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Shengwei Meng,1,&ast; Derong Xu,1,&ast; Shuo Han,1 Guanghui Li,1 Yan Wang,1 Yanqing Shen,2 Kai Zhu,1 Antao Lin,1 Ruiting Wang,3 Xuexiao Ma,1 Chuanli Zhou1 1Department of Spinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China; 2Operating Room, Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China; 3Medical Insurance Audit Department, Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chuanli Zhou; Xuexiao Ma, Department of Spinal Surgery, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Qingdao, Shandong, 266000, People’s Republic of China, Tel +8618661809796 ; +8618661807895, Email justin_5257@hotmail.com; maxuexiaospinal@163.comPurpose: To evaluate the outcomes, feasibility, and safety of endoscopic unilateral laminectomy, bilateral decompression and discectomy (Endo-ULBDD) for central lumbar spinal stenosis (CLSS) combined with disc herniation (DH).Methods: This study includes 39 patients diagnosed with CLSS combined with DH who met the inclusion criteria and underwent surgery for Endo-ULBDD from April 2020 to March 2021. The mean age of the patients, operation time, hospitalization time, time in bed, and complications were recorded. Patients were followed up for at least 12 months. Visual analog scale (VAS) scores for low-back and lower-limb pain and Oswestry Disability Index (ODI) scores were evaluated preoperatively, before discharge, and at 3, 6, and 12 months postoperatively. To evaluate clinical effectiveness 12 months postoperatively, the modified MacNab criteria were used.Results: The mean age of the patients was 59.9 years, the mean operation time was 82.1 minutes, the mean hospitalization time was 3.7 days, and the mean time in bed was 20.9 hours. The mean VAS scores of low-back and lower-limb pain improved from 5.9 and 7.2 to 2.0 and 1.6, respectively (P < 0.05). The ODI score improved from 56.0 to 16.7 (P < 0.05). The overall excellent-good rate of the modified MacNab criteria was 89.7%. Two kinds of complications occurred in 4 patients (10.3%), including 1 patient whose inferior articular process was excessively removed and 3 patients who suffered from postoperative dysesthesia. No other severe complications were noted.Conclusion: Endo-ULBDD is a safe, feasible, efficient, and minimally invasive approach to treating CLSS combined with DH.Keywords: endoscopic spinal surgery, laminectomy, discectomy, lumbar spinal stenosis, intervertebral disc displacement

Yanyan Li,1,&ast; Qingqing Lou,2,&ast; Song Wen,1 Mingyue Zhou,3 Dongxiang Xu,1 Chaoxun Wang,1 Xingdang Liu,2 Ligang Zhou1,4 1Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, People’s Republic of China; 2Department of Nuclear Medicine, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, People’s Republic of China; 3Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA; 4Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling, Shanghai, 201399, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ligang Zhou, Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, People’s Republic of China, Tel +8613611927616, Email zhouligang@yahoo.comPurpose: This study aimed to reveal the relationship between the volume of sporadic renal cysts and renal function in patients with type 2 diabetes (T2D).Materials and Methods: One hundred and seventy-one patients that underwent renal imaging and other routine examinations at the Shanghai Pudong Hospital were included in this study. The Gates’ method of glomerular filtration rate (GFR) was measured by 99mTc-DTPA renal dynamic imaging in addition to the eGFR, calculated by the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI).Results: Our results showed that BMI, total iGFR, and eGFR showed significant differences between patients with T2D with or without SRC (p < 0.05). Spearman correlation analysis showed that cyst volume was positively correlated with Scr and gender but not iGFR (p > 0.05). The total iGFR positively correlated with eGFR (r = 0.83, p < 0.0001) and negatively with Scr (r = − 0.78, p < 0.0001), age (r = − 0.43, p < 0.0001), duration of T2D (r = − 0.25, p = 0.001), and BMI (r = − 0.21, p = 0.006) but not gender (r = − 0.03, p = 0.668). The multilinear regression model revealed that gender (β = 0.346, p < 0.001), iGFR (β = − 0.705, p < 0.001), and serum uric acid (β = 0.195, p = 0.032) were independent predictors of Scr. Moreover, we observed a significant increase in Scr in males (p < 0.05). Finally, we found that the split kidney function reflected by iGFR and related parameters such as time to peak (PTT) and half time of excretion (excrete t1/2) did not mutually distinguish from each other significantly whether they are measured in patients with renal cysts or in those without renal cysts (p > 0.05).Conclusion: Our preliminary results suggest that in T2D, SRCs may be a renal complication of diabetic nephropathy. Although we found that the patients with renal cysts may display reduced iGFR, the volume of simple cysts seems not to exacerbate renal insufficiency. Isotope renography is a useful tool to evaluate the split kidney functions in diabetic patients who acquire single-side cysts.Keywords: type 2 diabetes, SRCs, kidney function, isotope glomerular filtration rate, cysts volume, gender disparity

Siwei Xing,1,&ast; Xiaohao Ruan,1,&ast; Jingyi Huang,1,&ast; Jiaqi Yan,1 Wenhao Lin,1 Jinlun Huang,1 Jiacheng Liu,1 Da Huang,1 Rong Na,2 Danfeng Xu1 1Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Division of Urology, Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Hong Kong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rong Na, Division of Urology, Department of Surgery, Queen Mary Hospital, The University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, People’s Republic of China, Email narong.hs@gmail.com Da Huang, Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, People’s Republic of China, Email huangdasjtu@gmail.comPurpose: To explore the impact of family history (FH) on renal cell carcinoma (RCC) and its pathological subtype clear cell RCC (ccRCC) in a Chinese population; a significant association has previously been determined not only in familial cancer syndrome but also in sporadic cases in western populations.Methods: Consecutive patients with kidney tumors from October 2017 to May 2021 at a tertiary hospital in Shanghai were enrolled in the study. Demographic and clinical information was collected, including age, gender, FH (positive or negative, types of cancers, degree of relatives, etc.), pathological diagnosis, and Fuhrman grades.Results: A positive FH of any cancer was observed in 26.5% of the RCC patients, while only 16.8% patients with benign kidney tumor were found to have a positive FH. A strong correlation was observed between FH of any cancers in first-degree relatives and RCC (odds ratio [OR]=4.60, 95% confidence interval [CI]: 1.95– 10.85, P=5.50× 10− 5) or ccRCC (OR=4.63, 95% CI: 1.95– 11.02, P=9.63× 10− 5). In subgroup analysis, FH of digestive cancers was significantly associated with RCC (OR=4.42, 95% CI: 1.35– 14.51, P=0.005) or ccRCC (OR=4.14, 95% CI: 1.25– 13.75, P=6.84× 10− 4). Similar results were found in multivariate analyses. However, no significant association was observed between FH and age at onset.Conclusion: FH was an independent risk factor for RCC and ccRCC in this Chinese population. FH of any cancer in first-degree relatives and FH of digestive cancers were found to be the most significant risk factors for kidney cancers.Keywords: Chinese population, family history, renal cell carcinoma, risk factor, multivariate regression analysis

Weihu Ma,1 Yujie Peng,2 Song Zhang,2 Yulong Wang,2 Kaifeng Gan,3 Xuchen Zhao,2 Dingli Xu2 1Orthopedic Department, Ningbo No.6 Hospital, Zhejiang, Ningbo, People’s Republic of China; 2Clinical Medical Department, Medical School of Ningbo University Zhejiang, Ningbo, People’s Republic of China; 3Orthopedic Department, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, People’s Republic of ChinaCorrespondence: Dingli Xu, Email xudingliwo@126.comObjective: To compare the clinical and radiological outcomes between microscopic anterior cervical discectomy and fusion (ACDF) and percutaneous endoscopic cervical keyhole foraminotomy (PECF) for single level unilateral cervical radiculopathy.Methods: A total of 127 patients (59 in PECF VS 68 in ACDF) were enrolled in this study from April 2016 to May 2018 with a minimum follow-up of 2 years. Clinical data including baseline data, Neck Disability Index (NDI), and Visual Analogue Scale for neck and arm (VAS-n, VAS-a) were collected and compared. Radiological evaluation such as disc height, ROM of cervical, Cobb’s angle of cervical and Cobb’s angle of operated segment was measured by two experienced radiologists in twice.Results: There was no significant difference between the two groups in the baseline data, and hospital stay was significantly decreased in PECF group than ACDF group (P < 0.001). PECF group did not yield superior better outcomes in NDI, VAS-a and VAS-n than ACDF group except at 1-month follow-up. As for radiological outcomes, PECF group has significantly better cervical motion, cervical angle and segmental angle than ADCF group at 12- and 24-month follow-up visit (P < 0.05); however, ACDF had shown better disc height restoration and maintenance than PECF (P < 0.05). More complications including surface hematoma and swallowing difficulty were occurred in ADCF group.Conclusion: Percutaneous endoscopic cervical keyhole foraminotomy could be the alternative method for anterior cervical discectomy and fusion in selective cases. However, the indication should be fulfilled, more studies need to be conducted to further testify the efficacy of PECF.Keywords: unilateral cervical radiculopathy, percutaneous endoscope cervical keyhole foraminotomy, microscopic anterior cervical discectomy and fusion

Xiyan Zhang,1 Xude Zhang,1 Shaojie Feng,1 Xijuan Wang,1 Beibei Guo,1 Jingjing Liu,1 Donghua Xu,2,3 Fengxia Liu1 1Department of Allergy, Weifang People’s Hospital, Weifang, People’s Republic of China; 2Clinical Medicine College, Weifang Medical University, Weifang, People’s Republic of China; 3Department of Rheumatology, The First Affiliated Hospital of Weifang Medical University, Weifang, People’s Republic of ChinaCorrespondence: Fengxia Liu; Donghua Xu, Email wf_lfx@163.com; xudh@wfmc.edu.cnBackground: Allergic asthma is the most common type of asthma and often occurs in early life with increasing comorbidities, including atopic dermatitis and allergic rhinitis. MicroRNAs (miRNAs) are involved in the pathogenesis of numerous immune and inflammatory disorders, particularly allergic inflammation. The specific miRNA profiles of children with allergic asthma have not been fully delineated and still require in-depth study.Objective: This study aimed to identify the expression profile of miRNAs and constructed a network of the interactions between differentially expressed miRNAs and target mRNAs to provide novel insights into understanding the pathogenesis of allergic asthma.Materials and Methods: In this study, we performed high-throughput sequencing of peripheral blood mononuclear cells (PBMCs) from children in the acute phase of asthma. Bioinformatics approaches, including miRanda, Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, were employed to predict novel therapeutic and diagnostic targets for allergic asthma. Real-time quantitative PCR was conducted to detect the expression of aberrantly expressed miRNAs.Results: One hundred and sixty-one differentially expressed miRNAs were identified in children with allergic asthma, including 140 conserved miRNAs and 21 novel miRNAs. A total of 8929 targeted mRNAs (44,186 transcripts) associated with differentially expressed miRNAs were predicted and significantly enriched in the cGMP-PKG signalling pathway, cholinergic synapse, and salivary secretion. We also found that miRNA-370-3p targeted PKG and MLCP molecules in the cGMP-PKG signalling pathway and was involved in the pathogenesis of allergic asthma.Conclusion: We identified the miRNA profile of PBMCs in children with allergic asthma and also found that miRNA-370-3p targeted PKG and MLCP molecules in the cGMP-PKG signalling pathway, which provides a novel insight into understanding the pathogenesis of allergic asthma and investigating new targets for the treatment of allergic asthma in children.Keywords: allergic asthma, MicroRNAs, inflammation, house dust mite, children

