Background Insulin can promote the occurrence of myopia.It has been proven that insulin receptor exists in human retinal pigment epithelial (RPE) cells and can promote RPE cells to secrete transforming growth factor-β2(TGF-β2),which is one of the most important myopic signal molecules.Objective This study was to investigate if PI3K/Akt mediates the promotive effects of insulin on proliferation of human RPE cells and secretion of TGF-β2.Methods Human RPE cell line,ARPE-19 cells,were regularly cultured using DMEM containing 10％ fetal bovine serum,and 10× 103 U/ml insulin,LY294002,10× 103 U/ml insulin+LY294002,Wortmanin,10× 103 U/ml insulin+Wortmanin were added into the medium respectively for 48 hours,and the regularly cultured cells served as blank controls.The proliferation value (absorbance,A) of the cells was evaluated by MTS,and the TGF-β2 level in the cell supernatant was detected by ELISA.The relative expression of TGF-β2 mRNA in the cells was assayed using reverse transcription PCR (RT-PCT) 1 hour and 2 hours after the addition of reagents.Results MTS showed that the proliferation value of the cells in the insulin+LY294002 group was 0.75±0.03,which was significantly lower than that in the insulin group (0.98± 0.04).No significant difference was seen in the proliferative value between the insulin+Wortmanin group and the insulin group (0.97±0.07 versus 0.98± 0.04,P＞0.05).ELISA revealed that the content of TGF-β2 in the the cell supernatant was (11.59±2.85) pg/ml and (49.16± 10.94) pg/ml in the insulin + LY294002 group and the insulin + Wortmanin group,respectively,showing a significant decline in comparison with (548.50±35.18) pg/ml in the insulin group (both at P＜0.05).A significant difference was found in the TGF-β2 content between the insulin+LY294002 group and the insulin+Wortmanin group (t =8.131,P =0.000).The RT-PCR showed that 1 hour and 2 hours after addition of the reagents,the expression levels of TGF-β2 mRNA in the cells were lower in both insulin+LY294002 group and insulin+Wortmanin group than those in the insulin group (P＜0.05).The decline range of TGF-β2 mRNA expression level was more significant in the insulin+LY294002 group than that in the insulin+Wortmanin group at 1 hour (t=4.176,P=0.014) rather than at 2 hours (t=0.756,P=0.492).Conclusions Insulin can promote the proliferation of human RPE cells and secretion of TGF-β2 through PI3K/Akt pathway.This may be one of the mechanisms of insulin causes myopia.

In this paper, taking Shijiazhuang city, Hebei province as an example, a random sampling of 30 streets in three districts were investigated the use of tactile ground surface indicator. The survey showed that 69% of the existing tactile ground surface indicator were used normally, while 8%were laid unreasonable, 11%were occupied and 12%were damaged. Suggestions were set from three aspects:sci-entific and reasonable laying, strengthening supervision and maintenance, and strengthening publicity and education, so as to improve the current situation of tactile ground surface indicator, improve the utilization rate, promote the participation of visually impaired persons in so-cial life and improve their quality of life.

Objective:To investigate the molecular epidemiological characteristics of norovirus (NoV) in hospitalized children with sporadic acute gastroenteritis in Tianjin in 2019.Methods:Fecal specimens and clinical data were collected from 3 116 hospitalized children with sporadic acute gastroenteritis possibly caused by viral infection in Tianjin Children′ Hospital between January and December, 2019. Real-time quantitative PCR was used to detect NoV. Partial sequences of RNA-dependent RNA polymerase (RdRp) and capsid genes of NoV were amplified by RT-PCR. Sequence alignment and phylogenetic analysis were performed for further analysis.Results:Among the 3 116 specimens, 809 (26.0%) were positive for NoV. There were significant differences in NoV detection rate between different age groups ( P=0.000), and the highest NoV detection rate (31.6%) was observed in the age group of 7-12 months. Moreover, the detection rate of NoV varied with seasons ( P=0.000), and the NoV detection rate was highest in winter (39.0%). Based on the sequence analysis of RdRp and capsid genes, 286 identified NoV strains belonged to six genotypes, which were GⅡ.P12-GⅡ.3, GⅡ.P16-GⅡ.2, GⅡ.P17-GⅡ.17, GⅡ.Pe-GⅡ.2, GⅡ.Pe-GⅡ.3 and GⅡ.Pe-GⅡ.4. The predominant genotype was GⅡ.Pe-GⅡ.4 Sydney 2012 (61.2%), followed by GⅡ.P12-GⅡ.3 (33.6%, 96/286), GⅡ.Pe-GⅡ.3 (2.4%, 7/286), GⅡ.P16-GⅡ.2 (2.1%, 6/286), GⅡ.Pe-GⅡ.2 (0.3%, 1/286) and GⅡ.P17-GⅡ.17 (0.3%, 1/286). Patients carrying the NoV of GⅡ.Pe-GⅡ.4 Sydney 2012 genotype were likely to suffer from vomiting than those positive for NoV of GⅡ.P12-GⅡ.3 genotype. Conclusions:NoV was an important pathogen causing acute gastroenteritis in children. GⅡ.Pe-GⅡ.4 Sydney 2012 and GⅡ.P12-GⅡ.3 were the major genotypes of NoV in hospitalized children with sporadic acute gastroenteritis in Tianjin in 2019.

