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Yinying Li,1 Qiuming Li,2 Haihua Lei,3 Xiaorong Wei,4 Tao Feng,2 Huajiao Qin,2 Hongchun Huang,2 Minchao Duan1,2 1The Second Clinical Medical College, Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Wuming Hospital of Guangxi Medical University, Nanning, Guangxi, 530199, People’s Republic of China; 3Radiological department, Wuming Hospital of Guangxi Medical University, Nanning, Guangxi, 530199, People’s Republic of China; 4Clinical Laboratory, Wuming Hospital of Guangxi Medical University, Nanning, Guangxi, 530199, People’s Republic of ChinaCorrespondence: Minchao Duan, Department of Respiratory and Critical Care Medicine, Wuming Hospital of Guangxi Medical University, Nanning, Guangxi, 530199, People’s Republic of China, Tel/Fax +86 15507711966, Email musicladyd@sina.comBackground: Pulmonary infection is a common clinical complication associated with glucocorticoid. There have been no reported cases of mixed infections involving Nocardia and Pneumocystis jirovecii combined with anti-synthetase syndrome (ASS) activity.Methods: This study conducted a retrospective analysis of the clinical data from a patient with active ASS, treated for a pulmonary coinfection.Results: The patient exhibited fever, asthma, and cough as initial symptoms. Chest CT scan revealed multiple infiltration shadows, consolidation shadows, nodules, mass shadows, and internal cavities in both lungs. BALF mNGS detected Nocardia terpene and Pneumocystis jiroveci. Treatment with sulfamethoxazole/trimethoprim and corticosteroids led to an improvement. However, the patient experienced recurrent fever and a new rash with the reduction of the glucocorticoid dosage. Further investigation identified positive anti-Jo-1 and anti-Ro-52 antibodies and myogenic lesions on electromyography, which confirmed the diagnosis of ASS. Following treatment with immunoglobulin, methylprednisolone, and cyclosporine, the patient’s condition significantly improved.Conclusion: Immunodeficiency patients are susceptible to opportunistic infections. mNGS is valuable for diagnosis and treatment. Although the image of Nocardia terpene and Pneumocystis jiroveci infections lack specificity, they exhibit distinctive features. Should fever and skin lesions reoccur post-effective anti-infective therapy, it is imperative to explore non-infectious causes and expedite autoantibody testing.Keywords: co-infection, Nocardia terpene, Pneumocystis jiroveci, anti-synthetase syndrome, anti-Ro-52 antibody, anti-Jo-1 antibody

Tingting Shao,1 Chengwei Zhu,2 Hanning Lei,2 Yiru Jiang,3 Haitao Wang,4 Cai Zhang2 1Institute of Early Childhood Education, Faculty of Education, Beijing Normal University, Beijing, People’s Republic of China; 2Collaborative Innovation Center of Assessment for Basic Education Quality, Beijing Normal University, Beijing, People’s Republic of China; 3School of Education Science, Shangrao Normal University, Shangrao, People’s Republic of China; 4Department of education, Ocean University of China, Qingdao, People’s Republic of ChinaCorrespondence: Cai Zhang, Collaborative Innovation Center of Assessment for Basic Education Quality, Beijing Normal University, No. 19 Xinjiekouwai Street, Beijing, 100875, People’s Republic of China, Email caizhangbj@163.comPurpose: With the increasing ubiquity of smartphones in our daily lives, technoference has emerged as a novel threat to family relationships and child development. This study explored the impact of parent-child technoference on child problematic smartphone use and its underlying mechanism and potential gender difference among children.Participants and Methods: The participants were 3032 fourth-grade students (42.6% female; 80.6% one-child families; 32.9% lower income level families, 33.3% middle income level families; Mage = 10.59 years, SD=0.32) from 535 primary schools. Students in the target classes were invited to participate anonymously in the questionnaire survey in classrooms. Then, SPSS, AMOS and other software were used to analyze the data.Results: 1) Parent-child technoference, negative parenting styles and child problematic smartphone use were positively correlated with each other, while they were negatively correlated with parent-child relationship; 2) Parent-child technoference can not only directly and positively predict child problematic smartphone use, but also indirectly and positively predict child problematic smartphone use through parent-child relationship and negative parenting styles respectively; 3) Parent-child relationship and negative parenting styles play a chain mediating role between parent-child technoference and child problematic smartphone use; 4) There are significant gender differences in the chain mediation model.Conclusion: The results showed that parent-child technoference significantly affected child problematic smartphone use through a chain mediation of parent-child relationship and negative parenting styles. Gender differences were observed, with girls experiencing a more pronounced disruption in the parent-child relationship, while boys were more likely to develop problematic smartphone use. In cases of strained parent-child relationships due to technoference, girls also tended to perceive more negative parenting styles. These findings promote parents’ understanding of the influencing factors and mechanisms of child problematic smartphone use, especially helpful for follow-up measures to prevent and intervene child problematic smartphone use from the perspective of families and parents.Keywords: parent-child technoference, parent-child relationship, negative parenting styles, child problematic smartphone use, gender difference

Jiao Chen, Danmei Luo, Chengxia Sun, Xiaolan Sun, Changmao Dai, Xiaohong Hu, Liangqing Wu, Haiyan Lei, Fang Ding, Wei Chen, Xueping Li Geriatric Department, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Xueping Li, Chengdu University of Traditional Chinese Medicine, No. 37, Shier Bridge Road, Chengdu, Sichuan, People’s Republic of China, Tel +86-18380251086, Email 3173907@qq.comPurpose: Building and validating a clinical prediction model for novel coronavirus (COVID-19) re-positive cases in malnourished older adults.Patients and Methods: Malnourished older adults from January to May 2023 were retrospectively collected from the Department of Geriatrics of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine. They were divided into a “non-re-positive” group and a “re-positive” group based on the number of COVID-19 infections, and into a training set and a validation set at a 7:3 ratio. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to identify predictive factors for COVID-19 re-positivity in malnourished older adults, and a nomogram was constructed. Independent influencing factors were screened by multivariate logistic regression. The model’s goodness-of-fit, discrimination, calibration, and clinical impact were assessed by Hosmer-Lemeshow test, area under the curve (AUC), calibration curve, decision curve analysis (DCA), and clinical impact curve analysis (CIC), respectively.Results: We included 347 cases, 243 in the training set, and 104 in the validation set. We screened 10 variables as factors influencing the outcome. By multivariate logistic regression analysis, preliminary identified protective factors, risk factors, and independent influencing factors that affect the re-positive outcome. We constructed a clinical prediction model for COVID-19 re-positivity in malnourished older adults. The Hosmer-Lemeshow test yielded χ2 =5.916, P =0.657; the AUC was 0.881; when the threshold probability was > 8%, using this model to predict whether malnourished older adults were re-positive for COVID-19 was more beneficial than implementing intervention programs for all patients; when the threshold was > 80%, the positive estimated value was closer to the actual number of cases.Conclusion: This model can help identify the risk of COVID-19 re-positivity in malnourished older adults early, facilitate early clinical decision-making and intervention, and have important implications for improving patient outcomes. We also expect more large-scale, multicenter studies to further validate, refine, and update this model.Keywords: malnutrition, COVID-19, re-positive, clinical prediction model

Chunhong Li,1,* Zhen Wang,1,* Yifeng Zhang,1 Yuqing Zhu,1 Maochang Xu,1 Hui Lei,1 Dan Zhang1,2 1Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 2Green Pharmaceutical Technology Key Laboratory of Luzhou, School of Pharmacy, Southwest Medical University, Luzhou, 646000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hui Lei; Dan Zhang, Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, 1-1 Xianglin Road, Luzhou, Sichuan, 646000, People’s Republic of China, Tel +86 17360593759 ; +86 18982700067, Email huilei@swmu.edu.cn; zhangdan@swmu.edu.cnPurpose: Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer. However, the effect of current treatment strategies by inducing tumor cell apoptosis alone is not satisfactory. The growth, metastasis and treatment sensitivity of tumors can be strongly influenced by cancer-associated fibroblasts (CAFs) in the microenvironment. Effective cancer therapies may need to target not only the tumor cells directly but also the CAFs that protect them.Methods: Celastrol and small-sized micelles containing betulinic acid were co-encapsulated into liposomes using the thin-film hydration method (CL@BM). Folic acid was further introduced to modify liposomes as the targeting moiety (F/CL@BM). We established a novel NIH3T3+4T1 co-culture model to mimic the tumor microenvironment and assessed the nanocarrier’s inhibitory effects on CAFs-induced drug resistance and migration in the co-culture model. The in vivo biological distribution, fluorescence imaging, biological safety evaluation, and combined therapeutic effect evaluation of the nanocarrier were carried out based on a triple-negative breast cancer model.Results: In the present study, a novel multifunctional nano-formulation was designed by combining the advantages of sequential release, co-loading of tretinoin and betulinic acid, and folic acid-mediated active targeting. As expected, the nano-formulation exhibited enhanced cytotoxicity in different cellular models and effectively increased drug accumulation at the tumor site by disrupting the cellular barrier composed of CAFs by tretinoin. Notably, the co-loaded nano-formulations proved to be more potent in inhibiting tumor growth in mice and also showed better anti-metastatic effects in lung metastasis models compared to the formulations with either drug alone. This novel drug delivery system has the potential to be used to develop more effective cancer therapies.Conclusion: Targeting CAFs with celastrol sensitizes tumor cells to chemotherapy, increasing the efficacy of betulinic acid. The combination of drugs targeting tumor cells and CAFs may lead to more effective therapies against various cancers.Keywords: liposomes, targeted delivery, triple-negative breast cancer, anti-tumor, combination therapy, sequential drug delivery

