Objective To study the regulation effect of salvianolic acid A and C molecular compatibility on inflammatory chemokine monocyte chemotaxis protein 1(CCL2)and CXC chemokine ligand 10(CXCL10)in human renal tubular epithelial(HK-2)cells intervened by human serum albumin(HSA),and to explore the anti-inflammatory and antioxidation effects of salvianolic acid A,C molecular medicine-pair compatibility.Methods The cultured human renal tubular epithelial cells were randomly divided into 5 groups:control group,model group,salvianolic acid A group(20 μmol/L),salvianolic acid C group(20 μmol/L),salvianolic acid A+C group(10 μmol/L salvianolic acid A+10 μmol/L salvianolic acid C).Except for the control group,the other groups were added with HSA intervention for 24,48,72 h,then the each treatment group was simultaneously added with the drug treatment.The enzyme linked immunosorbent assay(ELISA)method was used to detect the expression of CCL2,CC chemokine 7(CCL7)and CXCL10,and SOD,GSH and MDA were detected by WST-1,DTNB,TBA.Results Compared with the control group,the levels of CCL2,CCL7,CXCL10 and MDA at 3 time points of 24,48 72 h in other groups were significantly increased,while the GSH and SOD levels were significantly decreased(P＜0.05).Compared with the model group,the levels of CCL2,CCL7,CXCL10 and MDA in each treatment group were relatively decreased,while the GSH and SOD levels were relatively increased(P＜0.05).In the comparison of various treatment groups,the levels of CCL2,CCL7,CXCL10 and MDA in the salvianolic acid A+C group were lower than those in the salvianolic acid A group and salvianolic acid C group(P＜0.05),while the GSH and SOD levels were higher than those in the salvianolic acid A group and salvianolic acid C group(P＜0.05).Conclusion The salvianolic acid A and B molecular medicine-pair compatibility may improve renal fibrosis by decreasing the expression of inflammatory chemokines and antioxidation.

Prostate cancer is one of the most common malignant tumors in the world.Without typical early manifestations in the early stage, it is often too late when found. Therefore, early diagnosis, treatment, and prognosis are critical to improving the survival rate of patients with prostate cancer. Over the past few years, artificial intelligence(AI) has developed rapidly in the field of prostate cancer. In terms of diagnosis, AI is used as a tool to screen the images to reduce the error caused by the professionalism and subjectivity of the technician and to improve the repeatability of the results; In the prediction of prognosis, the algorithm calculates and evaluates disease-related parameters such as recurrence rate, lymph node metastasis rate and mortality rate, so as to assistant clinicians in decision-making and treatment improvements. This reviews aims to introduce the application of artificial intelligence in the diagnosis, treatment and prognosis of prostate cancer in recent years, as well as the prospect and challenges faced by artificial intelligence in the medical field.

