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Kai Yao,1,* Yongbo Peng,2,* Qiyu Tang,3 Kaixuan Liu,3 Cheng Peng3 1Department of Vascular Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 2College of Pharmacy, Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Plastic Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Cheng Peng, Email pcheng83@csu.edu.cnIntroduction: Photoaging-induced skin damage leads to appearance issues and dermatoma. Selenium nanoparticles (SeNPs) possess high antioxidant properties but are prone to inactivation. In this study, human serum albumin/SeNPs (HSA-SeNPs) were synthesized for enhanced stability.Methods: HSA-SeNPs were prepared by self-assembling denatured human serum albumin and inorganic selenite. The cytotoxicity of HSA-SeNPs was assessed using the MTT method. Cell survival and proliferation rates were tested to observe the protective effect of HSA-SeNPs on human skin keratinocytes against photoaging. Simultaneously, ICR mice were used for animal experiments. H&E and Masson trichromatic staining were employed to observe morphological changes in skin structure and collagen fiber disorders after UVB irradiation. Quantitative RT-PCR was utilized to measure changes in mRNA expression levels of factors related to collagen metabolism, inflammation, oxidative stress regulation, and senescence markers.Results: The HSA-SeNPs group exhibited significantly higher survival and proliferation rates of UVB-irradiated keratinocytes than the control group. Following UVB irradiation, the back skin of ICR mice displayed severe sunburn with disrupted collagen fibers. However, HSA-SeNPs demonstrated superior efficacy in alleviating these symptoms compared to SeNPs alone. In a UVB-irradiated mice model, mRNA expression of collagen type I and III was dysregulated while MMP1, inflammatory factors, and p21 mRNA expression were upregulated; concurrently Nrf2 and Gpx1 mRNA expression were downregulated. In contrast, HSA-SeNPs maintained the mRNA expression of those factors to be stable In addition, the level of SOD decreased, and MDA elevated significantly in the skin after UVB irradiation, but no significant differences in SOD and MDA levels between the HSA-SeNPs group with UVB irradiation and the UVB-free untreated group.Discussion: HSA-SeNPs have more anti-photoaging effects on the skin than SeNPs, including the protective effects on skin cell proliferation, cell survival, and structure under photoaging conditions. HSA-SeNPs can be used to protect skin from photoaging and repair skin injury caused by UVB exposure.Keywords: selenium nanoparticles, human serum albumin, skin photoaging, senescence, SOD

Wei Zhang,1,* Jiayu Zhang,2,* Dian Jiao,1,* Qisheng Tang,1 Xiaoping Gao,1 Zhenyu Li,1 Fa Yang,3 Zhiguang Zhao,1 Longfei Yang4 1Department of Urology, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi, 710038, People’s Republic of China; 2Department of Urology, Air Force Hospital of Southern Theater Command, Guangzhou, Guangdong, 510062, People’s Republic of China; 3Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China; 4Department of Transfusion Medicine, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi, 710038, People’s Republic of China*These authors contributed equally to this workCorrespondence: Longfei Yang; Zhiguang Zhao, Email y68lf@163.com; zzg13991809889@163.comPurpose: Lichen sclerosus urethral stricture disease (LS USD) is a refractory and progressive disease primarily affecting the anterior urethra in males. Various potential etiological factors, such as genetics, autoimmunity, infection, and exposure to infectious urine, have been suggested. However, the accurate etiology of LS in the male urethra remains unclear.Patients and Methods: In this study, we conducted single-cell RNA sequencing to identify the transcriptional profiles of three patients with LS USD and three patients with non-LS USD. Immunofluorescence was used to confirm the single-cell sequence results.Results: Our study revealed distinct subsets of vein endothelial cells (ECs), smooth muscle cells (SMCs), and fibroblasts (FBs) with high proportions in LS USD, contributing to the tissue microenvironment primarily involved in proinflammatory and immune responses. In particular, FBs displayed a unique subset, Fib7, which is exclusively present in LS USD, and exhibited high expression levels of SAA1 and SAA2. The accumulation of macrophages, along with the dysregulated ratios of M1/M2-like phenotype macrophages, may be engaged in the pathogenesis of LS USD. Through cell–cell communication analysis, we identified significant interactions involving CXCL8/ACKR1 and CCR7/CCL19 in LS USD. Remarkably, Fib7 exhibited exclusive communication with IL-1B macrophages through the SAA1/FPR2 receptor–ligand pair.Conclusion: Our study provides a profound understanding of the tissue microenvironment in LS USD, which may be valuable for understanding the pathogenesis of LS USD. Keywords: lichen sclerosus, urethral stricture disease, single-cell RNA sequencing, heterogeneity, fibroblasts, macrophages

Chenxi Li,1,&ast; Xiaolei Chen,2,&ast; Xiaowen Zhu,1 Mengjiao Cao,3 Qunfeng Tang,3 Wenjun Wu1,4 1Department of Endocrinology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, People’s Republic of China; 2Department of Neurology, Jiangnan University Medical Center, Wuxi No. 2 People’s Hospital, Wuxi, People’s Republic of China; 3Department of Radiology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, People’s Republic of China; 4Jinshan Branch of Shanghai Sixth People’s Hospital, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenjun Wu, Department of Endocrinology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, People’s Republic of China, Tel +86-15358008856, Fax +86-510-85737592, Email wuwenjung@163.comPurpose: Arterial stiffness is often increased in overweight or obese individuals before the development of hypertension (HT). This study aimed to determine the connection between pancreatic fat and atherosclerosis in overweight and obese people without HT.Patients and methods: We included 128 patients who were non-hypertensive and overweight or obese in a study between December 2019 and November 2022. Medical history was collected, and all participants underwent a physical examination and blood tests. Pancreatic fat content was measured by magnetic resonance imaging (MRI) and was grouped into quartiles based on pancreatic fat fraction (PFF). The upper three quartiles (PFF≥ 10.33%) were defined as non-alcoholic fatty pancreas disease (NAFPD) and the first quartile (PFF< 10.33%) as non-NAFPD. High baPWV (H-baPWV) and low baPWV (L-baPWV) were classified according to the median baPWV (1159 cm/s). The effect of NAFPD on baPWV was examined using binary logistic regression. The study population consisted of 96 NAFPD and 32 non-NAFPD cases.Results: Participants with NAFPD had significantly higher levels of baPWV than people without. The rates of NAFPD and the PFF values varied significantly in the L-baPWV and H-baPWV groups. Logistic regression analysis suggested that the presence of NAFPD was independently correlated with increased baPWV after adjusting for age, smoking, body mass index, blood pressure, lipid profiles, and glycemic index.Conclusion: NAFPD is an independent risk factor for increased baPWV in individuals with overweight and obesity but no HT, suggesting that the presence of NAFPD may be a warning signal of early atherosclerosis.Keywords: obesity, non-alcoholic fatty pancreas disease, overweight, arterial stiffness, brachial-ankle pulse wave velocity

Qiaofei Tang,1,2 Honggan Yi,1,2 Siping Chen,1,2 Yantian Zheng,1,2 Yitao Wen,1,2 Man Yang1,2 1Reproductive Medicine Center, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 2Meizhou Municipal Engineering and Technology Research Center for Molecular Diagnostics of Major Genetic Disorders, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of ChinaCorrespondence: Man Yang, Reproductive Medicine Center, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, No. 63 Huangtang Road, Meizhou, Meijiang District, People’s Republic of China, Email 13751992388@163.comBackground: The causes of pregnancy failure after intrauterine insemination (IUI) are controversial. The purpose of this study was to investigate the influencing factors on clinical pregnancy after IUI.Methods: This study retrospectively analyzed 1464 cycles of IUI performed at the Meizhou People’s Hospital between March 2014 and June 2023. The χ2 test and logistic regression analysis was applied to assess the associations between the some factors (maternal age, paternal age, cycle type (natural cycle or ovulation induction cycle), hormone level on the day of endometrial transformation (estradiol (E2), luteinizing hormone (LH), and progesterone (P)), endometrial thickness on the day of endometrial transformation, and forward motile sperm concentration after treatment) and pregnancy failure.Results: Among the 1464 IUI cycles in this study, 268 cycles of assisted reproduction resulted in clinical pregnancy, with a clinical pregnancy rate of 18.3%. During the cycles with clinical pregnancy, there were 25 (12.9%) preterm births and 169 (87.1%) full-term births. The E2 level on the day of endometrial transformation in clinical pregnancy group was higher than that in the pregnancy failure group (658.79± 656.02 vs 561.21± 558.83 pg/mL)(P=0.025). The clinical pregnancy group had a higher percentage of endometrial thickness between 8 and 13mm on the day of endometrial transformation than the pregnancy failure group (83.2% vs 75.0%)(P=0.002). The results of regressions analysis showed that low E2 level on the day of endometrial transformation (< 238.3 pg/mL vs ≥ 238.3 pg/mL: OR 1.493, 95% CI: 1.086– 2.052, P=0.014), and endometrial thickness < 8mm on the day of endometrial transformation (< 8mm vs 8– 13mm: OR 1.886, 95% CI: 1.284– 2.771, P=0.001) may increase risk of pregnancy failure performed IUI.Conclusion: Low estradiol level, and endometrial thickness on the day of endometrial transformation may increase risk of pregnancy failure performed intrauterine insemination.Keywords: intrauterine insemination, pregnancy failure, estradiol, endometrial thickness

Yi-Can Yang,1 Qiong Tang,1 Li-Juan Yan,1 Shi-Bin Zhang,2 Xiao-Min Ye,1 Dai Gong,1 Li Zou,1 Xiang-Lan Wen1 1Department of Children Health Care Center, Zhuzhou Hospital Affiliated to Xiangya Medical College, Central South University, Zhuzhou City, Hunan Province, 412007, People’s Republic of China; 2Department of Pediatrics, Zhuzhou Hospital Affiliated to Xiangya Medical College, Central South University, Zhuzhou City, Hunan Province, 412007, People’s Republic of ChinaCorrespondence: Xiang-Lan Wen, Department of Children Health Care Center, Zhuzhou Hospital Affiliated to Xiangya Medical College, Central South University, No. 116 of Changjiang South Road, Tianyuan District, Zhuzhou City, Hunan Province, 412007, People’s Republic of China, Tel/Fax +8673128561905, Email wenxianglianwxl@126.comBackground: Floating-Harbor syndrome (FHS) is a rare autosomal dominant inherited disease characterized primarily by short stature, delayed language development, and typical facial features. There are currently few case reports, diagnoses and treatments for these syndromes at home and abroad.Case Description: This study reports a case of a boy with “growth and language development delay” as the predominant clinical manifestation. FHS was clinically diagnosed based on his growth hormone (GH) deficiency, significant bone age delay, left testicular hydrocele, and the whole exon gene in peripheral blood, which indicated heterozygous mutation of SRCAP gene. Following the treatment with recombinant human GH (rhGH), the child exhibited height increase benefits, and his articulation improved after language therapy.Conclusion: Genetic testing facilitates early detection, diagnosis, and treatment of the FHS. Additionally, treatment with rhGH effectively increases the height of these children, and language rehabilitation is especially important for their language development.Keywords: Floating-Harbor syndrome, language development, growth and development, rhGH, language rehabilitation

Hongxia Wang,1,&ast; Fating Zhou,2,&ast; Zhilin Li,1 Yulan Ding,1 Qian Wen,1 Quanxing Tang1 1Department of General Practice, People’s Hospital of Deyang City, Deyang, Sichuan, People’s Republic of China; 2Emergency Department, Chongqing Emergency Medical Center, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongxia Wang, Department of General Practice, People’s Hospital of Deyang City, Deyang, Sichuan, People’s Republic of China, Email HongXia.W@hotmail.comBackground: Streptococcus constellatus rarely causes pyopneumothorax, which is a serious state and requires a surgery. However, not every patient can tolerate surgery and individualized solutions are needed. Furthermore, many known situations are risk factors of S. constellatus infection, but S. constellatus pyopneumothorax associated with Hashimoto’s thyroiditis has not been reported.Case Presentation: We present the case of a 74-year-old male with multiple encapsulated pyopneumothorax caused by S. constellatus. Given his respiratory failure, we provided two-stage percutaneous right empyema radiography for catheter drainage in the radiology interventional department instead of surgery. Moreover, an occult Hashimoto’s thyroiditis was discovered in the patient, which was possibly associated with S. constellatus pyopneumothorax. Levothyroxine was administered to improve his situation.Conclusion: To our knowledge, it is the first case described in this context. We provided an alternative treatment for S. constellatus encapsulated pyopneumothorax in patient who might not tolerate surgery. We also revealed the possible relationship between S. constellatus pyopneumothorax and Hashimoto’s thyroiditis.Keywords: radiology interventional, Streptococcus constellatus, pyopneumothorax, Hashimoto’s thyroiditis

