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Jia-Xin Guan,1,2 Yan-Ling Wang,1,2,* Jia-Lin Wang1,2,* 1Department of Ophthalmology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Institute of Ophthalmology, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jia-Lin Wang; Yan-Ling Wang, Department of Ophthalmology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People’s Republic of China, Email wangjialin@bjmu.edu.cn; wangyanl@ccmu.edu.cnAbstract: Subretinal injection (SR injection) is a commonly used method of ocular drug delivery and has been mainly applied for the treatment of neovascular age-associated macular degeneration (nAMD) and sub-macular hemorrhage (SMH) caused by nAMD, as well as various types of hereditary retinopathies (IRD) such as Stargardt’s disease (STGD), retinitis pigmentosa (RP), and a series of fundus diseases such as Leber’s congenital dark haze (LCA), choroidal defects, etc. The commonly used carriers of SR injection are mainly divided into viral and non-viral vectors. Leber’s congenital amaurosis (LCA), choroidal agenesis, and a series of other fundus diseases are also commonly treated using SR injection. The commonly used vectors for SR injection are divided into two categories: viral vectors and non-viral vectors. Viral vectors are a traditional class of SR injection drug carriers that have been extensively studied in clinical treatment, but they still have many limitations that cannot be ignored, such as poor reproduction efficiency, small loading genes, and triggering of immune reactions. With the rapid development of nanotechnology in the treatment of ocular diseases, nanovectors have become a research hotspot in the field of non-viral vectors. Nanocarriers have numerous attractive properties such as low immunogenicity, robust loading capacity, stable structure, and easy modification. These valuable features imply greater safety, improved therapeutic efficacy, longer duration, and more flexible indications. In recent years, there has been a growing interest in nanocarriers, which has led to significant advancements in the treatment of ocular diseases. Nanocarriers have not only successfully addressed clinical problems that viral vectors have failed to overcome but have also introduced new therapeutic possibilities for certain classical disease types. Nanocarriers offer undeniable advantages over viral vectors. This review discusses the advantages of subretinal (SR) injection, the current status of research, and the research hotspots of gene therapy with viral vectors. It focuses on the latest progress of nanocarriers in SR injection and enumerates the limitations and future perspectives of nanocarriers in the treatment of fundus lesions. Furthermore, this review also covers the research progress of nanocarriers in the field of subretinal injection and highlights the value of nanocarrier-mediated SR injection in the treatment of fundus disorders. Overall, it provides a theoretical basis for the application of nanocarriers in SR injection.Keywords: nanoparticles, subretinal injection, drug delivery, non-viral vectors, nanomedicine, gene therapy

Qi-Feng Chen,1,* Xiong-Ying Jiang,1,2,* Yue Hu,1,* Song Chen,1 Jun-Zhe Yi,1 Sui-Xing Zhong,1 Jiong-Liang Wang,1 Ning Lyu,1 Ming Zhao1 1Department of Minimally Invasive Interventional Therapy, Liver Cancer Study and Service Group, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 2Department of Interventional Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510210, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ming Zhao, Department of Minimally Invasive Interventional Therapy, Liver Cancer Study and Service Group Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, Guangdong, 510060, People’s Republic of China, Tel +862087343272, Email zhaoming@mail.sysu.edu.cnPurpose: The combination of sorafenib and hepatic arterial infusion chemotherapy (SoHAIC) has shown to enhance overall survival rates in patients with advanced hepatocellular carcinoma and major portal vein tumor thrombosis (HCC-Vp3-4) compared to sorafenib alone. Our objective was to evaluate the cost-effectiveness of SoHAIC versus sorafenib for the treatment of HCC-Vp3-4, taking into account the viewpoint of Chinese healthcare payers.Methods: This pharmacoeconomic study employed a Markov model to assess the cost-effectiveness of treating HCC-Vp3-4 with SoHAIC in comparison to sorafenib. The patient characteristics were drawn from individuals from the trial conducted between June 2017 and November 2019, with cost and health value data sourced from published literature. The primary outcome measure in this research was the incremental cost-effectiveness ratio (ICER), which indicates the additional cost per quality-adjusted life year (QALY). The willingness-to-pay (WTP) threshold per QALY was set at $30,492.00. Furthermore, 1-way sensitivity and probabilistic sensitivity analyses were carried out to validate the consistency of the results.Results: In the baseline scenario, sorafenib resulted in 0.42 QALY at a cost of $10,507.89, while SoHAIC generated 1.66 QALY at a cost of $32,971.56. When comparing SoHAIC to sorafenib, the ICER was $18,237.20 per QALY, which was below the WTP threshold per QALY. Furthermore, the 1-way sensitivity analysis demonstrated that the ICER remained within the WTP threshold despite fluctuations in variables. In the probabilistic sensitivity analysis, SoHAIC had a 98.8% probability of being cost-effective at the WTP threshold, considering a wide range of parameters.Conclusion: In this cost-effectiveness evaluation, SoHAIC demonstrated cost-effectiveness over sorafenib for HCC with major portal vein tumor thrombosis, as observed from the perspective of a Chinese payer.Keywords: HCC, portal vein tumor thrombosis, sorafenib, HAIC, Cost-effectiveness

