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Fengsong Chen,1,* Yanhua Huang,1,* Yongxia Liu,2 Yanwen Zhuang,3 Xiaowei Cao,3 Xiaogang Qin2 1Department of Gastroenterology, Nantong Haimen People’s Hospital, Nantong, Jiangsu, 226100, People’s Republic of China; 2Department of gastroenterology, Traditional Chinese Medicine Hospital of Tongzhou District, Nantong, Jiangsu, 226300, People’s Republic of China; 3Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu, 225001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaogang Qin, Email tzqinxiaogang@163.comBackground: Colorectal cancer (CRC) has become a significant global public health challenge, demanding immediate attention due to its high incidence and mortality rates. Regular CRC screening is essential for the early detection of precancerous lesions and CRC.Methods: : We developed a novel surface-enhanced Raman scattering (SERS) analysis platform that employs high-throughput microarray chips as carriers and Au/SnO2 nanoring arrays (Au/SnO2 NRAs) as substrates. This platform utilizes an aptamer recognition-release strategy to achieve efficient and sensitive detection of protein tumor markers. In the detection process, the strong affinity and high specificity between the aptamer and the target protein result in competitive replacement of the SERS nanoprobes originally bound to the substrate surface. As a result, the SERS nanoprobes carrying Raman reporter genes are dislodged, leading to a reduction in the SERS signal intensity.Results: The platform demonstrated excellent detection performance, with rapid detection completed within 15 minutes and limits of detection (LOD) as low as 6.2× 10− 12 g/mL for hnRNP A1 and 6.51× 10− 12 g/mL for S100P. Clinical samples analyzed using the SERS platform showed high consistency with enzyme-linked immunosorbent assay (ELISA) results.Conclusion: This platform offers strong support for the early detection, risk assessment, and treatment monitoring of colorectal cancer precancerous lesions, with broad potential for clinical applications.Keywords: colorectal cancer, precancerous lesions, surface enhanced raman scattering, aptamer, microarray chip

Xuanling Chen,1,&ast; Xuewei Qin,1,&ast; Yutong Zhuang,2 Zhengqian Li,3 Zhenhu Liang,4 Hua Zhang,5 Lan Yao,1 Xiaoli Li,6 Jianghong He,7 Xiangyang Guo3 1Department of Anesthesiology, Peking University International Hospital, Beijing, People’s Republic of China; 2Department of Neurosurgery, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 3Department of Anesthesiology, Peking University Third Hospital, Beijing, People’s Republic of China; 4Institute of Electrical Engineering, Yanshan University, Qinhuangdao, People’s Republic of China; 5Clinical Epidemiology Research Center, Peking University Third Hospital, Beijing, People’s Republic of China; 6The State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, People’s Republic of China; 7Department of Neurosurgery, Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangyang Guo, Peking University, Third Hospital, 49 huayuan North Road, Haidian District, Beijing, 100191, People’s Republic of China, Email puthmzk@hsc.pku.edu.cn Jianghong He, Beijing Tiantan Hospital, 119 South Fourth Ring Road West, Fengtai District, Beijing, 100069, People’s Republic of China, Email hejianghong@sina.cnObjective: To observe whether maintaining the appropriate depth of anesthesia with Bispectral Index (BIS) can improve the prognosis of Spinal Cord stimulation (SCS) implantation in patients with chronic Disorders of consciousness (DoC).Methods: 103 patients with DoC undergoing SCS implantation were reviewed, and 83 patients with DoC were included according to the standard of inclusion and exclusion Criteria. Patients were divided into a BIS group (n =45) and a non-BIS group (n =38) according to whether BIS monitoring was used during the operation. The depth of anesthesia in the BIS group was maintained between 40– 60. The anesthesiologist adjusted the depth of anesthesia in the non-BIS group according to clinical experience. Relevant information such as disease course, cause, anesthesia time, and operation time were collected. Preoperative CRS-R(preoperative) score, postoperative CRS-R(24h), and postoperative CRS-R(3m) changes were collected.Results: The CRS-R(3m) score in the BIS group was higher than that in the non-BIS group (preoperative), and the difference was statistically significant (P < 0.05). In CRS-R (24h), the BIS group was higher than the non-BIS group, and the difference was statistically significant (X2=8.787, P =0.004). The improvement of consciousness was included in the multivariate Logistic regression analysis model, and it was found that the thalamus was an independent factor affecting the improvement of consciousness (P < 0.05). During follow-up, 1 patient in the BIS group had a decrease in consciousness from MCS− to VS/ UWS and 2 patients in the non-BIS group died during follow-up.Conclusion: Patients can be benefit in hearing in CRS-R (24h). We recommend the use of BIS to monitor the depth of anesthesia in patients with DoC to improve patient outcomes.Keywords: chronic disturbance of consciousness, vegetative state/unresponsive wakefulness syndrome, spinal cord stimulation, general anesthesia, bispectral index, improved coma recovery scale

