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Yawen Cai,1,2,* Guiqin Huang,2,* Menghui Ren,2 Yuhui Chai,3 Yu Fu,2 Tianhua Yan,2 Lingpeng Zhu1 1The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu, 214023, China; 2School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, 210009, China; 3Department of Pharmacy, Shanghai Changhai Hospital, Second Military University, Shanghai, 200433, China*These authors contributed equally to this workCorrespondence: Tianhua Yan, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China, Email 1020050806@cpu.edu.cn Lingpeng Zhu, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Nanjing, China, Email zhulingpeng@njmu.edu.cnBackground: The phenomenon of “kidney-brain crosstalk” has stimulated scholarly inquiry into the correlations between kidney injury (KI) and Alzheimer’s disease (AD). Nonetheless, the precise interactions and shared mechanisms between KI and AD have yet to be fully investigated. The primary goal of this study was to investigate the link between KI and AD, with a specific focus on identifying diagnostic biomarkers for KI-related AD.Methods: The first step of the present study was to use Mendelian randomization (MR) analysis to investigate the link between KI and AD, followed by verification of in vivo and in vitro experiments. Subsequently, bioinformatics and machine learning techniques were used to identify biomarkers for KI-associated ferroptosis-related genes (FRGs) in AD, which were validated in following experiments. Moreover, the relationship between hub biomarkers and immune infiltration was assessed using CIBERSORT, and the potential drugs or small molecules associated with the core biomarkers were identified via the DGIdb database.Results: MR analysis showed that KI may be a risk factor for AD. Experiments showed that the combination of D-galactose and aluminum chloride was found to induce both KI and AD, with ferroptosis emerging as a bridge to facilitate crosstalk between KI and AD. Besides, we identified EGFR and RELA have significant diagnostic value. These biomarkers are associated with NK_cells_resting and B_cells_memory and could be targeted for intervention in KI-related AD by treating gefitinib and plumbagin.Conclusion: Our study elucidates that ferroptosis may be an important pathway for kidney-brain crosstalk. Notably, gefitinib and plumbagin may be therapeutic candidates for intervening in KI-associated AD by targeting EGFR and RELA. Keywords: kidney injury, Alzheimer’s disease, kidney-brain crosstalk, ferroptosis, bioinformatics, machine learning

Yaoyao Jing,1 Minghan Ren,2 Xiaoxiao Li,1 Xiaoyuan Sun,1 Yan Xiao,3 Juan Xue,2 Zimin Liu1 1Center for GI Cancer Diagnosis and Treatment, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China; 2Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China; 3Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of ChinaCorrespondence: Zimin Liu, Email liuzimin301@126.comBackground: In recent years, the systemic immune-inflammatory index (SII) and prognostic nutritional index (PNI) have been considered potential predictors of survival outcomes in various solid tumors, including gastric cancer. However, there is a notable lack of research focusing on their prognostic implications specifically in the early stage of gastric cancer. This study aims to investigate the prognostic indicators of early gastric cancer (EGC), including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), SII, PNI, and lymph node metastasis (LNM).Methods: In this retrospective analysis, we examined 490 patients diagnosed with EGC (pT1Nx). The peripheral blood indices of interest were SII, PNI, PLR, and NLR. The receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were used to determine optimal cutoff values and prognostic efficacy for each parameter. Additionally, Kaplan-Meier survival curves and multivariate Cox regression models were utilized to delineate independent prognostic factors.Results: The optimal cutoff values for SII and PNI were determined as 613.05 and 42.21, respectively. Patients in the low SII (SII-L) group demonstrated significantly higher 5-year Disease-Free Survival (DFS) and Overall Survival (OS) rates of 94.7% and 96.2%, compared to the high SII (SII-H) group (DFS: 78.7%; OS: 81.9%), with both differences proving statistically significant (P < 0.001, P < 0.001). Similarly, patients in the high PNI (PNI-H) group showed superior 5-year DFS (93.3%) and OS rates (95.1%) versus the low PNI (PNI-L) group (DFS: 71.4%; OS: 74.3%), also demonstrating statistical significance (P < 0.001, P < 0.001). Multivariate analysis identified SII, PNI, and LNM as independent prognostic factors for EGC. A combined analysis of SII, PNI, and LNM yielded a C-index of 0.723 (P = 0.008).Conclusion: SII, PNI, and LNM are effective markers for predicting the survival outcomes of patients undergoing radical gastrectomy for EGC.Keywords: early gastric cancer, systemic inflammatory response index, prognostic nutritional index, lymph node metastasis, prognosis