Cong Xia,1 Ting Wei,2,3 Qi Tang,2,3 Hongying Zheng,2,3 Mei Sun,2,3 Gang Chen,2,3 Jun Lv2,3 1School of Health Management Anhui Medical University, Hefei, People’s Republic of China; 2School of Public Health, Fudan University, Shanghai, People’s Republic of China; 3China Research Center on Disability, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Gang Chen; Jun Lv, School of Public Health, Fudan University, 130 Dong’an Road, Xuhui District, Shanghai, 200032, People’s Republic of China, Tel +86-13661432703 ; +86-13671684324, Email gchen@shmu.edu.cn; lujun@shmu.edu.cnPurpose: To investigate the family support, anxiety, depression, health-related quality of life (HRQoL), and their associations among parents and grandparents of children with disabilities.Methods: This is a cross-sectional study and a total of 327 family caregivers were included. Chi-square test, Mann–Whitney U-test, and two independent t-test were used to identify the intergenerational differences in sociodemographic characteristics, received family support, anxiety, depression, and HRQoL. Eight generalized linear models were developed to examine the associations in both generations.Results: Parents and grandparents were most in need of rehabilitation and financial support, but both populations received the least amount of financial support. 33.6% and 36.1% of family caregivers had the risk of anxiety and depression and found no significant intergenerational differences. As for HRQoL, intergenerational differences were found in the physical component score, but not found in the mental component score. Among parents, childcare support of respite care and household tasks assistance was negatively associated with their depression (p< 0.05), professional support of appropriate surgery for children (p< 0.05) and psychological support from professional psychologists (p< 0.01) were negatively associated with their anxiety and depression, psychological support from relatives and friends was negatively associated with their depression (p< 0.05) whereas was positively associated with their mental HRQoL (p< 0.01). As for grandparents, financial support for daily living expenses was negatively associated with depression (p< 0.05), and psychological support from families was negatively associated with depression (p< 0.05) whereas was positively associated with mental HRQoL (p< 0.05). However, no relationship was found between family support and anxiety among grandparents. Notably, no association was found between family support and physical HRQoL among both populations.Conclusion: Both parents and grandparents had high risks of anxiety, depression and low levels of mental HRQoL. To efficiently improve psychological health, care providers and policymakers may consider intergenerational differences and provide targeted family support.Keywords: mental health, health-related quality of life, family support, children with disabilities, intergenerational differences

Dongyi Yu,1,2,&ast; Libo Wang,2,&ast; Xin Zhou,2,&ast; Lili Liu,2 Shuang Wu,2 Qing Tang,3 Xiaofeng Zhang1 1Department of Ophthalmology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, 215006, People’s Republic of China; 2Department of Ophthalmology, Kunshan First People’s Hospital Affiliated to Jiangsu University, Suzhou, Jiangsu, 215300, People’s Republic of China; 3Department of Neurology, Kunshan First People’s Hospital Affiliated to Jiangsu University, Suzhou, Jiangsu, 215300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaofeng Zhang, Email zhangxiaofeng@suda.edu.cnPurpose: To identify potential demographic and lifestyle factors associated with progression of myopia with orthokeratology (ortho-k) treatment via follow-up of axial length (AL).Methods: In this retrospective observational study, demographics, ocular parameters, near-work distance, outdoor activities, and sleep quality were analyzed in 134 children with myopia aged 8~15 years using ortho-k and a follow-up for one year.Results: Compared with the slow progression group, the participants in the fast progression group were younger in age (10.55 ± 1.70 years vs 9.90 ± 1.18 years, P = 0.009), demonstrated higher spherical equivalent (SE) value (− 2.52 ± 0.63 diopters (D) vs − 3.05 ± 0.89 D, P < 0.001), shorter near-work distance (P = 0.010), and poorer sleep quality (Pittsburgh sleep quality index [PSQI], 4.79 ± 1.29 vs 3.81 ± 1.38, P < 0.001) in the one-year follow-up. Furthermore, multivariate linear regression analyses showed that baseline age (B =− 0.020, P = 0.020), SE (B = 0.0517, P < 0.001), and total PSQI (B=0.026, P = 0.001) were associated with axial elongation. Advanced logistic regression analyses demonstrated that shorter average near-work distance (P = 0.034), higher SE value (P = 0.023), and poorer sleep quality (P = 0.003) were associated with fast axial elongation.Conclusion: Sleep quality is one of the key factors associated with axial elongation in children with myopia after using ortho-k for one year. Further studies are required to confirm this observation and expand its practical applications.Keywords: orthokeratology, myopia, axial length, sleep quality, retrospective study

Chen He,1– 3,&ast; Huiyan Ding,4,&ast; Lubo Li,5 Jing Chen,6 Xiaofei Mo,1– 3 Yinan Ding,4 Wenjing Chen,4 Qiusha Tang,4 Yuetao Wang1– 3 1Department of Nuclear Medicine, the Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, People’s Republic of China; 2Institute of Clinical Translation of Nuclear Medicine and Molecular Imaging, Soochow University, Changzhou, Jiangsu Province, People’s Republic of China; 3Changzhou Clinical Medical Center, Changzhou, Jiangsu, People’s Republic of China; 4Medical School of Southeast University, Nanjing, People’s Republic of China; 5The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, People’s Republic of China; 6Taikang Xianlin Drum Tower Hospital, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiusha Tang; Yuetao Wang, Email panyixi-tqs@163.com; yuetao-w@163.comBackground: Radiation therapy (RT) is commonly used to treat glioblastoma, but its immunomodulatory effect on tumors, through mechanisms such as immunogenic cell death (ICD), is relatively weak. Gold nanoparticles (AuNPs) have been suggested as potential radio-sensitizers, but it is unclear if they can enhance radiation-induced ICD. This study aimed to investigate the potential of AuNPs to improve the effectiveness of radiation-induced ICD.Methods: G422 cells were treated with a combination of AuNPs and RT to induce cell death. Various assays were conducted to assess cell death, surface expression of CRT, and release of HMGB1 and ATP. In vitro co-culture experiments with bone marrow-derived dendritic cells (BMDCs) were performed to analyze the immunogenicity of dying cancer cells. Flow cytometry was used to measure the maturation rate of BMDCs. An in vivo mouse tumor prophylactic vaccination model was employed to assess immunogenicity.Results: The study findings presented here confirm that the combination of radiotherapy (RT) with AuNPs can induce a stronger ICD effect on glioblastoma cells compared to using RT alone. Specifically, treatment with AuNPs combined with RT resulted in the emission of crucial damage-associated molecular patterns (DAMPs) such as CRT, HMGB1 (479.41± 165.34pg/mL vs 216.04± 178.16 pg/mL, &ast;P< 0.05) and ATP (The release of ATP in the AuNPs + RT group was 1.2 times higher than in the RT group, &ast;P< 0.05). The proportion of BMDC maturation rate was higher in the group treated with AuNPs and RT compared to the group treated with RT alone. (32.53± 0.52% vs 25.03± 0.28%,&ast;&ast;&ast;P < 0.001). In the tumor vaccine experiment, dying tumor cells treated with AuNPs and RT effectively inhibited tumor growth in mice when exposed to living tumor cells.Conclusion: These results indicate that AuNPs have the ability to enhance RT-induced ICD.Keywords: Immunogenic cell death, Gold nanoparticles, Radiation therapy, Glioblastoma

Lantian Wang,1,2 Xiawei Li,1,2 Jian Wu,1,2 Qiang Tang1,2 1Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Lantian Wang, Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, People’s Republic of China, Email wanglantian@zju.edu.cnBackground: Cancers trigger systemic metabolic disorders usually associated with glucose intolerance, which is an initially apparent phenomenon. One of the features of pancreatic cancer (PC) metabolic reprogramming is the crosstalk between PC and peripheral tissues (skeletal muscle and adipose tissues), emphasized by insulin resistance (IR). Our previous study reported that mice pancreatic cancer-derived exosomes could induce skeletal muscle cells (C2C12) IR, and exosomal microRNAs (miRNAs) may exert an important effect. However, the underlying mechanism remains to be further elucidated.Methods: qPCR was used to determine the expression of let-7b-5p in normal pancreatic islet cells and PC cells. Exosomes were purified from PC cell culture medium by ultracentrifugation. The role let-7b-5p on IR-mediated by PC cells-derived exosomes was asses by Oil Red O staining using miRNA inhibitor. Western blot assay was performed to examine the expression of IR-related genes and the activation of signaling pathways. A Luciferase experiment was applied to confirm how let-7b-5p regulated the expression of RNF20. IP/WB analysis further determined whether RNF20 promoted STAT3 ubiquitination. Rescue experiment using RNF20 overexpression plasmid was performed to confirm the role of RNF20 on IR-mediated using PC cell-derived exosomes in C2C12 myotube cells.Results: miRNA-let-7b-5p was identified as the key exosomal miRNA, which could promote the IR in C2C12 myotube cells supported the lipid accumulation, the activation of STAT3/FOXO1 axis, and the decreased expression of IRS-1 and GLUT4. RNF20, an E3 ubiquitin ligase, was confirmed as the target gene of let-7b-5p and was found to improve IR by downregulating STAT3 protein expression via ubiquitination-mediated protein degradation. The ectopic expression of RNF20 could effectively attenuate the IR mediated by the pancreatic cancer-derived exosomes in C2C12 myotube cells.Conclusion: Our data suggest that exosomal miRNA-let-7b-5p may promote IR in C2C12 myotube cells by targeting RNF20 to activate the STAT3/FOXO1 axis.Graphical Abstract: Keywords: insulin resistance, exosome, let-7b-5p, RNF20, STAT3, FOXO1

Xuejiao Liao,1,&ast; Yuan Guan,1,2,&ast; Zixun Lin,1 Qingrong Tang,3 Zhenghua Ma,1 Shuting Wu,1 Xiaobin Wang,1 Jingke Dong,1 Liping Zhang,1 Jiayu Deng,1 Zhonghui Liao,1,4 Sumei Yang,1,4 Cheng Wang,1,4 Shuo Song,1 Hongyang Yi,1 Song Wu,5 Tetsuya Asakawa,6 Hongzhou Lu1 1Institute for Hepatology, National Clinical Research Center for Infectious Disease, The Third People’s Hospital of Shenzhen, The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, People’s Republic of China; 2Department of Epidemiology, School of Public Health Fudan University, Shanghai, People’s Republic of China; 3The First Hospital of Changsha, Infectious Diseases Department, Changsha, People’s Republic of China; 4School of Public Health, Bengbu Medical College, Bengbu, People’s Republic of China; 5Department of Central Laboratory, South China Hospital, Medical School, Shenzhen University, Shenzhen, People’s Republic of China; 6Institute of Neurology, National Clinical Research Center for Infectious Diseases, the Third People’s Hospital of Shenzhen, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongzhou Lu, Institute for Hepatology, National Clinical Research Center for Infectious Disease, The Third People’s Hospital of Shenzhen, The Second Hospital Affiliated with the School of Medicine, Southern University of Science and Technology, No. 29 Bulan Road, Long Gang District, Shenzhen, Guangdong, 518112, People’s Republic of China, Email luhongzhou@fudan.edu.cn Tetsuya Asakawa, Institute of Neurology, National Clinical Research Center for Infectious Diseases, the Third People’s Hospital of Shenzhen, No. 29 Buji Bulan Road, Shenzhen, Guangdong, 518112, People’s Republic of China, Email asakawat1971@gmail.comPurpose: The purpose was to review relevant clinical data and formulate recommendations supporting the use of saline as a simple rinse for an early reassuring intervention to reduce the occurrence of re-positive COVID-19 patients.Methods: We conducted a single-centre retrospective cohort study, which enrolled patients with confirmed re-testing positive COVID-19 during 7– 60 days after discharge from Third People’s Hospital of Shenzhen. By one-to-two propensity score matching for age and sex, the control group of those not re-testing positive during the same period served as matched control.Results: A total of 223 patients were included in our study, 94 in re-positive group and 129 in non-re-positive group. The result shows that the rates of nasal douche treatment in the non-re-positive group were considerably higher than that of the re-positive group. And the Ct value of nasal douche group increased faster than that of non-nasal douche group after the Ct value reaching ≥ 35. Further analysis revealed that the higher the Ct value at the time of readmission, the shorter the time of average Ct values to reach ≥ 35.Conclusion: These findings suggest that nasal douche is beneficial to shorten the time of virus nucleic acid turning negative, thereby reducing the incidence of re-positive. The prevention and control of epidemics focuses on re-positive patients with Ct values < 35.Keywords: COVID-19, nasal douche, re-positive, RT-PCR

Qiong Tang, Dai Gong, Xiao-Min Ye, Jun-Ru Xu, Yi-Can Yang, Li-Juan Yan, Li Zou, Xiang-Lan Wen Department of Children Health Care Center, Zhuzhou Hospital Affiliated to Xiangya Medical College, Central South University, Zhuzhou, People’s Republic of ChinaCorrespondence: Xiang-Lan Wen, Department of Children Health Care Center, Zhuzhou Hospital Affiliated to Xiangya Medical College, Central South University, No. 116 of Changjiang South Road, Tianyuan District, Zhuzhou City, Hunan Province, 412007, People’s Republic of China, Tel +86 13873317331, Email wenxianglianwxl@126.comAbstract: Craniofacial dysmorphism, cardiac abnormalities, ectodermal abnormalities, psychomotor delay, intellectual disability, and short stature are all hallmarks of the extremely rare disorder known as cardiofaciocutaneous syndrome (CFCS). Although CFCS is considered rare, approximately 300 cases have been documented in the literature. In this report, we discuss a patient diagnosed with CFCS without the typical heart malformations but with craniofacial features, skin abnormalities, intellectual disability, and short stature. Genetic testing revealed the presence of three potentially harmful variants: one in the MAP2K1 gene and two in the ATP2B3 and CDC42BPB genes, the significance of which is currently not yet found. Our findings in this case report suggest that the clinical symptoms of CFCS may be atypical, thereby expanding our understanding of the symptom spectrum of the disease. Simultaneously, the link between the clinical symptoms of the patient and the two unknown pathogenic variants has not been established. This case report supplements existing clinical reference material by providing valuable insights into the specific scenario.Keywords: cardiofaciocutaneous syndrome, gene detection, intellectual disability, neurodevelopmental syndrome, short stature, spinocerebellar ataxia