Shaojie Li,1,&ast; Qiangqiang Feng,1,&ast; Jiayin Wang,1 Baofang Wu,1 Weizhi Qiu,1 Yiming Zhuang,2 Yong Wang,3 Hongzhi Gao1 1Department of Neurosurgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, 362000, People’s Republic of China; 2Internal Medicine, Quanzhou Quangang District Hillside Street Community Health Service Center, Quanzhou, Fujian, 362000, People’s Republic of China; 3Child and Adolescent Psychiatry, The Third Hospital of Quanzhou, Quanzhou, Fujian, 362000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong Wang; Hongzhi Gao, Email 120432246@qq.com; gaohongzhi@fjmu.edu.cnObjective: To develop a validated machine learning (ML) algorithm for predicting the risk of hospital-acquired pneumonia (HAP) in patients with traumatic brain injury (TBI).Materials and Methods: We employed the Least Absolute Shrinkage and Selection Operator (LASSO) to identify critical features related to pneumonia. Five ML models—Logistic Regression (LR), Extreme Gradient Boosting (XGB), Random Forest (RF), Naive Bayes Classifier (NB), and Support Vector Machine (SVC)—were developed and assessed using the training and validation datasets. The optimal model was selected based on its performance metrics and used to create a dynamic web-based nomogram.Results: In a cohort of 858 TBI patients, the HAP incidence was 41.02%. LR was determined to be the optimal model with superior performance metrics including AUC, accuracy, and F1-score. Key predictive factors included Age, Glasgow Coma Score, Rotterdam Score, D-dimer, and the Systemic Immune Response to Inflammation Index (SIRI). The nomogram developed based on these predictors demonstrated high predictive accuracy, with AUCs of 0.818 and 0.819 for the training and validation datasets, respectively. Decision curve analysis (DCA) and calibration curves validated the model’s clinical utility and accuracy.Conclusion: We successfully developed and validated a high-performance ML algorithm to assess the risk of HAP in TBI patients. The dynamic nomogram provides a practical tool for real-time risk assessment, potentially improving clinical outcomes by aiding in early intervention and personalized patient management.Keywords: traumatic brain injury, machine learning, hospital-acquired pneumonia, dynamic nomogram, imaging metrics

Junhua Zhu, Yue Zhuang, Wenjing Li School of Safety Science and Emergency Management, Wuhan University of Technology, Wuhan, People’s Republic of ChinaCorrespondence: Yue Zhuang, Email zhuangyue@whut.edu.cnPurpose: The use of multi-source precursor data to predict the epidemic risk level would aid in the early and timely identification of the epidemic risk of infectious diseases. To achieve this, a new comprehensive big data fusion assessment method must be developed.Methods: With the help of the Functional Resonance Analysis Method (FRAM) model, this paper proposes a risk portrait for the whole process of a pandemic spreading. Using medical, human behaviour, internet and geo-meteorological data, a hierarchical multi-source dataset was developed with three function module tags, ie, Basic Risk Factors (BRF), the Spread of Epidemic Threats (SET) and Risk Influencing Factors (RIF).Results: Using the dynamic functional network diagram of the risk assessment functional module, the FRAM portrait was applied to pandemic case analysis in Wuhan in 2020. This new-format FRAM portrait model offers a potential early and rapid risk assessment method that could be applied in future acute public health events.Keywords: epidemic risk, FRAM, model, big data portrait

Xian Du,1,&ast; Jun Hu,1,&ast; Jianhua Xue,1 Yuan Zhuang,2 Xuefeng Tang,1 Zhiyue Xu1 1Health Examination Center, Shanghai Health and Medical Center (Huadong Sanatorium), Wuxi, People’s Republic of China; 2The Affiliated Hospital of Nantong University, Nantong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiyue Xu; Xuefeng Tang, Health Examination Center, Shanghai Health and Medical Center (Huadong Sanatorium), 67 Dajishan, Wuxi, 214065, People’s Republic of China, Email hepenxiaozi@163.com; 978665164@qq.comPurpose: Fatigue was a common symptom of non-alcoholic fatty liver disease (NAFLD), which seriously affected patients’ quality of life. The aim of this study was to detect fatigue rate and to evaluate factors associated with fatigue in NAFLD patients.Patients and Methods: A cross-sectional study was carried out from the Huadong Sanatorium between April 2022 and May 2023, and 133 NAFLD patients were included in this study. They completed Fatigue Severity Scale to assess fatigue, the Hospital Anxiety and Depression Scale to estimate psychological status, and the Pittsburgh Sleep Quality Index for sleep quality. Data were analyzed by independent samples t-tests, χ 2 tests and logistic regression models.Results: We found that 51.1% of NAFLD patients had fatigue. Exercise, anxiety, depression, subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disorders, daytime dysfunction and overall sleep quality were related to fatigue among NAFLD patients. Moreover, logistic regression models indicated anxiety, habitual sleep efficiency and sleep disorders as important predictors of fatigue.Conclusion: This was the first time to explore demographic, clinical, psychological and sleeping correlated factors for fatigue in Chinese NAFLD patients. Our study showed that more than half of NAFLD patients had fatigue, and anxiety, habitual sleep efficiency and sleep disorders were significantly associated with fatigue in NAFLD. The findings indicated that it was very necessary to pay more attention to fatigue of NAFLD patients, especially those with negative emotions and poor sleep quality by favorable intervention to relieve fatigue symptoms, so as to improve quality of life.Keywords: non-alcoholic fatty liver disease, fatigue, exercise, anxiety, sleep

