1.Effects of kaempferol on airway inflammation in rats with chronic obstructive pulmonary disease
Zheng-Ye WANG ; Sheng-Lin XU ; Wen-Wen WANG ; Ting LU ; Li-Li LIN
The Chinese Journal of Clinical Pharmacology 2024;40(2):215-219
Objective To explore the mechanism of kaempferol in improving airway inflammation in chronic obstructive pulmonary disease(COPD)rats.Methods Twenty-for male SD rats were randomly divided into control group,model group(exposed to second-hand smoke for 36 weeks)and experimental group(intragastric administration of 20 mg·kg-1 kaempferol from the 7th day of exposure to secondhand smoke).Pulmonary function was measured by small animal pulmonary function test system,lung index was calculated by body weight and lung weight,inflammatory infiltration and fibrosis changes in lung tissue were observed histologically,the expression of interleukin-1(IL-1),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in bronchoalveolar lavage fluid was detected by enzyme linked immunosorbent assay(ELISA);the expression of superoxide dismutase(SOD)and malondialdehyde(MDA)was detected by the detection kit;and the protein expression of Toll-like receptor 4(TLR4)and nuclear factor-κB(NF-κB)p65 in lung tissue was detected by Western blotting.Results The peak expiratory flow in the control group,model group and experimental group were(19.48±1.61),(15.86±1.00)and(18.07±0.83)mL·s-1;valsalva maneuver were(231.22±10.26),(244.94±9.32)and(225.71±3.80)mL·min-1;lung compliance were(0.53±0.08),(0.29±0.02)and(0.48±0.03)mL·cm-1 H2O;total airway resistance were(0.19±0.12),(0.21±0.01)and(0.20±0.01)cmH2O·mL-1;running economy were(0.19±0.01),(0.26±0.03)and(0.21±0.01)mL·s-1;lung weight were(2.76±0.10),(2.94±0.18)and(2.29±0.26)g;body weight were(375.13±23.55),(243.00±26.75)and(325.38±23.80)g;lung index were 0.74±0.02,1.22±0.09 and 0.70±0.05;the expression levels of cytokines IL-1 in bronchoalveolar lavage fluid(BALF)were(32.39±3.37),(161.88±9.02)and(66.44±6.81)pg·mL-1;IL-6 were(75.07±8.87),(129.58±13.29)and(99.94±9.92)pg·mL-1;TNF-α were(441.76±9.92),(814.47±122.02)and(656.70±70.06)pg·mL-1;MDA expression were(135.73±6.20),(179.05±15.18)and(149.40±13.83)nmol·mL-1;SOD expression were(4 258.55±384.12),(1 232.24±237.08)and(2 134.33±197.99)U·mL-1;TLR4 protein expression level in lung tissue were 0.98±0.02,1.55±0.04,1.34±0.02;NF-κB p65 protein expression level were 0.98±0.02,1.61±0.03,1.09±0.03;the above indicators,control group compared with model group,experimental compared with and model group,the differences were all statistically significant(all P<0.05).Conclusion Kaempferol ameliorates lung injury induced by airway inflammation in COPD rats by inhibiting TLR4/NF-κB signaling pathway.
2.Clinical trial of montelukast sodium combined with desloratadine citrate disodium in the treatment of patients with chronic urticaria
Cui-Hua REN ; Zheng-Wen LU ; Hao SHENG ; Zhang XU
The Chinese Journal of Clinical Pharmacology 2024;40(5):659-662
Objective To observe the clinical efficacy and safety of montelukast sodium chewable tablets combined with desloratadine citrate disodium tablets in the treatment of patients with chronic urticaria.Methods Patients with chronic urticaria were divided into control group and treatment group according to cohort method.Control group was treated with montelukast sodium chewable tablets 10 mg per night,orally chewed.On the basis of control group,the treatment group was treated with desloratadine citrate disodium tablets 8.8 mg each time,qd,orally.Two groups of patients were treated for 4 weeks.The clinical efficacy,serum levels of immunoglobulin E(IgE),interleukin-4(IL-4)and interferon-γ(INF-γ),and adverse drug reactions were compared between two groups.Results The treatment group and control group were enrolled with 68 and 66 cases,respectively.After treatment,the total effective rates of treatment and control groups were 95.59%(65 cases/68 cases)and 83.33%(55 cases/66 cases)with significant difference(P<0.05).After treatment,the IgE levels of treatment and control groups were(70.55±8.50)and(92.57±9.65)U·mL-1;the IL-4 levels were(6.87±1.35)and(8.49±1.23)pg·mL-1;the INF-γ levels were(23.24±6.87)and(19.83±6.75)pg·mL-1;the differences were statistically significant(all P<0.05).The adverse drug reactions of treatment group were drowsiness and fatigue,while those in the control group were drowsiness and fatigue.The total incidences of adverse drug reactions in the treatment and control groups were 8.82%and 4.55%without significant difference(P>0.05).Conclusion Montelukast sodium chewable tablets combined with desloratadine citrate disodium tablets have a definitive clinical efficacy in the treatment of patients with chronic urticaria,which can effectively regulate the serum levels of IgE,IL-4 and INF-γ,without increasing the incidence of adverse reactions.