Jihui Lu, Zhijia Wang, Desheng Cai, Xiaoyu Lin, Xuemei Huang, Zhihua Yuan, Yaozhi Zhang, Haimin Lei, Penglong Wang School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of ChinaCorrespondence: Penglong Wang, School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China, Email wpl581@126.com Haimin Lei, School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China, Email hm_lei@126.comBackground: Deaths from bacterial infections have risen year by year. This trend is further aggravated as the overuse antibiotics and the bacterial resistance to all known antibacterial agents. Therefore, new therapeutic alternatives are urgently needed.Methods: Enlightenment the combination usage of traditional herb medicine, one carrier-free binary nanoparticles (GA-BBR NPs) was discovered, which was self-assembled from gallic acid and berberine through electrostatic interaction, π-π stacking and hydrophobic interaction; and it could be successfully prepared by a green, cost-effective and “one-pot” preparation process.Results: The nanoparticles exhibited strong antibacterial activity and biofilm removal ability against multidrug-resistant S. aureus (MRSA) by downregulating mRNA expression of rpsF, rplC, rplN, rplX, rpsC, rpmC and rpsH to block bacterial translation mechanisms in vitro and in vivo, and it had well anti-inflammatory activity and a promising role in promoting angiogenesis to accelerate the wound healing on MRSA-infected wounds model in vivo. Additionally, the nanoparticles displayed well biocompatibility without cytotoxicity, hemolytic activity, and tissue or organ toxicity.Conclusion: GA-BBR NPs originated from the drug combination has potential clinical transformation value, and this study provides a new idea for the design of carrier-free nanomedicine derived from natural herbals.Graphical Abstract: Keywords: carrier-free binary self-assemblies, natural herbal ingredients, antibacterial, wound healing, anti-inflammatory, angiogenesis

Ziyang Wang,1,2 Meng Liu,1,2 Hao Lei,1,2 Panpan Lei,3 Xinyi Liu,1,2 Jing Zhang,1,2 Shengxiang Xiao,2 Yan Zheng,1,2 Yi-Guo Feng2 1Department of Dermatology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Department of Dermatology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 3Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Xi’an Jiaotong University School of Life Science and Technology, Xi’an, People’s Republic of ChinaCorrespondence: Yi-Guo Feng, Department of Dermatology, the Second Affiliated Hospital of Xi’an Jiaotong University, School of Medicine, Xi’an, 730070, People’s Republic of China, Email fengyiguo70@163.comBackground: Eruptive syringoma (ES) is a clinical variant of the appendageal tumor syringoma. Around 75% of ES arise in the head or neck, which makes them unsightly. ES is common in patients with amyloidosis, diabetes, and Down’s syndrome, suggesting that it may be associated with potential systemic effects. ES is a rare tumor with the unclear pathogenesis and no effective treatment.Methods: A PubMed search of ES was conducted. Plasma samples of patients with ES were acquired from the Department of Dermatology at Xi’an Jiaotong University’s Second Affiliated Hospital. After removing highly abundant proteins, plasma samples were subjected to proteomics and metabolomics analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS).Results: LC-MS/MS revealed 71 differentially expressed proteins and 18 differentially abundant metabolites. The functional analysis highlighted the importance of complement binding, coagulation, secretory granules and vesicle lumen. Further, the study revealed 15 hub genes associated with FGG, GC, APOE, FGA, FGB, C4A, C3, CRP, C4B, FLNA, TAGLN2, ANXA5, MYL6, MYL12B, and TLN1 organized into three clusters. The seed genes in each cluster were GC, FLNA, and MYL6. In addition, glycol metabolism was associated with variable abundance of serum metabolites, which explains the relatively high rate of ES among diabetics.Conclusion: This study suggests that immunological inflammation and tumor glycol metabolism may play significant role in the pathophysiology of ES.Keywords: eruptive syringomas, proteomics and metabolomics analysis, complement and coagulation cascades, glycol-metabolism

Pingping Su,1 Jian An,1,2 Lirui Yu,1 Huifang Lei,1 Lixiang Huang,1 Xiaodan Mao,1,3 Pengming Sun1,3 1Department of Gynecology, Laboratory of Gynecologic Oncology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, 350001, People’s Republic of China; 2Department of Gynecology, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, People’s Republic of China; 3Fujian Key Laboratory of Women and Children’s Critical Diseases Research, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, 350001, People’s Republic of ChinaCorrespondence: Pengming Sun; Xiaodan Mao, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350001, People’s Republic of China, Tel +86-591-87558732, Fax +86-591-87551247, Email fmsun1975@fjmu.edu.cn; maodan1985@yeah.netPurpose: This study aimed to explore lymphocyte subsets for the personalized prediction of endometrioid endometrial cancer (EEC) risk and evaluated the correlation between immune cells and International Federation of Gynecology and Obstetrics (FIGO) staging in patients with EEC.Patients and Methods: A case-control study was conducted to analyze the clinical data of 421 patients admitted to Fujian Maternity and Child Health Hospital from October 2017 to December 2021. t-tests or Mann–Whitney U-tests were used to analyze the percentages and absolute counts of peripheral blood lymphocyte subsets in patients with EEC and patients without cancer. The independent risk factors for ECC and FIGO stage were analyzed via multivariate binary logistic regression. The receiver operating characteristic curve was calculated to evaluate the prediction efficacy of risk factors on ECC.Results: The CD4+ T% in the 121 patients with EEC was lower than in the 300 patients without cancer (P = 0.013). The absolute counts of peripheral CD4+ T (P = 0.002) and T cells (P = 0.007) in 37 patients with EEC were lower than in 51 patients without cancer. Multivariate binary logistic regression analysis showed that CD4+ T% and natural killer cell (NK)% were independent risk factors for FIGO staging in patients with EEC. NK% was significantly higher in patients with advanced stage (FIGO III and IV) than those with early EEC (FIGO I and II) (P = 0.004). To determine the early and advance FIGO stage of EEC, the cutoff value of NK% was calculated as 19.94%.Conclusion: With the decrease of CD4+ T counts, the immune status of patients with EEC is impaired. NK cells may help in the evaluation of the prognosis of patients with EEC and are likely to be an independent risk factor for FIGO staging in patients with EEC.Keywords: CD4+ T lymphocyte, NK cells, endometrioid endometrial cancer, lymphocyte subsets, immune

Ningning Zhang,1 Dan Tao,2 Haike Lei,3 Qing Shao,1 Yumin Liu,4 Hua Long,4 Xiaohua Zeng1 1Department of Breast Cancer Center, Chongqing University Cancer Hospital, Chongqing, People’s Republic of China; 2Department of Radiation Oncology, Chongqing University Cancer Hospital, Chongqing, People’s Republic of China; 3Department of Appointment and Follow-up Center, Chongqing University Cancer Hospital, Chongqing, People’s Republic of China; 4Department of Medical Record, Chongqing University Cancer Hospital, Chongqing, People’s Republic of ChinaCorrespondence: Xiaohua Zeng, Department of Breast Cancer Center, Chongqing University Cancer Hospital, 181 Han Yu Road, Shapingba District, Chongqing, 400030, People’s Republic of China, Tel/Fax +86-23-65310859, Email zxiaohuacqu@126.comPurpose: This study aimed to evaluate the influence of hepatitis B virus (HBV) infection status on the initial metastatic pattern and prognosis in metastatic breast cancer (MBC).Methods: MBC patients admitted to Chongqing University Cancer Hospital between January 2011 and December 2019 were enrolled. The association of HBV infection status with clinicopathological features was analyzed. The impact of HBV infection status on initial metastatic pattern and survival was evaluated.Results: A total of 1124 patients with MBC, including 310 with de novo (cohort A) and 814 with relapsed metastatic disease (cohort B), were eligible for this study. Seropositive HBsAg was identified in 28 (9.0%) and 68 (8.4%) patients in cohort A and B, respectively. The clinicopathological features are similar between HBsAg-positive and HBsAg-negative patients. There was no significant association of HBV infection status with the rate of metastasis at each site in de novo and relapsed MBC. HBsAg-positive patients tended to have longer metastasis-free survival (MFS) and/or overall survival (OS) time, but it was not the independent prognostic factor.Conclusion: In conclusion, HBV infection status does not influence the initial metastatic pattern and the prognosis of MBC patients.Keywords: hepatitis B virus, infection status, metastatic breast cancer, initial metastatic pattern, prognosis

