Objective:To investigate the role and potential regulation mechanism of miR-22-3p in lipotoxic hepatocyte inflam-matory injury and apoptosis caused by palmitic acid(PA).Methods:Human normal immortalized hepatocytes(LO2 cells)were treated with different concentrations of PA for 24 h.CCK-8 and qRT-PCR were used to detect cell proliferation and miR-22-3p expression.miR-22-3p mimics or inhibitors were transfected into LO2 cells and then treated with 0.32 mmol/L PA for 24 h,the expression level of miR-22-3p was determined by qRT-PCR;cell viability was determined by CCK-8;biochemical kits to determine the ALT and AST contents;the mRNA and protein expression levels of inflammatory cytokines TNF-α,IL-1β and IL-6 in intracellular and culture super-natants were determined by qRT-PCR and ELISA;the cell apoptosis rate in each group was determined by flow cytometry;the expres-sion levels of NF-κB signaling pathway-related proteins were detected by Western blot and immunofluorescence.Results:With the increaseing of PA concentration,the cell survival rate and the expression of miR-22-3p decreased in a dose-dependent manner.After PA treatment,the cell proliferation activity decreased significantly,the activities of ALT and AST enzymes were increased,the expressions of inflammatory cytokines TNF-α,IL-1β and IL-6 were increased,cell apoptosis was increased,and NF-κB signaling pathway was activated.Transfection of miR-22-3p mimics significantly increased the proliferation activity of LO2 cells,and decreased the levels of ATL,AST,TNF-α,IL-1β,IL-6 and apoptosis,and inhibited the activation of NF-κB signaling pathway.Transfection of miR-22-3p inhibitor further activated NF-κB signaling pathway,and promoted cell inflammatory injury and apoptosis(all P<0.05).Conclusion:Overexpression of miR-22-3p can alleviate PA-induced apoptosis and inflammation,and the mechanism is related to inhibit the activation of NF-κB signaling pathway.

Objective:To investigate the role and potential regulation mechanism of miR-22-3p in lipotoxic hepatocyte inflam-matory injury and apoptosis caused by palmitic acid(PA).Methods:Human normal immortalized hepatocytes(LO2 cells)were treated with different concentrations of PA for 24 h.CCK-8 and qRT-PCR were used to detect cell proliferation and miR-22-3p expression.miR-22-3p mimics or inhibitors were transfected into LO2 cells and then treated with 0.32 mmol/L PA for 24 h,the expression level of miR-22-3p was determined by qRT-PCR;cell viability was determined by CCK-8;biochemical kits to determine the ALT and AST contents;the mRNA and protein expression levels of inflammatory cytokines TNF-α,IL-1β and IL-6 in intracellular and culture super-natants were determined by qRT-PCR and ELISA;the cell apoptosis rate in each group was determined by flow cytometry;the expres-sion levels of NF-κB signaling pathway-related proteins were detected by Western blot and immunofluorescence.Results:With the increaseing of PA concentration,the cell survival rate and the expression of miR-22-3p decreased in a dose-dependent manner.After PA treatment,the cell proliferation activity decreased significantly,the activities of ALT and AST enzymes were increased,the expressions of inflammatory cytokines TNF-α,IL-1β and IL-6 were increased,cell apoptosis was increased,and NF-κB signaling pathway was activated.Transfection of miR-22-3p mimics significantly increased the proliferation activity of LO2 cells,and decreased the levels of ATL,AST,TNF-α,IL-1β,IL-6 and apoptosis,and inhibited the activation of NF-κB signaling pathway.Transfection of miR-22-3p inhibitor further activated NF-κB signaling pathway,and promoted cell inflammatory injury and apoptosis(all P<0.05).Conclusion:Overexpression of miR-22-3p can alleviate PA-induced apoptosis and inflammation,and the mechanism is related to inhibit the activation of NF-κB signaling pathway.

