95% CI) = 1.26– 8.85, P = 0.016]. Receiver operating characteristic curve analysis indicated that SIRI with an optimal cutoff value of 0.987 predicted the POD with a sensitivity of 88.2% and specificity of 74.4%, and the area under the curve was 0.82 (95% CI, 0.74– 0.90, P < 0.01).Conclusion: Preoperative SIRI and NLR levels in the blood are associated with the occurrence of POD. Moreover, preoperative SIRI level is a useful candidate biomarker to identify delirium after elective hip arthroplasty surgery in older patients.Keywords: geriatric, hip arthroplasty, neutrophil to lymphocyte ratio, postoperative delirium, platelet to lymphocyte ratio, systemic inflammation response index

Mingyang Ren,1 Xianhong Yang,2 Yan Teng,2 Wei Lu,2 Yang Ding,2 Xiaohua Tao2 1Department of Graduate School, Bengbu Medical College, Bengbu, People’s Republic of China; 2Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, People’s Republic of ChinaCorrespondence: Xiaohua Tao, Email txhtxh@sina.comAbstract: Granulomatous rosacea (GR) is a rare inflammatory skin disease characterized by persistent, hard, yellow, brown, red, or flesh-colored papules, plaques, or nodules on the face. Limited data are available on patients treated for GR, with only case reports and case series published. Herein, we describe the case of a 53-year-old woman who presented to the hospital with persistent red to brown and pink patches on both cheeks accompanied by a burning sensation for one month. Histopathological examination of a cutaneous biopsy revealed granulomatous inflammation in focal areas. Both acid-fast and Periodic acid-Schiff staining were negative. The patient was diagnosed with GR based on her clinical presentation and laboratory test results. She was treated with abrocitinib, a JAK-1 inhibitor, for 20 weeks. This resulted in substantial improvement in her rash and the associated burning sensation. Subsequent follow-up visits indicated no adverse effects or relapses. Additionally, a literature review was conducted to compare with the current case, which concluded that abrocitinib is a viable treatment option for GR, exhibiting a relatively high safety profile with minimal side effects.Keywords: JAK inhibitor, granulomatous rosacea, abrocitinib, efficacy

Jiangmei Pan,1,2,&ast; Xiuxian Huang,1,&ast; Qiu Wang,1,&ast; Jingxia Sun,1,&ast; Zhenwei Zhai,1,&ast; Jiacheng Mo,3 Jianhao Huang,1 Wensheng Lu1 1Department of Endocrinology and Metabolism, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China; 2Youjiang Medical University for Nationalities, Baise, Guangxi, 533000, People’s Republic of China; 3Information Network Center 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, Email Lwswxqz@163.comPurpose: The triglyceride glucose (TyG) index serves as an indicator of insulin resistance (IR), which is also associated with bone metabolism. However, research on the relationship between the TyG index and a fragility fracture in individuals with type 2 diabetes mellitus (T2DM) or osteoporosis (OP) remains sparse. This study aims to explore the association between the TyG index and fragility fracture risk in postmenopausal elderly females with T2DM combined with OP based on an ambispective cohort study.Patients and Methods: A total of 220 postmenopausal women hospitalized with T2DM combined with OP between January 2015 and December 2020 were eligible for inclusion in this study. All participants were followed up every 6 months for 6 years with a median of 42 months. According to the tertiles of the TyG index, participants were divided into three groups: low-level (≤ 8.79, n =73), moderate-level (8.80– 9.32, n=73), and high-level (≥ 9.33, n=74). The association between the TyG index and fragility fracture risk was then assessed.Results: Out of 220 patients, 46 experienced fragility fracture events (20.9%). Multivariate Cox regression analysis showed that the TyG index was positively associated with a fragility fracture in postmenopausal women with T2DM combined with OP. Furthermore, compared to the low-level group, with the TyG index level increase by 1.0, the risk for fragility fracture increased 1.293-fold in the high-level group (HR=2.293, 95% CI=1.007– 5.221, P < 0.05). Kaplan-Meier survival analysis indicated that fragility fractures were more likely to occur in patients with high levels of TyG index (log-rank, all P < 0.05).Conclusion: Our study showed that the TyG index was strongly associated with a fragility fracture in postmenopausal women with T2DM combined with OP. Therefore, special attention should be paid to postmenopausal elderly females with T2DM combined with OP in routine clinical practice.Keywords: type 2 diabetes mellitus, osteoporosis, triglyceride glucose index, fragility fracture

Wei Lu,1 Yan Cao,2 Fanhua Zeng,1,3 Chun Chen,1,4 Zhenyu Yang,1 Zuoliang Qi,1 Xiaonan Yang1 1The Department of Hemangioma and Vascular Malformation, Plastic Surgery Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, People’s Republic of China; 2The Department of Pathology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, People’s Republic of China; 3The Department of Burn and Plastic Surgery, Hengyang No.1 People’s Hospital, Hunan, People’s Republic of China; 4E.N.T. Department, Shenzhen Longgang District Third People’s Hospital, Guangdong, People’s Republic of ChinaCorrespondence: Xiaonan Yang, The Department of Hemangioma and Vascular Malformation, Plastic Surgery Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, 100144, Tel +86 18810601889, Fax +86 01088964614, Email yxnan@aliyun.comAbstract: Benign lymphangioendothelioma (BL) is a rare, poorly identified, slow-growing benign vascular lesion characterized by asymptomatic, solitary, well-demarcated macules, or by mildly infiltrated plaque. We report a case of an atypical BL that arose as a tender, protuberant, flesh-colored mass with cyanotic vesicles, and then progressed to a persistent exudative wound after two incomplete excisions. The patient was also diagnosed with thoracic duct narrowing. Although the stenosis was removed by surgery, the right lower extremity ulceration and exudation did not improve. Thus, we performed a thorough excision and split-thickness skin graft transplant following vacuum sealing drainage, and eventually the patient had a favorable functional and cosmetic outcome. A biopsy revealed irregular, dilated vascular spaces lined with a single layer of flat endothelial cells extending from the superficial dermis to the subcutis that did not reach the striated muscles. Additionally, by reviewing the literature on BL, in this paper we summarize the diverse pathogenic, morphological, and immunohistochemical presentations for this rare disease, as well as the histopathological differential diagnosis of lymphangiomatosis, Kaposi’s sarcoma, and angiosarcoma.Keywords: acquired progressive lymphangioma, angiosarcoma, benign lymphangioendothelioma, Kaposi’s sarcoma, lymphangioma, lymphangiomatosis

