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Hanxiang Gong,1,2,* Tao Zhang,1,* Xi Wang,1 Baoxin Chen,3 Baoling Wu,1 Shufang Zhao1 1Faculty of Humanities and Social Sciences, Macao Polytechnic University, Macao, 999078, People’s Republic of China; 2The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510260, People’s Republic of China; 3Pingshan Hospital, Southern Medical University, Shenzhen, Guangdong, 518118, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xi Wang, Faculty of Humanities and Social Sciences, Macao Polytechnic University, Macao, 999078, People’s Republic of China, Tel +86-18029928803, Fax +86-853-28718003, Email xwang@mpu.edu.moPurpose: This study explores regional differences, dynamic evolution, and influencing factors of medical service levels in Guangzhou under the Health China Strategy to provide a basis for improving service quality and reducing disparities.Patients and Methods: An evaluation system was constructed using the entropy weight TOPSIS method. The Dagum Gini coefficient analyzed regional differences, Kernel density estimation assessed service levels’ distribution, and Tobit regression explored influencing factors. Data were collected from the “Guangzhou Statistical Yearbook”, Guangzhou Health Commission reports, and government work reports from 2017 to 2022.Results: The study shows that from 2017 to 2022, there were significant differences in medical service levels among different regions of Guangzhou, with higher service quality in central urban areas compared to remote and peripheral areas. The application of the entropy weight method revealed the importance of indicators such as medical business costs and the number of registered nurses per thousand population in evaluating service quality. According to the Dagum Gini coefficient decomposition method, regional differences in medical services in Guangzhou are the main factor causing uneven overall development quality. Kernel density estimation indicates a bimodal distribution of medical service quality, suggesting heterogeneity in service quality and an increasing trend in low-quality service areas. The Tobit model confirms that factors such as medical institution drug costs, bed occupancy rate, and medical human resources have a positive impact on improving service quality.Conclusion: This study uniquely integrates the entropy weight TOPSIS method, Dagum Gini coefficient decomposition, and Kernel density estimation to dissect regional disparities in Guangzhou’s medical services, offering a novel perspective on healthcare evolution under the Health China Strategy. The findings provide an innovative framework for optimizing resource allocation and enhancing service quality, guiding balanced development across regions.Keywords: Healthcare evaluation, Service quality disparities, Dynamic distribution, Resource optimization, Medical resource allocation

Tuo Han,1,&ast; Ying Li,1,&ast; Jing Xiao,1,&ast; Hong Gong,2 Fuxue Deng,1 Wei Jiang,1 Congxia Wang,1 Fangyao Chen,3 Chunyan Zhang,1 Jie Deng,1 Yan Zhang1 1Department of Cardiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710004, People’s Republic of China; 2Department of Health Management, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710004, People’s Republic of China; 3Department of Epidemiology and Health Statistics, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, 710061, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Zhang; Jie Deng, Email zy1985525@126.com; jie.deng@xjtu.edu.cnBackground: Approximately 10– 20% of individuals with non-alcoholic fatty liver disease (NAFLD) are lean, and the underlying pathophysiology is not yet understood. This study aims to explore the characteristics and the diagnostic value of triglyceride-glucose index (TyG) in early diagnosis of lean NAFLD.Methods: 99 patients with lean NAFLD and 1891 healthy controls were included in the health examination. The characteristics were compared between groups. Restricted cubic spline was utilized to analyze the relationship between TyG index and the risk of lean NAFLD. Logistic regression and receiver operating curve (ROC) were applied to explore the diagnostic value of TyG index for lean NAFLD.Results: Overall, 99 (4.97%) patients had lean NAFLD. Patients with lean NAFLD have significant abnormal glycolipid metabolism and higher TyG index. Restriction cube spline analysis showed a significant dose-response relationship between the TyG index and risk of lean NAFLD. After adjusting for confounders, the relationship remained and the risk of developing lean NAFLD increased 2.99 times for per unit increase of TyG index (95% CI: 1.94, 4.67, P< 0.001). The areas under the ROC of the TyG index for lean NAFLD detection were 0.851 (0.815 to 0.886).Conclusion: The TyG index is positively associated with the risk of developing lean NAFLD and could be a useful marker for early diagnosis of lean NAFLD.Keywords: lean non-alcoholic fatty liver disease, triglyceride-glucose index, insulin resistance

Gongjie Zhang,1 Xinlyu Huang,1 Hanlin Li,1 Huizi Gong,1 Yabin Zhou,2 Fang Liu1 1Department of Dermatology, Venereology and Cosmetology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China; 2Department of Dermatology, Beijing Children’s Hospital, Capital Medical University, National Centre for Children’s Health, Beijing, 100045, People’s Republic of ChinaCorrespondence: Yabin Zhou, Department of Dermatology, Beijing Children’s Hospital, Capital Medical University, National Centre for Children’s Health, No. 56 Nan Lishi Road, Xicheng District, Beijing, 100045, People’s Republic of China, Tel +86 10 59616884, Email chouyabin@163.com Fang Liu, Department of Dermatology, Venereology and Cosmetology, Beijing Chaoyang Hospital, Capital Medical University, No. 8 Gongti Nan Road, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel +86 18611369216, Email roseliufang@qq.comBackground: Hair loss is common in hypothyroidism patients. However, the link with alopecia areata (AA) and androgenetic alopecia (AGA) is unclear. Previous observational studies have presented completely opposite results. This study aims to causally link hypothyroidism with AA and AGA.Methods: A two-sample Mendelian Randomization (MR) study, utilizing data from FinnGen Consortium, investigated the causal link between hypothyroidism and AA and AGA. We employed Inverse Variance Weighted (IVW), MR-Egger, Weighted Median, Simple Mode, and Weighted Mode to assess the risk association.Results: The discovery samples included 13,429 hypothyroidism cases (94,436 controls), 767 alopecia areata cases (394,105 controls), and 220 androgenetic alopecia cases (219,249 controls). MR analysis showed a causal link between hypothyroidism and AA, with significant results from IVW (OR, 1.34; CI, 1.16– 1.56; P = 0.0001), MR-Egger (OR, 1.56; CI, 1.09– 2.23; P = 0.0240), and weighted median (OR, 1.34; CI, 1.06– 1.69; P = 0.0140). However, no clear causal relationship was found between genetically predicted hypothyroidism and AGA risk (p > 0.05).Conclusion: The results show hypothyroidism causally associated with AA onset, but not AGA. These findings address contentious issues in observational studies. Comprehensive thyroid function assessments are crucial for AA patients, emphasizing thorough clinical examinations’ importance.Keywords: hypothyroidism, alopecia areata, androgenetic alopecia, Mendelian randomization study, causality

Xinlyu Huang,1 Pengxiang Zhao,2 Gongjie Zhang,1 Xiangxi Su,1 Hanlin Li,1 Huizi Gong,1 Xuemei Ma,2 Fang Liu1 1Department of Dermatology, Venereology and Cosmetology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2College of Chemistry and Life Science, Beijing University of Technology, Beijing, People’s Republic of ChinaCorrespondence: Fang Liu, Department of Dermatology, Venereology and Cosmetology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China, Email roseliufang@qq.comPurpose: Alopecia significantly affects the appearance and psychology of patients, and pharmacological therapies and hair transplantation are the main treatments for alopecia, but both have limitations. This review aimed to summarize the non-pharmacological therapies that promote hair growth and regeneration.Patients and Methods: This is a non-systematic review. Multiple databases was searched with relevant data published between 1997 and 2024. Searching and screening followed the PRISMA guidelines.Results: Novel therapeutic modalities, such as gas molecules, platelet-rich plasma, laser, and microneedling, can change the microenvironment of hair follicles, activate hair follicle stem cells, and promote hair growth and regeneration.Conclusion: This paper reviews research on the application of non-pharmacological therapies in alopecia treatment and hair regeneration, with a view to providing an important basis for future research on alopecia treatment and the postoperative treatment of patients after hair transplantation.Keywords: alopecia, hair regrowth, non-pharmacologic, gas therapy, regenerative cellular therapy, laser therapy, microneedle therapy

Zhou Zhu,1– 3,&ast; Huizi Gong,4,&ast; Mingjuan Liu,1– 3 Hanlin Zhang,1,2 Leyan Yang,1,2 Xinyi Zhang,5 Heyi Zheng,1,2 Yanfeng Li,6 Mingli Li,7 Jun Li1,2 1Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 3 4+4 Medical Doctor Program, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 4Department of Dermatology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 5Departments of Internal Medicine and Cellular & Molecular Physiology, Yale School of Medicine, New Haven, CT, USA; 6Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 7Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingli Li, Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, People’s Republic of China, Email limingli@pumch.cn Jun Li, Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, People’s Republic of China, Email lijun35@hotmail.comBackground: Tabes dorsalis is a late manifestation of neurosyphilis, characterized by progressive ataxia, lightning pains, loss of proprioception, and urinary incontinence. The absence of a definitive diagnostic standard and the non-specific clinical manifestations have led to a significant rate of misdiagnoses.Methods: Hospitalized patients with tabes dorsalis at Peking Union Medical College Hospital between January 2010 and December 2023 were reviewed.Results: A total of 13 patients were included, with 10 males and 3 females. The median age was 50 years (range, 34– 64). The most frequent initial symptoms were limb numbness (30.8%) and lightning pains (30.8%). Eleven patients (84.6%) received misdiagnoses prior to the final diagnosis. The most frequently observed physical sign was positive Romberg’s sign (84.6%). Notably, Argyll Robertson pupil was presented in 7 subjects (53.8%). Serological tests revealed positive rapid plasma regain (RPR) and Treponema pallidum particle agglutination (TPPA) for all patients. All CSF samples were TPPA-reactive. Intramedullary hyperintensity on T2-weighted imaging of spinal MRI was found in 5 patients (38.5%). All patients received anti-syphilitic treatment, with effective treatment recorded in five cases.Conclusion: This study underscores the importance of neurological symptoms and signs in diagnosing tabes dorsalis. Individuals with progressive ataxia and positive Romberg’s sign should be closely monitored for potential neurosyphilis. Integrating clinical features, laboratory tests, and neuroimaging could reduce misdiagnosis and expedite the initiation of anti-syphilitic therapy.Keywords: tabes dorsalis, neurosyphilis, ataxia, cerebrospinal fluid

