Potential drug targets for gastroesophageal reflux disease and Barrett's esophagus identified through Mendelian randomization analysis.

Gastroesophageal reflux disease (GERD) is a prevalent chronic ailment, and present therapeutic approaches are not always effective. This study aimed to find new drug targets for GERD and Barrett's esophagus (BE). We obtained genetic instruments for GERD, BE, and 2004 plasma proteins from recently published genome-wide association studies (GWAS), and Mendelian randomization (MR) was employed to explore potential drug targets. We further winnowed down MR-prioritized proteins through replication, reverse causality testing, colocalization analysis, phenotype scanning, and Phenome-wide MR. Furthermore, we constructed a protein-protein interaction network, unveiling potential associations among candidate proteins. Simultaneously, we acquired mRNA expression quantitative trait loci (eQTL) data from another GWAS encompassing four different tissues to identify additional drug targets. Meanwhile, we searched drug databases to evaluate these targets. Under Bonferroni correction (P < 4.8 × 10-5), we identified 11 plasma proteins significantly associated with GERD. Among these, 7 are protective proteins (MSP, GPX1, ERBB3, BT3A3, ANTR2, CCM2, and DECR2), while 4 are detrimental proteins (TMEM106B, DUSP13, C1-INH, and LINGO1). Ultimately, C1-INH and DECR2 successfully passed the screening process and exhibited similar directional causal effects on BE. Further analysis of eQTLs highlighted 4 potential drug targets, including EDEM3, PBX3, MEIS1-AS3, and NME7. The search of drug databases further supported our conclusions. Our study indicated that the plasma proteins C1-INH and DECR2, along with 4 genes (EDEM3, PBX3, MEIS1-AS3, and NME7), may represent potential drug targets for GERD and BE, warranting further investigation.

Trends in the burden and determinants of HIV in the Asia-Pacific region (1990-2019): An age-period-cohort analysis of the 2019 Global Burden of Disease Study.

Although the burden of the human immunodeficiency virus (HIV) in the Asia-Pacific region is increasingly severe, comprehensive evidence of the burden of HIV is scarce. We aimed to report the burden of HIV in people aged 15-79 years from 1990 to 2019 using data from the Global Burden of Disease Study (GBD) 2019. We analyzed rates of age-standardized disability-adjusted life years (ASDR), age-standardized mortality (ASMR), and age-standardized incidence (ASIR) in our age-period-cohort analysis by sociodemographic index (SDI). According to HIV reports in 2019 from 29 countries in the Asia-Pacific region, the low SDI group in Papua New Guinea had the highest ASDR, ASMR, and ASIR. From 1990 to 2019, the ASDR, ASIR, and ASMR of persons with acquired immune deficiency syndrome (AIDS) increased in 21 (72%) of the 29 countries in the Asia-Pacific region. During the same period, the disability-adjusted life years (DALYs) of AIDS patients in the low SDI group in the region grew the fastest, particularly in Nepal. The incidence of HIV among individuals aged 20-30 years in the low-middle SDI group was higher than that of those in the other age groups. In 2019, unsafe sex was the main cause of HIV-related ASDR in the region's 29 countries, followed by drug use. The severity of the burden of HIV/AIDS in the Asia-Pacific region is increasing, especially among low SDI groups. Specific public health policies should be formulated based on the socioeconomic development level of each country to alleviate the burden of HIV/AIDS.

Develop a bone mineral density T-score distribution nomograms based on osteoporosis risk factors for middle-aged and older adults.

PURPOSE: This study aimed to understand how age, health status, and lifestyle impact bone mineral density (BMD) in middle-aged and older adults, focusing on predicting osteoporosis risk. METHODS: This study included 2836 participants aged 50-88 from the Health Improvement Program of Bone (HOPE) conducted from 2021 to 2023. We used logistic regression to make a prediction tool. Then checked its accuracy and reliability using receiver operating characteristic (ROC) and calibration curves. RESULTS: Factors like age, body weight, prior fractures, and smoking were independently found to affect BMD T-score distribution in men. In women, age and body weight were identified as independent factors influencing BMD T-score distribution. A nomogram was created to visually illustrate these predictive relationships. CONCLUSIONS: The nomogram proved highly accurate in identifying men aged 50 and above and postmenopausal women based on their BMD T-score distribution, improving clinical decision-making and patient care in osteoporosis evaluation and treatment.

