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Lili Zhang,1 Han Jiang,1 Lihua Li,2 Zhen Sun,1 Yongjiang Qian,1 Zhongqun Wang1 1Department of Cardiology, Affiliated Hospital of Jiangsu University, Institute Cardiovascular Disease of Jiangsu University, Zhenjiang, 212001, People’s Republic of China; 2Department of Pathology, Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, People’s Republic of ChinaCorrespondence: Zhongqun Wang, Department of Cardiology, Affiliated Hospital of Jiangsu University, 438 Jiefang, Zhenjiang, 212001, People’s Republic of China, Tel +86 511 85030586, Email wangtsmc@126.comBackground: Atherosclerosis (AS) is the major cause of cardiovascular disease. Using integrated single-cell and bulk RNA sequencing data of atherosclerosis, we aimed to investigate the cell phenotype, intercellular communication, and potential therapeutic target in AS.Methods: Single-cell sequencing data from aortic arch of Apoeko mice in normal diet (ND) and high fat diet (HFD) groups (obtained from GSE206239) were analyzed by Seurat, singleR, ReactomeGSA, and cellchat package. scRNA-seq dataset GSE159677 from the carotid artery of the patients with carotid endarterectomy were used to validate the distribution of fascin actin-bundling protein 1 (FSCN1) in cell populations. Bulk RNA sequencing data (GSE43292 and GSE28829) were used to analyzed the expression of FSCN1in AS. A cross-sectional clinical study was utilized to examine the association between FSCN1 and AS. Circulating concentrations of FSCN1 were measured using ELISA kits and assessed using logistic regression analysis and receiver operating characteristic (ROC) curves. Apoeko mice fed with HFD and MAECs treated with oxidized low-density lipoprotein (ox-LDL) were established to detect the expression of FSCN1. Furthermore, we knocked down FSCN1 in MAECs to observe its influence on pyroptosis and migration.Results: The HFD group had a significantly lower percentage of T cells, fibroblasts, and B cells and a significantly higher percentage of monocytes/macrophages cells. Strong interactions between endothelial cell (EC) and fibroblast in ND groups, while EC interactions with smooth muscle cells (SMC) and T cells were stronger in HFD groups. Semaphorin 7 (SEMA7) mediated signaling pathways were enriched in HFD groups and targeted EC driving by SMC. FSCN1was mainly expressed in EC and had a high expression in human AS samples. The cross-sectional study identified that high level of FSCN1 was associated with increased risk of AS. We also observed that high expression of FSCN1 in ox-LDL-induced MAECs and Apoeko mice fed with HFD. Knockdown of FSCN1 reduced pyroptosis and increased the migration in MAECs.Conclusion: Knockdown of FSCN1 in EC could alleviate the development and progression of AS. FSCN1 may be a potential prognostic biomarker and therapeutic target in AS.Keywords: FSCN1, atherosclerosis, endothelial cells, pyroptosis, migration

Qi Wu,1,* Kexin Liu,2,* Ruijuan Hou,1 Xingxing Wu,3 Xiaoyu Ruan,4 Mao Wang,5 Zhiting Sun,6 Lingchang Meng,6 Guoliang Dai,7 Changyin Li,7 Jing Wu,1,6 Genglin Mu6 1Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, 210008, People’s Republic of China; 2Department of Gastroenterology, The 981th Hospital of the Joint Logistics Support Force of the Chinese People’s Liberation Army, Chengde, Hebei, 067000, People’s Republic of China; 3Department of Gastroenterology, Henan Province Hospital of Traditional Chinese Medicine, Zhengzhou, 450053, People’s Republic of China; 4Internal Medicine Department, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China; 5Ethics Committee, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China; 6Institute of Chinese Medicine of Nanjing University, Nanjing Drum Tower Hospital, Drum Tower Clinical Medicine College of Nanjing University of Chinese Medicine, Nanjing, 210008, People’s Republic of China; 7Clinical Pharmacology Laboratory, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing Wu, Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Institute of Chinese Medicine of Nanjing University, 321, Zhongshan Road, Nanjing, Jiangsu, People’s Republic of China, Tel +86 13451825475, Email wujing@njucm.edu.cnPurpose: Inflammatory bowel disease (IBD) is a serious disease that affects the metabolism and inflammatory responses of human beings. From the perspective of traditional Chinese medicine, damp-heat syndrome is one of the main syndromes of IBD. Rhizoma Paridis, also known as the root of Paris polyphylla, a well-known herbal medicine used in China, is used to treat IBD with damp-heat syndrome (IBD-DH). However, uncertainty still exists regarding the underlying mechanisms and the impact of Rhizoma Paridis on IBD-DH.Methods: The rats in the model (DAT) and medication administration (Rhizoma Paridis total saponins (RPTS) and Pennogenin (PN)) groups were given a high temperature and high humidity environment, high fat and high sugar diet combined with 2,4,6-trinitrobenzene sulfonic acid (TNBS) to establish the model of experimental colitis of damp-heat type, and the normal control group (RNC) rats were given a normal diet at normal temperature and humidity. Damp-heat control group (DNC) was set with the same condition as DAT without TNBS. Hematoxylin-Eosin (HE) staining was used to observe the histopathological morphology of the rat colorectum. The expression of the metabolism-related genes (Phospholipase A2 (sPLA2, cPLA2), and phosphatidylethanolamine N-methyltransferase (PEMT)) was assessed by using real-time quantitative PCR analysis (RT–qPCR). And the levels of the metabolism-related proteins (sPLA2, cPLA2), S100A8/9, Arg-1, and cytokines were detected by enzyme-linked immunosorbent assay (ELISA) kit. To investigate lipids and amino acids which closely associated with the IBD and IBD-DH, lipid pseudotargeted metabolomics with UHPLC-TQ/MS analysis method, as well as targeted quantitative amino acid analysis were performed.Results: Our data showed that RPTS (50 mg/kg) and PN (20 mg/kg) significantly ameliorated the severity of TNBS-induced colitis and downregulated the levels of circulating proinflammatory cytokines. Compared with RNC group, lipid pseudotargeted metabolomics demonstrated that glycerophospholipids, sphingolipids, carnitine, and glycerolipids were the four most perturbed lipid classes, and amino acids targeted metabolomics demonstrated that serine, N-acetylneuraminic acid, histidine, proline, taurine, and kynurenine changed significantly in DAT group . Correlation analyses showed tight associations between most of differential metabolites and proinflammatory cytokines. RPTS and PN both regulated glycerophospholipid metabolism and sphingolipid metabolism. However, both of them did not have a significant effect on amino acid modulation. RPTS and PN potentially regulated sPLA2, cPLA2, and PEMT.Conclusion: These results showed that RPTS (50 mg/kg) and PN (20 mg/kg) effectively alleviated rats’ colitis of damp-heat type, affected cytokines, and altered lipid metabolism without significant modulation on amino acid metabolism.Keywords: inflammatory bowel disease, lipid pseudotargeted metabolomics, amino acids targeted metabolomics, Rhizoma Paridis saponins, cytokines

Jiaying Li,1,2,&ast; Minhui Zhou,2,&ast; Yahan Tong,3 Haibo Chen,1 Ruisi Su,2 Yinghui Tao,2 Guodong Zhang,1 Zhichao Sun1 1Department of Radiology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, 310006, People’s Republic of China; 2The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 3Department of Radiology, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, 310005, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhichao Sun, Department of Radiology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), 54 Youdian Road, Hangzhou, People’s Republic of China, Tel/Fax +86-571-87077272, Email sunzhichao@zcmu.edu.cnPurpose: Non-invasive methods are urgently needed to assess the efficacy of transarterial chemoembolization (TACE) and to identify patients with hepatocellular carcinoma (HCC) who may benefit from this procedure. This study, therefore, aimed to investigate the predictive ability of tumor growth patterns and radiomics features from contrast-enhanced magnetic resonance imaging (CE-MRI) in predicting tumor response to TACE among patients with HCC.Patients and Methods: A retrospective study was conducted on 133 patients with HCC who underwent TACE at three centers between January 2015 and April 2023. Enrolled patients were divided into training, testing, and validation cohorts. Rim arterial phase hyperenhancement (Rim APHE), tumor growth patterns, nonperipheral washout, markedly low apparent diffusion coefficient (ADC) value, intratumoral arteries, and clinical baseline features were documented for all patients. Radiomics features were extracted from the intratumoral and peritumoral regions across the three phases of CE-MRI. Seven prediction models were developed, and their performances were evaluated using receiver operating characteristic (ROC) and decision curve analysis (DCA).Results: Tumor growth patterns and albumin-bilirubin (ALBI) score were significantly correlated with tumor response. Tumor growth patterns also showed a positive correlation with tumor burden (r = 0.634, P = 0.000). The Peritumor (AUC = 0.85, 0.71, and 0.77), Clinics_Peritumor (AUC = 0.86, 0.77, and 0.81), and Tumor_Peritumor (AUC = 0.87, 0.77, and 0.80) models significantly outperformed the Clinics and Tumor models (P < 0.05), while the Clinics_Tumor_Peritumor model (AUC = 0.88, 0.81, and 0.81) outperformed the Clinics (AUC = 0.67, 0.77, and 0.75), Tumor (AUC = 0.78, 0.72, and 0.68), and Clinics_Tumor (AUC = 0.82, 0.83, and 0.78) models (P < 0.05 or 0.053, respectively). The DCA curve demonstrated better predictive performance within a specific threshold probability range for Clinics_Tumor_Peritumor.Conclusion: Combining tumor growth patterns, intra- and peri-tumoral radiomics features, and ALBI score could be a robust tool for non-invasive and personalized prediction of treatment response to TACE in patients with HCC.Keywords: hepatocellular carcinoma, radiomics, tumor growth pattern, transarterial chemoembolization

