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.

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.

Objective To investigate the expression of Nanog and its regulatory relationship with MMP-2/MMP-9 proteins in esophageal squamous cell carcinoma(ESCC).Methods We detected Nanog and MMP-2/MMP-9 protein expressions in 127 ESCC tissues and 82 adjacent normal tissues using immunohistochemistry and explored their correlations with the clinicopathological parameters and prognosis of the patients.GEO database was utilized to analyze the pathways enriched with the stemness-related molecules including Nanog,and TIMER online tool was used to analyze the correlations among TβR1,MMP-2,and MMP-9 in esophageal cancer.Results Nanog and MMP-2/MMP-9 proteins were significantly upregulated in ESCC tissues and positively intercorrelated.Their expression levels were closely correlated with infiltration depth and lymph node metastasis of ESCC but not with age,gender,or tumor differentiation.The patients with high expressions of Nanog and MMP-2/MMP-9 had significantly shorter survival time.Bioinformatics analysis showed enrichment of stemness-associated molecules in the TGF-β signaling pathway,and the expressions of MMP-2/MMP-9 and TβR1 were positively correlated.In cultured ESCC cells,Nanog knockdown significantly decreased the expression of TβR1,p-Smad2/3,MMP-2,and MMP-9 and strongly inhibited cell migration.Conclusion The high expressions of Nanog,MMP-2,and MMP-9,which are positively correlated,are closely related with invasion depth,lymph node metastasis,and prognosis of ESCC.Nanog regulates the expressions of MMP-2/MMP-9 proteins through the TGF-β signaling pathway,and its high expression promotes migration of ESCC cells.

Objective To investigate the expression of Nanog and its regulatory relationship with MMP-2/MMP-9 proteins in esophageal squamous cell carcinoma(ESCC).Methods We detected Nanog and MMP-2/MMP-9 protein expressions in 127 ESCC tissues and 82 adjacent normal tissues using immunohistochemistry and explored their correlations with the clinicopathological parameters and prognosis of the patients.GEO database was utilized to analyze the pathways enriched with the stemness-related molecules including Nanog,and TIMER online tool was used to analyze the correlations among TβR1,MMP-2,and MMP-9 in esophageal cancer.Results Nanog and MMP-2/MMP-9 proteins were significantly upregulated in ESCC tissues and positively intercorrelated.Their expression levels were closely correlated with infiltration depth and lymph node metastasis of ESCC but not with age,gender,or tumor differentiation.The patients with high expressions of Nanog and MMP-2/MMP-9 had significantly shorter survival time.Bioinformatics analysis showed enrichment of stemness-associated molecules in the TGF-β signaling pathway,and the expressions of MMP-2/MMP-9 and TβR1 were positively correlated.In cultured ESCC cells,Nanog knockdown significantly decreased the expression of TβR1,p-Smad2/3,MMP-2,and MMP-9 and strongly inhibited cell migration.Conclusion The high expressions of Nanog,MMP-2,and MMP-9,which are positively correlated,are closely related with invasion depth,lymph node metastasis,and prognosis of ESCC.Nanog regulates the expressions of MMP-2/MMP-9 proteins through the TGF-β signaling pathway,and its high expression promotes migration of ESCC cells.

The latest epidemiological data suggests that the situation of adult diabetes in China is severe, and metabolic diseases have become significant chronic illnesses that have a serious impact on public health and social development. After more than six years of practice, the National Metabolic Management Center(MMC) has developed distinctive approaches to manage metabolic patients and has achieved a series of positive outcomes, continuously advancing the standardized diagnosis and treatment model. In order to further improve the efficiency, based on the first edition, the second edition guideline was composed by incorporating experience of the past six years in conjunction with the latest international and domestic guidelines.

Anti-seizure medications (ASMs) are the main therapy for epilepsy.There are many kinds of ASMs with complex mechanism of action, so it is difficult for pharmacists to examine prescriptions.This paper put forward some suggestions on the indications, dosage forms/routes of administration, appropriateness of usage and dosage, combined medication and drug interaction, long-term prescription review, individual differences in pathophysiology of children, and drug selection when complicated with common epilepsy, for the reference of doctors and pharmacists.

Hepatocellular carcinoma (HCC) is a malignant tumor with high incidence in China and the whole world, and early diagnosis and treatment are the key to improving the prognosis of patients. To facilitate the communication and cooperation between doctors of different centers and specialties, American College of Radiology issued the first edition of contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) in 2016 to standardize the technical terms, techniques, interpretation, reporting, and data collection for liver imaging and perform HCC risk stratification for different focal liver lesions. This article reviews the development and clinical application of CEUS LI-RADS and believes that the application of CEUS LI-RADS has a great potential value in the clinical management of focal liver lesions in the population at a high risk of HCC, and the applicable population and indications for CEUS LI-RADS will continue to expand in the near future, so as to provide better service to clinical practice.