AIM:To explore the synergistic sensitization effect of human umbilical cord mesenchymal stem cell culture supernatant(hUMSC-CM)combined with temozolomide(TMZ)on various glioma cell lines,and to elucidate the underlying mechanisms.METHODS:The hUMSC-CM was harvested using two different serum deprivation tech-niques at 24 and 48 h,and was converted into freeze-dried powder,which was then given to rat malignant glioma cell line RG-2,human astrocytoma cell line U251 and human glioblastoma cell line LN-428 at 5 concentrations(0,1,3,6 and 9 g/L).The effectiveness and sensitivity of hUMSC-CM for inhibiting growth of glioma cells at 24,48 and 72 h were as-sessed using CCK-8 assay.Hematoxylin-eosin(HE)staining combined with CCK-8 assay was employed to evaluate the chemotherapy sensitivity of glioma cells after 48 h of treatment with TMZ at 6 concentrations(0,25,50,100,200 and 400 μmol/L).Two concentrations(3 and 9 g/L)of hUMSC-CM and 3 concentrations(50,100 and 200 μmol/L)of TMZ were chosen for concurrent treatment of glioma cells to assess the proliferation and pathological alterations.TUNEL staining was utilized to detect apoptosis.Flow cytometry was utilized to analyze cell cycle modifications.The expression alterations of apoptosis-inducing proteins,cleaved caspase-3,cleaved caspase-8 and cleaved PARP1,as well as autophagy-inducing proteins beclin-1 and LC3,were examined using Western blot to investigate the synergistic sensitization mechanism of hUMSC-CM combined with TMZ in vitro.RESULTS:The susceptibility of glioma cell lines to hUMSC-CM and TMZ varied,with RG-2 showing the highest sensitivity,followed by U251,and then LN-428.The inhibitory effect of hUMSC-CM(3 and 9 g/L)and TMZ(50,100 and 200 μmol/L)combined treatment on glioma cells was significantly greater than that that of single-agent treatments(P＜0.05),demonstrating a dose-and concentration-dependent enhancement.Notably,the combination of 9 g/L hUMSC-CM(C9)with 50 μmol/L TMZ(T50)effectively suppressed glioma cell growth.CCK-8 as-say indicated a significant reduction of cell viability in C9+T50 group compared with either C9 or T50 alone(P＜0.05).HE staining and TUNEL staining revealed pronounced morphological changes and significant apoptotic features in glioma cells treated with C9+T50.Flow cytometric analysis confirmed that C9+T50 induced cell cycle arrest in glioma cells.Fur-thermore,compared with control group,the levels of cleaved caspase-3,cleaved caspase-8,cleaved PARP1,beclin-1,and LC3-Ⅱ/LC3-Ⅰ were significantly elevated in the C9+T50-treated glioma cells(P＜0.01).CONCLUSION:(1)The concomitant administration of hUMSC-CM and TMZ exerts a broad inhibitory effect on glioma cells,with a synergistic sen-sitization observed across different cell lines.(2)The enhancement of glioma cell sensitivity to TMZ by hUMSC-CM may be attributed to the modulation of caspase-8/caspase-3/PARP1 signaling pathway and the induction of both apoptosis and autophagy in glioma cells.

Objective:To investigate the role of modification level of lysine trimethylation at position 27 of histone 3 (H3K27me3) on expression of anti-apoptotic protein B lymphocyte tumor-2 gene (BCL2) during arsenic-induced hepatocyte apoptosis.Methods:Rat liver BRL-3A cells were cultured in vitro. According to the arsenic treatment factor, the experiment was divided into two parts, in the first part arsenic was not added, the experiment was divided into normal, transfection reagent, negative transfection, H3K27me3 specific demethylase (JMJD3) small interfering RNA (siRNA) transfection and H3K27me3 methyltransferase (EZH2) siRNA transfection groups. In the second part arsenic was added, the experiment was divided into control, arsenic treatment, arsenic + negative transfection, arsenic + JMJD3siRNA transfection and arsenic + EZH2siRNA transfection groups. When arsenic was not added, the corresponding siRNA and transfection reagent was used