1.Research progress of anti-gout small molecules targeting the NLRP3 inflammasome
Zhen-qian WANG ; Zhi-jiao ZHANG ; Xin-yong LIU ; Peng ZHAN
Acta Pharmaceutica Sinica 2024;59(3):543-553
Currently, clinically used drugs for the treatment of gout inflammation, such as colchicine, nonsteroidal anti-inflammatory drugs, and glucocorticoids, can only relieve the pain of joint inflammation and have severe hepatorenal toxicity and multiple organ adverse reactions. The NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome is a key complex that induces the onset of gout inflammation and has become a crucial target in the development of anti-gout drugs. This article reviews the research progress of anti-gout small molecules targeting the NLRP3 inflammasome and their bioactivity evaluation methods in the past five years, in order to provide information for the development of specific drugs for the treatment of gout inflammation.
2.Analysis of hypothermia factors for elderly patients with malnutrition during proximal femoral nail antirota-tion internal fixation under general anesthesia
Qian-Nan FAN ; Zhi-Yong YAN ; Hao WU ; Jing-Ying LIU ; Ying GENG ; Ti-Jun DAI
Journal of Regional Anatomy and Operative Surgery 2024;33(2):145-148
Objective To analyze the incidence and risk factors of hypothermia in elderly patients with malnutrition during proximal femoral nail antirotation(PFNA)internal fixation under general anesthesia.Methods A total of 139 elderly patients underwent PFNA internal fixation under general anesthesia were selected,and the nutritional status scores 1 day before surgery ranged from 0 to 11 points.Univariate and multivariate Logistic binary regression analysis was performed to analyze the related factors that may lead to intraoperative hypothermia.Results Among 139 elderly patients with preoperative nutritional scores of 0 to 11 points,79 cases(56.83%)developed intraoperative hypothermia.The results of univariate and multivariate Logistic binary regression analysis suggested that age≥75 years old,mini nutritional assessment short form(MNA-SF)nutritional score 0 to 7 points,BMI<18.5 kg/m2,duration of general anesthesia≥2 hours,intraoperative flushing fluid volume≥1 000 mL and intraoperative fluid volume≥1 000 mL were the risk factors for the occurrence of intraoperative hypothermia in elderly patients(OR>1,P<0.05).The use of warm blanket insulation was the protective factor against the occurrence of intraoperative hypothermia(OR<1,P<0.05).Conclusion The incidence of intraoperative hypothermia during PFNA internal fixation under general anesthesia in elderly patients with mainutrition before operation is high,and patients with poor nutritional status are more likely to develop intraoperative hypothermia.Patients with older age,poor nutritional status,lower BMI,longer duration of general anesthesia,and more intraoperative flushing fluid volume and intraoperative fluid volume are likely to lead to intraoperative hypothermia.The use of warm blanket can reduce the incidence of intraoperative hypothermia.
3.A quantitative evaluation of China's digital health policy based on PMC index model
Chinese Journal of Health Policy 2024;17(10):59-67
Objective:To quantitatively evaluate China's digital health policies since the new healthcare reform,and provide recommendations for future policy formulation and optimization.Methods:Employing ROSTCM6 software,we conducted text mining analysis on 130 national-level digital health policies.Based on the findings,we constructed a PMC Index Model evaluation system comprising 9 primary variables and 42 secondary variables.From these policies,20 representative texts were selected for in-depth quantitative analysis.Results:The average PMC score of the 20 policies analyzed was 5.47,indicating overall excellence.One policy achieved the perfect standard,12 were rated as excellent,and 7 fell within the acceptable range.Notably,no policies were classified as inadequate.Conclusion:While China's digital health policies demonstrate considerable success,there are opportunities for improvement.It is crucial to fortify the temporal effectiveness of policies and implement systems for continuously monitoring the dynamic shifts within the policy environment.Furthermore,clarifying the roles of various policy actors and establishing a diversified collaborative governance mechanism are essential to ensuring effective policy implementation.Increase economic incentives to promote digital technology innovation and focus on policy balance to promote the development of the digital health industry.
