ObjectiveTo investigate the mechanism by which Feixin decoction treats hypoxic pulmonary hypertension （HPH） by regulating the peroxisome proliferator-activated receptor gamma （PPARγ）/nuclear factor-kappa B （NF-κB）/NOD-like receptor pyrin domain containing 3 （NLRP3） signaling pathway. MethodsForty-eight male SD rats were randomly allocated into normal， hypoxia， and low-， medium- and high-dose （5.85， 11.7， 23.4 g·kg^-1， respectively） Feixin decoction groups， with 8 rats in each group. Except the normal group， the remaining five groups were placed in a hypoxia chamber with an oxygen concentration of （10.0±0.5）% for 8 h per day， 28 days， and administrated with corresponding drugs during the modeling process. After 4 weeks of treatment， echocardiographic parameters ［pulmonary artery acceleration time （PAT）， pulmonary artery ejection time （PET）， right ventricular anterior wall thickness （RVAWd）， and tricuspid annular plane systolic excursion （TAPSE）］ were measured for each group. The right ventricular systolic pressure （RVSP） was measured by the right heart catheterization method， and the right ventricular hypertrophy index （RVHI） was calculated by weighing the heart. The pathological changes in pulmonary arterioles were observed by hematoxylin-eosin staining. The co-localization of α-smooth muscle actin （α-SMA） with NLRP3， N-terminal gasdermin D （N-GSDMD）， and cysteinyl aspartate-specific proteinase-1 （Caspase-1） in pulmonary arteries was detected by immunofluorescence. The protein levels of PPARγ， NF-κB， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， N-GSDMD， interleukin-1β （IL-1β）， interleukin-18（IL-18）， and cleaved Caspase-1 in the lung tissue was determined by Western blot. The ultrastructural changes in pulmonary artery smooth muscle cells （PASMCs） were observed by transmission electron microscopy. ResultsCompared with the normal group， the hypoxia group showed increased RVSP and RVHI （P<0.01）， decreased right heart function （P<0.01）， increased pulmonary vascular remodeling （P<0.01）， increased co-localization of α-SMA with NLRP3， N-GSDMD， and Caspase-1 in pulmonary arterioles （P<0.01）， up-regulated protein levels of NF-κB， NLRP3， ASC， N-GSDMD， IL-1β， IL-18， and cleaved Caspase-1 in the lung tissue （P<0.05， P<0.01）， a down-regulated protein level of PPARγ （P<0.05， P<0.01）， and pyroptosis in PASMCs. Compared with the hypoxia group， Feixin decoction reduced RVSP and RVHI， improved the right heart function and ameliorated pulmonary vascular remodeling （P<0.05， P<0.01）， decreased the co-localization of α-SMA with NLRP3， N-GSDMD， and Caspase-1 （P<0.05， P<0.01）， down-regulated the protein levels of NF-κB， NLRP3， ASC， N-GSDMD， IL-1β， IL-18， and cleaved Caspase-1 in the lung tissue （P<0.05， P<0.01）， up-regulated the protein level of PPARγ （P<0.05， P<0.01）， and alleviated pyroptosis in PASMCs. ConclusionFeixin decoction can ameliorate pulmonary vascular remodeling and right heart dysfunction in chronically induced HPH rats by regulating pyroptosis in PASMCs through the PPARγ/NF-κB/NLRP3 pathway.