Nan Jiang,1,2 Chun Mei Yang,1,2 Jia Le Wang,1,2 Xiao Fei Ye,1 Bin Yang1,2 1Children’s Medical Centre of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2The Fifth Clinical College Affiliated to Anhui Medical University, Hefei, Anhui, People’s Republic of ChinaCorrespondence: Bin Yang, Children’s Medical Centre of Anhui Medical University, The Fifth Clinical College Affiliated to Anhui Medical University, Hefei, People’s Republic of China, Tel +86-13866127496, Email yangbin691202@163.comPurpose: To investigate sleep problems in children with self-limited epilepsy with central temporal spiking (SeLECTS) and to assess the relationship between sleep problems and attention network dysfunction.Patients and methods: 107 children 6– 14 years of age with SeLECTS and 90 age- and sex-matched healthy controls were recruited for this study. The sleep status of these participants was evaluated using the Children’s Sleep Habits Questionnaire (CSHQ), while attentional network function was assessed with the attention network function test (ANT).Results: Together, these analyses revealed that children with SeLECTS exhibited higher total CSHQ scores and sleep disorder incidence relative to healthy controls (P< 0.001). Children with SeLECTS had higher scores in delayed sleep onset, sleep duration, night awakenings, parasomnias, daytime sleepiness and sleep anxiety (P< 0.01). Total CSHQ scores were negatively correlated with average ANT correct rates (ρ= − 0.253, P< 0.01), while they were positively correlated with total reaction time (ρ=0.367, P< 0.01) and negatively correlated with the efficiency of the alerting and executive control networks (ρ=− 0.344 P< 0.01; ρ=− 0.418 P< 0.01).Conclusion: Children with SeLECTS face a higher risk of experiencing sleep disorders relative to age-matched healthy children, while also demonstrating that the magnitude of the impairment of attentional network function in these children is positively correlated with sleep disorder severity. Thus, the prognosis and quality of life of children with SeLECTS can be improved by interventions addressing sleep disorders.Keywords: SeLECTS, attention network function, sleep disorders, CSHQ

Lu Hua,1,2,&ast; Kaiyuan Sha,1,2,&ast; HongCheng Lu,1,2 Ying Han,1,2 Cehua Ou,1,2 Jiang-Lin Wang,1 Yue Zhang1,2 1Department of Pain Management, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 2Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou Southwest Medical University, Luzhou, Sichuan Province 646000 People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiang-Lin Wang; Yue Zhang, Department of Pain Management, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China, Email jianglin523@swmu.edu.cn; zhangyue0518@swmu.edu.cnPurpose: To explore the therapeutic effect of C2 dorsal root ganglion pulsed radiofrequency (PRF) combined with stellate ganglion block (SGB) in patients with cervicogenic headache (CEH).Patients and Methods: We retrospectively reviewed 90 patients diagnosed with CEH who were admitted to our hospital between May 2019 and May 2022. All patients were divided into three groups (n = 30 each) according to the actual treatment method used: ultrasound-guided SGB, ultrasound-guided C2 dorsal root ganglion PRF treatment, and ultrasound-guided C2 dorsal root ganglion PRF combined with SGB treatment. Patients’ pain intensity, sleep, and mood changes were assessed by statistically analyzing their pain visual analog scale (VAS), Pittsburgh Sleep Quality Inventory (PSQI), and short-form McGill Pain Questionnaire affective item scores before and after treatment.Results: The post-treatment VAS, PSQI, and McGill scores were significantly decreased in all patients (P < 0.05), and all three scores in ultrasound-guided C2 dorsal root ganglion PRF combined with SGB were lower than those in ultrasound-guided SGB alone and ultrasound-guided C2 dorsal root ganglion PRF alone (P < 0.05).Conclusion: The use of ultrasound-guided C2 dorsal root ganglion PRF combined with SGB in patients with CHE is effective in alleviating pain and improving sleep, and deserves to be replicated in the clinic.Keywords: cervicogenic headache, C2 dorsal root ganglion, pulsed radiofrequency, stellate ganglion block

