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Cheng Wang,1,* Jiaoyang Pan,1,* Shaoqing Chen,2 Lin Qiu,1 Huaanzi Hu,1 Li Ji,3 Jianhao Wang,1 Wenjia Liu,4 Xinye Ni2 1School of Pharmacy, Changzhou University, Changzhou, Jiangsu Province, People’s Republic of China; 2Department of Radiology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, People’s Republic of China; 3Department of Otorhinolaryngology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China; 4Department of Gastroenterology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenjia Liu; Xinye Ni, Email 13813016290@126.com; nxy@njmu.edu.cnBackground: The in vivo barriers and multidrug resistance (MDR) are well recognized as great challenges for the fulfillment of antitumor effects of current drugs, which calls for the development of novel therapeutic agents and innovative drug delivery strategies. Nanodrug (ND) combining multiple drugs with distinct modes of action holes the potential to circumvent these challenges, while the introduction of photothermal therapy (PTT) can give further significantly enhanced efficacy in cancer therapy. However, facile preparation of ND which contains dual drugs and photothermal capability with effective cancer treatment ability has rarely been reported.Methods: In this study, we selected curcumin (Cur) and doxorubicin (Dox) as two model drugs for the creation of a cocktail ND (Cur-Dox ND). We utilized polyvinylpyrrolidone (PVP) as a stabilizer and regulator to prepare Cur-Dox ND in a straightforward one-pot method.Results: The size of the resulting Cur-Dox ND can be easily adjusted by tuning the charged ratios. It was noted that both loaded drugs in Cur-Dox ND can realize their functions in the same target cell. Especially, the P-glycoprotein inhibition effect of Cur can synergistically cooperate with Dox, leading to enhanced inhibition of 4T1 cancer cells. Furthermore, Cur-Dox ND exhibited pH-responsive dissociation of loaded drugs and a robust photothermal translation capacity to realize multifunctional combat of cancer for photothermal enhanced anticancer performance. We further demonstrated that this effect can also be realized in 3D multicellular model, which possibly attributed to its superior drug penetration as well as photothermal-enhanced cellular uptake and drug release.Conclusion: In summary, Cur-Dox ND might be a promising ND for better cancer therapy. Keywords: one-pot synthesis, size-tunable, multifunctional, cancer

Yanling Li,* Li Ji,* Tian Liu, Guang Xu, Kaihe Wang, Leixin Mu, Yuying Guo, Qun Ma School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qun Ma, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China, Email maqun99@126.comBackground: Qiguiyin decoction (QGYD) is a traditional Chinese medicine (TCM) and its combined application with levofloxacin (LVFX) has been confirmed effective in the clinical treatment of multidrug-resistant Pseudomonas aeruginosa (MDR PA) infection. This study investigated the therapeutic effect and possible mechanism of QGYD in sensitizing LVFX against MDR PA infection.Materials and Methods: Pulmonary infections were induced in rats by MDR PA. The changes in pharmacokinetics-pharmacodynamics (PK-PD) parameters of LVFX after combined with QGYD were investigated in MDR PA-induced rats. Subsequently, the correlation between PK and PD was analyzed and PK-PD models were established to elucidate the relationship between QGYD-induced alterations in LVFX metabolism and its sensitization to LVFX. Antibody chip technology was used to detect the levels of inflammatory factors, suggesting the relationship between the beneficial effect of immune regulation and the sensitization of QGYD.Results: QGYD significantly enhanced the therapeutic efficacy of LVFX against MDR PA infection. The combination of QGYD changed the PK parameters of LVFX such as Tmax, t1/2, MRT, Vd/F, CL/F and PD parameters such as MIC, AUC0-24h/MIC. Predicted results from PK-PD models demonstrated that the antibacterial effect of LVFX was significantly enhanced with the combination of QGYD, consistent with experimental findings. Antibody chip results revealed that the combination of QGYD made IL-1 β, IL-6, TNF- α, IL-10, and MCP-1 levels more akin to those of the blank group.Conclusion: These findings indicated that QGYD could change the PK-PD behaviors of LVFX and help the body restore immune balance faster. This implied that a potential drug interaction might occur between QGYD and LVFX, leading to improved clinical efficacy when combined.Keywords: multidrug-resistant Pseudomonas aeruginosa infection, combination therapy, PK/PD model, Qiguiyin decoction, levofloxacin

Yu Liu,* Hongying Guo,* Wei Yuan, Ying Zou, Zhiping Qian, Xue Mei, Liujuan Ji, Jiefei Wang, Yuyi Zhang Department of Liver Intensive Care Unit, Shanghai Public Health Clinical Center, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuyi Zhang, Email zhangyuyi@shaphc.orgBackground: Talaromyces marneffei (TM) is the third most prevalent opportunistic infection in HIV-positive patients after tuberculosis and cryptococcosis. However, such infection of non-HIV individuals has rarely been reported.Case Presentation: We describe a very rare case of a 52-year-old male who presented with a single space-occupying lesion on the right lung and was eventually diagnosed with pulmonary TM infection. The patient was HIV-negative and had liver cirrhosis with portal vein thrombosis. Lung tissue next-generation sequencing (NGS) revealed TM infection. We successfully treated the patient with voriconazole for 8 weeks and observed lesion absorption via subsequent CT. The patient consumed wild bamboo rats two months before admission. Mutations related to congenital immune deficiency were not detected by whole-exome sequencing.Conclusion: Early and timely diagnosis is critical for improving patient prognosis. NGS plays a vital role in the diagnosis of pulmonary TM infection in patients. To our knowledge, this is the first published case of pulmonary TM infection in an HIV-negative patient with liver cirrhosis.Keywords: Talaromyces marneffei, pulmonary infection, HIV-negative, PVT

Lei Ji,1 Tingting Jiang,1 Xin Zhao,2 Damin Cai,1 Kouzhen Hua,1 Peng Du,1 Yuanyuan Chen,3 Jianping Xie4 1School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 2Department of International Registration, Ustar Biotechnologies (Hangzhou) Ltd, Hangzhou, Zhejiang, People’s Republic of China; 3Tuberculosis Diagnosis and Treatment Center, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang, People’s Republic of China; 4Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Ministry of Education Eco-Environment of the Three Gorges Reservoir Region, Ministry of Education, Chongqing Municipal Key Laboratory of Karst Environment, School of Life Sciences, Southwest University, Chongqing, People’s Republic of ChinaCorrespondence: Lei Ji, School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, No. 481 Binwen Road, Hangzhou, Zhejiang, 310053, People’s Republic of China, Tel +86 571 8769 2681, Fax +86 571 8769 2673, Email jilei@hmc.edu.cnPurpose: Fatty acid metabolism plays an important role in the survival and pathogenesis of Mycobacterium tuberculosis. During dormancy, lipids are considered to be the main source of energy. A previous study found that Rv0494 is a starvation-inducible, lipid-responsive transcriptional regulator. However, the role of Rv0494 in bacterial persister survival has not been studied.Methods: We constructed a Rv0494 deletion mutant strain of Mycobacterium tuberculosis H37Rv and evaluated the susceptibility of the mutant strain to antibiotics using a persistence test.Results: We found that mutations in Rv0494 lead to survival defects of persisters, which reflected in increased sensitivity to isoniazid.Conclusion: We conclude that Rv0494 is important for persister survival and may serve as a good target for developing new antibiotics that kill persister bacteria for improved treatment of persistent bacterial infections.Keywords: drug target, drug tolerance, lipids, persisters