Weiwei Liu,&ast; Yiru Wang,&ast; Kaizheng Chen,&ast; Min Ye, Weisha Lu, Keyu Chen, Xia Shen Department of Anesthesiology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xia Shen, Department of Anesthesiology, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai, 200031, People’s Republic of China, Email shenxiash@fudan.edu.cnPurpose: To examine whether intraoperative dexmedetomidine reduces postoperative delirium (POD) in elderly patients who underwent a laryngectomy.Methods: Patients were randomly assigned to receive dexmedetomidine or a saline placebo infused during surgery. The study period was July 2020 to January 2022. Participants were elderly individuals (≥ 65 years) who underwent a laryngectomy. Immediately after induction of anesthesia, a 0.5 μg.kg− 1 bolus of study solution was administered for 10 min, followed by a maintenance infusion of 0.2 μg.kg− 1.hr− 1 until the end of surgery. Patients were assessed daily for POD (primary outcome). Plasma inflammatory factors were measured at baseline, on the first postoperative day, and on the third postoperative day.Results: In total, 304 male patients were randomized; 299 patients [median (interquartile range) age, 69.0 (67.0– 73.0) years] completed in-hospital delirium assessments. There was no difference in the incidence of POD between the dexmedetomidine and control groups (21.3% [32 of 150] vs 24.2% [36 of 149], P=0.560). However, dexmedetomidine reduced POD in patients with laryngeal cancer and a higher tumor stage (21.6% vs 38.5%; OR, 0.441; 95% CI, 0.209– 0.979; P=0.039). Dexmedetomidine reduced levels of C-reactive protein (CRP) (P=0.0056) and interleukin 6 (IL-6) (P< 0.001) on the first and third postoperative days, respectively. More patients had intraoperative hypotension in the dexmedetomidine group (29.3% [44 of 150] vs 17.4% [26 of 149], P=0.015).Conclusion: Intraoperative dexmedetomidine administration did not prevent POD in patients with laryngeal cancer. Dexmedetomidine reduced serum CRP and IL-6 levels postoperatively but caused a higher occurrence of intraoperative hypotension in elderly patients after a laryngectomy.Keywords: dexmedetomidine, laryngectomy, postoperative delirium, inflammatory factors, surgery complication

Xiuxian Huang,1,&ast; Licai Deng,1,&ast; Jianhao Huang,1,&ast; Jingxia Sun,1 Qiu Wang,1 Jiacheng Mo,2 Zhenwei Zhai,1 Yuechou Nong,1 Wensheng Lu1,&ast; 1Department of Endocrinology and Metabolism, Guangxi Academy of Medical Sciences and the 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 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, Email Lws2613676@sohu.comAim: To clarify the relationship between serum uric acid (UA) and glycosylated hemoglobin (UA/HbA1c) ratio and all-cause mortality in patients with diabetic foot ulcers (DFUs).Methods: A total of 172 inpatients with DFUs (PEDIS grades 2– 4) were eligible for inclusion in this study from 2018 to 2023. This was a retrospective, longitudinal cohort study. All subjects were followed up every 6 months for a median of 60 months. According to the cutoff value of the UA/HbA1c ratio of 39.07 obtained from ROC analysis, the participants were divided into two groups: low-level (≤ 39.07, n = 107) and high-level (> 39.07, n = 65) groups. The correlation between UA/HbA1c ratio and all-cause mortality was also evaluated by Cox regression analysis TheKaplan-Meier survival curve analysis and Log rank tests were used to assess the incidence rates of all-cause mortality. The contribution rate of risk factors was estimated by the population-attributable risk percentage (PAR%) analysis.Results: ROC analysis showed that the optimal cutoff values for UA and the UA/HbA1c ratio were 372 μmol/L and 39.07, respectively. Multivariate Cox regression analysis indicated that a high UA/HbA1c ratio (HR =4.63; 95% CI = 2.004– 10.7, P < 0.001) was independently associated with a high risk of all-cause mortality in patients with DFUs. Stratified analysis indicated that subjects aged ≥ 60 years had a greater risk of all-cause mortality associated with a high UA/HbA1c ratio (HR = 4.450; 95% CI = 1.711– 11.574, P = 0.002). Kaplan-Meier survival analysis showed that all-cause mortality had a significant positive association with a high UA/HbA1c ratio (log-rank, P < 0.001) and a significant negative correlation with the lowered HbA1c level (< 6.5%) after a follow-up of 32 months (log-rank, P < 0.001). The population attributable risk percentage (PAR%) analysis suggested that the contribution rate of the high-level UA/HbA1c ratio to all-cause mortality was 33.7%, which was much greater than the 19.69% of UA.Conclusion: In brief, our study showed that for every 1.0% increase in the UA/HbA1c ratio, the all-cause mortality rate in elderly patients with DFUs aged ≥ 60 years increased by 3.45-fold. For elderly patients with DFUs, a safe and effective strategy to reduce all-cause mortality is to strictly control serum UA levels to < 372 μmol/L and appropriately loosen the control goal of HbA1c to ≥ 6.5%.Keywords: diabetic foot ulcer, uric acid to glycosylated hemoglobin ratio, all-cause mortality

Xianhong Yang,1 Yunlin Ren,1,2 Huachu Liu,1,3 Yan Ten,1 Yang Ding,1 Shasha Fan,1 Xiaohua Tao,1 Wei Lu1 1Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, 310014, People’s Republic of China; 2Department of Dermatology and Venereology, The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 3Department of Dermatology and Venereology, The Third Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Zhong Shan Hospital), Hangzhou, 310009, People’s Republic of ChinaCorrespondence: Xiaohua Tao; Wei Lu, Email txhtxh@sina.com; miniluwei@163.comAbstract: We report a case of 32-year-old patient who presented with painless erythematous plaque gradually ulcerated for 9 years. He had a history of pulmonary tuberculosis 12 years ago and was cured by the treatment of 2HRZE/4HR. The laboratory examination of t-spot and PPD skin test was positive. Histopathology examinations of left cervical lymph node as well as skin revealed granulomatous inflammation with caseous necrosis. A diagnosis of scrofuloderma was made. Negative sputum culture and chest CT scan results excluded pulmonary tuberculosis. The patient was treated with a standard antituberculosis therapy and recovered well after 5 months’ follow-up. Scrofuloderma is a rare manifestation of mycobacterial infection. Early diagnosis and treatment are very important.Keywords: case report, cutaneous tuberculosis, scrofuloderma, caseous necrosis

Ya-Ming Xie,1 Wenfeng Lu,2 Jian Cheng,1 Mugen Dai,3 Si-Yu Liu,4 Dong-Dong Wang,1 Tian-Wei Fu,1 Tai-Wei Ye,1 Jun-Wei Liu,1 Cheng-Wu Zhang,1 Dong-Sheng Huang,1 Lei Liang1 1Department of Hepatobiliary & Pancreatic Surgery and Minimally Invasive Surgery, General Surgery, Cancer Center, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, People’s Republic of China; 3Department of Gastroenterology, The Fifth Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China; 4Department of Laboratory Medicine, The Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research of Zhejiang Province, Zhejiang University Lishui Hospital, Lishui, Zhejiang, People’s Republic of ChinaCorrespondence: Lei Liang; Dong-Sheng Huang, Department of Hepatobiliary & Pancreatic Surgery and Minimally Invasive Surgery, General Surgery, Cancer Center, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China, Email liangl1992@hotmail.com; huangdshz88@hotmail.comBackground: Nutritional and inflammatory status has been reported to be associated with the prognosis of hepatocellular carcinoma (HCC), but many studies did not include all biomarkers simultaneously. The present study aimed to determine the impact of Naples prognostic score (NPS) on the long-term survival in patients undergoing hepatectomy for HCC.Methods: Patients with HCC after curative resection were eligible. Then, all patients were stratified into three groups according to the NPS. Clinical features and survival outcomes were compared among the three groups. Independent prognostic factors were determined by COX analysis. The time dependent receiver operating characteristic (ROC) curves were used to compare prognostic performance with other immunonutrition scoring systems.Results: A total of 476 patients were enrolled eventually. Baseline characteristics showed that patients with higher NPS had a higher proportion of poor liver function and advanced tumor features. Accordingly, Kaplan-Meier survival curves showed that patients with higher NPS had a lower rate of overall survival (OS) and recurrence-free survival (RFS). Multivariable COX analysis demonstrated that NPS was an independent risk factor of OS (NPS group 2 vs 1: HR=1.958, 95% CI: 1.038– 3.369, p = 0.038; NPS group 3 vs 1: HR=2.608, 95% CI: 1.358– 5.008, p=0.004, respectively) and RFS (NPS group 2 vs 1: HR=2.014, 95% CI: 1.299-2-3.124, p=0.002; NPS group 3 vs 1: HR=2.002, 95% CI: 1.262– 3.175, p=0.003, respectively). The time-dependent ROC curve showed that NPS was superior to other models in prognostic performance and discriminatory power for long-term survival (median AUC 0.675, 95% CI: 0.586– 0.712, P < 0.05).Conclusion: The NPS is a simple tool strongly associated with long-term survival in patients undergoing curative hepatectomy for HCC.Keywords: hepatocellular carcinoma, Naples prognostic score, nutritional indicator, inflammatory indicator, prognostic performance

