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1.
Shanghai Journal of Preventive Medicine ; (12): 173-178, 2024.
Article in Chinese | WPRIM | ID: wpr-1016547

ABSTRACT

ObjectiveTo analyze the interannual fluctuation, seasonal fluctuation, habitat distribution and the correlation of the 3 monitoring indicators of Aedes albopictus in Yangpu District of Shanghai from 2017 to 2021, and to provide a scientific basis for A. albopictus control and rational use of the indicators. MethodsThe density surveillance data of A. albopictus recorded by Breteau index (BI), Path index (PI) and the mosquito ovitrap index (MOI) from 2017 to 2021 in Yangpu District, Shanghai were compared. Microsoft Excel 2019 software was used for data summary and SPSS 25.0 software was used for statistical analysis. ResultsFrom 2017 to 2021, there were two months with BI>5, and the PI were all above the density control level of Class C, and there were nine months with MOI≥5. In 2017, BI was higher than in the other four years, with statistically significant differences (all P≤0.001). MOI in 2017 and 2020 was higher than in 2019 (P=0.029, P=0.004) and 2021 (P=0.005, P=0.001), with statistical significance. MOI for different types of habitats varied significantly, with a statistically significant difference (P=0.004). A linear correlation was observed between BI and PI (r=0.462, P=0.010). ConclusionBI, PI and MOI are used simultaneously to reflect the density of A. albopictus in Yangpu District of Shanghai. However, these three monitoring indicators show poor linear correlation. Comprehensively considering the scientific aspects of monitoring methods and seasonal fluctuations of indicators, it is suggested that MOI should be used as the main index to evaluate the density of A. albopictus. In the MOI, attention should be paid to factors such as the distribution of the habitats, the standardization of operating methods, and quality control, which are essential for enhancing the reliability of the MOI.

2.
Journal of Clinical Hepatology ; (12): 712-719, 2024.
Article in Chinese | WPRIM | ID: wpr-1016514

ABSTRACT

ObjectiveTo investigate the mechanism of action of Xiayuxue decoction in inhibiting nonalcoholic fatty liver disease (NAFLD) induced by high-fat diet in mice by regulating nucleotide binding oligomerization domain like receptor containing pyrin domain protein 6 (NLRP6). MethodsA total of 15 male C57BL/6 mice were randomly divided into low-fat diet (LFD) group, high-fat diet (HFD) group, and Xiayuxue decoction-HFD group (XYXD group), with 5 mice in each group. Liver function parameters (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) and blood lipid metabolic indicators (triglycerides [TG] and total cholesterol [TC]) were measured; HE staining and oil red O staining were performed for liver tissue to observe histomorpholoty and lipid droplet deposition; quantitative real-time PCR was used to measure the expression levels of inflammatory factors (tumor necrosis factor-α [TNF-α], interleukin-1β [IL-1β], interleukin-18 [IL-18], and NLRP6) in liver tissue; Western blot was used to measure the protein expression levels of NLRP6, nuclear factor-kappa B (NF-κB), and NF-κB p65; immunohistochemistry was used to measure the expression of NLRP6 and CD68. Mouse Raw264.7 cells were treated with palmitic acid (PA), lipopolysaccharide, and serum containing Xiayuxue decoction to observe inflammation. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the LFD group, the HFD group had significant increases in the serum levels of ALT, AST, TC, and TG (all P<0.05). Liver histopathological examination showed that the HFD group had marked hepatic steatosis and a signficant increase in NAS score (P<0.05), and quantitative real-time PCR showed significant increases in the inflammatory factors such as IL1β and IL-18 and a significant reduction in the expression of NLRP6 (all P<0.05). Immunohistochemistry showed that the expression of NLRP6 showed a similar trend as that of the macrophage marker CD68. Western blot showed that after the downregulation of NLRP6 expression, there was a significant increase in phosphorylated NF-κB p65 (P<0.05). Compared with the HFD group, Xiayuxue decoction effectively improved liver inflammation, upregulated the expression of NLRP6, and downregulated phosphorylated NF-κB p65 in HFD mice (all P<0.05). After Raw264.7 cells were treated with PA, NLRP6 was downregulated to promote the progression of inflammation (P<0.05), and treatment with Xiayuxue decoction could upregulate NLRP6 and inhibit inflammation NF-κB (P<0.05). ConclusionXiayuxue decoction can effectively improve hepatic steatosis and liver inflammation in a mouse model of NAFLD, possibly by regulating NLRP6/NF-κB to alleviate macrophage activation.