Yuan Zhuang,1,2 Ru Zhang,3,4 Miaomiao Li,3,4 Yaru Zou,1 Shui Jiang,1 Yanan Zhang,1 Shiguo Liu,3,4 Bo Yu1 1Dermatological Department, The Affiliated Hospital of QingdaoUniversity, Qingdao, People’s Republic of China; 2dermatological department, Women and Children’s hospital, Qingdao University, Qingdao, People’s Republic of China; 3Medical Genetic Department, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 4Prenatal Diagnosis Center, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of ChinaCorrespondence: Bo Yu, Dermatological department, The Affiliated Hospital of QingdaoUniversity, Qingdao, People’s Republic of China, Email yubo@qduhospital.cn Shiguo Liu, Medical Genetic Department, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China, Email liushiguo@qdu.edu.cnIntroduction: Hypohidrotic ectodermal dysplasia (HED) is a genetic disorder that influences structures of ectodermal origin, such as teeth, hair, and sweat glands. Compared with autosomal recessive and dominant modes of inheritance, the X-linked HED (XLHED) characterized by Hypodontia/Oligodontia teeth, Absent/sparse hair, Anhidrosis/hypohidrosis, and characteristic facial features, is the most frequent and its primary cause is the mutation of ectodysplasin A (EDA) gene. This research aimed to expound the clinical and molecular features of a Chinese male with XLHED and to summarize and compare several previous findings.Methods: Genomic DNA was obtained from the peripheral blood of the proband and his family members, then Sanger sequencing was used to perform a mutational analysis of EDA. Real-time quantitative PCR and Western blotting were used to detect EDA expression. The transcriptional activity of NF-κB was detected using a luciferase assay.Results: The probandwith XLHED was identified a novel EDA mutation, c.1119G>C(p.M373I), that affected the molecular analysis of transmembrane protein exon8 mutations, inherited from the mother. He showed a severe multiple-tooth loss, with over 20 permanent teeth missing and sparse hair and eyebrows, dry, thin, and itching skin. Furthermore, his sweating function was abnormal to a certain extent.Discussion: The functional study showed that this novel mutant led to a significant decrease in the EDA expression level and transcriptional activity of NF-κB. Our findings extend the range of EDA mutations in XLHED patients, which provides the basis and idea for further exploring the pathogenesis of XLHED.Keywords: EDA, X-linked hypohidrotic ectodermal dysplasia, gene mutation

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

Yubin Zhu,1 Yilu Zhuang,2 Yawen Yu,2 Jinyue Wang,2 Yongtai Liu,3 Zhi Ruan,2,4 Wei Xiao,5 Yingying Kong2,4 1Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3The First Division Hospital of XinJiang Production and Construction Group, XinJiang, People’s Republic of China; 4Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Hangzhou, People’s Republic of China; 5Department of Emergency Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Yingying Kong; Wei Xiao, Email kongyy@zju.edu.cn; Xiaowei 2022@zju.edu.cnAbstract: Raoultella planticola is an emerging bacterial pathogen responsible for causing infections in both humans and animals. Unfortunately, sporadic reports of carbapenem-resistant R. planticola (CRRP) have been documented worldwide. Here we first reported the complete genome sequence of a CRRP isolate RP_3045 co-carrying blaIMP-4 and blaSHV-12, recovered from a patient in China, and its genetic relatedness to 82 R. planticola strains deposited in the NCBI GenBank database, sourced from humans, animals, and the environment. Whole-genome sequencing was performed using the Illumina NovaSeq 6000 and Oxford Nanopore MinION platforms. Phylogenetic analysis was also performed and visualized using a single nucleotide polymorphism (SNP)-based strategy. The complete genome of R. planticola strain RP_3045 was determined to be 6,312,961 bp in length, comprising five contigs that included one chromosome and four plasmids. RP_3045 was found to be multidrug-resistant and harbored several antimicrobial resistance genes, including both blaIMP-4 and blaSHV-12 genes located on a single plasmid. The most closely related strain was hkcpe63, recovered from humans in Hong Kong, China, in 2014, with 506 SNP differences. R. planticola strains were distributed globally and exhibited strong associations among isolates obtained from different sectors. This study provides evidence for the potential of R. planticola to disseminate carbapenem resistance across different sectors, highlighting the critical need for active and continuous surveillance of CRRP.Keywords: Raoultella planticola, blaIMP-4, blaSHV-12, antimicrobial resistance

Junning Cheng,&ast; Yuewen Lao,&ast; Xiangping Chen, Xiaoting Qiao, Weijing Sui, Xiaoyan Gong, Yiyu Zhuang Nursing Department, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yiyu Zhuang, Nursing Department, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, People’s Republic of China, Tel +8613588708076, Email zhuangyy@zju.edu.cnPurpose: To develop a dynamic nomogram of subsyndromal delirium (SSD) in intensive care unit (ICU) patients and internally validate its efficacy in predicting SSD.Patients and Methods: Patients who met the inclusion and exclusion criteria in the ICU of a tertiary hospital in Zhejiang from September 2021 to June 2022 were selected as the research objects. The patient data were randomly divided into the training set and validation set according to the ratio of 7:3. The least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression were used to screen the predictors of SSD, and R software was used to construct a dynamic nomogram. Receiver operating characteristic (ROC) curve, calibration band and decision curve were used to evaluate the discrimination, calibration and clinical effectiveness of the model.Results: A total of 1000 eligible patients were included, including 700 in the training set and 300 in the validation set. Age, drinking history, C reactive protein level, APACHE II, indwelling urinary catheter, mechanical ventilation, cerebrovascular disease, respiratory failure, constraint, dexmedetomidine, and propofol were predictors of SSD in ICU patients. The ROC curve values of the training set was 0.902 (95% confidence interval: 0.879– 0.925), the best cutoff value was 0.264, the specificity was 78.4%, and the sensitivity was 88.0%. The ROC curve values of the validation set was 0.888 (95% confidence interval: 0.850– 0.930), the best cutoff value was 0.543, the specificity was 94.9%, and the sensitivity was 70.9%. The calibration band showed good calibration in the training and validation set. Decision curve analysis showed that the net benefit in the model was significantly high.Conclusion: The dynamic nomogram has good predictive performance, so it is a precise and effective tool for medical staff to predict and manage SSD in the early stage.Keywords: subsyndromal delirium, intensive care unit, nomogram, prediction model, LASSO