Jianhao Huang,1,2,&ast; Jingxia Sun,2,&ast; Qiu Wang,2,&ast; Jianming Mo,2,&ast; Yuechou Nong,2 Zhenwei Zhai,2 Xiuxian Huang,2 Jiacheng Mo,3 Wensheng Lu2 1The Department of Endocrinology and Metabolism, Jinan University, Guangzhou, Guangdong, 510632, People’s Republic of China; 2The Department of Endocrinology and Metabolism, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China; 3Information Network Center 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, Email Lwswxqz@163.comAim: To explore the therapeutic efficacy of autologous wound edge-dotted full-thickness skin grafting in improving diabetic foot ulcer healing.Methods: Sixty-three patients were divided into three groups: conventional wound therapy (CWT) (n = 23), platelet-rich plasma (PRP) (n = 20), and graft (n = 20). All participants were followed up for 12 weeks. The therapeutic efficacy of the three different wound treatment modalities was analyzed.Results: After follow-up, 37 (58.7%) patients showed complete wound re-epithelialization, of which 10 (43.5%) occurred in the CWT group, 14 (70.0%) in the PRP group, and 13 (65.0%) in the graft group. Multivariate Cox analysis showed that the independent predictive factors for ulcer healing were different treatment modalities (graft: HR = 3.214, 95% CI=1.300– 7.945, P < 0.05; platelet-rich plasma: HR = 3.075, 95% CI=1.320– 7.161, P < 0.01), ABI (HR = 9.917, 95% CI=2.675– 36.760, P < 0.01), and TcPO2 (HR = 1.040; 95% CI=1.005– 1.076; P < 0.05). Stratified analysis showed that higher ABI in graft group or PRP group had higher wound healing rate (graft group: HR = 3.748, 95% CI=1.210– 11.607, P < 0.05; PRP group: HR = 5.029, 95% CI=1.743– 14.509, P < 0.05); higher TcPO2 in the graft group had higher wound healing rate (HR = 15.805, 95% CI=4.414– 56.594, P < 0.01). Additionally, the wound healing time (P < 0.0167) and cumulative healing rate (P < 0.05) in both the PRP group and graft group were more advantageous. The graft group promotes wound re-epithelialization earlier and faster than in the CWT group and PRP group (P < 0.05). Meanwhile, the graft group had lower medical costs (P < 0.0167).Conclusion: Autologous wound edge dotted full-thickness skin grafting has a higher cost-performance ratio than traditional diabetic foot ulcer wound care and is worthy of further clinical application.Keywords: diabetic foot ulcers, autologous wound edge dotted full-thickness skin graft, platelet-rich plasma

Cong Chen,1,&ast; Jian Liu,2,&ast; Zhuxin Gu,1 Yanjun Sun,1 Wenwu Lu,3 Xiaokan Liu,4 Kang Chen,1 Tianzhi Ma,5 Suming Zhao,1 Hui Zhao1 1Department of Interventional & Vascular Surgery, Affiliated Hospital of Nantong University, Nantong, 226001, People’s Republic of China; 2Dalian Medical University and Affiliated Hospital of Nantong University, Nantong, 226001, People’s Republic of China; 3Department of Medical Ultrasound, Affiliated Hospital of Nantong University, Nantong, 226001, People’s Republic of China; 4Department of Interventional Radiology, Affiliated Hospital 2 of Nantong University, Nantong, 226001, People’s Republic of China; 5Nanjing University of Aeronautics and Astronautics, Nanjing, 210000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Suming Zhao; Hui Zhao, The Affiliated Hospital of Nantong University, No. 20, Xisi Road, Chongchuan District, Nantong City, Jiangsu Province, People’s Republic of China, Tel +86-513-85052071, Email 5201120@ntu.edu.cn; zhaohui8868@sina.comBackground: Hepatocellular carcinoma (HCC) is one of the most lethal malignancies in the world. Patients with HCC choose postoperative adjuvant transarterial chemoembolization (PA-TACE) after surgical resection to reduce the risk of recurrence. However, many of them have recurrence within a short period.Methods: In this retrospective analysis, a total of 173 patients who underwent PA-TACE between September 2016 and March 2020 were recruited. Radiomic features were derived from the arterial and venous phases of each patient. Early recurrence (ER)-related radiomics features of HCC and the spleen were selected to build two rad-scores using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Logistic regression was applied to establish the Radiation (Rad)_score by combining the two regions. We constructed a nomogram containing clinical information and dual-region rad-scores, which was evaluated in terms of discrimination, calibration, and clinical usefulness.Results: All three radiological scores showed good performance for ER prediction. The combined Rad_score performed the best, with an area under the curve (AUC) of 0.853 (95% confidence interval [CI], 0.783– 0.908) in the training set and 0.929 (95% CI, 0.789– 0.988) in the validation set. Multivariate analysis identified total bilirubin (TBIL) and the combined Rad_score as independent prognostic factors for ER. The nomogram was found to be clinically valuable, as determined by the decision curves (DCA) and clinical impact curves (CIC).Conclusion: A multimodal dual-region radiomics model combining HCC and the spleen is an independent prognostic tool for ER. The combination of dual-region radiomics features and clinicopathological factors has a good clinical application value.Keywords: hepatocellular carcinoma, radiomics, nomogram, transcatheter arterial chemoembolization, computed tomography

RiHui Deng,1 LiYan Liu,2 WeiKe Xie,3 Weiguo Lu,1 Zhihui Liu,1 Yang Wang1 1Department of Clinical Laboratory, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Shanghai Xinchao Medical Laboratory, Shanghai, People’s Republic of China; 3Equipment Management Department, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of ChinaCorrespondence: Yang Wang, Department of Clinical Laboratory, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 16, Airport Road, Baiyun District, Guangzhou, 510405, People’s Republic of China, Tel +86-188-2513-5951, Email wangyang90611@gzucm.edu.cnPurpose: Helicobacter pylori (H. pylori) infection is a high-risk factor for the occurrence of gastric cancer. The quadruple therapy has been widely used as the first-line treatment for H. pylori in China. However, the increasing resistance rate to antibiotics has become a major challenge in the treatment of H. pylori. Therefore, there is an urgent need for rapid and cost-effective detection of antibiotic resistance to different antibiotics. To evaluate the prevalence of H. pylori antibiotic resistance in Guangzhou and the diagnostic performance of DOB value of 13C UBT in predicting antibiotic resistance.Patients and Methods: In this retrospective study, we collected data from 193 H. pylori culture-positive patients in Guangzhou on their DOB values and resistance to antibiotics. We analyzed the antibiotic resistance rate of commonly used antibiotics in quadruple therapy, and the diagnostic efficacy of DOB value was evaluated.Results: The resistance rates of clarithromycin (CLA) and levofloxacin (LEV) were 46.1% and 44.0%, respectively. In the age group under 40, the resistance rate of LEV was lower than that of CLA. However, the diagnostic efficacy of DOB value was found to be low and it could not serve as an independent indicator for diagnosing resistance to CLA and LEV.Conclusion: The high resistance rates of CLA and LEV in H. pylori patients in Guangzhou indicate the urgent need for effective detection methods. The DOB value is not a direct indicator of antibiotic resistance to CLA and LEV. Therefore, it is important to use a combination of diagnostic methods to accurately assess antibiotic resistance in H. pylori infection.Keywords: Helicobacter pylori, urea breath test, DOB value, antibiotic resistance