3.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 54-61, 2024.
Article in Chinese | WPRIM | ID: wpr-1016462

ABSTRACT

ObjectiveTo investigate the interventional effects of Shugan Jianpi Yangxin prescription on the expression of orexin-A (OXA), orexin-1 receptor (OX1R), and orexin-2 receptor (OX2R) in the mouse model of insomnia. MethodThe mouse model of insomnia was established by intraperitoneal injection of DL-4-chlorophenylalanine (PCPA). Fifty BALB/c mice were randomized into a blank group, a model group, an eszopiclone (0.13 mg·kg-1) group, and low- and high-dose (8.4 and 33.6 g·kg-1, respectively) Shugan Jianpi Yangxin prescription groups and treated with the corresponding drugs for 14 consecutive days. The weight changes of mice were monitored, and Morris water maze and pentobarbital-induced sleep tests were conducted. Immunohistochemistry (IHC) was employed to examine the expression of OXA in the hypothalamus. Enzyme-linked immunosorbent assay was used to measure the levels of OXA and 5-hydroxytryptamine (5-HT) in the hypothalamus, serum, and spleen. Real-time fluorescence quantitative polymerase chain reaction was employed to determine the mRNA levels of OXA, OX1R, and OX2R in the hypothalamus. ResultCompared with the blank group, the model group had decreased body weight (P<0.01), increased escape latency (P<0.01), increased sleep latency (P<0.01), shortened sleep duration (P<0.01), elevated OXA level and lowered 5-HT level in the hypothalamus, serum, and spleen (P<0.05), and up-regulated mRNA levels of OXA, OX1R, and OX2R in the hypothalamus (P<0.01). Compared with the model group, the low- and high-dose groups of Shugan Jianpi Yangxin prescription showed increased body weight (P<0.05, P<0.01), shortened escape latency (P<0.05), shortened sleep latency and prolonged sleep duration (P<0.01), and lowered OXA level and elevated 5-HT level in the hypothalamus, serum, and spleen (P<0.05, P<0.01). Moreover, the two doses of Shugan Jianpi Yangxin prescription down-regulated the mRNA levels of OXA, OX1R, and OX2R in the hypothalamus (P<0.01). ConclusionShugan Jianpi Yangxin prescription exerts sedative and hypnotic effects in mice by increasing the content of 5-HT in the brain and inhibiting the expression of OXA and its receptors in the hypothalamus.

4.
Acta Anatomica Sinica ; (6): 88-97, 2024.
Article in Chinese | WPRIM | ID: wpr-1015151

ABSTRACT

Objective To study the stress change characteristics of the cervical disc after removing different ranges of the uncinate process by establishing a three⁃dimensional finite element model of the C

5.
Chinese Journal of Rehabilitation Theory and Practice ; (12): 238-242, 2024.
Article in Chinese | WPRIM | ID: wpr-1013383