OBJECTIVE To study the pharmacodynamics and pharmacokinetics of semaglutide(Sem)capsules in type 2 diabetic model rats.METHODS Male SD rats were divided into the normal control group,type 2 diabetic model group and model+Sem capsules(0.839,1.678 and 2.517 mg·kg-1)groups.A type 2 diabetic rat model was induced by high sugar and high fat diet feeding combined with ip given streptozotocin(STZ)injection.Seven days after modeling,the model+Sem capsules group was ig given Sem capsules at the corresponding dose in a fasting state,once a day,for 14 d.Body mass,fasting blood glucose(FBG),and glycosylated hemoglobin(HbA1c)levels were regularly mea-sured in each group of rats.Plasma from rats in the model+Sem capsules 0.839,1.678 and 2.517 mg·kg-1 groups at different time points was collected at the end of the continuous administration of Sem capsules,and the content of Sem in the plasma of rats was determined by liquid chromatography-tandem mass spectrometry.Concentration-time curves were plotted,and the main pharmacokinetic parameters were fitted by the WinNonlin non-atrial model method.RESULTS Compared with the model group,the body mass of rats in model+Sem capsules dosing groups decreased significantly after 7 and 14 d of Sem capsules intervention(P<0.05,P<0.01),so did FBG(P<0.01)and the HbA1c level(P<0.01).Meanwhile,FBG and HbA1c levels of rats in model+Sem capsules 1.678 and 2.517 mg·kg-1 groups were not significantly different from those of the normal control group after 14 d of Sem capsules intervention,suggesting that FBG and HbA1c levels were basically restored to normal.Phar-macokinetic results showed that the elimination half-life(t1/2)of Sem in plasma after ig administration of Sem capsules 0.839,1.678,and 2.517 mg·kg-1 for 14 d in rats was 7.40±1.34,7.48±0.33 and(8.23±0.90)h,respectively,the peak concentration(Cmax)was 18±9,81±23 and(256±53)μg·L-1,time to peak(Tmax)was 0.06±0.13,1.56±0.88,(1.50±1.00)h,respectively,the area under the curve(AUC0-t)was 158±76 μg·h·L-1,858±310 and(3795±1539)μg·h·L-1,and the accumulation index was 1.12±0.05,1.12±0.01 and 1.15±0.04,respectively.CONCLUSION Sem capsules ig administrated can effectively reduce body mass,FBG and HbA1c levels in type 2 diabetic model rats,and lead to glucose reduction and by mass loss.After 14 d of continuous administration of Sem capsules,there is no accu-mulation of semaglutide in rats in the dose range of 0.839-2.517 mg·kg-1,and the exposure increases with the dose.

Graduate students are the main practitioners of animal experiments in universities.However,a lack of professional skills and management standards for education on laboratory animals in medical graduate student courses has led to frequent violations of animal experimental guidelines and poses a significant biosafety risks.To ensure the quality of animal experiments and improve the research quality and skills of graduate students,with reference to current practices,this article proposes an innovative teaching model combining a Laboratory Animal Science course with training for medical graduate students.We suggest reforms to teaching content according to scientific research needs,recommend improvements in teaching method,and analyze the significance of the teaching-training model.Our review was written to propose new ideas for strengthening graduate students'awareness of animal experiment standardization and improve their scientific research literacy,as well as provide a reference for animal experiment standardization for educators of domestic medical students.

In order to develop a positive quality control products for the detection of porcine repro-ductive and respiratory syndrome virus(PRRSV)nucleic acid by real-time fluorescent quantitative PCR(RT-qPCR),the positive quality control products of PRRSV-1 and PRRSV-2 M genes were prepared using armored RNA technology of MS2 phage.PRRSV-1 and PRRSV-2 M genes were amplified,purified and recovered,and ligated into pET28b vector containing MS2 mature enzyme protein gene and capsid protein.After transformed into BL21(DE3),the gene products were in-duced by IPTG and purified by PEG6000 precipitation method to prepare the armored RNA virus-like particles(AR-PRRSV)containing PRRSV M gene.Following the performance evaluation,as the positive quality control products of PRRSV-1 and PRRSV-2 M genes,AR-PRRSV1M and AR-PRRSV2M were calculated using YY/T 1652-2019 standard.Results showed that it had a good u-niformity,stable storage for the armored virus-like particles at-20,4,25 ℃ for 60 d,and 37 ℃ for 30 d.The prepared armored virus-like particles AR-PRRSV1M and AR-PRRSV2M were deter-mined by digital quantitative PCR(ddPCR)after preliminary quantification by RT-qPCR.The 104 copies/μL of AR-PRRSV1M and AR-PRRSV2M ddPCR fixation was(1.33+0.50)× 104 cop-ies/μL.The above results indicates that the AR-PRRSVM can be used as the quality control of the whole detection process(nucleic acid extraction,reverse transcription and RT-qPCR).

