OBJECTIVE:To evaluate the bioequiavailability of the domestic and the imported paracetamol and oxycodone tablets.METHODS:The blood concentrations of paracetamol and oxycodone in22healthy male volunteers were determined by HPLC-MS after a single dose orally1tablet of domestic or imported oxycodone tablet by a randomized crossover way.RE?SULTS:The main pharmacokinetic parameters of the domestic and the imported oxycodone tablets were as follows:C max were(10.4?2.2),(11.1?3.3)?g/L,respectively;t max were(1.05?0.35),(0.92?0.40)h,respectively;t 1/2 ke were(5.36?0.91),(5.53?1.25)h,respectively;AUC 0～t were(44.2?7.9),(44.5?8.3)(?g?h)/L,respectively;AUC 0～∞ were(49.3?9.4),(51.0?11.6)(?g?h)/L,respectively;the relative bioavailability of the domestic preparation was(102.8?27.4)%.The main pharmacokinetic parameters of the domestic and the imported paracetamol were the following:C max were(4612?696),(4592?825)?g/L,respectively;t max were(0.94?0.28),(0.96?0.23)h,respectively;t 1/2 ke were(3.99?0.77),(4.05?0.83)h,re?spectively;AUC 0～t were(15732?3450),(16265?3858)(?g?h)/L,respectively;AUC 0～∞ were(16618?3545),(17205?4194)(?g?h)/L,respectively;the relative bioavailability of the domestic one was(97.6?10.3)%.CONCLUSIONS:The2preparations are bioequivalent.

Thin endometrium is an important factor influencing the in vitro fertilization and embryo transfer, and there is a lack of effective therapy in the treatment of thin endometrium.The aim of this study was to explore a stable animal model of effective thin endometrium, and to promote the research on thin endometrium pathogenesis and provide experimen-tal basis of treatment.To analyze a variety of establishments of endometrial damage animal model reported in the domestic and foreign literatures,it is concluded that perfusing 95% ethanol into uterine cavities of rats can establish a rat model of thin endometrium,and put forward some experience and methods for its improvement.

BACKGROUND: Thin endometrial diseases are a challenge in clinical treatment at present. Scholars have found that bone marrow mesenchymal stem cells (BMSCs) transplantation has its unique curative effect and advantages, but few studies have been conducted on pathway or gene control. OBJECTIVE: To observe the effect of BMSCs transplantation in rats with thin endometrium based on the HOXA10 regulatory network. METHODS: Twenty-one adult female Sprague-Dawley rats of SPF grade (provided by the Animal Experimental Center, Guangzhou University of Chinese Medicine in China) were randomly divided into three groups (n=7/group): control group, model group, and BMSCs group. In the latter two groups, a thin endometrium model was prepared in each rat by filling the uterine cavity with 95％ ethanol. In the control group, normal saline was injected to fill the uterine cavity of rats. After extraction of ethanol or normal saline, the rats in the BMSCs group were injected intrauterinely with 1 mL of BMSCs suspension (1×1010 cells/L) , and those in the control and model groups were given the same volume of normal saline. After two estrous cycles, the uterus of each rat was removed. Hematoxylin-eosin staining was used to measure the thickness of the endometrium. Immunohistochemistry was used to detect the expression of vimentin, keratin, vascular endothelial growth factor, leukemia inhibitory factor and integrin αvβ3. qRT-PCR was used to detect the relative transcription of HOXA10 and miR-196 b. RESULTS AND CONCLUSION: (1) Compared with the control group, the endometrial thickness of the rats were significantly thinner in the model and BMSCs groups (P < 0.05) , while the endometrial thickness in the BMSCs group was thicker than that in the model group (P < 0.05). (2) The mean absorbance values of endometrial vimentin, keratin, vascular endothelial growth factor, leukemia inhibitory factor and integrin αvβ3 were highest in the control group, higher in the BMSCs group and lowest in the model group, and there were significant differences between groups (P < 0.05). (3) The relative transcript level of HOXA10 gene in the model and BMSCs group was significantly lower than that in the control group, while the relative transcript level of HOXA10 gene in the BMSCs group was significantly higher than that in the model group (P < 0.05). The relative transcript level of miR-196 b in the model and BMSCs groups was significantly higher than that in the control group (P < 0.05) , while the relative transcript level of miR-196 b in the BMSCs group was lower than that in the model group (P < 0.05). (4) HOXA10 was negatively correlated with miR-196 b gene, HOXA10 was positively correlated with the protein expression to different extents, and miR-196 b gene was negatively correlated with the protein expression to different extents. These findings suggest that BMSCs transplantation can improve the endometrial thickness and relevant protein levels of thin endometrium rats to some extent, which may be attributed to the negative regulation of HOXA10 gene by miR-196 b, and HOXA10 gene further promotes the expression of vascular endothelial growth factor, leukemia inhibitory factor and integrin αvβ3 proteins.

