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Tiantian Tang,1,2,* Yujiao Wang,1,2,* Taotao Li,1,2,* Ding Liu,1,2 Kai Yang,1,2 Jing Sun,1,2 Yajun Shi,1,2 Dongyan Guo,1,2 Junbo Zou,1,2 Fengyun Bai,3 Ying Sun,3 Mei Wang,1,2 Xiaofei Zhang1,2 1Key Laboratory of Basic and New Drug Research in Chinese Medicine, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People’s Republic of China; 2Shaanxi Provincial University Engineering Research Center of Chinese Medicine Aromatic Industry, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People’s Republic of China; 3Shaanxi Dongtai Pharmaceutical Co., Ltd., Xianyang, Shaanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mei Wang; Xiaofei Zhang, Key Laboratory of Basic and New Drug Research in Chinese Medicine; Shaanxi Provincial University Engineering Research Center of Chinese Medicine Aromatic Industry, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, 712046, People’s Republic of China, Email wangmei0708@163.com; 2051028@sntcm.edu.cnObjective: To explore the mechanism and active components of the anti-colitis effects of myrrh essential oil (MEO).Methods: In this study, we investigated the anti-inflammatory effects and molecular mechanisms of MEO on dextran sulfate sodium (DSS)-induced colitis with in vitro cell experiments, RNA-seq (RNA Sequencing), Weighted gene co-expression network analysis (WGCNA), combined with “weighting coefficient” network pharmacology, as and in vivo pharmacodynamic experiments. A 3% DSS solution was used to induce colitis in BALB/c mice and MEO was administered orally. We performed gas chromatography-mass spectrometry (GC-MS) analysis of the MEO components. The disease activity index (DAI) was evaluated by observing body weight, fecal characteristics, and blood in the stool of mice. The levels of inflammatory cytokines (TNF-α and IL-1β) in mouse serum were measured using ELISA (Enzyme-linked immunosorbent assay) kits. Additionally, the expression of MAPK-related proteins (JNK, p-JNK, ERK, and p-ERK) in mouse colonic tissues was detected by Western blotting and immunohistochemistry.Results: MEO (0.0625– 0.125μg/g, p.o). significantly inhibited the expression of the inflammatory mediator Nitric oxide (NO) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. After treatment, there was a significant increase in body weight and alleviation of diarrhea and bloody stools in colitis mice. It also reduced inflammatory cell infiltration. Furthermore, it decreased the serum levels of TNF-α and IL-1β, and reduced the activity of p-JNK and p-ERK in the MAPK pathway.Conclusion: MEO relieved DSS-induced colitis by modulating the MAPK pathway. The experimental results indicate that the MAPK pathway might be inhibited by the synergistic effect of gamma-Muurolene, Curzerene, beta-Elemene, and Furanoeudesma 1.3-diene in MEO, which provides a novel idea for subsequent research and development of new anti-colitis drugs. Keywords: colitis, myrrh essential oil, MAPK signaling pathway, RNA sequencing, weighted gene co-expression network analysis

Lei Liu,1,* Shanshan Liu,2,* Fuyan Bai,1 Yangxin Deng,1 Xinhuan Zhang,1 Li Wang3 1Department of Endocrinology, the Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong, People’s Republic of China; 2General Gynecology, the Tai ‘an Central Hospital, Taian, Shandong, People’s Republic of China; 3Department of Pharmacy, the Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinhuan Zhang; Li Wang, Email zhangxh22009@126.com; suxinlan1027@126.comBackground: An important factor in the pathogenesis of polycystic ovary syndrome (PCOS) is chronic low-grade inflammation. However, the exact pathophysiology of PCOS is currently unknown, which makes clinical diagnosis and the development of effective treatments more difficult. We aimed to investigate the role of the inflammatory response in initiating and progressing PCOS.Methods: 13 control granulosa cell samples and 15 granulosa cell samples from patients with PCOS were obtained from the GSE102293, GSE34526, and GSE5850 datasets. The gene set variation analysis (GSVA) method was used to calculate the inflammatory response score. Subsequently, the genes associated with inflammation in the hub were identified using differential expression analysis and weighted gene co-expression network analysis (WGCNA). The findings were confirmed by analysis of independent datasets and examination of clinical samples by qRT-PCR analysis. A consensus cluster analysis was conducted to categorize the PCOS samples into subtypes related to inflammation. Functional enrichment and analysis of immune cell infiltration were conducted to explore the potential mechanisms involved. Additionally, the CMap database was utilized to predict potential drugs, and the results were confirmed through molecular docking.Results: During the training cohort analysis, we identified five distinct genes (TGFBR2, ICAM3, WIPF1, SLC11A1, and NCF2) that could serve as potential diagnostic markers for PCOS. The expression levels of these genes were confirmed through validation in both the test set and clinical samples. In training cohort, two distinct inflammatory patterns (C1 and C2) were identified, and the C2 subtype exhibited activated immune- and inflammation-related pathways. Esmolol was shown to have potential as a drug to treat PCOS and it showed good results for molecular binding at TGFBR2, ICAM3, WIPF1, SLC11A1, and NCF2 proteins.Conclusion: Five diagnostic biomarkers and two inflammation-related molecular types associated with PCOS were identified, and esmolol was a potential drug for PCOS treatment. Our findings provided new diagnostic markers and potential small-molecule drugs for PCOS diagnosis and prevention.Keywords: polycystic ovary syndrome, inflammatory response, diagnostic biomarkers, molecular subtypes, esmolol