ABSTRACT

ObjectiveTo explore the effect of core muscles training based on spinal fine-tuning manipulation on lumbar facet joint disorders. MethodsFrom February, 2021 to February, 2022, 80 patients with lumbar facet joint disorders in Huadong Hospital Affiliated to Fudan University were randomly divided into control group (n = 40) and observation group (n = 40) randomly. Both groups received routine treatment and spinal fine-tuning manipulation, while the observation group received core muscles training in addition, for six weeks. They were assessed with Japanese Orthopaedic Association (JOA) scores, Short-Form of McGill Pain Questionnaire and World Health Organization Quality of Life-BREF before and after treatment. The recurrence rate was observed after three months follow-up. ResultsThe scores of all the scales improved after treatment (t > 5.751, P < 0.001), and improved more in the observation group than in the control group (t > 2.051, P < 0.05). After three months follow-up, the recurrence rate was 7.89% (3/38) in the observation group, less than 28.13% (9/32) in the control group (χ2 = 5.005, P = 0.025). ConclusionCombination of core muscles training may improve lumbar function, reduce lumbar pain, reduce recurrence and improve quality of life for patients with lumbar facet joint disorders.

6.
Journal of Clinical Otorhinolaryngology Head and Neck Surgery ; (12): 44-49, 2024.
Article in Chinese | WPRIM | ID: wpr-1011100

ABSTRACT

Objective:To investigate long-term auditory changes and characteristics of Alport syndrome(AS) patients with different degrees of renal injury. Methods:Retrospectively analyzing clinical data of patients diagnosed AS from January 2007 to September 2022, including renal pathology, genetic detection and hearing examination. A long-term follow-up focusing on hearing and renal function was conducted. Results:This study included 70 AS patients, of which 33(25 males, 8 females, aged 3.4-27.8 years) were followed up, resulting in a loss rate of 52.9%.The follow-up period ranged from 1.1to 15.8 years, with 16 patients followed-up for over 10 years. During the follow-up, 10 patients presenting with hearing abnormalities at the time of diagnosis of AS had progressive hearing loss, and 3 patients with new hearing abnormalities were followed up, which appeared at 5-6 years of disease course. All of which were sensorineural deafness. While only 3 patients with hearing abnormalities among 13 patients received hearing aid intervention. Of these patients,7 developed end-stage renal disease(ESRD), predominantly males (6/7). The rate of long-term hearing loss was significantly different between ESRD group and non-ESRD group(P=0.013). There was no correlation between the progression of renal disease and long-term hearing level(P>0.05). kidney biopsies from 28 patients revealed varying degrees of podocyte lesion and uneven thickness of basement membrane. The severity of podocyte lesion was correlated with the rate of long-term hearing loss(P=0.048), and there was no correlation with the severity of hearing loss(P>0.05). Among 11 cases, theCOL4A5mutationwas most common (8 out of 11), but there was no significant correlation between the mutation type and hearing phenotype(P>0.05). Conclusion:AS patients exhibit progressive hearing loss with significant heterogeneity over the long-term.. THearing loss is more likely to occur 5-6 years into the disease course. Hearing abnormalities are closely related to renal disease status, kidney tissue pathology, and gene mutations, emphasizing the need for vigilant long-term hearing follow-up and early intervention.


Subject(s)
Male , Child , Female , Humans , Nephritis, Hereditary/pathology , Retrospective Studies , Kidney , Deafness , Hearing Loss/genetics , Kidney Failure, Chronic/pathology , Mutation
7.
Chinese Medical Journal ; (24): 2459-2467, 2023.
Article in English | WPRIM | ID: wpr-1007556

