The Model for End-Stage Liver Disease （MELD） score is currently used to prioritize liver allocation for cirrhotic patients awaiting liver transplantation in the world. With the application of MELD score in transplantation for patients with severe conditions， several models have been proposed to refine and improve MELD score. MELD score has also been used for the management of non-transplantation patients with chronic liver disease. This article briefly reviews the background of these models and believes that the original intention of MELD is to determine the priority of organ allocation for liver transplantation. The expanded application of MELD score beyond liver transplantation assessment should be performed with reference to clinical practice， and different MELD models should be selected rationally based on individual conditions， in order to help patients achieve optimal prognosis assessment， intervention measures， and benefits.

ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.

Objective To investigate the effect and mechanism of pomalidomide(POM)on airway inflammation and mucus hypersecretion in rats with chronic obstructive pulmonary disease(COPD).Methods Thirty-six SD rats were randomly divided into control group,model group and POM group,with 12 in each group,half male and half female.The COPD model was established by smoke exposure combined with Klebsiella pneumoniae infection in model group and POM group.The rats in POM group were treated with POM(0.5 mg/kg,once a day for 1 week).The lung function,lung tissue pathology,the proportion of inflammatory cells in bronchoalveolar lavage fluid(BALF)and the levels of serum inflammatory factors tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,IL-6 and IL-13 were observed and detected in each group.AB-PAS staining and immunohistochemistry were used to analyze the proliferation of goblet cells and the secretion of mucin(MUC)5AC and MUC5B in airway epithelium of rats.The expression levels of TNF-α receptor 1(TNFR1),IκB kinase(IKK),phosphorylated IKK(p-IKK)and P65 protein in lung tissue were detected by Western blotting.Results Compared with control group,model group showed significant decreased of tidal volume(TV),minute ventilation(MV),forced expiratory vital capacity(FVC),0.1s forced expiratory volume(FEV0.1)and 0.3 s forced expiratory volume(FEV0.3)(P<0.05),increased of the mean linear intercept(MLI)of the alveoli(P<0.01),decreased of the mean alveolar number(MAN)(P<0.01),increased of the proportion of neutrophils and lymphocytes in BALF sediment(P<0.05),and decreased of the proportion of macrophages in BALF sediment(P<0.01);increased of the levels of serum inflammatory factors TNF-α,IL-1β,IL-13 and IL-6(P<0.05),the proportion of goblet cells in airway epithelium(P<0.01),the secretion of MUC5AC and MUC5B in lung tissue(P<0.01),the content of TNFR1 and the ratio of p-IKK/IKK(P<0.01),the content of P65 in nucleus(P<0.01);and decreased of the content of P65 in cytoplasm(P<0.05).Compared with model group,after one week of POM treatment,POM group showed significant improved of the TV,MV,FVC,FEV0.1,FEV0.3,MLI and MAN of rats(P<0.05);decreased of the proportion of neutrophils and lymphocytes in BALF(P<0.05);increased of the proportion of macrophages(P<0.01);decreased of the levels of serum TNF-α,IL-1β,IL-6 and IL-13(P<0.05),the proportion of goblet cells in airway(P<0.01),the secretion of MUC5AC and MUC5B(P<0.01),and the expression of TNFR1,P-IKK and P65(nucleus)(P<0.05);and increased of the level of P65(cytoplasm)(P<0.01).Conclusions POM can improve airway inflammation and mucus hypersecretion in COPD rats,which may be achieved by inhibiting TNF-α/NF-κB signaling pathway.

The clinical data of one child with metanephric stromal tumor (MST) and BRAF V600E gene mutation admitted to the First Affiliated Hospital of Zhengzhou University in June 2022 was analyzed retrospectively.Literature was reviewed.The patient, a 2-year-old girl, was diagnosed with a tumor in the left abdomen.The maximum diameter of the tumor was 10.5 cm.A radical nephrectomy was performed on the left kidney, and postoperative pathology revealed MST.Microscopically, the tumor had no envelope and exhibited expansive growth.The tumor cells were fusiform or stellate, and nuclear division was visible in the cell-rich region.Dysplastic blood vessels were seen inside the tumor.The tumor cells around the blood vessels and invaginated renal tubules were arranged like onion skin.CD34 was detected positive by immunohistochemical staining, and BRAF V600E mutation was also detected positive by fluorescent polymerase chain reaction.A total of 21 relevant case reports were retrieved, including 16 in English and 5 in Chinese.Fifty-eight MST patients, including the one in this report were analyzed.These patients were aged 2 days to 15 years, with a median age of 2 years.Except for 2 patients with unknown sex, the ratio of male to female was about 1.4∶1.0.Most MST patients were asymptomatic, with an average tumor size of 5.3 cm.The tumor cell CD34 showed positive expression in different degrees.Eight patients received the BRAF V600E mutation detection, and the results were all positive.Fifty-eight patients underwent nephrectomy and were followed up for 0-156 months, of which 7 patients were assisted with radiotherapy and chemotherapy.During the follow-up, 1 patient died, and 1 patient had a relapse.MST is a rare benign renal stromal tumor. BRAF V600E mutations are detected in a variety of malignancies.This paper is the first to report MST with BRAF V600E mutation in China and points out the importance of molecular detection of BRAF mutation for accurate diagnosis of MST.

