Objective To assess the effect of polygonum peffoliatum L on the expression of Hypoxia inducible factor-1 (HIF-1α) and vascular endothelia growth factor (VEGF) in hepatic fibrosis rats induced by Dimethylnitrosamine (DMN) . Methods Seventy-two SD rats were randomly divided into six groups, after the model of HF rat induced by DMN and intervened by different concentrations of Polygonum perfoliatum L. Conventional flaking of liver and HE were used to observed histopathological change. Immunohistochemstry was used to detect HIF-1αand VEGF in hepatic tissues of hepatic fibrosis rats. Results The expression of HIF-1α and VEGF in hepatic fibrosis rats of the high dose of Polygonum perfoliatum L from (-) to (3 +) were one , nine, one, zero and one, eight, two, zero, respectively. The expression of HIF-1α and VEGF in hepatic fibrosis rats of the middle dose of Polygonum perfoliatum L from (-) to (3 +)were one , seven, two, zero and one, six, three, zero, respectively. Compared with the model group, the high and middle dose of Polygonum perfoliatum L can reduce the expression of HIF-1 oand VEGF in hepatic fibrosis rats (P ＜ 0. 01). Conclusions Polygonum peffoliatum L has a good curative effect of anti hepatic fibrosis. Its therapeutic mechanism mainly maybe due to adjust the metabolism of extracellular matrix by decreasing HIF-1 αand VEGF expression.

Objective To assess the characteristics of magnetic resonance imaging (MRI) for spinal cavernous angiomas.Methods The examinations of plain scan and contrast enhanced scan of magnetic resonance (MR) were performed in three patients with spinal cavernous angiomas.Results The focus of two cases was located in thorax segment of the spinal cord and one in lower cervical segment.All focuses were single and the shape of spinal cord was normal or slightly thick. MRI characteristic of spinal cavernous angiomas was just like popcorn or mulberry with a jumbled gobbet signal. Low and short T2 signal appeared around the focus. In all cases, there were no obvious contrast enhanced signal in 2 cases and one case with moderate contrast enhanced signal. The diameter of hemorrhage was smaller than that of the spinal cord.Conclusion MRI has higher sensitivity and specificity in the diagnosis of spinal cavernous angioma.

Objective To compare the degree of cell injury induced by 3D protein (SDLY11 and SDLY107) of enterovirus 71 (EV71) strains.Methods EV71 strains SDLY11 and SDLY107 were respectively isolated from children with mild and severe hand foot mouth disease.The target genes 11-3D-Flag and 107-3D-Flag were amplified by reverse transcription-polymerase chain reation (RT-PCR) and inserted into the eukaryotic expression vector pcDNA3.1.The recombinant plasmids 11-3D-Flag-pcDNA3.1 and 107-3D-Flag-pcDNA3.1 were transformed into Escherichia.coli DH5α, respectively, and were identified by enzyme digestion and sequencing.The recombinant plasmids were transfected into rhabdomyosarcoma (RD) cells, respectively.Expression of 3D protein was detected by indirect immunofluorescence assay and western blot.Cell injury induced by 3D protein was detected with lactate dehydrogenase (LDH) test, cell proliferation was detected by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenylthiazolium bromide (MTT) test, and cell apoptosis was detected with Annexin-V and PI.Multiple comparisons among groups were analyzed using LSD-t test if multiple sets of variables were consistent with homogeneity of variance.If not, Dunnett T3 test was used.Results The 1 400 bp fragments were amplified by reverse tramscription (RT)-polymerase chain reaction (PCR), and the recombinant plasmids were digested by enzyme and the 1 400 bp and 5 400 bp fragments were obtained and identified.Gene sequencing showed that the sequences were consistent with the target genes.The specific fluorescence was observed by indirect immunofluorescence assay, and the western blot showed that the molecular weight of the target protein was 55×103.The LDH test showed that the A490 of SDLY11 3D protein transfection group (0.790±0.048) was higher than that of SDLY107 3D protein transfection group (0.641±0.018).The difference was statistically significant (t=5.14, P<0.05).The cell membrane damage caused by SDLY11 3D protein was more severe than SDLY107 3D protein.The MTT test showed that the A570 of SDLY11 3D protein transfection group (1.028±0.020) was lower than that of SDLY107 3D protein transfection group (1.081±0.002), and the difference was statistically significant (t=3.31, P<0.05).The effect on cell proliferation activity of SDLY11 3D protein was greater than SDLY107 3D protein.The results of Annexin-V/PI showed that the percentage of apoptotic cells of SDLY11 3D protein transfection group and SDLY107 3D protein transfection group were (1.471±0.246)% and (1.465±0.237)%, respectively, and the difference was not statistically significant (t=0.04, P=0.973).Conclusions Compared with the SDLY11 3D protein, SDLY107 3D protein induces slighter cell injury, has weaker effect on cell proliferation activity, and is more favorable for virus replication in cells.

