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Ganzhe Xu,1 Guoyu Dai,2 Zhongli Huang,3 Qiunong Guan,2 Caigan Du,2 Xiaoming Xu4 1Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 2Department of Biomedical Engineering, Guoke Ningbo Life Science and Health Industry Research Institute, Ningbo, Zhejiang, People’s Republic of China; 3Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4Department of Urology, Ningbo No. 2 Hospital, Ningbo, Zhejiang, People’s Republic of ChinaCorrespondence: Caigan Du, Department of Biomedical Engineering, Guoke Ningbo Life Science and Health Industry Research Institute, Ningbo, Zhejiang, People’s Republic of China, Email ducaigan@ucas.ac.cn Xiaoming Xu, Department of Urology, Ningbo No. 2 hospital, Ningbo, Zhejiang, People’s Republic of China, Email xiaomingxu6@sohu.comAbstract: Benign prostatic hyperplasia (BPH) mainly causes lower urinary tract symptoms in ageing men, but its exact etiology and pathogenesis have not been established. The objective of this review was to design an update on the advances of human BPH research. We undertook a literature search for identifying studies of the roles of sex hormones (androgens and estrogens) in the onset and development of human BPH using the Pubmed database. In literature, many studies have indicated that ageing and obesity are the factors for preceding the onset of BPH. No evidence for the role of testosterone (T) or dihydrotestosterone (DHT) is found in BPH initiation. Since BPH exclusively occurs in the transitional zone (TZ) surrounding the urethra, it is postulated that years of exposure to uncharacterized urinary toxins could disrupt the homeostasis of the stroma and/or epithelium of this prostatic zone that are typically occurring in ageing men. After cellular damage and subsequent inflammation generated, the intraprostatic DHT produced mainly from T by 5α-reductase promotes BPH development. Further, estrogens could take part in the nodular proliferation of stromal cells in some BPH patients. The confounding of BPH may attenuate the development of prostate tumor in the TZ. In conclusion, evidence in literature suggests that androgens are not etiological factors for BPH, and intraprostatic DHT along with chronic inflammation are mainly responsible for nodular proliferation of stromal and/or epithelial cells in prostatic TZ. The urinary factors for the etiology of BPH and BPH as a prediction of PCa progression still need further investigation.Keywords: benign prostatic hyperplasia, tissue homeostasis, etiology, nodular proliferation, stroma, epithelium, androgens, steroid sex hormones

Xinyi Hong,1,* Shanhu Qiu,2,* Xia Wu,3 Sizhen Chen,4 Xiaoxiang Chen,5 Bei Zhang,6 Aiqin He,3 Yun Xu,7 Jianqing Wang,8 Yingchun Gao,9 Xizhong Xu,10 Li Sun,11 Yang Zhang,12 Libing Xiang,13 Jundong Zhou,14 Qun Guan,15 Yanling Zhu,16 Haiyan Liu,17 Hao Xu,18 Ying Zhou,19 Bingwei Chen,4 Yang Shen1 1Department of Obstetrics and Gynecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, People’s Republic of China; 2Department of General Practice, Zhongda Hospital, Institute of Diabetes, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 3Department of Gynecological Oncology, Tumor Hospital Affiliated to Nantong University, Nantong, Jiangsu, People’s Republic of China; 4Department of Epidemiology and Biostatistics, School of Public Health, Southeast University, Nanjing, People’s Republic of China; 5Department of Gynecological Oncology, Jiangsu Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 6Department of Obstetrics and Gynecology, Xuzhou Central Hospital, Xuzhou, People’s Republic of China; 7Department of Obstetrics and Gynecology, The First People’s Hospital of Changzhou, Changzhou, People’s Republic of China; 8Department of Obstetrics and Gynecology, The Yancheng Clinical College of Xuzhou Medical University, The First People’s Hospital of Yancheng, Yancheng, People’s Republic of China; 9Department of Obstetrics and Gynecology, Huai’an First People’s Hospital, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huai’an, People’s Republic of China; 10Department of Obstetrics and Gynecology, The Affiliated Hospital of Jiangnan University, Wuxi, People’s Republic of China; 11Department of Gynecological Oncology, Qingdao Central Hospital, The Second Affiliated Hospital of Medical College of Qingdao University, Qingdao, People’s Republic of China; 12Gynecology Department, The First People’s Hospital of Lianyungang, Lianyungang, People’s Republic of China; 13Ovarian Cancer Program, Department of Gynecologic Oncology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 14Radio-oncology