Publications by authors named "Shi-Jin Li"

43 Publications

COVID-19 and Tuberculosis Coinfection: An Overview of Case Reports/Case Series and Meta-Analysis.

Front Med (Lausanne) 2021 24;8:657006. Epub 2021 Aug 24.

Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.

Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are two major infectious diseases posing significant public health threats, and their coinfection (aptly abbreviated COVID-TB) makes the situation worse. This study aimed to investigate the clinical features and prognosis of COVID-TB cases. The PubMed, Embase, Cochrane, CNKI, and Wanfang databases were searched for relevant studies published through December 18, 2020. An overview of COVID-TB case reports/case series was prepared that described their clinical characteristics and differences between survivors and deceased patients. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) for death or severe COVID-19 were calculated. The quality of outcomes was assessed using GRADEpro. Thirty-six studies were included. Of 89 COVID-TB patients, 19 (23.46%) died, and 72 (80.90%) were male. The median age of non-survivors (53.95 ± 19.78 years) was greater than that of survivors (37.76 ± 15.54 years) ( < 0.001). Non-survivors were more likely to have hypertension (47.06 vs. 17.95%) or symptoms of dyspnea (72.73% vs. 30%) or bilateral lesions (73.68 vs. 47.14%), infiltrates (57.89 vs. 24.29%), tree in bud (10.53% vs. 0%), or a higher leucocyte count (12.9 [10.5-16.73] vs. 8.015 [4.8-8.97] × 10/L) than survivors ( < 0.05). In terms of treatment, 88.52% received anti-TB therapy, 50.82% received antibiotics, 22.95% received antiviral therapy, 26.23% received hydroxychloroquine, and 11.48% received corticosteroids. The pooled ORs of death or severe disease in the COVID-TB group and the non-TB group were 2.21 (95% CI: 1.80, 2.70) and 2.77 (95% CI: 1.33, 5.74) ( < 0.01), respectively. In summary, there appear to be some predictors of worse prognosis among COVID-TB cases. A moderate level of evidence suggests that COVID-TB patients are more likely to suffer severe disease or death than COVID-19 patients. Finally, routine screening for TB may be recommended among suspected or confirmed cases of COVID-19 in countries with high TB burden.
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http://dx.doi.org/10.3389/fmed.2021.657006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421570PMC
August 2021

[Spectrum-effect relationship of hemostatic effects of Notoginseng Radix et Rhizoma with different commodity specifications].

Zhongguo Zhong Yao Za Zhi 2021 Aug;46(16):4157-4166

School of Chinese Materia Medica, Beijing University of Chinese Medicine Beijing 102488, China.

This article aims to establish the fingerprints, determine the hemostatic pharmacodynamic indicators, and explore the spectrum-effect relationship of Notoginseng Radix et Rhizoma in 12 different specifications. Firstly, HPLC and liquid chromatography-mass spectrometry(LC-MS) were employed to establish the fingerprints of Notoginseng Radix et Rhizoma. The rat plasma recalcification experiment and the rat gastric bleeding experiment were conducted to determine the pharmacodynamic indicators, including plasma recalcification time(PRT), thrombin time(TT), prothrombin time(PT), and activated partial thromboplastin time(APTT). Afterwards, the partial least squares method was employed to explore the spectrum-effect relationship of Notoginseng Radix et Rhizoma in different specifications. Twenty-six common peaks were detected in the HPLC fingerprints of different specifications of Notoginseng Radix et Rhizoma, and 11 out of the 26 common peaks represented saponins. The content of dencichine was determined by LC-MS. The rat experiments showed that the pharmacodynamic indicators were significantly different among different specifications of Notoginseng Radix et Rhizoma. The spectrum-effect relationship was explored between 27 common components and pharmacodynamic indicators. Among them, 16 components had positive effects on the pharmacodynamic indicators of Notoginseng Radix et Rhizoma, and 11 exerted negative effects. This study provides a basis for the precision medication and quality control of Notoginseng Radix et Rhizoma.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20210331.203DOI Listing
August 2021

Nardosinone Alleviates Parkinson's Disease Symptoms in Mice by Regulating Dopamine D2 Receptor.

Evid Based Complement Alternat Med 2021 13;2021:6686965. Epub 2021 Aug 13.

CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, 4A Datun Road, Chaoyang District, Beijing 100101, China.

Nardostachyos Radix et Rhizoma (nardostachys) is the root and rhizome of DC. Recent studies have shown that nardostachys may exert an anti-PD effect. In this study, the UHPLC-LTQ-Orbitrap-MS method was used to analyze the brain components of nardostachys in rats. Based on the results of UHPLC-LTQ-Orbitrap-MS analysis, nardosinone was identified to be the most effective anti-PD compound in nardostachys. To further verify this inference, a mouse PD model was established and the effect of nardosinone on PD mice was determined using classic behavioral tests. The results showed that nardosinone was indeed effective for relieving PD symptoms in mice. Moreover, network pharmacology analysis was used to elucidate the mechanism underlying the anti-PD effect of nardosinone. Dopamine receptor D2 (DRD2) was identified as the key target of nardosinone-PD interaction network, which was further verified by molecular docking and Western blotting. The results demonstrated that nardosinone and DRD2 could interact with each other. Furthermore, the expression level of DRD2 was decreased in the brain tissue of PD mice, and nardosinone could restore its expression to a certain extent. In conclusion, our findings suggest that nardosinone may reduce the motor and cognitive symptoms in the animal PD model by regulating DRD2 expression.
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http://dx.doi.org/10.1155/2021/6686965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380167PMC
August 2021

Anthocyanins in Lycium ruthenicum Murray reduce nicotine withdrawal-induced anxiety and craving in mice.

Neurosci Lett 2021 Oct 10;763:136152. Epub 2021 Aug 10.

Shcool of Chinese Medicines, Beijing University of Chinese Medicine, No. 11 North Third Ring East Road, Chaoyang District, Beijing 100029, China. Electronic address:

Lycium ruthenicum Murray is widely used in traditional Chinese medicine and is believed to have antimicrobial, antioxidant, and anti-fatigue effects. Anthocyanins are considered to be one of the main active components. The previous work by our research team found that the anthocyanins in Lycium ruthenicum extract (ALRM) produce a stable anti-anxiety effect. The mechanisms of action include reducing the level of corticotropin-releasing factor (CRF) as well as regulating extracellular signal-regulated kinase/mitogen activation, protein kinase (ERK/MAPK) pathways, and others, all of which are related to the mechanisms of nicotine addiction. To investigate the effects of ALRM on anxiety and craving behavior after nicotine withdrawal, the components of ALRM were analyzed using the UPLC-Orbitrap MS method. The effects of ALRM on anxiety behavior induced by nicotine withdrawal were investigated in mice using the elevated plus maze (EPM) and light-dark box (LDB) tests. The effects of ALRM on craving behavior after nicotine withdrawal were further investigated using the conditional place preference (CPP) test. The EPM and LDB tests demonstrated that ALRM could alleviate the anxiety behavior induced by nicotine withdrawal and reduce nicotine craving in mice. Based on the identified ALRM components, the network pharmacology method was used to predict the mechanism of ALRM alleviating anxiety after nicotine withdrawal in mice. It was speculated that ALRM was involved in the production and transmission of dopamine, choline, and other nervous system functions and exhibited a potential role in treating nicotine addiction.
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http://dx.doi.org/10.1016/j.neulet.2021.136152DOI Listing
October 2021

Krüppel-Like Factor 15/Interleukin 11 Axis-Mediated Adventitial Remodeling Depends on Extracellular Signal-Regulated Kinases 1 and 2 Activation in Angiotensin II-Induced Hypertension.