AIM:To investigate the effect of circular RNA MYO9A-006(circMYO9A_006)on hypertrophic phenotype of cardiomyocytes and the underlying mechanism.METHODS:The effect of adenovirus-mediated overexpres-sion of circMYO9A_006 on the expression of hypertrophy-related proteins,including β-myosin heavy chain(β-MHC),skeletal muscle actin alpha 1(ACTA1)and atrial natriuretic peptide(ANP),was evaluated in neonatal mouse ventricular cardiomyocytes(NMVCs).Moreover,a neonatal rat ventricular cardiomyocyte(NRVC)model of phenylephrine(PE)-in-duced hypertrophy was established.The effect of circMYO9A_006 overexpression on NRVC size was ascertained using Phalloidin-iFluor 647 staining method.Dual-luciferase reporter assay was employed to measure the activity of potential in-ternal ribosome entry sites(IRES)in circMYO9A_006.The translation and intracellular location of the circMYO9A_006-translated protein,MYO9A-208aa,were verified using Western blot.To investigate the role of MYO9A-208aa in the ef-fect of circMYO9A_006 on the cardiomyocyte hypertrophic phenotype,we prepared and used the following adenoviruses:the recombinant circMYO9A_006-ORF adenovirus to express MYO9A-208aa,the recombinant circMYO9A_006-ATG-mut adenovirus that does not express MYO9A-208aa,the recombinant circMYO9A_006 adenovirus,and the adenovirus vector control.These were then employed to infect NRVCs.RESULTS:Successful adenovirus-mediated overexpression of circMYO9A_006 was observed in NMVCs.The increased expression of circMYO9A_006 notably reduced the expres-sion of hypertrophy-related proteins in NMVCs(P<0.01).Concurrently,overexpression of circMYO9A_006 substantially reduced the expression of hypertrophy-associated proteins and diminished the size of PE-induced NRVCs(P<0.05).Dual-luciferase reporter assay identified the activity of 2 IRES in circMYO9A_006.Western blot results indicated that circ-MYO9A_006 could produce the MYO9A-208aa protein with an anticipated molecular weight of 28 kD in NRVCs,primari-ly found in the cytoplasm.Elevated expression of both circMYO9A_006 and MYO9A-208aa consistently reduced the ex-pression of hypertrophy-associated proteins(P<0.01),and counteracted the enlarged size of PE-induced NRVCs(P<0.05).However,increased expression of circMYO9A_006-ATG-mut did not counteract the PE-induced hypertrophic phe-notype of NRVCs.CONCLUSION:circMYO9A_006 attenuates the hypertrophic phenotype of cardiomyocytes by synthe-sizing the MYO9A-208aa protein.

Objective:To investigate the clinical efficacy of Cyclosporine A(CsA)in patients with unexplained repeated implantation failure(URIF),and to analyze the changes of peripheral blood lymphocyte subsets after CsA treatment.Methods:105 patients with URIF who underwent frozen-thawed embryo transfer(FET)in the De-partment of Reproductive Medicine in The Second Affiliated Hospital of Kunming Medical University from Septem-ber 30,2021 to March 1,2022 were selected.After informed consent,the patients were divided into CsA group(n=52)and control group(n=53)according to whether they received CsA treatment or not.Pregnancy outcomes and changes in lymphocyte subset were compared between the two groups.Results:The embryo implantation rate and clinical pregnancy rate in CsA group were higher than those in the control group,the difference was statisti-cally significant(48.91%vs.32.56%,P=0.027;53.85%vs.32.08%,P=0.024).The CsA group had a lower ear-ly abortion rate than the control group(10.71%vs.23.53%),but the difference was not statistically significant(P=0.25).The percentage of CD3-CD16+CD56+in CsA group was significantly decreased after treatment[(16.15±5.37)%vs.(18.23±7.10)%,P=0.012],it was also lower than that in the control group[(16.15±5.37)%vs.(18.67±5.16)%,P=0.018].Conclusions:CsA treatment can significantly improve the clinical preg-nancy rate and embryo implantation rate of frozen-thawed embryo transfer in patients with URIF,which may be a-chieved by promoting the distribution of peripheral blood lymphocytes to the direction of embryo implantation,es-pecially by down-regulating the percentage of CD3-CD16+CD56+.CsA has a certain application prospect in the field of assisted reproduction.