Department, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, People’s Republic of China; 15Gynecology Department, Jiangsu Province Hospital of Chinese Medicine, Nanjing, People’s Republic of China; 16Gynecology Department, Xuzhou Cancer Hospital, Xuzhou, People’s Republic of China; 17Department of Obstetrics and Gynecology, Affiliated Hospital of Yangzhou University, Yangzhou, People’s Republic of China; 18Gynecology Department, Huangshi Love & Health Hospital Affiliated to Hubei Polytechnic University, Huangshi, People’s Republic of China; 19The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yang Shen, Department of Obstetrics and Gynecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, People’s Republic of China, Tel +86 15366166769, Fax +86 +25 83272111, Email shenyang@seu.edu.cn Bingwei Chen, Department of Epidemiology and Biostatistics, School of Public Health, Southeast University, Nanjing, 210009, People’s Republic of China, Email drchenbw@126.comPurpose: Anlotinib is a novel oral small-molecule multi-target tyrosine kinase inhibitor that has been approved for treating non-small cell lung cancer. However, its efficacy and safety among patients with advanced gynecological cancer have not been comprehensively evaluated. We conducted this study to address this issue in the real-world setting.Patients and Methods: Data from patients treated with Anlotinib for persistent, recurrent or metastatic gynecological cancer were collected from 17 centers from August 2018. The database lock-time was on March 2022. Anlotinib was administered orally on days 1– 14 every 3 weeks until disease progression, severe toxicity occurred, or death. In this study, disease-specific advanced gynecological cancer was mainly referred to cervical, endometrial, and ovarian cancer. The outcomes included objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS).Results: A total of 249 patients were analyzed, with a median follow-up of 14.5 months. The overall ORR and DCR were 28.1% [95% confidence interval (CI) 22.6% to 34.1%] and 80.7% (95% CI 75.3% to 85.4%), respectively. Specifically, the ORR varied from 19.7% to 34.4% and the DCR differed from 81.7% to 90.0% in disease-specific advanced gynecological cancer. The median PFS was 6.1 months and ranged from 5.6 to 10.0 months in the overall and disease-specific advanced gynecological cancer, respectively. Larger cumulative dosage of Anlotinib (> 700 mg) was in general associated with longer PFS in the overall and disease-specific advanced gynecological cancer. The most common adverse event related to Anlotinib treatment was pain/arthralgia (18.3%).Conclusion: In conclusion, Anlotinib holds promise in treating patients with advanced gynecological cancer including its disease-specific types, with reasonable efficacy and tolerable safety.Keywords: molecular-targeting therapy, angiogenesis inhibitors, real-world study

Yajie Ding,1,&ast; Zongzhe Tang,1,&ast; Ru Zhang,1 Mengting Zhang,1 Qing Guan,1 Liuxin Zhang,2 Hongliang Wang,3 Yue Chen,1 Wei Zhang,4 Jie Wang1 1Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2The Nethersole School of Nursing, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong (SAR), People’s Republic of China; 3Department of General Practice, Ninghai Road Community Health Service Center, Nanjing, Jiangsu, People’s Republic of China; 4Department of Epidemiology, Shanghai Cancer Institute, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Wang, Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, 101 Longmian Avenue, Nanjing, Jiangsu, 211166, People’s Republic of China, Tel +86-25-86869557, Fax +86-25-86868501, Email wangjienjmu@126.comPurpose: Protein kinase B (PKB/AKT) has shown a high profile in the research of metabolic diseases. This research sought to determine whether the AKT1 gene’s single nucleotide polymorphisms (SNPs) and the risk of developing non-alcoholic fatty liver disease (NAFLD) were related.Patients and Methods: Recruited in this case–control study were 2693 subjects, including 815 with NAFLD and 1878 without NAFLD. Three SNPs of AKT1 (rs2494732, rs2494752 and rs1130233) were genotyped. To examine the correlation between SNPs and NAFLD susceptibility, logistic regression was performed.Results: After adjusting for sex, age, triglyceride and glucose, AKT1 rs2494732-C (all P < 0.05 in co-dominant model, dominant model and additive model) and rs2494752-G (P < 0.05 in co-dominant model) were linked to a lower risk of NAFLD. The combined effect of both SNPs on NAFLD risk was statistically significant, showing a dose dependence (Ptrend = 0.010). Sex, body mass