Yong Li,1,2,* Senbo Zhu,2,* Junchao Luo,2 Yu Tong,2 Yixuan Zheng,1 Lichen Ji,2 Zeju He,2 Qiangan Jing,1 Jiaqing Huang,2 Yinjun Zhang,1 Qing Bi2 1College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, Zhejiang, 310014, People’s Republic of China; 2Laboratory Medicine Center, Department of Laboratory Medicine, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yinjun Zhang, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, Zhejiang, 310014, People’s Republic of China, Tel +86-13735494556, Email zhangyj@zjut.edu.cn Qing Bi, Laboratory Medicine Center, Department of Laboratory Medicine, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China, Tel +86-13588302991, Email bqzjsrmyy@163.comIntroduction: Osteoarthritis (OA) is a common chronic joint disease characterized by articular cartilage degeneration. OA usually manifests as joint pain, limited mobility, and joint effusion. Currently, the primary OA treatment is non-steroidal anti-inflammatory drugs (NSAIDs). Although they can alleviate the disease’s clinical symptoms and signs, the drugs have some side effects. Selenium nanoparticles (SeNPs) may be an alternative to relieve OA symptoms.Materials and Results: We confirmed the anti-inflammatory effect of selenium nanoparticles (SeNPs) in vitro and in vivo experiments for OA disease in this study. In vitro experiments, we found that SeNPs could significantly reduce the expression of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), the major inflammatory factors, and had significant anti-inflammatory and anti-arthritic effects. SeNPs can inhibit reactive oxygen species (ROS) production and increased glutathione peroxidase (GPx) activity in interleukin-1beta (IL-1β)-stimulated cells. Additionally, SeNPs down-regulated matrix metalloproteinase-13 (MMP-13) and thrombospondin motifs 5 (ADAMTS-5) expressions, while up-regulated type II collagen (COL-2) and aggrecan (ACAN) expressions stimulated by IL-1β. The findings also indicated that SeNPs may exert their effects through suppressing the NF-κB p65 and p38/MAPK pathways. In vivo experiments, the prevention of OA development brought on by SeNPs was demonstrated using a DMM model.Discussion: Our results suggest that SeNPs may be a potential anti-inflammatory agent for treating OA.Keywords: osteoarthritis, NF-κB p65 signaling pathway, p38/MAPK signaling pathway, selenium nanoparticles

Jiaming Hu,1 Lili Ji,2 Ping Li,3 Xinyu Ni,1 Ying Huang,1 Jinxin Tao,1 Hua Zhu1 1Department of Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Clinical Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Department of Out-Patient, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of ChinaCorrespondence: Hua Zhu, Department of Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China, Tel +86-13505777090, Fax +86-577-55578033, Email ZHwenzhou@126.comPurpose: This study aimed to investigate male HPV infection, re-examination rate, clearance rate and relevant influencing factors as well as HPV infection between heterosexual partners in Wenzhou, China.Methods: The study enrolled 2359 men who accepted ≥ 1 HPV detection in the First Affiliated Hospital of Wenzhou Medical University between June 2014 and June 2020. An outpatient follow-up was carried out for collecting HPV re-test results among males who were tested HPV positive. In addition, we collected female sexual partners’ HPV infection state through outpatient information system or telephone call. For males who had not re-tested HPV more than half a year after the first HPV positive result, a telephone follow-up would be provided.Results: Male HPV prevalence was 39.39% (928/2359) at baseline, of which the median age was 38.00 years. The percentage of co-infection and HR HPV infection was 35.24% (327/928) and 61.08% (874/1431). Genotype-specific concordance of HPV infection among heterosexual partners was 61.19% (123/201). The most common types were HPV6, HPV52, HPV16, HPV53, HPV11, HPV43 and HPV58. Percentage of males finishing HPV re-examination was low (40.09%). Infection with HR HPV, discomfort or HPV-related diseases and sexual partners with HPV infection were possible motivator for male HPV re-test. The medium time to male HPV clearance was 300.000 (95% CI=274.845– 325.155) days. Infection with HR HPV, sexual partners with HPV infection and growth of age might prolong HPV persistence time included.Conclusion: Males are susceptible population for genital HPV infection as well as females. Whereas, males are generally less aware of HPV and its influence on their couples. The study showed that male HPV testing as well as the role of males in the diagnosis and treatment of HPV-associated cervical diseases for females should be popularized and co-treatment of couples was necessary.Keywords: human papillomavirus, males, heterosexual couples, prevalence, persistence, re-test rate

Minyuan Chen,1,&ast; Puhong Zhang,1,2,&ast; Yang Zhao,1,3 Nadila Duolikun,1 Linong Ji4 1The George Institute for Global Health, China, Beijing, 100600, People’s Republic of China; 2The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, 2050, Australia; 3WHO Collaborating Centre on Implementation Research for Prevention and Control of Noncommunicable Diseases, Melbourne, VIC, Australia; 4Department of Endocrinology and Metabolism, Peking University People’s Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Puhong Zhang, Diabetes Research Program, The George Institute for Global Health, China, Room 052A, Unit 1, Tayuan Diplomatic Office Building No. 14 Liangmahe Nan Lu, Chaoyang District, Beijing, 100600, People’s Republic of China, Tel/Fax +86 10 8280 0177, Email zpuhong@georgeinstitute.org.cn Linong Ji, Department of Endocrinology and Metabolism, Peking University People’s Hospital, No. 11, Xizhimen Nan Da Jie, Xicheng District, Beijing, 100044, People’s Republic of China, Tel +86 10 88325578, Fax +86 10 68358517, Email jiln@bjmu.edu.cnBackground: This study aims to compare the effectiveness of initiating insulin therapy in inpatient and outpatient settings during a 6-month follow-up period among patients with type 2 diabetes mellitus (T2DM) in real-world settings.Materials and Methods: The study was based on the ORBIT study, a real-world observational study which recruited patients with inadequate glycemic control by oral antidiabetic drugs (OAD) and initiated basal insulin (BI). We compare difference in initiation and evolution of insulin therapy and glycemic control after six months were compared between patients initiating basal insulin in the inpatient department (inpatient initiators) and those starting in outpatient (outpatient initiators) among participants without rehospitalization during the six months follow-up.Results: Among all 18,995 participants in the ORBIT study, 56.0% were inpatient initiators and 44.0% outpatient. We conducted in-depth analysis among 14,860 patients without rehospitalization, 8129 inpatient initiators and 6731 outpatient initiators. (1) Inpatient initiators had lower insulin therapy persistence during six months (64.2%) than outpatient ones (78.6%) (p< 0.001), which was mainly explained by more therapy switches from basal-bolus regimen to other therapies among inpatient initiators (50.1%) than that among outpatient initiators (37.5%) (p< 0.001). (2) Inpatient initiation had a higher proportion of people achieving glucose targets (HbA1c < 7%) than outpatient initiation. However, the benefit of inpatient initiation versus outpatient initiation was mainly observed among patients persisting with the initial insulin therapies (46.3% vs 39.5% p< 0.001), rather than those nonpersistent (37.3% vs 36.2%, p=0.723). (3) Among patients with HbA1c < 9%, taking only one OAD and without complications at baseline, inpatient insulin initiation did not show a higher proportion of people achieving glucose target than outpatient initiation (adjusted odds ratio=0.96, 95% CI: 0.76– 1.21).Conclusion: For patients with HbA1c ≥ 9%, who were taking more than one OAD and had complications at baseline, initiating insulin treatment during hospitalization has a higher proportion of people achieving glucose target than that in the outpatient department, but the premise is that the initial therapy is acceptable and can be maintained after discharge. Patient-centered approach with co-agreed decision-making to select a suitable insulin regimen should be strengthened.Keywords: type 2 diabetes mellitus, T2DM, basal insulin, BI, hospitalization, outpatient, glycemic control