Daya Zhang,1,&ast; Fen-jiao Mao,1,&ast; Shimei Huang,1,&ast; Chen Chen,1 Da Li,1 Fan Zeng,1 Feihu Bai2,3 1Graduate School, Hainan Medical University, Haikou, People’s Republic of China; 2Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, People’s Republic of China; 3The Gastroenterology Clinical Medical Center of Hainan Province, Haikou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feihu Bai, Chief Physician and Professor of the Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Yehai Avenue, &num;368, Longhua District, Haikou, Hainan Province, People’s Republic of China, Tel +86-18995181963, Fax +86-89866809168, Email baifeihu_hy@163.comPurpose: Recurrence rate of Helicobacter pylori (H. pylori) infection after successful eradication have gained attention. This study was to assess the recurrence rate of H. pylori infection after successful eradication in the southern coastal provinces of China and to analyze its factors.Patients and Methods: 975 patients with upper gastrointestinal symptoms who were diagnosed with H. pylori infection using the 13C or 14C-urea breath test (UBT) underwent eradication treatment between August 2021 and December 2022. After eight to twelve weeks, repeat UBT was performed. Besides, 824 patients with successful eradication underwent a repeat UBT by completing questionnaires after a year. The 1-year recurrence rate was calculated, and the differences were analyzed based on baseline data, sociological characteristics, and lifestyle.Results: A total of 734 patients completed the 1-year follow-up, out of which 26 (3.5%) patients experienced a recurrence of H. pylori infection. Exposure to other individuals infected with H. pylori (χ2=12.852, P< 0.001), poor hygiene conditions at dining out places (χ2=6.839, P=0.009), frequent dining out (χ2=24.315, P< 0.001), smoking (χ2=7.510, P=0.006), consumption of non-purified water (χ2=16.437, P< 0.001), consumption of pickled foods (χ2=5.682, P=0.017), irregular meal patterns (χ2=16.877, P< 0.001) and age (χ2=9.195, P=0.010) were significant factors for H. pylori infection recurrence. Exposure to other individuals infected with H. pylori, poor hygiene conditions at dining out places, consumption of non-purified water, frequent dining out and irregular meal patterns were independent risk factors (P=0.022, 0.016, 0.002, < 0.001, < 0.001; 95% CI 0.146– 0.861, 0.121– 0.806, 1.715– 10.845, 0.085– 0.521, 2.291– 14.556).Conclusion: The one-year recurrence rate of H. pylori infection post-eradication in the southern coastal provinces of China is 3.5%. Contacting with infected individuals, poor hygiene in dining places, consumption of non-purified water, frequent dining out, and irregular meal patterns were identified as significant independent factors influencing H. pylori recurrence.Keywords: Helicobacter pylori, successful eradication, Southern Coastal Provinces of China, risk factors, 1-year follow-up

Xiaoyu Li,1 Feng Bai,2 Xinmei Liu,1 Guangyu Yang1 1Department of Otorhinolaryngology Head and Neck Surgery, First Hospital of Jilin University, Changchun, People’s Republic of China; 2Department of Otorhinolaryngology Head and Neck Surgery, the Second Hospital of Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Guangyu Yang, Department of Otorhinolaryngology Head and Neck Surgery, First Hospital of Jilin University, No. 1 of Xinmin Street, Chaoyang District, Changchun, 130021, People’s Republic of China, Tel +86-43188785539, Fax +86-43188785505, Email sryyxf@jlu.edu.cnAbstract: Hospice care is to improve the quality of life and help patients die comfortably, peacefully and dignified by controlling pain and discomfort symptoms and providing physical, psychological and spiritual care and humanistic care in the final stage of the patient’s life. Hospice care clients were primarily cancer patients at first and then slowly extended to other critically patients. Hospice care can alleviate the physical, psychosocial and mental problems of patients with advanced cancer, meet the diversified and multi-level health service needs of patients, improve the quality of life of patients and their families, and also save medical expenditure and improve the efficiency of medical resources. At present, there were few studies on hospice care for Chinese patients with advanced cancer. In this study, the needs of hospice care for patients with advanced cancer were reviewed from physical comfort and pain reduction, dignity maintenance, social support, and help calm death, and specific screening and evaluation tools for hospice care for patients with advanced cancer. And this study was summarized to review the influencing factors of hospice care in order to provide a reference for clinical hospice care practice for patients with advanced cancer in China.Keywords: advanced cancer, hospice care, influencing factors, clinical practice, evaluation tools

Zhenzhen Sun,1,&ast; Kun Wang,1,&ast; Chuan Yun,1 Fang Bai,1 Xiaodan Yuan,2 Yaujiunn Lee,3 Qingqing Lou1 1The First Affiliated Hospital of Hainan Medical University, Hainan Clinical Research Center for Metabolic Disease, Haikou, Hainan, People’s Republic of China; 2Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 3Department of Endocrinology, Lee’s Clinic, Pingtung City, Pingtung County, Taiwan&ast;These authors contributed equally to this workCorrespondence: Qingqing Lou, The First Affiliated Hospital of Hainan Medical University, Hainan Clinical Research Center for Metabolic Disease, No. 31, Longhua Road, Haikou, 570102, Hainan, People’s Republic of China, Tel +86 15312019129, Email 2444890144@qq.comPurpose: To investigate the association of five obesity indices and the variability of these indices with diabetic kidney disease (DKD) in patients with type 2 diabetes and compare the predictive validity of these markers for the risk of DKD in this large longitudinal cohort study.Patients and Methods: A total of 2659 patients with type 2 diabetes who did not have DKD were enrolled between 2006 and 2019 at Lee’s United Clinic in Taiwan. Data were collected for each subject, including demographic data, personal medical history, clinical parameters and calculated Body mass index (BMI), visceral adiposity index (VAI), lipid accumulation product (LAP), body roundness index (BRI) and variability of five obesity indices. Cox regression analysis was performed to determine the relationship between different obesity indicators and DKD risk. Cox’s proportional hazards model was evaluated the predictive effect of obesity indices on DKD.Results: The risk of developing DKD increased with an increase in the BRI, LAP, VAI, WC and BMI (all P trend< 0.05), and the variability of VAI was significantly associated with DKD [HR=1.132, 95% CI (1.001, 1.281)] after adjusting for corresponding variables. BRI had the strongest predictive effect on DKD. BRI had the best predictive performance, with AUC of 0.807, 0.663 and 0.673 at 1, 3 and 5 years, respectively. Cox regression analysis of risk factors for DKD in patients stratified by BRI quartiles showed that patients in the Q4 group had the highest risk of developing DKD [HR=1.356, 95% CI (1.131, 1.626)].Conclusion: BMI, WC, VAI, LAP, BRI and VAI variability were associated with a significant increase in the risk of DKD events, and BRI was superior and alternative obesity index for predicting DKD.Keywords: visceral adiposity index, lipid accumulation product, body roundness index, diabetic kidney disease