Objective:To establish a disk (CD) microfluidic chip detection platform for the rapid detection of CALR-1 and CALR-2 mutations in patients with cerebral infarction, and summarize its clinical application value.Methods:Based on microfluidic technology and loop mediated isothermal amplification technology, a CD microfluidic chip detection platform for simultaneous detection of CALR-1 and CALR-2 gene mutations were established, and the sensitivity, specificity, repeatability and accuracy of the platform were verified. A total of 124 patients with cerebral infarction treated in Huashan Hospital, Shanghai Medical College, Fudan University from November 2019 to March 2021 were prospectively selected into the experimental group; and 80 healthy subjects were included in the control group. The CALR-1 and CALR-2 gene mutations in anticoagulant peripheral blood samples were detected by the CD microfluidic chip. Each chip could detect 4 samples at the same time and synchronously detect 3 indexes of each sample. The detection results could be obtained after isothermal amplification for 40 min. At the same time, sequencing method was used to verify the test results, and the consistency of the results of the two detection methods was compared.Results:Using this CD microfluidic chip platform, the synchronous amplification of 3 indexes in the sample could be completed within 40 min without the need of thermal circulation, and the whole detection process of the sample could be completed within 60 min. For samples with a high concentration of target nucleic acid, typical positive signals could be visualized after amplification for 10 min, and the test results would be available within 30 minutes after receiving the samples. The detection sensitivity of CD microfluidic chip method for CALR-1 and CALR-2 mutation load concentration was 1.0% and 0.5% respectively. Nonspecific amplification was not observed for the non-target nucleic acid samples, indicating the high specificity of this method. The coincidence rates of intra and inter batch repeatability were 100% (20/20) respectively. Two samples with CALR gene mutation were found in the cerebral infarction group, both of which were CALR-1 mutations (L367fs*46). There was no CALR-1 or CALR-2 mutation in the control group. The detection results of CD microfluidic chip method were completely consistent with the sequencing verification results (100% [204/204]).Conclusions:The CD microfluidic chip method could be used for the detection of CALR-1 and CALR-2 gene mutations in clinical samples of patients with cerebral infarction. This method has the advantages of high detection sensitivity, good detection specificity, fast detection speed and high detection flux, which is helpful to clarify the etiology of patients with cerebral infarction.

Objective    To systematically evaluate the effects of telemedicine on the management of warfarin therapy. Methods    We searched PubMed, EMbase, Cochrane Library, Web of Science, CNKI, VIP, Wanfang Database (from inception to February 2020) and conducted retrospective literature searching to identify studies about the management of warfarin using telemedicine intervention techniques. R language software was used to evaluate the efficacy and safety of telemedicine on warfarin management. Results    A total of 7 239 articles were retrieved, and 12 articles were finally included according to inclusion and exclusion criteria, totaling 8 112 patients, including 3 726 patients in the intervention group and 4 386 patients in the control group. The results of meta-analysis showed that there was a statistical difference in the accurate international normalized ratio (INR) treatment target range time ratio between the intervention group and the control group (MD=6.52, 95%CI 2.13 to 10.92, P<0.01, I2=89%). The incidence of bleeding events (RR=0.61, 95%CI 0.46 to 0.81, P=0.97, I2=0%) and the incidence of thromboembolic events (RR=0.50, 95%CI 0.29 to 0.85, P=0.63, I2=0%) were not statistically different between the two groups. Conclusion    Existing evidence indicates that telemedicine management has a benefit in anticoagulant efficacy compared with conventional anticoagulant management in patients with thrombotic diseases, but there is no statistical difference in safety. Limited by the quantity and quality of the included studies, the above conclusion needs to be verified by more high-quality studies.