Su’e Shao,1 Meifang Huang,2 Heng Zhang,1 Gangqiang Peng,1 Min Song,1 Jing Liu,1 Dan Xu1 1Department of Gastroenterology, The Central Hospital of Wuhan, Wuhan, People’s Republic of China; 2Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of ChinaCorrespondence: Meifang Huang, Department of Gastroenterology, Zhongnan Hospital of Wuhan University, No. 169 East Lake Road, Wuchang District, Wuhan, Hubei, 430061, People’s Republic of China, Tel +86-13307110223, Email 1657791068@qq.com Heng Zhang, Department of Gastroenterology, the Central Hospital of Wuhan, No. 26 Shengli Street, Jiang’an District, Wuhan, Hubei, 430014, People’s Republic of China, Tel +86-18627886610, Email 653262549@qq.comPurpose: To retrospectively collect and analyze demographic information as well as symptoms, laboratory results, endoscopic and pathologic findings, and treatment of ulcerative colitis (UC) and Crohn’s disease (CD) patients in Wuhan, China.Methods: Patients who were diagnosed as inflammatory bowel disease (IBD) and hospitalized from January 2012 to December 2017 were enrolled in this study. The clinical characteristics including symptoms, laboratory results, and treatment were reviewed and analyzed.Results: Totally 821 cases were screened, and finally 430 UC patients and 286 CD patients were selected and enrolled in this study. The most common symptom in UC patients was bloody stool (90.7%) followed by diarrhea (87.7%), mucus in stool (72.1%), and abdominal pain (66.3%), which were significantly different from those of CD patients (P < 0.01). In contrast, the most common symptom in CD patients was abdominal pain (80.0%) followed by diarrhea (58.4%), bloody stool (27.6%), and fever (18.2%). Erythrocyte sedimentation, C-reactive protein, and platelets were significantly increased, while hemoglobin was decreased, in the moderately or highly active IBD. The percentage of positive perinuclear anti-neutrophil cytoplasmic antibody was significantly higher in UC patients (31.1%) than that in CD patients (4.8%, P < 0.001), while the percentage of positive anti-intestinal goblet cell antibody was significantly higher in CD patients (23.1%) than that in UC patients (14.9%, P = 0.037).Conclusion: The findings of the current study may provide evidence-based information for Chinese gastroenterologists to treat IBD more effectively in the future.Keywords: inflammatory bowel disease, Crohn’s disease, ulcerative colitis

Yunchen Meng,1 Dan Xu,1 Weinan Zhang,1 Wenshu Meng,2 Xingyu Lan,3 Xiaoxi Wang,3 Mingjuan Li,3 Xiaoyan Zhang,1 Yu Zhao,1 Haodong Yang,1 Rong Zhang,3– 6 Zhiping Zhen1 1College of P.E and Sports, Beijing Normal University, Beijing, People’s Republic of China; 2College of Life Sciences, Beijing Normal University, Beijing, People’s Republic of China; 3Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, People’s Republic of China; 4Neuroscience Research Institute, Peking University, Beijing, People’s Republic of China; 5Key Laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, People’s Republic of China; 6Autism Research Center of Peking University Health Science Center, Beijing, People’s Republic of ChinaCorrespondence: Zhiping Zhen; Rong Zhang, Email zzpxt@bnu.edu.cn; zhangrong@bjmu.edu.cnBackground: Autism spectrum disorder (ASD) is a developmental disorder characterized by social behavior deficits and stereotyped behaviors in childhood that lacks satisfactory medical intervention. Early swimming intervention is a noninvasive method combining enriched environment and exercise, which has been proven to improve brain development in young children and to treat neurodevelopmental diseases.Methods: In this study, we tested the autism-like behavior of rats with deletions in exons 11– 21 of the Shank3 gene and evaluated the effect of early swimming intervention (from postnatal day 8 to 60) on the behavior of this animal model of autism. In addition, the transcriptomes of the striatal tissues of wild-type, Shank3 knockout and Shank3 knockout swimming groups rats were analyzed.Results: Shank3 knockout rats exhibit core symptoms of autism, and early swimming improved the social and stereotyped behaviors in this autism rat model. Transcriptomics results revealed that compared to the wild-type group, 291 differentially expressed genes (DEGs) were identified in the striatum of the Shank3 knockout group. Compared to Shank3 knockout group, 534 DEGs were identified in the striatum of Shank3 knockout swimming group. The DEGs annotated by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway shows that the impacts of Shank3 deletion were primarily reflected in synaptic structure, development, morphology, receptor function and signaling, and swimming primarily changed the terms related to the synapses in the striatum of Shank3 knockout rats, including the morphology, structure, composition, development and regulation of synapses.Conclusion: Early swimming intervention can ameliorate behavioral abnormalities caused by Shank3 knockout, by a mechanism that may involve the process of striatal synaptic development and should be further investigated.Keywords: Shank3, autism, early swimming, behavior, transcriptome

Dingli Xu,1,2,&ast; Kaifeng Gan,3,&ast; Yang Wang,1 Zeting Wu,1 Yulong Wang,1 Song Zhang,1 Yujie Peng,2 Xuguang Fang,4 Hua Wei,5 Yansheng Zhang,5 Weihu Ma,2 Jing Chen5 1The Affiliated Hospital of Ningbo University Medical School, Ningbo, 315000, People’s Republic of China; 2Ningbo No.6 Hospital, Ningbo, 315000, People’s Republic of China; 3The Affiliated Lihuili Hospital of Ningbo University, Ningbo, 31500, People’s Republic of China; 4The First Affiliated Hospital of Xi ‘an Medical University, Xi’an, 710082, People’s Republic of China; 5Zhejiang International Scientific and Technological Cooperative Base of Biomedical Materials and Technology, Zhejiang Engineering Research Center for Biomedical Materials, Cixi Institute of Biomedical Engineering, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, 315300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weihu Ma; Jing Chen, Email 944973034@qq.com; jing.chen@nimte.ac.cnIntroduction: Bone delay union is mostly caused by lack of blood supply. Although autografts, allografts and artificial bone have been widely used to treat bone delay union, the bone regeneration fails in the ischemic site accompanied by the bone donor site complications and disease transmission. Recently, there is a growing recognition of the importance of hydrogel scaffolds which are regarded as an eligible engineer tissue for bone repair. However, hydrogel is still limited in improving neovascularization.Methods: In this work, black phosphorus nanosheet and deferoxamine (BPN-DFO) were loaded in the gelatin hydrogel to overcome the high risk of bone delay union and systemically investigated the regeneration capability of BPN-DFO hydrogel in vitro and vivo.Results: The resulting BPN-DFO hydrogel scaffold showed superior swollen, degradation and release rate, as well as satisfied biocompatibility. BPN-DFO hydrogel shown the significant up-expression of mRNA related to bone regeneration and cell proliferation. In vivo, the proposed BPN-DFO hydrogel significantly improved osteogenesis and neovascularization in the ischemic tibial bone site of SD rats with acute femoral artery occlusion. Both macroscopic and histological evaluation of new regenerated bone showed newly formed blood vessel and collagen using BPN-DFO hydrogel. The immunohistochemistry and RT-PCR revealed that the bone regeneration could be improved via BMP/Runx2 pathway.Conclusion: The BPN-DFO hydrogel possesses potential tissue engineer material for ischemic bone defect treatment. However, furthermore studies are needed to testify the safety and efficacy of BPN-DFO hydrogel.Keywords: ischemic bone defect regeneration, hydrogel scaffolds, black phosphorus nanosheets, deferoxamine

Luqi Dai,1,2,&ast; Dan Xu,1,&ast; Chun Wan,1,2 Lian Liu,1 Fuqiang Wen1,2 1Division of Pulmonary Diseases, State Key Laboratory of Biotherapy, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fuqiang Wen; Lian LiuDepartment of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, and Division of Pulmonary Diseases, State Key Laboratory of Biotherapy, Guoxuexiang 37 Road, Chengdu, Sichuan, 610041, People’s Republic of ChinaTel +86 28 8542 2350Fax +86 28 8558 2944Email wenfuqiang@scu.edu.cn; desertfoxliu@hotmail.comPurpose: WNT/β-catenin signal pathway is a potential hope for lung tissue repair. We investigated the levels of Dickkopf‐1 (DKK1), an endogenous inhibitor of WNT/β-catenin signal pathway, in chronic obstructive pulmonary disease (COPD) patients and airway inflammation.Patients and Methods: Collected the demographic and clinical characteristics of 36 healthy controls, 25 stable COPD patients and 10 acute exacerbation of COPD (AECOPD) patients, then performed pulmonary function and detected serum DKK1 levels. After over-expression of DKK1, detect the levels of DDK1, lipoprotein-related protein 6 (LRP6) and inflammatory factors in bronchial epithelial cells stimulated with cigarette smoke extract (CSE).Results: Serum DKK1 were reduced in stable COPD patients compared to healthy controls (3866.72 ± 775.33 pg/mL vs 5317.61 ± 1317.20 pg/mL, p< 0.0001), but there was no significant difference between stable and acutely exacerbated patients (3866.72 ± 775.33 pg/mL vs 3482.10 ± 841.25 pg/mL, p> 0.05). DKK1 was positively correlated with FEV1 (r = 0.570, p< 0.0001), FEV1/FVC (rho = 0.590, p< 0.0001), FEV1/Pre (r = 0.517, p< 0.0001). Multiple linear regression analysis also suggested that FEV1 levels were higher with increasing DKK1. In vitro, elevated IL-6, IL-8, TNF-α and decreased DKK1, LRP6 were found in Beas-2B cells after CSE treatments, and increased LRP6 and decreased inflammatory factors were found after overexpression of DKK1. Andrographolide restored the CSE-induced decrease in DKK1 and increase in IL-6 and IL-8.Conclusion: DKK1 levels were decreased in COPD patients and positively correlated with lung function, overexpression of DKK1 and andrographolide attenuated airway cell inflammation, both suggesting a potential role in pathophysiology and providing a disease-specific biomarker pattern.Keywords: LRP6, lung function, biomarker, andrographolide