Jing Luo,1,2 Yi Luo,2 Maoru Zhao,3 Yulong Liu,2 Jiayin Liu,2 Zhulin Du,2 Hong Gong,2 Lian Wang,2 Jinghui Zhao,2 Xiaqing Wang,2 Zhanjun Gu,3 Wenhui Zhao,1 Tianyao Liu,2 Xiaotang Fan2 1School of Life Sciences, Chongqing University, Chongqing, 401331, People’s Republic of China; 2Department of Military Cognitive Psychology, School of Psychology, Third Military Medical University (Army Medical University), Chongqing, 400038, People’s Republic of China; 3Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, Institute of High Energy Physics and National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing, 100049, People’s Republic of ChinaCorrespondence: Xiaotang Fan; Tianyao Liu, Email fanxiaotang2005@163.com; squall277@163.comBackground: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition that affects social interaction and communication and can cause stereotypic behavior. Fullerenols, a type of carbon nanomaterial known for its neuroprotective properties, have not yet been studied for their potential in treating ASD. We aimed to investigate its role in improving autistic behaviors in BTBR T+Itpr3tf/J (BTBR) mice and its underlying mechanism, which could provide reliable clues for future ASD treatments.Methods: Our research involved treating C57BL/6J (C57) and BTBR mice with either 0.9% NaCl or fullerenols (10 mg/kg) daily for one week at seven weeks of age. We then conducted ASD-related behavioral tests in the eighth week and used RNA-seq to screen for vital pathways in the mouse hippocampus. Additionally, we used real-time quantitative PCR (RT-qPCR) to verify related pathway genes and evaluated the number of stem cells in the hippocampal dentate gyrus (DG) by Immunofluorescence staining.Results: Our findings revealed that fullerenols treatment significantly improved the related ASD-like behaviors of BTBR mice, manifested by enhanced social ability and improved cognitive deficits. Immunofluorescence results showed that fullerenols treatment increased the number of DCX+ and SOX2+/GFAP+ cells in the DG region of BTBR mice, indicating an expanded neural progenitor cell (NPC) pool of BTBR mice. RNA-seq analysis of the mouse hippocampus showed that VEGFA was involved in the rescued hippocampal neurogenesis by fullerenols treatment.Conclusion: In conclusion, our findings suggest that fullerenols treatment improves ASD-like behavior in BTBR mice by upregulating VEGFA, making nanoparticle- fullerenols a promising drug for ASD treatment. Keywords: fullerenols, BTBR, neurogenesis, autism spectrum disorder, hippocampus

Chao Zuo,1 Yi Liu,1 Ziqiang Wang,2 Jing Cheng,1 Dongli Yang,1 Huasong Gong,1 Yu Wang,3 Yongchao Qiao1 1Department of Clinical Laboratory, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, People’s Republic of China; 2Research Center of Clinical Laboratory Science, Bengbu Medical College, Bengbu, Anhui, People’s Republic of China; 3Department of Geriatrics, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, People’s Republic of ChinaCorrespondence: Yongchao Qiao, Department of Clinical Laboratory, Affiliated Hospital of Guilin Medical University, Le Qun Road 15, Guilin, Guangxi, 541001, People’s Republic of China, Email qiaoyc@glmc.edu.cn Yu Wang, Department of Geriatrics, Affiliated Hospital of Guilin Medical University, Le Qun Road 15, Guilin, Guangxi, 541001, People’s Republic of China, Tel +86 773 2822730, Email wangyu101101@163.comIntroduction: This study aimed to investigate the association of Nicotinamide phosphoribosyl transferase (NAMPT) rs61330082 polymorphism with co-morbid hypertension (HTN) and the progression of hypertension in Chinese patients with type 2 diabetes mellitus (T2DM).Methods: A total of 453 T2DM patients were genotyped for the polymorphism of rs61330082 using SNP-scan high-throughput technology. These patients were divided into T2DM group (261 patients) and T2DM combined with hypertension group (T2MH, 192 patients). The T2MH group was further categorized into Grade I, Grade II, and Grade III based on the results of the Hypertension Grade Score. Peripheral blood plasma urea, plasma creatinine, renin-angiotensin system (RAS) indexes, and lipid biochemistry indexes were measured in patients and analyzed in relation to NAMTP polymorphisms.Results: We found that the presence of the NAMPT rs61330082-AA genotype was associated with a significantly increased risk of developing higher-grade hypertension in patients with T2MH. In addition, the A allele of the NAMPT rs61330082 gene displayed more associated in developing a higher grade of hypertension compared to the G allele. Also, the level of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) increased with hypertension grade in the NAMPT rs61330082-GG genotype.Conclusion: NAMPT rs61330082 polymorphism was significantly associated with the progression of hypertension grade in T2MH patients and also affected plasma creatinine and LDL-c levels.Keywords: NAMPT, polymorphism, T2DM, hypertension classification

Yu Sun,&ast; Haixiang Miao,&ast; Han Gong, Yaxin Zhang, Weishi Hong Department of Orthopedics, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Northern Jiangsu People’s Hospital Affiliated to Nanjing University, Yangzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu Sun; Weishi Hong, Email docsunyu@126.com; dochws@163.comBackground: Total hip arthroplasty (THA) has become the first-choice treatment for elderly patients with end-stage hip disease. The high amount of hidden blood loss (HBL) in overweight and obese patients after THA not only affects rapid recovery, but also results in a greater economic burden. We aimed to identify risk factors that contribute to elevated HBL in overweight and obese patients after THA by retrospective analysis, and establish a nomogram prediction model for massive HBL in overweight and obese patients after THA.Methods: A total of 505 overweight and obese patients treated with THA were included and randomly divided into modeling and validation sets according to a 7:3 ratio. The demographic and relevant clinical data of the patients were collected. The independent risk factors affecting HBL after THA in overweight and obese patients were obtained by Pearson, independent sample T-test, and multiple linear regression analyses. R software was used to establish a nomogram prediction model for postoperative HBL, as well as a receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA).Results: HBL was 911± 438 mL, accounting for 79.5± 13.1% of the total perioperative blood loss (1104± 468 mL). A multiple linear regression analysis showed that HBL was associated with necrosis of the femoral head, absence of hypertension, longer operative time, higher preoperative erythrocytes, and higher preoperative D-dimer levels. The areas under the ROC curve (AUC) for the modeling and validation sets were 0.751 and 0.736, respectively, while the slope of the calibration curve was close to 1. The DCA curve demonstrated a better net benefit at a risk of HBL ≥ 1000 ml in both the training and validation groups.Conclusion: HBL was an important component of total blood loss (TBL) after THA in overweight and obese patients. Necrosis of the femoral head, absence of hypertension, longer operative time, higher preoperative erythrocytes, and higher preoperative D-dimer levels were independent risk factors for postoperative HBL in these patients. The predictive model constructed based these data had better discriminatory power and accuracy, and could result in better net benefit for patients.Keywords: total Hip arthroplasty, hidden blood loss, overweight and obese, risk factors, nomogram prediction model

Xing Zhang,1,&ast; Yuanyuan Song,1,&ast; Hongyang Gong,1,&ast; Chunyan Wu,1 Binquan Wang,1 Wenxuan Chen,2 Jiawei Hu,2 Hanhui Xiang,2 Ke Zhang,1 Mingkuan Sun1 1Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2The Second Clinical Medical School, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingkuan Sun, Department of Toxicology, School of Public Health, Nanjing Medical University, No. 101 Longmian Avenue, Jiangning District, Nanjing, 211166, People’s Republic of China, Email sunmk@njmu.edu.cnAbstract: The increasing use of titanium dioxide nanoparticles (TiO2 NPs) across various fields has led to a growing concern regarding their environmental contamination and inevitable human exposure. Consequently, significant research efforts have been directed toward understanding the effects of TiO2 NPs on both humans and the environment. Notably, TiO2 NPs exposure has been associated with multiple impairments of the nervous system. This review aims to provide an overview of the documented neurotoxic effects of TiO2 NPs in different species and in vitro models. Following exposure, TiO2 NPs can reach the brain, although the specific mechanism and quantity of particles that cross the blood-brain barrier (BBB) remain unclear. Exposure to TiO2 NPs has been shown to induce oxidative stress, promote neuroinflammation, disrupt brain biochemistry, and ultimately impair neuronal function and structure. Subsequent neuronal damage may contribute to various behavioral disorders and play a significant role in the onset and progression of neurodevelopmental or neurodegenerative diseases. Moreover, the neurotoxic potential of TiO2 NPs can be influenced by various factors, including exposure characteristics and the physicochemical properties of the TiO2 NPs. However, a systematic comparison of the neurotoxic effects of TiO2 NPs with different characteristics under various exposure conditions is still lacking. Additionally, our understanding of the underlying neurotoxic mechanisms exerted by TiO2 NPs remains incomplete and fragmented. Given these knowledge gaps, it is imperative to further investigate the neurotoxic hazards and risks associated with exposure to TiO2 NPs. Keywords: TiO2 NPs, neurotoxic effects, oxidative stress, neuronal damage, neurotoxic mechanisms