Lingwang An,1 Kuei-Chun Yeh,1 Yunxia Liu,1 Dandan Wang,1 Xianglan Li,1 Qi Tang,1 Juming Lu1,2 1Department of Endocrinology, Beijing Ruijing Diabetes Hospital, Beijing, 100079, People’s Republic of China; 2Department of Endocrinology, The General Hospital of the People’s Liberation Army, Beijing, 100853, People’s Republic of ChinaCorrespondence: Juming Lu, Department of Endocrinology, The General Hospital of the People’s Liberation Army, No. 28 of Fuxing Road, Haidian District, Beijing, 100853, People’s Republic of China, Tel +86 10 8822 9999, Email lujuming_jm@126.comObjective: We explore the effect of a structured online DSMES program on glycaemic control and the self-management behaviour of adolescents and young adults with T1DM.Methods: We used a pre–post uncontrolled intervention design over a period of 6 months. A total of 37 youths with T1DM aged 10– 45 years were enrolled. The intervention comprised 11 structured online DSMES course sessions; these were video-based and delivered by a diabetes specialist, nurses and a dietitian. The primary outcome was a change in (glycated hemoglobin) HbA1c. The secondary outcomes were changes in hypoglycaemia frequency, time in target range (TIR) among patients using a continuous glucose monitoring (CGM) system and self-management behaviour; the latter was measured using a T1DM self-management scale for Chinese adults (SMOD-CA) and the Chinese version of the diabetic behaviour rating scale in adolescents with T1DM (DBRS).Results: Twenty-three (85.2%) participants attended ≥ 8 of the online sessions. There was a significant reduction in HbA1c (from 6.92% to 6.47%, P = 0.002), hypoglycaemic episodes (from 6.0 to 4.0 during the preceding month, P = 0.026) and a significant increase in TIR (from 74.0% to 80.5%, P = 0.027) and an increase in the SMOD-CA score (from 79.6 to 84.6, P = 0.026) in young adults. No significant change in glucose control, hypoglycaemic events or DBRS score were found among children and adolescents. The score of the 12-item version of the Barrett–Lennard Relationship Inventory (B-L RI:mini) indicated that more than half of the participants experienced congruence, positive regard, and an empathic understanding in this programme.Conclusion: The online structured DSMES programme was effective in improving the glycaemic control and self-management behaviour of young adults with T1DM; however, integrating offline visits or appointments with online consultations may be necessary for youth patients.Keywords: children and adolescents, youth, type 1 diabetes, structured diabetes self-management education and support, online

Bisheng Shen,1 Baoxin Chen,2 Kuangyi Li,1 Weiyin Cheng,3 Mohammad Mofatteh,4 Robert W Regenhardt,5 Jack Wellington,6 Zhangrong Liang,1 Qi Tang,1 Jingli Chen,1 Yimin Chen7 1Department of Emergency Medicine, Foshan Hospital of Traditional Chinese Medicine, Foshan City, Guangdong Province, People’s Republic of China; 2Faculty of Humanities and Social Sciences, Macao Polytechnic University, Macao, People’s Republic of China; 3Department of Clinical Nutrition, Foshan Hospital of Traditional Chinese Medicine, Foshan City, People’s Republic of China; 4School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, UK; 5Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; 6School of Medicine, Cardiff University, Cardiff, Wales, UK; 7Department of Neurology and Advanced National Stroke Center, Foshan Sanshui District People’s Hospital, Foshan, People’s Republic of ChinaCorrespondence: Baoxin Chen, Faculty of Humanities and Social Sciences, Macao Polytechnic University, Macao, People’s Republic of China, Email P2009495@ipm.edu.mo Kuangyi Li, Department of Emergency Medicine, Foshan Hospital of Traditional Chinese Medicine, Foshan City, Guangdong Province, People’s Republic of China, Email 13809211066@163.comPurpose: This study aimed to highlight the impact of the COVID-19 pandemic lockdown on emergency department (ED) visits of non-COVID-19 patients in a tertiary hospital and evaluate protocol development during this period.Patients and Methods: Clinical data of patients who visited the ED of Foshan Hospital of Traditional Chinese Medicine during the first-level response in Foshan, Guangdong province in 2020 (from January 23 to February 24) and the same period in 2019 and 2021 were collected. A retrospective cross-sectional analysis was performed to understand the characteristics of critically ill patients and compare the proportion of hospitalizations, deaths, and emergency ambulance calls (EACs).Results: The number of patients presenting to the ED was significantly decreased, with a 37.75% reduction in 2020 (6196) compared to the same period in 2019 (9954). A rise in patient ED presentations was observed in the same period in 2021 (10,503). This decline was mostly in the 15– 45 age group. In 2019, 2020, and 2021, critically ill patients treated by the ED totaled 568 (5.706%), 339 (5.495%), and 590 (5.617%), respectively. Compared to the same period in 2019 and 2021, the proportion of critically ill patients with respiratory system involvement, severe trauma, and poisoning decreased most significantly in 2020 (P< 0.05). In contrast, the rates of EACs, hospitalizations, and deaths increased significantly (P< 0.05).Conclusion: The number of ED visits to hospitals was decreased during the 2020 lockdown, while the rates of EACs, hospitalizations, and deaths increased significantly though there were no documented COVID-19 cases. Optimizing emergency medical resources and ensuring the safety of healthcare providers and patients were essential to provide efficient emergency diagnosis and treatment during the lockdown.Keywords: COVID-19 pandemic, emergency medicine, coping strategies, emergency visit, non-COVID-19 patients

Wanyi Chen,1,&ast; Po-Han Fang,2,&ast; Bin Zheng,3 Yue Liang,1 Yiwen Mao,1 Xuefeng Jiang,1 Qionglan Tang4 1Department of Obstetrics and Gynecology, the First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 2International School, Jinan University, Guangzhou, People’s Republic of China; 3Guangdong Research Center for Organoid Engineering and Technology, Guangzhou, People’s Republic of China; 4Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qionglan Tang, Email qionglantang@126.comAbstract: So far, ovarian cancer has still been the most lethal gynecological malignancy. The chemotherapy and targeted medication are the mainstay for the recurrent ovarian cancer treatment. About 70% of the advanced-stage cases will relapse. Ascites-derived organoid is a pre-clinical model for the precise prediction of the therapeutic effectiveness for the ovarian cancer: it can be used to assess the drug sensitivity, to guide individualized precise treatment, and to improve advanced stage as well as recurrent ovarian cancer patient’ survival and prognosis. Until now, there has been no report concerning the establishment of the organoid out of the patient’s ascites and the concurrent usage of drug sensitivity test to guide the individualized precise treatment for the ovarian cancer. Here, we report a case of recurrent ovarian cancer of a 59-year-old female patient whose CA125 at its peak increased to 4523.4 U/mL. Then, patient’s own ovarian cancer organoid was constructed from the ascites by the abdominocentesis; concurrently, medication sensitivity test was performed on the organoid to guide individualized precise treatment. After the treatment, CA125 decreased to 33.7 U/mL, and the patient’s condition relieved effectively. This is the first published case report using ascites-derived organoid and the drug sensitivity test thereof to guide the precise treatment of recurrent ovarian cancer.Keywords: ascites-derived organoid, ovarian cancer organoid, recurrent ovarian cancer, drug sensitivity test, precise treatment

Dai Gong, Qiong Tang, Li-Juan Yan, Xiao-Min Ye, Yi-Can Yang, Li Zou, Qing Ji, Xiang-Lan Wen Department of Children Health Care Center, Zhuzhou Hospital Affiliated to Xiangya Medical College, Central South University, Zhuzhou, Hunan, 412007, People’s Republic of ChinaCorrespondence: Xiang-Lan Wen, Department of Children Health Care Center, Zhuzhou Hospital Affiliated to Xiangya Medical College, Central South University, No. 116 Changjiang Road, Tianyuan District, Zhuzhou, Hunan, 412007, People’s Republic of China, Tel/Fax +86 13873317331, Email wenxianglianwxl@126.comBackground: Primary ciliary dyskinesia (PCD) is a group of autosomal recessive genetic diseases caused by abnormal ciliary ultrastructure and/or function, resulting in reduced ciliary clearance function or other dysfunctions. PCD is one of the causes of recurrent respiratory tract infections in children. At present, there is no gold standard for diagnosis. In patients clinically suspected with PCD, a variety of examination methods are available to assist in diagnosis, such as high-speed video microscopic imaging to analyze ciliary movement patterns, transmission electron microscopy to observe ciliary ultrastructure, genetic testing, and detection of nitric oxide content in nasal expiratory air.Case Description: We present a case summary of the clinical data and treatment process of a child with PCD and short stature induced by Novel exon 1 of CCNO mutation (NM-021147.5) at c.323del, and the proband father and mother were heterozygous mutators, who was diagnosed and treated in the Pediatric Healthcare Department of our hospital. We treated the child with recombinant human growth hormone to increase the height, and the patient was also advised to improve nutrition, prevent and control infections, and encouraged sputum expectoration. We also recommended regular follow-up visits to the outpatient department, and to seek other symptomatic and supportive treatments as necessary.Conclusion: The height and nutritional status of the child improved after treatment. We also reviewed relevant literature to help clinicians improve their understanding of this disease.Keywords: gene test, primary ciliary dyskinesia, reduced ciliary clearance function, short stature

Qinqin Tang, Yanjun Zhou, Yujuan Chen, Jie Chen, Xincai Xiong Department of Dermatology, Affiliated Hospital of North Sichuan Medical College, Nanchong, People’s Republic of ChinaCorrespondence: Xincai Xiong, Department of Dermatology, Affiliated Hospital of North Sichuan Medical College, No. 1 Maoyuan South Road, Shunqing District, Nanchong City, Sichuan Province, 637000, People’s Republic of China, Tel +86 13551686620, Email xiongxincai@163.comAbstract: Sporotrichosis is a deep fungus infection caused by the Sporothrix. In China, the most common species is Sporothrix globosa which is difficult to treat with most antifungal drugs. Atypical clinical forms of sporotrichosis can be a hinder to clinicians for an early diagnosis and treatment. We report a case of fixed cutaneous sporotrichosis of the face caused by S. globosa in a healthy adult that was initially misdiagnosed as rosacea due to its unusual clinical features. We made an effort to dermoscopically track changes in skin lesions both before and after treatment, confirming that itraconazole was effective in the treatment of sporotrichosis.Keywords: skin disease, dermatology, sporotrichosis, fixed cutaneous sporotrichosis, dermoscopy, Sporothrix globosa, fungus infection

Han Li,1,&ast; Yinan Ding,2,&ast; Jiayan Huang,1 Yanyan Zhao,1 Wei Chen,3 Qiusha Tang,2 Yanli An,4 Rong Chen,5 Chunmei Hu1 1Department of Tuberculosis, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2Medical School of Southeast University, Nanjing, People’s Republic of China; 3Department of Clinical Research Center, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 4Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, People’s Republic of China; 5Department of Oncology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunmei Hu, Department of tuberculosis, the Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210009, People’s Republic of China, Email njyy003@njucm.edu.cnBackground: Central nervous system tuberculosis (CNS-TB) is the most devastating form of extrapulmonary tuberculosis. Rifampin (RIF) is a first-line antimicrobial agent with potent bactericidal action. Nonetheless, the blood-brain barrier (BBB) limits the therapeutic effects on CNS-TB. Exosomes, however, can facilitate drug movements across the BBB. In addition, exosomes show high biocompatibility and drug-loading capacity. They can also be modified to increase drug delivery efficacy. In this study, we loaded RIF into exosomes and modified the exosomes with a brain-targeting peptide to improve BBB permeability of RIF; we named these exosomes ANG-Exo-RIF.Methods: Exosomes were isolated from the culture medium of BMSCs by differential ultracentrifugation and loaded RIF by electroporation and modified ANG by chemical reaction. To characterize ANG-Exo-RIF, Western blot (WB), nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) were performed. Bend.3 cells were incubated with DiI labeled ANG-Exo-RIF and then fluorescent microscopy and flow cytometry were used to evaluate the targeting ability of ANG-Exo-RIF in vitro. Fluorescence imaging and frozen section were used to evaluate the targeting ability of ANG-Exo-RIF in vivo. MIC and MBC were determined through microplate alamar blue assay (MABA).Results: A novel exosome-based nanoparticle was developed. Compared with untargeted exosomes, the targeted exosomes exhibited high targeting capacity and permeability in vitro and in vivo. The MIC and MBC of ANG-Exo-RIF were 0.25 μg/mL, which were sufficient to meet the clinical needs.Conclusion: In summary, excellent targeting ability, high antitubercular activity and biocompatibility endow ANG-Exo-RIF with potential for use in future translation-aimed research and provide hope for an effective CNS-TB treatment.Graphical Abstract: Keywords: exosome, central nervous system tuberculosis, blood-brain barrier, rifampin

Yuru Wu,1– 4 Qin Wan,1– 4 Yong Xu,1– 4 Jia Li,1– 4 Ke Li,1– 4 Zhihong Zhang,5 Qian Tang,1– 4 Ying Miao,1– 4 Pijun Yan1– 4 1Department of Endocrinology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2Metabolic Vascular Disease Key Laboratory of Sichuan Province, Luzhou, Sichuan, People’s Republic of China; 3Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan, People’s Republic of China; 4Cardiovascular and Metabolic Diseases Key Laboratory of Luzhou, Luzhou, People’s Republic of China; 5Department of General Medicine, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of ChinaCorrespondence: Pijun Yan, Department of Endocrinology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China, Tel/Fax +86-830-3165361, Email peter2007110361@126.comObjective: There is preliminary evidence that visceral fat area (VFA) was associated with the presence of type 2 diabetic peripheral neuropathy (DPN) in the Korean population; however, no studies have reported the association in Chinese population. The purpose of this study was to explore the possible correlation of VFA with DPN in such a population.Methods: A total of 2498 hospitalized patients with type 2 diabetes mellitus (T2DM) undergone VFA measurement, and were divided into DPN group (n=900) and non-DPN group (n=1594). The association of VFA with the presence of DPN was evaluated by correlation and multiple logistic regression analyses, generalized additive model with a smooth curve fitting, and receiver operating characteristic (ROC) curve analysis.Results: The VFA was significantly lower in the DPN group than in the non-DPN group (P < 0.001). VFA was significantly and positively associated with sural nerve conduction velocity (SNCV) and amplitude potential (SNAP) and negatively associated with the presence of DPN (all P< 0.001); there was no significant difference in the curve fitting (P = 0.344). Multivariate logistic regression analysis showed that the risk of presence of DPN decreased progressively across the VFA quartiles (P for trend < 0.001) and was significantly lower in patients in the highest VFA quartile than in those in the lowest quartile (OR: 0.382, 95% CI 0.151– 0.968, P< 0.001) after multivariate adjustment. The ROC analysis revealed that the best cut-off value of VFA for predicting the presence of DPN was 50.5cm2 (sensitivity 84.40%; specificity 34.00%).Conclusion: These results suggest that lower VFA level may be associated with increased risk of the presence of DPN in T2DM patients.Keywords: visceral fat area, diabetic peripheral neuropathy, sural nerve conduction velocity, sural nerve amplitude potential, Chinese population