index, hypertension, hyperglycemia, hypertriglyceridemia, high-density lipoprotein-cholesterol, alanine aminotransferase, and beneficial alleles were all significant predictors of NAFLD risk (all P < 0.05). The prediction model achieved good discrimination, with an area under the receiver operating characteristic curve of 0.779. The Hosmer–Lemeshow test suggested an inadequate calibration of the model (χ2 = 21.073, P = 0.007).Conclusion: AKT1 rs2494732 and rs2494752 may be related to Chinese NAFLD susceptibility. The prediction model combining both SNPs with clinical factors displays a strong ability to discriminate NAFLD patients. Both SNPs may be exploited to design new models for early screening of NAFLD high-risk population.Graphical Abstract: Keywords: NAFLD, susceptibility, AKT1 gene, polymorphism, risk screening

Dong Xi,1 Mengying Xu,1 Meiwen Han,1 Qianting Guan,1 Qinghao Guo,1 Fangfei Yan,1 Junxia Yao,2 Qin Ning1 1Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China; 2Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of ChinaCorrespondence: Junxia Yao, Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China, Tel +86-18502711578, Email yaojunxia@163.com Qin Ning, Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Huazhong University of Science and Technology, Wuhan, People’s Republic of China, Tel/Fax +86-27-83665959, Email qning@vip.sina.comPurpose: A retrospective analysis of hepatocellular carcinoma (HCC) patients treated with transarterial chemoembolization (TACE) to identify risk factors was conducted, and a novel predictive nomogram model was constructed.Patients and Methods: A total of 346 HCC patients who underwent TACE as initial treatment were retrospectively included, of which 208 were randomly allocated to the derivation cohort and 138 were allocated to the validation cohort. Progression-free survival (PFS) was used as the follow-up endpoint according to mRECIST. Kaplan‒Meier analysis and the Cox regression model screened out some indicators associated with short-term prognosis, and R language was further used to construct a nomogram model. The nomogram was compared with the classical BCLC staging system.Results: The independent predictors affecting PFS in HCC patients undergoing TACE included the following: 1. Baseline indicators: age (P=0.013), albumin-bilirubin (ALBI) grade (grade 2 vs grade 1, P=0.029; grade 3 vs grade 1, P< 0.001), and portal vein tumour thrombus (PVTT, P< 0.001); 2. Indicators at the 1-month follow-up: Neutrophil To Lymphocyte Ratio (NLR, P=0.032) and changes in alpha-fetoprotein (AFP, P< 0.05) and des-γ-carboxy prothrombin (DCP, P< 0.001); and 3. Cumulative treatment numbers of TACE in 6 months (P=0.007). In the derivation cohort, the calibration curve of the nomogram showed a high consistency between the predicted and actual PFS probability, and the nomogram outperformed the BCLC staging system (P=0.004). This result was also confirmed in the validation cohort (P=0.012).Conclusion: The constructed nomogram was suggested to have good predictive efficacy and could be used as a complementary assessment to predict the survival and prognosis of HCC patients treated with TACE.Keywords: primary liver cancer, transarterial chemoembolization, progression-free survival, modified response evaluation criteria in solid tumours, prognosis, nomogram

Ru Zhang,1,&ast; Qing Guan,1,&ast; Mengting Zhang,1 Yajie Ding,1 Zongzhe Tang,1 Hongliang Wang,2 Wei Zhang,3 Yue Chen,1 Rong Jiang,1 Yan Cui,1 Jie Wang1 1School of Nursing, Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of General Practice, Community Health Service Center, Nanjing, People’s Republic of China; 3Department of Epidemiology, Shanghai Cancer Institute, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Wang; Yan Cui, School of Nursing, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, Jiangsu, 211166, People’s Republic of China, Tel +86-25-86869557, Email wangjienjmu@126.com; cyan_njmu@163.comObjective: Insulin resistance (IR) is a major factor involved in the pathogenesis of metabolic dysfunction-associated fatty liver disease (MAFLD). Triglyceride-glucose (TyG) index, an easily detected surrogate marker of IR, has not been explored sufficiently on its relationship with incident MAFLD risk. This study sought to investigate the association of baseline TyG index with the risk of MAFLD in a Chinese cohort.Methods: This health check-up cohort was constructed with eligible 2056 Chinese from a community. The TyG index was calculated as ln (fasting triglyceride [mg/dL]×fasting glucose [mg/dL]/2). Cox proportion hazard models were used to evaluate the longitudinal association between baseline