Xinrui Luo,1,&ast; Yan Wang,1,2,&ast; Liping Wang,2 Yang Shen,1,2 Mulan Ren2 1Department of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Obstetrics and Gynecology, Zhongda Hospital, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Wang, Department of Obstetrics and Gynecology, Zhongda Hospital, Southeast University, 87 Dingjiaqiao Street, Nanjing, Jiangsu, People’s Republic of China, Tel +86-1-381-417-6185, Email xlswy1984@163.comBackground: The impact of androgens on metabolic diseases, cardiovascular diseases (CVD), and long-term mortality in the general female population remains poorly understood. This study, utilizing data from the National Health and Nutrition Examination Survey (NHANES) database managed by the Centers for Disease Control and Prevention, seeks to elucidate the relationship between androgen levels and metabolic syndrome (MS), CVD, and mortality in adult women.Methods: After excluding ineligible individuals, descriptive analyses were conducted on demographic characteristics, metabolic-related indicators, and disease prevalence, based on the presence of high androgenemia and androgen quartile grouping. Logistic regression models were developed to assess the associations of androgen markers, including total testosterone (TT), Free Androgen Index (FAI), with MS, CVD, and cox regression models were used to explore the relationships with mortality.Results: Our results show that, even without adjustment for age, age at menarche, marital status, and smoking status, both in patients with hyperandrogenemia and across the general population stratified by quartiles of FAI, higher androgen levels are associated with increased waist circumference, weight, Body Mass Index, fasting insulin, and the monocyte/high-density lipoprotein cholesterol ratio. In adjusted correlational analysis, MS remained positively correlated with FAI, even after controlling for age, tobacco use, and alcohol consumption. As FAI quartiles increased, the correlation strengthened, achieving an odds ratio (OR) of 1.45 (95% CI 1.04 to 2.02, P=0.03) in the highest quartile. This indicates that androgen levels are strongly associated with metabolic syndrome, with FAI proving more sensitive than TT.Conclusion: The greater sensitivity of FAI may be attributed to its ability to reflect bioavailable testosterone more accurately than TT, underscoring its potential utility in clinical assessments of metabolic risk. This study found no significant correlation between androgen levels and CVD or mortality.Keywords: androgen, free androgen index, metabolic syndrome, cardiovascular disease, NHANES

Kaige Ma,1,&ast; Chanyuan An,1,&ast; Mai Li,1 Yuming Zhang,2 Minghe Ren,1 Yuyang Wei,3 Wenting Xu,1 Ruoxi Wang,4 Yudan Bai,1 Hanyue Zhang,1 Xiyue Liu,1 Shengfeng Ji,4 Xinlin Chen,1,5 Kun Zhu6 1Department/Institute of Neurobiology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, 710061, People’s Republic of China; 2Department of Anesthesiology, Shaanxi Provincial People’s Hospital, Xi’an, 710068, People’s Republic of China; 3School of Forensic Medicine, Southern Medical University, Guangdong, 510515, People’s Republic of China; 4Department of Optometry, Fenyang College Shanxi Medical University, Fenyang, 032200, People’s Republic of China; 5Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, 710061, People’s Republic of China; 6Department of Neurology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinlin Chen; Kun Zhu, Email chenxl@xjtu.edu.cn; kunzhu@xjtu.edu.cnPurpose: β-amyloid overload-induced neuroinflammation and neuronal loss are key pathological changes that occur during the progression of Alzheimer’s disease (AD). Dexmedetomidine (Dex) exhibits neuroprotective and anti-inflammatory effects on the nervous system. However, the effect of Dex in AD mice remains unclear, and its neuroprotective regulatory mechanism requires further investigation. This study aimed to reveal how Dex protects against Aβ induced neuropathological changes and behavior dysfunction in AD mice.Methods: An AD mouse model was established by the injection of Aβ into the brains of mice, followed by intraperitoneal injection with Dex. CXCL2 overexpression and Yohimbine, a Dex inhibitor, were used to investigate the role of Dex and CXCL2 in the regulation of neuronal loss, cognitive decline, and anxiety-like behavior in AD mice. Behavioral tests were performed to evaluate the cognitive and anxiety status of the mice. Nissl staining and immunofluorescence experiments were conducted to evaluate the status of the hippocampal neurons and astrocytes. qRT-PCR was performed to detect the expression of CXCL2, IL-1β, INOS, SPHK1, Bcl2, IFN-γ, and Caspase 1. The malondialdehyde (MDA) level was detected using an ELISA kit. Terminal TUNEL and Fluoro-Jade C (FJC) staining were used to measure the cell apoptosis rate.Results: In AD mice, cognitive decline and anxiety-like behaviors were significantly improved by the Dex treatment. The number of neurons was increased in mice in the Dex + AD group compared to those in the AD group, and the number of astrocytes was not significantly different between the two groups. CXCL2, IL-1β, iNOS, and SPHK1 levels were significantly lower in Dex-treated AD mice than those in AD mice. Overloading of CXCL2 or Yohimbine reversed the protective effect of Dex on neuron number and cognitive and anxiety symptoms in AD mice.Conclusion: Our results suggest that Dex exerts neuroprotective effects by downregulating CXCL2. Dex shows potential as a therapeutic drug for AD.Keywords: dexamethasone, Alzheimer’s disease, chemokine CXCL2, anxiety, cognitive dysfunction, behavioral Tests