[Changes in fingerprint and chromaticity values of Mori Cortex during stir-frying process].

This study aims to reveal the dynamics of the HPLC fingerprint, chromaticity values, and main chemical components of Mori Cortex during the stir-frying process. The fingerprints of raw and processed products of Mori Cortex were established. The content of mulberroside A, oxyresveratrol, kuwanon G, and kuwanon H in the samples and the chromaticity values of the samples were determined. Furthermore, the similarity evaluation of fingerprints and the correlation analysis between fingerprints and chromaticity values were carried out. The results showed that the fingerprints of raw and processed products of Mori Cortex had high similarity, and the overall changes in the content of the main chemical components in the stir-frying process were similar. According to the experience, when the stir-frying is moderate, the total chromaticity value difference |ΔE~*_(ab)| is above 1.5. With the extension of stir-frying time, the L~* and E~*_(ab) values keep decreasing, and the a~* value keeps increasing. The results of the correlation analysis between fingerprints and chromaticity values showed that peaks 1(5-hydroxy maltol), 2(mulberroside A), 3, 4, 6, 7, 11(oxyresveratrol), 14, 17(kuwanon G), and 18(kuwanon H) had significant correlations with the chromaticity values. Quantitative analysis of the four components with higher content showed that the content of the four components decreased to varying degrees when the stir-frying was excessive. In addition, 5-hydroxy maltol was produced after stir-frying of Mori Cortex, and the fingerprint and chromaticity values showed regular changes during the stir-frying process. The chromaticity can be included in the evaluation of the stir-frying process of Mori Cortex, which provides a reference for standardizing the quality of stir-fried Mori Cortex.

[Comparison of HPLC fingerprints and determination of main components of Viticis Fructus from different species].

In order to comprehensively evaluate the quality of Viticis Fructus, this study established HPLC fingerprints and evaluated the quality of 24 batches of Viticis Fructus samples from different species by similarity evaluation and multivariate statistical analysis(PCA, HCA, PLS-DA). On this basis, an HPLC method was established to compare the content differences of the main components, including casticin, agnuside, homoorientin, and p-hydroxybenzoic acid. The analysis was performed on the chromatographic column(Waters Symmetry C_(18)) with a gradient mobile phase of acetonitrile(A)-0.05% phosphoric acid solution(B) at the flow rate of 1 mL·min~(-1) and detection wavelength of 258 nm. The column temperature was 30 ℃ and the injection volume was 10 µL. The HPLC fingerprint of 24 batches of Viticis Fructus samples was established with 21 common peaks, and nine peaks were identified. Similarity analysis was carried out based on chromatographic data of 24 batches of chromatographic data of Viticis Fructus, and the results showed that except for DYMJ-16, the similarity of Vitex trifolia var. simplicifolia was ≥0.900, while that of V. trifolia was ≤0.864. In addition, the similarity analysis of two different species showed that the similarity of 16 batches of V. trifolia var. simplicifolia was 0.894-0.997 and that of the eight batches of V. trifolia was between 0.990 and 0.997. The results showed that the similarity of fingerprints of these two species was different, but the similarity between the same species was good. The results of the three multivariate statistical analyses were consistent, which could distinguish the two different species. The VIP analysis results of PLS-DA showed that casticin and agnuside contributed the most to the distinction. The content determination results showed that there was no significant difference in the content of homoorientin and p-hydroxybenzoic acid in Viticis Fructus from different species, but the content of casticin and agnuside was significantly different in different species(P<0.01). The content of casticin was higher in V. trifolia var. simplicifolia, while agnuside was higher in V. trifolia. The findings of this study show that there are differences in fingerprint similarity and component content of Viticis Fructus from different species, which can provide references for the in-depth study of the quality and clinical application of Viticis Fructus.

Identification of C-glycosyl flavones and O-glycosyl flavones in five Dendrobium species by high-performance liquid chromatography coupled with electrospray ionization multi-stage tandem MS.

