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Dan Ye,1,2 Yuanyuan Li,2 Kangkang Yan,1 Wenzhong Peng2 1Department of Pharmacy, Xi’an No.3 Hospital, the Affiliated Hospital of Northwest University, Xi’an, People’s Republic of China; 2Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Wenzhong Peng, Department of Respiratory Medicine, Xiangya Hospital, Central South University, Xiangya Road No. 87, Kaifu District, Changsha, Hunan, 410008, People’s Republic of China, Tel +86-0731-89753287, Fax +86-89753287, Email pengwenzhong@csu.edu.cnBackground: Chlamydia abortus is a zoonotic pathogen that causes miscarriage, stillbirth, and sepsis of pregnancy in pregnant women when it infects humans. However, it rarely causes pneumonia in humans.Case Presentation: This case reports a case of severe pneumonia characterized by high fever and cough, and the disease rapidly progressed to dyspnea. The patient was treated with moxifloxacin and doxycycline. Chlamydia abortus was detected in bronchoscopy examination and bronchoalveolar lavage fluid (BALF) through metagenomic next-generation sequencing (mNGS)-DNA. A weak positive for influenza A (H1N1) antigen was also found in the throat swab tested. Subsequently, we added mabaloxavir and replaced doxycycline with an intravenous infusion of omadacycline. After effective treatment, the patient developed a urinary tract infection, and the treatment plan was adjusted to meropenem combined with omadacycline. The patient’s condition improved, and she was discharged on the 14th day of admission.Conclusion: This is the first report of cases of non-pregnant female patients with Chlamydia abortus infection pneumonia. Consequently, infections with Chlamydia abortus can result in severe respiratory distress, disturbance of water and electrolyte balance, and abnormal liver function, which requires timely diagnosis and correct use of antibiotics by clinicians. Consequently, the mixed infection of H1N1 and Chlamydia abortus aggravated the complexity of the condition and treatment. Combining tetracycline and quinolone is effective for treating severe pneumonia with Chlamydia abortus infection.Keywords: chlamydia abortus, severe pneumonia, metagenomics next-generation sequencing, case report

Dan Ye,1 Ding Ding,1 Ling-Yun Pan,2 Qing Zhao,3 Long Chen,2 Min Zheng,1 Tong Zhang,1 Bing-Liang Ma1 1Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 3Department of Pharmacy, Jing’an District Zhabei Central Hospital, Shanghai, 200070, People’s Republic of ChinaCorrespondence: Bing-Liang Ma; Tong Zhang, Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, No. 1200 Cai Lun Road, Pudong New District, Shanghai, 201203, People’s Republic of China, Tel +86-021-5132 2199 ; +86-021-5132 2318, Fax +86-021-5132 2192, Email bingliang.ma@hotmail.com; zhangtongshutcm@hotmail.comPurpose: Docetaxel (DTX) is a valuable anti-tumor chemotherapy drug with limited oral bioavailability. This study aims to develop an effective oral delivery system for DTX using natural nanoparticles (Nnps) derived from Coptidis Rhizoma extract.Methods: DTX-loaded self-assembled nanoparticles (Nnps-DTX) were created using an optimized heat-induction strategy. Nnps-DTX’s shape, size, Zeta potential, and in vitro stability were all carefully examined. Additionally, the study investigated the encapsulation efficiency, loading capacity, crystal form, and intermolecular interactions of DTX in Nnps-DTX. Subsequently, the solubility, release, cellular uptake, metabolic stability, and preclinical pharmacokinetics of DTX in Nnps-DTX were systematically evaluated. Finally, the cytotoxicity of Nnps-DTX was assessed in three tumor cell lines.Results: Nnps-DTX was spherical in shape, 138.6 ± 8.2 nm in size, with a Zeta potential of − 20.8 ± 0.6 mV, a DTX encapsulation efficiency of 77.6 ± 8.5%, and a DTX loading capacity of 6.8 ± 1.9%. Hydrogen bonds, hydrophobic interactions, and electrostatic interactions were involved in the formation of Nnps-DTX. DTX within Nnps-DTX was in an amorphous form, resulting in enhanced solubility (23.3 times) and release compared to free DTX. Following oral treatment, the mice in the Nnps-DTX group had DTX peak concentrations 8.8, 23.4, 44.6, and 5.7 times higher in their portal vein, systemic circulation, liver, and lungs than the mice in the DTX group. Experiments performed in Caco-2 cells demonstrated a significant increase in DTX uptake by Nnps-DTX compared to free DTX, which was significantly inhibited by indomethacin, an inhibitor of caveolae-mediated endocytosis. Furthermore, compared to DTX, DTX in Nnps-DTX demonstrated better metabolic stability in liver microsomes. Notably, Nnps-DTX significantly reduced the viability of MCF-7, HCT116, and HepG2 cells.Conclusion: The novel self-assembled nanoparticles considerably enhanced the cellular absorption, solubility, release, metabolic stability, and pharmacokinetics of oral DTX and demonstrated strong cytotoxicity against tumor cell lines. Keywords: docetaxel, oral delivery, self-assembly, nanoparticles, pharmacokinetics, coptidis rhizoma

Beibei Luo, Wenbo Xu, Dan Ye, Xuejing Bai, Mengna Wu, Chunting Zhang, Rui Shi Clinical Laboratory, People’s Hospital of Yuxi City, the Sixth Affiliated Hospital of Kunming Medical University, Yuxi City, Yunnan Province, 653100, People’s Republic of ChinaCorrespondence: Wenbo Xu, Clinical Laboratory, People’s Hospital of Yuxi City, the Sixth Affiliated Hospital of Kunming Medical University, 21 Nieer Road, Yuxi City, Yunnan Province, 653100, People’s Republic of China, Email xwb103196@sina.comIntroduction: Dyslipidemia commonly complicates type 2 diabetes mellitus, yet the relationship between glycosylated hemoglobin and blood lipid levels remains uncertain.Methods: This retrospective cross-sectional study included 27,158 participants from the People’s Hospital of Yuxi. Statistical comparisons for continuous variables utilized analysis of variance (ANOVA), while chi-square analysis was employed for categorical variables. Boxplots assessed the concentration, dispersion, and deviation of total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL-C), and high-density lipoprotein (HDL-C) distribution. A linear regression analysis examined the association between HbA1c and lipid profile, complemented by a fitting curve to visualize trends.Results: Participants who developed diabetes exhibited higher age and elevated Body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), TC, TG, LDL-C, and FPG levels compared to those without diabetes (p < 0.001). Linear regression analysis demonstrated significant associations between HbA1c values and TC, TG, LDL-C, and HDL-C (p < 0.001). The plotted curve indicated that as TC, TG, and LDL levels increased, HbA1c levels rose, while HDL levels decreased.Conclusion: HbA1c was positively correlated with TC, TG, LDL-C, and negatively correlated with HDL-C in the population in the central Yunnan Plateau.Keywords: dyslipidemia, HbA1c, lipid profile

