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AIM:This study aims to investigate the histopathological and ultrastructural alterations in the lung tissues of rats induced by a single intratracheal administration of bleomycin,with the objective of establishing a reliable model for future applications.METHODS:Six to eight-week-old SD rats were randomly allocated into two groups:the control group and the model group(n=12).Pulmonary fibrosis was induced in the rat models by a single intratracheal in-stillation of bleomycin(3 mg/kg),while an equivalent volume of saline was administered to the control group.The rats were executed on the 42nd day.Twelve rats remained in the control group,while nine rats remained in the model group.Lung tissue imaging was conducted using CT scans.Lung function tests were performed to assess changes in forced vital capacity(FVC)and dynamic lung compliance(Cdyn).Lung stiffness was determined through Young's modulus testing using a rheometer.The pathological structure of lung tissues was examined using both HE and Masson staining methods.Additionally,transmission electron microscopy was employed to evaluate collagen deposition in lung tissues,alveolar type Ⅱ epithelial cells,macrophages,and ultrastructural changes of the respiratory membrane.RESULTS:CT scans revealed honeycomb patterns in the lungs of model rats,along with partial bronchiectasis/bronchiectasis.In comparison to the con-trol group,the model group exhibited significantly lower FVC and Cdyn values,while lung stiffness were increased.HE and Masson staining demonstrated that rats in the model group exhibited alveolar structure destruction,alveolar septum thickening,inflammatory cell infiltration,and collagen deposition in alveolar septum.Transmission electron microscopy revealed several abnormalities in the model group:increased collagen fibers in the alveolar septa,misalignment of micro-villi in alveolar type Ⅱ epithelial cells,wrinkled nuclei with increased heterochromatin,swollen cytoplasmic mitochon-dria,fractured or haphazardly structured mitochondrion cristaes,and a significant decrease in their number(P＜0.05).Furthermore,lamellar bodies were vacuolated and reduced in number(P＜0.05),and dilated endoplasmic reticulums with degranulation were observed.There was an increase in alveolar macrophages and interstitial macrophages(P＜0.01).The respiratory membrane displayed structural disruptions and an increase in thickness(P＜0.01).CONCLUSION:Bleomycin induces decreased lung compliance,alveolar epithelial injury,alveolar septum thickening,collagen deposi-tion,and an increase in interstitial macrophages,ultimately resulting in pulmonary fibrosis in rats.
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Objective:To investigate the expression changes of farnesoid X receptor (FXR) in the evolution of normal intestinal mucosa, colorectal adenoma (CRA) and colorectal cancer (CRC), and the correlation of FXR expression with clinicopathological features and prognosis of patients with colorectal tumors.Methods:The UALCAN website tool was used to analyze the expression level of FXR gene transcripts of CRC and normal colorectal tissues in The Cancer Genome Atlas (TCGA) database. The patients undergoing colonoscopy and treatment in the Aerospace Center Hospital from January 2019 to September 2020 were selected, and the immunohistochemistry was used to detect the expression of FXR protein in 100 CRA tissues, 47 CRC tissues and 11 normal colonic mucosal tissues from healthy people (healthy control). Combining with clinical data, the relationship between FXR protein expression and clinicopathological characteristics of patients with colorectal tumors was analyzed. According to the Kaplan-Meier Plotter online database, the median expression level of FXR gene transcripts in CRC patients was analyzed, and the patients were divided into FXR low-expression group and high-expression group, the relationship between the expression of FXR gene and prognosis of CRC patients was investigated.Results:The analysis of data from TCGA database showed that the expression level of FXR gene transcripts in CRC tissues was lower than that in normal colorectal tissues ( P < 0.01). Immunohistochemical examination of the collected tissues showed that the positive rate of FXR protein gradually decreased from the cecum to the rectum. The positive rates of FXR protein in healthy control, CRA patients and CRC patients were 90.9% (10/11), 24.0% (24/100), 6.3% (3/47), and the difference was statistically significant ( χ2 = 35.56, P < 0.01); the positive rate of FXR protein in cancer tissues from CRC patients was lower than that in normal tissues adjacent to cancer [6.3% (3/47) vs. 65.2% (15/23)], and the difference was statistically significant ( χ2 = 27.98, P < 0.01). There was no statistical difference in the positive rate of FXR among CRA patients with different gender, age, maximum diameter of adenoma, and aggression (all P > 0.05). There was also no statistical difference in the positive rate of FXR among CRC patients with different gender, age, tumor site, maximum diameter of tumor, degree of differentiation, TNM staging, and vascular tumor thrombus (all P > 0.05). According to the survival analysis of Kaplan-Meier Plotter online database, the recurrence-free survival of CRC patients with high expression of FXR was better than that of patients with low expression of FXR ( P = 0.003). Conclusions:The expression level of FXR gradually decreases in the intestinal tissues of healthy people, CRA patients and CRC patients. The prognosis of CRC patients with low FXR expression is poor.
