To explore the effect of growth hormone releasing peptide (GHRP) on myocardial cell apoptosis in heart failure (HF) rats. Methods: Rat's HF model was established by the ligation of left anterior descending coronary artery induced ischemia. 40 male SD rats were randomly assigned into 4 groups: Normal control group, Sham operation group, HF group and GHRP treated HF group. n=10 in each group and the rats were fed for 4 weeks after the operation. Cardiac function was examined and myocardial cell morphology was observed; protein expressions of Smac/DIABL0 and Bcl-2 were measured by Western blot analysis; cell apoptosis was evaluated by FCM technique. The differences for above parameters were compared among groups to explore the effect of GHRP on myocardial cell apoptosis in HF rats. Results: Compared with HF group, GHRP treated HF group showed the less heart dilation, higher LVEF, lighter pathological changes in myocardial cells and decreased protein expression of Smac/DIABL0, all P<0.05. Bcl-2 level was lower in HF group than the other 3 groups, P<0.05. Compare with Normal control group, GHRP treated HF group had elevated Bcl-2 level, all P<0.05. Myocardial cell apoptosis index was different between HF group and GHRP treated HF group, P<0.05. Conclusion: The effect of GHRP on anti-HF should be via inhibiting myocardial cell apoptosis; the mechanism may partly be through promoting Bcl-2 protein expression and depressing Smac/DIABLO mediated mitochondrial pathway of apoptosis.

Background and purpose:Integrinαvβ3 receptor plays an important role in promoting, sustaining and regulating the angiogenesis. It is overexpressed on neovascular endothelial cells and tumor cells. RGD peptide specifically binds to integrinαvβ3, which could evaluate growth status and invasiveness of tumor. This study aimed to investigate the biodistribution in healthy KM mice and micro PET/CT imaging in U87MG tumor-bearing mice of 18F-E[c(RGDfK)2]. Methods: 18F-E[c(RGDfK)2] was produced using an automated synthesis module via a simple one-step 18F-labeling strategy of the precursor 4-NO2-3-TFMBz-E[c(RGDfK)2]. The percentage activity of injection dose per gram of tissue (%ID/g) was calculated at 0.5, 1, 2, 4 h post injection of the probe. Micro PET/CT images of U87MG tumor-bearing nude mice with or without 18F-E[c(RGDfK)2] blocking were acquired at each time point. Results: The labeling efficiency and radiochemical purity of 18F-E[c(RGDfK)2] were 10% and 98%, respectively. 18F-E[c(RGDfK)2] was excreted via renal route, with a high blood clearance. The other organs had background-level activity accumulation. At 1 h, the%ID/g of kidney, liver, intestine, muscle and blood was (1.02±0.16)%ID/g,(0.24±0.06)%ID/g, (0.35±0.03)%ID/g, (0.13±0.03)%ID/g and (0.11±0.03)%ID/g 18F-E[c(RGDfK)2] had initial high tumor uptake [(5.2±0.56)%ID/g] and good tumor-to-background contrast (5.36) at 1 h post injection. Tumor uptake for blocking group was lower than those without blocking, and T/M reduced to 1.57. Conclusion: 18F-E[c(RGDfK)2] appears a promising PET molecular imaging probe targeting integrin αvβ3, with high tumor uptake. It could be suitable for prognosis evaluation of integrin-positive tumor, selection of vascular targeting therapy and therapy effect monitoring.