Objective To prepare a recombinant pneumococcal surface protein A clade 4 ( PspA4) and to analyze its immunogenicity.Methods The gene encoding PspA4 protein was synthesized and inserted into pET-20b to construct the recombinant expression plasmid.The transformed E.coli strains carrying expression plasmid were induced to express PspA4 protein.ELISA was performed to analyze the ti-ters of PspA4-specific IgG in a mouse model.Results The recombinant PspA4 protein of high purity ( 90%) was successfully prepared.The titers of PspA4-specific antibody in mice received PspA4 immuniza-tion were 106 times higher than those of the blank control group, suggesting that the expressed PspA4 protein had the advantage of high immunogenicity.Conclusion This study suggested that the PspA4 protein might be used as one of the candidate protein for the development of pneumovax and laid a foundation for further in-vestigation on pneumococcal protein based vaccine.

Objective To establish a LC-MS-MS method for determining febuxostate in human plasma .Methods Febuxostate added into blank plasma was sedimented by acetonitrile , and the supernatant was determined by LC-MS-MS.Analytical column was Thermo Biobasic-8,5 μm,50 mm ×2.1 mm(ID).The mobile phase consisted of acetonitrile-10 mmol/L ammonium acetate (0.05%acid=70:30 at a flow rate of 0.2 ml/min.Mass spectrum conditions:ESI-was performed in the SRM mode using target ions m/z 315→271 (10 eV)(febuxostate), m/z 360→274 (18 eV)(bezafibrate), SP 3 500 kV, SGP 10 Arb, AGP45 Arb, TEM 270℃.Results The calibration curve was linear over the range of 10-8 000 μg/L.The LLOQ of Febuxostate in plasma was 10 μg/L.The extracted recovery was >85%.The intra-and inter-day RSD were <15%.Conclusion The method was sensitive , simple and accurate to deter-minate febuxostate plasma concentration and to study pharmacokinetics of febuxostate .

Objective To investigate the levels and significance of Th17 cells and regulatory T cells (Treg) in peripheral blood of children with allergic rhinitis during pollen and non-pollen seasons.Methods Thirteen children with hay fever, 10 children with house dust mite(HDM)-allergic asthma and 10 healthy children were recruited into this study.Percentages of Th17 and Treg cells were detected by flow cytometry.Levels of IL-17, IL-10 and TGF-β in cell culture supernatants were measured by ELISA.Results (1) The percentages of Th17 cells in children with allergic rhinitis [(3.4±2.4)%] were significantly higher than those in HDM-allergic asthmatics [(2.1±1.6)%] and those in healthy children [(0.5±0.3)%] during pollen season (both P<0.05).The levels of Treg cells in allergic rhinitis group [(2.1±1.3)%] and in HDM-allergic asthma group [(3.6±1.9)%] were significantly lower than those in healthy control group [(5.5±2.8)%] (both P<0.05).The levels of Th17 cells [(3.0±1.9)% vs (3.4±2.4)%, P<0.05] and ratios of Th17/Treg cells [(1.4±1.0)% vs (1.7±1.5)%, P<0.05] in children with allergic rhinitis were significantly decreased during non-pollen season as compared with those during pollen season, but the levels of Treg cells were up-regulated [(2.4±1.6)% vs (2.1±1.3)%, P<0.05].(2) Correlation analysis revealed that the ratios of Th17/Treg cells were positively correlated with the concentrations of FeNO (fractional concentration of exhaled NO) (r=0.321, P<0.05) and the counts of circulating eosinophils (r=0.198, P<0.05) in children with allergic rhinitis during pollen season.Conclusion The imbalanced Th17 and Treg cells in children with allergic rhinitis during pollen season might play a vital role in the regulation of allergic airway inflammation.

Objective To evaluate the accuracy of CT-guided stereotactic biopsy in making correct pathological diagnosis and choosing corresponding management of brain tumors. Methods From 1991 to 1995, CT-guided stereotactic biopsy was performed in 310 patients with intra-cerebral lesions which were deep-seated or located in certain main functional areas. The patients were 198 men and 112 women. Their ages ranged from 4.5 to 70 years (average: 39.3 years). The lesions were located in the deep cerebrum (74 patients), the sellar area (62), the basal ganglion (51), the posterior part of the third ventricle (38), other intraventricleular area (21), the cerebellum (17) and the brain stem (9), and intracranial multiple lesions were found in 38 patients.Results Brain tumors were diagnosed pathologically in 266 patients (85.8%); inflammatory process in 25 (8.1%), other lesions in 8 (2.6%) and uncertain cases were 11 (3.6%). The overall positive rate of biopsy was 96.4% and the positive rate for brain tumor was 85.8%. Intracranial hematomas after biopsy were found in 5 patients (1.6%). There were no deaths induced by the biopsy or other serious complications.Conclusions The results suggest that CT-guided stereotactic biopsy is a reliable method for histopathological diagnosis of brain tumors and it is also of great help in selecting appropriate management.