3.Effects of puerarin apioside on hepatic lipid metabolism in non-alcoholic fatty liver disease mice
Zhi SHANG ; Yin-Lu HU ; Sheng-Lin XU ; Li-Li LIN
The Chinese Journal of Clinical Pharmacology 2024;40(11):1598-1602
Objective To investigate the preventive effects of puerarin apioside on a non-alcoholic fatty liver disease(NAFLD)mouse model and its influence on hepatic lipid metabolism.Methods Thirty-two male C57BL/6J mice were randomly divided into the normal group,model group and experimental-L,-H groups,with 8 mice in each group.The normal group was given regular maintenance feed;the other 3 groups were fed to construct NAFLD model.Experimental-L,-H groups were given 5 and 10 mg·kg-1 puerarin apioside by gavage.Normal and model groups were treated with an equal amount of dimethylsulfoxide by gavage.Four groups were administered once a day for 8 weeks.Changes in mouse body weight were measured.Serum levels of glutamic-pyruvic transaminase(GPT)and glutamic-oxaloacetic transaminase(GOT)and the levels of total cholesterol(TC)and triglycerides(TG)in hepatic tissue were determined by kit.Western blot was used to evaluate the expression levels of acetyl-coenzyme A carboxylase 1(ACC1)and phosphorylated 5'-adenosine monophosphate-activated protein kinase(p-AMPK).Results The body weights of mice in the normal,model and experimental-L,-H groups were(32.69±1.37),(45.51±3.29),(41.18±3.22)and(38.28±2.62)g;serum GPT levels were(36.53±6.44),(134.56±39.91),(121.54±43.38)and(75.92±25.98)U·L-1;serum GOT levels were(60.81±8.74),(188.51±39.70),(156.02±41.67)and(126.79±16.49)U·L-1;hepatic TC levels were(2.17±0.24),(6.46±1.22),(5.86±0.66)and(3.62±0.45)mmol·L-1;hepatic TG levels were(0.57±0.09),(1.39±0.27),(1.28±0.34)and(0.73±0.19)mmol·L-1;the relative expression levels of ACC1 protein were 1.01±0.04,2.00±0.02,1.47±0.08 and 1.20±0.09;the relative expression levels of p-AMPK protein were 1.03±0.09,0.33±0.02,0.66±0.04 and 0.95±0.08,respectively.The differences between the model group and the normal and experimental-H groups were statistically significant for all the above indicators(all P<0.05).Conclusion Puerarin apioside can improve the hepatic lipid metabolism in NAFLD mice by regulating the AMPK signaling pathway.
4.Consideration of countermeasures to promote family doctor contracting rate and first-return-visit rate in primary care institutions
Fei SHENG ; Ping LU ; Liqing ZHOU ; Bihua CHEN ; Chuntao YI ; Jiangen CHEN ; Fulai SHEN ; Tiantian DENG ; Dongjian XU ; Liling MAO
Chinese Journal of General Practitioners 2024;23(2):180-184
Based on the analysis of the existing problems and implementation dilemmas in family doctor contracting and first-return-visits faced by primary medical institutions in China, the authors propose countermeasures to provide reference for managers of primary health care institutions.