Gabriel Quesada,1 Daniel H Chang,2 Kevin L Waltz,3 Andrew A Kao,2 Rodrigo Quesada,1 Ying Wang,4 Leilei Ji,4 Dari Parizadeh,4 Luis Atiles4 1Grupo Oftalmo & Plastico, San Salvador, El Salvador; 2Empire Eye and Laser Center, Bakersfield, CA, USA; 3Central American Ophthalmic Research Consultants, Indianapolis, IN, USA; 4Johnson & Johnson Surgical Vision, Inc, Santa Ana, CA, USACorrespondence: Gabriel Quesada, Grupo Oftalmo & Plastico, 9 C Pte, 4625, Col Escalon, San Salvador, El Salvador, Tel +1 (503) 22579003, Email gabriel.quesadalarez@gmail.comPurpose: The purpose of this first in-human study was to evaluate the overall clinical performance of the VERITAS™ Vision System in patients scheduled to undergo cataract extraction and to confirm overall surgeon acceptability.Patients and methods: This prospective, open-label multinational study included adults with cataracts scheduled for planned cataract extraction and posterior chamber IOL implantation. Standard small-incision phacoemulsification cataract surgery with the VERITAS Vision System was conducted. Surgeons completed a questionnaire regarding their clinical experience with the VERITAS Vision System for each patient following surgery and 1-day postoperative. Corneal clarity and adverse events (AEs) were assessed. Surgeon acceptability was scored on a 5-point scale, with acceptability considered favorable for scores of 4 and 5.Results: A total of 115 eyes (79 patients) were treated. The El Salvador site treated 41 patients (58 eyes), and the US site treated 38 patients (57 eyes). Overall, surgeons were satisfied with the clinical performance regardless of the cataract grade. The satisfaction with anterior chamber stability, post-occlusion surge, followability, holdability, cutting efficiency, usability, and overall satisfaction with the VERITAS Vision System was clinically favorable in ≥ 99% of cases. Overall satisfaction with the swivel handpiece, foot pedal, and enhanced ergonomics were clinically favorable in ≥ 97% of cases regardless of the cataract grade. Satisfaction with corneal clarity at same-day postoperative and 1-day postoperative, and 1-day overall clinical results of surgery with the VERITAS Vision System were clinically favorable in ≥ 94% of cases regardless of cataract grade.Conclusion: The new dual-mode phacoemulsification system with dual-durometer tubing, gas forced infusion, new swivel handpiece, and ergonomics improvements resulted in a high rate of user satisfaction with clinical performance and ergonomics. The VERITAS Vision System is safe and effective when used as indicated.Keywords: VERITAS Vision System, cataract, ergonomics, fluidics, satisfaction

Yanlei Li,1,2,&ast; Jinlong Tian,1,2,&ast; Meng Ge,1,2,&ast; Lichen Ji,1,3 Yao Kang,1 Chen Xia,1 Jun Zhang,1,2 Yazeng Huang,1,2 Fabo Feng,1 Tingxiao Zhao,1,2 Haiyu Shao1 1Center for Plastic & Reconstructive Surgery, Department of Orthopedics, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, People’s Republic of China; 2Bengbu Medical College, Bengbu, People’s Republic of China; 3Wenzhou Medical University, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haiyu Shao; Tingxiao Zhao, Center for Plastic & Reconstructive Surgery, Department of Orthopedics, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Shangtang Road 158#, Hangzhou, 310014, People’s Republic of China, Email shaohaiyu@163.com; spinezhaotingxiao@163.comBackground: With the aging population growth in the world, the prevalence of osteoporotic vertebral compression fracture (OVCF) is rapidly increasing and receiving widespread attention. Although there are numerous articles on the topic, the research status and hotspot analysis are unclear.Objective: The goal of this study is to identify trends in the OVCF field and to analyze the most highly cited original articles published in the Web of Science Index on OVCF using bibliometric analysis.Methods: All OVCF data were obtained from the Web of Science Core Collection, and the number of citations, institutions, journals, countries, and years of publication in this field were visually analyzed using VOSviewer, the bibliometrics online analysis platform, and Excel software. Simultaneously, the top 100 most cited articles were extracted and analyzed.Results: A total of 756 publications were related to OVCF were included from 1900 to 2022. In recent years, the number of articles on OVCF significantly increased. They are mainly from 41 countries/regions and 202 journals, led by China and the United States. Among all countries, China had the most significant contribution on OVCF (n = 363), and it also was cited most often (n = 3337). The institution with the most articles was Soochow University (n = 40). Osteoporosis International was the journal with most studies and has published 50 on this field. The journal of Spine was cited most often (n = 1968). The most productive periods were from 2016 to 2020, which received 294 articles and 4868 citations. After the analysis, the “vertebroplasty” and “kyphoplasty” of OVCF have been the most common research hotspots.Conclusion: This study represents an updated bibliometric analysis of OVCF. The aim is to identify current research hotspots and future trends to guide clinicians and researchers in this field.Keywords: osteoporotic vertebral compression fracture, OVCF, bibliometric analysis, VOSviewer, Web of Science, research trends

A new giant outburst of the Be X-ray binary RX J0520.5–6932 was detected and subsequently observed with several space-borne and ground-based instruments. This study presents a comprehensive analysis of the optical and X-ray data, focusing on the spectral and timing characteristics of selected X-ray observations. A joint fit of spectra from simultaneous observations performed by the X-ray telescope (XRT) on the Neil Gehrels Swift Observatory (Swift) and Nuclear Spectroscopic Telescope ARray (NuSTAR) provides broad-band parameter constraints, including a cyclotron resonant scattering feature (CRSF) at |$32.2_{-0.7}^{+0.8}$|  keV with no significant energy change since 2014, and a weaker Fe line. Independent spectral analyses of observations by the Lobster Eye Imager for Astronomy, Einstein Probe (EP), Swift –XRT, and NuSTAR demonstrate the consistency of parameters across different bands. Luminosity variations during the current outburst were tracked. The light curve of the Optical Gravitational Lensing Experiment (OGLE) aligns with the X-ray data in both 2014 and 2024. Spin evolution over 10 yr is studied after adding Fermi Gamma-ray Burst Monitor data, improving the orbital parameters, with an estimated orbital period of 24.39 d, slightly differing from OGLE data. Despite intrinsic spin-up during outbursts, a spin-down of |$\sim$| 0.04 s over 10.3 yr is suggested. For the new outburst, the pulse profiles indicate a complicated energy-dependent shape, with decreases around 15 and 25 keV in the pulsed fraction, a first for an extragalactic source. Phase-resolved NuSTAR data indicate variations in parameters such as flux, photon index, and CRSF energy with rotation phase. [ABSTRACT FROM AUTHOR]

