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Xian Du,1,* Jun Hu,1,* 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*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,* Yuewen Lao,* 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*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

Huiying Lv, Yawen Zhuang, Weijing Wu Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Fujian Medical University, Quanzhou City, Fujian Province, People’s Republic of ChinaCorrespondence: Weijing Wu, Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Fujian Medical University, No. 34, Zhongshan Bei Road, Lichen District, Quanzhou, Fujian Province, People’s Republic of China, Tel +8615159883230, Fax +86 595 22770258, Email wuweijing2010@163.comBackground: Tannerella forsythia is a gram-negative anaerobic bacterium commonly found in the oral cavity. It is among the common pathogenic bacteria associated with gingivitis, chronic periodontitis, and aggressive periodontitis. However, there is currently no literature discussing lung abscesses primarily caused by T. forsythia infection.Presentation: This article presents the case of a 55-year-old male with a massive lung abscess. The patient underwent ultrasound-guided percutaneous drainage, and the sample was sent for pathogen metagenomic next-generation sequencing (mNGS) testing. The test indicated that the lung abscess was primarily caused by T. forsythia infection. A literature review was conducted to understand the characteristics of this pathogen as well as its clinical features and suitable treatment approaches.Conclusion: Currently, there is no literature specifically mentioning T. forsythia as a primary pathogen causing lung abscesses. This anaerobic bacterium is commonly found in the oral cavity and is difficult to cultivate using routine culture methods. mNGS emerges as a value diagnostic method for identifying this pathogen. Treatment recommendations include drainage and antibiotic selection encompassing common periodontal pathogens such as red complex bacteria and Actinomyces.Keywords: Tannerella forsythia, lung abscess, metagenomic next-generation sequencing, drainage

Junying Jiang,1,&ast; Yan Zhuang,2,&ast; Shuting Si,2 Haoyue Cheng,2 Xialidan Alifu,2 Minjia Mo,2 Haibo Zhou,2 Hui Liu,3 Yunxian Yu2 1Department of Women’s Health, Yiwu Maternity and Children Hospital, Yiwu, People’s Republic of China; 2Department of Epidemiology & Health Statistics, School of Public Health, School of Medicine, Zhejiang University, Hangzhou City, People’s Republic of China; 3Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunxian Yu, Department of Epidemiology & Health Statistics, School of Public Health, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China, Email yunxianyu@zju.edu.cnObjective: This study aimed to investigate the association of reproductive hormones with primary dysmenorrhea in Chinese women.Methods: A case–control study was conducted and patients with primary dysmenorrhea and non-dysmenorrhea participants were recruited. Oxytocin, PGF2α, vasopressin, estriol and estradiol were respectively measured in plasma collected three to five days after menstruation. Restricted cubic spline and multiple logistic regression models were adopted to analyze the association between hormones and primary dysmenorrhea.Results: There were 604 participants enrolled in our study including 300 patients with primary dysmenorrhea. After adjustment for the potential confounders, oxytocin levels (Q3: OR (95% CI) = 0.50 (0.27~0.95) (p=0.035); Q4: 0.34 (0.17~0.66) (p=0.001)) and PGF2α levels (Q3: 0.45 (0.24~0.87) (p=0.017); Q4: 0.43 (0.22~0.84) (p=0.013)) were respectively associated with an decreased risk of primary dysmenorrhea, but estradiol (Q2: 2.18 (1.13~4.19) (p=0.020); Q3: 2.17 (1.12~4.19) (p=0.022)) and vasopressin (Q3: 2.88 (1.48~5.63) (p=0.002); Q4: 3.20 (1.65~6.22) (p< 0.001)) with an increased risk of primary dysmenorrhea, respectively. Among patients with primary dysmenorrhea, the higher estriol level was associated with higher frequent dysmenorrhea (Q2: 3.12 (1.32~7.34) (p=0.009); Q3: 4.97 (2.08~11.85) (p< 0.001)) and always dysmenorrhea (Q2: 2.51 (1.03~6.11) (p=0.041); Q3: 3.10 (1.25~7.73) (p=0.015)). Similarly, high estriol levels were associated with the higher degree of pain significantly only when hormone levels were at a high level (Q3: 2.06 (1.03~4.18) (p=0.043)).Conclusion: Higher serum vasopressin and estradiol concentrations as well as lower oxytocin and PGF2α levels were associated with higher risk of primary dysmenorrhea. Estrogen showed a reverse U-shape association on the frequency and degree of pain among patients with primary dysmenorrhea.Keywords: primary dysmenorrhea, reproductive hormone, restricted cubic spline

Meng-qin Wang,1,&ast; Ying Zhuang,1,&ast; Ya-ning Zheng2 1Department of Obstetrics, Nanjing Drum Tower Hospital, Nanjing, People’s Republic of China; 2Department of Gynecology Otolaryngology, Nanjing Drum Tower Hospital, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ya-ning Zheng, Email zhengyaqinzyq@126.comBackground: Neonatal hypoglycemia (NH) is a common clinical symptom that can occur in both normal and critically ill neonates. The placenta is the site of material exchange between the mother and the fetus, a special organ shared by the mother and the fetus during pregnancy, and one of its important functions is to transfer nutrients from the mother to the fetus. Terbutaline is used to relax frequent uterine contractions before delivery, and it can penetrate the placental barrier and affect the normal decomposition of neonatal glycogen. The situation is neonatal hypoglycemia if not timely detection and interventions in time, the neonate may have recurrent hypoglycemia, leading to irreversible nervous system damage, such as neonatal hypoglycemic encephalopathy, and visual and cognitive impairment.Case Report: The male neonate was a single fetus, with a birth weight of 3660 g and a length of 50 cm. The blood glucose at birth was 5 mmol/L, Apgar score was 9– 10, and body temperature was normal. The mother was healthy, was not diabetic, and had no other risk factors for neonatal hypoglycemia. She was injected with 0.25 mg of terbutaline 6 hours before delivery due to frequent uterine contractions. However, it was found that recurrent hypoglycemia occurred in the neonate even after adequate oral feeding.Conclusion: We included evidence-based use of terbutaline 48 hours before delivery as a high-risk factor for hypoglycemia in the rooming-in neonatal hypoglycemia care program, and formulate the corresponding nursing process, with good effect.Keywords: hypoglycemia, neonatal recurrent hypoglycemia, neonate, terbutaline

