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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

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

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

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

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

Peripheral coupled waveguide (PCW) design has been deployed in InGaAsP multiple quantum-well (MQW) electroabsorption modulator (EAM) at 1.55-mum wavelength. PCW enhances the optical saturation power and reduces the optical insertion loss and the equivalent V-pi simultaneously. A radio-frequency link using a 1.3-mm-long lumped-element PCW EAM has achieved experimentally a link gain of -3 dB, at 500 MHz and at input optical power of 80 mW. The corresponding two-tone multioctave spurious-free dynamic range (SFDR) at the same bias is measured at 118 dB (.) Hz(2/3). The single-octave SFDR at the third-order null bias is 132 dB (.) Hz(4/5).