In this study, the degradation behavior of flexible GaInP/GaAs/InGaAs (IMM3J) solar cells and their metamorphic subcells under 1 MeV electron irradiation was investigated. The remaining factors such as short-circuit current density (Jsc), open-circuit voltage (Voc), and maximum power (Pmax) were 95.62, 85.52, and 79.73%, respectively, at an irradiation fluence of 2 × 1015 e/cm2. The spectral responses of the InGaAs and GaAs subcells degraded significantly, and the InGaAs subcell experienced greater degradation than the GaAs subcell after irradiation. In addition, the current-limiting unit was switched from GaInP to InGaAs after irradiation. Defect analysis by deep-level transient spectroscopy (DLTS) revealed that with increasing irradiation fluence, the defects that had the greatest impact on the performance of GaAs subcells were EV + 0.36 and EV + 0.42 eV. For InGaAs subcells, the defects that had the greatest impact on the performance were EV + 0.29 and EV + 0.24 eV. The decrease in the minority carrier lifetime is the main reason for the decrease in the electrical performance of solar cells, and the variation in the effective minority carrier lifetime (τeff) in the subcells with the irradiation fluence was calculated based on the DLTS results. At a fluence of 2 × 1015 e/cm2, the τeff of the GaAs and InGaAs subcells decreased from 2.93 × 10−10 and 9.10 × 10−10 s to 1.56 × 10−11 and 1.60 × 10−12 s, respectively. These results provide a reference for predicting the degradation of short-circuit current and open-circuit voltage of flexible IMM3J. [ABSTRACT FROM AUTHOR]

Yangfan Zhuang,1 Hao Tu,1 Quanrui Feng,2 Huiming Tang,3 Li Fu,1 Yuchang Wang,1 Xiangjun Bai1 1Trauma Center/Department of Emergency and Traumatic Surgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Department of Intensive Care Unit, First Hospital of Wuhan, Wuhan, Hubei Province, People’s Republic of China; 3Department of Intensive Care Unit, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Xiangjun Bai, Trauma Center/Department of Emergency and Traumatic Surgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China, Email whtj_bxj@163.comPurpose: Currently, assessing trauma severity alone in geriatric trauma patients (GTPs) cannot accurately predict the risk of serious adverse outcomes during hospitalization. As an emerging concept in recent years, frailty syndrome is closely related to the poor prognosis of many diseases in elderly patients, including trauma. A logistic model for predicting adverse outcomes in elderly trauma patients during hospitalization was constructed in elderly patients, and the predictive efficacy of the model was verified.Patients and Methods: Trauma patients aged ≥ 65 years between June 2020 and September 2021 were selected and randomly divided into a training set and validation set at a ratio of 3:1. Mid arm muscle circumference (MAMC) was measured to determine the degree of frailty. LASSO regression was used to screen appropriate variables for the construction of a prognostic model. The logistic regression model was established and presented in the form of a nomogram. Calibration curves and ROC curves were used to verify the performance of the model.Results: A total of 209 patients were enrolled, including 143 (68.4%) males and 66 (31.6%) females, with an average age of 70.8 ± 4.8 years. Ageless Charlson comorbidity index, BT unit, ISS, GCS, MAMC, prealbumin and lactic acid levels were screened by LASSO regression to construct a prognostic model. The AUC of the ROC analysis prediction model was 0.89 (95% CI 0.80– 0.97) in the validation set. The results of the Hosmer–Lemeshow test for the validation set were χ 2 = 11.23, P = 0.189.Conclusion: The prognostic model of adverse outcomes in GTPs has good accuracy and differentiation, which can improve the prediction results of risk stratification of GTPs during hospitalization by medical staff and provide a new idea for prognostic prediction.Keywords: geriatric trauma patients, frailty, MAMC, prognostic model for adverse outcomes