Objective:To compare the amino acid sequences difference of HA,NA novel influenza virus A/H7N9 isolates, decipher possible B cell epitopes and T cell epitopes of HA,NA protein,and analyze the association between susceptibility and HLA polymorphisms.Methods:The amino acid sequences of novel influenza A ( H7N9) virus were downloaded from Genbank.Phylogenetic trees were constructed based on the amino acid sequences of HA and NA by using software Clustal X and MEGA 4.0.B cell and T cell epitopes were respectively predicted with Protean software and NetMHCⅡ2.2 Server online server.Results:The homology of HA and NA proteins of H7N9 virus was high.10 B cell epitopes and 15 T cell epitopes were randomly distributed throughout HA sequence and 12 B cell epitopes and 9 T cell epitopes were randomly distributed throughout NA sequence.HLA-DRB1*0701 allele which was commonly observed in Northern Chinese population have a high binding affinity for 9-mer peptides of HA and NA proteins.Conclusion:The prediction of B and T cell epitopes of HA and NA proteins with multiple methods benefits the research and development of vaccine against human infection with avian influenza A H7N9 virus.HLA-DRB1*0701 allele may contribute to susceptibility to novel influenza A (H7N9) virus.H7N9 influenza virus is more easily spread in Urumqi,Harbin,Shandong Province,Liaoning Province,Beijing, Shijiazhuang and Tianjin of China.

Glaucoma is a potentially blinding complication of uveitis.Management of uveitic glaucoma remains challenging.Vision can be partly recovered if correct diagnosis and timely treatment are given.The mechanisms of intraocular pressure (IOP) elevation include peripheral anterior synechia, pupillary block, trabecular meshwork inflammation, cyclitis and prolonged corticosteroid use.Treatment is targeted at identifying the cause of raised IOP first, followed by etiological treatment and IOP lowering medications.The indications for surgery include uncontrolled IOP despite maximum-tolerated medical management or definite optic nerve damage.Recently, selective laser trabeculopasty for steroid-induced intraocular hypertension/open angle glaucoma, CO₂ laser-assisted sclerectomy surgery or micro-invasive glaucoma surgery for uveitic glaucoma have been gradually applied in clinical practice.

Objective:To investigate the changes in adaptive phenotypes of Yersinia pestis ( Yp) during successive passages in macrophages. Methods:A Yp strain of 201-MI was induced by 50 successive passages of Yp 201 strain in Raw264.7 cells. Phenotypic characteristics of 201 and 201-MI strains were compared by analyzing their survival rates in macrophages, growth curves, biofilm formation abilities, acid and hydrogen peroxide-stress tolerance, and virulence to mammal cells (Raw264.7 and HeLa cells) and mice. Results:Comparing with 201 strain, 201-MI strain showed various phenotypic changes, including higher survival rate in Raw264.7 cells, faster growth in iron-deficient medium, higher tolerance to acid and hydrogen peroxide, decreased biofilm formation ability, and less damages to Raw264.7 and HeLa cells. More-over, 201-MI strain showed decreased virulence to mice in both subcutaneous and intraperitoneal challenges. Preliminary comparative genomics analysis revealed some indel and nonsense mutations in 201-MI strain, which might account for its phenotype changes.Conclusions:After successive passages in macrophages, Yp showed some phenotypic changes, which might reflect its adaptive evolution under the pressure of macrophages. Detailed multi-omics analysis would be of great help to understand the underlying genetic mechanisms of these changes, and the related Yp-macrophage interaction processes as well.