TyG index and the risk of MAFLD.Results: During an average follow-up of 2.5 ± 0.5 years, about 12.8% of the subjects developed MAFLD, and the incidence of MAFLD trended to increase with the quartile TyG index (Ptrend < 0.05). After adjusting for all confounders, TyG index was independently correlated with the risk of incident MAFLD (HR = 1.784, 95% CI = 1.383– 2.302, P < 0.001), and the risk of MAFLD in the highest quartile of TyG index was two times higher than that in the lowest quartile (95% CI = 1.377– 2.992, P = 0.001). The restricted cubic spline analysis showed that the relationship between TyG index and the risk of MAFLD was linear in males (P for total < 0.001; P for non-linearity = 0.746), but nonlinear in females (P for non-linearity = 0.040).Conclusion: A high baseline TyG index was independently associated with a high risk of incident MAFLD, and we might develop the strategy of MAFLD prevention based on the TyG index.Keywords: triglyceride-glucose index, metabolic dysfunction-associated fatty liver disease, insulin resistance, risk, cohort study

Xiaoyan Huang,1– 3,* Yingyi Kuang,1– 3,* Qiyuan Qin,1– 3,* Miaomiao Zhu,1– 3 Yanjiong He,1– 3 Zixu Yuan,1– 3 Huaiming Wang,1– 3 Qinghua Zhong,1,2,4 Qi Guan,1– 3 Hui Wang,1– 3,* Tenghui Ma,1– 3,* Xinjuan Fan1,2,5,* 1Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, People’s Republic of China; 3Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, People’s Republic of China; 4Department of Endoscopic Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, People’s Republic of China; 5Department of Pathology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinjuan FanDepartment of Pathology, Sun Yat-sen University Sixth Affiliated Hospital, No. 26 Yuancun Erheng Road, Guangzhou, 510655, Guangdong, People’s Republic of ChinaFax +86 20-38737621Email fanxjuan@mail.sysu.edu.cnTenghui MaDepartment of Colorectal Surgery, Sun Yat-sen University Sixth Affiliated Hospital, No. 26 Yuancun Erheng Road, Guangzhou, 510655, Guangdong, People’s Republic of ChinaFax +86 20-38737621Email matengh@mail.sysu.edu.cnBackground: Chronic radiation intestinal injury (CRII) is the most common complication after pelvic malignancy radiation. Once hemorrhagic CRII patients suffer from lower extremity deep venous thrombosis (LE-DVT), hemostasis and anticoagulation therapy will be adopted simultaneously, but the treatment strategy is a paradox, as the condition is extremely intractable and serious. The aim of this study was to investigate the prevalence of and risk factors for LE-DVT in CRII patients and explore the treatment of hemorrhagic CRII patients with LE-DVT.Methods: This was a retrospective study, and a total of 608 hospitalized CRII patients after pelvic radiotherapy were included from November 2011 to October 2018. Univariate and multivariate analyses were conducted to investigate the potential risk factors for LE-DVT in CRII patients. Furthermore, the treatment of hemorrhagic CRII patients with LE-DVT was explored.Results: Among the CRII patients, 94 (15.5%) were with suspicious symptoms of LE-DVT in the lower limbs, and 32 (5.3%) were diagnosed with LE-DVT. Among the patients with LE-DVT, 65.6% (21/32) had bleeding simultaneously, and 29 (90.6%) had anemia with 24 (75.0%) having moderate to severe anemia. Multivariate analysis showed that a recent surgical history (≤ 6 months) (OR = 5.761, 95% CI: 2.506∼ 13.246, p < 0.001), tumor recurrence or metastasis (OR = 3.049, 95% CI: 1.398∼ 6.648, p = 0.005) and the hemoglobin (Hb) level (OR = 0.960, 95% CI: 0.942∼ 0.979, p < 0.001) were significantly associated with the development of LE-DVT. ROC curve analysis showed that the AUC of the merged risk score of the independent risk factors was 0.822 (95% CI: 0.789∼ 0.852), and the optimal Hb cutoff was 82.5 g/L. After colostomy, obvious bleeding remission was rapidly found in 84.6% of hemorrhagic CRII patients with LE-DVT.Conclusion: The prevalence of LE-DVT in hospitalized CRII patients was 5.3%. A recent surgical history, tumor recurrence or metastasis and a lower Hb level were independently associated with LE-DVT development in CRII patients. Colostomy could be a good choice for intractable hemorrhagic CRII patients with LE-DVT.Keywords: chronic radiation intestinal injury, lower extremity deep venous thrombosis, pelvic malignancy radiation, risk factor, colostomy, hemorrhagic