J Am Heart Assoc 2021 Aug 5;10(16):e020554. Epub 2021 Aug 5.

Department of Cardiovascular Medicine Department of Hypertension Ruijin Hospital and State Key Laboratory of Medical GenomicsShanghai Key Laboratory of HypertensionShanghai Institute of HypertensionShanghai Jiao Tong University School of Medicine Shanghai China.

Background Adventitial remodeling is a pathological hallmark of hypertension that results in target organ damage. Activated adventitial fibroblasts have emerged as critical regulators in this process, but the precise mechanism remains unclear. Methods and Results Interleukin 11 (IL-11) knockout and wild-type mice were subjected to angiotensin II (Ang II) infusion to establish models of hypertension-associated vascular remodeling. IL-11 mRNA and protein were increased especially in the adventitia in response to Ang II. Compared with wild-type mice, Ang II-treated IL-11 knockout mice showed amelioration of vascular hypertrophy, adventitial fibrosis, macrophage infiltration, and inflammatory factor expression. Recombination mouse IL-11 exacerbated adventitial fibrosis in Ang II-infused wild-type mice. Interestingly, IL-11 neutralizing antibody attenuated adventitial fibrosis, macrophage infiltration, and inflammatory factor expression after Ang II infusion for 7 days. Mechanistically, in primary cultured adventitial fibroblasts, Krüppel-like factor 15 negatively regulated Ang II-induced IL-11 expression. Ang II increased extracellular signal-regulated kinases 1 and 2 activation, especially in adventitia, and caused biphasic extracellular signal-regulated kinases 1 and 2 activation in adventitial fibroblasts. A rapid and early activation increased IL-11 production through decreasing Krüppel-like factor 15 expression, which, in turn, induced the second extracellular signal-regulated kinases 1 and 2 activation, resulting in posttranscriptional profibrotic gene expression. Conclusions These results demonstrate that extracellular signal-regulated kinases 1 and 2 activation is important for Krüppel-like factor 15-mediated IL-11 expression in adventitial fibroblasts to promote adventitial remodeling in Ang II-induced hypertension. Therefore, targeting the Krüppel-like factor 15/IL-11 axis might serve as a new therapeutic strategy for vascular diseases.
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http://dx.doi.org/10.1161/JAHA.120.020554DOI Listing
August 2021

Phylogenomic framework of the IRLC legumes (Leguminosae subfamily Papilionoideae) and intercontinental biogeography of tribe Wisterieae.

Mol Phylogenet Evol 2021 Oct 17;163:107235. Epub 2021 Jun 17.

Key Laboratory of Plant Resources Conservation and Sustainable Utilization, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou 510650, China. Electronic address:

The inverted repeat-lacking clade (IRLC) is one of the most derived clades within the subfamily Papilionoideae of the legume family, and includes various economically important plants, e.g., chickpeas, peas, liquorice, and the largest genus of angiosperms, Astragalus. Tribe Wisterieae is one of the earliest diverged groups of the IRLC, and its generic delimitation and spatiotemporal diversification needs further clarifications. Based on genome skimming data, we herein reconstruct the phylogenomic framework of the IRLC, and infer the inter-generic relationships and historical biogeography of Wisterieae. We redefine tribe Caraganeae to contain Caragana only, and tribe Astragaleae is reduced to the Erophaca-Astragalean clade. The chloroplast capture scenario was hypothesized as the most plausible explanation of the topological incongruences between the chloroplast CDSs and nuclear ribosomal DNA trees in both the Glycyrrhizinae-Adinobotrys-Wisterieae clade and the Chesneyeae-Caraganeae-Hedysareae clade. A new name, Caragana lidou L. Duan & Z.Y. Chang, is proposed within Caraganeae. Thirteen genera are herein supported within Wisterieae, including a new genus, Villosocallerya L. Duan, J. Compton & Schrire, segregated from Callerya. Our biogeographic analyses suggest that Wisterieae originated in the late Eocene and its most recent common ancestor (MRCA) was distributed in continental southeastern Asia. Lineages of Wisterieae remained in the ancestral area from the early Oligocene to the early Miocene. By the middle Miocene, Whitfordiodendron and the MRCA of Callerya-Kanburia-Villosocallerya Clade became disjunct between the Sunda area and continental southeastern Asia, respectively; the MRCA of Wisteria migrated to North America via the Bering land bridge. The ancestor of Austrocallerya and Padbruggea migrated to the Wallacea-Oceania area, which split in the early Pliocene. In the Pleistocene, Wisteria brachybotrys, W. floribunda and Wisteriopsis japonica reached Japan, and Callerya cinerea dispersed to South Asia. This study provides a solid phylogenomic for further evolutionary/biogeographic/systematic investigations on the ecologically diverse and economically important IRLC legumes.
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http://dx.doi.org/10.1016/j.ympev.2021.107235DOI Listing
October 2021

Risk factors for drug-resistant tuberculosis, the association between comorbidity status and drug-resistant patterns: a retrospective study of previously treated pulmonary tuberculosis in Shandong, China, during 2004-2019.

BMJ Open 2021 06 16;11(6):e044349. Epub 2021 Jun 16.

Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China

Objective: This study was designed to identify the risk factors for drug-resistant tuberculosis (DR-TB) and the association between comorbidity and drug resistance among retreated pulmonary tuberculosis (PTB).

Design: A retrospective study was conducted among all the 36 monitoring sites in Shandong, China, over a 16-year period. Baseline characteristics were collected from the TB Surveillance System. Categorical variables were compared by Fisher's exact or Pearson's χ test. The risk factors for drug resistance were identified using univariable analysis and multivariable logistic models. The influence of comorbidity on different types of drug resistance was evaluated by performing multivariable logistic models with the covariates adjusted by age, sex, body mass index, drinking/smoking history and cavity.

Results: A total of 10 975 patients with PTB were recorded during 2004-2019, and of these 1924 retreated PTB were finally included. Among retreated PTB, 26.2% were DR-TB and 12.5% had comorbidity. Smoking (adjusted OR (aOR): 1.69, 95% CI 1.19 to 2.39), cavity (aOR: 1.55, 95% CI 1.22 to 1.97) and comorbidity (aOR: 1.44, 95% CI 1.02 to 2.02) were risk factors for DR-TB. Of 504 DR-TB, 9.5% had diabetes mellitus, followed by hypertension (2.0%) and chronic obstructive pulmonary disease (1.8%). Patients with retreated PTB with comorbidity were more likely to be older, have more bad habits (smoking, alcohol abuse) and have clinical symptoms (expectoration, haemoptysis, weight loss). Comorbidity was significantly associated with DR-TB (aOR: 1.44, 95% CI 1.02 to 2.02), overall rifampin resistance (aOR: 2.17, 95% CI 1.41 to 3.36), overall streptomycin resistance (aOR: 1.51, 95% CI 1.00 to 2.27) and multidrug resistance (aOR: 1.96, 95% CI 1.17 to 3.27) compared with pan-susceptible patients (p<0.05).

Conclusion: Smoking, cavity and comorbidity lead to an increased risk of drug resistance among retreated PTB. Strategies to improve the host's health, including smoking cessation, screening and treatment of comorbidity, might contribute to the control of tuberculosis, especially DR-TB, in China.
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http://dx.doi.org/10.1136/bmjopen-2020-044349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211042PMC
June 2021

[Study on mechanism of Valerianae Jatamansi Rhizoma et Radix against post-traumatic stress disorder based on molecular docking and network pharmacology].

Zhongguo Zhong Yao Za Zhi 2021 May;46(10):2380-2391

School of Chinese Materia Medica, Beijing University of Chinese Medicine Beijing 102488, China.

