Objective: To study the effect of angiogenesis inhibitor TNP-470 combination with 5-FU on liver metastasis of human colon cancer. Methods: Human colon cancer cell line, LOVO cells, were injected intrasplenically into BALB/c nude mice to produce diffuse liver metastases. Mice were randomly divied into four groups; TNP-470 treated group, 5-FU treated group, TNP-470 +5-FU treated group and control group. Animals were sacrificed after 4 weeks, and their livers were processed for histological examination. Liver metastatic rate and tumor foci in liver were counted. Tumor microvessel density (MVD) and vascular endothelial growth factor (VEGF) were determined by immunohistochemistry SABC method with image analyse system. Results: TNP-470 in combination with 5-FU and TNP-470 alone display a significant inhibitory effect on liver metastasis compared to the control ( P

BACKGROUND: In recent years, increasing studies have shown that abnormally activated Hedghog signaling pathway is widely involved in the injury repair of systemic multi-tissue organ diseases, but its related role in myocardial fibrosis is still unclear. OBJECTIVE: To study the effect of blocking Hedgehog-Gli signaling pathway on epithelial-mesenchymal transition of myocardial fibroblasts induced by transforming growth factor-β1 (TGF-β1). METHODS: (1) Animal experiment: The model of myocardial infarction in mice was established by left coronary artery ligature. The pathological changes of myocardial tissue were observed by hematoxylin-eosin staining and Masson staining at 3, 7, and 14 days after infarction. The mRNA, protein and spatio-temporal expressions of Gli1 at different time points were detected by RT-PC, western blot and immunofluorescence. The mRNA and protein expression changes of Gli1 before and after adding inhibitor were detected using RT-PCR and immunofluorescence. (2) Cell experiment: The primary cultured myocardial fibroblasts of neonatal Sprague-Dawley rats were cultured by differential adherent method. The cultured myocardial fibroblasts were cultured with 0, 1, 5, and 10 μg/L TGF-β1 intervention. The expression of Gli1 mRNA and protein was detected by RT-PCR and western blot, respectively. Myocardial fibroblasts were induced by TGF-β1 of 10 μg/L for 24 hours, and the spatio-temporal expression of Gli1 protein and expression of epithelial-mesenchymal transition markers were detected by immunofluorescence. Gli1 and Smo in Hedgehog signaling pathway were specifically blocked by GANT61 and Cyclopamine for 24 hours, respectively, and 10 μg/L TGF-β1 was added. The mRNA expression level of Gli1 was detected by RT-PCR, and the spatio-temporal expression of Gli1 and expression of epithelial-mesenchymal transition markers were detected by immunofluorescence. RESULTS AND CONCLUSION: (1) Results of the animal experiment: As the time after infarction prolonged, the mRNA and protein expression levels of Gli1 in the mouse myocardium gradually increased, but the mRNA and protein expressions of Gli1 in the infarcted tissue decreased after addition of the Hedgehog pathway specific blocker. (2) Results of the cell experiment: After stimulation with TGF-β1, the epithelial mesenchyme of myocardial fibroblasts transformed into myofibroblasts (positive for a-SMA). As the intervention dose of TGF-β1 increased, the mRNA and protein expression of Gli1 gradually increased. After specifically blocking Gli1 and Smo in the Hedgehog signaling pathway for 24 hours, the mRNA and protein expression levels of Gli1 were inhibited, accompanied by the changes in the expression of E-Cadherin and Vimentin during epithelial-mesenchymal transition, indicating the existence of epithelial-mesenchymal transition. By the combination of in vivo and in vitro experiments, this study confirmed that the Hedgehog-Gli signal pathway is involved in the occurrence and development of myocardial fibrosis and myocardial fibroblast transdifferentiation.

BACKGROUND:Semi-shoulder or total shoulder arthroplasty for complicated proximal humerus fractures is better in the rapid elimination of pain and restoration of joint function.
OBJECTIVE:To analyze the surgical techniques and clinical effects of semi-shoulder arthroplasty on the treatment of complicated proximal humerus fractures.
METHODS:The surgical efficacy of 12 cases of complicated proximal humerus fractures who had al received semi-shoulder arthroplasty was analyzed. According to Neer classification, there were two cases of three-part fractures and 10 cases of four-part fractures. X-ray observation and Neer scoring criteria were also used to conduct a clinical evaluation of shoulder joint function after operation.
RESULTS AND CONCLUSION:Al the patients were fol owed up for 18 months in average (6 to 48 months). Based on Neer scoring, excellent was in 10 cases, good in one case, fair in one case. The excellent rate was 92%. During the fol ow-up period, prosthesis location was good and there were no complications, such as periarticular fractures, nerve injury, infection, dislocation or looseness. Attention should be paid for the effective restoration of shoulder cuff and the correct reconstruction of the large and smal nodules in semi-shoulder arthroplasty. Besides, it also should be combined with the early and standard functional exercises. The clinical effect of semi-shoulder arthroplasty is satisfactory and it is an effective way to treat complicated proximal humerus fractures.