Heng Yang, Lixia Chen, Danjuan Ye, Ying Wu, Huafang Zhang Department of Nursing, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, 322000, People’s Republic of ChinaCorrespondence: Huafang Zhang, Department of Nursing, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, N1 Shangcheng Avenue, Yiwu, Zhejiang, 322000, People’s Republic of China, Email wuyizhangyichi@zju.edu.cnPurpose: The objective of this study was to investigate latent classes of oral health and the factors associated with them in acutely admitted elderly inpatients.Patients and Methods: A cross-sectional study was conducted using purposive sampling to survey Chinese older-adult acutely inpatients. Data was collected utilizing several instruments, including a general information questionnaire, Brief Oral Health Status Examination (BOHSE), Oral Frailty Index-8 (OFI-8), Mini-Nutritional Assessment Short Form (MNA-SF), and Frailty Screening Questionnaire (FSQ). Latent class analysis was applied to identify distinct categories of oral health among elderly inpatients, and multinomial logistic regression was employed to analyze the factors associated with different oral health categories.Results: In this study, a total of 504 elderly patients were ultimately included, leading to the identification of three latent classes of oral health: “oral health-low level group (41.27%)”, “oral health-moderate level group (25.4%)”, and “oral health-high level group (33.33%)”. The findings revealed that patients with advanced age, elevated neutrophil percentage, and higher C-reactive protein (CRP) values were more likely to be classified in the low oral health group. Additionally, individuals experiencing malnutrition and frailty had a higher risk of falling into the low oral health category. Those with comorbidities and oral frailty were more prevalent in the moderate oral health group. At the same time, elderly patients with higher BMI (22.95± 3.043) ratios were more likely to be categorized in the high oral health group.Conclusion: This study sheds light on three distinct latent classes of oral health among acutely admitted elderly inpatients. These findings underscore the importance of healthcare professionals focusing on the assessment and health education of elderly patients’ oral health. Furthermore, personalized interventions should be developed to promote healthy aging, with particularly attention to enhancing oral health outcomes in this population.Keywords: emergency department, oral health, factors, older people, latent class analysis, frailty

Pengwei Hou,1,&ast; Yang Yang,2,&ast; Ziqi Li,1,&ast; Dan Ye,2 Li Chen,1 Tianshun Feng,3 Jiateng Zeng,4 Liangfeng Wei,1 Shousen Wang1,5 1Department of Neurosurgery, Fuzong Clinical Medical College of Fujian Medical University (The 900TH Hospital), Fuzhou, Fujian Province, People’s Republic of China; 2Fuzhou General Teaching Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian Province, People’s Republic of China; 3Department of Neurosurgery, Dongfang Affiliated Hospital of Xiamen University School of Medicine, Xiamen University, Xiamen, Fujian Province, People’s Republic of China; 4Department of Neurosurgery, Neurosurgery Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 5Fujian Provincial Clinical Medical Research Center for Minimally Invasive Diagnosis and Treatment of Neurovascular Diseases, Fuzhou, Fujian Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liangfeng Wei; Shousen Wang, Department of Neurosurgery, Fuzong Clinical Medical College of Fujian Medical University (The 900TH Hospital), No. 156, Xierhuanbei Road, Fuzhou, Fujian Province, 350025, People’s Republic of China, Tel +8613960760177 ; +8613950482966, Email wlf74@163.com; wshsen1965@126.comPurpose: The activation of the inflammatory response is regarded as a pivotal factor in the pathogenesis of TBI. Central nervous system infection often leads to the exacerbation of neuroinflammation following TBI, primarily caused by Gram-negative bacteria. This study aims to elucidate the effects of the novel anti-inflammatory drug TAK-3 on LPS-induced neuroinflammation in TBI rats.Methods: In conjunction with the rat controlled cortical impact model, we administered local injections of Lipopolysaccharide to the impact site. Subsequently, interventions were implemented through intraperitoneal injections of TAK-3 and NF-κB activitor2 to modulate the TLR4/NF-κB axis The impact of LPS on neurological function was assessed using mNSS, open field test, and brain water content measurement. Inflammatory markers, including TNF-α, IL-1β, IL-6 and IL-10 were assessed to evaluate the condition of neuritis by Elisa. The activation of the TLR-4/NF-κB signaling pathway was detected by immunofluorescence staining and Western blot to assess the anti-inflammatory effects of TAK-3.Results: The administration of LPS exacerbated neurological damage in rats with TBI, as evidenced by a reduction in motor activity and an increase in anxiety-like behavior. Furthermore, LPS induced disruption of the blood-brain barrier integrity and facilitated the development of brain edema. The activation of microglia and astrocytes by LPS at the cellular and molecular levels has been demonstrated to induce a significant upregulation of neuroinflammatory factors. The injection of TAK-3 attenuated the neuroinflammatory response induced by LPS.Conclusion: The present study highlights the exacerbating effects of LPS on neuroinflammation in TBI through activation of the TLR-4/NF-κB signaling pathway. TAK-3 can modulate the activity of this signaling axis, thereby attenuating neuroinflammation and ultimately reducing brain tissue damage.Keywords: NF-κB activator2, CNS infection, CCI, inflammation, TAK-3

Ke Liu,1,&ast; Meng-Ying Zhang,2,&ast; Lu-Lu Sun,2 Qiao-Huo Liao,2 Yuan-Yuan Yi,3 Yi-Ling Ji,1 Dan Ye,1 Qiu Yu1 1Department of Emergency, The Third People’s Hospital of Shenzhen, Shenzhen, 518000, People’s Republic of China; 2Department of Pediatrics, The Third People’s Hospital of Shenzhen, Shenzhen, 518000, People’s Republic of China; 3Department of Transplantation, The Third People’s Hospital of Shenzhen, Shenzhen, 518000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lu-Lu Sun, Department of pediatrics, The Third People’s Hospital of Shenzhen, No. 29 of Bulan Road, Longgang District, Shenzhen, 518000, People’s Republic of China, Tel +86-13510332310, Fax +86-755-61238983, Email sunlulurainbow@126.comObjective: The primary aim of this study was to examine the extent of nutritional awareness concerning dietary requisites within a cohort comprising pediatric recipients of liver and kidney transplants, along with their respective caregivers. The overarching goal was to establish a foundation for enhancing the dietary nutrition of this specific population.Methods: This was a qualitative research study, involving in-depth interviews and subsequent qualitative data analysis. Our sample included pediatric patients in a specific age range who had undergone a liver or kidney transplant, as well as their parents. The data analysis technique we used was content analysis.Results: The survey focused on knowledge of dietary requirements and restrictions, nutritional needs, and adherence to daily dietary requirements among pediatric patients and their respective caregivers. Approximately 30% of the parents lacked relevant nutritional awareness, 30% relied on a single source for acquiring nutritional knowledge, and 40% expressed a considerable need for nutritional guidance. Our findings revealed a deficiency in the understanding of nutritional and dietary requirements for children who have undergone a liver or kidney transplant. Their nutrient intake was unbalanced, and their dietary habits were irregular, highlighting the need for better nutritional guidance and monitoring.Conclusion: The nutritional awareness and knowledge of dietary requirements among pediatric liver and kidney transplant recipients and their care providers are inadequate. Medical professionals are urged to tackle this concern by imparting comprehensive education to parents regarding the nutritional prerequisites essential for their children post-transplant. This approach empowers parents to implement requisite dietary modifications effectively. Furthermore, healthcare institutions should augment the nutritional proficiency of their medical staff through meticulously structured training initiatives.Keywords: kidney transplant in children, liver transplant in children, nutritional awareness, nutritional support, qualitative study