Yuhui Geng,1,&ast; Furong Li,2,&ast; Chen Chen,3 Zhuo Liu,1 Xiaojuan Ma,1 Xinya Su,1 Hua Meng,1 Wenwen Lu,1 Xingtian Wang,1 Dongfeng Pan,4 Peifeng Liang5 1School of Public Health, Ningxia Medical University, Yinchuan, People’s Republic of China; 2Department of Clinical Laboratory, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan, People’s Republic of China; 3Department of Public Health, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan, People’s Republic of China; 4Department of Emergency Medicine, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan, People’s Republic of China; 5Department of Medical Records and Statistics, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peifeng Liang, Department of Medical Records and Statistics, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan, People’s Republic of China, Tel +86 951 13895085519, Email doctor_pf@126.comPurpose: To investigate changes in the incidence of infections by extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) and analyzed whether there was an association between endogenous changes in the organism due to COVID-19 infection and the infections by ESBL-E.Patients and Methods: The study was a single-center retrospective case-control design. A total of 107 patients infected by ESBL-E during the COVID-19 pandemic were selected as the case group, while 214 uninfected patients selected by 1:2 propensity score matching (PSM) acted as the control group. Univariate analysis, LASSO logistic regression, and multivariate logistic regression were used to determine the risk factors for ESBL-E infection. An interrupted time series was used to analyze the changes in the incidence of ESBL-E infections in hospitalized patients during the COVID-19 pandemic.Results: The incidence of infection with ESBL-E showed a significant increase during COVID-19 (3.42 vs 4.92 per 1000 patients, p = 0.003). The incidence of ESBL-E infections increased at an average rate of 0.45 per 1000 patients per week compared to the pre-pandemic period (p = 0.022). Multivariate logistic regression analysis showed that a length of hospitalization ≥ 15 days (OR: 2.98 (1.07– 8.28), chronic kidney disease (OR: 4.25 (1.32– 13.70), white blood cell (WBC) > 9.5× 10^9/L (OR: 3.04 (1.54– 6.01), use of hormonal drugs (OR: 2.38 (1.04– 5.43), antibacterial drug use 1 type (OR: 5.38 (2.04– 14.21), antibacterial drug use 2 types (OR: 23.05 (6.71– 79.25) and antibacterial drug use ≥ 3 types (OR: 88.35 (8.55– 912.63) were independent risk factors for infection with ESBL-E, while chronic obstructive pulmonary disease (COPD) was a protective factor (OR: 0.14 (0.03– 0.66). COVID-19 was not an independent risk factor for infection by ESBL-E.Conclusion: During the COVID-19 pandemic, the incidence of infections by ESBL-E increased significantly. Increased exposure to traditional risk factors were the main reasons, however, COVID-19 was not an independent risk factor for ESBL-E infection.Keywords: β-lactamases, COVID-19, risk factor, antibacterial drugs, case-control study, LASSO

Jingjing Huang,1,2,&ast; Minju Qin,3,&ast; Weisha Lu,3 Xia Shen3 1ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital of Fudan University, Shanghai, People’s Republic of China; 2Shanghai Municipal Key Clinical Specialty, Eye & ENT Hospital of Fudan University, Shanghai, People’s Republic of China; 3Department of Anesthesiology, Eye & ENT Hospital of Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xia Shen, Department of Anesthesiology, Eye & ENT Hospital of Fudan University, Fenyang Road No. 83, Xuhui District, Shanghai, People’s Republic of China, Tel +86-13611874118, Fax +86-21-64373416, Email zlsx@yahoo.comPurpose: To examine whether nighttime dexmedetomidine infusion improved sleep quality in patients after laryngectomy.Patients and Methods: Thirty-five post-laryngectomy patients admitted to the intensive care unit (ICU) were randomly assigned to a 9-h (from 2100 h on surgery day to 0600 h the morning after laryngectomy) dexmedetomidine (0.3 μg/kg/h continuous infusion) or placebo group. Polysomnography results were monitored during the dexmedetomidine infusion period. The percentage of stage 2 non-rapid eye movement (stage N2) sleep was the primary outcome measure.Results: Thirty-five patients (18 placebo group; 17 dexmedetomidine group) had complete polysomnogram recordings. The percentage of stage N3 sleep was significantly increased in the dexmedetomidine infusion group (from median 0% (0 to 0) in placebo group to 0% (interquartile range, 0 to 4) in dexmedetomidine group (difference, − 2.32%; 95% CI, − 4.19 to − 0.443; P = 0.0167)). Infusion had no effect on total sleep time, stage N1 or N2 sleep percentages, or sleep efficiency. It decreased muscle tensity and snore non-rapid eye movement. Subjective sleep quality improved. Hypotension incidence increased in the dexmedetomidine group, but significant intervention was not required.Conclusion: Dexmedetomidine infusion improved overall patient sleep quality in the ICU after laryngectomy.Keywords: dexmedetomidine infusion, postoperative, polysomnography, sleep disordered

Yuexing Gu,1,2,&ast; Yan Li,3,&ast; Shengjie Ge,1,2 Wenbo Lu,4 Yu Mao,1,2 Miao Chen,1,2 Yayun Qian1,2 1Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, People’s Republic of China; 2Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou, People’s Republic of China; 3Department of Obstetrics and Gynecology, The Second People’s Hospital of Taizhou City, Taizhou, People’s Republic of China; 4Shanxi Normal University, College of Chemistry and Material Science, Linfen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yayun Qian, Email yyqian@yzu.edu.cnPurpose: This paper aims to construct a surface-enhanced Raman spectroscopy (SERS) biosensor based on functionalized Au-Si nanocone arrays (Au-SiNCA) using a dual signal amplification strategy (SDA-CHA) to evaluate telomerase activity during epithelial-mesenchymal transition (EMT) in laryngeal carcinoma (LC).Methods: A SERS biosensor based on functionalized Au-SiNCA was designed with an integrated dual-signal amplification strategy to achieve ultrasensitive detection of telomerase activity during EMT in LC patients.Results: Labeled probes (Au-AgNRs@4-MBA@H1) and capture substrates (Au-SiNCA@H2) were prepared by modifying hairpin DNA and Raman signal molecules. Using this scheme, telomerase activity in peripheral mononuclear cells (PMNC) could be successfully detected with a limit of detection (LOD) as low as 10− 6 IU/mL. In addition, biological experiments using BLM treatment of TU686 effectively mimicked the EMT process. The results of this scheme were highly consistent with the ELISA scheme, confirming its accuracy.Conclusion: This scheme provides a reproducible, selective, and ultrasensitive assay for telomerase activity, which is expected to be a potential tool for the early screening of LC in future clinical applications.Keywords: surface-enhanced Raman scattering, telomerase, laryngeal carcinoma, epithelial-mesenchymal transition, Au-SiNCA