Dan Liu,1,&ast; YiWen Fan,2,&ast; YuGang Zhuang,1 Hu Peng,1 ChengJin Gao,3 YanQing Chen1 1Emergency Department, Shanghai Tenth People’s Hospital, Affiliated with Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Department of Pathology and Medical Biology, Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; 3Emergency Department, Xinhua Hospital, affiliated with the Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: ChengJin Gao, Emergency Department, Xinhua Hospital, Affiliated to the Shanghai Jiao Tong University School of Medicine, No. 1665, Kongjiang Road, Yangpu District, Shanghai, People’s Republic of China, Tel +86 25076045, Email gaochengjin@xinhuamed.com.cn YanQing Chen, Emergency Department, Shanghai Tenth People’s Hospital, affiliated with Tongji University School of Medicine, No. 301, Yanchang Middle Road, Jingan District, Shanghai, People’s Republic of China, Tel +86 18917683768, Email 18917683768@189.cnPurpose: Sepsis-related disseminated intravascular coagulation (DIC) is closely associated with poor prognosis and high mortality. Higher blood glucose (BG) variability indicates an increased risk of mortality in sepsis; however, its relationship with sepsis-related DIC has not been investigated. This study aimed to determine the association between glucose variability and sepsis-related DIC.Patients and Methods: Patients with sepsis admitted to the intensive care unit were enrolled between October 2017 and January 2021. Baseline data and BG records from the first 72 h were collected. We calculated the glucose liability index (GLI), largest amplitude of glucose excursion, BG standard deviation, and coefficient of variation on days 1 and 3. The relationship between GLI and morbidity of sepsis-related DIC was explored using a competing risk model. In subgroup analysis, we divided patients with and without diabetes into three groups according to the BG range.Results: Of the 238 patients enrolled, 28.2% developed DIC during hospitalization (n=67). GLI on day 3 was found to have the closest relationship with DIC incidence as it has the largest area under the ROC curve and the highest associated odds ratio of death per unit change (GLI3-day: AUC=0.891 OR=1.84), also independently increased the occurrence of DIC after adjusting for the competing risk of death (sub-distribution hazard ratios=1.866, p< 0.01). In subgroup analysis, patients with diabetes had worse outcomes under hypoglycemia than under hyperglycemia. Patients without diabetes having stable BG had the best outcomes.Conclusion: Our study suggested that a higher GLI in patients with sepsis at 72 h was independently associated with an increased risk of sepsis-related DIC, which was not associated with pre-existing diabetes.Keywords: blood disorder, glycemic variability, hypoglycemia, sepsis

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

Yangfan Zhuang,1 Quanrui Feng,2 Huiming Tang,3 Yuchang Wang,1 Zhanfei Li,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, 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: The Geriatric Trauma Outcome Score (GTOS) has been developed and indicate to be a valid prognostic tool for the prediction of mortality in geriatric trauma patients (GTPs) during hospitalization. However, the predictive value of the GTOS for morbidity is still unclear. We aimed to evaluate the association between GTOS, morbidity and mortality in GTPs.Patients and Methods: We performed a retrospective cohort study between June 1, 2016, and May 31, 2020, and collected data for patients aged 65 years or older. These patients were treated at the Trauma Center of Tongji Hospital, Wuhan, China. Clinical data were retrieved from the trauma registry. The GTOS was calculated with the following formula: age + ISS &ast; 2.5 + 22 (if any packed red blood cells were transfused within 24 hours after admission). The outcomes were mortality, morbidity, length of hospital stay (LOS), and functional outcome at discharge.Results: A total of 485 patients were enrolled: 214 (44.1%) were classified into the low-GTOS group, and 271 (55.9%) were classified into the high-GTOS group. The median (IQR) age was 68 (66– 71) years; 361 (74.4%) were male. The most common mechanism of injury was vehicle collision (66.4%), followed by falls < 2 m (19.6%). The median (IQR) ISS was 18 (14– 22). The median (IQR) GCS was 13 (9– 15). A high GTOS was associated with high rates of all-cause mortality (13.3% vs 0.9%, P < 0.001), complications (88.2% vs 31.8%, P < 0.001), unplanned intubation (19.2% vs 1.4%, P < 0.001), and unplanned admissions to the intensive care unit (8.5% vs 0.5%, P < 0.001). In multivariable logistic regression analysis, GTOS was associated with morbidity (OR 1.07, 95% CI, 1.05– 1.09, p < 0.001) and mortality (OR 1.04, 95% CI, 1.02– 1.06, p < 0.001).Conclusion: The GTOS is an independent predictor of morbidity and mortality in GTPs, and it will help us identify patients at high risk on admission.Keywords: Geriatric Trauma Outcome Score, geriatric trauma patients, predictive value

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

Yue Zhuang, Tiantian Zhao, Xuanrong Shao School of Safety Science and Emergency Management, Wuhan University of Technology, Wuhan City, Hubei Province, People’s Republic of ChinaCorrespondence: Tiantian ZhaoSchool of Safety Science and Emergency Management, Wuhan University of Technology, 122 Luoshi Road, Wuhan City, Hubei Province, People’s Republic of ChinaEmail ztt220@whut.edu.cnPurpose: Taking COVID-19 as an example, this paper explores the mechanism of WeChat’s impact on risk information transmission in social media and builds a model of WeChat’s impact on public risk perception based on risk communication.Methods: Research primarily utilised the questionnaire survey method to collect and analyse public attitudes towards COVID-19 to achieve the research goals. We checked the adequacy of measurements and tested the hypotheses with regression analysis based on 801 participants in China.Results: The results indicated that the levels of the public WeChat COVID-19 risk information attention and trust had a significant positive impact on the public’s risk perception and willingness of pandemic prevention. The improved public risk perception of COVID-19 as a mediator enhanced the public pandemic prevention ability, which allowed WeChat to play a more effective role in major disaster emergency.Keywords: COVID-19, WeChat, public risk perception, pandemic prevention