Menglong Wang,1– 3,&ast; Wei Pan,1– 3,&ast; Cheng Wei,1– 3,&ast; Jianfang Liu,1– 3 Jishou Zhang,1– 3 Junping Yu,1– 3 Mengmeng Zhao,1– 3 Shuwan Xu,1– 3 Jing Ye,1– 3 Zhen Wang,1– 3 Di Ye,1– 3 Yongqi Feng,1– 3 Yao Xu,1– 3 Jun Wan1– 3 1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China; 2Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, People’s Republic of China; 3Hubei Key Laboratory of Cardiology, Wuhan, 430060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Wan; Yao Xu, Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, People’s Republic of China, Tel +86-27-88041911, Fax +86-27-88042293, Email wanjun@whu.edu.cn; whuxuyao@163.comBackground: Increased inflammation contributes to pressure overload-induced myocardial remodeling. 17(R)-Resolvin D1 (17(R)-RvD1), a potent lipid mediator derived from docosahexaenoic acid, possesses anti-inflammatory and pro-resolving properties. However, the association between 17(R)-RvD1 and pressure overload-induced cardiac hypertrophy remains unclear.Methods: Transverse aortic constriction (TAC) surgery was performed to establish a cardiac hypertrophy model. C57BL/6J mice were randomly assigned to the Sham, TAC and TAC+17(R)-RvD1 groups. 17(R)-RvD1 was injected (2 μg/kg, i.p.) before TAC surgery and once every other day after surgery for 4 weeks. The same volume of saline was injected into the mice in both Sham group and TAC group. Then, cardiac function was evaluated and heart tissues were collected for biological analysis.Results: 17(R)-RvD1 treatment attenuated TAC-induced increase in left ventricular diameter and decrease in left ventricular contractility, mitigated increased cardiomyocyte cross-sectional area, and downregulated the expression of hypertrophic genes. Besides, 17(R)-RvD1 attenuated myocardial fibrosis, as indicated by the decreased LV collagen volume and expression of fibrotic genes. In addition, 17(R)-RvD1 ameliorated the inflammatory response in cardiac tissue, as illustrated by the decreased infiltration of CD68+ macrophages and reduced production of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6. 17(R)-RvD1 treatment significantly suppressed the activation of NLRP3 inflammasome after TAC surgery, which might be responsible for the attenuation of inflammation in cardiac tissue.Conclusion: 17(R)-RvD1 attenuated pressure overload-induced cardiac hypertrophy and fibrosis, and the possible mechanism may be associated with the inhibition of NLRP3 inflammasome. 17(R)-RvD1 may serve as a potential drug for the treatment of cardiac hypertrophy.Keywords: inflammation resolution, resolvin D1, cardiac hypertrophy, NLRP3 inflammasome, transverse aortic constriction

Lixia Chen,1 Heng Yang,2 Shaomei Cui,2,&ast; Danjuan Ye2,&ast; 1Department of Nursing, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, People’s Republic of China; 2Department of Emergency, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lixia Chen, Department of Nursing, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, N0.N1 Shangcheng Avenue, Yiwu City, Zhejiang Province, People’s Republic of China, Tel +1 596 882 9886, Email chenzheda@zju.edu.cnPurpose: This study aimed to investigate the potential impact of the Target Management Card on patient safety in the emergency department.Patients and Methods: A mixed method design was developed, combining a one-group pretest-posttest design with a qualitative study. Target Management Cards were formulated for 32 emergency nurse practitioners and focus group interviews were conducted after the intervention. Wilcoxon’s signed rank test was used to compare pre-test and post-test scores. The interview data were subject to content analysis.Results: After developing the Target Management Card, there were significant improvements in safety behaviors (Z = 4.709, p < 0.01) and perception of patient safety (Z = 4.257, p < 0.01) among emergency nurse practitioners. The nurses in the focus group interviews agreed that the Target Management Card could improve patient safety by warning and supervising nursing work in the emergency department, promoting a positive change in nurses’ attitudes and behaviors toward patient safety.Conclusion: Our study found that nurses and nursing managers jointly formulating Target Management Cards in emergency departments significantly enhances patient safety.Keywords: target management card, patient safety, patient safety culture, mixed methods, emergency department

BACKGROUND: Non-pharmacological treatments are an integral part of the treatment of all patients with type 2 diabetes (T2D). However, due to many factors, doctors and patients themselves tend to underestimate or completely neglect such effective methods in managing the course of the disease. Despite the high level of evidence of the effectiveness of this type of treatment for T2D, every year scientists around the world continue to actively study the effect of various non-drug methods on the course of the disease.AIM: To study the effect of a 24-week structured non-pharmacological treatment program on glycated hemoglobin reduction and weight loss in middle-aged patients with compensated T2D taking metformin.MATERIALS AND METHODS: A two-group, randomized, parallel-group, blinded trial was designed. Patients with an established diagnosis of T2D in the stage of compensation (HbA1c ≤7%), aged 45–59 years, taking metformin, were randomized to receive either standard non-pharmacological treatment of diabetes according to clinical protocol of T2D treatment in Kazakhstan, or an intensive course of non-pharmacological treatment according to a structured program developed by researchers. The duration of the intervention was 24 weeks. Primary outcomes were glycated hemoglobin, body weight. Secondary outcomes: blood pressure, waist circumference, insulin resistance index (HOMA-IR), lipid profile: total cholesterol, high and low density lipoproteins, triglycerides. The outcomes of the participants in both groups were assessed at baseline, 12 and 24 weeks after randomization. The study is registered with ClinicalTrials.gov NCT04632823.RESULTS: The study included 200 patients, 67 patients completed the study: intervention group n=33, control group n=34. After 24 weeks of observation, patients in the intervention group showed a significant decrease in HbA1c from 6.34% to 6.22%, p

