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Longyin Zhu,* Juan Cai,* Jia Fang, Lingyu Ran, Huan Chang, Huhai Zhang, Jiamin Zeng, Qin Yang, Chunxiao Fu, Qingping Li, Qianguang Pan, Hongwen Zhao Department of Nephrology, the First Hospital Affiliated to Army Military Medical University (Southwest Hospital), Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongwen Zhao; Qianguang Pan, Email zhaohw212@126.com; panqianguang@163.comObjective: Analyze risk factors for cardiac surgery-associated acute kidney injury (CSA-AKI) in adults and establish a nomogram model for CSA-AKI based on plasma soluble urokinase-type plasminogen activator receptor (suPAR) and clinical characteristics.Methods: In a study of 170 patients undergoing cardiac surgery with cardiopulmonary bypass, enzyme-linked immunosorbent assay (ELISA) measured plasma suPAR levels. Multivariable logistic regression analysis identified risk factors associated with CSA-AKI. Subsequently, the CSA-AKI nomogram model was developed using R software. Predictive performance was evaluated using a receiver operating characteristic (ROC) curve and the area under the curve (AUC). Internal validation was performed through the Bootstrap method with 1000 repeated samples. Additionally, decision curve analysis (DCA) assessed the clinical applicability of the model.Results: Multivariable logistic regression analysis revealed that being male, age ≥ 50 years, operation time ≥ 290 minutes, postoperative plasma suPAR at 2 hours, and preoperative left ventricular ejection fraction (LVEF) were independent risk factors for CSA-AKI. Employing these variables as predictive factors, a nomogram model was constructed, an ROC curve was generated, and the AUC was computed as 0.817 (95% CI 0.726– 0.907). The calibration curve indicated the accuracy of the model, and the results of DCA demonstrated that the model could benefit the majority of patients.Conclusion: Being male, age ≥ 50 years, operation time ≥ 290 minutes, low preoperative LVEF, and elevated plasma suPAR at 2 hours are independent risk factors for CSA-AKI. The nomogram model established based on these risk factors has high accuracy and clinical value, serving as a predictive tool for assessing the risk of CSA-AKI.Keywords: nomogram, acute kidney injury, prediction model, risk factors, cardiac surgery

Jiawen Kuang,1,* Wei Zhang,1,* Haoran Zhang,2,* Nan Lin,1 Jialie Fang,3 Rui Song,4 Zhaohua Xin,2 Jingyi Wang1 1School of Public Health; NHC Key Laboratory of Health Technology Assessment, Fudan University, Shanghai, People’s Republic of China; 2Lingqiao Community Health Center, Pudong New Area, Shanghai, People’s Republic of China; 3Jing’an District Center for Disease Control and Prevention, Shanghai, People’s Republic of China; 4Xiaodongmen Subdistrict Community Health Center, Huangpu District, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jingyi Wang, School of Public Health; NHC Key Laboratory of Health Technology Assessment, Fudan University, 446-2 Zhaojiabang Road, Shanghai, 200032, People’s Republic of China, Tel/Fax +86 21 3356 3933 ; +86 21 6416 9553, Email jingyi_wang@fudan.edu.cn Zhaohua Xin, Lingqiao Community Health Center, 1236 Jiangdong Road, Pudong New Area, Shanghai, 200131, People’s Republic of China, Tel/Fax +86 21 5864 2003, Email 115013251@qq.comPurpose: Psychosocial factors have been found to profoundly impact mental health of older adults, but the main focus in the current literature has been on one particular aspect of these factors. This study aimed to identify latent classes of older adults based on four psychosocial factors (loneliness, social isolation, perceived social support, and social capital) and the transition of classes over 6 months. We also sought to assess the predictive role of changes in these classes in relation to depression, anxiety, and stress at 18-month follow-up.Methods: We analyzed longitudinal data from 581 community-dwelling older adults in Shanghai, China. The data were collected at baseline (T0), 6-month follow-up (T1) and 18-month follow-up (T2) between March 2021 and April 2023. Using latent class analysis, we identified three underlying classes (Social Connectors, Subjective Social Isolates, and Social Isolates) of the sample. We also established five transition categories from T0 to T1 (Social Connectors T0-T1, Subjective Social Isolates T0-T1, Social Isolates T0-T1, Good Transition, and Bad Transition) using latent transition analysis. Logistic regression was employed to examine the temporal relationships between these transition categories and subsequent symptoms of depression, anxiety and stress, adjusting for age, sex, education, marital status, family income level, sleep quality, health status and outcome variables at T0.Results: Multivariable associations revealed that compared to older adults with persistent good social environment (Social Connectors T0-T1), those with persistent high levels of loneliness and social isolation and low levels of perceived social support and social capital (Social Isolates T0-T1), and those who shifted towards a poorer social environment (Bad Transition) were more likely to experience depression, anxiety and stress at T2. Sustained subjective social isolation (Subjective Social Isolates T0-T1) was associated with more severe depressive symptoms at T2.Conclusion: Our study indicated that adverse psychosocial environment worsened mental health in older adults. These findings highlight the importance of early identification of older individuals at long-term psychosocial risk and development of tailored interventions to improve their social environment and mental health.Keywords: older adults, psychosocial factors, depression, anxiety, stress

Fengfeng Li,1 Yang Jia,1 Jun Fang,2 Linqiang Gong,3 Yazhou Zhang,4 Shanshan Wei,5 Linlin Wu,6 Pei Jiang5 1Neurosurgery Department, Tengzhou Central People’s Hospital Affiliated to Xuzhou Medical University, Tengzhou, Shandong, 277500, People’s Republic of China; 2Anesthesiology Department, Tengzhou Central People’s Hospital Affiliated to Xuzhou Medical University, Tengzhou, Shandong, 277500, People’s Republic of China; 3Gastroenterology Department, Tengzhou Central People’s Hospital Affiliated to Xuzhou Medical University, Tengzhou, Shandong, 277500, People’s Republic of China; 4Foot and Ankle Surgery Department, Tengzhou Central People’s Hospital Affiliated to Xuzhou Medical University, Tengzhou, Shandong, 277500, People’s Republic of China; 5Translational Pharmaceutical Laboratory, Jining First People’s Hospital, Jining, Shandong, 272000, People’s Republic of China; 6Oncology Department, Tengzhou Central People’s Hospital Affiliated to Xuzhou Medical University, Tengzhou, Shandong, 277500, People’s Republic of ChinaCorrespondence: Linlin Wu, Oncology Department, Tengzhou Central People’s Hospital Affiliated to Xuzhou Medical University, Tengzhou, Shandong, 277500, People’s Republic of China, Tel +86 632-5513457, Email linlinliff@163.com Pei Jiang, Translational Pharmaceutical Laboratory, Jining First People’s Hospital, Jining, Shandong, 272000, People’s Republic of China, Tel +86 537-2106208, Email jiangpeicsu@sina.comBackground: Traumatic brain injury (TBI) is a condition characterized by structural and physiological disruptions in brain function caused by external forces. However, as the highly complex and heterogenous nature of TBI, effective treatments are currently lacking. Mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) has shown notable antinociceptive and anti-inflammatory effects, yet its detailed neuroprotective effects and mode of action remain incompletely understood. This study investigated the neuroprotective effects and the underlying mechanisms of MOTS-c.Methods: Adult male C57BL/6 mice were randomly divided into three groups: control (CON) group, MOTS-c group and TBI group. Enzyme-linked immunosorbent assay (ELISA) kit method was used to measure the expression levels of MOTS-c in different groups. Behavioral tests were conducted to assess the effects of MOTS-c. Then, transcriptomics and metabolomics were performed to search Differentially Expressed Genes (DEGs) and Differentially Expressed Metabolites (DEMs), respectively. Moreover, the integrated transcriptomics and metabolomics analysis were employed using R packages and online Kyoto Encyclopedia of Genes and Genomes (KEGG) database.Results: ELISA kit method showed that TBI resulted in a decrease in the expression of MOTS-c. and peripheral administration of MOTS-c could enter the brain tissue after TBI. Behavioral tests revealed that MOTS-c improved memory, learning, and motor function impairments in TBI mice. Additionally, transcriptomic analysis screened 159 differentially expressed genes. Metabolomic analysis identified 491 metabolites with significant differences. Integrated analysis found 14 KEGG pathways, primarily related to metabolic pathways. Besides, several signaling pathways were enriched, including neuroactive ligand–receptor interaction and retrograde endocannabinoid signaling.Conclusion: TBI reduced the expression of MOTS-c. MOTS-c reduced inflammatory responses, molecular damage, and cell death by down-regulating macrophage migration inhibitory factor (MIF) expression and activating the retrograde endocannabinoid signaling pathway. In addition, MOTS-c alleviated the response to hypoxic stress and enhanced lipid β-oxidation to provide energy for the body following TBI. Overall, our study offered new insights into the neuroprotective mechanisms of MOTS-c in TBI mice.Keywords: MOTS-c, TBI, transcriptomics, metabolomics, neuroprotective

Tianwen Lai,1,* Chaole Luo,1,* Yalian Yuan,2,* Jia Fang,1,* Yun Wang,1 Xiantong Tang,1 Lihuan Ouyang,1 Keyan Lin,1 Bin Wu,2 Weimin Yao,1 Ruina Huang1 1Department of Respiratory and Critical Care Medicine, the First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, 523121, People’s Republic of China; 2Respiratory Diseases Research Institute, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ruina Huang; Weimin Yao, Email wolidedd@163.com; yaoweimin@gdmu.edu.cnIntroduction: Chronic obstructive pulmonary disease (COPD), an incurable chronic respiratory disease, has become a major public health problem. The relationship between the composition of intestinal microbiota and the important clinical factors affecting COPD remains unclear. This study aimed to identify specific intestinal microbiota with high clinical diagnostic value for COPD.Methods: The fecal microbiota of patients with COPD and healthy individuals were analyzed by 16S rDNA sequencing. Random forest classification was performed to analyze the different intestinal microbiota. Spearman correlation was conducted to analyze the correlation between different intestinal microbiota and clinical characteristics. A microbiota-disease network diagram was constructed using the gut MDisorder database to identify the possible pathogenesis of intestinal microorganisms affecting COPD, screen for potential treatment, and guide future research.Results: No significant difference in biodiversity was shown between the two groups but significant differences in microbial community structure. Fifteen genera of bacteria with large abundance differences were identified, including Bacteroides, Prevotella, Lachnospira, and Parabacteroides. Among them, the relative abundance of Lachnospira and Coprococcus was negatively related to the smoking index and positively related to lung function results. By contrast, the relative abundance of Parabacteroides was positively correlated with the smoking index and negatively correlated with lung function findings. Random forest classification showed that Lachnospira was the genus most capable of distinguishing between patients with COPD and healthy individuals suggesting it may be a potential biomarker of COPD. A Lachnospira disease network diagram suggested that Lachnospira decreased in some diseases, such as asthma, diabetes mellitus, and coronavirus disease 2019 (COVID-19), and increased in other diseases, such as irritable bowel syndrome, hypertension, and bovine lichen.Conclusion: The dominant intestinal microbiota with significant differences is related to the clinical characteristics of COPD, and the Lachnospira has the potential value to identify COPD.Keywords: chronic obstructive pulmonary disease, intestinal microbiota, 16S rDNA sequencing, Lachnospira, gut-lung axis

Ziwen Wang,1,2 Jiaxuan Fang,1,2 Shigao Zu,1,2 Qianru Sun,1,2 Zixin Song,1,2 Jiman Geng,1,2 Dongdong Wang,1,2 Meng Li,1,2 Changtao Wang1,2 1Beijing Key Laboratory of Plant Resource Research and Development, Beijing Technology and Business University, Beijing, 100048, People’s Republic of China; 2School of Light Industry Science and Engineering, Beijing Technology and Business University, Beijing, 100048, People’s Republic of ChinaCorrespondence: Dongdong Wang; Changtao Wang, Beijing Technology and Business University, Beijing, 100048, People’s Republic of China, Tel/Fax +86 158 1135 7756, Email wdd@btbu.edu.cn; wangct@th.btbu.edu.cnPurpose: To produce Panax notoginseng extract as a cosmetic ingredient through Saccharomyces cerevisiae fermentation.Methods: We first compared the total sugar content, polysaccharide content, reducing sugar content, total phenolic content, total saponin content, DPPH free radical, ABTS free radical, hydroxyl free radical scavenging ability and ferric reducing antioxidant power (FRAP) of Panax notoginseng fermented extract (pnFE) and unfermented extract (pnWE). Their potential correlations were analyzed by Pearson’s correlation analysis. Then, the oxidative stress model of H2O2-induced MSFs was used to evaluate the effects of different pnFE on MSF viability, reactive oxygen species (ROS), malondialdehyde (MDA), and the activities of catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) to explore their protective effects on MSFs subjected to H2O2-induced cellular oxidative damage. Finally, their safety and stability were evaluated by using the red blood cell (RBC) test and hen’s egg test-chorioallantoic membrane (HET-CAM) assay, and changes in pH and content of soluble solids, respectively.Results: Compared with pnWE, pnFE has more active substances and stronger antioxidant capacity. In addition, pnFE has a protective effect on H2O2-induced oxidative stress in MSFs with appropriate safety and stability.Conclusion: PnFE has broad application prospects in the field of cosmetics.Keywords: Panax notoginseng, Saccharomyces cerevisiae, fermentation, oxidative stress, fibroblast cells, cosmetic ingredients

Qiwei Li,1 Zhiyun Zhang,1,2 Jiajia Fang1 1Department of Neurology, The Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University School of Medicine, Yiwu, Zhejiang Province, 322000, People’s Republic of China; 2Department of Neurology, The Mianyang Central Hospital, Mianyang, Sichuan Province, 621000, People’s Republic of ChinaCorrespondence: Jiajia Fang, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, 322000, People’s Republic of China, Email fangjjiaj@zju.edu.cnAbstract: Epilepsy is a prevalent neurological disorder among women globally, often requiring long-term treatment. Hormonal fluctuations in women with epilepsy (WWE) can have reciprocal effects on epilepsy and antiseizure medications (ASMs), posing significant challenges for WWE. Notably, WWE commonly experience endocrine alterations such as thyroid dysfunctions, low bone metabolism, and reproductive hormone irregularities. On the one hand, the presence of hormones in women with epilepsy affects their susceptibility to epilepsy as well as the metabolism of antiseizure medications in various ways. On the other hand, epilepsy itself and the use of antiseizure medications impact the production, secretion, and metabolism of hormones, resulting in low fertility, increased risk of pregnancy complications, negative offspring outcomes, and so on. In order to develop more precise treatment strategies in the future, it is necessary to comprehend the explicit relationships between hormones, epilepsy, and antiseizure medications, as well as to elucidate the currently known mechanisms underlying these interactions.Keywords: women with epilepsy, antiseizure medications, endocrine, hormonal changes

