AIM:To investigate the therapeutic effect of enteric-coated sustained-release new dosage form of tadalafil on mice with renal fibrosis caused by unilateral ureteral obstruction(UUO).METHODS:Eight-week-old male C57BL/6J mice were divided into four groups randomly:sham group,UUO group,UUO+new dosage form of tadalafil(1 mg/kg)group and UUO+original patented drug of tadalafil(5 mg/kg)group.Surgery was performed to create a mouse UUO model,and therapeutic drugs were administered intragastrically for 7 d after modeling.A fully automated biochemi-cal analyzer was used to detect serum creatinine(SCr)levels of each group.Through renal histopathological staining(HE staining,Masson trichrome staining,and immunohistochemistry staining)and Western blot,we assessed the therapeutic effect of enteric-coated sustained-release new dosage forms of tadalafil on kidney fibrosis in mice,as well as its effect on the expression and distribution of fibronectin(FN)and α-smooth muscle actin(α-SMA).RESULTS:Compared with sham group,the SCr levels were significantly increased in mice with renal fibrosis,and renal tubules were dilated and in-filtrated with inflammation.Moreover,the expressions of FN and α-SMA were increased significantly(P<0.05).New dosage form and the original patented drug tadalafil both significantly reduced SCr levels in mice with renal fibrosis,im-proved the renal tissue structure on the affected side,reduced collagen fiber deposition,and inhibited FN and α-SMA ex-pression(P<0.05).CONCLUSION:Enteric-coated sustained-release new dosage form of tadalafil reduces the deposit of extracellular matrix in kidney interstitial tissue and attenuates fibrosis and renal function damage caused by ureteral ob-struction.New dosage form of tadalafil has significant advantages over the original patented drug because the low dose and high effectiveness.

Aim To explore the application value of a predictive model constructed based on superb microvascu-lar imaging(SMI)blood flow grading indicators and serological indicators in evaluating the risk of carotid plaque shedding.Methods A total of 122 patients diagnosed with carotid plaque in Lishui Central Hospital from February 2019 to February 2021 were selected.SMI was used to observe the blood flow grading and plaque characteristics in carotid plaque,and baseline clinical data of the patients were recorded.All patients were followed up for a period of 2 years,with the occur-rence of transient ischemic attack(TIA)or acute ischemic stroke(AIS)as the endpoint event,and were divided into plaque shedding group and non-shedding group.Clinical data of the two groups were compared and analyzed,and multiple regression analysis was conducted to identify the relevant factors affecting carotid plaque shedding.According to the SMI ultrasound characteristics and serological indicators,R software was adopted to establish the nomogram model and evaluate effectiveness of the model.Results During the 2-year follow-up period,21 TIA cases and 14 AIS cases were found in the remaining 112 patients excluding 10 lost to follow up.The SMI blood flow grading,neutrophil to lymphocyte ratio(NLR),matrix metalloproteinase-9(MMP-9),and low density lipoprotein cholesterol(LDLC)levels in the plaque shedding group were higher than those in the non-shedding group,and the differences were statistically significant(P＜0.05).Multivariate Logistic regression analysis showed that SMI blood flow grade 3(OR=38.095),LDLC(OR=19.730),NLR(OR=34.525)and MMP-9(OR=1.225)were independent risk factors for carotid plaque shedding(P＜0.05).The R software established a column chart model and applied it to the ROC curve analysis.The AUC of the col-umn chart model in early prediction of plaque shedding was 0.917,with a sensitivity of 82.86％and a specificity of 90.91％.Conclusion The predictive model constructed by combining blood flow grading within carotid artery plaques and serological indicators through SMI can provide early warning of plaque shedding and guide clinical early intervention to reduce the risk of TIA and AIS.

Patients with skeletal ClassⅡ often show symptoms such as protrusion of maxillary anterior teeth,mandibular retraction,open lips and teeth,deep overbite,and deep overjet,which seriously affect the facial appearance.This article reports a case of an ado-lescent male patient with skeletal Class Ⅱ combined with impacted teeth treated by one-stage early correction and two-stage fixation.After treatment,the patient's skeletal Class Ⅱ symptoms improved significantly,including the improvement of mandibular retraction.The problem of open lips and teeth was solved;the facial appearance tended to be straight,and there was no obvious abnormality of the temporomandibular joint.This case shows that early correction can achieve good therapeutic effects on this kind of patients and can avoid or reduce the possibility of orthognathic surgery for these patients in adulthood.