Shaoxue Yang1 &ast;, Jie Song2 &ast;, Hong Yang,2 Wei Liu,2 Yuqing Jiang,2 Xiaohui Sun,2 Ding Ye,2 Songxiao Xu,1 Yingying Mao2 1The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Hangzhou, 310022, People’s Republic of China; 2Department of Epidemiology, Zhejiang Chinese Medical University School of Public Health, Hangzhou, 310053, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingying Mao, Department of Epidemiology, Zhejiang Chinese Medical University School of Public Health, 548 Binwen Road, Hangzhou, 310053, People’s Republic of China, Email myy@zcmu.edu.cn Songxiao Xu, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Hangzhou, 310022, People’s Republic of China, Email xusx1979@126.comObject: Prostate cancer is one of the leading malignancies in men worldwide. Previous observational studies have linked amino acids and transaminase with altered risk of prostate cancer. However, whether these associations were causal remained unclear. Therefore, we conducted a Mendelian randomization (MR) to assess their potential causal associations.Methods: Summary-level data for prostate cancer were obtained from a meta-analysis of genome-wide association studies (GWAS) including 79,148 prostate cancer cases and 61,106 controls of European descent. Instrumental variables (IVs) of amino acids and alanine aminotransferase (ALT) were obtained from a GWAS of 86,507 European individuals and a GWAS of 312,572 participants from the UK Biobank, respectively. MR analyses were performed using inverse-variance-weighted (IVW), likelihood-based, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test and MR-Egger regression.Results: Genetically predicted circulating concentrations of alanine were associated with an increased risk of prostate cancer (odds ratio (OR): 1.16, 95% confidence interval (CI): 1.01– 1.33, P=0.037 by IVW). Consistently, genetically predicted ALT was inversely associated with the risk of prostate cancer (OR: 0.43, 95% CI: 0.27– 0.68, P=3.28× 10− 4 by IVW). MR-Egger regression did not indicate evidence of directional pleiotropy and sensitivity analyses yielded consistent associations.Conclusion: Our study revealed that genetically predicted circulating alanine and ALT levels were associated with an altered risk of prostate cancer, suggesting their potential roles in the development of prostate cancer. Whether targeting alanine, ALT or its downstream effectors are helpful in reducing prostate cancer incidence warrants further investigation.Keywords: alanine, alanine aminotransferase, amino acids, Mendelian randomization, prostate cancer

Resonant soft X-ray scattering (RSoXS) leverages chemical specificity to characterize thin films but is limited near the nitrogen edge. The challenge is that commercially available X-ray transparent substrates are composed of Si 3 N 4 and thereby absorb incident X-rays and generate incoherent fluorescence. To overcome this challenge, we designed and fabricated Al 2 O 3 free-standing films for use as RSoXS windows. Al 2 O 3 films offer higher X-ray transmittance and minimal fluorescence near the nitrogen edge. As an example, Al 2 O 3 windows allow for nitrogen RSoXS of conjugated block copolymer thin films that reveal domain spacings, which are not apparent with commercially available Si 3 N 4 substrates.

Linshuoshuo Lv,1,&ast; Xiaohui Sun,1,&ast; Bin Liu,1 Jie Song,1 David JH Wu,2 Yun Gao,3 Aole Li,3 Xiaoqin Hu,4 Yingying Mao,1 Ding Ye1 1Department of Epidemiology, School of Public Health, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 2University of Minnesota Medical School, Minneapolis, MN, 55455, USA; 3Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 4Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ding Ye; Yingying Mao, Department of Epidemiology, School of Public Health, Zhejiang Chinese Medical University, 548 Binwen Road, Zhejiang, Hangzhou, 310053, People’s Republic of China, Tel +86-571-8663-3305, Email yeding@zcmu.edu.cn; myy@zcmu.edu.cnPurpose: Colorectal cancer (CRC) is the third–most frequently diagnosed cancer globally. Studies have linked low serum albumin with increased risk of CRC, but the causal nature of the association remains unclear. In the present study, we explored the potential causal relationship using bidirectional Mendelian randomization (MR).Methods: Instrumental variants for albumin were obtained from a genome-wide association study (GWAS) on 102,223 Eastern Asian participants to investigate the effect of albumin on CRC. Summary statistics of CRC were obtained from a GWAS on 7,062 CRC cases and 195,745 controls of Eastern Asian ancestry. Bidirectional MR analysis was performed using inverse variance weighting (IVW) for primary analysis, supplemented with a maximum likelihood–based method, MR-PRESSO test, leave-one-out analysis, and MR-Egger regression. Stratification analyses were further performed.Results: We found that genetically predicted serum albumin per unit was associated with a lower risk of CRC (OR 0.75, 95% CI 0.59– 0.95 with IVW). No evidence of pleiotropy was observed. Sex-stratified MR analysis showed that serum albumin was inversely associated with risk of CRC in men (OR 0.71, 95% CI 0.53– 0.96), but not in women (OR 0.81, 95% CI 0.55– 1.19) using IVW. Reverse MR analysis suggested a genetic predisposition toward CRC was not associated with serum albumin.Conclusion: Our study revealed a suggestive sex disparity in the effect of albumin, which deserves further exploration of the potential biological mechanism.Keywords: albumin, colorectal cancer, Mendelian randomization, single-nucleotide polymorphism, genome-wide association study, instrumental variables

Bian Hu,1,2 Jingyu Zhang,3 Mengdan Gong,1 Yongqin Deng,1 Yujie Cao,1 Yizhen Xiang,1 Dong Ye1 1Department of Otorhinolaryngology-Head and Neck Surgery, Lihuili Hospital of Ningbo University, Ningbo, 315040, Zhejiang, People’s Republic of China; 2Department of Otorhinolaryngology-Head and Neck Surgery, Ninghai First Hospital, Ningbo, 315699, Zhejiang, People’s Republic of China; 3Shanghai Jiao Tong University, Shanghai, 200030, People’s Republic of ChinaCorrespondence: Dong Ye, Department of Otorhinolaryngology-Head and Neck Surgery, Lihuili Hospital of Ningbo University, Ningbo, 315040, Zhejiang, People’s Republic of China, Tel +86 13819861213, Fax +86 574-87392232, Email yedong518@sina.comAbstract: The olfactory nerve (ON) is the only cranial nerve exposed to the external environment. Hence, it is susceptible to damage from head trauma, viral infection, inflammatory stimulation, and chemical toxins, which can lead to olfactory dysfunction. However, compared with all other cranial nerves, the ON is unique due to its inherent ability to regenerate. This characteristic provides a theoretical basis for treatment of olfactory dysfunction. Olfactory training (OT) is one of the main treatments for olfactory dysfunction. It is easy to apply and has few side-effects, and has been shown to be efficacious for patients with olfactory dysfunction of various causes. To further understand the application value of ON regeneration and OT on olfactory dysfunction, we review the research progress on the mechanism of ON regeneration and OT.Keywords: olfaction, regeneration, olfactory training, olfactory dysfunction