Xianling Feng,1,&ast; Fucheng Tao,2,&ast; Min Ren,3,&ast; Mao Niu4 1School of Medical, Shenzhen University, Shenzhen, 518060, People’s Republic of China; 2Department of Stomatology, Shenzhen University General Hospital, Shenzhen, 518055, People’s Republic of China; 3Department of Stomatology, Rizhao Traditional Chinese Medicine Hospital, Rizhao, 276800, People’s Republic of China; 4School of Medical Technology and Nursing, Shenzhen Polytechnic University, Shenzhen, 518055, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mao Niu, School of Medical Technology and Nursing, Shenzhen Polytechnic University, 7098 Liuxian Avenue, Nanshan District, Shenzhen, 518055, People’s Republic of China, Tel +86 755 26011160, Fax +86 755 26018477, Email niu1037@szpu.edu.cnObject: The present study intended to evaluate the effect of simvastatin-loaded nanomicelles (SVNs) on promoting new bone formation and reducing alveolar ridge resorption at the tooth extraction sites at the early healing of the extraction sockets.Methods: SVNs were synthesized using a dialysis method. The rabbit tooth extraction model was established, SVNs and simvastatin (SV) were loaded on gelatin sponge and inserted into the extraction socket. CBCT scans were performed at 0, 2, and 4 weeks postoperatively to evaluate bone formation and alveolar ridge absorption in the extraction sockets. And all the animals were sacrificed and the mandibles were harvested. And HE staining and Masson staining were used for histological evaluation of the bone formation in the extraction sockets.Results: Radiographic evaluation showed that compared with the blank control group, at 2 and 4 weeks after extraction, SVNs increased the new bone density in the extraction sockets by 75.7% and 96.5%, and reduced the absorption rate of alveolar ridge length at the extraction sites by 60.8% and 49.1%, respectively. Histological evaluation showed that SVNs significantly improved the maturation of new bone tissue in the extraction sockets.Conclusion: SVNs can significantly accelerate healing and effectively reduce the absorption of alveolar ridge at the extraction sites in the early stage of tooth extraction socket healing.Keywords: alveolar ridge preservation, simvastatin-loaded nanomicelles, tooth extraction sites, bone formation

Mingyuan Ren,1,2,&ast; Yijia He,1,&ast; Jianzhong Zhang,3 Jinfang Zhang,1,2 Guoqiang Zhang1,2 1Department of Dermatology, the First Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Hebei Technical Innovation Center for Dermatology and Medical Cosmetology Technology, Shijiazhuang, People’s Republic of China; 3Department of Dermatology, Affiliated Hospital of Hebei University of Engineering, Handan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinfang Zhang; Guoqiang Zhang, Email 58303110@hebmu.edu.cn; 57702800@hebmu.edu.cnAbstract: Tjalma’s syndrome is a benign combination of ascites, pleural effusion, and elevated CA-125 occurring in patients with systemic lupus erythematosus. Reports of Tjalma’s syndrome are scarce. An elevated CA-125 level often suggests the possibility of the presence of a malignant tumor. We report a case of generalised erythema and blisters with pruritus, massive unilateral pleural effusion and elevated CA-125. This patient was finally diagnosed with bullous systemic lupus erythematosus after exclusion of tumour and other maculopapular disorders. We hope that this particular case may provide a more comprehensive and novel diagnostic idea of systemic lupus erythematosus and pleural effusion, avoiding unnecessary anxiety, laboratory tests and surgical interventions.Keywords: systemic lupus erythematosus, bullous systemic lupus erythematosus, pleural effusion, Tjalma’s syndrome, CA-125

Ramya Manoharan,1 Chythra Somanathan Nair,1 Nermin Eissa,2 Hao Cheng,3 Pengliang Ge,4 Maozhi Ren,3 Abdul Jaleel1 1Department of Integrative Agriculture, College of Agriculture and Veterinary Medicine, United Arab Emirates University, Al Ain, United Arab Emirates; 2Department of Biomedical Sciences, College of Health Sciences, Abu Dhabi University, Abu Dhabi, United Arab Emirates; 3Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu National Agricultural Science and Technology Center, Chengdu, People’s Republic of China; 4College of Plant Science & Technology, Huazhong Agricultural University, Wuhan, People’s Republic of ChinaCorrespondence: Abdul Jaleel, Department of Integrative Agriculture, College of Agriculture and Veterinary Medicine, United Arab Emirates University, Al Ain, United Arab Emirates, Tel +9713-7134558, Email abdul.jaleel@uaeu.ac.aeAbstract: Cancer has emerged as a formidable global health challenge, with treatment methods like chemotherapy and radiation often exacerbating the situation due to their associated side effects. Opting for natural sources like plants as a safer and environmentally friendly alternative seems promising. Historically, plants have served as valuable sources for treating diverse health conditions, attributable to their rich composition of therapeutic phytochemicals. Within this array of phytochemicals, alkaloids, especially those found in the Solanaceae plant family, are notably prominent. Alkaloids from Solanaceae plant family called Solanum alkaloids demonstrate noteworthy anti-tumour characteristics and exert a potent inhibitory influence on cancer cell proliferation. They trigger programmed cell death in cancerous cells through various molecular pathways, whether administered alone or combined with other medications. Solanum alkaloids act upon cancer cells via multiple mechanisms, including apoptosis induction, suppression of cell growth and migration, as well as inhibition of angiogenesis. This review provides insights into the anti-cancer attributes of Solanum alkaloids found in various Solanum plant species, along with a brief overview of their other medicinal properties.Keywords: Solanum alkaloids, anticancer, apoptosis, molecular mechanism, structure function relationship, therapeutic values