Qin Tang, Hui Ke, Wen-wen Sun, Shao-jun Zhang, Lin Fan Department of Tuberculosis, Shanghai Clinical Research Center for Tuberculosis, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai Clinical Research Center for Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai, 200433, People’s Republic of ChinaCorrespondence: Lin Fan, Email fanlinsj@163.comObjective: It is a challenge to obtain satisfactory treatment outcomes for patients with multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB); the study aims to correlate the Minimum Inhibitory Concentration (MIC) value of drugs with the outcome of patients with MDR/RR-TB to obtain an understanding for better regimens and optimal outcomes.Methods: The patients diagnosed with MDR/RR-TB were retrospectively enrolled from January 1, 2018 to December 31, 2019, recorded clinical characteristics, MIC DST (Drug Susceptibility Test) results, and followed the treatment outcome. The data were analyzed on the correlations of MIC DST values with outcomes and clinical characteristics.Results: A total of 276 patients with MDR/RR-TB were included, containing 98 cases (35.5%) with newly treated patients and 178 cases (64.5%) with re-treated patients. A total of 220 cases recorded treatment success (79.7%) and 49 cases recorded treatment failure or died. MIC values of isoniazid (H), moxifloxacin (Mfx), and ethionamide (Eto) in newly treated patients were lower than those in retreated patients, and resistance levels of Mfx and H were closely associated with the treatment outcome (P < 0.05) while those of other drugs had no close association with treatment outcome.Conclusions: MIC values of some anti-TB drugs, such as fluoroquinolones (FQs) and H, can reflect the treatment outcome for patients with MDR/RR-TB, which can contribute to making regimens for better treatment outcomes.Keywords: MIC value, resistance, MDR/RR-TB, newly treated, retreated, treatment outcome

Yimin Chen,1 Thanh N Nguyen,2 James E Siegler,3 Mohammad Mofatteh,4 Jack Wellington,5 Rongshen Yang,6,7 Lihong Zeng,1 Jiale Wu,6,7 Xi Sun,6,7 Daiyu Liang,6,7 Qiubi Tang,8 Sijie Chen,6,7 Xisheng Huang,6,7 Shuiquan Yang,1 Xuxing Liao9,10 1Department of Neurology and Advanced National Stroke Center, Foshan Sanshui District People’s Hospital, Foshan, People’s Republic of China; 2Department of Neurology, Radiology, Boston University School of Medicine, Boston, MA, USA; 3Cooper Neurological Institute, Cooper University Hospital, Camden, NJ, USA; 4School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, UK; 5School of Medicine, Cardiff University, Cardiff, UK; 6Medical Intern of Neurology Department, Foshan Sanshui District People’s Hospital, Foshan, People’s Republic of China; 7School of Medicine, Shaoguan University, Shaoguan, People’s Republic of China; 8Chronic Disease Department, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 9Dean Office and Advanced National Stroke Center, Foshan Sanshui District People’s Hospital, Foshan, People’s Republic of China; 10Department of Neurosurgery, First People’s Hospital of Foshan, Foshan, People’s Republic of ChinaCorrespondence: Shuiquan Yang, Department of Neurology and Advanced National Stroke Center, Foshan Sanshui District People’s Hospital, No. 16, Guanghaidadaoxi, Sanshui District, Foshan, People’s Republic of China, Email yangshuiquan1969@126.com Xuxing Liao, Dean Office and Advanced National Stroke Center, Foshan Sanshui District People’s Hospital, Foshan, People’s Republic of China, Email drliao210409@163.comPurpose: This study aimed to investigate the impact of characteristic ischemic stroke and outcomes during the first COVID-19 pandemic lockdown.Patients and Methods: A retrospective, observational cohort study of a comprehensive tertiary stroke center was conducted. Patients with ischemic stroke were divided into pre-COVID-19 lockdown (11/1/2019 to 1/30/2020) and COVID-19 lockdown (1/31/2020 to 4/30/2020) period groups. Patient data on stroke admission, thrombolysis, endovascular treatment, and 3-month routine follow-up were recorded. Data analysis was performed using SPSS according to values following a Gaussian distribution.Results: The pre-COVID-19 lockdown period group comprised 230 patients compared to 215 patients in the COVID-19 lockdown period group. Atrial fibrillation was more predominant in the COVID-19 lockdown period group (11.68% vs 5.65%, p=0.02) alongside patients who were currently smoking (38.8% vs 28.7%, p=0.02) and drinking alcohol (30.37% vs 20.00%, p=0.012) compared with that of the pre-COVID-19 lockdown period group. For patients receiving thrombolysis, the median door-to-CT time was longer in the COVID-19 lockdown period group (17.0 min (13.0, 24.0) vs 12.0 min (8.0, 17.3), p=0.012), median door to needle time was 48.0 minutes (35.5, 73.0) vs 43.5 minutes (38.0, 53.3), p=0.50, compared with that of the pre-COVID-19 lockdown period group. There were no differences for patients receiving mechanical thrombectomy. The median length of hospitalization (IQR) was no different. Discharge mRS scores (IQR) were higher in the COVID-19 lockdown period group (1.0 (1.0, 3.0) vs 1.0 (1.0, 2.0), p=0.022). Compared with the pre-COVID-19 lockdown period, hospitalization cost (Chinese Yuan) in the COVID-19 period group was higher (13,445.7 (11,009.7, 20,030.5) vs 10,799.2 (8692.4, 16,381.7), p=0.000). There was no difference observed in 3-month mRS scores.Conclusion: Patients presenting with ischemic stroke during the COVID-19 pandemic lockdown period had longer median door-to-CT time and higher hospitalization costs. There were no significant differences in 3-month outcomes. Multidisciplinary collaboration and continuous workflow optimization may maintain stroke care during the COVID-19 pandemic lockdown.Keywords: ischemic stroke, COVID-19 pandemic, thrombolysis, thrombectomy, hospitalization cost

Sijie Jiang,1– 3 Shaobing Xie,1– 3 Ruohao Fan,1– 3 Qingping Tang,4 Hua Zhang,1– 3 Fengjun Wang,1– 3 Shumin Xie,1– 3 Kelei Gao,1– 3 Junyi Zhang,1– 3 Zhihai Xie,1– 3 Weihong Jiang1– 3 1Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 2Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 3National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 4Department of Rehabilitation, Brain Hospital of Hunan Province, Hunan University of Chinese Medicine, Changsha, People’s Republic of ChinaCorrespondence: Weihong Jiang, Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, People’s Republic of China, Tel +86-731-8975-3045, Email jiangwh68@126.comPurpose: Subcutaneous immunotherapy (SCIT) is an effective treatment for pediatric allergic rhinitis (AR), but its efficacy fluctuates among individuals. This study aims to identify the profile of serum exosomes derived microRNAs (miRNAs) and evaluate their capacities to early predict SCIT efficacy in pediatric AR.Patients and Methods: High-throughput sequencing was applied to identify the miRNA of serum exosomes in AR children. GO enrichment and KEGG pathway analysis were performed to enrich the biological annotations of target mRNAs of miRNAs. Then we validated differentially expressed miRNAs in two independent cohorts by RT-qPCR. Logistic regression and receiver operating characteristic curve (ROC) were applied to evaluate the abilities of identified miRNAs in predicting the efficacy of SCIT in AR children.Results: A total of 812 miRNAs were detected in the serum exosomes, including 16 upregulated and 14 downregulated. Differentially expressed genes are enriched in the biological process of developmental process and regulation of cellular process, and gathered in pathways such as the signaling pathways regulating pluripotency of stem cells and the Wnt signaling pathway. In the first validation cohort, hsa-miR-4669 (P=0.009) and hsa-miR-4686 (P=0.032) were significantly downregulated in the effective group than the ineffective group, while hsa-miR-3196 (P=0.015) was upregulated. In the second cohort, hsa-miR-4669 level (P< 0.0001) was downregulated in the effective group than the ineffective group. In addition, logistic regression revealed that hsa-miR-4669 level was correlated with the visual analogue scale (r=0.323, P=0.001) and total nasal symptoms score (r=0.269, P =0.007). ROC curve highlighted that hsa-miR-4669 level exhibited a reliable accuracy in predicting SCIT efficacy in pediatric AR (AUC=0.785).Conclusion: Serum exosomes derived miRNA were associated with the efficacy of SCIT. Serum exosomes derived hsa-miR-4669 might serve as a novel biomarker for early predicting the response of SCIT in AR children.Keywords: allergic rhinitis, subcutaneous immunotherapy, miRNA, exosome, children

Qi Tang, Jiafen Liao, Xi Xie Department of Rheumatology and Immunology, the Second Xiangya Hospital, Central South University, Changsha, People’s Republic of ChinaCorrespondence: Xi Xie, Department of Rheumatology and Immunology, the Second Xiangya Hospital, Central South University, Changsha, 410011, People’s Republic of China, Tel/Fax +86 0731 8529 5255, Email Hsixie1997@csu.edu.cnAbstract: To strengthen the understanding of rheumatic diseases (RDs) as the most common underlying conditions associated with acquired hemophilia (AH), a potentially fatal bleeding condition due to the development of autoantibodies or inhibitors to coagulation factor VIII, and rarely to factor IX, here we presented two cases of RDs associated AH to elucidate the disease progression, treatment, and prognosis. The presented 2 cases showed good responses to glucocorticoid (GC) and immunosuppressive agents. And then, a case-based systematic review was conducted to better understand the clinically practiced diagnosis and treatment of RDs associated AH. A total of 14 articles were included in the final literature review. All the identified 14 patients with underlying RDs and AH presented with bleeding symptoms, increased APTT, decreased FVIII activity, and positive FVIII inhibitors. Twelve of the 14 patients (85.7%) started an eradication of autoantibodies treatment with GC and immunosuppressive agents. Among which six patients achieved partial or complete remission, and four patients (28.6%) switched to Rituximab and responded well. Nine of the 14 patients received hemostasis therapy, including recombinant human FVIIa (rFVIIa). Two patients (14.3%) died due to mass bleeding and key organ failure. AH should be highly suspected in patients with RDs presenting spontaneous mucocutaneous or internal bleeding and an isolated prolonged APTT. Given the high morbidity of AH, it is important to facilitate efficient and proper management.Keywords: acquired hemophilia, systemic lupus erythematosus, Sjogren syndrome, rheumatoid arthritis, connective tissue disease

Shanshan Guo,1 Xiaoyun Zhang,2 Qianjue Tang,1 Mengyun Zhou,2 Dan Jiang,2 Erkai Yu1 1Departments of Gynecology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China; 2Departments of Pathology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of ChinaCorrespondence: Erkai Yu, Longhua Hospital, 725 Wanping South Road, Xuhui District, Shanghai, People’s Republic of China, Tel/Fax +8618117209488, Email yuerkai2911@163.comAbstract: Carcinosarcoma, also known as malignant Mullerian mixed tumour, is a rare and aggressive ovarian malignant tumour. The prognosis of ovarian carcinosarcoma is very poor, accounting for the vast majority of ovarian cancer deaths. Due to the rarity of ovarian carcinosarcoma, no unified treatment plan exists at present. Here, we report the case of a 69-year-old patient with stage IC ovarian carcinosarcoma. She underwent right salpingo-oophorectomy and R0 resection, inclouding extrafascial hysterectomy, left salpingo-oophorectomy, omentectomy, appendectomy, right pelvic lymph node dissection and multipoint biopsy. Full-exome sequencing was performed with normal ovarian tissue, cancer tissue, sarcoma tissue and carcinosarcoma tissue, and the results showed that the sarcoma and carcinosarcoma tissue shared more mutated genes. A TP53 mutation occurred in the cancer tissue and carcinosarcoma tissue. By analysing the lychee tree, we found that the sarcoma tissue and carcinosarcoma tissue shared more subclones and determined that they were more closely related; the cancer tissue carried fewer subclones and was the main clone. The sarcoma may have evolved from the cancer tissues. Six rounds of postoperative chemotherapy (carboplatin + paclitaxel + ifosfamide (IFO) (paclitaxel 200 mg, D1 + carboplatin 600 mg, D1 + IFO 2G, D1-D3)) were administered. The patient has been followed up for six years and is currently in good health. In conclusion, the disease was diagnosed in the early stage, and the use of a R0 resection + a three-drug combination chemotherapy may have contributed to the patient’s long-term disease-free survival. The results of the gene study suggested that the sarcoma component may be differentiated from the cancer component. We thus speculated that the origin of this case may have been the fallopian tube.Keywords: OCS, literature review, gene analysis, origin