Objective:To investigate the diagnosis and treatment value of intraoperative ultrasound (IOUS) in video-assisted thoracic surgery (VATS) of small solitary pulmonary nodule (SSPN).Methods:Of the 35 SSPN patients who received VATS in Tianjin Third Central Hospital from January 2016 to January 2020, the visual and touch examination (VTE) and IOUS method were used to locate pulmonary nodules during the operation. The differences between the two methods in the locating success rate and locating time were compared. The imaging findings of SSPN were classified and the sonographic characteristics of SSPN were summarized by univariate analysis.Results:The success rate of IOUS locating was 91.43%(32/35), which was higher than that of VTE 48.57%(17/35), and the difference was statistically significant (χ 2=15.310, P<0.001). The time of IOUS locating (6.23±1.93)min was shorter than that of VTE(9.98±1.56)min, and the difference was statistically significant ( t=6.940, P<0.001). The sonograms of 32 SSPN(17 malignancy and 15 benign) patients were all hypoechoic, univariate analysis showed that heterogeneous echo (χ 2=10.615, P=0.01) and unclear borderline (χ 2=10.041, P<0.001) were helpful to judge the benign or malignant. Conclusions:In video-assisted thoracic surgery, using IOUS could quickly and accurately locate and diagnose SSPN, which can shorten the operation time, improve the resection efficiency and guide the operation.

Objective:To investigate the feasibility and safety of ultrasound-guided percutaneous submandibular region puncture and drainage(PSPD) for treating parapharyngeal space abscess (PPSA).Methods:The clinical data of 26 patients with PPSA receiving PSPD from January 2015 to December 2019 in the Third Central Hospital of Tianjin were retrospectively analyzed.Results:All 26 patients successfully underwent puncture and catheterization with a primary success rate of 100%. After catherization, pain relieved within 12-24 hours, body temperature returned to normal within 24-48 hours, white blood cell(WBC) and C-reactive protein(CRP) returned to normal within 48-96 hours. The catheterization duration ranged from 5 to 14 days and the average time was 7 days. There were statistically significant differences in the body temperature, maximum abscess diameter, WBC and CRP between pre-operation and 7 days after operation(all P<0.001). None of the 26 patients experienced any serious complications such as major vessels, nerve or glands injury. Bacterial cultures were positive in 18 patients and the most common bacteria was hemolytic streptococcus. Conclusions:PSPD is an effective, safe and minimally invasive method for the treatment of PPSA as an alternative to operative incision and drainage.

Objective: To investigate the efficacy of alternative donor (AD) in the treatment of aplastic anemia (AA) in children. Methods: The clinical data of AA children who received AD HSCT in our center from Apr. 2010 to Dec. 2016 were retrospectively analyzed. The overall survival (OS) rate, implant success rate, incidence of acute and chronic graft-versus-host disease (GVHD) were statistically analyzed. Results: A total of 109 children with acquired AA, including 64 severe AA (SAA) , 32 very severe AA (VSAA) and 13 transfusion dependent non-severe AA (NSAA) , were recruited in this retrospective AD HSCT study, the median age was 6 (0.8-18) years old. Of them, 44 patients with 10/10 matched unrelated donor (MUD) , 44 patients with mismatched unrelated donor (MMUD) and 21 patients with mismatched related donor (MMRD) . All patients did not receive ATG before HSCT and the active infection was excluded. Except 3 patients suffered from a second graft failure (2 of them rescued by second HSCT) , 106/109 (97.2%) were engrafted with neutrophil and platelet recovery occurring at a median of 13 days (range, 9-19) and 16 days (range, 10-81) post-transplant. Until day 100 post transplantation, the incidence was 74.3% (81/109) for acute GVHD (aGVHD) and 39.4% (43/109) for grade Ⅱ-Ⅳ aGVHD, 30.7% (31/101) and 9.9% (10/101) for overall chronic GVHD (cGVHD) and moderate cGVHD, respectively, and nobody developed an extend cGVHD. After median follow up of 39 (0.7-103) months for all patients, 13 of 109 patients died. The estimated 5-year overall survival (OS) of the entire cohort was 88.1% (95%CI 81.1%-91.4%) with no difference among the MUD, MMUD and MMRD cohort (93.2%, 84.1% and 85.7%, respectively, P=0.361) . Conclusion These excellent outcomes suggest that unmanipulated AD PBSC is a good HSCT source for children with SAA. It’s reasonable to consider AD HSCT as first line therapy for SAA children without matched sibling donor. Better strategies are required to prevent GVHD.