Attached cavitation often occurs on the blade surface of hydraulic machinery, negatively affecting its performance. The SST k-ω turbulence model and SS cavitation model are employed to calculate the attached cavitation on the surface of the NACA0015 hydrofoil to explore the interaction between attached cavitation and the velocity boundary layer. The findings are systematically analyzed from four aspects: flow field characteristics, vortex dynamics, boundary layer characteristics, and energy loss. The results indicated that the spanwise effect of the surface flow field of the hydrofoil is more pronounced at low cavitation numbers. From the perspective of vortex dynamics, each vortex transport term is sensitive to the change in cavitation number, and the trend of each vortex transport term varies with the change in cavitation number. The inverse pressure gradient region of the velocity boundary layer is primarily distributed in the tail of the attached cavity, significantly affecting the formation of the phase interface at the tail of the cavity and the cavity shedding. The energy loss on the suction surface of the hydrofoil is mainly concentrated in the velocity boundary layer, with PL1 and PL3 being the primary ones. When the interface of the attached cavity phase overlaps with the velocity boundary layer, it promotes the energy loss of the local fluid. When the attached cavity completely covers the velocity boundary layer, the energy loss in the boundary layer is significantly reduced. [ABSTRACT FROM AUTHOR]

Objective: To investigate the optimal interval between self-expanding metal stent (SEMS) placement and radical surgery in patients with obstructive colorectal cancer. Method: In this study, a retrospective research design was used to select 125 patients with obstructive colorectal cancer who underwent colonoscopic SEMS placement with subsequent radical surgery between February 2011 and November 2022 at Shanghai Changhai Hospital. In addition, their clinical data and therapeutic efficacy were examined. Grouping: grouping on the basis of the interval of bridge to surgery (BTS). Group A: interval of BTS ≤ 14 days; group B: 14 days < interval of BTS ≤ 21 days; group C1: interval of BTS > 21 days; group C2: interval of BTS > 21 days, excluding patients who received neoadjuvant therapy; group D: patients who received neoadjuvant therapy. Patients were grouped according to their different surgical methods, group E: patients who received open surgery and group F: patients undergoing laparoscopic surgery. Results: A total of 125 patients were included in this study, the mean age of the patients was 61.34 ± 13.99 years, with the median follow-up time was 39 (25–61) months. Of these, 84 cases (67.2%) underwent open surgery, while 41 cases (32.8%) underwent laparoscopic surgery. Among the cohort, 15 patients received neoadjuvant radiotherapy and chemotherapy after placement of SEMS. There was a significant difference in preoperative hemoglobin levels between group A and both group B and group C1. The laparoscopic surgery rate was significantly higher in group B than in the other two groups (48.57% versus 3.33% and 22.81%, P = 0.038). The 5-year disease-free survival (DFS) of group C1 patients was lower than that in group A and group B (32.4% versus 56.3%, 62.3%, P = 0.038; P = 0.043), whereas there was no statistical difference in the 5-year overall survival (OS) (60.7% versus 62.1%, 69.6%, P = 0.365, P = 0.339). group D showed a higher proportion of open surgery and a higher T-stage (P < 0.05), resulting in a 5-year DFS that was inferior to group A and group B (17.7% versus 56.3%, 62.3%, P = 0.045; P = 0.047). However, there was no significant difference compared with group C2 (17.7% versus 36.9%, P > 0.05). The 5-year OS of group D was not statistically significantly different from that of group A, group B, and group C2 (28.4% versus 62.1%, 69.6%, 73.4%, P = 0.089, P = 0.090, P = 0.183). In addition, no statistically significant differences were identified in 5-year DFS (49.9% versus 37.0%, P = 0.555) or 5-year OS (66.2% versus 62.6%, P = 0.062) between group E and group F Conclusions: Radical surgery performed 14–21 days apart after SEMS placement has been shown to improve minimally invasive rates and 5-year DFS rates. The addition of neoadjuvant radiotherapy and chemotherapy during the interval does not appear to improve long-term survival, although this conclusion is based on the results of only 15 patients. [ABSTRACT FROM AUTHOR]

Jerry G Hu,1 Vin T Dang,2 Daniel H Chang,2 Damien F Goldberg,3 Cheryl McKinnon,4 Katherine Makedonsky,4 Michal Laron,4 Leilei Ji5 1Texas Eye & Laser Center, P.A., Hurst, TX, USA; 2Empire Eye and Laser Center, Bakersfield, CA, USA; 3Wolstan & Goldberg Eye Associates, Torrance, CA, USA; 4Johnson & Johnson Surgical Vision, Inc., Milpitas, CA, USA; 5Johnson & Johnson Surgical Vision, Inc., Irvine, CA, USACorrespondence: Cheryl McKinnon, Johnson & Johnson Surgical Vision, Inc., 510 Cottonwood Drive, Milpitas, CA, 95035, USA, Tel +1 408 273 4014, Email cmckinno@its.jnj.comPurpose: Investigator feedback was used to assess the clinical use of the LipiFlow® System with the new translucent Activator Clear to successfully complete LipiFlow® treatments.Patients and Methods: This was a prospective, open-label clinical investigation. A total of 88 eyes (44 subjects) were treated using the LipiFlow® System with the new Activator Clear. Subjects diagnosed with bilateral meibomian gland dysfunction (MGD) were enrolled in the study. Each investigator performed a complete LipiFlow® treatment with the translucent Activator on both eyes of each subject. Investigators completed a questionnaire assessing the clinical use of the Activator Clear on a 5-point scale (1 – very difficult or strongly disagree, 3 – neutral, 5 – very easy or strongly agree).Results: The new translucent Activator provided successful LipiFlow® treatments in 100% of cases, with 95% confidence interval of (96%, 100%). Additionally, the investigators agreed or strongly agreed that the translucent components of the Activator Clear made it easy to access and position the activator with confidence on the subject’s eye.Conclusion: The overall investigators’ impressions on usage and functionality of LipiFlow® System with the translucent Activator were very positive. The Activator Clear enables doctors with efficient and confident positioning around patient eyelids to ensure successful LipiFlow® treatment when used as indicated.Keywords: LipiFlow® vectored thermal pulsation, Activator Clear

Yuyao Li,1,&ast; Yue Li,1,&ast; Jinghao Zhang,2 Longshan Ji,3 Man Li,3 Xuehua Sun,2 Hai Feng,1 Zhuo Yu,2 Yueqiu Gao1,2 1Institute of Infectious Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Laboratory of Cellular Immunity, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhuo Yu; Yueqiu Gao, Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, No. 528 Zhangheng Road, Pudong New District, Shanghai, 201203, People’s Republic of China, Tel +86 21 2025 6507, Fax +86 21 20256699, Email zhuoyu@shutcm.edu.cn; gaoyueqiu@shutcm.edu.cnAbstract: Hepatocellular carcinoma (HCC) is one of the leading lethal tumors worldwide, and the treatment remains a great medical challenge. Surgery and chemotherapy are current standard curative methods for patients with HCC, but the prognosis is still dismal. Based on unique medical theories and rich practical experience, traditional Chinese medicine (TCM) has been broadly employed to effectively treat HCC for a long history. Recently, systematic clinical trials have been well designed to study the efficacy of TCMs in the treatment of HCC, and the underlying antitumor mechanisms were also deeply explored. Here, we reviewed the published clinical evaluation of some commonly used TCMs in the treatment of HCC, and the related anti-HCC mechanisms through in vitro and in vivo study, promoting the modernization of TCM study in oncology for achieving a substantial reduction of HCC burden in the future.Keywords: traditional Chinese medicine, hepatocellular carcinoma, antitumor mechanism, tumor therapy, active ingredient

