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AIM:To investigate the regulatory role of retinoid X receptor(RXR)in oxidative stress response of rat type Ⅱ alveolar epithelial cells(AECII)induced by hypoxia/reoxygenation(HR).METHODS:The AECII were di-vided into control(C)group,HR group,HR+solvent dimethyl sulfoxide(DMSO)group(HD group),HR+RXR agonist 9-cis-retinoic acid(9-RA)group(RA group),and HR+RXR antagonist HX531 group(HX group).Cell Counting Kit-8(CCK-8)method was used to measure the cell viability.Immunofluorescence staining was used to detect the expression of surfactant protein A(SP-A)and RXRα in AECII.Kits were detected to the levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in cells.Transmission electron microscopy was used to observe the ultrastructural changes of the cells.Western blot was used to detect the protein level of nuclear factor E2-related factor 2(Nrf2).RT-PCR was used to detect the expression level of Nrf2 mRNA.RESULTS:Compared with C group,the cell viability and SOD activity in HR,HD,RA and HX groups were decreased significantly(P<0.05),the MDA content were increased significantly(P<0.05),the Nrf2 mRNA and protein expression levels were decreased significantly(P<0.05 or P<0.01),and the immuno-fluorescence expression of RXRα was significantly increased(P<0.01).Compared with HR and HX groups,the cells in RA group showed significantly increased cell viability(P<0.05),increased SOD activity(P<0.05),decreased MDA con-tent(P<0.05),increased Nrf2 mRNA and protein expression levels(P<0.01),and significantly increased immunofluo-rescence expression of RXRα(P<0.01).CONCLUSION:Hypoxia/reoxygenation can aggravate the oxidative stress re-sponse of rat AECII,and RXR agonist intervention can alleviate HR-induced rat AECII injury by inhibiting oxidative stress.
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Objective:To preliminarily explore the long-term improvement of low-frequency deep brain stimulation (DBS) on the nucleus basalis of Meynert (NBM) in cognitive disorders, neuropsychiatric symptoms and sleep disorders of patients with early-onset severe Alzheimer's disease (AD).Methods:A retrospective study was performed; 18 patients with early-onset severe AD admitted to Department of Neurosurgery, First Medical Center of PLA General Hospital from January 2016 to December 2022 were included. These patients were divided into NBM-DBS group and control group according to different treatments; 6 patients received low-frequency NBM-DBS on basis of conservative treatments; 12 patients accepted conservative treatments. Changes in Brief Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Neuropsychiatric Inventory (NPI), Hamilton Depression Rating Scale (HAMD), Becker-Lavanson Mania Scale (BRMS), Pittsburgh Sleep Quality Index (PSQI), and Zarit Caregiver Burden Interview (ZBI) were observed before treatment and 1 year after follow up.Results:MMSE and MoCA scores 1 year after follow up obviously reduced compared with those before treatment in both NBM-DBS and control patients; MMSE and MoCA scores in NBM-DBS patients showed no significant differences between 1 year after follow up and before treatment ( P>0.05), while significant differences were noted in the control group between 1 year after follow-up and before treatment ( P<0.05); and no significant differences in MMSE and MoCA scores were noted between the 2 groups 1 year after follow up ( P>0.05). NPI, HAMD, BRMS and ZBI scores in the NBM-DBS group 1 year after follow up were significantly different compared with those before treatment ( P<0.05); no significant differences were noted in NPI, HAMD and ZBI scores in the control group between 1 year after follow up and before treatment ( P>0.05), while significant difference was noted in BRMS scores ( P<0.05); significant differences in NPI, HAMD, BRMS and ZBI scores were noted between the 2 groups 1 year after follow up ( P<0.05). Conclusion:Low-frequency NBM-DBS is not only effective in improving cognitive disorders, but also effective in improving neuropsychiatric symptoms and sleep disorders, as well as reducing caregiver burden in patients with early-onset severe AD.