Ning Sun,1,&ast; Yan Zhuang,1,&ast; Junling Zhang,2 Shiqing Chen,2 Yuwen Dai,2 Renhong Guo1 1Department of Medical Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2The Medical Department, 3D Medicines Inc., Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Renhong GuoDepartment 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 ChinaEmail guorh610@sina.comBackground: With the development of next-generation sequencing (NGS), several anaplastic lymphoma kinase (ALK) fusion partner genes have been identified. However, ALK fusion is extremely rare in small cell lung cancer (SCLC), and there is no standard treatment option. Here, we report a patient with SCLC who carried an ALK- Intergenic Region (IR) rearrangement and responded to Alectinib.Case Presentation: A 26-year-old man was pathologically diagnosed with extensive-stage SCLC. After 2 cycles of first-line chemotherapy, CT showed a large soft tissue mass in the middle lobe of the right lung and increased liver nodules, left kidney lesions and right kidney lesions. To seek potential therapeutic regimens, ALK rearrangement was identified. The patient achieved a rapid and durable partial response with Alectinib (600 mg BID). The patient experienced a significant clinical response with a progression-free survival of more than 6 months. There were no grade 3 or more adverse events reported, and there was no dose reduction during treatment. Following Alectinib treatment, the allele frequency of ALK rearrangement and RB1 and TP53 mutations in plasma circulating tumor DNA decreased with the reduction in tumor size.Conclusion: This case provides a meaningful reference for the treatment of SCLC patients with ALK rearrangement. This case also provides valuable information on the response to ALK inhibitors in patients with ALK-IR rearrangement and better understanding of ALK-TKI applications in the future.Keywords: small-cell lung cancer, ALK rearrangement, ALK inhibitor, immunohistochemistry, genetics

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

Yongliang Li,1,&ast; Mi Tian,2,&ast; Dongqing Zhang,1 Yifei Zhuang,1 Zhimin Li,1 Shenqi Xie,1 Keyu Sun1 1Department of Emergency, Minhang Hospital, Fudan University, Shanghai, 200040, People’s Republic of China; 2Department of Intensive Care Unit, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Keyu SunDepartment of Emergency, Minhang Hospital, Fudan University, Shanghai, 200040, People’s Republic of ChinaTel +86 18930536861Email hoceima@126.comBackground: Long non-coding RNAs (lncRNAs) have been reported to play critical roles in human tumours, including gallbladder carcinoma (GBC). However, their biological functions and molecular mechanisms in tumorigenesis and progression remain largely unknown.Methods: Quantitative polymerase chain reaction (qPCR) was used to verify the expression of lncRNA myosin light chain kinase antisense RNA 1 (MYLK-AS1) in 120 pairs of GBC tissues and paired adjacent non-tumour tissues, as well as in six different GBC cell lines (NOZ, EH-GB1, OCUG-1, GBC-SD, SGC-996 and QBC-939). Cell counting kit 8 was applied to explore cell proliferation and drug sensitivity assays. The target miRNAs (miR) of MYLK-AS1 and downstream target genes were predicted using Starbase 3.0 software and confirmed by double luciferase reporting test. The expression of proteins was assessed using Western blot assay.Results: Here, we demonstrated that MYLK-AS1 was significantly upregulated and correlated with a poor prognosis and poor clinical characteristics in GBC. Furthermore, the forced expression of MYLK-AS1 significantly promoted GBC cell proliferation and resistance to gemcitabine in vitro. Mechanistically, MYLK-AS1 functioned as an efficient miR-217 sponge, thereby releasing the inhibition of enhancer of zeste 2 polycomb repressive complex 2 (EZH2) subunit expression. MYLK-AS1 promoted GBC cell proliferation and resistance to gemcitabine by upregulating EZH2 expression, and EZH2 was confirmed as a direct target of miR-217.Discussion: Our results confirmed that the chemoresistant driver MYLK-AS1 might be a promising candidate as a therapeutic target for the treatment of advanced GBC.Keywords: chemoresistance, GBC, lncRNA, proliferation

Qingshan Huang,1 Lijun Xie,2 Liyan Huang,2 Weili Wei,2 Haiying Li,2 Yunfang Zhuang,2 Xinxiu Liu,2 Shuqiang Chen,2 Sufang Zhang2 1Musculoskeletal Tumor Center, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China; 2Department of Ultrasound, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, People’s Republic of ChinaCorrespondence: Sufang ZhangDepartment of Ultrasound, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, People’s Republic of ChinaTel/Fax +86-591-87981961Email zsufang@fjmu.edu.cnQingshan HuangMusculoskeletal Tumor Center, Peking University People’s Hospital, Beijing, 100044, People’s Republic of ChinaTel/Fax +86-10-88324471Email hqingshan@pku.edu.cnBackground: High-resolution ultrasound is the first choice for the diagnosis of thyroid nodules, but it is still difficult to distinguish between follicular thyroid carcinoma (FTC) and follicular adenoma (FA). Our research aimed to develop and validate an ultrasonic diagnostic model for differentiating FTC from FA.Methods: This study retrospectively analyzed 196 patients who were diagnosed as FTC (n=83) and FA (n=113). LASSO regression analysis was used to screen clinical and ultrasonic features. Multivariate logistic regression analysis was used to establish the ultrasonic diagnostic model of FTC. Nomogram was used for the visualization of diagnostic models. C-index, ROC, and calibration curves analysis were used to evaluate the accuracy of the diagnostic model. Decision curve analysis (DCA) was used to evaluate the net benefits of the ultrasonic diagnostic model for FTC diagnosis under different threshold probabilities. The bootstrap method was used to verify the ultrasonic diagnostic model.Results: After Lasso regression analysis, 10 clinical and ultrasonic features were used to construct the ultrasonic diagnostic model of FTC. The C-index and AUC of the model were 0.868 and 0.860, respectively. DCA showed that the ultrasonic model had good clinical application value. The C-index in the validation group was 0.818, which was close to the C-index in the model.Conclusion: Ultrasonic diagnostic model constructed with 10 clinical and ultrasonic features can better distinguish FTC from FA.Keywords: follicular thyroid carcinoma, follicular adenoma, diagnostic, ultrasonic