Qiping Liu,1,&ast; Huiling Gong,1,&ast; Qiqi Chen,1 Chunyan Yuan,2 Bin Hu1 1Department of Ultrasound, Minhang Hospital, Fudan University, Shanghai, 201199, People’s Republic of China; 2Department of Pathology, Minhang Hospital, Fudan University, Shanghai, 201199, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Hu; Chunyan Yuan, Email Niuniuhu1213@qq.com; masterychy@126.comObjective: To study the clinical application value of contrast-enhanced ultrasound (CEUS) in diagnosing renal space-occupying lesions.Methods: Sixty-seven patients with renal space-occupying lesions detected by routine ultrasound examination received the contrast-enhanced ultrasound examination. When observing the perfusion mode of the mass, we analyzed the perfusion characteristics of contrast-enhanced ultrasound and compared them with the surgical pathological results.Results: Sixty-seven lesions, which were identified in 67 patients with renal space-occupying lesions, included 55 renal malignant tumors and 12 benign ones. The sensitivity of qualitative diagnosis by CEUS imaging was 96.4%, the specificity was 66.7%, and the accuracy was 91.0%.Conclusion: The real-time blood supply of renal space-occupying lesions helps judge their nature according to the enhancement mode. It has high clinical application value in diagnosing benign and malignant lesions.Keywords: ultrasound examination, renal lesions, contrast-enhanced ultrasound

Hanxiang Gong,1,2 Xi Wang,1 Tao Zhang,1 Jinghua Li,3 Baoxin Chen1 1Faculty of Humanities and Social Sciences, Macao Polytechnic University, Macao, People’s Republic of China; 2The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 3School of Public Health, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Xi Wang, Faculty of Humanities and Social Sciences, Macao Polytechnic University, Macao, 999078, People’s Republic of China, Tel +8618029928803, Fax +86853-28718003, Email xwang@mpu.edu.moPurpose: The new round of medical reform is a significant exploration of reform in the public service sector in China. Health insurance regulatory departments, medical institutions, and patients, as critical stakeholders in China’s medical reform, play a crucial role in the success of the reform through their strategic interactions.Patients and Methods: Starting from the perspective of bounded rationality, applies evolutionary game theory to establish an evolutionary game model for the collaborative governance of health insurance regulatory departments, medical institutions, and patients and analyzes the stability of each party’s strategy and the sensitivity of parameters in the tripartite game system.Results: The study shows that an equilibrium point will be formed when medical institutions provide reasonable treatment, patients choose to accept treatment, and health insurance regulatory departments adopt a lenient regulatory strategy, maximizing the interests of all parties involved in the game. Factors such as the benefits of unreasonable treatment by medical institutions, fines, and regulatory costs impact the decision-making of health insurance regulatory departments. To maximize social welfare, health insurance regulatory departments should reform payment methods, adjust medical service behaviors of medical institutions, and guide the rational allocation of medical resources; the government should increase subsidies for the operation of medical institutions and the intensity of penalties; regulatory departments should reduce regulatory costs and introduce third-party forces to strengthen health insurance supervision further.Conclusion: The research findings of this paper will provide valuable insights into some countries’ medical and health reform.Keywords: new health care reform, health insurance regulators, medical institutions, patients, evolutionary game

Meenakashi Gupta,1 Jae Young Heo,2 Haiyan Gong,3 Elliot Cha,3 Mark Latina,4,5 Douglas J Rhee2 1Department of Ophthalmology, New York Eye & Ear Infirmary of Mt. Sinai, New York, NY, USA; 2Department of Ophthalmology & Visual Sciences, University Hospitals, Cleveland, OH, USA; 3Department of Ophthalmology, Boston University, Boston, MA, USA; 4Department of Ophthalmology, Massachusetts Eye & Ear Infirmary, Boston, MA, USA; 5Department of Ophthalmology, Advanced Glaucoma Specialists, Reading, MA, USACorrespondence: Douglas J Rhee, Department of Ophthalmology & Visual Sciences, 10900 Euclid Ave, Lakeside, 4129, Cleveland, OH, 44105, USA, Tel +1 216-844-8590, Fax +1 216-983-0544, Email douglas.rhee@uhhospitals.orgPurpose: Selective laser trabeculoplasty is a safe and effective procedure for reducing IOP, but its mechanism of action is not fully elucidated. We evaluated the morphologic and cellular changes as well as DNA synthesis after SLT treatment of human trabecular meshwork (TM) tissue explants.Methods: Corneoscleral rim tissues that underwent SLT treatment were compared to control segments that had no laser treatment. Light microscopy (LM), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) were used to assess cell morphology. The Click-iT 5-ethynyl-2’-deoxyuridine (EdU) imaging kit was used to compare DNA synthesis/cell proliferation with a confocal microscope. All tissues were assessed for vitality.Results: SLT treatment does not reveal notable cell damage in the juxtacanalicular (JCT) region, but mildly disrupts superficial trabecular beams and uveal TM, ablates TM endothelial cells from the undamaged beams as detected by both LM and TEM. This superficial destruction was not observed in some SLT treatment spots on higher magnification by SEM. SLT treatment increased mitotic activity and DNA synthesis near the lining of Schlemm’s canal after several days.Conclusion: SLT treatment disrupts endothelial cells in the corneoscleral TM and causes superficial ultrastructural changes to the uveal TM. SLT treatment also shows a trend towards dynamic time-dependent changes in (DNA synthesis) with an increase in mitotic activity at 7 days cell proliferation.Keywords: DNA synthesis, electron microscopy, selective laser trabeculoplasty, glaucoma

Xiaofeng Fu,1 Luwei Hong,2 Haiying Gong,3 Guangjuan Kan,4 Pengfei Zhang,1 Ting-Ting Cui,5 Gonglin Fan,6 Xing Si,7 Jiang Zhu1 1Department of Ultrasound, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310000, People’s Republic of China; 2Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310000, People’s Republic of China; 3Department of Ultrasound, Yiwu Traditional Chinese Medicine Hospital, Jinhua, Zhejiang, 321000, People’s Republic of China; 4Department of Ultrasound, The Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310000, People’s Republic of China; 5Department of Ultrasound, Taizhou Traditional Chinese Medicine Hospital, Taizhou, Zhejiang, 318000, People’s Republic of China; 6Department of Ultrasound, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310000, People’s Republic of China; 7Hangzhou Normal University, Hangzhou, Zhejiang, 310000, People’s Republic of ChinaCorrespondence: Jiang Zhu, Department of Ultrasound, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 31000, People’s Republic of China, Tel +86 13757122629, Email zhujiang1046@zju.edu.cnBackground: Glioma is a common type of tumor in the central nervous system characterized by high morbidity and mortality. Autophagy plays vital roles in the development and progression of glioma, and is involved in both normal physiological and various pathophysiological progresses.Patients and Methods: A total of 531 autophagy-related genes (ARGs) were obtained and 1738 glioma patients were collected from three public databases. We performed least absolute shrinkage and selection operator regression to identify the optimal prognosis-related genes and constructed an autophagy-related risk signature. The performance of the signature was validated by receiver operating characteristic analysis, survival analysis, clinic correlation analysis, and Cox regression. A nomogram model was established by using multivariate Cox regression analysis. Schoenfeld’s global and individual test were used to estimate time-varying covariance for the assumption of the Cox proportional hazard regression analysis. The R programming language was used as the main data analysis and visualizing tool.Results: An overall survival-related risk signature consisting of 15 ARGs was constructed and significantly stratified glioma patients into high- and low-risk groups (P < 0.0001). The area under the ROC curve of 1-, 3-, 5-year survival was 0.890, 0.923, and 0.889, respectively. Univariate and multivariate Cox analyses indicated that the risk signature was a satisfactory independent prognostic factor. Moreover, a nomogram model integrating risk signature with clinical information for predicting survival rates of patients with glioma was constructed (C-index=0.861± 0.024).Conclusion: This study constructed a novel and reliable ARG-related risk signature, which was verified as a satisfactory prognostic marker. The nomogram model could provide a reference for individually predicting the prognosis for each patient with glioma and promoting the selection of optimal treatment.Keywords: glioma, autophagy, risk signature, prognosis, nomogram

Zulipikaer Abudureheman,1,&ast; Li Li,2,&ast; XueMei Zhong,2,&ast; JingRan Xu,2 Hui Gong,1 Subinuer Yilamujiang,1 Jie Ren,2 ChengXin Xie,2 AiFang Zheng,2 Dilala Tuerxun,2 Ayiguzali Abudukadeer,2 Paierda Aini,2 AiMin Xu,3 XiaoGuang Zou2 1Department of Clinical Research Center of Infectious Diseases (Pulmonary Tuberculosis), First People’s Hospital of Kashi, Kashi, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, First People’s Hospital of Kashi, Kashi, People’s Republic of China; 3Department of Clinical Laboratory, First People’s Hospital of Kashi, Kashi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: AiMin Xu; XiaoGuang Zou Email 519202069@qq.com; ZXGKS11@yeah.netBackground: Kashi city is situated near the Taklamakan desert and has a high incidence rate of chronic obstructive pulmonary disease (COPD). In this study, we aimed to explore the relationship between the SNP of the SREK1 gene locus rs74794265 and the susceptibility to COPD among the Uyghur population in Kashi, XinJiang, China.Methods: A total of 541 patients with COPD and 534 control subjects were included in this study. Sanger sequencing was used to analyze the SNP of the SREK1 gene locus rs74794265 site. The distribution of genotypes in different genetic models between the case and control group were analyzed by logistic regression analysis after adjusting for age, sex, and smoking history.Results: The SREK1 gene SNP locus rs74794265 included two genotypes, namely, C/C and C/T, of which C/C was the wildtype; The risk of COPD was significantly lower in patients with heterozygous C/T in rs74794265 [p=0.0236, OR=0.3677 (0.1547– 0.8742)], and the allele frequency of T was also significantly lower in the patient group [p=0.0245, OR=0.3728 (0.1577– 0.8811)]. The heterozygous C/T of rs74794265 among non-smoking COPD patients was significantly lower than other COPD patients [p=0.0298, OR=0.3217 (0.1156– 0.8949)], and there was no significant correlation of the heterozygous C/T genotype in smokers.Conclusion: We found that the rs74794265 heterozygous C/T genotype significantly reduces the risk of COPD. The C/T genotype is likely a protective factor for COPD in the Kashi region. We speculate that the occurrence of COPD in this area is probably more related to desert climate condition and genetic factors than smoking status.Keywords: COPD, SREK1 gene polymorphism, rs74794265 locus, Uyghur population