Hong Xiao,1 Dan Xu,2 Rui Mao,3 Minqin Xiao,1 Yang Fang,4 Yin Liu1 1Department of Plastic Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 2Department of Dermatology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 3School of Stomatology, Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 4Wushi Jiamei Beauty Hospital, Kunming, Yunnan, People’s Republic of ChinaCorrespondence: Yin LiuDepartment of Plastic Surgery, The Second Affiliated Hospital of Kunming Medical University, No. 374, Dianmian Road, Kunming, Yunnan, 650103, People’s Republic of ChinaTel +86-136 5888 3652Email liuyinsky@163.comPurpose: Platelet-rich plasma (PRP) is a promising noninvasive technique for facial rejuvenation. This systematic literature review aims to appraise the nature and quality of published evidence evaluating the effectiveness and safety of PRP in facial rejuvenation.Patients and Methods: A systematic literature review was conducted with the search string “Platelet-rich plasma AND Facial rejuvenation” in PubMed and Embase. Clinical studies evaluating the outcomes after PRP-based facial rejuvenation either as monotherapy or in combination with other treatment modalities were included. Studies evaluating wound-healing properties of PRP were excluded. The outcomes included both patient-reported and physician-assessed outcomes. Nonstatistical synthesis of evidence was performed by qualitative assessment. The results are reported by the Synthesis Without Meta-analysis (SWiM) reporting standard.Results: A total of 36 studies that included a total of 3172 patients were considered for the evidence synthesis. The number of patients in the included studies ranging from 11 to 2005 with a median of 27.5 patients that reflects the challenges in clinically assessing the aesthetic outcomes after PRP-based facial rejuvenation. Among the 36 studies, 17 were observational studies and 18 were interventional studies with 1 being case report PRP was evaluated either alone or in combination with hyaluronic acid, lipofilling, micro-needling technique, and laser-based interventions. Among the studies, 1 study reported the enhanced platelet concentrate in a fibrin matrix to be relatively safe and effective with a maximum benefit observed at 12 weeks suggesting the platelet-rich fibrin matrix may provide desired aesthetic outcomes and it requires further studies to substantiate.Conclusion: The results suggest very limited clinical evidence, and further clinical studies are warranted to establish the effectiveness of PRP in facial rejuvenation. Furthermore, a consensus for end points used for establishing clinical utility in patients requiring facial rejuvenation is warranted.Keywords: fibrin, hyaluronic acid, platelet-rich plasma, rejuvenation, wound healing

Jianyun Long, Xupin Xie, Dong Xu, Changpin Huang, Yongchang Liu, Xiaohu Meng, Xuchao Cai, Xin Fang Department of Vascular Surgery, Affiliated Hangzhou First People’s Hospital, ZheJiang University School of Medicine, Hangzhou, Zhejiang, 310014, People’s Republic of ChinaCorrespondence: Xin FangDepartment of Vascular Surgery, Affiliated Hangzhou First People’s Hospital, ZheJiang University School of Medicine Hangzhou, Zhejiang, 310014, People’s Republic of ChinaTel +86 571-56005600Email hzfhfx@126.comObjective: Red blood cell distribution width (RDW) is a predictor of adverse outcomes in aortic aneurysms. Recent recommendations suggest that combining RDW with other biomarkers could yield better results. We, therefore, propose evaluating the biomarker of vascular aging, albumin with RDW to predict the risk of aortic aneurysms. This study aims to explore whether the combination of RDW with albumin can effectively predict the prognosis of aortic aneurysm patients.Methods: This retrospective cohort study was conducted among adults (age > 18) with aortic aneurysms in the Medical Information Mart for Intensive Care Database III V1.4 (MIMIC-III). RAR was measured according to the red blood cell distribution width and albumin. The primary outcome was the 30-day mortality rate, and the secondary outcome was the 90-day and one-year mortality rates. Estimation of hazard ratios (HR) was obtained from Cox regression models for all-cause mortality related to red cell distribution width-to-albumin ratio (RAR) values.Results: In total, 312 patients were involved, with an average age of 74.9 ± 10.9 years and an average RAR value of 5.4 ± 1.6 mL/g. In 30 days for all-cause mortality, the HR (95% CI) in the highest RAR group (> 5.8 mL/g) in tertiles was 2.54 (1.25, 5.14) in the unadjusted model, with a significant difference compared with the reference group (P < 0.05). After adjusting for race, gender and age, there was still a correlation (P < 0.05), and the HR (95% CI) was 2.51 (1.23, 5.10). Further adjustment of possible covariates showed similar correlation in model 3 (P < 0.05), and HR (95% CI) was 2.66 (1.17, 6.01). Multivariable logistic regression shows that RAR is an independent risk factor for the outcome of aortic aneurysms after adjusting the covariates. In the subgroup analysis, we analyzed the patient’s complications, and no significant interaction was observed.Conclusion: RAR is a risk factor for patients with aortic aneurysms. However, more in-depth research is warranted to further analyze and substantiate our findings on the role of RAR in aortic aneurysm patients.Keywords: red blood cell distribution width–albumin ratio, aortic aneurysms, retrospective cohort study, MIMIC-III

Ma-chao Li,1,&ast; Jie Lu,2,&ast; Yao Lu,1,3,&ast; Tong-yang Xiao,4,&ast; Hai-can Liu,1 Shi-qiang Lin,5 Da Xu,1 Gui-lian Li,1 Xiu-qin Zhao,1 Zhi-guang Liu,1 Li-li Zhao,1 Kang-lin Wan1 1State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China; 2Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of China; 3School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, People’s Republic of China; 4Guangdong Key Laboratory for Diagnosis & Treatment of Emerging Infectious Diseases, Shenzhen Third People’s Hospital, Southern University of Science and Technology, Shenzhen, People’s Republic of China; 5Department of Bioinformatics, College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li-li Zhao; Kang-lin WanNational Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, P.O. Box 5, Changping, Beijing, 102206, People’s Republic of ChinaTel/Fax +86 10 58900779Email zhaolili@icdc.cn; wankanglin@icdc.cnObjective: To investigate the mutations within the whole rpoB gene of Mycobacterium tuberculosis and analyze their effects on rifampin (RIF) resistance based on crystal structure.Methods: We sequenced the entire rpoB gene in 175 tuberculosis isolates and quantified their minimum inhibitory concentrations using microplate-based assays. Additionally, the structural interactions between wild-type/mutant RpoB and RIF were also analyzed.Results: Results revealed that a total of 34 mutations distributed across 17 different sites within the whole rpoB gene were identified. Of the 34 mutations, 25 could alter the structural interaction between RpoB and RIF and contribute to RIF resistance. Statistical analysis showed that S450L, H445D, H445Y and H445R mutations were associated with high-level RIF resistance, while D435V was associated with moderate-level RIF resistance.Conclusion: Some mutations within the rpoB gene could affect the interaction between RpoB and RIF and thus are associated with RIF resistance. These findings could be helpful to design new antibiotics and develop novel diagnostic tools for drug resistance in TB.Keywords: Mycobacterium tuberculosis, rifampin resistance, structure, mutation

Dingli Xu, 1 Yujie Peng, 2 Haojie Li, 2 Yang Wang, 2 Weihu Ma 2 1Department of Orthopedics, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, Zhejiang, People’s Republic of China; 2Department of Spine, Ningbo No.6 Hospital, Ningbo, Zhejiang, People’s Republic of ChinaCorrespondence: Weihu MaDepartment of Spine, Ningbo No.6 Hospital, Ningbo, Zhejiang, People’s Republic of ChinaEmail 944973034@qq.comBackground: Anterior occipital condyle screw (AOCS) could be a feasible alternative technique for occipitocervical fusion for reconstruction of craniovertebral junction. This study aimed to analyze the feasibility of AOCS.Methods: The craniovertebral junction computed tomography (CT) scans of 40 adults were enrolled and imported into Mimics software. Then, the three-dimensional reconstruction digital model of craniovertebral junction was established to determine entry point, insertion angle, and screw’s trajectory. After AOCS insertion into ten human cadaver spine specimens, CT scans were performed to verify the location between screws and important structures.Results: The optimal entry point was located caudally and medial to the ventral of occipital condyle. The optimal trajectory was in inclination angle (5.9°± 3.4°) in the sagittal plane and divergence angle (26.7°± 6.0°) in the axial plane with the screw length around 21.6± 1.2mm. None of the screws invaded the hypoglossal canal and vertebral artery in any of the specimens.Conclusion: AOCS fixation is a feasible, novel technique for anterior craniovertebral junction reconstruction, and it could be an effective alternative operation for anterior reconstruction with titanium mesh cage.Keywords: anterior occipital condyle screw, craniovertebral reconstruction, optimal trajectory, cadaveric study

Mei Yang,&ast; Ting Yang,&ast; Xiaoou Li,&ast; Diandian Li, Zenglin Liao, Yongchun Shen, Dan Xu, Lei Chen, Fuqiang Wen Department of Respiratory and Critical Care Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Chen; Fuqiang WenDepartment of Respiratory and Critical Care Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of ChinaEmail lchens@126.com; wenfuqiang@scu.edu.cnPurpose: Elevated blood eosinophils have been implicated in chronic obstructive pulmonary disease (COPD) progression and exacerbation. We aim to investigate clinical predictors of high blood eosinophils in a Chinese COPD cohort.Patients and Methods: We conducted a retrospective cohort study in Sichuan province, a Southwest province with high prevalence of COPD in China. All patients in this cohort were extracted from the Chinese Pulmonary Health study, a large cross-sectional study on COPD epidemiology in China. Demographics, personal and family history, living condition, spirometry and blood eosinophil counts were obtained. Univariate and multiple linear regression analyses were performed to determine predictors of high blood eosinophils.Results: A total of 375 COPD patients were included in this cohort. The median absolute blood eosinophil count was 138.8 cells/μL, and the prevalence of COPD with high blood eosinophils was 66.7% and 14.7% when using the thresholds of 100 cells/μL and 300 cells/μL, respectively. Univariate analyses indicated that male gender, lower body mass index, high-density lipoprotein (HDL), lower family income, raising pets and biomass use were significantly associated with high blood eosinophils (p < 0.05). Multiple linear regression model further revealed male gender (unstandardized coefficient (B)=66.125, 95% confidence intervals (CI) 16.350 to 115.900, p=0.009), age (B=2.819, 95% CI 0.639 to 5.000, p=0.012) predicted high blood eosinophil level, whereas HDL (B=− 64.682, 95% CI − 123.451 to − 5.914, p=0.031) was a negative predictor for high blood eosinophils.Conclusion: This retrospective cohort study suggests male gender, oldness and lower HDL could be clinical predictors of high blood eosinophils in Chinese COPD patients.Keywords: chronic obstructive pulmonary disease, blood eosinophil count, high-density lipoprotein, predictor, retrospective study