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Objective:To investigate the efficacy of Kechuanning combined with western medicine on acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and its effects on serum amyloid A, interleukin 1β and procalcitonin levels. Methods:A total of 104 patients with AECOPD who received treatment in Yongkang Hospital of Traditional Chinese Medicine from January 2019 to December 2020 were included in this study. They were randomly assigned to receive either symptomatic treatment with western medicine alone ( n = 52, control group) or symptomatic treatment with western medicine combined with Kechuanning ( n = 52, observation group). Therapeutic effects, latency to clinical symptom relief, pre- and post-treatment pulmonary function, serum inflammatory factor levels, and blood gas analysis indexes were compared between the two groups. Results:Total response rate in the observation group was significantly higher than that in the control group [86.54% (45/52) vs. 67.31%(35/52), χ2 = 4.99, P < 0.05]. Latency to rale disappearance, latency to cough disappearance, length of hospital stay in the observation group were (8.25 ± 1.38) days, (10.05 ± 1.53) days, and (12.65 ± 2.28) days, which were significantly shorter than those in the control group [(9.41 ± 1.46) days, (12.19 ± 1.61) days, (14.36 ± 2.14) days, t = 4.16, 6.98, 3.61, all P < 0.05]. After treatment, forced vital capacity (FVC), forced expiratory volume in the first second (FEV 1), and FEV 1/FVC value in the observation group were (1.88 ± 0.5) L, (64.13 ± 5.72)%pred, (59.43 ± 5.57)%, respectively, which were significantly higher than those in the control group [(1.65 ± 0.51) L, (60.22 ± 5.60)% pred, (54.16 ± 5.19)%, t = 2.17, 3.52, 4.99, all P < 0.05]. Arterial partial pressure of oxygen (PaO 2) and blood oxygen saturation (SpO 2) in the observation group were (9.18 ± 0.89) kPa and (96.26 ± 2.13)%, respectively, which were significantly higher than those in the control group [(8.74 ± 0.76) kPa, (94.07 ± 2.08)%, t = 2.71, 5.305, both P < 0.05]. Partial pressure of carbon dioxide (PaCO 2) in the observation group was significantly lower than that in the control group [(7.32 ± 0.27) kPa vs. (7.63 ± 0.32) kPa, t = 5.34, P < 0.05]. Serum amyloid protein, interleukin-1β and procalcitonin levels in the observation group were (43.84 ± 6.15) mg/L, (3.24 ± 0.51) μg/L, (1.55 ± 0.37) ng/L, respectively, which were significantly lower than those in the control group [(55.26 ± 3.46) mg/L, (4.19 ± 0.56) μg/L, (2.03 ± 0.46) ng/L, t = 9.23, 9.04, 5.86, all P < 0.05]. Conclusion:Kechuanning as an adjuvant therapy for AECOPD can greatly improve lung function and hypoxia, alleviate clinical symptoms, reduce inflammatory reactions, and have a definite clinical effect. The study is innovative and scientific and is worthy of clinical reference.
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Objective:To explore the effect of urapidil combined with nitroglycerin on blood pressure in elderly patients with acute hypertension.Methods:From July 2016 to September 2018, 60 elderly patients with acute hypertension admitted to the First People's Hospital of Yongkang were selected as the observation objects.They were divided into control group and observation group according to random number table method, with 30 cases in each group.The control group was treated with nitroglycerin intravenous drip, while the observation group was treated with urapidil hydrochloride injection by intravenous micropump on the basis of the control group.The total effective rate, diastolic blood pressure, systolic blood pressure and heart rate were compared between the two groups at the time of admission and 60 minutes after treatment.Results:The effective rate of the observation group was 96.67%, which was significantly higher than 76.67% of the control group (χ 2=5.19, P<0.05). There were no statistically significant differences in blood pressure and heart rate between the two groups at the time of admission (all P>0.05). After treatment, the blood pressure of the two groups decreased significantly (all P<0.05), and the decrease levels of the observation group was significantly better than those of the control group, the difference were statistically significant (all P<0.05). The heart rate of the observation group was significantly lower than that of the control group ( P<0.05). The incidence of adverse reactions in the observation group (10.00%) was significantly lower than that in the control group (33.33%), and the difference was statistically significant (χ 2=4.81, P<0.05). Conclusion:Intravenous micropump injection of urapidil hydrochloride injection combined with nitroglycerin has remarkable antihypertensive effect, less adverse reactions and high safety in the treatment of elderly patients with acute hypertension.