Luna Liu,1,2 Shuang Liu,1,2 Qianmei Song,1,2 Dandan Luo,1,2 Yu Su,1,2 Xiangyu Qi,1,2 Qian Wang,3 Jing Ning,1,2 Youyuan Lv,1,2 Qingbo Guan1,2,4 1Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, People’s Republic of China; 2Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, Shandong 250021, People’s Republic of China; 3Department of Ultrasound, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, People’s Republic of China; 4Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, People’s Republic of ChinaCorrespondence: Qingbo Guan Tel +86-531-68776375Fax +86-531-87068707Email doctorguanqingbo@163.comObjective: Obesity and metabolic syndrome have been reported to exert an impact on the male reproductive system with decreasing levels of serum total testosterone (TT); however, the effect of different metabolic obesity phenotypes on testosterone has been poorly studied. We aimed to evaluate the association of metabolic obesity phenotypes and total testosterone levels in a Chinese male population.Methods: We performed a retrospective study based on an epidemiological investigation, a total of 4,081 male individuals aged from 40– 75 years old were recruited. The population was classified as metabolically healthy normal weight (MHNW), metabolically healthy overweight/obese (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy overweight/obese (MUO) according to normal weight (BMI< 25.0) and overweight/obesity (BMI≥ 25.0) with or without metabolic syndrome.Results: We collected 563 hypotestosteronemia among 4,081 male individuals. The odds ratios (ORs) (95% CIs) of hypotestosteronemia in obesity and metabolic syndrome were 3.072 (2.414– 3.911) and 3.294 (2.631– 4.125), respectively, after adjusting for age, luteinizing hormone, smoking status, and alcohol consumption. Compared to the MHNW group, male subjects in MHO, MUNW, and MUO groups had decreased serum TT levels. Additionally, the MUO group had a lowest concentration of serum TT and a highest proportion of hypotestosteronemia. There was no significant difference of TT levels between the MHO and MUNW groups.Conclusion: Obesity and metabolic syndrome are independent risk factors of hypotestosteronemia in Chinese male populations. Our study also suggested that individuals with MHO, MUNW, and MUO have a higher risk of developing hypotestosteronemia.Keywords: metabolic obesity phenotypes, testosterone, metabolically healthy overweight/obese, metabolically unhealthy normal weight, hypotestosteronemia

Yanping Wang,1 Congying Xu,1 Liping Zhai,1 Xudong Lu,1 Xiaoqiang Wu,1 Yahui Yi,2 Ziyun Liu,1 Qiaobing Guan,1 Xiaoling Zhang1 1Department of Neurology, the Second Hospital of Jiaxing City, Jiaxing, Zhejiang, 2Department of Radiology, the Second Hospital of Jiaxing City, Jiaxing, Zhejiang, China Abstract: Resting-state functional magnetic resonance imaging (R-fMRI) signals are spatiotemporally organized. R-fMRI studies in patients with classic trigeminal neuralgia (CTN) have suggested alterations in functional connectivity. However, far less attention has been given to investigations of the local oscillations and their frequency-specific changes in these patients. The objective of this study was to address this issue in patients with CTN. R-fMRI data from 17 patients with CTN and 19 age- and gender-matched healthy controls (HCs) were analyzed using amplitude of low-frequency fluctuation (ALFF). The ALFF was computed across different frequencies (slow-4: 0.027–0.073 Hz; slow-5: 0.01–0.027 Hz; and typical band: 0.01–0.08 Hz) in patients with CTN compared to HCs. In the typical band, patients with CTN showed increases of ALFF in bilateral temporal, occipital, and left middle frontal regions and in the left middle cingulate gyrus, as well as decreases of ALFF in the right inferior temporal region and in regions (medial prefrontal regions) of default mode network. These significant group differences were identified in different sub-bands, with greater brainstem findings in higher frequencies (slow-4) and extensive default mode network and right postparietal results in lower frequencies (slow-5). Furthermore, significant relationships were found between subjective pain ratings and both amplitudes of higher frequency (slow-4) blood oxygen level-dependent (BOLD) signals in pain localization brain regions and lower frequencies (slow-5) in pain signaling/modulating brain regions in the patients, and decreased ALFF within the prefrontal regions was significantly correlated with pain duration in the patients. This result supports our hypothesis that trigeminal pain has a characteristic spatiotemporal distribution of low-frequency BOLD signals. These findings might contribute to a better understanding of the impact of CTN on the brain’s intrinsic architecture. Future studies should take the frequencies into account when measuring brain resting BOLD signals of patients with CTN. Keywords: frequency dependent, resting fMRI, slow-4, slow-5