Shangtao Wang,1 Chenghao Zhu,1 Shurui Zhang,1 Siyu Ma,1 Baoshan Li,1 Shengbo Zhao,2 Wei Zhang,3 Zhirong Sun1 1School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Ningqiang Tianma Research Institution Limited Liability Company, Hanzhong, Shaanxi, People’s Republic of China; 3Ningqiang County Traditional Chinese Medicinal Industry Development Center, Hanzhong, Shaanxi, People’s Republic of ChinaCorrespondence: Zhirong Sun, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Northeast Corner of the Intersection of Yangguang South Street and Baiyang East Road, Fangshan District, Beijing, 102401, People’s Republic of China, Email szrbucm67@163.comBackground: Hypertension (HTN) is closely related to endothelial damage. While tianma (TM) and gouqizi (GQZ) have the potential to be effective in the treatment of HTN in traditional Chinese medicine, their main active ingredients and whether its exert synergistic effects and the underlying mechanisms of synergistic effects are still unclear.Objective: This study screened the active ingredients of TM and GQZ, investigated the synergistic effects of the active ingredients and explored possible mechanisms.Methods: The potential targets and mechanisms of TM and GQZ were screened using network pharmacology, and gastrodin (GAS) and gallic acid (GA) were identified as compounds with significant antihypertensive activity. The synergistic effects of the combination of GAS and GA was assessed by measuring biomarkers of AngII-induced human umbilical vein endothelial cell (HUVECs) dysfunction model. Furthermore, the anti-apoptotic and anti-inflammatory effects were evaluated by measuring inflammatory cytokine secretion, and apoptosis-related markers. Finally, key targets of the sphingolipid signaling pathway were experimentally validated by Western blotting.Results: In network pharmacology, the herb-pair exerted a synergetic effect by regulating sphingolipid pathways. The GAS and GA exerted synergistic protective effects in AngII-induced HUVECs injury by improving Nitric Oxide Content (NO) levels, alleviating lactate Endothelin-1 (ET-1), and Thromboxane B2 (TX-B2) release, reducing the secretion of inflammatory factors like interleukin-6 (IL-6), interleukin-1β (IL-1β), Tumor Necrosis Factor Alpha (TNF-α)), decreasing the pro-apoptotic protein BAX, and increasing the anti-apoptotic protein BCL-2. Furthermore, the results showed that the GAS and GA combination could elevate the level of S1PR1 and inhibit the expression of ROCK2 and the phosphorylation of NF-κB, which are key targets involved in sphingolipid pathways.Conclusion: Our study revealed that the combination of GAS and GA could suppress inflammation and apoptosis, which are highly correlated with sphingolipid signaling pathways, making it a potential candidate for the treatment of HTN. Keywords: gastrodin, gallic acid, synergistic effects, inflammation, apoptosis, sphingolipid pathways

Yali Yuan,1,2,&ast; Hairong Hu,1,&ast; Zhongmei Sun,3,&ast; Wenting Wang,4 Zhibin Wang,1 Mengyu Zheng,5 Yunqi Xing,1 Wenji Zhang,1 Muyuan Wang,1 Xinyu Lu,1 Yitong Li,1 Chengtao Liang,1 Zhengdao Lin,1 Chune Xie,6 Junxiang Li,1 Tangyou Mao1 1Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Hebei North University, Zhangjiakou, Hebei, People’s Republic of China; 3Tianjin Nankai Hospital, Tianjin, People’s Republic of China; 4Beitaipingzhuang Community Health Service Center, Beijing, People’s Republic of China; 5King’s College, London, UK; 6Shenzhen Bao’an Traditional Chinese Medicine Hospital, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tangyou Mao; Junxiang Li, Email maotangyouqun@126.com; lijunxiang1226@163.comBackground: Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disease that lacks effective treatments. Qingchang Wenzhong Decoction (QCWZD) is a clinically effective herbal prescription that has been proven to attenuate intestinal inflammation in IBD. However, its molecular mechanism of action has not been clearly elucidated.Purpose: We aimed to probe the mechanism of QCWZD for the treatment of IBD.Methods: The dextran sulfate sodium (DSS)-induced mouse model of IBD was used to identify the molecular targets involved in the mechanism of action of QCWZD. Metagenomics sequencing was utilized to analyze the differences in gut microbiota and the functional consequences of these changes. Network pharmacology combined with RNA sequencing (RNA-seq) were employed to predict the molecular targets and mechanism of action of QCWZD, and were validated through in vivo experiments.Results: Our results demonstrated that QCWZD treatment alleviated intestinal inflammation and accelerated intestinal mucosal healing that involved restoration of microbial homeostasis. This hypothesis was supported by the results of bacterial metagenomics sequencing that showed attenuation of gut dysbiosis by QCWZD treatment, especially the depletion of the pathogenic bacterial genus Bacteroides, while increasing the beneficial microorganism Akkermansia muciniphila that led to altered bacterial gene functions, such as metabolic regulation. Network pharmacology and RNA-seq analyses showed that Th17 cell differentiation plays an important role in QCWZD-based treatment of IBD. This was confirmed by in vivo experiments showing a marked decrease in the percentage of CD3+CD4+IL-17+ (Th17) cells. Furthermore, our results also showed that the key factors associated with Th17 cell differentiation (IL-17, NF-κB, TNF-α and IL-6) in the colon were significantly reduced in QCWZD-treated colitis mice.Conclusion: QCWZD exerted beneficial effects in the treatment of IBD by modulating microbial homeostasis while inhibiting Th17 cell differentiation and its associated pathways, providing a novel and promising therapeutic strategy for the treatment of IBD. Keywords: intestinal bowel disease, Qingchang Wenzhong Decoction, microbial homeostasis, Th17 cells, mucosal immunity

Zhiwei Sun,1,&ast; Xiangru Chen,1,&ast; Fang Miao,2,&ast; Na Meng,3 Keqiang Hu,1 Shaotang Xiong,4 Ximing Peng,1 Liya Ma,5 Chuchao Zhou,1 Yanqing Yang1 1Department of Plastic Surgery, Tongren Hospital of Wuhan University (Wuhan Third Hospital), Wuhan, 430060, People’s Republic of China; 2Department of Dermatology, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China; 3Department of Cardiovascular Medicine, Tongren Hospital of Wuhan University (Wuhan Third Hospital), Wuhan, 430060, People’s Republic of China; 4The Second People’s Hospital of China Three Gorges University·the Second People’s Hospital of Yichang, Hubei, People’s Republic of China; 5The Centre of Analysis and Measurement of Wuhan University, Wuhan University, Wuhan, 430072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanqing Yang; Chuchao Zhou, Email yangyq0106@163.com; chuchaozhou@163.comIntroduction: Graphene oxide (GO) nanoparticles have emerged as a compelling photothermal agent (PHTA) in the realm of photothermal antibacterial therapy, owing to their cost-effectiveness, facile synthesis, and remarkable photostability. Nevertheless, the therapeutic efficacy of GO nanoparticles is commonly hindered by their inherent drawback of low photothermal conversion efficiency (PCE).Methods: Herein, we engineer the Ag/GO-GelMA platform by growing the Ag on the surface of GO and encapsulating the Ag/GO nanoparticles into the GelMA hydrogels.Results: The resulting Ag/GO-GelMA platform demonstrates a significantly enhanced PCE (47.6%), surpassing that of pure GO (11.8%) by more than fourfold. As expected, the Ag/GO-GelMA platform, which was designed to integrate the benefits of Ag/GO nanoparticles (high PCE) and hydrogel (slowly releasing Ag+ to exert an inherent antibacterial effect), has been shown to exhibit exceptional antibacterial efficacy. Furthermore, transcriptome analyses demonstrated that the Ag/GO-GelMA platform could significantly down-regulate pathways linked to inflammation (the MAPK and PI3K-Akt pathways) and had the ability to promote cell migration.Discussion: Taken together, this study presents the design of a potent photothermal antibacterial platform (Ag/GO-GelMA) aimed at enhancing the healing of infectious wounds. The platform utilizes a handy method to enhance the PCE of GO, thereby making notable progress in the utilization of GO nano-PHTAs. Keywords: Ag/GO nanoparticles, photothermal therapy, photothermal conversion efficiency, hydrogel, infectious wound healing

Ting Dai,&ast; Qimeihui Wang,&ast; Lingyu Zhu, Qiang Luo, Jiayu Yang, Xia Meng, Hui Wang, Zhixia Sun Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Wang; Zhixia Sun, Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, 130033, People’s Republic of China, Email whui66@jlu.edu.cn; sunzx@jlu.edu.cnIntroduction: The effective accumulation of nanoparticles (NPs) in the tumour area is an important goals of current nanotechnology research, and a targeted nanoplatform is an effective solution. So we designed a multifunctional sound-sensitive targeted NP that combines a sonosensitizer to enable precisely targeted, deep-penetration sonodynamic therapy (SDT) in combination with multimodal imaging for the diagnosis and monitoring of renal cell carcinoma (RCC).Methods: ZnPP@PP NPs (ZnPP@PLGA- PFP NPs) were prepared via a double emulsion method, and G250 was covalently attached to the NPs shell via the carbon diimide method. Physicochemical property tests were conducted on the ZnPP@G-PP NPs, including tests of particle size, potential distribution, encapsulation efficiency and drug loading capability. We assessed the targeting ability, the production of reactive oxygen species (ROS) and permeability of the NPs in vitro. Moreover, we evaluated the nanoparticle’s multimodal imaging capabilities and therapeutic ability against RCC, both in vitro and in vivo.Results: The Znpp@G-PP NPs were successfully constructed, and their general properties showed uniform particle size, negative potential and good stability. The nanoparticles were successfully loaded with ZnPP and connected with G250, showing tumor-specific targeting ability. Under LIFU irradiation, the nanoparticles produced 1O2 by SDT. For RCC, PA/US multi-modal imaging of Znpp@G-PP NPs provide diagnostic information and monitor therapies in real time in 786-O RCC xenografts, with good biocompatibility. With the UTMD, nanoparticles can be effectively targeted into the tumor cells and penetrate into the tumor interior, significantly improving the SDT effect. Experiments in vitro and in vivo showed that the combination of the nanoparticles and LIFU could suppress the tumor, and the therapeutic effect was confirmed by immunohistochemistry.Conclusion: ZnPP@G-PP NPs provide a promising theranostic strategy for RCC and a platform for further research on improving the efficacy of diagnosis and treatment.Keywords: targeted therapy, deep-penetration, sonodynamic therapy, multimodal imaging

Zhangnan Sun,1,&ast; Ji Shi,2,&ast; Chaolei Liu,1 Jingjing Zhang,1 Yue Liu,1 Yini Wu,3 Xin Han,3 Hong Dai,3 Jimin Wu,3 Lijun Bo,1 Faxing Wang3 1Department of Anesthesiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Anesthesiology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 3Department of Anesthesiology, Lishui People’s Hospital, Lishui Hospital of Wenzhou Medical University, Lishui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Faxing Wang, Department of Anesthesiology, Lishui People’s Hospital, Lishui Hospital of Wenzhou Medical University, No. 15, Dazhong Street, Lishui, Zhejiang Province, 323000, People’s Republic of China, Email wfx2023@wmu.edu.cn Lijun Bo, Department of Anesthesiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China, Email 27901566@hebmu.edu.cnObjective: This study investigates the effect of low-dose dexmedetomidine infusion on perioperative neurocognitive function in elderly patients undergoing endoscopic retrograde cholangiopancreatography (ERCP).Patients and Methods: This double-blind trial enrolled 80 elderly ERCP patients randomized to receive dexmedetomidine (Group D) or placebo (Group S). Group D received dexmedetomidine at 0.4 μg·kg− 1·h− 1 starting 15 minutes before surgery until completion, along with propofol at 1.5 mg/kg for anesthesia. Group S received saline and propofol in a similar manner. Anesthesia was maintained with dexmedetomidine at 0.4 μg·kg− 1·h− 1 and propofol at 1– 2 mg/kg during surgery. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) preoperatively and on postoperative days 1, 3, and 5. Primary outcome was perioperative neurocognitive disorder (PND) incidence on day 5; secondary outcomes included changes in perioperative IL-6, cortisol, S100-β, hemodynamics, anesthesia parameters, postoperative pain, agitation scores, and adverse events.Results: All 80 patients completed the trial. On postoperative day 5, the cumulative probability of PND incidence was significantly lower in Group D than in Group S (12.5% vs 35%, P=0.018). Group D also had lower levels of IL-6 (F=199.472, P< 0.001), S100-β (F=2681.964, P< 0.001), and cortisol (F=137.637, P< 0.001). Propofol doses were lower in Group D (706.1 ± 202.4 vs 1003.3 ± 203.7, P< 0.001), and bradycardia rates were higher (45% vs 15%, P=0.003), though atropine use did not significantly differ between groups. Group D showed greater stability in mean arterial pressure. Postoperative complications and adverse reactions were similar across groups.Conclusion: Perioperative low-dose dexmedetomidine infusion with propofol in elderly ERCP patients ensures safe and effective monitored anesthesia care (MAC), reducing PND incidence by mitigating peripheral inflammation and stress responses. Long-term follow-up is needed to fully evaluate PND incidence.Keywords: ERCP, PND, dexmedetomidine, elderly patients