5.Survey on availability of dental services in Shanghai community health service centers and differences between urban and suburban areas
Bin CHEN ; Xianguo XU ; Lu SHENG
Chinese Journal of General Practitioners 2024;23(3):251-257
O bjective To survey the availability of dental services in Shanghai community health service centers and the differences between urban and suburban areas. Methods:A questionnaire survey on dental service in Shanghai community health service centers were conducted from March 10 to 17, 2023. The availability of dental services and the differences among health service centers in central urban area, urban area and suburban area were analyzed.Results:A total of 249 community health service center participated in the survey and 249 effective questionnaires were returned with a response rate of 100.0%. Among 249 centers, 220 (88.4%) had set up dental clinics. The proportion of community health service centers with dental clinics in the urban areas, central urban areas and suburban areas is 95.0% (76/80), 98.2% (107/109) and 61.7% (37/60), respectively ( H=35.44, P<0.05). Among the 220 centers with dental clinics, the floor space of dental clinic was 40.00 (28.50, 73.24), 31.70 (24.40, 49.35) and 20.00 (16.75, 34.00) square meters in suburban areas, central urban areas, and suburban areas, respectively. There were significant differences in the inspection equipment including comprehensive dental chairs, X-ray panoramic machine, X-ray dental machine, dental implants, ultrasonic dental cleaning machine, portable dental chairs, light curing lamps, and enzyme cleaning machine among community health service centers in three types of city areas ( H=35.44, 8.32, 25.53, 7.46 20.95, 43.00, 23.22, 13.35, all P<0.05). Among 220 centers with dental services, all provided dental caries filling, 175 (79.55%) provided root canal treatment, 161 (73.18%) provided extraction of various impacted teeth, 104 (47.27%) provided minor maxillofacial surgery, 132 (60.00%) provided fixed denture restoration, and 139 (63.18%) provided removable local denture restoration. Only a few centers provided orthodontics and dental implant services, including 20 provided removable orthodontics (9.09%), 11 provided fixed orthodontics (5.00%), and 9 provided dental implants (4.09%). There were significant differences in provision of services for root canal treatment, gingival scaling, subgingival scraping, various types of impacted tooth extraction, maxillofacial surgery minor surgery, fixed denture restoration, removable local denture restoration, mobile correction, and oral implant restoration among centers in three types of city areas ( H=29.19, 51.73, 25.32, 31.93, 8.23, 25.98, 28.26, 10.46, 7.84, all P<0.05). There were total 511 dentists in 220 community health service centers, including 24(4.70%) with master degree, 53(10.37%) with associate senior professional titles. There were significant differences in number of dentists, those with undergraduate and below education, those with master degree, those with intermediate and below professional titles among centers in three types of city areas ( H=66.35, 50.33, 11.19, 42.17, all P<0.05). Conclusion:Community health service centers in Shanghai generally have basic capacity of dental service, but there are significant differences among the central urban areas, suburban areas, and suburban areas, indicating that it need to be further strengthened in terms of facilities, equipment, and talent team development in different city areas accordingly.
6.Prognostic risk score model and bioinformatics analysis of antioxidant-associated lncRNAs in gastric cancer
Xiao-Xin ZHANG ; Zi-Peng XU ; Yan-Sheng LU ; Jie CHENG ; Zheng-Hai ZHU
Chinese Journal of Current Advances in General Surgery 2024;27(2):122-128
Objective:To investigate the value of antioxidant-associated long non-coding RNAs(lncRNAs)risk score model in prognosis and the association with immune microenvironment of the gastric cancer patients.Methods:Gastric cancer transcriptome data and clinical information were downloaded from TCGA database.Antioxidant-associated lncRNAs were obtained by co-ex-pression analysis of lncRNAs and antioxidant genes.Risk score was constructed using univariate cox regression analysis and lasso regression analysis.Log-Rank test was used to compare the survival differences between two groups.Receiver operating characteristic curve(ROC)was used to assess the specificity and sensitivity of the prognostic risk score model.Nomogram was constructed com-bining risk score and clinical parameters.Immune cell infiltration was assessed by TIMER 2.0.Im-munotherapy sensitivity of each sample was analyzed at TIDE website.Results:A risk score in-cluding 12 IncRNAs was constructed by univariate cox regression analysis and lasso regression anal-ysis.The risk score was an independent factor influencing patient prognosis[HR=5.406(3.131~9.335),P<0.001].Risk score was positively correlated with multiple suppressive immune cells infil-tration(M2 macrophage,tumor-associated fibroblast).Meanwhile,multiple aberrant expression of immune checkpoint genes and higher TIDE score were found in high-risk group,suggesting that high-risk groups may be more sensitive to immunotherapy.Conclusion:The antioxidant-associ-ated IncRNAs risk score is a good prognostic predictor and can act as a reference in individualized immunotherapy for gastric cancer patients.