Daya Zhang,1,&ast; ZhengJin Liu,2,&ast; Feihu Bai2,3 1Graduate School, Hainan Medical University, Haikou, People’s Republic of China; 2Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, People’s Republic of China; 3The Gastroenterology Clinical Medical Center of Hainan Province, Haikou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feihu Bai, Chief Physician and Professor of Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Yehai Avenue, &num;368, Longhua District, Haikou, Hainan Province, 570216, People’s Republic of China, Tel +86-18995181963, Fax +86898-66809168, Email 328473521@qq.comAbstract: Alcoholic liver disease (ALD)—one of the most common liver diseases — involves a wide range of disorders, including asymptomatic hepatic steatosis, alcoholic hepatitis (AH), liver fibrosis, and cirrhosis. Alcohol consumption induces a weakened gut barrier and changes in the composition of the gut microbiota. The presence of CYP2E1 and its elevated levels in the gastrointestinal tract after alcohol exposure lead to elevated levels of ROS and acetaldehyde, inducing inflammation and oxidative damage in the gut. At the same time, the influx of harmful molecules such as the bacterial endotoxin LPS and peptidogly from gut dysbiosis can induce intestinal inflammation and oxidative damage, further compromising the intestinal mucosal barrier. In this process, various oxidative stress-mediated post-translational modifications (PTMs) play an important role in the integrity of the barrier, eg, the presence of acetaldehyde will result in the sustained phosphorylation of several paracellular proteins (occludin and zona occludens-1), which can lead to intestinal leakage. Eventually, persistent oxidative stress, LPS infiltration and hepatocyte damage through the enterohepatic circulation will lead to hepatic stellate cell activation and hepatic fibrosis. In addition, probiotics, prebiotics, synbiotics, fecal microbial transplantation (FMT), bioengineered bacteria, gut-restricted FXR agonists and others are promising therapeutic approaches that can alter gut microbiota composition to improve ALD. In the future, there will be new challenges to study the interactions between the genetics of individuals with ALD and their gut microbiome, to provide personalized interventions targeting the gut-liver axis, and to develop better techniques to measure microbial communities and metabolites in the body.Keywords: alcoholic liver disease, gut dysbiosis, modulators

Shengqi You,1 Tingyu Lv,1 Ruomeng Qin,2 Zheqi Hu,2 Zhihong Ke,2 Weina Yao,1 Hui Zhao,2 Feng Bai2,3 1Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210008, People’s Republic of China; 2Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, People’s Republic of China; 3Geriatric Medicine Center, Taikang Xianlin Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, People’s Republic of ChinaCorrespondence: Feng Bai, Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, 210009, Jiangsu Province, People’s Republic of China, Tel +86-25-83105960, Email baifeng515@126.comStudy Objectives: By examining spontaneous activity changes of sleep-related networks in patients with the Alzheimer’s disease (AD) spectrum with or without insomnia disorder (ID) over time via neuro-navigated repetitive transcranial magnetic stimulation (rTMS), we revealed the effect and mechanism of rTMS targeting the left-angular gyrus in improving the comorbidity symptoms of the AD spectrum with ID.Methods: A total of 34 AD spectrum patients were recruited in this study, including 18 patients with ID and the remaining 16 patients without ID. All of them were measured for cognitive function and sleep by using the cognitive and sleep subscales of the neuropsychiatric inventory. The amplitude of low-frequency fluctuation changes in sleep-related networks was revealed before and after neuro-navigated rTMS treatment between these two groups, and the behavioral significance was further explored.Results: Affective auditory processing and sensory-motor collaborative sleep-related networks with hypo-spontaneous activity were observed at baseline in the AD spectrum with ID group, while substantial increases in activity were evident at follow-up in these subjects. In addition, longitudinal affective auditory processing, sensory-motor and default mode collaborative sleep-related networks with hyper-spontaneous activity were also revealed at follow-up in the AD spectrum with ID group. In particular, longitudinal changes in sleep-related networks were associated with improvements in sleep quality and episodic memory scores in AD spectrum with ID patients.Conclusion: We speculated that left angular gyrus-navigated rTMS therapy may enhance the memory function of AD spectrum patients by regulating the spontaneous activity of sleep-related networks, and it was associated with memory consolidation in the hippocampus-cortical circuit during sleep.Clinical Trial Registration: The study was registered at the Chinese Clinical Trial Registry, registration ID: ChiCTR2100050496, China.Keywords: Alzheimer’s disease, insomnia disorder, sleep-related functional connectivity network, neuro-navigated repetitive transcranial magnetic stimulation, spontaneous activity

Jiaxin Liao, Yuting Li, Xiaoting Gui, Yong Zhang, Xu Hu, Liang Cheng, Wen Hu, Feng Bai Department of Endocrinology, The Huai’an Hospital Affiliated to Xuzhou Medical University and The Second People’s Hospital of Huai’an, Xuzhou Medical University, Huai’an, People’s Republic of ChinaCorrespondence: Feng Bai, Department of Endocrinology, The Huai’an Hospital Affiliated to Xuzhou Medical University and The Second People’s Hospital of Huai’an, Xuzhou Medical University, No. 62 South Huaihai Road, Huai’an, 223001, People’s Republic of China, Tel +86-13420182598, Email jiefu6887579@163.comPurpose: This study aimed to investigate the relationship between serum isthmin-1 (ISM1) and type 2 diabetes mellitus (T2DM), and the alteration of serum ISM1 level in both diabetic sensorimotor peripheral neuropathy (DSPN) and diabetic adults with obesity.Patients and Methods: We recruited 180 participants (120 T2DM and 60 controls) in the cross-sectional study. First, we compared the serum ISM1 concentration in diabetic patients and non-diabetic controls. Secondly, according to DSPN, patients were divided into DSPN and non-DSPN groups. Last, patients were categorized as lean T2DM (15 males, 15 females), overweight T2DM (35 males, 19 females), and obese T2DM groups (23 males, 13 females) according to gender and body mass index (BMI). All participants were collected with clinical characteristics and biochemical profiles. Serum ISM1 was detected in all subjects by ELISA.Results: Higher serum ISM1 [7.78 ng/mL (IQR: 6.33– 9.06) vs 5.22 (3.86– 6.04), P < 0.001] was observed in diabetic patients compared to non-diabetic controls. Binary logistic regression analysis showed that serum ISM1 was a risk factor for type 2 diabetes after adjustment (OR=4.218, 95% CI: 1.843– 9.653, P=0.001). Compared to the non-DSPN group, serum ISM1 level was not changed significantly in patients who suffered from DSPN. Diabetic females with obesity had lower level of serum ISM1 (7.10± 1.29 ng/mL) when compared to the lean T2DM (8.42± 1.36 ng/mL, P < 0.05) and the overweight T2DM (8.33± 1.27 ng/mL, P < 0.05). However, serum ISM1 was not changed significantly in male groups or all patients together.Conclusion: Serum ISM1 was a risk factor for type 2 diabetes, and it was associated with diabetic adults with obesity while there was sexual dimorphism. However, serum ISM1 levels were not correlated with DSPN.Keywords: isthmin-1, type 2 diabetes, diabetic sensorimotor peripheral neuropathy, obesity, inflammation