Hong Xu,1 Zuoli Sun,1 Gang Wang,1,2 Rena Li1 1Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Gang Wang; Rena Li, Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, 100088, People’s Republic of China, Email gangwangdoc@ccmu.edu.cn; renali@ccmu.edu.cnBackground: Several clinical studies have examined the connection between depression and bone loss, but the cause-and-effect relationship between the two conditions, especially in animal models, is not well-studied.Methods: A total of 32 female mice were, randomly divided into control group (CON, n=19) and depression group (DEP, n=13). The mice in the DEP group were subjected to 21 consecutive days of restraint stress, following depressive-like behaviors were assessment. The femurs were collected using Micro-Computed Tomography (μCT) and histochemical staining. In parallel, levels of serotonin-related proteins in the brain were measured using Western blot analysis, and sex hormone profiles were determined through liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS).Results: The mice in the DEP group exhibited clear signs of depressive-like behaviors and an increase in serotonin transporter levels (t=-2.435, P< 0.05). In comparison to the CON mice, the DEP mice showed a decrease in bone mineral density (t =3.741, P< 0.05), bone surface area density (t =8.009, P< 0.01), percent bone volume (t =4.293, P< 0.05), trabecular number (t =5.844, P< 0.01), and connected density (t =11.000, P< 0.05). Additionally, there was an increase in trabecular separation (t =-7.436, P< 0.01) in DEP mice. Furthermore, the DEP mice displayed a significant reduction in serum estrogen levels (t =4.340, P< 0.05) and changes in its metabolite (t =-3.325, P< 0.05), while the levels of androgens remained unchanged.Conclusion: The restraint stress not only led to the development of depressive-like behaviors but also disrupted the estrogen metabolism pathway, resulting in damage to bone mass and microstructure in female mice. These findings suggest that stress-induced depression may pose a risk for bone loss in female mice by altering estrogen metabolism pathways.Keywords: depression, bone mineral density, bone structure, estrogen, female

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

Zhanying Sun,1,2,&ast; Jie Song,2,&ast; Jingru Chen,1 Xueyang Gan,1 Yi Li,3 Chen Qiu,2 Weili Zhang,1 Yuan Gao2 1Graduate School, Chinese PLA Medical School, Beijing, 100853, People’s Republic of China; 2Nursing Department, the First Medical Center, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 3Department of Orthopedics, the Forth Medical Center, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuan Gao, Email gaoyuanzd@163.comPurpose: Resilience is considered as a protective factor that can assist individuals to reduce post-traumatic stress reactions. In recent years, armies in many countries have widely implemented resilience training programs before deployment to prevent or reduce post-deployment combat stress reactions. Therefore, this study aims to review what is known about resilience interventions for military personnel in pre deployment.Methods: Based on Arskey and O’Malley’s framework, a scoping review was completed. This review was performed through searching databases including PubMed, Embase, Web of Science, Medline and the Cochrane Library, and screening literature to extract data, finally summarizing the findings.Results: A total of 25 studies focusing on resilience interventions for military personnel in pre deployment were involved and analyzed using intervention approaches, outcome measures, intervention effects, and so on.Conclusion: Based on the existing evidence in this review, it is cautiously believed that the resilience intervention program for military personnel before deployment is effective. However, there is no single effective best method even the same type intervention can make different effects in different situations and populations. Therefore, the population differences and context should be fully considered in constructing and implementing program to build military personnel resilience.Keywords: resilience, military personnel, prevention, post-traumatic stress response

Yinan Cao,1– 3,&ast; Fan Li,1– 3,&ast; Zhenxuan Sun,1– 3 Jin Liu,1– 3 Jie Liu,1– 3 Qi Yang,1– 3 Peng Ge,1– 3 Yalan Luo,1– 3 Hailong Chen1– 3 1Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China; 2Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, 116044, People’s Republic of China; 3Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yalan Luo; Hailong Chen, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Zhongshan Road 222, Dalian, 116011, Liaoning, People’s Republic of China, Tel +86-411-83635963, Fax +86-411-83622844, Email luoyalanxueshu@163.com; chenhailong@dmu.edu.cnPurpose: Explore the therapeutic effects and regulatory mechanism of Qingyi Decoction (QYD) on severe acute pancreatitis (SAP) associated acute lung injury (ALI).Methods: We identified the constituents absorbed into the blood of QYD based on a network pharmacological strategy. The differentially expressed genes from the GEO database were screened to identify the critical targets of QYD treatment of SAP-ALI. The SAP-ALI rat model was constructed.Some methods were used to evaluate the efficacy and mechanism of QYD in treating SAP-ALI. LPS-stimulated pulmonary microvascular endothelial cell injury simulated the SAP-induced pulmonary endothelial injury model. We further observed the therapeutic effect of QYD and CDK5 plasmid transfection on endothelial cell injury.Results: 18 constituents were absorbed into the blood, and 764 targets were identified from QYD, 25 of which were considered core targets for treating SAP-ALI. CDK5 was identified as the most critical gene. The results of differential expression analysis showed that the mRNA expression level of CDK5 in the blood of SAP patients was significantly up-regulated compared with that of healthy people. Animal experiments have demonstrated that QYD can alleviate pancreatic and lung injury inflammatory response and reduce the upregulation of CDK5 in lung tissue. QYD or CDK5 inhibitors could decrease the expression of NFAT5 and GEF-H1, and increase the expression of ACE-tub in SAP rat lung tissue. Cell experiments proved that QYD could inhibit the expression of TNF-α and IL-6 induced by LPS. Immunofluorescence results suggested that QYD could alleviate the cytoskeleton damage of endothelial cells, and the mechanism might be related to the inhibition of CDK5-mediated activation of NFAT5, GEF-H1, and ACE-tub.Conclusion: CDK5 has been identified as a critical target for pulmonary endothelial injury of SAP-ALI. QYD may partially alleviate microtubule disassembly by targeting the CDK5/NFAT5/GEF-H1 signaling pathway, thus relieving SAP-induced pulmonary microvascular endothelial cell injury. Keywords: Qingyi decoction, severe acute pancreatitis, acute lung injury, CDK5, microtubule

Dan Zhu,1 Zongbin Sun,1 Jiayun Wei,2 Yulin Zhang,2 Wenjing An,2 Yan Lin,1 Xun Li1– 3 1First Clinical Medical College, Lanzhou University, Lanzhou, People’s Republic of China; 2Gansu Province Key Laboratory of Biotherapy and Regenerative Medicine, First Hospital of Lanzhou University, Lanzhou University, Lanzhou, People’s Republic of China; 3General Surgery Department, First Hospital of Lanzhou University, Lanzhou University, Lanzhou, People’s Republic of ChinaCorrespondence: Xun Li, First Hospital of Lanzhou University, 1st West Donggang Road, Chengguan District, Lanzhou, Gansu Province, 730000, People’s Republic of China, Tel +86-931-8356056, Fax +86-931-8629797, Email lxdr21@126.comPurpose: Human umbilical cord mesenchymal stem cell (hucMSC)-derived small extracellular vesicles (sEVs) are natural nanocarriers with promising potential in treating liver fibrosis and have widespread applications in the fields of nanomedicine and regenerative medicine. However, the therapeutic efficacy of natural hucMSC-sEVs is currently limited owing to their non-specific distribution in vivo and partial removal by mononuclear macrophages following systemic delivery. Thus, the therapeutic efficacy can be improved through the development of engineered hucMSC-sEVs capable to overcome these limitations.Patients and Methods: To improve the anti-liver fibrosis efficacy of hucMSC-sEVs, we genetically engineered hucMSC-sEVs to overexpress the anti-fibrotic gene bone morphogenic protein 7 (BMP7) in parental cells. This was achieved using lentiviral transfection, following which BMP7-loaded hucMSC-sEVs were isolated through ultracentrifugation. First, the liver fibrosis was induced in C57BL/6J mice by intraperitoneal injection of 50% carbon tetrachloride (CCL4) twice a week for 8 weeks. These mice were subsequently treated with BMP7+sEVs via tail vein injection, and the anti-liver fibrosis effect of BMP7+sEVs was validated using small animal in vivo imaging, immunohistochemistry (IHC), tissue immunofluorescence, and enzyme-linked immunosorbent assay (ELISA). Finally, cell function studies were performed to confirm the in vivo results.Results: Liver imaging and liver histopathology confirmed that the engineered hucMSC-sEVs could reach the liver of mice and aggregate around activated hepatic stellate cells (aHSCs) with a significantly stronger anti-liver fibrosis effect of BMP7-loaded hucMSC-sEVs compared to those of blank or negative control-transfected hucMSC-sEVs. In vitro, BMP7-loaded hucMSC-sEVs promoted the phenotypic reversal of aHSCs and inhibited their proliferation to enhance the anti-fibrotic effects.Conclusion: These engineered BMP7-loaded hucMSC-sEVs offer a novel and promising strategy for the clinical treatment of liver fibrosis. Keywords: hucMSCs, sEVs, aHSCs, nanocarrier, BMP7

Wei Peng, Yin Zhuang, Wei Cui, Wenjin Chen, Rupeng Chu, Zhenzhong Sun, Shujun Zhang Department of Spine Surgery, Wuxi Ninth People’s Hospital Affiliated to Soochow University, Wuxi, Jiangsu, People’s Republic of ChinaCorrespondence: Shujun Zhang, Department of Spine Surgery, Wuxi Ninth People’s Hospital Affiliated to Soochow University, No. 999 Liangqing Road, Binhu District, Wuxi, Jiangsu, People’s Republic of China, Tel +86-13861741839, Email spine_zhang@vip.163.comAbstract: This study describes a patient with an intradural extramedullary (IDEM) tumor removed entirely using the unilateral biportal endoscopic technique (UBE), achieving satisfactory clinical outcomes. A 60-year-old woman had a diagnosis of meningioma with sensations and motor dysfunction in the lower extremities and perineum and gait disturbances for three years, which has worsened over the last month. Preoperative imaging data showed a sizeable IDEM tumor at the T10 level, significantly compressing the thoracic spinal cord to the right side, with 80% intraspinal encroachment. The IDEM tumor was removed entirely by UBE surgery. To the best of our knowledge, this study may be the first to report the application of UBE techniques for IDEM tumor treatment. In this case, UBE provides a magnified and clear surgical field, greater maneuverability, and a less invasive surgical procedure. The procedure objectives were pathological confirmation, spinal cord decompression, and complete tumor removal; all were met. The patient was satisfied with her dramatically improved clinical symptoms. UBE may be an alternative surgical treatment option for benign IDEM tumors presenting with symptomatic, especially the non-giant lateral and posterior tumors.Keywords: unilateral biportal endoscopy, endoscopic spine surgery, intradural extramedullary, tumor, meningioma