Yu-Guo Yuan,1,2 Jia-Lin Wang,1,2 Ya-Xin Zhang,1,2 Ling Li,1,2 Abu Musa Md Talimur Reza,3 Sangiliyandi Gurunathan4 1Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China; 2Jiangsu Co-Innovation Center of Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China; 3Department of Molecular Biology and Genetics, Faculty of Science, Gebze Technical University, Gebze, Kocaeli, Türkiye; 4Department of Biotechnology, Rathinam College of Arts and Science, Coimbatore, TN, IndiaCorrespondence: Yu-Guo Yuan; Sangiliyandi Gurunathan, Email yyg9776430@163.com; gsangiliyandi@yahoo.comAbstract: Exosomes are nanovesicles with a wide range of chemical compositions used in many different applications. Mesenchymal stem cell-derived exosomes (MSCs-EXOs) are spherical vesicles that have been shown to mediate tissue regeneration in a variety of diseases, including neurological, autoimmune and inflammatory, cancer, ischemic heart disease, lung injury, and liver fibrosis. They can modulate the immune response by interacting with immune effector cells due to the presence of anti-inflammatory compounds and are involved in intercellular communication through various types of cargo. MSCs-EXOs exhibit cytokine storm-mitigating properties in response to COVID-19. This review discussed the potential function of MSCs-EXOs in a variety of diseases including neurological, notably epileptic encephalopathy and Parkinson’s disease, cancer, angiogenesis, autoimmune and inflammatory diseases. We provided an overview of exosome biogenesis and factors that regulate exosome biogenesis. Additionally, we highlight the functions and potential use of MSCs-EXOs in the treatment of the inflammatory disease COVID-19. Finally, we covered a strategies and challenges of MSCs-EXOs. Finally, we discuss conclusion and future perspectives of MSCs-EXOs.Keywords: extracellular vesicle, biogenesis, mesenchymal stem cells, exosomes, autoimmune disease, angiogenesis

Yu-Guo Yuan,1,2,&ast; Ya-Xin Zhang,1,&ast; Song-Zi Liu,1,&ast; Abu Musa Md Talimur Reza,3 Jia-Lin Wang,1,2 Ling Li,1,2 He-Qing Cai,1,2 Ping Zhong,1 Il-Keun Kong4 1College of Veterinary Medicine, Yangzhou University, Yangzhou, People’s Republic of China; 2Jiangsu Co-Innovation Center of Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, People’s Republic of China; 3Department of Molecular Biology and Genetics Faculty of Basic Sciences, Gebze Technical University, Kocaeli, Republic of Turkiye; 4Division of Applied Life Science (BK21 Four), Institute of Agriculture and Life Science, Gyeongsang National University, Jinju, Gyeongnam Province, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Yu-Guo Yuan; Il-Keun Kong, Email yyg9776430@163.com; ikong7900@gmail.comIntroduction: The increasing industrial and biomedical utilization of graphene oxide silver nanoparticles (GO-AgNPs) raises the concern of nanosafety: exposure to the AgNPs or GO-AgNPs increases the generation of reactive oxygen species (ROS), causes DNA damage and alters the expression of whole transcriptome including mRNA, miRNA, tRNA, lncRNA, circRNA and others. Although the roles of different RNAs in epigenetic toxicity are being studied during the last decade, but still we have little knowledge about the role of circle RNAs (circRNAs) in epigenetic toxicity.Methods: Rabbit fetal fibroblast cells (RFFCs) were treated with 0, 8, 16, 24, 32 and 48 μg/mL GO-AgNPs to test the cell viability and 24 μg/mL GO-AgNPs was selected as the experimental dose. After 24 h treatment with 24 μg/mL GO-AgNPs, the level of ROS, malondialdehyde (MDA), superoxide dismutase (SOD), intracellular ATP, glutathione peroxidase (GPx), and glutathione reductase (Gr) were measured in the RFFCs. High-throughput whole transcriptome sequencing was performed to compare the expression of circRNAs, long non-coding RNAs (lncRNA) and mRNA between 24 μg/mL GO-AgNPs-treated RFFCs and control cells. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was performed to validate the accuracy of circRNA sequencing data. Bioinformatics analyses were performed to reveal the potential functional roles and related pathways of differentially expressed circRNAs, lncRNA and mRNA and to construct a circRNA–miRNA–mRNA interaction network.Results: We found that 57 circRNAs, 75 lncRNAs, and 444 mRNAs were upregulated while 35 circRNAs, 21 lncRNAs, and 186 mRNAs were downregulated. These differentially expressed genes are mainly involved in the transcriptional mis-regulation of cancer through several pathways: MAPK signaling pathway (circRNAs), non-homologous end-joining (lncRNAs), as well as PPAR and TGF-beta signaling pathways (mRNAs).Conclusion: These data revealed the potential roles of circRNAs in the GO-AgNPs induced toxicity through oxidative damage, which would be the basis for further research to determine their roles in the regulation of different biological processes.Keywords: circRNAs, GO-AgNPs, oxidative stress, epigenetic toxicity