Fengjin Shao,1– 3 Rui Liu,1 Xun Tan,1– 4 Qiaoyan Zhang,1– 3 Lujie Ye,1– 3 Bingxuan Yan,1– 3 Ying Zhuang,1,2,4 Jiaxue Xu1,2,4 1Department of Veterinary Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China; 2Veterinary Medical Center, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China; 3Institute of Preventive Veterinary Sciences, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China; 4Hainan Institute of Zhejiang University, Sanya, Hainan Province, People’s Republic of ChinaCorrespondence: Xun Tan, Department of Veterinary Medicine, Zhejiang University, Yuhangtang Road 866, Hangzhou, 310058, People’s Republic of China, Tel +86 571 8898 2393, Fax +86 571 8898 2310, Email tanxun@zju.edu.cnPurpose: Pulmonary arterial hypertension (PAH) is a progressive and fatal pulmonary vascular disease initiated by endothelial dysfunction. Mesenchymal stromal cells (MSCs) have been shown to ameliorate PAH in various rodent models; however, these models do not recapitulate all the histopathological alterations observed in human PAH. Broiler chickens (Gallus gallus) can develop PAH spontaneously with neointimal and plexogenic arteriopathy strikingly similar to that in human patients. Herein, we examined the protective effects of MSC transplantation on the development of PAH in this avian model.Methods: Mixed-sex broilers at 15 d of age were received 2× 106 MSCs or PBS intravenously. One day later, birds were exposed to cool temperature with excessive salt in their drinking water to induce PAH. Cumulative morbidity from PAH and right-to-left ventricle ratio were recorded. Lung histologic features were evaluated for the presence of endothelial damage, endothelial proliferation and plexiform lesions. Expression of proinflammatory mediators and angiogenic factors in the lung was detected. Matrigel tube formation assay was performed to determine the angiogenic potential of endogenous MSCs.Results: MSC administration reduced cumulative PAH morbidity and attenuated endothelial damage, plexiform lesions and production of inflammatory mediators in the lungs. No significant difference in the expression of paracrine angiogenic factors including VEGF-A and TGF-β was determined between groups, suggesting that they are not essential for the beneficial effect of MSC transplantation. Interestingly, the endogenous MSCs from birds receiving MSC transplantation demonstrated endothelial differentiatial capacity in vitro whereas those from the mock birds did not.Conclusion: Our results support the therapeutic use of MSC transplantation for PAH treatment and suggest that exogenous MSCs produce beneficial effects through modulating inflammation and endogenous MSC-mediated vascular repair.Graphical Abstract: Keywords: plexiform lesion, right ventricular hypertrophy, VEGF-A, TGF-β, angiogenesis, bone marrow

Lifang Wei,1,&ast; Ye Li,2 Yue Yu,1 Minmin Xu,1 Huilan Chen,1 Lijie Li,1 Ting Peng,1 Kang Zhao,1 Yongze Zhuang3,&ast; 1Department of Nephrology, The Third People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China; 2The Third People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China; 3Department of Nephrology, 900 Hospital of the Joint Logistics Team, PLA, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lifang Wei; Yongze Zhuang Tel +86 591 62091295Fax +86 591 22869300Email liwlf2008@163.com; Doczhuang@aliyun.comAbstract: Obesity-related glomerulopathy (ORG) is a secondary glomerular disease caused by obesity, with clinical manifestations such as proteinuria and glomerulomegaly. Currently, the high incidence of obesity brings a change in the spectrum of kidney diseases across the globe, including China. ORG has become another important secondary nephropathy leading to end-stage renal disease (ESRD), and its incidence has increased significantly. This trend is bound to bring about a serious socioeconomic burden. Therefore, it is urgent to study its pathogenesis and intervention measures. Currently, the occurrence and development mechanisms in ORG are complicated by many factors, which are still unclear. In the past 20 years, with the continuous intensive research on mechanisms such as hypoxia in the metabolic process, immune inflammation, and pyroptosis, there have been new advances in the mechanism of ORG, especially the important role of inflammation in podocyte injury and its impact on the progress of ORG. Here, we briefly review the possible pathogenic role of the inflammasome in the podocyte damage in ORG and summarize the possible therapeutical strategies targeting inflammasome.Keywords: obesity, NLRP3 inflammasome, ORG, podocyte, Chinese herbal medicines

Yifang Chen,1,&ast; Yang Li,1,&ast; Han Guo,1,2,&ast; Zhaoqi Zhang,1,2 Jiayu Zhang,1,2 Xue Dong,1 Yi Liu,3 Yuan Zhuang,3 Yong Zhao1,4 1Department of State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, People’s Republic of China; 2Savaid Medical School, University of Chinese Academy of Sciences, Beijing, People’s Republic of China; 3Department of Blood Transfusion, First Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 4Department of State Key Laboratory of Membrane Biology, Institute for Stem Cell and Regeneration, Chinese Academy of Science, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong Zhao; Yuan Zhuang Email zhaoy@ioz.ac.cn; zhuangyuan0215@126.comBackground: Neutrophils present great diverse phenotypes in various microenvironments and play different immune regulatory functions. Neutrophils generally classified into inflammatory phenotype N1 and anti-informatory phenotype N2. Our recent studies showed that IL-23 alone stimulated neutrophils to express IL-17A, IL-17F and IL-22 and displayed a gene transcriptional profile similar to Th17 cells. In the present study, we tried to identify potential cytokines to promote IL-23-induced neutrophil polarization.Methods: Mouse bone marrow-derived neutrophils and human peripheral blood neutrophils were treated with IL-23 (10 ng/mL) plus IL-18 (25 ng/mL) to induce Th17-like subset in vitro and detected by real-time PCR, flow cytometry, ELISA, immunofluorescence and RNA-seq assays. In vivo, collagen-induced arthritis (CIA) mouse model and EL4 tumor-bearing mouse model were used to characterize the potential roles of N(IL-23+IL-18) in inflammation and tumor.Results: Real-time PCR, ELISA and flow cytometry assays showed that IL-18 could significantly enhance IL-23-induced IL-17A, IL-17F and IL-22 expressions in mouse and human neutrophils in a synergistic way, although IL-18 alone failed to induce these cytokines expression. RNA-seq and molecular studies showed that the polarization of N(IL-23+IL-18) is mainly mediated by the JNK/p38-STAT3-BATF signaling pathway. Adoptive transfer of the induced N(IL-23+IL-18) neutrophils significantly accelerated the tumor growth in EL4 tumor-bearing mice and enhanced disease progression in the CIA mouse model. IL-17A-deficient N(IL-23+IL-18) neutrophils failed to enhance the CIA pathogenesis in this model, suggesting that IL-17A may be involved in the N(IL-23+IL-18) neutrophils-promoted arthritis in mice.Conclusion: The Th17-type subpopulation N(IL-23+IL-18) has pro-tumor and pro-inflammatory properties. Recognizing the different functional polarization of neutrophils would significantly help us to understand the distinctive protective/pathological roles of neutrophils in physiological and different pathological situations.Keywords: IL-23, IL-18, neutrophils, polarization, tumor, arthritis