to transfect cells at a ratio of 100 pmol : 7.5 μl for 6 h [the normal group was treated with phosphate buffer solution (PBS) of the same volume as transfection reagent], then the medium was changed and the cells were incubated for a total of 48 h. After 24 h of treatment with the above transfection and culture method in arsenic added group, a final concentration of 30 μmol/L sodium arsenite (NaAsO 2) was added and the cells were incubated for 24 h (the control group was treated with PBS with the same volume of NaAsO 2 for 24 h). Real-time cell analysis (RTCA) was used to measure the proliferation of BRL-3A cells in arsenic added group. Apoptosis of BRL-3A cells was analyzed by flow cytometry in arsenic added group. Western blotting was used to detect JMJD3, EZH2, H3K27me3 and BCL2 in no-arsenic and arsenic-added BRL-3A cells. The modification levels of H3K27me3 in BCL2 gene promoter regions were detected by chromatin immunoprecipitation of the cells exposed to arsenic. Results:There were statistically significant differences of the proliferation rates [control, arsenic treatment, arsenic + negative transfection, arsenic + JMJD3siRNA transfection and arsenic + EZH2siRNA transfection groups: (100.00 ± 10.43)%, (12.19 ± 3.37)%, (31.86 ± 1.95)%, (24.58 ± 3.64)%, (11.53 ± 1.11)%] and the apoptosis rates [(1.15 ± 0.04)%, (13.06 ± 1.33)%, (17.39 ± 0.22)%, (23.90 ± 1.66)%, (15.07 ± 0.88)%] between groups ( F = 146.50, 194.30, P < 0.001), correspondingly. The protein expression level of H3K27me3 in JMJD3siRNA transfection group was higher than that of normal, transfection reagent and negative transfection groups, while EZH2siRNA transfection group had an opposite result ( P < 0.05). The protein expression level of BCL2 in JMJD3siRNA transfection group was lower than that of normal, transfection reagent and negative transfection groups, while EZH2siRNA transfection group had an opposite result ( P < 0.05). The protein expression levels of H3K27me3 and BCL2 were not statistically significant differences between normal, transfection reagent and negative transfection groups ( P > 0.05). The protein expression levels of JMJD3, EZH2, H3K27me3 and BCL2 among control, arsenic treatment, arsenic + negative transfection, arsenic + JMJD3siRNA transfection and arsenic + EZH2siRNA transfection groups were compared, and the differences were statistically significant ( F = 26.56, 7.82, 9.81, 31.19, P < 0.05). Compared with control group, the protein expression levels of JMJD3 and EZH2 in arsenic treatment group were significantly reduced ( P < 0.05), and the protein expression level of H3K27me3 was higher ( P < 0.05), meanwhile the protein expression level of BCL2 was lower ( P < 0.05). Compared with arsenic + negative transfection group, the protein expression level of JMJD3 was significantly reduced in arsenic + JMJD3siRNA group, and the protein expression level of EZH2 was significantly reduced in arsenic + EZH2siRNA group ( P < 0.05). In addition, arsenic + JMJD3siRNA increased the level of H3K27me3 modification while reducing the protein expression of BCL2, while arsenic + EZH2siRNA had an opposite result ( P < 0.05). Compared with control group, the enrichment levels of H3K27me3 in BCL2 gene promoter regions (CHIP1 and CHIP2) in arsenic treatment group were significantly higher ( P < 0.05). Conclusion:Arsenic may inhibit the expression of BCL2 by increasing the enrichment level of H3K27me3 in the promoter regions of BCL2 gene, and promoting hepatocyte apoptosis.