Objective:To assess the feasibility of wavelet index (WLI) in monitoring the depth of sedation with propofol in pediatric patients.Methods:This was a prospective observational trial. One hundred and sixty-five pediatric patients, aged >1-12 yr, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, undergoing elective surgery requiring general anesthesia with endotracheal intubation or laryngeal mask airway from July to December 2016 in our hospital, were divided into 11 age groups ( n=15 each): >1-2 yr group, >2-3 yr group, >3-4 yr group, >4-5 yr group, >5-6 yr group, >6-7 yr group, >7-8 yr group, >8-9 yr group, >9-10 yr group, >10-11 yr group, and >11-12 yr group. General anesthesia was induced by injection of propofol 3 mg/kg for more than 30 s. WLI and BIS values were recorded immediately before administration and at 30, 40, 50, 60, 90, 120, 180 and 240 s after the end of administration. If there were differences among age groups, age groups with no statistically significant differences were combined and re-grouped. Pearson linear correlation analysis and Bland-Altman consistency analysis were performed. Results:A total of 149 pediatric patients were actually included. There were no significant differences in BIS values between 4 groups aged > 1-5 yr and between 7 groups aged > 5-12 yr ( P>0.05). Regrouping was performed based on the aforementioned results, 4 groups of children aged > 1-5 yr were divided into > 1-5 yr group ( n=60), and 7 groups of children aged > 5-12 yr were divided into > 5-12 yr group ( n=89). WLI values and BIS values were significantly decreased at each time point after administration compared with immediately before administration in group aged > 1-5 yr and in group aged >5-12 yr ( P<0.05). The BIS values were the lowest at 60 s after the end of the administration, and the WLI values were the lowest at 120 and 180 s after the end of the administration in two groups ( P<0.05). There were no statistically significant differences between WLI values and BIS values at 90 s and 240 s after the end of the administration ( P>0.05), and there was statistically significant difference at the other time points in group aged > 1-5 yr ( P<0.05). There was no significant difference between WLI values and BIS values at 180 s and 240 s after the end of the administration ( P>0.05), but there were significant differences at the other time points in group aged > 5-12 yr ( P<0.05). The Pearson correlation coefficients between WLI values and BIS values were 0.61 and 0.56 in group aged > 1-5 yr and group aged > 5-12 yr, respectively ( P<0.001). Bland-Altman agreement analysis: In group aged > 1-5 yr and group aged > 5-12 yr, the 95% agreement limits were -0.484-0.621 and -0.551-1.015, respectively, and there were 4.6% (23/504) and 5.1% (40/777) of the points outside the 95% agreement limits, respectively, and both limits exceeded the clinically acceptable range. Conclusions:WLI is feasible for monitoring the depth of sedation with propofol in pediatric patients aged > 1-12 yr, but the accuracy is lower than BIS.

Objective:To explore the molecular mechanism through which repetitive transcranial magnetic stimulation (rTMS) promotes nerve regeneration after ischemic stroke.Methods:The miRNA expression profile in rats after rTMS was downloaded from the GEO database. Differentially-expressed miRNAs were identified using R software, and their corresponding mRNAs were predicted using the online database in order to construct miRNA-mRNA regulatory networks and identify the key miRNAs. The protein interaction network encoded by each gene was constructed by functional enrichment analysis, and the core mRNAs in the network were identified. Twenty-four male Sprague-Dawley rats of a specific pathogen-free grade were randomly divided into a sham operation group, a model group and a magnetic stimulation group, each of 8, and a stroke model was induced in the model and magnetic stimulation groups. The magnetic stimulation group then received rTMS for 7 consecutive days, while the other 2 groups did not. Modified neural function scores (mNSSs) were used to quantify neural function deficits before the experiment and 1, 3 and 7 days after the modeling. Eight days after the modeling, brain tissues were sampled for hematoxylin-eosin and Nishin staining to observe tissue loss and neuron morphology. Real-time fluorescence quantitative polymerase chain reactions were employed to verify the differential gene expression in the ischemic cortex.Results:A total of 167 different miRNAs were screened, and 25 mRNAs were predicted. Enrichment analysis showed that those genes are related to the positive regulation of cell migration and the positive regulation of neurotrophic factor receptor signaling pathways, including adenylate-activated protein kinase, the neurotrophic factor pathway, and rat sarcoma signaling pathways. The miRNA-mRNA regulatory network highlighted miR-206-3p, miR-378a-3p, miR-107-3p, miR-92a-3p and miR-29b-3p as key miRNAs. Integrin subunit β1, aquaporin 4, brain-derived nerve growth factor (BDNF), and member 4 of solutes vector family 2 were identified as key mRNAs by the protein interaction network analysis. Seven days after the modeling, the average mNSS score of the magnetic stimulation group was significantly lower than the model group′s average. Compared with the model group, the expression of miR-206-3p in the right cortex of the magnetic stimulation group had decreased significantly, while BDNF expression had increased significantly.Conclusions:miR-206-3p-BDNF pathways play an important role in neural repair promoted by rTMS.