ABSTRACT

BACKGROUND@#We have recently developed a new Coronary Artery Tree description and Lesion EvaluaTion (CatLet) angiographic scoring system. Our preliminary studies have demonstrated its superiority over the the Synergy between percutaneous coronary intervention (PCI) with Taxus and Cardiac Surgery (SYNTAX) score with respect to outcome predictions for acute myocardial infarction (AMI) patients. The current study hypothesized that the residual CatLet (rCatLet) score predicts clinical outcomes for AMI patients and that a combination with the three clinical variables (CVs)-age, creatinine, and ejection fraction, will enhance its predicting values.@*METHODS@#The rCatLet score was calculated retrospectively in 308 consecutively enrolled patients with AMI. Primary endpoint, major adverse cardiac or cerebrovascular events (MACCE) including all-cause mortality, non-fatal AMI, transient ischemic attack/stroke, and ischemia-driven repeat revascularization, was stratified according to rCatLet score tertiles: rCatLet_low ≤3, rCatLet_mid 4-11, and rCatLet_top ≥12, respectively. Cross-validation confirmed a reasonably good agreement between the observed and predicted risks.@*RESULTS@#Of 308 patients analyzed, the rates of MACCE, all-cause death, and cardiac death were 20.8%, 18.2%, and 15.3%, respectively. Kaplan-Meier curves for all endpoints showed increasing outcome events with the increasing tertiles of the rCatLet score, with P values <0.001 on trend test. For MACCE, all-cause death, and cardiac death, the area under the curves (AUCs) of the rCatLet score were 0.70 (95% confidence intervals [CI]: 0.63-0.78), 0.69 (95% CI: 0.61-0.77), and 0.71 (95% CI: 0.63-0.79), respectively; the AUCs of the CVs-adjusted rCatLet score models were 0.83 (95% CI: 0.78-0.89), 0.87 (95% CI: 0.82-0.92), and 0.89 (95% CI: 0.84-0.94), respectively. The performance of CVs-adjusted rCatLet score was significantly better than the stand-alone rCatLet score in terms of outcome predictions.@*CONCLUSION@#The rCatLet score has a predicting value for clinical outcomes for AMI patients and the incorporation of the three CVs into the rCatLet score will enhance its predicting ability.@*TRIAL REGISTRATION@#http://www.chictr.org.cn , ChiCTR-POC-17013536.


Subject(s)
Humans , Coronary Artery Disease/complications , Death , Myocardial Infarction/etiology , Percutaneous Coronary Intervention , Retrospective Studies , Risk Assessment , Risk Factors , Treatment Outcome
8.
Journal of Xi'an Jiaotong University(Medical Sciences) ; (6): 315-322, 2023.
Article in Chinese | WPRIM | ID: wpr-1005762

ABSTRACT

【Objective】 To analyze the literature on the relationship between gut microbiota and bone metabolism, identify the current research hotspots and difficulties, and provide research ideas and directions for the clinical prevention and treatment of bone metabolism related diseases. 【Methods】 Based on the Citespace literature visualization analysis software, the co-occurrence and cluster analysis of keywords and other information of the included 394 literatures were performed, and the visual map was drawn. 【Results】 Among the included literatures, the keywords such as inflammatory bowel disease, T cells, dendritic cells, short-chain fatty acids, and chronic kidney disease appeared with high frequency. The cluster of intestinal alkaline phosphatase, metabolic osteoarthritis, dendritic cells, and signaling pathway was the current research hotspot. Recent years have witnessed a rapid increase in published articles in this field, with the United States as the leading origin. 【Conclusion】 The mechanism by which gut microbiota interferes with the immune system and regulates bone metabolism to maintain bone homeostasis is still the core of current research.

9.
Journal of Xi'an Jiaotong University(Medical Sciences) ; (6): 46-54, 2023.
Article in Chinese | WPRIM | ID: wpr-1005499

ABSTRACT

【Objective】 M3 muscarinic acetylcholine receptor(M3 receptor), encoded by CHRM3 gene, is widely distributed in the cardiovascular system and plays an important role in cardiac regulation. The aim of this study was to assess the association of genetic variants in M3 receptor with blood pressure(BP) responses to controlled dietary sodium and potassium interventions. 【Methods】 A total of 333 subjects from 124 families were recruited from the rural areas of northern China. After a three-day baseline observation, they were sequentially on a seven-day low-salt diet, a seven-day high-salt diet, and a seven-day high-salt diet plus potassium supplementation. Thirteen CHRM3 single nucleotide polymorphisms(SNPs) were selected for analysis. 【Results】 SNP rs10802811 of the CHRM3 was significantly associated with diastolic BP(DBP) and mean arterial pressure(MAP) responses to both low-salt and high-salt diets while SNPs rs6429147, rs373288072, rs114677844 and rs663148 showed significant associations with systolic BP(SBP) and MAP responses to high-salt diet. In addition, SNP rs6692904 was significantly associated with SBP, DBP and MAP responses to high-salt diet with potassium supplementation. 【Conclusion】 Genetic variants in M3 receptor are significantly associated with BP responses to sodium and potassium intervention, suggesting that M3 receptor may be mechanistically involved in BP salt and potassium sensitivity.