Zhongqi Sun,1 Xin Li,1 Hongwei Liang,1 Zhongxing Shi,2 Hongjia Ren3 1Department of Radiology, the Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, People’s Republic of China; 2Department of Interventional Radiology, the Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, People’s Republic of China; 3School of Information Science and Engineering, Yanshan University, Qinhuangdao, 066004, People’s Republic of ChinaCorrespondence: Zhongqi Sun, Email sunzhongqi2021@163.com; Hongjia Ren, Email renhj@ysu.edu.cnBackground: To develop and validate an overall survival (OS) prediction model for transarterial chemoembolization (TACE).Methods: In this retrospective study, 301 patients with hepatocellular carcinoma (HCC) who received TACE from 2012 to 2015 were collected. The residual network was used to extract prognostic information from CT images, which was then combined with the clinical factors adjusted by COX regression to predict survival using a modified deep learning model (DLOPCombin). The DLOPCombin model was compared with the residual network model (DLOPCTR), multiple COX regression model (DLOPCox), Radiomic model (Radiomic), and clinical model.Results: In the validation cohort, DLOPCombin shows the highest TD AUC of all cohorts, which compared with Radiomic (TD AUC: 0.96vs 0.63) and clinical model (TD AUC: 0.96 vs 0.62) model. DLOPCombin showed significant difference in C index compared with DLOPCTR and DLOPCox models (P < 0.05). Moreover, the DLOPCombin showed good calibration and overall net benefit. Patients with DLOPCombin model score ≤ 0.902 had better OS (33 months vs 15.5 months, P < 0.0001).Conclusion: The deep learning model can effectively predict the patients’ overall survival of TACE.Keywords: deep learning, transarterial chemoembolization, hepatocellular carcinoma

Yepeng Wang,1,&ast; Chao Ma,2,&ast; Xuekun Yang,3 Jun Gao,1 Zhigang Sun2 1Department of Neurosurgery, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, People’s Republic of China; 2Department of Thoracic Surgery, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, People’s Republic of China; 3Department of Neurology, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhigang Sun, Department of Thoracic Surgery, Central Hospital Affiliated to Shandong First Medical University, 105 Jiefang Road, Jinan, Shandong Province, People’s Republic of China, Tel +0086 133 7058 2825, Email sunszg@126.comAbstract: Zinc finger protein 217 (ZNF217) is one of the well-researched members of the Krüppel-like factor transcription factor family. ZNF217 possesses a characteristic structure of zinc finger motifs and plays a crucial role in regulating the biological activities of cells. Recent findings have revealed that ZNF217 is strongly associated with multiple aspects of cancer progression, impacting patient prognosis. Notably, ZNF217 is subject to regulation by non-coding RNAs, suggesting the potential for targeted manipulation of such RNAs as a robust therapeutic avenue for managing cancer in the future. The main purpose of this article is to provide a detailed examination of the role of ZNF217 in human malignant tumors and the regulation of its expression, and to offer new perspectives for cancer treatment.Keywords: oncogene, regulation, non-coding RNA, targeted therapy

Run Hua,1,&ast; Gangjie Qiao,2,&ast; Guoshan Chen,1,&ast; Zhaonan Sun,3 Haowen Jia,3 Peiyuan Li,1 Baotong Zhang,1 Feng Qi1 1Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2Department of Colorectal Surgery, Shanxi Provincial People’s Hospital, Shanxi, People’s Republic of China; 3General Surgery Department, Tianjin Medical University General Hospital Airport Hospital, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Qi, Email qifengtmu2017@163.comBackground: Ulcerative colitis (UC) is a severe threat to humans worldwide. Single-cell RNA sequencing (scRNA-seq) can be used to screen gene expression patterns of each cell in the intestine, provide new insights into the potential mechanism of UC, and analyze the development of immune cell changes. These findings can provide new ideas for the diagnosis and treatment of intestinal diseases. In this study, bioinformatics analysis combined with experiments applied in dextran sulfate sodium (DSS)-induced colitis mice was used to explore new diagnostic genes for UC and their potential relationship with immune cells.Methods: We downloaded microarray datasets (GSE75214, GSE87473, GSE92415) from the Gene Expression Omnibus and used these datasets to screen differentially expressed genes (DEGs) and conduct Weighted Gene Co-expression Network Analysis (WGCNA) after quality control. The hub genes were screened, and ROC curves were drawn to verify the reliability of the results in both training set (GSE75214, GSE87473, GSE92415) and validation cohort (GSE87466). Also, we explored the relation of diagnostic genes and immune cells by CIBERSORT algorithm and single-cell analysis. Finally, the expression of hub genes and their relation with immune cells were verified in DSS-induced colitis mice.Results: Diagnostic genes (ANXA5, MMP7, NR1H4, CYP3A4, ABCG2) were identified. In addition, we found these five genes firmly related to immune infiltration. The DSS-induced colitis mice confirm that the expression of ANXA5 mainly increased in the intestinal macrophages and had a strong negative correlation with M2 macrophages, which indicated its possible influence on the polarization of macrophages in UC patients.Conclusion: We identified ANXA5, MMP7, NR1H4, CYP3A4, and ABCG2 as diagnostic genes of UC that are closely related to immune infiltration and ANXA5 maintains a negative correlation with M2 macrophages which indicated its possible influence on the polarization of macrophage in UC patients.Keywords: ulcerative colitis, ANXA5, diagnostic genes, single-cell analysis, macrophages

Qi Yang,1– 4 Yalan Luo,1– 3 Peng Ge,1– 3 Bowen Lan,1– 3 Jin Liu,1– 3 Haiyun Wen,1– 3 Yinan Cao,1– 3 Zhenxuan Sun,1– 3 Guixin Zhang,1– 3 Huiming Yuan,5 Lihua Zhang,5 Hailong Chen1– 3 1Department of General Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China; 2Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China; 3Laboratory of Integrative Medicine, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China; 4Department of Traditional Chinese Medicine, the Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, People’s Republic of China; 5CAS Key Laboratory of Separation Science for Analytical Chemistry, National Chromatographic Research and Analysis Center, Dalian Institute of Chemical Physics, Chinese Academy of Science, Dalian, 116023, People’s Republic of ChinaCorrespondence: Hailong Chen, Email chenhailong@dmu.edu.cnBackground: Numerous preclinical investigations have exhibited the beneficial impact of emodin (EMO) on the management of severe acute pancreatitis (SAP)-associated acute lung injury (ALI). However, the potential of EMO to mitigate organ damage through the modulation of exosome (Exo)-specific miRNA expression profiles remains unclear.Methods: The SAP rat model was established by retrograde injection of 5% sodium taurocholate into the pancreatic bile duct. Rats received intragastric administration of EMO at 2 h and 12 h post-modeling. Plasma and bronchoalveolar lavage fluid (BALF)-derived exosomes were isolated and purified from SAP rats treated with EMO. The therapeutic effects of these Exos in SAP rats were assessed using hematoxylin-eosin staining and measurement of inflammatory factor levels. MicroRNA (miRNA) sequencing was conducted on plasma and BALF-derived Exos, and rescue experiments were performed to investigate the function of NOVEL miR-29a-3p in the treatment of SAP using EMO.Results: EMO exhibits ameliorative effects on pancreatic and lung injury and inflammation in rats with SAP. Plasma/BALF-derived Exos from EMO-treated SAP rats also have therapeutic effects on SAP rats. The miRNA expression profile of plasma and BALF-derived Exos in SAP rats underwent significant changes upon exposure to EMO. In particular, 34 differentially expressed miRNAs (DEmiRNAs) were identified when comparing BALF-SAP+EMO-Exo and BALF-SAP-Exo. 39 DEmiRNAs were identified when comparing plasma-SAP+EMO-Exo to plasma-SAP-Exo. We found that SAP rats treated with Exos derived from BALF exhibited a more potent therapeutic response than those treated with Exos derived from plasma. EMO may rely on NOVEL-rno-miR-29a-3p expression to prevent pulmonary injury in SAP rats.Conclusion: The mechanism of action of EMO is observed to have a significant impact on the miRNA expression profile of Exos derived from plasma and BALF in SAP rats. NOVEL-rno-miR-29a-3p, which is specific to Exos, and is derived from BALF, may play a crucial role in the therapeutic efficacy of EMO. Plain Language Summary: Exosomes extracted from plasma/BALF of EMO-treated SAP rats show a substantial therapeutic impact on SAP-Associated ALI, with BALF-derived exosomes having a higher therapeutic effect than plasma-derived exosomes.EMO dramatically altered the miRNA expression patterns of plasma and BALF-derived exosomes in SAP rats.The lung protective effect of EMO in SAP rats is somewhat reliant on Novel-rno-miR-29a-3p expression.Keywords: severe acute pancreatitis, acute lung injury, emodin, exosome, microRNA

Ximing Peng,1,&ast; Xin Liu,2,&ast; Yanqing Yang,1,&ast; Mingwei Yu,1 Zhiwei Sun,1 Xiangru Chen,1 Keqiang Hu,1 Jing Yang,1 Shaotang Xiong,2 Bin Wang,2 Liya Ma,3 Zhenxing Wang,4 Hanxiao Cheng,5,&ast; Chuchao Zhou1,&ast; 1Department of Plastic Surgery, Tongren Hospital of Wuhan University (Wuhan Third Hospital), Wuhan, 430060, People’s Republic of China; 2Medical Aesthetic Department, The Second People’s Hospital of China Three Gorges University, The Second People’s Hospital of Yichang, Yichang, Hubei, People’s Republic of China; 3The Centre of Analysis and Measurement of Wuhan University, Wuhan University, Wuhan, 430072, People’s Republic of China; 4Department of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 5Department of Plastic Surgery, Hangzhou First People’s Hospital, Hangzhou, Zhejiang, 310006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hanxiao Cheng; Chuchao Zhou, Email chxmomo@sina.com; chuchaozhou@163.comIntroduction: The formation of bone-like apatite (Ap) on natural polymers through biomimetic mineralization using simulated body fluid (SBF) can improve osteoconductivity and biocompatibility, while lowering immunological rejection. Nonetheless, the coating efficiency of the bone-like Ap layer on natural polymers requires improvement. Carbonyls (-COOH) and hydroxyls (-OH) are abundant in graphene oxide (GO), which may offer more active sites for biomimetic mineralization and promote the proliferation of rat bone marrow stromal cells (BMSCs).Methods: In this study, gelatin methacryloyl (GelMA) microgels were infused with GO (0, 0.5, 1, and 2 mg/mL) and embedded into microgels in SBF for 1, 7, and 14 days. Systematic in vitro and in vivo experiments were performed to evaluate the structure of the microgel and its effect on cell proliferation and ability to repair bone defects in rats.Results: The resulting GO-GelMA-Ap microgels displayed a porous, interconnected structure with uniformly coated surfaces in bone-like Ap, and the Ca/P ratio of the 1 mg/mL GO-GelMA-Ap group was comparable to that of natural bone tissue. Moreover, the 1 mg/mL GO-GelMA-Ap group exhibited a greater Ap abundance, enhanced proliferation of BMSCs in vitro and increased bone formation in vivo compared to the GelMA-Ap group.Discussion: Overall, this study offers a novel method for incorporating GO into microgels for bone tissue engineering to promote biomimetic mineralization.Graphical-Abstract: Keywords: graphene oxide, gelatin methacryloyl, bone-like apatite, biomimetic mineralization, simulated body fluid, bone repair