Hai-Li Li,1,2 Min Lin,1,2 Xing-Ping Tan,1,2 Jiang-Lin Wang1,2 1Department of Pain Management, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, 646000, People’s Republic of China; 2Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, Sichuan Province, 646000, People’s Republic of ChinaCorrespondence: Jiang-Lin Wang, Pain Department, The Affiliated Hospital of Southwest Medical University, No. 25 Pacific Street, Luzhou, Sichuan Province, 646000, People’s Republic of China, Tel +8618090880626, Fax +86830-3165469, Email jianglin523@swmu.edu.cnAbstract: Central post-stroke pain (CPSP) is a severe chronic neuropathic pain syndrome that is a direct result of cerebrovascular lesions affecting the central somatosensory system. The pathogenesis of this condition remains unclear owing to its extensive clinical manifestations. Nevertheless, clinical and animal experiments have allowed a comprehensive understanding of the mechanisms underlying CPSP occurrence, based on which different theoretical hypotheses have been proposed. We reviewed and collected the literature and on the mechanisms of CPSP by searching the English literature in PubMed and EMBASE databases for the period 2002– 2022. Recent studies have reported that CPSP occurrence is mainly due to post-stroke nerve injury and microglial activation, with an inflammatory response leading to central sensitization and de-inhibition. In addition to the primary injury at the stroke site, peripheral nerves, spinal cord, and brain regions outside the stroke site are involved in the occurrence and development of CPSP. In the present study, we reviewed the mechanism of action of CPSP from both clinical studies and basic research based on its sensory pathway. Through this review, we hope to increase the understanding of the mechanism of CPSP.Keywords: central post-stroke pain, pathogenetic mechanism, spinothalamic tract, thalamus

Yu He,1 Jun-Li Wang,2 Yan-An Zhang,3,4 Mao-Shui Wang4– 6 1Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China; 2Department of Laboratory Medicine, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, People’s Republic of China; 3Department of Cardiovascular Surgery, Shandong Public Health Clinical Center, Cheeloo College of Medicine, Shandong University, Jinan, 250013, People’s Republic of China; 4Shandong Key Laboratory of Infectious Respiratory Disease, Jinan, Shandong, People’s Republic of China; 5Department of Laboratory Medicine, Shandong Provincial Chest Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250013, People’s Republic of China; 6Department of Lab Medicine, Shandong Public Health Clinical Center, Cheeloo College of Medicine, Shandong University, Jinan, 250013, People’s Republic of ChinaCorrespondence: Yan-An Zhang, Department of Cardiovascular Surgery, Shandong Public Health Clinical Center, 46# Lishan Road, Jinan, 250013, People’s Republic of China, Email zhangtbgroup@163.com Mao-Shui Wang, Department of Laboratory Medicine, Shandong Public Health Clinical Center, 46# Lishan Road, Jinan, 250013, People’s Republic of China, Email wangmaoshui@gmail.comBackground: Currently, the prevalence of nontuberculous mycobacteria (NTM) strains isolated from mycobacterial cultures has been well characterized. However, the data on the prevalence of tuberculosis (TB) in patients with NTM disease remain unclear.Methods: Between January 2012 and August 2020, consecutive patients with positive mycobacterial cultures were included for analysis. The identification of Mycobacteria spp. was performed using the DNA array method or sequencing of 16S rDNA. NTM disease is diagnosed when the same infectious agent is identified in at least two sputum or is identified in sterile samples.Results: A total of 997 strains were isolated from 828 inpatients. Of them, 261 inpatients (31.5%) were diagnosed as NTM disease. The mean age of the 261 patients was 55.7 ± 15.5 years old and 64.0% (n = 167) of them were male. The prevalence of culture-confirmed TB patients among patients with NTM disease was estimated as 8.0% (21/261).Conclusion: TB is common in NTM disease and caution should be taken when initiating the treatment of NTM disease.Keywords: prevalence, tuberculosis, culture, nontuberculous mycobacteria, diagnosis

