Objective To Study wheather the endogenous arginine vasopressin(AVP)is involved in the effect of oxotremorine(a muscarinic receptor agonist)-induced hypothermic response.Methods Core temperature and motor activity were monitored in undisturbed rats using radiotelemetry.Effect of AVP V1 antagonist on oxotremorine(OXO)-induced changes in body temperature and motor activity were observed in the rats.Results Administration of OXO led to a marked hypothermia.Core temperature recovered to basal levels at 4 hours after OXO administration.AVP V1 antagonist blocked markedly the hypothermia effect of OXO.Conclusion The AVP V1-receptor antagonist block the hypothermic effect of OXO,which suggests that OXO-induced hypothermia is mediated by AVP releasing.

Objective To investigate the effects of sex difference on the body weight and body fat in mice.Methods Seventy-seven FVB/NJ background mice models were used and divided into the male mice and female mice.The body weight was measured once a week at 3 to 8 weeks of age.The content of body fat in mice was detected by the small animal nuclear magnetic resonance spectrometer.The glucose metabolism was evaluated by the glucose tolerance test and insulin resistance test.The oxygen consumption,carbon dioxide ex-halation volume and energy consumption of mice were recorded in the energy metabolism experiment.In addi-tion,the differences in body weight,body fat content,glucose metabolism and insulin sensitivity under normal and high fat diet conditions between male mice and female mice were analyzed.Results Starting from 4 weeks of age,the body weight of male mice was significantly higher than that of female mice,while the fat/body weight ratio was lower than that of female mice,and the differences were statistically significant (P<0.05). The glucose tolerance degree[(694.8±129.4)mg·dL-1·h-1 vs. (492.6±130.7)mg·dL-1·h-1]and in-sulin sensitivity[(1008.4±137.0)mg·dL-1·h-1 vs. (798.5±119.9)mg·dL-1·h-1]in the male mice were worse than those in the female mice,and the differences were statistically significant (P<0.05).The ox-ygen consumption volume[(1.60±0.12)mL-1·h-1·g-1 vs. (1.47±0.08)mL-1·h-1·g-1],carbon diox-ide expiration volume[(1.40±0.06)mL-1·h-1·g-1 vs. (1.33±0.08)mL-1·h-1·g-1]and energy con-sumption value[(0.49±0.04)kcal·h-1·g-1 vs. (0.44±0.03)kcal·h-1·g-1]in the male mice were high-er than those in the female mice,and the differences were statistically significant (P<0.05).In the short high lipid diet,the body weight in the male mice was significantly higher than that in the female mice[(23.17±2.67)g vs. (17.96±0.78)g],and the difference was statistically significant (P<0.05).But the body lipid content had statistical difference (P>0.05).Conclusion The sex differences significantly affect the body weight and body fat of mice,meanwhile the male mice are more likely to generate more fat under high fat diet.

Objective To investigate the relationship between multi‐dimensional myocardial strain and global cardiac function in different stages of cardiac dysfunction in spontaneously hypertensive rats ( SHR ) by two‐dimensional strain echocardiography . MethodsAccording to cardiac function measurements ,SHR of 28 to 102 weeks were divided into 3 groups :Normal group[ Group A , normal left ventricular ejection fraction( LVEF) and left ventricular end‐diastolic pressure( LVEDP) , n ＝13] ,diastolic dysfunction group ( Group B , normal LVEF but increased LVEDP , n ＝24) ,and systolic dysfunction group ( Group C ,decreased LVEF and increased LVEDP , n ＝ 17 ) ,with WKY rats at similar weeks of age as controls ( group a , n ＝ 7 ;group b , n ＝ 12 ; and group c , n ＝ 16 ) . Morphological parameters of left ventricular were measured by echocardiography . Using EchoPac workstation ,systolic peak longitudinal strain ,circumferential and radial strain were calculated at the left ventricular middle levels . Extracellular collagen content was observed histologically . Results Left atrial dimension increased in group B and larger in group C ,and dilated left ventricular and thickened wall were only found in group C .Systolic peak longitudinal strain of group B was significantly lower than group A and group a ( all P ＜ 0 .05 ) ,and deteriorated in group C( P ＜ 0 .05 ) ,while systolic peak circumferential and radial strain and LVEF were only significantly decreased in group C ( all P＜ 0 .05 ) ,w hile there was no significant difference between Group A and Group B( all P ＞0 .05) . Collagen content in endocardial and mid‐layer myocardium increased in group B and C , and increased epicardial collagen occurred in group C . Systolic peak longitudinal strain , circumferential and radial strain were correlated positively with LVEF( r ＝0 .65 ,0 .80 ,0 .80 ,all P ＜0 .01) . Conclusions In SHR ,systolic peak longitudinal strain obtained by echocardiography is decreased in the period of diastolic dysfunction ,w hile the damage of systolic peak circumferential and radial strain leads to the systolic dysfunction .