Purpose: This study aimed to investigate the changes in microRNA-130a (miR-130a) and its correlation with cardiotoxicity during epirubicin/cyclophosphamide followed by docetaxel plus trastuzumab (EC-D+T) adjuvant chemotherapy in human epidermal growth factor receptor-2-positive (HER2+) breast cancer patients. Methods: A total of 72 HER2+ breast cancer patients who underwent resection and were scheduled to receive EC-D+T adjuvant therapy were consecutively enrolled. The expression of miR-130a and cardiotoxicity (defined as any of the following situations: 1) absolute decline of left ventricular ejection fraction (LVEF) ≥ 10% and LVEF < 53%; 2) heart failure; 3) acute coronary artery syndromes; and 4) fatal arrhythmia) were assessed every 3 months throughout the 15-month EC-D+T treatment. Results: The accumulating cardiotoxicity rate was 12 (16.7%), of which the incidence of heart failure, acute coronary syndrome, life-threatening arrhythmias, ΔLVEF ≥ 10%, and LVEF < 53% was 0 (0.0%), 1 (1.4%), 0 (0.0%), and 12 (16.7%), respectively. Baseline miR-130a expression was negatively correlated with LVEF (%) and positively correlated with cardiac troponin I. The expression of miR-130a gradually increased in both cardiotoxicity and noncardiotoxicity patients during EC-D+T treatment, while the increment of miR-130a was more obvious in cardiotoxicity patients compared with non-cardiotoxicity patients. Further logistic regression and receiver operating characteristic curve analysis indicated that miR-130a was an independent predictive factor for increased cardiotoxicity risk. Conclusion MiR-130a increases constantly and predicts high cardiotoxicity risk during ECD+T adjuvant chemotherapy in HER2+ breast cancer patients.

Objective To investigate the mechanism of matrine in inhibition of proliferation the proliferation of human chronic myeloid leukemia (CML) K562 cells via MEK-ERK signaling pathway. Methods Western blot was used to detect the expression of MEK1, ERK1/2, Shc and SHP2 (the signal effect molecules of MEK-ERK pathway) in K562 cells. The transcription and translation of bcr-abl and target protein (bcl-xL, Cyclin D1, c-myc and p27) were detected by RT-PCR and Western blot. Results Matrine was able to significantly inhibit the phosphorylation of MEK1, ERK1/2, Shc and SHP2 in K562 cells and suppress the protein and mRNA expression of bcr-abl. Moreover, the expressions of bcl-xL, Cyclin D1 and c-myc were down-regulated significantly, while the expression level of p27 (a negative regulator of cell cycle progression) was increased markedly after matrine treatment. Conclusions Suppression of the growth of human CML K562 cells is related to the inhibition of bcr-abl-mediated MEK-ERK pathway activity. The down-regulation of phosphorylated proteins or protein kinases activity in signaling pathways might be an important molecular mechanism in control the activity of MEK-ERK pathway.

