Objective To investigate expressions of the vascular endothelial growth factor (VEGF) family and their receptors in cardiac repair/remodeling after myocardial infarction (MI).Methods The infarcted rat heart model were constructed,real time PCR (RT-PCR) and Western blots (WB) were used.Results Compared to the normal myocardium,VEGF-A was significantly decreased in MI group during the 42 days observation period but decreased at day 1,which was 0.89 ±0.04 of control group in D1,0.25 ±0.03 of control in D14; VEGF-B was significantly suppressed in the infarcted heart,which level was 0.09 ± 0.04 of control; However,VEGF-C and VEGF-D were markedly increased in the infarcted heart in MI group,which was 5.31 ± 0.21 and 9.24 ± 0.47 times of control.Meanwhile,VEGFR-1 and 2 were 0.11 ± 0.02 and 0.14 ± 0.04 of control in the infarcted heart,but VEGFR-3 was significantly increased in blood vessels,6.81 ± 0.42 times of control group.Conclusions VEGF isoforms and VEGFR subtypes were differentially expressed in the infarcted heart.It suggests that these isoforms may regulate multiple responses during cardiac repair/remodeling.

Objective To compare the prescrotal orchiopexy and traditional inguinal orchiopexy in the clinical treatment of children with low cryptorchidism.Methods Seventy-two patients(78 testes)who underwent orchiopexy in our hospital during March 2006 to May 2011 were retrospectively analyzed.And the undescended testis could be manipulated beyond the external inguinal ring under anaesthesia.Matching conditions were age differences among 3 months,same preoperative testicular positioning,same surgeon and same side.Using the paired study of 1 to 1,all the patients were divided into 2 groups: prescrotal orchiopexy(group A)and the traditional inguinal orchiopexy(group B),each group included 36 patients(39testes).Mean age was 5.4 years(group A)and 5.5 years(group B).The time of operation and restore standing,success rate and complications,including hernia,hydrocele,testicular atrophy and ascent were compared between the 2 groups.Results All the patients were successfully operated.The average surgical time for the prescrotal and inguinal groups were 33 and 41 min(P =0.0022),and average time of standing was 1.2 and 5.4 d(P =0.0003).All the patients had no wound infection.Followup ranged from 3 to 65 months.No hernia,hydrocele,testicular atrophy and ascent were identified in either group.The ratios of successful surgery were 100％ in the two groups.Conclusions The prescrotal orchiopexy is simple,safe,and effective in the cases that testis could be pushed down through the external inguinal ring.Compared with traditional inguinal approach,the advantages of prescrotal approach are shorter operative time,fewer traumas,less pain,faster recovery and cosmetic results.

Objective:To analyse the differences of related genes between serum alpha-fetoprotein (AFP) positive gastric cancer and AFP negative gastric cancer, and the relationship between related genes and prognosis of serum AFP positive gastric cancer.Methods:A total of 1 144 gastric cancer patients undergoing surgery at the 940th Hospital , Joint Logistic Support Force, People's Liberation Army from Jan 2013 to Dec 2018 were retrospectively analyzed. Of them, 47 cases were of AFP positive gastric cancer, and 47 serum AFP negative case were obtained by proper matching method.Results:Forty-seven patients with serum AFP positive gastric cancer, accounting for 4.1% of all gastric cancer patients during the same period. The prognosis of serum AFP negative gastric cancer is better than that of serum AFP positive gastric cancer. The 1-, 3- and 5-year cumulative survival rates were 95.6% vs. 63.8%, 48.9% vs. 23.4% and 26.7% vs. 14.9%, respectively. There were statistical differences in the immunohistochemistry of AFP, HER2, VEGF, GPC3, SALL4, P53 and Ki67 between the two groups ( χ2=67.758, P<0.001; χ2=4.004, P=0.044; χ2=19.299, P<0.001; χ2=5.232, P=0.022; χ2=6.359, P=0.012; χ2=6.224, P=0.013; χ2=5.232, P=0.022). The more co-positive expressions of AFP, GPC3, VEGF and SALL4, the more likely they were to affect pTNM stage, vascular invasion and liver metastasis ( χ2=5.328, P=0.021; P=0.013; χ2=5.887, P=0.015; χ2=3.923, P=0.048). Univariate and multivariate survival analysis of serum AFP positive gastric cancer showed:AFP, GPC3, VEGF and SALL4 were risk factors for AFP positive gastric cancer ( HR=3.700, P=0.036; HR=4.237, P=0.003; HR=3.916, P=0.004; HR=3.412, P=0.001). Conclusions:Serum AFP positive gastric cancer is a rare and highly invasive special type of gastric cancer. AFP, GPC3, VEGF and SALL4 are overexpressed in serum AFP positive gastric cancer, which is correlated with tumor stage, vascular invasion and liver metastasis. The final diagnosis of serum AFP positive gastric cancer still needs immunohistochemical examination. Preoperative serum AFP level is an important basis for AFP positive gastric cancer screening and AFP immunohistochemical examination.