Objective The aim of this study is to explore the mechanism of canonical Wnt signaling pathway in type 2 diabetes mice peripheral neuropathy. Methods Male C57BL6 mice were randomly assigned to three groups. One group treated with normal diet as control. And the rest were used to establish the diabetic model through the combination of 60 kcal% high fat diet and an administration of multipleand low dose of streptozotocin on 5 consecutive days. When the model of type 2 diabetes mice peripheral neuropathy was successfully established, one group was injected with the canonical Wnt signaling pathway inhibitor XAV 939 ( T2DM-XAV 939 group) and the other one was injected with phosphate buffer saline (PBS) as control (T2DM-PBS group). The 21stweek was the end point of the experiment, and fasting blood glucose, insulin level, homeostasis model assessment for insulin resistance (HOMA-IR), plantar test, and exercise tolerance were measured, realtime PCR were adopted to detect the related mRNA expression of the canonical Wnt signaling pathway. Results T2DM-XAV 939 group had higher total cholesterol, triglyceride, fasting blood glucose, and HOMA-IR than T2DM-PBS group, but showed no statistical difference. The enzymatic activity of glutamic oxaloacetic transaminase was lower level than that in T2DM-PBS group (P＜0.05); T2DM-XAV 939 group had significantly higher plantar test and poorer exercise tolerance than those in T2DM-PBS group (P＜0.05). The mRNA levels of genes in canonical Wnt signaling pathway such as β-catenin, c-myc, mitochondrial transcription factor A (TFAM) had slightly lower level than those in T2DM-PBS group, without statistical difference, and the protein expression of c-myc was lower than that of T2DM-PBS group (P＜0.05). The insulin receptor substeate 2 (IRS-2) mRNA expression was higher than that in T2DM-PBS group (P＜0.05). With the development of the experiment, we found that the survival rate of the T2DM-XAV 939 group was significantly reduced compared with the other groups. Conclusion Inhibition of the canonical Wnt signaling pathway may aggravate diabetic peripheral neuropathy.

Objective:To explore the differences of risk stratification of very high-risk or extreme high-risk atherosclerotic cardiovascular diseases (ASCVD) and the attainment rates of low-density lipoprotein cholesterol (LDL-C) management targets evaluated by three different criteria, and the causal attributions of these differences.Methods:Patients with ASCVD were consecutively enrolled from January 1 to December 31 in 2019, and were evaluated for very high-risk or extreme high-risk and LDL-C goal attainment rates with 2018 American guideline on the management of blood cholesterol (2018AG), 2019 China Cholesterol Education Program (CCEP) Expert Advice for the management of dyslipidemias (2019EA) and 2020 Chinese expert consensus on lipid management of very high-risk ASCVD patients(2020EC), respectively. The causal attributions of the differences in attainment rates were analyzed as well.Results:A total of 1 864 ASCVD patients were included in this study. According to 2018AG, 2019EA and 2020EC, the proportions of the patients with very high-risk or extreme high-risk were 59.4%, 90.7%, and 65.6%, respectively. The absolute LDL-C target attainment rates were 37.2%, 15.7%, and 13.7%, respectively, the differences between each two rates were statistically significant (all P<0.001). As to the differences in attainment rates between 2020EC and 2018AG, 61.5% were due to the different LDL-C goal attainment values and 38.5% were caused by the different risk stratifications, while for the differences between 2020EC and 2019EA attainment rates, different LDL-C goal attainment values were responsible for 13.2%, and different risk stratifications were responsible for 86.8% of the differences. Conclusions:There are significant differences in the proportions and LDL-C attainment rates among the three different criteria for very high-risk or extreme high-risk ASCVD. 2020EC showed a moderate proportion of patients with extreme high-risk, and had the lowest LDL-C attainment rate. The differences between 2020EC and 2018AG are mainly due to the LDL-C target values, and the differences between 2020EC and 2019EA are mainly caused by the risk stratifications.

OBJECTIVE To provide reference for improving the working efficiency of prescription review for pharmacists and ensuring the safe use of parenteral nutrition solution in patients.　METHODS The review module of parenteral nutrition prescription was developed with the pharmacy intravenous admixture services（PIVAS） MATE system. According to the instructions and relevant information of parenteral nutrition solution， the parameters to the review module for parenteral nutrition solution prescriptions were assigned， thresholds and calculation formulas were set， and the prescription was automatically determined by the system. The type and quantity of the inappropriate prescriptions of parenteral nutrition solution in our hospital from January to August 2020 and from January to August 2022 were counted， and the review efficiency of inappropriate prescriptions was compared before and after the application of the review module of parenteral nutrition solution prescription.　RESULTS The module realized the informatized review of basic attribute parameters and custom parameters of parenteral nutrition solution prescription， such as ion concentration， ratio of heat to nitrogen， ratio of sugar to lipid， glucose concentration， ratio of sugar to insulin， maximum dosage of compound preparation， necessary drug collocation， incompatibility， repeated drug use， age limit， etc. The module also shortened the review time greatly. It took about 33 minutes for two pharmacists to review 100 prescriptions， and only took 6 seconds after the module went online. Compared with January to August in 2020， the average approval rate of inappropriate prescriptions for parenteral nutrition solution increased from 0.582% to 1.416% during the corresponding period in 2022 （P＜0.05）.　CONCLUSIONS The review module of parenteral nutrition solution prescription established by parameter assignment method in our hospital can greatly reduce the phenomenon of missed and wrong review by pharmacists， reduce the risk of parenteral nutrition solution dispensing， reduces the work pressure of pharmacists reviewing prescriptions， and ensures the drug safety of patients.