Objective To study the relationship of insulin-like growth factor-Ⅰ receptor(IGF-ⅠR)and carcinogenesis of gastric cancer.Methods The expression of IGF-ⅠR was detected in 40 cases of resected gastric cancer tissues and adjacent normal gastric mucosa by immunohistochemistry.The expression of IGF-ⅠR in gastric cancer cell lines(MGC803 and SGC7901)was detected by Western Blot.siRNAs targeted to IGF-ⅠR were designed,synthesized and transfected into MGC803 cells,the changes of IGF-IR protein level were detected by Western Blot at 48 h after transfection,the cell proliferation was examined by MTT,and then the growth curve was obtained.Results The positive rate of IGF-IR expression in gastric cancer tissues was 75.5%,significantly higher than that of adjacent normal tissues (25%,P＜0.01).The expression level of IGF-IR was related with TNM stage,lymphnode metastasis (P＜0.05),but not related with sex,age,histological differentiation,invasion depth of gastric cancer (P＞0.05).Intense expression of IGF-ⅠR was showed in gastric cancer cell lines.The inhibition ratio of IGF-ⅠR expression in sigNAl group were 89.80%±4.10%,the cell proliferation decreased to mininlunl level at the fifth day aftertransfection(by 29.0%±4.0%of mock-treated group),the cell number decreased by 21.15%±1.10%of mock treated group at the same time.Conclusions IGF-ⅠR is over-expressed in gastric cancer cells and can be effectively silenced by RNA interferes,therefore the growth of tmnor cell Was inhibited.Thus,it indicates that IGF-ⅠR may be a promising target for gene therapy of gastric cancer.

ObjectiveTo investigate the population with an advantage of clinical cure previously treated with nucleos(t)ide analogues (NAs), and to provide more methods for clinicians in pursuing the clinical cure of hepatitis B. MethodsA total of 42 chronic hepatitis B patients with low-level HBsAg who received NAs treatment in Hebi Third People’s Hospital from October 2017 to October 2019 were enrolled as subjects and divided into combination treatment group (group A) and NA monotherapy group (group B). The 22 subjects in group A were treated with NAs combined with PEG-IFN antiviral therapy for 48 weeks, and some patients withdrew from PEG-IFN after 24 weeks and continued to receive NA monotherapy, while the 20 subjects in group B received NA antiviral therapy alone. Both groups were observed till week 48, and the five makers for hepatitis B were measured to evaluate clinical outcome. The t-test was used for comparison of continuous data between two groups, and the Fisher’s exact test was used for comparison of categorical data between two groups; a multivariate logistic regression analysis was used to perform a multivariate analysis. ResultsCompared with group B at the 48-week treatment endpoint, group A had significantly higher HBsAg clearance rate (45.5% vs 0, P＜0.01) and HBsAg seroconversion rate (31.8% vs 0, P＜0.01). The population with HBsAg ＜1000 IU/ml, ＜500 IU/ml, ＜100 IU/ml, and ＜10 IU/ml had an HBsAg clearance rate of 52.6%, 61.5%, 66.7%, and 100%, respectively, and the population with an HBsAg level of 500-1000 IU/ml, 100-500 IU/ml, 10-100 IU/ml, and ＜10 IU/ml had an HBsAg clearance rate of 33.3%, 50%, 40%, and 100%, respectively. The 4 patients with baseline HBsAg ＜10 IU/ml (accounting for 18.2% in group A) achieved clinical cure at week 12 of combined treatment, and after observation to week 48, 2 patients had an anti-HBs level of ＞100 IU/ml and 2 had an anti-HBs level of ＞1000 IU/ml. The multivariate logistic regression analysis of HBsAg clearance showed that age at the initiation of combined treatment affected HBsAg clearance (odds ratio ［OR］=0.877, 95% confidence interval ［CI］: 0.781-0.985, P=0.026), and most of the patients with HBsAg clearance had an age of 36-49 (44.20±4.49) years; baseline HBsAg level also had an impact on HBsAg clearance (OR=0.996, 95% CI: 0.992-1.000, P=0.050). ConclusionThe addition of interferon therapy in chronic hepatitis B patients with low-level HBsAg previously treated with NAs can significantly improve the clinical cure rate. The younger the age and the lower the HBsAg level, the shorter the duration of combined treatment. Age and baseline HBsAg level are more important than the duration and type of NA medication.