Tumor vaccine is a promising strategy for cancer immunotherapy by introducing tumor antigens into the body to activate specific anti-tumor immune responses. Along with the technological breakthroughs in genetic engineering and delivery systems, messenger ribonucleic acid (mRNA) technology has achieved unprecedented development and application over the last few years, especially the emergency use authorizations of two mRNA vaccines during the COVID-19 pandemic, which has saved countless lives and makes the world witness the powerful efficacy of mRNA technology in vaccines. However, unlike infectious disease vaccines, which mainly induce humoral immunity, tumor vaccines also need to activate potent cellular immunity to control tumor growth, which creates a higher demand for mRNA delivery to the lymphatic organs and antigen-presenting cells (APCs). Here we review the existing bottlenecks of mRNA tumor vaccines and advanced nano-based strategies to overcome those challenges, as well as future considerations of mRNA tumor vaccines and their delivery systems.

The blood-brain barrier (BBB) and the poor ability of many drugs to cross that barrier greatly limits the efficacy of chemotherapies for glioblastoma multiforme (GBM). The present study exploits albumin as drug delivery vehicle to promote the chemotherapeutic efficacy of paclitaxel (PTX) by improving the stability and targeting efficiency of PTX/albumin nanoparticles (NPs). Here we characterize PTX-loaded human serum albumin (HSA) NPs stabilized with intramolecular disulfide bonds and modified with substance P (SP) peptide as the targeting ligand. The fabricated SP-HSA-PTX NPs exhibited satisfactory drug-loading content (7.89%) and entrapment efficiency (85.7%) with a spherical structure (about 150 nm) and zeta potential of -12.0 mV. The drug release from SP-HSA-PTX NPs occurred in a redox-responsive manner. Due to the targeting effect of the SP peptide, cellular uptake of SP-HSA-PTX NPs into brain capillary endothelial cells (BCECs) and U87 cells was greatly improved. The low IC, prolonged survival period and the obvious pro-apoptotic effect shown by TUNEL analysis all demonstrated that the fabricated SP-HSA-PTX NPs showed a satisfactory anti-tumor effect and could serve as a novel strategy for GBM treatment.

Oncogenic microRNAs are essential components in regulating the gene expression of cancer cells. Especially miR21, which is a major player involved of tumor initiation, progression, invasion and metastasis in several cancers. The delivery of anti-miR21 sequences has significant potential for cancer treatment. Nevertheless, since anti-miR21 sequences are extremely unstable and they need to obtain certain concentration to function, it is intensely difficult to build an effective delivery system for them. The purpose of this work is to construct a self-assembled glutathione (GSH)-responsive system with tumor accumulation capacity for effective anti-miR21 delivery and cancer therapy. A novel drug delivery nanosphere carrying millions of anti-miR21 sequences was developed through the rolling circle transcription (RCT) method. GSH-responsive cationic polymer polyethyleneimine (pOEI) was synthesized to protect the nanosphere from degradation by Dicer or other RNase in normal cells and optimize the pompon-like nanoparticle to suitable size. Dehydroascorbic acid (DHA), a targeting molecule, which is a substrate of glucose transporter 1 (GLUT 1) and highly expressed on malignant tumor cells, was connected to pOEI through PEG, and then the polymer was used for contracting a RNA nanospheres into nanopompons. The anti-miR21 nanopompons showed its potential for effective cancer therapy.

Retinal pigment epithelial (RPE) is primarily impaired in age-related macular degeneration (AMD), leading to progressive loss of photoreceptors and sometimes choroidal neovascularization (CNV). mTOR has been proposed as a promising therapeutic target, while the usage of its specific inhibitor, rapamycin, was greatly limited. To mediate the mTOR pathway in the retina by a noninvasive approach, we developed novel biomimetic nanocomplexes where rapamycin-loaded nanoparticles were coated with cell membrane derived from macrophages (termed as MRaNPs). Taking advantage of the macrophage-inherited property, intravenous injection of MRaNPs exhibited significantly enhanced accumulation in the CNV lesions, thereby increasing the local concentration of rapamycin. Consequently, MRaNPs effectively downregulated the mTOR pathway and attenuate angiogenesis in the eye. Particularly, MRaNPs also efficiently activated autophagy in the RPE, which was acknowledged to rescue RPE in response to deleterious stimuli. Overall, we design and prepare macrophage-disguised rapamycin nanocarriers and demonstrate the therapeutic advantages of employing biomimetic cell membrane materials for treatment of AMD.