Qi Tang, Qiang Guo, Ke Li, Fan Fei Department of Anesthesiology, First People’s Hospital of Taicang, Soochow University, Suzhou, Jiangsu Province, People’s Republic of ChinaCorrespondence: Qiang Guo; Ke Li, Tel +86 15862329291 ; +86 15962297450, Email gq393166@163.com; 522287965@qq.comBackground: Perioperative neurocognitive disorders (PND) are common surgical complications in the elderly. Pyroptosis-associated inflammation has been suggested to participate in a series of neurocognitive diseases, including Alzheimer’s disease. Given that VRT-043198 can reportedly inhibit caspase-1-induced pyroptosis, this study sought to determine whether VRT-043198 reduced PND in a mouse model following abdominal exploratory laparotomy.Methods: 20-month-old male C57/BL mice were used to establish an abdominal exploratory laparotomy (AEL) model of PND. VRT-043198 (1, 10 and 100 mg/kg) was administered intraperitoneally immediately after surgery. Thirty days post-surgery, the mice were evaluated in the Morris water maze test. Their number of neurons, neurotrophin nerve growth factor (NGF) levels and brain-derived neurotrophic factor (BDNF) were measured. In the hippocampus, A1-type astrocytes and M1-type microglia were assessed using an immunofluorescence assay and Western blot, respectively. Caspase-1 activity, IL-1β, IL-18, and PPAR-γ were also measured 24h after surgery.Results: VRT-043198 administration increased the time to cross the platform and increased the ratio of distance and time in the targeted quadrant after surgery. Furthermore, it was found that VRT-043198 restored neuronal amount, increased NGF and BDNF and decreased the number of A1-type astrocytes and M1-type microglia. VRT-043198 also attenuated caspase-1 activity, downregulated IL-1β and IL-18, but increased PPAR-γ 24h post-surgery.Conclusion: VRT-043198 improved PND in aged mice after abdominal exploratory laparotomy by restoring the NGF and BNDF expression. These results indicate that VRT-043198 may be a potential therapy for PND.Keywords: cognitive dysfunction, elderly, caspase-1, pyrpotosis, inflammation

Zhiqiao Hu,&ast; Hao Zhang,&ast; Jiaqi Wang, Huan Xiong, Yunxiao Liu, Yihao Zhu, Zewen Chang, Hanqing Hu, Qingchao Tang Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingchao Tang, Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, People’s Republic of China, Tel +86-13945052628, Email 13945052628@qq.comPurpose: To develop and validate the risk nomogram to predict the likelihood of postoperative anxiety and depression in colorectal cancer (CRC) patients.Methods: A total of 602 CRC patients from the Second Affiliated Hospital of Harbin Medical University were included in the study and divided into development set and validation set with the 2:1 ratio randomly. Logistic regression model was used to determine independent factors contributing to postoperative anxiety and depression, which were subsequently applied to build the nomogram for predicting postoperative anxiety and depression. The performance of the risk nomogram was appraised by the area under the receiver operating curve (AUC), calibration curves and decision curve analyses (DCA).Results: Gender, personal status, income, adjuvant therapy, the Eastern Cooperative Oncology Group Scale (ECOG) score, comorbidity, postoperative complications and stoma status were significant indicators for postoperative anxiety and depression. The AUCs for the development and validation sets were 0.792 and 0.812 for the postoperative anxiety nomogram and 0.805 and 0.825 for the postoperative depression nomogram. Additionally, calibration curves and decision curve analyses also determined the reliable clinical importance of the proposed nomogram.Conclusion: The current study constructed the risk nomogram for postoperative anxiety and depression and could help clinicians determine high-risk patients to some extent.Keywords: nomogram, colorectal cancer, postoperative, anxiety and depression

Wei Cheng, Fen Li, Jing Tian, Xi Xie, Jin-Wei Chen, Xiao-Fei Peng, Qi Tang, Yan Ge Department of Rheumatology and Immunology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People’s Republic of ChinaCorrespondence: Yan Ge, Department of Rheumatology and Immunology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People’s Republic of China, Email geyan2003@csu.edu.cnAbstract: Synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome is a rare autoinflammatory disease characterized by dermatological disorders and osteoarticular inflammatory lesions. This article reviews the application of biologics and other treatments based on the therapeutic target and the size of molecules in SAPHO syndrome. We found that drugs, especially biologics, have different effects on bone, joint, and skin damage. This may relate to the different inflammatory pathways involved in the osteoarticular and cutaneous symptoms in SAPHO patients. In this study, we provide stratified medication recommendations for SAPHO syndrome. Patients with osteoarticular symptoms can consider tumor necrosis factor blockers, JAK inhibitor, interleukin (IL)-1 inhibitor, and IL-17 inhibitor. Patients with cutaneous symptoms should consider IL-17 and JAK inhibitors. Apremilast, Tripterygium wilfordii Hook F, and bisphosphonates are other effective treatments.Keywords: SAPHO, osteoarticular symptoms, cutaneous symptoms, immune pathway pathways, biologics, targeted small molecule compounds

Yu Li,1,&ast; Mei-Ling Wang,1,&ast; Bo Zhang,1 Xiao-Xu Fan,1 Qin Tang,1 Xue Yu,2 Li-Na Li,2 Ang-Ran Fan,2 Hong-Sheng Chang,1 Lan-Zhen Zhang1 1School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China; 2School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lan-Zhen Zhang; Hong-Sheng Chang, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Northeast Corner of the Intersection of Sunshine South Street and Baiyang East Road, Fangshan District, Beijing, 102488, People’s Republic of China, Tel +86 10 5391 2122, Email zhanglanzhen01@126.com; chs1971@sina.comBackground: There is growing evidence to suggest that ginsenoside Rd (GRd) has a therapeutic effect on depression, but the specific mechanisms behind its activity require further study.Objective: This study is designed to investigate the antidepressant-like effect and underlying mechanisms of GRd.Methods: In this study, the behavioral despair mouse model of depression and chronic unpredictable mild stress (CUMS) rat model of depression were established to explore the effects of GRd on depression-like behavior and its underlying mechanisms. Behavioral tests were used to evaluate the replication of animal models and depression-like behaviors. The hypoxia-inducible factor-1α (HIF-1α) blocker 2-methoxyestradiol (2-ME) was injected to determine the role of HIF-1α in the antidepressant-like effect of GRd. In addition, molecular biology techniques were used to determine the mRNA and protein expression of HIF-1ɑ signaling pathway and synaptic plasticity-related regulators, that is synapsin 1 (SYN 1) and postsynaptic density protein 95 (PSD 95). In silico binding interaction studies of GRd with focused target proteins were performed using molecular docking to predict the affinity and optimal binding mode between ligands and receptors.Results: Our data show that GRd significantly reversed depression-like behavior and promoted mRNA and protein expression of HIF-1ɑ signaling pathway and synaptic plasticity-related regulators. However, the antidepressant-like effect of GRd disappeared upon inhibition of HIF-1α expression following administration of 2-ME. Furthermore, molecular docking results showed that GRd possessed significant binding affinity for HIF-1α, VEGF, and VEGFR-2.Conclusion: Our results show that GRd exhibits significant antidepressant-like effect and that HIF-1α signaling pathway is a promising target for the treatment of depression.Keywords: ginsenoside Rd, antidepressant effect, HIF-1α-VEGF signaling pathway, VEGFR-2, synaptic plasticity-related regulators, molecular docking

Chen Pan,1 Honghong Wang,2 Minzhen Chen,3 Yu Cai,1 Peihuan Li,4 Changgen Xiao,5 Qiuping Tang,1 Deborah Koniak-Griffin6 1Department of Clinical Psychology, The Third Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 2Department of Fundamental Nursing, Xiangya School of Nursing, Central South University, Changsha, People’s Republic of China; 3Department of AIDS, The First Hospital of Changsha, Changsha, People’s Republic of China; 4College of Resources of Environment, Hunan Agricultural University, Changsha, People’s Republic of China; 5Department of Applied Psychology, Hunan University of Chinese Medicine, Changsha, People’s Republic of China; 6School of Nursing, University of California Los Angeles, Los Angeles, CA, USACorrespondence: Qiuping Tang, Department of Clinical Psychology, The Third Xiangya Hospital of Central South University, Changsha, People’s Republic of China, Tel +86 731 88618567, Email tt96@sina.comBackground/Purpose: Nurses engaged in the care of people living with HIV (PLWH) are commonly exposed to workplace stress. This study aimed to explore the stress experiences and coping strategies among nurses taking care of PLWH in China.Methods: Nurses were recruited from the AIDS department of a public, general, third-grade class-A hospital, which has the largest HIV care department in the Hunan Province of China. Thirty-three nurses working in the AIDS Department were recruited in this qualitative study. Eight nurses participated in a focus group and 25 nurses underwent in-depth individual interviews aimed at characterizing the nurse’s feelings and struggles with stress during caregiving for PLWH. The interviews were audio-recorded, transcribed verbatim, anonymized, and imported into NVivo 8.0 software. The data were coded and subjected to thematic analysis.Results: Concerns about occupational exposure, heavy workload, mental health problems and risk behaviors of patients, and discrimination towards nurses caring for PLWH were the four main sources of stress. The negative impact of stress included problems with emotion regulation, somatic health and sleep, and work performance. Some participants also reported a positive impact of work stress on their mental health. Using personality strengths, problem-solving, help-seeking, concealing and avoiding/suppression were common coping strategies employed by nurses caring for PLWH.Conclusion: Our findings help characterize the stress experienced by nurses caring for PLWH in the Chinese cultural context, and may inform specific interventions to help manage stress and promote mental health of nurses.Keywords: HIV, nurses, stress, job burnout, coping

Yongli Zhang,1,2 Mengyao Xie,1,2 Ruoyan Xue,1,2 Qi Tang,1,2 Xiaohui Zhu,1,2 Jian Wang,1,2 Hua Yang,1,2 Chao Ma3– 5 1Department of Otolaryngology, Chinese Academy of Medical Sciences and Peking Union Medical College, Peking Union Medical College Hospital, Beijing, 100730, People’s Republic of China; 2Translational Medicine Center, Peking Union Medical College Hospital, Beijing, 100730, People’s Republic of China; 3Institute of Basic Medical Sciences, Department of Human Anatomy, Histology and Embryology, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, 100005, People’s Republic of China; 4Joint Laboratory of Anesthesia and Pain, Peking Union Medical College, Beijing, 100730, People’s Republic of China; 5Chinese Institute for Brain Research, Beijing, 102206, People’s Republic of ChinaCorrespondence: Jian Wang; Hua YangDepartment of Otolaryngology, Peking Union Medical College Hospital, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, People’s Republic of ChinaTel +86 13673164261; +86 13701127757Fax +86-10-69156311Email wangjianent@163.com; dr_yanghua2021@163.comPurpose: Rapid and accurate diagnosis of the pathological characteristics of head and neck cancer and tumor resection margins is important. The DiveScope cell morphology analyzer (DiveScope) is a new endomicroscope that can rapidly image living tissues and cells. In this study, we preliminarily examined the accuracy of the DiveScope for determining the malignancy of head and neck cancers and the positivity/negativity of tumor resection margins and determined the consistency between diagnostic results with the DiveScope and those of frozen section pathology to provide a foundation for further clinical trials in pathological diagnosis of head and neck cancers and tumor resection margins.Methods: Head and neck cancer samples and resection margin samples were rapidly stained ex vivo before observation under the DiveScope cell morphology analyzer. Experienced pathologists distinguished the benignity and malignancy of the tumors based on images obtained by the DiveScope in a double-blind manner to validate the diagnostic performance of the analyzer.Results: We found that the cell morphology, cell nucleus morphology, karyoplasmic ratio, and even the nucleolus could be clearly distinguished. The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) of benign and malignant head and neck cancer according to DiveScope results were 10.55 and 0.04, respectively. The PLR and NLR of the head and neck cancer resection margins according to the DiveScope were 19.01 and 0, respectively.Conclusion: The DiveScope showed high accuracy in determining the benignity and malignancy of head and neck cancer and the positivity/negativity of resection margins, and its results were highly consistent with those of intraoperative frozen section pathology tests.Keywords: the DiveScope cell morphology analyzer, head and neck cancer, resection margins, pathological diagnosis

Deku Liang,1,2 Min Hu,1 Qin Tang,1 Mao Huang,1 Liangdan Tang1 1Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Obstetrics and Gynecology, Chengdu Women and Children’s Central Hospital Affiliated to University of Electronic Science and Technology of China, Chengdu, Sichuan Province, People’s Republic of ChinaCorrespondence: Liangdan Tang Email 201608@hospital.cqmu.edu.cnBackground: Endometrial carcinoma (EC) is one of the most common malignancies. Immunotherapy has shown promising effects in the treatment against specific subtypes of EC.Methods: The RNA and clinical information of patients with EC were acquired from The Cancer Gene Atlas (TCGA) database. Firstly, the differentially expressed pyroptosis-related lncRNAs (PRLs) were screened between the tumor and normal control tissue. Secondly, the PRLs closely related to survival were identified by univariate and multivariate regression analysis, based on which, we evaluated the risk score for each EC patient to construct a risk signature. Moreover, we assessed the prognostic value, clinical relevance immunity, and immunotherapy based on this signature.Results: We screened out 9 individual PRLs (AC087491.1, AL353622.1, AL035530.2, LINC02036, AL021578.1, AL390195.2, AC009097.2, AC004585.1, and AC244517.7) closely related to the prognosis of EC. Kaplan–Meier analyses showed a poorer prognosis for the patients in the high-risk FRLs signature (P < 0.001). The area under the curve (AUC) for 1 year, 2 years, 3 years was 0.693, 0.694, 0.750, respectively. Our risk model could be considered as an independent prognostic marker for EC (P < 0.001, HR:2.172, 95% CI:1.532– 3.079). Moreover, immune functions and checkpoints were generally different in the 2 groups. Simulation analysis by termed immunophenoscores hinted that immunotherapy might bring optimal therapeutic effect in the low-risk group.Conclusion: We successfully developed a novel signature with 9 lncRNAs related to pyroptosis, which may be used as biomarkers to evaluate the prognosis and immune treatment of EC.Keywords: endometrial carcinoma, pyroptosis, immunotherapy, lncRNAs, immune infiltration