Objective:To observe and analyze the macular microvascular system changes in unilateral pediatric uveitis (PU) and healthy contralateral eyes.Methods:A cross-sectional case-control study. From January 2019 to July 2021, 21 eyes of 21 patients with PU diagnosed in one eye (PU group), 21 unaffected contralateral eyes (contralateral eye group), and 21 age-matched volunteers with 21 eyes (NC group) during the same period were examined in Peking Union Medical College Hospital. Optical coherence tomography angiography was used to scan the 6 mm × 6 mm fundus macular area in the three groups of selected eyes to measure the vessel density of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) of the retina, the area of the avascular zone (FAZ) in the fovea of the macula, the choroidal thickness under the fovea (SFCT), and the retinal thickness in the fovea of the macula (CRT). The device comes with a software choriocapillary flow measurement tool, which can obtain the macula's choriocapillary density (CCD) with the fovea as the center and the diameter of the annular area of 1.0 mm, 1.5 mm, and 3.0 mm, respectively. They were recorded as CCD-1.0, CCD-1.5, and CCD-3.0. The measurement data of multiple groups were compared by analysis of variance; if the variance of the three groups of data was not uniform, the Kruskal-Wallis test was used. Multiple linear regression analysis was used to evaluate the potentially related factors of CCD.Results:Compared with the contralateral eye group and the NC group, the vessel density of SCP ( H=-13.857,-25.500; P=0.043, P<0.001), DCP ( H=-15.333, -31.595; P=0.007, P<0.001) and CCD-1.0 ( H=-14.000,-16.214; P=0.040, 0.012) of the clinically quiescent PU group were significantly decreased. CRT and FAZ were not statistically different between PU and NC groups ( F=0.955; P=1.000, 0.661). Compared with the NC group, the mean vessel density of SCP and DCP in the contralateral eye group decreased, and the difference in DCP vessel density was statistically significant ( H=-16.262, P=0.004). There was no statistically significant difference between the CCD of two groups ( P=1.000). The SFCT of the PU group was significantly thicker than that of the NC group ( F=5.552, P=0.004), however, difference was not statistically significant from the fellow eye group ( F=5.552, P=0.270). The results of multiple linear regression analysis revealed that the CCD-1.0, CCD-1.5, and CCD-3.0 showed a linear correlation with the area of FAZ ( β=-0.494, -0.527, -0.566; P=0.015, 0.009, 0.010) and CRT ( β=-0.322, -0.466, -0.342; P=0.026, 0.002, 0.028). CCD-1.0 and CCD-1.5 showed a linear correlation with the vessel density of DCP ( β=0.277, 0.275; P=0.047, 0.045). Conclusion:Both retinal and choroidal microvasculature are abnormal in resting eyes with PU, and macular circulation disorders may be present in the unaffected fellow eye.

Objective: To investigate the safety and feasibility of laparoscopic operation in thetreatment of gastric gastrointestinal stromal tumor (GIST) at unfavorable positions. Methods: A retrospective cohort study was conducted to analyze the clinical data of patients with gastric GIST at unfavorable positions confirmed by pathology after surgery (laparoscopy or laparotomy) at the Southwest Hospital of the Army Medical University and the Minda Hospital of Hubei Minzu University from June 2008 to June 2018. The unfavorable positions of stomach are defined as the esophagogastric junction, the proximal cardia of gastric lesser curvature, the pylorus of stomach, the posterior wall of stomach and the antrum of stomach.Exclusion criteria:(1) preoperative chemotherapy or imatinib therapy; (2) diameter of tumor > 10 cm; (3) tumor metastasis or concurrence of other malignant tumors. A total of 244 patients (238 in Southwest Hospital and 6 in Minda Hospital) were enrolled, including 122 males and 122 females with age of 41-70years. Operative methods should be adopted according to patients' wishes. There were 146 cases in the laparoscopic surgery group and98 cases in the open surgery group. The intraoperative blood loss, operative time, postoperative first flatus time, postoperative firstfeeding time,average hospital stay, morbidity of postoperative complication,1-,3-,and 5-year recurrence free survival(RFS) and overall survival (OS)rate were compared between the two groups. Results: There were no significant differences in sex, age, tumor size, tumor risk grade or growth pattern between the laparoscopic and the open surgery groups (all P>0.05),and these two groups were comparable. Compared with open group, laparoscopic group had less intraoperative blood loss [(31.4±2.3) ml vs. (143.9±3.7) ml, t=292.800, P<0.001], shorter postoperative first flatus time [(2.1±0.7) days vs.(3.8±0.8) days, t=17.550,P<0.001], shorter postoperative first feeding time [(2.1±0.5) days vs.(2.3±1.7) days, t=1.339,P=0.020], shorter hospital stay [(8.6±2.6) days vs. (13.6±3.2) days, t=13.410, P<0.001], and lower morbidity of postoperative complication [16(11.0%) vs. 21(21.4%),χ²=4.996,P=0.025], whose differences were statistically significant. While the operation time was similar in two groups [(124.7±15.8) minutes vs. (120.9±14.5) minutes, t=1.903,P=0.058]. The median follow-up of all the patients was 43 (1 to 119) months.In laparoscopic group and open group, the 1-, 3- and 5-year RFS were 94.5% vs. 93.9%, 91.1% vs. 90.8%,and 82.2% vs. 81.6%, respectively, and 1-, 3- and 5-year OS were 98.6% vs. 95.9%, 95.9% vs. 94.9%,and 91.1% vs. 88.8%, respectively, whose differences were not statistically significant (all P>0.05). Conclusion In the experienced gastrointestinal surgery center, laparoscopic resection of gastric GIST at unfavorable position is safe and feasible, achieving the same efficacy of open surgery.

