Organ shortage has become one of the major challenges hindering the development of organ transplantation. Xenotransplantation is one of the most valuable methods to resolve global organ shortage. In recent years, the development of genetic engineering technique and research and development of new immunosuppressant have provided novel theoretical basis for xenotransplantation. International scholars have successively carried out researches on xenotransplantation in genetically modified pigs to non-human primates or brain death recipients, making certain substantial progresses. However, most of the researches are still in the preclinical stage, far from clinical application. Therefore, according to the latest preclinical experimental research progress at home and abroad, the history of xenotransplantation, the development of gene modification technology, xenotransplantation rejection and immunosuppression regimens were reviewed, aiming to provide reference for subsequent research of xenotransplantation, promote clinical application of xenotransplantation and bring benefits to more patients with end-stage diseases.

Objective To explore the mechanism of plumbagin for protecting against sepsis-induced myocardial injury in mice.Methods Network pharmacology analysis was used to obtain the key targets of plumbagin and diseases,which were subjected to GO and KEGG analysis,and the binding energy was verified using molecular docking.In a mouse model of cecal ligation and puncture(CLP),the protective effect of plumbagin treatment prior to CLP against sepsis-induced myocardial injury was evaluated by examination of myocardial function and pathology using echocardiography and HE staining.Serum levels of CK-MB,LDH,MDA,IL-1β and IL-18 and myocardial ROS level in the mice were detected,and Western blotting was used to determine the protein expression levels of STAT3,GSDMD,caspase-11,JAK2,P-STAT3,P-JAK2,GSDMD-N and HMGB1 in the myocardial tissues.Results Five core targets were screened from the 10 intersecting genes.Molecular docking showed strong binding affinity of plumbagin to STAT3,p-STAT3,and JAK2.Compared with the sham-operated mice,the mouse models of CLP-induced sepsis had significantly decreased CO,LVEF,LVFS and SV and increased serum levels of CK-MB,LDH,MDA and myocardial inflammatory factors and ROS.HE staining and Western blotting showed obvious myocardial injury in the septic mice with increased expressions of JAK2/STAT3 signaling pathway and pyroptosis-related proteins(P<0.05).Pretreatment with plumbagin significantly improved cardiac functions of CLP mice,lowered serum levels of CK-MB,LDH,MDA,inflammatory factors and myocardial ROS,and decreased the expression levels of JAK2/STAT3 signaling pathway and pyroptosis-related proteins.Conclusion Plumbagin pretreatment alleviates myocardial injury in septic mice possibly by inhibiting the STAT3 signaling pathway to reduce cardiomyocyte pyroptosis.

Objective To explore the effects of different side tension pneumothorax on hemodynamics in pigs,providing data support for the optimization of on-site first-aid procedures for pneumothorax.Methods Twelve Bama pigs were randomly divided into left-sided tension pneumothorax group and right-sided tension pneumothorax group(6 in each group).During the occurrence of pneumothorax and as the pleural pressure gradually increases by 1 mmHg increments,the key indicators were collected using pulse indicator continuous cardiac output(PICCO)technology:hemodynamic indicators[global ejection fraction(GEF),cardiac output(CO),global end-diastolic volume(GEDV),intrathoracic blood volume(ITBV),stroke volume(SV),mean arterial pressure(MAP)],basic vital signs[heart rate(HR),diastolic blood pressure(DBP),systolic blood pressure(SBP)],and arterial blood gas parameters[partial pressure of oxygen(PO2),partial pressure of carbon dioxide(PCO2)].Mediastinal localization was subsequently performed using radiographs.Differences were investigated through comparison between the two groups and within each group before and after the procedure.Results By comparing the hemodynamic changes and X-ray examination results,twelve Bama pigs tension pneumothorax models were successfully constructed.Hemodynamic analysis showed that in left-sided tension pneumothorax model when the pleural pressure reached 8 mmHg,SBP,DBP,MAP,CO,GEF,SV,GEDV and ITBV were significantly lower than those during the occurrence of ipsilateral pneumothorax(P<0.05).In right-sided tension pneumothorax model,when the pleural pressure reached about 3 mmHg,SBP,DBP,MAP,SV,GEDV,and ITBV were significantly lower than those during the occurrence of ipsilateral pneumothorax(P<0.05).Blood gas analysis showed that at 8 mmHg for left-sided and 3 mmHg for right-sided tension pneumothorax,compared with the occurrence of their respective ipsilateral pneumothorax,PO2 was significantly lower(P<0.05)and PCO2 was significantly higher(P<0.05).Conclusions There are different effects on hemodynamics in different side tension pneumothorax.Compared with left tension pneumothorax,right tension pneumothorax can lead to serious consequences under a smaller pleural pressure.Different side tension pneumothorax models can be constructed according to the actual situation when performing pneumothorax related experiments.