Xinrui Feng,1,2,&ast; Yan Liu,1,&ast; Yang Zhao,3 Zhe Sun,1,4 Ning Xu,5 Chen Zhao,1 Wei Xia4 1College of Public Health, Jilin Medical University, Jilin, 132013, People’s Republic of China; 2Medical College, Yanbian University, Yanji, 136200, People’s Republic of China; 3Department of Emergency and Intensive Medicine, No. 965 Hospital of PLA Joint Logistic Support Force, Jilin, 132013, People’s Republic of China; 4College of Medical Technology, Beihua University, Jilin, 132013, People’s Republic of China; 5State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, 130062, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chen Zhao; Wei Xia, Email zhaochen0115@jlmu.edu.cn; xiawei4016@126.comAbstract: Recent, outbreaks of new emergency zoonotic diseases have prompted an urgent need to develop fast, accurate, and portable screening assays for pathogen infections. Recombinase polymerase amplification (RPA) is sensitive and specific and can be conducted at a constant low temperature with a short response time, making it especially suitable for on-site screening and making it a powerful tool for preventing or controlling the spread of zoonoses. This review summarizes the design principles of RPA-based biosensors as well as various signal output or readout technologies involved in fluorescence detection, lateral flow assays, enzymatic catalytic reactions, spectroscopic techniques, electrochemical techniques, chemiluminescence, nanopore sequencing technologies, microfluidic digital RPA, and clustered regularly interspaced short palindromic repeats/CRISPR-associated systems. The current status and prospects of the application of RPA-based biosensors in zoonoses screening are highlighted. RPA-based biosensors demonstrate the advantages of rapid response, easy-to-read result output, and easy implementation for on-site detection, enabling development toward greater portability, automation, and miniaturization. Although there are still problems such as high cost with unstable signal output, RPA-based biosensors are increasingly becoming one of the most important means of on-site pathogen screening in complex samples involving environmental, water, food, animal, and human samples for controlling the spread of zoonotic diseases. Keywords: recombinase polymerase amplification, biosensor, zoonoses, rapid detection, nanomaterials

Ziyu Jiang,1,2,&ast; Xiaoli Chen,2,3,&ast; Zhaoshen Sun,2,4 Xiaowei Shen,2,3 Yaju Huang,2,3 Jingbing Liu1,2 1Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People’s Republic of China; 2Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People’s Republic of China; 4Department of Dermatology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingbing Liu; Yaju Huang, Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People’s Republic of China, Tel +86 025 85637121 ; +86 025 85639241, Email ljb0427@sina.com; huangyaju1113@163.comAbstract: Immune checkpoint inhibitors such as monoclonal antibodies have been used recently with greater effect for the management of non-small cell lung cancer (NSCLC). Sintilimab, a fully human IgG4 monoclonal antibody is specific for the immune checkpoint protein programmed cell death receptor-1 (PD-1). It is a common medication adopted for treating Hodgkin’s lymphoma and NSCLC. The adverse effects associated with the use of monoclonal antibodies should be closely monitored and in the current report, the use of sintilimab for treating NSCLC led to skin-associated adverse effects such as Stevens-Johnson syndrome and toxic epidermal necrolysis. Genetic testing showed that genes such as KRAS, CREBBP, NTRK1, RAF1, and TP53 were mutated. Initial visible symptom included the formation of a vesicular rash on the skin that had spread to the upper limbs, chest, and dorsum 1 week after the administration of sintilimab. The patient received anti-inflammatory agents to prevent worsening of the rashes and further infections. When the vesicles in back and limbs enlarged and the neck skin began to desquamate, the patient was diagnosed with Stevens-Johnson syndrome and sintilimab-induced toxic epidermal necrolysis. Toxic epidermal necrolysis was diagnosed via clinical symptoms and physical examination. The patient also reported the symptoms of oral mucositis. As soon as the dose of sintilimab was reduced to 20 mg/day, the skin-associated condition of the patient began to improve. Although the lump in the lungs decreased considerably 45 days after initial administration of sintilimab, the medication was stopped from use as soon as the skin-related symptoms improved after its withdrawal. This report suggests that close monitoring, personal care, and proper use of medications such as sintilimab should be implemented to avoid such rare skin-associated toxicities as an adverse effect.Keywords: sintilimab, checkpoint inhibitor, monoclonal antibody, NSCLC, adverse effects

Jiatong Chai,1 Zeyu Sun,1 Qi Zhou,2 Jiancheng Xu1 1Department of Laboratory Medicine, First Hospital of Jilin University, Changchun, People’s Republic of China; 2Department of Pediatrics, First Hospital of Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Jiancheng Xu, Email xjc@jlu.edu.cnBackground: Trace elements play an important role in reflecting physical metabolic status, but have been rarely evaluated in diabetes ketoacidosis (DKA). Since clinical biochemical parameters are the first-line diagnostic data mastered by clinical doctors and DKA has a rapid progression, it is crucial to fully utilize clinical data and combine innovative parameters to assist in assessing disease progression. The aim of this study was to evaluate the levels of trace elements in DKA patients, followed by construction of predictive models combined with the laboratory parameters.Methods: A total of 96 T1D individuals (48 DKA patients) were collected from the First Hospital of Jilin University. Serum calcium (Ca), magnesium (Mg), zinc (Zn), copper (Cu), iron (Fe) and selenium (Se) were measured by Inductively Coupled Plasma Mass Spectrometry, and the data of biochemical parameters were collected from the laboratory information system. Training and validation sets were used to construct the model and examine the efficiency of the model. The lambda-mu-sigma method was used to evaluate the changes in the model prediction efficiency as the severity of the patient’s condition increases.Results: Lower levels of serum Mg, Ca and Zn, but higher levels of serum Fe, Cu and Se were found in DKA patients. Low levels of total protein (TP), Zn and high levels of lipase would be an efficient combination for the prediction of DKA (Area under curves for training set and validation set were 0.867 and 0.961, respectively). The examination test confirmed the clinical applicability of the constructed models. The increasing predictive efficiency of the model was found with NACP.Conclusion: More severe oxidative stress in DKA led to further imbalance of trace elements. The combination of TP, lipase and Zn could predict DKA efficiently, which would benefit the early identification and prevention of DKA to improve prognosis.Keywords: type 1 diabetes, diabetes ketoacidosis, diabetic complication, trace elements, prediction model

Zhe Sun,1,&ast; Ruijie Zhou,2,&ast; Jinjin Dai,2,&ast; Jihua Chen,2 Yu Liu,2 Mengyi Wang,2 Runlong Zhou,2 Fengchen Liu,2 Qinxing Zhang,3 Yao Xu,2 Tongcun Zhang1,2 1College of Biotechnology, Tianjin University of Science and Technology, Tianjin, People’s Republic of China; 2Institute of Biology and Medicine, College of Life Sciences and Health, Wuhan University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 3Wuhan Bio-Raid Biotechnology Co., Ltd, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yao Xu; Tongcun Zhang, Institute of Biology and Medicine, College of Life Science and Health, Wuhan University of Science and Technology, No. 2 Huangjiahu West Road, Wuhan, Hubei, 430081, People’s Republic of China, Tel +86-027-68897343, Fax +86-027-68893590, Email xuyao0307@wust.edu.cn; zhangtongcun@wust.edu.cnBackground: Ovarian cancer (OV) is the highest prevalent gynecologic tumor with complicated pathogenesis; high-grade serous ovarian cystadenocarcinoma (HGSOC) is the most epidemiological and malignant subtype of OV. Keratin type I cytoskeleton 19 (KRT19) is an intermediate filament protein which plays essential roles in the maintenance of epithelial cells. However, its role in OV remains largely unknown.Methods: Bioinformatic analysis with various databases was conducted in this study. In details, KRT19 expression was assessed using databases including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Gene Expression Omnibus (GEO) and Human Protein Atlas (HPA). GO-KEGG and GSEA analysis were performed by R packages. The biological function of KRT19 was analyzed based on the single-cell sequencing information from CancerSEA database. The association of KRT19 expression with immunomodulator and chemokine was predicted via the TISIDB database.Results: The expression of KRT19 was significantly upregulated in ovarian samples compared with normal controls. KRT19 expression was negatively associated with prognosis in OV, and further analysis revealed that KRT19 had promising diagnostic significance in distinguishing OV cancer from normal samples. GO-KEGG and GSEA analysis indicated that KRT19 was associated with multiple biological functions and pathways including epidermis development, apical junction, inflammatory response, and epithelial mesenchymal transition. By using different GEO series, we found that KRT19 was differentially expressed in OV-associated tissues. Furthermore, the increased KRT19 expression was positively correlated with the immune infiltration levels of the most immune cells in OV.Conclusion: This study demonstrated that KRT19 is a promising prognosis and diagnosis biomarker that determines cancer progression and is correlated with tumor immune cells infiltration in OV, suggesting being a molecular target for immunotherapies.Keywords: KRT19, OV cancer, prognosis, biomarker, immune infiltration

Zhenni Zhao,1 Jiawei Li,2 Jiamin Wen,2 Yanyan He,2 Zhiling Sun2 1Nursing Department, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Zhejiang, People’s Republic of China; 2School of Nursing, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of ChinaCorrespondence: Zhiling Sun, School of Nursing, Nanjing University of Chinese Medicine, 138 Xian Lin Road, Nanjing, People’s Republic of China, Tel +86 13813892093, Email szl@njucm.edu.cnBackground and Objective: Moxibustion is effective for low back pain (LBP), and inflammatory cytokines may play an important role in the mechanism of moxibustion treatment. The purpose of this meta-analysis was to explore the mechanism of moxibustion in LBP in terms of inflammatory cytokines.Methods: We searched China National Knowledge Infrastructure, Wanfang database, Cochrane Central Register of Controlled Trials, Ovid MEDLINE, Embase, PubMed, and Web of Science to identify eligible randomized controlled trials (RCTs). There was no restriction on the publication date.Results: Thirty RCTs measuring interleukin (IL-) 1, IL-1β, IL-6, IL-12, IL-17, IL-23, and tumor necrosis factor (TNF-) α were included in this meta-analysis. Compared to controls: single moxibustion could effectively decrease levels IL-6 and IL-23 (SMD, − 0.71, 95% CI: − 1.25 to − 0.17, p = 0.01; SMD, − 1.61, 95% CI: − 2.20 to − 1.03, p < 0.01, respectively); combined moxibustion had significant effects on IL-1, IL-1β, IL-6, IL-12, IL-17, and TNF-α (p < 0.05). Overall, for LBP, single or combined moxibustion could effectively down-regulate levels of pro-inflammatory cytokines (p = 0.007 and p < 0.00001, respectively). For safety of moxibustion, the incidence rate of side effects was similar to that of controls (RD, − 0.01, 95% CI: − 0.02 to 0.01, p = 0.59). Sensitivity analysis showed that the pooled estimates were robust, and publication bias analysis showed there was a significant small study effect (Egger’s test p = 0.0000). High statistical heterogeneity existed between included RCTs, meta-regression showed there was no potential factor explaining the source of heterogeneity.Conclusion: For LBP, moxibustion can effectively decrease levels of IL-1, IL-1β, IL-6, IL-12, IL-17, IL-23, and TNF-α to achieve analgesia. Because the side effects of moxibustion are transient, it is relatively safe for clinical use. However, based on high heterogeneity in this meta-analysis, rigorously designed RCTs are required to further confirm the results in this review.Keywords: low back pain, moxibustion, cytokines, tumor necrosis factors, interleukins