Objective:To evaluate the prevalence of human rhinovirus (HRV) infection in hospitalized children in Tianjin and investigate the clinical impact of HRV infections.Methods:From July 2017 to December 2019, 2 945 nasopharyngeal secretion specimens were screened for HRV using polymerase chain reaction (PCR). VP4/VP2 sequences of HRV were further characterized. The clinical characteristics of the HRV infection were analyzed. The detection results of HRV for different groups and different months were compared using SPSS 19.0.Results:HRV-positive specimens accounted for 8.15% (240/2 945), of which 74.78% (86/115) were diagnosed with pneumonia, 40.83%(98/240) had co-infections with other common pathogens. HRV infections could be detected throughout the year with peaks in spring (11.00%, 66/660) and autumn (9.29%, 81/872). The positive rate of HRV was 4.14%(29/700) in winter. By VP4/VP2 sequence analysis, HRV-A was the most frequently detected strain(50.00%, 78/156), followed by HRV-C (41.67%, 65/156).46.15% (30/65) of HRV-C infections occurred in October and November. There were several different HRV-A types and HRV-C types. The most commonly detected HRV-A types were A12(11.54%, 9/78), A49(6.41%, 5/78), A22, A101, and A66(5.13%, 4/78), etc. The most common HRV-C types were C2(20.00%, 13/65), C22(9.23%, 6/65), C26, C43, C54 and C53(4.62%,3/65). Patients with HRV-A infections are more likely to show fever symptoms than HRV-C (χ2=5.411, P<0.05). No significant difference in other symptoms were found between the two types. Conclusions:HRV was a commonly detected virus among infants and had a clear seasonal distribution. It′s also possible for the HRV patients to have co-infections with other pathogens.HRV showed high genetic diversity.

Objective:To investigate the prevalence and clinical characteristics of Mycoplasma pneumoniae( Mp) genotypes and subtypes in children in Tianjin. Methods:Children with pneumonia admitted to Tianjin Children′s Hospital from December 2017 to December 2019 were selected as the research objects. Bronchoalveolar lavage fluid was collected by fiberoptic bronchoscopy. The positive samples were detected by real-time fluorescent quantitative PCR and Mp culture. PCR-restriction fragment length polymorphism(RFLP) and multiple variable number tandem repeats were used for genotyping. Detailed clinical and laboratory data were collected for all cases. Results:The results of RFLP showed that there were 138 cases (78.9%) of typeⅠand 37 cases (21.1%) of type Ⅱ; 37 cases of type M3-5-6-2, including six subtypes B, G, M, S, V and Y; 138 cases of M4-5-7-2 were detected, including seven subtypes of E, J, P, U, X, Z and a. In M3-5-6-2 type, there were 1 case of P1-Ⅰtype (2.7%), 36 cases of P1-Ⅱtype (97.3%), 137 cases of P1-Ⅰ type (99.2%) and 1 case of P1-Ⅱ type (0.7%) in M4-5-7-2 type. There was no significant difference in genotype distribution among different age groups. There were statistical differences in the distribution of four seasons among the 13 genotypes of B, G, M, S, V, Y and E, J, P, U, X, Z, a. All Mp infected children had symptoms of fever and cough. The hospitalization time, fever duration, high fever (>39℃), cough duration, skin changes, digestive system symptoms and liver function injury rate of P1-Ⅰ/M4-5-7-2 pneumonia children were higher than those of P1-Ⅱ/M3-5-6-2 pneumonia children, but the difference was not statistically significant. The WBC count of P1-Ⅱ/M3-5-6-2 types was higher than that of typeⅠand M4-5-7-2; the LDH of P1-Ⅰ/M4-5-7-2 was higher than that of Ⅱ and M3-5-6-2, with statistical difference. There was no significant difference in the incidence of inflammatory consolidation, atelectasis, pleural thickening and pleural effusion among different genotypes. Conclusions:Mp infection in children with pneumonia in Tianjin is mainly P1-Ⅰ/ M4-5-7-2, and P1-Ⅱ is on the rise. P1-Ⅰ and M4-5-7-2 were associated with fever and severe symptoms.

Objective:To understand the pathogen infection and epidemiological characteristics of children with diarrhea in Tianjin.Methods:Stool samples from 1 466 children with diarrhea in Tianjin Children's Hospital from August 2017 to July 2018 were collected, and all samples were tested for five intestinal-related pathogens (norovirus, rotavirus, Clostridium difficile toxin, adenovirus, and astrovirus). Results:Among the 1 466 samples, 627 samples were positive for nucleic acid detection of intestinal pathogens, with a positive rate of 42.8%. The detection rate of norovirus was the highest (26.3%), followed by rotavirus (15.3%), Clostridium difficile toxin (4.6%), adenovirus (4.1%), and astrovirus (1.84%). The infection has obvious seasonality. The positive detection rates of the five pathogens were similar among children of different sexes, and only the positive detection rates of norovirus and rotavirus were statistically significant among different ages ( P<0.05). There were 110 cases of mixed infection, and the mixed infection of norovirus and rotavirus was the most common, with a total of 37 cases. Conclusions:The pathogen spectrum of infant infectious diarrhea in Tianjin is complex and diverse, and the main pathogens are norovirus and rotavirus.