Qinge Wang,1 Min Gu,2 Yun Zhuang,1 Jianping Chen1 1Department of Digestive Disease, The First People’s Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, People’s Republic of China; 2Department of Pediatrics, Changzhou Children’s Hospital, Changzhou, Jiangsu, People’s Republic of ChinaCorrespondence: Jianping ChenDepartment of Digestive Disease, The First People’s Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Juqian Road, Tianning District, Changzhou, Jiangsu, 213003, People’s Republic of ChinaEmail Chenjianping123abc@126.comBackground: MAGI1-IT1 is a long non-coding RNA (lncRNA) previously reported to regulate several cancer types, but its functional role in gastric cancer (GC) remains to be defined. This study therefore explored the mechanistic role played by MAGI1-IT1 in the regulation of GC cell proliferation.Methods: 120 pairs of GC patient tumor, paracancerous tissues, human GES-1 control cells and human AGS, MKN-74, MKN-45, and MGC-803 GC cell lines were used to detected MAGI1-IT1, miR-302d-3p, and IGF1 expression by a qPCR approach. An shRNA approach was used to knock down MGI1-IT1 in order to examine the effect of such treatment on GC cell proliferation, and rescue experiments were subsequently conducted. In addition, the functional role of MAGI1-IT1 in GC in vivo was evaluated with a xenograft model system. P < 0.05 was the significance threshold.Results: Elevated MAGI1-IT1 expression was detected in GC cell lines and tissues, and was linked to poorer patient overall survival. Knocking down this lncRNA disrupted GC cell proliferation in vitro and in vivo, and miR-302d-3p was identified as a MAGI1-IT1 target. Notably, miR-302d-3p inhibition partially reversed the impact of MAGI1-IT1 knockdown on GC cell proliferation. IGF1 was subsequently identified as a miR-302d-3p target gene that was upregulated by MAGI1-IT1 through miR-302d-3p.Conclusion: Overall, these results indicated that MAGI1-IT1 controlled GC cell proliferation by modulating the miR-302d-3p/IGF1 axis, suggesting that this may be a viable treatment target in those with GC.Keywords: MAGI1-IT1, cell proliferation, gastric cancer, miR-302d-3p, IGF1

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

Yuntao Shi,1,* Yingying Zhuang,2,* Jialing Zhang,1 Mengxue Chen,1 Shangnong Wu1 1Department of Gastroenterology, The Affiliated Huai’an No. 1 People’s Hospital of Nanjing Medical University, Huai’an, People’s Republic of China; 2Department of Medical Imaging, The Affiliated Huai’an No. 1 People’s Hospital of Nanjing Medical University, Huai’an, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shangnong WuDepartment of Gastroenterology, The Affiliated Huai’an No. 1 People’s Hospital of Nanjing Medical University, No. 1, Huanghe West Road, Huai’an 223300, People’s Republic of ChinaTel +86 517-80872251Email shangnong193@163.comPurpose: Hepatocellular carcinoma (HCC) ranks as the fourth leading cause of cancer-related deaths worldwide. N6-methyladenosine (m6A) RNA methylation is the most common modification of messenger RNAs (mRNAs). The prognosis of HCC patients with metastasis remains poor. Our study aimed to elucidate the regulatory role of m6A on HCC metastasis.Patients and Methods: All HCC patients were enrolled from The Affiliated Huai’an No. 1 People’s Hospital of Nanjing Medical University. The expression levels of gene were tested by quantitative polymerase chain reaction (qPCR), Western blot, or immunohistochemistry (IHC) analysis. Wound healing assay, Transwell invasion assay, and lung metastasis model were implemented to investigate the migration and invasion ability of HCC cells. Candidate targets were selected by a comprehensive analysis of RNA-sequencing and m6A-sequencing of HepG2 cells.Results: In this study, we demonstrated that METTL14 was significantly downregulated in HCC and significantly associated with the prognosis of HCC patients. METTL14 knockdown promoted the migration, invasion, and epithelial–mesenchymal transition (EMT) of HCC cells in vitro and in vivo. In addition, overlapping RNA-sequencing and m6A-sequencing data, we identified EGFR as a direct target of METTL14 in HCC. Mechanistically, METTL14 was found to inhibit HCC cell migration, invasion, and EMT through modulating EGFR/PI3K/AKT signaling pathway in an m6A-dependent manner.Conclusion: Targeting METTL14/EGFR/PI3K/AKT signaling pathway may facilitate the development of a new treatment strategy against the metastasis of HCC.Keywords: hepatocellular carcinoma, N6-methyladenosine, METTL14, EGFR

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

Xinyu Li,1,* Wen Chen,2,* Jing Jia,1,* Zhicheng You,3 Changjin Hu,4 Yihuang Zhuang,1 Zhibin Lin,1 Yan Liu,1 Chunkang Yang,5 Rongyu Xu1 1Quanzhou First Hospital, Quanzhou, Fujian Province, People’s Republic of China; 2The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, People’s Republic of China; 3Yongchun County Hospital, Quanzhou, Fujian Province, People’s Republic of China; 4Jinjiang Hospital of Traditional Chinese Medicine Affiliated to Fujian University of Traditional Chinese Medicine, Jinjiang, Fujian Province, People’s Republic of China; 5Fujian Tumor Hospital, Fuzhou, Fujian Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunkang YangDepartment of Gastroenterology, Fujian Tumor Hospital, Fuzhou, Fujian Province, People’s Republic of ChinaEmail chunyangy03@163.comRongyu XuDepartment of Surgical Oncology, Quanzhou First Hospital, Quanzhou, Fujian Province, People’s Republic of ChinaEmail xry641127@sina.comBackground: Long non-coding RNA regulator of reprogramming (LINC-RoR) has shown different expressions in a variety of tumors as a stem cell inducer through reprogramming regulation. However, its role and regulation mechanisms in colorectal cancer (CRC) are still unclear.Materials and Methods: Quantitative real-time PCR and Western blot were performed to examine LINC-RoR expression in paired CRC samples and cell lines. The relationship of LINC-RoR expression with clinicopathological characteristics and clinical outcomes was analyzed. The biological functions of LINC-RoR were studied by MTS and colony formation in vitro. Cell apoptosis was analysed by the flow cytometry. The Dual-luciferase reporter assays and RIP assays were performed to explore the regulatory relationship of LINC-RoR.Results: In this study, we found that LINC-RoR was upregulated in CRC cell lines and tissues. High expression of LINC-RoR was associated with poorer survival time and multivariate analysis results showed that LINC-RoR was an independent risk factor of tumor malignancy progression. Overexpression of LINC-RoR promoted the cell proliferation and knocked down it can reverse the effect in vitro. The regulatory network of LINC-ROR/miR-6833-3p/SMC4 was predicted with bioinformatics analysis tools and validated via dual-luciferase reporter assays and RIP. Further study revealed that in overexpression LINC-RoR cell lines the expression of miR-6833-3p was downregulated and miR-6833-3p can inhibit its target gene SMC4, the apoptosis-related protein.Conclusion: We concluded that LINC-RoR functions as an oncogene in CRC through the miR-6833-3p/SMC4 pathway.Keywords: LINC-RoR, colorectal cancer, miR-6833-3p, SMC4, non-coding RNA, apoptosis