Objective To investigate the changes in percentage and function of CD4+CD25+regu-latory T cells ( Tregs) in peripheral blood of patients with hay fever. Methods A total of 20 patients with hay fever, 20 patients with house dust mite-induced allergic asthma and 20 healthy subjects were enrolled in this study. Peripheral blood samples were collected from all subjects to isolate PBMCs. Percentages of Tregs in PBMCs were measured by flow cytometry. CD4+CD25+ Tregs and CD4+CD25-T cells ( Teffs) were isola-ted by immunomagnetic cell sorting. Effects of CD4+CD25+Tregs on the proliferation of Teffs were evaluated by MTT assay. Expression of Foxp3 and TGF-β1 at mRNA level was analyzed by RT-PCR. Results During the pollen season, the percentage of circulating Tregs in patients with hay fever [(1. 82+0. 82)％] was sig-nificantly lower than that in patients with house dust mite-induced allergic asthma [(2. 96±1. 34)％] and health subjects [(5. 78±2. 29)％] (both P<0. 05). Expression of Foxp3 at mRNA level was significantly reduced in patients with hay fever (0. 46±0. 25) as compared with that of the house dust mite-induced aller-gic asthma (0. 64±0. 31) and healthy control (1. 04±0. 21) groups (both P<0. 05). Expression of TGF-β1 at mRNA level in both hay fever (0. 34±0. 27) and house dust mite-induced allergic asthma (0. 43±0. 31) groups was lower than that of the healthy control group (0. 99±0. 34). Treg-mediated suppression of Teff proliferation was significantly decreased in patients with hay fever [(17. 1±8. 4)％] as compared with that in patients with house dust mite-induced allergic asthma [(21. 4±9. 1)％]) and healthy subjects [(36. 0± 13. 9)％] (P<0. 05). Conclusion Decreased percentage and defective function of Tregs might be one of the major causes for the occurrence and development of hay fever in children during the pollen season.

Objective:To utilize routinely available clinical parameters to uncover the clinical features of different clusters in patients with chronic rhinosinusitis with nasal polyp (CRSwNP) through unsupervised clustering analysis.Methods:The clinical data from 155 CRSwNP patients undergoing nasal endoscopic surgery at Renmin Hospital of Wuhan University from 2021 to 2023 were prospectively collected, including 112 males and 43 females, aged from 7 to 87 years. Unsupervised clustering analysis was conducted using various clinical parameters, including age, gender, smoking and drinking history, local eosinophil (EOS) and neutrophil (NEU) counts, comorbid allergic rhinitis (AR), comorbid asthma, recurrence status, serum-specific IgE, total IgE, cytokine levels, peripheral blood EOS count and percentage, Lund-Mackay CT score, the ratio of CT scores for the maxillary sinus and ethmoid sinus (E/M ratio), visual analogue scale (VAS) score, Lund-Kennedy endoscopic score, and other common clinical indicators to elucidate the clinical characteristics of each cluster. Statistical analysis was conducted using GraphPad Prism 9.5 software.Results:Hierarchical clustering analysis identified four main clusters (Cluster A1-A4), showcasing distinct characteristics such as mild nasal polyps with higher peripheral blood cytokines levels, nasal polyps accompanied by allergies and asthma, a subtype of nasal polyps with high recurrence rates dominated by neutrophils, and nasal polyps with high eosinophil levels. Further subset clustering revealed two clusters of mild polyps (Cluster B1-B2) featuring high cytokine expression and comorbid AR; and two clusters of severe polyps (Cluster B3-B4) presented with severe symptoms, high Lund-Mackay CT score, and high Lund-Kennedy endoscopic score. Variations between Cluster B3 and B4 included symptom complexity, the degree of eosinophil infiltration, and the probability of comorbid asthma. Further clustering analysis for eosinophilic nasal polyps revealed a cluster characterized by highly neutrophilic infiltration and recurrent nasal polyps. The comprehensive analysis of multi-index correlations demonstrated valuable insights into the relationships between common clinical parameters of nasal polyps, providing valuable information for a deeper understanding of the pathogenesis of CRSwNP.Conclusion:The clustering analysis in this study categorizes CRSwNP patients into different clusters based on clinical features and disease outcomes, providing a new perspective for more precise clinical treatment strategies.