Huaqiao Tang,1,&ast; Liying Dong,1,&ast; Xue Xia,1,&ast; Xinling Chen,1 Meichen Ren,1 Gang Shu,1 Hualin Fu,1 Juchun Lin,1 Ling Zhao,1 Li Zhang,2 Guoqiang Cheng,2 Xianxiang Wang,3 Wei Zhang1 1College of Veterinary, Sichuan Agricultural University, Chengdu, 611130, People’s Republic of China; 2Sichuan Academy of Chinese Medicine Sciences, Chengdu, 610041, People’s Republic of China; 3College of Science, Sichuan Agricultural University, Chengdu, 611130, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Zhang, Email Zhangwei26510c@126.comIntroduction: Chrysin has a wide range of biological activities, but its poor bioavailability greatly limits its use. Here, we attempted to prepare casein (cas)-based nanoparticles to promote the biotransfer of chrysin, which demonstrated better bioavailability and anti-infection activity compared to free chrysin.Methods: Cas-based chrysin nanoparticles were prepared and characterized, and most of the preparation process was optimized. Then, the in vitro and in vivo release characteristics were studied, and anti-pulmonary infection activity was evaluated.Results: The constructed chrysin-cas nanoparticles exhibited nearly spherical morphology with particle size and ζ potential of 225.3 nm and − 33 mV, respectively. These nanoparticles showed high encapsulation efficiency and drug-loading capacity of 79.84% ± 1.81% and 11.56% ± 0.28%, respectively. In vitro release studies highlighted a significant improvement in the release profile of the chrysin-cas nanoparticles (CCPs). In vivo experiments revealed that the relative oral bioavailability of CCPs was approximately 2.01 times higher than that of the free chrysin suspension. Further investigations indicated that CCPs effectively attenuated pulmonary infections caused by Acinetobacter baumannii by mitigating oxidative stress and reducing pro-inflammatory cytokines levels, and the efficacy was better than that of the free chrysin suspension.Conclusion: The findings underscore the advantageous bioavailability of CCPs and their protective effects against pulmonary infections. Such advancements position CCPs as a promising pharmaceutical agent and candidate for future therapeutic drug innovations.Keywords: chrysin, nanoparticles, Acinetobacter baumannii, casein

Yifu Chen,1– 3 Yu Xia,1,3,4 Menghao Ren,1,3,4 Wei Zheng,2 Xiao Wang,2 Feng Gao2 1Center for Mind and Brain Sciences, Hunan Normal University, Changsha, 410081, People’s Republic of China; 2Hunan Railway Professional Technology College, Zhuzhou, 412001, People’s Republic of China; 3China Research Center for Mental Health Education of Hunan Province, Hunan Normal University, Changsha, 410081, People’s Republic of China; 4Cognition and Human Behavior Key Laboratory of Hunan Province, Hunan Normal University, Changsha, 410081, People’s Republic of ChinaCorrespondence: Feng Gao, Hunan Railway Professional Technology College, Zhuzhou, 412001, People’s Republic of China, Email 542322378@qq.comPurpose: We aim to explore the relationship between overparenting and social avoidance among emerging adults, and the mediating effects of peer attachment and gender differences.Participants and Methods: A total of 1161 Chinese college students completed the questionnaire. The structural equation model was established to validate the main effect model and the mediation model.Results: The results found that both paternal and maternal overparenting positively predicted social avoidance among emerging adults. Both attachment avoidance and attachment anxiety played a significant mediating role in the relationship between paternal overparenting and social avoidance. Attachment anxiety played a significant mediating role in the relationship between maternal overparenting and social avoidance, while, the mediating effect of attachment avoidance was not significant. In addition, gender differences were found in the mediating effects of peer attachment. The mediating effect of attachment anxiety in males’ families had an opposite-gender matching effect, while in females’ families, the mediating effect of attachment avoidance had an opposite-gender matching effect.Conclusion: This study contributes to the understanding of the effects of overparenting on emerging adults, enriching empirical research in related fields.Keywords: overparenting, social avoidance, peer attachment, gender differences, emerging adults