RATIONALE: Flavones are widely used in traditional Chinese medicine (TCM) and are the pharmacologically active ingredients of many medicinal plants, such as Dendrobium. With the increasing demand for medicinal Dendrobium, the identification of characteristic flavones that can serve as chemical markers for quality control is critical step for quality assurance and safety in the TCM industry. METHODS: High-performance liquid chromatography coupled with electrospray ionization multi-stage tandem mass spectrometry (HPLC/ESI-MSn ) was used to identify the chemical constituents in five types of Dendrobium: D. crystallinum, D. falconeri, D. strongylanthum, D. moniliforme, and D. gratiosissimum. RESULTS: A total of seventy-six C-glycosyl flavones and three O-glycosyl flavones were identified, of which fifteen C-glycosyl flavones were found in D. crystallinum, twenty four were found in D. falconeri, thirty were found in D. strongylanthum, seven were found in D. moniliforme (also called "Huangtongpi", from Anhui, China), fifteen were found in D. moniliforme (also called "Zitongpi", from Yunnan, China) and seventeen were found in D. gratiosissimum. Additionally, three flavone O-glycosides were all found in D. strongylanthum. CONCLUSIONS: The results of this study may be useful for the quality assessment and for the application of D. crystallinum, D. falconeri, D. strongylanthum, D. moniliforme, and D. gratiosissimum. This study provides comprehensive information for identification of flavones from other Chinese herbs.

MiR-135b Alleviates Airway Inflammation in Asthmatic Children and Experimental Mice with Asthma via Regulating CXCL12.

OBJECTIVE: To clarify the possible influence of miR-135b on CXCL12 and airway inflammation in children and experimental mice with asthma. METHODS: The expressions of miR-135b and CXCL12 were detected using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) in the serum of asthmatic children. Besides, the experimental asthmatic mice were established by aerosol inhalation of ovalbumin (OVA) followed by the treatment with agomiR-135b and antagomir-135b. Pathological changes of lung tissues were observed via HE staining and PAS staining. Besides, the airway hyperresponsiveness of mice was elevated and bronchoalveolar lavage fluid (BALF) was isolated for cell categorization and counting. The inflammatory cytokines in BALF were determined by enzyme-linked immunosorbent assay (ELISA), and the infiltration of Th17 cells in lung tissues was measured using flow cytometry. RESULTS: MiR-135b was downregulated and CXCL12 was upregulated in asthmatic children and mice. Overexpression of miR-135b may down-regulate CXCL12 expression in the lung of OVA mice, resulting in significant decreases in inflammatory infiltration, hyperplasia of goblet cell, airway hyperresponsiveness, cell quantity, as well as the quantity of eosinophilic granulocytes, neutrophils and lymphocytes in BALF. Also, the levels of inflammatory cytokines (IL-4, IL-5, IL-13 and IL-17) and the ratio of Th17 cells and IL-17 levels in lung tissues were decreased. However, miR-135b downregulation reversed these changes in OVA mice. CONCLUSION: MiR-135b may inhibit immune responses of Th17 cells to alleviate airway inflammation and hyperresponsiveness in asthma possibly by targeting CXCL12, showing the potential value in asthma treatment.

Prescreening for osteoporosis with forearm bone densitometry in health examination population.