Shijuan Zhang,1 Yuhong Wei,2 Jinxia Liu,3 Yutian Zhuang1 1Department of Critical Care Medicine, Yidu Central Hospital of Weifang, Weifang, Shandong, 262500, People’s Republic of China; 2Department of Gastroenterology First Ward, Yidu Central Hospital of Weifang, Weifang, Shandong, 262500, People’s Republic of China; 3Department of Neurology First Ward, Yidu Central Hospital of Weifang, Weifang, Shandong, 262500, People’s Republic of ChinaCorrespondence: Yutian ZhuangDepartment of Critical Care Medicine, Yidu Central Hospital of Weifang, Weifang, Shandong, 262500, People’s Republic of ChinaTel +86-13573698900Fax +86-0536-3277731Email zhuang76349@163.comIntroduction: Sepsis is a heterogeneous syndrome with a life-long threat caused by infection. This study aimed to investigate the clinical function of miR-940 and its influence on cardiomyocyte models.Methods: The relative expression of miR-940 was assessed by qRT-PCR and the roles in the clinical diagnosis of miR-940 were revealed by the ROC curve. The relationship between miR-940 and clinical parameters was validated by Pearson analysis. The sepsis rat models were established by treatment with cecal ligation and perforation (CLP) and clinical items including left ventricular systolic pressure (LVSP), left ventricular and end-diastolic pressure (LVEDP), maximum rate of increase/decrease in left ventricular blood pressure (± dp/dtmax) as well as troponin (cTnl), creatine kinase isoenzyme (CK-MB), TNF-α, IL-1β, and IL-6 were detected.Results: The finding of qRT-PCR accentuated that the relative expression of miR-940 was significantly decreased in sepsis patients and CLP-stimulated models. The ROC curve proposed that miR-940 could be a satisfactory diagnostic biomarker for sepsis patients. Pearson analysis reinforced the expression of miR-940 was negatively associated with the PCT, WBC, CRP, Scr, SOFA score, and APACHE II score. The outcome of CLP-steered rat verified that overexpression of miR-940 inhibited the detrimental effects of CLP on myocardial dysfunction and inflammation reactions.Conclusion: The downregulation of miR-940 was reported and it might be an underlying diagnostic marker in sepsis patients. Overexpression of miR-940 protected myocardial function from damage and inflammation induced by CLP.Keywords: miR-940, sepsis, inflammation, myocardial disorder

Arun Venkataraman,1 Yuchuan Zhuang,2 Jennifer Marsella,3 Madalina E Tivarus,4,5 Xing Qiu,6 Lu Wang,6 Jianhui Zhong,1,4 Giovanni Schifitto3,4 1Department of Physics and Astronomy, University of Rochester, Rochester, NY, USA; 2Department of Electrical and Computer Engineering, University of Rochester, Rochester, NY, USA; 3Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA; 4Department of Imaging Sciences, University of Rochester Medical Center, Rochester, NY, USA; 5Department of Neuroscience, University of Rochester Medical Center, Rochester, NY, USA; 6Department of Biostatistics and Computational Biology, University of Rochester, Rochester, NY, USACorrespondence: Arun Venkataraman Email Arun_Venkataraman@urmc.rochester.eduObjective: To examine resting-state functional MRI (rs-fMRI) networks related to sleep in the context of HIV infection.Methods: rs-fMRI data were collected in 40 HIV-infected (HIV+) individuals at baseline (treatment-naive), 12 week (post-treatment) and one year timepoints. A group of 50 age-matched HIV-negative (HIV-) individuals were also imaged at baseline and one year timepoints. The Pittsburgh Sleep Quality Index (PSQI) questionnaire was administered at all timepoints. Using group independent component analysis (ICA), maps of functional networks were generated from fMRI data; from these, sleep-related networks were selected. A generalized linear model (GLM) was used to analyze if these networks were significantly associated with the PSQI score, and if this relationship was influenced by HIV status/treatment or timepoint.Results: HIV+ individuals had significantly lower PSQI score after treatment (p=0.022). Networks extracted from group ICA analysis included the anterior and posterior default mode network (DMN), central executive network (CEN), bilateral frontoparietal networks (FPNs), and the anterior cingulate cortex salience network (ACC SN). We found the posterior DMN, right FPN, and ACC SN GLMs showed significantly higher goodness-of-fit after incorporating PSQI data (p = 0.0204, 0.044, 0.044, respectively). Furthermore, the correlation between ACC SN and posterior DMN connectivity was significantly decreased in the HIV+ cohort.Conclusion: Functional networks such as the DMN, FPN, CEN, and ACC SN are altered in poor sleep, as measured by the PSQI score. Furthermore, the relationship between these networks and PSQI is different in the HIV+ and HIV- populations.Keywords: HIV, fMRI, sleep quality, functional connectivity

Herein, composites based on Ni-doped ZnO nanorods and Ti3C2 MXene structure (Ni-ZnO NR/Ti3C2) were produced via a simple hydrothermal method for photocatalytic applications. Special attention was paid to their structural and optical properties. The composite exhibited a photocatalytic effectiveness of 88.2% in degrading methyl orange (MO) within a duration of 75 minutes when exposed to a xenon lamp. The enhancement of the catalytic activity was due to the one-dimensional ZnO nanostructure, the Ni doping, and the Schottky heterojunction is formed by the interface within ZnO and Ti3C2. Therefore, this work provides an effective strategy to fabricate metal oxide/MXene photocatalysts. [ABSTRACT FROM AUTHOR]