10.
Journal of Xi'an Jiaotong University(Medical Sciences) ; (6): 38-45, 2023.
Article in Chinese | WPRIM | ID: wpr-1005498

ABSTRACT

【Objective】 Based on our previously established salt-sensitive hypertension cohort, we aimed to examine the association of genetic variants in uromodulin with blood pressure(BP) responses to dietary interventions of sodium and potassium intake. 【Methods】 In 2004, 514 subjects from 124 families in Mei County, Shaanxi Province, were recruited to establish the salt-sensitive hypertension study cohort. Among them, 333 non-parent subjects were selected and sequentially maintained on a normal-diet for 3 days, low-salt diet for 7 days, then a high-salt diet for 7 days and a high-salt diet with potassium supplementation for another 7 days. Thirteen single nucleotide polymorphisms(SNPs) in the uromodulin gene were genotyped on the MassARRAY platform. 【Results】 BP levels decreased from the baseline to low-salt diet, increased from low-salt to high-salt diet, and decreased again from the high-salt diet to the high-salt plus potassium supplementation intervention. SNPs rs77875418 and rs4997081 of the uromodulin gene were significantly associated with diastolic BP(DBP) and mean arterial pressure(MAP) responses to high-salt diet. In addition, SNPs rs77875418, rs79245268, rs4293393, rs6497476, rs4997081, rs13333226, and rs12917707 were significantly associated with systolic BP(SBP), DBP, and MAP responses to high-salt diet with potassium supplementation. 【Conclusion】 Genetic variants in uromodulin gene are significantly associated with BP responses to sodium and potassium supplementation, suggesting that uromodulin may be mechanistically involved in BP sodium-sensitivity and potassium-sensitivity.

11.
Journal of Xi'an Jiaotong University(Medical Sciences) ; (6): 30-37, 2023.
Article in Chinese | WPRIM | ID: wpr-1005497

ABSTRACT

【Objective】 4-like protein with down-regulated expression and development in neural precursor cells (NEDD4L) plays an important role in blood pressure (BP) regulation and sodium homeostasis by regulating epithelial sodium channel protein. In this study, we aimed to explore the relationship of NEDD4L gene polymorphisms with BP responses to sodium and potassium intake. 【Methods】 In 2004, 514 subjects from 124 families in Meixian County, Shaanxi Province, were recruited to establish a salt-sensitive hypertension study cohort. All the subjects received a 3-day baseline survey, a 7-day low-salt diet, a 7-day high-salt diet, and finally a 7-day high-salt and potassium supplementation. Their BP was measured and peripheral blood samples were collected at different intervention periods. The 14 gene polymorphisms of NEDD4L gene were genotyped and analyzed by MassARRAY platform. 【Results】 BP decreased on a low-salt diet, and significantly increased on a high-salt diet, and decreased again after potassium supplementation. NEDD4L SNPs rs74408486 were significantly associated with systolic BP, diastolic BP and mean arterial pressure responses to the low-salt diet. SNPs rs292449 and rs2288775 were significantly associated with pulse pressure response to the high-salt diet. In addition, SNPs rs563283 and rs292449 were significantly associated with diastolic BP, mean arterial pressure, and pulse pressure responses to high-salt and potassium supplementation diet. 【Conclusion】 NEDD4L gene polymorphisms were significantly associated with BP responses to sodium and potassium intake, suggesting that NEDD4L gene may be involved in the development of salt sensitivity and potassium sensitivity.