Jin Tu,1– 3,* Feng Jiang,4,* Jieni Fang,2 Luhua Xu,2 Zhicong Zeng,2 Xuanyue Zhang,1 Li Ba,1 Hanjiao Liu,1,3 Fengxia Lin2 1Department of Nursing, Seventh Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, 518100, People’s Republic of China; 2Department of Cardiovascular, Shenzhen Bao’an Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, 518100, People’s Republic of China; 3Department of Nursing, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, Guangdong, 518100, People’s Republic of China; 4School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fengxia Lin, Department of Cardiovascular, Shenzhen Bao’an Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, 518100, People’s Republic of China, Email szlinfx@163.com Hanjiao Liu, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, Guangdong, 518100, People’s Republic of China, Email liuhanjiao000@163.comBackground: Dendrobium, with profound botanical importance, reveals a rich composition of bioactive compounds, including polysaccharides, flavonoids, alkaloids, and diverse amino acids, holding promise for skin regeneration. However, the precise mechanism remains elusive. Seeking a potent natural remedy for wound healing, exocyst vesicles were successfully isolated from Dendrobium.Aims of the Study: This investigation aimed to employ bioinformatics and in vivo experiments to elucidate target genes of Dendrobium-derived nanovesicles in skin wound healing, focusing on immune infiltration and senescence characteristics.Materials and Methods: C57 mice experienced facilitated wound healing through Dendrobium-derived nanovesicles (DDNVs). Bioinformatics analysis and GEO database mining identified crucial genes by intersecting immune-related, senescence-related, and PANoptosis-associated genes. The identified genes underwent in vivo validation.Results: DDNVs remarkably accelerated skin wound healing in C57 mice. Bioinformatics analysis revealed abnormal expression patterns of immune-related, senescence-related, and pan-apoptosis-related genes, highlighting an overexpressed IL-1β and downregulated IL-18 in the model group, Exploration of signaling pathways included IL-17, NF-kappa B, NOD-like receptor, and Toll-like receptor pathways. In vivo experiments confirmed DDNVs’ efficacy in suppressing IL-1β expression, enhancing wound healing.Conclusion: Plant-derived nanovesicles (PDNV) emerged as a natural, reliable, and productive approach to wound healing. DDNVs uptake by mouse skin tissues, labeled with a fluorescent dye, led to enhanced wound healing in C57 mice. Notably, IL-1β overexpression in immune cells and genes played a key role. DDNVs intervention effectively suppressed IL-1β expression, accelerating skin wound tissue repair.Keywords: plant-derived nanovesicles, Dendrobium, immune infiltration factors, cellular aging, skin injury recovery

Yongjun Huang,1,* Yong Chen,2,* Guoyun Cheng,1,* Wenqiang Li,3 Hongan Zhang,1,4 Chaoqun Yu,1 Jia Fang,1 Jieyi Zuo,1 Ying Li,1 Lei Xu,1 Dawei Sun1 1Department of Orthopedics, Guangdong Second Provincial General Hospital, Guangzhou, 510317, People’s Republic of China; 2Department of Orthopedics, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan, People’s Hospital, Qingyuan, 511518, People’s Republic of China; 3Engineering Technology Research Center for Sports Assistive Devices of Guangdong, Guangzhou Sport University, Guangzhou, 510500, People’s Republic of China; 4The Second Clinical School of Medicine, Southern Medical University, Guangzhou, 510260, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lei Xu; Dawei Sun, Department of Orthopedics, Guangdong Second Provincial General Hospital, 11th Floor, Building 3, No. 466, Xingang Middle Road, Guangzhou, Guangdong Province, 510317, People’s Republic of China, Email orthoxl@163.com; sundw@gd2h.org.cnBackground: As the first line of immune defense and the largest organ of body, skin is vulnerable to damage caused by surgery, burns, collisions and other factors. Wound healing in the skin is a long and complex physiological process that is influenced by a number of different factors. Proper wound care can greatly improve the speed of wound healing and reduce the generation of scars. However, traditional wound dressings (bandages, gauze, etc.) often used in clinical practice have a single function, lack of active ingredients and are limited in use. Hydrogels with three-dimensional network structure are a potential biomedical material because of their physical and chemical environment similar to extracellular matrix. In particular, hydrogel dressings with low price, good biocompatibility, degradability, antibacterial and angiogenic activity are favored by the public.Methods: Here, a carboxymethyl chitosan-based hydrogel dressing (CMCS-TA/Cu2+) reinforced by copper ion crosslinked tannic acid (TA/Cu2+) nanoparticles was developed. This study investigated the physical and chemical characteristics, cytotoxicity, and angiogenesis of TA/Cu2+ nanoparticles and CMCS-TA/Cu2+ hydrogels. Furthermore, a full-thickness skin defect wound model was employed to assess the in vivo wound healing capacity of hydrogel dressings.Results: The introduction of TA/Cu2+ nanoparticles not only could increase the mechanical properties of the hydrogel but also continuously releases copper ions to promote cell migration (the cell migration could reach 92% at 48 h) and tubule formation, remove free radicals and promote wound healing (repair rate could reach 90% at 9 days).Conclusion: Experiments have proved that CMCS-TA/Cu2+ hydrogel has good cytocompatibility, antioxidant and wound healing ability, providing an advantageous solution for skin repair. Keywords: TA/Cu2+ nanoparticles, carboxymethyl chitosan, wound dressing, antioxidant activity

Longyin Zhu,1,* Huhai Zhang,1,* Jia Fang,1 Shuang Xiao,2 Fu Xiong,3 Caixia Deng,3 Qin Yang,1 Chunxiao Fu,1 Qianguang Pan,1 Hongwen Zhao1 1Department of Nephrology, the First Hospital Affiliated to Army Military Medical University (Southwest Hospital), Chongqing, 400038, People’s Republic of China; 2Department of Infectious Disease, the First Hospital Affiliated to Army Military Medical University (Southwest Hospital), Chongqing, 400038, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, the First Hospital Affiliated to Army Military Medical University (Southwest Hospital), Chongqing, 400038, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongwen Zhao; Qianguang Pan, Email zhaohw212@126.com; panqianguang@163.comIntroduction: We report a fatal case of massive airway bleeding caused by pulmonary strongyloidiasis in a patient with a transplanted kidney.Case Presentation: A 47-year-old male, regularly taking immunosuppressants post-kidney transplant, visited our hospital with symptoms of abdominal bloating, nausea, and emesis persisting for three days. After hospitalization, he developed a cough, hemoptysis, and respiratory failure. Sputum analysis confirmed an infestation with Strongyloides stercoralis. Despite receiving albendazole therapy and bronchoscopic management for bronchial hemorrhage, the patient ultimately died due to acute respiratory and circulatory collapse triggered by severe airway bleeding.Conclusion: Patients undergoing immunosuppressive therapy following kidney transplantation are at increased risk for disseminated strongyloidiasis. Consequently, infectious disease screening prior to transplantation, along with essential preventive pharmacotherapy, is of paramount importance.Keywords: strongyloides stercoralis, kidney transplantation, airway bleeding, disseminated infection

Bang Liu,1,2,* Jia Liu,3,* Xuan Mei,1,* Zhi-Qiang Zhang,1,2 Jian Fang,4 Li-Li Zhou,2 Jiao-Long Zheng,2 Hai-Yan Lin,2 Xiu-Ling Zhu,2 Dong-Liang Li1,2 1Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, 350025, People’s Republic of China; 2Department of Hepatobiliary Disease, 900TH Hospital of Joint Logistics Support Force, Fuzhou, 350025, People’s Republic of China; 3Department of Hepatobiliary Surgery, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, People’s Republic of China; 4Department of Hepatobiliary Medicine, The Third Affiliated People’s Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dong-Liang Li, Department of Hepatobiliary Disease, Fuzong Clinical Medical College of Fujian Medical University & 900TH Hospital of Joint Logistics Support Force, Fuzhou, 350025, People’s Republic of China, Email ldliang900@163.comBackground: PVTT is a hallmark of advanced hepatocellular carcinoma (HCC). We aim to explore the influence of non-invasive biomarkers on the occurrence of PVTT and develop and validate models for predicting prognosis in HBV-related HCC patients without PVTT.Methods: A total of 1026 HBV-related HCC patients without PVTT were enrolled, with 515 in the training cohort, 216 in the internal validation cohort, and 295 in the external validation cohort. We conducted Cox regression analyses to discern the independent risk factors associated with PVTT events, PFS, and OS, then constructed and validated predictive models. The predictive and discriminatory capabilities of models were assessed using the calibration, time-dependent ROC, and DCA curves.Results: In our study, 136 patients (13.3%) experienced PVTT events during the follow-up period. The Cox regression analysis unveiled that male gender, AAPR ≤ 0.49, APRI > 0.48, extrahepatic metastasis, and multiple tumors were independent risk factors for PVTT. In the training cohort, non-invasive biomarkers (AAR and APRI), AFP, ascites, and tumor-related characteristics (extrahepatic metastasis, tumor diameter, tumor number, and PVTT event) were independent risk factors for both OS and PFS, whereas age and ALBI grade independently correlated with OS. The C-indexes of OS and PFS nomogram models were 0.795 and 0.733 in the training cohort, 0.765 and 0.716 in the internal validation cohort, and 0.780 and 0.722 in the external validation cohort, respectively. Our models demonstrated strong predictive and discriminative abilities in all cohorts and yielded a greater net benefit compared to three traditional staging systems.Conclusion: Non-invasive biomarkers are expected to be reliable predictors for assessing PVTT risk and predicting prognosis among HBV-related HCC patients without PVTT.Keywords: non-invasive biomarker, portal vein tumor thrombosis, HBV-related HCC, nomogram, prognosis

Sangsang Xiong,1,* Mingqi Tu,1,* Xiaoting Wu,1 Siying Qu,1 Nisang Chen,1 Junyan Jin,1 Haiqin Rong,1 Shuangyi Pei,2 Jianqiao Fang,1 Xiaomei Shao1 1Key Laboratory for Research of Acupuncture Treatment and Transformation of Emotional Diseases, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaomei Shao; Jianqiao Fang, Zhejiang Chinese Medical University, No. 548, Binwen Road, Binjiang District, Hangzhou City, Zhejiang Province, People’s Republic of China, Tel +86 189 5713 0287, Email shaoxiaomei@zcmu.edu.cn; fangjianqiao7532@163.comBackground: Major depressive disorder (MDD) is highly prevalent, affecting more than 300 million individuals worldwide, and its occurrence may be related to the abnormality of the prefrontal cortex and bilateral temporal cortex. Acupuncture, rooted in the theories of acupoints and meridians, has demonstrated its efficacy in regulating cortical blood flow (CBF) in the brains of MDD patients. As one form of acupuncture, intradermal acupuncture (IA) can alleviate clinical symptoms such as depressive mood and insomnia in MDD patients. However, it remains unknown whether IA will have a specific effect on the prefrontal cortex and bilateral temporal cortex in MDD patients.Methods: In total, 60 participants will be recruited: 20 healthy control participants and 40 MDD patients. All healthy control participants will be allocated to the control group, whereas the 40 MDD patients will be randomly divided into two groups: the gallbladder meridian acupoint (GBA) group and the non-acupoint (NA) group, at a 1:1 allocation ratio. All groups will undergo a one-time IA intervention while their cortical activity is monitored using functional near-infrared spectroscopy (fNIRS). Total hemoglobin, oxygenated hemoglobin, and deoxygenated hemoglobin of the prefrontal and bilateral temporal cortices will be measured by fNIRS during the test procedure.Discussion: This trial aims to use fNIRS to compare real-time hemodynamic changes in the prefrontal and bilateral temporal cortices of healthy individuals and MDD patients during IA. The primary objective is to investigate whether MDD patients exhibit specific real-time responses to IA stimulation in these brain regions. The findings from this study will provide clinical data and a possible theoretical basis for the assumption that stimulation of IA may treat MDD by modulating the relevant brain regions.Trial Registration: The study protocol has been registered in the clinicaltrials.gov with the code NCT05707299.Keywords: major depressive disorder, intradermal acupuncture, functional near-infrared spectroscopy, prefrontal cortex, temporal cortex

Hong-Ping Wang,1,&ast; Yuan-Ying Xu,1,&ast; Bi-Lin Xu,1 Jun Lu,1 Juan Xia,1 Tian Shen,1 Ji Fang,1,2 Tao Lei1 1Department of Endocrinology, Putuo Hospital, Shanghai University of Traditonal Chinese Medicine, Shanghai, 200333, People’s Republic of China; 2Department of Nephrology, Putuo Hospital, Shanghai University of Traditonal Chinese Medicine, Shanghai, 200333, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Lei, Department of Endocrinology, Putuo Hospital, Shanghai University of Traditonal Chinese Medicine, No. 164 of Lanxi Road, Putuo District, Shanghai, 200333, People’s Republic of China, Tel +86 021-22233222-58142, Email leitao5899@126.com Ji Fang, Department of Nephrology, Putuo Hospital, Shanghai University of Traditonal Chinese Medicine, No. 164 of Lanxi Road, Putuo District, Shanghai, 200333, People’s Republic of China, Tel +86 021-22233222-58082, Email 13601833102@163.comObjective: To investigated the link between the distribution of abdominal fat and the concentration of serum uric acid (SUA) in individuals recently diagnosed with type 2 diabetes.Methods: Studied 364 individuals had been diagnosed with type 2 diabetes within one month, and evaluated factors such as the distribution of fat in the abdomen, indicators related to glucose and lipid metabolism. The participants’ SUA concentrations were divided into a normal control group (CG) and a hyperuricemia group (HG).Results: The HG group had elevated abdominal subcutaneous fat area (SFA), visceral fat content (VFA), body mass index (BMI), fasting blood glucose (FBG), 2-hour postprandial blood glucose (PBG), glycosylated albumin (GA), serum creatinine (SCr), triacylglycerol (TG), and lower values in glomerular filtration rate (eGFR), high-density lipoprotein cholesterol (HDL-C) when compared to the CG group (P < 0.05). Among the obese individuals, the hyperuricemia subgroup exhibited higher measurements in waistline, hipline, VFA, SFA, BMI, PBG, SCr, TG, and lower HDL-C (P < 0.05) compared to the subgroup with normal uric acid levels. In the non-obese group, the hyperuricemia subgroup showed higher VFA, SCr, and FBG levels, and lower HDL-C (P < 0.05). There was a positive correlation between VFA and serum uric acid (SUA) levels (r = 0.329, P < 0.0001). Logistic regression analysis indicated a 24% increased risk of hyperuricemia with every 10cm2 increase in abdominal VFA. Generate the Receiver Operating Characteristic (ROC) curve analysis revealed that VFA was the most effective predictor of hyperuricemia and insulin resistance (P < 0.05).Conclusion: Newly diagnosed type 2 diabetes patients exhibit a strong correlation between abdominal visceral fat and SUA concentration, the former is identified as an autonomous risk factor for hyperuricemia and an effective indicator for assessing the presence of hyperuricemia and predicting insulin resistance.Keywords: abdominal fat distribution, newly diagnosed type 2 diabetes, serum uric acid, visceral fat area

