Abtract: Acute coronary syndrome is a common clinical and frequently occurring disease, belonging to the chest discomfort, heartache, and true heart pain of TCM category. The clinical observation shows that the heat and blood stasis, and poison damage heart nutrient is one of the important mechanisms of triggering coronary syndrome. Therefore, the method of promoting blood circulation to remove meridian obstruction and the Qing Ying detoxication was established as the basic treatment, and Danshen Tongluo Jiedu Decoction is applied as the main formula. According to the different types of disease and syndrome differentiation, flexible modification can achieve good efficacy. It is expected that these will provide new ideas and methods for clinical treatment of acute coronary syndrome.

Objective To investigate the effects of PJ34,a poly ADP-ribose polymerase(PARP)inhibitor,on the expression of matrix metallopro-teinases-9( MMP-9 )and Claudin-5 in ischemic cortex of rats with focal cerebral ischemia-reperfusion(I/R)injury. Methods The focal cerebral ischemia-reperfusion model of middle cerebral artery occlusion(MCAO)was established by intraluminal suture . PJ34 was injected intraperitoneal-ly. Blood-brain barrier(BBB)permeability was quantitatively determined by Evans blue assay. Infarct volume changes were observed by 2,3,5-tri-phenyltetrazolium chloridedyeing(TTC)staining. The expression of the MMP-9 and Claudin-5 in rats of cerebral cortex were measured by immuno-histochemistry assay and western blot analysis . Results Compared with sham group,the expression of MMP-9,the contents of EB and infarct vol-ume increased progressively over time after I/R,and reached maximum levels at 48 h(P<0.05);The expression of Claudin-5,the contents of EB and infarct volume reduced significantly over time after I/R,and reached the minimum levels at 48 h in model group(P<0.05). Compared with model group,the expression of MMP-9,the contents of EB and infarct volume was reduced significantly and the expression of Claudin-5,the con-tents of EB and infarct volume was increased at the same time point in PJ34 group(P<0.05). Conclusion PJ34 maintained the blood-brain barri-er permeability by inhibiting the expression of MMP-9,and increasing the expression of Claudin-5,which had neuroprotection on cerebral ischemia-reperfusion injury.

Objective To investigate the influence of poly(ADP-ribose)polymerase inhibitor PJ34 on blood brain barrier(BBB)in rats with cere-bral ischemia-reperfusion injury. Methods Rat model of cerebral ischemia-reperfusion injury was established by the middle cerebral artery occlu-sion. A total of 135 SD rats were randomly divided into 3 groups:sham-operated group(sham group),ischemia-reperfusion group(IR group)and PJ34 group(PJ34 group). 45 animals in each group were then equally divided into subgroups and the rats were sacrificed at 6 h,24 h,48 h after re-perfusion,respectively. BBB permeability was evaluated by detection of extravasated Evans blue(EB). The expression of tumor necrosis factorα(TNF-α)and matrix metalloproteinase 9(MMP-9)activity were measured by immunohistochemistry and western blot at different time points. Re?sults Compared with sham group,the contents of EB and the expressions of TNF-αand MMP-9 in IR group were increased significantly(P<0.05). Compared with IR group,the contents of EB and the expressions of TNF-αand MMP-9 in PJ34 group were markedly decreased at the same time point(P<0.05). Conclusion The present study provided in vivo evidence that PARP inhibitor PJ34 can protect against cerebral ischemia re-perfusion injury,and the mechanism might be related to maintaining the stability of blood-brain barrier by suppressing the expression of TNF-αand MMP-9 in ischemic cortex.

Objective To investigate the effects of soothing liver and activating blood Chinese medicine on myocardial cell apoptosis and related gene expression of BMSCs transplanting on myocardial ischemia reperfusion injury (IRI) of rats;To discuss its mechanism of protecting myocardium. Methods Model of myocardial IRI was established in rats. BMSCs were isolated, cultivated, and transplanted in IRI rats. SD rats were randomly divided into sham-operation group, IRI group, BMSCs group, and combined group. Rats in combined group received gavage with soothing liver and activating blood Chinese medicine, while rats in other groups received gavage with the same dose of normal saline. After 4 weeks, myocardial cell apoptosis, Bcl-2, and Bax protein expression in myocardial cells were detected by TUNEL method and immunohistochemical method. Results Compared with IRI group, myocardial cell apoptosis index in the combined group and BMSCs group was lower, Bax expression decreased, Bcl-2 expression significantly increased (P<0.01);Compared with BMSCs group, myocardial cell apoptosis index in the combined group was lower;Bax expression decreased, Bcl-2 expression increased (P<0.05, P<0.01). Conclusion Soothing liver and activating blood Chinese medicine can inhibit BMSCs transplantation in IRI rat myocardial cell apoptosis, promote myocardial regeneration, and protect myocardial cells.

