The combination of chemotherapy with anti-epidermal growth factor receptor antibodies such as cetuximab and panitumumab which prolong the survival time in the past few years have been widely adopted for the treatment of metastatic colorectal cancer.However,a large number of patients develop resistance to these agents,while there is no standard treatment after acquired resistance yet.Therefore,finding out the mechanisms of acquired drug resistance and putting forward reasonable methods to overcome the acquired resistance will be improve its curative effect.

Objective To study the gene mutations and clinical features of mandibuloacral dysplasia with type A lipodystrophy (MADA) in a Chinese family. Methods The information of 5 family members including 2 siblings suspected atyp-ical progeria was assembled. Genomic DNA was extracted from peripheral blood of 5 family members, the 12 exons of LMNA gene were ampliifed by PCR and then the PCR products were directly sequenced and analyzed by using Blast software online. The SIFT and PolyPhen-2 software were used to predict the harmfulness of mutations. Results The 2 siblings were clinically diagnosed as MADA. Heterozygous c.1579C>T (p.Arg527Cys) and c.1583C>T (p.Thr528Met) mutations were detected in this family. The father carried c.1583C>T (p.Thr528Met) mutation, the mother carried c.1579C>T (p.Arg527Cys) mutation, and their normal daughter were all heterozygous carriers with c.1583C>T (p.Thr528Met) mutation. Compound heterozygous c.1579C>T (p.Arg527Cys) and c.1583C>T (p.Thr528Met) mutations in 2 siblings led to MADA. The MADA showed an autosomal re-cessive inheritance pattern in this family. Conclusions The 2 siblings with MADA in this family were caused by compound heterozygous mutations in LMNA gene.

Abstract Socioeconomic status is an important factor affecting all-cause mortality. Income, education and occupation alone or in combination have been employed as a measure of socioeconomic status; however, the study results vary in measures. Material mechanism, lifestyle mechanism, psychological mechanism and community neighborhood mechanism have been accepted as the main intermediate mechanisms for the impact of socioeconomic status on all-cause mortality; however, the contribution of these mechanisms remains controversial. Based on the international and national publications pertaining to the association between socioeconomic status and all-cause mortality from 2012 to 2021, this review summarizes the relationship between socioeconomic status and all-cause mortality in different metrics and the intermediate mechanism of the impact of socioeconomic status on all-cause mortality, so as to provide insights for further studies.

Objective To evaluate the outcome of endovascular treatment with coarctation of aorta (CoA).Methods Between November 2007 and March 2012,11 patients,including 8 male and 3 female from 17 to 43 years old,with native CoA who were diagnosed by computed tomography angiography accepted the endovascular treatment.The arterial pressure difference between the femoral artery and the narrow segment was measured during the operation,and the stent was released by expanding the balloon.Results Endovascular treatment were successful in all cases without any major adverse events.Significant reduction of systohc blood pressure was observed from (64.09 ± 7.81) mmHg (1 mmHg =0.133 kPa) to (11.18 ± 3.37) mmHg.The mean CoA diameter pre-stent (4.000 ± 0.775) mm,post-stent (17.090 ± 2.427) mm.1 patient associated with patent ductus arteriosis had no persistent left-to-right shunt after covered stent implantation.The follow up range was 33 months.1 patient in simple balloon was retreatment by surgical because of restenosis.And no retraction was observed of 10 patients after stent implantation.Conclusion The early and midterm result of endovascular treatment with CoA is satisfactory,and longer follow-up is needed for its longterm outcomes.