7.Two new isoflavones from Dalbergia rimosa Roxb.
Wei-yu WANG ; Wen-jiao CHEN ; Mei-fang HUANG ; Cheng-sheng LU ; Xu FENG ; Chen-yan LIANG ; Jian-hua WEI
Acta Pharmaceutica Sinica 2024;59(7):2053-2057
Studies on chemical constituents in the rhizome of
8.Two new dalbergiphenols from Zhuang medicine Dalbergia rimosa Roxb
Cheng-sheng LU ; Wei-yu WANG ; Min ZHU ; Si-si QIN ; Zhao-hui LI ; Chen-yan LIANG ; Xu FENG ; Jian-hua WEI
Acta Pharmaceutica Sinica 2024;59(2):418-423
Twelve compounds were isolated from the ethyl acetate fraction of the 80% aqueous ethanol extract of the roots and stems of
9.PRMT7 Regulates Adipogenic Differentiation of hBMSCs by Modulating IGF-1 Signaling
Qian GUO ; Jia QING ; Da-Zhuang LU ; Xu WANG ; Yang LI ; Hui ZHANG ; Ying-Fei ZHANG ; Yun-Song LIU ; Yong-Sheng ZHOU ; Ping ZHANG
Progress in Biochemistry and Biophysics 2024;51(6):1406-1417
ObjectiveProtein arginine methyltransferases (PRMTs) play pivotal roles in numerous cellular biological processes. However, the precise regulatory effects of PRMTs on the fate determination of mesenchymal stromal/stem cells (MSCs) remain elusive. Our previous studies have shed light on the regulatory role and molecular mechanism of PRMT5 in MSC osteogenic differentiation. This study aims to clarify the role and corresponding regulatory mechanism of PRMT7 during the adipogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Methods(1) Human bone marrow-derived mesenchymal stem cells (hBMSCs) were cultured in a medium that induces adipogenesis. We used qRT-PCR and Western blot to monitor changes in PRMT7 expression during adipogenic differentiation. (2) We created a cell line with PRMT7 knocked down and assessed changes in PRMT7 expression and adipogenic capacity using Oil Red O staining, qRT-PCR and Western blot. (3) We implanted hBMSCs cell lines mixed with a collagen membrane subcutaneously into nude mice and performed Oil Red O staining to observe ectopic lipogenesis in vivo. (4) A cell line overexpressing PRMT7 was generated, and we examined changes in PRMT7 expression using qRT-PCR and Western blot. We also performed Oil Red O staining and quantitative analysis after inducing the cells in lipogenic medium. Additionally, we assessed changes in PPARγ expression. (5) We investigated changes in insulin-like growth factor 1 (IGF-1) expression in both PRMT7 knockdown and overexpressing cell lines using qRT-PCR and Western blot, to understand PRMT7’s regulatory effect on IGF-1 expression. siIGF-1 was transfected into the PRMT7 knockdown cell line to inhibit IGF-1 expression, and knockdown efficiency was confirmed. Then, we induced cells from the control and knockdown groups transfected with siIGF-1 in lipogenic medium and performed Oil Red O staining and quantitative analysis. Finally, we assessed PPARγ expression to explore IGF-1’s involvement in PRMT7’s regulation of adipogenic differentiation in hBMSCs. Results(1) During the adipogenesis process of hBMSCs, the expression level of PRMT7 was significantly reduced (P<0.01). (2) The adipogenic differentiation ability of PRMT7 knockdown group was significantly stronger than that of control group (P<0.001). (3) The ectopic adipogenic differentiation ability of PRMT7 knockdown group was significantly stronger than that of control group. (4) The adipogenic differentiation ability of the PRMT7 overexpression group was significantly weaker than that of the control group (P<0.01). (5) The expression level of IGF-1 increased after PRMT7 knockdown (P<0.000 1). The expression level of IGF-1 decreased after PRMT7 overexpression (P<0.000 1), indicating that PRMT7 regulates the expression of IGF-1. After siIGF-1 transfection, the expression level of IGF-1 in all cell lines decreased significantly (P<0.001). The ability of adipogenic differentiation of knockdown group transfected with siIGF-1 was significantly reduced (P<0.01), indicating that IGF-1 affects the regulation of PRMT7 on adipogenic differentiation of hBMSCs. ConclusionIn this investigation, our findings elucidate the inhibitory role of PRMT7 in the adipogenic differentiation of hBMSCs, as demonstrated through both in vitro cell-level experiments and in vivo subcutaneous transplantation experiments conducted in nude mice. Mechanistic exploration revealed that PRMT7’s regulatory effect on the adipogenic differentiation of hBMSCs operates via modulation of IGF-1 signaling pathway. These collective findings underscore PRMT7 as a potential therapeutic target for fatty metabolic disorders, thereby offering a novel avenue for leveraging PRMT7 and hBMSCs in the therapeutic landscape of relevant diseases.