BACKGROUND: Early detection and timely prophylaxis can retard the progression of osteoporosis. The purpose of this study was to determine the validity of peripheral Dual Energy X-ray Absorptiometry (DXA) test for osteoporosis screening. We examined peripheral bone mineral density (BMD) using AKDX-09 W-I DXA densitometer. Firstly, we acquired BMD data from manufacturer-supplied density-gradient phantoms and 30 volunteers to investigate its accuracy and precision, then we measured BMD for 150 volunteers using both AKDX (left forearm) and Hologic Discovery Wi (left forearm, left hip and L1 - L4 vertebrae) simultaneously. Correlation relationship of BMD results acquired from two instruments was assessed by simple linear regression analysis, the Receiver Operating Characteristic (ROC) curves and Areas Under the Curves (AUCs) were evaluated for the diagnostic value of left forearm BMD measured by AKDX in detecting osteoporosis. RESULTS: In vitro precision errors of AKDX BMD were 0.40, 0.20, 0.19%, respectively, on low-, medium-, and high-density phantom; in vivo precision was 1.65%. Positive correlation was observed between BMD measured by AKDX and Hologic at the forearm (r = 0.670), L1-L4 (r = 0.430, femoral neck (r = 0.449), and total hip (r = 0.559). With Hologic measured T-score as the gold standard, the sensitivity of AKDX T-score < - 1 for identifying suboptimal bone health was 63.0 and 76.1%, respectively, at the distal one-third radius and at any site, and the specificity was 73.9 and 90.0%, respectively; the AUCs were 0.708 and 0.879. The sensitivity of AKDX T-score ≤ - 2.5 for identifying osteoporosis at the distal one-third radius and at any site was 76.9 and70.4%, respectively, and the specificity was 80.4 and 78.0%, respectively; the AUCs were 0.823 and 0.778. CONCLUSIONS: Peripheral DXA appears to be a reliable tool for prescreening for osteoporosis.

[Hesperidin Regulates Jagged1/Notch1 Pathway to Promote Macrophage Polarization and Alleviate Lung Injury in Mice with Bronchiolitis].

Objective To explore the effect and mechanism of hesperidin in treating the lung injury in the mouse model of respiratory syncytial virus (RSV)-induced bronchiolitis. Methods A mouse model of RSV-induced bronchiolitis was established,and 60 BALB/c mice were assigned into a control group,a model group,a low-dose hesperidin (18 mg/kg) group,a high-dose hesperidin (36 mg/kg) group,and a high-dose hesperidin (36 mg/kg)+Jagged1(1 mg/kg) group by random number table method,with 12 mice in each group. Corresponding doses of drugs were administrated for intervention,and the control group and model group were administrated with the same amount of saline.The bronchoalveolar lavage fluid (BALF) samples were collected and alveolar macrophages were isolated.ELISA was employed to detect the levels of interleukin (IL)-4,IL-6,tumor necrosis factor-α (TNF-α),and IL-10 in BALF,and flow cytometry to detect the M1/M2 polarization of macrophages.qRT-PCR and Western blotting were respectively conducted to detect the mRNA and protein levels of inducible nitric oxide synthase (iNOS),arginase 1 (Arg-1),Jagged1,and Notch1 in the lung tissue. Results Compared with the control group,the modeling of RSV-induced bronchiolitis elevated the IL-4,IL-6,and TNF-α levels,increased the proportion of M1-type macrophages and the lung inflammation and mucus secretion scores,and up-regulated the mRNA and protein levels of iNOS,Jagged1,and Notch1 in BALF (all P<0.001).Meanwhile,the modeling lowered the IL-10 level,decreased the proportion of M2-type macrophages,and down-regulated the mRNA and protein levels of Arg-1 (all P<0.001).Compared with the model group,low- and high-dose hesperidin lowered the IL-4,IL-6,TNF-α levels,decreased the proportion of M1-type macrophages and the lung inflammation and mucus secretion scores,and down-regulated the mRNA and protein levels of iNOS,Jagged1,and Notch1 in BALF (all P<0.05).Moreover,hesperidin elevated the IL-10 level,increased the proportion of M2-type macrophages,and up-regulated the mRNA and protein levels of Arg-1 (all P<0.001).Using recombinant Jagged1 protein to activate Notch1 signaling pathway can significantly attenuate the promotion of high-dose hesperidin on M2 macrophage polarization and amelioration of lung inflammation damage (all P<0.01). Conclusion Hesperidin may alleviate the lung inflammation damage in mice with RSV-induced bronchiolitis by inhibiting the Jagged1/Notch1 signaling pathway and promoting the M2-type polarization of macrophages.

Age-related impairment of navigation and strategy in virtual star maze.