Objective:To observe the clinical features, treatment and prognosis of ciliary body tumors.Methods:A retrospective clinical study. From November 2011 to March 2023, 8 cases (8 eyes) with ciliary body tumours confirmed by pathohistological examination at the Department of Ocular Oncology, Beijing Tongren Hospital were included in the study. Patients' age, gender, involved eyes, symptoms, best corrected visual acuity (BCVA), intraocular pressure, cataract, lens subluxation, and imaging manifestations were collected in detail. All affected eyes were treated surgically. The follow-up time after surgery ranged from 1 to 10 years. The patients' clinical presentation as well as imaging, pathohistological features and treatment and prognosis were analysed retrospectively.Results:Among 8 cases (8 eyes), there were 3 males (3 eyes) and 5 females (5 eyes), 3 and 5 eyes in the right and left eyes, respectively. The median age was 44 years. Ciliary body medulloepitheliomas, melanoma, squamous cell carcinoma, leiomyoma, schwannoma, and adenoma of the nonpigmcnted ciliary epithelium were in 2, 2, 1, 1, 1, and 1 eyes, respectively. All reported decreased or loss of vision. Cataract, vitreous opacity, red eye and or (ocular pain), retinal detachment, lens subluxation, and secondary glaucoma were 6, 4, 4, 2, 1, and 1 eyes, respectively. Diagnostic imaging was consistent with pathological findings in 3 eyes. The first surgery was performed for enucleation and orbital implantation in 2 eyes, the patients were 9 and 10 years old with medullary epithelioma; the follow-up time after surgery was 1 and 5 years, respectively. Local tumour resection was performed in 6 eyes. Among them, 3 eyes with benign tumours were followed up for 1 to 9 years after surgery; 2 eyes showed significant improvement in visual acuity, 1 eye with adenoma of the nonpigmcnted ciliary epithelium had a preoperative BCVA of finger count/1 m, and a postoperative BCVA of 0.5, and 1 eye with leiomyoma had a preoperative BCVA of 0.06, and a postoperative BCVA of 0.5; and 1 eye was lost to follow-up. Malignant tumour in 3 eyes, of which 2 eyes recurred after surgery. Re-operation for enucleation and local tumour excision combined with local cryotherapy in 2 eyes of recurrence were 1 eye each, respectively. The follow-up period after surgery was 2 and 4 years, respectively. No recurrence after surgery in 1 eye, but there was no significant improvement in visual acuity during follow-up. No recurrence or metastasis was observed in any of the eyes during the follow-up period or at the final follow-up.Conclusions:Ciliary body tumour types and clinical presentations are complex and varied; imaging can detect tumours but is poor at determining the nature of the lesion. Benign tumours do well with local excision surgery; malignant tumours do well with enucleation.