Objective To explore the effects ofDanshen Tongluo Detoxication Decoction on the inflammatory response of rats with bone marrow stem cell (BMSC) transplantation in acute myocardial infarction (AMI); To discuss its mechanism of action.Methods The whole bone marrow adherent method was adopted for BMSCs separation and culture. The AMI model was established by closing the left anterior descending coronary artery of SD rats. After the modeling, SD rats were randomly divided into sham-operation group, model group and BMSCs group (BMSCs transplantation group),Danshen Tongluo Detoxication Decoction group, Danshen Tongluo Detoxication Decoction + BMSCs group, 10 rats in each group. BMSCs cell suspension was injected directly into the edge of the myocardial tissue infarction area; Chinese medicine or normal saline were administered for gavage. 4 weeks later, the contents of MCP-1 and sICAM-1 in each group were detected by ELISA. TLR-4 expression was measured by Western blot method, and HE staining was used to observe the myocardial tissue pathological changes.Results Compared with the model group, the contents of MCP-1 and sICAM-1 and the protein expression of TLR-4 in BMSCs group,Danshen Tongluo Detoxication Decoction group, andDanshen Tongluo Detoxication Decoction + BMSCs group decreased, Danshen Tongluo Detoxication Decoction group was better than BMSCs group (P<0.05,P<0.01), andDanshen Tongluo Detoxication Decoction + BMSCs group was better than BMSCs group andDanshen Tongluo Detoxication Decoction group(P<0.05,P<0.01).Conclusion BMSCs transplantation combined withDanshen Tongluo Detoxication Decoction can restrain the inflammatory response of AMI model rats and repair ischemic myocardium issue, which mechanism may be related to regulating TLR-4 induced inflammatory response.

PURPOSE: Long non-coding RNA taurine upregulated gene 1 (TUG1) is reported to be a vital regulator of the progression of various cancers. This study aimed to explore the exact roles and molecular mechanisms of TUG1 in osteosarcoma (OS) development. MATERIALS AND METHODS: Real-time quantitative PCR was applied to detect the expressions of TUG1 and microRNA-132-3p (miR-132-3p) in OS tissues and cells. Western blot was performed to measure protein levels of sex determining region Y-box 4 (SOX4). Cell viability was assessed using XTT assay. Cell apoptosis was evaluated using flow cytometry and caspase-3 activity detection assays. Bioinformatics analysis and luciferase reporter experiments were employed to confirm relationships among TUG1, miR-132-3p, and SOX4. RESULTS: TUG1 was highly expressed in human OS tissues, OS cell lines, and primary OS cells. TUG1 knockdown hindered proliferation and induced apoptosis in human OS cell lines and primary OS cells. Moreover, TUG1 inhibited miR-132-3p expression by direct interaction, and introduction of miR-132-3p inhibitor partly abrogated the effect of TUG1 knockdown on the proliferation and apoptosis of OS cells. Furthermore, SOX4 was validated as a target of miR-132-3p. Further functional analyses revealed that miR-132-3p inhibited proliferation and induced apoptosis of OS cells, while this effect was greatly abated following SOX4 overexpression. Moreover, TUG1 knockdown suppressed proliferation and promoted apoptosis by upregulating miR-132-3p and downregulating SOX4 in primary OS cells. CONCLUSION: TUG1 facilitated proliferation and suppressed apoptosis by regulating the miR-132-3p/SOX4 axis in human OS cell lines and primary OS cells. This finding provides a potential target for OS therapy.
Apoptosis/*genetics ; Biomarkers, Tumor ; Bone Neoplasms/genetics/metabolism/*pathology ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic/genetics ; Gene Knockdown Techniques ; Humans ; MicroRNAs/*genetics/metabolism ; Osteosarcoma/genetics/metabolism/*pathology ; RNA, Long Noncoding/*genetics/metabolism ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; SOXC Transcription Factors/genetics/*metabolism ; Transcriptional Activation ; Tumor Cells, Cultured ; Up-Regulation