Matrix protein p17 is a structural protein of human immunodeficiency virus（HIV）. It not only plays a key role in multiple stages of HIV life cycle，but also is closely associated with HIV-related lymphoma，neurocognitive impairment and breast cancer. This article reviews the role of matrix protein p17 in HIV infection and HIV-related diseases.

OBJECTIVE: To investigate the mechanism by which epigallocatechin gallate (EGCG) induces gene demethylation and promotes the apoptosis of acute myeloid leukemia KG-1 and THP-1 cell lines. METHODS: KG-1 and THP-1 cells treated with 25, 50, 75, 100 or 150 μg/mL EGCG for 48 h were examined for gene methylation using MSP and for cell proliferation using MTT assay. The changes in cell cycle and apoptosis of the two cell lines after treatment with EGCG for 48 h were detected using flow cytometry. The mRNA and protein expressions of DNMT1, CHD5, p19, p53 and p21 in the cells were detected using RT-quantitative PCR and Western blot. RESULTS: EGCG dose-dependently reversed hypermethylation of gene and reduced the cell viability in both KG-1 and THP-1 cells ( < 0.05). EGCG treatment caused obvious cell cycle arrest in G1 phase, significantly increased cell apoptosis, downregulated the expression of DNMT1 and upregulated the expressions of CHD5, p19, p53 and p21 in KG-1 and THP-1 cells ( < 0.05). CONCLUSIONS EGCG reduces hypermethylation of gene in KG-1 and THP-1 cells by downregulating DNMT1 to restore its expression, which results in upregulated expressions of p19, p53 and p21 and induces cell apoptosis.

SARS-CoV-2 has caused tens of thousands of infections and more than one thousand deaths. There are currently no registered therapies for treating coronavirus infections. Because of time consuming process of new drug development, drug repositioning may be the only solution to the epidemic of sudden infectious diseases. We systematically analyzed all the proteins encoded by SARS-CoV-2 genes, compared them with proteins from other coronaviruses, predicted their structures, and built 19 structures that could be done by homology modeling. By performing target-based virtual ligand screening, a total of 21 targets (including two human targets) were screened against compound libraries including ZINC drug database and our own database of natural products. Structure and screening results of important targets such as 3-chymotrypsin-like protease (3CLpro), Spike, RNA-dependent RNA polymerase (RdRp), and papain like protease (PLpro) were discussed in detail. In addition, a database of 78 commonly used anti-viral drugs including those currently on the market and undergoing clinical trials for SARS-CoV-2 was constructed. Possible targets of these compounds and potential drugs acting on a certain target were predicted. This study will provide new lead compounds and targets for further and studies of SARS-CoV-2, new insights for those drugs currently ongoing clinical studies, and also possible new strategies for drug repositioning to treat SARS-CoV-2 infections.

Cancer cell membrane (CCM) derived nanotechnology functionalizes nanoparticles (NPs) to recognize homologous cells, exhibiting translational potential in accurate tumor therapy. However, these nanoplatforms are majorly generated from fixed cell lines and are typically evaluated in cell line-derived subcutaneous-xenografts (CDX), ignoring the tumor heterogeneity and differentiation from inter- and intra- individuals and microenvironments between heterotopic- and orthotopic-tumors, limiting the therapeutic efficiency of such nanoplatforms. Herein, various biomimetic nanoplatforms (CCM-modified gold@Carbon, i.e., Au@C-CCM) were fabricated by coating CCMs of head and neck squamous cell carcinoma (HNSCC) cell lines and patient-derived cells on the surface of Au@C NP. The generated Au@C-CCMs were evaluated on corresponding CDX, tongue orthotopic xenograft (TOX), immune-competent primary and distant tumor models, and patient-derived xenograft (PDX) models. The Au@C-CCM generates a photothermal conversion efficiency up to 44.2% for primary HNSCC therapy and induced immunotherapy to inhibit metastasis via photothermal therapy-induced immunogenic cell death. The homologous CCM endowed the nanoplatforms with optimal targeting properties for the highest therapeutic efficiency, far above those with mismatched CCMs, resulting in distinct tumor ablation and tumor growth inhibition in all four models. This work reinforces the feasibility of biomimetic NPs combining modular designed CMs and functional cores for customized treatment of HNSCC, can be further extended to other malignant tumors therapy.
Animals ; Humans ; Squamous Cell Carcinoma of Head and Neck/therapy* ; Heterografts ; Photothermal Therapy ; Biomimetics ; Disease Models, Animal ; Head and Neck Neoplasms/therapy* ; Cell Line, Tumor ; Tumor Microenvironment