Purpose: This study aimed to investigate the changes in microRNA-130a (miR-130a) and its correlation with cardiotoxicity during epirubicin/cyclophosphamide followed by docetaxel plus trastuzumab (EC-D+T) adjuvant chemotherapy in human epidermal growth factor receptor-2-positive (HER2+) breast cancer patients. Methods: A total of 72 HER2+ breast cancer patients who underwent resection and were scheduled to receive EC-D+T adjuvant therapy were consecutively enrolled. The expression of miR-130a and cardiotoxicity (defined as any of the following situations: 1) absolute decline of left ventricular ejection fraction (LVEF) ≥ 10% and LVEF < 53%; 2) heart failure; 3) acute coronary artery syndromes; and 4) fatal arrhythmia) were assessed every 3 months throughout the 15-month EC-D+T treatment. Results: The accumulating cardiotoxicity rate was 12 (16.7%), of which the incidence of heart failure, acute coronary syndrome, life-threatening arrhythmias, ΔLVEF ≥ 10%, and LVEF < 53% was 0 (0.0%), 1 (1.4%), 0 (0.0%), and 12 (16.7%), respectively. Baseline miR-130a expression was negatively correlated with LVEF (%) and positively correlated with cardiac troponin I. The expression of miR-130a gradually increased in both cardiotoxicity and noncardiotoxicity patients during EC-D+T treatment, while the increment of miR-130a was more obvious in cardiotoxicity patients compared with non-cardiotoxicity patients. Further logistic regression and receiver operating characteristic curve analysis indicated that miR-130a was an independent predictive factor for increased cardiotoxicity risk. Conclusion MiR-130a increases constantly and predicts high cardiotoxicity risk during ECD+T adjuvant chemotherapy in HER2+ breast cancer patients.

BACKGROUND:In recent years,the treatment of anterior cruciate ligament injury has become more and more mature.However,there are still disputes about the timing of surgery,the choice of surgical methods,the choice of grafts,and the methods to promote graft healing after anterior cruciate ligament injury. OBJECTIVE:To summarize the latest research progress of surgical timing,surgical methods,graft selection and methods to promote graft healing after anterior cruciate ligament injury,and to find new treatment directions for anterior cruciate ligament injury. METHODS:Relevant articles concerning anterior cruciate ligament injury were retrieved from PubMed,CNKI,WanFang Date,VIP,SinoMed,ScienceDirect,Springer and Cochrane Library.After the screening,72 related articles were finally included. RESULTS AND CONCLUSION:(1)Surgical timing:Compared with delayed anterior cruciate ligament reconstruction,early reconstruction can reduce meniscus injury,elevate quality of life,and improve functional recovery.However,it is still uncertain whether the different operation timing will accelerate cartilage injury.(2)Surgical methods:Arthroscopic anterior cruciate ligament reconstruction is a common surgical method for anterior cruciate ligament injury.Dynamic internal stabilization repair of anterior cruciate ligament can bring similar results to traditional anterior cruciate ligament reconstruction in short-term and long-term effects.(3)Graft selection:Autogenous hamstring tendon is the first choice of anterior cruciate ligament graft,while bone-patellar tendon-bone grafts and allografts are the secondary choices.(4)Among the methods to promote graft healing,suture band strengthening can increase knee joint stability and ensure graft healing.Stem cells promote the tendon-bone healing of grafts through anti-inflammatory action,angiogenesis,inhibition of osteolysis and promotion of chondrocyte differentiation.Preserving the residual end of the anterior cruciate ligament can maintain the stability of the knee joint,promote the recovery of proprioception,and provide a prerequisite for the healing of the graft.The effectiveness of platelet-rich plasma in promoting graft healing remains to be discussed.However,biomaterials,gene therapy,stem cell application and other methods to promote tendon healing remain in the stage of molecular and animal researches.Clinical transformation is also needed in the future.

