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OBJECTIVE To study the pharmacokinetic changes in the plasma and cerebrospinal fluid of bronchial asthma model rats after the complication of Ephedra sinica and Prunus armeniaca. METHODS SD male rats were randomly divided into blank group， model group， E. sinica group （12 g/kg， calculated by raw drug， similarly hereinafter）， P. armeniaca group （6 g/kg） and E. sinica-P. armeniaca drug-pair group （12 g/kg of E. sinica+6 g/kg of P. armeniaca）， with 6 rats in each group. Except for the blank group， the bronchial asthma model was induced by spraying rats in each group with an equal volume mixture of 2% acetylcholine chloride and 0.4% histamine phosphate， once a day， for 7 d. One hour before modeling every time， rats in each group were gavaged with the corresponding drug/normal saline， once a day， for 7 d. After the final administration and provocation of asthma， blood and cerebrospinal fluid collection were performed at different time points. The plasma and cerebrospinal fluid samples were pre-treated （with geranylgeranyl as the internal standard）， and the mass concentrations of ephedrine/pseudoephedrine， methyl ephedrine and amygdalin in both samples were determined by liquid chromatography-tandem mass spectrometry. DAS 2.0 pharmacokinetic software was used to determine the main pharmacokinetic parameters through the non-atrial chamber model and to compare the changes of the pharmacokinetic parameters before and after the combination of the two drugs. RESULTS Compared with E. sinica group， cmax and AUC0-21.33 h （or AUC0-10.67 h） of ephedrine/pseudoephedrine and methyl ephedrine in the plasma and cerebrospinal fluid of rats were significantly reduced in E. sinica-P. armeniaca drug-pair group， while CLZ/F and VZ/F were significantly increased （P＜0.05 or P＜0.01）； tmax of methyl ephedrine in the cerebrospinal fluid was significantly shortened （P＜ 0.05）.Compared with P. armeniaca group， the t1/2 of amygdalin in the plasma of rats in E. sinica-P. armeniaca drug-pair group was significantly shortened， and CLZ/F was significantly increased （P＜0.01）； the tmax of bitter amygdalin in the cerebrospinal fluid was significantly shortened， and the AUC0-10.67 h， CLZ/F， and VZ/F were significantly increased （P＜0.01）. CONCLUSIONS The combination of E. sinica and P. armeniaca accelerates the absorption and elimination of ephedra alkaloids， thus reducing the accumulation of ephedra alkaloids in the bronchial asthma model rats.
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Objective:To evaluate the clinical effect of treatment of activating blood and removing blood stasis, invigorating the spleen and soothing the liver for the patients with gastric collateral stasis syndrome and chronic atrophic gastritis (CAG).Methods:Randomized controlled trial. A total of 68 CAG patients admitted to the Huairou Hospital of Traditional Chinese Medicine from January 2018 to January 2021 who met the selection criteria were divided into 2 groups according to the random number table method, with 34 in each group. The control group received conventional western medicine treatment, such as inhibition of acid, protecting the gastric mucosa, and the observation group was treated with Traditional Chinese Medicine (TCM) herbal prescription of activating blood and removing blood stasis, invigorating the spleen and soothing the liver. Both groups were treated for 12 weeks. TCM symptom scores were performed before and after treatment. The serum level of pepsinogen Ⅰ(PG Ⅰ), pepsinogen Ⅱ (PGⅡ) were detected by ELISA, and the PG Ⅰ/PG Ⅱ ratio was calculated. Gastroscopic biopsy was performed to observe the changes of intestinal metaplasia of gastric mucosa and glandular atrophy, and to evaluate the clinical efficacy.Results:The total responsive rate was 85.3% (29/34) in the study group and 58.8% (20/34) in the control group. There was significant difference between the two groups ( χ2=9.35, P=0.030). After treatment, the scores of stomachache, fullness of feeling in the observation group were significantly lower than those in the control group ( t=2.97, 3.80, P<0.05). After treatment, the level of serum PG Ⅰ[(76.21 ± 17.35) mg/L vs. (66.8 ± 18.77) mg/L, t=2.15] and PG Ⅰ/PG Ⅱ [(4.67 ± 0.99) vs. (3.90± 1.25), t=2.81] in the study group were significantly higher than those in the control group ( P<0.05), and PG Ⅱ [(16.36 ± 1.85) mg/L vs. (17.42 ± 2.05) mg/L, t=2.24] was significantly lower than that of the control group ( P<0.05). After treatment, intestinal metaplasia and glandular atrophy was significantly more improved or reversed than those in the control group ( χ2=20.67,9.33, P<0.05). Conclusion:The methods of activating blood and removing blood stasis, invigorating the spleen and soothing the liver can reverse the precancerous lesions of patients with gastric collateral stasis syndrome of chronic atrophic gastritis and have a good prognosis.