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

The main task in the production of steel in the basic oxygen furnace (BOF) is dephosphorization Therefore, the prediction and control of the end-point phosphorus content of molten steel is of great significance. Four machine learning regression models (Lasso, Random Forest, Xgboost, and Neural Network) were established to predict the end-point phosphorus content of molten steel in the BOF based on raw and auxiliary material data, process parameters, and production quality data. The prediction effect of the four models was further compared, and their prediction results were interpreted based on the interpretability of the models and the permutation importance method. The results showed that compared with linear regression and neural network regression model, two types of ensemble tree model have higher prediction accuracy, better stability with small data sets, and lower data preprocessing requirements. The factors influencing the end-point phosphorus (P) content in BOF were ranked in order of importance as: Tapping temperature > Turning down times > Steel scrap quantity> Operation habits of different working groups > Amount of oxygen injection> Sulfur and phosphorus content of molten iron > Addition amount of lime, limestone, and lightly burnt dolomite in the slag > Slag-splashing amount.

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

Qingen Da,1,2,&ast; Mingming Ren,2,&ast; Lei Huang,2 Jianhua Qu,1 Qiuhua Yang,3 Jiean Xu,4 Qian Ma,4 Xiaoxiao Mao,4 Yongfeng Cai,4 Dingwei Zhao,4 Junhua Luo,5 Zilong Yan,1 Lu Sun,2 Kunfu Ouyang,2 Xiaowei Zhang,6 Zhen Han,2 Jikui Liu,1 Tao Wang2 1Department of Hepatobiliary Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, People’s Republic of China; 2Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, People’s Republic of China; 3Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA, USA; 4Shenzhen Graduate School, Peking University, Shenzhen, People’s Republic of China; 5Department of Urological Surgery, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China; 6School of Basic Medical Sciences, Peking University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jikui Liu, Department of Hepatobiliary Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, People’s Republic of China, Email liu8929@126.com Tao Wang, Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, People’s Republic of China, Email szwangtao@126.comObjective: We aimed to explore the prognostic patterns of ferroptosis-related genes in papillary renal cell carcinoma (PRCC) and investigate the relationship between ferroptosis-related genes and PRCC tumor immune microenvironment.Methods: We obtained the mRNA expression and corresponding clinical data of PRCC from the public tumor cancer genome atlas database (TCGA). The PRCC patients were randomly divided into two cohort, training cohort and verification cohort, respectively. Univariate Cox regression, LASSO Cox regression, multivariate Cox regression analysis were utilized to construct ferroptosis signature for PRCC patients. And then, risk prognostic model was established and verified. The correlation of ferroptosis-related signature with survival and immune microenvironment was systematically analyzed.Results: A 4-genes ferroptosis signature (CDKN1A, MIOX, PSAT1, and RRM2) was constructed. Multivariate Cox regression assay indicates that the risk score of ferroptosis signature was an independent prognostic indicator (HR=1.391, p< 0.001). The survival curve shows that the high-risk group has a poorer prognosis than the low-risk group (p< 0.001). The risk prognostic model was established based on prognostic factors of clinical-stage, hemoglobin, and risk score. The time-dependent receiver operating characteristic curve (ROC) analysis proves the predictive capacity of the ferroptosis signature, the 3 years area under the curve (AUC) is 0.890, and the 5 years AUC is 0.733. Further analysis suggested that cell cycle, pentose phosphate pathway, P53 signaling pathway were significantly enriched in the high-risk group. The significantly different fractions of dendritic cells resting, macrophage cells, and T cells follicular helper were observed in risk groups.Conclusion: This study implicates a ferroptosis signature which has a good predict capacity of the prognosis in PRCC patients. Ferroptosis-related genes may have a key role in the process of anti-tumor and serve as therapeutic targets for PRCC.Keywords: papillary renal cell carcinoma, ferroptosis, gene signature, prognosis model, tumor immune microenvironment