Objective: To investigate the efficacy and safety of anlotinib hydrochloride capsules for the treatment of advanced soft tissue sarcoma based on the data from Department of Bone and Soft Tissue Tumor, Peking University Cancer Hospital&Institute. Methods: Patients were randomized allocated at 2:1 ratio for the anlotinib treatment and placebo group. The treatment group received 12 mg/day of anlotinib for 14 consecutive days in a 21-day cycle. The primary end-point was progression-free survival (PFS), and the secondary end-points were disease control rate (DCR), overall survival (OS), and adverse event rate. Results: A total of 46 patients were enrolled in this study; 7 of them were excluded from per protocol set (PPS). Among the remaining 39 patients, 28 were included in the anlotinib group and 11 in the placebo group. In the anlotinib group, 4 patients had partial remission and 13 had stable disease (SD), whereas in the placebo group, 3 patients had SD. The difference in DCR between the 2 groups was statistically significant (60.7% vs . 27.3%, P=0.082). The DCR of the advanced soft tissue sarcoma in the anlotinib group was 78.6% (11/14). The median PFS in the anlotinib group was 12.4 (95% confidence interval [CI]: 7.6 to 17.2) months, which was significantly longer than 4 months in the placebo group (95% CI: 1.7 to 6.3 months, P=0.043); however, the difference in OS between the 2 groups was not significant (19.4 vs . 17.6 months, P=0.961). Regarding the safety, 2 patients had severe adverse events (7.14%) possibly related with treatment in the anlotinib group; one of them had pneumothorax. The other adverse events were grade 1 to 2. Conclusions: Soft tissue sarcoma is highly responsive to anlotinib, with prolonged PFS. Anlotinib is well tolerated and can be used as a treatment option for advanced soft tissue sarcoma.

Objective The inhibitory effect of the PARP inhibitor olaparib on human acute myeloid leukemia HL-60 cells was studied. Methods The HL-60 cells in logarithmic growth phase were treated with different concentrations(1. 25,2. 5,5 and 10 μmol/L) of olaparib for different time. The CCK-8 assay was used to detect the inhibitory effect of olaparib on HL-60 cells. The apoptotic level of HL-60 cells was detected by Annexin-V/PI double staining method,and the expression of related signal proteins ( PARP-1 and caspase-3)in HL-60 cells was detected by Western blot. Results HL-60 cells were inhibited by olaparib at dif-ferent concentrations(1. 25,2. 5,5 and 10 μmol/L) for 48 h,and the inhibition rate gradually increased with the prolongation of the action time;at the same time,the apoptotic rate was increased in HL-60 cells after olaparib treatment for 48 h,showing a dose-de-pendent manner;the PARP activity was inhibited and caspase-3 was activated in HL-60 cells treated with olaparib. Conclusion The PARP inhibitor olaparib not only inhibits proliferation of HL-60 cells,but it also promotes apoptosis of HL-60 cells by inhibi-ting PARP activity and activating caspase-3.

Objective:This study sought to investigate the feasibility, anatomical indications and operating points of transcatheter aortic valve replacement (TAVR) procedure in the treatment of pure aortic regurgitation (AR).Methods:The medical records of 4 elderly patients with pure AR who were treated in the cardiology department, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from March 2020 to March 2021 were retrospectively analyzed. All patients were implanted with self-expandable valve stents via peripheral artery approach for TAVR treatment. The feasibility, anatomical indications and key points of TAVR were analyzed.Results:The 4 patients with pure AR who were carefully screened had an average age of 66 years, and all achieved TAVR treatment success without serious perioperative complications and death. Postoperative examination and follow-up data showed that cardiac functions and cardiac remodeling indexes were significantly improved.Conclusions:This exploratory study shows that TAVR is technically feasible and effective treatment option for selected elderly patients with native pure AR, which is worthy of further study.