Weifeng Zou,1 Xiaoqian Wang,2 Ruiting Sun,3 Jinxing Hu,1 Dong Ye,4 Ge Bai,3 Sha Liu,5 Wei Hong,6 Meihua Guo,1 Pixin Ran3 1State Key Laboratory of Respiratory Disease, Guangzhou Chest Hospital, Guangzhou, Guangdong, People’s Republic of China; 2The Third Hospital of Mianyang, Mianyang, Sichuan, People’s Republic of China; 3National Center for Respiratory Medicine, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 4State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 5The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, People’s Republic of China; 6GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Pixin RanNational Center for Respiratory Medicine, State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Road, Yuexiu District, Guangzhou, Guangdong, 510120, People’s Republic of ChinaTel +86 13922765811Email pxran@gzhmu.edu.cnBackground: Fine-particulate matter ≤ 2.5 μm in diameter (PM2.5)-associated airway remodeling has recently been recognized as a central feature of COPD. Activation of the Wnt/β-catenin pathway is closely related to the occurrence of airway remodeling. Accordingly, the goal of this study was to determine whether the Wnt5a/β-Catenin pathway is involved in PM2.5-induced smooth muscle proliferation in vivo and in vitro, which promotes the development of airway remodeling in subjects with COPD.Methods: The effect of Wnt5a on β-Catenin-mediated airway remodeling was assessed using an in vivo model of PM2.5-induced COPD and PM2.5-exposed human bronchial smooth muscle cells (HBSMCs) in vitro. Small animal spirometry was used to measure lung function in mice. H&E staining and immunohistochemistry were performed to inspect emphysema and airway remodeling indices. Real-time PCR was used to detect Wnt5a, β-Catenin, TGF-β 1, CyclinD1 and c-myc mRNA expression. The CCK8 assay was performed to detect cellular activity. Western blotting was performed to assess PCNA, α-SMA, Wnt5a, β-Catenin, PDGFRβ and TenascinC protein expression. β-Catenin expression was detected using cellular immunofluorescence.Results: Exposure to PM2.5 led to emphysema, airway wall thickening, an increased smooth muscle layer thickness, decreased lung function and increased expression of the Wnt5a, β-Catenin, PDGFRβ and Tenascin C proteins in the mouse lung tissue. BOX5 (a Wnt5a antagonist) alleviated these PM2.5-induced outcomes in mice. Moreover, PM2.5 induced the expression of the Wnt5a, β-Catenin, TGF-β 1, CyclinD1 and c-myc mRNAs in HBSMCs. BOX5 also inhibited the PM2.5-induced increases in PCNA, α-SMA, Wnt5a, β-Catenin, PDGFRβ and Tenascin C protein expression in HBSMCs.Conclusion: Our findings suggest that PM2.5 exposure induces HBSMC proliferation, contributing to airway remodeling via the Wnt5a/β-Catenin signaling pathway in vivo and in vitro, which might be a target for COPD treatment.Keywords: COPD, airway remodeling, PM2.5, Wnt5a/β-Catenin

Weifeng Zou,1 Dong Ye,2 Sha Liu,3 Jinxing Hu,1 Tao Zhu,1 Fang He,4 Pixin Ran5 1State Key Laboratory of Respiratory Disease, Guangzhou Chest Hospital, Guangzhou, Guangdong, People’s Republic of China; 2State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 3The Second Hospital, University of South China, Hengyang, Hunan, People’s Republic of China; 4School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 5State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Pixin RanState Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Road, Yuexiu District, Guangzhou, Guangdong, 510120, People’s Republic of ChinaTel +86 13922765811Email pxran@gzhmu.edu.cnBackground and Purpose: PM2.5-associated airway inflammation has recently been recognized as pivotal to the development of COPD. Aberrant glycogen synthase kinase (GSK)-3β signaling is linked to the inflammatory response. Therefore, we investigated the effects of GSK-3β inhibitors on the PM2.5-induced inflammatory response in bronchial epithelial cells.Methods: The production of phosphorylated GSK-3β (p-GSK-3β) was analyzed by immunohistochemistry with PM2.5-induced mice. HBECs were treated with various inhibitors targeting GSK-3β or JNK before PM2.5 stimulation. The production of GSK-3β signaling was analyzed by Western blotting. Inflammatory cytokine production was detected by qRT–PCR and ELISA.Results: PM2.5 exposure caused lung inflammation, upregulated serum concentrations of HMGB1 and IL-6, decreased IL-10 expression, and significantly attenuated p-GSK-3β production in mice. HBECs exposed to PM2.5 showed significantly reduced p-GSK-3β production, an increased ratio of p-JNK/JNK, increased NF-κB activation and IκB degradation, and upregulated the inflammatory cytokines HMGB1 and IL-6. Intervention with GSK-3β inhibitors TDZD-8 and SB216763 significantly suppressed PM2.5-induced outcomes. Moreover, the JNK inhibitor SP600125 also reduced the level of NF-κB phosphorylation induced by PM2.5. The differences in the levels of inflammation-related cytokines in the TDZD-8 groups were greater than those in the SB216763 groups.Conclusion: Inhibition of GSK-3β weakens the PM2.5-induced inflammatory response by regulating the JNK/NF-κB signaling pathway in bronchial epithelial cells.Keywords: PM2.5, COPD, GSK-3β, inflammatory response, HBECs

Chenchen Wang,1,2 Demei Ye,1 Zuoling Xie,1,2 Xi Huang,1 Zheng Wang,2 Haiyan Shangguan,2,3 Wenwen Zhu,2 Shaohua Wang1 1Department of Endocrinology, The Affiliated ZhongDa Hospital of Southeast University, Nanjing, 210009, People’s Republic of China; 2School of Medicine, Southeast University, Nanjing, 210009, People’s Republic of China; 3Nanjing Central Hospital, Nanjing, 210008, People’s Republic of ChinaCorrespondence: Shaohua WangDepartment of Endocrinology, The Affiliated ZhongDa Hospital of Southeast University, Nanjing, 210009, People’s Republic of ChinaTel +86 25 83262810Fax +86 25 83285132Email gyjwsh@126.comPurpose: In addition to hyperglycemia and hyperlipidemia, obesity and hypertension are important cardiovascular risk factors for coronary heart disease (CHD) in patients with type 2 diabetes mellitus (T2DM). This study aims to explore the interaction of these risk factors.Patients and Methods: Data of hospitalized patients with T2DM from 2013 to 2018 were collected. A multivariate logistic regression model was established. Patients with normal weight and blood pressure were recruited as controls. The interaction on the risk of CHD was evaluated by relative excess risk due to interaction (RERI).Results: Among the 30,693 patients with T2DM, 7202 (23.5%) had CHD. In the low weight group, the prevalence of CHD in patients with hypertension was nearly four times higher than that in patients without hypertension (42.7% vs 11.3%, P < 0.01). The OR value of hypertension alone on CHD increased from 1.29 (95% CI 1.06– 1.56) in the body mass index (BMI) 30.0– 34.9 kg/m2 group to 1.35 (95% CI 1.11– 1.62) in the BMI ≤ 18.5 kg/m2 group. Additive interaction was observed between hypertension and BMI in CHD risk, especially in the low weight group (RERI:2.2, 95% CI 0.9– 3.5). BMI and CHD risk showed a smile curve relationship. The attributive proportion in the low weight group was higher than that in the severe obesity group, that is, 0.52 (95% CI 0.35– 0.69) vs 0.18 (95% CI − 0.59 to 0.95).Conclusion: Maintaining normal weight and avoiding low weight are particularly important for patients with co-occurring diabetes and hypertension to prevent the risk of CHD.Keywords: type 2 diabetes, cardiovascular, hypertension, body mass index, interaction