Haitong Gong, 1 Stephen X Zhang, 2 Khaled Nawaser, 3 Asghar Afshar Jahanshahi, 4, 5 Xingzi Xu, 6 Jizhen Li, 6 Afsaneh Bagheri 7 1Collegue of Nursing and Health Sciences, Flinders University, Adelaide, SA, Australia; 2Faculty of Professions, University of Adelaide, Adelaide, SA, Australia; 3Universidad Católica Los Ángeles de Chimbote, Instituto de Investigación, Chimbote, Peru; 4CENTRUM Católica Graduate Business School (CCGBS), Lima, Peru; 5School of Economics and Management, Pontificia Universidad Católica del Perú (PUCP), Lima, Peru; 6School of Economics and Management, Tsinghua University, Beijing, People’s Republic of China; 7Faculty of Entrepreneurship, University of Tehran, Tehran, IranCorrespondence: Stephen X ZhangFaculty of Professions, University of Adelaide, 9-28 Nexus10 Tower, 10 Pulteney St, Adelaide, SA, 5000, AustraliaTel +61 8831 39310Email stephen.x.zhang@gmail.comPurpose: Healthcare staff operate at the forefront of the fight against COVID-19 and hence face enormous physical and mental pressures. We aim to investigate healthcare staff’s mental health issues and the associated predictors during the COVID-19 pandemic. Specifically, this paper aims to identify some unique predictors of healthcare staff’s mental health issues in Iran, the second country after China to experience a major COVID-19 crisis.Methods: An online survey of 280 healthcare staff in all 31 provinces of Iran assessed staff’s mental distress (K6), depression, and anxiety (PHQ-4) during April 5– 20, 2020 during the COVID-19 crisis.Results: Nearly a third of healthcare staff surpassed the cutoff for distress, depression, and anxiety symptoms. Females or more educated healthcare staff were more likely to experience distress. Those who were unsure whether they had COVID-19 were more likely to experience distress and depression symptoms. The number of COVID-19 cases among a healthcare worker’s colleagues or friends positively predicted the worker’s anxiety symptoms. Amongst healthcare staff, doctors were less likely than radiology technologists to experience distress and anxiety symptoms. Technicians and obstetrics staff experienced fewer anxiety symptoms. The age and the weekly working days of healthcare staff interacted such that age is asignificant predictor of mental health issues among younger but not older healthcare staff.Conclusion: The identification of the predictors of mental health issues can guide healthcare organizations to screen healthcare workers who are more likely to be mentally vulnerable in the ongoing COVID-19 pandemic.Keywords: healthcare staff, mental health, working time, age, COVID-19, epidemic, Iran

Guojin Xia,1,2 Zhenzhen Hu,3 Fuqing Zhou,1,2 Wenfeng Duan,1,2 Min Wang,1,2 Honghan Gong,1,2 Yulin He,1,2 Yanxing Guan4 1Department of Radiology, The First Affiliated Hospital of Nanchang University, Jiangxi, People’s Republic of China; 2Jiangxi Province Medical Imaging Research Institute, Jiangxi, People’s Republic of China; 3Department of Thoracic Oncology, Jiangxi Cancer Hospital, Jiangxi, People’s Republic of China; 4Department of Nuclear Medicine, The First Affiliated Hospital of Nanchang University, Jiangxi, People’s Republic of ChinaCorrespondence: Yulin He; Yanxing Guan 17 Yongwaizheng Street, Nanchang City, Jiangxi Province, People’s Republic of ChinaTel +86-791-88692585Email 33heyulin@163.com; yanxingguan2000@aliyun.comPurpose: We explored changes in spontaneous brain connectivity in patients with diffuse axonal injury (DAI), assessed via functional connectivity density (FCD) tests using different frequency bands.Patients and Methods: In all, 23 patients with DAI (17 males and 6 females) and 23 healthy controls (HCs; 17 males and 6 females) were included. Functional magnetic resonance imaging scans were performed when the participants were in a resting state and the FCD levels in three frequency bands (slow-4: 0.027– 0.073 Hz, slow-5: 0.01– 0.027 Hz, and typical: 0.01– 0.08 Hz) were measured. In addition, Pearson’s correlation coefficient was used to explore the relationship between clinical indices and brain regions with abnormal FCD values.Results: Compared to HCs, DAI patients had significantly greater FCD values in the right extranuclear/limbic lobe/cingulate gyrus and left limbic lobe/hippocampus/parahippocampal gyrus, and significantly lower FCD values in the left precuneus/posterior cingulate gyrus, in the slow-4 band. In the slow-5 band, the DAI patients had higher FCD values in the left inferior temporal gyrus/superior temporal gyrus, left parahippocampal gyrus/limbic lobe, left extranuclear/cingulate gyrus, and right medial frontal gyrus, and lower values in the right inferior frontal gyrus, right inferior parietal lobule, and left cingulate gyrus/limbic lobe. Moreover, compared to HCs, the values in the typical band were higher in the right extranuclear/limbic lobe/hippocampus/parahippocampal gyrus, but were significantly lower in the right precuneus/posterior cingulate gyrus and right inferior parietal lobule/supramarginal gyrus. The abnormal FCD values of these brain regions were linearly correlated with different clinical scale scores.Conclusion: DAI patients had abnormal FCD values in various brain regions, indicating disruption to the brain functional network. Moreover, the values were frequency dependent. Our results provide new evidence for the pathogenesis of functional impairment and may explain the neuropathological or compensatory mechanism of the disease.Keywords: diffuse axonal injury, functional connectivity density, functional magnetic resonance imaging, frequency bands

Chenglong Zhao,* Yao Wang,* Xiaopan Cai,* Wei Xu,* Dongsheng Wang, Ting Wang, Qi Jia, Haiyi Gong, Haitao Sun, Zhipeng Wu, Jianru Xiao Spine Tumor Center, Department of Orthopedic Oncology, Changzheng Hospital, Navy Medical University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianru Xiao; Zhipeng WuSpine Tumor Center, Department of Orthopedic Oncology, Changzheng Hospital, Navy Medical University, No. 415 Fengyang Road, Huangpu District, Shanghai, People’s Republic of ChinaTel +86-21-81886843Fax +86-21-63520020Email cz_xiaojianru@163.com; eaglewzp@163.comBackground: Surgery remains the mainstay of treatment for breast cancer spinal metastasis (BCSM) to relieve symptoms and improve the quality of life of BCSM patients. Therefore, it is important to effectively predict the prognosis of patients to determine whether they can undergo surgical operation. However, the prevalent methods for prognosis evaluation lack specificity and sensitivity for indicated malignancies like breast cancer because they are built on a relatively small number of heterogeneous types of primary tumors. The aim of the present study was to explore a novel predictive model based on the clinical, pathological and blood parameters obtained from BCSM patients before they received surgical intervention.Methods: Altogether, 144 patients were included in this study. Univariate and multivariate analyses were performed to investigate the significance of preoperative parameters and identify independent factors for prognostic prediction of BCSM. A nomogram for survival prediction was then established and validated. Time-dependent ROC (TDROC) curves were graphed to evaluate the accuracy of the novel model vs other scoring systems including Tomita Score, revised Tokuhashi Score, modified Bauer Score and New England Spinal Metastasis Score. P values < 0.05 were considered statistically significant.Results: Independent factors, including preoperative postmenopausal (P=0.034), visceral metastasIs (P=0.021), preoperative Frankel Score (P=0.001), estrogen receptor status (P=0.014), platelet-to-lymphocyte ratio (P=0.012), lymphocyte-monocyte ratio (P< 0.001) and albumin-globulin ratio (P=0.017), were selected into the nomogram model with the C-index of 0.834 (95% CI, 0.789– 0.890). TDROC curves showed that the Changzheng Hospital (CZ) Score system had the best performance and exhibited the largest IAUC value in comparison with the other scoring systems.Conclusion: We constructed a nomogram model known as CZ Score based on the significant factors to predict the prognosis for BCSM patients. The result showed that CZ Score had a better value for prognostic evaluation and surgical decision-making as compared with the other scoring systems.Keywords: breast cancer, spine metastases, nomogram, scoring system, prognosis