Wei Sun,1,2,&ast; Songyi Xu,3,&ast; Tianlun Shen,1,3,&ast; Guangyao Li,1 Jingfeng Zhang,2 Chunshu Pan,1,2 Wei Lu,1,2 Xiangrui Liu,1 Jianjun Zheng,2 Jun Ling,1,3 Jihong Sun1 1Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Radiology, Ningbo No. 2 Hospital, Ningbo, People’s Republic of China; 3MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jihong Sun, Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Tel +86 13857176538, Email sunjihong@zju.edu.cn Jianjun Zheng, President of Ningbo No. 2 Hospital, Ningbo, People’s Republic of China, Tel +86 574 83870280, Email zhjjnb2@163.comPurpose: Chemotherapy treatments for cancer are always accompanied by a low concentration of drug delivered in the tumor area and severe side effects including systemic toxicity. Improving the concentration, biocompatibility, and biodegradability of regional chemotherapy drugs is a pressing challenge in the field of materials.Methods: N-Phenyloxycarbonyl-amino acids (NPCs) which exhibit significant tolerance to nucleophiles, such as water and hydroxyl-containing compounds, are promising monomers for the synthesis of polypeptides and polypeptoids. Cell line and mouse models were used to comprehensively explore how to enhance the tumor MRI signal and evaluate the therapeutic effect of Fe@POS-DOX nanoparticles.Results: In this study, poly(3,4-dihydroxy-L-phenylalanine)-b-polysarcosine (PDOPA-b-PSar, simplified as POS) was synthesized by the block copolymerization of DOPA-NPC with Sar-NPC. Fe@POS-DOX nanoparticles were prepared in order to utilize the strong chelation of catechol ligands to iron (III) cations and the hydrophobic interaction between DOX and DOPA block to deliver chemotherapeutics to tumor tissue. The Fe@POS-DOX nanoparticles exhibit high longitudinal relaxivity (r1 = 7.06 mM− 1·s− 1) and act as T1-weighted magnetic resonance (MR) imaging contrast agents. Further, the main focus was improving tumor site-specific bioavailability and achieving therapeutic effects through the biocompatibility and biodegradability of Fe@POS-DOX NPs. The Fe@POS-DOX treatment exhibited excellent antitumor effects.Conclusion: Upon intravenous injection, Fe@POS-DOX delivers DOX specifically to the tumor tissues, as revealed by MR, and leads to the inhibition of tumor growth without overt toxicity to normal tissues, thus displaying considerable potential for use in clinical applications.Graphical Abstract: Keywords: poly (α-amino acid)s, polypeptides, polypeptoids, MRI, chemotherapy, nanoparticles

Jiamin Wen,1 Jitian Weng,2 Wei Lu,3 Xiaohua Tao,3 Hao Cheng,4,&ast; Yi Tang3,&ast; 1Department of Dermatology, People’s Hospital of Tiantai County, Zhejiang University, Taizhou, People’s Republic of China; 2School of Public Health, Hangzhou Normal University, Zhejiang University, Hangzhou, People’s Republic of China; 3Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Zhejiang University Hangzhou 310014 People’s Republic of China; 4Department of Dermatology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Tang, Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Zhejiang University, 158 Shangtang Road, Xiacheng District, Hangzhou, 310014, People’s Republic of China, Tel +86-13968076453, Fax +86-0571-85335800, Email tangyi@hmc.edu.cn Hao Cheng, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, Zhejiang, 310016, People’s Republic of China, Tel +86-13588706943, Fax +86-571-86006975, Email chenghao1@zju.edu.cnPurpose: To investigate the expression of Plasmacytoid Dendritic Cells (pDCs) and TLR7/9-MyD88-IRAKs pathway in chronic eczema lesions.Patients and Methods: Lesional tissues and the surrounding healthy tissues were collected from 25 individuals with chronic eczema, and immunohistochemistry was used to detect and comparatively analyze the expression profile of CD123, CD2AP, toll-like receptor 7 (TLR7), toll-like receptor 9 (TLR9) along with interleukin-1 receptor-associated kinase 1 (IRAK1) and interferon regulatory factor 7 (IRF7) in signaling pathways.Results: The positive rates of CD2AP + pDC and CD123 + pDC in lesional tissues were significantly elevated compared to the surrounding healthy tissues (P < 0.05). They were distributed in both the epidermal and dermal layers of the lesional tissue, but the majority were in the dermal layer. The TLR7, TLR9, IRAK1 and IRF7 were more expressed in dermal layers of the lesional tissue with higher positive rates of expression compared to the surrounding healthy tissues (P < 0.05). IRAK1 and IRF7 were expressed in a small amount in the epidermal layer with higher positive rates of expression than in the surrounding healthy tissues (P < 0.05), while the positive rates of TLR7 and TLR9 expression in the epidermal layer were not statistically different from those in the surrounding healthy tissues (P > 0.05).Conclusion: PDC and TLR7/9-MyD88-IRAKs pathways are actively expressed in chronic eczema lesions and may be involved in pathogenesis and disease progression.Keywords: eczema, plasmacytoid dendritic cells, toll-like receptor 7, toll-like receptor 9, immunohistochemistry

Wenjing Ta, Xingyue Li, Jihong Song, Ruochen Hua, Yuting Zheng, Wen Lu School of Pharmacy, Health Science Center, Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaCorrespondence: Wen Lu, School of Pharmacy, Health Science Center, Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of China, Email lvlu2004@xjtu.edu.cnPurpose: Nanotechnology-based drug delivery systems (nano-DDS) have been developed to be a promising strategy to improve the efficacy, safety, physicochemical and pharmacokinetic/pharmacodynamics properties of drugs. It is very necessary to elucidate the delivery process in vivo or in cells for the rational design and accurate preparation of nano-DDS. The aim of this study was to construct a nano-DDS to visualize and quantify the intracellular behavior of the loaded cargo and carrier in such a system.Methods: A carboxyl-terminal end of poly(lactic-co-glycolic acid) polymer was fluorescently labeled with rhodamine B by conjugation of ethylenediamine. Dual-fluorescent nanoparticles (DFPs) were prepared from this fluorescently labeled polymer to encapsulate a fluorescent cargo, coumarin 6. The carrier and cargo of DFPs were monitored by confocal fluorescence microscopy during cellular uptake. Furthermore, the transcellular transportation of DFPs was evaluated quantitatively by measuring the fluorescence intensity.Results: The obtained fluorescent polymer showed stable and quantifiable characteristics. DFPs could be customized in terms of coumarin 6 content (97.7± 1.0%), size (367.3± 1.7 nm) and dual-emission fluorescence (green cargo and red carrier). DFPs did not significantly affect cell viability, the integrity of cell monolayers and the microscopic morphology at concentrations below 0.7 mg/mL within 3 h of co-incubation with Caco-2 cells. Multichannel fluorescence monitoring revealed that the fluorescence intensity of the carrier and cargo increased with time, but not synchronously. By calculating the residual, intracellular, and transport amounts of DFPs, the material balance between the total amount of cellular transport and the dose administered was obtained.Conclusion: Based on the advantages of dual fluorescent labeling, the differential behavior of cell trafficking can be visualized and quantitatively analyzed for the cargo and carrier of DFPs. These results provide insights into the cellular transport process of holistic nanoparticles and complement our understanding of the biological behaviors of nano-DDS.Keywords: dual-fluorescent nanoparticles, tracking cellular uptake, fluorescence imaging, quantitative cell transport, drug delivery