This paper aims to investigate the active components and mechanism of Valerianae Jatamansi Rhizoma et Radix against post-traumatic stress disorder(PTSD) based on network pharmacology and molecular docking. The main components and targets of Valerianae Jatamansi Rhizoma et Radix were obtained by literature mining methods, SwissTargetPrediction, BATMAN and ETCM database. PTSD-related genes were collected from DrugBank, TTD and CTD databases. The protein-protein interaction(PPI) network was constructed based on STRING, and the core targets of Valerianae Jatamansi Rhizoma et Radix in the treatment of PTSD were selected according to the topological parameters. Cytoscape 3.7.2 was used to construct the compound-target network. DAVID database was used for GO enrichment analysis and KEGG enrichment analysis. The relationship network of "compound-target-pathway" was constructed through Cytoscape 3.7.2 to analyze and obtain the key targets and their corresponding components in the network, and their results were verified by molecular docking. The results showed that a total of 47 components(such as valeraldehyde, dihydrovalerin, valerate, chlorovaltrate K, 8-hydroxypinoresinol, 6-hydroxyluteolin, apigenin, farnesin, vanillin, luteolin, kaempferol, glycosmisic acid and pogostemon) of Valerianae Jatamansi Rhizoma et Radix may act on 94 key targets such as CNR1, MAOA, NR3 C1, MAPK14, MAPK8, HTR2 C and DRD2. Totally 29 GO terms were obtained by GO functional enrichment analysis(P<0.05), and 20 signaling pathways were obtained from KEGG pathway enrichment, mainly involving neuroactive ligand-receptor interaction, serotonergic synapse, calcium signaling pathway, cAMP signaling pathway, dopaminergic synapse, retrograde endocannabinoid signaling, neurotrophin signaling pathway, gap junction, cholinergic synapse, estrogen signaling pathway, glutamatergic synapse and long-term potentiation. Molecular docking analysis showed that hydrogen bonding, π-π interaction and hydrophobic effecting may be the main forms of interaction. This study used the network of compound-target-pathway and molecular docking technology to screen the effective components of Valerianae Jatamansi Rhizoma et Radix against PTSD, and explore its anti-PTSD mechanism, so as to provide scientific basis for exploring the anti-PTSD drugs from traditional Chinese medicine and clarifying its mechanism of action.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20201229.401DOI Listing
May 2021

Ambient air pollutants, diabetes and risk of newly diagnosed drug-resistant tuberculosis.

Ecotoxicol Environ Saf 2021 Aug 25;219:112352. Epub 2021 May 25.

Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong University, 250021 Jinan, Shandong, People's Republic of China; Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 250021 Jinan, Shandong, People's Republic of China; College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, 250355 Jinan, Shandong, People's Republic of China. Electronic address:

Background: Drug-resistant tuberculosis (DR-TB), diabetes and exposure to air pollution are thought to be important threat to human health, but no studies have explored the effects of ambient air pollutants on DR-TB when adjusting diabetes status so far.

Methods: We performed a study among 3759 newly diagnosed TB cases with drug-susceptibility testing results, diabetes status, and individual air pollution data in Shandong from 2015 to 2019. Generalized linear mixed models (GLMM) including three models (Model 1: without covariates, Model 2: adjusted by diabetes status only, Model 3: with all covariates) were applied.

Results: Of 3759 TB patients enrolled, 716 (19.05%) were DR-TB, and 333 (8.86%) had diabetes. High exposure to O was associated with an increased risk of RFP-resistance (Model 2 or 3: odds ratio (OR) = 1.008, 95% confidence intervals (CI): 1.002-1.014), ethambutol-resistance (Model 3: OR = 1.015, 95%CI: 1.004-1.027) and any rifampicin+streptomycin resistance (Model 1,2,3: OR = 1.01, 95%CI: 1.002-1.018) at 90 days. In contrast, NO was associated with a reduced risk of DR-TB (Model 3: OR = 0.99, 95%CI: 0.981-0.999) and multidrug-resistant TB (MDR-TB) (Model 3: OR = 0.977, 95%CI: 0.96-0.994) at 360 days. Additionally, SO (Model 1, 2, 3: OR = 0.987, 95%CI: 0.977-0.998) showed a protective effect on MDR-TB at 90 days. PM (90 days, Model 2: OR = 0.991, 95%CI: 0.983-0.999), PM (360 days, Model 2: OR = 0.992, 95%CI: 0.985-0.999) had protective effects on any RFP+SM resistance.

Conclusions: O contributed to an elevated risk of TB resistance but PM, PM, SO, NO showed an inverse effect. Air pollutants may affect the development of drug resistance among TB cases by adjusting the status of diabetes.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112352DOI Listing
August 2021

Using a risk model for probability of cancer in pulmonary nodules.

Thorac Cancer 2021 06 11;12(12):1881-1889. Epub 2021 May 11.

Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Background: Considering the high morbidity and mortality of lung cancer and the high incidence of pulmonary nodules, clearly distinguishing benign from malignant lung nodules at an early stage is of great significance. However, determining the kind of lung nodule which is more prone to lung cancer remains a problem worldwide.

Methods: A total of 480 patients with pulmonary nodule data were collected from Shandong, China. We assessed the clinical characteristics and computed tomography (CT) imaging features among pulmonary nodules in patients who had undergone video-assisted thoracoscopic surgery (VATS) lobectomy from 2013 to 2018. Preliminary selection of features was based on a statistical analysis using SPSS. We used WEKA to assess the machine learning models using its multiple algorithms and selected the best decision tree model using its optimization algorithm.

Results: The combination of decision tree and logistics regression optimized the decision tree without affecting its AUC. The decision tree structure showed that lobulation was the most important feature, followed by spiculation, vessel convergence sign, nodule type, satellite nodule, nodule size and age of patient.

Conclusions: Our study shows that decision tree analyses can be applied to screen individuals for early lung cancer with CT. Our decision tree provides a new way to help clinicians establish a logical diagnosis by a stepwise progression method, but still needs to be validated for prospective trials in a larger patient population.
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http://dx.doi.org/10.1111/1759-7714.13991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201526PMC
June 2021

Population aging and trends of pulmonary tuberculosis incidence in the elderly.

BMC Infect Dis 2021 Mar 25;21(1):302. Epub 2021 Mar 25.

Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwuweiqi Road, Huaiyin District, 250021, Jinan, Shandong, People's Republic of China.

Background: To explore population aging and the epidemic trend of pulmonary tuberculosis (PTB) in the elderly, and provide a basis for the prevention and control of pulmonary tuberculosis among the elderly.

Methods: We collected clinical information of 239,707 newly active PTB patients in Shandong Province from 2005 to 2017. We analyzed and compared the clinical characteristics, reported incidence and temporal trend of PTB among the elderly group (≥60 years) and the non-elderly group (< 60 years) through logistic model and Join-point regression model.

Results: Among the total PTB cases, 77,192(32.2%) were elderly. Compared with non-elderly patients, newly active elderly PTB patients account for a greater proportion of male cases (OR 1.688, 95% CI 1.656-1.722), rural population cases (OR 3.411, 95% CI 3.320-3.505) and bacteriologically confirmed PTB cases (OR 1.213, 95%CI 1.193-1.234). The annual reported incidence of total, elderly, pulmonary bacteriologically confirmed cases were 35.21, 68.84, 35.63 (per 100,000), respectively. The annual reported incidence of PTB in the whole population, the elderly group and the non-elderly group has shown a slow downward trend since 2008. The joinpoint regression model showed that the overall reported incidence of PTB in the elderly significantly decreased from 2007 to 2017 (APC = -5.3, P < 0.05). The reported incidence of bacteriologically confirmed PTB among elderly patients declined rapidly from 2005 to 2014(2005-2010 APC = -7.2%, P < 0.05; 2010-2014 APC = -22.6%, P < 0.05; 2014-2017 APC = -9.0%, P = 0.1). The reported incidence of clinically diagnosed PTB among elderly patients from 2005 to 2017 (11.48-38.42/100,000) increased by about 235%. It rose significantly from 2007 to 2014 (APC = 9.4, P<0.05).

