Objectives:The ORION-18 study has demonstrated that inclisiran can significantly reduce low-density lipoprotein cholesterol(LDL-C)and has good safety in Asian atherosclerotic cardiovascular disease(ASCVD)patients or ASCVD high-risk population.This subgroup analysis aims to further evaluate the efficacy and safety of inclisiran in Chinese mainland population.Methods:ORION-18 study is a multi-center,randomized,double-blind,placebo-controlled,phase Ⅲ clinical trial among Asian subjects,Chinese mainland subgroup included 232 ASCVD patients or ASCVD high-risk subjects who had already been treated with diet control and maximum tolerated doses of statins treatment(with or without other lipid-lowering treatments)but still had elevated LDL-C levels.Subjects were randomized in a 1:1 ratio to the inclisiran group and the placebo group(n=116 each),and received 300 mg of inclisiran or placebo respectively on day 0,90 and 270.The primary endpoint was the percentage change in LDL-C from baseline to day 330.The secondary endpoints included the time-adjusted percentage change and absolute change in LDL-C from baseline after day 90 and up to day 360,the absolute change in LDL-C from baseline to day 330,and the percentage changes from baseline to day 330 in proprotein convertase subtilisin/kexin type 9(PCSK9),total cholesterol,apolipoprotein B(ApoB),non-high-density lipoprotein cholesterol(non-HDL-C).Other secondary endpoints included the proportion of participants reaching LDL-C levels of<1.8 mmol/L at day 330,the proportion of participants with≥50%LDL-C reduction from baseline to day 330 and the proportion of participants who attained global lipid targets(the LDL-C target was<1.4 mmol/L for ASCVD patients and<1.8 mmol/L for ASCVD high-risk subjects)at day 330.Safety endpoints included adverse events during treatment,aboratory test abnormalities during treatment,serious adverse events,and assessed their severity and relation to treatment.Results:The inclisiran group showed a placebo-corrected percentage change in LDL-C from baseline to day 330 of-61.16%,and an absolute change of-1.73 mmol/L(both P<0.0001).Compared to the placebo group,the inclisiran group's time-adjusted percentage change in LDL-C from baseline between day 90 and day 360 was-58.51%,and an absolute change of was-1.64 mmol/L(both P<0.0001).At day 330,reductions from baseline were observed in the inclisiran group for PCSK9,total cholesterol,ApoB,non-HDL-C,with placebo-corrected percentage changes of-77.44%,-35.65%,-43.43%,-50.90%(all P<0.0001),respectively.At day 330,79.6%(74/93)of patients in the inclisiran group and 7.8%(6/77)in the placebo group achieved LDL-C levels<1.8 mmol/L,69.9%(65/93)of patients in the inclisiran group and 0%(0/77)in the placebo group achieved≥50%LDL-C reduction from baseline,66.7%(62/93)of patients in the inclisiran group and 2.6%(2/77)in the placebo group achieved their global LDL-C targets.The safety profile of inclisiran treatment over 12 months was comparable to that of the placebo,with no occurrence of treatment-related serious adverse events.Conclusions:In ASCVD patients or ASCVD high-risk subjects in Chinese mainland who have received diet control and maximum tolerable dose statins treatment(with or without other lipid-lowering treatments)and still have elevated LDL-C,inclisiran has a definite efficacy and good safety in reducing LDL-C.The efficacy and safety results of inclisiran assessed in Chinese mainland population are consistent with those of the general Asia population.