Dan Lu,1,* Tao Ma,1,* Gemin Zhu,2,* Tao Zhang,3 Naibing Wang,1 Hui Lei,2 Jing Sui,1 Zhiguo Wang,1 Shiming He,1 Lei Chen,1 Jianping Deng3 1Department of Neurosurgery, Xi’an International Medical Center Hospital, Xi’an, People’s Republic of China; 2Department of Neurology, Xi’an Central Hospital, Xi’an, People’s Republic of China; 3Department of Neurosurgery, Tangdu Hospital, Air Force Medical University, Xi’an, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianping DengDepartment of Neurosurgery, Tangdu Hospital, Air Force Medical University, Xi’an, People’s Republic of China, Email 13991139395@163.com; Lei ChenDepartment of Neurosurgery, Xi’an International Medical Center Hospital, Xi’an, People’s Republic of China, Email clzx1986@126.comObjective: This work aimed to retrospectively analyze Willis covered stent (WCS)’s therapeutic efficacy in intracranial pseudoaneurysms (PSAs) of the internal carotid artery (ICA).Methods: Between June 2018 and July 2021, 56 individuals with intracranial PSAs of the ICA treated with WCS in three centers were included to analyze information regarding medical records, operative parameters, imaging findings and follow-up data.Results: All WCSs were successfully targeted to the ICA lesions. Total exclusion of PSA was found in 53 cases (94.6%) right upon surgery, and mild endoleak into the aneurysm remained in 3 cases (5.4%). Intraoperative thrombosis occurred in 1 case (1.8%), and tirofiban was utilized for recanalization. Follow-up by angiography showed total aneurysm occlusion in the total number of individuals, including in the 3 above cases with residual endoleak. In-stent stenosis occurred in 7 (12.5%) patients. No stent-related ischemic event was encountered. Predictive factors of late in-stent stenosis following WCS implantation in this patient group were irregular post-operative antiplatelet treatment (p = 0.015) and C4-C5 segment of the ICA (p = 0.043).Conclusion: WCSs are effective in treating intracranial PSAs of the ICA.Keywords: Willis covered stent, intracranial pseudoaneurysms, internal carotid artery, endoleak, in-stent stenosis

HuiFang Lei,1,2,&ast; ShuXia Xu,3,&ast; XiaoDan Mao,1,2 XiaoYing Chen,4 YaoJia Chen,1,2 XiaoQi Sun,4 PengMing Sun1,2,4 1Laboratory of Gynecologic Oncology, Department of Gynecology, Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 2Fujian Key Laboratory of Women and Children’s Critical Diseases Research, Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 3Department of Pathology, Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 4Department of Gynecology, Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: XiaoQi Sun; PengMing SunLaboratory of Gynecologic Oncology, Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, No. 18 Daoshan Road, Fuzhou, 350001, Fujian, People’s Republic of ChinaEmail sunfemy@hotmail.com; fmsun1975@fjmu.edu.cnPurpose: This study assessed the predictive value of the preoperative systemic immune-inflammatory index (SII) for lymph node metastasis (LNM) in endometrial cancer (EC) patients.Methods: We retrospectively included 392 EC patients between January 2013 and January 2019. Data on clinical indicators including age, body mass index (BMI), menopause, serum inflammatory immune index, serum tumor markers, history of diabetes and hypertension, stage, histological type, and myometrial invasion (MI) were collected. The association between clinical indicators and LNM was evaluated.Results: The results indicated that neutrophil (NE), monocyte (MO) counts, SII, cancer antigen 125 (CA125), cancer antigen 153 (CA153), cancer antigen 199 (CA199), and the expression of estrogen receptor (ER) and Ki67 were higher in EC patients with LNM than in those without LNM (P< 0.05). Lymph vascular space invasion (LVSI) was also associated with LNM (P< 0.05). Consequently, the SII, CA125, CA153 and LVSI were found to be independent risk factors for LNM, and a nomogram including these indicators was performed. The ROC curve analysis showed that compared with a single index, the combination of the SII, CA125, CA153 and LVSI significantly improved the efficiency of diagnosing LNM in EC patients (AUC=0.865, P < 0.001). Moreover, the SII was significantly associated with age, menopause, and FIGO stage (P < 0.05). Further logistic regression analysis suggested that elevated serum SII was an independent risk factor for MI and progression to a higher pathological grade in young premenopausal EC patients. In addition, elevated SII was an independent risk factor for advanced EC progression in age ≥ 55 or postmenopausal EC patients.Conclusion: An elevated SII is an independent risk factor for LNM in patients with EC. In addition, the SII can be used as a predictor of MI and higher pathological grade in young premenopausal EC patients.Keywords: systemic immune-inflammatory index, neutrophil, platelet, lymphocyte count, lymph node metastasis, endometrial cancer

Bing Xu, Mengmeng Yan, Fei Zhou, Desheng Cai, Wenbo Guo, Xiaohui Jia, Runping Liu, Tao Ma, Tong Li, Feng Gao, Penglong Wang, Haimin Lei School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of ChinaCorrespondence: Penglong Wang; Haimin Lei Email wpl581@126.com; hm_lei@126.comBackground: The clinical utility of camptothecin (CPT) is restricted by poor aqueous solubility, high lipophilicity, active lactone ring instability, and off-targeted toxicities. We report here a prostate-specific membrane antigen (PSMA) and esterase dual responsive self-assembled nanoparticles (CPT-WT-H NPs) for highly efficient CPT delivery and effective cancer therapy.Methods and Results: In this study, smart self-assembled nanoparticles CPT-WT-H NPs were elaborately designed and synthesized by combing hydrophobic CPT with hydrophilic PSMA-responsive penta-peptide via a cleavable ester bond. This dual responsive nanoparticle with negatively charged surface first respond to the extracellular PSMA and then to the intracellular esterase, achieving a programmable release of CPT at the tumor site and producing the byproducts of biocompatible glutamic acid and aspartic acid. Our data demonstrated that CPT-WT-H NPs exhibited greatly improved water solubility and stability. Results from MTT and flow cytometry showed CPT-WT-H NPs exhibited significantly higher cytotoxicity as well as apoptosis-inducing activity against PSMA-expressing LNCaP-FGC cells than the non-PSMA-expressing cancer cells, showing excellent cytotoxic selectivity. Moreover, the unique nanostructure provided the efficient transportation of CPT to tumor site, which resulted in the effective inhibition of tumor growth and low systemic toxicity in vivo.Conclusion: CPT-WT-H NPs exhibited excellent in vitro PSMA-response ability and in vivo antitumor activity and safety, holding the promise to become a new and potent anticancer drug. The current research presents a promising strategy for efficient drug delivery.Keywords: CPT prodrug, dual responsive, sequential drug release, prostate-specific membrane antigen, self-assembly

Tianxin Mao,1,2 David Dinges,3 Yao Deng,1,2 Ke Zhao,2 Zijing Yang,2,4 Hui Lei,2 Zhuo Fang,2 Fan Nils Yang,2 Olga Galli,3 Namni Goel,5 Mathias Basner,3 Hengyi Rao1– 3 1Key Laboratory of Applied Brain and Cognitive Sciences, School of Business and Management, Shanghai International Studies University, Shanghai, People’s Republic of China; 2Center for Functional Neuroimaging, Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA; 3Division of Sleep and Chronobiology, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA; 4School of Medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China; 5Biological Rhythms Research Laboratory, Department of Psychiatry and Behavioral Sciences, Rush University Medical Center, Chicago, IL, USACorrespondence: Hengyi RaoCenter for Functional Neuroimaging & Department of Neurology, University of Pennsylvania Perelman School of Medicine, Room D502, Richards Medical Research Building, 3700 Hamilton Walk, Philadelphia, PA, 19104-4202, USATel +1 215-746-2470Email hengyi@pennmedicine.upenn.eduPurpose: Sleep loss impairs a range of neurobehavioral functions, particularly vigilant attention and arousal. However, the detrimental effects of sleep deprivation on inhibition control and its relationship to vigilant attention impairments remain unclear. This study examined the extent to which vigilant attention deficits contribute to inhibition control performance after one night of total sleep deprivation (TSD) and two nights of partial sleep restriction (PSR).Participants and Methods: We analyzed data from N = 49 participants in a one-night of TSD experiment, N=16 participants in a control experiment without sleep loss, and N = 16 participants in a two-nights of PSR experiment (time in bed, TIB = 6 h for each night). Throughout waking periods in each condition, participants completed the psychomotor vigilance test (PVT), which measures vigilant attention, and the Go/No-Go task, which measures inhibition control.Results: After TSD and PSR, participants displayed significantly slower reaction times (RT) and more lapses in PVT performance, as well as slower Go RT and more errors of omission during the Go/No-Go task. PVT deficits accounted for 18.0% of the change in Go RT and 12.4% of the change in errors of omission in the TSD study, and 23.7% of the change in Go RT and 20.3% of the change in errors of omission in the PSR study.Conclusion: Both TSD and PSR impaired inhibition control during the Go/No-Go task, which can be partly accounted for by vigilant attention deficits during the PVT. These findings support the key role of vigilant attention in maintaining overall neurobehavioral function after sleep loss.Keywords: total sleep deprivation, partial sleep restriction, vigilant attention, inhibition control