Objective:To analyze the efficacy and influencing factors of cyclosporine(CsA)alone in the treatment of children with acquired aplastic anemia(AA).Methods:The clinical data of children diagnosed with AA and treated with CsA alone from January 1,2016 to December 31,2020 in the Children's Hospital of Chongqing Medical University were collected,and the efficacy and influencing factors of CsA treatment were evaluated.Results:Among the 119 patients,there were 62 male and 57 female,with a median age of 7 years and 1 month.There were 45 cases of very severe AA(VSAA),47 cases of severe AA(SAA),and 27 cases of non-severe AA(NSAA).At 6 months after treatment,the efficacy of VSAA was lower than that of SAA and NSAA,and there was a statistical difference(P＜0.01).6 cases died early,16 cases relapsed,2 cases progressed to AML and ALL.The results of univariate analysis showed that the high proportion of lymphocyte in the bone marrow at 6 months was an adverse factor for the efficacy of CsA,while high PLT count was a protective factor(P=0.008,P=0.002).The ROC curve showed that the cut-off values of PLT count and the proportion of bone marrow lymphocyte at 6 months were 16.5 × 109/L,68.5％,respectively.Multivariate analysis showed that the high proportion of lymphocyte in bone marrow at 6 months was an independent adverse factor for IST(P=0.020,OR=0.062),and high PLT count was a protective factor(P=0.044,OR=1.038).At 3 months of treatment,CsA response and NSAA were the risk factor for recurrence(P=0.001,0.031).Conclusion:The efficacy of NSAA was higher than that of SAA and VSAA after 6 months of treatment with CsA alone.A high PLT count at the initial diagnosis was a good factor for the effectiveness of CsA,and a high proportion of bone marrow lymphocyte was an unfavorable factor.CsA response at 3 months and NSAA were risk factors for recurrence.

Objective:To investigate the effect of Chinese medicine He's Yangchao recipe on premature ovarian insufficiency(POI)and its relationship with mitochondrial function of ovarian granulose cells in an animal model.Methods:Thirty-six female C57BL/6J mice were randomly divided into blank control group,model group,low-,medium-and high-dose He's Yangchao recipe treatment group and coenzyme Q10(Q10)treatment group(positive control).The POI model was induced by a single intraperitoneal injection of cyclophosphamide(90 mg/kg).The animals were sacrificed after 21 days.Primary granulose cells were obtained from POI mice and treated with He's Yangchao recipe,ERβ inhibitor PHTPP,and He's Yangchao recipe+PHTPP in vitro for 24 h,respectively.Ovarian histopathological changes were observed by hematoxylin-eosin(HE)staining,ATP levels were detected by luciferase assay,mtDNA copy numbers were detected by quantitative reverse transcriptase-polymerase chain reaction(qRT-PCR),mitochondrial structure changes were observed by transmission electron microscopy,protein and mRNA expression levels of estrogen receptor β(ERβ),peroxisome proliferator-activated receptor γ coactivator 1α(PGC1α),mitochondrial transcription factor A(TFAM),and superoxide dismutase 2(SOD2)were detected by Western blotting and qRT-PCR.Results:The ovarian tissue in model group exhibited few secondary and tertiary follicles,whereas the He's Yangchao recipe groups and Q10 group had abundant secondary and tertiary follicles.Compared with the blank control group,ATP and mtDNA levels in model group decreased(P＜0.01),mitochondrial crista disappeared or abnormal vacuolated structure increased;the protein and mRNA levels of ERβ,PGC1α,TFAM,and SOD2 decreased(all P＜0.01).ATP production increased in granulose cells of high-dose He's Yangchao recipe group and Q10 group;mtDNA copy numbers increased(P＜0.05 or P＜0.01);abnormal mitochondrial structure was reduced;the protein and mRNA expressions of ERβ,PGC1α,TFAM,and SOD2 increased(P＜0.05 or P＜0.01).Compared with the PHTPP intervention group,the proportion of normal mitochondrial structure in the granulose cells of He's Yangchao recipe+PHTPP group was higher;ATP content increased(P＜0.05 or P＜0.01);mtDNA copy numbers increased(P＜0.05 or P＜0.01);the protein and mRNA expression of ERβ,PGC1α,TFAM and SOD2 increased(P＜0.05 or P＜0.01).Conclusions:He's Yangchao recipe can regulate mitochondrial biogenesis through ERβ/PGC1α/TFAM pathway to improve ovarian function in POI mice.