Objective:To evaluate the effect of propofol on proliferation, invasion and migration of human melanoma cells and role of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2)/matrix metalloproteinase (MMP) signaling pathway.Methods:SKMEL-5 cells were cultured in vitro and divided into 4 groups ( n=36 each) using the random number table method: control group (group C), propofol group (group P), COX-2 overexpression group (group COX-2), and COX-2 overexpression plus propofol group (group COX-2+ P). Propofol at the final concentration of 60 μmol/L was added in group P. The COX-2 overexpression plasmid pcDNA3.1-COX-2 was transfected into SKMEL-5 cells in group COX-2 and group COX-2+ P, and propofol at the final concentration of 60 μmol/L was added in group COX-2+ P.After incubation for 48 h, the cell proliferation rate was determined by CCK-8 method, the cell invasion and migration ability was determined by Transwell assay, the expression of COX-2 in cells was detected by Western blot, the expression of COX-2 mRNA in cells was detected by quantitative real-time polymerase chain reaction, and the concentrations of serum PGE2, MMP-2 and MMP-9 were determined by enzyme-linked immunosorbent assay. Results:Compared with group C, the cell proliferation rate was significantly decreased, the number of cell invasion and migration was decreased, the expression of COX-2 protein and mRNA was down-regulated, and the concentrations of PGE2, MMP-2 and MMP-9 in the supernatant were decreased in group P, and the cell proliferation rate was significantly increased, and the number of cell invasion and migration was increased, the expression of COX-2 protein and mRNA was up-regulated, and the concentrations of PGE2, MMP-2 and MMP-9 in the supernatant were increased in group COX-2 ( P<0.05). Compared with group P, the cell proliferation rate was significantly increased, and the number of cell invasion and migration was increased, the expression of COX-2 protein and mRNA was up-regulated, and the concentrations of PGE2, MMP-2 and MMP-9 in the supernatant were increased in group COX-2+ P ( P<0.05). Conclusions:Propofol can inhibit the proliferation, invasion and migration of human melanoma cells, and the mechanism may be related to inhibition of the COX-2/PGE2/MMP signaling pathway.

Objective:To investigate the early and middle term clinical efficacies of 3D-printed metal prostheses in the reconstruction of bone defects after osteotomy in malignant bone tumors.Methods:A total of 34 patients with malignant bone tumors of lower extremity femur and tibia who underwent 3D printing individualized metal prosthesis replacement surgery in the Department of Bone and Soft Tissue of Affiliated Cancer Hospital of Zhengzhou University from March 2019 to March 2022 were retrospectively analyzed. There were 23 males and 11 females, with an average age of 19.1±15.2 years (range, 7-80 years). There were 22 children and adolescents younger than 18 years old. There were 3 cases in the proximal femur, 15 cases in the middle and distal femur, 10 cases in the proximal tibia and 6 cases in the distal tibia. According to the final pathological diagnosis, 24 cases of osteosarcoma, 6 cases of Ewing's sarcoma, 2 cases of undifferentiated sarcoma, 1 case of osteosarcoma, and 1 case of malignant giant cell tumor of bone were enrolled in this study. Postoperative complications, wound healing, periprosthetic fracture and aseptic loosening, tumor outcome (evaluated by tumor control evaluation criteria), and length difference of lower limbs were recorded. Response evaluation criteria in solid tumor (RECIST) was used to evaluate tumor outcomes. Prosthetic-bone interface healing was evaluated postoperatively, and the function was evaluated based on Musculoskeletal Oncology Society (MSTS) 93.Results:The length of lesions was 70-240 mm in 34 patients, with an average of 125.5±35.4 mm. The length of osteotomy was 80-275 mm, with an average of 160.2±33.9 mm. No tumor was found on the osteotomy surface. The customized prosthesis was firmly installed and closely matched with the side of the preserved articular surface. There were 2 patients with local incision fat liquefaction and 4 patients with superficial wound infection, which healed after debridement and antibiotic treatment. One distal tibia osteosarcoma case developed severe periprosthetic infection 2 months after surgery, resulting in prosthesis implantation failure, limb movement pain and poor ankle function. After removal of the prosthesis, infection control and osteogenesis with the Ilizarov technique, the infection was completely controlled and local osteogenesis was possible. The remaining 33 patients had a good prosthetic-bone interface union. One case was found to have localized bone resorption on the contact surface of the prosthesis 7 months after operation, but the metal prosthesis and screws were not loose. The incisions healed well in other patients, without infection, prosthesis loosening, fracture or other complications. All patients survived and were followed up for 13.8±5.6 months (range, 7-27 months). During the follow-up, there was no recurrence of tumor at the osteotomy end in all patients, but 5 patients developed lung metastasis. At the end of the last follow-up, all patients survived. Among them, 16 patients had unequal length of lower limbs, including 10 cases within 2 cm, 3 cases between 2-5 cm, and 3 cases over 5 cm. With the exception of one patient whose prosthesis was removed due to infection, the MSTS 93 of the other patients was 24.9±2.2 (range, 19-28), and were rated as excellent in 26 cases and good in 7 cases. According to the RECIST evaluation criteria, 26 of 34 patients had complete response, 5 had disease progression, and 3 had stable disease.Conclusion:3D printed metal prosthesis is one of the effective methods for the treatment of bone defects after resection of malignant bone tumors in lower limbs, which is safe, reliable and has satisfactory early curative effect.