Xixuan Lu,1,&ast; Qiang Wang,2,&ast; Haiyan Liang,1 Li Xu,3 Liping Sha,1 Yuemei Wu,1 Liting Ma,1 Ping Yang,1 Hong Lei1 1Department of Endocrinology, Cardiovascular and Cerebrovascular Disease Hospital, Ningxia Medical University General Hospital, Yinchuan, Ningxia, People’s Republic of China; 2Department of Medical Office, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan, Ningxia, People’s Republic of China; 3Department of Radiology, People’s Liberation Army’s Joint Service for the 942nd Hospital, Yinchuan, Ningxia, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xixuan LuDepartment of Endocrinology, Cardiovascular and Cerebrovascular Disease Hospital, Ningxia Medical University General Hospital, No. 804, Shengli South Street, Xingqing District, Yinchuan, 750004, Ningxia, People’s Republic of ChinaTel +860951-6746645Email xixuan86@163.comBackground: This study has been conducted to explore the correlation between phenotypes of obesity and metabolic comorbidities.Methods: This cross-sectional study recruited 14,724 adults aged ≥ 18 years with a randomized stratified sampling strategy. Obesity was classified into four types according to body mass index (BMI) and waist-to-height ratio (WHtR): normal weight with central obesity (NWCO) and without (NW) CO, and obese or overweight with (OBCO) and without (OB) central obesity. Uric acid (UA), fasting blood glucose (FBG), and lipid profile were measured.Results: The prevalence of hyperuricemia in the 4 groups (NW, NWCO, OB and OBCO) was 3.7%, 5.6%, 8.7% and 12.4%, whilst the prevalence of hypertriglyceridemia was 13.4%, 27.4%, 30.3% and 43.7%, separately. The prevalence of hypo-high-density lipoprotein cholesterolemia (hypo-HDL emia) was 20.1%, 21.4%, 30.8% and 27.9%, while the prevalence of hyper-low-density lipoprotein cholesterolemia (hyper-LDL emia) was 9.8%, 24.4%, 12.3% and 27.9%. The prevalence of hypercholesterolemia was 11.2%, 23.5%, 14.7%, 28.5% and the prevalence of hyperglycemia was 9.7%, 22.6%, 18.5%, and 27.0%, respectively. The prevalence of hypertension was 6.9%, 13.1%, 14.7%, and 20.6%. For various metabolic abnormalities, OBCO have the highest risks compared with NW (hyperuricemia: adjusted OR (aOR)= 2.60; hypertriglyceridemia: aOR= 3.19; hypercholesterolemia: aOR= 1.48; hyper LDLemia: aOR= 2.21; hypo HDLemia: aOR= 1.42; hyperglycemia: aOR= 1.95; hypertension: aOR= 2.16). The risk of hyper LDLemia, hypercholesterolemia and hyperglycemia in the NWCO group was higher than that in the OB group (hyperLDLemia: aOR: 1.69 vs 0.97; hypercholesterolemia: aOR: 1.27 vs 1.24; hyperglycemia: aOR: 1.62 vs 1.28).Conclusion: Different phenotypes of obesity are significantly associated with metabolic abnormalities. NWCO is more closely associated with hypercholesterolemia, hyperglycemia and hyper LDLemia. General obesity and central obesity have a synergistic effect on the diseases.Keywords: obesity, central obesity, metabolic abnormalities, BMI, WHtR

Huyi Lei,1,2 Yongyong Ma,1 Jie Tan,1 Qifa Liu1 1Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 2Department of Hematology, The Affiliated Hospital of Shao Xing University (Shao Xing Municipal Hospital), Shaoxing, 312000, Zhejiang, People’s Republic of ChinaCorrespondence: Qifa LiuDepartment of Hematology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Road, Guangzhou, 510515, People’s Republic of ChinaEmail liuqifa628@163.comObjective: To investigate the role of Helicobacter pylori (HP) on the regulation of NF-κB/IL-17 signaling, mechanisms underlying apoptosis in human megakaryocyte cell lines Dami.Methods: Firstly, the mouse model of immune thrombocytopenia (ITP) was established. Then, the mice were subjected to gastric perfusion with HP. Next, the changes in platelet and bone marrow megakaryocyte classification were assessed in each group. Human megakaryocyte Dami cells were treated with HP in vitro for 3, 6, or 9 h; and the rates of apoptosis in each group were then evaluated with flow cytometry. Fluorescent quantitative PCR and Western blotting were implemented for assessing the expression of Bcl-2 and Bax, which are related to apoptosis, and p65, which is associated with the NF-κB pathway. The expression of these proteins was also evaluated after treatment with PDTC, an inhibitor of the NF-κB pathway inhibitor.Results: In vivo, exogenous administration of HP was found to increase the optical density value for the anti-HP antibody in HP-infected BALB/c mice. Meanwhile, the platelet counts in the HP-infected ITP mice model were significantly reduced compared with non-infected ITP mice. In vitro, the apoptotic rate of Dami cells increased gradually with the prolongation of the exposure to HP; the most noticeable change was at 6 h, and there was a significant difference between 0 h and 6 h. The expression of Bax, p-p65, and IL-17 also increased progressively with the prolongation HP exposure, while the expression of anti-apoptotic Bcl-2 protein decreased gradually, especially at 6 h, and the expression of total p65 did not change significantly compared with baseline. Anecdotally, these effects were reversed by the application of pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB signaling.Conclusion: HP can promote platelet destruction in ITP mice, and the underlying mechanisms may be related to accelerating apoptosis of megakaryocytes by the activation of the NF-κB/IL-17 pathway.Keywords: Helicobacter pylori, megakaryocytes, apoptosis, NF-κB, IL-17

Haoran Lei, Ming Shi, Hang Xu, Shengjiang Bai, Xingyu Xiong, Qiang Wei, Lu Yang Department of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Lu YangDepartment of Urology, West China Hospital, Sichuan University, Chengdu, 37 Guoxue Alley, Chengdu, Sichuan, 610041, People’s Republic of ChinaTel +86-18980606829Fax +86-028-85422451Email wycleflue@163.comAbstract: Although it has always been believed that radiation has immunosuppressive effects, more and more preclinical and clinical trials have shown that the combination of radiotherapy and immunotherapy has a potential synergistic effect to treat cancers including urological malignancies. When radiotherapy is combined with immunotherapy, improved prognosis has been observed in different urinary tumors. However, there is no standard treatment, such as the optimal dose/fractionation and the sequence of immunotherapy and radiotherapy. In this review, we discussed the effects of radiotherapy on the cancer immune system and emphasized the synergy of radiotherapy combined with immunotherapy. Although it has significantly improved the prognosis of tumors, there are still some unresolved questions about how to best use this combination in clinical practice. Ongoing trials will provide further information on the interaction of radiotherapy combined with immunotherapy, and are expected to guide clinical practice and improve clinical outcomes.Keywords: radiotherapy, immunotherapy, urological malignancies, abscopal effect

Hongmei Yuan,1,2 Huilan Lei,2 Peng Gu,2 Lang Ma,1 Li Qiu1 1Department of Medical Ultrasound, Laboratory of Ultrasound Imaging Drug, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China; 2Department of Ultrasound, Sichuan Key Laboratory of Medical Imaging, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, People’s Republic of ChinaCorrespondence: Li QiuDepartment of Medical Ultrasound, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu 610041, People’s Republic of ChinaTel +86-18980602044Fax +86-28-85164146Email qiulihx@scu.edu.cnAbstract: Multiple myeloma (MM) in the breast has been rarely documented. However, there are no reports on concurrent masses of chest wall soft tissue and breast as the primary symptoms for MM. Herein, we report a case of a 68-year-old woman presented with masses in her right breast and chest wall for 1 month. She recalled having xerophthalmia and xerostomia for 2 years without taking any test to search for the cause of these symptoms. Ultrasonography (US) and computed tomography (CT) examination revealed masses in the right breast and chest wall. Both lesions of the breast and chest wall were confirmed to be plasma cell tumors by ultrasound-guided puncture biopsy and MM was confirmed by bone marrow examination. Meanwhile, Sjogren’s syndrome (SS) was diagnosed by the positive expression of antibodies against antinuclear, Ro/SSA and La/SSB. After three courses of chemotherapy for MM, the symptoms of SS were significantly alleviated and the masses in the chest wall and breast disappeared.Keywords: multiple myeloma, Sjogren’s syndrome, breast neoplasms, chest wall tumors