Yunxiao Liu, Hao Zhang, Mingyu Zheng, Chunlin Wang, Zhiqiao Hu, Yang Wang, Huan Xiong, BoYang Fan, Yuliuming Wang, Hanqing Hu, Qingchao Tang, Guiyu Wang Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of ChinaCorrespondence: Guiyu WangDepartment of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of ChinaTel +86-451-86296599Email guiywang@163.comPurpose: Distant metastasis (DM) is relatively rare in T1 colon cancer (CC) patients, especially in those with negative lymph node metastasis. The aim of this study was to explore the main clinical factors and build nomogram for predicting the occurrence and prognosis of DM in T1N0 colon cancer patients.Methods: Patients with T1N0 stage CC were collected from the Surveillance, Epidemiology, and End Result (SEER) database. All patients were divided into development and validation cohorts with the 3:1 ratio. Logistic regressions were performed to analyze the clinical risk factors for DM. Cox regression model was used to identify potential prognostic factors for patients with DM. The performance of nomogram was evaluated by concordance index (C-index), calibration curves, receiver operating characteristic (ROC) curves and decision curve analyses (DCAs). Based on cancer-specific survival (CSS), Kaplan–Meier curves were generated and analyzed using Log rank tests.Results: A total of 6770 patients were enrolled in this study, including 428 patients (6.3%) with DM. Age, size, grade, CEA were independent risk factors associated with DM. Age, grade, CEA, surgery and chemotherapy were independent prognostic factors for CSS. Nomograms were applied and C-index, calibration curves, ROC curves and DCA curves proved good discrimination, calibration and clinical practicability of the nomogram in predicting the occurrence and prognosis of DM in T1N0 CC patients. In the DM nomogram, the AUCs for development and validation cohort were 0.901 (95% CI = 0.879– 0.922) and 0.899 (95% CI=0.865– 0.940), respectively. The calibration curves (development cohort: S: p = 0.712; validation cohort: S: p = 0.681) showed the relatively satisfactory prediction accuracy. Similarly, the AUCs of the nomogram at 1-, 2-, and 3-year were 0.763 (95% CI=0.744– 0.782), 0.794 (95% CI=0.775– 0.813), and 0.822 (95% CI=0.803– 0.841) for the development cohort, and 0.785 (95% CI=0.754– 0.816), 0.748 (95% CI=0.717– 0.779) and 0.896 (95% CI=0.865– 0.927) for the validation cohort in the CSS nomogram. The C-indices of the development and validation cohort were 0.718 (95% CI=0.639– 0.737) and 0.712 (95% CI=0.681– 0.743).Conclusion: The population-based nomogram could help clinicians predict the occurrence and prognosis of DM in T1N0 CC patients and provide a reference to perform appropriate metastatic screening plans and rational therapeutic options for the special population.Keywords: T1N0 colon cancer, distant metastasis, nomogram, SEER

Jingbin Huang,&ast; Wenjing Lai,&ast; Qing Wang, Qin Tang, Changpeng Hu, Min Zhou, Fengling Wang, Dandan Xie, Qian Zhang, Wuyi Liu, Zhe Zhang, Rong Zhang Department of Pharmacy, The Second Affiliated Hospital of Army Medical University, ChongQing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rong Zhang; Zhe Zhang Email xqpharmacylab@126.com; 15086988023@163.comIntroduction: Triple-negative breast cancer (TNBC) has the high degree of malignancy and aggressiveness. There is no targeted therapy drug. Many studies have shown that RBC membrane-coated nanoparticles achieve biological camouflage. In addition, the RGD module in the iRGD mediates the penetration of the vector across the tumor blood vessels to the tumor tissue space. Therefore, we developed iRGD-RM-(DOX/MSNs) by preparing MSNs loaded with doxorubicin as the core, and coating the surface of the MSNs with iRGD-modified RBC membranes.Methods: iRGD-RM-(DOX/MSNs) were fabricated using physical extrusion. In addition, their physical and chemical characterization, hemolytic properties, in vivo acute toxicity and inflammatory response, in vitro and in vivo safety, and qualitative and quantitative cellular uptake by RAW 264.7 cells and MDA-MB-231 cells were evaluated and compared. Furthermore, we examined the antitumor efficacy of iRGD-RM-(DOX/MSN) nanoparticles in vitro and in vivo.Results: iRGD-RM-(DOX/MSNs) have reasonable physical and chemical properties. iRGD-RM-(DOX/MSNs) escaped the phagocytosis of immune cells and achieved efficient targeting of nanoparticles at the tumor site. The nanoparticles showed excellent antitumor effects in vivo and in vitro.Conclusion: In this study, we successfully developed biomimetic iRGD-RM-(DOX/MSNs) that could effectively target tumors and provide a promising strategy for the effective treatment of TNBC.Keywords: RBC membrane, iRGD peptide, biological camouflage, targeted treatment, Triple-negative breast cancer

Yanan Zhang,1 Xiaodan Wu,1 Qingqing Sun,1 Qi Tang,1 Zhen-Ni Guo,2 Zan Wang,1 Yi Yang2 1Department of Neurology and Neuroscience Center, the First Hospital of Jilin University, Changchun, People’s Republic of China; 2Department of Neurology and Neuroscience Center, Clinical Trial and Research Center for Stroke, the First Hospital of Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Zan WangDepartment of Neurology and Neuroscience Center, the First Hospital of Jilin University, Changchun, People’s Republic of ChinaEmail wangzan@jlu.edu.cn; wangzanprof@163.comYi YangDepartment of Neurology and Neuroscience Center, Clinical Trial and Research Center for Stroke, the First Hospital of Jilin University, Changchun, People’s Republic of ChinaEmail yang_yi@jlu.edu.cn; doctoryangyi@163.comObjective: Patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) have impaired dynamic cerebral autoregulation (dCA). This study aimed to explore whether serum levels of apolipoprotein B-100 (ApoB-100), fibronectin (FN), and ceruloplasmin (CP) were related to impaired dCA in OSAHS.Methods: A total of 90 patients with OSAHS from our database management system were enrolled and further divided into three subgroups according to the apnea-hypopnea index (AHI) using polysomnography results: mild (5 ≤ AHI ≤ 15), moderate (15 < AHI ≤ 30), and severe OSAHS (AHI > 30), with 30 patients in each group. Thirty sex- and age-matched healthy controls were recruited for this study. The serum levels of ApoB-100, FN, and CP were measured by enzyme-linked immunosorbent assays. dCA was assessed by analyzing the phase difference (PD) using transfer function analysis.Results: Serum levels of ApoB-100, FN, and CP were significantly higher in the mild, moderate, and severe OSAHS groups than that in the control group (P< 0.001, respectively). The average PD of the moderate and severe OSAHS groups was lower than that of the control group (P=0.001 and P< 0.001, respectively). Receiver operating curve analysis revealed that ApoB-100, FN, and CP might be able to distinguish patients with OSAHS from healthy individuals (area under the curve = 0.959 [95% CI 0.92– 1.00], 0.987 [95% CI 0.96– 1.01], 0.982 [95% CI 0.96– 1.00]), respectively, P< 0.001). The average PD was linearly correlated with the serum levels of ApoB-100, FN, and CP in patients with OSAHS. Multivariable analysis showed that FN and arousal index in polysomnography were associated with impaired average PD (P< 0.001 and P=0.025, respectively).Conclusion: Serum levels of ApoB-100, FN, and CP increased in patients with OSAHS. dCA was compromised in patients with OSAHS and was positively correlated with ApoB-100, FN, and CP serum levels, and FN serum levels and arousal index in polysomnography were independently associated with impaired dCA.Keywords: obstructive sleep apnea-hypopnea syndrome, apolipoprotein B-100, fibronectin, ceruloplasmin, dynamic cerebral autoregulation

Shanshan Guo, Yijia Chen, Qianjue Tang, Lian Liu, Lianwei Xu Gynecology Department, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of ChinaCorrespondence: Lianwei XuGynecology Department, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 South Wanping Road, Shanghai, 200032, People’s Republic of ChinaTel/Fax +86-21-64385700Email lianweixu_2800@163.comPurpose: This study aims to evaluate clinical efficiency and side effects of combined therapy of traditional Chinese medicine in female treating chronic pelvic pain.Methods: A retrospective study was conducted by analyzing 179 patients with chronic pelvic pain. They were divided into the 3-course group and the 1-course group. Patients in the 3-course group received combined therapy of traditional Chinese medicine 10 days per menstrual cycle for three months, while the 1-course group received the same combined therapy for only one menstrual cycle. VAS scores of five kinds of pain were compared between the two groups. Meanwhile, SF-36 scores, menstruation, leucorrhea and major accompanying symptoms were analyzed. To assess side effects of the combined therapy, safety indices were recorded before and after treatment as well.Results: VAS scores of patients in the 3-course group after treatment were significantly lower than that before the treatment. Total scores of SF-36 were significantly improved after the treatment, and persistently improved even after the discontinuation of the treatment. The menstrual and leucorrhea condition improved as well after the treatment. In addition, among the concomitant symptoms, insomnia, loss of appetite, mental fatigue symptoms were significantly improved after the treatment. More importantly, significances were observed in the improvement of most VAS scores between patients who underwent a 1-course treatment and patients with a 3-course treatment. Meanwhile, no significant change was observed in safety indices before and after treatment. Possible adverse events related to the treatment plan for all enrolled patients included mild skin rash in 16 patients, stomachache in 3 patients after taking medicine on an empty stomach, and oral ulcer in 1 patient.Conclusion: Combined therapy of traditional Chinese medicine alleviated symptoms of chronic pelvic pain, soothed the accompanying symptoms, and hence helped to improve the life quality of women.Keywords: combined therapy of traditional Chinese medicine, chronic pain in pelvic area, retrospective study, efficacy

Chen He,1 Huiyan Ding,1 Jing Chen,1 Yinan Ding,1 Rui Yang,2 Chunmei Hu,3 Yanli An,1 Dongfang Liu,1 Peidang Liu,1 Qiusha Tang,1 Zhiyuan Zhang4 1Medical School of Southeast University, Nanjing, People’s Republic of China; 2Research Institute for Reproductive Health and Genetic Diseases, The Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University, Wuxi, People’s Republic of China; 3Department of Tuberculosis, The Second Affiliated Hospital of Southeast University (The Second Hospital of Nanjing), Nanjing, People’s Republic of China; 4Department of Neurosurgery, Nanjing Jinling Hospital, Nanjing University, Nanjing, People’s Republic of ChinaCorrespondence: Qiusha TangMedical School of Southeast University, 87 Dingjiaqiao Road, Nanjing, People’s Republic of ChinaEmail panyixi-tqs@163.comZhiyuan ZhangDepartment of Neurosurgery, Nanjing Jinling Hospital, Nanjing University, Nanjing, People’s Republic of ChinaEmail zzy8896@163.comBackground: Inducing the immunogenic cell death of tumour cells can mediate the occurrence of antitumour immune responses and make the therapeutic effect more significant. Therefore, the development of treatments that can induce ICD to destroy tumour cells most effectively is promising. Previously, a new type of pH-sensitive polymersome was designed for the treatment of glioblastoma which represents a promising nanoplatform for future translational research in glioblastoma therapy. In this study, the aim of this work was to analyse whether chemoradiotherapy of the novel pH-sensitive cargo-loaded polymersomes can induce ICD.Methods: Cell death in U87-MG and G422 cells was induced by Au-DOX@PO-ANG, and cell death was analysed by CCK-8 and flow cytometry. The release of CRT was determined by using laser scanning confocal microscopy and flow cytometry. ELISA kits were used to detect the release of HMGB1 and ATP. The dying cancer cells treated with different treatments were cocultured with bone-marrow-derived dendritic cells (BMDCs), and then flow cytometry was used to determine the maturation rate of BMDCs (CD11c+CD86+CD80+) to analyse the in vitro immunogenicity. Tumour vaccination experiments were used to evaluate the ability of Au-DOX@PO-ANG to induce ICD in vivo.Results: We determined the optimal treatment strategy to evaluate the ability of chemotherapy combined with radiotherapy to induce ICD and dying cancer cells induced by Au-DOX@PO-ANG+RT could induce calreticulin eversion to the cell membrane, promote the release of HMGB1 and ATP, and induce the maturation of BMDCs. Using dying cancer cells induced by Au-DOX@PO-ANG+RT, we demonstrate the efficient vaccination potential of ICD in vivo.Conclusion: These results identify Au-DOX@PO-ANG as a novel immunogenic cell death inducer in vitro and in vivo that could be effectively combined with RT in cancer therapy.Keywords: immunogenic cell death, ICD, glioblastoma, radiotherapy, polymersomes, nanodrug delivery system

Yuchen Zhong,1,2 Tianyi Ma,1 Tianyu Qiao,1 Hanqing Hu,1 Zhengliang Li,1 Kangjia Luo,1 Yuliuming Wang,1 Qingchao Tang,1 Guiyu Wang,1,2 Rui Huang,1 Xishan Wang3 1Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150080, People’s Republic of China; 2Department of Colorectal Surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, 310002, People’s Republic of China; 3Department of Colorectal Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, National Clinical Research Center for Cancer, Beijing, 100021, People’s Republic of ChinaCorrespondence: Guiyu Wang; Rui HuangDepartment of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150080, People’s Republic of ChinaTel/Fax +86-19558225177; +86-15204620800Email guiyWang@163.com; huangrui2019@163.comObjective: To investigate the relationship between circulating tumor cells (CTCs) and their subpopulations and colorectal cancer (CRC). To explore the application of CTCs’ numbers and positive rates in the diagnosis and treatment of CRC, and to assess the effect of surgery on CTCs numbers and positivity.Methods: We identified CTCs using the CanPatrol technique after enrollment. Peripheral blood samples were collected from 74 CRC patients before anti-tumor treatment. CTCs can be divided into the following three phenotypes: epithelial CTCs (E-CTCs) (EpCAM+, Vimentin-), mesenchymal CTCs (M-CTCs) (EpCAM-, Vimentin+), and mixed CTCs (E/M-CTCs) (EpCAM+, Vimentin+). CTCs and the proportion of subtypes were statistically compared with clinicopathological characteristics.Results: The positive rate of M-CTCs was significantly higher in patients with tumor size ≥ 5 cm (85.7% vs 49.1%, P = 0.004) and carcinoembryonic antigen (CEA) > 5 ng/mL (83.3% vs 51.0% p = 0.024). Moreover, the T stage (T1 0, T2 33.3%, T3 59.4%, T4 100%, p < 0.0005) and TNM stage (stage I 11.8%, stage II 79.2%, stage III 64.3%, stage IV 100%, p < 0.0005) were correlated with the positive rate of M-CTCs. We also found that the proportion of M-CTCs was correlated with the T stage (p < 0.0005) and TNM stage (p=0.0200), but not with the N stage (p=0.6889). In survival analysis, M-CTCs > 1 were found associated with worse disease-free survival (p=0.007). After treatment, the number and proportion of CTCs and M-CTCs were significantly reduced.Conclusion: The positive rate of M-CTCs was associated with tumor size, T stage, TNM stage, vascular invasion, and CEA. As the disease progressed, the proportion of M-CTCs gradually increased, and the survival performance was worse in patients with a high positive rate of M-CTCs.Keywords: circulating tumor cells, colorectal cancer, surgery, EMT