Conclusions: Compared with the non-elderly population, the reported incidence of PTB in the elderly population is higher. The main burden of PTB will shift to the elderly, men, rural population, and clinically diagnosed patients. With the intensification of aging, more researches on elderly PTB prevention and treatment will facilitate the realization of the global tuberculosis (TB) control targets.
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http://dx.doi.org/10.1186/s12879-021-05994-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993467PMC
March 2021

Renal Natriuretic Peptide Receptor-C Deficiency Attenuates NaCl Cotransporter Activity in Angiotensin II-Induced Hypertension.

Hypertension 2021 03 25;77(3):868-881. Epub 2021 Jan 25.

From the Department of Cardiovascular Medicine, Department of Hypertension, Ruijin Hospital and State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, China.

Genome-wide association studies have identified that NPR-C (natriuretic peptide receptor-C) variants are associated with elevation of blood pressure. However, the mechanism underlying the relationship between NPR-C and blood pressure regulation remains elusive. Here, we investigate whether NPR-C regulates Ang II (angiotensin II)-induced hypertension through sodium transporters activity. Wild-type mice responded to continuous Ang II infusion with an increased renal NPR-C expression. Global NPR-C deficiency attenuated Ang II-induced increased blood pressure both in male and female mice associated with more diuretic and natriuretic responses to a saline challenge. Interestingly, Ang II increased both total and phosphorylation of NCC (NaCl cotransporter) abundance involving in activation of WNK4 (with-no-lysine kinase 4)/SPAK (Ste20-related proline/alanine-rich kinase) which was blunted by NPR-C deletion. NCC inhibitor, hydrochlorothiazide, failed to induce natriuresis in NPR-C knockout mice. Moreover, low-salt and high-salt diets-induced changes of total and phosphorylation of NCC expression were normalized by NPR-C deletion. Importantly, tubule-specific deletion of NPR-C also attenuated Ang II-induced elevated blood pressure, total and phosphorylation of NCC expression. Mechanistically, in distal convoluted tubule cells, Ang II dose and time-dependently upregulated WNK4/SPAK/NCC kinase pathway and NPR-C/Gi/PLC/PKC signaling pathway mediated NCC activation. These results demonstrate that NPR-C signaling regulates NCC function contributing to sodium retention-mediated elevated blood pressure, which suggests that NPR-C is a promising candidate for the treatment of sodium retention-related hypertension.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15636DOI Listing
March 2021

Discovery and proteomics analysis of effective compounds in Valeriana jatamansi jones for the treatment of anxiety.

J Ethnopharmacol 2021 Jan 15;265:113452. Epub 2020 Oct 15.

School of Chinese Materia Medica, Beijing University of Chinese Medicine, 11A North Third Ring East Road, Chaoyang District, Beijing, 100029, China. Electronic address:

Ethnopharmacological Relevance: Zhizhu Xiang (ZZX for short) is the root and rhizome of Valeriana jatamansi Jones, which is a Traditional Chinese Medicine (TCM) used to treat various mood disorders for more than 2000 years, especially anxiety. However, there have been few investigations to clarify the compounds in ZZX for the treatment of anxiety.

Aim Of The Study: Our previous study has identified five anti-anxiety components, including hesperidin, isochlorogenic acid A, isochlorogenic acid B and isochlorogenic acid C and chlorogenic acid, from extract of ZZX. In order to find the optimal combination and the underlying mechanism of these five components in the treatment of anxiety disorder, researches were designed based on uniform design method and proteomic technology.

Materials And Methods: The samples with different proportion and content of the five active components were arranged by uniform design method. Then a mathematical model was formulated using partial least square method and stepwise regression analysis. Moreover, the empty bottle stress-induced anxiety rat model was established, and the anti-anxiety effect was recorded by the unconditioned reflex elevated maze test and the open field test. In addition, the isobaric tags for relative and absolute quantitation (iTRAQ) technique, along with the multidimensional liquid chromatography and high-resolution mass spectrometry were applied in proteomic study. At last, the result of proteomic analysis was further confirmed by Western blot.

Results: The optimal combination of the components from the extract of ZZX was 1.153 mg/kg hesperidin, 2.197 mg/kg Isochlorogenic acid A, 0.699 mg/kg Isochlorogenic acid B and 1.249 mg/kg Chlorogenic acid. Total 6818 proteins were identified using proteomic analysis and 80 differentially expressed proteins were used for further bioinformatic analysis. These proteins were involved in the neuroactive ligand-receptor interaction, protein digestion and absorption, cholesterol metabolism, Chagas disease, and AGE/RAGE signaling pathway.

Conclusions: The composition and proportion of anti-anxiety components in extract of ZZX was disclosed, and there was an anti-anxiety effect for the combined components of flavonoids and phenolic acids. Through proteomic analysis and Western blot, it was found that the effective components of extract of ZZX can exert synergistic anti-anxiety effects via the regulation of multi-signaling pathways. These findings could provide a preliminary research basis for the development of new low-toxic, efficient, stable and controllable anti-anxiety drugs.
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http://dx.doi.org/10.1016/j.jep.2020.113452DOI Listing
January 2021

Association between economic development level and tuberculosis registered incidence in Shandong, China.

BMC Public Health 2020 Oct 16;20(1):1557. Epub 2020 Oct 16.

Department of Respiratory Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324, Jingwuweiqi Road, Huaiyin District, Jinan, 250021, Shandong, China.

Background: Tuberculosis (TB) is one of the major infectious diseases that seriously endanger people's health. In Shandong province, the relationship between the level of economic development and TB incidence has not been studied. This study aims to provide more research basis for the government to prevent and control TB by exploring the impact of different economic factors on TB incidence.

Methods: By constructing threshold regression model (TRM), we described the extent to which different economic factors contribute to TB registered incidence and differences in TB registered incidence among seventeen cities with different levels of economic development in Shandong province, China, during 2006-2017. Data were retrieved from the China Information System for Disease Control and Prevention.

Results: Per capita medical expenditure (regression coefficient, -0.0314462; SD, 0.0079305; P > |t|, 0.000) and per capita savings (regression coefficient, 0.0001924; SD, 0.0000566; P > |t|, 0.001) passed the significance test at the level of 1%.They are the two economic indicators that have the greatest impact on TB registered incidence. Through the threshold test, we selected the per capita savings as the threshold variable. In the three stages of per capita savings (<9772.8086 China Yuan(CNY); 9772.8086-33,835.5391 CNY; >33,835.5391 CNY), rural per capita income always has a significant negative impact on the TB registered incidence (The regression coefficients are - 0.0015682, - 0.0028132 and - 0.0022253 respectively. P is 0.007,0.000 and 0.000 respectively.).In cities with good economies, TB registered incidence was 38.30% in 2006 and dropped to 25.10% by 2017. In cities with moderate economies, TB registered incidence peaked in 2008 at 43.10% and dropped to 27.1% by 2017.In poorer cities, TB registered incidence peaked in 2008 at 56.30% and dropped to 28.9% in 2017.