Jing Zhao,1,&ast; Qing Zhao,1,&ast; Jing-Ze Lu,1 Dan Ye,1 Sheng Mu,1 Xiao-Di Yang,2 Wei-Dong Zhang,3,4 Bing-Liang Ma1 1Department of Pharmacology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 3Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 4School of Pharmacy, Second Military Medical University, Shanghai, 200433, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei-Dong Zhang; Bing-Liang Ma Email wdzhangy@hotmail.com; bingliang.ma@hotmail.comPurpose: This study aimed to evaluate the pharmaceutical and pharmacokinetic effects of the natural nanoparticles (Nnps) isolated from Coptidis Rhizoma extract on berberine hydrochloride (BBR) and systematically explore the related mechanisms.Methods: Firstly, Nnps were isolated from Coptidis Rhizoma extract and then an Nnps-BBR complex was prepared. After qualitative and quantitative analysis in terms of size, Zeta potential, morphology, and composition of the Nnps and the Nnps-BBR complex, the effects of the Nnps on the crystallization of BBR were characterized. The effects of the Nnps on the solubility and dissolution of BBR were then evaluated. In addition, the effects of the Nnps on BBR in terms of cellular uptake, transmembrane transport, metabolic stability, and pharmacokinetics in mice were studied.Results: The Nnps had an average size of 166.6 ± 1.3 nm and Zeta potential of − 12.5 ± 0.2 mV. The Nnps were formed by denaturation of co-existing plant proteins with molecular weight < 30 kDa. The Nnps adsorbed or dispersed BBR, thereby promoting BBR transformation from crystal to amorphous form and improving its solubility and dissolution. The Nnps carried and promoted BBR uptake by human colonic adenocarcinoma (Caco-2) cells via caveolae-mediated endocytosis, reducing P-gp-mediated efflux of BBR in mice gut sacs and Madin-Darby canine kidney cells stably expressing the transporter P-gp (MDCK-MDR1) cells. Moreover, the Nnps improved BBR metabolic stability in mouse intestinal S9, promoting BBR intestinal absorption in mice, as shown by increased peak BBR concentration (Cmax, 1182.3 vs 310.2 ng/mL) and exposure level (AUC0– 12 h, 2842.8 vs 1447.0 ng·h/mL) in mouse portal vein. In addition, the Nnps increased BBR exposure level in mouse livers (95,443.2 vs 43,586.2 ng·h/g liver).Conclusion: The proteinaceous nanoparticles isolated from Coptidis Rhizoma extract can form a natural nano-drug delivery system with BBR, thereby significantly improving the pharmacokinetics of oral BBR.Keywords: natural nanoparticles, drug delivery system, pharmacokinetic synergy, berberine hydrochloride, herbal extract

Yingli Tao,1 Bin Liu,2 Ying Chen,2 Yiduoduo Hu,2 Rui Zhu,3 Ding Ye,2 Yingying Mao,2 Xiaohui Sun2 1Department of Reproductive Immunology, Tongde Hospital, Hangzhou, 310012, People’s Republic of China; 2Department of Epidemiology and Biostatistics, School of Public Health, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 3Institute of Pharmacology, College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of ChinaCorrespondence: Xiaohui Sun; Yingying MaoDepartment of Epidemiology and Biostatistics, School of Public Health, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310053, People’s Republic of ChinaTel +86-571-8663-3143; +86-571-8661-3603Fax +86-571-8663-3143; +86-571-8661-3693Email 20191030@zcmu.edu.cn; myy@zcmu.edu.cnBackground: Evidence from observational studies has suggested a link between cigarette smoking and the risk of polycystic ovary syndrome (PCOS). However, it remains uncertain whether the observed relationship is causal or due to biases inherent in observational studies. Therefore, we adopted two-sample Mendelian randomization (MR) design to assess the potential causal association between smoking and the risk of PCOS.Methods: Summary level data of PCOS was obtained from a genome-wide association study (GWAS) meta-analysis including 4,138 cases and 20,129 controls of European ancestry. Single-nucleotide polymorphisms (SNPs) associated with smoking initiation (n=360) were selected and used as genetic instrumental variables (IVs). MR analysis was performed using inverse-variance weighted (IVW) method, supplemented with the likelihood-based method, weighted median method, MR pleiotropy residual sum and outlier (MR-PRESSO) test, and MR-Egger regression.Results: Genetically predicted smoking initiation was associated with an increased risk of PCOS in the primary analysis (odds ratio (OR) =1.38, 95% confidence interval (CI) =1.12– 1.69). MR-Egger regression did not detect the horizontal pleiotropy. Sensitivity analyses using alternative MR methods and restricted IVs produced similar results.Conclusion: Our study provided evidence to support a potential causal association between smoking initiation and an increased risk of PCOS, providing a better understanding of the etiology and prevention of PCOS. Further studies are warranted to clarify the underlying biological mechanisms of smoking in the development of PCOS.Keywords: causal inference, cigarette smoking, Mendelian randomization, polycystic ovary syndrome, single-nucleotide polymorphism

Dong Ye,1 Yongqin Deng,2 Zhisen Shen1 1Department of Otorhinolaryngology-Head and Neck Surgery, Lihuili Hospital of Ningbo University, Ningbo, 315040, Zhejiang, People’s Republic of China; 2Department of Otorhinolaryngology-Head and Neck Surgery, Ningbo University School of Medicine, Ningbo, 315211, People’s Republic of ChinaCorrespondence: Dong Ye; Zhisen ShenDepartment of Otorhinolaryngology-Head and Neck Surgery, Lihuili Hospital of Ningbo University, Ningbo, 315040, People’s Republic of ChinaTel +86-13819861213; +86-13906687216Fax +86-574-87392232Email yedong518@sina.com; szs7216@sina.comAbstract: Head and neck squamous cell carcinoma (HNSCC) is the most common malignant tumor of the head and neck. HNSCC mainly affects the oral cavity and the laryngeal, laryngopharyngeal, and oropharyngeal tracts. The high incidence, hidden onset, low survival rate, and unsatisfactory effects of treatment effect underscore the importance of identify the mechanisms of HNSCC occurrence and development. Although there is a very urgent need for early diagnosis and treatment, there are currently no reliable early HNSCC diagnosis biomarkers or effective treatment targets. Long non-coding RNA (lncRNA) is widely involved in biological processes, especially as a key regulator of tumorigenesis and development. Lung adenocarcinoma metastasis-associated transcript 1 (MALAT1) is an important member of the lncRNA family that can regulate the occurrence and development of a variety of malignant tumors and is anticipated to be an ideal marker for early tumor diagnosis and an effective therapeutic target. Here, we review the research progress into the role of MALAT1 in the diagnosis and treatment of HNSCC and its regulatory mechanism.Keywords: head and neck squamous cell carcinoma, MALAT1, diagnosis, treatment, mechanism