Qiqing Gao,&ast; Yao Cheng,&ast; Zhuohong Li, Qingyun Tang, Rong Qiu, Shaohang Cai, Xuwen Xu, Jie Peng, Hongyan Xie Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Peng; Hongyan XieDepartment of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of ChinaTel +86 20 62787428Fax +86 20 87719653Email pjie138@163.com; 492577598@qq.comBackground: Malnutrition is one of the most critical factors affecting patients’ risk of infection and length of stay, and it may affect the prognosis of patients with sepsis. There have been no studies that have applied nutritional risk screening tools to stratify patients with sepsis according to prognosis.Methods: We retrospectively analyzed the clinical data of 425 adult sepsis inpatients who were grouped based on nutritional risk screening (NRS) score, including a nutrition score, disease severity score, and age score. Prognostic factors were analyzed using univariate and multivariate regression analyses.Results: Of the enrolled patients, 174 had an NRS score of ≥ 3; these patients were older and had a longer hospitalization time but lower body mass index (BMI), albumin (ALB) than others. Univariate Cox regression analysis showed that age, ALB, C-reactive protein (CRP), and NRS score were significantly (P< 0.05) associated with in-hospital mortality. Multivariate analysis showed that age (hazard ratio [HR]=1.020, 95% confidence interval [CI]: 1.005– 1.036; P=0.008) and ALB (HR=0.924, 95% CI: 0.885– 0.966; P< 0.001) were independent risk factors for sepsis-related mortality. The Kaplan–Meier analysis revealed that the cumulative in-hospital mortality of sepsis patients with an NRS score of ≥ 3 was significantly higher than that of patients with an NRS score of < 3 (P=0.022).Conclusion: NRS scores can effectively risk stratify sepsis patients. Patients with high NRS scores should be monitored more closely to halt further disease progression.Keywords: sepsis, malnutrition, NRS, risk stratification, prognostic assessment

Hui Huang,1,2 Qinhui Liu,1 Ting Zhang,2 Jinhang Zhang,1,2 Jian Zhou,1,2 Xiandan Jing,2 Qin Tang,1 Cuiyuan Huang,1,2 Zijing Zhang,1 Yingnan Zhao,1,2 Guorong Zhang,1,2 Jiamin Yan,1,2 Yan Xia,1,2 Ying Xu,1,2 Jiahui Li,1,2 Yanping Li,1 Jinhan He1,2 1Laboratory of Clinical Pharmacy and Adverse Drug Reaction, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Pharmacy, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Yanping LiLaboratory of Clinical Pharmacy and Adverse Drug Reaction, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaTel +86-28-85164128Email liyanping_512@163.comJinhan HeDepartment of Pharmacy, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaTel +86-28-85426416Email jinhanhe@scu.edu.cnBackground: Renal fibrosis is the common pathway in chronic kidney diseases progression to end-stage renal disease, but to date, no clinical drug for its treatment is approved. It has been demonstrated that the inhibitor of proto-oncogene Ras, farnesylthiosalicylic acid (FTS), shows therapeutic potential for renal fibrosis, but its application was hindered by the water-insolubility and low bioavailability. Hence, in this study, we improved these properties of FTS by encapsulating it into bovine serum albumin nanoparticles (AN-FTS) and tested its therapeutic effect in renal fibrosis.Methods: AN-FTS was developed using a classic emulsification-solvent ultrasonication. The pharmacokinetics of DiD-loaded albumin nanoparticle were investigated in SD rats. The biodistribution and therapeutic efficacy of AN-FTS was assessed in a mouse model of renal fibrosis induced by unilateral ureteral obstruction (UUO).Results: AN-FTS showed a uniform spherical shape with the size of 100.6 ± 1.12 nm and PDI < 0.25. In vitro, AN-FTS displayed stronger inhibitory effects on the activation of renal fibroblasts cells NRK-49F than free FTS. In vivo, AN-FTS showed significantly higher peak concentration and area under the concentration-time curve. After intravenous administration to UUO-induced renal fibrosis mice, AN-FTS accumulated preferentially in the fibrotic kidney, and alleviated renal fibrosis and inflammation significantly more than the free drug. Mechanistically, the improved anti-fibrosis effect of AN-FTS was associated with greater inhibition in renal epithelial-to-mesenchymal transformation process via Ras/Raf1/p38 signaling pathway.Conclusion: The study reveals that AN-FTS is capable of delivering FTS to fibrotic kidney and showed superior therapeutic efficacy for renal fibrosis.Keywords: albumin nanoparticle, epithelial–mesenchymal transition, farnesylthiosalicylic acid, Ras, renal fibrosis

Jian Yang,1,2 Xin Gao,1,2 Xiaotao Xing,1,2 Haisen Huang,1,2 Qi Tang,1,3 Shixing Ma,1,2 Xun Xu,1,2 Cheng Liang,1,2 Maojiao Li,1,2 Li Liao,1,2 Weidong Tian1,2 1State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Engineering Research Center of Oral Translational Medicine, Ministry of Education & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, People’s Republic of China; 3West China School of Public Health & West China Fourth Hospital, Sichuan University, Chengdu, 610041, People’s Republic of ChinaCorrespondence: Li Liao; Weidong TianState Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Engineering Research Center of Oral Translational Medicine, Ministry of Education & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, People’s Republic of ChinaTel/ Fax +86-28-85503499Email lliao@scu.edu.cn; drtwd@sina.comPurpose: Extracellular vesicles (EVs) are membrane-encapsulated nanoparticles that function as carriers and play a role in intercellular communication. There are a large number of EVs in the blood and serve as an indicator of pathophysiological conditions. Studies on the basics and application of EVs are hampered by the limitations of current protocols to isolate EVs from blood. However, current isolation methods are difficult to achieve a balance between yield and purity.Methods: Firstly, we use Sepharose-4B to build a self-made size exclusion chromatography (SEC) column and perform separation and characteristics. Then, we use the SEC column to systematically compare the efficiency with the most common EV isolation methods: Ultracentrifugation (UC) and total exosomes isolation commercial kit (TEI). The EVs isolated through different methods were characterized the yield and size of EVs, analyzed their protein profiles, the morphology and purity were observed under the transmission electron microscope. To further improve the quality and purity, we combined SEC and UC methods and established a two-steps method to isolated EVs from serum.Results: Self-made SEC column can well separate EVs from complex serum protein, and EVs enriched in the 8– 13 fractions with good morphology and yield. By systematically compare SEC with the commonly used UC and TEI kit, SEC is outstanding in all aspects and balances both isolation purity and yield. However, using the SEC method alone still has certain limitations and residual impurities. The SEC+UC combined method can cleverly solve the shortcomings of SEC and optimize the quality and purity of EVs from serum, which is much better than using one method alone.Conclusion: Our study presents the combination of size-exclusion chromatography and ultracentrifugation as a feasible and time-saving method to isolate high-quality and purity extracellular vesicles from serum.Keywords: extracellular vesicles, size-exclusion chromatography, ultracentrifugation, total exosomes isolation, combination methods

Xiaoning Cen,1,&ast; Yunmei Huang,2,&ast; Zhuangnian Lu,3,&ast; Wenjun Shao,4 Chenyi Zhuo,1 Chongchan Bao,5 Shi Feng,5 Cheng Wei,5 Xiqiang Tang,5 Lijun Cen,5 Wenwen Guo,5 Xinru Tian,5 Qianli Tang,5 Xusen Huang1 1General Surgery, Affiliated Hospital of YouJiang Medical University for Nationalities, Baise, 533000, Guangxi, People’s Republic of China; 2Department of Pathology, Affiliated Hospital of YouJiang Medical University for Nationalities, Baise, 533000, Guangxi, People’s Republic of China; 3Department of Pediatrics, Affiliated Hospital of YouJiang Medical University for Nationalities, Baise, 533000, Guangxi, People’s Republic of China; 4Medical college of Soochow University, Suzhou, Jiangsu, 215000, People’s Republic of China; 5YouJiang Medical University for Nationalities, Baise, 533000, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qianli TangYouJiang Medical University for Nationalities, Baise, 533000, Guangxi, People’s Republic of ChinaEmail htmgx@163.comXusen HuangGeneral Surgery, Affiliated Hospital of YouJiang Medical University for Nationalities, Baise, 533000, Guangxi, People’s Republic of ChinaEmail hxsfy@163.comBackground: LncRNAs play an important role in tumor initiation and development. However, the underlying involvement of lncRNA expression in colorectal carcinoma remains to be clarified.Methods: All analyses were performed in R software v4.0, SPSS v13.0, and GraphPad Prism 8. The “limma” package was used to identify differentially expressed lncRNAs between two groups with the threshold of |logFC| > 1 and P < 0.05. The “Survival” package was used to conduct survival analysis. HCT8 and SE480 cell lines were used to conduct further phenotype experiments, including transwell, wound-healing, CCK8 and colony formation assay. Gene set enrichment analysis was used to explore the biological pathway difference in high and low IGFL2-AS1 patients.Results: The lncRNA IGFL2-AS1 was highly expressed in colon adenocarcinoma (COAD) tissue and cell lines (HCT116, HCT8, HCT129, and SW480). The COAD patients with high IGFL2-AS1 were associated with a worse prognosis. Meanwhile, the knockdown of IGFL2-AS1 could significantly suppress the proliferation and invasion of COAD cells. Gene set enrichment analysis showed that the top five biological pathways involving IGFL2-AS1 were angiogenesis, epithelial–mesenchymal transition, KRAS signaling, myogenesis, and coagulation. Western blot results showed that the inhibition of IGFL2-AS1 could significantly reduce the N-cadherin, HIF1A and KRAS protein expression, yet increase the E-cadherin protein level. IGFL2-AS1 was also positively correlated with M0 macrophages, M2 macrophages, and neutrophils but negatively correlated with CD4+ memory T cells and CD8+ T cells.Conclusion: IGFL1-AS1 could seriously worsen patient outcomes and facilitate COAD progression, thus serving as an independent tumor marker.Keywords: IGFL2-AS1, lncRNA, colon cancer, immune

Qiao Tang, Li Wei, Xiaoqing Liu, Peng Hu Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Peng HuDepartment of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, 74 Linjiang Road, Yuzhong District, Chongqing, 400000, People’s Republic of ChinaTel +86 13608338064Email hp_cq@163.comBackground: Previous studies have shown that sofosbuvir-based regimens yield high sustained virological response rates in patients with hepatitis C virus (HCV) infection except for genotype 3b complicated with cirrhosis. This real-world study aims to explore the efficacy and safety of sofosbuvir-based regimens in Chinese patients with genotypes 3 and 6 infections, especially the impact of ribavirin coadministration on sustained virological response in cirrhotic patients with genotype 3b infection.Methods: This is a retrospective cohort study that included 101 patients initiated on sofosbuvir-based regimens. The main endpoint of treatment was sustained virological response at posttreatment week 12 (SVR12).Results: Overall, the SVR12 rates were 95.0% (96/101); specifically, the rates were 100% in sofosbuvir, 88.2% in sofosbuvir+ribavirin, 100% in sofosbuvir+daclatasvir, 100% in sofosbuvir+daclatasvir+ribavirin, 95.0% in sofosbuvir/velpatasvir, and 97.1% in sofosbuvir/velpatasvir+ribavirin (p=0.534). The SVR12 rates were comparable in patients infected with genotypes 3 and 6 (93.2% versus 97.6%, p=0.339). The SVR12 rate was 93.9% in cirrhotic patients (31/33). Among those infected with genotype 3, the SVR12 rate was 91.7% (22/24); the rate was 95.0% in those with ribavirin coadministration regimens, which was numerically higher than the 75.0% in those without ribavirin. However, no statistical difference was found (p=0.312). In total, five patients failed to achieve SVR12, including 3 patients with genotype 3b infection treated with ribavirin coadministration regimens (one of them was cirrhotic), 1 cirrhotic patient with genotype 3k infection, and 1 noncirrhotic patient with genotype 6a infection. No severe adverse event occurred.Conclusion: Real-world data show that sofosbuvir-based regimens are highly effective and safe for patients with HCV genotypes 3 and 6 infections.Keywords: daclatasvir, hepatitis C virus, ribavirin, sofosbuvir, velpatasvir