BACKGROUND: Although it is well known that aging impairs navigation performance, the underlying mechanisms remain largely unknown. Egocentric strategy requires navigators to remember a series of body-turns without relying on the relationship between environmental cues. Previous study suggested that the egocentric strategy, compared with non-egocentric strategy, was relatively unimpaired during aging. In this study, we aimed to examine strategy use during virtual navigation task and the underlying cognitive supporting mechanisms in older adults. METHODS: Thirty young adults and thirty-one older adults were recruited from the local community. This study adapted star maze paradigm using non-immersive virtual environment. Participants moved freely in a star maze with adequate landmarks, and were requested to find a fixed destination. After 9 learning trials, participants were probed in the same virtual star maze but with no salient landmarks. Participants were classified as egocentric or non-egocentric strategy group according to their response in the probe trial. RESULTS: The results revealed that older adults adopting egocentric strategy completed the navigation task as accurate as young adults, whereas older adults using non-egocentric strategy completed the navigation task with more detours and lower accuracy. The relatively well-maintained egocentric strategy in older adults was related to better visuo-spatial ability. CONCLUSIONS: Visuo-spatial ability might play an important role in navigation accuracy and navigation strategy of older adults. This study demonstrated the potential value of the virtual star maze in evaluating navigation strategy and visuo-spatial ability in older adults.

Association between diabetes mellitus and lung cancer: Meta-analysis.

BACKGROUND: This study aimed to summarize the association between diabetes mellitus (DM) and the incidence of lung cancer using a meta-analysis of cohort studies. MATERIALS AND METHODS: We systematically searched PubMed, Embase and the Cochrane Library to identify potential cohort studies. Relative risk (RR) was used to calculate the association between DM and the risk of lung cancer. Subgroup analysis, sensitivity analysis and test for publication bias were performed. Twenty cohort studies were selected. RESULTS: The participants with DM showed little or no significant effect on the risk of lung cancer (RR: 1.10; 95% CI: 0.99-1.23; P = .087). DM was not associated with the risk of lung cancer in men (RR: 1.11; 95%CI: 0.92-1.35; P = .270), but a significant association was observed in women (RR: 1.18; 95%CI: 1.10-1.28; P < .001). Subgroup analysis suggested that smoker status was confounding variables that could bias the relationship between DM and the incidence of lung cancer. CONCLUSIONS: This meta-analysis suggests that DM has no significant impact on the incidence of lung cancer in men but has a harmful effect on women.

Determination of risk factors for predicting the onset of symptoms in asymptomatic COVID-19 infected patients.

Background: The number of asymptomatic infected patients with coronavirus disease 2019 (COVID-2019) is rampaging around the world but limited information aimed on risk factors of asymptomatic infections. The purpose of this study is to investigate the risk factors of symptoms onset and clinical features in asymptomatic COVID-19 infected patients. Methods: A retrospective study was performed in 70 asymptomatic COVID-2019 infected patients confirmed by nucleic acid tests in Hunan province, China between 28 January 2020 and 18 February, 2020. The epidemiological, clinical features and laboratory data were reviewed and analyzed. Presence or absence at the onset of symptoms was taken as the outcome. A Cox regression model was performed to evaluate the potential predictors of the onset of symptoms. Results: The study included 36 males and 34 females with a mean age of 33.24±20.40 years (range, 0.5-84 years). There were 22 asymptomatic carriers developed symptoms during hospitalization isolated observation, and diagnosed as confirmed cases, while 48 cases remained asymptomatic throughout the course of disease. Of 70 asymptomatic patients, 14 (14/70, 20%) had underlying diseases, 3 (3/70, 4.3%) had drinking history, and 11 (11/70, 15.7%) had smoking history. 22 patients developed symptoms onset of fever (4/22, 18.2%), cough (13/22, 59.1%), chest discomfort (2/22, 9.1%), fatigue (1/22, 4.5%), pharyngalgia (1/22, 4.5%) during hospitalization; only one (1/22, 4.5%) patient developed signs of both cough and pharyngalgia. Abnormalities on chest CT were detected among 35 of the 69 patients (50.7%) after admission, except for one pregnant woman had not been examined. 4 (4/70, 5.7%) and 8 (8/70, 11.4%) cases showed leucopenia and lymphopenia. With the effective antiviral treatment, all the 70 asymptomatic infections had been discharged, none cases developed severe pneumonia, admission to intensive care unit, or died. The mean time from nucleic acid positive to negative was 13.2±6.84 days. Cox regression analysis showed that smoking history (P=0.028, hazard ratio=4.49, 95% CI 1.18-17.08) and existence of pulmonary disease (P=0.038, hazard ratio=7.09, 95% CI 1.12-44.90) were risk factors of the onset of symptoms in asymptomatic carries. Conclusion: The initially asymptomatic patients can develop mild symptoms and have a good prognosis. History of smoking and pulmonary disease was prone to illness onset in asymptomatic patients, and it is necessary to be highly vigilant to those patients.