Conclusion: We found that per capita savings and per capita medical expenditure are most closely related to the TB incidence. Therefore, relevant departments should formulate a more complete medical system and medical insurance policy to effectively solve the problem of "difficult and expensive medical treatment". In order to further reduce the TB incidence, in addition to timely and accurate diagnosis and treatment, it is more important for governments to increase investment in medicine and health care.
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http://dx.doi.org/10.1186/s12889-020-09627-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565316PMC
October 2020

Histone methyltransferase G9a inhibitor-loaded redox-responsive nanoparticles for pancreatic ductal adenocarcinoma therapy.

Nanoscale 2020 Aug 20;12(29):15767-15774. Epub 2020 Jul 20.

Department of Pancreato-Biliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.

Survival data have shown little therapeutic improvement in pancreatic ductal adenocarcinoma (PDAC) over the past several decades, mostly due to aggressive growth and resistance to therapy. Glutathione (GSH) depletion in PDAC may serve as a strategy to suppress tumour malignancy and sensitize tumour cells to therapy. Herein, novel l-cysteine-based poly(disulfide amide) polymers were fabricated to deliver a histone methyltransferase G9a inhibitor (UNC0638) that can simultaneously block GSH biosynthesis and clear cellular GSH levels in PDAC. The optimal UNC0638 nanodrug (NP) had the desired particle size, reasonable drug loading capacity, and GSH-controlled drug release. Moreover, compared to UNC0638 alone, NP showed better efficacy in inhibiting cell viability, arresting the cell cycle, inducing apoptosis, and suppressing the invasion and self-renewal capacity of PDAC cells. Furthermore, NP was found to be tumour-specific and well tolerated with no apparent toxicity to vital organs and haematopoietic stem and progenitor cells. Additionally, treatment with NP provided favourable outcomes in the PDAC xenograft model. Therefore, this work presents a potent drug delivery platform to overcome the GSH-induced malignant potential of PDAC.
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http://dx.doi.org/10.1039/d0nr03138kDOI Listing
August 2020

Anxiolytic Effect of Alcohol-Water Extracted Suanzaoren-Wuweizi Herb-Pair by Regulating ECS-BDNF-ERK Signaling Pathway Expression in Acute Restraint Stress Male Rats.

Evid Based Complement Alternat Med 2020 17;2020:2078932. Epub 2020 Jun 17.

CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, 4A Datun Road, Chaoyang District, Beijing 100101, China.

Herb-pairs are the basic units of composition in Chinese herbal formulae, where the bridge linking Chinese medicine and prescription consists of two Chinese medicine herbs. The Suanzaoren-Wuweizi herb-pair (SWHP) is commonly used as a sedative or tranquilizer. SWHP has been demonstrated to exert an antianxiety effect in animal models of anxiety. However, little information about its mechanism is available and the effects of SWHP have not been investigated. This study examined the effects of SWHP on ameliorating anxiety-like behaviors by regulating endocannabinoids system (ECS)-brain-derived neurotrophic factor (BDNF)-extracellular regulated protein kinases (ERK) signaling pathway expression, induced by restraint stress (RS) procedures. The antianxiety effects of SWHP on RS rats were then examined through the open-field test (OF) and the elevated plus maze test (EPM). The concentration of BNDF, ERK1/2, p-ERK1/2, cAMP-response element binding protein (CREB), and p-CREB expression in the prefrontal cortex and hippocampus of the rats was then measured by western blot. The number of positive cells of CB1 and CB2 in the rats' hippocampus CA1 region was measured by immunohistochemistry. These results gave compelling evidence that SWHP could modify anxiety-like behaviors of RS rats through regulation of the ECS-BDNF-ERK signaling pathway. Our study demonstrated that SWHP improved anxiety-like behaviors in RS rat models by regulating the ECS-BDNF-ERK signaling pathway. The findings indicate that SWHP may have a therapeutic application in the RS model of anxiety disorder, which proposes a potential new direction for research into anxiety disorders regarding mechanisms and the development of novel antianxiety drugs.
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http://dx.doi.org/10.1155/2020/2078932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317328PMC
June 2020

Targeting Super-Enhancers via Nanoparticle-Facilitated BRD4 and CDK7 Inhibitors Synergistically Suppresses Pancreatic Ductal Adenocarcinoma.

Adv Sci (Weinh) 2020 Apr 16;7(7):1902926. Epub 2020 Feb 16.

RNA Biomedical Institute Sun Yat-sen Memorial Hospital Sun Yat-sen University Guangzhou 510120 China.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignant cancer with complex genomic variations, and no targetable genomic lesions have been found yet. Super-enhancers (SEs) have been found to contribute to the continuous and robust oncogenic transcription. Here, histone H3 lysine 27 acetylation (H3K27ac) is profiled in PDAC cell lines to establish SE landscapes. Concurrently, it is also shown that PDAC is vulnerable to the perturbation of the SE complex using bromodomain-containing protein 4 (BRD4) inhibitor, JQ1, synergized with cyclin-dependent kinase 7 (CDK7) inhibitor, THZ1. Formulations of hydrophobic l-phenylalanine-poly (ester amide) nanoparticles (NPs) with high drug loading of JQ1 and THZ1 (J/[email protected]) are further designed and developed. J/[email protected] is assessed for size, encapsulation efficiency, morphology, drug release profiles, and drug uptake in vitro. Compared to conventional free drug formulation, the nanodelivery system dramatically reduces the hepatotoxicity while significantly enhancing the tumor inhibition effects and the bioavailability of incorporated JQ1 and THZ1 at equal doses in a Gemcitabine-resistant PDAC patient-derived xenograft (PDX) model. Overall, the present study demonstrates that the J/[email protected] can be a promising therapeutic treatment against the PDAC via suppression of SE-associated oncogenic transcription, and provides a strategy utilizing NPs to assist the drug delivery targeting SEs.
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http://dx.doi.org/10.1002/advs.201902926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140991PMC
April 2020

Therapeutic Targeting of CDK7 Suppresses Tumor Progression in Intrahepatic Cholangiocarcinoma.

Int J Biol Sci 2020 10;16(7):1207-1217. Epub 2020 Feb 10.

Department of Pancreato-Biliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.

Intrahepatic cholangiocarcinoma (ICC) is a lethal malignancy with high mortality and lack of effective therapeutic targets. Here, we found that expression of cyclin-dependent kinase 7 (CDK7) was significantly associated with higher tumor grade and worse prognosis in 96 ICC specimens. Depletion of CDK7 significantly inhibited cell growth, induced a G2/M cell cycle arrest, and reduced the migratory and invasive potential in ICC cells. Subsequent experiments demonstrated that ICC cells were highly sensitive to the CDK7 inhibitor THZ1. A low concentration of THZ1 markedly inhibited cell growth, cell cycle, migration, and invasion in ICC cell lines. RNA-sequencing (RNA-seq) analysis revealed that THZ1 treatment decreased the levels of massive oncogene transcripts, particularly those associated with cell cycle and cell migration. Quantitative reverse transcriptase PCR (qRT-PCR) analysis confirmed that transcription of oncogenes involved in cell cycle regulation (, , and ) and the c-Met pathway (, and ) was selectively repressed by THZ1. In addition, THZ1 exhibited significant anti-tumor activity in a patient-derived xenograft (PDX) model of ICC, without causing detectable side effects.
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http://dx.doi.org/10.7150/ijbs.39779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053328PMC
February 2020

Drug resistance of previously treated tuberculosis patients with diabetes mellitus in Shandong, China.

Respir Med 2020 03 7;163:105897. Epub 2020 Feb 7.

Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 250021, Jinan, Shandong, PR China; College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, 250355, Jinan, Shandong, PR China. Electronic address:

Background: Although the association between diabetes mellitus (DM) and tuberculosis (TB) has been well-documented for centuries, evidence of the link between diabetes and drug resistance among previously treated TB patients remains limited and inconsistent.

Methods: An observational study was performed that involved 1791 retreated TB-no DM patients (refers to TB cases without diabetes) and 93 retreated TB-DM patients (refers to TB cases with diabetes) in Shandong, China from 2004 to 2017. Baseline data including demographic and clinical characteristics, drug susceptibility test (DST) results, and diabetes status were collected. Categorical baseline characteristics were compared by Fisher's exact or Pearson Chi-square test. Univariable analysis and multivariable logistic models were used to estimate the association between diabetes and different drug resistance profiles.

Results: Retreated TB-DM patients have a higher rate of drug resistance than TB-no DM patients (34.41% vs 25.00%, P < 0.01). Diabetes co-morbidity was significantly associated with any drug-resistant tuberculosis (DR-TB, odds ratio (OR):1.56, 95% confidence interval (CI): 1.01-2.43), multidrug resistant tuberculosis (MDR-TB, OR: 2.48, 95%CI:1.39-4.41; adjusted OR (aOR):2.94, 95%CI:1.57-5.48), isoniazid-related resistance (OR:1.71, 95%CI:1.04-2.81), rifampin-related resistance (OR:2.56, 0.54, 95%CI: 1.54-4.26; aOR:2.69, 95%CI:1.524-4.74), isoniazid + rifampin resistance (OR: 3.55, 95%CI:1.33-9.44; aOR:4.13, 95%CI:1.46-11.66), any resistance to isoniazid + streptomycin (OR:2.34, 95%CI:1.41-3.89; aOR:2.22, 95%CI:1.26-3.94), and any resistance to rifampin + isoniazid (OR:2.48, 95%CI:1.39-4.41; aOR:2.94, 95%CI: 1.57-5.48), compared with pan susceptible TB cases, P < 0.05.

Conclusions: The risk of acquired drug resistance increased significantly among retreated TB-DM patients compared with retreated TB-no DM patients, underlining the necessity of more interventions during the clinical management of TB-DM cases.
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http://dx.doi.org/10.1016/j.rmed.2020.105897DOI Listing
March 2020

MFAP5 facilitates the aggressiveness of intrahepatic Cholangiocarcinoma by activating the Notch1 signaling pathway.

J Exp Clin Cancer Res 2019 Nov 27;38(1):476. Epub 2019 Nov 27.

Department of Pancreato-Biliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China.

Background: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer. The dismal outcome of ICC patients is due to lack of early diagnosis, the aggressive biological behavior of ICC and the lack of effective therapeutic options. Early diagnosis and prognosis of ICC by non-invasive methods would be helpful in providing valuable information and developing effective treatment strategies.

Methods: Expression of microfibrillar-associated protein 5 (MFAP5) in the serum of ICC patients was detected by ELISA. Human ICC specimens were immunostained by MFAP5 antibodies. The growth rate of human ICC cell lines treated with MFAP5 or MFAP5 shRNAs was examined by CCK8 and colony formation assays. Cell cycle analysis was performed with PI staining. The effect of MFAP5 inhibition was assessed by xenograft models in nude mice. RNA-seq and ATAC-seq analyses were used to dissect the molecular mechanism by which MFAP5 promoted ICC aggressiveness.

Results: We identified MFAP5 as a biomarker for the diagnosis and prognosis of ICC. Upregulated MFAP5 is a common feature in aggressive ICC patients' tissues. Importantly, MFAP5 level in the serum of ICC patients and healthy individuals showed significant differential expression profiles. Furthermore, we showed that MFAP5 promoted ICC cell growth and G1 to S-phase transition. Using RNA-seq expression and ATAC-seq chromatin accessibility profiling of ICC cells with suppressed MFAP5 secretion, we showed that MFAP5 regulated the expression of genes involved in the Notch1 signaling pathway. Furthermore, FLI-06, a Notch signaling inhibitor, completely abolished the MFAP5-dependent transcriptional programs.

Conclusions: Raised MFAP5 serum level is useful for differentiating ICC patients from healthy individuals, and could be helpful in ICC diagnosis, prognosis and therapies.
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http://dx.doi.org/10.1186/s13046-019-1477-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882185PMC
November 2019

Primary drug resistance of mycobacterium tuberculosis in Shandong, China, 2004-2018.

Respir Res 2019 Oct 18;20(1):223. Epub 2019 Oct 18.

Department of Respiratory Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, Shandong, China.

Background: Primary drug-resistant tuberculosis (DR-TB) has contributed to a significant health and economic burden on a global scale, especially in China. we sought to estimate epidemiological characteristics of primary DR-TB in China from 2004 to 2018.

Methods: Eleven thousand four hundred sixty-seven newly diagnosed and 1981 retreated TB cases with drug susceptibility data were included. Chi-Square test for trends, linear regression, a joinpoint regression model and temporal trend in proportions of the different resistance patterns were carried out.

Results: The proportion of primary DR-TB and mono-resistant TB (MR-TB) in China had reduced by more than 12% since 2004, and were 21.38%, 13.35% in 2018 respectively. Among primary DR-TB cases (2173,18.95%), the percentage of multiresistant TB (MDR-TB, from 5.41 to 17.46%), male (from 77.03 to 84.13%), cavity (from 13.51 to 43.92%), rifampicin(RFP)-resistant TB (from 8.11 to 26.98%), streptomycin(SM)-resistant TB (from 50.00 to 71.43%) increased significantly (P < 0.05). On the contrary, the proportion of female, non-cavity, isoniazide(INH)-resistant TB (from 55.41 to 48.15%) and MR-TB (from 82.43 to 62.43%) decreased significant (P < 0.05). The primary drug resistance rate among female, cavity, smoking, drinking, 15 to 44 year-old TB subgroups increased by 0.16, 6.24, 20.95, 158.85, 31.49%, respectively. The percentage of primary DR-TB, RFP-resistant TB dropped significantly during 2004-2007 in Joinpoint regression model.

Conclusion: The total rate of drug resistance among new TB cases showed a downward trend in Shandong, China, from 2004 to 2018. Primary drug resistance patterns were shifting from female, non-cavity, INH-resistant TB, and MR-TB groups to male, cavity, RFP/SM-resistant TB, and MDR-TB groups. Considering the rising drug resistance rate among some special population, future control of primary DR-TB in China may require an increased focus on female, cavity, smoking, drinking, or 15 to 44 year-old TB subgroups.
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http://dx.doi.org/10.1186/s12931-019-1199-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6798379PMC
October 2019

Primary drug resistance among tuberculosis patients with diabetes mellitus: a retrospective study among 7223 cases in China.

Infect Drug Resist 2019 2;12:2397-2407. Epub 2019 Aug 2.

Department of Respiratory Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, People's Republic of China.

Background: Given the high burden of tuberculosis (TB) and diabetes mellitus (DM) in China and the worse outcome of TB-DM cases (refers to TB patients with diabetes), and drug-resistant tuberculosis cases (DR-TB), it is of great significance to explore the association between diabetes and primary DR-TB for TB elimination target in China. We assessed the clinical characteristics, drug-resistance profile, and increased risk of resistance among TB-DM patients across China from 2004 to 2017.

Method: 7223 cases with drug-susceptibility data were collected from Shandong, China. Categorical baseline characteristics of new TB cases were compared by DM status using Fisher's exact or Pearson Chi-square test. Univariable analysis and multivariable logistic models were used to estimate the association between diabetes and different drug-resistance profiles and the risk factors of primary drug resistance among TB-DM cases.