4.Predictive Ability of Hypertriglyceridemic Waist,Hypertriglyceridemic Waist-to-Height Ratio,and Waist-to-Hip Ratio for Cardiometabolic Risk Factors Clustering Screening among Chinese Children and Adolescents
Li Tian XIAO ; Qian Shu YUAN ; Yu Jing GAO ; S.Baker JULIEN ; De Yi YANG ; Jie Xi WANG ; Juan Chan ZHENG ; Hui Yan DONG ; Yong Zhi ZOU
Biomedical and Environmental Sciences 2024;37(3):233-241
Objective Hypertriglyceridemic waist(HW),hypertriglyceridemic waist-to-height ratio(HWHtR),and waist-to-hip ratio(WHR)have been shown to be indicators of cardiometabolic risk factors.However,it is not clear which indicator is more suitable for children and adolescents.We aimed to investigate the relationship between HW,HWHtR,WHR,and cardiovascular risk factors clustering to determine the best screening tools for cardiometabolic risk in children and adolescents. Methods This was a national cross-sectional study.Anthropometric and biochemical variables were assessed in approximately 70,000 participants aged 6-18 years from seven provinces in China.Demographics,physical activity,dietary intake,and family history of chronic diseases were obtained through questionnaires.ANOVA,x2 and logistic regression analysis was conducted. Results A significant sex difference was observed for HWHtR and WHR,but not for HW phenotype.The risk of cardiometabolic health risk factor clustering with HW phenotype or the HWHtR phenotype was significantly higher than that with the non-HW or non-HWHtR phenotypes among children and adolescents(HW:OR = 12.22,95%CI:9.54-15.67;HWHtR:OR = 9.70,95%CI:6.93-13.58).Compared with the HW and HWHtR phenotypes,the association between risk of cardiometabolic health risk factors(CHRF)clustering and high WHR was much weaker and not significant(WHR:OR = 1.14,95%CI:0.97-1.34). Conclusion Compared with HWHtR and WHR,the HW phenotype is a more convenient indicator with higher applicability to screen children and adolescents for cardiovascular risk factors.
5.Mechanism of Yi Sui Sheng Xue Fang in improving renal injury induced by chemotherapy in mice based on Keap1/Nrf2 signaling pathway
Yu LIU ; Li-Ying ZHANG ; Ya-Feng QI ; Yang-Yang LI ; Shang-Zu ZHANG ; Qian XU ; Guo-Xiong HAO ; Fan NIU ; Yong-Qi LIU ; Zhi-Ming ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(5):703-707
Objective To study the effect and mechanism of action of Yi Sui Sheng Xue Fang(YSSX)in ameliorating chemotherapy-induced renal injury in mice through The Kelch-like ECH-associated protein 1(KEAP1)/Nuclear factor erythroid-derived 2-like 2(NRF2)signalling pathway.Methods A mouse kidney injury model was induced by intraperitoneal injection of carboplatin(40 mg·kg-1).C57BL/6 mice were randomly divided into blank group(0.9%NaCl),model group(kidney injury model)and experimental-L,experimental-M,experimental-H groups(0.53,1.05 and 2.10 g·kg-1·d-1 YSSX by gavage for 7 d).Keap1 and Nrf2 were determined by Western blot;superoxide dismutase(SOD)and malondialdehyde(MDA)activities were determined by spectrophotometry.Results The protein expression levels of Keap1 in blank group,model group and experimental-L,experimental-M,experimental-H groups were 0.26±0.02,0.64±0.03,0.59±0.01,0.45±0.05 and 0.34±0.02;the protein expression levels of Nrf2 were 0.69±0.06,0.35±0.01,0.36±0.01,0.48±0.02 and 0.56±0.01;the enzyme activities of catalase(CAT)were(572.49±912.92),(334.60±4.92),(402.76±9.80),(475.35±5.21)and(493.00±12.03)U·mg-1;glutathione(GSH)were(2.79±0.06),(0.51±0.01),(0.59±0.07),(1.29±0.04)and(1.70±0.08)μmol·L1;SOD were(477.00±4.32),(260.67±6.13),(272.67±2.87),(386.33±3.68)and(395.00±12.25)U·mL-1;MDA were(3.89±0.02),(7.32±0.03),(6.94±0.14),(4.60±0.01)and(4.34±0.02)nmol·mg prot-1.The differences of the above indexes in the model group compared with the blank group were statistically significant(P<0.01,P<0.001);the differences of the above indexes in experimental-M,experimental-H groups compared withe model group were statistically significant(P<0.01,P<0.001).Conclusion YSSX can activate Keap1/Nrf2 signaling pathway and regulate the oxidative stress state of the organism,thus improving the renal injury caused by chemotherapy in mice.