Daya Zhang,1,&ast; Lijun Zhang,2,&ast; Shiju Chen,1,&ast; Runxiang Chen,1 Xiaodong Zhang,1 Feihu Bai3,4 1Graduate School, Hainan Medical University, Haikou, People’s Republic of China; 2Medical Examination Center, The Second Affiliated Hospital of Hainan Medical University, Haikou, People’s Republic of China; 3Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, People’s Republic of China; 4The Gastroenterology Clinical Medical Center of Hainan Province, Haikou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feihu Bai, Chief Physician and Professor of Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Yehai Avenue, &num;368, Longhua District, Haikou, Hainan Province, People’s Republic of China, Tel +86-18995181963, Fax +86 898-66809168, Email 328473521@qq.comBackground: The prevalence of metabolism-related fatty liver disease (MAFLD) has been rarely reported in hospital staffs. The aim of this study was to assess the prevalence and risk factors for MAFLD in hospital staffs aged ≥ 18 years.Methods: Based on type B ultrasonic, hospital staffs who underwent medical examinations at the second Affiliated Hospital of Hainan Medical University from January 2022 to March 2022 were classified into health control group (661 subjects) and MAFLD group (223 subjects), demographic, biochemical and blood examination information were compared between 2 groups. Independent risk factors for MAFLD were determined by logistic regression. Predictive values of risk factors of MAFLD were evaluated by receiver operating characteristic (ROC) curves.Results: The prevalence of MAFLD was 33.7%. Older age (OR=1.08, p< 0.001), H. pylori infection (OR=0.234, p=0.02), triglyceride-glucose (TyG) (OR=7.001, p< 0.001), low-density lipoprotein cholesterol (LDL-C) (OR=2.076, p= 0.028), red blood cell (RBC) (OR=2.386, p=0.001), eating out (OR=0.048, p=0.001), regular exercise (OR=23.017, p< 0.001), and overweight (OR=3.891, p= 0.003) were independently associated factors for MAFLD. The AUC of model predicting MAFLD is 0.910 [95% CI (0.886, 0.934)], with 0.794 sensitivity, 0.908 specificity. The diagnostic value of model was higher in the female MAFLD group after stratified analysis according to gender. The model showed that TyG was the factor contributing more to MAFLD. The diagnostic value of TyG was higher in the female MAFLD group than male MAFLD group.Conclusion: The prevalence of MAFLD among hospital staffs was 33.7%. TyG can be used to predict MAFLD especially for female hospital staffs for early intervention.Keywords: metabolic-associated fatty liver disease, MAFLD, hospital staffs, risk factors, triglyceride-glucose index, TyG, red blood cell, RBC, H. pylori infection

We report the pulsed-laser deposition of epitaxial double-perovskite Bi2FeCrO6(BFCO) films on the (001)-, (110), and (111)-oriented single-crystal SrTiO3 substrates. All of the BFCO films with various orientations show the 1/2 1/2 1/2 and 3/2 3/2 3/2 superlattice-diffraction peaks. The intensity ratios between the 1/2 1/2 1/2-superlattice and the main 111-diffraction peak can be tailored by simply adjusting the laser repetition rate and substrate temperature, reaching up to 4.4%. However, both optical absorption spectra and magnetic measurements evidence that the strong superlattice peaks are not correlated with the B-site Fe3+/Cr3+ cation ordering. Instead, the epitaxial (111)-oriented Bi2FeCrO6 films show an enhanced remanent polarization of 92 μC/cm2 at 10 K, much larger than the predicted values by density-functional theory calculations. Positive-up-negative-down (PUND) measurements with a time interval of 10 μs further support these observations. Therefore, our experimental results reveal that the strong superlattice peaks may come from A- or B-site cation shifts along the pseudo-cubic [111] direction, which further enhance the ferroelectric polarization of the BFCO thin films.

Mingdi Zhang, Kejin Wu, Peng Zhang, Yiran Qiu, Fang Bai, Hongliang Chen Department of Breast Surgery, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Hongliang ChenDepartment of Breast Surgery, Obstetrics and Gynecology Hospital of Fudan University, 419 Fangxie Road, Shanghai, 200011, People’s Republic of ChinaTel/Fax +86-21-33189900Email 13671852284@163.comBackground: To summarize the regulatory role of mRNA-miRNA-lncRNA network associated with endocrine therapy resistance (ETR) in breast cancer.Methods: We analyzed the differentially expressed genes (DEGs), differentially expressed lncRNAs (DELs), and differentially expressed miRNAs (DEMs) in long-term estrogen-deprived (LTED) estrogen receptor (ER)-positive breast cancer cells (LTED MCF7) (modeling relapse on endocrine therapy) and MCF7 cells in the presence of estrogen (E2) (modeling a patient at primary diagnosis) by mining GSE120929 and GSE120930 datasets. The mRNA-miRNA-lncRNA network was constructed by multiple bioinformatic tools. The prognosis of genes from the network was validated in breast cancer patients with following systemic treatment (endocrine therapy) by GEPIA, Kaplan–Meier plotter and UALCAN database.Results: Totally, 769 DEGs, 33 DEMs, and 10 DELs were selected. The mRNA-miRNA-lncRNA network was established including 60 mRNA nodes, 6 miRNA nodes and 3 lncRNA nodes. A significant module containing 3 nodes and 3 edges was calculated based on the mRNA-miRNA-lncRNA network. The hub genes in the network are ABCG2, ESR1 and GJA1. ESR1/miR-130b-3p/HOTAIR are significantly correlated with the prognosis of breast cancer patients with endocrine therapy.Conclusion: This study provides a novel ETR-related mRNA-miRNA-lncRNA network. Further, we suggest that ESR1/miR-130b-3p/HOTAIR may be promising targets for clinical treatment of endocrine therapy-resistant breast cancer.Keywords: endocrine therapy resistance, breast cancer, bioinformatic analysis, mRNA-miRNA-lncRNA network, GEO