Miao Wang,1,&ast; Jin Shi,2,&ast; Kepei Zhang,1,&ast; Jie Hong,2,&ast; Xinwei Peng,2 Yu Tian,1 Wei Lu,3 Ke Li,2 Zengliang Wang,4 Feng Li,1 Zhijie Zhang,2 Guojiang Mei1 1Department of Internal Medicine of Traditional Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Epidemiology and Health Statistics, Fudan University, Shanghai, People’s Republic of China; 3Department of Nursing, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Department of Epidemiology, School of Public Health, Shandong University, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhijie Zhang, Department of Epidemiology and Health Statistics, School of Public Health, Fudan University, Xuhui District, School of Medicine Road, 130, Shanghai, People’s Republic of China, Tel +86-21-54237410, Email epistat@gmail.com; Guojiang Mei, Department of Internal Medicine of Traditional Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 South Wanping Road, Shanghai, 200032, People’s Republic of China, Tel + 86-21-64385700, Email mgj_761014@sina.comPurpose: This study aimed to evaluate the clinical efficacy of Longyizhengqi granule, a traditional Chinese medicine, in patients with mild COVID-19.Patients and Methods: We conducted a prospective study including mild COVID-19 participants conducted at Mobile Cabin Hospital in Shanghai, China. Participants were assigned to receive Longyizhengqi granule or conventional treatment. The primary outcome was the time for nucleic acid to turn negative and the secondary outcomes are hospital stay and changes in cycle threshold (Ct) values for N gene and Orf gene. Multilevel random-intercept model was performed to analyze the effects of treatment.Results: A total of 3243 patients were included in this study (Longyizhengqi granule 667 patients; conventional treatment 2576 patients). Age (43.5 vs 42.1, p< 0.01) and vaccination doses (not vaccinated: 15.8% vs 21.7%, 1 dose: 3.5% vs 2.9%, 2 doses: 27.9% vs 25.6%, 3 doses: 52.8% vs 49.8%. p< 0.01) show statistical difference between Conventional treatment group and LYZQ granules group. The use of Longyizhengqi granule could significantly reduce the time for nucleic acid to turn negative (14.2 days vs 10.7 days, p< 0.01), shorten hospital stay (12.5 days vs 9.9 days, p< 0.01), and increase the changes in Ct value for N gene (8.44 vs 10.33, p< 0.01) and Orf gene (7.31 vs 8.44, p< 0.01) to approximately 1.5. Moreover, the difference in the changes of Ct values on the 4th, 6th, 8th, and 10th days seem to increase between two groups. No serious adverse events were reported.Conclusion: Longyizhengqi granule might be a promising drug for the treatment of mild COVID-19, and it might be beneficial to effectively shorten the negative transition time of nucleic acid, the total days of hospitalization, and increase the changes of Ct values. Long-term randomized controlled trials with follow-up evaluations are required to confirm its long-term efficacy.Keywords: COVID-19, Omicron variant, traditional Chinese medicine, prospective study

Wei Lu,1– 3 Zhaowei Teng,1,2 Jiayu Chen,1– 3 Rongmao Shi,4 Tiannan Zou,1– 3 Ming Gao,1– 3 Weichao Li,1– 3 Zhi Peng,1– 3 Long Wang,1– 3 Yonghui Zhao,1– 3 Sheng Lu1– 3 1Yunnan Key Laboratory of Digital Orthopedics, the First People’s Hospital of Yunnan Province, Kunming, People’s Republic of China; 2Department of Orthopedics, the First People’s Hospital of Yunnan Province, Kunming, People’s Republic of China; 3Department of Orthopedics, the Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650032, People’s Republic of China; 4Department of Orthopedics, Clinical College of the 920th Hospital of Joint Logistics Support Force of Kunming Medical University, Kunming, People’s Republic of ChinaCorrespondence: Sheng Lu, Department of Orthopedics, the First People’s Hospital of Yunnan Province, No. 157 Jinbi Road, Kunming, 650032, People’s Republic of China, Tel +86-0871-63633071, Fax +86-0871-63633071, Email drlusheng@163.comPurpose: The objective of this study was to analyze the clinical characteristics and the therapeutic effects of treatment at our spinal center in OVCF patients associated with referred pain. The underlying goals were to deepen the understanding of referred pain caused by OVCFs, improve the currently low early diagnosis rate of OVCFs, and improve the effectiveness of treatment.Methods: The patients who had referred pain from OVCFs and met the inclusion criteria were retrospectively analyzed. All patients were treated with percutaneous kyphoplasty (PKP). Visual analog scale (VAS) scores and Oswestry Disability Index (ODI) were used to evaluate the therapeutic effect at different time points.Results: There were 11 males (19.6%) and 45 females (80.4%). Their corresponding mean bone mineral density (BMD) value was − 3.3 ± 0.4. The regression coefficient of BMD in the linear regression equation was − 4.51 (P< 0.001). According to the classification system for referred pain in OVCFs, there were 27 cases of type A (48.2%), 12 cases of type B (21.2%), 8 cases of type C (14.3%), 3 cases of type D (5.4%), and 6 cases of type E (10.7%). All patients were followed up for at least 6 months, and both VAS scores and ODI were found to be significantly better postoperatively than preoperatively (P< 0.001). There was no significant difference in VAS scores and ODI between different types preoperatively or 6 months postoperatively (P > 0.05). Within each type, there were significant differences in VAS scores and ODI between the pre- and postoperative timepoints (P < 0.05).Conclusion: Attention should be paid to referred pain in OVCF patients, which is not uncommon in clinical practice. Our summary of the characteristics of referred pain caused by OVCFs can improve the early diagnosis rate of OVCFs patients and provide a reference for their prognosis after PKP.Keywords: referred pain, radicular pain, vertebral fracture, percutaneous kyphoplasty, osteoporosis, spinal fracture