To assess the left ventricular regional relaxation abnormalities in patients with hypertrophic cardiomyopathy (HCM) by quantitative tissue velocity imaging (QTVI), Doppler echocardiography and QTVI were performed in HCM (n=10) and healthy subjects (n=11) at apical long-axis, two-chamber and four-chamber views. Regional early diastolic velocity (rVe) and regional atrial contraction (rVa) were measured at each segment of ventricular middle, basal and annular levels. Mean rVe and mean rVa at three levels as well as mean rVe/rVa ratio were calculated. Our results showed that transmitral inflow peak velocities during early diastole (E) and atrial contraction (A) were also measured and E/A ratio was calculated. The rVe of all left ventricular segments in HCM were lower than those in healthy subjects (P<0.05), but compared with healthy subjects majority of rVa in HCM were not different except inferior wall and anterior wall. E between HCM and healthy subjects was different (P=0.036), while mean rVe between them was significantly different (P<0.0001). Mean rVa and mean rVe/rVa of three levels were lower in HCM than in healthy subjects (P<0.05), but there were no differences in A and E/A between them (P=0.22, P=0.101). Left ventricular regional myocardial relaxation is reduced in HCM. Transmitral inflow E and A are influenced by preload, relaxation of myocardium and atrial contraction, etc., while rVe and rVa reflect myocardial relaxation function independently. QTVI is more sensitive and more accurate than conventional Doppler imaging for characterizingregional diastolic properties in HCM.
Cardiomyopathy, Hypertrophic/*physiopathology ; Cardiomyopathy, Hypertrophic/*ultrasonography ; Diastole ; Echocardiography, Doppler, Color/methods ; Hypertrophy, Left Ventricular/*physiopathology ; Hypertrophy, Left Ventricular/ultrasonography ; Ventricular Function, Left

Objective:To observe the clinical efficacy of brain-benefiting and collateral-unblocking needling technique for chronic alcoholic gastritis complicated with depression. Methods:A total of 92 cases with chronic alcoholic gastritis complicated with depression were included in this trial. They were randomly allocated into an observation group (n=46) and a control group (n=46) by random number (envelope) method. Patients in the observation group received the brain-benefiting and collateral-unblocking needling technique. Scalp points included Shenting (GV 24), Xinhui (GV 22), Qianding (GV 23), Baihui (GV 20), Chengguang (BL 6), Tongtian (BL 7) and Luoque (BL 8). Body points included Neiguan (PC 6), Zusanli (ST 36), Zhongwan (CV 12), Gongsun (SP 4), Shenmen (HT 7), Daling (PC 7), Qimen (LR 14), Xinshu (BL 15) and Taichong (LR 3). The control group only received the same body acupuncture as the observation group. The treatment was conducted once a day, 30 min for each treatment, and 10 times made up a course of treatment. The efficacy was observed after 3 courses of treatment, and there was a 2-d interval between two courses. Results:After 3 courses of treatment, the clinical symptoms and gastroscopic features were significantly improved in the observation group than that in the control group. The clinical efficacy, self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were significantly better than those in the control group (allP<0.05). Conclusion:The brain-benefiting and collateral-unblocking needling technique can significantly improve clinical symptoms in patients with chronic alcoholic gastritis complicated with depression and substantially alleviate their gastroscopic features, anxiety and depression.

Objective To evaluate the correlation between left ventricular function and arterial stiffness of left femoral artery in patients with lower extremity atherosclerotic disease (LEAD).Methods Thirty-three patients with LEAD and 37 healthy subjects (control group) were enrolled in this study.The intima-media thickness (IMT),diameter and parameters of arterial stiffness [dispensability coefficient (DC),compliance coefficient (CC),stiffness α,stiffness β,pulse wave velocity (PWVβ) ]were measured by ultrasonography with the technology of QIMT and QAS.The thickness of the interventricular septum (IVSd),end-diastolic left ventricular diameter (LVDd) and left ventricular mass (LVM),and parameters of the left ventriculsr function (EF,E/A,E'/A',E/E' and Tei index) were measured by echocardiography.These parameters were compared between two groups.Correlations between the parameters of the arterial stiffness and those of the cardiac function were evaluated by Pearson correlative analysis.Results ①The IVSd,LVM and E/E' ratio were significantly higher in LEAD group than those in control group ( P ＜0.05).There were no significant differences in EF,E/A,E'/A',and Tei index between two groups ( P ＞0.05).②The IMT,α,β,PWVβ of left femoral artery were significantly higher in LEAD group than those in control group,while DC and CC were significantly lower in LEAD group than those in control group ( P ＜0.05).③The E/E' ratio,one of the parameters representing the left ventricular diastolic function,was correlated negatively with CC and positively with α,β,and PWVβ ( P ＜0.05 or P ＜0.01 ).The E'/A' ratio was correlated positively with DC and CC,and negatively with α,β,and PWVβ ( P ＜0.05 or P ＜0.01 ).Both EF and Tei index were not significantly correlated with the above parameters of arterial stiffness ( P ＞0.05).Conclusions Patients with LEAD have thickened femoral IMT,higher arterial stiffness of left femoral artery,as well as impaired left ventricular function.There is a close correlation between the atherosclerosis of the femoral artery and the early left vcntricular dysfunction.