Dandan Xu,1– 3,&ast; Yue Yu,1,4,&ast; Yayun Xu,5,&ast; Jinfang Ge1– 3 1School of Pharmacy, Anhui Medical University, Hefei, People’s Republic of China; 2Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, Hefei, People’s Republic of China; 3The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, People’s Republic of China; 4Department of Pharmacy, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 5Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinfang GeSchool of Pharmacy, Anhui Medical University, 81 Mei-Shan Road, Hefei, Anhui, 230032, People’s Republic of ChinaTel +86 551 65172131Fax +86 551 65161115Email gejinfang@ahmu.edu.cnPurpose: Nesfatin-1 plays a crucial role in glucose metabolism and cognitive function. This study aimed to investigate the correlation between plasma nesfatin-1 levels and clinical indicators and cognitive function in patients with type 2 diabetes mellitus (T2DM).Methods: Demographic and medical history data, physical examination, and biochemical test results of 132 T2DM patients were collected. The plasma concentrations of nesfatin-1, C-reactive protein (CRP), interleukin-6 (IL-6), soluble triggering receptors expressed on myeloid cells 1 (sTREM1), and sTREM2 in T2DM patients were measured. Cognitive function was evaluated using the Behavior Rating Inventory of Executive Function-Adult (BRIEF-A). The patients were divided into two groups: a low-nesfatin-1 group (n = 75) and a high-nesfatin-1 group (n = 57) based on a plasma nesfatin-1 concentration less than or above the 50th percentile value of all the samples.Results: The results showed that plasma HbA1c levels were positively correlated with CRP, IL-6, sTREM1, and sTREM2 levels in patients with T2DM (P < 0.05). Plasma nesfatin-1 concentrations were positively associated with diabetes-related biochemical indicators including glycated haemoglobin (HbA1c), insulin, and homeostatic model assessment of insulin resistance (HOMA-IR), and inflammation-related indicators including CRP, IL-6, sTREM1, and sTREM2 among patients with T2DM (P < 0.05). Moreover, T2DM patients with high nesfatin-1 levels showed higher HbA1c and fasting plasma glucose (FPG) levels (P < 0.05). Furthermore, T2DM patients with high nesfatin-1 levels also showed higher BRIEF-A scores (P = 0.01). Additionally, T2DM patients with high total scores of BRIEF-A (scores > 50th percentile) could be identified with a sensitivity of 59.1% and a specificity of 72.7% by nesfatin-1.Conclusion: These findings indicate that plasma nesfatin-1 might be involved in the T2DM-associated comorbidities and the development of cognitive dysfunction, and the mechanism underlying this involvement is related to the imbalance in the expression of CRP, IL-6, sTREM1, and sTREM2 levels.Keywords: type 2 diabetes mellitus, cognitive dysfunction, nesfatin-1, inflammatoryresponse, sTREM1/2

Chong Zhao,&ast; Hao Zhang,&ast; Yan Wang, Derong Xu, Shuo Han, Shengwei Meng, Jialuo Han, Houchen Liu, Chuanli Zhou, Xuexiao Ma Department of Spine Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuexiao Ma; Chuanli ZhouDepartment of Spine Surgery, The Affiliated Hospital of Qingdao University, No.59 Haier Road, Qingdao, Shandong, 266000, People’s Republic of ChinaTel +86 18661807895; +86 18661809796Email ma_xuexiao@126.com; justin_5257@hotmail.comPurpose: To investigate the preoperative radiological risk factors for recurrent lumbar disc herniation (rLDH) within 1 year after percutaneous endoscopic transforaminal discectomy (PETD).Patients and Methods: A retrospective case–control study was conducted. Between January 2013 and November 2019, a total of 1210 patients with single-level L4/5 LDH who underwent PETD were enrolled in the present study. In total, 62 rLDH patients were diagnosed and collected based on the clinical and radiological manifestations, and 224 non-rLDH controls were selected from the remaining 1148 patients. Preoperative radiological parameters were collected and measured. An age threshold to distinguish patients into subgroups was established using the Youden index. The relationships between the risk factors and rLDH were evaluated by univariate and multivariate analyses in two subgroups. Predictive models were established based on logistic analysis. The area under the curve (AUC) of receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA) were used to assess the predictive models.Results: In the present study, logistic analysis identified six significant predictors associated with rLDH in the young group: superior endplate concave angle (ECA), sacral slope, Modic changes, sagittal range of motion (sROM), extension intervertebral angle (IVA), and lumbar lordosis. Four significant predictors were identified in the elderly group: disc height index (DHI), retrolisthesis (posterior spondylolisthesis), sROM, and extension IVA. Validation of both models demonstrated excellent model discrimination (AUC= 0.940 and 0.946, respectively). DCA also showed excellent clinical utility and benefits.Conclusion: The nomograms that we constructed could accurately predict individual patient recurrence risk. Individualized measures should be taken for patients of different ages with the above risk factors, and tailored postoperative surveillance of patients who underwent PETD can be planned.Keywords: lumbar disc herniation, percutaneous endoscopic transforaminal discectomy, recurrent LDH, risk factor

Wentao Huang,1 Dagfinn Aune,2– 4 Gerson Ferrari,5 Lei Zhang,6 Yutao Lan,1 Jing Nie,7 Xiong Chen,8 Dali Xu,9 Yafeng Wang,10 Leandro FM Rezende11 1School of Nursing, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 2Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK; 3Department of Nutrition, Bjørknes University College, Oslo, Norway; 4Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway; 5Universidad de Santiago de Chile (USACH), Escuela de Ciencias de la Actividad Física, el Deporte y la Salud, Santiago, Chile; 6Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital of Fudan University, Shanghai, People’s Republic of China; 7Department of Sociology & Institute for Empirical Social Science Research, School of Humanities and Social Sciences, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 8Department of Endocrinology, Wenzhou Medical University First Affiliated Hospital, Wenzhou, Zhejiang, People’s Republic of China; 9Department of Psychiatry and Neuroimaging Centre, Wenzhou Seventh People’s Hospital, Wenzhou, Zhejiang, People’s Republic of China; 10Department of Epidemiology and Biostatistics, School of Health Sciences, Wuhan University, Wuhan, People’s Republic of China; 11Universidade Federal de São Paulo, Escola Paulista de Medicina, Departamento de Medicina Preventiva, Sao Paulo, BrazilCorrespondence: Dali XuDepartment of Psychiatry and Neuroimaging Centre, Wenzhou Seventh People’s Hospital, Wenzhou, Zhejiang, People’s Republic of ChinaEmail dali0421@163.comWentao HuangSchool of Nursing, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of ChinaEmail huangwentau@outlook.comAim: To examine the association of psychological distress with all-cause, cardiovascular disease (CVD) and cancer mortality in US adults, and verified whether the associations differed between participants with and without diabetes.Methods: A total of 485,864 adults (446,288 without diabetes and 39,576 with diabetes) who participated in the National Health Interview Survey from 1997 to 2013 were linked to the National Death Index through December 31, 2015. Psychological distress was measured by the Kessler 6 distress scale (K6). Multivariable Cox proportional hazards regression models were performed to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for the association between psychological distress and mortality.Results: We ascertained 11,746 deaths (mean follow-up, 7. 7 years) among people with diabetes and 51,636 deaths (9.9 years) among those without diabetes. Psychological distress was associated with higher all-cause, CVD, and cancer mortality. Compared to non-diabetic adults without psychological distress, HRs (95% CI) were 1.07 (1.04 to 1.09) for mild, 1.26 (1.22 to 1.30) for moderate and 1.46 (1.38 to 1.55) for severe psychological distress. Compared to the same reference group, in diabetic participants the HRs were 1.39 (1.33 to 1.44) for no psychological distress, 1.59 (1.53 to 1.66) for mild, 1.90 (1.80 to 2.00) for moderate and 1.98 (1.82 to 2.17) for severe psychological distress. Similar associations were also observed for CVD and cancer mortality but with non-statistically significant interaction.Conclusion: Psychological distress was associated with higher mortality, particularly in participants with diabetes. Strategies to ameliorate psychological distress may be important to reduce mortality in this population.Keywords: diabetes mellitus, psychological distress, mortality, cohort

Huajun Zhao,1 Haigang Wang,1 Yifei Hu,1 Dongqing Xu,1 Chunlai Yin,2 Qiuju Han,1 Jian Zhang1 1Institute of Immunopharmaceutical Sciences, School of Pharmaceutical Sciences, Shandong University, Jinan, People’s Republic of China; 2Department of Immunology, Dalian Medical University, Dalian, People’s Republic of ChinaCorrespondence: Jian ZhangInstitute of Immunopharmaceutical Sciences, School of Pharmaceutical Sciences, Shandong University, Jinan, People’s Republic of ChinaTel +86-531-8838-3781Fax +86-531-8838-3782Email zhangj65@sdu.edu.cnPurpose: Alum adjuvant in HBV prophylactic vaccines is poor in inducing cellular immunity with the inhibition of IL-12 secretion, and approximately 5– 10% of immunised individuals fail to clear HBV upon infection. IL-12 plasmids (pIL-12) as adjuvants enhance significant humoral and cellular immune response in vaccines. However, finding a novel delivery system to protect pIL-12 from enzymatic degradation and achieve efficient delivery remains a major challenge.Methods: We prepared the chitosan nanovaccine-loaded IL-12 expression plasmid (termed as “Ng(-)pIL-12”) and analysed the physicochemical properties, encapsulation efficiency and safety. Then, we evaluated the efficiency of Ng(-)pIL-12 for prophylactic HBV vaccine. Serum samples were collected and analysed for IL-12, HBsAg, anti-HBs IgG, IgG1 and IgG2b. Liver tissues were collected and analysed for HBV DNA and RNA. BMDCs and lymphocytes were collected and analysed for HBV-specific immune responses. To further confirm the long-term protective immune response against HBV, these immunised mice were challenged with hydrodynamic injection of pAAV/HBV 1.2 plasmid on day 56 after the initiation of immunisation.Results: Chitosan nanovaccine prepared with CS and γ-PGA could load pIL-12 effectively and safely, and IL-12 was efficiently produced in vivo. Interestingly, Ng(-)pIL-12 adjuvant combined with HBsAg induced higher levels of anti-HBs IgG, IgG1 and IgG2b, promoted maturation and presentation capacity of DCs, especially CD8α+/CD103+ DCs. Meanwhile, Ng(-)pIL-12 adjuvant generated robust HBV-specific CD8+ T and CD4+ T cell responses. More importantly, Ng(-)pIL-12 adjuvant triggered terminally differentiated effector memory responses with strong anti-HBV effects.Conclusion: Chitosan nanovaccines as an efficient carrier adjuvant system for pIL-12 combined with HBsAg induced protective anti-HBs IgG and enhanced HBV-specific CD8+ T and CD4+ T cell responses, and achieved long-term memory response against HBV, making it a promising candidate for prophylactic HBV vaccines.Keywords: nanovaccines, hepatitis B, prophylactic vaccine, CD8+ T cells, long-term memory