Peng Cui,1– 3 Peng Wang,1– 3 Chao Kong,1– 3 Xiang Yu Li,1– 3 Shuai Kang Wang,1– 3 Jia Lin Wang,1– 3 Xu Liu,1– 3 Shi Bao Lu1– 3 1Department of Orthopedics, Xuanwu Hospital Capital Medical University, Beijing, People’s Republic of China; 2National Clinical Research Center for Geriatric Diseases, Beijing, People’s Republic of China; 3Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Shi Bao Lu, Email spinelu@163.comPurpose: To compare pain scores (visual analog scale) on postoperative days 1– 3 and length of stay after implementing enhanced recovery after surgery (ERAS) in elderly patients undergoing multi-segments lumbar fusion surgery.Methods: We performed a retrospective analysis of prospectively collected data, patients older than 75 years were enrolled in the study. We selected two periods, before (Pre-ERAS, n =54 patients) and after (ERAS, n =46 patients) implementation of ERAS. Data were collected on patient demographics, operative and perioperative details, 30-day readmission. The primary outcome was the length of stay (LOS), and the secondary outcomes were postoperative mean pain scores on postoperative days (POD) 1– 3 and 30-day readmission rates.Results: A total of 100 patients (46 in ERAS and 54 in pre-ERAS) were enrolled in this study. There were no significant differences in age, sex, body mass index (BMI), smoking and comorbidities between the groups. However, there was a significant difference in pain on postoperative day (POD) 1 (5.31 ± 1.98 vs 4.37 ± 0.85, p = 0.002), while there was no difference in postoperative complications. The mean LOS was significantly shorter in the ERAS than in the pre-ERAS group, it reduced from 12.29 ± 3.93 to 9.45 ± 2.72 days (p < 0.001).Conclusion: To our knowledge, this is the first ERAS protocol used in patients (older than 75 years) undergoing polysegmental lumbar fusion surgery. Pain scores on POD 1 and LOS were significantly lower without increased adverse events after implementation of ERAS. This finding suggests that elderly people (> 75 years of age) undergoing polysegmental lumbar fusion surgery could also benefit from ERAS.Keywords: enhanced recovery after surgery, elderly, multi-segment, lumbar fusion surgery

Qian Zhao,&ast; Xue-Yu Sun,&ast; Shu-Qi Ma, Meng-Wei Miao, Gai-Ling Li, Jing-Lu Wang, Rui-Xia Guo, Liu-Xia Li Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rui-Xia GuoDepartment of Gynecology, The First Affiliated Hospital of Zhengzhou University, No. 1 of Jianshe Dong Street, Erqi District, Zhengzhou, 450000, People’s Republic of ChinaTel +86 13525569376Email guoruixia70@163.comObjective: This study aims to evaluate the clinical value of laparoscopic temporary internal iliac artery blockage (TIIAB) compared with uterine artery embolization (UAE) in type III cesarean scar pregnancy (CSP).Methods: A total of 76 patients with type III CSP admitted to the Department of Gynecology the First Affiliated Hospital of Zhengzhou University between September 2017 and June 2019 were selected for this retrospective study. Thirty-six of them in the study group received TIIAB, and the rest in control group received UAE. Laparoscopic pregnancy tissue was removed from all patients, and the uterine defects were repaired. The absence of remnants was then confirmed using ultrasonography. Follow-ups were performed in the two groups for six months, and the factors of intraoperative blood loss, operation and menelipsis time, 24-h human chorionic gonadotropin decline rate, postoperative complications, hospitalization days, hospitalization costs, peri-operative hormone levels, and ovarian function indicators were compared between the two groups and within each group.Results: There were statistically significant differences in the hospitalization cost, menelipsis time, and postoperative complication incidence between the two groups (p < 0.05). There were statistically significant differences between ovarian function at one month and three months after surgery (p < 0.05) as well as among the follicle-stimulating hormone, luteinizing hormone, and estradiol levels at one, three, and six months after surgery in the control group (p < 0.05).Conclusion: Compared with uterine artery embolization, laparoscopic TIIAB has the advantages of a low hospitalization cost, lower postoperative complication rate, and shorter menelipsis time. Moreover, it avoids ovarian function damage. It is a safe method worthy of clinical popularization.Keywords: type III cesarean scar pregnancy, laparoscopic internal iliac artery, occlusion, uterine artery embolization, ovarian function

Photochemical smog, characterized by high concentrations of ozone (O3) and fine particles (PM2.5) in the atmosphere, has become one of the top environmental concerns in China. Volatile organic compounds (VOCs), one of the key precursors of O3 and secondary organic aerosol (SOA) (an important component of PM2.5), have a critical influence on atmospheric chemistry and subsequently affect regional and global climate. Thus, VOCs have been extensively studied in many cities and regions in China, especially in the North China Plain, the Yangtze River Delta and the Pearl River Delta regions where photochemical smog pollution has become increasingly worse over recent decades. This paper reviews the main studies conducted in China on the characteristics and sources of VOCs, their relationship with O3 and SOA, and their removal technology. This paper also provides an integrated literature review on the formulation and implementation of effective control strategies of VOCs and photochemical smog, as well as suggestions for future directions of VOCs study in China.