Yuan Zhuang, Chang Liu, Jiaqing Liu, Guang Li Department of Radiation Oncology, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning, People’s Republic of ChinaCorrespondence: Guang LiDepartment of Radiation Oncology, The First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang, Liaoning 110001, People’s Republic of ChinaTel +86-13804058616Email zyyannis0701@163.comAbstract: In recent years, the PD-1/PD-L1 axis blockade has become a very promising therapy with significant clinical benefits for multiple tumor types. However, some patients still do not respond sufficiently to PD-1/PD-L1 targeted monotherapy. Therefore, investigating the mechanism of PD-1 blockade resistance will assist in exploring new immunotherapy strategies, controlling the progress of the disease, and thus bringing more sustainable survival benefits to patients. The tumor-immune cycle is divided into the following seven steps: the release of cancer antigens, cancer antigen presentation, priming and activation, trafficking of T cells to tumors, infiltration of T cells into tumors, recognition of cancer cells by T cells, and killing of cancer cells. Given that PD-1/PD-L1 blockade is primarily involved in step 7, any abnormalities in the previous steps may affect the efficacy of PD-1/PD-L1 inhibitors and lead to drug resistance. This review discussed the resistance mechanisms of PD-1/PD-L1 blockade in each cancer-immunity step to finding a more suitable treatment population and an optimized combination therapy to exert immunotherapy in tumor treatment to a greater extent.Keywords: immunotherapy, PD-1, PD-L1, resistance

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

Xiaodong Tian, Yongsu Ma, Hongqiao Gao, Yan Zhuang, Yinmo YangDepartment of General Surgery, Peking University First Hospital, Beijing 100034, People’s Republic of ChinaBackground: Long lasting and unbearable abdominal pain is the most common symptom of chronic pancreatitis (CP). This study aimed to evaluate surgical options for the control of chronic pancreatic pain based on anatomical morphological changes.Methods: A retrospective review of patients who underwent surgery for treatment of chronic pancreatic pain in Peking University First Hospital between January 2000 and December 2017 was performed. The surgical options included modified Puestow procedure, Frey procedure, Beger procedure, pancreaticoduodenectomy (PD) or pylorus preserving pancreaticoduodenectomy (PPPD), distal pancreatectomy and total pancreatectomy.Results: Among 116 patients, pain relief rate after surgery was 82.6% (95/115) while 22 (23.2%) cases suffered recurrent chronic pancreatic pain during follow-up. Pain relief rate was 83.1% (54/65) after modified Puestow procedure, 63.6% (7/11) after distal pancreatectomy, 83.3% (10/12) after PD/PPPD, 86.7% (13/15) after Frey procedure, and 90% (9/10) after Beger procedure. Pain recurrence rate was 27.8% (15/54) after modified Puestow procedure, 42.9% (3/7) after distal pancreatectomy, 10% (1/10) after PD/PPPD, 15.4% (2/13) after Frey procedure, and 11.1% (1/9) after Beger procedure.Conclusion: The surgical options for the control of chronic pancreatic pain according to the anatomical morphological changes of CP is reasonable and effective. The procedure of distal pancreatectomy alone should be cautiously used for pain relief.Keywords: chronic pancreatitis, abdominal pain, surgical treatment, pathological anatomy

Yan Zhuang,*,1,2 Ying Bai,*,1,2 Yan Hu,*,3 Yueqin Guo,1,2 Lingyuan Xu,1,2 Wanle Hu,4 Lehe Yang,1,2 Chengguang Zhao,1,2 Xiaokun Li,1,2 Haiyang Zhao1,21The Institute of Life Sciences, Wenzhou University, Wenzhou, Zhejiang 325035, People’s Republic of China; 2School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, People’s Republic of China; 3Department of Pharmacy, Taizhou Enze Medical Center (Group), Taizhou Hospital of Zhejiang Province, Taizhou, Zhejiang 317000, People’s Republic of China; 4Department of Coloproctology, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, People’s Republic of China*These authors contributed equally to this workBackground: Activation of epidermal growth factor receptor (EGFR) has been reported in a variety of cancer types, including colorectal cancer (CRC), and represents a potential chemotherapeutic drug target. EGFR tyrosine kinase inhibitors (EGFR-TKIs) have been increasingly applied in the clinical treatment of CRC, but development of drug resistance during the treatment has greatly limited their application. Signal transducer and activator of transcription 3 (STAT3) and its mediated signal transduction pathway play an important role in the occurrence, development and metastasis of CRC, and are related to the development of EGFR-TKI resistance in CRC.Methods: Cell viability, colony formation and cellular morphology were examined to evaluate the potent antiproliferative effect of the STAT3 inhibitor napabucasin, LY5 and rhein on the human CRC cell lines HCT116, SW620, RKO and DLD-1. Flow cytometry-based analysis was employed to determine whether rhein can affect the cell cycle and apoptosis. The expression level of phosphorylated STAT3 (P-STAT3), and cell cycle- and apoptosis-related proteins BCL2, CDC2 BAX, Cyclin D1 and Cyclin B1 were detected by Western blot analysis.Results: This study revealed that rhein can significantly reduce cell viability and stimulate apoptosis in human CRC cells in a dose-dependent manner. In addition, rhein induced cell cycle arrest at the G2/M phase in CRC cells and dose-dependently inhibited the expression of cell cycle-related proteins. Additionally, it was found that napabucasin, LY5 and rhein considerably sensitized cells to the EGFR-TKI erlotinib, thus suppressing CRC cell proliferation. Rhein also inhibited the phosphorylation of its downstream target STAT3. Inhibition of STAT3 and EGFR phosphorylation was also observed after treatment with a combination of rhein and EGFR inhibitors.Conclusion: This study confirmed the synergistic effect of STAT3 inhibitor and EGFR inhibitor in CRC cell lines. Additionally, we found that rhein sensitizes human CRC cells to EGFR-TKIs by inhibiting STAT3 pathway. When combined with EGFR-TKIs, rhein may be a novel STAT3 inhibitor in CRC.Keywords: rhein, STAT3, colorectal cancer, EGFR, tyrosine kinase inhibitor