Xiaoqi Sun,1 Huifang Lei,2 Xiaoyan Xie,1 Guanyu Ruan,2 Jian An,2 Pengming Sun1,2 1Department of Gynecology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350001, People’s Republic of China; 2Laboratory of Gynecologic Oncology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350001, People’s Republic of ChinaCorrespondence: Jian An; Pengming Sun Laboratory of Gynecologic OncologyFujian Provincial Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, 18 Daoshan Road, Fuzhou, Fujian 350001, People’s Republic of ChinaEmail anjian1994@foxmail.com; sunfemy@hotmail.comBackground: Post-menopausal patients with cervical intraepithelial neoplasia (CIN) have a high rate of residual or recurrent lesions after treatment, and their risk for cervical cancer later in life is higher than the general population. Hence, management for this specific group of post-menopausal patients needs more attention.Objective: The study aimed to identify risk factors associated with the presence of residual disease in hysterectomy specimens in post-menopausal patients with cervical intraepithelial neoplasia grade 3 (CIN 3).Methods: This study was a retrospective analysis of data from post-menopausal women who had undergone hysterectomy following conization for CIN 3 from 2012 to 2018 at Fujian Maternity and Child Health Hospital. Factors extracted from the database included age, parity, Thinprep cytology results, human papillomavirus (HPV) genotype, biopsy results, pre-cone endocervical curettage (ECC) results, conization method, operating surgeon, cone dimension, margin status and glandular involvement. Univariate and multivariate analyses were performed to identify risk factors associated with residual disease in hysterectomy specimens.Results: Analysis of data from 129 women was performed. The proportion of residual disease was 43.41% overall. A higher grade according to colposcopy biopsy, abnormal pre-cone ECC results, the cone method (LEEP vs CKC), a cone volume > 1.57 cm3, and positive margins in conization specimens were found to be significantly associated with residual lesions on univariable analysis. After multivariate analysis, only an abnormal pre-cone ECC result (odds ratio 3.99; 95% confidence interval (CI) 1.41– 11.33; p = 0.009) remained significant.Conclusion: The rate of residual lesions in uterine specimens was high regardless of the cone margin status in post-menopausal women with CIN 3. Risk-based strategies are needed to identify patients who have abnormal pre-cone ECC results, and definitive treatment with hysterectomy should be considered in post-menopausal patients with an elevated risk for residual lesions.Keywords: cervical intraepithelial lesion, menopause, margin status, endocervical curettage

Yao Tong,1,* Xiaoyan Xie,2,* Xiaodan Mao,1,3 Huifang Lei,1 Yaojia Chen,1 Pengming Sun1– 3 1Laboratory of Gynecologic Oncology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou 350001, People’s Republic of China; 2Department of Gynecology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou 350001, People’s Republic of China; 3Fujian Key Laboratory of Women and Children’s Critical Diseases Research, Fujian Maternity and Child Health Hospital, Fuzhou 350001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Pengming SunLaboratory of Gynecologic Oncology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, No. 18 Daoshan Road, Fuzhou 350001, Fujian, People’s Republic of ChinaTel +86 591 8755 8732Fax +86 591 8755 1247Email sunfemy@hotmail.comPurpose: We investigated the relationship between metabolic syndrome (MetS) and its components and erythrocyte parameters such as red blood cell count (RBC) and hemoglobin (Hb) levels, and their association with the risk of deep myometrial invasion in endometrioid endometrial carcinoma (EEC).Patients and Methods: A total of 473 women diagnosed with EEC between January 2012 and December 2018 were included in the study. MetS was diagnosed using a modified version of the Chinese Diabetes Society 2004 criteria. Demographic and clinical characteristics were stratified by MetS and compared. Logistic regression analyses were performed to calculate the odds ratios (ORs) of myometrial invasion.Results: The prevalence of MetS was 18.8% (89/473). RBC and Hb levels were significantly higher in EEC patients with MetS. RBC and Hb values increased linearly with the number of MetS components. The OR of the MetS risk increased across the RBC quartiles (OR=2.212, 95% confidence interval [Cl]=1.125-4.350, P˂0.05). Among EEC patients with MetS, the OR of deep myometrial invasion increased with the decrease of the RBC quartiles (P=0.037). Similarly, in EEC patients with obesity and hyperglycemia or with ≥ 2 MetS criteria, the lowest RBC level (Q1) was a risk factor for deep myometrial invasion compared with the reference RBC group (Q4, P˂0.05). However, this trend was not evident in EEC patients without MetS and its components.Conclusion: EEC with MetS and its components had higher RBC and Hb levels. The association between the erythrocyte parameters and myometrial invasion differed with MetS. RBC was identified as a risk factor of myometrial invasion in EEC patients with MetS and its components.Keywords: metabolic syndrome, endometrioid endometrial carcinoma, red blood cell count, hemoglobin, myometrial invasion

Wenyu Lin,1,2,* Liqing Lin,3,* Binhua Dong,2,4 Lihua Chen,1 Huifang Lei,1,2 Yuqin Gao,1,2 Yaojia Chen,1,2 Pengming Sun1,2,4 1Department of Gynecology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 2Fujian Key Laboratory of Women and Children’s Critical Diseases Research, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, 350001, People’s Republic of China; 3Department of Women’s Health Care, Quanzhou Women’s and Children’s Hospital, Quanzhou, 362000, People’s Republic of China; 4Laboratory of Gynecologic Oncology, Department of Gynecology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, 350001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Pengming SunDirector of Laboratory of Gynecologic Oncology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, No. 18 Daoshan Road, Fuzhou, Fujian 350001, People’s Republic of ChinaEmail sunfemy@hotmail.comBackground: The diagnosis of postpartum pelvic organ prolapse (POP) relies on symptoms combined with pelvic organ prolapse-quantification (POP-Q) and lacks serological indicators. The objective of this study was to assess serum elastin, type I collagen, miRNA-30d, and miRNA-181a in the early postpartum period to identify hematologic predictors of POP.Material and Methods: The study included 1013 42- to 60-day-postpartum women who had delivered at Quanzhou Women’s and Children’s Hospital from October 1, 2016, to October 31, 2017. This study was performed in accordance with the Declaration of Helsinki. The pregnancy and childbirth characteristics and pelvic floor function were evaluated. Forty cases with and without POP were matched, and serum elastin and type I collagen were determined by enzyme-linked immunosorbent assay (ELISA). Reverse-transcription polymerase chain reaction (RT-PCR) was used to detect miRNA-30d and miRNA-181a in 15 pairs.Results: Of the 1013 women recruited, 699 (69.00%) were diagnosed with POP. The mean age was 29.00 years old, and the mean body mass index (BMI) was 22.6 kg/m2. In the univariate analysis, age ≥ 35 years (OR, 1.449; 95% CI, 0.965, 2.298), postpartum BMI ≥ 24 (OR, 4.402; 95% CI, 2.657, 6.148), neonatal weight ≥ 4 kg (OR, 4.832; 95% CI, 1.373, 17.290) and vaginal delivery (OR, 2.751; 95% CI, 1.855, 4.081) were risk factors for postpartum POP. There were no significant differences in the concentrations of serum elastin and type I collagen between the groups (P=0.52; P=0.26). There were significant differences in the concentrations of miRNA-30d and miRNA-181a between the groups (P=0.004; P=0.003).Conclusion: miRNA-30d and miRNA-181a tended to be increased in women with POP and could be potential clinical predictors.Keywords: elastin, miRNA-30d, miRNA-181a, pelvic organ prolapse, type I collagen