Candida is a polyphyletic genus of asexually reproducing yeasts in the Saccharomycotina with more than 400 species that occur in almost all families of the subclass and its name is strongly connected with the infectious disease candidiasis. During the last two decades, approximately half of the Candida species have been reassigned into more than 36 already existing genera and 14 newly proposed genera, but the polyphyletic feature of the genus largely remained. Candida auris is an important, globally emerging opportunistic pathogen that has caused life-threatening outbreaks in healthcare facilities worldwide. This species belongs to the Candida auris-Candida haemuli (CAH) clade in the Metschnikowiaceae, a clade that contains multidrug-resistant clinically relevant species, but also species isolated from natural environments. The clade is phylogenetically positioned remotely from the type species of the genus Candida that is Candida vulgaris (currently interpreted as a synonym of Candida tropicalis) and belongs to the family Debaryomycetaceae. Although previous phylogenetic and phylogenomic studies confirmed the position of C. auris in the Metschnikowiaceae, these analyses failed to resolve the position of the CAH clade within the family and its delimitation from the genera Clavispora and Metschnikowia. To resolve the position of the CAH clade, phylogenomic and comparative genomics analyses were carried out to address the phylogenetic position of C. auris and related species in the Metschnikowiaceae using several metrics, such as the average amino acid identity (AAI) values, the percentage of conserved proteins (POCP) and the presence-absence patterns of orthologs (PAPO). Based on those approaches, 13 new genera are proposed for various Candida and Hyphopichia species, including members of the CAH clade in the Metschnikowiaceae. As a result, C. auris and related species are reassigned to the genus Candidozyma. Fifty-five new combinations and nine new species are introduced and this will reduce the polyphyly of the genus Candida. [ABSTRACT FROM AUTHOR]

The global diversity of fungi has been estimated between 2 to 11 million species, of which only about 155 000 have been named. Most fungi are invisible to the unaided eye, but they represent a major component of biodiversity on our planet, and play essential ecological roles, supporting life as we know it. Although approximately 20 000 fungal genera are presently recognised, the ecology of most remains undetermined. Despite all this diversity, the mycological community actively researches some fungal genera more commonly than others. This poses an interesting question: why have some fungal genera impacted mycology and related fields more than others? To address this issue, we conducted a bibliometric analysis to identify the top 100 most cited fungal genera. A thorough database search of the Web of Science, Google Scholar, and PubMed was performed to establish which genera are most cited. The most cited 10 genera are Saccharomyces, Candida, Aspergillus, Fusarium, Penicillium, Trichoderma, Botrytis, Pichia, Cryptococcus and Alternaria. Case studies are presented for the 100 most cited genera with general background, notes on their ecology and economic significance and important research advances. This paper provides a historic overview of scientific research of these genera and the prospect for further research. [ABSTRACT FROM AUTHOR]

Fengfeng Bai,1,* Tao Li,1,* Baozhu Li,1 Xiaozheng Li,1 Lifeng Zhu2 1Department of Psychiatry, Anding Hospital, Tianjin 300222, People’s Republic of China; 2Nursing Department, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250033, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lifeng ZhuNursing Department, The Second Hospital, Cheeloo College of Medicine, Shandong University, 247 Beiyuan Street, Jinan, Shandong 250033, People’s Republic of ChinaTel +86 17660087098Email 2814539930@qq.comBackground: Previous studies have reported that patients with diabetes mellitus (DM) have a higher incidence of cognitive decline and an increased risk of developing all types of dementia. The aim was to elucidate the association between serum human epididymal protein 4 and cognitive function in patients with DM.Methods: Serum levels of HE4 were measured in 205 patients with DM. All DM patients were followed up for a median period of 48 months (range=5– 49) prospectively. Cox proportional hazard analysis was used to evaluate the predictive value of serum HE4 for predicting cognitive decline (end point).Results: Multivariate linear regression analysis revealed that serum HE4 was independently associated with MOCA score after adjusting for age, gender, BMI, current smoker, current drinker, admission systolic and diastolic BP, CVD history and laboratory measurements in patients with DM at baseline (Sβ= − 0.120; 95% CI, − 0.151– − 0.069; P< 0.001). The multivariate Cox proportional hazard analysis revealed that serum HE4 (HR=2.408, 95% CI 1.669– 5.238, P< 0.001) was an independent prognostic factor for cognitive decline in these DM patients.Conclusion: Our results showed that serum HE4 was significantly and independently associated with cognitive decline and had independent predictive value for cognitive decline in patients with DM. Serum HE4 might enable early recognition of senile dementia among DM patients.Keywords: human epididymis protein 4, diabetes mellitus, cognitive decline, prognostic value

Huijun Zhou,1 Xianli Yin,2 Fei Bai,3 Wu Liu,2 Shaofeng Jiang,2 Jinfeng Zhao1 1Key Laboratory of Nanobiological Technology of National Health Commission of China, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Gastroenterology and Urology, Hunan Cancer Hospital & the Affiliated Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, Hunan, People’s Republic of China; 3Department of Gastroduodeno Pancreatic Surgery, Hunan Cancer Hospital & the Affiliated Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, Hunan, People’s Republic of ChinaCorrespondence: Jinfeng ZhaoKey Laboratory of Nanobiological Technology of National Health Commission of China, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Kaifu District, Changsha, Hunan 410008, People’s Republic of ChinaTel +86-15874856567Email 447620788@qq.comPurpose: To investigate the role and mechanism of S1PR5 in colon cancer.Materials and Methods: Lentiviral infection and drug screening helped to establish colon cancer cell lines with stable overexpression and knockdown of S1PR5. Effects of S1PR5 expression on cell growth, proliferation, migration, and invasion were analyzed using a subcutaneous xenograft model in nude mice. Western blot (WB) was used to detect the effects of S1PR5 expression on p-AKT, STAT3, NF-κB, and p-JNK. The distribution of p65 was evaluated in nuclear and cytoplasmic fractions using WB. CCK-8, Transwell migration, and Transwell invasion assays analyzed cell growth, proliferation, migration, and invasion. qRT-PCR analysis revealed that S1PR5 expression was associated with altered expression levels of NF-κB downstream target genes, such as IL-6, TNF-α, and indoleamine 2, 3-dioxygenase 1 (IDO1).Results: qRT-PCR and WB analysis showed that the S1PR5 level in colon cancer cell lines—SW480, SW620, HCT116, and LoVo—was significantly higher than in NCM460, a healthy colonic epithelial cell line. SW620 and SW480, with high and low expression of S1PR5, respectively, were selected as model cell lines. S1PR5 knockdown in SW620 caused the growth rate, proliferation, migration, invasion, and subcutaneous tumor formation rate to decrease in mice, whereas S1PR5 overexpression in SW480 caused all of these parameters to increase. WB analysis showed an increase in phospho-p65 and its nuclear translocation. S1PR5 knockdown caused a decrease in phospho-p65 levels and its nuclear import, thereby inhibiting its activity. In S1PR5 knockdown and overexpressing cells, p65 was overexpressed and knocked down, respectively. qRT-PCR and WB showed that S1PR5 over-expression up-regulates IDO1, and S1PR5 knockdown inhibits IDO1. CCK-8 and Transwell assays showed that p65 and IDO1 overexpression antagonizes the antitumor effect of S1PR5 knockdown, and that p65 and IDO1 knockdown antagonizes the tumorigenic effect of S1PR5 overexpression.Conclusion: S1PR5 overexpression promotes the growth, migration, and invasion of cancer by activating the NF-κB/IDO1 signaling pathway.Keywords: S1PR5, NF-κB, IDO1, colon cancer