Yan Zhuang, Yuxia Yan, Xia Yang, Jie Cao Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, People’s Republic of ChinaCorrespondence: Xia Yang; Jie CaoDepartment of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin 300052, People’s Republic of ChinaTel +86 13682187319; +86 13132088076Fax +86 22 60361720Email xiaoxia20050111@163.com; tjcaojie@sina.comPurpose: There are few studies on osteoporosis in chronic obstructive pulmonary disease-obstructive sleep apnea overlap syndrome, and the results obtained are inconsistent. The purpose of our study is to observe the occurrence of osteoporosis and its possible mechanism in rat model co-exposed to cigarette smoke and intermittent hypoxia.Materials and Methods: The rats were randomly divided into four groups: air exposed group, cigarette smoke (CS) exposed group, 10% concentration of intermittent hypoxia exposed group, CS combined with 10% concentration of intermittent hypoxia exposed group. All animals completed lung function and lung tissue morphology assessment. The femurs were examined by microcomputer tomography (microCT). Tartrate-resistant acidic phosphatase (TRAP) staining was used to evaluate the osteoclasts. We also assessed the interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in peripheral blood.Results: There was no difference in the femoral length between each group, but the quantitative analyses of microCT showed that compared with the air exposed group, the percent bone volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), cortical thickness (Ct.Th) and bone mineral density (BMD) decreased, and the trabecular separation (Tb.Sp) and the proportion of trap-positive cells increased significantly in the overlapping exposed group. There were higher levels of BV/TV in the overlapping group than CS exposed group. Compared with the intermittent hypoxia exposed group, there were lower levels of Tb.Th and Ct.Th and higher levels of Tb.Sp in the overlapping exposed group. However, there was no statistical difference of trap-positive cell between the overlapping exposed group and the CS exposed single group or the intermittent hypoxia exposed group. There were higher levels of IL-6 and TNF-α in the overlapping exposed group than those in the air-exposed group.Conclusion: Bone destruction increased in the overlapping exposed rat model compared with the rat exposed to air, which may be related to the upregulation of inflammation.Keywords: osteoporosis, cigarette smoke exposure, intermittent hypoxia exposure, overlapping exposed rat model

Kai Zhang,1 Yanling Zhuang,2 Jiwen Li,1 Xiaochang Liu,3,4 Shaoheng He4 1College of Science and Technology, Hebei Agricultural University, Cangzhou, People’s Republic of China; 2College of Humanities and Management, Hebei Agricultural University, Cangzhou, People’s Republic of China; 3School of Pharmacy, Shenyang Medical College, Shenyang, People’s Republic of China; 4Translational Medicine Research Centre, Shenyang Medical College, Shenyang, People’s Republic of ChinaCorrespondence: Xiaochang LiuSchool of Pharmacy, Shenyang Medical College, Shenyang, People’s Republic of ChinaTel +86-24-62216610Fax +86-24-62214089Email liuxiaochang1991@163.comIntroduction: Hypertension is a major health problem worldwide and is typically treated using oral drugs. However, the frequency of oral administration may result in poor patient compliance, and reduced bioavailability owing to the first-pass effect can also prove problematic.Methods: In this study, we developed a new transdermal-drug-delivery system (TDDS) for the treatment of hypertension using atenolol (ATE) based on poly(acrylic acid) (PAA)-decorated three-dimensional (3D) flower-like MoS2 nanoparticles (PAA-MoS2 NPs) that respond to NIR laser irradiation. The PAA-modified MoS2 NPs were synthesized and characterized using attenuated total reflection Fourier-transform infrared spectroscopy, X-ray diffraction measurements, scanning electron microscopy, transmission electron microscopy, dynamic light scattering, and the sedimentation equilibrium method. The drug-loading efficiency and photothermal conversion effect were also explored.Results: The results showed that the colloidally stable PAA-MoS2 NPs exhibited a high drug-loading capacity of 54.99% and high photothermal conversion ability. Further, the capacity of the PAA-MoS2 NPs for controlled release was explored using in vitro drug-release and skin-penetration studies. The drug-release percentage was 44.72 ± 1.04%, and skin penetration was enhanced by a factor of 1.85 in the laser-stimulated group. Sustained and controlled release by the developed TDDS were observed with laser stimulation. Moreover, in vivo erythema index analysis verified that the PAA-MoS2 NPs did not cause skin irritation.Discussion: Our findings demonstrate that PAA-MoS2 NPs can be used as a new carrier for transdermal drug delivery for the first time.Keywords: transdermal drug delivery, poly(acrylic acid), atenolol, MoS2 nanoparticles