We report a detailed timing and spectral analysis of the X-ray pulsar 2S 1417−624 using the data from Insight-HXMT during the 2018 outburst. The pulse profiles are highly variable with respect to both unabsorbed flux and energy. A double-peaked pulse profile from the low flux evolved to a multi-peaked shape in the high-flux state. The pulse fraction is negatively correlated to the source flux in the range of ∼(1 − 6)×10−9 erg cm−2 s−1, consistent with Rossi X-ray Timing Explorer (RXTE) studies during the 2009 giant outburst. The energy-resolved pulse profiles around the peak outburst showed a four-peak shape in the low-energy bands and gradually evolved to triple peaks at higher energies. The continuum spectrum is well described by typical phenomenological models, such as the cut-off power law and the power law with high-energy cut-off models. Notably, we discovered high-energy cyclotron resonant scattering features (CRSFs) for the first time, which are around 100 keV with a statistical significance of ∼7σ near the peak luminosity of the outburst. This CRSF line is significantly detected with different continuum models and provides very robust evidence for its presence. Furthermore, pulse-phase-resolved spectroscopy confirmed the presence of the line, whose energy varied from 97 to 107 keV over the pulse phase and appeared to have a maximum value at the narrow peak phase of the profiles. [ABSTRACT FROM AUTHOR]

Yanjie Wang,1 Josephine Etowa,2 Bishwajit Ghose,3 Shangfeng Tang,4 Lu Ji,5 Rui Huang6 1Xinxiang Medical University, Xinxiang, 453003, Henan, People’s Republic of China; 2School of Nursing, Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada; 3Organisation pour l’environnement et Développement Durable, Lomé, BP: 80867, Togo; 4School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 5School of Medicine and Health Management, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 6School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of ChinaCorrespondence: Rui HuangSchool of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of ChinaEmail hys19810612@163.comIntroduction: Using data from Malawi Demographic and Health Survey (2015– 16), in the present study, we aimed to assess the role of exposure to family planning information through various mass media on the utilization of maternal healthcare services.Methods: The sample population included 13,217 women aged 15– 49 years with a history of at least one childbirth. Outcome measures included essential maternal healthcare services such as early and adequate use of antenatal care, skilled delivery service. Multivariate logistic regression models were used to find the association between maternal healthcare services and exposure to family planning messages by controlling for sociodemographic characteristics.Results: Women who reported receiving family planning message through internet [odds ratio=1.48, 95% CI=1.15, 1.91], radio [odds ratio=1.15, 95% CI=1.05, 1.26], TV [odds ratio=1.53, 95% CI=1.32, 1.76] and mobile phone [odds ratio=1.23, 95% CI=1.02, 1.48] had higher odds of having timely ANC care. For using adequate number of ANC, the associations were significant for TV [odds ratio=1.41, 1.23, 1.62] and mobile phone [odds ratio=1.20, 95% CI=1.01, 1.43] only. For the use of facility delivery, a strong association was observed for poster [odds ratio=1.43, 95% CI=1.12, 1.82] and TV [odds ratio=2.99, 95% CI=1.78, 5.03]. The odds of using all three services varied noticeably between urban and rural areas, eg, receiving family planning messages through internet increased the odds of antenatal care and facility delivery services in the urban areas only, whereas that from poster was associated only for facility delivery and only in the rural areas.Conclusion: The findings indicate a positive association on media communication regarding family planning on the uptake of maternal healthcare services.Keywords: mass media, family planning, health communication, maternal healthcare utilisation, Malawi

Liechen Ji,1,* Shuo Chen,1,* Liqiang Gu,1 Juan Wang,2 Xipeng Zhang1 1Department of Colorectal Surgery, Tianjin Union Medical Center, Nankai University, Tianjin, 300121, People’s Republic of China; 2Department of General Surgery, Tianjin Union Medical Center, Nankai University, Tianjin, 300121, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xipeng ZhangDepartment of Colorectal Surgery, Tianjin Union Medical Center, Nankai University, No. 190 Jieyuan Road, Hongqiao District, Tianjin, 300121, People’s Republic of ChinaTel +862287729595Email xipengzhang1976@163.comIntroduction: It has been reported that lncRNA AGAP2-AS1 promotes the development of gastric cancer, lung cancer and breast cancer. This study aimed to investigate the role of AGAP2-AS1 in colon cancer.Methods: A total of 66 patients with colon cancer were enrolled. RT-qPCR was performed to detect the differential expression of AGAP2-AS1 in tumor tissues and adjacent normal tissues. To test the interaction between AGAP2-AS1 and LINC-PINT in colon cancer, overexpression vector or inhibitor of AGAP2-AS1 and LINC-PINT were transfected into RKO and HCT 116 cells. CCK-8 assay was used to detect cell proliferation. Transwell assays were performed to evaluate cell migration and invasion. The expression of p-LATS1, p-YAP and nuclear YAP were detected by Western blot and immunofluorescence.Results: The expression of AGAP2-AS1 was upregulated in colon cancer tissues compared with that in adjacent normal tissues, and the expression of AGAP2-AS1 in colon cancer tissues was not significantly affected by tumor stages. In addition, we found that the expression of LINC-PINT was downregulated in colon cancer tissues compared with that in adjacent normal tissues and had a reverse correlation with the expression of AGAP2-AS1 in colon cancer tissues. Moreover, overexpression of AGAP2-AS1 downregulated the expression of LINC-PINT, and overexpression of LINC-PINT also altered the expression of AGAP2-AS1 in colon cancer cells. Inhibition of AGAP2-AS1 upregulated the expression of LINC-PINT, and inhibition of LINC-PINT promoted the expression levels of AGAP2-AS1 in colon cancer cells. Furthermore, overexpression of AGAP2-AS1 could increase the proliferation, invasion and migration of colon cancer cells, while overexpression of LINC-PINT could attenuate the effects of overexpression of AGAP2-AS1 on the proliferation, migration and invasion of colon cancer cells. We also found that AGAP2-AS1 promoted colon cancer cell proliferation, migration and invasion through the Hippo signaling.Conclusion: Upregulated expression of AGAP2-AS1 promoted proliferation, invasion and migration in colon cancer by forming a negative feedback loop with LINC-PINT.Keywords: colon cancer, lncRNA AGAP2-AS1, lncRNA LINC-PINT, proliferation, migration, invasion