Wangxing Lu,1,&ast; Wenjie Liu,1,&ast; Anna Hu,1 Jian Shen,1 Hanxi Yi,2 Zeneng Cheng1 1Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410000, People’s Republic of China; 2School of Basic Medical Science, Central South University, Changsha, 410000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hanxi Yi; Wenjie Liu, Email hanxiyi2022@csu.edu.cn; wenjie.liu@csu.edu.cnIntroduction: Drug delivery systems (DDSs) based on liposomes are potential tools to minimize the side effects and substantially enhance the therapeutic efficacy of chemotherapy. However, it is challenging to achieve biosafe, accurate, and efficient cancer therapy of liposomes with single function or single mechanism. To solve this problem, we designed a multifunctional and multimechanism nanoplatform based on polydopamine (PDA)-coated liposomes for accurate and efficient combinatorial cancer therapy of chemotherapy and laser-induced PDT/PTT.Methods: ICG and DOX were co-incorporated in polyethylene glycol modified liposomes, which were further coated with PDA by a facile two-step method to construct PDA-liposome nanoparticles (PDA@Lipo/DOX/ICG). The safety of nanocarriers was investigated on normal HEK-293 cells, and the cellular uptake, intracellular ROS production capacity, and combinatorial treatment effect of the nanoparticles were assessed on human breast cancer cells MDA-MB-231. In vivo biodistribution, thermal imaging, biosafety assessment, and combination therapy effects were estimated based on MDA-MB-231 subcutaneous tumor model.Results: Compared with DOX·HCl and Lipo/DOX/ICG, PDA@Lipo/DOX/ICG showed higher toxicity on MDA-MB-231 cells. After endocytosis by target cells, PDA@Lipo/DOX/ICG produced a large amount of ROS for PDT by 808 nm laser irradiation, and the cell inhibition rate of combination therapy reached up to 80.4%. After the tail vein injection (DOX equivalent of 2.5 mg/kg) in mice bearing MDA-MB-231 tumors, PDA@Lipo/DOX/ICG significantly accumulated at the tumor site at 24 h post injection. After 808 nm laser irradiation (1.0 W/cm2, 2 min) at this timepoint, PDA@Lipo/DOX/ICG efficiently suppressed the proliferation of MDA-MB-231 cell and even thoroughly ablated tumors. Negligible cardiotoxicity and no treatment-induced side effects were observed.Conclusion: PDA@Lipo/DOX/ICG is a multifunctional nanoplatform based on PDA-coated liposomes for accurate and efficient combinatorial cancer therapy of chemotherapy and laser-induced PDT/PTT.Keywords: reactive oxygen species, photodynamic therapy, photothermal therapy, polydopamine, liposome

Weihong Lu,1,2 Silan Zheng,3 Jingqi Zhou,3 Shunfa Huang,4 Ning Chen,3 Zhibin Li5 1Department of Gynecology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, People’s Republic of China; 2Xiamen Clinical Research Center for Cancer Therapy, Xiamen, People’s Republic of China; 3Department of Endocrinology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, People’s Republic of China; 4Department of Radiology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, People’s Republic of China; 5Epidemiology Research Unit, Translational Medicine Research Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of ChinaCorrespondence: Ning Chen, Department of Endocrinology, Zhongshan Hospital (Xiamen), Fudan University, No. 668 Jinhu Road, Xiamen, 361000, People’s Republic of China, Tel/Fax +86-0592-3569583, Email chen.ning@zsxmhospital.com Zhibin Li, Epidemiology Research Unit, Translational Medicine Research Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, No. 55 Zhenhai Road, Xiamen, 361003, People’s Republic of China, Tel +86-592-2137364, Fax +86-592-2137557, Email zhibinli33@hotmail.comObjective: This study aimed to examine associations between plasma sex-related hormones with bone mineral density (BMD) and risks of osteoporosis or osteopenia in men and postmenopausal women patients with type 2 diabetes mellitus (T2DM).Methods: Baseline information on an ongoing cohort of 149 men and 102 postmenopausal women with T2DM in Xiamen, China were analyzed. Plasma estradiol (E2), total testosterone (T), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and prolactin (PRL) were measured. BMD of lumbar spine (L2-4), femoral neck (FN) and total hip (TH) were determined by dual-energy X-ray absorptiometry (DXA). Osteoporosis or osteopenia was defined as the minimum T-scores of BMD of these three different sites of − 1.0 or below.Results: T2DM patients with osteoporosis/osteopenia (66.4% in men and 79.4% in postmenopausal women), compared to those without, showed significantly decreased level of E2 (75.3± 28.9 vs. 107.8± 25.9pmol/L and 18.4 (18.4– 29.5) vs. 22.8 (18.4– 40.5) pmol/L for men and postmenopausal women, respectively, both p-values < 0.05), but not other sex-related hormones (including T, FSH, LH, or PRL). For all T2DM patients together and men separately, multivariable linear regression and logistic regression analyses showed that higher E2 levels were significantly associated with higher BMD T-scores in L2-4, FN, TH and minimum of these three different sites, lower 10-year probability of major osteoporotic fractures (MOF) and hip fractures (HFs) estimated by Fracture Risk Assessment Tool score, as well as decreased risk of osteoporosis/osteopenia. As for postmenopausal women T2DM patients, E2 level was positively associated with BMD T-scores in L2-4 and minimum of three different sites but was not independently associated with risk of osteoporosis/osteopenia.Conclusion: Higher plasma E2 was significantly associated with increased BMD and lower risk of osteoporosis or osteopenia in T2DM patients, especially for men. Screening of BMD and estradiol levels as well as evaluating risks of osteoporosis/osteopenia are important for T2DM patients.Keywords: estradiol, bone mineral density, osteoporosis, osteopenia, diabetes, BMD

Yuyuan Shi,1,&ast; Ying Zhao,2,&ast; Wen Kang,2 Wei Lu,3 Dong Chen,3 Jun Tao,3 Jing Li,3 Ruifa Yu,3 Jiajia Zhao,3 Rui Tang,3 Zhaogang Teng,3 Lixing Weng1 1College of Geography and Biological Information, Nanjing University of Posts and Telecommunications, Nanjing, People’s Republic of China; 2Department of Radiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 3Key Laboratory for Organic Electronics & Information Displays and Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials, Jiangsu National Synergetic Innovation Centre for Advanced Materials, Nanjing University of Posts and Telecommunications, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhaogang Teng; Lixing Weng, Email iamzgteng@njupt.edu.cn; lxweng@njupt.edu.cnIntroduction: Photodynamic therapy (PDT) has attracted increasing attention for tumor treatment because of its minimal invasiveness and specific spatiotemporal selectivity. However, insufficient tumor accumulation and low cellular uptake of photosensitizers limit its therapeutic efficacy.Methods: In this study, flexible hollow human serum albumin/catalase nanocapsules (HSA/CATs) were created using a core-assisted protein-coating method and combined with the photosensitizer chlorin e6 (HSA/CAT@Ce6) for PDT.Results and Discussion: Transmission electron microscopy (TEM) images demonstrate that HSA/CAT nanocapsules are flexible, with a uniform diameter (310 nm) and a well-defined hollow structure. Thanks to their flexibility, HSA/CAT@Ce6 nanocapsules show a higher cellular uptake than rigid nanoparticles. The nanocapsules effectively generate reactive oxygen species (ROS) in 4T1 cells because of their high cellular uptake and catalytic capacity, remarkably enhancing their in vitro PDT efficacy. In addition, the in vivo tumor accumulation of HSA/CAT@Ce6 nanocapsules is significantly larger than that of rigid nanoparticles and Ce6, meaning they are highly effective in tumor cell ablation. This demonstrates that our flexible nanoplatform holds great promise for enhancing PDT of tumor.Keywords: flexible nanoplatform, human serum albumin, sufficient tumor accumulation, high cellular uptake, photodynamic therapy