Xin-Yu Liao,1,* Yang Lei,2,* Song-Feng Chen,2 Jing Cheng,3 Dan Zhao,4 Zhi-Feng Zhang,2 Xin Han,5 Ya Zhang,2 Hua-Bao Liao,2 Yang Zhuang,2 Juan Chen,6 Hai-Bing Zhou,5 Qi Wan,7 Ying-Ying Zou,11Department of Pathology and Pathophysiology, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming 650500, People’s Republic of China; 2Department of Physiology, School of Basic Medical Sciences, Wuhan University School of Medicine, Wuhan 430071, People’s Republic of China; 3Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan 430060, People’s Republic of China; 4Department of Physiology, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, People’s Republic of China; 5School of Pharmacy, Wuhan University, Wuhan 430071, People’s Republic of China; 6Department of Neurology, The Central Hospital of Wuhan, Tongji Medical College of Huazhong University of Science & Technology, Wuhan 430013, People’s Republic of China; 7Institute of Neuroregeneration & Neurorehabilitation, Collaborative Innovation Center for Brain Science, Department of Neurosurgery of the Affiliated Hospital, Qingdao University, Qingdao 266071, People’s Republic of China*These authors contributed equally to this work Background: The authors have recently designed a new compound bisperoxovandium (pyridin-2-squaramide) [bpV(pis)] and verified that bpV(pis) confers neuroprotection through suppressing PTEN and activating ERK1/2, respectively. Intracerebral hemorrhage (ICH) is the second most common cause of stroke and has severe clinical outcome. In this study, we investigate the effect of bpV(pis) in ICH model both in vivo and in vitro.Materials and methods: The novel drug bpV(pis) was synthesized in the Faculty of Pharmacy, Wuhan University School of Medicine. An ICH model was generated on both SD rats and cells. bpV(pis) was injected into intracerebroventricular or culture media. Western blotting was applied to test the signal pathway. To determine the effect of bpV(pis) on PTEN inhibition and ERK1/2 activation, we measured the phosphorylation level of AKT (a direct downstream target of PTEN that negatively regulates AKT) and ERK1/2. FJC, MTT, and LDH were applied to measure the cell viability. Neurobehavioral tests were performed to measure the effect of bpV(pis).Results: The in vivo results showed that intracerebroventricular administration of bpV(pis) significantly alleviates hematoma, the damage of brain–blood barrier and brain edema. The in vitro results demonstrated that bpV(pis) treatment reduces ICH-induced neuronal injury. Western blotting results identified that bpV(pis) exerts a neuroprotective effect by significantly increasing the phosphorylation level of AKT and ERK1/2 after experimental ICH. Neurobehavioral tests indicate that bpV(pis) promotes functional recovery in ICH animals.Conclusion: This study provides first and direct evidence for a potential role of bpV(pis) in ICH therapy.Keywords: bpV(pis), intracerebral hemorrhage, PTEN, AKT, ERK1/2, neuroprotection

Chong Meng,1–3 Xun Yang,1–3 Yuzhou Liu,1–3 Yingjie Zhou,1–3 Jing Rui,1–3 Shenqian Li,1–3 Ce Xu,1–3 Yongqing Zhuang,4 Jie Lao,1–3 Xin Zhao1–31Department of Hand Surgery, Huashan Hospital, Fudan University, Shanghai 200040, People’s Republic of China; 2Key Laboratory of Hand Reconstruction, Ministry of Health, Shanghai 200032, People’s Republic of China; 3Shanghai Key Laboratory of Peripheral Nerve and Microsurgery, Shanghai 200032, People’s Republic of China; 4Hand Surgery Department, Shenzhen People’s Hospital, Shenzhen 518020, People’s Republic of ChinaPurpose: Neuropathic pain (NP) is a challenging clinical problem due to its complex pathogenesis. In our previous study using microarray, we found that the levels of lncRNA Malat1 were decreased in the spinal cord of NP rat after brachial plexus avulsion, but its contribution to NP remain unclear. The purpose of this study was to investigate its role in the pathogenesis of NP.Methods: In the NP model of complete brachial plexus avulsion rat, spinal cords were harvested, and fluorescence in situ hybridization (FISH) was used to test the spatial expression of Malat1 and qRT-PCR was used to confirm the quantitative expression of Malat1. In primary cultured neurons, Malat1 expression interfered with adenovirus. Spontaneous electric activities of neurons were tested using multi-electrode arrays and apoptosis of neurons was tested using TUNEL method. The change of intracellular calcium concentration was analyzed using calcium imaging method.Results: Decreased Malat1 expression was confirmed using qRT-PCR, and Malat1 was identified in the cytoplasm of neurons in spinal cord, but not in glia. In vitro, the decrease of Malat1 resulted in an increase in the frequency of spontaneous electric activity in neurons but had no effect on neuronal apoptosis. Further analysis indicated during glutamate stimulation, the change of intracellular calcium concentration in neurons with downregulated Malat1 expression was significantly greater than that in normal neurons.Conclusion: Reduced Malat1 expression may induce NP by increasing neuronal excitability in the spinal cord via regulation of calcium flux.Keywords: neuropathic pain, lncRNA, Malat1, spinal cord, neuron, multielectrode array, brachial plexus avulsion