Objectives:The ORION-18 study has demonstrated that inclisiran can significantly reduce low-density lipoprotein cholesterol(LDL-C)and has good safety in Asian atherosclerotic cardiovascular disease(ASCVD)patients or ASCVD high-risk population.This subgroup analysis aims to further evaluate the efficacy and safety of inclisiran in Chinese mainland population.Methods:ORION-18 study is a multi-center,randomized,double-blind,placebo-controlled,phase Ⅲ clinical trial among Asian subjects,Chinese mainland subgroup included 232 ASCVD patients or ASCVD high-risk subjects who had already been treated with diet control and maximum tolerated doses of statins treatment(with or without other lipid-lowering treatments)but still had elevated LDL-C levels.Subjects were randomized in a 1:1 ratio to the inclisiran group and the placebo group(n=116 each),and received 300 mg of inclisiran or placebo respectively on day 0,90 and 270.The primary endpoint was the percentage change in LDL-C from baseline to day 330.The secondary endpoints included the time-adjusted percentage change and absolute change in LDL-C from baseline after day 90 and up to day 360,the absolute change in LDL-C from baseline to day 330,and the percentage changes from baseline to day 330 in proprotein convertase subtilisin/kexin type 9(PCSK9),total cholesterol,apolipoprotein B(ApoB),non-high-density lipoprotein cholesterol(non-HDL-C).Other secondary endpoints included the proportion of participants reaching LDL-C levels of<1.8 mmol/L at day 330,the proportion of participants with≥50%LDL-C reduction from baseline to day 330 and the proportion of participants who attained global lipid targets(the LDL-C target was<1.4 mmol/L for ASCVD patients and<1.8 mmol/L for ASCVD high-risk subjects)at day 330.Safety endpoints included adverse events during treatment,aboratory test abnormalities during treatment,serious adverse events,and assessed their severity and relation to treatment.Results:The inclisiran group showed a placebo-corrected percentage change in LDL-C from baseline to day 330 of-61.16%,and an absolute change of-1.73 mmol/L(both P<0.0001).Compared to the placebo group,the inclisiran group's time-adjusted percentage change in LDL-C from baseline between day 90 and day 360 was-58.51%,and an absolute change of was-1.64 mmol/L(both P<0.0001).At day 330,reductions from baseline were observed in the inclisiran group for PCSK9,total cholesterol,ApoB,non-HDL-C,with placebo-corrected percentage changes of-77.44%,-35.65%,-43.43%,-50.90%(all P<0.0001),respectively.At day 330,79.6%(74/93)of patients in the inclisiran group and 7.8%(6/77)in the placebo group achieved LDL-C levels<1.8 mmol/L,69.9%(65/93)of patients in the inclisiran group and 0%(0/77)in the placebo group achieved≥50%LDL-C reduction from baseline,66.7%(62/93)of patients in the inclisiran group and 2.6%(2/77)in the placebo group achieved their global LDL-C targets.The safety profile of inclisiran treatment over 12 months was comparable to that of the placebo,with no occurrence of treatment-related serious adverse events.Conclusions:In ASCVD patients or ASCVD high-risk subjects in Chinese mainland who have received diet control and maximum tolerable dose statins treatment(with or without other lipid-lowering treatments)and still have elevated LDL-C,inclisiran has a definite efficacy and good safety in reducing LDL-C.The efficacy and safety results of inclisiran assessed in Chinese mainland population are consistent with those of the general Asia population.

Objective:To explore the application effect of structural formula based continuous nursing in colorectal cancer patients with ostomy.Methods:Using the convenient sampling method, a total of 128 patients with colorectal cancer stoma who were admitted to Liuzhou Worker's Hospital from July 2019 to September 2021 were selected as the research objects. According to the random number table method, they were divided into the observation group and the control group, with 64 cases in each group. Patients in the observation group received structural continuous nursing, while patients in the control group received traditional continuous care. Exercise of Self-Care Agency Scale (ESCA) and the Medical Outcomes 36-items Short Form Health Survey (SF-36) scores were compared between the two groups.Results:After 3 months of intervention, ESCA and SF-36 scores in the observation group were higher than those in the control group, and the differences were statistically significant ( P<0.05) . Conclusions:Structural formula based continuous nursing can improve the self-care ability and quality of life of colorectal cancer patients with ostomy.

The progress of molecular biology and tumor biology has greatly changed the mode of cancer treatment. A large number of scientific studies have revealed the mechanism of tumor immune evasion, and a variety of new types of tumor immunotherapy have emerged, which has become another effective treatment of cancer after surgery, radiotherapy, chemotherapy and targeted therapy. This paper introduces the mechanism of tumor cell immune evasion, and focuses on the design principle, biological drugs and the latest research progress of immunotherapy, such as cytokine immunotherapies, therapeutic monoclonal antibody immunotherapy, PD-1/PD-L1 therapy, CAR-T therapy, tumor vaccine, oncolytic virus and so on. At the same time, the advantages and disadvantages of various immunotherapies are compared to provide reference for drug research and development in tumor immunotherapy.

Moschus chrysogaster (sifanicus) viral hemorrhagic disease (McVHD) is an acute and highly lethal infectious disease caused by Moschus chrysogaster hemorrhagic disease virus (McHDV) whose genome sequence is highly homologous with rabbit hemorrhagic disease virus. To screen the protective antigen of McHDV and set the basis for study of McVHD vaccine, the antigen epitope of major structural protein VP60 of McHDV was analyzed, and the specific primers were designed to obtain three amplified DNA sequences encoding the main antigen epitope of VP60 from McHDV by using RT-PCR. Then the three DNA fragments were sequenced and cloned to prokaryotic expression vector with pET-28a(+) by using overlap extension PCR, and finally the prokaryotic expression plasmid pET-truncated-VP60 was constructed. Subsequently, the pET-truncated-VP60 was transformed into Escherichia coli BL21(DE3), and the recombinant proteins were expressed by IPTG induction. Finally, the expressed protein was purified and applied to immunize that without immunizing with RHD vaccine, then the antiserum titers were evaluated by the hemagglutination inhibition test, and the immune-protective efficacy of the recombinant proteins was observed and analyzed through animal challenge test. The results showed that the multi-epitope DNA fragments of VP60 of McHDV was successfully expressed in the form of inclusion bodies in E. coli, and the relative molecular weight of recombinant proteins is about 45 kDa. After immunized with the recombinant proteins, 100% of New Zealand white rabbits were resistant to attack of McHDV, which indicates efficient immune-protective efficacy of chosen epitope recombinant protein. The study laid a foundation for the development of the new subunit vaccines of McVHD.