Xing-Chen Li,1,* Yang-Yang Dong,1,* Yuan Cheng,1 Jing-Yi Zhou,1,2 Xiao Yang,1 Bo-Qiang Shen,1 Xiao-Tong Wu,1,2 Xiao-Ping Li,1 Jian-Liu Wang1,2 1Department of Obstetrics and Gynecology, Peking University People’s Hospital, Beijing 100044, People’s Republic of China; 2Beijing Key Laboratory of Female Pelvic Floor Disorders Diseases, Beijing 100044, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian-Liu WangDepartment of Obstetrics and Gynecology, Peking University People’s Hospital, Beijing 100044, People’s Republic of ChinaTel +86 10 8832 4474Email wangjianliu1203@163.comPurpose: The early predictive values of diagnostic markers for lymph node metastasis (LNM) in endometrial cancer (EC) are still unclear at present. The purpose of this study is to explore the relationship between serum calcium and LNM in EC.Methods: We identified all patients with EC who underwent surgery between January 2012 and December 2016. Patient characteristics and various preoperative clinicopathologic data were obtained from medical records and were reviewed retrospectively. These patients were divided into two groups according to the pathology of their lymph node. Logistic regression models analyzed the relationship between the ionized calcium and LNM of EC patients, while adjusting for the potential confounders.Results: A total of 448 patients were assessed. Univariate analysis showed that ionized calcium, CA125 level, tumor grade, peritoneal cytology, FIGO stage, histological type, LVSI, and myometrial invasion were positively correlated with LNM (all P< 0.05). The risk of LNM increased with the promotion of serum ionized calcium (P for trend < 0.01). Ionized calcium level was significant before and after the adjustment of cofounders (unadjusted: OR=11.9, 95% CI: 4.8– 29.6, P< 0.01; model I: OR=11.3, 95% CI: 4.5– 28.8, P< 0.01; model II: OR=5.2, 95% CI: 1.6– 17.2, P< 0.05). Additionally, the risk of ionized calcium was especially evident in patients whose age was older than 60, BMI< 28 kg/m2, grade 3, negative peritoneal cytology and endometrioid endometrial adenocarcinoma.Conclusion: Ionized calcium level was highly associated with LNM in EC and acted as a potential biomarker in predicting the risk of LNM in EC.Keywords: serum calcium level, EC, lymph node metastasis, stratification analysis

Tzu-Hao Liu,1,2 Hsiao-Ping Wang,1,3 Fu-Nang Cho,3,4 Jiun-Ling Wang,5,6 Chih-Hsin Hung,7 Yee-Hsuan Chiou,1,3 Yao-Shen Chen,3,8 Susan Shin-Jung Lee,3,8 Ming-Fang Cheng1,3,7,91Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan; 2Department of Pediatrics, Zuoying Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung 81342, Taiwan; 3School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan; 4Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan; 5Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan; 6Department of Medicine, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan; 7Department of Chemical Engineering and Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung 84001, Taiwan; 8Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan; 9School of Nursing, Fooyin University, Kaohsiung 83102, TaiwanCorrespondence: Ming-Fang ChengDepartment of Pediatrics, No. 386, Dazhong 1st Road, Zuoying District, Kaohsiung 813, TaiwanTel +886-7342-2121Fax +886-7346-8207Email mfcheng@vghks.gov.twPurpose: The role of pathogenic Escherichia coli colonization in asymptomatic pregnant women is not well understood. The purpose of this work was to determine the prevalence, antimicrobial susceptibility, and neonatal outcomes of pathogenic E. coli colonization in pregnant women.Patients and methods: A total of 137 women from southern Taiwan with singleton pregnancies were enrolled between March 2016 and June 2017. The women were prospectively screened for E. coli colonization in the rectovaginal region during prenatal examination. The exclusion criteria are twin pregnancy of the mother and major anomaly of the neonate. All E. coli isolates were identified as either pathogenic or commensal strains, and their susceptibility to various antimicrobials was investigated. Clinical data of the infants were retrieved from their medical records.Results: Results showed that 35.8% of asymptomatic pregnant women had pathogenic E. coli colonization in the rectovaginal region. Neonates born to such mothers showed significant morbidities, including hospitalization (OR= 3.74, 95% CI= 1.18∼11.87), hyperbilirubinemia (OR= 2.81, 95% CI= 1.24∼6.38), and gastrointestinal symptoms (OR= 5.53, 95% CI= 1.39∼21.94). Maternal colonization with pathogenic E. coli at rectoanal site was a risk factor for neonatal hyperbilirubinemia after Benjamini–Hochberg (BH) adjustment (52% vs 24%, adjusted P= 0.048).Conclusion: The prevalence of pathogenic E. coli colonization in Taiwanese asymptomatic pregnant women was high, and the neonates born to colonized mothers exhibited potential neonatal morbidities. Larger studies are necessary to confirm these findings.Keywords: maternal-neonatal transmission, respiratory distress, hyperbilirubinemia, gastrointestinal symptoms