Congying Liu,1 Junhong Pan,1 Song Wen,1 Thiquynhnga Nguyen,1 Dongxiang Xu,1 Chaoxun Wang,1 Xinlu Yuan,1 Zhongqiu Wen,2 Ligang Zhou1,3 1Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, People’s Republic of China; 2Department of Information Center, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, People’s Republic of China; 3Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, People’s Republic of ChinaCorrespondence: Ligang ZhouDepartment of Endocrinology, Shanghai Pudong Hospital, Fudan University, 2800 Gongwei Road, Huinan Town, Pudong New Area, Shanghai, 201399, People’s Republic of ChinaTel +8613611927616Email zhouligang@yahoo.comObjective: We aimed to evaluate the relationship between thyroid-stimulating hormone (TSH) and bone mineral density (BMD) in euthyroid type 2 diabetes (T2D).Methods: This retrospective analysis enrolled 439 T2D patients with normal thyroid function, including 226 males and 213 females. All the female patients were postmenopausal. Serum glycosylated hemoglobin A1c (HbA1c), TSH, free triiodothyronine (FT3), and free thyroxine (FT4) concentrations were analyzed. BMD of the lumbar spine (L1–L4), femoral neck, and hip joint was determined using dual-energy X-ray absorptiometry.Results: The patients were grouped based on tri-sectional quantiles of the TSH levels: 0.55∼ 1.70mIU/L (Group 1), 1.71∼ 2.58mIU/L (Group 2), and 2.59∼ 4.74mIU/L (Group 3). Our data showed that, in male patients, no difference in BMD was identified among groups. In postmenopausal women, unlike at the lumbar spine (P = 0.459), the mean BMD at the femoral neck (P = 0.014) and hip joint (P = 0.014) had a statistical difference among groups and increased with TSH level. In addition, our analysis demonstrated that TSH levels shown no correlation with BMD at all sites in males. However, in females, BMD at the femoral neck (r = 0.156, P = 0.023) and hip joint (r = 0.172, P = 0.012) had a positive correlation with TSH levels. After adjusting for age and BMI, multiple regression analysis showed that TSH levels influenced BMD at the femoral neck (β = 0.188, P = 0.001) and hip joint (β = 0.204, P = 0.001) in female patients.Conclusion: In summary, our data demonstrates that low TSH levels are associated with decreased BMD at the femoral neck and hip joint in postmenopausal T2D women with euthyroidism.Keywords: type 2 diabetes, thyroid-stimulating hormone, bone mineral density, menopause

Haihong Zhang,1 Fang Wu,1 Hongli Yi,2 Dongjuan Xu,3 Nana Jiang,4 Yonghong Li,5 Ming Li,1 Kefang Wang1 1School of Nursing and Rehabilitation, Shandong University, Jinan City, Shandong Province, People’s Republic of China; 2Department of Respiratory Medicine, Shandong Provincial Hospital, Jinan City, Shandong Province, People’s Republic of China; 3School of Nursing, Purdue University, West Lafayette, IN, USA; 4Department of Respiratory Medicine, Dongfang Hospital Affiliated to Tongji University, Shanghai City, People’s Republic of China; 5Department of Respiratory Medicine, Jinan Central Hospital, Jinan City, Shandong Province, People’s Republic of ChinaCorrespondence: Ming LiSchool of Nursing and Rehabilitation, Shandong University, No.44 Wenhua Xi Road, Lixia District, Jinan City, Shandong Province, 250012, People’s Republic of ChinaTel +86-531-88382000Email liming74@sdu.edu.cnPurpose: Previous research has indicated that female and male patients may experience different levels of symptoms. However, no studies of chronic obstructive pulmonary disease (COPD) patients have compared the number and types of symptom clusters identified in male and female patients. Therefore, the purpose of this study was to investigate gender differences in symptom clusters among COPD patients.Patients and Methods: A total of 371 eligible patients were enrolled in the study. We assessed nine COPD symptoms, namely, dyspnea, cough, sputum, chest tightness, sleep quality, fatigue, frailty, anxiety, and depression. Exploratory factor analyses were used to explore the underlying clusters of the COPD symptoms.Results: Underlying the nine symptoms, female patients had 2 clusters, and male patients had 3 clusters. Specifically, the three general symptoms poor sleep, fatigue, and frailty loaded on the same symptom cluster with anxiety and depression in female patients, while the same 3 general symptoms loaded on the same symptom cluster with chest tightness and dyspnea in male patients. Moreover, cough and sputum not only were more common in male patients but also loaded together on a separate symptom cluster.Conclusion: Our findings suggest that in order to improve fatigue, frailty, and poor sleep quality, symptom management strategies should more closely address anxiety and depression in female patients as well as chest tightness and dyspnea in male patients. Smoking cessation is particularly important in male COPD patients because they account for a much higher proportion of smokers and are more likely to have cough and sputum. These findings signify the importance of identifying and implementing gender-tailored symptom management strategies to relieve symptom burden in COPD patients to enhance their quality of life.Keywords: quality of life, symptom burden, symptom management, factor analysis

Fuyu Jin,1 Fei Geng,2 Dingjie Xu,3 Yaqian Li,1 Tian Li,1 Xinyu Yang,1 Shupeng Liu,1 Hui Zhang,1 Zhongqiu Wei,1 Shifeng Li,2 Xuemin Gao,2 Wenchen Cai,2 Na Mao,2 Xue Yi,4 Heliang Liu,2 Ying Sun,1 Fang Yang,2 Hong Xu1,2 1Basic Medical College, Hebei Key Laboratory for Chronic Diseases, North China University of Science and Technology, Tangshan, Hebei Province, 063210, People’s Republic of China; 2School of Public Health, Hebei Key Laboratory for Organ Fibrosis Research, North China University of Science and Technology, Tangshan, Hebei Province, 063210, People’s Republic of China; 3Traditional Chinese Medicine College, North China University of Science and Technology, Tangshan, Hebei Province, 063210, People’s Republic of China; 4Key Laboratory of Functional and Clinical Translational Medicine, Xiamen Medical College, Xianmen, Fujian Province, 361023, People’s Republic of ChinaCorrespondence: Hong Xu 21 Bohai Road, Caofeidian District, Tangshan, Hebei Province, 063210, People’s Republic of ChinaTel +86 315-8816236Email xuhong@ncst.edu.cnBackground: Silica-induced inflammatory activation is associated with silicosis and various non-respiratory conditions. The present study was designed to examine the anti-inflammatory effects of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) on lung macrophages and bone osteoclasts after silica inhalation in rats.Methods: Wistar rats and NR8383 and RAW 264.7 cell lines were used in the present study. The receptor activator of nuclear factor kappa-B ligand (RANKL) and toll-like receptor 4 (TLR4) signaling pathways was measured in the lung tissue of rats or NR8383/RAW 264.7 cells exposed to silica. The microarchitecture of the trabecular bone in the tibia and femur was evaluated in silicotic rats. Furthermore, the roles of Ac-SDKP on silicotic rats, silica-treated NR8383/RAW 264.7 cells, and RANKL-induced osteoclast differentiation were studied.Results: The data indicated that silica inhalation might activate the RANKL and TLR4 signaling pathways in lung macrophages, thus inducing the lung inflammatory and proteolytic phenotype of macrophages and osteoclasts in lung and bone. Ac-SDKP maintained the lung elastin level by inhibiting lung inflammation and macrophage activation via the RANKL and TLR4 signaling pathways. Ac-SDKP also attenuated the reduction in femoral bone mineral density in silicotic rats by inhibiting osteoclast differentiation via the RANKL signaling pathway.Conclusion: Our findings support the hypothesis that inhalation of crystalline silica induces activation of lung macrophages and bone osteoclasts via the RANKL and TLR4 signaling pathways. Ac-SDKP has the potential to stabilize lung homeostasis and bone metabolism.Keywords: silicosis, N-acetyl-seryl-aspartyl-lysyl-proline, macrophage, osteoclast

Hui Wang,1,* Cui-Ying Li,1,* Hai-Ling Zha,1 Di Xu,1 Zhi-Bin Hu2 1Department of Ultrasound, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People’s Republic of China; 2Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhi-Bin HuDepartment of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, No. 101 Longmian Avenue, Jiangning District, Nanjing, 211166, Jiangsu, People’s Republic of ChinaTel +86-25-86868437Email Zhibin_hu@njmu.edu.cnDi XuDepartment of Ultrasound, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, People’s Republic of ChinaTel +86-25-83714511Email xudi_doctor@163.comPurpose: To investigate the diagnostic and predictive value of strain ratios in the regions of interests (ROIs) in reference tissue for breast tumor.Patients and Methods: A total of 707 lesions in 665 consecutive patients were examined with B-mode Breast Imaging-Reporting and Data System (BI-RADS) and Ultrasonic elastography (UE). Elasticity score (ES) and strain ratio (SR) in each lesion were calculated. Receiver operating characteristic (ROC) curves were used to assess the diagnostic value of BI-RADS, ES, SR1, SR2, BI-RADS combined with ES (BI-RADS+ES), BI-RADS combined with SR1 (BI-RADS+SR1), and BI-RADS combined with SR2 (BI-RADS+SR2). The sensitivity, specificity, and areas under the ROC curves (Az) were obtained. Scatter plots were generated to demonstrate the correlation between SR1 and SR2. Kruskal-Walls H-test, Mann–Whitney U-test and one-way ANOVA were performed to evaluate SRs and tumor-related variables. Multiple linear regression analysis was carried out to determine variables independently associated with SRs.Results: BI-RADS had high sensitivity and low specificity in the diagnosis of breast tumor. The specificity of BI-BADS combined with ES or SR was even higher. The Az value of BI-RADS+ES or BI-RADS+SRs was higher than that of BI-RADS (P < 0.001). The Az value of ES was higher than those of SR1 and SR2 (P < 0.001), and those of SR1 and SR2 were similar. SR1 and SR2 were highly positively correlated. There was no statistical difference between Az values of BI-RADS+ES, BI-RADS+SR1, and BI-RADS+SR2. Indistinct margin, high histologic grade, histological type, and negative human epidermal growth factor receptor (Her-2) were associated with SR1 and SR2. Progesterone receptor (PR) status and molecular subtype were associated with SR2. Histologic grade and tumor margin were significantly associated with SR1, and tumor margin was associated with SR2.Conclusion: SRs in different ROIs in the reference tissue at the same depth showed no different diagnostic value for breast tumor. Both SR1 and SR2 could be useful in assessing the biological characteristics of invasive breast carcinoma.Keywords: conventional ultrasonography, Breast Imaging-Reporting and Data System, ultrasonic elastography, elasticity score, strain ratio