Objective To investigate the correlations between the ocular biometric optical parame-ters and refractive dioptres in adults, assess the influence of the biometric optical parameters on the develop-ment of myopia, and provide a reference of prevention and treatment for myopia.Methods A total of 188 adults (376 eyes) aged 18 to 40 years old was enrolled in this study.Dioptres were measured with phorop-ter, A-mode ultrasound was used to measure the vitreous length and lens thickness, the axis length, anterior corneal surface semidiameter anterior chamber depth were measured with intraocular len-master ( IOL-mas-ter) .SPSS 17.0 software was used to analyze the date.Results ⑴Of the 376 eyes, the results showed a statistically significant difference between myopia and emetropia in the axis length, vitreous depth, anterior corneal surface semidiameter, anterior chamber depth and lens thickness( P <0.01).⑵The partial corre-lation analysis indicated a significant positive correlation between the refraction dioptres and axial length, vitreous length ( r =-0.90, -0.88, respectively, P <0.01);and significant strong correlation was also found between dioptres and anterior corneal surface horizontal and vertical semidiameter ( r =0.81, 0.84, respectively, P <0.01);But correlations between dioptres and lens thickness and anterior chamber depth were very weak ( r =-0.11, 0.12, respectively, P <0.01);the correlation between axial length and vit-reous depth was very high ( r =0.95, P <0.01).and the data indicated that the anterior corneal surface horizontal and vertical semidiameter were high positive correlation( r =0.91, P <0.01);the same high positive correlation between the axial length and the anterior corneal surface semidiameter ( horizontal/verti-cal) was also found ( r =0.78,0.81, P <0.01).Conclusions Two chief factors (corneal surface semi-diameter and ocular axial length) influencing the level of dioptres were high positive correlation, seeking the mutual coordination factors which promote corneal curvature change and axial growth and finding out the feedback mechanism of promoting the cornea sphericity might be conducive to further explore how to control the occurrence and development of myopia.

The radiobiological effect of 131I radiolabeled recombinant human epidermal growth factor (131I-rhEGF) on nude mice with human breast cancer was assessed in this study. The tissue mainly uptaking 131I-rhEGF was found by tissue distribution assay in mice. The radiation breakdown of the tissue greatly collecting 131I-rhEGF was examined by biochemical test and biopsy in nude mice with human breast cancer. The tissue distribution assay of 131I-rhEGF in mice showed that 131I-rhEGF greatly accumulated in kidney, liver, spleen and blood. The biochemical test and biopsy revealed that 131I -rhEGF injected twice (dosing once is analogous to 14.58 GBq in a person with 50 kg, once every 14 days) had an effective killing effect on tumor but had no effect of radiation breakdown on kidney, liver,spleen and blood-cell forming tissue in mice with human breast cancer. Therefore, 131I-rhEGF is a drug unharmful to normal tissues in the course of the receptor-mediated target radiotherapy for breast cancer.
Animals ; Breast Neoplasms ; metabolism ; pathology ; radiotherapy ; Cell Line, Tumor ; Drug Delivery Systems ; Epidermal Growth Factor ; biosynthesis ; genetics ; pharmacokinetics ; therapeutic use ; Humans ; Iodine Radioisotopes ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Radiopharmaceuticals ; Random Allocation ; Recombinant Proteins ; biosynthesis ; genetics ; pharmacokinetics ; therapeutic use

This experiment was designed to study the effect of 131I-recombinant human epidermal growth factor (131I-rhEGF) on the growth of tumor in nude mice loaded with human breast cancer. Bioactivity of 131I-rhEGF and uptake of 131I-rhEGF in breast cancer tissue were verified using biodistribution experiment of 131I-rhEGF in the nude mice loaded with human breast cancer. The effect of 131I-rhEGF on the growth of tumor was assessed via the growth experiment of tumor in the nude mice loaded with human breast cancer. The ultrastructural change of the tumor cell treated with 131I-rhEGF was observed under transmission electron microscope, and the pathological change of the tumor tissue treated with 131I-rhEGF was detected by biopsy. The results showed that the tumor tissue of nude mice bearing human breast cancer obviously takes in 131I-rhEGF; that intravenous administration and intratumoral administration of 131I-rhEGF both obviously inhibit the growth of tumor, the inhibition rates (82.00% and 80.70%) being remarkably higher than that of 131I (7.49%) and that of 131I-HSA (6.91%) (P<0.05); and that intravenous and intratumoral administration of 131I-rhEGF both obviously damage and kill tumor cells. Therefore, 131I-rhEGF can inhibit the growth of human breast cancer cell in nude mice; it is a potential receptor-mediated radioactivity targeting drug for treating breast cancer.
Animals ; Breast Neoplasms ; pathology ; ultrastructure ; Drug Delivery Systems ; Epidermal Growth Factor ; biosynthesis ; genetics ; pharmacology ; Female ; Humans ; Iodine Radioisotopes ; administration & dosage ; pharmacology ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Receptor, Epidermal Growth Factor ; metabolism ; Recombinant Proteins ; biosynthesis ; genetics ; pharmacology