6.Pathological mechanism of hypoxia-inducible factor-1α in tumours and the current status of research on Chinese medicine intervention
Yu LIU ; Li-Ying ZHANG ; Guo-Xiong HAO ; Ya-Feng QI ; Qian XU ; Ye-Yuan LIU ; Chao YUAN ; Peng ZHU ; Yong-Qi LIU ; Zhi-Ming ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(11):1670-1674
Traditional Chinese medicine can regulate the hypoxia-inducible factor-1α(HIF-1α)signalling pathway and slow down tumour progression mainly by inhibiting tumour angiogenesis,glycolysis,epithelial mesenchymal transition and other pathological processes.This paper,starting from HIF-1α and related factors,reviews its pathological mechanism in tumours and the research of traditional Chinese medicine interventions with the aim of providing theoretical references for the treatment of tumours with traditional Chinese medicine.
7.Integrated Metagenomics and UPLC-Q-TOF-MS/MS to Explore the Mechanism of Dexamethasone on Pneumonia in Rats
Si-ju LI ; Qian ZHANG ; Yun LENG ; Bi-yan PAN ; Zhi-yong XIE ; Hong-ying CHEN
Journal of Sun Yat-sen University(Medical Sciences) 2023;44(2):232-243
ObjectiveUsing multi-omics technology, we conducted the present study to determine whether dexamethasone has therapeutic effect on pneumonia rats through the regulation of intestinal flora and metabolites. MethodsTotally 18 Sprague-Dawley rats were randomly divided into 3 groups (n = 6 each): Control group, Model group and Dexamethasone (Dex) group. Lipopolysaccharide (LPS) was continuously injected intraperitoneally into rats at a dose of 4 mg/kg for 7 days to induce pneumonia except the Control group. Then the Dex group was given Dex at a dose of 2 mg/kg via oral gavage for 12 days, and both the other two groups received continuously equal volume of sterile PBS buffer for 12 days. On the 19th day, lung, plasma, feces and intestinal contents of rat were collected. Hematoxylin-eosin (H&E) staining and Bio-plex suspension chip system were applied to evaluate the effect of Dex on pneumonia. Furthermore, metagenomic sequencing and UPLC-Q-TOF-MS/MS technology were employed to determine the intestinal flora and metabolites of rats, respectively. ResultsH&E staining results showed that the lung tissue of the Model group was infiltrated with inflammatory cells, the alveolar septum was increased, alveolar hemorrhage, and histological lesions were less severe in Dex group than in the model group. The levels of 3 inflammatory cytokines including TNF-α (P < 0.000 1), IL-1α (P = 0.009 6) and IL-6 (P < 0.000 1) in the Model group were increased compared with the Control group, while Dex treatment reduced the levels of the three inflammatory factors. Taken together, Dex treatment effectively reversed the features of pneumonia in rats. Metagenomic analysis revealed that the intestinal flora structure of the three groups of rats was changed. In contrast with the Model group, an increasing level of the Firmicutes and an elevated proportion of Firmicutes/Bacteroidetes were observed after Dex treatment. Dex-treated rats possessed notably enrichment of Bifidobacterium, Lachnospiraceae and Lactobacillus. Multivariate statistical analysis showed a great separation between Model group and Dex group, indicating metabolic profile changes. In addition, 69 metabolites (P < 0.05) were screened, including 38 up-regulated in the Model group and 31 elevated in the Dex group, all of which were mainly involved in 3 metabolic pathways: linoleic acid metabolism, tryptophan metabolism and primary bile acid biosynthesis. ConclusionsIn summary, we demonstrate the beneficial effects of Dex on the symptoms of pneumonia. Meanwhile, integrated microbiome-metabolome analysis reveals that Dex improves LPS-induced pneumonia in rats through regulating intestinal flora and host metabolites. This study may provide new insights into the mechanism of Dex treatment of pneumonia in rats.