Yanping Wang,1,2 Xiaoling Zhang,2 Qiaobing Guan,2 Lihong Wan,2 Yahui Yi,2 Chun-Feng Liu1 1Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 2Department of Neurology, The Second Hospital of Jiaxing City, Jiaxing, Zhejiang Province, People’s Republic of China Abstract: The pathophysiology of idiopathic trigeminal neuralgia (ITN) has conventionally been thought to be induced by neurovascular compression theory. Recent structural brain imaging evidence has suggested an additional central component for ITN pathophysiology. However, far less attention has been given to investigations of the basis of abnormal resting-state brain activity in these patients. The objective of this study was to investigate local brain activity in patients with ITN and its correlation with clinical variables of pain. Resting-state functional magnetic resonance imaging data from 17 patients with ITN and 19 age- and sex-matched healthy controls were analyzed using regional homogeneity (ReHo) analysis, which is a data-driven approach used to measure the regional synchronization of spontaneous brain activity. Patients with ITN had decreased ReHo in the left amygdala, right parahippocampal gyrus, and left cerebellum and increased ReHo in the right inferior temporal gyrus, right thalamus, right inferior parietal lobule, and left postcentral gyrus (corrected). Furthermore, the increase in ReHo in the left precentral gyrus was positively correlated with visual analog scale (r=0.54; P=0.002). Our study found abnormal functional homogeneity of intrinsic brain activity in several regions in ITN, suggesting the maladaptivity of the process of daily pain attacks and a central role for the pathophysiology of ITN. Keywords: trigeminal neuralgia, resting fMRI, brain, chronic pain, local connectivity

Xijin Wang,1 Qiang Guan,2 Meihua Wang,1 Liu Yang,1 Jie Bai,1 Zhiqiang Yan,3 Yuhong Zhang,4 Zhenguo Liu11Department of Neurology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 2Department of Neurology, Tongji Hospital, Tongji University, 3Shanghai Laboratory Animal Center, Chinese Academy of Sciences, 4Department of Neurology, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, People’s Republic of ChinaAbstract: Aging is one of the strongest risk factors for Parkinson’s disease (PD). SIRT2 has been implicated in the aging process. It is pertinent to investigate the role of SIRT2 in aging-related dopaminergic neurotoxicity and to develop effective therapeutic strategies for PD through the use of aging animals. In this study, we observed that rotenone induced significant behavior abnormality and striatal dopamine depletion in aging rats, while it did not do so in young rats. No significant change in striatal serotonin level was observed in the aging rats after rotenone administration. There was also aging-related rotenone-induced increase in substantia nigra (SN) SIRT2 expression in the rats. In addition, there was aging-related rotenone-induced SN malondialdehyde (MDA) increase and glutathione (GSH) decrease in the rats. No significant changes in cerebellar SIRT2, MDA, or GSH levels were observed in the aging rats after rotenone administration. Striatal dopamine content was significantly inversely correlated with SN SIRT2 expression in the rats. AK-7 significantly diminished striatal dopamine depletion and improved behavior abnormality in the rotenone-treated aging rats. Furthermore, AK-7 significantly decreased MDA content and increased GSH content in the SN of rotenone-treated aging rats. Finally, the effect of AK-7 on dopaminergic neurons and redox imbalance was supported by the results from primary mesencephalic cultures. Our study helps to elucidate the mechanism for the participation of aging in PD and suggests that SN SIRT2 may be involved in PD neurodegeneration, that AK-7 may be neuroprotective in PD, and that maintaining redox balance may be one of the mechanisms underlying neuroprotection by AK-7. Keywords: Parkinson’s disease, environmental toxin, dopamine, oxidative stress, sirtuin