Liang Zhao,1,* Xiyi Liao,1,* Ganji Hong,1 Yanzhen Zhuang,2 Kaili Fu,1 Peiqiong Chen,2 Yuhuan Wang,2 Haojun Chen,3 Qin Lin1 1Department of Radiation Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, China; 2Department of Pathology, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, China; 3Department of Nuclear Medicine & Minnan PET Center, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, China *These authors contributed equally to this work Purpose: To analyze the mismatch repair (MMR) status and PD-L1 expression in nasopharyngeal carcinoma (NPC), and investigate whether PD-L1 and MMR status could be used as a biomarker for predicting response of immune checkpoint blockades (ICBs) treatment.Patients and methods: A total of 108 patients were initially histopathologically diagnosed with NPC between December 2017 and September 2018. All tissue specimens were collected before any treatment. Tumor tissue MMR status was determined by both immunohistochemistry and PCR. The expression of PD-L1 in NPC tissue was analyzed immunohistochemically. High PD-L1 expression in tumor cells (TC) or tumor-infiltrating immune cells (TIIC) was defined as ≥50% of corresponding cells with membranous staining.Results: Tissue samples were obtained from 102 patients after written informed consent was obtained. Seventy-one (69.6%) patients were treated in our hospital after diagnosis. Disease in stages I–III accounted for 35 (49.3%) cases, while stage IVa–IVb was identified in 36 (50.7%) cases. Only two of 102 patients were identified as MMR-deficient (dMMR) by IHC and PCR. High PD-L1 expression in TC was confirmed in 77 of the 102 (75.5%) NPC cases, while only 13 of the 102 (12.7%) NPC cases were considered to exhibit high PD-L1 expression in TIIC. PD-L1 expression in TC was positively correlated with T stage (P=0.033), while PD-L1 expression in TIIC was negatively associated with plasma Epstein–Barr virus DNA load (P=0.021), N stage (P=0.009), M stage (P=0.014), and clinical stage (P=0.001).Conclusion: dMMR is a rare event in NPC and may not be a prospective biomarker to predict the effectiveness of treatment with ICBs in clinical practice. It was also determined that high PD-L1 expression in NPC is quite common and the importance of distinguishing PD-L1 expression in TC and TIIC was highlighted. Keywords: immunotherapy, biomarker, microsatellite instability, PD-L1, tumor-infiltrating immune cells

Feimin Yang,1 Qian Zhang,1 Wei Kong,1 Hongdan Shen,1 Jing Lu,1 Xiaolong Ge,1 Yiyu Zhuang2 1Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, China; 2Nursing Department, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, China Objective: The aim of this study is to investigate the attitudes of hospitalized patients with gastrointestinal cancer toward being informed of the truth and to provide references for informing patients of their gastrointestinal cancer diagnosis.Methods: Nine patients with gastrointestinal cancer were selected for this study by using a purposive sampling technique from a general surgery ward in a tertiary-level general hospital in Zhejiang Province from June 2016 to October 2016. Semi-structured, in-depth interviews were conducted, and the descriptive phenomenological method (developed by Amedeo Giorgi) was used to analyze the interview data.Results: Five themes were developed through reading, analysis, reflection, and classification of the data: Theme 1, guessing the diagnosis of gastrointestinal cancer before being informed of the truth; Theme 2, eagerness to know the diagnosis results; Theme 3, expectations related to beginning treatment for cancer; Theme 4, stress and anxiety during treatment; and Theme 5, providing patients with hope and optimism at the early diagnosis stage.Conclusion: Patients have a strong desire to survive and can confidently confront their gastrointestinal cancer diagnosis. Medical staff should carefully select the appropriate time to inform patients of their diagnosis by evaluating their attitudes toward being informed, thereby actively meeting patients’ needs for information and treatment. Keywords: patient with gastrointestinal cancer, disclosure of diagnosis, qualitative study

Xian Du,1,2,* Qian Zhao,2,* Yuan Zhuang,2,* Haoyang Chen,1 Biyu Shen1,2 1Department of Nursing, The Second Affiliated Hospital of Nantong University, Nantong, China; 2School of Nursing, Nantong University, Nantong, China *These authors contributed equally to this work Objective: Fatigue is a very common symptom of systemic lupus erythematosus (SLE), which significantly impairs patients’ quality of life. The purpose of this study is to evaluate contributors of fatigue and effects of fatigue on the quality of life in Chinese SLE patients.Methods: A survey of 119 SLE patients using the Fatigue Severity Scale (FSS) to assess the severity of fatigue was carried out. SLE patients completed the Systemic Lupus Erythematosus Disease Activity Index, the Hospital Anxiety and Depression Scale, the Short Form 36 health survey and the Pittsburgh Sleep Quality Index. Meanwhile, 105 healthy individuals completed FSS, the Hospital Anxiety and Depression Scale and Short Form 36 health survey. We used chi-squared analysis, independent samples t-tests and logistic regression models to analyze data.Results: Our results found that the FSS score of patients with SLE was higher than that of healthy controls. The disease duration, anxiety, depression, subjective sleep quality and sleep disorders significantly correlated with fatigue in SLE patients. Moreover, logistic regression models showed depression and sleep disorders as predictors of fatigue. In SLE patients, fatigued patients had lower quality of life than those who were non-fatigued.Conclusion: This is the first time to explore contributors of fatigue and the influence of fatigue on SLE patients’ quality of life in China. Our study showed that depression and sleep disorders were predictors of fatigue, and fatigue seriously damaged SLE patients’ quality of life. The results indicate that it is necessary to conduct holistic assessment and effective intervention, such as systemic psychiatric screening, psychological care and practical sleep guidance, to relieve symptoms of fatigue and finally improve their quality of life in SLE patients. Keywords: systemic lupus erythematosus, fatigue, quality of life, depression, sleep disorders