Xiuting Huang,1,* Xiuying Zhang,1,* Xianghai Zhou,1 Xueyao Han,1 Zuodi Fu,2 Yufeng Li,2 Linong Ji1 1Department of Endocrinology and Metabolism, Peking University People’s Hospital, Peking University Diabetes Center, Beijing 100044, People’s Republic of China; 2Department of Endocrinology and Metabolism, Capital Medical University Pinggu Teaching Hospital, Beijing 101200, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yufeng LiDepartment of Endocrinology and Metabolism, Capital Medical University Pinggu Teaching Hospital, No. 59, Xinping North Street, Pinggu District, Beijing 101200, People’s Republic of ChinaTel/Fax +86 10 89978790Email doctorlyf@126.comLinong JiDepartment of Endocrinology and Metabolism, Peking University People’s Hospital, Peking University Diabetes Center, No. 11, Xizhimen South Street, Xicheng District, Beijing 100044, People’s Republic of ChinaTel +86 10 88324108Fax +86 10 88325534Email jilinong@gmail.comAim: Impaired glucose metabolism and thyroid dysfunction (TD) are the two most common chronic metabolic disorders. This study aimed to investigate the epidemiological characteristics of TD in different status of glucose tolerance in a community-based Chinese population and to understand the association between TD and glucose metabolism.Methods: A community-based population study of metabolic disease was conducted from June 2013 to September 2014 in Beijing, China. Residents aged 26– 76 years were selected according to gender and age composition using multi-stage stratified random sampling process. All participants underwent serum thyroid function and thyroid-associated antibody tests. The status of glucose tolerance was determined using 75g-oral glucose tolerance test. Chi-square test was used to compare the differences in prevalence. Multivariate logistic regression analysis was used to determine the impact of insulin resistance (IR) on thyroid function.Results: By analyzing 3986 participants who were included in the survey, the prevalence of type 2 diabetes (T2DM) and pre-diabetes (pre-DM) was 18.59% and 26.79%, respectively. The prevalence of TD was 8.81%, with overt hyperthyroidism accounting for 0.38%; subclinical hyperthyroidism, 1.86%; overt hypothyroidism, 0.70%; and subclinical hypothyroidism, 5.87%. The prevalence of TD increased with gradually deteriorated glucose tolerance (7.63% in those with normal glucose tolerance, 9.27% in pre-DM, and 11.61% in T2DM) in both men and women. Each unit of higher HOMA-IR was associated with 7% higher likelihood of having subclinical hypothyroidism.Conclusion: The coexisting of TD with T2DM and pre-DM is high in this community-based Chinese population, suggesting a close relationship between TD and glucose metabolism.Keywords: type 2 diabetes, pre-diabetes, thyroid dysfunction, epidemiology

Guangxu Liu,1,2 Jingtao Dou,3,4 Deqiang Zheng,1,2 Jie Zhang,1,2 Meiping Wang,1,2 Wei Li,1,2 Jing Wen,1,2 Juming Lu,3 Linong Ji,5 Yan He1,2 1Department of Epidemiology and Biostatistics, School of Public Health, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, People’s Republic of China; 3Department of Endocrinology, Chinese PLA General Hospital, Beijing, People’s Republic of China; 4Department of Endocrinology, Hainan Branch of Chinese PLA General Hospital, Sanya, People’s Republic of China; 5Department of Endocrinology and Metabolism, Peking University People’s Hospital, Beijing, People’s Republic of ChinaCorrespondence: Yan He; Jingtao Dou Email yanhe1220@126.com; jingtaodou@163.comPurpose: The objective of this study was to investigate the association of abnormal glycemic phenotypes with microvascular complications in type 2 diabetes patients.Participants and Methods: A total of 24,266 participants who were from the multicenter cross-sectional survey of China National HbA1c Surveillance System across China were included in the present study. Diabetes patients with abnormal glucose were divided into three groups according to phenotype: isolated fasting hyperglycemia (IFH), isolated postprandial hyperglycemia (IPH), or combined hyperglycemia (CH). The main outcomes were isolated diabetic retinopathy, isolated diabetic nephropathy, and combined diabetic retinopathy with nephropathy. Multivariate logistic regression was used to assess the association of abnormal glycemic phenotypes with microvascular complications.Results: The CH phenotype had the highest prevalence of isolated diabetic retinopathy, isolated diabetic nephropathy and combined diabetic retinopathy with nephropathy, followed by IPH. Multivariate analysis showed that the CH phenotype was associated with the highest risk of isolated diabetic retinopathy (OR: 1.20, 95% CI: 1.02– 1.41), isolated diabetic nephropathy (OR: 1.59, 95% CI: 1.27– 2.01) and combined diabetic retinopathy with nephropathy (OR: 1.93, 95% CI: 1.44– 2.59). More importantly, participants with IPH phenotype also showed significantly higher risks of isolated diabetic retinopathy (OR: 1.16, 95% CI: 1.05– 1.28), isolated diabetic nephropathy (OR: 1.37, 95% CI: 1.09– 1.37) and combined diabetic retinopathy with nephropathy (OR:1.64, 95% CI: 1.21– 2.21) compared to the IFH phenotype. After stratifying by age, sex, diabetes duration and BMI, the higher risks of isolated diabetic retinopathy, isolated diabetic nephropathy and combined diabetic retinopathy with nephropathy were confirmed in IPH phenotype group, compared to the IFH phenotype group.Conclusion: Diabetic patients with IPH phenotype had higher risks of isolated diabetic retinopathy, isolated diabetic nephropathy and combined diabetic retinopathy with nephropathy compared with the participants phenotype of IFH, but lower than the phenotype of CH.Keywords: abnormal glycemic phenotype, diabetic nephropathy, diabetic retinopathy, type 2 diabetes mellitus

Meng Li,1,* Xiuying Zhang,1,* Xianghai Zhou,1 Xueyao Han,1 Rui Zhang,1 Zuodi Fu,2 Lianying Wang,2 Ying Gao,1 Yufeng Li,2 Linong Ji1 1Department of Endocrinology and Metabolism, Peking University People’s Hospital, Peking University Diabetes Center, Beijing, People’s Republic of China; 2Department of Endocrinology and Metabolism, Capital Medical University Pinggu Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Linong JiDepartment of Endocrinology and Metabolism, Peking University People’s Hospital, Beijing 100044, People’s Republic of ChinaTel/Fax +86-10-88324371Email jiln@bjmu.edu.cnYufeng LiDepartment of Endocrinology and Metabolism, Capital Medical University Pinggu Hospital, Beijing 101200, People’s Republic of ChinaTel/Fax +86-10-89978790Email doctorlyf@126.comPurpose: We aimed to ascertain the association between thyrotropin (TSH) levels in euthyroid state and the prevalence of metabolic syndrome (MetS) in a community-based Chinese population.Participants and Methods: Based on a large and well-characterized community cohort in Beijing, China, 1831 men and 1742 women with serum TSH levels within the reference range (0.50– 4.78 μIU/mL) were stratified by quartiles of TSH (Q1-4). MetS was identified according to the criteria of International Diabetes Federation guidelines. Poisson regression models were used to estimate the association between serum TSH and the prevalence of MetS and its components before and after adjustment for potential confounding factors. The reported association was measured using the prevalence ratio (PR) with its respective 95% confidence interval (95% CI).Results: The prevalence of MetS in euthyroid population across TSH quartiles (Q1-4) was 38.9%, 44.6%, 41.0%, and 47.7%, respectively, in men (P = 0.045), and 47.7%, 46.6%, 46.9%, and 54.6%, respectively, in women (P = 0.032). Compared with the reference group TSH-Q1, the prevalence of MetS was higher among TSH-Q4 group both in men (PR = 1.27; 95% CI: 1.09, 1.48, P = 0.002) and women (PR = 1.21; 95% CI: 1.07, 1.37, P = 0.003) even after adjustment for age, lifestyle factors, serum levels of free triiodothyronine (FT3), and free thyroxine (FT4). Most of the components of MetS were common in higher serum TSH levels within the normal range.Conclusion: The prevalence of MetS and most of its components increased in the higher TSH group in euthyroid Chinese population.Keywords: thyroid hormones, obesity, hypertension, hyperglycemia