Linglong Chen,1 Yaru Zhan,2 Fei He,3 Shouhua Zhang,3 Lin Wu,2,4 Honghan Gong,2,4 Fuqing Zhou,2,4 Xianjun Zeng,2,4 Haibo Xu1 1Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan 430071, People’s Republic of China; 2Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang 330006, People’s Republic of China; 3Department of Hematology, Jiangxi Provincial Children’s Hospital, Nanchang, 330000, People’s Republic of China; 4Jiangxi Medical Imaging Research Institute, Nanchang 330006, People’s Republic of ChinaCorrespondence: Haibo XuDepartment of Radiology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of ChinaEmail xuhaibo1120@hotmail.comHonghan GongDepartment of Radiology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, People’s Republic of ChinaEmail 2805794252@qq.comObjective: Using functional connectivity density (FCD) mapping measured by resting-state functional magnetic resonance imaging (rs-fMRI), an ultrafast data-driven graph theory approach, we attempted to study the abnormalities in neural activity of young survivors of acute lymphoblastic leukemia (ALL) and to explore the neuropathological evidence of chemotherapy-related cognitive impairment of patients.Methods: Twenty young survivors of ALL and 18 well-matched healthy controls (HCs) were recruited in this study. All ALL patients and healthy controls underwent rs-fMRI scans and completed neurocognitive testing. The between-group differences in short-range and long-range FCD were calculated by the option of degree centrality (DC) in MATLAB software after preprocessing. The correlations between the FCD value and each of the neurocognitive outcomes were analyzed in the ALL patients.Results: The group-averaged FCD maps showed similar spatial patterns between the two groups. Compared with the HCs, ALL patients showed decreased long-range FCD in regions of the bilateral lingual gyrus, cingulate cortex, hippocampal gyrus, and right calcarine fissure. Simultaneously, decreased regions in the short-range FCD map were the bilateral lingual gyrus, cingulate cortex, parahippocampal gyrus and right calcarine fissure. Increased functional connectivity (FC) was observed between the region with decreased long-range FCD and the posterior cerebellar lobe, and decreased FC was observed between the region and the middle occipital gyrus, cuneus and lingual gyrus. Thus, there existed no brain areas with increased FCD. The decreased short-range FCD value of ALL patients was positively correlated with the score on the Digit Span Test (Forward), and the increased FC value was negatively correlated with the score on the Trail Making Test part A.Conclusion: Our results suggest the altered functional connectivity of young survivors of ALL in the posterior region of the brain and posterior lobe of the cerebellum. Alterations in spontaneous neuronal activity seem to parallel the neurocognitive testing, which indicates that the rs-fMRI could be used as a neuroimaging marker for neurological impairment in ALL patients.Keywords: acute lymphoblastic leukemia, resting-state fMRI, functional connectivity density, chemotherapy-related cognitive impairment, executive function

Qimin Tu,1,2,* Hongjian Gong,3,4,* Chunhui Yuan,3 Gao Liu,5 Jinqi Huang,1 Zhichao Li,4 Jianfei Luo2 1Department of Cardio-Thoracic Surgery, Central Hospital of Enshi Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi, Hubei, People’s Republic of China; 2Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 3Clinical Research Center, Wuhan Medical and Health Center for Women and Children, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 4Department of Rheumatism Immunology, Wuhan Medical and Health Center for Women and Children, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 5Department of Gastrointestinal Surgery, Central Hospital of Enshi Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhichao LiDepartment of Rheumatism Immunology, Wuhan Medical and Health Center for Women and Children, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of ChinaTel +86-27-82433423Email linyuanmuchun@sina.comJianfei LuoDepartment of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of ChinaTel +86-27-88041911Email afei099@163.comBackground: p53 isoform Δ 133p53 is directly transactivated by p53 and antagonizes p53 activities in cancer progression. However, its correlation with prognosis and cancer recurrence in esophageal squamous cell carcinoma (ESCC) is still unclear.Patients and Methods: Expression of Δ 133p53 and Δ 133p53/full-length p53 (FLp53) in tissues and serums of 180 ESCC patients was evaluated using qRT-PCR. Patients were divided into high- and low-expression groups according to the cutoff value determined by X-tile 3.6.1 software. Survival analysis was performed by the Kaplan–Meier method. Univariate and multivariate Cox survival analyses were applied to assess the hazard ratios (HRs).Results: Tissue Δ 133p53 expression and Δ 133p53/FLp53 ratio were significantly increased in ESCC tissue compared with adjacent normal tissue. Pre-operative Δ 133p53 expression and Δ 133p53/FLp53 ratio in tissue or serum samples were positively associated with TNM stage and post-operative recurrence. Kaplan–Meier curve and multivariate cox regression analyses revealed that the tissue and serum Δ 133p53/FLp53 ratios (cutoff value: 2.9160) were independent prognostic factors for overall survival (OS) and progression-free survival (PFS) in ESCC patients and showed no statistical difference in receiver-operating characteristic curve (ROC) analysis, while serum Δ 133p53 showed no significant prognostic value. More importantly, the serum Δ 133p53/FLp53 ratio in ESCC patients was significantly decreased within 72 h post tumor resection and patients with a consistently high serum Δ 133p53/FLp53 ratio (≥ 2.9160) had higher recurrence rates than those with consistently low ratio values. In addition, dynamic detection in each follow-up timepoint showed that serum Δ 133p53/FLp53 ratios were higher than 2.9160 upon recurrence, and they even increased prior to radiologic progression.Conclusion: The serum Δ 133p53/FLp53 ratio can be a novel predictor for survival outcome and may serve as a real-time parameter for monitoring recurrence in ESCC patients after surgery.Keywords: esophageal squamous cell carcinoma, p53, Δ 133p53, prognosis, recurrence

Yixiu Pei,1,2 Yong Zhang,3 Yanyan Zhu,1,2 Yanlin Zhao,1,2 Fuqing Zhou,1,2 Muhua Huang,1,2 Lin Wu,1,2 Honghan Gong1,2 1Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang 330006, People’s Republic of China; 2Neuroradiology Laboratory, Jiangxi Province Medical Imaging Research Institute, Nanchang 330006, People’s Republic of China; 3Department of Pain Clinic, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province 330006, People’s Republic of ChinaCorrespondence: Fuqing ZhouDepartment of Radiology, The First Affiliated Hospital, Nanchang University, 17 Yongwaizheng Street, Nanchang, Jiangxi 330006, People’s Republic of ChinaTel +86 791 8869 5132Email fq.chou@yahoo.comObjective: To investigate the functional connectivity (FC) and its variability in the primary somatosensory cortex (S1) of patients with low-back-related leg pain (LBLP) in the context of the persistent stimuli of pain and numbness.Patients and Methods: We performed functional magnetic resonance imaging on LBLP patients (n = 26) and healthy controls (HCs; n = 34) at rest. We quantified and compared static FC (sFC) using a seed-based analysis strategy, with 6 predefined bilateral paired spherical regions of interest (ROIs) in the S1 cortex. Then, we captured the dynamic FC using sliding window correlation of ROIs in both the LBLP patients and HCs. Furthermore, we performed a correlational analysis between altered static and dynamic FC and clinical measures in LBLP patients.Results: Compared with controls, the LBLP patients had 1) significantly increased static FC between the left S1back (the representation of the back in the S1) and right superior and middle frontal gyrus (SFG/MFG), between the left S1chest and right SFG/MFG, between right S1chest and right SFG/MFG, between the left S1face and right MFG, and between the right S1face and right inferior parietal lobule (P < 0.001, Gaussian random field theory correction); 2) increased dynamic FC only between the right S1finger and the left precentral and postcentral gyrus and between the right S1hand and the right precentral and postcentral gyrus (P < 0.01, Gaussian random field theory correction); and 3) a negative correlation between the Barthel index and the increased static FC between the left S1face and right inferior parietal lobule (P = 0.048).Conclusion: The present study demonstrated the hyperconnectivity of the S1 cortex to the default mode and executive control network in a spatial pattern and an increase in the tendency for signal variability in the internal network connections of the S1 cortex in patients with LBLP.Keywords: primary somatosensory cortex, static functional connectivity, dynamic functional connectivity, chronic low-back-related leg pain, chronic pain, resting-state functional MRI

Na Li,1 Hao Zuo,1 Luojun Chen,1 Huali Liu,1 Jin Zhou,1 Yi Yao,1 Bin Xu,1 Hongyun Gong,1 Yiming Weng,1 Qinyong Hu,1 Qibin Song,1 Min Peng,1 Yanxiang Cheng2 1Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of ChinaCorrespondence: Min PengDepartment of Oncology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, People’s Republic of ChinaTel +86 133 1713 3140Email mpeng320@whu.edu.cnYanxiang ChengDepartment of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, People’s Republic of ChinaTel +86 27 8804 1911Email doctornancy@qq.comPurpose: Circulating tumor cell (CTC) detection methods based on epithelial cell adhesion molecule (EpCAM) have low detection rates in epithelial ovarian cancer (EOC). Meanwhile, folate receptor alpha (FRα) has high expression in EOC cells. We explored the feasibility of combining FRα and EpCAM as CTC capture targets in EOC.Patients and methods: EpCAM and FRα antibodies were linked to magnetic nanospheres (MNs) using the principle of carbodiimide chemistry. Blood samples from healthy donor spiked with A2780 ovarian cancer cells were used for detecting the capture rate. Ninety-five blood samples from 30 patients with EOC were used for comparing the positive rate of detection when using anti-EpCAM-MNs alone with that when using combination of anti-EpCAM-MNs and anti-FRα-MNs. Samples from 28 patients initially diagnosed with EOC and 20 patients with ovarian benign disease were used for evaluating the sensitivity and specificity of combination of anti-EpCAM-MNs and anti-FRα-MNs.Results: Regression analysis between the number of recovered and that of spiked A2780 cells revealed yEpCAM = 0.535x (R2 = 0.99), yFRα = 0.901x (R2 = 0.99), and yEpCAM+FRα = 0.928x (R2 = 0.99). In mixtures of A2780 and MCF7 cells, the capture rate was 92% using the combination of anti-EpCAM-MNs and anti-FRα-MNs, exceeding the rate when using anti-EpCAM-MNs or anti-FRα-MNs alone by approximately 20% (P < 0.01). The combination of anti-EpCAM-MNs and anti-FRα-MNs showed a significantly increased positive rate of CTC detection in EOC patients compared with anti-EpCAM-MNs alone (χ2 = 14.45, P < 0.001). Sensitivity values were 0.536 and 0.75 and specificity values were 0.9 and 0.85 when using anti-EpCAM-MNs alone and when using the combination of anti-EpCAM-MNs and anti-FRα-MNs, respectively.Conclusion: The combination of FRα and EpCAM is feasible as a CTC capture target of CTC detection in patients with EOC.Keywords: circulating tumor cells, ovarian cancer, epithelial cell adhesion molecule, folate receptor alpha