Kai Yang,1 Beibei Sun,2 Shicheng Zhang,3 Ying Pan,1 Jun Fang4 1Department of Medical Technology, Anhui Medical College, Hefei, Anhui, 230601, People’s Republic of China; 2Department of Clinical Laboratory, the Second Hospital of Anhui Medical University, Hefei, Anhui, 230601, People’s Republic of China; 3School of Public Health and Health Management, Anhui Medical College, Hefei, Anhui, 230601, People’s Republic of China; 4Faculty of Pharmaceutical Science, Sojo University, Kumamoto, 860-0082, JapanCorrespondence: Jun Fang, Faculty of Pharmaceutical Science, Sojo University, Ikeda 4-22-1, Kumamoto, 860-0082, Japan, Email fangjun@ph.sojo-u.ac.jpPurpose: The clinical significance of the red blood cell distribution width (RDW)-coefficient of variation (RDW-CV) has been recognized in numerous diseases, but few studies have investigated the usefulness of RDW-standard deviation (RDW-SD). This study aimed to compare the utility of RDW-SD and RDW-CV in evaluating liver fibrosis stage in patients with chronic hepatitis B (CHB).Patients and Methods: In this retrospective study, we enrolled 720 treatment-naïve CHB patients and 578 healthy controls, and evaluated their clinical parameters. In CHB patients, the associations between RDW-CV and liver fibrosis stage were analyzed as compared to RDW-SD using one-way analysis of variance (ANOVA), Spearman’s rank correlation, student’s t-test, binary logistic regression, and receiver operating characteristic (ROC) curve.Results: RDW-SD, rather than RDW-CV was significantly elevated in CHB patients compared with healthy controls. Correlation analysis showed a stronger association between RDW-SD and liver fibrosis stage than RDW-CV in CHB patients. RDW-CV and RDW-SD are both independent predictors of significant fibrosis. For the diagnosis of significant fibrosis, the area under the receiver operating characteristic curve (AUC) for RDW-CV was 0.599, while for RDW-SD, it was 0.706. RDW-to-platelet ratio (RPR), a novel index for liver fibrosis calculated as RDW-CV/platelet, exhibited an AUC of 0.730. This AUC increased to 0.752 when RDW-CV in the RPR formula was replaced with RDW-SD. Additionally, subgroup analyses based on age, gender, and HBeAg status showed that the AUC for RDW-SD in diagnosing significant fibrosis was significantly greater than that for RDW-CV, with statistically significant differences.Conclusion: RDW-SD showed superiority in reflecting liver fibrosis stage and diagnosing liver significant fibrosis than RDW-CV in treatment-naïve CHB patients.Keywords: red blood cell distribution width, liver fibrosis, chronic hepatitis B

Xin Jiang,&ast; Lijie Gao,&ast; Jian Wang, Jiajia Bao, Jinghuan Fang, Li He Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinghuan Fang; Li He, Department of Neurology, West China Hospital, Sichuan University, No. 37 Guoxue Lane, Chengdu, Sichuan Province, 610041, People’s Republic of China, Email jinghuan_fang@126.com; heli2003new@126.comBackground: Blood pressure variation and collateral status have been reported to be associated with clinical outcome in patients with acute ischemic stroke who received endovascular treatment; however, the relationship between blood pressure variation within 72 hours after EVT and clinical outcome in different collateral status remains unclear.Methods: Acute ischemic stroke patients due to large vessel occlusion with EVT were retrospectively enrolled. We classified participants into poor collateral (ASITN/SIR grade < 2) and good collateral subgroups (ASITN/SIR grade ≥ 2). The primary outcome was unfavorable neurological outcome defined as a 3-month modified Rankin Scale (mRS) score ≥ 2. The interactive effect was tested to determine the influence of collateral status on the association between BP variation and clinical outcome.Results: A total of 545 patients were included. The poor collateral subgroup was detected in 198 patients with an average age of 70.2 years. The association between BP variation and primary outcome did not differ under different collateral status (P for interaction > 0.05). However, the association between the mean and coefficient of variation (CV) values of DBP and 3-month mortality was significantly discrepant under different collateral status (P for interaction < 0.05). In the good collateral subgroup, higher mean DBP was associated with a lower risk of 3-month mortality (OR 0.95, 95% CI 0.91– 1, P = 0.033) compared with the poor subgroup (OR 1.04, 95% CI 0.97– 1.1, P = 0.286). In addition, a higher CV of DBP was associated with a higher risk of 3-month mortality (OR 1.24, 95% CI 1.13– 1.36, P < 0.01) compared with poor status (OR 1.08, 95% CI 0.94– 1.23, P=0.275).Conclusion: For patients who received EVT with good collateral status, increased CV of DBP was significantly associated with higher 3-month mortality, while higher mean DBP within 72 h after EVT was associated with a decrease in 3-month mortality.Keywords: acute ischemic stroke, blood pressure variability, clinical outcome, collateral status, endovascular treatment

Nisang Chen,1,&ast; Xiaoting Wu,1,&ast; Mingqi Tu,1 Sangsang Xiong,1 Junyan Jin,1 Siying Qu,1 Shuangyi Pei,1,2 Jianqiao Fang,1,2 Xiaomei Shao1,2 1Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Key Laboratory for Research of Acupuncture Treatment and Transformation of Emotional Diseases, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaomei Shao; Jianqiao Fang, Zhejiang Chinese Medical University, No. 548, Binwen Road, Binjiang District, Hangzhou City, Zhejiang Province, People’s Republic of China, Email 13185097375@163.com; shaoxiaomei@zcmu.edu.cn; fangjianqiao7532@163.comBackground: Major depressive disorder (MDD) exhibits a pronounced occurrence among adolescents, aligning closely with the lifetime prevalence rate of 16.6% observed in adults. It is difficult to treat and prone to recurrence. Acupuncture has shown potential in enhancing treatment effectiveness. Nonetheless, there is a lack of research on the use of intradermal acupuncture (IA) in treating adolescent MDD.Methods: This study is a double-blind, randomized controlled trial. A cohort of 120 participants will be assigned randomly to three distinct groups, namely a Selective Serotonin Reuptake Inhibitors (SSRIs)-only group, a sham intradermal acupuncture combined with SSRIs (SIA) group, and an active intradermal acupuncture combined with SSRIs (AIA) group. Hamilton Depression Rating Scale will serve as the primary outcome, while Patient Health Questionnaire-9, Self-Rating Depression Scale, Pittsburgh Sleep Quality Index, and Short Form 36 Questionnaire will serve as secondary outcomes in assessing the amelioration of depressive symptoms in patients. These data will be analyzed using SPSS26.0 software.Results: We will assess the efficacy and safety of IA for MDD using commonly employed clinical psychiatric scales.Conclusion: The efficacy of IA in treating adolescent MDD may be demonstrated in this study, suggesting its potential for optimizing MDD treatment schemes.Trial Registration: ClinicalTrials.gov Identifier: NCT 05832619 (April 27, 2023).Keywords: major depressive disorder, intradermal acupuncture, selective serotonin reuptake inhibitors, adolescent, randomized controlled trial, protocol

Wei Jiang, Xiaofei Deng, Ting Zhu, Jing Fang, Jinyao Li Department of Ultrasound, Huazhong University of Science and Technology Union Shenzhen Hospital (Nanshan Hospital), Shenzhen, Guangdong province, People’s Republic of ChinaCorrespondence: Wei Jiang, Department of Ultrasound, Huazhong University of Science and Technology Union Shenzhen Hospital (Nanshan Hospital), No. 89 Taoyuan Road, Nanshan District, Shenzhen, Guangdong province, 518052, People’s Republic of China, Tel + 86- 13026628099, Email 2646748175@qq.comBackground: Neoadjuvant chemotherapy (NAC) plays a significant role in breast cancer (BC) management; however, its efficacy varies among patients. Current evaluation methods may lead to delayed treatment alterations, and traditional imaging modalities often yield inaccurate results. Radiomics, an emerging field in medical imaging, offers potential for improved tumor characterization and personalized medicine. Nevertheless, its application in early and accurately predicting NAC response remains underinvestigated.Objective: This study aims to develop an automated breast volume scanner (ABVS)-based radiomics model to facilitate early detection of suboptimal NAC response, ultimately promoting personalized therapeutic approaches for BC patients.Methods: This retrospective study involved 248 BC patients receiving NAC. Standard guidelines were followed, and patients were classified as responders or non-responders based on treatment outcomes. ABVS images were obtained before and during NAC, and radiomics features were extracted using the PyRadiomics toolkit. Inter-observer consistency and hierarchical feature selection were assessed. Three machine learning classifiers, logistic regression, support vector machine, and random forest, were trained and validated using a five-fold cross-validation with three repetitions. Model performance was comprehensively evaluated based on discrimination, calibration, and clinical utility.Results: Of the 248 BC patients, 157 (63.3%) were responders, and 91 (36.7%) were non-responders. Radiomics feature selection revealed 7 pre-NAC and 6 post-NAC ABVS features, with higher weights for post-NAC features (min > 0.05) than pre-NAC (max < 0.03). The three post-NAC classifiers demonstrated AUCs of approximately 0.9, indicating excellent discrimination. DCA curves revealed a substantial net benefit when the threshold probability exceeded 40%. Conversely, the three pre-NAC classifiers had AUCs between 0.7 and 0.8, suggesting moderate discrimination and limited clinical utility based on their DCA curves.Conclusion: The ABVS-based radiomics model effectively predicted suboptimal NAC responses in BC patients, with early post-NAC classifiers outperforming pre-NAC classifiers in discrimination and clinical utility. It could enhance personalized treatment and improve patient outcomes in BC management.Keywords: breast cancer, neoadjuvant chemotherapy, radiomics, automated breast volume scanner, prediction model, model validation comparison

Jihai Chen,1,2 Lijun Wei,2 Xiaoxia Zhu,2 Wenli Xu,2 Yuxin Zou,2 Xinyu Qi,2 Jia Fang,2 Xiaodong Wang,2 Xiaolan Shi,1 Yunlu Sheng,2 Guoxian Ding,2 Xiaojun Ouyang,1 Yu Duan2 1Department of Geriatric, Geriatric Hospital of Nanjing Medical University, Nanjing, 210024, People’s Republic of China; 2Department of Geriatric Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People’s Republic of ChinaCorrespondence: Yu Duan, Department of Geriatric Endocrinology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People’s Republic of China, Email duanyujsph@163.com Xiaojun Ouyang, Department of Geriatric, Geriatric Hospital of Nanjing Medical University, Luojia Road 30, Nanjing, 210024, People’s Republic of China, Email xiaojun_ouyang@aliyun.comBackground and Aims: Sarcopenia is a common disease in the elderly, and the thyroid hormone (TH) might participate in the pathogenesis of sarcopenia. However, the results of previous studies were not completely consistent. We performed this study to investigate the association between THs and sarcopenia in a Chinese elderly euthyroid population.Subjects and Methods: A total of 309 Chinese elderly euthyroid subjects with an average age of 85.19 ± 7.8 years were enrolled. Participants were divided into four groups (non-sarcopenia, possible sarcopenia, sarcopenia and serve sarcopenia) according to the consensus update of AWGS in 2019. Serum levels of TT3, FT3, TT4, FT4, TSH, rT3 and TBG were measured. Muscle mass was measured by multifrequency bioelectrical impedance analysis, hand grip (HG) was represented by spring-type dynamometer, and gait speed (GS) was determined by 6-metre walk test. The FRAIL scale was used to assess frailty.Results: Compared to the non-sarcopenia group, the sarcopenia group showed a significant increase in age and FRIAL score, while FT3 and TT3 levels decreased significantly. Partial correlation analysis (adjusted by age, gender and the scores of FRIAL scale) indicated that FT3, TT3 and TSH had significant positive correlations with HG, and there also was a significant positive correlation between TT3 and GS. In addition, after adjusting for age, gender, BMI, ALT, sCr, and score on the FRAIL scale, the multivariate linear regression analysis showed that TT3 was positively associated with muscle strength and negatively associated with sarcopenia risk.Conclusion: There is an association between the low TT3 level and sarcopenia. Therefore, maintaining higher T3 concentrations within the normal range appears to be beneficial for sarcopenia in the elderly. In addition, due to the fluctuation of FT3, TT3 is a more stable and practical indicator to evaluate the relationship between sarcopenia and thyroid hormone in the elderly euthyroid population.Graphical Abstract: Keywords: sarcopenia, thyroid hormone, elderly, muscle strength

Xinnan Xu,1 Yu Zheng,1,2 Minjian Jiang,1,2 Hantong Hu,1,2 Xiaofen He,1,2 Jianqiao Fang,1,2 Yongliang Jiang1,2 1The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou City, Zhejiang Province, People’s Republic of China; 2Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Hangzhou City, Zhejiang Province, People’s Republic of ChinaCorrespondence: Jianqiao Fang; Yongliang Jiang, Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical University, 548 Binwen Road, Binjiang District, Hangzhou, Zhejiang Province, People’s Republic of China, Email fangjianqiao7532@163.com; jyl2182@126.comObjective: Currently, acupuncture for shoulder pain has been widely used in clinical and scientific research worldwide, but the bibliometric literature on acupuncture for shoulder pain is still scarce. This study reviews the application of acupuncture in the treatment of shoulder pain over the past 15 years, to analyze the current state of research, research hotspots, and trends. The article can also provide a reference for future research.Methods: This paper searches the core collection of the Web of Science database for publications related to acupuncture therapy for shoulder pain between 2008 and 2022. And the data were visualized and analyzed using VOSviewer and CiteSpace for annual publications, countries, institutions, journals and co-cited journals, authors and co-cited authors, keywords, and emergent keywords.Results: A total of 135 papers were included, with an overall increasing trend in the number of annual publications. The country with the highest centrality in publishing articles is the United States (0.28). In terms of research institutions, Kyung Hee University has the highest number of publications (18). In terms of authors, Lewith George, Lind Klaus, MacPherson Hugh, Sherman Karen J, and Vickers Andrew J are the five most published authors. Vickers, Andrew J. is the most co-cited author (50 times). In terms of journals, PAIN has the highest number of publications (82) and co-cited frequency (232), while the highest impact factor was BMJ-BRIT MED J (96.216). “Acupuncture” was the most frequently mentioned keyword (65 times), with the keyword “protocol” appearing the most recently. Emerging keywords that are still in vogue are “stroke”, “systematic review” and “stimulation”.Conclusion: This study provides statistics on current research on the treatment of shoulder pain with acupuncture, which may be able to inform future research directions for all researchers and physicians, as well as facilitate closer communication and collaboration.Keywords: shoulder pain, acupuncture, bibliometric analysis, VOSviewer, CiteSpace