12.
Journal of Xi'an Jiaotong University(Medical Sciences) ; (6): 6-13, 2023.
Article in Chinese | WPRIM | ID: wpr-1005494

ABSTRACT

【Objective】 Dyslipidemia has shown to be associated with cardiovascular, metabolic and renal diseases. This study aimed to investigate the association between residual cholesterol and the risk of subclinical renal damage (SRD). 【Methods】 A total of 2 342 participants were recruited from the previously established Hanzhong Adolescent Hypertension Study cohort. According to estimated glomerular filtration rate(eGFR) and urinary albumin-to-creatine ratio(uACR), the subjects were divided into SRD group and non-SRD group. The associations of residual cholesterol with eGFR, uACR, and the risk of SRD were analyzed by multiple linear and Logistic regression analyses. 【Results】 Residual cholesterol was positively correlated with uACR(r=0.081, P<0.001) but negatively correlated with eGFR (r=-0.091, P<0.001). Multiple linear regression analysis revealed that residual cholesterol was an influencing factor of uACR (β=0.075, P<0.001) and eGFR (β=-0.027, P<0.001) after adjustment for gender, age, smoke, alcohol, exercise, BMI, hypertension, diabetes and serum uric acid. In addition, Logistic regression analysis revealed that residual cholesterol was significantly associated with the risk of SRD independently of potential confounders [OR(95% CI)=1.387 (1.113-1.728), P<0.001]. Further subgroup analysis showed that residual cholesterol was significantly associated with the risk of SRD in women but not in men. 【Conclusion】 Residual cholesterol is a contributing factor in the risk of subclinical renal damage with gender-specific association.

13.
Acta Anatomica Sinica ; (6): 87-91, 2023.
Article in Chinese | WPRIM | ID: wpr-1015251

ABSTRACT

Objective To establish the spatial course of distal tubule and afferent arterioles after macula densa, and to locate and detect the proteins in the adjacent parts by using three-dimensional visualization technology of microstructure. Methods C57 BL/6J mice were fixed by perfusion and embedded in epon 812. Tissue blocks were cut perpendicular to the longitudinal axis of the kidney. And a total of 720, 2. 5 μm-thick consecutive sections were obtained from the renal capsule to the outer stripe of the renal outer medulla. After aligning the digital microscopic images through computer registration procedures, the tubules and vessels were traced by 3D reconstruction program edited by C Language. Selecting the tissue sections of the contact site and applying the improved immunoperoxidase staining method to detect H

14.
Acta Anatomica Sinica ; (6): 593-598, 2023.
Article in Chinese | WPRIM | ID: wpr-1015185

ABSTRACT

[Abstract] Objective To investigate the branching pattern of the ureteric bud and the number of the nephron induced by each ureteric bud tip, through the three-dimensional tracing of the ureteric tree, combined with the morphological analysis and measurement of the ureteric tree. Methods The kidneys were obtained from three mice at various developing time points and prepared for paraffin and epoxy sections. Then the microscopic images were digitized and aligned from these sections. Based on the computer-assisted tracing and visualization of ureteric tree, the number of branches and the nephron induced by each ureteric bud tip were obtained by counting. In addition, paraffin sections were stained with HE staining for morphological observation of nephrogenic zone and ureteric bud, while in order to reflect the density of the ureteric bud tips at nephrogenic zone, the distance between two neighboring ureteric bud tips was measured aided with the Claudin-7 immunohistochemical staining. Results The ureteric bud branching tree revealed that the initial bifid iterative branching formed the framework of renal medulla, the branching became complicated and dense in cortex and nephrogenic zone, while the distance between ureteric bud tips were also decreasing. The number of the nephron induced by each ureteric bud tip increased from one (E14. 5) to two (E17. 5), and occasionally to three. Conclusion Threedimeasional Visualization of ureteric bud branching tree reveals regional complication, suggesting molecules in different regions drive different branching patterns; While the density of the ureteric bud tips at nephrogenic zone increases corresponding to decreasing of thickness of the nephrogenic zone, and the disappearance of the ureteric bud tips after birth is also consistent with the gradual consumption of nephron progenitor cells.