Bin-Fei Zhang,* Xing Wei,* Hai Huang, Peng-Fei Wang, Ping Liu, Shuang-Wei Qu, Jia-Hao Li, Hu Wang, Yu-Xuan Cong, Yan Zhuang, Kun Zhang Department of Orthopedic Trauma, Hong-Hui Hospital, Xi’an Jiaotong University College of Medicine, Beilin District, Xi’an, Shaanxi, China *These authors contributed equally to this work Objective: To investigate the incidences of deep vein thrombosis (DVT) before and after operation in inpatients with hip fractures in both lower extremities.Patients and methods: We collected the clinical data of 463 patients with lower extremities fractures who presented at Xi’an Honghui Hospital between July 1, 2014, and October 31, 2016 and met all the inclusion criteria. Doppler ultrasonography was used to diagnose DVT. The patients were examined preoperatively and postoperatively and divided into the thrombosis and non-thrombosis group according to the ultrasonographic findings. We divided the DVT cases into central, peripheral, and mixed thromboses.Results: The incidence of preoperative DVT was 34.98%, and the prevalence of DVT on the uninjured side was 13.60%. This composition ratio increased to 57.23% postoperatively, and the prevalence of DVT on the uninjured side was 25.05%. Age (odds ratio [OR], 1.03; 95% CI: 1.01–1.04; P=0.002), venous thrombosis at admission (OR, 4.05; 95% CI, 2.30–7.13; P=0.000), and the days between the fracture and the operation (OR, 1.10; 95% CI, 1.02–1.20; P=0.020) were the independent risk factors of preoperative DVT. Coronary heart disease (OR, 1.85; 95% CI: 1.18–2.89; P=0.007), venous thrombosis at admission (OR, 22.35; 95% CI: 6.78–73.60; P=0.000), days between fracture and operation (OR, 1.06; 95% CI: 1.01–1.11; P=0.021), and blood loss (OR, 1.002; 95% CI: 1.000–1.003; P=0.014) were independent risk factors of postoperative DVT.Conclusion: The actual incidence of DVT after hip fracture may be underestimated. The incidences of preoperative and postoperative DVTs and the incidence of DVT on the uninjured limb were high. Keywords: deep vein thrombosis, ultrasonography, hip fracture, anticoagulation, low-molecular-weight heparin

Ting Ting Ma,1–3 Yan Zhuang,1 Hai Ying Gong,4 Anthony Chauang Yii,5 Xue Yan Wang,1 Huan Zhong Shi2,3 1Department of Allergy, Beijing Shijitan Hospital, Capital Medical University, 2Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, 3Center of Medical Research, Beijing Institute of Respiratory Diseases, 4Fangshan District Center for Disease Control and Prevention, Beijing, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore, Singapore Background: The diagnosis of asthma is made on the basis of variable respiratory symptoms and supported by objective evidence of variable airflow limitation. However, spirometry and bronchoprovocation tests may not be routinely available in resource-scarce settings or in the context of large-scale epidemiological studies. There is a gap in knowledge about the predictive value of respiratory symptoms for the diagnosis of pollen-induced asthma.Objective: The aim of this study was to investigate the predictive value of self-reported respiratory symptoms for diagnosing pollen-induced asthma.Patients and methods: We recruited 1,161 patients with respiratory symptoms who presented to the respiratory medicine outpatient clinic of two central hospitals in Inner Mongolia during the pollen season of July–September 2015. All patients were interviewed by a respiratory physician and completed a questionnaire survey, lung function tests and skin prick tests for common inhaled allergens.Results: A total of 392 patients (33.8%) were diagnosed with asthma and 292 (25.2%, 160 adults, 132 children) with pollen-induced asthma. Respiratory symptoms of cough, wheezing, dyspnea, chest pain and nocturnal awakenings due to breathlessness were all associated with increased odds of being diagnosed with pollen-induced asthma, with cough being the most common symptom in both adults and children, giving a sensitivity of 90.6% in adults and 88.6% in children. Wheezing was the most specific symptom (78% and 89.5% in adults and children, respectively) compared to other symptoms. Overall, the positive predictive value of respiratory symptoms was poor for diagnosing pollen-induced asthma, with the exception of wheezing in children which had a high positive predictive value of 72.7%.Conclusion: Cough was the predominant symptom in adults and children with pollen-induced asthma. Wheezing was a reliable predictor of pollen-induced asthma in children. In adults, respiratory symptoms were not sufficiently reliable for diagnosing pollen-induced asthma. Keywords: pollen-induced asthma, asthma symptoms, wheezing, cough, shortness of breath

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

Fuqing Zhou,1,2,* Ying Zhuang,3,* Lingling Wang,4 Yue Zhang,5 Lin Wu,1,2 Xianjun Zeng,1,2 Honghan Gong1,2 1Department of Radiology, The First Affiliated Hospital, Nanchang University, 2Jiangxi Province Medical Imaging Research Institute, 3Department of Oncology, The Second Hospital of Nanchang, Nanchang, Jiangxi Province, 4Department of Geriatrics, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong Province, 5Department of Radiology, The Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi Province, People’s Republic of China *These authors contributed equally to this work Background and purpose: Little is known about the functional and structural connectivity (FC and SC) of the hippocampus and amygdala, which are two important structures involved in cognitive processes, or their involvement in relapsing–remitting multiple sclerosis (RRMS). In this study, we aimed to examine the connectivity of white-matter (WM) tracts and the synchrony of intrinsic neuronal activity in outer regions connected with the hippocampus or amygdala in RRMS patients.Patients and methods: Twenty-three RRMS patients and 23 healthy subjects participated in this study. Diffusion tensor probabilistic tractography was used to examine the SC, the FC correlation coefficient (FC-CC) and combined FC strength (FCS), which was derived from the resting-state functional magnetic resonance imaging used to examine the FC, of the connection between the hippocampus or the amygdala and other regions, and the correlations of these connections with clinical markers. Results: Compared with healthy subjects, the RRMS patients showed significantly decreased SC and increased FCS of the bilateral hippocampus, and left amygdala. Their slightly increased FC-CC was positively correlated with WM tract damage in the right hippocampus (ρ=0.57, P=0.005); an increased FCS was also positively correlated with WM tract damage in the right amygdala. A relationship was observed between the WM lesion load and SC alterations, including the lg(N tracts) of the right hippocampus (ρ=-0.68, P

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]