Zhenzhen Sun,1,&ast; Kun Wang,1,&ast; Chuan Yun,1 Fang Bai,1 Xiaodan Yuan,2 Yaujiunn Lee,3 Qingqing Lou1 1The First Affiliated Hospital of Hainan Medical University, Hainan Clinical Research Center for Metabolic Disease, Haikou, Hainan, People’s Republic of China; 2Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 3Department of Endocrinology, Lee’s Clinic, Pingtung City, Pingtung County, Taiwan&ast;These authors contributed equally to this workCorrespondence: Qingqing Lou, The First Affiliated Hospital of Hainan Medical University, Hainan Clinical Research Center for Metabolic Disease, No. 31, Longhua Road, Haikou, 570102, Hainan, People’s Republic of China, Tel +86 15312019129, Email 2444890144@qq.comPurpose: To investigate the association of five obesity indices and the variability of these indices with diabetic kidney disease (DKD) in patients with type 2 diabetes and compare the predictive validity of these markers for the risk of DKD in this large longitudinal cohort study.Patients and Methods: A total of 2659 patients with type 2 diabetes who did not have DKD were enrolled between 2006 and 2019 at Lee’s United Clinic in Taiwan. Data were collected for each subject, including demographic data, personal medical history, clinical parameters and calculated Body mass index (BMI), visceral adiposity index (VAI), lipid accumulation product (LAP), body roundness index (BRI) and variability of five obesity indices. Cox regression analysis was performed to determine the relationship between different obesity indicators and DKD risk. Cox’s proportional hazards model was evaluated the predictive effect of obesity indices on DKD.Results: The risk of developing DKD increased with an increase in the BRI, LAP, VAI, WC and BMI (all P trend< 0.05), and the variability of VAI was significantly associated with DKD [HR=1.132, 95% CI (1.001, 1.281)] after adjusting for corresponding variables. BRI had the strongest predictive effect on DKD. BRI had the best predictive performance, with AUC of 0.807, 0.663 and 0.673 at 1, 3 and 5 years, respectively. Cox regression analysis of risk factors for DKD in patients stratified by BRI quartiles showed that patients in the Q4 group had the highest risk of developing DKD [HR=1.356, 95% CI (1.131, 1.626)].Conclusion: BMI, WC, VAI, LAP, BRI and VAI variability were associated with a significant increase in the risk of DKD events, and BRI was superior and alternative obesity index for predicting DKD.Keywords: visceral adiposity index, lipid accumulation product, body roundness index, diabetic kidney disease

Guangjun Wang,1,&ast; Yinghua Tan,2,&ast; Yongjie Jiang,1 Jia Liu,1 Yuanhui Su,3 Zhengang Sun,4 Bo Liu3,5 1Department of General Surgery, Qingdao West Coast New Area Central Hospital, Qingdao, Shandong, People’s Republic of China; 2Department of Paediatrics, Qingdao West Coast New Area Central Hospital, Qingdao, Shandong, People’s Republic of China; 3Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu, People’s Republic of China; 4Department of Spine Surgery, Qingdao West Coast New Area Central Hospital, Qingdao, Shandong, People’s Republic of China; 5Department of Gastrointestinal Surgery, the Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo Liu, Email drliubo@outlook.comPurpose: The AJCC (the American Joint Committee on Cancer) ypTNM (post-neoadjuvant pathologic stage group) staging was established based on patients with lymphadenectomy scope less than D2 and did not include ypT0N0 patients with pathologically complete response (PCR). The purpose of this study was to construct a survival predictive model for gastric cancer patients after neoadjuvant chemotherapy and gastrectomy combined with D2 lymphadenectomy.Patients and Methods: The multicenter data of 838 gastric cancer patients who received neoadjuvant chemotherapy and gastrectomy combined with D2 lymphadenectomy were analyzed retrospectively. These dual center patients were divided into training (n = 671, the Affiliated Hospital of Qingdao University) and validation (n = 167, Qingdao West Coast New Area Central Hospital) cohorts. Based on training cohort, univariate and multivariable COX regression analyses were performed to select the clinicopathological characteristics significantly correlating with overall survival and construct a nomogram. Based on training and validation cohorts, the distinguishing and calibrating capabilities of nomogram was evaluated by the receiver operating characteristic (ROC) curve, Harrell’s concordance index (C-index), decision curve analysis (DCA) curve and calibration curve.Results: Platelet-to-lymphocyte ratio (PLR), pathologic stage after neoadjuvant treatment: ypT and ypN stage, tumor regression grade (TRG) became independent variables intimately related to the prognosis and was used to construct nomograms of 3/5-year prognosis. The nomograms showed an accuracy in predicting OS (overall survival) rate, with area under the ROC curve (AUC) of 0.818 (95% CI = 0.753~0.883) and C-index of 0.801 (95% CI = 0.744~0.858) in validation cohort. Calibration curves showed satisfactory agreement between nomogram prediction and actual result, and DCA curves indicated the large positive net benefit and excellent clinical usefulness of nomogram.Conclusion: This study successfully developed a nomogram to predict overall survival of gastric cancer patients after neoadjuvant chemotherapy and gastrectomy combined with D2 lymphadenectomy, which might have excellent predictive performance and clinical application value.Keywords: gastric cancer, neoadjuvant therapy, gastrectomy, nomogram, survival analysis

Lei Zhu,1,2 Chuanqing Yu,2 Yueyue Chang,2 Shiyu Sun,2 Zhongwu Sun1 1Department of Neurology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 2Department of Neurology, First Affiliated Hospital of Anhui University of Science and Technology, First People’s Hospital of Huainan, Huainan, Anhui Province, People’s Republic of ChinaCorrespondence: Zhongwu Sun, Department of Neurology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China, Email sunzhwu@126.comPurpose: Cystatins are associated with neuronal degeneration and nervous system healing. Cystatin C (Cys C) has recently been linked to brain injury and immunological inflammation. This study aimed to determine the relationship between serum Cys C levels and depression following intracranial hemorrhage (ICH).Patients and Methods: Between September 2020 and December 2022, 337 patients with ICH were sequentially recruited and followed up for three months. The post-stroke depression (PSD) and non-PSD groups were separated based on the 17-item Hamilton Depression Rating Scale (HAMD). The PSD diagnosis was established based on the DSM-IV criteria. Cys-C levels were documented within twenty-four hours of admission.Results: Three months after ICH, 93 (27.6%) of 337 enrolled patients were diagnosed with depression. The Cys C levels were significantly higher in depressed patients than in nondepressed patients after ICH (1.32 vs 1.01; p< 0.001). After adjusting for potential confounding variables, depression after ICH was associated with the highest quartile of Cys C levels (odds ratio (OR) = 3.195, 95% CI: 1.562– 6.536; p=0.001). The receiver operating characteristic curve (ROC) curve predicted that the ideal cut-off for CysC levels as a predictor of depression after ICH would be 0.730, resulting in 84.5% sensitivity and 88.4% specificity, with an area under curve (AUC) of 0.880 (95% CI: 0.843– 0.917; p< 0.0001).Conclusion: Increased CysC concentrations were independently related to depression three months after ICH, highlighting that CysC levels at admission may be a potential biomarker for predicting the onset of depression following ICH.Keywords: cystatin C, depression, intracerebral hemorrhage, post-stroke depression

Qi Wu,1,&ast; Xingxing Wu,1,&ast; Mao Wang,2,&ast; Kexin Liu,1 Yuge Li,1 Xiaoyu Ruan,1 Lin Qian,1 Lingchang Meng,3 Zhiting Sun,3 Lei Zhu,1 Jing Wu,3 Genglin Mu3 1Gastroenterology Department, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2Ethics Committee, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 3Institute of Chinese Medicine, Nanjing University, Nanjing Drum Tower Hospital, Drum Tower Clinical Medicine College of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Wu; Genglin Mu, Nanjing Drum Tower Hospital, Drum Tower Clinical Medicine College of the Nanjing University of Chinese Medicine, 321, Zhongshan Road, Nanjing, Jiangsu, People’s Republic of China, Tel +86 13451825475, Email wujing@njucm.edu.cn; glyydwsj@163.comBackground: Baicalin is an important active flavonoid isolated from the roots of Scutellaria baicalensis (S. baicalensis), a well-known traditional Chinese herb used in treating inflammatory bowel disease (IBD). The objectives of this study were to assess the potential benefit of baicalin in experimental colitis, as well as to investigate metabolic biomarkers of experimental colitis in conjunction with network pharmacology.Methods: Using a widely utilized network pharmacology technique, baicalin’s targets and pathways were predicted. Simultaneously, experimental colitis was induced by intrarectal administration of TNBS. Histopathology examinations were performed to confirm pathological changes. Plasma samples were examined by using an untargeted metabolomics technique based on ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) to screen differential metabolites and associated metabolic pathways. Additionally, network pharmacology and integrated analysis of metabolomics were used to identify the primary targets.Results: Through network pharmacology research, tumor necrosis factor (TNF), interleukin 6 (IL6), serine/threonine-protein kinase (AKT1), and other 7 proteins were found to be the main targets of baicalin against IBD. The untargeted metabolomics results showed that 47 metabolites in glycerophospholipids and sphingolipid metabolism were involved as key pathways in the experimental colitis model group. 19 metabolites, including Sphingomyelin (SM d42:2, SM d42:1, SM d34:1), Lysophosphatidic acids (LPA 18:4), 1-Palmitoylglycerophosphocholine, and 17(18)-EpETE were demonstrated as key metabolites for baicalin to exert effects. Moreover, udp-glucose ceramide glucosyltransferase (UGCG), sphingomyelin synthase 1 (SGMS1), and sphingosine kinase (SPHK1) were predicted as sphingolipids-linked targets of baicalin against experimental colitis by integrative analysis.Conclusion: Based on these results, it implies that sphingolipid metabolism and sphingolipid signaling pathway might be acted as therapeutic mechanism for baicalin against experimental colitis.Keywords: baicalin, inflammatory bowel disease, sphingolipid metabolism, metabolomics, network pharmacology, inflammation