Ning Luo,1,&ast; Rongrong Li,2,&ast; Baitian Fu,1 Yichen Zeng,1 Jianqiao Fang1,2 1The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou City, Zhejiang Province, People’s Republic of China; 2Department of Acupuncture and Moxibustion, Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou City, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianqiao Fang, The Third Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou City, Zhejiang Province, People’s Republic of China, Email fangjianqiao7532@163.comBackground: Evidence has shown that dry needling (DN) is effective for myofascial pain syndrome (MPS). However, bibliometrics has rarely been used to analyze the literature related to DN for MPS. The purpose of this study is to provide a systematic overview of global frontiers and research hotspots of DN in the treatment of MPS from 2000 to 2022.Methods: A search was conducted on Web of Science Core Collection (WoS CC) for literature on DN for MPS from 2000 to 2022. Based on the basic information provided by WoS CC, CiteSpace software was used to conduct bibliometric analysis of the countries, institutions, categories, journals, authors, references and keywords involved in this topic.Results: A total of 458 papers were obtained, with the number of publications increasing over time. Journal of Bodywork and Movement Therapies (31) was the most productive journal based on the number of publications, while Arch Phys Med Rehab (329) was the most co-cited journal. The most productive countries and institutions were USA (112) and Universidad Rey Juan Carlos (39), respectively. Fernandez-de-las-penas, Cesar has the highest number of publications (24) and Simons DG, who was an author with the highest number of citations (250). The article published by Gattie et al (co-citations: 65), and Mejuto-Vazquez et al (centrality: 0.36) were the most representative and symbolic. Based on the co-cited literature and keywords, myofascial trigger point, research methods, and acupuncture were the hot research topics and trends in the field.Conclusion: The current status and trends in clinical research of DN for MPS are revealed according to the results of this bibliometric study, which may facilitate researchers to identify hot topics and new directions for future research.Keywords: dry needling, myofascial pain syndrome, bibliometric analysis, research trends, hotspots

Hao Wang,1 Jun Guo,1 Yujie Zhang,2 Jin Fang,2 Shaobo Qiu,3 Yanwei He,4 Lijie Fan,4 Xulu Lei2 1Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Department of Preventive Care Center, Beijing Fengtai Hospital of Integrated Chinese and Western Medicine, Beijing, People’s Republic of China; 3Department of Neurology, Beijing Fengtai Hospital of Integrated Chinese and Western Medicine, Beijing, People’s Republic of China; 4Department of Functional Section, Beijing Fengtai Hospital of Integrated Chinese and Western Medicine, Beijing, People’s Republic of ChinaCorrespondence: Xulu Lei, Department of Preventive Care Center, Beijing Fengtai Hospital of Integrated Chinese and Western Medicine, Beijing, People’s Republic of China, Email lxl2524@126.comBackground: In China, acupuncture has been widely used in treating cerebrovascular diseases since time immemorial. Scalp acupuncture using the long-stay method is a traditional acupuncture treatment. However, previous studies have concluded that the clinical efficacy of scalp acupuncture for the treatment of stroke remains uncertain. In addition, no randomized controlled trials have been conducted on scalp acupuncture using the long-stay method. This study aimed to evaluate the efficacy and safety of the long-stay method of scalp acupuncture for limb movement dysfunction in patients after acute ischemic stroke (AIS).Methods: Seventy-two patients with acute strokes were randomly divided into treatment and control groups. The control group received conventional acupuncture with a half-hour needle stay each time, whereas the treatment group underwent scalp needling using a long retention method, with each retention of needles lasting 24 hours. Both groups received acupuncture treatment for 2 weeks and were followed up for 6 months. Cerebrovascular reserve (CVR), breath-holding index (BHI), pulsatility index (PI), Fugl–Meyer, and Barthel index (BI) were assessed at baseline, week 1, week 2, and during follow-up.Results: Compared with the baseline, both groups showed a significant improvement in CVR, Fugl–Meyer, BI, PI, and BHI (P < 0.05). Compared with the control group, the treatment group showed more significant improvements in Fugl–Meyer scores, BI, CVR, PI, and BHI (P < 0.05). Correlation analysis showed that Fugl–Meyer and BI scores increased significantly with CVR recovery over the course of treatment.Conclusion: Scalp acupuncture with the long-stay method can improve neurological deficits and the ability to perform daily activities among AIS patients, which may be related to the improvement of CVR function in patients.Keywords: scalp acupuncture, stroke, motor dysfunction, cerebrovascular reserve

Shuai Gao,1,&ast; Yuanjie Sun,1,&ast; Hangyu Shi,1,2 Jiufei Fang,1 Zhishun Liu1 1Department of Acupuncture, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Graduate School, Beijing University of Chinese Medicine, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhishun Liu, Department of Acupuncture, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, No. 5 Beixiange Street, Xicheng District, Beijing, People’s Republic of China, Email zhishunjournal@163.comPurpose: Cyclic mastalgia is prevalent among women and negatively impairs their daily life and work. There is still a lack of effective therapies for mastalgia, and acupuncture may be a promising method. We design this multicenter randomized trial to evaluate the efficacy and safety of acupuncture on cyclic mastalgia.Study Design and methods: Sixty participants with moderate-to-severe cyclic breast pain (with a duration of 5– 21 days and the worst pain scoring 5 points or more on Numerical Rating Scale [NRS]) will be recruited at three hospitals in China. They will be randomly assigned to acupuncture group or sham-acupuncture group at 1:1 ratio to receive 16-session treatment during 3 consecutive menstrual cycles, and follow-up for 6 menstrual cycles after treatment. The primary outcome is the change from baseline in the NRS score on the worst breast pain during the third cycle of treatment period. All statistical tests will be two-sided and P value < 0.05 will be considered statistically significant.Keywords: cyclic breast pain, complementary and alternative medicine, RCT, sham acupuncture

Mingqi Tu,1,&ast; Sangsang Xiong,1,&ast; Shengxia Lv,2,&ast; Xiaoting Wu,1 Hantong Hu,3 Renjie Hu,4 Jianqiao Fang,1 Xiaomei Shao1 1Key Laboratory for Research ofAcupuncture Treatment and Transformation of Emotional Diseases, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2The School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 4The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaomei Shao, Key Laboratory for Research of Acupuncture Treatment and Transformation of Emotional Diseases, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, The Third Clinical Medical College, Zhejiang Chinese Medical University, No. 548, Binwen Road, Binjiang District, Hangzhou, Zhejiang Province, People’s Republic of China, Tel +86 189 5713 0287, Email 13185097375@163.comIntroduction: Acupuncture has a long history of treating major depressive disorder (MDD), yet the acupoint selection of acupuncture for MDD varies greatly. This study aimed to explore the characteristics and principles of acupuncture for MDD by analyzing clinical trials of acupuncture for MDD using data mining techniques.Methods: In this study, clinical trials of acupuncture for MDD were retrieved and relevant data were extracted, and then the data were analyzed by data mining techniques. In addition, association rule mining, network analysis and hierarchical cluster analysis were used to determine the correlation between different acupoints.Results: The results revealed that GV20, LR3, PC6, SP6 and GV29 were used most frequently; acupoints in the Yang meridian were used more often than those in the Yin meridian, with the most applied acupoints in the Governor Vessel; the percentage of specific acupoints applied was 69.39%, with the most applied being five-shu points; the frequency of acupoints used was highest in the lower limbs, while the head, face, and neck had the most acupoints used; GV29 combined with GV20 were the most used acupoint groups; the core acupoints used for MDD were GV20, PC6 and SP36; there were 5 acupoint groups according to the cluster analysis. The most used acupuncture method was manual acupuncture; the frequency of treatment was mostly 7 times per week and the duration of treatment was mostly 42 days.Discussion: We discussed the current character of acupuncture treatment on MDD, including the frequency used of acupoints, the property of used acupoints, the acupoint combination, the acupuncture method, and the frequency and duration of treatment. These findings may provide new ideas for the clinical treatment of MDD. However, further clinical/experimental studies are needed to demonstrate the significance of this concept and approach.Keywords: acupuncture treatment, data mining technology, association rule mining, network analysis, cluster analysis

Yan Lin,1,&ast; Jiaoning Fang,1,&ast; Ruilan Ni,1,&ast; Li Zhang,1 Jie Zhao,1 Xiumin Jiang,2 Yuping Lin,2 Mian Pan1 1Department of Obstetrics, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China; 2Department of Nurse, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mian Pan, Department of Obstetrics, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, 18 Daoshan Road, Fuzhou, Fujian, 350001, People’s Republic of China, Tel +86-13178031273 ; +86-591-86329321, Email panmian1973@126.com Xiumin Jiang, Department of Nurse, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, 18 Daoshan Road, Fuzhou, Fujian, 350001, People’s Republic of China, Email jzc0427@163.comObjective: Cervical cerclage is an effective method to prevent preterm birth. However, the clinical indicators that can predict cervical cerclage remain limited. This study aimed to explore whether dynamically inflammatory markers are valuable biomarkers for the prognosis of cervical cerclage.Methods: This study included 328 participants. Inflammatory markers were calculated using maternal peripheral blood before and after the cervical cerclage procedure. The Chi-square test, linear regression, and logistic regression were performed to evaluate the dynamic change of inflammatory markers with the prognosis of cervical cerclage. And the optimal cut-off values of inflammatory markers were calculated.Results: Totally 328 pregnant women were analyzed in the study. 223 (67.99%) participants obtained successful cervical cerclage. This study revealed that the maternal age, the baseline BMI (cm2/kg), the times of gravida, the rate of recurrent abortion, the PPROM, cervical length shorter (< 1.5cm), cervical dilation (≥ 2cm), the bulging membrane, the Pre-SII, the Pre-SIRI, the Post-SII, the Post-SIRI, and the ΔSII were significantly associated with outcomes after cervical cerclage (all P< 0.05). Pre-SII, Pre-SIRI, Post-SII, Post-SIRI, and ΔSII levels were mainly related to maternal-neonatal outcomes. Furthermore, the results demonstrated that the ΔSII level had the highest OR (OR=14.560; 95% CI (4.461– 47.518)). In addition, we revealed that Post-SII and ΔSII levels had the highest AUC (0.845/0.840) and relatively higher sensitivity/specificity (68.57/92.83% and 71.43/90.58%) and PPV/ NPV (81.82/86.25% and 78.13/87.07%) compared with other indicators.Conclusion: This study suggested that the dynamic change of SII level and SIRI level are important biochemical markers to predict the prognosis of cervical cerclage and maternal-neonatal prognosis, especially the Post-SII and ΔSII levels. They can help to determine candidates for cervical cerclage before surgical procedure and enhance postoperative surveillance.Keywords: cervical cerclage, maternal-neonatal, outcome, inflammatory markers, peripheral blood

Zhiru Xiu,1 Yiquan Li,1 Jinbo Fang,1 Jicheng Han,1 Shanzhi Li,1 Yaru Li,1,2 Xia Yang,1 Gaojie Song,3 Yue Li,1 Ningyi Jin,1,4,5 Yilong Zhu,1 Guangze Zhu,1 Lili Sun,6 Xiao Li1,4,7 1Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 2Medical College, Yanbian University, Yanji, People’s Republic of China; 3Medical College, Jiujiang· University, Jiujiang, People’s Republic of China; 4Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, People’s Republic of China; 5Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, People’s Republic of China; 6Department of Head and Neck Surgery, Tumor Hospital of Jilin Province, Changchun, People’s Republic of China; 7College of Life Sciences, Shandong Normal University, Jinan, People’s Republic of ChinaCorrespondence: Lili Sun; Xiao Li, Boshuo Road, 1035, Jingyue Economic & Technological Development Zone, Changchun, Jilin, 130122, People’s Republic of China, Tel +86-431-86985923, Fax +86-431-87985861, Email skylee6226@163.com; linjiaxiaoya@163.comObjective: To explore the effects of Esculetin on liver cancer and explore potential mechanisms of Esculetin-inducing cells death.Methods: Esculetin’s effects on the proliferation, migration and apoptosis of HUH7 and HCCLM3 cells were detected by using CCK8, crystal violet staining, wound healing, TranswellTM and Annexin V-FITC/PI. Flow cytometry, fluorescence staining, Western blot, T-AOC, DPPH radical scavenging assay, hydroxyl radical’s inhibitory capability and GSH test were used to examine the esculetin’s effects on the ROS level, the oxidation-related substances and proteins’ expression in hepatoma cells. In vivo experiment was performed by xenograft model. Ferrostatin-1 was used to determine the death way of hepatoma cells induced by esculetin. Live cell probe, Western blot, Fe2+ content, MDA, HE staining, Prussian blue staining and immunohistochemistry were used to examine the ferritinophagy-related phenomenon induced by esculetin in hepatoma cells. The relationship between esculetin and NCOA4-mediated ferritinophagy was confirmed through gene silence and overexpression, immunofluorescence staining and Western blot.Results: Esculetin suppressed the proliferation, migration and apoptosis of HUH7 and HCCLM3 cells significantly, influenced the oxidative stress level, altered the autophagy and iron metabolism levels in cells, and produced a ferritinophagy-related phenomena. Esculetin increased the levels of cellular lipid peroxidation and reactive oxygen species. In vivo, esculetin could decrease tumour volume, promote LC3 and NCOA4 expressions, suppresse hydroxyl radical‘s inhibiting capacity and GSH, increase Fe2+ and MDA levels, decrease antioxidant proteins expression in tumour tissue. In addition, Esculetin could also increase the iron deposition of tumour tissues, promote ferritinophagy, and induce tumours’ ferroptosis.Conclusion: Esculetin has an inhibitory effect on liver cancer in vivo and in vitro through triggering NCOA4 pathway-mediation ferritinophagy.Keywords: esculetin, ferritinophagy, liver cancer, anti-tumour, NCOA4