Pingping Wu,1,2 Huayun Zhu,2 Yan Zhuang,2 Xiaofeng Sun,2 Ning Gu1 1State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Sciences and Medical Engineering, Southeast University, Nanjing 210096, People’s Republic of China; 2Department of Medical Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, People’s Republic of ChinaCorrespondence: Ning GuState Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Sciences and Medical Engineering, Southeast University, Nanjing 210096, People’s Republic of ChinaTel +86 130 7253 2619Email guning@seu.edu.cnBackground: Owing to its combined effects, the co-delivery of different therapeutics is a promising option for the treatment of cancer. In the present study, tumor-targeting poly(ethylene glycol)-poly(lactic acid) (PEG-PLA) nanoparticles were developed for the transportation of two molecules, namely chemotherapeutic drug 5-fluorouracil (5Fu) and radionuclide iodine-131 (131I), in a single platform.Methods: The obtained nanoparticles (Cetuximab [Cet]-PEG-PLA-5Fu-131I) were spherical (diameter approximately 110 nm) and pH-sensitive. The targeting effect of nanoparticles via Cet was confirmed in colorectal cancer cells using a fluorescent assay. The combined effects of Cet-PEG-PLA-5Fu-131I on cell viability and apoptosis were evaluated in colorectal cancer cells by Cell Counting Kit-8 and flow cytometry assays.Results: Blank nanoparticles (Cet-PEG-PLA) showed good biocompatibility, and Cet-PEG-PLA-5Fu-131I nanoparticles were the most effective in terms of inhibition of cell viability and induction of apoptosis compared with monotherapy using Cet-PEG-PLA-5Fu or Cet-PEG-PLA-131I. In the xenograft mouse model, compared with using Cet-PEG-PLA-5Fu or Cet-PEG-PLA-131I alone, Cet-PEG-PLA-5Fu-131I nanoparticles exhibited prolonged circulation in the blood and accumulation in the tumor, thus resulting in enhanced antitumor efficacy. Additionally, combined radio-chemotherapy with Cet-PEG-PLA-5Fu-131I nanoparticles was associated with smaller tumor sizes than monotherapy, revealing the superior antitumor effects of Cet-PEG-PLA-5Fu-131I nanoparticles. These effects were further evidenced by histological and immunohistochemical analyses.Conclusion: The multifunctional Cet-PEG-PLA-5Fu-131I nanoparticles are promising candidates for the co-delivery of 5Fu-mediated chemotherapy and 131I-mediated radiotherapy.Keywords: PEG-PLA, 5Fu, 131I, drug delivery, radio-chemotherapy, colorectal cancer

Yuan Zhuang, Bao-Ying Yuan, Yong Hu, Gen-Wen Chen, Li Zhang, Xiao-Mei Zhao, Yi-Xing Chen,* Zhao-Chong Zeng* Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yi-Xing Chen; Zhao-Chong ZengDepartment of Radiation Oncology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, People’s Republic of ChinaTel +86-139-1605-6575Fax +86-21-6404-8472Email chen.yixing@zs-hospital.sh.cn; zeng.zhaochong@zs-hospital.sh.cnPurpose: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are inflammatory indexes that may reflect immune response to tumors and prognosis. We investigated the prognostic values of pre-treatment and post-treatment NLR and PLR and changes in those ratios in patients with small hepatocellular carcinoma (sHCC) treated with stereotactic body radiation therapy (SBRT).Patients and methods: Sixty patients who received SBRT were retrospectively reviewed. NLR and PLR were calculated by division of neutrophil and platelet counts, respectively, by lymphocyte counts. Independent factors for progression-free survival (PFS) and overall survival (OS) were determined by the Kaplan–Meier method, log-rank test, and Cox multivariate regression. Hazard ratios (HRs) and 95% confidence intervals (CIs) were also calculated.Results: The median follow-up was 36.9 (range: 4.1–73.5) months. Median PFS was 21.4 (range: 1.8–66.9) months. The 1-year and 2-year PFS rates were 76.7% and 55.0%, respectively. The 1-year and 2-year OS rates were 95.0% and 78.3%, respectively. In multivariate analysis, post-treatment PLR ≥263.0 indicated both poor PFS (HR: 3.70; 95% CI: 1.07–12.76, p=0.038) and OS (HR: 3.23; 95% CI: 1.01–9.11, p=0.043) for sHCC patients treated with SBRT. In addition, the presence of hepatitis infection and a low level of red blood cell count were also proved to be significantly associated with patients’ poor prognosis (pp=0.029).Conclusion: High post-treatment PLR and change in NLR ≥2.7-fold were associated with poor prognosis in patients treated with SBRT and might be considered as reliable and independent prognostic biomarkers for patients with sHCC.Keywords: stereotactic body radiation therapy, hepatocellular carcinoma, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, progression-free survival

Interbasin water transfers and diversions are among the most controversial water-resources-planning topics worldwide. They provide supply alternatives to receiving basins and potential challenges to the donor basins within a context of changing global water problems. This study presents a bibliometric analysis of global interbasin water transfer research between 1900 and 2014. The bibliometric analysis analyzes general characteristics of publications, the national, institutional, and personal research outputs, participating regions and their research activity, and global trends and hot issues in the field of water transfers. Our results show that the rate of annual publication of interbasin water transfer research grew steadily after 1972 and is rising quickly at present. The United States produced the largest number of single-country publications (37.4 %) and international collaborative publications (46.6 %). However, China had a high growth rate of publications after 2001, and surpassed the United States and ranked 1st in 2012, with the Chinese Academy of Sciences playing a leading role in the emergence of China’s research output. The global geographic distribution of publication activity shows that an increasing number of countries, agencies, and scholars have become part of the research enterprise. There is ample opportunity for cooperation between them to be strengthened in the future. The results of keyword evolution generally indicate that the research on interbasin water transfers expanded from 1991 through 2014. The hydrological and eco-environmental impacts of the South-to-North Water Transfer/Diversion Project in China and the corresponding long-term monitoring and conservation strategy have become one of the top topics of attention.