Jinlu Liu,1,&ast; Ling Yang,1,&ast; Xin Yuan,2,&ast; Meimei Xiong,1 Jiao Zhu,1 Wenbi Wu,1 Min Ren,1 Jianlin Long,3 Xuewen Xu,2 Maling Gou1 1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Plastic and Burn Surgery, West China Hospital of Sichuan University, Chengdu, 610041, People’s Republic of China; 3Department of Medical Oncology, Chongqing University Cancer Hospital, Chongqing, 400030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Maling GouState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of ChinaEmail goumaling@scu.edu.cnXuewen XuDepartment of Plastic and Burn Surgery, West China Hospital of Sichuan University, Chengdu, 610041, People’s Republic of ChinaEmail xxw_0826@163.comIntroduction: β-lactamase (LACTB) is a tumor suppressor gene in various tumors including melanoma. However, it remains challenging to efficiently deliver the LACTB gene into melanoma. Recently, we designed a nonviral nanocarrier iRGD/DOTAP/MPEG-PDLLA (iDPP) that could deliver gene targetedly to melanoma efficiently without obvious adverse effects.Methods: In this study, the tumor-targeted nanoparticle iDPP was prepared to deliver LACTB gene to treat melanoma in vitro and in vivo. First, the expression level of LACTB in 6 clinical specimens of melanoma patients was evaluated. Subsequently, the characteristics of iDPP/LACTB nanocomplexes were studied. Afterwards, the in vitro and in vivo anti-tumor efficacy of the iDPP/LACTB nanocomplexes were explored utilizing the B16-F10 mouse melanoma cell line and the B16-F10 subcutaneous melanoma model.Results: Compared with the normal epithelium, the expression level of LACTB in melanoma tissues was significantly downregulated. In vitro B16-F10 cell tests showed iDPP/LACTB nanocomplexes could increase the mRNA levels of P21, Bid, Bax, Pidd1, and Sival genes and up-regulate the p53 signaling pathway of melanoma cells, thus promoting cell apoptosis and blocking the cell cycle. Injected intravenously, iDPP nanoparticles could deliver DNA to the subcutaneous melanoma targetedly. Based on in vivo mouse xenograft model, iDPP/LACTB nanocomplexes could effectively inhibit tumor proliferation and induce tumor apoptosis, thus significantly inhibiting melanoma growth (tumor inhibition rate is about 68%) in the subcutaneous B16-F10 melanoma model.Conclusion: The downregulated LACTB might be a potential target for melanoma therapy. The iDPP/LACTB nanocomplexes could inhibit the growth of the mouse melanoma without obvious side effects, which provide a new option for melanoma gene therapy research.Keywords: melanoma, LACTB, nanocomplexes, gene therapy

Meteorites represent the only samples available for study on Earth of a number of planetary bodies. The minerals within meteorites therefore hold the key to addressing numerous questions about our solar system. Of particular interest is the Ca-phosphate mineral merrillite, the anhydrous end-member of the merrillite-whitlockite solid solution series. For example, the anhydrous nature of merrillite in Martian meteorites has been interpreted as evidence of water-limited late-stage Martian melts. However, recent research on apatite in the same meteorites suggests higher water content in melts. One complication of using meteorites rather than direct samples is the shock compression all meteorites have experienced, which can alter meteorite mineralogy. Here we show whitlockite transformation into merrillite by shock-compression levels relevant to meteorites, including Martian meteorites. The results open the possibility that at least part of meteoritic merrillite may have originally been H+-bearing whitlockite with implications for interpreting meteorites and the need for future sample return.

Yingyi Zhang,1 Libin Ren,1 Min Ren,2 Hua Yang,1 Kunmeng Li,1 Hongliang Cong,1 Zhigang Guo3 1Department of Cardiology, Tianjin Chest Hospital, Tianjin, 300222, People’s Republic of China; 2Tianjin Cardiovascular Institute, Tianjin, 300222, People’s Republic of China; 3Department of Cardiac Surgery, Tianjin Chest Hospital, Tianjin, 300222, People’s Republic of ChinaCorrespondence: Hongliang CongDepartment of Cardiology, Tianjin Chest Hospital, No. 261 of Taierzhuang South Road, Jinnan District, Tianjin, 300222, People’s Republic of ChinaTel +86 13702102871Email chlcong@163.comZhigang GuoDepartment of Cardiac Surgery, Tianjin Chest Hospital, No. 261 of Taierzhuang South Road, Jinnan District, Tianjin, 300222, People’s Republic of ChinaTel +86 13821002900Email zgguohosp@163.comObjective: This study aims to investigate the correlation between triglyceride–glucose index (TyG) and the risk of cardiovascular disease (CVD).Methods: A total of 102,061 permanent residents of Tianjin, China, aged 35– 75 years were surveyed. A questionnaire, physical examination, and blood tests for biochemical markers were conducted for all subjects. The risk of CVD was judged based on the results, identifying the population with a high risk of CVD. TyG was calculated for all subjects who were then grouped into TyG quartiles. The correlation between TyG and the detection rate of subjects with a high risk of CVD was analyzed using the chi-square test and Pearson’s correlation analysis. The cut-off points and the magnitude of the predictive effect of TyG in determining a high risk of CVD were identified by calculating the TyG through analysis of the receiver operator characteristic (ROC) curve.Results: The surveyed population consisted of 39,598 males (38.8%) and 62,463 females (61.2%). The average age was 55.84 ± 10.27 years. A statistically significant difference in the incidence of a high CVD risk between subjects in the four groups divided by the TyG levels was identified (p < 0.01). Pearson’s correlation analysis showed that TyG was correlated with all risk factors for CVD (p < 0.01). The maximum Youden’s J statistic for determining the high risk of CVD was found at a TyG of 9.04 (specificity 0.575, sensitivity 0.754). The area under the ROC curve was 0.780 (confidence interval [CI]: 0.777, 0.783, p < 0.01).Conclusion: TyG index is closely related to the aggregation of cardiovascular risk factors and is correlated with the judgment results of the screening population’s high risk of CVD, suggesting that more attention should be paid to the identification and control of multiple risk factors in the population with significantly elevated TyG.Keywords: triglyceride–glucose index, cardiovascular disease, risk, insulin resistance