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<p><b>OBJECTIVE</b>To observe the early reperfusion therapy status for patients with ST elevation acute myocardial infarction (STEMI) hospitalized in tertiary and secondary hospitals in Henan province.</p><p><b>METHODS</b>Baseline data, early reperfusion treatment and in-hospital mortality of STEMI patients hospitalized in 17 hospitals in Henan province (8 tertiary hospitals, 9 secondary hospitals) from June 2011 to June 2012 were obtained using a uniformed questionnaire.</p><p><b>RESULTS</b>One thousand six hundred and eighty six patients were enrolled, of which 886 patients were hospitalized in tertiary hospitals and 880 patients were early hospitalized in secondary hospitals. Six hundred and fifty four patients (38.8%, 654/1 686) underwent early reperfusion therapy (543 with thrombolysis and 111 with primary percutaneous coronary intervention (PCI)). There was no difference in the proportion of early reperfusion therapy between tertiary and secondary hospitals (40.1% (355/886) vs. 37.4% (299/800), P = 0.257). The median time from symptom onset to first medical contact, door-to-needle and door-to-balloon was 132 min, 18 min and 60 min, respectively. The median time from symptom onset to first medical contact (150 min vs. 120 min, P = 0.001), door-to-needle (30 min vs. 18 min, P = 0.003) and symptom onset-to-thrombolysis (3.5 h vs. 2.7 h, P = 0.001) were significantly longer in tertiary hospitals than in secondary hospitals. No difference was found in median time of door-to-balloon, symptom onset-to-primary PCI or symptom onset-to-elected PCI between tertiary and secondary hospitals (all P > 0.05). The proportion of door-to-needle ≤ 30 min was lower in tertiary hospitals than in secondary hospitals (46.4% (84/181) vs. 62.2% (153/246), P = 0.001). However, there was no difference in the proportion of door-to-balloon ≤ 90 min between tertiary and secondary hospitals (58.8% (60/102) vs. 57.1% (4/7), P = 1.000). In-hospital mortality was also similar between tertiary and secondary hospitals (5.8% (51/886) vs. 5.5% (44/800), P = 0.820).</p><p><b>CONCLUSIONS</b>Early reperfusion rate is low, and thrombolysis is the main early reperfusion therapy in both tertiary and secondary hospitals in Henan province. Tertiary hospitals did not take advantage of their primary PCI capability. There is great room for improvement in early reperfusion therapy in tertiary and secondary hospitals.</p>
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Humans , Hospital Mortality , Hospitals , Myocardial Infarction , Myocardial Reperfusion , Percutaneous Coronary Intervention , Secondary Prevention , Surveys and QuestionnairesABSTRACT
The present study was to estimate pharmacokinetic parameters of metformin hydrochloride in 20 Chinese healthy volunteers with a limited sampling strategy (LSS), which will provide scientific data for bioequivalence and clinical application. A single dose of metformin was administrated to 20 healthy volunteers. The concentration of metformin in whole blood was determined by validated high performance liquid chromatography (HPLC) method. Multi-linear regression analysis was performed to establish a model to estimate AUC(0-24 h) and Cmax of metformin by LSS method. The LSS models were validated by the Jackknife method. The result indicated: the linearity relationship between AUC(0-24 h) or Cmax and single concentration point was poor. Several models for metformin AUC(0-24 h) or Cmax, estimation were better (r2 > 0.9, P < 0.05). Validation tests indicated that most informative sampling points (C2, C6 for AUC(0-24 h), C1.5, C2 for Cmax) provided accurate estimations of these parameters. So, a multi-linear regression model for estimation pharmacokinetic parameters of metformin by using LSS method is feasible.