Yuheng Li*, Zongping Fang*, Nan Gu*, Fuhai Bai, Yongyuan Ma, Hailong Dong, Qianzi Yang, Lize Xiong Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lize Xiong; Qianzi YangDepartment of Anesthesiology and Perioperative Medicine, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi’an, Shaanxi 710032, People’s Republic of ChinaTel +86 298 477 1262Email mzkxlz@126.com; qianziyang@hotmail.comPurpose: Chemokine CX3CL1 and its receptor CX3CR1 in the lumbar spinal cord play crucial roles in pain processing. Electroacupuncture (EA) is recognized as an alternative therapy in pain treatment due to its efficacy and safety. However, the analgesic mechanism of EA remains unclear. The aim of this study was to investigate whether EA suppressed complete Freund’s adjuvant (CFA)-induced pain via modulating CX3CL1-CX3CR1 pathway.Materials and methods: Inflammatory pain was induced by intraplantar injection of CFA to the left hind paw of Sprague-Dawley rats. EA with 2 Hz for 30 mins was given to bilateral Zusanli acupoints (ST36) on the first and third day after CFA injection. Mechanical allodynia and thermal hyperalgesia were tested with von Frey tests and Hargreaves tests, respectively. The expressions of CX3CL1, CX3CR1 and p38 mitogen-activated protein kinase (MAPK) were quantified with Western blots. The release of IL-1β, IL-6 and TNF-α were evaluated with ELISA. Recombinant CX3CL1 or control IgG were then injected through intrathecal catheters in the EA-treated CFA model rats. The behavioral tests, p38 MAPK activation and cytokine release were then evaluated.Results: EA significantly inhibited inflammatory pain induced by CFA for 3 days. Meanwhile, EA downregulated the expression of CX3CL1 but not CX3CR1 in the lumbar spinal cord of the CFA rats. Besides, activation of p38 MAPK and the release of pain-related cytokines (IL-1β, IL-6 and TNF-α) were inhibited by EA. Intrathecal injection of CX3CL1 largely reversed the analgesic effect of EA treatment and re-activated p38 MAPK signaling, and resulted in pro-inflammatory cytokines increase in acupuncture-treated rats.Conclusion: Our findings indicate that EA alleviates inflammatory pain via modulating CX3CL1 signaling in lumbar spinal cord, revealing a potential mechanism of anti-nociception of EA in inflammatory pain.Keywords: inflammatory pain, electroacupuncture, CX3CL1, p38 MAPK, cytokine

Rong-Hua Zheng,1,2 Xiao-Jie Bai,1 Wei-Wei Zhang,1 Jing Wang,1 Feng Bai,1 Cai-Ping Yan,1 Erskine A James,3 Himangshu S Bose,4 Ning-Ping Wang,1,4 Zhi-Qing Zhao1,41Department of Physiology, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2Department of Medicine, Linfen Vocational and Technical College, Linfen, Shanxi, People’s Republic of China; 3Department of Internal Medicine, Navicent Health, Macon, GA, USA; 4Basic Biomedical Sciences, Mercer University School of Medicine, Savannah, GA, USAObjective: Angiotensin II (Ang II) is known to contribute to the pathogenesis of heart failure by eliciting cardiac remodeling and dysfunction. The glucagon-like peptide-1 (GLP-1) has been shown to exert cardioprotective effects in animals and patients. This study investigates whether GLP-1 receptor agonist liraglutide inhibits abdominal aortic constriction (AAC)-induced cardiac fibrosis and dysfunction through blocking Ang II type 1 receptor (AT1R) signaling.Methods: Sprague-Dawley rats were subjected to sham operation and abdominal aortic banding procedure for 16 weeks. In treated rats, liraglutide (0.3 mg/kg) was subcutaneously injected twice daily or telmisartan (10 mg/kg/day), the AT1R blocker, was administered by gastric gavage.Results: Relative to the animals with AAC, liraglutide reduced protein level of the AT1R and upregulated the AT2R, as evidenced by reduced ratio of AT1R/AT2R (0.59±0.04 vs. 0.91±0.06, p

Zhongjian Xie,1 Yun Chen,2 Sirel Gurbuz,3 Bin Zhang,2 Yujie Li,2 Fan Bai,2 Yu Chen2 1Department of Metabolism and Endocrinology, Hunan Provincial Key Laboratory of Metabolic Bone Diseases and National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; 2Eli Lilly Suzhou Pharmaceutical Co., Ltd, Shanghai, People’s Republic of China; 3Eli Lilly and Company, Indianapolis, IN, USA Objective: To bridge the efficacy and compare the safety of the 24-week teriparatide treatment in a Chinese osteoporosis study (NCT00414973) to a large international trial (FPT, NCT00670501) to determine whether long-term results from the international study were applicable to Chinese patients. Methods: In this post-hoc analysis, a propensity score matching method was used to select patients with similar baseline characteristics. Patients were female with osteoporosis at high risk of fracture, aged ≥55 years, and had no history of rheumatoid arthritis or corticosteroid use. Outcomes included percentage changes in lumbar-spine bone mineral density (LS-BMD) from baseline to 24 weeks, safety in matched-pair patients, and long-term percentage changes in LS-BMD and fragility fracture incidence in the matched fracture prevention trial (FPT) population. The determination of the acceptability of bridging results was based on the International Conference on Harmonization E5 guidelines. Results: A total number of 228 patients from each study were matched and paired. Patients were similar at baseline (P-values >0.33) except for ethnicity (98% Caucasian for FPT). For changes in LS-BMD from baseline to week 24, treatment with teriparatide showed significantly greater increases (P-values