Huan Gao,1 Tao Tian,1 Suoni Li,2 Yinbin Zhang,3 Xiao Fu,1 Xiaoqiang Zheng,1 Na Liu,1 Aimin Jiang,1 Mengdi Ren,1 Xiaoni Zhang,1 Xuan Liang,1 Zhiping Ruan,1 Zhimin Geng,4,* Yu Yao1,* 1Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Department of Medical Oncology, Tumor Hospital of Shaanxi, Xi’an, People’s Republic of China; 3Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 4Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yu YaoDepartment of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an, Shaanxi 710061, People’s Republic of ChinaTel/Fax +86-29-85323422Email 13572101611@163.comZhimin GengDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an, Shaanxi 710061, People’s Republic of ChinaTel/Fax +86-29-85323893Email gengzhimin@mail.xjtu.edu.cnPurpose: Biliary tract cancers (BTCs) have a poor overall prognosis, as patients who underwent curative surgery frequently experience disease recurrence. At present, there is a paucity of well-documented adjuvant chemotherapy regimen. This study aimed to assess whether gemcitabine plus platinum or S-1 adjuvant chemotherapy have different impact on relapse-free survival (RFS).Patients and Methods: We selected patients undergoing radical biliary tract cancer surgery, pathologically confirmed adenocarcinoma and received gemcitabine plus platinum (cisplatin or oxaliplatin) or S-1 adjuvant chemotherapy from September 2013 to May 2020. The primary study endpoint was RFS. The secondary endpoint was safety.Results: Overall 136 patients were enrolled. The median follow-up was 32.3 months and the median RFS was 17.0 months (95% CI 8.9– 25.1). The median RFS was 14.1 months (95% CI 6.7– 21.5) in gemcitabine plus platinum group and 33.0 months (95% CI 9.3– 56.7) in gemcitabine plus S-1 (GS) group, a non-significant difference both in univariate (P=0.092) and in multivariate analysis (P=0.058). Lymph node status (N- vs N+: HR=0.477, 95% CI 0.285– 0.799; P=0.005) and chemotherapy cycles (< 6 vs 6– 8: HR=1.828, 95% CI 1.117– 2.993; P=0.016) were independent impact factors for RFS. GS group had lower incidence of adverse reactions.Conclusion: Compared with gemcitabine plus platinum, GS regimen has a tendency to obtain longer RFS (although there is no statistically significant difference) and less toxic. GS regimen has the potential to be investigated as a standard regimen for adjuvant chemotherapy.Keywords: biliary tract cancer, adjuvant chemotherapy, gemcitabine, platinum, S-1

Feng Qiu,1,* Kunyu Wang,1,* Tingting Li,2 Dandan Song,3 Zhiwei Wang,1 Hailing Zhang,4 Jianguo Liu,1 Ming Ren,5 Xiaokun Qi1 1Department of Neurology, Sixth Medical Center of Chinese PLA General Hospital, Beijing, 100048, People’s Republic of China; 2Department of Gastroenterology, Second Medical Center of Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 3Department of Medicine, Beijing Northern Hospital of China North Industries Group Corporation, Beijing 100089, People’s Republic of China; 4Department of Neurology, Changhai Hospital, Shanghai 200433, People’s Republic of China; 5Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Beijing 100191, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaokun QiDepartment of Neurology, Sixth Medical Center of PLA General Hospital, 6 Fucheng Road, Haidian District, Beijing 100048, People’s Republic of ChinaTel +86 139 1079 7081Email bjqxk@sina.com Ming RenBeijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, 37 Xueyuan Road, Haidian District, Beijing 100191, People’s Republic of ChinaTel +86 139 1079 7081Email mren201017@hotmail.comBackground: The differential diagnosis of Parkinson’s disease (PD) with multiple-system atrophy (MSA) is difficult because of their similarity in symptoms and signs. The objective of this study was to investigate the value of external anal-sphincter electromyography (EAS-EMG) and urethral-sphincter electromyography (US-EMG) in differentiating MSA from PD.Methods: A total of 201 patients, — 101 MSA and 100 PD — were recruited in this study. Average duration and amplitude of motor unit potentials (MUPs), percentage of polyphasic MUPs, amplitude during strong contractions, and recruitment patterns during maximal voluntary contractions were recorded and analyzed to assess diagnostic efficiency of EAS-EMG and US-EMG for MSA.Results: Significant differences in average MUP duration and recruitment patterns during maximal voluntary contractions were found between patients with MSA and patients with PD using both EAS-EMG (P