Qi Zhang,1,&ast; Wenjuan Yan,1,&ast; Yingjie Zhu,2,&ast; Nan Jing,1 Shanmei Wang,1 Youhua Yuan,1 Bing Ma,1 Junhong Xu,1 Yafei Chu,1 Jiangfeng Zhang,1 Qiong Ma,1 Baoya Wang,1 Wenbo Xu,1 Liqiang Zhu,3 Ying Sun,2 Caiqin Shi,4 Juan Fang,5 Yi Li,1 Shengqun Liu6 1Department of Clinical Microbiology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, and People’s Hospital of Henan University, Zhengzhou, People’s Republic of China; 2Department of Clinical Microbiology, Henan No.3 Provincial People’s Hospital, Zhengzhou, People’s Republic of China; 3Department of Clinical Microbiology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 4Department of Microbiology Laboratory, KingMed Diagnostics Group Co., Ltd, Zhengzhou, People’s Republic of China; 5Department of Research and Development, Autobio Diagnostics Co., Ltd, Zhengzhou, People’s Republic of China; 6Department of Anesthesia and Perioperative Medicine, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, and People’s Hospital of Henan University, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Li; Shengqun Liu, Department of Anesthesia and Perioperative Medicine, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, and People’s Hospital of Henan University, Weiwu Road 7, Zhengzhou, Henan, 450003, People’s Republic of China, Tel +8613526882118, Fax +8637187160318, Email liyilabmed@henu.edu.cn; tim2002627@163.comPurpose: To evaluate the performance of five widespread commercial products for colistin and polymyxin B susceptibility testing in China for mcr-positive and -negative Escherichia coli and Klebsiella pneumoniae.Methods: A total of 132 E. coli and 83 K. pneumoniae strains (including 68 mcr-1-positive E. coli and 28 mcr-8-positive K. pneumoniae) were collected. We analysed the performance of colistin susceptibility (with Vitek 2 and Phoenix M50) and the performance of polymyxin B susceptibility (with DL-96II, MA120, and a Polymyxin B Susceptibility Test strip; POL E-strip). Broth microdilution was used as the gold standard. Categorical agreement (CA), essential agreement (EA), major error (ME), and very major error (VME) were calculated for comparisons.Results: For E. coli, the total CA, EA, ME, and VME to colistin were as follows: Vitek 2, 98.5%/98.5%/0%/2.9%; and Phoenix M50, 98.5%/97.7%/0%/2.9%. The total CA, EA, ME, and VME to polymyxin B were as follows: POL E-strip, 99.2%/63.6%/1.6%/0%; MA120, 70.0%/-/0%/58.8%; and DL-96II, 80.2%/-/1.6%/36.8%. Only Vitek 2 and Phoenix M50 presented satisfactory performances for mcr-1-positive E. coli. For K. pneumoniae, the total CA, EA, ME, and VME to colistin were as follows: Vitek 2, 73.2%/72.0%/0%/61.6%; and Phoenix M50, 74.7%/74.7%/0%/58.3%. The total CA, EA, ME, and VME to polymyxin B were as follows: POL E-strip, 91.6%/74.7%/2.1%/16.7%; MA120, 92.8%/-/2.1%/13.9%; and DL-96II, 92.2%/-/2.1%/8.3%. All systems were unsatisfactory for mcr-8-positive K. pneumoniae. When the susceptibility of mcr-negative strains was tested, all systems presented excellent performance.Conclusion: Vitek 2 and Phoenix M50 with colistin for E. coli showed acceptable performance regardless of mcr-1 expression, while DL-96II, MA120, and the POL E-strip performed worse for mcr-1-positive strains. Furthermore, mcr-8 greatly affected the performance of all systems with both colistin and polymyxin B for K. pneumoniae isolates.Keywords: polymyxin B, colistin, mobilised colistin resistance, broth microdilution, susceptibility testing, semi-automated systems

Jiaoning Fang,1,&ast; Yingying Lin,2,&ast; Zhiwei Chen,3,&ast; Yan Lin,1 Mian Pan1 1Department of Obstetrics, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China; 2Department of Healthcare, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China; 3Department of Gynecologic, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mian Pan; Yan Lin, Department of Obstetrics, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Medical University, Fuzhou, People’s Republic of China, Tel +86-13178031273 ; +86-591-86329321 ; +86-13665051036, Email panmian1973@126.com; 571313649@qq.comObjective: Cervical cerclage is effective in prolonging the number of weeks gestation in patients with cervical insufficiency(CI). However, valuable predictors with successful cervical cerclage remain limited. It aimed to evaluate the value of the systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) to predict the outcomes of cervical cerclage.Methods: This study analyzed 374 participants. Inflammatory markers were calculated using maternal peripheral blood. The association of inflammatory markers and the outcome of cervical cerclage were analyzed. And the optimal cut-off values of inflammatory markers were calculated. Also, the Chi-square test and logistic and linear regression analyses were performed to evaluate inflammatory markers with the maternal outcome and neonatal outcomes.Results: 374 pregnancies were included in this study. Finally, 268 (71.7%) participants suffered successful cervical cerclage. This study demonstrated that the baseline BMI (cm2/kg), the bulging membrane, cervical dilation (≥ 2cm), the amniotic sac herniation, the neutrophils counts, the systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) were significant difference between the successful and unsuccessful groups (all P< 0.05). Additionally, maternal blood inflammatory markers, such as WBC, lymphocyte, neutrophils, monocyte, platelet counts, SII, and SIRI, were significantly associated with maternal-neonatal outcomes. Furthermore, the results demonstrated that the SII level had the highest OR (OR=4.626; 95% CI (2.500– 8.560)), as well as the following: SIRI level (OR = 3.795; 95% CI (1.989– 7.242)), cervical dilation (≥ 2cm) (OR =3.477; 95% CI (1.458– 10.844)), and amniotic sac herniation (OR = 1.796; 95% (0.473– 4.975)).Conclusion: This study demonstrated that the baseline SII level and SIRI level are important biochemical markers for predicting the outcome of cervical cerclage and maternal-neonatal outcomes with non-invasive procedures. They can help to provide personalized treatment before surgery and enhance postoperative surveillance.Keywords: cervical cerclage, maternal-neonatal, outcome, inflammatory markers, peripheral blood

Yuansheng Xu, Yi Wang, Jinhong Wu, Xue Zhao, Ganying Huang, Jinyan Fang Department of Emergency, Affiliated Hangzhou First People`s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Jinyan Fang, Department of Emergency, Affiliated Hangzhou First People`s Hospital, Zhejiang University School of Medicine, No. 261 Huansha Road, Hangzhou, Zhejiang Province, 310006, People’s Republic of China, Email fjy830818@126.comAbstract: Pulmonary aspergillosis is generally categorized into three groups: allergic bronchopulmonary aspergillosis, chronic pulmonary aspergillosis and invasive pulmonary aspergillosis. Aspergillus overlap syndromes (AOS) defined as the occurrence of more than one form of aspergillus disease in a single individual is not common. We present a 62-year-old-male patient with tachypnea, hypoxemia and shock after 4 weeks of cough, expectoration and intermittent hemoptysis, and 2 days of hyperpyrexia. Cardiac arrest occurring during tracheal intubation was resuscitated successfully. Laboratory examination showed acute kidney failure and severe myelosuppression with leukopenia and thrombocytopenia. Chest computed tomography (CT) scan showed the cavity with aspergilloma in the right upper lung lobe, a mass of consolidation in the right lower lung lobe and hyperdense shadow bronchiectasis in the left lower lobe. Bronchoscopy showed lots of sputum occluding the opening of the right airway bronchus. Laboratory examination showed significantly increased C-reactive protein (CRP) and procalcitonin concentration, serum (1,3)-β-D-glucan (BDG) and aspergillus immunoglobulin G (IgG) levels were also elevated. The metagenomic next-generation sequencing and sputum cultures revealed Klebsiella pneumoniae and Aspergillus flavus infection. Pulmonary aspergillosis, invasive aspergillosis infection and severe pneumonia were diagnosed. Initial caspofungin and meropenem followed by piperacillin-tazobactam sodium and voriconazole were administrated in combination. Continuous renal replacement therapy and mechanical ventilation were also performed. The patient’s condition gradually recovered. Oral antifungal therapy was continued for 1 year after discharge and CT images gradually improved. Coinfections with K. pneumoniae and A. flavus in a patient with AOS will complicate clinical conditions. A search of PubMed showed few reports of similar cases. Clinicians should pay enough attention to the polymicrobial interactions and improve clinical management strategies, especially in critically ill patient with AOS.Keywords: coinfection, Aspergillus overlap syndromes, Klebsiella pneumoniae, Aspergillus flavus, metagenomic next-generation sequencing

Jingya Li,1,2,&ast; Junqun Fang,3,&ast; Jiayou Luo,1 Yamei Duan,1 Xiang Xiao,1 Yamei Li,4 Miyang Luo5 1Department of Women and Children Health, Xiangya School of Public Health, Central South University, Changsha, People’s Republic of China; 2Department of Social Medicine and Health Management, Xiangya School of Public Health, Central South University, Changsha, People’s Republic of China; 3Department of Child Health Care, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, People’s Republic of China; 4Department of Women Health Care, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, People’s Republic of China; 5Department of Epidemiology and Biostatistics, Xiangya School of Public Health, Central South University, Changsha, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Miyang Luo, Department of Epidemiology and Biostatistics, Xiangya School of Public Health, Central South University, No. 238 Shang Ma Yuan Ling Road, Changsha, 410078, People’s Republic of China, Tel +86 731-84805465, Email miyangluo@csu.edu.cnPurpose: Anemia is a worldwide common condition during pregnancy, conferring a number of health risks to mothers. However, very little is known about the association between severity of anemia and severe maternal outcomes. This study aimed to assess the association between severity of anemia during pregnancy and the risk of severe maternal outcomes.Patients and Methods: This retrospective cohort study was based on data from China’s National Maternal Near Miss Surveillance System for the period 2017– 2018, which included 18 hospitals in southern China. Pregnant women admitted for delivery were divided into 4 groups based on severity of anemia during pregnancy: no anemia, mild anemia, moderate anemia, and severe anemia groups. Severe maternal outcomes were a composite of life-threatening conditions (ie, organ dysfunction) as defined by the WHO criteria, occurring at any time after admission until discharge or death. Modified Poisson regression analyses and propensity score-weighted regression analyses were used to estimate the relative risks (RRs) and 95% confidence intervals (CIs) of severe maternal outcomes among women with anemia of varying severity during pregnancy.Results: The incidence of severe maternal outcomes was 0.3% (417/138,556) in total, and the rates were 0.1% (85/99,755), 0.2% (30/18,502), 1.2% (234/19,697) and 11.3% (68/602) in no anemia, mild anemia, moderate anemia and severe anemia group, respectively. Compared with no anemia, the adjusted RR for severe maternal outcomes was 4.19 (95% CI, 3.20– 5.50) in moderate anemia group and 22.12 (95% CI, 15.43– 31.69) in severe anemia group; the weighted RR was 1.01 (95% CI, 1.01– 1.01) in moderate anemia group and 1.11 (95% CI, 1.07– 1.14) in severe anemia group.Conclusion: Moderate to severe anemia during pregnancy was independently associated with an increased risk of severe maternal outcomes. Maternal health care providers and pregnant women themselves should give more attention to the prevention and treatment of anemia during pregnancy, especially moderate to severe anemia.Keywords: anemia, severity, severe maternal outcome, retrospective cohort, propensity score weighting

Jinling Fang,&ast; Rifeng Chen,&ast; Donghua Liu&ast; Department of Dermatology, the First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Donghua Liu, Department of Dermatology, the First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Qingxiu District, Nanning, Guangxi Province, 530021, People’s Republic of China, Tel +86-13877113417, Email ldhgxmu@163.comBackground: Talaromyces marneffei (T. marneffei) is a thermally dimorphic fungus endemic to Southeast Asia that causes human systemic infection. Our earlier immunohistochemical studies revealed that the organisms were markedly labeled with the CD86 antigen in cutaneous lesions brought on by infection. However, the relationship between T. marneffei and the CD86 co-stimulatory molecule is still unknown.Objective: To explore the association between CD86 Protein and Talaromyces marneffei organisms in vitro and discuss the potential mechanisms.Methods: We created the CD86-EGFP fusion protein in THP-1 macrophages and co-cultured T. marneffei conidia with it. We used confocal fluorescence microscopy to view in vitro dynamics. The link between CD86 Protein and Talaromyces marneffei organisms in vitro was discovered using immunoelectron microscopy, indirect immunofluorescence test, and immunohistochemistry assay.Results: T. marneffei cells received soluble CD86-EGFP from THP-1 macrophages detected by confocal fluorescent microscopy. Both the indirect immunofluorescence assay and the immunohistochemical assay showed that T. marneffei conidia were stained by the CD86 marker. Immunoelectron microscopy showed that characteristic colloidal gold particles were observed in T. marneffei organisms when co-cultured with THP-1 macrophages.Conclusion: T. marneffei organisms have the ability to capture CD86 proteins from macrophages in vitro.Keywords: Talaromyces marneffei, macrophage, CD86, confocal microscopy, immunoelectron microscopy, immunohistochemistry

Caixia Fan,1,2 Li Gong,2 Mo An,3 Zhenglin Li,4 Xiang Li,2 Jinzhi Fang5 1Office of Drug Clinical Trials Institution, Affiliated Longhua People’s Hospital, Southern Medical University (Longhua People’s Hospital), Shenzhen, Guangdong, People’s Republic of China; 2Department of Pharmacy, Affiliated Longhua People’s Hospital, Southern Medical University (Longhua People’s Hospital), Shenzhen, Guangdong, People’s Republic of China; 3Neurosurgery Department, Affiliated Longhua People’s Hospital, Southern Medical University (Longhua People’s Hospital), Shenzhen, Guangdong, People’s Republic of China; 4Department of Pharmacy, Shenzhen Boai Shuguang Hospital, Shenzhen, Guangdong, People’s Republic of China; 5Department of Medical Imaging, Affiliated Longhua People’s Hospital, Southern Medical University (Longhua People’s Hospital), Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Caixia Fan, Office of Drug Clinical Trials Institution, Affiliated Longhua People’s Hospital, Southern Medical University (Longhua People’s Hospital), Shenzhen, Guangdong, 518109, People’s Republic of China, Tel +86-18824242858, Fax +86-75529407559, Email mydream0509@qq.comObjective: To explore the perioperative prophylactic medication, identification of Causative pathogen and the treatment strategy of post-craniotomy intracranial infection (PCII) caused by Corynebacterium.Patients and Methods: A 47-year-old overweight male patient with hypertension, diabetes, cerebral hemorrhage and recalcitrant syphilis was clinically diagnosed with PCII based on cerebrospinal fluid (CSF) routine examination (RT), biochemical test (BT), neuroimaging CT and MRI scans, bacterial culture and identification of CSF and clinical manifestations. The risk factors of PCII and perioperative antibiotic prophylaxis were analyzed based on some reviews. The identification of the Corynebacterium Jeikeium (C. Jeikeium) and Corynebacterium simulans (C. simulans) was confirmed by CSF bacterial culture, antibiotics sensitivity in vitro and Metagenomic next-generation sequencing (mNGS) of pathogenic microorganisms, respectively. In addition, individualized therapy schemes were modified according to antimicrobial susceptibility of pathogens and mNGS of pathogenic microorganisms combined with the pathologic and physiological conditions of patients. The efficacy was evaluated depending on the changes in patients’ body temperature, clinical manifestation, CSF RT, BT, and other infection-related indicators.Results: The patient recovered after 5 weeks of individualized comprehensive treatment and was discharged home, no recurrence had been observed for three months.Conclusion: This is likely the first reported case of chronic PCII caused by two species of Corynebacterium simultaneously in high risk patient. The PCII can not be prevented by the perioperative antibiotic prophylaxis recommended by the guidelines, prophylaxis need to be individualized based on the risk of infection and the colonization status of the patient. Causative pathogens can be identified by CSF culture and mNGS of pathogenic microorganisms. A judicious antimicrobial therapy plan should take into account not only the in vitro antimicrobial susceptibility, but also the penetration of the antimicrobial agent into the cerebrospinal fluid. It was an excellent choice to combine intrathecal vancomycin with intravenous linezolid to treat PCII resulted from Corynebacterium.Keywords: post-craniotomy intracranial infection, Corynebacterium jeikeiu, Corynebacterium simulans, perioperative antibiotic prophylaxis, identification of pathogenic bacteria, individual treatment schemes