Ji Li,1 Wenjing Guo,1 Wei Zhao,1 Xiang Wang,1 Wenmin Hu,1 Jie Zhou,2 Shiyuan Xu,1 Hongyi Lei1 1Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China; 2Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USACorrespondence: Hongyi Lei; Shiyuan Xu Department of AnesthesiologyZhujiang Hospital, Southern Medical University, Guangzhou 510282, People’s Republic of ChinaTel/Fax +86-20-62782898Email lhy2012@smu.edu.cn; xsy998@smu.edu.cnBackground: Peritoneal dialysis catheter placement can be performed under general anesthesia, local anesthesia or subarachnoid anesthesia (SA). Recently, studies have reported the successful placement of peritoneal dialysis catheters using a transversus abdominis plane (TAP) block and rectus sheath (RS) block. This study compared the TAP + RS block with SA for patients undergoing peritoneal dialysis catheter placement.Methods: Sixty patients were randomly divided into two groups, with 30 receiving unilateral ultrasound-guided TAP + RS block anesthesia and 30 receiving SA. The demographic characteristics, anesthesia efficacy, indicators related to anesthesia or operation, hemodynamic index, postoperative pain numeric rating score (NRS), postoperative recovery indicators, complications related to anesthesia or surgery, and dosage of sedative or analgesic medication were analyzed.Results: Anesthesia operation time was significantly shorter in the TAP + RS block group than in the SA group (P< 0.001), while there was no significant difference in success rates (TAP + RS 93.33% [95% confidence interval, 95% CI, 83.9– 102.8%] vs SA 100.00% [95% CI, 100– 100%], P=0.472). Two patients in the TAP + RS group needed extra analgesia, although the dermatome pinprick sensation test gave negative results for all patients. Patients who received the TAP + RS block expressed significantly less pain on movement or at rest at 4 h and 8 h postoperative. Fewer patients needed rescue analgesia with tramadol in the postoperative period in the TAP + RS block group than in the SA group (P< 0.05). The intraoperative MAP was more stable (P< 0.05) in the TAP + RS group compared to the SA group.Conclusion: The TAP + RS block is a safe, effective method for use as the principal anesthesia technique in PD catheter placement. Compared to SA, it has the advantages of less influence on hemodynamics and a better postoperative analgesic effect.Keywords: TAP block, rectus sheath block, peritoneal dialysis catheter placement, local anesthesia, subarachnoid anesthesia

Huang Lei,* Xingyou Dong,* Longkun Li,* Feng Huan, Xiao Zhong, Qingjian Wu, He Fang, Teng Zhang, Xinliang Yang, Jingzhen Zhu, Jia Li, Zhao Jiang Department of Urology, Second Affiliated Hospital, Army Military Medical University, Chongqing 400037, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhao JiangDepartment of Urology, Second Affiliated Hospital, Army Military Medical University, Chongqing 400037, People’s Republic of ChinaTel +86 23 68774624Email urologyzhaoj@sohu.comObjective: To explore the risk factors, pathogenic bacteria distribution and drug resistance of systematic transrectal ultrasound-guided prostate biopsy (TRUS-Bx), 329 cases of TRUS-Bx were collected, retrospectively, in the Second Affiliated Hospital, Army Military Medical University, from April 2017 to October 2019.Methods: A total of 329 cases were all qualified and grouped into the SIRS group (25 cases) and the non-SIRS group (304 cases). Of all the cases, incidence and risk factors of systemic inflammatory response syndrome (SIRS) were analyzed. Urine and blood samples of patients with SIRS after TRUS-Bx were also collected for bacterial culture and drug sensitivity test.Results: Multivariate logistic regression analysis showed that BMI ≥ 25 kg/m2 (OR = 1.66, 95% CI = 1.34– 2.12, P < 0.001), history of diabetes (OR = 5.48, 95% CI = 1.53– 19.68, P = 0.008), urinary infection before operation (OR = 9.19, 95% CI = 2.92– 20.93, P < 0.001) and erythrocyte sedimentation (ESR) ≥ 20 mm/h (OR = 1.04, 95% CI = 1.01– 1.08, P = 0.039) were independent risk factors of SIRS after TURS-PB.Conclusion: The incidence of SIRS and urinary sepsis was 7.59% and 2.13%, respectively, and major pathogens of SIRS after TRUS-Bx were Escherichia coli (58.33%), Klebsiella pneumoniae (12.5%) and Pseudomonas aeruginosa (12.5%). Imipenem, meropenem, tigecycline, piperacillin/tazobactam, teicoplanin, vancomycin, amikacin and cefoperazone/sulbactam had a very strong inhibitory effect to those pathogenic bacteria (sensitivity 85.72%∼ 100%). Levofloxacin, ciprofloxacin, gentamicin, penicillin G, compound neonomine and second-generation cephalosporins showed less but also worked as a good inhibitor to pathogenic bacteria (42.86%∼ 80.95%).Keywords: systematic transrectal ultrasound-guided prostate biopsy, systemic inflammatory response syndrome, prostate cancer, risk factors infection, pathogens

ShuQiong He,1,* XiaoDan Mao,2,3,* HuiFang Lei,2,3 BinHua Dong,2,3 DanHua Guo,1 BeiHong Zheng,4 PengMing Sun2,3 1Department of Prenatal Diagnosis, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, 350001, People’s Republic of China; 2Laboratory of Gynecologic Oncology, Department of Gynecology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, 350001, People’s Republic of China; 3Fujian Key Laboratory of Women and Children’s Critical Diseases Research, Fujian Maternity and Child Health Hospital, Fuzhou, 350001, People’s Republic of China; 4Department of Reproduction, Fujian, Affiliated Hospital of Fujian Medical University, Fuzhou, 350001, People’s Republic of China*These authors contributed equally to this workCorrespondence: PengMing SunLaboratory of Gynecologic Oncology, Department of Gynecology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, No. 18 Daoshan Road, Fuzhou 350001, Fujian, P.R. of ChinaEmail sunfemy@hotmail.comPurpose: This study aimed to investigate the inflammatory-immune cells in the peripheral blood of women with polycystic ovary syndrome (PCOS) and assessed the potential correlation between inflammatory-immune cells and infertility in PCOS women.Materials and Methods: In this case–control study, the profiles of lymphocyte subsets were analyzed by flow cytometry. White blood cells (WBC), neutrophils (Neu), lymphocytes, Ferriman–Gallwey (F–G) score, testosterone, prolactin, follicle-stimulating hormone, luteinizing hormone, fasting blood glucose, and fasting plasma insulin were measured, together with body mass index. Association between inflammatory-immune cells and PCOS was evaluated. Moreover, inflammatory-immune cells of the PCOS women with infertility were evaluated, and the relative operating characteristic (ROC) curve and cutoff values were calculated.Results: The number of WBC, Neu, and lymphocytes was higher in PCOS women than controls (P< 0.05). The percentages of total T lymphocytes, CD4+T, and NK were significantly increased in the PCOS group (P< 0.001). The CD4/CD8 ratio was obviously elevated for increasing CD4+T (P< 0.05). Consequently, T%, CD4+T%, and NK% were found to be the independent risk factors of PCOS by ROC curve and multivariate logistic regression analysis. Furthermore, only NK% was significantly higher in PCOS women with infertility than those who had PCOS without infertility (P< 0.001). To diagnose infertility in PCOS, the cutoff value of NK% was calculated as 16.43%.Conclusion: These findings suggest that the pathogenesis of PCOS is related to immune cells including T, CD4+T, and NK cells. NK cells are likely to be a potential predictive factor for PCOS women with infertility.Keywords: lymphocyte subsets, inflammatory cells, natural killer cells, immunocompetent cells, pathogenesis

Li-Na Guo,1,2 Shu-Ying Yu,1– 3 Meng Xiao,1,2 Chun-Xia Yang,4 Chun-Mei Bao,5 Yan-Hua Yu,6 Li-Yan Ye,7 Yang Yang,1,2 Ge Zhang,1,2 Jie Liu,8 Guo-Wei Liang,9 Rong Min,10 Yu Zhu,11 Hong Lei,12 Yu-Lei Liu,13 Lin-Juan Liu,14 Yun-Jian Hu,15 Po-Ren Hsueh,16 Ying-Chun Xu1,2 1Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences; 2Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases (BZ0447); 3Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences; 4Department of Infectious Diseases & Clinical Microbiology, Beijing Chao-Yang Hospital, Capital Medical University; 5Clinical Laboratory Medical Center, The Fifth Medical Center of Chinese PLA General Hospital; 6Department of Clinical Laboratory, You’an Hospital, Capital Medical University; 7Center for Clinical Laboratory Medicine, Chinese PLA General Hospital; 8Department of Clinical Laboratory, Seventh Medical Center, PLA General Hospital; 9Department of Clinical Laboratory, Aerospace Center Hospital; 10Department of Clinical Laboratory, Xuanwu Hospital, Capital Medical University; 11Department of Clinical Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College; 12Department of Clinical Laboratory, The 8th Medical Center of Chinese PLA General Hospital; 13Department of Clinical Laboratory, Beijing Anzhen Hospital, Capital Medical University; 14Department of Clinical Laboratory, Peking University Cancer Hospital and Institute; 15Department of Clinical Laboratory, Beijing Hospital, Beijing, People’s Republic of China; 16Departments of Laboratory Medicine & Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, TaiwanCorrespondence Ying-Chun XuDepartment of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1, Shuaifuyuan Wangfujing, Dongcheng District, Beijing 100730, People’s Republic of ChinaTel/ Fax +86 106 915 9766Email xycpumch@139.comPo-Ren HsuehDepartments of Laboratory Medicine & Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, TaiwanTel +886-2-23224262 ext. 65355Fax +886-2-23955072Email hsporen@ntu.edu.twObjective: Invasive candidiasis (IC), a life-threatening fungal infection prevalent among hospitalized patients, has highly variable regional epidemiology. We conducted a multicenter surveillance study to investigate recent trends in species distribution and antifungal susceptibility patterns among IC-associated Candida spp. in Beijing, China, from 2016 to 2017.Materials and Methods: A total of 1496 non-duplicate Candida isolates, recovered from blood and other sterile body fluids of IC patients, were identified using matrix-assisted laser desorption/ionization time of flight mass spectrometry combined with ribosomal DNA internal transcribed spacer (ITS) region sequencing. Broth microdilution-based susceptibility testing using six antifungal agents was also conducted.Results: Candida albicans was the most frequently isolated species (49.9%), followed by Candida tropicalis (15.5%), Candida glabrata (14.7%) and Candida parapsilosis (14.2%). No significant differences in species distribution were observed when compared with a 2012– 2013 dataset. Overall, the rates of susceptibility to fluconazole and voriconazole were high among C. albicans (98% and 97.2%, respectively) and C. parapsilosis species complex (91.1% and 92%, respectively) isolates but low among C. tropicalis (81.5% and 81.1%, respectively) isolates. In addition, the rate of azole resistance among C. tropicalis isolates increased significantly (1.8-fold, P< 0.05) compared with that observed in 2012– 2013, while micafungin resistance rates were < 5% for all tested Candida species.Conclusion: Our results suggest that species distribution has remained stable among IC-associated Candida isolates in Beijing. Resistance to micafungin was rare, but increased azole resistance among C. tropicalis isolates was noted. Our study provides information on local epidemiology that will be important for the selection of empirical antifungal agents and contributes to global assessments of antifungal resistance.Keywords: invasive fungal infections, Candida, species distribution, antifungal resistance, surveillance, Beijing