15.
Chinese Journal of Clinical Pharmacology and Therapeutics ; (12): 876-886, 2023.
Article in Chinese | WPRIM | ID: wpr-1014610

ABSTRACT

Since the beginning of the 21st century, with the continuous development of anti-HER2-targeted drugs, more treatment options have been provided for patients with HER2-positive breast cancer and the survival prognosis has been significantly improved. At present, anti-HER2 targeted drugs mainly include monoclonal antibody drugs such as trastuzumab and pertuzumab, small molecule tyrosine kinase inhibitors such as lapatinib and neratinib, and antibody-drug conjugates such as TDM1 and T-DXd, which play an extremely important role in different disease processes. The treatment of HER2-positive breast cancer is based on targeted therapy with trastuzumab. Early-stage patients with high risk factors can be treated with intensive targeted therapy to further improve the prognosis, while advanced patients need a reasonable arrangement of targeted therapy to overcome drug resistance and prolong survival. This article will review the current status, the latest research progress and the future prospects of anti-HER2 targeted therapy in different stages of the disease.

16.
Chinese Pharmacological Bulletin ; (12): 1417-1421, 2023.
Article in Chinese | WPRIM | ID: wpr-1013953

ABSTRACT

Methamphetamine abuse and HIV infection are extremely serious public health and social problems facing the world today. Methamphetamine and HIV-1 Tat protein can induce neurotoxicity in an individual and synergistic way, and neuroinflammation is one of the most important mechanisms for ca-using neurotoxicity. Neuroinflammation can be mediated by glial cells, cytokines, NLRP3 inflammasomes, etc. This paper reviews the research progress of neuroinflammation induced by methamphetamine and HIV-1 Tat protein in recent years, with the aim of providing reference and basis for further exploration of the mechanisms of neuroinflammation caused by them and effective drug intervention targets in the future.

17.
Chinese Pharmacological Bulletin ; (12): 917-925, 2023.
Article in Chinese | WPRIM | ID: wpr-1013935

ABSTRACT

Aim To investigate the inhibitory effect of ginsenoside Rg1 on sodium palmitate induced fibrosis in human glomerullar mesangial cells (HMCs) and its mechanism. Methods (1) HMCs were treated with different concentrations of PA for 24 h, the intracellular lipid accumulation was observed by oil red staining, and the intracellular ROS production was detected by H2DCFDA kit; (2) HMCs were divided into control, PA (160 μmol·L

18.
Chinese Pharmacological Bulletin ; (12): 1068-1073, 2023.
Article in Chinese | WPRIM | ID: wpr-1013899

ABSTRACT

Aim To analyze the genotype-phenotype characteristics of voltage-gated potassium channels (Kv) associated genetic epilepsy and evaluate the efficacy of anti-seizure medications(ASMs). Methods PubMed database was searched and patients meeting the inclusion criteria were included for analysis. We divided the patients into “benign”, “encephalopathic” and other phenotypes according to the clinical characteristics. We performed descriptive statistical analysis of patients' mutated genes, clinical phenotype and drug efficacy, and used logistic regression to explore the influencing factors of treatment outcome. Results Data of 474 children were included for analysis. There were significant differences among different phenotypes in mutated genes, source of mutations and so on. In terms of clinical characteristics, there were also significant differences between patients with different phenotypes in age of onset, combined developmental delay and so on. In terms of monotherapy, phenobarbital was the most common treatment choice for children with “benign” phenotype, and sodium channel blockers (SCBs) were the most common treatment choice for children with “encephalopathy” phenotype, and the efficacy of SCBs monotherapy was superior to that of other ASMs. Multivariate Logistic analysis of the children receiving monotherapy showed that whether the children were combined with developmental delay and whether SCBs were used were significant factors influencing the efficacy of drug therapy. Conclusions Patients with the “benign” and “encephalopathic” phenotypes differ in several aspects of genetic variation, clinical characteristics, and drug selection. These results suggest that SCBs may be one of the recommended options for monotherapy.