Objective:To investigate the distant metastasis after primary treatment of papillary thyroid cancer (PTC) in children and adolescents.Methods:A retrospective analysis of 180 cases (54 boys and 126 girls, with an age range of 6-18 years) with PTC treated at the Chinese Medical Academy Cancer Hospital and Zhejiang Cancer Hospital from January 1, 2001 to December 31, 2014 was performed. Patients’ clinical and pathological data were collected. The follow-up results were statistically analyzed. The distant metastasis rate during the follow-up period was analyzed by the Kaplan-Meier method. Log-Rank test was used for univariate analysis and Cox regression model was established in multivariate analysis.Results:Twenty-four cases (13.3%) had distant metastases during following-up with a median of 92 months. The Log-Rank test showed that the younger age ≤15 years old (χ 2=11.803, P=0.001), the larger tumor diameter >20 mm (χ 2=5.776, P=0.016), multifocal (χ 2=11.205, P=0.001), bilateral tumor distribution (χ 2=19.804, P=0.001), invaded capsule (χ 2=10.808, P=0.001), and bilateral lymph nodes metastasis (χ 2=6.278, P=0.012) were risk factors for distant metastasis after initial treatment. The Cox regression analysis showed that age ≤15 years (hazard ratio [95% confidence interval]: 4.08[1.504-11.111], P=0.006) and bilateral tumor distribution (hazard ratio [95% confidence interval]: 4.77[1.903-11.966], P=0.001) were independent risk factors for distant metastasis after initial treatment. The risk factors for local recurrence and distant metastasis were similar, but the local recurrence could not be a significant predictor for distant metastasis. It was indicated that distant metastasis rate was lower in patients with total thyroidectomy in multifocal lesions groups (χ 2=5.891, P=0.015). Conclusions:Age, tumor size, invaded capsule, bilateral lymph nodes metastasis, multifocal and bilateral lesions are factors for predicting distant metastasis after primary treatment of PTC in children and adolescents. Total thyroidectomy is recommended for patients with multifocal and bilateral lesions.

Objective To investigate the effects of Tirofiban combined with thrombus aspiration on myocardial reperfusion and no-reflow after percutaneous coronary intervention (PCI)in elderly patients with ST-segment elevation myocardial infarction (STEMI).Methods A total of 185 patients with STEMI were randomly divided into a control group(n=93)and a study group(n=92).The control group received direct stenting or percutaneous coronary angioplasty before stent placement.The study group received an intracoronary injection of Tirofiban 10 μg/kg,thrombus aspiration,and then balloon dilatation or direct coronary stenting.Postoperative recovery was compared between the groups,and major adverse cardiovascular events(MACE) were recorded.Results The incidence of no-reflow,the thrombolysis in myocardial infarction,the corrected (TIMI)frame count (CTFC)and the peak of plasma creatine kinase MB isoenzyme(CK MB)were lower in the study group than in the control group[(no reflow,8 cases or 8.7 ％ vs.21cases or 22.6 ％,x2 =6.752,P ＜0.05;CTFC,(26.4±8.7)frame vs.(34.5± 8.2)frame,t =6.517,P＜0.05;CK-MB peak,(114.5±25.7)U/L vs.(226.3 ± 27.6) U/L,t =28.506,P ＜ 0.05].The proportion of patients with descent of ST segment elevation of more than 50％ and the left ventricular ejection fraction(LVEF)were higher in the study group than in the control group[83 cases or 90.2％ vs.72 cases or 77.4％,x2=5.581,P＜0.05;(56.2±8.6) ％ vs.(48.8±10.5)％,t =5.241,P＜0.05].The TIMI grading was better in the study group than in the control group (Z =1.984,P ＜ 0.05).The incidence of mild bleeding during treatment had no significant difference between the study group and the control group(20.7％ or 19 cases vs.15.1％ or 14 cases,x2 =0.99,P =0.32).There was no significant difference in the incidence of MACE events during hospitalization or one-year follow-up between the two groups(x2=2.394,0.452,P ＞ 0.05).Conclusions Tirofiban combined with thrombus aspiration can improve myocardial reperfusion in elderly patients with STEMI after PCI,and has excellent clinical value.