Ding Xu,* Weigang Lou,* Ming Li, Jianming Chen Department of Orthopedic Trauma Surgery, Ningbo No.6 Hospital, Ningbo, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ding Xu Email xuding831129@126.comAbstract: Due to the traction of the Achilles tendon and osteoporosis, a large number of reports have shown that a series of complications such as skin flap necrosis and failure of internal fixation after surgery often cause nonunion or malunion of calcaneal tuberosity fractures. At the same time, there is no uniform standard for the operative procedure in the treatment of the avulsion fractures of the calcaneal tuberosity. We presented a new technique for the treatment of avulsion fractures of the calcaneal tuberosity, which is fixed with a 180-degree microplate. We aim to provide a simple, safe, and strong internal fixation technique for avulsion fractures of the calcaneal tuberosity as one of the treatment options.Keywords: 180-degree annular internal fixation, avulsion fractures of the calcaneal tuberosity, new technique

Meng Kong,1,2,* Derong Xu,1,* Changtong Gao,3 Kai Zhu,1 Shuo Han,1,2 Hao Zhang,1,2 Chuanli Zhou,1 Xuexiao Ma1 1Department of Spinal Surgery, The Affiliated Hospital of Qingdao University, Qing’dao, Shandong Province 266000, People’s Republic of China; 2Department of Medicine, Qingdao University, Qing’dao, Shandong Province 266000, People’s Republic of China; 3Minimally Invasive Interventional Therapy Center, Qingdao Municipal Hospital, Qing’dao, Shandong Province 266000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xuexiao Ma Tel +8618661807895Email ma_xuexiao@126.comChuanli ZhouDepartment of Spinal Surgery, The Affiliated Hospital of Qingdao University, No. 59, Hai Er Road, Qing’dao, Shandong Province 266000, People’s Republic of ChinaTel +86 18661809796Email justin_5257@hotmail.comBackground: Percutaneous endoscopic lumbar discectomy (PELD) is an increasingly applied minimally invasive procedure that has several advantages in the treatment of lumbar disc herniation (LDH). However, recurrent LDH (rLDH) has become a concerning postoperative complication. It remains difficult to establish a consensus and draw reliable conclusions regarding the risk factors for rLDH.Purpose: This retrospective study aimed to investigate the risk factors associated with rLDH at the L4-5 level after percutaneous endoscopic transforaminal discectomy (PETD).Methods: A total of 654 patients who underwent the PETD procedure at the L4-5 level from October 2013 to January 2020 were divided into a recurrence (R) group (n=46) and a nonrecurrence (N) group (n=608). Demographic and clinical data and imaging parameters were collected and analyzed using univariate and multiple regression analyses.Results: The current study found a 7% rate of rLDH at the L4/5 level after successful PETD. Univariate analysis showed that older age, high BMI, diabetes mellitus history, smoking, large physical load intensity, moderate disc degeneration, small muscle–disc ratio (M/D), more fat infiltration, large sagittal range of motion (sROM), scoliosis, small disc height index (DHI), small intervertebral space angle (ISA), and small lumbar lordosis (LL) were potential risk factors (P < 0.10) for LDH recurrence after PETD at the L4-5 level. Multivariate analysis suggested that high BMI, large physical load intensity, moderate disc degeneration, small M/D, more fat infiltration, large sROM, small ISA, and small LL were independent significant risk factors for recurrence of LDH after PETD.Conclusion: Consideration of disc degeneration, M/D, fat infiltration of the paravertebral muscles, sROM, ISA, LL, BMI, and physical load intensity prior to surgical intervention may contribute to the prevention of rLDH following PETD and lead to a more satisfactory operative outcome and the development of a reasonable rehabilitation program after discharge.Keywords: percutaneous endoscopic transforaminal discectomy, recurrent LDH, risk factor

Xinfang Wang,* Dong Xu,* Xin Pei, Yingying Zhang, Yuling Zhang, Yaxing Gu, Ying Li Department of Pediatrics, Shandong Provincial Western Hospital, Jinan 250022, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ying LiDepartment of Pediatrics, Shandong Provincial Western Hospital, No. 4 Duanxing West Road, Jinan, Shandong 250022, People’s Republic of ChinaTel +86-531 83086400Email dedfedx@163.comBackground: Medulloblastoma (MB) is the most common malignant brain tumor during childhood. Circular RNA (circSKA3) was identified to function as an oncogene in MB. However, the mechanism of circSKA3 in MB remains unclear.Methods: The levels of circSKA3, microRNA-383-5p (miR-383-5p), and forkhead box M1 (FOXM1) in MB tissues were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The cell viability and apoptotic rate were assessed via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and flow cytometry, respectively. The protein levels of B-cell lymphoma 2 (Bcl-2), C-Caspase3, and FOXM1 were detected via Western blot assay. Cell cycle was detected by flow cytometry. The migration and invasion abilities were monitored by Transwell assay. The dual-luciferase reporter assay was constructed to verify the interactions between miR-383-5p and circSKA3 or FOXM1. The mice model experiment was carried out to validate the effects of circSKA3 in vivo.Results: The levels of circSKA3 and FOXM1 were significantly elevated, while the level of miR-383-5p was notably declined in MB tissues. CircSKA3 was validated to sponge miR-383-5p, and FOXM1 was a candidate target of miR-383-5p. CircSKA3 silencing impeded cell proliferation, migration, and invasion while promoted apoptosis by targeting miR-383-5p in vitro and retarded xenograft tumor growth in vivo. miR-383-5p suppressed cell proliferation, migration, and invasion but promoted apoptosis in MB cells by regulating FOXM1. CircSKA3 depletion decreased FOXM1 expression via miR-383-5p in MB cells.Conclusion: CircSKA3 augmented MB progression partly through miR-383-5p/FOXM1 axis.Keywords: circSKA3, miR-383-5p, FOXM1, medulloblastoma

Yi-Man Teng,1,* Kun-Shan Wu,2,* Kuan-Ling Lin,3 Dan Xu1 1College of Modern Management, Yango University, Fuzhou 350015, People’s Republic of China; 2Department of Business Administration, Tamkang University, Taipei, Taiwan; 3College of Child Development and Education, Yango University, Fuzhou 350015, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kun-Shan Wu Email kunshan@mail.tku.edu.twBackground: The COVID-19 pandemic has had a far-reaching and unprecedented influence on economies worldwide. It has also impacted on the global population’s mental health and caused negative psychosocial effects, which may lead to psychological crises. During the pandemic, the challenges for quarantine hotel employees are not only the increased workloads created by operating a quarantine hotel but also high psychological stress associated with job insecurity, risk of exposure and contagion for themselves, their friends and families. This research attempts to explore COVID-19-related depression, anxiety, and stress among quarantine hotel employees in China. The mental health of quarantine hotel employees, who have faced unprecedented changes, is paramount while they provide hospitality and care for healthcare workers and quarantine guests during mandatory quarantine periods.Methods: This is a cross-sectional study that applied convenience sampling to collect questionnaire samples from 170 quarantine hotel employees in Xiamen, Fujian Province, China, during the COVID-19 pandemic, from May 20 to June 10, 2020. The Depression, Anxiety, and Stress Scale (DASS-21) was used to collect data. The study uses descriptive analysis, chi-square test and binary logistic regression to examine the sociodemographic factors associated with depression, anxiety and stress levels during the COVID-19 pandemic.Results: The results reveal that 43.5% of respondents report moderate to extremely severe symptoms of depression; 68.2% have moderate to extremely severe anxiety symptoms; and 8.2% indicated moderate to extremely severe stress symptoms. Quarantine hotel employees who have a higher level of education are less likely to experience anxiety, and those with higher incomes are less likely to experience depression.Discussion: In order to mitigate the increasing levels of anxiety and depression among their staff, quarantine hoteliers or managers urgently need to implement mental health assistance programs, such as providing extra training in hygiene and knowledge about COVID-19, offering online counseling and psychological support services, training in positive thinking, encouraging staff to keep in touch with their personal support networks, and constructing a resilience model.Keywords: COVID-19, quarantine hotel employee, Depression Anxiety and Stress Scale, DASS-21, mental health

Ying Qi, Qingqing Cui, Wenjing Zhang, Renjie Yao, Dong Xu, Fengyan Zhang Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, The Laboratory for Ophthalmology and Vision Science, Henan Eye Hospital, Zhengzhou 450052, Henan, People’s Republic of ChinaCorrespondence: Fengyan Zhang Department of OphthalmologyThe First Affiliated Hospital of Zhengzhou University, The Laboratory for Ophthalmology and Vision Science, Henan Eye Hospital, Zhengzhou 450052, Henan, People’s Republic of ChinaEmail zhangfengyanyanke@163.comObjective: Human uveal melanoma (UM) is a common ocular malignant tumor with a high risk of metastasis. Emerging evidence indicates that long non-coding RNAs (lncRNAs) are correlated with the development of UM. Here, we aimed to determine the biological significance of lncRNA growth arrest-specific transcript 5 (GAS5) in UM.Methods: The expression levels of GAS5 and microRNA-21 (miR-21) in UM tissues and cells were detected by qRT-PCR analysis. CCK-8 assay was performed to investigate the viability of UM cells after cell transfections, and the migration and invasion of UM cells were determined by transwell assay. The protein expression levels were detected by Western blot assay. The relationship between miR-21 and GAS5 in UM cells was confirmed by bioinformatics prediction and luciferase report assay.Results: Our experiments demonstrated that GAS5 was markedly downregulated in UM cells and clinical specimens. Overexpression of GAS5 inhibited, whereas knockdown of GAS5 promoted the viability, migration, and invasion of UM cells. The epithelial-to-mesenchymal transition (EMT) process of UM cells was also suppressed by upregulating of GAS5 and enhanced by downregulating of GAS5. Additionally, as a competitive endogenous RNA (ceRNA), GAS5 directly binded to the oncogenic miR-21 in UM cells, and overexpression of miR-21 attenuated the EMT-suppressing effect of GAS5.Conclusion: Taken together, our findings suggest that GAS5/miR-21 axis is implicated in the pathogenesis of UM and might serve as a potential therapeutic target.Keywords: GAS5, uveal melanoma, invasion, epithelial–mesenchymal transition, microRNA-21