10.Value of cerebral small vessel disease burden in predicting prognosis after endovascular therapy for acute ischemic stroke
Gao MA ; Zixin YIN ; Xiaoquan XU ; Shanshan LU ; Guangchen SHEN ; Yue CHU ; Sheng LIU ; Haibin SHI ; Feiyun WU
Chinese Journal of Radiology 2024;58(1):41-47
Objective:To assess the value of cerebral small vessel disease (CSVD) burden in predicting prognosis in acute ischemic stroke (AIS) patients with anterior circulation large vessel occlusion (LVO) after endovascular therapy (EVT).Methods:The study was a cross-sectional study. A total of 242 patients with AIS due to anterior circulation LVO received EVT in the First Affiliated Hospital of Nanjing Medical University from February 2018 to September 2022. The clinical and imaging data of all patients were analyzed retrospectively. On follow-up MRI within 7 days after EVT, CSVD features [white matter hyperintensity (WMH), lacune, perivascular space, cerebral microbleed, cerebral atrophy] and CSVD burden score (0-5) was evaluated. Modified Rankin scale (mRS) score at 90 days after EVT was assessed. Patients were categorized into a mild burden group (0-1 points) and a moderate-severe burden group (2-5 points) based on CSVD burden score. Meanwhile, patients were categorized into a good prognosis group (0-2 points) and a bad prognosis group (3-6 points) based on mRS score at 90 days after EVT. Mann-Whitney U test and χ2 test were used to compare the difference of clinical and imaging indexes between the 2 groups, and variables with P<0.1 in the univariate analysis were included in the multifactorial logistic regression to screen for independent factors to predict the prognosis. Results:There were 169 patients in the good prognosis group and 73 patients in the bad prognosis group out of 242 patients. Compared with the good prognosis group, age, incidence of hyperlipidemia, baseline National Institutes of Health Stroke Scale (NIHSS) scores, incidence of hemorrhagic conversion, CSVD burden scores, incidence of periventricular WMH scores of 3 and/or deep WMH scores≥2, and incidence of moderate-severe cerebral atrophy of patients in the bad prognosis group were higher, and the incidence of complete recanalization was lower (all P<0.05). Multivariate analysis showed hyperlipemia ( OR=8.438, 95% CI 1.691-42.119, P=0.009), baseline NIHSS score ( OR=1.103, 95% CI 1.047-1.162, P<0.001), complete recanalization ( OR=0.131, 95% CI 0.038-0.454, P=0.001) and hemorrhage transformation ( OR=1.952, 95% CI 1.031-3.697, P=0.040) were independent factors for the prognosis of EVT in patients with LVO AIS. There were 157 cases in the mild burden group and 85 cases in the moderate-severe burden group. The 90-day mRS score was higher in the moderate-severe burden group compared with the mild burden group ( Z=-2.24, P=0.025). Conclusion:CSVD burden has some clinical implications in predicting the prognosis of EVT in patients with anterior circulation LVO AIS.

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