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OBJECTIVE:To establish the detection method for anti-inflammatory compound HB0314 in plasma of rats,and study on its pharmacokinetic characteristics in rats in vivo. METHODS:UPLC-MS/MS was performed on the column of Waters Ac-quity UPLCTM BEH C18 with mobile phase of 0.1% formic acid aqueous solution(A)-methanol(B)by gradient elution(0-2 min, 70%-90% B) at flow rate of 0.25 mL/min,column temperature was 30 ℃,and injection volume was 5 μL. Electrospray ion source was used,capillary voltage was 3 kV,ion source temperature was 150 ℃,desolvation gas temperature was 450 ℃,desol-vent air flow volume was 600 L/h,cone air flow volume was 45 L/h,and the inner standard was tetrahydropalmatine. 12 rats were randomly divided into iv group and ig group,6 in each group. Rats were intravenously injected and intragastrically administrated HB0314 solution 5,10 mg/kg. Sample blood 0.4 mL were taken from the jugular vein blood before administration and after 5,15, 30,60,120,240,360,480,600,720,1440 min of administration to determine the HB0314 plasma concentration. DAS 2.0 software was used to calculate the pharmacokinetic parameters and absolute bioavailability. RESULTS:The linear range of HB0314 was 1-1000 ng/mL(r=0.9955),and the lower limit of quantification was 1 ng/mL. RSDs of extra-day and daytime precision,sta-bility were not higher than 8.45%(n=5);recovery were 68.21%-90.29%(RSD≤11.20%,n=5),and matrix effects were 82.63%-106.90%(RSD≤6.75%,n=5). After intravenous injection and intragastric administration,AUC0-24 h were (270.267 ± 21.164), (252.755 ± 26.169)μg·h/L (n=6);t1/2z were (8.722 ± 2.266),(11.877 ± 4.517) h (n=6);and absolute bioavailability was 56.79%. CONCLUSIONS:The method is rapid,simple,and can be used for the determination of HB0314 content in plasma of rats. HB0314 shows high oral absolute bioavailability in rats in vivo,indicating that post-dosage form design may be considered as oral anti-inflammatory drugs.
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OBJECTIVE:To establish the detection method for anti-inflammatory compound HB0314 in plasma of rats,and study on its pharmacokinetic characteristics in rats in vivo. METHODS:UPLC-MS/MS was performed on the column of Waters Ac-quity UPLCTM BEH C18 with mobile phase of 0.1% formic acid aqueous solution(A)-methanol(B)by gradient elution(0-2 min, 70%-90% B) at flow rate of 0.25 mL/min,column temperature was 30 ℃,and injection volume was 5 μL. Electrospray ion source was used,capillary voltage was 3 kV,ion source temperature was 150 ℃,desolvation gas temperature was 450 ℃,desol-vent air flow volume was 600 L/h,cone air flow volume was 45 L/h,and the inner standard was tetrahydropalmatine. 12 rats were randomly divided into iv group and ig group,6 in each group. Rats were intravenously injected and intragastrically administrated HB0314 solution 5,10 mg/kg. Sample blood 0.4 mL were taken from the jugular vein blood before administration and after 5,15, 30,60,120,240,360,480,600,720,1440 min of administration to determine the HB0314 plasma concentration. DAS 2.0 software was used to calculate the pharmacokinetic parameters and absolute bioavailability. RESULTS:The linear range of HB0314 was 1-1000 ng/mL(r=0.9955),and the lower limit of quantification was 1 ng/mL. RSDs of extra-day and daytime precision,sta-bility were not higher than 8.45%(n=5);recovery were 68.21%-90.29%(RSD≤11.20%,n=5),and matrix effects were 82.63%-106.90%(RSD≤6.75%,n=5). After intravenous injection and intragastric administration,AUC0-24 h were (270.267 ± 21.164), (252.755 ± 26.169)μg·h/L (n=6);t1/2z were (8.722 ± 2.266),(11.877 ± 4.517) h (n=6);and absolute bioavailability was 56.79%. CONCLUSIONS:The method is rapid,simple,and can be used for the determination of HB0314 content in plasma of rats. HB0314 shows high oral absolute bioavailability in rats in vivo,indicating that post-dosage form design may be considered as oral anti-inflammatory drugs.
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OBJECTIVE:To prepare anti-tumor drug H6(lactone compound)polymeric micelles,and to investigate its in vitro anti-tumor effects. METHODS:Using mPEG2000-PCL4000 as carrier,H6/mPEG2000-PCL4000 micelles were prepared. Using particle size, PDI and 48 h whether to produce precipitation as indexes,feeding ratio,H6 concentration,volume ratio of organic solvent were screened. The encapsulation efficiency and drug-loading amount of micelle were all detected. MTT assay was used to detect the tox-icity of micelles and H6 solution to human non-small cell lung cancer cell A549 and human lung cancer cell H460. RESULTS:The screened formulation was as follows as feeding ratio of 1∶25,H6 concentration of 2 mg/mL,the ratio of ethanol to chloroform of 1∶1(V/V). The parameters of prepared H6/mPEG2000-PCL4000 micelles were as follows as particle size of(40.74±0.116 3)nm,PDI of(0.101±0.006),encapsulation efficiency of(94.87±0.016 3)%,drug-loading amount of(7.07±0.001 5)%(n=3). IC50 of mi-celles and H6 solution to A549 cell were 15.62 and 12.57 nmol/L;IC50 of micelles and H6 solution to H460 cell were 27.68 and 15.19 nmol/L. CONCLUSIONS:H6/mPEG2000-PCL4000 micelles are prepared successfully and show in vitro anti-tumor effects.