19.
Chinese Pharmacological Bulletin ; (12): 1566-1576, 2023.
Article in Chinese | WPRIM | ID: wpr-1013745

ABSTRACT

Aim To investigate the mechanism of corn silk decoction on diabetic nephropathy (DN) rats using metabolomics technology. Methods DN rat model was established by feeding with high-sugar and high-fat diet, combined with intraperitoneal injection of low dose streptozotocin. Renal organ index, fasting blood glucose, albumin creatinine ratio, serum creatinine, blood urea nitrogen, triglyceride, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol indexes were measured, and the pathological changes of renal tissues were also observed to evaluate the intervention effect of corn silk on DN model rats. Further, UPLC/Q-TOF-MS technology was used to screen potential biomarkers in renal tissues and urine, combined with principal component analysis (PC A) and orthogonal partial least squares discriminant analysis (OPLS-DA). After identification by HM-DB and KEGG database, the biomarkers were imported into MetaboAnalyst for metabolic pathway analysis. Results All indexes and pathological damage of kidneys were improved in groups with different doses of corn silk, indicating that corn silk had a good intervention effect on DN. Metabolomic analysis showed that 18 biomarkers could be significantly called back by corn silk, and it involved 18 metabolic pathways mainly including phenylalanine, tyrosine and tryptophan biosynthesis, riboflavin metabolism, arachidonic acid metabolism, and tyrosine metabolism. Conclusions The mechanism of corn silk decoction intervention on DN may be related to amino acid metabolism, riboflavin metabolism, and arachidonic acid metabolism.

20.
Acta Pharmaceutica Sinica B ; (6): 4945-4962, 2023.
Article in English | WPRIM | ID: wpr-1011213

ABSTRACT

The bacterial ATP-competitive GyrB/ParE subunits of type II topoisomerase are important anti-bacterial targets to treat super drug-resistant bacterial infections. Herein we discovered novel pyrrolamide-type GyrB/ParE inhibitors based on the structural modifications of the candidate AZD5099 that was withdrawn from the clinical trials due to safety liabilities such as mitochondrial toxicity. The hydroxyisopropyl pyridazine compound 28 had a significant inhibitory effect on Gyrase (GyrB, IC50 = 49 nmol/L) and a modest inhibitory effect on Topo IV (ParE, IC50 = 1.513 μmol/L) of Staphylococcus aureus. It also had significant antibacterial activities on susceptible and resistant Gram-positive bacteria with a minimum inhibitory concentration (MIC) of less than 0.03 μg/mL, which showed a time-dependent bactericidal effect and low frequencies of spontaneous resistance against S. aureus. Compound 28 had better protective effects than the positive control drugs such as DS-2969 ( 5) and AZD5099 ( 6) in mouse models of sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. It also showed better bactericidal activities than clinically used vancomycin in the mouse thigh MRSA infection models. Moreover, compound 28 has much lower mitochondrial toxicity than AZD5099 ( 6) as well as excellent therapeutic indexes and pharmacokinetic properties. At present, compound 28 has been evaluated as a pre-clinical drug candidate for the treatment of drug-resistant Gram-positive bacterial infection. On the other hand, compound 28 also has good inhibitory activities against stubborn Gram-negative bacteria such as Escherichia coli (MIC = 1 μg/mL), which is comparable with the most potent pyrrolamide-type GyrB/ParE inhibitors reported recently. In addition, the structure-activity relationships of the compounds were also studied.

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