ObjectiveTo evaluate the effect and safety of Buyang Huanwutang in treatment of connective tissue disease-associated pulmonary fibrosis in the patients with syndrome of Qi deficiency and blood stasis and explore the possible anti-fibrosis mechanism of Buyang Huanwutang. MethodSixty-six patients with connective tissue disease-associated pulmonary fibrosis with syndrome of Qi deficiency and blood stasis were randomized to receive either Buyang Huanwutang combined with routine therapy or routine therapy for 4 weeks. The primary outcome indicator was change in forced vital capacity （FVC） from the baseline， and the secondary outcome indicators included the changes in percentage of predicted forced vital capacity （FVC%pred）， percentage of forced expiratory volume in first second to predicted value （FEV₁%pred）， King's Brief Interstitial Lung Disease （K-BILD） total score， 6 minute walking distance （6MWD）， hydroxyproline （HYP）， matrix metalloproteinase （MMP）， tissue inhibitor of metalloproteinase-1 （TIMP-1）， and transforming growth factor-β （TGF-β） from baseline. Patients in line with the inclusion criteria were included in the primary analysis， and sensitivity analysis was performed after multiple imputation of missing data. Safety set was adopted for safety analysis. ResultThe 66 patients （included in the sensitivity analysis） meeting the inclusion criteria included 34 in the observation group and 32 in the control group， and 60 patients finally received the whole trial intervention （included for primary analysis）. Compared with the baseline， the FVC increased in the observation group and decreased in the control group after intervention （P<0.01）， which was consistent between the sensitivity analysis and the primary analysis. The changes in FVC%pred， FEV₁%pred， 6MWD， and K-BILD total score from baseline in the observation group were superior to those in the control group （P<0.01）， with consistent results between the sensitivity analysis and the primary analysis. TIMP-1 in the observation group decreased compared with baseline （P<0.05）， while TIMP-1 in the two groups showed no significant changes from the baseline The observation group outperformed the control group in the changes in HYP， MMP-9， and TGF-β from baseline （P<0.05）. The common adverse events were cough， diarrhea， nausea， rash， and upper gastrointestinal tract infection， the incidence of which showed no statistical difference between the two groups. ConclusionBuyang Huanwutang can improve lung function， motor function， and quality of life in patients with connective tissue disease-associated pulmonary fibrosis and has good safety. The mechanism may be related to the reduction of TGF-β， MMP-9， and TIMP-1 levels and maintaining of MMP-9/TIMP-1 balance.

The clinical application of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of hepatocellular carcinoma (HCC) patients. With the widespread applica-tion of ICIs in HCC, the management of immune-related adverse events (irAE) gained more and more attention. However, the complicated disease characteristics and various combination therapies in HCC throw out challenges to irAE management. Therefore, the editorial board of the 'Chinese expert consensus on the management of immune-related adverse events of hepatocellular carcinoma treated with immune checkpoint inhibitors (2021 edition)' organizes multidisciplinary experts to discuss and formulate this consensus. The consensus focuses on issues related to HCC irAE manage-ment, and puts forward suggestions, in order to improve standardized and safety clinical medication, so as to maximize the benefits of immunotherapy for patients.