Animal experiments play an important role in the process of biomedical research, and is a necessary way to transform basic medicine into clinical medicine. The standardization of animal experimental studies and reports determines the reliability and reproducibility of research results, and is also the key to transforming the results of animal experiments into clinical trials. In view of how to design and implement animal experiments, write animal experiment reports, and publish relevant academic papers in a more standardized way, LACM (Laboratory Animal and Comparative Medicine) has launched a new column of comparative medical research and reporting standards from 2023, focusing on the introduction and interpretation of international general norms related to laboratory animal and comparative medicine, such as ARRIVE 2.0 guidelines (Animal Research: Reporting of In Vivo Experiments). This article focuses on the development and application, basic content and priority of ARRIVE 2.0, as well as the scheme of implementing ARRIVE 2.0 guidelines in international biomedical journals, and explains the current situation and future plans of LACM following ARRIVE 2.0 guidelines. The research and report of animal experimental medicine following the ARRIVE 2.0 guidelines and other international norms is one of the important driving forces to promote the high-quality development of experimental animal science and biomedicine in China, and also a powerful means to implement the 3R principle and improve the welfare of laboratory animals. Through this article, we hope the majority of scientific researchers and editors will attach great importance and actively implement these international standards.

Scaffold-free tissue engineered cell sheet is an emerging technology in biomedical field. It can avoid the adverse effects of scaffold materials, and can be further assembled to form more complex three-dimensional functional tissues. The construction of cell sheet is mainly based on the culture substrate composed of sensitive materials. By changing the stimulation factors such as temperature, enzyme, light, ion, redox, pH and sugar, the adhesion behavior of the substrate to the cells could be changed to make the cells detach naturally, thus generating the cell sheet. Recent years have seen the development of various simple and efficient construction technologies of cell sheet due to the development of a variety of novel sensitive culture substrates. The resulted cell sheets with excellent performance have greatly expanded their applications. This review summarized the construction methods of tissue engineered cell sheet and discussed the challenges and future perspectives in this field.
Temperature ; Tissue Engineering ; Tissue Scaffolds

To explore the pharmacogenomic markers that affect the platinum-based chemotherapy response in non-small-cell lung carcinoma (NSCLC), we performed a two-cohort of genome-wide association studies (GWAS), including 34 for WES-based and 433 for microarray-based analyses, as well as two independent validation cohorts. After integrating the results of two studies, the genetic variations related to the platinum-based chemotherapy response were further determined by fine-mapping in 838 samples, and their potential functional impact were investigated by eQTL analysis and in vitro cell experiments. We found that a total of 68 variations were significant at P < 1 × 10^-3 in cohort 1 discovery stage, of which 3 SNPs were verified in 262 independent samples. A total of 541 SNPs were significant at P < 1 × 10^-4 in cohort 2 discovery stage, of which 8 SNPs were verified in 347 independent samples. Comparing the validated SNPs in two GWAS, ADCY1 gene was verified in both independent studies. The results of fine-mapping showed that the G allele carriers of ADCY1 rs2280496 and C allele carriers of rs189178649 were more likely to be resistant to platinum-based chemotherapy. In conclusion, our study found that rs2280496 and rs189178649 in ADCY1 gene were associated the sensitivity of platinum-based chemotherapy in NSCLC patients.