Zhe Sun,1,&ast; Lu Liu,1,&ast; Hongbing Liu,2 Fang Luo1,2 1Department of Day Surgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 2Department of Pain Management, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fang Luo, Department of Pain Management, Beijing Tiantan Hospital, Capital Medical University, No. 119 West Road, South 4th Ring Road, Fengtai District, Beijing, 100070, People’s Republic of China, Tel +86 010 59976664, Fax +86 010 67050177, Email luofangwt@yahoo.comPurpose: To evaluate the effectiveness and safety of CT-guided radiofrequency thermocoagulation (RFT) for the treatment of infraorbital neuralgia following the failure of conservative management.Patients and Methods: This was a single center, retrospective study which included 196 patients between the ages of 37 to 90 years, who suffered from infraorbital neuralgia, and had undergone CT-guided RFT treatment. The medical records of these patients were retrieved between January 7, 2015 and February 5, 2020, and the patients were followed up for 2 years. Follow-up outcomes included Numerical Rating Scale (NRS) scores, dosage of carbamazepine, time to take effect, status of recurrence and side effects. The effective rate was defined as the percentage of patients with postoperative NRS score reduction of > 50%.Results: The effective rates were 92.9%, 100%, 100%, 100%, 93.4% and 85.7% on the same day, week 1, month 1, month 6, year 1 and year 2 after RFT, respectively. After RFT, the postoperative NRS scores and dosage of carbamazepine were significantly reduced than those preoperatively (P < 0.05). The median time to take effect was zero day. Twenty-eight patients with recurrence underwent RFT again and achieved complete pain relief. All patients experienced numbness in the infraorbital nerve innervation area and the numbness scores gradually decreased over time.Conclusion: CT-guided RFT treatment may be an effective and safe technique for pain relief in patients with infraorbital neuralgia following failed results from conservative treatment.Keywords: infraorbital neuralgia, radiofrequency thermocoagulation, effectiveness, safety, retrospective study

Zuoya Sun,1 Zhiyuan Chen,1 Ruihong Liu,1 Gang Lu,1 Zhuo Li,1 Yi Sun2 1Department of Family Medicine, the University of Hong Kong-Shenzhen Hospital, Shenzhen, People’s Republic of China; 2Department of Nephrology, Beijing Huairou Hospital, Beijing, People’s Republic of ChinaCorrespondence: Yi Sun, Department of Nephrology, Beijing Huairou Hospital, No. 9 Yongtai North Street, Huairou District, Beijing, 101400, People’s Republic of China, Tel +86-010-69644822, Fax +86-010-69622761, Email Sunyihuairou@163.comAbstract: The mineralocorticoid receptor antagonist spironolactone has been shown to improve cardiac function and reverse left ventricular hypertrophy in heart failure patients, but there are no consistent findings on the efficacy and safety in hemodialysis patients. Abnormal aldosterone secretion plays a critical role in the formation of left ventricular hypertrophy. Because of the existence of “aldosterone escape”, the routine use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers does not completely inhibit aldosterone secretion. Low-dose spironolactone (25 mg/d) has been found in small-sample clinical studies to have a significant positive impact with respect to decreasing left ventricular mass index, increasing left ventricular ejection fraction, reversing left ventricular hypertrophy, and improving cardiovascular function while still being safe. More prospective multicenter clinical trials with large sample sizes are needed, however, to provide convincing evidence.Keywords: spironolactone, hemodialysis, left ventricular hypertrophy, LVH, mineralocorticoid receptor antagonists, MRA, hyperkalemia

Yang Liu,1 Chao Zhang,2 Qianwen Wang,1 Kangze Wu,3 Zhouyi Sun,1 Zhe Tang,1 Bo Zhang3 1The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, 322000, People’s Republic of China; 2Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, People’s Republic of China; 3The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310000, People’s Republic of ChinaCorrespondence: Bo Zhang, The Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, Zhejiang, 310000, People’s Republic of China, Tel/Fax +86-0571-87783563, Email jjs10@zju.edu.cnBackground: This study aimed to evaluate the global colorectal cancer(CRC) trend and the relevant risk factors from 1990 to 2019 and for better policymaking and resource allocation.Methods: Data on CRC, including incidence, mortality and disability adjusted life year (DALY) rates, were extracted from the 2019 Global Burden of Disease (GBD) study. The estimated annual percentage changes (EAPCs) were calculated to assess the temporal trend of incidence, mortality and DALYs. The Bayesian age-period-cohort model(BAPC) was used to predict the future burden of CRC.Results: In 2019, a total of 2.17 million CRC cases were reported worldwide, a 157% increase from 1990. In high-social demographic index (SDI) regions, the trend of age-standardized incidence rate(ASIR) tended to decrease, while the proportion of people under 50 years of age tended to increase. Although the number of deaths and DALYs increased, the age-standardized death rate (ASDR) and age-standardized DALY rate decreased. The CRC burden was growing fastest in middle-SDI regions, especially in East Asia, followed by low SDI regions. In addition, the milk intake, High-BMI and high fasting plasma glucose play a more important role in on CRC. The predicted cases and deaths in global continued to increase to 2044. And there is an upward trend in ASIR for both men and women.Conclusion: In developed regions, the CRC burden continues to decrease, while the CRC burden become more and more severe in developing regions. Overall, the burden of CRC will rising in the near future. Therefore, reasonable resource allocation and prevention policies should be implemented. Developing countries needs more attention.Keywords: global burden of disease, colorectal cancer, disability-adjusted life year, estimated annual percentage change, age-standardized incidence rate, Bayesian age-period-cohort

Xueqing Guan, Zhijun Sun Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Zhijun Sun, Department of Cardiology, Shengjing Hospital, No. 39 of Huaxiang Road, Tiexi District, Shenyang, 110021, People’s Republic of China, Tel +86 18940251218, Fax +86 18940251218, Email sunzhijunszj8@126.comAbstract: Intestinal flora is a complex collection of microbial communities that participate in the physiological and pathological activities of the human body through various pathways. In recent years, numerous studies have reported that intestinal flora are involved in the occurrence and development of heart failure (HF) and its metabolic products could play an important role in this progression, suggesting a great value in the clinical treatment of this condition. This study reported the interaction between intestinal flora and HF, and with intestinal flora metabolites, such as short-chain fatty acids, trimethylamine N-oxide and bile acids and urotoxins, considered as the starting point, the mechanism of the roles in HF was summarized. Additionally, the current research status and the development prospects of applying flora and metabolites to the clinical therapeutic decision of HF were discussed.Keywords: intestinal flora, heart failure, trimethylamine N-oxide, inflammation, probiotics, targeted therapy, fecal microbiota transplantation

Hongyan Xu, Wenjing Wang, Junlei Yin, Chengcun Song, Lin Li, Zhi Sun Department of Chemotherapy, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, People’s Republic of ChinaCorrespondence: Hongyan Xu, Department of Chemotherapy, Weihai Municipal Hospital, No. 248, Tongyi Road, Huancui District, Weihai, Shangdong, 264200, People’s Republic of China, Tel +860631-5287510, Email xuhongyan19701212@163.comAim: To investigate the efficacy and safety of preoperative neoadjuvant therapy (PD-1 inhibitor plus nab-PTX and nedaplatin) for resectable stage III lung squamous cell carcinoma (SCC) patients.Methods: Patients with locally advanced lung SCC (stage IIIA, IIIB) who received PD-1 inhibitor combined with nab-PTX and NED between February 2019 and June 2021 in Weihai Municipal Hospital were included and underwent surgical treatment 4 weeks after 2– 4 cycles neoadjuvant therapy. The rate of resection R0, the effective rate, the complete pathological remission rate (pCR) and the rate of major pathological remission (MPR) were observed.Results: A total of 14 initially unresectable male patients with lung SCC were included and received neoadjuvant treatment after evaluation. Nine out of 14 patients (64.3%) experienced treatment-related adverse events (TRAE), among which 8 (57.1%) experienced grade (G) I–II TRAEs including nausea, vomiting, fatigue, constipation, elevated ALT and AST, hyperthyroidism, hypothyroidism, rash, granulocytopenia, and thrombocytopenia, and 1 (7.1%) experienced grade III–V TRAEs (G), including granulocytopenia and atelectasis. Thirteen patients (92.86%) achieved RECIST-assessed partial remission (PR), while 1 patient (7.14%) achieved stable disease (SD) on imaging assessment after neoadjuvant treatment and continued to be progression-free for 26 months. Of the 11 patients who underwent resection, all were alive and recurrence/progression-free. MPR and pCR were observed in 2 (18.18%) and 9 (81.82%), respectively. IHC results exhibited that all NSCLC patients exhibited positive PD-L1 expression (9/14, TPS ≥ 50% or greater; 5/14, 1% < TPS < 50%). Two were negative for ALK, EGFR, and ros-1, and the rest were not examined for driver oncogene mutation.Conclusion: The neoadjuvant therapy of the PD-1 inhibitor combined with nab-PTX and NED demonstrated remarkable therapeutic efficacy and good safety on stage III lung SCC without increasing the risk of TRAE, mortality and surgery-related complications, or impede surgery feasibility.Keywords: lung squamous cell lung cancer, neoadjuvant therapy, immunotherapy, complete pathological remission, pCR, major pathological remission, MPR

Fei Wu,1– 3,&ast; Jie Chen,4,&ast; Kang Yao,1 Daming Fan,5 Minglei Wang,2 Yongjun Liu,1 Shouhu Xin,1 Zeqiang Sun,1 Shun Li,1 Yang Sun,6 Qingyong Liu1 1Department of Urology, the First Affiliated Hospital of Shandong First Medical University, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250014, People’s Republic of China; 2Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, People’s Republic of China; 3Department of Urology, Shandong Provincial Hospital, Shandong First Medical University, Jinan, 250021, People’s Republic of China; 4Department of Urology, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250013, People’s Republic of China; 5Department of Pathology, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250013, People’s Republic of China; 6Department of Dermatology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Sun; Qingyong Liu, Email sunyang@qiluhospital.com; liuqingyong@sdhospital.com.cnIntroduction: A primary impediment to the efficacy of immune checkpoint inhibitors is the lack of biomarkers for therapeutic responses and prognosis. Although patients with clear cell renal cell carcinoma (ccRCC) could be precisely selected for targeted therapy based on somatic mutations, it remains controversial to choose the suitable patients with a high response rate to immune checkpoint inhibitors (ICIs). The immune-dependent roles of tumor suppressor PTEN in the formation of tumor immune microenvironment remain elusive.Methods: We comprehensively analyzed the genomic and transcriptomic data from multiple ccRCC datasets, including bulk-RNA sequencing and single-cell RNA sequencing data. In vitro, immunoblotting, qRT-PCR, and RNA sequencing were conducted in ccRCC cell lines upon PTEN depletion. Gene ontology and gene set enrichment analysis were performed to screen the critical pathway and molecules in response to PTEN deletion. Immunohistochemistry staining and further bioinformatic analysis were used to validate our data.Results: Based on multi-omics analysis of public datasets of renal cancer, the frequently mutated or deleted PTEN was found to be correlated with a suppressive tumor immune microenvironment in ccRCC. Furthermore, we depleted PTEN via CRISPR-Cas9 in Caki-1 cells, which led to the upregulation of multiple neutrophil chemokines, particularly CXCL1, CXCL2, CXCL5, CXCL6, and CXCL8. The roles of neutrophil chemokines and neutrophil markers were further validated and investigated for the association with prognosis in vitro, clinical samples, and the publicly available databases. The expression of CXCL1, CXCL8, and neutrophil markers, S100A9 and BCL2A1, were significantly associated with a poor immunotherapy-related prognosis in public dataset of renal cancer patients receiving ICIs treatment.Conclusion: These results add a new layer to understanding the association between PTEN status and the role of neutrophil infiltration in ccRCC. Moreover, our findings propose low expression of PTEN as candidate factor of resistance to anti-PD-1-based immunotherapy in ccRCC.Keywords: PTEN, kidney cancer, CXCL1, renal cancer, prognosis