Objective:To observe the application effect of outcome-based education (OBE) concept on the teaching of otorhinolaryngology nursing.Methods:A total of 97 nursing interns from the Department of Otorhinolaryngology in The Second Affiliated Hospital of Army Medical University were selected as the research objects. Among them, 46 ones from March 2017 to February 2019 were collected as the control group, and 51 ones from March 2019 to February 2021 as the observation group. The control group adopted traditional nursing clinical teaching, and the observation group adopted the nursing clinical teaching based on the OBE concept. All the nursing students had an internship for 3 weeks, and had an evaluation in terms of the clinical communication ability of the two groups of nursing students when they leave the department (the nursing students' clinical communication ability assessment scale), the daily life problem solving ability (simplified Chinese version of the daily life problem solving questionnaire), theoretical and operational assessment results, and the internship satisfaction (nursing student internship satisfaction scale). SPSS 19.0 was used for independent-sample t test. Results:When leaving the department, the observation group's clinical communication ability scores were significantly higher than those of the control group in such dimensions as establishing a harmonious relationship, keen listening, confirming patient problems, participating together, transmitting effective information, and verifying feelings ( P<0.05). The scores of simplified Chinese version of the daily life problem solving questionnaire of rational problem solving and positive problem orientation of the observation group were significantly higher than those of the control group ( P<0.05), while the scores of negative problem orientation, avoidance style and impulsivity/carelessness style were significantly lower than those of the control group ( P<0.05). The scores of theoretical and operational evaluations of the observation group were significantly higher than those of the control group ( P<0.05). The practice satisfaction scores on each dimension of the observation group, including clinical teaching, classroom teaching, and internship plan, support and resources were significantly higher than those of the control group ( P<0.05). Conclusion:The OBE concept applied in the teaching of otorhinolaryngology nursing can enhance the clinical communication ability and daily life problem-solving ability of nursing students, increase the theoretical and operational assessment results, and improve the satisfaction of internship.

Objective:To observe the glycemic profiles and emotion management in diabetic patients after the outbreak of novel coronavirus disease 2019(COVID-19).Methods:A questionnaire survey was used to observe the blood glucose levels and metabolic indexes before and after the outbreak of COVID-19, and to detect emotion ratings after the outbreak of COVID-19. The aim of the study is to present the effects of the COVID-19 on glycemic and emotional management in diabetic patients.Results:A total of 136 patients were included in this survey. The average age of the patients was 62.5 years old, and the average duration of diabetes was 10.1 years. Glycemic profiles(fasting blood glucose, 2 h postprandial blood glucose, HbA 1C), lipid profiles(triglycerides, low-density lipoprotein cholesterol), and body weight were not significantly different before and after the outbreak of COVID-19( P>0.05). According to emotional scales(scores of anxiety, depression, and sleep-related scales), 76.5% diabetic patients did not develop anxiety symptoms, 61.0%~69.9% diabetic patients did not have depressive symptoms and 52.0% diabetic patients did not have sleep disorder. 19.9% diabetic patients had mild anxiety symptoms, 25.7%~30.9% diabetic patients presented mild depression symptoms and 28.3% diabetic patients had mild sleep disorders. 2.9% diabetic patients had moderate anxiety, 2.2%~8.1% diabetic patients had moderate depression and 14.2% diabetic patients had moderate sleep disorder. Only a very small part of patients presented severe emotional symptoms including 0.7% patients with anxiety symptoms(GAD-7 15 points and above), 2.2% patients with depressive symptoms(PHQ9 and PHQ15 15 points and above)and 5.6% patients with sleep symptoms(PSQI 15 points and above). Compared with asymptomatic patients, neither patients with mild and moderate/severe depression and sleep disorder showed significant difference in HbA 1C, nor did patients with moderate/ severe anxiety symptoms. However, patients with mild anxiety symptoms showed significant lower HbA 1C than asymptomatic patients. Conclusion:After the outbreak of COVID-19, there was an increasing trend in blood glucose, but there was no statistical difference. Body weight, lipids profiles were not different in diabetic patients, either. Most of diabetic patients had mild symptoms of anxiety, depression and sleep disorders. Very few patients presented moderate to severe symptoms of anxiety, depression and sleep disorders.

Objective: To evaluate the practical efficacy of a colloidal gold (CG) detection reagent of rabies virus antibody. Methods: Series dilutions of rabies immunoglobulin and serum samples of rabies vaccine immunized population were tested by a CG detection reagent of rabies virus antibody and rapid fluorescent focus inhibition test (RFFIT). The consistency of the qualitative results of rabies virus antibodies between the two methods were compared. The comparison of rates was made by Chi-square test. Results: For rabies immunoglobulin diluent, the detection limit of the rabies virus antibody CG detection reagent was higher than 6.53 IU/ml but lower than 9.53 IU/ml. For the serum samples, the detection limit of the rabies virus antibody CG detection reagent was higher than 2.80 IU/ml but lower than 3.30 IU/ml. The positive rates of serum rabies virus antibodies detected by CG and RFFIT were 26% and 67% respectively, and the difference was statistically significant (χ² =13.66, P=0.000). The results of RFFIT were regarded as gold standard, false negative results but no false positive results were observed when CG was used to detect serum rabies virus antibodies. Conclusions The sensitivity of the rabies virus antibody CG detection reagent is poor, and attention should be paid to the phenomenon of missing some practically positive results in practical application of CG detection reagent.