Yongqin Deng, Yujie Cao, Liuqian Wang, Dong Ye Department of Otorhinolaryngology-Head and Neck Surgery, Lihuili Hospital of Ningbo University, Ningbo, Zhejiang, 315040, People’s Republic of ChinaCorrespondence: Dong YeDepartment of Otorhinolaryngology-Head and Neck Surgery, Lihuili Hospital of Ningbo University, Ningbo, Zhejiang, 315040, People’s Republic of ChinaTel +86-138 1986 1213Fax +86-574-8739 2232Email yedong518@sina.comAbstract: The study of salivary exosomes in malignant neoplasms has attracted widespread attention in the clinical setting. Although a variety of diagnostic and treatment approaches have been proposed, there are some limitations to their application. In recent years, the role of salivary exosomes in cancer has been increasingly studied. Salivary exosomes not only renew and regulate the biological behavior of tumor cells, such as malignant proliferation, migration, and invasion, but they also serve as ideal markers for early diagnosis of diseases and may represent an effective therapeutic target. This article reviews the current research on salivary exosomes in malignant neoplasms.Keywords: liquid biopsy, exosome, malignant neoplasm, diagnosis, treatment

Adama Ouattara,1 Abdoul-Karim Pare,1 Fasnewinde Aristide Kabore,2 Clotaire Yameogo,2 Desire Ky,2 Dramane Bayané,1 Delphine Ye,1 Timothee Kambou1 1Division of Urology, Souro Sanou Teaching Hospital, Bobo-Dioulasso, Burkina Faso; 2Division of Urology, Yalgado Ouedraogo Teaching Hospital, Ouagadougou, Burkina FasoCorrespondence: Adama OuattaraDivision of Urology, P.O. Box:1465, Bobo-Dioulasso, Burkina-FasoEmail adamsouat1@hotmail.comAim: To describe the epidemiological aspects, etiology and outcome of iatrogenic ureteral injury repair at the urology division of Souro Teaching Hospital of Bobo Dioulasso (Burkina-Faso).Patients and Methods: This was a retrospective descriptive study of consecutive patients with iatrogenic ureteric injuries who were referred and managed in the urology division of Souro Sanou Teaching Hospital (Bobo-Dioulasso) from January 2012 to December 2017. Variables studied were age, the time at the diagnosis, the causative event, the method of repair, and the outcome of the management.Results: The mean age was 37.72± 3.5 years coming from the rural population in most cases. The mean time at the diagnosis was 15 days. The injuries were due to gynecologic surgeries with hysterectomy (66%) and caesarian section (33%). Ureteric reimplantation with anti-reflux system was performed in seventeen patients. The rate of treatment success was 94% and the postoperative course was uneventful for all the patients.Conclusion: Iatrogenic ureteric lesions at the department of urology of Sanou Sourou teaching hospital of Bobo Dioulasso were mainly caused by gynecologic and obstetric surgeries like hysterectomy and caesarian section.Keywords: iatrogenic, ureter, injury, pelvic surgery

Objectives. Catalytically active materials are required in different chemical engineering processes. This makes the development of new materials with high efficiency and original ways in which to obtain them of significant interest. The present work investigates the synthesis of catalytically active material including electrode materials, as well as their improved efficiency due to the nanodecoration of their surface.Methods. An aluminum folio was nanoperforated (nanoscalloped) by high-voltage anodization in an acidic medium. The effective electrode material was obtained as a metallic nickel replica rather than an oxide layer of the product. To study the surface state of aluminum obtained in this manner, a scanning electron microscope (Hitachi-SU8200) was used. The elementary composition of the aluminum was determined by back-scattered X-ray irradiation.Results. The nickel replica obtained in the above-described process exceeded the catalytic activity estimated by methanol oxidation of the unprocessed nickel 70–150 times.Conclusions. The present paper demonstrates the potential of creating effective catalytically active nanopillar materials using the metallic rather than metal-oxide part of a layer of anodized aluminum as a matrix template.

Xiaohong Quan,1,* Huihui Liu,1,* Dongmei Ye,2 Xinling Ding,3 Xiulan Su4 1Experiment & Teaching Center for Basic Medicine, Chifeng University School of Basic Medical Sciences, Chifeng, Inner Mongolia, 024000, People’s Republic of China; 2Core Facility Center for Functional Experiments, CUSBMS, Chifeng University School of Basic Medical Sciences, Chifeng, Inner Mongolia, 024000, People’s Republic of China; 3Department of Human Anatomy, CUSBMS, Chifeng University School of Basic Medical Sciences, Chifeng, Inner Mongolia, 024000, People’s Republic of China; 4Clinical Research Center for Medical Sciences, IMMU, Chifeng University School of Basic Medical Sciences, Chifeng, Inner Mongolia, 024000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaohong QuanExperiment & Teaching Center for Basic Medicine, Chifeng University School of Basic Medical Sciences, No. 1 Yingbin Road, Chifeng City, Inner Mongolia, 024000, People’s Republic of ChinaEmail quanxiaohongxh@163.comBackground: Podocyte injury serves an important role during the progression of diabetic nephropathy (DN). The aim of this study was to investigate the effects of forsythoside A (FA) on high glucose (HG)-induced podocyte injury and to identify the possible mechanisms.Methods: MPC-5 podocytes were cultured under HG conditions. After exposure to different doses of FA, cell viability and apoptosis were respectively evaluated with CCK-8 assay and flow cytometry. Then, the levels of oxidative stress-related markers and inflammatory factors were examined by corresponding kits. Western blot analysis was employed to detect the expression of Nox2, Nox4, COX-2, iNOS and matrix metalloproteinases 12 (MMP12). Subsequently, MMP12 was overexpressed to assess whether the effects of FA on HG-stimulated podocyte injury were mediated by MMP12 and MAPK signaling.Results: Results indicated that FA dose-dependently elevated cell viability, reduced cell apoptosis in HG-induced MPC-5 cells. Additionally, FA significantly inhibited oxidative stress, which could be certified by decreased content of malondialdehyde (MDA), enhanced activities of superoxide dismutase (SOD) and catalase (CAT), and downregulated expression of Nox2 and Nox4. Moreover, notably reduced levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were observed in FA-treated MPC-5 cells under HG conditions, accompanied by decreased COX-2 and iNOS expression. Remarkably, FA suppressed MMP12 expression in a dose-dependent manner, and the effects of FA on MPC-5 cells exposed to HG were partially counteracted by MMP12 overexpression. Mechanically, FA inactivated the expression of phospho-ERK (p-ERK), p-p38 and p-JNK, which was restored after MMP12 overexpression.Conclusion: These findings demonstrate a protective mechanism of FA by inactivating MAPK signaling via MMP12 inhibition in HG-induced podocyte injury, providing a promising therapeutic candidate for the treatment of DN.Keywords: diabetic nephropathy, high glucose, oxidative stress, inflammation, apoptosis