OBJECTIVE: To investigate the mechanism by which dripping pills (STDP) improves coronary microcirculation disorder (CMD) and cardiac dysfunction in a porcine model of myocardial ischemia-reperfusion injury. METHODS: Fourteen minipigs were randomly selected for interventional balloon occlusion of the middle left anterior descending branch to induce CMD, and another 7 pigs received sham operation. The pig models of CMD were randomized equally into the model group and STDP-treated group. All the animals were fed with common feed for 8 weeks, and in STDP-treated group, the pigs were given STDP at the daily dose of 3 mg/kg (mixed with feed) for 8 weeks. Before and at the 8th week after the operation, the pigs underwent coronary angiography and echocardiography to determine the vessel lumen diameter and TIMI frame count (CTFC). The pathologies of the myocardium and the microvessels were examined with HE staining at the 8th week. Western blotting was used to detect the expression of silencing information regulator (Sirt1), peroxidase proliferator-activated receptor-γ coactivator-1α (PGC-1α), peroxisome proliferator-activated receptor α (PPARα), extracellular signal-regulated kinase1/2 (ERKI/2), Toll-like receptor 4 (TLR4), and uncoupling protein 2 (UCP2) in myocardial tissue. RESULTS: Before and at the 8th week after the operation, the diameter of the anterior descending vessel in the 3 groups did not differ significantly ( > 0.05). At the 8th week, the number of CTFC frames in the model group increased significantly compared with that in the sham-operated group, but was obviously lowered by treatment with STDP ( < 0.05). Myocardial ischemia-reperfusion injury significantly increased the interventricular septal thickness at end-diastole, left ventricular end-diastole dimension, end-diastole volume, interventricular septal thickness at end-systole and left ventricular mass at 8 weeks after the modeling ( < 0.05), but such changes were significantly alleviated by treatment with STDP (P < 0.05). STDP treatment markedly alleviated myocardial microvascular congestion, thrombosis and peripheral inflammatory cell infiltration induced by myocardial ischemia-reperfusion, but atrophy of the myocardial muscle fiber remained distinct. STDP obviously suppressed the down-regulation of Sirt1, PGC-1α, and PPARα and the up-regulation of ERK1/ 2, TLR4, and UCP2 in the myocardial tissues induced by myocardial ischemia-reperfusion injury. CONCLUSIONS STDP has anti-inflammatory effects and regulates energy metabolism in the myocardium through modulating Sirt1, PGC-1α, PPARα, ERKI/2, TLR4, and UCP2 to improve CMD and cardiac dysfunction after myocardial ischemia-reperfusion.
Animals ; Drugs, Chinese Herbal ; Microcirculation ; Myocardial Reperfusion Injury ; Myocardium ; Rats ; Rats, Sprague-Dawley ; Swine

Objective:To investigate the changes of microRNA-153 (miR-153) expression and the mechanism of regulating histone H3 lysine 4 (H3K4) methyltransferase (SET7/9) and histone H3K4 methylation (H3K4me1) in the process of arsenic-induced endoplasmic reticulum stress-related hepatocytes apoptosis.Methods:Human normal hepatocytes (L-02 cells) were cultured in vitro and divided into control, arsenic treatment, arsenic + negative transfection, arsenic + miR-153 up-regulation and arsenic+ miR-153 down-regulation groups according to different treatment methods. Arsenic+ negative transfection, arsenic+ miR-153 up-regulation and arsenic+ miR-153 down-regulation groups were transfected with transfection plasmid and transfection reagent according to a certain proportion (3 μg: 8 μl). After 24 h, arsenic treatment, arsenic+ negative transfection, arsenic+ miR-153 up-regulation and arsenic+ miR-153 down-regulation groups were all treated with 100 μmol/L sodium arsenite (NaAsO 2) as the final concentration for 24 h. The control group was treated with phosphate buffer solution (PBS) of the same volume as NaAsO 2 for 24 h. The expression of miR-153 was detected by real-time quantitative polymerase chain reaction (RT-qPCR); cell apoptosis and cell cycle were detected by flow cytometry; real-time cell dynamic analyzer (RTCA) was used to detect cell proliferation; Western blotting was used to detect the expression of endoplasmic reticulum marker proteins glucose regulatory protein 78 (GRP78), SET7/9 and H3K4me1. Results:The expression levels of miR-153 in each group were significantly different ( F = 10.73, P < 0.05). Compared with the control group [(41.10 ± 6.08)%], the expression level of miR-153 in arsenic treatment group [(4.35 ± 0.20)%] was significantly decreased ( P < 0.05); compared with the arsenic+ negative transfection group [(10.00 ± 2.40)%], the expression level of miR-153 in arsenic+ miR-153 up-regulation group [(157.70 ± 42.70)%] was significantly increased ( P < 0.05), and that in arsenic+ miR-153 down-regulation group [(4.20 ± 0.28)%] was significantly decreased ( P < 0.05). There were significant differences in the total cell apoptosis rate and G1 phase cell proportion among the five groups ( F = 29.69, 104.32, P < 0.05). Compared with the control group, the total cell apoptosis rates and G1 phase cell proportions in arsenic treatment, arsenic+ miR-153 up-regulation and arsenic+ miR-153 down-regulation groups were significantly increased ( P < 0.05); compared with the arsenic+ negative transfection group, the total cell apoptosis rate and G1 phase cell proportion in arsenic+ miR-153 up-regulation group were significantly decreased ( P < 0.05), and those in arsenic+ miR-153 down-regulation group were significantly increased ( P < 0.05). The difference of cell proliferation rate in each group was statistically significant ( F = 799.35, P < 0.05). Compared with the control group, the cell proliferation rates in arsenic treatment, arsenic+ miR-153 up-regulation and arsenic+ miR-153 down-regulation groups were significantly decreased ( P < 0.05); compared with the arsenic+ negative transfection group, the cell proliferation rate in arsenic+ miR-153 up-regulation group was significantly increased ( P < 0.05), and that in arsenic+ miR-153 down-regulation group was significantly decreased ( P < 0.05). The protein expression levels of SET7/9, GRP78 and H3K4me1 in each group were significantly different ( F = 78.52, 52.13, 54.32, P < 0.05). Compared with the control group, the protein expression levels of SET7/9, GRP78 and H3K4me1 in arsenic treatment group were significantly increased ( P < 0.05); compared with the arsenic+ negative transfection group, the protein expression levels of SET7/9, GRP78 and H3K4me1 in arsenic+ miR-153 up-regulation group were significantly decreased ( P < 0.05), and those in arsenic + miR-153 down-regulation group were significantly increased ( P < 0.05). Conclusion:miR-153 plays an important role in arsenic-induced endoplasmic reticulum stress-related hepatocytes apoptosis, the expression and regulation are related to the changes of SET7/9 and H3K4me1 levels.

In order to suppress the geometrical artifacts caused by random jitter in ray source scanning, and to achieve flexible ray source scanning trajectory and meet the requirements of task-driven scanning imaging, a method of free trajectory cone-beam computed tomography (CBCT) reconstruction is proposed in this paper. This method proposed a geometric calibration method of two-dimensional plane. Based on this method, the geometric calibration phantom and the imaging object could be simultaneously imaged. Then, the geometric parameters could be obtained by online calibration method, and then combined with the geometric parameters, the alternating direction multiplier method (ADMM) was used for image iterative reconstruction. Experimental results showed that this method obtained high quality reconstruction image with high contrast and clear feature edge. The root mean square errors (RMSE) of the simulation results were rather small, and the structural similarity (SSIM) values were all above 0.99. The experimental results showed that it had lower image information entropy (IE) and higher contrast noise ratio (CNR). This method provides some practical value for CBCT to realize trajectory freedom and obtain high quality reconstructed image.