Kehan Xu,1,* Jialin Li,1,* Mengzi Hu,2,* Hao Zhang,1 Jian Yang,1 Haiyi Gong,1 Bo Li,1 Wei Wan,1 Jianru Xiao1 1Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, People’s Republic of China; 2Department of Orthopedics, Xuzhou Central Hospital, Xuzhou, Jiangsu 221009, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianru Xiao; Wei Wan Email jianruxiao83@smmu.edu.cn; ggflyfish@126.comPurpose: The purpose of this retrospective study was to identify preoperative inflammatory biomarkers and clinical parameters and evaluate their prognostic significance in patients with spinal metastasis from clear cell renal cell carcinoma (CCRCC).Patients and methods: Correlations of overall survival (OS) with traditional clinical parameters and inflammatory indicators including the neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), lymphocyte–monocyte ratio (LMR), albumin–globulin ratio (AGR), and C-reactive protein to albumin ratio (CRP/Alb ratio) were analyzed in 95 patients with spinal metastasis from CCRCA using the Kaplan–Meier method to identify potential prognostic factors. Factors with P values ≤ 0.1 were subjected to multivariate analysis by Cox regression analysis. P values ≤ 0.05 were considered statistically significant.Results: The 95 patients included in this study were followed up by a mean of 48.8 months (median 51 months; range 6–132 months), during which 21 patients died, with a death rate of 22.1%. The statistical results indicated that patients with total piecemeal spondylectomy (TPS), targeted therapy, NLR < 3.8 and PLR < 206.9 had a significantly longer OS rate.Conclusion: TPS and targeted therapy could significantly prolong the OS of patients with spinal metastasis from CCRCC. In addition, NLR and PLR are robust and convenient prognostic indicators that have a discriminatory ability superior to other inflammatory biomarkers.Keywords: clear cell renal cell carcinoma, spinal metastasis, overall survival, prognosis, inflammatory biomarkers

Yunfei Wang, 1, 2,* Zhengrong Li, 2,* Boxue Liu, 1, 2 Rumeng Wu, 1, 2 Haifeng Gong, 2 Zhanhai Su, 2 Shoude Zhang 1, 2 1State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining, Qinghai 810016, People’s Republic of China; 2Medical College of Qinghai University, Xining, Qinghai 810016, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shoude ZhangState Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, 251# Ningda Road, Xining, Qinghai 810016, People’s Republic of ChinaTel +86-971-5366433Fax +86-971-5201533Email shoude.zhang@qhu.edu.cnPurpose: Isoborneol has been used in the treatment of cardiovascular disease for several years in China. However, the mechanism is still unclear. The aim of this study was to identify the novel mechanism of isoborneol for its application in atherosclerotic disease.Materials and Methods: The whole-genome gene expression profiles of MCF-7 cells treated with/or without isoborneol were detected by mRNA microarray analysis. The degree of similarity between the gene expression profiles was compared with the Connectivity Map (CMAP) database. An MTT assay was used to assess the toxicity of isoborneol on RAW 264.7 cells. Oil red O staining and a Dil-ox-LDL uptake assay in RAW 264.7 cells were also used to detect the accumulation of lipids in the macrophages and the uptake of oxidized low-density lipoprotein (ox-LDL).Results: Isoborneol was proved to have mRNA expression profiles similar to that of ikarugamycin which can inhibit the uptake of ox-LDL. This process has proved to be an important cause of foam cell formation and early atherosclerotic lesions. It is speculated, therefore, that isoborneol may show similar activity to that shown by ikarugamycin. Subsequently, it was shown that RAW 264.7 cells reduced the absorption of ox-LDL and the accumulation of intracellular lipids after treatment with different concentrations of isoborneol.Conclusion: The results indicate that isoborneol inhibits macrophage consumption of ox-LDL, thereby preventing the accumulation of lipids in the macrophages. These results provide evidence for the application of isoborneol in atherosclerotic disease.Keywords: isoborneol, ikarugamycin, connectivity map, ox-LDL, atherosclerosis, macrophage

Yong Zhang,1 Yanyan Zhu,2,3 Yixiu Pei,2,3 Yanlin Zhao,2,3 Fuqing Zhou,2,3 Muhua Huang,2,3 Lin Wu,2,3 Daying Zhang,1 Honghan Gong2,31Department of Pain Clinic, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province 330006, People’s Republic of China; 2Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang 330006, People’s Republic of China; 3Neuroradiology Lab, Jiangxi Province Medical Imaging Research Institute, Nanchang 330006, People’s Republic of ChinaCorrespondence: Fuqing ZhouDepartment of Radiology, The First Affiliated Hospital, Nanchang University, 17 Yongwaizheng Street, Nanchang, Jiangxi 330006, People’s Republic of ChinaTel +86 7 918 869 5132Email fq.chou@yahoo.comDaying ZhangDepartment of Pain Clinic, The First Affiliated Hospital, Nanchang University, 17 Yongwaizheng Street, Nanchang, Jiangxi 330006, People’s Republic of ChinaTel +86 7 918 869 3825Email dyzsino@ncu.edu.cnObjective: Chronic low back pain has been observed to decrease movement coordination. However, it is unclear whether the existing alteration of inter-hemispheric synchrony of intrinsic activity in patients with chronic low back-related leg pain (cLBLP). The present study aims to investigate the alteration of homotopic connectivity and its clinical association with the cLBLP patients.Participants and methods: A cohort of cLBLP patients (n=25) and well-matched healthy controls (HCs) (n=27) were recruited and underwent MRI scanning and a battery of clinical tests. The voxel-mirrored homotopic connectivity (VMHC) was used to analyze the interhemispheric coordination in the typical (0.01–0.1 Hz) as well as five specific (slow-6 to slow-2) frequency bands and associated with clinical index in cLBLP patients.Results: We observed that cLBLP patients with lower homotopic connectivity than HCs in the inferior temporal gyrus, the superior temporal gyrus, the basal ganglia, the middle frontal gyrus, and the medial prefrontal cortex in the typical and five specific frequency bands, respectively. In the typical and five specific frequency bands, significant positive correlations were observed between the VMHC values of medial prefrontal cortex and the visual analogue scale scores, while the VMHC values of basal ganglia negative correlated with the values of two-point tactile discrimination (2PD) test for the right hand in cLBLP patients, etc. Further receiver operating characteristic curve analysis revealed that VMHC in the above regions with decreased could be used to differentiate the cerebral functional plasticity of cLBLP from healthy individuals with high sensitivity and specificity.Conclusion: Our results imply that multiscale frequency-related interhemispheric disconnectivity may underlie the central pathogenesis of functional coordination in patients with cLBLP.Keywords: interhemispheric integration, voxel-mirrored homotopic connectivity, chronic low back-related leg pain, chronic pain, resting-state fMRI

Muhua Huang,1,2 Fuqing Zhou,1,2 Lin Wu,1,2 Bo Wang,1,2 Hui Wan,3 Fangjun Li,3 Xianjun Zeng,1,2 Honghan Gong1,2 1Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang, People’s Republic of China; 2Neuroradiology Laboratory, Jiangxi Province Medical Imaging Research Institute, Nanchang, People’s Republic of China; 3Department of Neurology, The First Affiliated Hospital, Nanchang University, Nanchang, People’s Republic of China Background and purpose: The effects of the interactions between the default mode network (DMN) and the dorsal attention network (DAN), which present anticorrelated behaviors, in relapsing-remitting multiple sclerosis (RRMS) are poorly understood. This study used resting-state functional connectivity (FC) and the Granger causality test (GCT) to examine changes in the undirected and effective functional network connectivity (FNC) between the two networks during the remitting phase in RRMS patients.Patients and methods: Thirty-three patients experiencing a clinically diagnosed remitting phase of RRMS and 33 well-matched healthy control subjects participated in this study. First, an independent component (IC) analysis was performed to preprocess the functional magnetic resonance imaging data and select resting-state networks. Then, an FNC analysis and the GCT were combined to examine the temporal correlations between the ICs of the DMN and DAN and to identify correlations with clinical markers.Results: Compared with the healthy subjects, the RRMS patients in the remitting phase showed the following: 1) significantly decreased FC within the DAN in the postcentral gyrus and decreased FC within the DMN in several regions except the parahippocampal gyrus, where increased FC was observed; 2) a relatively stable interaction between the two anticorrelated networks as well as a driving connectivity from the DAN to DMN (IC15); and 3) significantly positive correlations between the connectivity coefficient of the right superior temporal gyrus and the Modified Fatigue Impact Scale score (ρ = 0.379, p = 0.036).Conclusion: Adaptive mechanisms that maintain stable interactions might occur between the DMN and DAN during the remitting phase in RRMS patients. Keywords: default mode network, dorsal attention network, multiple sclerosis, resting-state functional MRI, Granger causality test, anticorrelation