Shuang Feng, Hui Cong, Lei Ji The Second People’s Hospital of Nantong, Nantong, Jiangsu, People’s Republic of ChinaCorrespondence: Lei Ji Email jileiyaoyao@163.comIntroduction: Osteoarthritis (OA), a chronic joint disease, combines with massive inflammation and plays a vital role in cartilage degeneration. The main strategy in clinic is controlling inflammation, thereby treating osteoarthritis. Salvianolic acid A (SAA) is a type of phenolic acid, derived from a traditional chinese herbal medicine Danshen that is extensively used clinically.Methods and Results: We observed the anti-inflammatory and antiarthritic effects of SAA in IL-1β-stimulated cells. We found that SAA evidently decreased the expression of mainly inflammatory factors, exerted the remarkable effects of anti-inflammation and anti-arthritis. Furthermore, SAA inhibited the expression of Matrix metalloproteinases (MMP1, MMP13), and ADAMTS-5 and raised the synthesis of collagen II and aggrecan. Additionally, the results indicated that SAA gave rise to the effects by down-regulation of NF-κB and p38/MAPK pathways.Discussion: Our study demonstrates that SAA may be a promising anti-inflammatory for the treatment of OA in clinic.Keywords: Salvianolic acid A, Osteoarthritis, MMPs, NF-κB pathway

Xiaoling Cai,1 Fang Zhang,1 Chu Lin,1 Xiaomei Zhang,2 Zhufeng Wang,3 Huifang Xing,4 Lin Nie,5 Xueyao Han,1 Linong Ji1 1Department of Endocrinology and Metabolism, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Department of Endocrinology and Metabolism, Peking University International Hospital, Beijing, People’s Republic of China; 3Department of Endocrinology and Metabolism, Guanganmen Traditional Medicine Hospital, Beijing, People’s Republic of China; 4Department of Endocrinology and Metabolism, Beijing Mentougou Hospital, Beijing, People’s Republic of China; 5Department of Endocrinology and Metabolism, Beijing Airport Hospital, Beijing, People’s Republic of ChinaCorrespondence: Linong Ji Email prof_jilinong@aliyun.comAim: To evaluate the effectiveness of the mobile health application (APP) education in basal insulin optimal management program for insulin-naive type 2 diabetes (T2D) patients in China.Methods: The basal insulin optimal management program was launched in 297 hospitals in China, throughout the six main regions of China. A total of 17,208 insulin-naive patients with T2D who started to use basal insulin were screened. The mobile health APP was downloaded in each recruited patient’s mobile phone and the doctor’s mobile phone. Then, according to the instructions and education materials in the APP, these patients began their self-management of insulin dosage titrations and contacted their doctors by APP if they need help.Results: Overall, 12,530 patients with T2D were finally included in the analysis. The average age was 51.97± 12.76 years, and 58% of them were males. The average body mass index is 24.46± 3.83 kg/m2, and the average HbA1c at baseline was 8.33± 2.11% with 24% of the subjects reaching the target of HbA1c< 7.0% at baseline. After 3 months of treatment and educations through the APP, HbA1c decreased significantly from baseline (− 1.02± 1.72%), with 59% of the patients reaching HbA1c< 7.0%. After 6 months, the glycemic control of HbA1c also decreased from baseline significantly (− 1.01± 1.67%). Dosage of insulin daily was 0.23± 0.09 IU/kg at baseline, and 0.23± 0.23 IU/kg after 6 months of treatment. Regarding the profiles of hypoglycemia treatment, 3145 patients received basal insulin in combination with mono oral anti-diabetic drug (OAD), 1204 patients with dual OADs, 208 patients with triple OADs, and 17 patients with quarter OADs.Conclusion: Patients could benefit from the basal insulin optimal management program in self-management by using mobile health APP educations. For T2D patients who are going to start insulin treatment, mobile health APP can help them to reach the target of glycemic control with appropriate dosage of insulin.Keywords: basal insulin, HbA1c, insulin-naive, type 2 diabetes

Mengdie Hu, Xiuting Huang, Xueyao Han, Linong Ji Department of Endocrinology and Metabolism, Peking University People’s Hospital, Peking University Diabetes Center, Beijing 100044, People’s Republic of ChinaCorrespondence: Linong Ji; Xueyao HanDepartment of Endocrinology and Metabolism, Peking University People’s Hospital, Peking University Diabetes Center, Beijing 100044, People’s Republic of ChinaTel +86 10-8832 5578Fax +86 10-8832 4371Email prof_jilinong@aliyun.com; xueyaohan@sina.comPurpose: Mutations in hepatocyte nuclear factor 1α (HNF1α) are the cause of maturity-onset diabetes of the young type 3 (MODY3) and involved in the development of hepatocellular adenoma and abnormal lipid metabolism. Previously, we have found that the serum microRNA (miR)-122 levels in MODY3 patients were lower than those in type 2 diabetes mellitus and healthy controls. This study aimed to investigate the mechanism of decreased miR-122 levels in patients with MODY3 and whether low levels of miR-122 mediate tumorigenesis and abnormal lipid metabolism associated with HNF1α deficiency in human hepatocytes.Methods: The expression of miR-122 was examined by real-time PCR. Dual-luciferase reporter assay was performed to confirm the transcriptional regulation of miR-122 by HNF1α. HepG2 cells were transfected with siRNA or miRNA mimic to downregulate or upregulate the expression of HNF1α or miR-122, respectively. CCK-8 and colony formation assay were used to determine cell proliferation. Lipid accumulation was examined by Oil Red O staining and intracellular triglyceride and cholesterol quantification assays.Results: HNF1α regulated the expression of miR-122 by directly binding to its promoter. Knockdown of HNF1α in HepG2 cells reduced the expression of miR-122, increased proliferation and promoted intracellular cholesterol accumulation. Overexpression of miR-122 partially rescued the phenotypes associated with HNF1α deficiency in human hepatocytes. Mechanistically, HNF1α modulated cholesterol homeostasis via miR-122-dependent activation of sterol regulatory element-binding protein-2 (SREBP-2) and regulation of proprotein convertase subtilisin/kexin type 9 (PCSK9). Moreover, circulating miR-122 levels were associated with serum cholesterol levels.Conclusion: Loss of HNF1α function led to hepatocyte proliferation and abnormal cholesterol metabolism by downregulating miR-122. Our findings revealed a novel mechanism that low levels of miR-122 mediate tumorigenesis and abnormal lipid metabolism associated with MODY3. MiR-122 may be a potential therapeutic target for the treatment of MODY3.Keywords: MODY3, HNF1α, miR-122, cholesterol metabolism, hepatocellular adenoma

The experimental data collected during the S515 experiment performed by the R3B collaboration at GSI/FAIR represent a great opportunity to investigate nucleon knockout reactions of exotic nuclei in the region of Sn using complete kinematics measurements. These cross sections can be used in the future to investigate the quenching in the knockout of the minority species (neutrons or protons) in nuclei far from stability. Some of the arguments put forward are the underestimation of the knockout of deeply bound nucleons, final state interactions or the role of short-range correlations (SRC). Recently, several works based on inclusive measurements have shown that these SRCs could reduce the single nucleon knockout cross sections by around 50%, depending on the neutron excess (N/Z) of the initial projectile. The S515 data can help us to go further in this investigation because it allows to correlate the knockout cross sections of one, two or more nucleons with the number of protons and neutrons emitted from the target and which can be detected by the CALIFA and NeuLAND detectors, respectively, and perform complete kinematical studies on the nature of the event (SRC, evaporation, emission of clusters, final-state interactions...). Here the results obtained for the charge distribution of reaction residues are presented, which is one of the first steps of the still on-going analysis.