Jianmiao Wang,1 Yuping Zhang,1 Yuanyuan Chen,2 Mei Li,1 Hongyan Yang,2 Jinhua Chen,2 Qiaomin Tang,2 Jingfen Jin1,3 1Nursing Department, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 2Neurology Department, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 3Changxing Branch Hospital, The Second Affiliated Hospital of Zhejiang University School of Medicine, Huzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Jingfen JinThe Second Affiliated Hospital of Zhejiang University School of Medicine, No. 88 Jiefang Road, Shangcheng District, Hangzhou, Zhejiang Province, 310009, People’s Republic of ChinaFax +86-0571-87783778Email zrjzkhl@zju.edu.cnPurpose: To determine the effectiveness of rehabilitation nursing program interventions in patients with acute ischemic stroke.Patients and Methods: An assessment-blinded randomized controlled trial was conducted at a tertiary referral hospital in China. Eligible patients were stratified according to their weighted corticospinal tract lesion load and then randomly assigned to an experimental group (n = 121) or a control group (n = 103). The experimental group received rehabilitation nursing from well-trained, qualified nurses (30 minutes per session, two sessions per day for seven consecutive days). The control group received therapist-led rehabilitation with the same timing and frequency. Comparative analysis of the primary outcomes was performed to determine non-inferiority with a predetermined non-inferiority margin. The primary outcomes were the Motor Assessment Scale, Fugl-Meyer Assessment, and the Action Research Arm Test assessed at baseline and after seven days of treatment. The secondary outcomes were the modified Barthel Index, the National Institutes of Health Stroke Scale, and the modified Rankin Scale, evaluated before and after the intervention and at 4 and 12 weeks of follow-up.Results: Two hundred participants completed the trial. In both groups, all outcomes improved significantly after seven days and at follow-ups. The rehabilitation nursing program was non-inferior to therapist-led treatment with lower 95% confidence limits beyond the margins for primary outcomes (P < 0.001).Conclusion: Both treatments had comparable effects; however, no definite conclusion could be drawn. Adequately powered studies are required.Keywords: rehabilitation, nursing, acute ischemic stroke, motor function

Yanhui Tang,1,2,* Qi Tang,1,2,* Haicheng Wei,1,2,* Pinzhang Hu,1,2 Donghua Zou,3 Rixiong Liang,1,2 Yu Ling1,2 1Department of Ophthalmology, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530022, People’s Republic of China; 2Department of Ophthalmology, The First People’s Hospital of Nanning, Nanning, Guangxi, 530022, People’s Republic of China; 3Department of Neurology, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rixiong Liang; Yu LingDepartment of Ophthalmology, The Fifth Affiliated Hospital of Guangxi Medical University, 89 Qixing Road, Nanning, Guangxi, 530022, People’s Republic of ChinaTel +86 7713919709; +86 7712636273Email lrx4896@163.com; lingyu3919709@163.comPurpose: This study aimed to identify genes that may be effective in diagnosing or treating diabetic retinopathy (DR), the most common complication of diabetes mellitus (DM).Methods: Differentially expressed genes (DEGs) were identified between DR and DM in GSE146615 dataset. DEGs that were consistently up- or down-regulated under both standard glucose and high glucose conditions were identified as common genes and used to generate a protein–protein interaction network and modules. The module genes were assessed for the area under the receiver operating characteristic curve (AUC), leading to the identification of hub genes. Differentially methylated probes in GSE76169 were also compared with common DEGs to identify specific methylation markers of DR. Enrichment analysis was used to explore the biological characteristics. The Short Time-series Expression Miner algorithm was used to identify genes that were progressively dysregulated in the sequence: healthy controls < DM < DR.Results: A total of 1917 common genes were identified for seven modules. The eight genes with AUC > 0.8 under high glucose and standard glucose conditions were considered as hub genes. The module genes were significantly enriched during vascular smooth muscle cell development and regulation of oxygen metabolism, while 92 methylation markers were involved in the similar terms. Among the progressively dysregulated genes, three intersection genes under both standard glucose and high glucose conditions were found to be module genes and were considered as key genes.Conclusion: We identified eight potential DR-specific diagnostic and therapeutic genes, whose abnormal expression can cause oxidative stress, thus favoring the course of the disease.Keywords: diabetic retinopathy, oxidative stress, glucose, cluster analysis, hub genes

Yingnan Zhao,1,2 Yanping Li,2 Qinhui Liu,1 Qin Tang,1,2 Zijing Zhang,1,2 Jinhang Zhang,1,2 Cuiyuan Huang,1,2 Hui Huang,1,2 Guorong Zhang,1,2 Jian Zhou,1,2 Jiamin Yan,1,2 Yan Xia,1,2 Zhiyong Zhang,1,2 Jinhan He1,2 1Department of Pharmacy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2Laboratory of Clinical Pharmacy and Adverse Drug Reaction, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of ChinaCorrespondence: Zhiyong Zhang; Jinhan HeDepartment of Pharmacy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of ChinaTel/Fax +86-28-85426416Email asg-yong@163.com; jinhanhe@scu.edu.cnBackground and Purpose: Cholesterol is an essential lipid and its homeostasis is a major factor for many diseases, such as hyperlipidemia, atherosclerosis, diabetes, and obesity. Sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin (Cana) is a new kind of hypoglycemic agent, which decreases urinary glucose reabsorption and reduces hyperglycemia. Cana has been shown to regulate serum lipid, decrease serum triglyceride and increase serum high-density lipoprotein-cholesterol (HDL-C), and improve cardiovascular outcomes. But evidence of how Cana impacted the cholesterol metabolism remains elusive.Methods: We treated Cana on mice with chow diet or western diet and then detected cholesterol metabolism in the liver and intestine. To explore the mechanism, we also treated hepG2 cells and Caco2 cells with different concentrations of Cana.Results: In this study, we showed that Cana facilitated hepatic and intestinal cholesterol efflux. Mechanically, Cana via activating adenosine monophosphate-activated protein kinase (AMPK) increased the expression of ATP-binding cassette (ABC) transporters ABCG5 and ABCG8 in liver and intestine, increased biliary and fecal cholesterol excretion.Conclusion: This research confirms that Cana regulates cholesterol efflux and improves blood and hepatic lipid; this may be a partial reason for improving cardiovascular disease.Keywords: canagliflozin, ATP-binding cassette (ABC) transporters G5/8, cholesterol efflux, AMPK

Li Chen,1 Zhi-xing Liu,1 Qiu-chen Bi,2 Jun Zhao,3 Qing-rong Liang,2 Qun Tang2– 4 1Department of Ultrasonic Radiology, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 2Institute for Advanced Study, Nanchang University, Nanchang, People’s Republic of China; 3Jiangxi Provincial Key Laboratory of Preventive Medicine, School of Public Health, Nanchang University, Nanchang, People’s Republic of China; 4Jiangxi Province Key Laboratory of Laboratory Animal, Nanchang, People’s Republic of ChinaCorrespondence: Qun TangJiangxi Provincial Key Laboratory of Preventive Medicine, School of Public Health, Nanchang University, Xuefu Avenue No. 999, Honggutan District, Nanchang, 330031, People’s Republic of ChinaTel/Fax +86 791-83969963Email tangqun@ncu.edu.cnBackground: It is difficult to achieve whole tumor ablation using percutaneous ethanol ablation therapy (PEAT) due to the limited diffusion of ethanol.Purpose: To determine whether chemotherapy can be an adjuvant therapy to benefit PEAT, we investigated ultrasound-guided percutaneous ethanol-paclitaxel combined therapy (PEPCT) of VX2 carcinoma, a rabbit liver cancer model.Materials and Methods: A six-arm study was designed to quantify the correlation between paclitaxel (PTX) dose and tumor necrosis or cell proliferation, including sham group (2 mL saline, n=6), incremented dose of PTX (0, 12.5, 25, 37.5 mg) in 2.0 mL ethanol (n=6) and a conventional PEAT group (n=6) as comparison. The test was followed by contrast-enhanced ultrasonic (CEUS) before 7-day sacrifice, tumor harvest, and sectioning. Tumor necrosis ratio was radiologically and histologically quantified; modified proliferation index (m-PI) was proposed to quantify the PTX’s pharmacological effects. A linear regression model was set to correlate the PTX dose with tumor necrosis ratio or cell proliferation index. The difference of radiological, histological necrosis ratio (HNR) and modified PI in six groups was analyzed via Kruskal–Wallis H-test, Welch analysis of variance and one-way ANOVA.Results: Incremental increases of PTX (0, 12.5, 25, 37.5 mg) correlated with greater fraction of tumor necrosis (R2 = 0.946, P< 0.001 for radiological necrosis ratio [RNR], R2 = 0.843, P< 0.001 forHNR), indicating that one week after procedure PTX’s anti-proliferation and ethanol’s dehydration co-induced severe tumor necrosis. Correlation analysis further testified a significant association between PTX dose and m-PI (R2 = 0.860, P< 0.001).Conclusion: These results suggest a clear role for PTX-induced cytotoxicity and support the use of chemotherapeutic drugs in ablation therapy.Keywords: percutaneous ethanol ablation therapy, PEAT, paclitaxel, PTX, new indication, combined therapy, VX2 liver cancer model

Qingchao Tang,1 Yihao Zhu,1 Huan Xiong,1 Xiangzong Sheng,1 Zhiqiao Hu,1 Hanqing Hu,1 Rui Huang,1 Qian Zhang,1 Ziming Yuan,1 Lei Xie,2 Zhifeng Gao,1 Yuliuming Wang,1 Guiyu Wang,1 Xishan Wang3 1Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 2Heilongjiang Agricultural Reclamation General Hospital, Harbin, People’s Republic of China; 3Department of Colorectal Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Xishan WangDepartment of Colorectal Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Beijing, People’s Republic of ChinaTel +86 135 52367779Email wxshan1208@126.comGuiyu WangDepartment of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, People’s Republic of ChinaTel +86 451 86296599Email guiywang@163.comBackground: Natural orifice specimen extraction surgery (NOSES) has been successfully applied to the treatment of gastric, colorectal cancer (CRC). However, the development of NOSES is still in the exploratory stage, and there is still no strong evidence-based medical evidence.Patients and Methods: From January 2013 to June 2017, consecutive patients with colorectal cancer who underwent transluminal resection, anastomosis, and specimen extraction and those who underwent conventional laparoscopic resection were enrolled. Propensity score matching was used to align clinicopathological features between the two groups.Results: A total of 372 patients were eventually included in this study, 186 in each group. According to perioperative information and postoperative follow-up in both groups, the NOSES group had less blood loss (P = 0.011), shorter time to recovery of gastrointestinal function (P < 0.001), shorter postoperative hospital stay (P = 0.037). The NOSES group had fewer postoperative analgesics (P < 0.001), lower postoperative pain scores (P < 0.001), and lower incidence of postoperative complications (P = 0.017). Compared with the LA (laparoscopic) group, the NOSES group had better physical function (P< 0.05), role function (P< 0.001), emotional function (P< 0.001) and global health status than LA group, while symptoms such as pain (P< 0.001), insomnia (P< 0.001), constipation (P< 0.001) and diarrhea (P< 0.05) were less severe in the NOSES group. In addition, the NOSES group had higher body image scores. Overall survival (OS) and disease-free survival (DFS) were not significantly different between the two groups.Conclusion: For surgical treatment of colorectal cancer, NOSES has advantages in reducing postoperative pain, recovery of gastrointestinal function, postoperative quality of life, and improving patients’ satisfaction with abdominal wall aesthetics. There was no difference in long-term survival between NOSES and conventional laparoscopic surgery.Keywords: colorectal cancer, laparoscopic surgery, perioperative efficacy, natural orifice specimen extraction, survival

Ziming Yuan,1 Zhixun Zhao,2 Hanqing Hu,1 Yihao Zhu,1 Weiyuan Zhang,1 Qingchao Tang,1 Rui Huang,1 Feng Gao,1 Chaoxia Zou,3 Guiyu Wang,1 Xishan Wang1,2 1Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 2Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang, People’s Republic of ChinaCorrespondence: Xishan Wang Email wxshan_1208@126.comGuiyu Wang Email guiywang@163.comBackground: The liver is the most frequent site for metastatic spread in colorectal cancer (CRC) patients, and these patients have much poorer prognosis than those without metastasis. Previous studies have shown that IgG Fc binding protein (FCGBP) plays important roles in tumorigenesis, progression, and prognosis, but its role in CRC metastasis remains unclear.Purpose: In this study, we are aimed to explore the significance of FCGBP in liver metastatic CRC (LMCRC) patients.Methods: We analyzed the expression of FCGBP RNA between CRC primary samples and liver metastatic samples in the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA). Next, we assessed the expression of FCGBP protein in 135 paired primary CRC (PC) samples and LMCRC samples. Finally, we explored the relationship between the expression features and clinicopathological characteristics.Results: The expression data of FCGBP were obtained from the GEO and TCGA databases. FCGBP RNA expression was evaluated between primary lesions (PC) and liver metastatic lesions (LM). FCGBP RNA was down-regulated in PC and LM, and especially lower in LM (p< 0.001). Next, the expression of FCGBP protein was evaluated by an immunohistochemistry array in 135 paired primary tumor tissues and metastatic tissues. We found that FCGBP protein was down-regulated in primary lesions and metastatic lesions, especially in metastatic lesions. According to the immunohistochemistry score (SI), each cohort was divided into FCGBP-positive (SI=4– 12) and FCGBP-negative (SI=0– 3) groups. In both groups, the levels of CEA (PC group, 3.880 vs 77.049, p< 0.001; LM group, 3.890 vs 14.239, p=0.008) and CA19-9 (PC group, 8.610 vs 111.700, p< 0.001; LM group, 7.660 vs 19.380, p=0.037) were lower than those in the FCGBP-negative group. FCGBP positivity in the LM cohort was an independent risk factor in both overall survival (HR 1.573, 95% Cl [1.017– 2.433], p=0.042) and disease-free survival (HR 1.869, 95% Cl [1.256– 2.781], p=0.002).Conclusion: This study found a relationship between FCGBP expression and clinical information of LMCRC patients, and found that FCGBP expression decreased with disease development. The expression of FCGBP in liver metastasis is associated with both the overall and progression-free survival. Our results show that FCGBP could be a promising prognostic factor for LMCRC.Keywords: colorectal cancer, IgG Fc binding protein, liver metastasis, prognosis, biomarker