HPLC coupled with electrospray ionization multistage MS/MS and TLC analysis of flavones-C-glycosides and bibenzyl of Dendrobium hercoglossum.

Dendrobium hercoglossum Rchb. f. (D. hercoglossum), as one of the origins of medicinal Dendrobium, has been widely used as a health food and nutrient source promoting fluid production. Due to a lack of quality control, it is often counterfeited or mixed with other Dendrobium. In this study, a high-performance liquid chromatography characteristic chromatogram method is established for the quality evaluation of D. hercoglossum. Based on the high-performance liquid chromatography characteristic chromatogram, D. hercoglossum is divided into two classes, each with different flavone peaks. These flavone peaks were identified using high-performance liquid chromatography coupled with electrospray ionization multistage tandem mass spectrometry. Among them, the acylated (3-hydroxy-3-methylglutaryl, p-coumaroyl, feruloyl, or sinapoyl) flavones-C-glycosides are first found in D. hercoglossum in this study. In addition, one unique band was found in D. hercoglossum by thin-layer chromatography, which can be used to distinguish it from other Dendrobium species as a characteristic marker of this plant. Combining the high-performance liquid chromatography characteristic chromatogram and high-performance liquid chromatography coupled with electrospray ionization multistage tandem mass spectrometry, the unique band was identified as 4,5-dihydroxy-3,3'-dimethoxybibenzyl. These analysis methods can be applied for the quality control and identification of D. hercoglossum as well as providing reference for the identification of similar constituents in other Dendrobium species.

Eliciting α7-nAChR exerts cardioprotective effects on ischemic cardiomyopathy via activation of AMPK signalling.

Our previous studies have reported that agonist of α7 nicotinic acetylcholine receptors prevented electrophysiological dysfunction of rats with ischaemic cardiomyopathy (ICM) by eliciting the cholinergic anti-inflammatory pathway (CAP). Adenosine monophosphate-activated protein kinase (AMPK) signalling is widely recognized exerting cardioprotective effect in various cardiomyopathy. Here, we aimed to investigate whether the protective effects of the CAP are associated with AMPK signalling in ICM. In vivo, coronary artery of rats was ligated for 4 weeks to induce the ICM and then treated with PNU-282987 (CAP agonist) and BML-275 dihydrochloride (AMPK antagonist) for 4 weeks. In vitro, primary macrophages harvested from rats were induced inflammation by Lipopolysaccharide (LPS) treatment and then treated with PNU-282987 and BML-275 dihydrochloride. In vivo, exciting CAP by PUN-282987 elicited an activation of AMPK signalling, alleviated ventricular remodeling, modified the cardiac electrophysiological function, reduced the cardiac expression of collagens and inflammatory cytokines and maintained the integrity of ultrastructure in the ischemic heart. However, the benefits of CAP excitation were blunted by AMPK signaling antagonization. In vitro, excitation of the CAP was observed inhibiting the nuclear transfer of NF-κB p65 of macrophages and promoting the transformation of Ly-6Chigh macrophages into Ly-6Clow macrophages. However, inhibiting AMPK signalling by BML-275 dihydrochloride reversed the CAP effect on LPS-treated macrophages. Finally, our findings suggest that eliciting the CAP modulates the inflammatory response in ICM through regulating AMPK signalling.

Identification of flavonoids in Dendrobium huoshanense and comparison with those in allied species of Dendrobium by TLC, HPLC and HPLC coupled with electrospray ionization multi-stage tandem MS analyses.