A new experimental fission approach is presented in the context of the R3B (Reactions with Relativistic Radioactive Beams) collaboration, at the GSI/FAIR facility, in which knockout reactions in inverse kinematics are used to induce fission of 238U that will allow to characterise the excitation energy of the fission process and all the fission products. The CALIFA (CALorimeter for In-Flight detection of γ-rays and high energy charged pArticles) calorimeter, a key part of the R3B set-up, is used to reconstruct the momenta of the two protons from the (p, 2p) reactions. Preliminary results show that kinematic variables and first estimates for nucleon-removal cross sections are well reconstructed and in good agreement with other experimental measurements.

Nuclear fission is a complex dynamical process, whose description involves the coupling between intrinsic and collective degrees of freedom, as well as different quantum-mechanical phenomena. For this reason, to this day it still lacks a satisfactory and complete microscopic description. In addition to the importance of describing fission itself, studies of the r-process in astrophysics depend on fission observables to constrain the theoretical models that explain the isotopic abundances in the Universe. To improve on the existing data, fission reactions of heavy nuclei in inverse kinematics are produced in quasi-free (p,2p) scattering reactions, which induce fission through particle-hole excitations that can range from few to tens of MeV. In order to study the evolution of the fission yields with temperature, the excitation energy of the fissioning system must be reconstructed, which is possible by measuring the four-momenta of the two outgoing protons. Performing this kind of experiment requires a complex experimental setup, providing full isotopic identification of both fission fragments and an accurate measurement of the momenta of the two outgoing protons. This was realized recently at the GSI/FAIR facility and some of the results obtained for the charge distributions are presented in this work.

Yu Chen, 1–3,* Wei Zhu, 4,* Fan Shu, 5 Yan Fan, 1, 2 Ning Yang, 1, 2 Tao Wu, 1, 2 Le Ji, 1, 2 Wei Xie, 1, 2 Rengui Bade, 1, 2 Shuyuan Jiang, 1, 2 Xiaolei Liu, 1, 2 Guo Shao, 1–3 Gang Wu, 1, 2 Xiaoe Jia 1–3 1Biomedicine Research Center, Neuroscience Institute, Baotou Medical College, Baotou 014040, People’s Republic of China; 2Inner Mongolia Key Laboratory of Hypoxic Translational Medicine, Baotou Medical College, Baotou 014040, People’s Republic of China; 3Beijing Key Laboratory of Hypoxic Conditioning Translational Medicine, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 4School of Pharmacy, Baotou Medical College, Baotou 014040, People’s Republic of China; 5Third Hospital of Baotou, Baotou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoe Jia Email evangeline2004@163.comGang Wu Tel/Fax +86-472-7167830Email wugang0525@163.comIntroduction: Rare-earth nanoparticles in the environment and human body pose a potential threat to human health. Although toxic effects of rare-earth nanoparticles have been extensively studied, the effects on the early development are not well understood. In this study, we attempted to explain the toxic effects of neodymium oxide (Nd 2O 3) nanoparticles on early development.Methods: We added the Nd 2O 3 nanoparticles at different concentrations and recorded the mortality and malformation rate per 24 hrs under a microscope. The live embryos treated with Nd 2O 3 nanoparticles were imaged as movies and Z step lapses with a confocal microscope, and heart rates were counted for 30 s to measure the cardiac function. The live Tg (Flk1:EGFP) transgenic embryos exposed to Nd 2O 3 nanoparticles were observed under confocal microscope to measure the cerebrovascular development. Subsequently, we extracted the total protein for Western blot at 5 days post-fertilisation (dpf). Embryos were collected to undergo TUNEL staining for apoptosis detection.Results: Nd 2O 3 nanoparticles disturbed embryo development at high concentrations (> 200 μg/mL). The mortality and malformation rate gradually increased in a dose-dependent manner by morphological observation, while the Nd 2O 3 median lethal concentration (LD50) was 203.4 μg/mL at 120 hrs post-fertilisation (hpf). Furthermore, the Nd 2O 3-treated embryos showed severe arrhythmia and reduced heart rate. We also observed the markedly cerebrovascular disappearance at middle concentration (100 and 200 μg/mL). The downregulated autophagy flux in brain blood vessels and increased apoptosis level in neurons might affect vessels sprouting and contribute to the vanished cerebrovascular.Conclusion: The results suggested that the embryos exposed to Nd 2O 3 activated the apoptosis pathway and induced toxicity and abnormal cardiac/cerebrovascular development.Keywords: Nd 2O 3, zebrafish, toxicity, arrhythmias, cerebrovascular

Xiaojing Shi, Guizhou Tao, Lili Ji, Ge Tian Department of Cardiology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, People’s Republic of ChinaCorrespondence: Xiaojing ShiDepartment of Cardiology, The First Affiliated Hospital of Jinzhou Medical University, No. 2, the Fifth Section of Renmin Street, Guta District, Jinzhou, Liaoning Province 121001, People’s Republic of ChinaTel/Fax +86-416-4605305Email shixiaojing3000@163.comBackground: Oxidative stress is a major contributor to the onset and development of myocardial ischemia reperfusion injury (MIRI). Sappanone A (SA), a homoisoflavanone extracted from the heartwood of Caesalpinia sappan L., has been demonstrated to possess powerful antioxidant activity. Therefore, this study aimed to determine the protective effect of SA on MIRI and investigate its underlying mechanism.Methods: The rat hearts were isolated and underwent 30-min ischemia, followed by 120-min reperfusion to establish the MIRI model, using the Langendorff method. SA was administrated intraperitoneally into rats 1 h prior to heart isolation. The myocardial infarct size and apoptosis were measured by TTC and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Myocardial enzyme activity, MDA content and the activities of SOD and GSH-Px were detected by colorimetric spectrophotometric method. Reactive oxygen species (ROS) level was detected by DCFH-DA probe. The change in Keap1/Nrf2 signaling pathway was evaluated by Western blotting.Results: SA reduced myocardial infarct size and the release of CK-MB and LDH in a dose-dependent manner. Moreover, SA improved the recovery of cardiac function, inhibited MIRI-induced apoptosis, repressed the production of ROS and MDA, and enhanced the activities of SOD and GSH-Px. Mechanistically, SA downregulated Keap1, induced Nrf2 nuclear accumulation, and enhanced Nrf2 transcriptional activity, subsequently resulting in an increase in the expression of the Nrf2 target genes heme oxygenase-1 and NAD(P)H quinone dehydrogenase 1. Moreover, SA enhanced the phosphorylation of Nfr2, but the enhancement in Nfr2 phosphorylation was abrogated by PKC or PI3K inhibitor.Conclusion: Collectively, it was demonstrated that SA prevents MIRI via coordinating the cellular antioxidant defenses and maintaining the redox balance, by modulation of Nrf2 via the PKC or PI3K pathway. Therefore, SA was a potential therapeutic drug for treating MIRI.Keywords: Sappanone A, oxidative stress, apoptosis, myocardial ischemia reperfusion injury, Nrf2