Yinghui Liu,1,2,* Hongbo Lei,3,* Jingjing Ma,1,2 Huan Deng,1,2 Pengzhan He,1,2 Weiguo Dong1 1Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of China; 2Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of China; 3Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weiguo DongDepartment of Gastroenterology, Renmin Hospital of Wuhan University, No. 238 JieFang Road, Wuhan 430060, Hubei Province, People’s Republic of ChinaTel +86-27-88041911Fax +86-27-88042992Email dongweiguo@whu.edu.cnIntroduction: Gastric cancer remains an important cancer worldwide, and conventional chemotherapeutic drugs have the defects of drug resistance and cell toxicity. α-Hederin has been found to have certain therapeutic effects on various types of human cancers. However, studies on the α-hederin that exert biological activities on the cisplatin-resistant gastric cancer cells are limited. In this study, we evaluated the effects of α-hederin in HGC27/DDP and the potential mechanisms both in vivo and in vitro.Methods: HGC27/DDP cells were cultured in DMEM/F12 medium. Cell proliferation and viability were assessed quantitatively using Cell Counting Kit-8. Cell invasion and migration were detected by Transwell invasion assay and wound healing assay. Cell apoptosis was examined by employing Hoechst 33258 Staining Kit and an Annexin V-PE apoptosis kit. Intracellular GSH levels were examined by using a GSH Assay Kit. DCFH-DA and JC-1 Kit were used to detect levels of intracellular reactive oxygen species (ROS) and changes in mitochondrial membrane potential (∆Ψm). The protein levels of Apaf-1, AIF, Bax, Bcl-2, Cyt C, Survivin, cleaved caspase-3, cleaved caspase-9, MMP-9 and MMP-2 were detected by Western blot analysis. The effect of α-hederin in vivo was observed by xenograft tumor models in nude mice.Results: The α-hederin treatment significantly inhibited the proliferation in a dose- and time-dependent manner of HGC27/DDP and induced obvious apoptosis compared with the control group (P

Du Meng,1,* Hongwei Lei,2,* Xiaoqiang Zheng,3 Yaxuan Han,4 Ronggang Sun,5 Dongli Zhao,1 Rui Liu11Department of Radio Oncology, The First Affiliated Hospital of Xi’an Jiaotong University School of Medicine, Xi’an, Shaanxi Province, 710061, People’s Republic of China; 2Department of Radio Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, 116027, People’s Republic of China; 3Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University School of Medicine, Xi’an, Shaanxi Province, 710061, People’s Republic of China; 4Department of Oncology, The Xi’an Chest Hospital, Xi’an, Shaanxi Province, 710000, People’s Republic of China; 5Department of Radio Oncology, The People’s Hospital of YangZhong City, YangZhong, Jiangsu Province, 212200, People’s Republic of China*These authors contributed equally to this workBackground: Breast cancer is one of the foremost threats to female health nowadays. Tamoxifen, an antagonist of estrogen receptor-α (ERα), is the first choice for endocrine-dependent breast cancer (ERα-positive breast cancer) treatment. However, ERα has an important function in the normal physical regulation of estrogen, and current oral administration of tamoxifen has potential side effects on normal endocrine secretion. In the present work, we aim to develop novel approaches to increase the antitumor effect of tamoxifen on breast cancer cells and decrease the potential side effects in the human body during treatment.Methods: A temperature-sensitive phase-change hydrogel for tamoxifen (Tam-Gel) was generated. After establishing subcutaneous tumors formed by MCF-7, an ERα-positive breast cancer cell line, in nude mice, an intratumoral injection of Tam-Gel was performed to examine whether Tam-Gel facilitated the slow-release or antitumor effect of tamoxifen. A metastatic breast cancer model was established using the intrahepatic growth of MCF-7 cells in immunodeficient rats.Results: Tam-Gel can transform from liquid to hydrogel at room temperature. An intratumoral injection of Tam-Gel facilitated the slow-release or antitumor effect of tamoxifen. Once Tam-Gel, but not Tam-Sol, was administered by intratumoral injection, it significantly decreased the uptake of radionuclide probes (18F-fluoroestradiol or 18F-fluorodeoxyglucose) by cells in rats’ livers and the intrahepatic growth of MCF-7 cells in rats’ livers.Conclusion: A novel slow-release system was successfully prepared to facilitate the long-term release of tamoxifen in breast cancer tissues, and achieved an antitumor effect in the long term.Keywords: breast cancer, estrogen receptor-α, tamoxifen nanoparticle, temperature-sensitive phase-change hydrogel

Li-Xia Hu,1,* Shi-Fu Hu,2,* Meng Rao,2,3 Jing Yang,2,4 Hui Lei,2,5 Zhuo Duan,6 Wei Xia,2,7 Changhong Zhu2,7 1Department of Histology and Embryology, Preclinical Medicine College, Xinxiang Medical University, Xinxiang, Henan, People’s Republic of China; 2Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 3Department of Reproduction and Genetics, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 4Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 5Department of Gynaecology and Obstetrics, Taikang Tongji Hospital, Wuhan, Hubei, People’s Republic of China; 6Dayu Medical Devices Co., Ltd., Jingzhou, Hubei, People’s Republic of China; 7Reproductive Medicine Center, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China *These authors contributed equally to this work Introduction: The physiologic safety of devices and materials intended for clinical implantation should be evaluated. This study, a logical extension of our previous work, aimed to investigate the safety of a novel contraceptive device, the copper/low-density polyethylene nanocomposite intrauterine device (nano-Cu/LDPE IUD), through studies of its potential toxicity after acute and subchronic administration in mice and rats. Methods: For the acute toxicity study, single 50 mL/kg doses of nano-Cu/LDPE IUD extracts were administered to mice via intravenous or intraperitoneal injection. General behavioral adverse effects, mortality, and body weights were evaluated for up to 72 hours. In the 13-week subchronic toxicity study, the nano-Cu/LDPE composite with 10-fold higher than the standard clinical dose was implanted subcutaneously into the dorsal skin of Wistar rats. The control group underwent a sham procedure without material insertion. Results: During all acute study observation times, the biologic reactions of the mice in the nano-Cu/LDPE group did not differ from those observed in the control group. The groups did not differ statistically in terms of body weight gain, and no macroscopic changes were observed in any organs. In the subchronic study, no clinical signs of toxicity or mortality were observed in either the nano-Cu/LDPE or control group during the 13-week period. The nano-Cu/LDPE composite did not cause any alterations in body weight, food consumption, hematologic and biochemical parameters, or organ weight relative to the control for any observed sample group. Histopathologic examinations of the organs revealed normal architecture, indicating that the inserted material did not cause morphologic disturbances in the rats. Conclusion: Overall, the results indicate that the nano-Cu/LDPE IUD did not induce systemic toxicity under experimental conditions of the recommended standard practices, suggesting that the novel material IUD is safe and feasible for future contraceptive applications. Keywords: intrauterine device, copper/low-density polyethylene nanocomposite intrauterine device, acute toxicity, subchronic toxicity