Pin-Chieh Wu,1,2,* Jiun-Ling Wang,3,4,* Po-Ren Hsueh,5 Po-Hsiang Lin,6 Ming-Fang Cheng,7–10 I-Fei Huang,7 Yao-Shen Chen,8,11 Susan Shin-Jung Lee,8,11 Mar Guang-Yuan,1,11 Hsien-Chung Yu,1,8,11–12 Chiao-Lin Hsu,1,2 Fu-Wei Wang,2,13 Chi-Shen Chen,1 Chih-Hsin Hung,9 Wen-Chien Ko3,41Department of Physical Examination Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 2Department of Nursing, Meiho University, Pingtung, Taiwan; 3Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan; 4Department of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 5Departments of Laboratory Medicine and Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; 6Department of Emergency Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 7Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 8School of Medicine, National Yang-Ming University, Taipei, Taiwan; 9Department of Chemical Engineering and Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung, Taiwan; 10Department of Nursing, Fooyin University, Kaohsiung, Taiwan; 11Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 12Institute of Health Care Management, Department of Business Management, National Sun Yat-sen University, Kaohsiung, Taiwan; 13Department of Family Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan*These authors contributed equally to this workPurpose: Fecal carriage of extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) is common in Asia, especially in China and Southeast Asia. There are no data about fecal carriage of ESBL-EC and mcr-1-positive E. coli in Taiwan, and few studies focusing on the risk factors of asymptomatic fecal carriage of epidemic ST131 E. coli have been published.Patients and methods: From healthy inhabitants attending health examinations at a medical center in southern Taiwan in 2017, we collected 724 stool samples, which were examined for ESBL-EC fecal carriage using chromogenic medium. ST131 and mcr1-positive E. coli were also investigated using multiplex PCR. Clinical data from all participating adults were collected to analyze the risk factors for fecal ESBL-EC or ST131 E. coli carriage.Results: The prevalence rate of asymptomatic ESBL-EC fecal carriage in adults was 1.9% (14/724). ST131 was found in 22 (3.0%) adults and mcr-1-positive E. coli was found in three (0.4%) adults. A multivariate analysis showed that the risk factors associated with ESBL-EC carriage were diabetes mellitus (adjusted odds ratio [aOR]: 5.5, 95% confidence interval [CI]: 1.3–22.7), a history of colonic polyps (aOR: 6.4, 95% CI: 1.6–24.9), and chronic renal insufficiency (aOR: 20.7, 95% CI: 1.4–305.7). Underlying cancer (aOR: 4.8, 95% CI: 1.0–22.5) and stroke (aOR: 18.0, 95% CI: 1.6–207.5) were associated with ST131 E. coli fecal carriage. In our cohort, travel to Asian countries and food habit were not associated with ST131 or ESBL-EC fecal carriage.Conclusions: The ESBL-EC or ST131 E. coli fecal carriage rate is low among asymptomatic adults in Taiwan. Certain underlying medical conditions were associated with their fecal carriage.Keywords: fecal colonization, extended-spectrum β-lactamase, sequence type, MCR1, Escherichia coli

Jiun-Ling Wang,1,* Chih-Feng Kuo,2,* Che-Ming Yeh,3 Jung-Ren Chen,4 Ming-Fang Cheng,5–7 Chih-Hsin Hung3 1Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC; 2Department of Nursing, I-Shou University, Kaohsiung, Taiwan, ROC; 3Department of Chemical Engineering and Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung, Taiwan, ROC; 4Department of Biological Science and Technology, I-Shou University, Kaohsiung, Taiwan, ROC; 5Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC; 6School of Medicine, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC; 7Department of Nursing, Fooyin University, Kaohsiung, Taiwan, ROC *These authors contributed equally to this work Purpose: Few effective antibiotics are available for treating extensively drug-resistant Acinetobacter baumannii (XDRAB) sepsis. Phage therapy may show potential in treating XDRAB infections. Materials and methods: We studied ϕkm18p phage therapy in BALB/c and C57BL/6 mice models of XDRAB bacteremia. Results: We observed survival rates of nearly 100% in groups given phage therapy concurrent with XDRAB at different multiplicities of infection. In mice that received phage therapy after a 1-hour delay, the survival rate decreased to about 50%. The bacterial load in the blood decreased from 108 to 102 and 103 colony-forming units (CFU)/mL in the concurrent treatment group. In the phage therapy group, the levels of the cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), were low at 3 hours after infection. Although some phage-resistant mutants were isolated after phage therapy, a cytotoxicity study showed that they had reduced fitness. Conclusion: Phage therapy in XDRAB bacteremia increased the animal survival rates, decreased the bacteremia loads, and decreased the levels of inflammatory markers TNF-α and IL-6. However, the reduced therapeutic effect with delayed administrations may be a concern in developing a successful phage therapy for treating acute infections of multidrug-resistant pathogens. Keywords: Acinetobacter baumannii, survival rates, bacteria, multiple antimicrobial drug resistance, phage therapy