Rui Ni,1– 3 Lele Huang,3 Zhen Li,4 Wenli Zhang,4 Yajie Wang,4 Yan Shen,4 Jianxin Wang,1 Weigen Lu2 1School of Pharmacy, Fudan University, Shanghai, People’s Republic of China; 2China State Institute of Pharmaceutical Industry, Shanghai, People’s Republic of China; 3National Advanced Medical Engineering Research Center, Shanghai, People’s Republic of China; 4Department of Pharmaceutics, China Pharmaceutical University, Nanjing, People’s Republic of ChinaCorrespondence: Jianxin Wang, School of Pharmacy, Fudan University, Shanghai, 201203, People’s Republic of China, Email jxwang@shmu.edu.cn Weigen Lu, China State Institute of Pharmaceutical Industry, Shanghai, 201203, People’s Republic of China, Email sipiluwg@163.comPurpose: To enhance tumor penetration by formulation design and tumor microenvironment (TME) modulation, herein a novel reactive oxygen species (ROS)-responsive size/shape transformable lipid-polymer hybrid nanoparticle (LPN) has been fabricated for the co-delivery of an anticancer and collagen-inhibition drug.Methods: A ROS-responsive poly(D, L-lactide)-thioketal-polyethylene glycol (PLA-TK-PEG) co-polymer was synthesized. LPNs were then fabricated by encapsulation of losartan (LST)-loaded micelles as the core to support paclitaxel (PTX)-loaded liposomes. The PEG content in the lipid shell of LPNs was then adjusted to obtain the size-/shape-transformable LPNs (M/LST-Lip/PTX-PEG5%). The ROS-responsiveness was observed in vitro by transmission electron microscopy and the tumor-penetration of the LPNs was evaluated in 3D tumor spheroids by confocal laser scanning microscopy. Tumor-targeting, tumor-penetrating, and antitumor efficacies of the NPs in 4T1 tumor-bearing mice were determined by in vivo imaging.Results: ROS-responsive micellar core degradation and the transformation of spherical LPNs (120nm) to smaller 40 mm discoid nanoparticles (NP) were observed. The transformable LPNs exhibited enhanced capacity of penetration in contrast to the un-transformable preparations in three-dimensional (3D) tumor spheroids. Furthermore, synergetic penetrating enhancement was achieved by LST-loaded transformable LPNs in 4T1 and fibroblast cell mixed 3D tumor spheroids. The improved tumor penetration of LST-loaded transformable LPNs was observed in vivo, which could be due to their collagen inhibiting and size/shape transformable effect. Due to their enhanced penetrability, LST and PTX-loaded transformable LPNs demonstrated significant in vivo antitumor efficacy in comparison to other preparations.Conclusion: The results confirmed the efficacy of M/LST-Lip/PTX-PEG5% in tumor targeting, collagen inhibition in TME, and enhanced tumor penetration. This novel drug delivery system can therefore play a substantial role in improving the therapeutic efficacy of antitumor drugs combined with TME-improving agents.Keywords: lipid-polymer hybrid nanoparticles, losartan, paclitaxel, ROS responsiveness, drug delivery, collagen inhibition, tumor penetration, combination therapy

Meng Zhang,1,&ast; Wenyi Lu,2,&ast; Danni Xie,1 Jiaxi Wang,1 Xia Xiao,2 Yedi Pu,2 Juanxia Meng,2 Hairong Lyu,2 Mingfeng Zhao2 1First Center Clinic College of Tianjin Medical University, Tianjin, 300192, People’s Republic of China; 2Department of Hematology, Tianjin First Central Hospital, Tianjin, 300192, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingfeng Zhao; Hairong Lyu, Department of Hematology, Tianjin First Central Hospital, Tianjin, 300192, People’s Republic of China, Email mingfengzhao@sina.com; 18802235939@163.comBackground: Metagenomic next-generation sequencing (mNGS) is a fast, sensitive and accurate diagnostic method for pathogens detection. However, reports on the application of mNGS in mucormycosis remain scarce.Methods: From January 2019 to December 2021, we recruited 13 patients with hematological malignancies who were suspected of mucormycosis and completed mNGS in D20. Then we retrospectively analyze the clinical data, diagnosis, therapeutic process, and outcomes. In order to evaluate the diagnostic value of mNGS in hematological malignancies patients with suspected mucormycosis.Results: All patients had high risk factors of Invasive Fungal Disease, including hematopoietic stem cell transplantation, immunosuppression, glucocorticoids, etc. The clinical presentations were pulmonary (n=9), rhino-orbito-cerebral (n=4). But the manifestations were nonspecific. All enrolled patients completed mNGS. And most (8/13, 61.54%) of the samples were from blood. Fungi can be detected in all specimens, including Rhizopus (n=7), Rhizomucor (n=4) and Mucor (n=2). In addition, 7/13 (53.85%) specimens were detected bacteria at the same time and virus were detected in 5/13 (38.46%). Histopathological examination was completed in 5 patients, 3 of which were completely consistent with the results of mNGS. After treatment, 6 patients were cured, while the other 7 patients died.Conclusion: mNGS may be a complementary method for early diagnosis, especially for patients who are not suitable for histopathology examination or unable to obtain culture specimen. mNGS can also help detect bacteria and viruses simultaneously, allowing for appropriate and timely antibiotic administration and thus improving patient outcomes.Keywords: metagenomic next-generation sequencing, mucormycosis, retrospectively, hematological malignancies, invasive fungal disease

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

Tao Zhang,1 Beiyin Lu,1 Zhongheng Yan,2 Xiaojun Huang,3 Wei Lu3,4 1Department of Health Policy and Management, Hangzhou Normal University, Hangzhou, People’s Republic of China; 2Office of the Vice President, Central Hospital of Hainan Province Western, Haikou, People’s Republic of China; 3School of Management, Hainan Medical University, Haikou, People’s Republic of China; 4Department of Science and Education, Hainan Women and Children’s Health Care Centre, Haikou, People’s Republic of ChinaCorrespondence: Wei Lu, School of Management, Hainan Medical University, No. 3 Xueyuan Road, Longhua District, Haikou, 5711993, People’s Republic of China, Tel +86 15971499800, Fax +8602767813016, Email hy0205044@hainmc.edu.cnPurpose: Based on the diagnosis-related groups payment, China developed an innovative episode-based payment scheme, called “payment method by disease types with point counting”, to control health expenditures inflation. This study aimed to investigate the impacts of this new payment method on volume, expenditures, and efficiency in Chinese public hospitals.Methods: The study sample consisted of 7 tertiary hospitals and 14 secondary hospitals in Jinhua (intervention group) and 4 tertiary hospitals and 14 secondary hospitals in Taizhou (control group). Monthly data points were collected for each sampled hospital from June 2016 to June 2019 using a self-administered questionnaire with impact evaluation indicators. Controlled interrupted time-series analysis was employed to estimate the effect of the new payment method.Results: The significant slowing trends in inpatient expenditures per visit (tertiary hospitals: β7=− 123.16, p=0.042; secondary hospitals: β7=− 89.24, p=0.021) and out-of-pocket payments (tertiary hospitals: β7=− 4.18, p=0.027; secondary hospitals: β7=− 4.87, p=0.019) were observed after policy intervention. However, outpatient expenditures per visit in tertiary (β7=1.67, p=0.018) and secondary hospitals (β7=1.24, p=0.003) rose faster with the new payment method. Additionally, payment reform also caused an increase in the number of inpatient visits (β7=100.01, p=0.038) and reduced the length of stay (β7=− 0.10, p=0.036) in tertiary hospitals.Conclusion: The introduction of payment method by disease types with point counting causes the cost containment for inpatient care, whereas the increase in outpatient expenditures. The findings suggest this new payment scheme has the potential for rollout in other areas, but the cost-shifting from the inpatient to outpatient setting should be prevented.Keywords: episode-based payment, expenditures, public hospitals, controlled interrupted time series, China