Li Qiao1,2, Chunjiang Yu,1 Hongwei Zhang,1 Mingshan Zhang,1 Yanming Qu,1 Ming Ren,1 Chunyu Gu,1 Haoran Wang11Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Neurosurgery, Gansu Provincial Hospital, Lanzhou, Gansu Province, People’s Republic of ChinaPurpose: The relationship of clinical results and survival analysis of operative patients with petroclival meningioma (PCM) was studied.Patients and methods: Data from a total of 176 PCM patients receiving surgical resection were retrospectively collected. Follow-up was conducted through outpatient review by reexamination telephone calls and letters. Clinical outcomes, survival, and Karnofsky Performance Scale (KPS) data were analyzed.Results: Seventy-two percent of patients (127/176) received only surgery, 8.5% (15/176) received surgery and adjuvant radiation therapy (RT) (surgery + RT), and 19.3% (34/176) received surgery and adjuvant gamma knife surgery (GKS) (surgery + GKS). Gross total resection (GTR) was performed in 34.7% of patients (61/176), subtotal resection (STR) in 58.0% (102/176), and partial resection (PR) in 7.4% (13/176). Recent follow-up KPS was higher than preoperative (80 vs 70, P

This study aimed to compare the efficacy and safety of oral and transdermal estradiol in alleviating menopausal symptoms. A total of 257 recently menopausal women were randomized into two groups. The t-E2 group received transdermal estradiol (2.5 g per day) (n = 128) and the o-E2V group received oral estradiol valerate (2 mg per day) (n = 129) for 24 weeks; both groups received micronized progesterone (200 mg per day). The primary outcome measure is the change in the modified Kupperman Menopausal Index (KMI) after 24 weeks of treatment. Menopausal symptoms were recorded at screening and at 4, 12 and 24 weeks using both the KMI and the Menopause Rating Scale (MRS). Significant amelioration was observed by KMI and MRS scores for both groups after treatment (p < 0.001). The mean KMI scores showed no difference between the two groups. The mean MRS scores were similar between the two groups at baseline and after 4 weeks of treatment. The results showed statistical differences after 12 weeks and 24 weeks of treatment (p = 0.005 and p = 0.011). Both the after-treatment scores minus the baseline scores of KMI and MRS and the incidence of adverse effects showed no difference between the two groups. This study shows that both transdermal and oral estradiol are effective in relieving menopausal symptoms, with little difference in treatment efficacy and safety. ChiCTR2300073146 [ABSTRACT FROM AUTHOR]

Heng-Cong Luo,1,2,* Na Li,1,* Li Yan,1 Kai-jin Mai,3 Kan Sun,1 Wei Wang,1 Guo-Juan Lao,1 Chuan Yang,1 Li-Ming Zhang,3 Meng Ren1 1Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Medical Research Center, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Department of Endocrinology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 3School of Materials Science and Engineering, School of Chemistry, Sun Yat-Sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Several biological barriers must be overcome to achieve efficient nonviral gene delivery. These barriers include target cell uptake, lysosomal degradation, and dissociation from the carrier. In this study, we compared the differences in the uptake mechanism of cationic, star-shaped polymer/MMP-9siRNA complexes (β-CD-(D3)7/MMP-9siRNA complexes: polyplexes) and commercial liposome/MMP-9siRNA complexes (Lipofectamine® 2000/MMP-9siRNA complexes: liposomes). The uptake pathway and transfection efficiency of the polyplexes and liposomes were determined by fluorescence microscopy, flow cytometry, and reverse transcriptase-polymerase chain reaction. The occurrence of intracellular processing was assessed by confocal laser scanning microscopy. Endosomal acidification inhibitors were used to explore the endosomal escape mechanisms of the polyplexes and lysosomes. We concluded that the polyplexes were internalized by non-caveolae- and non-clathrin-mediated pathways, with no lysosomal trafficking, thereby inducing successful transfection, while the majority of liposomes were internalized by clathrin-dependent endocytosis (CDE), caveolae-mediated endocytosis, and macropinocytosis, and only CDE induced successful transfection. Liposomes might escape more quickly than polyplexes, and the digestion effect of acidic organelles on liposomes was faint compared to the polyplexes, although both complexes escaped from endolysosomes via the proton sponge mechanism. This may be the key aspect that leads to the lower transfection efficiency of the β-CD-(D3)7/MMP-9siRNA complexes. The present study may offer some insights for the rational design of novel delivery systems with increased transfection efficiency but decreased toxicity. Keywords: β-CD-(D3)7, liposome, endocytosis, endolysosomal escape, intracellular trafficking