Algorithms ; Calibration ; Cone-Beam Computed Tomography ; Image Processing, Computer-Assisted ; Phantoms, Imaging

OBJECTIVE： To systematically evaluate the effects of dual-antiplatelet medication time on efficacy and safety of postoperative complications after transcatheter aortic valve implantation （TAVI）， and to provide evidence-based reference for the formulation of antiplatelet therapy after TAVI. METHODS： Retrieved from Cochrane clinical controlled trial registration center， PubMed， Embase， Web of Science， Wanfang database and CJFD， during database establishment to Feb. 2019， RCTs and observational study about efficacy （all-cause mortality and incidence of stroke） and  safety （the incidence of major bleeding events） the effects of dual-antiplatelet therapy for postoperative complications after TAVI at different time points were collected. After data extraction of clinical studies met inclusion criteria， quality evaluation with Cochrane bias risk evaluation tool 5.1.0 （for RCT） or Newcastle- Ottawa Scale （for observational study）， Meta-analysis was conducted by using Rev Man 5.3 and Stata 14.0 statistical software. Meta-regression analysis was also conducted for outcome and different treatment duration. RESULTS： A total of 3 RCTs and 10 observational studies were included， involving 2 868 patients. The results of Meta-analysis showed that the incidence of all-cause mortality one month and 6 months after medication were 0.05 [95％CI （0.03， 0.07）， P＜0.001] and 0.07 [95％CI （0.05， 0.08）， P＜0.001]. The incidence of major bleeding events 1， 3 and 6 months after medication were 0.14 [95％CI （0.08，0.19）， P＜0.001]， 0.11 [95％CI （0.03， 0.19）， P＝0.007] and 0.13 [95％CI （0.05， 0.22）， P＝0.002]. The incidence of stroke after one month after medication was 0.04 [95％CI （0.03， 0.05）， P＜0.001]. Results of Meta-regression analysis showed that the all-caused mortality [regression coefficient＝0.005 7， 95％CI （－0.001 6， 0.013 0）， P＝0.116]， major bleeding [regression coefficient＝－0.000 5，95％CI（－0.022 4，0.021 4）， P＝0.959] or the incidence of stroke [regression coefficient＝0.001 4， 95％CI （－0.003 8， 0.006 5）， P＝0.570] were not related to medication duration of dual-antiplatelet therapy.  CONCLUSIONS： The prolongation of the medication time of the dual-antiplatelet therapy has no significant effect on the efficacy and safety of TAVI.

OBJECTIVE: To evaluate the association between single nucleotide polymorphisms of calcium/calmodulin-dependent kinase 4 (CAMK4) and the therapeutic effect of amlodipine in essential hypertensive patients in Chinese Han nationality.
 METHODS: A total of 108 mild-to-moderate essential hypertension patients in Chinese Han nationality were treated with amlodipine for 8 weeks at a dosage of 5 mg/d. Polymerase chain reaction-restriction fragment length polymorphism was performed to detect the genotypes (rs10491334). Blood pressure was measured and analyzed.
 RESULTS: The result of rs10491334 polymorphism of CAMK4 was consistent with Hardy-Weinberg equilibrium distribution and the frequencies of C allele and T allele were 88.89% and 11.11%, respectively. The systolic blood pressure and diastolic blood pressure before amlodipine treatment were not statistically different among different genotype carriers (P>0.05). The blood pressure was significantly reduced in all patients after amlodipine treatment (P<0.05). Systolic blood pressure was significantly decreased in patients with rs10491334 CC genotype and CT genotype compared with those patients with rs10491334 TT genotype. Total effective rates of CT and TT carriers were higher than those of the CC genotype carriers (P<0.01).
 CONCLUSION The CAMK4 gene polymorphism might be associated with the efficacy of calcium channel blocker in treating mild-to-moderate essential hypertension patients.
Alleles ; Amlodipine ; Asian Continental Ancestry Group ; Blood Pressure ; Calcium-Calmodulin-Dependent Protein Kinase Type 4 ; Calmodulin ; Essential Hypertension ; Ethnic Groups ; Gene Frequency ; Genotype ; Humans ; Hypertension ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide

CD226 is an activated receptor on the surface of natural killer (NK) cells. It competes with TIGIT and CD96 to bind to ligands such as CD155 on the surface of tumor cells and mediates the killing function of NK cells. Although TIGIT and CD96 have other binding ligands in the tumor microenvironment, they compete to bind CD115 ligands with higher affinity and inhibit the activity of NK cells, which allows tumor cells to evade killing. Therefore, studying the expression patterns of these three NK cell surface receptors in different tumors and monitoring their binding ability with ligands will help us to explore new tumor treatment strategies. This article reviews the role and mechanism of CD226, TIGIT, CD96 and other NK cell receptor molecules in regulating NK cell function in anti-tumor immune response.
Ligands ; Receptors, Immunologic ; Receptors, Natural Killer Cell ; Killer Cells, Natural ; Antigens, CD