Objective:To explore the impact of sleep disorders on the therapeutic effects of different inhaled medications in patients with chronic obstructive pulmonary disease (COPD).Methods:A prospective observational study was conducted on 393 patients with stable COPD who visited the Department of Respiratory and Critical Care Medicine, the Second Xiangya Hospital, Central South University from December 2020 to September 2021. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the sleep quality of patients with chronic obstructive pulmonary disease, and patients were divided into a non sleep disorder group and a sleep disorder group. The Berlin questionnaire was used to assess the risk of obstructive sleep apnea syndrome (OSAS) in patients, and the hospital anxiety and depression questionnaire (HADS) was used to assess the presence of anxiety and depression in patients. The improvement of symptoms [minimum clinically significant difference (MCID)] and the deterioration of symptoms [clinical significant symptom deterioration (CID)] within six months of patient follow-up were evaluated. The moderate to severe acute exacerbation of the patient was recorded during the one-year follow-up period. The clinical characteristics of two groups of patients were compared, and multiple regression analysis was used to evaluate the relationship between sleep quality and the prognosis of chronic obstructive pulmonary disease, as well as the impact of sleep disorders on the treatment efficacy of different inhaled drugs.Results:The average age of 393 patients with chronic obstructive pulmonary disease was (62.9±8.3)years old, with a median percentage of forced expiratory volume in the first second (FEV 1%) of 53.7%(30.7%) and a mean PSQI score of (5.7±3.4)points. 186 cases (47.3%) of patients had sleep disorders. Compared with patients in the non sleep disorder group, patients in the sleep disorder group had a higher proportion of middle school education and below, lower FEV 1 and FEV 1/forced vital capacity (FVC), higher baseline COPD Assessment Test (CAT), modified Medical Research Council (mMRC) and Clinical COPD Questionnaire (CCQ) scores, and a higher proportion of comorbid anxiety (all P<0.05). Compared with patients without sleep disorders, patients with sleep disorders had a lower incidence of MCID ( P=0.030) and a higher incidence of CID ( P=0.005). During the one-year follow-up period, patients with sleep disorders experienced a higher proportion of moderate to severe acute exacerbation ( P=0.001), severe acute exacerbation ( P=0.003), and frequent acute exacerbation ( P=0.009). The results of multiple regression analysis showed that patients with sleep disorders had a lower likelihood of developing MCID ( OR: 0.288, 95% CI: 0.145-0.379, P<0.001), and an increased risk of developing CID ( OR: 3.150, 95% CI: 2.011-4.388, P<0.001) and acute exacerbation ( OR: 1.659, 95% CI: 1.162-2.368, P=0.005). Compared with patients using long-acting muscarinic antagonist (LAMA) or inhaled corticosteroids (ICS)+ long-acting β2-agonist (LABA), patients in the sleep disorder group who used LABA+ LABA were more likely to develop MCID ( OR: 1.420, 95% CI: 1.021-2.751, P=0.010; OR: 1.976, 95% CI: 1.123-2.227, P=0.023). Conclusions:Compared with patients without sleep disorders, COPD patients with sleep disorders have a lower likelihood of symptom improvement, and a higher risk of symptom deterioration and acute exacerbation.Patients with COPD with sleep disorders are more likely to achieve symptom improvement by using LABA+ LAMA.

Objective:To evaluate the effect of prior statins use on the in-hospital mortality of adult sepsis patients with type 2 diabetes (T2DM).Methods:A total of 3 545 sepsis patients with T2DM were retrospectively collected from the Critical Care Medical Information Market (MIMIC Ⅳ) database, with in-hospital mortality rate as the outcome variable. According to whether they have taken statins in the past, they were divided into two groups and propensity score matching was used. Multivariate Cox regression analysis was performed to calculate the adjusted hazard ratio ( HR) and 95% CI, and the relationship between past statins use and in-hospital mortality in sepsis patients with T2DM was analyzed. Results:A total of 3 545 sepsis patients with T2DM were included between 2008 and 2016. 1 556 patients used statins before admission, and 1 989 patients did not use statins. After propensity score matching, the number of patients who had previously used statins and those who had not used statins were 1 230 and 1 298, respectively. After adjusting for potential confounding factors, it was found that previous use of statins was associated with a reduced in-hospital mortality rate ( HR=0.82, 95% CI: 0.61-0.99, P=0.038). Kaplan Meier curves showed that sepsis patients with T2DM who used statins before admission had a lower in-hospital mortality rate (Log rank test: P<0.001). Conclusions:Pre admission use of statins may be associated with a reduced mortality rate in sepsis patients with concomitant T2DM.

IgG4-associated disease (gG4-RD) is a systemic immune-mediated fibroinflammatory disease that can involve almost all organs and systems, and the main clinical manifestations are enlargement or mass of the affected organs. The typical pathological features of the disease are a large number of lymphocytoplasmic infiltration in the pathological tissue, accompanied by mat fibrosis and obliterated phlebitis, and most patients may have elevated serum IgG4 levels. At present, the specific pathogenesis of the disease is not clear. In recent years, the mechanism of intestinal microbiome dysregulation in the occurrence and development of autoimmune diseases has been gradually clarified. However, the association between the gut microbiome and IgG4-RD is still poorly understood. Therefore, this article will review the progress of intestinal microbiome research of IgG4-RD.