Yongxin Yi,1 Jiayang Fang,1 Yunzhu Liu,1 Yidong Gao,1 Weizhi Lin,1 Dongdong Hao,2 Xing Zhang,3,4 Min Zhang1 1Department of Encephalopathy, the Third People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, People’s Republic of China; 2Department of Outpatient, Lanzhou 7th Rest Center for Retired Cadre, Gansu Military Region, Lanzhou, People’s Republic of China; 3Department of Medicine, the State Key Laboratory of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics Co., Ltd, Nanjing, People’s Republic of China; 4Department of Medicine, Nanjing Simcere Medical Laboratory Science Co., Ltd, Nanjing, People’s Republic of ChinaCorrespondence: Min Zhang, Department of Encephalopathy, the Third People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, People’s Republic of China, Email minzhang_2018@163.comIntroduction: There is no effective treatment plan for coronavirus disease 2019 (COVID-19). We employed a combination of Chinese and Western medicine treatment for some COVID-19 inpatients.Methods: This study was a prospective cohort study that observed non-critical COVID-19 inpatients. The differences will be observed in the time from admission to two consecutive 2019-nCoV nucleic acid test negatives and the Visual Analog Scale (VAS) score between the two groups.Results: A total of 254 confirmed COVID-19 patients were included in this study. The median time from the admission to two consecutive negative nucleic acid tests was 14 days for the integrated Chinese and Western Medicine (ICWM) group, while the Western Medicine (WM) group was 16 days. Besides, the median VAS score of the ICWM group was 0, which was an average decrease of 2 points compared to the time of admission.Conclusion: For non-critical COVID-19 patients, it was safe and have more benefits to add traditional Chinese medicine decoction based on WM treatment.Keywords: clinical characteristics, COVID-19 inpatients, efficacy, integrated Chinese and Western medicine treatment

Jiacheng Fang, Yuxuan Zhang, Delong Chen, Yiyue Zheng, Jun Jiang Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, People’s Republic of ChinaCorrespondence: Jun Jiang, Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou, Zhejiang, 310009, People’s Republic of China, Tel/Fax +86 135 8870 6891, Email jiang-jun@zju.edu.cnAbstract: Exosomes are a pluripotent group of extracellular nanovesicles secreted by all cells that mediate intercellular communications. The effective information within exosomes is primarily reflected in exosomal cargos, including proteins, lipids, DNAs, and non-coding RNAs (ncRNAs), the most intensively studied molecules. Cardiac resident cells (cardiomyocytes, fibroblasts, and endothelial cells) and foreign cells (infiltrated immune cells, cardiac progenitor cells, cardiosphere-derived cells, and mesenchymal stem cells) are involved in the progress of ventricular remodeling (VR) following myocardial infarction (MI) via transferring exosomes into target cells. Here, we summarize the pathological mechanisms of VR following MI, including cardiac myocyte hypertrophy, cardiac fibrosis, inflammation, pyroptosis, apoptosis, autophagy, angiogenesis, and metabolic disorders, and the roles of exosomal cargos in these processes, with a focus on proteins and ncRNAs. Continued research in this field reveals a novel diagnostic and therapeutic strategy for VR.Keywords: exosomes, ventricular remodeling, extracellular vesicles, heart failure, microRNAs, myocardial infarction

Jiali Wang1 &ast;, Fang Du1 &ast;, Yimei Ma,1 Yuncen Shi,1 Jie Fang,1 Jing Xv,1 Jing Cang,1 Changhong Miao,1 Xiaoguang Zhang1,2 1Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Anesthesiology, Jinshan Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoguang Zhang, Department of Anesthesiology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People’s Republic of China, Tel +86 13641995733, Fax +86 21-64041990, Email zhang.xiaoguang@zs-hosptial.sh.cnPurpose: Postoperative pain after open hepatectomy is significant. Preoperative coagulopathy limits the use of epidural analgesia, the gold standard for pain control in open abdominal surgery. Erector spinae plane block (ESPB) is a novel regional anesthesia technique that has been shown to provide effective analgesia in abdominal surgery. In this study, we compared the analgesic efficacy of patient-controlled continuous ESPB (CESPB) with hydromorphone patient-controlled intravenous analgesia (PCIA) after right subcostal incision hepatectomies in hepatocellular carcinoma patients with preoperative coagulopathy.Patients and Methods: In this randomized, controlled, unblinded, and noninferiority trial, 120 patients were randomized to receive either CESPB or PCIA as primary postoperative analgesia together with parecoxib (40mg Q12 h IV) for 3 days after surgery. The primary outcome was the average cough-elicited pain numeric rating scales (NRS) recorded at the seven follow-up time points of 20:00 on the day of surgery and 9:00 and 15:00 on the postoperative day 1 to day 3 (POD1 to POD3).Results: The average cough-elicited pain NRS score was 2.402 in the CESPB group and 2.676 in the PCIA group. The mean difference (95% CI) was − 0.274 (− 0.620 to 0.072), which demonstrated the noninferiority of CESPB to PCIA. Patients in the CESPB group had less intraoperative opioid consumption, a lower incidence of moderate-to-severe pain and PONV at POD3, and early resumption of oral intake.Conclusion: CESPB provides analgesic efficacy noninferior to opioid PCIA in the context of multimodal analgesia after right subcostal incision open hepatectomy.Keywords: acute pain, blood coagulation disorders, erector spinae plane block, hepatectomy, patient-controlled analgesia, ultrasonography

Anqi Lin,1,&ast; Jianbo Fang,1,&ast; Quan Cheng,2,3 Zaoqu Liu,4 Peng Luo,1 Jian Zhang1 1Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 3National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 4Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peng Luo; Jian Zhang, Department of Oncology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou, 510282, Guangdong, People’s Republic of China, Tel +86-18588447321 ; +86-13925091863, Email luopeng@smu.edu.cn; zhangjian@i.smu.edu.cnPurpose: The advent of immune checkpoint inhibitors (ICIs) is a revolutionary breakthrough. However, without the selection of a specific target population, the response rate of ICI therapy in lung adenocarcinoma (LUAD) is low, so a clinical challenge has arisen in effectively using biomarkers to determine which patients can benefit from ICI therapy.Methods: In this study, patients were divided according to whether or not nonsynonymous mutations were present in the BCR signaling pathway, and univariate and multivariate Cox regression models were established based on a LUAD cohort treated with ICIs (Miao-LUAD). Then the relationship between the mutation status of the BCR signaling pathway and the prognosis of immunotherapy was examined. Finally, data from The Cancer Genome Atlas (TCGA) LUAD cohort, the Rizvi-LUAD, the Samstein-LUAD, and the Zhujiang Hospital of Southern Medical University LUAD (Local-LUAD) cohort were combined, and the mutation panorama, immunogenicity, tumor microenvironment (TME) and pathway enrichment analysis between the BCR signaling pathway mutant group (BCR signaling MUT) and the BCR signaling pathway wild group (BCR signaling WT) were comprehensively compared.Results: It was found that, compared with the BCR signaling WT, the BCR signaling MUT had a significantly improved progression-free survival (PFS) rate and overall survival (OS) rate, higher immunogenicity (tumor mutational burden, neoantigen load, and DNA damage response signaling mutations), and anti-tumor immune microenvironment.Conclusion: These results revealed that the mutation state of the BCR signaling pathway has potential as a biomarker to predict the efficacy of ICIs in LUAD.Keywords: non-small cell lung cancer, B cell receptor, immune checkpoint inhibitor, biomarker, microenvironment

Chuanlong Zhou,1,&ast; Jie Bao,2,&ast; Hantong Hu,1 Siting Ye,3 Xiaomei Shao,4 Yi Liang,4 Jianqiao Fang4 1Department of Acupuncture, the Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3Department of Tuina, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 4Key Laboratory of Acupuncture and Neurology of Zhejiang Province, the Third Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chuanlong Zhou, Department of Acupuncture, the Third Affiliated Hospital of Zhejiang Chinese Medical University, No. 219 Moganshan Road, XiHu District, Hangzhou, 310005, People’s Republic of China, Email zhouchuanlong6255@163.comBackground: Migraine without aura (MWoA) is a nervous system disease, which is closely related to autonomic nerves dysfunction. As a popular non-pharmacological alternative treatment for preventing migraine, it remains unclear whether the acupuncture can prevent MWoA. Thus, this trial aims to evaluate the preventive effect and safety of the acupuncture method of stimulating acupoints that regulate autonomic nerves in MWoA patients.Methods: This is a single-center, prospective, double-dummy, randomized controlled clinical trial. A total of ninety-six patients with MWoA are randomly allocated to acupuncture combined with the placebo group and sham acupuncture combined with the medication group in a 1:1 ratio. All subjects will receive intervention for 8 weeks and follow-up assessments three times (one month, three months, and six months in follow-up visiting). The frequency of acupuncture in both groups is three times a week for eight weeks. The primary outcome will be evaluated using a visual analog scale (VAS) and the number of migraine attacks per four weeks. The secondary outcome measures will include the migraine-specific quality of life (MSQOL) scale and headache needs assessment survey (HANA) questionnaire scale.Results: The acupoint selection of this clinical trial is based on the combination of traditional Chinese medicine theory with modern medicine, thereby evaluating the efficacy and safety of the acupuncture method of stimulating acupoints that regulate autonomic nerves in the prevention of MWoA. The results may provide evidence of the beneficial effects of acupuncture on the prevention of MWoA by regulating autonomic nerves dysfunction.Trial Registration: ClinicalTrials.gov NCT04766762.Keywords: acupuncture, migraine without aura, autonomic nerves, randomized controlled clinical trial, protocol

Yunfan Xia,1 Ruohan Sun,1 Rongrong Li,1 Leilei Ren,1 Yiyi Wang,1 Jianqiao Fang2 1The Third Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou City, People’s Republic of China; 2The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou City, People’s Republic of ChinaCorrespondence: Jianqiao Fang, 23 Qingchun Road, Hangzhou City, People’s Republic of China, Tel +86(0)571-87238254, Fax +86(0)571-87238005, Email fangjianqiao7532@163.comBackground: Accumulate evidence indicated that moxibustion has a positive effect on pain treatment. However, the bibliometric analysis of moxibustion on pain remains uncertain. Herein, this study aimed to explore the current hotspots and the research trends over the past decade to bring a great panorama in this field.Methods: Publications were retrieved from the database Web of Science Core Collection (WoSCC) related to moxibustion therapy for pain treatment from January 1, 2012, to December 31, 2021. CiteSpace and Excel were applied to analyze the volume of publications, journals, cited journals, dual-map analysis, countries, institutes, authors, references, and keywords with citation bursts.Results: A total of 360 publications were retrieved from 2012 to 2021. The annual number of publications increased steadily with some fluctuations over the past 10 years. “The Evid Based Complement Alternat Med” and “the Gut” were the top-cited journals in frequency and centrality. China and Shanghai University of Traditional Chinese Medicine were the most prolific country and institutions, respectively. Among authors, Huangan Wu was the most active author with the highest cited frequency. Jun Xiong, Fanrong Liang and Guixing Xu held the articles with higher centrality. In the ranking of frequency and centrality in cited references, the top one was the article published by Shamseer L and Deng HY, respectively. “Acupuncture” was the keyword with the highest frequency. Pain disease (including rheumatoid arthritis, knee osteoarthritis, herpes zoster), research method (including randomized controlled trial), and risk (including quality of life, economic burden, physical and psychological problems) were the hotspots and frontier trends in this field.Conclusion: This bibliometric study reveals the current status and research trend in the treatment of pain with moxibustion. The formulation with bibliometric analysis further elicits hot spots and frontier issues in this field.Keywords: moxibustion, pain, CiteSpace, bibliometric analysis

Ziyuan Zhang,1,2 Yaling Hu,1,2 Wenyuan Liu,2 Xiaodong Zhang,2 Ruihua Wang,2 Hui Li,2 Dalin Sun,1,2 Jingai Fang2 1Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of Nephrology, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of ChinaCorrespondence: Jingai Fang, Department of Nephrology, First Hospital of Shanxi Medical University, 85 Jiefangnan Road, Taiyuan, 030001, People’s Republic of China, Email jingaifang2017003@126.comPurpose: To explore the mechanism of Yishen capsule against diabetic nephropathy (DN) based on the analysis of transcriptomics.Material and Methods: SD rats (Male, SPF grade) were randomly divided into four groups, the normal group, the DN group, the Yishen capsule group and the resveratrol group. Urine and renal tissue samples were collected after feeding with physiological saline and above drugs for 8 weeks. 24-hour urine microalbumin protein was detected by ELISA. HE staining and PAS staining were performed on renal tissues. Differential gene expression in renal tissues was analyzed by transcriptome sequencing. The differentially expressed genes were analyzed by GO enrichment and KEGG enrichment, and verified by RT-PCR and immunohistochemistry staining.Results: The level of 24-hour urinary microalbumin in DN group was increased, while Yishen capsule treatment reversed the increasement of urinary microalbumin. Mesangial cell proliferation, matrix accumulation, edema and vacuolar degeneration of renal tubular epithelial cells and glycogen accumulation were observed in DN group. However, pathological phenotypes mentioned above were alleviated after Yisen capsule administration. This result indicates that Yishen capsule reversed pathological phenotypes of DN in rats. The expression of 261 genes were changed in Yishen capsule group compared with DN group. GO enrichment analysis and KEGG pathway analysis showed that these genes were implicated in pathways, including mineral absorption, adipocytokine signaling pathway, fatty acid biosynthesis, thyroid hormone synthesis, renin–angiotensin system, and NOD-like receptor signaling pathway. Based on previous reported study, the expression of key factors in NOD-like receptor signaling pathway was verified. RT-PCR and immunohistochemistry staining showed that the expression of NLRP3, Caspase-1 and IL-1β in renal tissues of DN group were increased (P < 0.05), which were decreased in Yishen capsule group (P < 0.05).Conclusion: Yishen capsule reduced microalbuminuria and alleviated pathological changes in DN rats, which may be achieved by regulating NOD-like receptor signaling pathway.Keywords: Yishen capsule, diabetic nephropathy, transcriptome sequencing, NOD-like receptor signaling pathway