Objective To investigate the distribution of peripheral arterial stiffness,endothelial function and their correlations with cardiovascular risk factors in the 7-17 year-olds.Methods Normal weight and obese subjects aged 7-17 years with completed data on questionnaires,anthropometric and blood biochemical tests,were recruited from a cross-sectional population-based study on childhood hypertension in Minhang district of Shanghai.Automatic waveform analyzer (BP-203RPE-I) and Endopat 2000 were used to measure the arterial stiffness.Endothelial function with brachial-ankle pulse wave velocity (baPWV) and reactive hyperemia index (RHI) were recorded.BaPWV and RHI were standardized by age.Skewed biochemical variables were log transformed.Linear correlation analysis was performed to observe association between baPWV,RHI and other measured variables.Results A total of 452 normal-weight and 94 obese subjects were recruited,including 299 males.Data showed that baPWV and RHI increased with age in normal weight subjects (r=0.33,P＜0.01;r=0.36,P＜0.01).Results from Linear correlation analysis revealed that baPWV was positively correlated with BMI (r=0.13,P=0.002),systolic blood pressure (SBP) (r=0.20,P＜0.01),diastolic blood pressure (DBP) (r=0.27,P＜0.01),triglycerides (TG) (r=0.11,P=0.010),insulin (r=0.21,P=0.004) and the HOMA insulin resistance index (r=0.21,P=0.005),but negatively correlated with high-density lipoprotein cholesterol (r=-0.09,P=0.039).RH1 was positively correlated with BMI (r=0.10,P=0.018) but negatively correlated with DBP (r=-0.10,P=0.016).Males had higher baPWVs than females (P=0.04).However,RHI did not differ between genders.Conclusions The fact that baPWV and RHI increased along with age,indicated that the arterial stiffness and endothelial function continued to develop in normal weight childhood and adolescence.Arterial stiffness was correlated with cardiovascular risk-related parameters whereas endothelial function was not.BaPWV might be more sensitive in evaluating the cardiovascular risk in children and adolescents than RHI did.

A case of limb girdle muscular dystrophy type 2S (LGMD2S) caused by maternal uniparental disomy on chromosome 4 at the First Affiliated Hospital of Henan University of Chinese Medicine in March 2020 was reported.The female child, aged 9 months and 4 days, presented with developmental delay after bacterial meningitis in early infancy, decreased muscle strength in infancy and increased muscle and liver enzymes.Family genetic analysis showed that the child′s monodiploid in chromosome 4 was maternal origin, and the homozygous c. 1066T > G (p.Y356D) of TRAPPC11 gene may had pathogenic variation, which came from the child′s mother.The final diagnosis of LGMD2S was made according to the clinical manifestations and gene test results.LGMD2S is a rare autosomal recessive disease caused by the pathogenic variation of TRAPPC11 gene.Its clinical characteristics include proximal limb weakness, motor and intellectual retardation, seizures, motor disorders, elevated serum creatine kinase and muscular dystrophy like pathological changes in children.

Objective: To observe the effect of different expression levels of USP28 on the radiosensitivity of ECA109 cells by gene transfection method, aiming to provide theoretical basis for comprehensive treatment of esophageal cancer. Methods: The expression levels of USP28 and c-Myc in the esophageal epithelial cells Het-1A, ECA109 and ECA109R were quantitatively measured by qRT-PCR. The specific siRNA sequences were designed according to the USP28 and c-Myc genes. The pcDNA-USP28 and pcDNA-c-Myc plasmids were constructed. The esophageal cancer cell ECA109 was transfected with Lipofectamine 2000 to observe the transfection effect and related protein expression. ECA109 and ECA109R cells were exposed to 6 Gy X-ray radiation. The cell apoptosis in each group was detected by flow cytometry. The radiosensitivity was evaluated by clone formation assay. Results: The expression levels of USP28 and c-Myc in ECA109 were significantly higher than those in Het-1A (both P<0.05), and the expression levels of USP28 and c-Myc in ECA109R were remarkably higher than those in ECA109(both P<0.05). The pcDNA-USP28 and pcDNA-c-Myc recombinant plasmids were successfully constructed. Compared with the negative control group, the expression of USP28 at the protein and mRNA levels in the si-USP28 group was significantly down-regulated, whereas those in the pcDNA-USP28 group were remarkably up-regulated. Similar results were obtained in terms of c-Myc. Compared with the control group, the expression level of c-Myc protein was significantly up-regulated in the pcDNA-USP28 group, whereas considerably down-regulated in the si-USP28 group. After 6 Gy irradiation, the apoptosis rate and radiosensitivity of ECA109 cells were significantly declined. The apoptosis rate and radiosensitivity of ECA109R cells were increased in the si-USP28 group. Conclusions The expression of USP28 protein is closely correlated with the radiosensitivity of esophageal cancer cells. The underlying mechanism may be related to the regulation of c-Myc expression by USP28.

Anti-CD19 chimeric antigen receptor (CAR)-T cell therapy has achieved 40%-50% long-term complete response in relapsed or refractory diffuse large B-cell lymphoma (DLBCL) patients. However, the underlying mechanism of alterations in the tumor microenvironments resulting in CAR-T cell therapy failure needs further investigation. A multi-center phase I/II trial of anti-CD19 CD28z CAR-T (FKC876, ChiCTR1800019661) was conducted. Among 22 evaluable DLBCL patients, seven achieved complete remission, 10 experienced partial remissions, while four had stable disease by day 29. Single-cell RNA sequencing results were obtained from core needle biopsy tumor samples collected from long-term complete remission and early-progressed patients, and compared at different stages of treatment. M2-subtype macrophages were significantly involved in both in vivo and in vitro anti-tumor functions of CAR-T cells, leading to CAR-T cell therapy failure and disease progression in DLBCL. Immunosuppressive tumor microenvironments persisted before CAR-T cell therapy, during both cell expansion and disease progression, which could not be altered by infiltrating CAR-T cells. Aberrant metabolism profile of M2-subtype macrophages and those of dysfunctional T cells also contributed to the immunosuppressive tumor microenvironments. Thus, our findings provided a clinical rationale for targeting tumor microenvironments and reprogramming immune cell metabolism as effective therapeutic strategies to prevent lymphoma relapse in future designs of CAR-T cell therapy.