Ding Ye,1 Bin Liu,1 Zhixing He,2 Lin Huang,2 Yu Qian,1 Keding Shao,2 Chengping Wen,2 Yingying Mao1 1Department of Epidemiology and Biostatistics, Zhejiang Chinese Medical University School of Public Health, Hangzhou, Zhejiang, 310053, People’s Republic of China; 2Institute of Basic Research in Clinical Medicine, Zhejiang Chinese Medical University School of Basic Medical Sciences, Hangzhou, Zhejiang, 310053, People’s Republic of ChinaCorrespondence: Yingying MaoDepartment of Epidemiology and Biostatistics, Zhejiang Chinese Medical University School of Public Health, Hangzhou, Zhejiang, 310053, People’s Republic of ChinaTel +86-571-8661-3536Email myy@zcmu.edu.cnChengping WenInstitute of Basic Research in Clinical Medicine, Zhejiang Chinese Medical University School of Basic Medical Sciences, Hangzhou, Zhejiang, 310053, People’s Republic of ChinaTel +86-571-8663-3377Email wengcp@163.comObjective: To investigate the potential causal associations of circulating levels of growth differentiation factor 15 (GDF-15) with the risk of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) using a Mendelian randomization (MR) design.Methods: A genome-wide association study (GWAS) of GDF-15 among 5,440 individuals of European ancestry was used to identify genetic instruments. Summary statistics of SLE, RA and IBD were obtained from publicly available GWASs. We conducted an MR study using the inverse-variance weighted (IVW) method, supplemented with simple-median and weighted-median methods. Cochran Q test and MR-Egger regression were used to detect potential heterogeneity and directional pleiotropy. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated.Results: We found that genetically predicted high circulating GDF-15 levels were associated with a decreased risk of SLE (OR 0.80, 95% CI 0.68– 0.92 by IVW), with similar results in sensitivity analyses. In replication analysis using summary data from another SLE GWAS, the results were consistent (OR 0.82, 95% CI 0.71– 0.93 by IVW). Moreover, no evidence of heterogeneity or pleiotropy was detected. However, genetically determined circulating levels of GDF-15 were not associated with risk of RA or IBD in the primary analysis and subsequent sensitivity analyses.Conclusions: Our study suggested an inverse association between circulating GDF-15 levels and risk of SLE, and further studies are warranted to elucidate the underlying biological mechanisms. There was limited evidence supporting a causal association of circulating GDF-15 levels with risk of RA and IBD.Keywords: growth differentiation factor 15, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, Mendelian randomization, single nucleotide polymorphism

Enthesitis is a common clinical feature of spondyloarthritis (SpA), characterized by inflammation of the tendon or ligament attachment site to a bone or joint capsule. The importance of detecting enthesitis for the diagnosis of SpA is confirmed by its inclusion in the classification criteria for psoriatic arthritis (PsA) – CASPAR – and in the classification criteria for SpA of the international group for the study of spondyloarthritis – ASAS. Enthesitis may be the first clinical sign of SpA, as well as the leading symptom that significantly influences the therapeutic choice. Enthesitis occurs in 30–50% of patients with SpA and is associated with high disease activity, more severe pain and worse quality of life. The frequency of enthesitis detected by ultrasound in patients with PsA is approximately 4 times higher than in patients with ankylosing spondylitis and is associated with the severity of the disease. The review presents current data on the pathophysiology, diagnosis and treatment of enthesitis. Recent studies emphasize the role of imaging methods for the diagnosis of enthesitis due to their higher sensitivity and specificity compared to clinical examination. There is very limited information on the effect of synthetic disease-modifying antirheumatic drugs on enthesitis, while targeted drugs and biologic therapy have shown high efficacy in its treatment compared to placebo. Preliminary evidence suggests that targeting interleukin (IL) 17 or IL12/23 may be more effective in enthesises inflammation suppression than tumor necrosis factor α inhibition.

Qingquan Liu,1,* Yiru Wang,1,* Xuecheng Zhao,2 Lixuan Wang,2 Feng Liu,3 Tao Wang,4 Dawei Ye,5 Yongman Lv1,2 1Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China; 2Department of Health Management Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China; 3Department of Urology, Shaoyang Central Hospital, Shaoyang 422000, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China; 5Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yongman Lv; Dawei YeTongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan 430030, People’s Republic of ChinaTel +86-2783662848; +86-2783663409Fax + 86-2783662848Email lvyongman@126.com; dy0711@gmail.comBackground: The novel coronavirus disease (COVID-19) is leading to high morbidity and mortality. This aim of this study was to test whether blood urea nitrogen-to-creatinine ratio (BCR) is a predictor for mortality in patients with COVID-19.Methods: Ranges of “normal” BCR values were calculated from 9165 healthy subjects, and 337 and 79 COVID-19 patients were randomly assigned to the training cohort and the validation cohort, respectively. Prognostic factor of death incidence was selected by LASSO regression analyses. The prognostic ability of BCR range was assessed by logistic regression analysis. A nomogram for predicting in-hospital mortality based on BCR was developed. The performance of the nomogram was evaluated with respect to its calibration, discrimination, and clinical usefulness.Results: Among 337 COVID-19 patients, 13.4% and 11.3% were classified into higher and lower than normal range group, respectively. Kaplan–Meier curves for all-cause mortality showed that patients with higher BCR group had worse prognosis (P< 0.0001). BCR above the normal range was independently associated with death in COVID-19 patients (OR: 7.54; 95%CI: 1.55– 36.66; P=0.012). The nomogram had good discrimination in the training cohort (C-index 0.838; 0.795– 0.880) and the validation cohort (C-index 0.929; 0.869– 0.989), and good calibration. Using maximum Youden index, the cutoff values of 59.8 points, the sensitivity and specificity were 75.4% and 81%. Decision curve and clinical impact curve analysis demonstrated that the nomogram was clinically useful.Conclusion: BCR was a useful prognostic factor for COVID-19 patients. Development of an individualized BCR-based prediction nomogram can effectively predict the risk of mortality and help clinicians to make individual treatment early.Keywords: blood urea nitrogen, creatinine, coronavirus, COVID-19

Dan Ye, Hao-Ran Shen, Liangqing Yao Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, People’s Republic of ChinaCorrespondence: Liangqing YaoObstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, People’s Republic of ChinaTel/Fax +86-021-33189900Email sherryye1217@163.comBackground: Thinking of the rarity and malignancy of gynecologic tract carcinosarcomas (GTCS), the aim of the study was to investigate the possible predictors of relapse-free survival (RFS) and overall survival (OS) for GTCS patients.Methods: We performed a retrospective cohort study of women with GTCS at our hospital between January 2009 and December 2013. We used the Kaplan–Meier method to calculate RFS and OS, and Cox regression analysis to define the survival effects of risk factors.Results: A total of 45 GTCS patients were included in the study. The median follow-up time was 46 months. Cox regression analysis showed that lymph node metastasis was significantly associated with worse RFS (HR: 3.145; 95%CI: 1.181– 8.378; P=0.022) and OS (HR: 4.065; 95%CI: 1.57– 10.524; P=0.004). Pelvic lymphadenectomy had a favorable RFS (HR: 0.213; 95%CI: 0.057– 0.796; P= 0.021).Conclusion: Lymph node metastasis significantly affected the prognosis of uterine carcinosarcoma. Pelvic lymphadenectomy could reduce the relapse rate of GTCS patients.Keywords: pelvic lymphadenectomy, relapse-free survival, overall survival, gynecologic tract carcinosarcomas