Guohua Dai, Shuzhong Li, Chuqiang Yin, Yuanliang Sun, Derong Xu, Zhongying Wang, Liangrui Luan, Jianwen Hou, Ting Wang Affiliated Hospital of Qingdao University, Qingdao 266003, People’s Republic of ChinaCorrespondence: Ting Wang Tel +86 18661809505Email wangting20@hotmail.comObjective: In the present study, we aimed to describe the clinical features, diagnosis, treatment, and prognosis of spinal epidural abscess (SEA).Methods: The complete clinical data of 11 SEA patients who were treated in our hospital system from January 2015 to June 2018 were retrospectively analyzed. Moreover, the clinical features, diagnosis, treatment, and prognosis of 642 SEA cases collected from the foreign literature from 2010 to 2019 were also investigated.Results: Among our 11 SEA patients, nine cases had purulent inflammation, two cases had tuberculosis, two cases had infection caused by Staphylococcus aureus, one case had infection caused by Streptococcus constellatus, one case had infection caused by Klebsiella pneumoniae, five cases showed negative bacterial culture, and two cases had Mycobacterium tuberculosis. All 11 cases showed focal spinal pain, eight cases exhibited neurological deficits, and six cases experienced fever. Nine of the 11 cases involved the lumbosacral spine, one case involved the thoracic spine, and one case involved the cervical spine. Eight patients had a longer course of disease (> 2 weeks), all 11 patients had vertebral osteomyelitis, and nine patients had intervertebral discitis. One patient had motor dysfunction of arms and legs, one patient had lower limb motor dysfunction, one patient had limb numbness, one patient experienced relapse after the conservative treatment, and one patient experienced relapse after the surgical treatment. The follow-up time was 15– 24 months.Conclusion: The classic diagnosis of triads (focal spine pain, neurological deficit, and fever) was less specific for SEA. MRI examination, blood culture, tissue culture, and biopsy could be used for the diagnosis for SEA. Suppuritis was a common cause of SEA. Early detection, early diagnosis and early treatment, as well as the selection of the most suitable treatment regimen based on comprehensive evaluation, played crucial roles in a better prognosis of SEA. There was no statistically significant difference in terms of the general condition, diagnosis, treatment and prognosis between the patients with negative and positive culture results (P> 0.05). For SEA patient with negative culture, antibiotic treatment should be used empirically.Keywords: epidural abscess, clinical features, diagnosis and treatment, prognosis

Yue Zhu,1,* Rongjia Zhu,2,* Kun Liu,3,* Xin Li,1 Dezhong Chen,4 Dunyao Bai,5 Jieli Luo,5 Yixun Liu,6 Yan Zhang,7 Li Li,8 Junfang Hu,9 Dayong Xu,10 Yan Liu,10 Robert Chunhua Zhao2,11 1Stem Cell Lab, Puren Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei 430081, People’s Republic of China; 2Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, People’s Republic of China; 3Otorhinolaryngology, Puren Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei 430081, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Puren Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei 430081, People’s Republic of China; 5Molecular Laboratory, Puren Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei 430081, People’s Republic of China; 6Gonadal Biology Research Group, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, People’s Republic of China; 7National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, People’s Republic of China; 8The Ministry of Science and Education, Puren Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei 430081, People’s Republic of China; 9Department of Pharmacy, Puren Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei 430081, People’s Republic of China; 10Puren Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei 430081, People’s Republic of China; 11School of Life Sciences, Shanghai University, Shanghai 200444, People’s Republic of China*These authors contributed equally to this workCorrespondence: Robert Chunhua ZhaoInstitute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, People’s Republic of ChinaEmail zhaochunhua@vip.163.comYan LiuStem Cell Lab, Puren Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei 430081, People’s Republic of ChinaEmail liuyan@wust.edu.cnBackground: COVID-19 (coronavirus disease 2019) has become a global public health emergency since patients were first detected in Wuhan, China, in December 2019. Currently, there are no satisfying antiviral medications and vaccines available.Case Presentation: We reported the treatment process and clinical outcome of a 48-year-old man critically ill COVID-19 patient who received transfusion of allogenic human umbilical cord mesenchymal stem cells (UC-MSCs).Conclusions: We proposed that UC-MSC transfusion might be a new option for critically ill COVID-19. Although only one case we were shown, more similar clinical cases are inquired for further evidence providing the potential effectiveness of UC-MSC treatment.Keywords: COVID-19, UC-MSCs, critically ill, cell transplantation, case report

Shuang Xu,1 Dan Xu,1 Liang Wen,2 Chen Zhu,3 Ying Yang,1 Shuang Han,1 Peng Guan4 1School of Library and Medical Informatics, China Medical University, Shenyang, Liaoning, People’s Republic of China; 2Department of Neurosurgery, The General Hospital of Shenyang Military Command, Shenyang, Liaoning, People’s Republic of China; 3Department of Neurosurgery, The First Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China; 4Department of Epidemiology, School of Public Health, China Medical University, Shenyang, Liaoning, People’s Republic of ChinaCorrespondence: Peng GuanDepartment of Epidemiology, School of Public Health, China Medical University, Shenyang 110122, Liaoning, People’s Republic of ChinaEmail pguan@cmu.edu.cnBackground: The treatment of post-traumatic stress disorder (PTSD) has long been a challenge because the symptoms of PTSD are multifaceted. PTSD is primarily treated with psychotherapy and medication, or a combination of psychotherapy and medication. The present study was designed to analyze the literature on medications for PTSD and explore high-frequency common drugs and low-frequency burst drugs by burst detection algorithm combined with Unified Medical Language System (UMLS) and provide references for developing new drugs for PTSD.Methods: Publications related to medications for PTSD from 2010 to 2019 were identified through PubMed, Web of Science Core Collection, and BIOSIS Previews. SemRep and SemRep semantic result processing system were performed to extract the set of drug concepts with therapeutic relationship according to the semantic relationship of UMLS. Kleinberg’s burst detection algorithm was applied to calculate the burst weight index of drug concepts by a Java-based program. These concepts were sorted according to the frequency and the burst weight index.Results: Four hundred and fifty-nine treatment-related drug concepts were extracted. The drug with the highest burst weight index was “Psilocybine”, a hallucinogen, which was more likely to be a hotspot for the pharmacotherapy of PTSD. The highest frequency concept was “prazosin”, which was more likely to be the focus of research in the medications for PTSD.Conclusion: The present study assessed the medication-related literature on PTSD treatment, providing a framework of burst words detection-based method, a baseline of information for future research and the new attempt for the discovery of textual knowledge. The bibliometric analysis based on the burst detection algorithm combined with UMLS has shown certain feasibility in amplifying the microscopic changes of a specific research direction in a field, it can also be used in other aspects of disease and to explore the trends of various disciplines.Keywords: post-traumatic stress disorder, burst detection, Kleinberg’s algorithm, burst word, Unified Medical Language System, SemRep

Thiquynhnga Nguyen,* Song Wen,* Min Gong,* Xinlu Yuan, Dongxiang Xu, Chaoxun Wang, Jianlan Jin, Ligang Zhou Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai 201399, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ligang ZhouDepartment of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai 201399, People’s Republic of ChinaTel +86 13611927616Email zhouligang@yahoo.comPurpose: This study investigates the possible effect and central mechanism of novel antidiabetic medication sodium glucose transporter-2 (SGLT-2i) on the cardiovascular activity.Material and Methods: Thirty-four normal male C57BL/6 mice were randomly assigned to 2 groups to receive single Dapagliflozin (1.52mg/kg) dose via intragastric gavage or a comparable dose of saline. Glycemic level (BG), blood pressure (BP) and heart rate (HR) were measured 2 hours after administration of the respective treatments. Immunohistochemical tests were performed to determine the effect of SGLT-2i on neural localization of SGLT-2 and c-Fos, a neural activator. The distributional relationships of SGLT-2 and c-Fos were examined by immunofluorescence.Results: Administration of SGLT-2i significantly decreased BP but did not affect the HR. There was no difference in BG between the two groups. Results showed that SGLT-2 was localized to specific regions involved in autonomic control. Expression of c-Fos was significantly higher in major critical nuclei in the aforementioned regions in groups treated with Dapagliflozin.Conclusion: This study demonstrates that SGLT-2 is expressed in CNS tissues involved in autonomic control and possibly influence cardiovascular function. Dapagliflozin influences central autonomic activity via unidentified pathways by inhibiting central or peripheral SGLT-2. These results provide a new concept that sympathetic inhibition by SGLT-2i can be mediated by central autonomic system, a mechanism that explains how SGLT-2i improves the cardiovascular function.Keywords: sodium glucose co-transporter-2, dapagliflozin, c-Fos, cardiovascular activity, brain nuclei