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Aim To study effects of different dosage regimens of gentamicin(GTM) on impairment of renal functions, plasma concentrations and pharmacokinetics in rats. Method 108 rats were divided into 6 groups: control group; chronological once-daily dose groups (N100 and D100 group, in which 100 mg?kg -1 GTM were intramuscularly administrated at 01 ∶00 or 13 ∶[KG-*3]00 respectively), and chronological twice-daily different dose groups (N90+D10, N70+D30, N50+D50 group, in which 90 mg?kg -1+10 mg?kg -1, 70 mg?kg -1+30 mg?kg -1 and 50 mg?kg -1+50 mg?kg -1 GTM were given at 1:00 and 13:00 respectively). The blood urea nitrogen (BUN) and creatinine (Cr) levels were observed, the plasma concentrations of GTM at 0.25,0.5,1, 2, 5 and 8h were determined, the C-T curves were profiled and the pharmacokinetic parameters were calculated at the 1st, the 10th, and the 20th day of administrations. Results ① Impairment of renal function. At the 10th day of administration, the Cr and BUN levels of N50+D50 group were the highest. There was a significant difference when compared those of the 10th day of administration with those of the 1st day of administration and of control group at same time respectively (P
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0.05). Conclusion: With slow absorption rate and long half life of elimination, the epidural administration at one week interval can avoid the accumulation of triamcinolone A.
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To investigate epidural morphine(M) combined with triamcinolone A(TA) for advanced cancer pain and to study pharmacokineties of TA. Method.. TA 40mg/w was epidually combined with M3.84?3.94mg/d in 104 advanced cancer patients and TA blood concentration was measured with high performance liquid chromatography. Result: The rate of adverse reaction was 7.69% and visual analog scale was 3.16?2.83. The plasma elimination half life (t_(1/2)) was 1.63?0.36d; plasma accumulation coefficient (R) was 1.06-1-0.04?g/ml. Conclusion: The analgesic effect of M is potentiated by TA and there is no TA accumulation in plasma following long-term epidural administration.
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AIM To compare the pharmacokinetics and bioequivalence of between capsule and solution of benzoylmetronidazole. METHODS Ten chinese healthy male volunteers in a randomized 2-way crossover study were given a single oral dose 960 mg capsule(test) and solution (control) respectively. The serum concentrations of metronidazole, one of the metabolites of benzoylmetronidazole, was measured by high performance liquid chromatography. RESULTS The serum concentration-time curves appeared one-compartment open model. The results of the capsule and the solution of benzoylmetronidazole showed that T max (5.10?1.60) h and (3.12?0.90) h; C max (5.32?0.87) mg?L -1 and (6.51?1.25) mg?L -1 ; T 12 (10.56?1.75) h and (10.16?1.65) h; AUC (106.96?19.62) mg?h -1 ?L -1 and (113.59?19.84) mg?h?L -1 . CONCLUTION No significant difference appears in the pharmacokinetic parameters between the two formulations except of T max and C max ( P
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The effects of RFP and CMT on CRL antiarrhythmia were studied in rats. CRL increased AC accumulated dosages at the onset of VP ,VT and VF(P0.05). The results suggested that there is drug interaction between RFP and CRL, and no interaction between CRL and CMT.