Result: Of 7223 newly diagnosed TB patients, 426 (5.90%) were TB-DM cases. TB-DM csaes were more likely to be older,accompanied by higher body mass index (BMI) and hypertension than TB-no DM cases (refers to TB patients without diabetes). The rates of DR-TB (21.83% vs 16.96%), polydrug resistant TB (PDR-TB, 6.10% vs 3.80%), isoniazid (INH)+streptomycin (SM)-resistant TB (4.93% vs 3.13%), and SM-resistant TB (16.20% vs 11.7%) among TB-DM group were higher than TB-no DM group, <0.05. DM was significantly associated with any DR-TB (adjusted (aOR):1.30; 95% CI, 1.02-1.65), SM-related resistance (aOR: 1.43; 95% CI, 1.08-1.88), PDR-TB (OR: 1.57; 95% CI, 1.04-2.36; aOR: 1.59; 95% CI, 1.04-2.44), compared with pan-susceptible TB patients (<0.05).

Conclusion: Our study indicated that TB-DM groups had a higher proportion of drug resistance than TB groups, and diabetes was identified as a risk factor of total DR, PDR, SM resistance and INH+SM resistance among newly diagnosed TB cases. Good management of diabetes and TB infection screening program among DM patients might be necessary for improving TB control in China.
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http://dx.doi.org/10.2147/IDR.S217044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6684854PMC
August 2019

EYA4 inhibits hepatocellular carcinoma by repressing MYCBP by dephosphorylating β-catenin at Ser552.

Cancer Sci 2019 Oct 28;110(10):3110-3121. Epub 2019 Aug 28.

Department of Pancreatobiliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and the fourth leading cause of cancer-related death worldwide. Our previous study showed that EYA4 functioned by suppressing growth of HCC tumor cells, but its molecular mechanism is still not elucidated. Based on the results of gene microassay, EYA4 was inversely correlated with MYCBP and was verified in human HCC tissues by immunohistochemistry and western blot. Overexpressed and KO EYA4 in human HCC cell lines confirmed the negative correlation between EYA4 and MYCBP by qRT-PCR and western blot. Transfected siRNA of MYCBP in EYA4 overexpressed cells and overexpressed MYCBP in EYA4 KO cells could efficiently rescue the proliferation and G2/M arrest effects of EYA4 on HCC cells. Mechanistically, armed with serine/threonine-specific protein phosphatase activity, EYA4 reduced nuclear translocation of β-catenin by dephosphorylating β-catenin at Ser552, thereby suppressing the transcription of MYCBP which was induced by β-catenin/LEF1 binding to the promoter of MYCBP. Clinically, HCC patients with highly expressed EYA4 and poorly expressed MYCBP had significantly longer disease-free survival and overall survival than HCC patients with poorly expressed EYA4 and highly expressed MYCBP. In conclusion, EYA4 suppressed HCC tumor cell growth by repressing MYCBP by dephosphorylating β-catenin S552. EYA4 combined with MYCBP could be potential prognostic biomarkers in HCC.
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http://dx.doi.org/10.1111/cas.14159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778622PMC
October 2019

(Orchidaceae), a new species from Guangxi, China.

PhytoKeys 2019 15;119:31-37. Epub 2019 Mar 15.

Key Laboratory of Plant Resources Conservation and Sustainable Utilization, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou 510650, Guangdong, China South China Botanical Garden, Chinese Academy of Sciences Guangzhou China.

, a new orchid species belonging to section Cestichis from Guangxi, China is described and illustrated. It occurs in the karst limestone forest. The new species is morphologically similar to and , but can be readily distinguished by having narrowly oblong-falcate petals; flabellate-quadrate lip distinctly concave at base and emarginate at apex; conspicuously arcuate column with a pair of wedge-shaped wings.
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http://dx.doi.org/10.3897/phytokeys.119.32041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430743PMC
March 2019

Identification of Bioactive Chemical Markers in Improving Anxiety in Rat by Fingerprint-Efficacy Study.

Molecules 2018 Sep 12;23(9). Epub 2018 Sep 12.

School of Chinese Materia Medica, Beijing University of Chinese Medicine, 11A North Third Ring East Road, Chaoyang District, Beijing 100029, China.

(ZZX for short) is the root and rhizome of Jones, which is a Traditional Chinese Medicine (TCM) used to treat various mood disorders for more than 2000 years, especially anxiety. The aim of the present work was to identify the bioactive chemical markers in improving anxiety in rats by a fingerprint-efficacy study. More specifically, the chemical fingerprint of ZZX samples collected from 10 different regions was determined by High Performance Liquid Chromatography (HPLC) and the similarity analyses were calculated based on 10 common characteristic peaks. The anti-anxiety effect of ZZX on empty bottle stimulated rats was examined through the Open Field Test (OFT) and the Elevated Plus Maze Test (EPM). Then we measured the concentration of CRF, ACTH, and CORT in rat's plasma by the enzyme-linked immune sorbent assay (ELISA) kit, while the concentration of monoamine and metabolites (NE, DA, DOPAC, HVA, 5-HT, 5-HIAA) in the rat's cerebral cortex and hippocampus was analysed by HPLC coupled with an Electrochemical Detector. At last, the fingerprint-efficacy study between chemical fingerprint and anti-anxiety effect of ZZX was accomplished by partial least squares regression (PLSR). As a result, we screened out four compounds (hesperidin, isochlorogenic acid A, isochlorogenic acid B and isochlorogenic acid C) as the bioactive chemical markers for the anti-anxiety effect of ZZX. The fingerprint-efficacy study we established might provide a feasible way and some elicitation for the identification of the bioactive chemical markers for TCM.
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http://dx.doi.org/10.3390/molecules23092329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6225153PMC
September 2018

[Clinical study on compound prescription with Valerianae Jatamansi Rhizoma et Radix in treatment of generalized anxiety disorder].

Zhongguo Zhong Yao Za Zhi 2017 Dec;42(24):4888-4892

Institute of Psychology, Chinese Academy of Sciences, Key Laboratory of Mental Health, Beijing 100101, China.

This study was aimed to observe the clinical efficacy of anxiolytic compound prescription with Valerianae Jatamansi Rhizoma et Radix (ACPV) in treating liver Qi stagnation and feel ill at ease type generalized anxiety disorder (GAD). Sixty-seven patients diagnosed as GAD with stagnation of liver Qi and feel ill at ease were randomly divided into treatment group and control group. Patients in treatment group (n=34) was treated with ACPV decoction, and patients in control group (n=33) were treated with deanxit. Both groups were treated with respective drugs for 4 weeks. HAMA scale, traditional Chinese medicine (TCM) symptom scale (liver Qi stagnation and feel ill at ease type) and salivary cortisol levels were measured before and 2 weeks and 4 weeks after drug treatment. The life events scale (LES) and drug safety evaluation were performed before and after 4 weeks treatment. Two patients were excluded according to LES, and 5 patients were discontinued. Sixty patients were enrolled in the study finally (30 cases in each group). As compared with baseline, HAMA scores in both groups were significantly decreased at 2 weeks and 4 weeks (P<0.05, P<0.01). After 2 weeks and 4 weeks treatment, the TCM syndrome score in both group was also significantly improved (P<0.01). Moreover, the salivary cortisol levels in both groups were also decreased at 2 weeks and 4 weeks (P<0.05, P<0.01). The total efficiency between two groups had no statistically significant difference after 2 weeks treatment and 4 weeks treatment; moreover, no statistically significant differences were observed between two groups in HAMA scores, TCM syndrome scale scores and salivary cortisol levels between two groups. The incidence of adverse reactions in the treatment group was significantly lower than that in the control group (P<0.01), and there were no obvious side effects in general physical examination during the period of treatment. Thus, anxiolytic compound prescription with Valerianae Jatamansi Rhizoma et Radix is effective for GAD (stagnation of liver Qi and feel ill at ease type).
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20170919.007DOI Listing
December 2017

Acute and sub-acute oral toxicity studies of the aqueous extract from radix, radix with cortex and cortex of Psammosilene tunicoides in mice and rats.