The effect of insulin treatment on fatty liver was investigated in diabetic mice fed with high-fat diet.C57 BL/6J mice were fed with high fat diet for 12 weeks,and then treated with Glargine for 4 weeks.The results showed that during intraperitoneal glucose tolerance test,blood glucose,serum total cholesterol and triglyceride(TG) were significantly lower in insulin-treated high fat group than those in untreated ones(P<0.05).The hepatic histology showed minimal or barely visible fat in hepmic cells along with TG content in liver decreasing by 20.71%. The results suggest that insulin ameliorates hepatic intracellular lipid accumulation induced by high fat diet.

Objective To evaluate the association between the left carotid arterial stiffness and left ventricular diastolic function in patients with lower extremity atherosclerosis (AS).Methods ①A total of 32 patients with AS and 34 control objects were enrolled.The carotid arterial stiffness parameters:compliance coefficient (CC),distensibility coefficient (DC),stiffness parameter (α,β),pulse wave velocity β (PWVβ) were measured by using quality arterial stiffness(QAS) technology.And the values were compared between the two groups.②The parameters of left ventricular (LV) structure and function:LV end-diastolic interventricular septal thickness (IVSd),LV end-diastolic diameter (LVDd),LV end-diastolic wall thickness (PWd),LV ejection fraction (EF),systolic velocity (s'),early-diastolic velocity (e'),Tei index and E/e' ratio were measured by using two-dimensional echocardiography and tissue Doppler.These parameters were compared between the two groups.The association between the carotid arterial stiffness parameters and LV function parameters were analyzed by correlative analysis.Results ①Compared with the control group,the DC and CC were lower,and α,β,PWVβ,IMT were higer than the control group,with statistically significant differences(P ＜0.05).②The IVSd,Tei index and E/e'was significantly higher in the AS group than those in the control group.And the PWd,s',e' were lower than those in the control group (P ＜ 0.05).There was no significant difference in EF between the two groups (P ＞0.05).③The e' was correlated positively with DC and CC (r =0.39,0.36,P ＜0.01),and negatively with α,β,and PWVβ (r =-0.42,-0.42,-0.49,P ＜0.01).Tei index was correlated negatively with DC and CC (r =-0.50,-0.52,P ＜0.01),and positively with α,β,and PWVβ (r =0.58,0.58,0.62,P ＜0.01).The E/e' was correlated regatively with CC (r =-0.27,P ＜0.05),and positively with PWVβ (r =0.28,P ＜0.05).There were no significant correlation between s',EF and the stiffness parameters of carotid artery (P＞0.05).Conclusions In patients with AS,the left carotid artery stiffness increases and left ventricular systolic and diastolic function are impaired.The carotid artery stiffness and left ventricular diastolic function is correlated.Changes in carotid artery stiffness reflect the change in left ventricular diastolic function.

Objective To study the effect of siRNA of Rab25 on apoptosis induction in ovarian carci- noma cell.Methods According to Rab25 mRNA sequence in the Genebank,the plasmids expressing siRNA against Rab25 were constructed and stably transected into A2780 cells,MTY method were applied to measure cell growth and proliferation.Apoptosis rate and cell cycle phase distribution of A2780 cells were measured by flow cytometry(FCM).Apoptosis was confirmed by agarose gel electrophoresis(AGE)of DNA.Results Cells transected with the plasmids expressing siRNA targeting Rab25 gene effectively decreased cell growth, proliferation;blocked A2780 cells in the G_1 phase of cell cycle and induced cell apoptosis.A typical DNA ladder pattern appeared on AGE.Conclusion Rab25 gene siRNA can inhibit growth and induce apoptosis in ovarian carcinoma cell line,which will facilitate further studies of Rab25 function and its application in the treatment of ovarian cancer.