Background and purpose:Epidermal growth factor receptor exon 20 T790M(EGFR T790M)mutation is one of the acquired resistance mechanisms in non-small cell lung cancer(NSCLC)against first-/second-generation EGFR tyrosine kinase inhibitors(EGFR TKIs).Additionally,EGFR T790M mutation can also be observed in NSCLC patients who have not undergone EGFR TKIs treatment.This study aimed to compare the clinical pathological characteristics and prognostic differences between NSCLC patients with de novo and acquired EGFR T790M mutation,and further explore the immune microenvironment features of acquired T790M mutation in NSCLC.Methods:This study retrospectively included 3 762 cases of NSCLC diagnosed at Fudan University Shanghai Cancer Center from April 2020 to September 2022.Among them,2 070 cases(55.02%)exhibited EGFR mutations,and 556 cases(14.77%)received EGFR TKIs treatment.Specifically,there were 119 cases(3.16%)of NSCLC with EGFR T790M mutation,including 51 cases(1.35%)of de novo T790M mutation and 68 cases(1.81%)of acquired EGFR T790M mutation.Clinical data of the patients were collected for comparative analysis between NSCLC patients with de novo and acquired T790M mutation.Multiple immunofluorescence histochemistry(mIHC)was employed to explore the immune microenvironment characteristics of NSCLC patients with acquired T790M mutation.Results:The proportion of de novo and acquired T790M mutations was higher in female patients compared to males.Patients with de novo T790M mutation tended to be younger.Both de novo and acquired T790M mutations were more commonly found in poorly differentiated carcinomas.Among NSCLC patients with de novo T790M mutation,there was a higher rate of programmed death ligand-1(PD-L1)expression(60.00%).In contrast,among NSCLC patients with acquired T790M mutation,the rate of PD-L1 expression was lower(22.39%).Acquired T790M mutation in NSCLC was often accompanied by TP53 alterations(39.7%).Cox regression analysis results indicated that mesenchymal to epithelial transition(MET)factor alteration was a risk factor for the occurrence of acquired T790M mutation(P=0.000 5).The average overall survival(OS)showed no significant difference between de novo and acquired T790M mutations(35.4 and 37.3 months respectively).However,patients with acquired T790M mutation exhibited a higher proportion of recurrence and metastasis.In acquired T790M mutation,there was a higher presence of immune cell infiltration within the stromal compartment,such as CD20+B cells,CD23+B cells,CD8+T cells,CD8+PD-1-/+cells,CD20+PD-1-/+cells and CD23+PD-1-/+cells.Additionally,the study found that when EGFR was accompanied by tumor suppressor gene(TSG)alterations,the average distance between tumor cells and CD8+T cells,CD20+B cells,CD8+PD-1+cells,CD20+PD-1+cells and CD23+PD-1+cells was closer compared to cases with only EGFR mutations.Conclusion:In comparison to patients with de novo T790M mutation,patients with acquired T790M mutation exhibit a lower rate of PD-L1 positivity.Acquired T790M mutation often accompanies TP53 alterations,and MET alteration is identified as a risk factor triggering acquired T790M mutation.Although patients with acquired T790M mutation face higher risk of recurrence and metastasis,their average OS does not significantly differ from those with de novo T790M mutation.In cases of acquired T790M mutation,the presence of TSG mutations can alter the spatial distribution of immune cells,potentially leading to benefits from immunotherapy.

Objective: To investigate the relationship between multi-dimensional myocardial strain and global cardiac function in different stages of cardiac dysfunction in spontaneously hypertensive rats (SHR) by two-dimensional strain echocardiography. Methods: According to cardiac function measurements, SHR of 28 to 102 weeks were divided into 3 groups: Normal group[Group A, normal left ventricular ejection fraction(LVEF) and left ventricular end-diastolic pressure(LVEDP), n=13], diastolic dysfunction group (Group B, normal LVEF but increased LVEDP, n=24), and systolic dysfunction group (Group C, decreased LVEF and increased LVEDP, n=17), with WKY rats at similar weeks of age as controls (group a, n=7; group b, n=12; and group c, n=16). Morphological parameters of left ventricular were measured by echocardiography. Using EchoPac workstation, systolic peak longitudinal strain, circumferential and radial strain were calculated at the left ventricular middle levels. Extracellular collagen content was observed histologically. Results: Left atrial dimension increased in group B and larger in group C, and dilated left ventricular and thickened wall were only found in group C. Systolic peak longitudinal strain of group B was significantly lower than group A and group a(all P<0.05), and deteriorated in group C(P<0.05), while systolic peak circumferential and radial strain and LVEF were only significantly decreased in group C (all P<0.05), while there was no significant difference between Group A and Group B(all P>0.05). Collagen content in endocardial and mid-layer myocardium increased in group B and C, and increased epicardial collagen occurred in group C. Systolic peak longitudinal strain, circumferential and radial strain were correlated positively with LVEF(r=0.65, 0.80, 0.80, all P<0.01). Conclusions In SHR, systolic peak longitudinal strain obtained by echocardiography is decreased in the period of diastolic dysfunction, while the damage of systolic peak circumferential and radial strain leads to the systolic dysfunction.