Xiaobo Wang,1,* Qigang Guan,2,* Wei Chen,3 Xianming Hu,3 Li Li11Department of Hematology, The Second Hospital of Dalian Medical University, Dalian, 2Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, 3Department of Pharmaceutical, Shenyang Institute of Pharmaceutical Industry, Shenyang, People’s Republic of China *These authors contributed equally to this work Background: The objective of this study was to develop a novel polydatin (PLD)-loaded liposome system using the thin film hydration technique.Methods: The delivery system was characterized in terms of morphology, size, zeta potential, encapsulation efficiency, and in vitro release. In addition, a pharmacokinetic study was carried out in rats after oral administration of PLD-loaded liposomes in vivo.Results: Transmission electron microscopy revealed that the PLD-loaded liposomes had a homogeneous size and spherical shape. Dynamic light scattering showed that the PLD-loaded liposomes had a smaller size with a mean value of 80.2±3.7 nm and a polydispersity index of 0.12±0.06. The encapsulation efficiency of the prepared liposomes was 88.4%±3.7%. During the release process, liposome showed two distinct phases. The first was characterized by rapid release during the first 2 hours, which could be related to the release of the drug adsorbed on the surface of liposomes. In the second phase, the release rate slowed down, demonstrating a typical sustained and prolonged drug-release behavior. The release kinetic model for the PLD-loaded liposomes fitted well with the Weibull distribution equation. In vivo, relative oral bioavailability of the encapsulated PLD was 282.9%, ie, significantly enhanced (P

BACKGROUND: Allergic reactions to mosquito bites are an increasing clinical concern. Due to the lack of availability of mosquito salivary allergens, they are underdiagnosed. Here, we reported a newly cloned mosquito Aedes (Ae.) aegypti salivary allergen. METHODS: A cDNA encoding a 30-kDa Ae. aegypti salivary protein, designated Aed a 3, was isolated from an expression library. The full-length cDNA was cloned into a baculovirus expression vector, and recombinant Aed a 3 (rAed a 3) was expressed, purified, and characterized. Skin prick tests with purified rAed a 3 and Ae. aegypti bite tests were performed in 43 volunteers. Serum rAed a 3-specific IgE levels were measured in 28 volunteers. RESULTS: The primary nucleotide sequence, deduced amino acid sequence, and IgE-binding sites of Aed a 3 were identified. rAed a 3-selected antibodies recognized a 30-kDa Ae. aegypti saliva protein. rAed a 3 bound IgE in mosquito-allergic volunteers and the binding could be inhibited by the addition of natural mosquito extract dose dependently. Immediate skin test reactions to rAed a 3 correlated significantly with mosquito bite-induced reactions. Of the bite test-positive volunteers, 32% had a positive rAed a 3 skin test and 46% had specific IgE. No bite test-negative volunteers reacted to rAed a 3 in either the skin tests or the IgE assays, confirming the specificity of the assay. CONCLUSIONS: Aed a 3 that corresponds to the Aegyptin protein is a major mosquito salivary allergen. Its recombinant form has biological activity and is suitable for use in skin tests and specific IgE assays in mosquito-allergic individuals.

Background: Traumatic thoracolumbar spine injuries are associated with significant morbidity and mortality. Targeted for non-spine specialist trauma surgeons, this systematic scoping review aimed to examine literature for up-to-date evidence on presentation, management, and outcomes of thoracolumbar spine injuries in adult trauma patients. Methods: This review was reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. We searched four bibliographic databases: PubMed, EMBASE, Web of Science, and the Cochrane Library. Eligible studies included experimental, observational, and evidence-synthesis articles evaluating patients with thoracic, lumbar, or thoracolumbar spine injury, published in English between January 1, 2010 and January 31, 2021. Studies which focused on animals, cadavers, cohorts with N <30, and pediatric cohorts (age <18 years old), as well as case studies, abstracts, and commentaries were excluded. Results: A total of 2501 studies were screened, of which 326 unique studies were fully text reviewed and twelve aspects of injury management were identified and discussed: injury patterns, determination of injury status and imaging options, considerations in management, and patient quality of life. We found: (1) imaging is a necessary diagnostic tool, (2) no consensus exists for preferred injury characterization scoring systems, (3) operative management should be considered for unstable fractures, decompression, and deformity, and (4) certain patients experience significant burden following injury. Discussion: In this systematic scoping review, we present the most up-to-date information regarding the management of traumatic thoracolumbar spine injuries. This allows non-specialist trauma surgeons to become more familiar with thoracolumbar spine injuries in trauma patients and provides a framework for their management. [ABSTRACT FROM AUTHOR]