Fuqing Zhou,1,2 Yanlin Zhao,1,2 Muhua Huang,1,2 Xianjun Zeng,1,2 Bo Wang,1,2 Honghan Gong1,2 1Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang, China; 2Neuroradiology Lab, Jiangxi Province Medical Imaging Research Institute, Nanchang, China Background: Abnormalities in both cerebral structure and intrinsic activity have been increasingly reported in patients with chronic insomnia disorder (CID). However, the interhemispheric integration function in CID is still not well understood. Functional homotopy reflects an essential aspect of the intrinsic functional architecture involved in interhemispheric coordination. Methods: In this study, voxel-mirrored homotopic connectivity (VMHC) was used to analyze the patterns of interhemispheric intrinsic functional connectivity in patients with CID (n=29). Results: Reduced homotopic connectivity was observed in the middle occipital/posterior middle temporal gyrus in CID patients relative to control subjects. Further analyses demonstrated different insomnia-related heterotopic connectivity patterns in the right and left middle occipital/posterior middle temporal gyrus. Furthermore, within the CID group, the connectivity coefficient within the connectivity network of the middle occipital/posterior middle temporal gyrus was associated with anxiety measures. Conclusion: Negative significant findings of group differences were found in terms of both the local gray matter density and fractional anisotropy of the white matter skeletal measures in this study; this structural finding, together with the results of VMHC, suggested that disruptions in the intrinsic functional architecture of interhemispheric communication associated with CID can be observed in the absence of detectable microstructural or local morphometric changes in white and gray matter. Keywords: homotopic connectivity, interhemispheric integration, voxel-mirrored homotopic connectivity, chronic primary insomnia, sleep disorders, resting-state fMRI

Li-Ting Chen,1,* Xiao-Le Fan,2,* Hai-Jun Li,1 Cheng-Long Ye,1 Hong-Hui Yu,1 Hui-Zhen Xin,1 Hong-Han Gong,1 De-Chang Peng,1 Li-Ping Yan3 1Department of Radiology, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China; 2Department of General Surgery, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China; 3Department of Cardiology, People’s Hospital of Jiangxi Province, Nanchang, Jiangxi Province, China *These authors contributed equally to this work Objective: Obstructive sleep apnea (OSA) is accompanied by widespread abnormal spontaneous regional activity related to cognitive deficits. However, little is known about the topological properties of the functional brain connectome of patients with OSA. This study aimed to use the graph theory approaches to investigate the topological properties and functional connectivity (FC) of the functional connectome in patients with OSA, based on resting-state functional magnetic resonance imaging (rs-fMRI). Methods: Forty-five male patients with newly diagnosed untreated severe OSA and 45 male good sleepers (GSs) underwent a polysomnography (PSG), clinical evaluations, and rs-fMRI scans. The automated anatomical labeling (AAL) atlas was used to construct the functional brain connectome. The topological organization and FC of brain functional networks in patients with OSA were characterized using graph theory methods and investigated the relationship between functional network topology and clinical variables. Results: Both the patients with OSA and the GSs exhibited high-efficiency “small-world” network attributes. However, the patients with OSA exhibited decreased σ, γ, Eglob; increased Lp, λ; and abnormal nodal centralities in several default-mode network (DMN), salience network (SN), and central executive network (CEN) regions. However, the patients with OSA exhibited abnormal functional connections between the DMN, SN, and CEN. The disrupted FC was significantly positive correlations with the global network metrics γ and σ. The global network metrics were significantly correlated with the Epworth Sleepiness Scale (ESS) score, Montreal Cognitive Assessment (MoCA) score, and oxygen desaturation index. Conclusion: The findings suggest that the functional connectome of patients with OSA exhibited disrupted functional integration and segregation, and functional disconnections of the DMN, SN, and CEN. The aberrant topological attributes may be associated with disrupted FC and cognitive functions. These topological abnormalities and disconnections might be potential biomarkers of cognitive impairments in patients with OSA. Keywords: obstructive sleep apnea, graph theory, functional connectome, cognitive function, resting-state fMRI

Shunda Hong,1,* Lili Gu,2,* Fuqing Zhou,1 Jiaqi Liu,1 Muhua Huang,1 Jian Jiang,1 Laichang He,1 Honghan Gong,1 Xianjun Zeng1 1Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Pain, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, People’s Republic of China *These authors contributed equally to this work Purpose: The aim of this study was to explore intrinsic functional connectivity patterns in patients with herpes zoster (HZ) and postherpetic neuralgia (PHN). Patients and methods: Thirty-three right-handed HZ patients (13 males; mean age 57.15±9.30 years), 22 right-handed PHN patients (9 males; mean age 66.13±6.77 years), and 28 well-matched healthy controls (HC) (9 males; mean age 54.21±7.72 years) underwent resting-state functional magnetic resonance imaging for intrinsic functional connectivity analyses. Functional connectivity density (FCD) was calculated and compared among the PHN, HZ, and HC groups. In addition, the Pearson correlation coefficient was calculated to compare various clinical indices in the regions with abnormal FCD values. Results: Compared with the HC, both HZ and PHN patients showed significantly decreased FCD in the precuneus, and patients with HZ displayed significantly increased FCD in the brainstem/limbic lobe/parahippocampalgyrus, whereas patients with PHN displayed significantly increased FCD in the hippocampus (correlation thresholds r=0.25, voxel level of P

Fuqing Zhou,1,2 Lili Gu,3 Shunda Hong,1,2 Jiaqi Liu,1,2 Jian Jiang,1,2 Muhua Huang,1,2 Yong Zhang,3 Honghan Gong1,2 1Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Neuroradiology Laboratory, Jiangxi Province Medical Imaging Research Institute, Nanchang, Jiangxi, People’s Republic of China; 3Department of Pain Clinic, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, People’s Republic of China Objective: The aim of this study was to explore the amplitude of intrinsic low-frequency oscillations (LFOs) in patients with discogenic low-back and leg pain (LBLP).Participants and methods: We obtained and compared the LFO amplitude from 25 right-handed discogenic LBLP patients (13 males; mean age 55.16±1.83 years) and 27 well-matched healthy controls (15 males; mean age 52.96±1.63 years). The LFO amplitude was examined using the voxel-wise amplitude of low-frequency fluctuations (ALFFs), and partial correlation analysis was performed to determine the relationship between the regions with altered ALFF values and clinical parameters in discogenic LBLP patients.Results: Compared with healthy controls, the patients with discogenic LBLP showed a significant increase in ALFF in the affective system of the pain matrix (left anterior cingulate cortex, right anterior insula/frontal operculum, and bilateral orbitofrontal cortex) and information-processing regions (middle occipital/temporal gyrus). In addition, a significant decrease in ALFF was observed in the default mode network (DMN; inferior parietal lobule (IPL) and medial prefrontal cortex [mPFC]) and the processing system of the pain matrix (basal ganglia/thalamus/midbrain, postcentral gyrus [PoCG], and fusiform gyrus). Several regions with altered ALFF were associated with disease duration, visual analog scale scores, Barthel index, and fine sensory modality measurements (two-point tactile discrimination of the left and/or right leg). Further operating characteristic curves analysis suggested that the mean ALFF values in the right IPL, left IPL/PoCG, left anterior cingulate cortex, and left mPFC could serve as markers to separate individuals with discogenic LBLP from healthy subjects.Conclusion: Our results revealed widespread abnormalities in ALFF in the pain matrix and information-processing regions as well as a decrease in ALFF in the DMN. These results open up an important new avenue to better understand the nature of the link between intrinsic activity and peripheral pain and sensory impairment in discogenic LBLP patients. Keywords: amplitude of low-frequency fluctuations, resting state functional magnetic resonance imaging, discogenic low-back and leg pain, amplitude of low-frequency fluctuations

Fuqing Zhou,1,2 Muhua Huang,1,2 Lin Wu,1,2 Yongming Tan,1,2 Jianqiang Guo,1,2 Yong Zhang,3 Laichang He,1,2 Honghan Gong1,2 1Department of Radiology, the First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, People’s Republic of China; 2Jiangxi Province Medical Imaging Research Institute, Nanchang, Jiangxi Province, People’s Republic of China; 3Department of Pain Clinic, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, People’s Republic of China Objective: Advanced magnetic resonance imaging studies have shown functional plasticity or reorganization and metabolite alterations of N-acetyl aspartate in the sensorimotor cortex (SMC), a hallmark region and key brain network, in patients with cervical spondylotic myelopathy (CSM). However, the nature of perfusion in the SMC and the relationship between regional cerebral blood flow (CBF), motor function scores, and structural damage of the cervical cord in patients with CSM are not fully understood.Materials and methods: All right-handed participants underwent pseudo-continuous arterial spin labeling pulse sequence scanning, and CBF was then calculated and compared between CSM and healthy groups. Clinical and structural associations were assessed in the SMC. Receiver operating characteristic (ROC) and leave-one-out cross-validation analyses were used to estimate the sensitivity and specificity of the significantly altered CBF in the SMC to distinguish myelopathy-related impairment.Results: A total of 18 pairs of CSM patients and well-matched healthy subjects were included in the analyses. Compared with healthy subjects, CSM patients exhibited significantly decreased CBF in the left premotor ventral/precentral operculum (PMv/PrCO) and the bilateral dorsal anterior cingulate cortex (dACC); and increased CBF in the left paracentral lobule (PCL), the right PCL/supplementary motor area (PCL/SMA), and the right postcentral gyrus (PoCG; Gaussian random field correction at P

The drainage consolidation method has been efficiently used to deal with soft ground improvement. Nowadays, it has been suggested to use a new sand soil which is a composite of sand and recycled glass waste. The permeability performance of glass-sand soil was explored to judge the feasibility of glass-sand soil backfilled in the drainage consolidation of sand-drained ground. For comparison purposes, different mix proportions of recycled glass waste, fineness modulus, and glass particle size were analyzed to certify the impact on the permeability coefficient and the degree of consolidation. The numerical results show that adding a proper amount of recycled glass waste could promote the permeability performance of glass-sand soil, and the glasssand soil drain could be consolidated more quickly than a sand drain. Experiments showed that glass-sand soil with the a 20% mix of recycled glass waste reveals the optimum performance of permeability.