Ningyin Li, Ruixin Ma, Shixiong Wang, Yang Zhao, Ping Wang, Zhitao Yang, Lingling Jin, Panpan Zhang, Hong Ding, Feng Bai, Jing YuDepartment of Cardiology, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, Gansu 730000, People’s Republic of ChinaObjective: The aim of this study was to confirm the potential role of testosterone in hypertension and target organ damage (TOD) in hypertensive postmenopausal women.Methods: A matched group study was conducted. One hundred sixty-one hypertensive postmenopausal women between 45 and 65 years of age were enrolled as group 1. Another 161 age-matched hypertensive men were enrolled as group 2. Ambulatory blood pressure monitoring, echocardiographic imaging, vascular function, sex hormones and clinical characteristics were evaluated. Quantitative data were analyzed using independent Student’s t-test and multiple regression analysis.Results: The mean and load level of blood pressure were lower in women than in men (P0.05). However, the carotid-femoral pulse wave velocity (cf-PWV) in women was higher than that in men (9.68±2.23 m/s vs 8.03±2.82 m/s, P

Yanjie You,1,* Yuhong Ma,1,* Qiang Wang,2,* Zhengcai Ye,3 Yanhong Deng,1 Feihu Bai1 1Department of Gastroenterology, Ningxia Hui Autonomous Region People’s Hospital, Yinchuan 750021, China; 2Department of Science and Education, Ningxia Hui Autonomous Region People’s Hospital, Yinchuan 750021, China; 3Endoscopy Center, Ningxia Hui Autonomous Region People’s Hospital, Yinchuan 750021, China *These authors contributed equally to this work Background: The ZHX family has recently been in the spotlight as an integrator and an indispensable node in carcinogenesis, whose expression is frequently dysregulated in multiple cancers. The current study provides a novel investigation of the expression profiles of ZHX factors in breast cancer. Materials and methods: The mRNA levels of ZHXs and follow-up periods in breast cancer patients were mined through the Oncomine, Cancer Cell Line Encyclopedia, bc-GenExMiner, cBioPortal and Kaplan–Meier plotter databases. In addition, ZHX3 protein expression was examined in 98 primary tumor samples by immunohistochemistry to investigate its association with clinicopathological parameters and patient outcomes. Results: We found that the transcriptional levels of ZHX1, ZHX2 and ZHX3 were not significantly altered in tumor tissues compared with those in nontumor tissues. ZHX2 and ZHX3 mRNA levels were observed to be positively correlated with estrogen receptor and progesterone receptor expression, while ZHX2 mRNA levels were negatively associated with HER2 expression. Survival analyses revealed that high mRNA levels of ZHX2 and ZHX3 correlated with better overall survival in patients with breast cancer. Immunohistochemical analysis revealed that patients with decreased ZHX3 protein levels had poorer outcomes. Multivariate analysis exhibited that ZHX3 expression may serve as an independent high-risk prognostic predictor. Conclusion: Dysregulated expression of ZHXs may be involved in the progression of breast cancer and could serve as a novel biomarker and potential target for breast cancer. Keywords: ZHX, breast cancer, data mining, immunohistochemistry, prognosis

Zhou H, Yin X, Bai F, Liu W, Jiang S, Zhao J. Cancer Manag Res. 2020;12:4759—4775. The Editor-in-chief and Publisher of Cancer Management and Research wish to retract the published article. Concerns were raised of alleged image duplication in Figure 10A Migration panel SIPR5 OE-/IDO1 shRNA- and Figure 10B Invasion panel SIPR5 OE+/IDO1 shRNA+. The authors responded to our queries but were unable to provide a satisfactory explanation for the alleged duplication or provide adequate raw data for the study described. It was determined the findings of the study could not be supported and the decision was made to retract the article. The authors agree with this decision. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

Fei Bai,1–4,* Juan Ling,1–3,* Gloria Esoimeme,5 Liang Yao,1–3 Mingxia Wang,1,6 Jiajun Huang,1,7 Anchen Shi,1,6 Zehui Cao,1,7 Yaolong Chen,1–3 Jinhui Tian,1–3 Xiaoqin Wang,1–3 Kehu Yang1–3 1Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China; 2Key Laboratory of Evidence-Based Medicine and Knowledge Translation of Gansu Province, Lanzhou, China; 3WHO Collaborating Center for Guideline Implementation and Knowledge Translation, Lanzhou 730000, China; 4National Center for Medical Administration Service, Beijing, China; 5University of South Carolina, Arnold School of Public Health, Columbia, SC, USA; 6The Second Clinical Medical College of Lanzhou University, Lanzhou, China; 7The First Clinical Medical College of Lanzhou University, Lanzhou, China *These authors contributed equally in this work Objective: We conducted a systematic review to evaluate questionnaires about patient’s values and preferences to provide information on the most appropriate questionnaires to be used when developing clinical practice guidelines. Methods: A systematic literature search of the Cochrane Library, MEDLINE, Embase, Web of Science, Chinese Biomedical Database, China National Knowledge Infrastructure, and the Wanfang Database was performed to identify studies on questionnaires evaluating patient’s values and preferences. The articles that used fully structured questionnaires or scales with standardized questions and answer options were included. We assessed the questionnaires’ construction and content with a psychometric methodology and summarized the domains and items about patient’s preferences and values. Results: A total of 7,008 records were retrieved by the search strategy and scanned, and 20 articles were finally included. Of these, 10 (50%) articles described the process of item generation and only four questionnaires (20%, 4/20) mentioned the pilot testing. Regarding “validity”, seven questionnaires (35%, 7/20) assessed validity and only one (5%, 1/20) questionnaire assessed internal consistency, with Cornbrash’s α values of 0.74–0.87. For “acceptability”, the time to complete the questionnaires ranged from 10 to 30 minutes and only nine studies (45%, 9/20) reported the response rates. In addition, the results of domains and items about patient’s preferences and values showed that the “effectiveness” domain was the most considered item in the patient’s value questionnaire followed by “safety”, “prognosis”, and others, whereas the least considered domain was “physician’s experience”. Conclusion: Only a few studies have developed questionnaires with rigorous psychometric methods to measure patient’s preferences and values. Currently, still there is no valid or reliable questionnaire for patient’s preferences and values for use when developing clinical practice guidelines. Further study should be conducted to develop standardized instruments to measure patient’s preferences and values. This study provides the domains and items that may be used in formulating questionnaires about patient’s preferences and values. Keywords: questionnaires, guideline, patient’s values and preferences, systematic review, Patient Satisfaction