Yunyun Xu,1,&ast; Yangyun Chen,1,&ast; Yan Shi,2 Jianhua Lu,3 Zonglin Wu,1 Zhe Liu,1 Yuerong Chen,1 Wenqin Ni,1 Qike Ding,4 Wei Dai,4 Xinyuan Wu,4 Jianqiao Fang,1 Yuanyuan Wu5 1The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou City, Zhejiang Province, People’s Republic of China; 2Department of Acupuncture & Tuina, Hangzhou First People’s Hospital, Hang Zhou City, Zhejiang Province, People’s Republic of China; 3Department of Acupuncture & Moxibustion, Mishi Xiang Community Health Service Center, Hang Zhou City, Zhejiang Province, People’s Republic of China; 4The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou City, Zhejiang Province, People’s Republic of China; 5Department of Acupuncture & Moxibustion, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hang Zhou City, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanyuan Wu, Email runnaway@126.comObjective: The efficacy of conventional treatments for treating bladder pain syndrome (BPS) remains unsatisfactory. Electro-acupuncture (EA) is one of the complementary treatments with great analgesic effect and minimal side effect, but evidence of the efficacy of EA on BPS is limited. Thus, this study aims to investigate the efficacy and safety of EA for treating BPS and study on central mechanism of patients with BPS.Methods/Design: The study is a randomized controlled and assessor-blinded design trial. A total of 84 participants will be randomly assigned to medication group (n=21), EA group (n=42) and sham electro-acupuncture (SA) group (n=21) in a 1:2:1 allocation ratio. This trial will include baseline period, 4-week treatment period and 4-week follow-up period. Participants in medication group will undergo treatment of amitriptyline for a period of 4 weeks. Participants in EA and SA groups will receive a 30 min EA or SA treatment for a total of 12 sessions over 4 weeks. The primary outcome is the Visual Analog Scale (VAS). The secondary outcomes include the O’Leary-Sant questionnaire, 24-hour voiding diary, Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD) and functional magnetic resonance imaging (fMRI). The VAS will be collected at baseline, week 2, week 4, and week 8 after randomization. The O’Leary-Sant questionnaire, HAMA and HAMD will be assessed at baseline, week 4 and week 8 after randomization. The 24-hour voiding diary will be assessed every single day. The fMRI data will be collected at baseline and week 4.Discussion: The results will provide evidence on the efficacy and safety of EA in the management of BPS and investigate the central mechanism of EA in treating patients with BPS.Trial Registration: ClinicalTrials.gov identifier: NCT05279963. Registered on 15 March 2022.Keywords: electro-acupuncture, bladder pain syndrome, randomized controlled trial, functional magnetic resonance imaging

Ruohan Sun,1,2,&ast; Shimin Li,1,&ast; Leilei Ren,2 Yunfan Xia,2 Yiyi Wang,2 Zhiyuan Bian,2 Jianqiao Fang,2 Zuyong Zhang1 1Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Acupuncture, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zuyong Zhang, Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, No. 38 West Lake Road, Hangzhou, Zhejiang, People’s Republic of China, Email zzynwk@126.com Jianqiao Fang, The Third Affiliated Hospital of Zhejiang Chinese Medical University, No. 23 Qinchun Road, Hangzhou, Zhejiang, People’s Republic of China, Email fangjianqiao7532@163.comIntroduction: Postherpetic neuralgia (PHN) is a severe complication of herpes zoster (HZ), representing an important burden of disease in the elderly. Electroacupuncture (EA) has become growingly appreciated as a therapy of PHN with the situation that effectiveness of conventional therapy of PHN is less than ideal. Owing to its low price, no side effects, high safety and high patients acceptance, EA has been used in treating PHN more frequently. Therefore, the randomized controlled trial which is to evaluate the effectiveness and safety of EA in patients with PHN and whether EA could be an alternative therapy of medication is needed.Patients and Methods: A total of 88 patients with PHN will be recruited from 2 hospitals and randomized assigned to EA group or Medication group in a 1:1 ratio, utilizing a central randomization system. The trial will involve a 4-week treatment period, and a 4-week follow-up period. All variables will be evaluated at week 0 (baseline), week 2 (treatment), week 4 (treatment), week 8 (follow-up) and week 16 (follow-up). Primary outcomes will be pain intensity. Secondary outcomes will contain quality of life, mood state and sleep quality. All adverse effects will be assessed during the trial.Conclusion: This study will provide significant evidence that whether EA therapy is effective and safe for patients with PHN and whether EA could be an alternative therapy of medication.Ethics and Dissemination: Ethics approval has been obtained from the Ethics Committee of the Hangzhou Third People’s Hospital (No. 2021KAO43). Informed consent will be signed before enrolment. Results of this trial will be presented to international journals for publication and be reported in relevant international conferences.Trial Registration Number: This protocol has been registered in the Chinese Clinical Trial registry with the identification code ChiCTR2100054592.Keywords: postherpetic neuralgia, electroacupuncture, pain, randomized controlled trial, protocol

Ruoyao Xu,1 Jie Wang,1 Huimin Nie,1 Danyi Zeng,1 Chengyu Yin,1 Yuanyuan Li,1 Huina Wei,1 Boyu Liu,1 Yan Tai,2 Qimiao Hu,1 Xiaomei Shao,1 Jianqiao Fang,1 Boyi Liu1 1Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Hangzhou, 310053, People’s Republic of China; 2Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of ChinaCorrespondence: Boyi Liu; Jianqiao Fang, Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Hangzhou, 310053, People’s Republic of China, Email boyi.liu@foxmail.com; fangjianqiao7532@163.comBackground: Chronic postsurgical pain (CPSP) is common among patients receiving major surgeries. CPSP produces suffering in patients, both physically and mentally. However, the mechanisms underlying CPSP remain elusive. Here, a genome-wide expression profiling of ipsilateral spinal cord dorsal horn (SCDH) was performed to identify potential genes related with CPSP.Methods: A rat skin/muscle incision and retraction (SMIR) model was established to induce CPSP. Immunostaining was used to study glial cell and neuron activation in ipsilateral SCDH of SMIR model rats. RNA sequencing (RNA-Seq), combined with bioinformatics analysis, was undertaken to explore gene expression profiles. qPCR was applied to validate the expression of some representative genes.Results: The SMIR model rats developed persistent mechanical allodynia in ipsilateral hindpaw for up to 14 days. Ipsilateral SCDH of SMIR rats showed remarkable glial cell and neuron activation. A number of differentially expressed genes (DEGs) were identified in ipsilateral SCDH of SMIR rats by RNA-Seq. qPCR confirmed expression of some representative DEGs. Bioinformatics indicated that chemical synaptic transmission, sensory perception of pain and neuroactive ligand-receptor interaction were predominant functions. We compared our dataset with human pain-related genes and found that several genes exclusively participate in pain modulation and mechanisms.Conclusion: Our study provided novel understandings of the molecular mechanisms possibly contributing to CPSP. These findings may offer new targets for future treatment of CPSP.Keywords: postsurgical pain, spinal cord dorsal horn, RNA-Seq, microglia, genome

Yaling Hu,1,2 Shuang Liu,3 Wenyuan Liu,2 Ziyuan Zhang,2 Yuxiang Liu,1 Sufen Li,2 Dalin Sun,2 Guang Zhang,2 Jingai Fang2 1Shanxi Medical University, Taiyuan, Shanxi, 030001, People’s Republic of China; 2Department of Nephrology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, 030001, People’s Republic of China; 3Department of Urology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, 030001, People’s Republic of ChinaCorrespondence: Jingai Fang, Department of Nephrology, First Hospital of Shanxi Medical University, 85 Jiefangnan Road, Taiyuan, Shanxi, 030001, People’s Republic of China, Email jingaifang2017003@126.comPurpose: Using network pharmacology and molecular docking to explore the mechanism of Yishen Capsule in the treatment of diabetic nephropathy.Materials and Methods: Active components of Yishen Capsule were obtained using database such as TCMSP and TCMID. UniProt protein database was used to screen and standardize the human-derived targets of the active chemical components. Diabetic nephropathy (DN) targets were obtained from databases such as GeneCards, OMIM, TTD, DisGeNET and DrugBank. A network of “Yishen Capsule Components-diabetic nephropathy Targets-Pathways” was constructed by analyzing data above to screening out core targets for molecular docking verification. DN is induced by streptozocin in rats after left nephrectomy. Renal tubular epithelial cells (RTECs) was isolated and cultured under high glucose conditions. Based on these experimental models, key pathway target genes screened by network pharmacology were verified both in vitro and in vivo.Results: The main active components of Yishen Capsule in the treatment of DN include quercetin, kaempferol, gallic acid, astragaloside IV, etc. Some key targets (such as AR, AKT1, TP53, ESR1, JUN) and important signal pathways (such as AGE-RAGE, HIF-1 and JAK-STAT signal pathway) were included in the treatment of DN with Yishen Capsule. Molecular docking assay showed that most of the targets have good binding activity with the components of Yishen Capsule. Based on the results of network pharmacology, key target proteins in HIF-1α and JAK2/STAT3 signaling pathways were selected for experimental verification. Results presented that HIF-1α, JAK2, STAT3, TGF-β and MCP-1 were increased under high glucose environment. With the treatment of Yishen Capsule, the expression of HIF-1α further increased, while the expression of JAK2, STAT3, MCP-1 and TGF-β was decreased.Conclusion: This study revealed the mechanism of Yishen Capsule in the treatment of DN, which possesses the characteristics of multi-component, multi-target, and multi-pathway. Further experiments confirmed that Yishen Capsule interfered with HIF-1α and JAK/STAT signaling pathways to reduce inflammation and fibrosis damage in the kidney tissue of rats with diabetic nephropathy.Keywords: diabetic nephropathy, network pharmacology, molecular docking, HIF-1α, JAK/STAT

Jinzhang Fang,&ast; Zhao Chen,&ast; Jinxiu Li, Di Li, Wenxi Wang, Benfang Helen Ruan IDD & CB, College of Pharmaceutical Science & Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, 310014, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Benfang Helen Ruan; Wenxi Wang Email ruanbf@zjut.edu.cn; yjw@zjut.edu.cnIntroduction: Kidney-type glutaminase (KGA) has been an important anti-tumor drug target, and KGA allosteric inhibitors attracted much interest for their superior enzymatic specificity with good drug safety profiles. For glutaminase allosteric inhibitors such as BPTES, CB-839 and Selen derivatives, the low solubility remains as the main factor that limits in vivo efficacy. The 1,3,4-Selenadiazole compound CPD 23 showed improved in vivo efficacy but worse solubility; however, the graft polymer polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol (PVCap-PVA-PEG), Soluplus® (SOL) stood out as an excellent delivery carrier for CPD 23.Methods: The CPD 23@SOL micelles were prepared, optimized and evaluated through on the basis of solubility improvement and loading capacity. Characterizations of particle size and Zeta potential by dynamic light scattering, morphology by transmission electron microscopy and solid state by X-ray powder diffraction were closely conducted. The biological studies included the tumor cell growth inhibition, blood and liver microsomal stability, in vivo pharmacokinetics and tissue biodistribution.Results: At 1:20 ratio of CPD 23:SOL, CPD 23@SOL micelles were well-dispersed, spherical and stable, with size less than 200 nm with encapsulation efficiency of more than 90%. This SOL micellar system significantly increased the aqueous solubility of CPD 23 by 15,000 folds. Particularly, CPD 23@SOL micelles demonstrated higher stability in blood and liver microsomes, showing approximately 86% remaining at 2 h incubation and about 66% at 4 h, respectively. In addition, with or without micellar formulation, CPD 23 maintained essentially the same inhibitory activity in tumor cells. Interestingly, CPD 23@SOL micelles significantly improved the pharmacokinetic exposure, prolonged the in vivo circulation and dramatically changed tissue biodistributions of CPD 23.Conclusion: The current work provided an encouraging and practical delivery system for novel Selenadiazoles and glutaminase allosteric inhibitors whose poor water-soluble characteristic has been a bottleneck for the field.Keywords: glutaminase inhibitor, Selenadiazole compound, Soluplus®, polymeric micelles, stability, pharmacokinetics

Xuejing Li,1– 3,&ast; Meiqi Meng,1– 3,&ast; Junqiang Zhao,4,5 Xiaoyan Zhang,1– 3 Dan Yang,1– 3 Jiaxin Fang,1– 3 Junxin Wang,1– 3 Liu Han,6 Yufang Hao1– 3 1School of Nursing, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Beijing University of Chinese Medicine Collaborating Center of Joanna Briggs Institute, Beijing, People’s Republic of China; 3Beijing University of Chinese Medicine Best Practice Spotlight Organization, Beijing, People’s Republic of China; 4School of Nursing, University of Ottawa, Ottawa, Ontario, Canada; 5Center for Research on Health and Nursing, University of Ottawa, Ottawa, Ontario, Canada; 6Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yufang Hao Liangxiang High Education Park, Fangshan District, Beijing, 102488, People’s Republic of ChinaTel +86-13552850210Email bucmnursing@163.comAbstract: For most breast cancer (BC) patients who have undergone a mastectomy, the decision whether to proceed with breast reconstruction (BR) is complicated and requires deliberation. Shared decision-making (SDM) helps to address those needs and promote informed value-based decisions. However, little is known about the SDM status for BR in BC patients. This scoping review describes: 1) basic characteristics of studies on BR SDM in BC patients; 2) factors influencing BR SDM in BC patients; 3) experience and perception of BR SDM in BC patients; and 4) outcome measures reported. This review was performed in accordance with the Arksey and O’Malley methodology. A total of 5 English and 4 Chinese databases were searched, as well as different sources from grey literature. The data extraction form was developed by referring to the objectives and the Ottawa Decision Support Framework (ODSF). Data was analyzed using thematic analysis, framework analysis and descriptive statistics, with findings presented in the tables and diagrams. A total of 1481 records were retrieved and 42 of these included after screening. In 21 (21/42, 50%) of the studies, patient decision aids (PDAs) were utilized, and in 17 (17/42, 40.48%) of the studies, the factors influencing the implementation of SDM were explored. Of these 17 studies, the factors influencing the implementation of SDM were categorized into the following: the patient level (17/17, 100%), the healthcare level (2/17, 11.76%) and the organizational and system level (7/17, 41.18%). A total of 8 (19.05%) of the 42 studies focused on patients’ experiences and perceptions of SDM, and all studies used qualitative research methods. Of these 8 studies, a total of 7 (7/8, 87.50%) focused on patients’ experiences of SDM participation, and 4 (4/8, 50.00%) focused on patients’ perceptions of SDM. A total of 24 studies (24/42, 57.14%) involved quantitative outcome measures, where 49 items were divided into three classifications according to the outcomes of ODSF: the quality of the decision (17/24, 70.83%), the quality of the decision-making process (20/24, 83.33%), and impact (13/24, 54.17%). Although researchers have paid less attention to other research points in the field of SDM, compared to the design and application of SDM interventional tools, the research team still presents some equally noteworthy points through scoping review. For instance, the various factors influencing BC patients’ participation in SDM for BR (especially at the healthcare provider level and at the organizational system level), patients’ experiences and perceptions. Systematic reviews (SRs) should be conducted to quantify the impact of these different factors on BR SDM. Implementation of scientific theories and methods can inform the exploration and integration of these factors.Keywords: shared decision-making, patients’ decisional aids, breast reconstruction, breast cancer, mastectomy, Ottawa Decision Support Framework