Haipeng Yao,1 Zhen Sun,1 Wei Yuan,1 Chen Shao,1 Honghua Cai,2 Lihua Li,3 Yongjiang Qian,1 Zhongqun Wang1 1Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, People’s Republic of China; 2Department of Burns and Plastic Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, People’s Republic of China; 3Department of Pathology, Affiliated Hospital of Jiangsu University, Zhenjiang, People’s Republic of ChinaCorrespondence: Zhongqun Wang, Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212000, People’s Republic of China, Email wangtsmc@126.comPurpose: The research explores the relationship between the triglyceride-glucose index (TyG index) and the macroangiopathy risk in single-center hospitalized type 2 diabetes mellitus (T2DM) patients and develops a risk prediction nomogram model.Patients and Methods: A total of 858 patients with T2DM were studied retrospectively. Lasso regression was used to eliminate unimportant factors, and multivariate logistic regression analysis was used to investigate the association between the TyG index and macrovascular disease in T2DM. A nomogram model was constructed to predict macrovascular disease in T2DM and tested using the bootstrap technique, and the efficacy of the nomogram model was investigated using ROC curves. The multivariate Cox proportional hazards model estimated the association between the TyG index and all-cause mortality.Results: TyG index, high-density lipoprotein, red blood cell count, hypertension, history of taking ACEI/ARB drugs, and aortic calcification were closely related to macrovascular complications. In Cox proportional hazard model, the HRs of TyG index were 1.89 (95% confidence interval (CI) 1.29– 2.76, p < 0.001) after adjusting for covariates. The risk of all-cause mortality in T2DM with macrovascular complications was significantly higher than in diabetic patients without vascular disease. In the ROC curve analysis, the cut-off value of the TyG index for macrovascular complications of T2DM was 9.31 (AUC: 0.702, 95% CI 0.67– 0.74, p < 0.001).Conclusion: TyG index predicts future macrovascular disease in diabetic patients independently of known cardiovascular risk factors, suggesting that TyG index may be a useful marker for prognosis in diabetic patients.Keywords: diabetes, cardiovascular events, vascular complications, risk factors, triglyceride-glucose index

Yinuo Wen,1,2,&ast; Zefan Sun,1,&ast; Shuoyin Xie,1,2 Zixuan Hu,1,2 Qicheng Lan,1,2 Yupeng Sun,1,2 Linbo Yuan,3 Changlin Zhai1,2 1The Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310000, People’s Republic of China; 2The First Clinical College, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 3School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Changlin Zhai, The Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310000, People’s Republic of China, Email yesterdaygun@126.com Linbo Yuan, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China, Email ylb@wmu.edu.cnAbstract: In recent years, increasing evidence has shown that the gut microbiota and their metabolites play a pivotal role in human health and diseases, especially the cardiovascular diseases (CVDs). Intestinal flora imbalance (changes in the composition and function of intestinal flora) accelerates the progression of CVDs. The intestinal flora breaks down the food ingested by the host into a series of metabolically active products, including trimethylamine N-Oxide (TMAO), short-chain fatty acids (SCFAs), primary and secondary bile acids, tryptophan and indole derivatives, phenylacetylglutamine (PAGln) and branched chain amino acids (BCAA). These metabolites participate in the occurrence and development of CVDs via abnormally activating these signaling pathways more swiftly when the gut barrier integrity is broken down. This review focuses on the production and metabolism of TMAO and SCFAs. At the same time, we summarize the roles of intestinal flora metabolites in the occurrence and development of coronary heart disease and hypertension, pulmonary hypertension and other CVDs. The theories of “gut-lung axis” and “gut-heart axis” are provided, aiming to explore the potential targets for the treatment of CVDs based on the roles of the intestinal flora in the CVDs.Keywords: cardiovascular diseases, intestinal microecology, trimethylamine oxide, short-chain fatty acids, gut-heart axis

Qin Ding,1,&ast; Shuqi Huang,1,&ast; Zexu Sun,2 Kaifeng Chen,1 Xin Li,3 Qi Pei1 1Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, People’s Republic of China; 3Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qi Pei, Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, 410013, People’s Republic of China, Tel +86 1 317 041 9804, Email peiqi1028@126.com Xin Li, Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, 410013, People’s Republic of China, Email lixiner1975@163.comAbstract: Posaconazole is often used for the prophylaxis and treatment of invasive fungal infections (IFI). However, intra- and inter-individual differences and drug interactions affect the efficacy and safety of posaconazole. Precision dosing of posaconazole based on the population pharmacokinetic (PopPK) model may assist in making significant clinical decisions. This review aimed to comprehensively summarize the published PopPK models of posaconazole and analyze covariates that significantly influence posaconazole exposure. Articles published until May 2022 for PopPK analysis of posaconazole were searched in PubMed and EMBASE databases. Demographic characteristics, model characteristics, and results of PopPK analysis were extracted from the selected articles. In addition, the steady-state pharmacokinetic profiles of posaconazole were simulated at different covariate levels and dosing regimens. Out of the 13 studies included in our review, nine studies included adults, three included children, and one included both adults and children. All oral administration models were one-compartment models, and all intravenous administration models were two-compartment models. Body weight, proton pump inhibitors, and incidence of diarrhea were found to be important covariates. Clinically, the potential impact of factors such as patient physiopathologic characteristics and comorbid medications on posaconazole pharmacokinetics should be considered. Dose adjustment in combination with TDM or replacement with a tablet or intravenous formulation with higher exposure may be an effective way to ensure drug efficacy as well as to reduce fungal resistance. Meanwhile, published models require further external evaluation to examine extrapolation.Keywords: posaconazole, population pharmacokinetics, nonlinear mixed effects modeling, therapeutic drug monitoring

Jiang Liu,1,2,&ast; Hao Hu,1,3,&ast; Shanhu Qiu,4 Duolao Wang,5 Jianing Liu,1 Ziwei Du,1 Zilin Sun1 1Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, School of Medicine, Southeast University, Nanjing, 210009, People’s Republic of China; 2Department of Endocrinology, The Third Hospital of Nanchang, Nanchang, Jiangxi, People’s Republic of China; 3Department of Endocrinology, The First People’s Hospital of Xuzhou, Xuzhou, Jiangsu, People’s Republic of China; 4Department of General Practice, Zhongda Hospital; Institute of Diabetes, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 5Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK&ast;These authors contributed equally to this workCorrespondence: Zilin Sun, Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, School of Medicine, Southeast University, Nanjing, 210009, People’s Republic of China, Tel +8613951749490, Fax +862583262609, Email sunzilin1963@126.comPurpose: To investigate the prevalence and associated factors of diabetic retinopathy (DR) and advanced DR in Chinese adults with diabetes mellitus (DM).Patients and Methods: A cross-sectional study was performed on 4831 diabetic patients from 24 hospitals from April 2018 to July 2020. Non-mydriatic fundus of patients were interpreted by an artificial intelligence (AI) system. Fundus photos that were unsuitable for AI interpretation were interpreted by two ophthalmologists trained by one expert ophthalmologist at Beijing Tongren Hospital. Medical history, height, weight, body mass index (BMI), glycosylated hemoglobin (HbA1c), blood pressure, and laboratory examinations were recorded.Results: A total of 4831 DM patients were included in this study. The prevalence of DR and advanced DR in the diabetic population was 31.8% and 6.6%, respectively. In multiple logistic regression analysis, male (odds ratio [OR], 1.39), duration of diabetes (OR, 1.05), HbA1c (OR, 1.11), farmer (OR, 1.39), insulin treatment (OR, 1.61), region (northern, OR, 1.78; rural, OR, 6.96), and presence of other diabetic complications (OR: 2.03) were associated with increased odds of DR. The factors associated with increased odds of advanced DR included poor glycemic control (HbA1c > 7.0%) (OR, 2.58), insulin treatment (OR, 1.73), longer duration of diabetes (OR, 3.66), rural region (OR, 4.84), and presence of other diabetic complications (OR, 2.36), but overweight (BMI > 25 kg/m2) (OR, 0.61) was associated with reduced odds of advanced DR.Conclusion: This study shows that the prevalence of DR is very high in Chinese adults with DM, highlighting the necessity of early diabetic retinal screening.Keywords: diabetes mellitus, screening, artificial intelligence, glycemic control, rural region

Zhe Sun,1,&ast; Lu Liu,1,&ast; Hongbing Liu,2 Fang Luo1,2 1Department of Day Surgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 2Department of Pain Management, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fang Luo, Department of Pain Management, Beijing Tiantan Hospital, Capital Medical University, No. 119 West Road, South 4th Ring Road, Fengtai District, Beijing, 100070, People’s Republic of China, Tel +86 10 59976664, Fax +86 10 67050177, Email luofangwt@yahoo.comPurpose: To further evaluate the effects of gasserian ganglion block treatment with local anesthetics and steroids on patients with acute/subacute zoster-related trigeminal neuralgia.Patients and Methods: This is a multicenteric retrospective study which included patients between the ages of 26– 92 years, who suffered from acute/subacute zoster-related trigeminal neuralgia and had undergone CT-guided gasserian ganglion block. The medical records of these patients between January 13, 2016 and August 25, 2021 were retrieved, and the patients were followed up for 6 months. Follow-up outcomes were Numerical Rating Scale (NRS) scores, medications and dosage. The effective rate was defined as the number of cases with NRS score reduction of > 50%/total number of cases× 100% at 12 weeks postoperatively.Results: The postoperative NRS scores were significantly decreased in all patients (P < 0.05), and NRS scores in acute zoster group were lower than those in subacute zoster group at different time points (P < 0.05). The percentage of patients who had a reduction of medication use value of > 50% was 56.4% and the effective rate was 66.7% in all patients, at 3 months after the block treatment. There was no significant difference in the reduction of medication use value of > 50% and the effective rates between the two groups. There were no intracranial hemorrhage, infection or other serious adverse effects in either groups.Conclusion: CT-guided gasserian ganglion block with local anesthetics and steroids can be an effective and safe technique to relieve the pain of acute/subacute zoster-related trigeminal neuralgia.Keywords: acute/subacute zoster-related trigeminal neuralgia, gasserian ganglion block, local anesthetics, steroids, multicenter retrospective study