Jie Xiong,1 Binglei Jiang,1 Yong Luo,1 Jianzhong Zou,1 Xuan Gao,1 Die Xu,1 Yan Du,1,2 Lan Hao3 1State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing Key Laboratory of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, People’s Republic of China; 2Ultrasonography Department, The Fourth People’s Hospital of Chongqing, Central Hospital of Chongqing University, Chongqing 400014, People’s Republic of China; 3Institute of Ultrasound Imaging, Chongqing Medical University, Chongqing 400010, People’s Republic of ChinaCorrespondence: Jianzhong ZouCollege of Biomedical Engineering, Chongqing Medical University, Chongqing 400010, People’s Republic of ChinaTel +86 13783002390Email zoujzh@cqmu.edu.cnPurpose: Focused ultrasound (FUS) is a noninvasive method to produce thermal and mechanical destruction along with an immune-stimulatory effect against cancer. However, FUS ablation alone appears insufficient to generate consistent antitumor immunity. In this study, a multifunctional nanoparticle was designed to boost FUS-induced immune effects and achieve systemic, long-lasting antitumor immunity, along with imaging and thermal enhancement.Materials and Methods: PEGylated PLGA nanoparticles encapsulating astragalus polysaccharides (APS) and gold nanorods (AuNRs) were constructed by a simple double emulsion method, characterized, and tested for cytotoxicity. The abilities of PA imaging and thermal-synergetic ablation efficiency were analyzed in vitro and in vivo. The immune-synergistic effect on dendritic cell (DC) differentiation in vitro and the immune response in vivo were also evaluated.Results: The obtained APS/AuNR/PLGA-PEG nanoparticles have an average diameter of 255.00± 0.1717 nm and an APS-loading efficiency of 54.89± 2.07%, demonstrating their PA imaging capability and high biocompatibility both in vitro and in vivo. In addition, the as-prepared nanoparticles achieved a higher necrosis cell rate and induced apoptosis rate in an in vitro cell suspension assay, greater necrosis area and decreased energy efficiency factor (EEF) in an in vivo rabbit liver assay, and remarkable thermal-synergic performance. In particular, the nanoparticles upregulated the expression of MHC-II, CD80 and CD86 on cocultured DCs in vitro, followed by declining phagocytic function and enhanced interleukin (IL)-12 and interferon (INF)-γ production. Furthermore, they boosted the production of tumor necrosis factor (TNF)-α, IFN-γ, IL-4, IL-10, and IgG1 (P< 0.001) but not IgG2a. Immune promotion peaked on day 3 after FUS in vivo.Conclusion: The multifunctional APS/AuNR/PLGA-PEG nanoparticles can serve as an excellent synergistic agent for FUS therapy, facilitating real-time imaging, promoting thermal ablation effects, and boosting FUS-induced immune effects, which have the potential to be used for further clinical FUS treatment.Keywords: immune, immunoadjuvant, thermal ablation, PLGA, Chinese traditional medicine

Yaotai Wang,1 Chun Chen,1 Yong Luo,1 Jie Xiong,1 Yu Tang,1 Haiyan Yang,1 Lu Wang,1 Fujie Jiang,1 Xuan Gao,2 Die Xu,2 Huanan Li,1 Qi Wang,1 Jianzhong Zou1,2 1State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, People’s Republic of China; 2Chongqing Key Laboratory of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaCorrespondence: Jianzhong ZouState Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Yuzhong District, Chongqing 400016, People’s Republic of ChinaTel +86-13708302390Email zoujzh@cqmu.edu.cnPurpose: The high-intensity focused ultrasound (HIFU) ablation of tumors is inseparable from synergistic agents and image monitoring, but the existing synergistic agents have the defects of poor targeting and a single imaging mode, which limits the therapeutic effects of HIFU. The construction of a multifunctional biological targeting synergistic agent with high biosafety, multimodal imaging and targeting therapeutic performance has great significance for combating cancer.Methods: Multifunctional biological targeting synergistic agent consisting of Bifidobacterium longum (B. longum), ICG and PFH coloaded cationic lipid nanoparticles (CL-ICG-PFH-NPs) were constructed for targeting multimode imaging, synergistic effects with HIFU and imaging-guided ablation of tumors, which was evaluated both in vitro and in vivo.Results: Both in vitro and in vivo systematical studies validated that the biological targeting synergistic agent can simultaneously achieve tumor-biotargeted multimodal imaging, HIFU synergism and multimodal image monitoring in HIFU therapy. Importantly, the electrostatic adsorption method and the targeting of B. longum to tumor tissues allow the CL-ICG-PFH-NPs to be retained in the tumor tissue, achieve the targeting ability of synergistic agent. Multimodal imaging chose the best treatment time according to the distribution of nanoparticles in the body to guide the efficient and effective treatment of HIFU. CL-ICG-PFH-NPs could serve as a phase change agent and form microbubbles that can facilitate HIFU ablation by mechanical effects, acoustic streaming and shear stress. This lays a foundation for the imaging and treatment of tumors.Conclusion: In this work, a biological targeting synergistic agent was successfully constructed with good stability and physicochemical properties. This biological targeting synergistic agent can not only provide information for early diagnosis of tumors but also realize multimodal imaging monitoring during HIFU ablation simultaneously with HIFU treatment, which improves the shortcomings of HIFU treatment and has broad application prospects.Keywords: high-intensity focused ultrasound, nanoparticles, photoacoustic imaging, fluorescence imaging, ultrasound imaging, image-guided therapy

Qingqing Zong,1,* Jing Deng,1,* Wanli Ge,2,* Jie Chen,1 Di Xu3 1Department of Ultrasonography, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People’s Republic of China; 2Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People’s Republic of China; 3Department of Geriatric Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Di XuDepartment of Geriatric Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People’s Republic of ChinaTel/Fax +86 25 8371 4511Email 13951805973@126.comPurpose: Axillary lymph node (ALN) involvement is an important prognostic factor of early invasive breast cancer. The objective of this study was to establish simple nomograms for predicting ALN involvement based on ultrasound (US) characteristics and evaluate the predictive value of US in the detection of ALN involvement.Patients and Methods: A total of 1328 patients with cT1-2N0 breast cancer by physical exam were retrospectively analyzed. Univariate analysis was used for the comparison of variables, and multivariate analysis was performed by binary logistic regression analysis. The R software was used to establish simple nomograms based on the US characteristics alone. The receiver operating characteristic (ROC) curves of the prediction model and the verification group were drawn, and the area under the curve (AUC) was calculated to evaluate the discrimination of the prediction model. A calibration curve was plotted to assess the nomogram predictions vs the actual observations of the ALN metastasis rate and axillary tumor burden rate.Results: The ALN metastasis rates of the training group and the validation group were 35.1% and 34.1%, respectively. Multivariate analysis showed that molecular subtype, lymphovascular invasion, mass descriptors (size, margin, microcalcification and blood flow signal) and LN descriptors (shape, cortical thickness and long-to-short ratio) were independent impact factors in early breast cancer. The AUC of ALN metastasis rate of prediction model based on US features was 0.802, the AUC of high tumor burden rate was 0.873, and the AUC of external validation group was 0.731 and 0.802, respectively. The calibration curve of the nomogram showed that the nomogram predictions are consistent with the actual metastasis rate and the high tumor burden rate. The results showed that preoperative US had a sensitivity of 59.4% and a specificity of 88.9% for predicting the ALN metastasis rate.Conclusion: The successfully established nomograms based on US characteristics to predict ALN metastasis rate and high axillary tumor burden rate in early breast cancer can achieve individual prediction. Compared with other nomogram predictions, it is more intuitive, and can help clinical decision-making; thus, it should be promoted. However, at this time US features alone are insufficient to replace sentinel lymph node biopsy.Keywords: axillary lymph node involvement, early breast cancer, ultrasound, nomogram

Zhiping Yu,1 Yixuan Wang,2 Dan Xu,3 Lianhua Zhu,3 Ming Hu,1 Qiuli Liu,1 Weihua Lan,1 Jun Jiang,1 Luofu Wang1 1Department of Urology, Daping Hospital, Army Medical University, Chongqing, People’s Republic of China; 2The First Clinical College, Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Ultrasound, Southwest Hospital, Army Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Luofu WangDepartment of Urology, Daping Hospital, No. 10 Changjiangzhilu Road, Yuzhong District, Chongqing 400042, People’s Republic of ChinaTel +86-13320350708Fax +86-23-68757947Email wangluofu@aliyun.comPurpose: We intended to design G250 antigen-targeting temsirolimus-loaded nanobubbles (G250-TNBs) based on the targeted drug delivery system and to combine G250-TNBs with ultrasound targeted nanobubble destruction (UTND) to achieve a synergistic treatment for renal cell carcinoma (RCC).Methods: The filming-rehydration method was combined with mechanical shock and electrostatic interactions to prepare temsirolimus-loaded nanobubbles (TNBs). G250-TNBs were prepared by attaching anti-G250 nanobodies to the surface of TNBs using the biotin-streptavidin-bridge method. The ability of G250-TNBs to target the G250 antigen of RCC cells and the synergistic efficacy of G250-TNBs and UTND in the treatment of RCC were assessed.Results: The average diameter of the prepared G250-TNBs was 368.7 ± 43.4 nm, the encapsulation efficiency was 68.59% ± 5.43%, and the loading efficiency was 5.23% ± 0.91%. In vitro experiments showed that the affinity of G250-TNBs to the human RCC 786-O cells was significantly higher than that of TNBs (P

Xiaolang Tian, Changwu Huang, Xiaoli Ye, Hongyan Jiang, Rufang Zhang, Xiaofang Hu, Dongshuang Xu Department of Clinical Laboratory, University of Chinese Academy of Sciences Chongqing Renji Hospital (Fifth People’s Hospital of Chongqing), Chongqing, People’s Republic of ChinaCorrespondence: Dongshuang XuDepartment of Clinical Laboratory, University of Chinese Academy of Sciences Chongqing Renji Hospital (Fifth People’s Hospital of Chongqing), No. 24 Renji Road, Nanan District, Chongqing 400062, People’s Republic of ChinaTel +86 023-62895125Fax +86 023-62881980Email dongshuang_xu@163.comBackground: The emergence and spread of carbapenem-resistant Enterobacter cloacae (CR-ECL) have posed a serious threat to clinical management. This retrospective study assessed the epidemiological characteristics of CR-ECL to explore the risk factors and predictors of mortality in patients with CR-ECL infection.Methods: We performed a retrospective 1:2 case-control study of hospitalized patients from January 2014 to December 2017. A total of 85 consecutive unique CR-ECL strains comprised the case group, and 170 matched patients with carbapenem-susceptible Enterobacter cloacae (CS-ECL) infection at the same period as the control group. Isolates were screened for potential resistance genes by polymerase chain reaction (PCR) and molecular typing was performed by multilocus sequence typing (MLST).Results: The results of drug resistance gene detection showed that blaNDM-1 was the most common carbapenem resistance gene. The MLST results showed that ST51 was the predominant epidemic type, followed by ST88. ICU admission (P< 0.001), drainage tube (P=0.002), central venous catheter (P=0.005), and carbapenem exposure (P=0.003) were independent risk factors for CR-ECL infection. Significant predictors for 28-day mortality included solid tumours (P=0.005), septic shock (P=0.019), and mechanical ventilation (P=0.027).Conclusion: Our study indicated that ST51 and ST88, which are closely related, were the predominant epidemic types of CR-ECL producing blaNDM-1 in southwestern China. Strengthening the surveillance of patients with solid tumours, septic shock and mechanical ventilation is an urgent need.Keywords: carbapenem-resistant Enterobacter cloacae, epidemiological characteristics, risk factors, predictors of mortality