Jiong-Ze Fang,&ast; Yong Yang,&ast; Hong-Da Zhu, Jian-Nan Sun, Hong-Chao Mi, Cai-De Lu Department of Hepatopancreatobiliary Surgery, Ningbo Medical Centre Lihuili Hospital, Ningbo University, Ningbo, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Cai-De Lu Tel/Fax +86 574- 55835600Email lucaide@nbu.edu.cnObjective: The significance of surgical treatment was analyzed by retrospectively collecting data on the re-resection of intra-abdominal metastases after hepatocellular carcinoma (HCC) surgery in our center over the past 10 years.Methods: The clinical and pathological data of 15 patients who developed intra-abdominal metastases after HCC resection and underwent re-resection from January 2010 to January 2020 were collected to analyze the patients’ characteristics and prognosis.Results: Of the 15 cases of abdominal metastasis, the majority (8 cases) had greater omental metastasis. There were 4 cases of mesenteric metastases, 1 case of abdominal wall metastasis, 1 case of mesenteric plus rectal wall metastasis, and 1 case of colon and mesenteric metastasis. The 1-year, 3-year, and 5-year disease-free survival (DFS) rates were 31.1%, 23.3%, and 11.7%, respectively. The 1-year, 3-year, and 5-year overall survival rates were 93.3%, 28.7%, and 19.1%, respectively. Three patients are currently surviving disease-free, with survival times of 130.4 months, 43.3 months, and 9.4 months, respectively.Conclusion: Although the current guidelines do not recommend surgical resection as the preferred treatment for postoperative abdominal metastases of HCC, surgical resection is recommended for patients with limited or solitary metastasis in the abdominal cavity.Keywords: hepatocellular carcinoma, postoperative recurrence of HCC, intra-abdominal metastasis, disease-free survival, overall survival

Ding Tang,1 Xufen Zhang,1 Yani Xu,1 Linglin Dai,1 Jianlan Sun,1 Hantong Hu,2 Huangwei Jiang,3 Ping Jin,3 Lifang Chen,2 Jianqiao Fang4 1The Third Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Acupuncture, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Radiological, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 4The Third Clinical Medical College of Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Lifang ChenDepartment of Acupuncture, The Third Affiliated Hospital of Zhejiang Chinese Medical University, No. 219 Moganshan Road, XiHu District, Hangzhou, Zhejiang, 310005, People’s Republic of ChinaEmail clfang@163.comJianqiao FangZhejiang Chinese Medical University, NO. 548 Binwen Road, Binjiang District, Hangzhou, Zhejiang, 310053, People’s Republic of ChinaEmail fangjianqiao7532@163.comObjective: To verify the efficacy of electroacupuncture (EA) on classical trigeminal neuralgia (CTN), and to observe the brain functional status of patients with CTN and the intervention effects of EA on brain function by resting-state functional magnetic resonance imaging (rs-fMRI).Methods and Analysis: Thirty CTN patients will be randomly divided into EA combined with carbamazepine group and carbamazepine group in 2:1 ratio by using a random number table. Patients in EA combined with carbamazepine will receive EA treatment and carbamazepine for four weeks. The carbamazepine group will only receive carbamazepine treatment. VAS (visual analogue scale), HAMA (Hamilton Anxiety Scale), HAMD (Hamilton Depression Scale) and SF-36 (short form 36 health survey) will be performed before, after four-week treatments and at three-month follow-up in CTN patients. Six CTN patients will be randomly selected from EA combined with carbamazepine group and carbamazepine group, respectively, before treatment, and twelve paired healthy participants will be recruited at the same time. The twelve CTN patients will be scanned by rs-fMRI before and after treatment, and the healthy participants will be scanned by rs-fMRI only at baseline. Regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) analysis will be carried out to compare the dysfunctional brain regions between CTN patients and healthy participants, as well as the differences between two groups of patients with CTN after treatment.Trial Registration: ChiCTR-1900027873.Keywords: electroacupuncture, trigeminal neuralgia, pre-experimental, fMRI, randomized controlled trial, protocol

Si Zu,1 Dong Wang,1 Jiexin Fang,1 Le Xiao,2 Xuequan Zhu,2 Wenyuan Wu,3 Gang Wang,2,4 Yongdong Hu1 1Department of Psychiatry, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Psychiatry, Tongji Hospital of Tongji University, Shanghai, People’s Republic of China; 4Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Gang WangThe National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, No. 5 Ankang Lane, Xicheng District, Beijing Anding Hospital, Beijing, 100088, People’s Republic of ChinaEmail gangwangdoc@ccmu.edu.cnYongdong HuDepartment of Psychiatry, Beijing Chaoyang Hospital, Capital Medical University, No. 8 Gongtinanlu, Chaoyang District, Beijing Chaoyang Hospital, Beijing, 100020, People’s Republic of ChinaTel +86-10-85231754Email haiyong.xie@ustc.eduObjective: This prospective study aimed to investigate the prognosis and rehabilitation of patients with recurrent depression and first episode depression after acute treatment in China.Methods: A total of 434 patients with first-episode or recurrent depression who received acute treatment respectively from sixteen hospitals in thirteen cities in China were enrolled in this prospective study. All patients were followed up for 6 months after acute treatment. The following data were collected at baseline period and 1, 3, and 6 months after acute treatment: general information of patients, medication information and patient’s condition changes, brief 16-item quick inventory of depressive symptomatology self-report (QIDS-SR16), patient health questionnaire-15 (PHQ-15), quality of life enjoyment and satisfaction questionnaire-short form (Q-LES-Q-SF), Sheehan disability scale (SDS) and digit symbol substitution test (DSST).Results: During the baseline period, there was a significant difference in QIDS-SR16 between recurrent patients and first-episode patients (p < 0.05), and there was no significant difference in other indicators (p > 0.05). At one month after acute treatment, there were significant differences in the total QIDS-SR16 score, the total Q-LES-SF score, the social life score, and the family life/home responsibilities score of SDS in patients with recurrent depression and first-episode depression (p < 0.05). At three months after acute treatment, there were significant differences in the total Q-LES-SF score and social life score of SDS in patients with recurrent depression and first-episode depression (p < 0.05). At six months after acute treatment, there were significant differences in the total QIDS-SR16 score, the social life score, and the total Q-LES-SF score in patients with recurrent depression and first-episode depression (p < 0.05). Compared with that data during the baseline period, the QIDS-SR16 scores and the SDS scores of all patients decreased, and the Q-LES-SF scores of all patients gradually increased as time went on during the consolidation period.Conclusion: The recurrent patients have more severe social function impairment, depressive symptoms, and lower life quality than that of the first-episode depressed patients. Given the negative impact of depressed symptom on recurrent patient, more attention should be paid to the treatment of recurrent patient and recurrence prevention of first episode patient.Keywords: depression, first-episode, recurrent patient, prognosis

Lixiao Liu,1,&ast; Xuedan Du,2,&ast; Jintao Fang,3,&ast; Jinduo Zhao,1 Yong Guo,3 Ye Zhao,1 Chengyang Zou,1 Xiaojian Yan,1 Wenfeng Li2 1Department of Obstetrics and Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2Department of Chemoradiation Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 3Department of Urinary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenfeng Li; Xiaojian Yan Email liwenfeng@wmu.edu.cn; yxjbetter2016@hotmail.comBackground: Interferon plays a crucial role in the pathogenesis and progression of tumors. Clear cell renal cell carcinoma (ccRCC) represents a prevalent malignant urinary system tumor. An effective predictive model is required to evaluate the prognosis of patients to optimize treatment.Materials and Methods: RNA-sequencing data and clinicopathological data from TCGA were involved in this retrospective study. The IFN-γ response genes with significantly different gene expression were screened out. Univariate Cox regression, LASSO regression and multivariate Cox regression were used to establish a new prognostic scoring model for the training group. Survival curves and ROC curves were drawn, and nomogram was constructed. At the same time, we conducted subgroup analysis and experimental verification using our own samples. Finally, we evaluated the relatedness between the prognostic signature and immune infiltration landscapes. In addition, the sensitivity of different risk groups to six drugs and immune checkpoint inhibitors was calculated.Results: The IFN-γ response-related signature included 7 genes: C1S, IFI44, ST3GAL5, NUP93, TDRD7, DDX60, and ST8SIA4. The survival curves of the training and testing groups showed the model’s effectiveness (P = 4.372e-11 and P = 1.08e-08, respectively), the ROC curves showed that the signature was stable, and subgroup analyses showed the wide applicability of the model (P< 0.001). Multivariate Cox regression analysis showed that the risk model was an independent prognostic factor of ccRCC. A high-risk score may represent an immunosuppressive microenvironment, while the high-risk group exhibited poor sensitivity to drugs.Conclusion: Our findings strongly indicate that the IFN-γ response-related signature can be used as an effective prognostic indicator of ccRCC.Keywords: interferon gamma, nomogram, prognostic signature, drug sensitivity, qPCR

Xiaoyan Chen,1 Qingmei Yang,1 Jianxiu Fang,1 Haifeng Guo2 1Department of Ultrasound, Shanxi Bethune Hospital & Shanxi Academy of Medical Sciences, Taiyuan, Shanxi Province, People’s Republic of China; 2Department of Medical Imaging, Shanxi Armed Police Force Hospital, Taiyuan, Shanxi Province, People’s Republic of ChinaCorrespondence: Xiaoyan ChenDepartment of Ultrasound, Shanxi Bethune Hospital & Shanxi Academy of Medical Sciences, Taiyuan, Shanxi Province, People’s Republic of ChinaTel +8613934200119Email xiaoguoguo119@163.comBackground: A lower systolic blood pressure (SBP) target reduces major cardiovascular events and mortality from any cause of geriatric hypertension. However, the effect of different SBP targets on myocardial function remains unclear. This study aimed to determine changes in left ventricular (LV) strain in older hypertensive patients after 1 year of different SBP goals, and to evaluate its effects on myocardial mechanics in this population.Methods: We studied 313 hypertensive adults aged 60 years or older after 1 year of the Systolic Blood Pressure Intervention Trial. They were divided into the intensive group (target SBP: 110– 130 mmHg) and the standard group (target SBP: 130– 150 mmHg). All participants underwent echocardiography within 1 week after enrollment and 1 year after participating in the study. Global longitudinal strain (GLS) of the LV (endocardial, middle, and epicardial layer: GLS-end, GLS-mid, and GLS-epi, respectively) and the improvement of GLS at 1 year (ΔGLS-end, ΔGLS-mid, and ΔGLS-epi) were measured.Results: At 1 year, GLS-end in the intensive group was slightly improved compared with that before the trial (− 23.78%± 3.10% vs − 22.58%± 3.11%, P< 0.05). The ΔGLS-end and ΔGLS-mid in the intensive group were higher than those in the standard group (1.20± 0.23 vs 0.58± 0.59% and 0.70± 0.21 vs 0.52± 0.17, P< 0.05). Moreover, SBP at 1 year and an angiotensin II type 1 receptor antagonist were independent factors that affected ΔGLS-end (β= − 0.005, P=0.004; β= 0.080, P< 0.001, respectively).Conclusion: These trial results suggest that a lower SBP target can slightly improve myocardial function in older hypertensive patients at 1 year.Keywords: hypertension, blood pressure target, elder population, strain, left ventricular function

Yun Yan,1 Li Jiang,2 Jianjiang Fang,2 Yi Dai,3 Xingzi Chenyu,3 Jinhua Ding4 1Department of Ultrasound, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, 315000, People’s Republic of China; 2Department of General Practice, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, 315000, People’s Republic of China; 3Ningbo University School of Medicine, Ningbo, Zhejiang, 315000, People’s Republic of China; 4Department of Breast and Thyroid Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, 315000, People’s Republic of ChinaCorrespondence: Jinhua DingDepartment of Breast and Thyroid Surgery, Ningbo Medical Center Lihuili Hospital, No. 1111, Jiangnan Road, Ningbo, Zhejiang, 315000, People’s Republic of ChinaTel +86 13957498690Email cookie800128@sina.comPurpose: Interpectoral lymph nodes (IPNs) are one of the lymphatic drainage pathways in breast cancer. However, the clinical significance of IPN dissection is controversial, and there is no international consensus regarding the management of IPN for resectable breast cancer. Our study aims to identify the independent predictors of IPN metastasis in invasive breast cancer (IBC) and provide some evidence for rational decision-making.Methods: Data from 214 IBC patients who were treated with modified radical mastectomy (MRM) plus IPN dissection or biopsy in Ningbo Medical Center Lihuili Hospital were retrospectively reviewed. Univariate analysis and multivariate logistic regression analysis were used to analyse the correlations between IPN occurrence or metastasis and clinicopathological characteristics.Results: The occurrence rate of IPN in overall population was 75.2%. Univariate analysis showed that tumour size, involvement of axillary lymph nodes (ALNs), histological grading, Ki67 index and molecular subtype were associated with the occurrence of IPN. However, involvement of ALN was the only independent predictor by multivariate logistic regression analysis. In 161 patients whose IPNs were detected, 46 (28.6%) patients had one or more metastatic IPNs. Univariate analysis showed that tumour size, involvement of ALN, oestrogen receptor status and molecular subtype were associated with IPN metastasis. However, involvement of ALN was the only predictor by multivariate logistic regression analysis. In total, 0%, 5.0%, 26.1% and 84.2% of pN0, pN1, pN2, and pN3 patients had metastatic IPNs, respectively.Conclusion: The relatively low rate of IPN metastasis in patients with pN0/N1 breast cancer suggests that IPN dissection can be safely spared in patients with low tumour burden in axillary lymph nodes (pN0/N1), when MRM even breast conservation surgery is performed.Keywords: breast cancer, interpectoral lymph node, axillary lymph node, metastasis