Xiaoping Luo,1,2 Linghong Guo,1 Xi-Jian Dai,3 Qinglai Wang,2 Wenzhong Zhu,2 Xinjun Miao,2 Honghan Gong1 1Department of Radiology, The First Affiliated Hospital of Nanchang University, Nangchang, Jiangxi, People’s Republic of China; 2Department of Radiology, Wenzhou Chinese Medicine Hospital, Wenzhou, Zhejiang, People’s Republic of China; 3Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, People’s Republic of China Objective: To explore the abnormal intrinsic functional hubs in alcohol dependence using voxelwise degree centrality analysis approach, and their relationships with clinical features.Materials and methods: Twenty-four male alcohol dependence subjects free of medicine (mean age, 50.21±9.62 years) and 24 age- and education-matched male healthy controls (mean age, 50.29±8.92 years) were recruited. The alcohol use disorders identification test and the severity of alcohol dependence questionnaire (SADQ) were administered to assess the severity of alcohol craving. Voxelwise degree centrality approach was used to assess the abnormal intrinsic functional hubs features in alcohol dependence. Simple linear regression analysis was performed to investigate the relationships between the clinical features and abnormal intrinsic functional hubs.Results: Compared with healthy controls, alcohol dependence subjects exhibited significantly different degree centrality values in widespread left lateralization brain areas, including higher degree centrality values in the left precentral gyrus (BA 6), right hippocampus (BA 35, 36), and left orbitofrontal cortex (BA 11) and lower degree centrality values in the left cerebellum posterior lobe, bilateral secondary visual network (BA 18), and left precuneus (BA 7, 19). SADQ revealed a negative linear correlation with the degree centrality value in the left precentral gyrus (R2=0.296, P=0.006).Conclusion: The specific abnormal intrinsic functional hubs appear to be disrupted by alcohol intoxication, which implicates at least three principal neural systems: including cerebellar, executive control, and visual cortex, which may further affect the normal motor behavior such as an explicit type of impaired driving behavior. These findings expand our understanding of the functional characteristics of alcohol dependence and may provide a new insight into the understanding of the dysfunction and pathophysiology of alcohol dependence. Keywords: alcohol addiction, substance dependence, degree centrality, functional magnetic resonance imaging, functional connectivity driving behavior

Li-Ting Chen,1,* Xiao-Le Fan,2,* Hai-Jun Li,1 Si Nie,1 Hong-Han Gong,1 Wei Zhang,3 Xian-Jun Zeng,1 Ping Long,4 De-Chang Peng1 1Department of Radiology, 2Department of General Surgery, 3Department of Pneumology, 4Department of Otolaryngology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China *These authors contributed equally to this work Purpose: Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder that can damage cognitive function. However, the functional network organization remains poorly understood. The aim of this study was to investigate the topological properties of OSA patients using a graph theoretical analysis.Patients and methods: A total of 30 male patients with untreated severe OSA and 25 male education- and age-matched good sleepers (GSs) underwent functional magnetic resonance imaging (MRI) examinations. Clinical and cognitive evaluations were conducted by an experienced psychologist. GRETNA (a toolbox for topological analysis of imaging connectomics) was used to construct the brain functional network and calculate the small-world properties (γ, λ, σ, Eglob, and Eloc). Relationships between these small-world properties and clinical and neuropsychological assessments were investigated in OSA patients.Results: The networks of both OSA patients and GSs exhibited efficient small-world topology over the sparsity range of 0.05–0.40. Compared with GSs, the OSA group had significantly decreased γ, but significantly increased λ and σ. The OSA group’s brain network showed significantly decreased Eglob (P

Suhua Huang,1 Fuqing Zhou,2,3 Jian Jiang,2,3 Muhua Huang,2,3 Xianjun Zeng,2,3 Shan Ding,1 Honghan Gong2,3 1Department of Radiology, Jiangxi Province Children’s Hospital, 2Department of Radiology, The First Affiliated Hospital, Nanchang University, 3Jiangxi Province Medical Imaging Research Institute, Nanchang, People’s Republic of China Abstract: Several neuroimaging studies have suggested that brain impairment and plasticity occur in patients with chronic primary insomnia (CPI); however, the effects of insomnia on the intrinsic organization of the brain remain largely unknown. In this study, a voxel-based functional connectivity strength (FCS) assessment, a data-driven method based on a theoretical approach, was applied to investigate the effects of insomnia on the intrinsic organization of the whole brain in 27 treatment-naïve CPI patients and 26 well-matched healthy controls (HCs). Compared with HCs, CPI patients exhibited decreased FCS primarily in the right dorsolateral prefrontal cortex, the right medial prefrontal cortex (MPFC), the left basal ganglia/insula, and the right cerebellum anterior lobe (CAL) due to decreased functional connectivity patterns. These results suggest that poor sleep quality could impair FCS within the brain, including the MPFC and the CAL, which are important for cognitive control and modulating motor and limbic functions. Additionally, a receiver operator characteristic analysis revealed that altered FCS has moderate sensitivity (76.9%–88.5%) and specificity (59.3%–70.4%) as a reference indicator to discriminate CPI patients from HCs. Taken together, these findings provide evidence for abnormal intrinsic brain activity in CPI patients and might improve our understanding of the pathophysiological processes that occur in insomnia patients. Keywords: functional connectivity strength, disconnection, chronic primary insomnia, sleep disorders, resting-state fMRI

Zheyong Huang,1,* Yanan Song,1,* Zhiqing Pang,2 Bo Zhang,3 Hongbo Yang,1 Hongtao Shi,1 Jing Chen,1 Hui Gong,1,4 Juying Qian,1 Junbo Ge1,4 1Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 2School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai, 3Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, 4Institute of Biomedical Science, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Purpose: Thymosin beta 4 (Tβ4) has multiple beneficial facets for myocardial injury, but its efficiency is limited by the low local concentration within the infarct. Here, we established a Tβ4 delivery system for cardiac repair based on the interaction between the abundant fibrin in the infarct zone and the fibrin-targeting moiety clot-binding peptide cysteine–arginine–glutamic acid–lysine–alanine (CREKA). Methods and results: CREKA and Tβ4 were conjugated to nanoparticles (CNP–Tβ4). In vitro binding test revealed that CNP–Tβ4 had a significant binding ability to the surface of fibrin clots when compared to the control clots (NP–Tβ4). Based on the validation of fibrin expression in the early stage of ischemia injury, CNP–Tβ4 was intravenously administered to mice with acute myocardial ischemia–reperfusion injury. CNP–Tβ4 revealed a stronger fibrin-targeting ability than the NP–Tβ4 group and accumulated mainly in the infarcted area and colocalized with fibrin. Subsequently, treatment with CNP–Tβ4 resulted in a better therapeutic effect. Conclusion: CRKEA modification favored Tβ4 accumulation and retention in the infarcted region, leading to augmented functional benefits. Fibrin-targeting delivery system represents a generalizable platform technology for regenerative medicine. Keywords: thymosin beta 4, fibrin, CREKA, targeting delivery, ischemia reperfusion, cardiovascular

Minzhi Zhao,* Haiyun Li,* Yan Ma, He Gong, Shu Yang, Qiaojun Fang, Zhiyuan Hu Chinese Academy of Sciences Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: Abraxane (Abr), a US Food and Drug Administration-approved albumin-bound nanoparticle applied for the treatment of non-small-cell lung cancer, has been reported to be more effective than paclitaxel (PTX). To further understand the molecular mechanisms that produce this superior drug efficacy of Abr, a quantitative proteomic approach has been applied to investigate the global protein expression profiles of lung cancer cell A549 treated with Abr and PTX. Only one protein, namely, glucosamine 6-phosphate N-acetyltransferase 1 (GNA1), showed significant differential expression (P

Yan Peng,1,* Shenhong Li,2,* Ying Zhuang,3,* Xiaojia Liu,4 Lin Wu,2 Honghan Gong,2 Dewu Liu,1 Fuqing Zhou2 1Burn Center, 2Department of Radiology, The First Affiliated Hospital, Nanchang University, 3Department of Oncology, The Second Hospital of Nanchang, Nanchang, Jiangxi Province, 4Department of Orthopaedics and Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, People’s Republic of China *These authors contributed equally to this work Background and purpose: Little is known about the structural alterations within gray matter (GM) in middle-aged subjects with white matter hyperintense (WMH) lesions. Here, we aimed to examine the anatomical changes within the GM and their relationship to WMH lesion loads in middle-aged subjects. Participants and methods: Twenty-three middle-aged subjects with WMH lesions (WMH group) and 23 demographically matched healthy control subjects participated in the study. A Diffeomorphic Anatomical Registration Through Exponentiated Liealgebra-enhanced voxel-based morphometry was used to measure the GM density, and the correlations between WMH lesion volume and extracted GM values in abnormal regions were identified by voxel-based morphometry analysis. Results: Compared with the healthy control subjects, the WMH group had a significantly decreased GM density in the left middle frontal gyrus, bilateral anterior cingulate cortex, left and right premotor cortex, and left and right middle cingulate cortex and an increased GM density in the bilateral cerebellum anterior lobe, left middle temporal gyrus, right temporoparietal junction, left and right prefrontal cortex (PFC), and left inferior parietal lobule. A relationship was observed between the normalized WMH lesion volume and the decreased GM density, including the left middle frontal gyrus (ρ=-0.629, P=0.002), bilateral anterior cingulate cortex (ρ=-0.507, P=0.019), right middle cingulate cortex (ρ=-0.484, P=0.026), and right premotor cortex (ρ=-0.438, P=0.047). The WMH lesion loads also negatively correlated with increased GM density in the right temporoparietal junction (ρ=-0.484, P=0.026), left PFC (ρ=-0.469, P=0.032), and right PFC (ρ=-0.438, P=0.047). Conclusion: We observed that lesion load-associated structural plasticity corresponds to bidirectional changes in regional GM density in the WMH group. Keywords: white matter hyperintense lesion, voxel-based morphometry, normal-appearing gray matter, aging