Dendrobium huoshanense, a unique species in the genus Orchidaceae, is only found in China and is known as "mihu". Due to the lack of quality control, the use of D. huoshanense in the herbal market has been limited. In this study, methods based on thin-layer chromatography, high-performance liquid chromatography and high-performance liquid chromatography coupled with electrospray ionization multi-stage tandem mass spectrometry were used to identify the flavonoids in D. huoshanense and distinguish this species from other Dendrobium species. Using thin-layer chromatography, a characteristic band was observed for D. huoshanense, and this band was absent from the thin-layer chromatography plates of other Dendrobium species. Then, using high-performance liquid chromatography, nine peaks of flavonoids were observed in the chromatograms of ten batches of D. huoshanense. Ultimately, 22 flavonoids in D. huoshanense were identified by multi-stage tandem mass spectrometry, and 11 of these compounds are being reported from D. huoshanense for the first time. In addition, two compounds both with molecular weights of 710, were identified as being unique to D. huoshanense; one of these compounds, apigenin-6-C-α-L-rhamnosyl-(1→2)-ß-D-glucoside-8-C-α-L-arabinoside, was proven to be responsible for the characteristic thin-layer chromatography band of D. huoshanense. These analysis methods can be applied for the identification and quality control of D. Huoshanense.

Smart albumin-loaded Rose Bengal and doxorubicin nanoparticles for breast cancer therapy.

Objective: To synthesise HSA-RB-DOX nanoparticles, measure its characteristics and preliminarily evaluate its anti-cancer effects.Methods: Doxorubicin (DOX) and Rose Bengal (RB) were co-delivered using albumin as a carrier. HSA-RB-DOX nanoparticles were prepared by RB-induced self-assembly of albumin. Its characteristics were measured and anti-cancer effects were tested in MCF-7 cells and tumour-bearing mice.Results: HSA-RB-DOX nanoparticle with a mean size of 42 nm was stable in different medium and behaved controlled release characteristic. It was well took in MCF-7 cells and inhibited MCF-7 cells proliferation by inducing reactive oxygen species (ROS) production. It retained a much higher blood concentration up to 12 h and accumulated more in tumour tissues. In tumour-bearing mice, HSA-RB-DOX nanoparticles inhibited tumour growth and even decreased its volume from 100 to 50 mm3, with barely no influence on body weight.Conclusions: HSA-RB-DOX nanoparticles may be potentially used for enhanced treatment of breast cancer.

Factors associated with lower-extremity amputation in patients with diabetic foot ulcers in a Chinese tertiary care hospital.

Providing a better understanding of the risk factors for amputation in this particular region, Hunan province, in China might help patients with diabetic foot ulcers receive timely and appropriate medical care and help prevent amputation. Diabetic foot ulcer patients referred to the Third Xiangya Hospital during the period between December 2014 and September 2018 were enrolled. Participants who underwent amputations and received conservative treatments were compared using univariate and multivariate analyses to identify the independent predictors of amputation. Those who required amputation presented significantly higher levels of white blood cell counts, platelet counts, erythrocyte sedimentation rate, C-reactive protein, and glycated haemoglobin (HbA1c) levels. However, levels of haemoglobin, postprandial plasma C-peptide, triglyceride, high-density lipoprotein cholesterol, albumin, and uric acid were decreased in patients with amputations. Patients with more advanced Wagner grades had much higher rates of amputation. Multivariable-adjusted odds ratios in stepwise logistic regression model was 1.317 for HbA1c (95% CI: 1.015-1.709), 0.255 for triglyceride (95% CI: 0.067-0.975), and 20.947 for Wagner grades (95% CI: 4.216-104.080). Independent risk factors for amputation in these Chinese diabetic foot ulcer patients included an elevated HbA1c level, lower triglyceride level, and higher Wagner grades.

Common and distinctive electrocardiographic characteristics and effective catheter ablation of idiopathic ventricular arrhythmias originating from different areas of ventricular septum adjacent to atrioventricular annulus.