Jinling Wang, Lifang Wang, Ying Li, Xiaohui Wang, Pengfei Tu School of Chinese Materia Medica, Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China Introduction: Polymeric micelles (PMs) hold promise for improving solubility and oral absorption of poorly soluble drugs. Unfortunately, the oral absorption of PMs is also limited by intestinal epithelium. To improve the oral delivery efficiency of micelles, transporter-mediated micelles could enhance the transport efficiency across the epithelial barrier, and they have attracted more attention. Methods: Peptide transporter 1 (PepT1)-mediated micelles (Val-PMs/Phe-PMs) were designed by grafting valine (or phenylalanine) onto the surface of curcumin (Cur)-loaded-D-α-tocopheryl polyethylene glycol 1000 succinate micelles (TP-PMs). The oral absorption mechanism and oral bioavailability were further investigated in vitro and in vivo. Results: The cellular study showed that Val-PMs/Phe-PMs had a high PepT1 affinity, resulting in a higher drug uptake and transcellular transport than TP-PMs. In rats, Val-PMs/Phe-PMs exhibited higher intestinal accumulation in the apical side of the intestinal epithelium than TP-PMs, promoting drug diffusion across epithelial barrier. The oral bioavailability of Cur was significantly improved by Val-PMs/Phe-PMs, which was about 10.50- and 3.40-fold greater than that of Cur-Sol and TP-PMs, respectively. Conclusion: PepT-1-mediated micelles, using PepT1 as a target on intestinal epithelium, have unique functions with intestine and prove promising for oral delivery of poorly water-soluble drugs. Keywords: PepT1, micelles, epithelial barrier, curcumin, oral delivery

Bai-qiang Cai,1 Shao-xi Cai,2 Rong-chang Chen,3 Li-ying Cui,4 Yu-lin Feng,5 Yu-tong Gu,6 Shao-guang Huang,7 Rong-yu Liu,8 Guang-nan Liu,9 Huan-zhong Shi,10 Yi Shi,11 Yuan-lin Song,6 Tie-ying Sun,12 Chang-zheng Wang,13 Jing-lan Wang,1 Fu-qiang Wen,5 Wei Xiao,14 Yong-jian Xu,15 Xi-xin Yan,16 Wan-zhen Yao,17 Qin Yu,18 Jing Zhang,6 Jin-ping Zheng,3 Jie Liu,6 Chun-xue Bai6 1Department of Pulmonary Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 2Southern Medical University South Hospital, Guangzhou, 3The First Affiliated Hospital of Guangzhou Medical College and Guangzhou Institute of Respiratory Diseases, Guangzhou, 4Affiliate Hospital of Inner Mongolia Medical University, Huhehaote, 5Huaxi Hospital of Sichuan University, Chendu, 6Zhongshan Hospital, Shanghai Medical College, Fudan University and Shanghai Respiratory Research Institute, Shanghai, 7Ruijing Hospital of Shanghai Jiaotong University, Shanghai, 8The First Affiliated University of Anhui Medical University, Hefei, 9The First Affiliated University of Guangxi Medical University, Nanning, 10Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 11General Hospital of Nanjing Military Region, Nanjing, 12Beijing Hospital of the Ministry of Health, Beijing, 13Xinqiao Hospital, Third Military Medical University, Chongqing, 14Qilu Hospital of Shandong University, Jinan, 15Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 16The Second Affiliated Hospital of Hebei Medical University and Hebei Research Institute of Respiratory Medicine, Shijiazhuang, 17The Third Affiliated Hospital of Beijing University, Beijing, 18The First Affiliated University of Lanzhou University, Lanzhou, People's Republic of China Abstract: Chronic obstructive pulmonary disease (COPD) is a common disease that severely threatens human health. Acute exacerbation of COPD (AECOPD) is a major cause of disease progression and death, and causes huge medical expenditures. This consensus statement represents a description of clinical features of AECOPD in the People's Republic of China and a set of recommendations. It is intended to provide clinical guidelines for community physicians, pulmonologists and other health care providers for the prevention, diagnosis, and treatment of AECOPD. Keywords: COPD, AECOPD, recommendations, guidelines