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Objective:To evaluate the effects of remimazolam on gastrointestinal motor function in the patients undergoing gastrointestinal endoscopy.Methods:A total of 262 American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ patients, aged 18-64 yr, with body mass index of 18-28 kg/m 2, scheduled for elective gastrointestinal endoscopy from May 2022 to August 2022, were divided into 2 groups ( n=131 each) using a random number table method: remimazolam group (group R) and propofol group (group P). The patients in group R received intravenous remimazolam 0.20-0.25 mg/kg, and patients in group P received intravenous propofol 1.5-2.0 mg/kg. The gastrointestinal endoscopy was performed when the patients′ Modified Observer′s Assessment of Alertness/Sedation scores ≤3. During fasting before gastrointestinal preparation, before gastrointestinal endoscopy and while leaving the post-anesthesia care unit (PACU), the concentrations of serum motilin and gastrin were measured by enzyme-linked immunosorbent assay, the intestinal peristalsis rating assessed by the endoscopist during the examination was recorded, the occurrence of hypotension and hypoxemia during the examination and occurrence of abdominal distension, abdominal pain, and nausea and vomiting during stay in PACU were recorded. Results:Compared with group P, the intestinal peristalsis rating was significantly increased, the serum motilin and gastrin concentrations were increased while leaving PACU, the incidence of hypotension and hypoxemia was decreased during the examination, and the incidence of abdominal distention was decreased during stay in PACU in group R ( P<0.05). Conclusions:Remimazolam has a milder inhibitory effect on secretion of gastrointestinal hormones than propofol in the patients undergoing gastrointestinal endoscopy and is helpful for the recovery of gastrointestinal motility.
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Background:Crohn's disease(CD)was a kind of inflammatory bowel disease,whichwas chronic and recurrent attacked,seriously affect the quality of life of patients.Its pathogenesis is not clear.Aims:To study the effect of hsa_circRNA_103124 which was highly expressed in CD on its downstream gene expression,and the expression level of hsa_circRNA_103124 and its downstream genes in Crohn's disease.The mechanism of hsa_circRNA_103124 in the occurrence and development of CD was discussed in this study.Methods:Transcriptome sequencing revealed differentially expressed genes inhsa_circRNA_103124 overexpressed THP1 cells which was induced macrophage-like differentiation with PMA.IL4 was used to induce macrophage M2 differentiation in hsa_circRNA_103124 overexpressed THP1 cells.The expression levels of M2 differentiation markers CD206 and CD163 were detected by flow cytometry.The expression levels of hsa_circRNA_103124 and its downstream genes were analyzed by qPCR.The levels of hsa_circRNA_103124 and mRNA of its downstream genes in peripheral blood mononuclear cells of 30 patients with CD and 30 healthy controls were analyzed by qPCR.Results:Hsa_circRNA_103124 overexpressed and PMA-induced THP1 cells showed low expression of FGF18(P<0.01).Hsa_circRNA_103124 inhibited macrophage M2 differentiation and down-regulated the expression of CD206(P<0.05)and CD163(P<0.01).The expression of FGF18(P<0.05)and CCL2(P<0.05)was down-regulated in M2-polarized THP1 cells with hsa_circRNA_103124 overexpressed.The expression of hsa_circRNA_103124(P<0.05)in peripheral blood mononuclear cells of CD patients was up-regulated,and the expression of FGF18(P<0.01)and CCL2(P<0.05)was down-regulated.Conclusions:The high expression of hsa_circRNA_103124 in peripheral blood of patients with CD inhibits the M2 polarization of macrophages by down-regulating the expression levels of FGF18 and CCL2,which may play a role in promoting inflammation in the occurrence and development of CD.
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The fracture risk of patients with diabetes is higher than those of patients without diabetes due to hyperglycemia, usage of diabetes drugs, changes in insulin levels, and excretion, and this risk begins as early as adolescence. Many factors including demographic data (such as age, height, weight, and gender), medical history (such as smoking, drinking, and menopause), and examination (such as bone mineral density, blood routine, and urine routine) may be related to bone metabolism in patients with diabetes. However, most of the existing methods are qualitative assessments and do not consider the interactions of the physiological factors of humans. In addition, the fracture risk of patients with diabetes and osteoporosis has not been further studied previously. In this paper, a hybrid model combining XGBoost with deep neural network is used to predict the fracture risk of patients with diabetes and osteoporosis, and investigate the effect of patients' physiological factors on fracture risk. A total of 147 raw input features are considered in our model. The presented model is compared with several benchmarks based on various metrics to prove its effectiveness. Moreover, the top 18 influencing factors of fracture risks of patients with diabetes are determined.