Objective: To observe effects of exogenous high mobility group protein box 1 (HMGB1) on angiogenesis in ischemic zone of early scald wounds of rats. Methods: Thirty-six Sprague-Dawley rats were divided into HMGB1 group and simple scald (SS) group according to the random number table, with 18 rats in each group. Comb-like copper mould was placed on the back of rats for 20 s after being immersed in 100 ℃ hot water for 3 to 5 min to make three ischemic zones of wound. Immediately after scald, rats in HMGB1 group were subcutaneously injected with 0.4 μg HMGB1 and 0.1 mL phosphate buffer solution (PBS), and rats in SS group were subcutaneously injected with 0.1 mL PBS from boarders of ischemic zone of scald wound. At post scald hour (PSH) 24, 48, and 72, 6 rats in each group were collected. Protein expressions of vascular endothelial growth factor (VEGF) in ischemic zone of wound at PSH 24, 48, and 72 and protein expressions of CD31 in ischemic zone of wound at PSH 48 and 72 were detected by immunohistochemistry. The number of microvessel in CD31 immunohistochemical sections of ischemic zone of wound at PSH 48 and 72 was calculated after observing by the microscope. The mRNA expressions of VEGF and CD31 in ischemic zone of wound were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction at PSH 24, 48, and 72. Data were processed with analysis of variance of factorial design, t test, and Bonferroni correction. Results: (1) At PSH 24, 48, and 72, protein expressions of VEGF in ischemic zone of wound of rats in HMGB1 group were significantly higher than those of rats in SS group (t=7.496, 4.437, 5.402, P<0.05 or P<0.01). At PSH 48 and 72, protein expressions of CD31 in ischemic zone of wound of rats in HMGB1 group were 0.038 8±0.007 9 and 0.057 7±0.001 2 respectively, significantly higher than 0.013 4±0.004 9 and 0.030 3±0.004 0 of rats in SS group (t=10.257, 15.055, P<0.01). (2) At PSH 48 and 72, the number of microvessel in ischemic zone of wound of rats in HMGB1 group was obviously more than that of rats in SS group (t=3.536, 4.000, P<0.05). (3) At PSH 24, 48, and 72, mRNA expressions of VEGF in ischemic zone of wound of rats in HMGB1 group were significantly higher than those of rats in SS group (t=4.406, 3.821, 3.356, P<0.05). At PSH 24 and 48, mRNA expressions of CD31 in ischemic zone of wound of rats in HMGB1 group were significantly higher than those of rats in SS group (t=4.113, 3.466, P<0.05). At PSH 72, mRNA expressions of CD31 in ischemic zone of wound of rats in 2 groups were close (t=0.010, P>0.05). Conclusions Exogenous HMGB1 can promote angiogenesis in ischemic zone of early scald wounds of rats by increasing expressions of VEGF and CD31.

BACKGROUND:The decel ularized porcine smal intestinal submucosa is a kind of bioactive extracel ular matrix, which is mainly composed of col agen, glycoprotein, proteoglycan and rich in col agen, glycosaminoglycan and various growth factors, and these components play an important role in promoting the differentiation and proliferation of tissue cel s. OBJECTIVE:To prepare the injectable smal intestinal submucosa and to investigate its co-culture with rat adipose-derived mesenchymal stem cel s in vitro. METHODS:The injectable smal intestinal submucosa and rat adipose-derived stem cel s were prepared. Cel counting kit-8 test for cel proliferation:Passage 3 adipose-derived stem cel s were seeded onto the injectable smal intestinal submucosa (experimental group) and cel s cultured under normal condition as control group. The cel proliferation was observed at 1, 3, 5 and 7 days of incubation. Live/dead staining test for the survival of cel s:Passage 3 adipose-derived stem cel s were respectively cultured in the injectable smal intestinal submucosa extracts (experimental group) and complete culture medium (control group). Cel survival was determined at 1, 3, 5 and 7 days of culture. RESULTS AND CONCLUSION:Scanning electron microscope oval and strip adipose-derived stem cel s adhered onto the material. The absorbance values in the experimental group were higher than those in the control group at 1 and 5 days of incubation (P<0.05). Cel survival:The number of cel s appeared to be in a rising trend with time in both two groups;after 1-day co-culture, al cel s in the two groups survived. Then dead cel s appeared in both two groups, showing no significant difference. These results show that the injectable smal intestinal submucosa exhibits a good cytocompatibility.