Fang Bai,1–3,* You Yin,4,* Ting Chen,1,* Jihui Chen,1 Meixin Ge,2 Yunshu Lu,2 Fangyuan Xie,5 Jian Zhang,1 Kejin Wu,3 Yan Liu1,6 1Department of Pharmacy, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 2Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, 3Department of Breast Surgery, Obstetrics and Gynaecology Hospital, Fudan University, Shanghai, 4Department of Neurology, Changzheng Hospital Affiliated to Second Military Medical University, Shanghai, 5Department of Pharmacy, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 6Department of Pharmacy, Changzheng Hospital Affiliated to Second Military Medical University, Shanghai, People’s Republic of China *These authors contributed equally to this work Purpose: Breast cancer is the most common cancer among women. Pemetrexed, a new generation antifolate drug, is one of the primary treatments for breast cancer. However, multidrug resistance (MDR) in breast cancer greatly hampers the therapeutic efficacy of chemotherapies such as pemetrexed. Nanomedicine is emerging as a promising alternative technique to overcome cancer MDR. Thus, pemetrexed-loaded d-alpha tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) liposomes (liposomal pemetrexed) were developed as a strategy to overcome MDR to pemetrexed in breast cancer. Materials and methods: Liposomal pemetrexed was developed using the calcium acetate gradient method. The cytotoxic effects, apoptosis-inducing activity, in vivo distribution, and antitumor activity of liposomal pemetrexed were investigated. Results: Liposomal pemetrexed was small in size (160.77 nm), with a small polydispersity of

Chunyan Lu,1 Yun Chen,2 Bin Zhang,2 Yu Chen,2 Fan Bai,2 Decai Chen1 1Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China; 2Lilly Suzhou Pharmaceutical Co. Ltd, Shanghai, China Abstract: Teriparatide is the first anabolic agent for osteoporosis, and this analysis aimed to understand responses to teriparatide in Chinese patients with established osteoporosis in subgroups. In this Phase III study of teriparatide in China, 362 patients were randomized at a 2:1 ratio to receive subcutaneous teriparatide (20 µg/day) or intranasal salmon calcitonin (200 IU/day) for 24 weeks. Teriparatide treatment produced a significantly greater increase in lumbar spine bone-mineral density (LS-BMD) in postmenopausal women than calcitonin at the 24-week end point. The relationship between osteocalcin (OCN) and LS-BMD was evaluated, and the greatest correlation was found between absolute OCN change at week 12 and percentage change in LS-BMD for patients in the teriparatide group (r=0.24, P10 µg/L absolute OCN change from baseline in the teriparatide- and calcitonin-treated groups were 81% and 6% at week 12, respectively (P

Wei-Wei Zhang,1,2 Feng Bai,1 Jin Wang,1 Rong-Hua Zheng,1 Li-Wang Yang,1 Erskine A James,3 Zhi-Qing Zhao1,4 1Department of Physiology, Shanxi Medical University, 2Department of Anesthesiology, Shanxi Provincial People’s Hospital, Taiyuan, Shanxi, China; 3Department of Internal Medicine, Navicent Health, Macon, 4Department of Basic Biomedical Sciences, Mercer University School of Medicine, Savannah, GA, USA Abstract: Angiotensin II (Ang II) is known to be involved in the progression of ventricular dysfunction and heart failure by eliciting cardiac fibrosis. The purpose of this study was to demonstrate whether treatment with an antioxidant compound, edaravone, reduces cardiac fibrosis and improves ventricular function by inhibiting Ang II AT1 receptor. The study was conducted in a rat model of transverse aortic constriction (TAC). In control, rats were subjected to 8 weeks of TAC. In treated rats, edaravone (10 mg/kg/day) or Ang II AT1 receptor blocker, telmisartan (10 mg/kg/day) was administered by intraperitoneal injection or gastric gavage, respectively, during TAC. Relative to the animals with TAC, edaravone reduced myocardial malonaldehyde level and increased superoxide dismutase activity. Protein level of the AT1 receptor was reduced and the AT2 receptor was upregulated, as evidenced by the reduced ratio of AT1 over AT2 receptor (0.57±0.2 vs 3.16±0.39, p

Pang X, Zhang L, Bai F, et al. Drug Des Devel Ther. 15;9:6043–6054.The authors have advised there is an error in theWestern blot bands shown in Figure 6 on page 6050, pSmad2 at 2 weeks.Each band shown in Figure 6 represents one animal, and six or seven animals were used for each group. The statistical difference was calculated from the protein analysis using every animal tissue sample. Once the overall group statistical difference was found, three bands were chosen to represent the difference more closely between the control (Con) and curcumin (Cur) groups. The authors acknowledge the error in using the same bands in lanes two and three to show pSmad 2 at 2 weeks in the Con group. The data have been newly and independently validated from additional samples, and the results have demonstrated symmetrical expression of pSmad2 in the Con group as shown in the correct Figure 6 below.The authors apologize for this error.Read the original article

Xiangrong Zhang,1,2,* Yi Zhang,1,* Shuang Guo,3 Feifei Bai,1 Tong Wu,1 Yuqing Zhao1 1Department of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, 2Department of Pharmaceutics, School of Pharmacy, 3Department of Biomedical Science, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning, People’s Republic of China *These authors contributed equally to this work Abstract: The aim of the study was to improve the oral absorption of the compound 25-OCH3-PPD with poor hydrophilicity and lipophilicity. 25-OCH3-PPD-phospholipid complex was prepared by solvent evaporation, then characterized by differential scanning calorimetry, scanning electron microscopy, and infrared absorption spectroscopy. The aqueous solubility and oil–water partition coefficient were compared with the free compound. A nanoemulsion loaded with 25-OCH3-PPD-phospholipid complex was developed by dissolving the complex in water in the presence of hydrophilic surfactant under sonication. After oral administration of the nanoemulsion and the suspension of 25-OCH3-PPD in rats, the concentrations of 25-OCH3-PPD in plasma were determined by high-performance liquid chromatography–tandem mass spectrometry method. The results showed that the solubility of the complex in water and n-octanol was enhanced. The oil–water partition coefficient improved 1.7 times. Peak plasma concentration and area under the curve(0–24 h) of the nanoemulsion of 25-OCH3-PPD-phospholipid complex were higher than that of free compound by 3.9- and 3.5-folds. Keywords: 25-OCH3-PPD, phospholipid complex, solubility, bioavailability, LC–MS/MS