Objective To investigate the cumulative incidence of recurrence(CIR)in children with acute lymphoblastic leukemia(ALL)after treatment with the Chinese Children's Cancer Group ALL-2015(CCCG-ALL-2015)protocol and the risk factors for recurrence.Methods A retrospective analysis was conducted on the clinical data of 852 children who were treated with the CCCG-ALL-2015 protocol from January 2015 to December 2019.CIR was calculated,and the risk factors for the recurrence of B-lineage acute lymphoblastic leukemia(B-ALL)were analyzed.Results Among the 852 children with ALL,146(17.1%)experienced recurrence,with an 8-year CIR of 19.8%±1.6%.There was no significant difference in 8-year CIR between the B-ALL group and the acute T lymphocyte leukemia group(P>0.05).For the 146 children with recurrence,recurrence was mainly observed in the very early stage(n=62,42.5%)and the early stage(n=46,31.5%),and there were 42 children with bone marrow recurrence alone(28.8%)in the very early stage and 27 children with bone marrow recurrence alone(18.5%)in the early stage.The Cox proportional-hazards regression model analysis showed that positive MLLr fusion gene(HR=4.177,95%CI:2.086-8.364,P<0.001)and minimal residual disease≥0.01%on day 46(HR=2.013,95%CI:1.163-3.483,P=0.012)were independent risk factors for recurrence in children with B-ALL after treatment with the CCCG-ALL-2015 protocol.Conclusions There is still a relatively high recurrence rate in children with ALL after treatment with the CCCG-ALL-2015 protocol,mainly bone marrow recurrence alone in the very early stage and the early stage,and minimal residual disease≥0.01%on day 46 and positive MLLr fusion gene are closely associated with the recurrence of B-ALL.

Short-chain fatty acids are metabolites of the intestinal flora and serve as the main energy source for intestinal epithelial cells. At the same time, as important signaling molecules, it regulate a variety of cellular inflammatory responses and homeostatic proliferation through receptor-dependent and independent pathways. Short-chain fatty acids regulate the gut-liver axis and thereby directly act on the liver, participating in the pathogenesis and transformation of various liver diseases, including alcoholic liver disease, metabolic dysfunction-related liver disease, autoimmune liver disease, liver fibrosis, and hepatocellular carcinoma. In addition, short-chain fatty acids can inhibit HBV DNA replication. This article reviews the research progress on the role of short-chain fatty acids in aspects of the pathogenesis and transformation of chronic liver diseases.