8.Analysis of cockroach surveillance in Liaoning Province in 2021
ZHANG Jia-yong ; BAI Yu-yin ; WANG Chun-yu ; ZHANG Ji-bo ; LI Zhi ; ZHANG Qian ; DING Jun
China Tropical Medicine 2023;23(5):529-
Abstract: Objective To master the condition of cockroach population distribution, seasonal dynamics, cockroach density for different habitat, and to provide a basis for developing cockroach control strategies. Methods Six types of surveillance sites, including residential areas, hotels, restaurants, supermarkets, hospitals and farm product markets, were set up in 14 cities in Liaoning to monitor cockroaches using the sticky-trap method. The cockroach surveillance data from vector surveillance sites in fourteen cities of Liaoning Province in 2021 were collected and statistically analyzed using Excel 2010 and SPSS 23.0 software. The density and species composition of cockroaches were analyzed, and the density difference and seasonal dynamics trend of cockroaches in different habitats were compared. Results A total of 3 031 cockroaches were captured in 2021, of which Blattella germanica accounted for 94.66% (2 869/3 031) and was the dominant population. The total density of cockroaches was 0.230 0 cockroaches per sheet (3 031/13 234) and the total infestation rate of cockroaches was 5.59% (562/10 052). The density and infestation rate of cockroaches in different habitats were in the order of farm product markets, restaurants, and hotels and the difference in infestation rate between habitats was statistically significant (χ2=168.327, P<0.05). The seasonal dynamics trend of cockroach density and disoperation rate showed a unimodal curve, and the peaks were distributed in July. The seasonal dynamics of cockroach density and disoperation rate in different habitats showed a unimodal curve in the habitats of farm product markets, supermarkets, hotels, hospitals and residential areas all, while the habitats of restaurants were close to a double peak curve. Conclusions B. germanica is the dominant species of cockroaches in Liaoning Province in 2021. Compared with 2020 the density and disoperation rate of cockroach in 2021 showed a slight downward trend, and the seasonal dynamics trend of cockroach density and disoperation rate showed a unimodal curve. The farm product markets are the key places for cockroach prevention and control. According to the seasonal fluctuation trends in cockroach density and infestation rate in different habitats, comprehensive prevention and control measures should be taken before the peak periods to reduce cockroach density and control diseases.
9.The value of transanal multipoint full-layer puncture biopsy in determining the response degree of rectal cancer following neoadjuvant therapy: a prospective multicenter study.