Objective To evaluate and analyze the drug-drug interactions(DDI)of different antidiabetic drugs.Methods DDI database Lexi-InteractionTMwas used to evaluate DDI for 28 commonly used antidiabetic medications(including insulin and 27 non-insulin preparations).Results 882 DDIs were identified for 28 drugs.Category C was the top rated DDI(69.8%). Category C,D,X were accounted for 91.2% of the total DDI.28 medication combinations belonged to category X,which should be avoided to use together.Sulfonylureas had the most DDI,followed by metformin.Alpha-glucosidase inhibitors had least DDI.Conclusion Hypoglycemic drugs with less DDI,such as α-glycosidase inhibitors,glucagon-likepeptide1(GLP-1)an-alogs and sodium-dependent glucose transporters 2 inhibitor(SGLT2i)should be considered with high priority for patients tak-ing multiple antidiabetic medications,elderly patients and patients with liver-kidney dysfunction.

Objective To study the effect and mechanism of endoplasmic reticulum stress on hippocampal neuron apoptosis and cognitive impairment in type 1 diabetic rats. Methods Ten rats were randomly selected as normal control group (Con group) from thirty Wistar rats, and the remaining twenty rats were intraperitoneally injected with streptozotocin to prepared for type 1 diabetic rat model. The successful model rats were randomly divided into diabetic group (DM group) and diabetic +Salubrinal group (DM+Sal group). Rats of DM+Sal group were injected by lateral ventricle with Salubrinal ( 75μmol/L, 1μL). Rats of Con group and DM group were given the equal volume of normal saline. The rat cognitive function was assayed by Morris water maze test. The hippocampal neuron apoptosis was detected by TUNEL and flow cytometry methods. The protein levels of endoplasmic reticulum stress markers, GRP78, CHOP and Caspase12, and the mRNA levels of GRP78 and CHOP, were examined by Western blot assay and Real-time PCR, respectively. Results Compared with the Con group, the cognitive function was significantly decreased in DM group, and the apoptotic rate of hippocampal neurons was increased. The protein levels of endoplasmic reticulum stress markers GRP78, CHOP and Caspase12 were significantly increased (P<0.05), and the mRNA levels of GRP78 and CHOP were also higher in DM group (P<0.05). After the injection with Salubrinal, the cognitive function was improved and hippocampal neuron apoptotic rate was decreased in DM+Sal group compared with those of DM group. Moreover, the protein levels of GRP78, CHOP and Caspase12 were significantly decreased (P<0.05) and the mRNA levels of GRP78 and CHOP were also lowered in DM+Sal group (P<0.05). Conclusion The cognitive impairment and the higher apoptotic rate appear in the diabetic rats, and endoplasmic reticulum stress may play an important role in it.

The classification of diagnosis and treatment is based on the classification of disease, and medical institutions at different levels bear different diseases to achieve the first contact care in primary hospitals and two-way referral.As one of the common chronic diseases, diabetes is a serious threat to human health.The classification of diagnosis and treatment model is beneficial to controlling blood sugar and promoting the integrated management of chronic diseases.Clinical pharmacists as medical and pharmaceutical professionals can provide pharmacy services to promote rational drug use in the diagnosis and treatment of diabetes.The article summarized the current methods for the classification of diagnosis and treatment model (diabetes mellitus) and the participation ways of clinical pharmacists in the model in order to provide new ideas for the comprehensive management of diabetes mellitus.

Objective: To examine the association between polymorphism of rs10185316 in insulin-induced gene 2 (INSIG2) and blood pressure among children and adolescents. Methods: 9 junior middle schools in Dongcheng District of Beijing and 5 schools (3 primary junior middle schools, 2 primary schools) in Haidian District of Beijing were chosen in 2005 and 2007, respectively. According to the Chinese BMI percentile criteria for screening overweight and obesity in school children, we recruited 1 425 overweight or obese children and 605 normal weight children. A total of 2 018 students with complete data of blood pressure and genotype data were included in this study. According to the blood pressure criterion of children and adolescents, 702 participants were categorized into high blood pressure group and 1 316 into normal blood pressure group. Participants' information of gender, age, height, weight and blood pressure were collected by questionnaire and physical examination. Genomic DNA was extracted from peripheral blood sample for genotyping of INSIG2 rs10185316 polymorphism. Multiple linear regression was conducted to analyze the associations between rs10185316 polymorphism in INSIG2 and SBP, DBP, mean arterial pressure (MAP) and pulse pressure. Results: The age, BMI, SBP and DBP of the high blood pressure group were separately (14.3±1.4) years old, (27.3±4.2) kg/m², (130.5±10.9) and (76.7±13.3) mmHg (1 mmHg=0.133 kPa), all higher than that of the normal blood pressure group, which were (12.2±2.9) years old, (22.0±4.0) kg/m², (104.4±10.9) and(54.6±15.2) mmHg, respectively (all P values<0.001). After age, sex, district and BMI adjusted, compared with the participants carrying INSIG2 rs10185316 CC genotype, CG/GG genotype carriers had lower DBP (β(95%CI):-1.67(-2.84--0.50), P=0.005), higher PP(β(95%CI): 1.91(0.61-3.20), P=0.004), and lower MAP(β(95%CI):=-1.03(-2.01--0.05), P=0.039). Conclusion INSIG2 rs10185316 polymorphism was associated with DBP, PP and MAP among children and adolescents in an independent way from BMI.