Objective To study the effect of Hedysarum polysaccharides(HPS)on the expression of transforming growth factor-β,(TGF-β1),smad homologue 3 recombinant protein(smad3)and smad7 in renal tissue of db/db mice with diabetic nephropathy(DN).Methods According to their body weight,6-week-old male db/db mice were randomly divided into 5 groups:model group(0.9％NaCl 0.2 mL·d-1),positive control group(22.75 mg·kg-1·d-1 irbesartan)and experimental-H,-M,-L groups(200,100,50 mg kg-1·d-1 HPS),with 10 mice in each group;another 10 SPF grade male C57BL/6 mice of the same week were selected as normal group(0.9％NaCl 0.2mL·d-1).The mice in the 6 groups were given intragastric administration once a day for 12 weeks.The blood glucose concentration of mice was measured before treatment and at the 4th,8th and 12th week after treatment.The expression levels of TGF-β1,smad3 and smad7 were detected by Western blotting.Results After treatment,the blood glucose levels of the model group was significantly higher than those of the normal group(all P＜0.01);compared with the model group,the levels of blood glucose in the experimental-H,-M groups decreased significantly,and the differences were statistically significant(P＜0.05,P＜0.01).The relative expression levels of TGF-β,protein in normal group,model group,positive control group and experimental-H,-M groups were 0.71±0.16,1.66±0.18,1.00±0.17,0.88±0.15 and 1.23±0.15;the relative expression levels of smad3 protein were 0.89±0.32,2.26±0.35,1.24±0.31,1.05±0.30 and 1.67±0.35;the relative expression levels of smad7 protein were 1.66±0.03,0.60±0.03,1.10±0.07,1.48±0.08 and 0.97±0.09;there were statistically significant differences between the experimental-H,-M groups and the model group(P＜0.05,P＜0.01).Conclusion Hedysarum polysaccharides can improve renal fibrosis and delay the development of diabetic nephropathy by regulating the level of blood glucose,inhibiting TGF-β1,smad3 and increasing the expression of smad7.

Objective To explore the mechanism of plumbagin for protecting against sepsis-induced myocardial injury in mice.Methods Network pharmacology analysis was used to obtain the key targets of plumbagin and diseases,which were subjected to GO and KEGG analysis,and the binding energy was verified using molecular docking.In a mouse model of cecal ligation and puncture(CLP),the protective effect of plumbagin treatment prior to CLP against sepsis-induced myocardial injury was evaluated by examination of myocardial function and pathology using echocardiography and HE staining.Serum levels of CK-MB,LDH,MDA,IL-1β and IL-18 and myocardial ROS level in the mice were detected,and Western blotting was used to determine the protein expression levels of STAT3,GSDMD,caspase-11,JAK2,P-STAT3,P-JAK2,GSDMD-N and HMGB1 in the myocardial tissues.Results Five core targets were screened from the 10 intersecting genes.Molecular docking showed strong binding affinity of plumbagin to STAT3,p-STAT3,and JAK2.Compared with the sham-operated mice,the mouse models of CLP-induced sepsis had significantly decreased CO,LVEF,LVFS and SV and increased serum levels of CK-MB,LDH,MDA and myocardial inflammatory factors and ROS.HE staining and Western blotting showed obvious myocardial injury in the septic mice with increased expressions of JAK2/STAT3 signaling pathway and pyroptosis-related proteins(P<0.05).Pretreatment with plumbagin significantly improved cardiac functions of CLP mice,lowered serum levels of CK-MB,LDH,MDA,inflammatory factors and myocardial ROS,and decreased the expression levels of JAK2/STAT3 signaling pathway and pyroptosis-related proteins.Conclusion Plumbagin pretreatment alleviates myocardial injury in septic mice possibly by inhibiting the STAT3 signaling pathway to reduce cardiomyocyte pyroptosis.

Type 2 diabetes mellitus （T2DM） is a chronic metabolic disease characterized by insulin resistance， hyperinsulinemia， and disturbance of glucose and lipid metabolism， with elevated blood glucose as the main clinical manifestation. Due to its complex etiology and pathogenesis， there is no effective treatment， which critically threatens human health and places a heavy burden on society and families. Saponins are a class of glycosides with complex structures that have the advantage of a wide range of sources， elevated safety， and low adverse effects. As an essential active ingredient in Chinese medicine， Chinese medicine saponins have a variety of biological activities such as hypoglycemia， hypoglycaemia， anti-inflammation， antioxidation， anti-tumor， and immune modulation. In recent years， numerous studies have shown that Chinese medicine saponins are effective in preventing and treating T2DM. Although there have been numerous studies on the hypoglycemic effects and mechanisms of Chinese medicine saponins， there has been no systematic review of the mechanisms of Chinese medicine saponins in the treatment of T2DM. Therefore， to provide a theoretical basis for an in-depth study of the hypoglycemic effects of Chinese medicine saponins and a scientific basis for the development and clinical application of drugs， this paper systematically summarized the hypoglycemic mechanisms of Chinese medicine saponins， such as improving islet β-cell function， improving insulin resistance， inhibiting glycosidase activity， reducing the inflammatory response， anti-oxidative stress， and regulating intestinal flora， and analyzed the current research problems and development trends.