Jia Gang HAN ; Li Ting SUN ; Zhi Wei ZHAI ; Ping Dian XIA ; Hang HU ; Di ZHANG ; Cong Qing JIANG ; Bao Cheng ZHAO ; Hao QU ; Qun QIAN ; Yong DAI ; Hong Wei YAO ; Zhen Jun WANG
Chinese Journal of Surgery 2023;61(9):769-776
Objective: To verify the feasibility and accuracy of the transanal multipoint full-layer puncture biopsy (TMFP) technique in determining the residual status of cancer foci after neoadjuvant therapy (nCRT) in rectal cancer. Methods: Between April 2020 and November 2022, a total of 78 patients from the Beijing Chaoyang Hospital of Capital Medical University, the Beijing Friendship Hospital of Capital Medical University, the Qilu Hospital of Shandong University, the Zhongnan Hospital of Wuhan University with advanced rectal cancer received TMFP after nCRT participated in this prospective multicenter trial. There were 53 males and 25 females, aged (M(IQR)) 61 (13) years (range: 35 to 77 years). The tumor distance from the anal verge was 5 (3) cm (range: 2 to 10 cm). The waiting time between nCRT and TMFP was 73 (26) days (range: 33 to 330 days). 13-point transanal puncture was performed with a 16 G tissue biopsy needle with the residual lesion as the center. The specimens were submitted for independent examination and the complications of the puncture were recorded. The consistency of TMFP and radical operation specimen was compared. The consistency of TMPF with clinical remission rates for the diagnosis of complete pathological remission was compared by sensitivity, specificity, negative predictive value, positive predictive value and accuracy. Statistical analysis between groups was performed using the χ2 analysis, and a paired χ2 test was used to compare diagnostic validity. Results: Before TMFP, clinical complete response (cCR) was evaluated in 27 cases. Thirty-six cases received in vivo puncture, the number of punctures in each patient was 13 (8) (range: 4 to 20), 24 cases of tumor residue were found in the puncture specimens. The sensitivity to judgment (100% vs. 60%, χ2=17.500, P<0.01) and accuracy (88.5% vs. 74.4%, χ2=5.125, P=0.024) of TMFP for the pathologic complete response (pCR) were significantly higher than those of cCR. Implement TMFP based on cCR judgment, the accuracy increased from 74.4% to 92.6% (χ2=4.026, P=0.045). The accuracy of the in vivo puncture was 94.4%, which was 83.3% of the in vitro puncture (χ2=1.382, P=0.240). Overall, the accuracy of TMFP improved gradually with an increasing number of cases (χ2=7.112, P=0.029). Conclusion: TMFP is safe and feasible, which improves the sensitivity and accuracy of rectal cancer pCR determination after nCRT, provides a pathological basis for cCR determination, and contributes to the safe development of the watch and wait policy.
10.Quality evaluation methods of Poria based on yield and content of alkali extracted polysaccharide.
Yue WANG ; Xiao-Qian LIU ; Yong-Xin ZHANG ; Wei-Hong FENG ; Li-Hua YAN ; Zhi-Min WANG
China Journal of Chinese Materia Medica 2023;48(2):443-454
To improve the quality control methods of Poria and develop and utilize its resources fully, alkaline extraction was used in this study to determine the yield and content of alkali-soluble polysaccharides of Poria. The alkali-soluble extracts of Poria were obtained according to the optimum extraction conditions on the basis of single-factor test, and 30 batches of samples were determined. The structure and chemical composition of the alkali-soluble extracts was characterized by high-performance gel permeation chromatography(HPGPC), Fourier transform infrared spectrometry(FT-IR), nuclear magnetic resonance(NMR) spectroscopy and high-performance liquid chromatography(HPLC) with 1-phenyl-3-methyl-5-pyrazolone(PMP-HPLC). The results showed that the content of the alkali-soluble extracts was in the range of 46.98%-73.86%. The main component was β-(1→3)-glucan, and its molecular mass was about 1.093×10~5. Further, the content of alkali-soluble polysaccharides of Poria was measured by UV-Vis spectrophotometry and HPLC coupled with the evaporative light scattering detector(HPLC-ELSD), and 30 batches of samples were measured. The results indicated that the content of alkali-soluble polysaccharides determined by UV-Vis spectrophotometry was in the range of 73.70%-92.57%, and the content of samples from Hubei province was slightly higher than that from Yunnan province, Anhui province and Hunan province. The content of alkali-soluble polysaccharides determined by HPLC-ELSD was in the range of 51.42%-76.69%, and the samples from Hunan province had slightly higher content than that from the other three provinces. The content determined by UV-Vis spectrophotometry was higher than that by HPLC-ELSD. However, the content determined by HPLC-ELSD was close to that of alkali-soluble extract, which could accurately characterize the content of alkali-soluble polysaccharides in Poria, and the method was simple and repeatable. Therefore, it is recommended that the quantitative analysis method for alkali-soluble extract and alkali-soluble polysaccharides by HPLC-ELSD be used in the quality standards of Poria in Chinese Pharmacopeia.
Poria/chemistry*
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Spectroscopy, Fourier Transform Infrared
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China
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Polysaccharides/chemistry*
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Reference Standards
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Chromatography, High Pressure Liquid/methods*

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