J Ethnopharmacol 2018 Mar 11;213:199-209. Epub 2017 Nov 11.

Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, No. 4 Datun Road, Chaoyang District, Beijing 100101, China. Electronic address:

Ethnopharmacological Relevance: Psammosilene tunicoides is one of the important ingredients of a famous Chinese traditional medicine formulation "Yunnan Baiyao". Also, this plant is commonly used as an anodyne and hemostatic agent in southwest China. Currently, little toxicological information is available on its safety following prolonged use.

Aim Of The Study: In this study, we sought to evaluate the toxicity of the three different parts of Psammosilene tunicoides: Psammosilenes Radix (PR), Psammosilenes Radix with Cortex (PRC) and Psammosilenes Cortex (PC) by acute and sub-acute toxicity studies.

Materials And Methods: In the acute toxicity study, mice were orally administrated with different doses of PR, PRC and PC. General behavior and mortality were observed up to 14 days. In sub-acute toxicity study, these aqueous extracts were given orally as a single administration to rats at doses of 0.3, 0.6 and 1.2g/kg/day, respectively, for 28 days. General behavior, body weight, biochemical, hematological, organ coefficients and pathological morphology parameters were detected.

Results: In acute study, single oral administration of the aqueous extract of PR, PRC and PC caused dose-dependent general behavior adverse effects and mortality. The LD50 values of PR, PRC and PC were 4.64g/kg, 4.85g/kg and 6.40g/kg, respectively. In sub-acute study, the administration of the extract of PR, PRC and PC during 28 days at all doses reduced spontaneous activities with both genders. Occasional nasal secretion with blood at high doses (1.2g/kg) of PR, PRC and PC were observed. Daily single oral administration provoked varying degrees of growth retardation in female rats. The relative heart and spleen weight in the female rats were reduced after the administration. On the hematological and biochemical analyses, the administration of the extract of PR, PRC and PC during 28 days mainly caused variation of indexes in female rats. Histopathological analysis has shown vascular congestion in heart, thickened alveolar wall and emphysema in lung, and vascular congestion in kidney of rats after sub-acute oral administrations.

Conclusions: As shown in the results, Psammosilene tunicoides has a toxic potential in acute and sub-acute oral administrations. However, there is no direct relationship between toxicity and the cortex. Daily oral administration of three different parts from Psammosilene tunicoides (PR, PRC and PC) may cause damages to heart, lung and kidney in rats. Thus these extracts should be used with caution.
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http://dx.doi.org/10.1016/j.jep.2017.11.011DOI Listing
March 2018

Anti-Anxiety Effect of (-)-Syringaresnol-4-O-β-d-apiofuranosyl-(1→2)-β-d-glucopyranoside from Albizzia julibrissin Durazz (Leguminosae).

Molecules 2017 Aug 11;22(8). Epub 2017 Aug 11.

Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, 4ADatun Road, Chaoyang District, Beijing 100101, China.

Durazz, a Chinese Medicine, is commonly used for its anti-anxiety effects. (-)-syringaresnol-4--β-d-apiofuranosyl-(1→2)-β-d-glucopyranoside (SAG) is the main ingredient of Durazz. The present study investigated the anxiolytic effect and potential mechanisms on the HPA axis and monoaminergic systems of SAG on acute restraint-stressed rats. The anxiolytic effect of SAG was examined through an open field test and an elevated plus maze test. The concentration of CRF, ACTH, and CORT in plasma was examined by an enzyme-linked immune sorbent assay (ELISA) kit while neurotransmitters in the cerebral cortex and hippocampus of the brain were examined by High Performance Liquid Chromatography (HPLC). We show that repeated treatment with SAG (3.6 mg/kg, p.o.) significantly increased the number and time spent on the central entries in the open-field test when compared to the vehicle/stressed group. In the elevated plus maze test, 3.6 mg/kg SAG could increase the percentage of entries into and time spent on the open arms of the elevated plus maze. In addition, the concentration of CRF, ACTH, and CORT in plasma and neurotransmitters (NE, 5-HT, DA and their metabolites 5-HIAA, DOPAC, and HVA) in the cerebral cortex and hippocampus of the brain were decreased after SAG treatment, as compared to the repeated acute restraint-stressed rats. These results suggest that SAG is a potential anti-anxiety drug candidate.
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http://dx.doi.org/10.3390/molecules22081331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6152026PMC
August 2017

Involvement of 5-HT1A Receptors in the Anxiolytic-Like Effects of Quercitrin and Evidence of the Involvement of the Monoaminergic System.

Evid Based Complement Alternat Med 2016 19;2016:6530364. Epub 2016 May 19.

Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China.

Quercitrin is a well-known flavonoid that is contained in Flos Albiziae, which has been used for the treatment of anxiety. The present study investigated the anxiolytic-like effects of quercitrin in experimental models of anxiety. Compared with the control group, repeated treatment with quercitrin (5.0 and 10.0 mg/kg/day, p.o.) for seven days significantly increased the percentage of entries into and time spent on the open arms of the elevated plus maze. In the light/dark box test, quercitrin exerted an anxiolytic-like effect at 5 and 10 mg/kg. In the marble-burying test, quercitrin (5.0 and 10.0 mg/kg) also exerted an anxiolytic-like effect. Furthermore, quercitrin did not affect spontaneous locomotor activity. The anxiolytic-like effects of quercitrin in the elevated plus maze and light/dark box test were blocked by the serotonin-1A (5-hydroxytryptamine-1A (5-HT1A)) receptor antagonist WAY-100635 (3.0 mg/kg, i.p.) but not by the γ-aminobutyric acid-A (GABAA) receptor antagonist flumazenil (0.5 mg/kg, i.p.). The levels of brain monoamines (5-HT and dopamine) and their metabolites (5-hydroxy-3-indoleacetic acid, 3,4-dihydroxyphenylacetic acid, and homovanillic acid) were decreased after quercitrin treatment. These data suggest that the anxiolytic-like effects of quercitrin might be mediated by 5-HT1A receptors but not by benzodiazepine site of GABAA receptors. The results of the neurochemical studies suggest that these effects are mediated by modulation of the levels of monoamine neurotransmitters.
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http://dx.doi.org/10.1155/2016/6530364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4889836PMC
June 2016

[Advanced in studies on anxiolytic effects of natural flavonoids].

Zhongguo Zhong Yao Za Zhi 2016 Jan;41(1):38-44

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China.

Anxiety is one of the most common diseases endangering human health. Its pathogenesis is complex, the studies on the mechanisms of anxiety disorder are concentrated on neurotransmitter, neuroendocrine, immunologic system. Flavonoids are a kind of compounds which possess a variety of physiological activity, used in plenty of diseases. In recent years, researches of natural flavonoids on anti-anxiety were increasing, but contents were incomplete. It was just involved several neurotransmitters in research area. This paper is based on different anxiolytic effect mechanisms and structure-activity relationships of natural flavonoids, summarizing the researches of domestic and foreign, which can serve as a reference for further studies on anxiolytic effects of natural flavonoids.
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http://dx.doi.org/10.4268/cjcmm20160108DOI Listing
January 2016
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