OBJECTIVE: To investigate electrocardiographic (ECG) characteristics and radiofrequency catheter ablation (RFCA) efficacy for premature ventricular complexes (PVCs) and idiopathic ventricular tachycardias (IVTs) originating from ventricular septum areas adjacent to atrioventricular annulus (VS-AVA). METHODS: Among 1,505 consecutive PVCs/IVTs cases, 106 (7.04%) were confirmed as origin of VS-AVA guided by both fluoroscopy and three-dimensional mapping system during RFCA. Characteristics of surface 12-lead ECG were analyzed. RESULTS: The overall success rate for RFCA of PVCs/IVTs originating from VS-AVA was 82.08% (87/106), common ECG characteristics were: mainly positive R wave on lead I; dominant-positive R on aVL (91/106, 85.85%) for most, r (1/106, 0.94%) or qr (14/106, 13.21%) in few; QS or qs on aVR; and decreasing R wave amplitude and increasing S wave depth on II, III, and aVF from superior to inferior septum; and S wave on at least one inferior lead (generally III). Distinctive ECG features were: precordial transition zone before or after V2 for septum adjacent to mitral (MA, 19/19, 100.0%) or tricuspid (TA, 74/87,85.05%) annulus origin; initial r wave and rS on V1 for superior septum near TA (above His bundle) origin (9/10, 90.0%) with no initial r wave for most other origins; and QS on V1 for mid-inferior septum near TA origin (73/77, 94.81%) and QR (Qr, qR or qr) on V1 for septum near MA origin (17/19, 89.47%). CONCLUSION: Distinctive ECG characteristics of PVCs/IVTs originating from VS-AVA aid in origin localization guiding effective RFCA.

The expression of protease-activated receptors in esophageal carcinoma cells: the relationship between changes in gene expression and cell proliferation, apoptosis in vitro and growing ability in vivo.

BACKGROUND: Protease-activated receptors (PARs) are a family of four G protein-coupled receptors expressed widely in many types of cells. PAR1, 2, and 4 have been shown to play an important role in many of the physiological activities of cells and many types of cancer cells. Esophageal carcinoma has become the fourth most common clinically diagnosed cancer and one of the top three leading causes of cancer-related deaths in China. The functions and expression patterns of PAR1, 2, and 4 in esophageal carcinoma have not published previously. METHODS: Here, we systematically studied the expression of PAR1, 2, and 4 in clinical esophageal carcinoma patients and determined their role in esophageal carcinoma in vivo and in vitro through the overexpression or knockdown of PAR1, 2, and 4. RESULTS: We found that the expression of PAR1 and 2 expressed higher in esophageal carcinoma than in the paracarcinoma tissues on clinical patients. PAR1 and 2 enhanced cell proliferation both in vivo and in vitro and reduced apoptosis to strengthen cancer cell vitality in TE-1 cells. In contrast, the expression of PAR4 expressed decreased in esophageal carcinoma, and its expression induced apoptosis in vivo and vitro. CONCLUSION: In our previous studies and the present study, we noted that the expression of PAR1, 2, and 4 was almost absent in different stages of esophageal carcinoma. PAR1 and 2 might be potential molecular markers for esophageal carcinoma, and PAR4 might be an effective treatment target for esophageal carcinoma prevention and treatment.

TRPV4 regulates migration and tube formation of human retinal capillary endothelial cells.

BACKGROUND: Ca2+ entry plays an important role in modulating endothelial cell migration and tube formation. Transient receptor potential cation channel subfamily V member 4 (TRPV4) is a Ca2+-permeable channel that is widely expressed in endothelial cells. It has been reported that TRPV4 is expressed in HRCECs and regulates Ca2+ entry. However, the function of TRPV4 in human retinal capillary endothelial cells (HRCECs) remains unknown. METHODS: In this study we used western blot and immunostaining assay to verify TRPV4 expression in HRCECs. And then we pretreated HRCECs with HC067047 and transfected with specific shRNA of TRPV4. The functional presence of TrpV4 was determined by using fluorescence, migration and tube formation assay in TrpV4 knockdown cells or control cells. RESULTS: Using western blot and immunostaining, we confirmed TRPV4 expression in HRCECs. Moreover, inhibition of TRPV4 using the specific inhibitor HC067047 and the knockdown of TRPV4 with shRNA significantly suppressed tube formation and migration by HRCECs. CONCLUSIONS: TRPV4 is essential for HRCEC migration and tube formation, and maybe a potential therapeutic target for retinal vascular diseases.