Hongen Lei,1 Huixi Li,2 Long Tian,1 Meng Li,2 Zhongcheng Xin,2 Xiaodong Zhang,1 Ruili Guan2 1Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, People’s Republic of China; 2Andrology Center, Peking University First Hospital, Peking University, Beijing 100034, People’s Republic of China Aim: The aim of the study was to investigate whether miR-126, a regulator of MAPK signaling via targeting sprouty-related EVH1 domain-containing protein 1 (SPRED1) mRNA, is involved in the process by which icariside II (ICA II) ameliorates endothelial dysfunction in human cavernous endothelial cells (hCECs) exposed to a diabetic-like environment.Materials and methods: Primary hCECs were isolated and divided into three groups, normal control, diabetes mellitus (DM), and DM treated with ICA II. The cell proliferation and migration abilities of the hCECs were examined. The expression levels of endothelial-related microRNAs and relative target mRNAs (SPRED1, phosphoinositol-3 kinase regulatory subunit 2, and vascular cell adhesion molecule 1) of miR-126 were determined by real-time PCR. The protein expression of endothelial nitric oxide synthase, receptor for advanced glycation end products, and SPRED1, and MAPK signaling activities was determined by Western blot analysis. In addition, miR-126 agomir and antagomir were used for transfection into hCECs to further testify the association between miR-126 and its targeting mRNA SPRED1.Results: hCECs induced with glucose plus advanced glycation end product-BSA showed a significant decrease in endothelial nitric oxide synthase, Ki-67, and miR-126 expression; a downregulated cell migration ability and an increased receptor for advanced glycation end products level. ICA II could partially reverse these changes. SPRED1 mRNA showed a contrary tendency with the miR-126-3p changes. The level of SPRED1 protein increased after the hCECs were induced with glucose plus advanced glycation end product-BSA, and ICA II could rescue its aberrant expression. In addition, the MAPK pathway was downregulated in the hCECs under diabetic conditions, and ICA II could partially enhance its signaling activities. miR-126 was obviously downregulated, and SPRED1 was accordingly upregulated after miR-126 antagomir transfection, while ICA II treatment could recover the expressions of both miR-126 and SPRED1. Moreover, the upregulation of miR-126 and the inhibition of SPRED1 were noticed in the diabetic hCECs by further transfection with miR-126 agomir.Conclusion: ICA II could ameliorate endothelial dysfunction by regulating the MAPK pathway via miR-126/SPRED1 in hCECs exposed to a diabetic-like environment, and ICA II might be a protective agent for endothelial function in diabetic ED. Keywords: human cavernous endothelial cells, endothelial dysfunction, miR-126, diabetes mellitus, icariside II

Jing Yang,1,* Shifu Hu,1,* Meng Rao,1 Lixia Hu,2 Hui Lei,1 Yanqing Wu,1 Yingying Wang,1 Dandan Ke,1 Wei Xia,1,3 Chang-hong Zhu1,3 1Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 2Department of Histology and Embryology, Preclinical Medicine College, Xinxiang Medical University, Henan Province, Xinxiang, 3Reproductive Medicine Center, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China *These authors contributed equally to this work Abstract: Numerous studies have reported the accumulation of copper nanoparticles (Cu NPs) in organs and the corresponding damage, although whether Cu NPs can be translocated to the ovaries and their ovarian toxicity are still unknown. In this study, three groups of female rats were injected with 3.12, 6.25, or 12.5 mg/kg Cu NPs for 14 consecutive days. The pathological changes, hormone levels, apoptosis and apoptotic proteins, oxidative stress, and gene expression characteristics in the ovaries were then investigated. The results demonstrated that the Cu NPs exhibited obvious accumulation in the rat ovaries, leading to ovarian injury, an imbalance of sex hormones, and ovarian cell apoptosis. Cu NP exposure activated caspase 3, caspase 8, caspase 9, and tBid, decreased the protein levels of Bcl-2, increased the expression levels of the proteins Bax and cytochrome c, and promoted malondialdehyde (MDA) accumulation and superoxide dismutase (SOD) reduction. Furthermore, gene microarray analysis showed that Cu NPs (12.5 mg/kg/d) caused 321 differentially expressed genes. Of these, 180 and 141 genes were upregulated and downregulated, respectively. Hsd17b1, Hsd3b1, Hsd3b6, and Hsd3b were involved in steroid and hormone metabolism, whereas Mt3 and Cebpb were associated with apoptosis. Overall, these findings provide strong evidence that Cu NPs trigger both intrinsic and extrinsic apoptotic pathways and regulate key ovarian genes in oxidative stress-mediated ovarian dysfunction. Keywords: Cu NPs, apoptosis, oxidative stress, microarray

Hongen Lei,1 Yongde Xu,1 Ruili Guan,1 Meng Li,2 Yu Hui,3 Zhezhu Gao,1 Bicheng Yang,1 Zhongcheng Xin1 1Andrology Center, Peking University First Hospital, Peking University, Beijing, 2Department of Urology, General Hospital of Ningxia Medical University, Yinchuan, 3Department of Urology, The First Affiliated Hospital of Soochow University, Soochow, People’s Republic of China Purpose: To investigate the biological effect of gyromagnetic fields (GMFs) on cell proliferation and apoptosis of human prostatic adenocarcinoma cells and explore the underlying mechanisms.Methods: PC-3 cells were grouped into normal control (NC) and GMF treatment groups. Cell proliferation was analyzed with kit-8 and Ki67 immunofluorescence staining, while cell apoptosis was analyzed with flow cytometry double staining of Annexin V-PE/7-AAD. The Akt and p38 MAPK/Caspase signaling pathways were analyzed by western blotting and immunofluorescence staining, and cell polarization was analyzed with PARD3.Results: Cell proliferation and activity of the Akt pathway were significantly decreased by the GMF, while cell apoptosis, activity of p38 MAPK, and PARD3-positive cell number were significantly increased in the GMF group compared to the NC group.Conclusion: GMFs inhibit cell proliferation, induce apoptosis, and regulate tumor cell polarity conditions, potentially through down-regulating Akt, activating the p38 MAPK/Caspase pathway, and promoting PARD3 expression in PC-3 cells. Keywords: apoptosis, gyromagnetic fields, PC-3 cells, prostate cancer

Wenjie Tian,1,2,* Hongen Lei,1,* Ruili Guan,1 Yongde Xu,1 Huixi Li,1 Lin Wang,1 Bicheng Yang,1 Zhezhu Gao,1 Zhongcheng Xin1 1Andrology Center, Peking University First Hospital, Peking University, Beijing, 2Department of Urology, The Second Hospital of Jilin University, Jilin University, Changchun, People’s Republic of China *These authors contributed equally to this work Purpose: To investigate the therapeutic effects and potential mechanisms of icariside II (ICA II) on reversing diabetic nephropathy in streptozotocin (STZ)-induced type I diabetic rats.Methods: Newborn male Sprague Dawley rats were labeled with thymidine analog 5-ethynyl-2-deoxyuridine (EdU) for tracking endogenous label retaining progenitor cells (LRCs). At age of 8 weeks, 48 rats were randomly divided into three groups: normal control group (n=16), diabetes mellitus group (DM; n=16), and diabetes mellitus plus ICA II therapy group (DM+ICA II, n=16). Eight weeks induced for diabetes with STZ, rats in DM group and DM+ICA II group were treated with vehicle or ICA II (5 mg/kg/day) for another 8 weeks, respectively. Then, blood creatinine, 24-hour urine protein, blood urea nitrogen, and glycosylated hemoglobin were measured, as well as the expression of von Willebrand factor, malondialdehyde, transforming growth factor-β/drosophila mothers against decapentaplegic protein/connective tissue growth factor (TGF-β/Smad/CTGF) signaling, marker of proliferation Ki-67, and EdU+ LRCs in renal tissues.Results: Increased levels of creatinine, 24-hour urine protein, and blood urea nitrogen and remarkably decreased proportion of normal glomeruli and increased proportions of I, IIa, IIb, and III glomeruli were observed in diabetic rats, while ICA II could reverse these changes. Interestingly, ICA II could significantly downregulate the levels of malondialdehyde and TGF-β/Smad/CTGF signaling and increase the expression of von Willebrand factor, Ki-67, and EdU+ LRCs in the kidney.Conclusion: ICA II treatment could ameliorate diabetic nephropathy in STZ-induced diabetic rats by increasing endothelial cell contents, downregulating TGF-β/Smad/CTGF signaling pathway and oxidative stress level, and promoting cell proliferation both in kidney cortex and medulla. These beneficial effects appear to be mediated by its antioxidant capacity and recruitment of endogenous EdU+ progenitor cells into the kidney tissue. Keywords: diabetic nephropathy, icariside II, EdU, diabetes mellitus, label retaining progenitor cells