Objective:To investigate the clinical efficacy of Cyclosporine A(CsA)in patients with unexplained repeated implantation failure(URIF),and to analyze the changes of peripheral blood lymphocyte subsets after CsA treatment.Methods:105 patients with URIF who underwent frozen-thawed embryo transfer(FET)in the De-partment of Reproductive Medicine in The Second Affiliated Hospital of Kunming Medical University from Septem-ber 30,2021 to March 1,2022 were selected.After informed consent,the patients were divided into CsA group(n=52)and control group(n=53)according to whether they received CsA treatment or not.Pregnancy outcomes and changes in lymphocyte subset were compared between the two groups.Results:The embryo implantation rate and clinical pregnancy rate in CsA group were higher than those in the control group,the difference was statisti-cally significant(48.91%vs.32.56%,P=0.027;53.85%vs.32.08%,P=0.024).The CsA group had a lower ear-ly abortion rate than the control group(10.71%vs.23.53%),but the difference was not statistically significant(P=0.25).The percentage of CD3-CD16+CD56+in CsA group was significantly decreased after treatment[(16.15±5.37)%vs.(18.23±7.10)%,P=0.012],it was also lower than that in the control group[(16.15±5.37)%vs.(18.67±5.16)%,P=0.018].Conclusions:CsA treatment can significantly improve the clinical preg-nancy rate and embryo implantation rate of frozen-thawed embryo transfer in patients with URIF,which may be a-chieved by promoting the distribution of peripheral blood lymphocytes to the direction of embryo implantation,es-pecially by down-regulating the percentage of CD3-CD16+CD56+.CsA has a certain application prospect in the field of assisted reproduction.

Objective:To investigate the clinical efficacy of Cyclosporine A(CsA)in patients with unexplained repeated implantation failure(URIF),and to analyze the changes of peripheral blood lymphocyte subsets after CsA treatment.Methods:105 patients with URIF who underwent frozen-thawed embryo transfer(FET)in the De-partment of Reproductive Medicine in The Second Affiliated Hospital of Kunming Medical University from Septem-ber 30,2021 to March 1,2022 were selected.After informed consent,the patients were divided into CsA group(n=52)and control group(n=53)according to whether they received CsA treatment or not.Pregnancy outcomes and changes in lymphocyte subset were compared between the two groups.Results:The embryo implantation rate and clinical pregnancy rate in CsA group were higher than those in the control group,the difference was statisti-cally significant(48.91%vs.32.56%,P=0.027;53.85%vs.32.08%,P=0.024).The CsA group had a lower ear-ly abortion rate than the control group(10.71%vs.23.53%),but the difference was not statistically significant(P=0.25).The percentage of CD3-CD16+CD56+in CsA group was significantly decreased after treatment[(16.15±5.37)%vs.(18.23±7.10)%,P=0.012],it was also lower than that in the control group[(16.15±5.37)%vs.(18.67±5.16)%,P=0.018].Conclusions:CsA treatment can significantly improve the clinical preg-nancy rate and embryo implantation rate of frozen-thawed embryo transfer in patients with URIF,which may be a-chieved by promoting the distribution of peripheral blood lymphocytes to the direction of embryo implantation,es-pecially by down-regulating the percentage of CD3-CD16+CD56+.CsA has a certain application prospect in the field of assisted reproduction.

Objective:To investigate the clinical efficacy of Cyclosporine A(CsA)in patients with unexplained repeated implantation failure(URIF),and to analyze the changes of peripheral blood lymphocyte subsets after CsA treatment.Methods:105 patients with URIF who underwent frozen-thawed embryo transfer(FET)in the De-partment of Reproductive Medicine in The Second Affiliated Hospital of Kunming Medical University from Septem-ber 30,2021 to March 1,2022 were selected.After informed consent,the patients were divided into CsA group(n=52)and control group(n=53)according to whether they received CsA treatment or not.Pregnancy outcomes and changes in lymphocyte subset were compared between the two groups.Results:The embryo implantation rate and clinical pregnancy rate in CsA group were higher than those in the control group,the difference was statisti-cally significant(48.91%vs.32.56%,P=0.027;53.85%vs.32.08%,P=0.024).The CsA group had a lower ear-ly abortion rate than the control group(10.71%vs.23.53%),but the difference was not statistically significant(P=0.25).The percentage of CD3-CD16+CD56+in CsA group was significantly decreased after treatment[(16.15±5.37)%vs.(18.23±7.10)%,P=0.012],it was also lower than that in the control group[(16.15±5.37)%vs.(18.67±5.16)%,P=0.018].Conclusions:CsA treatment can significantly improve the clinical preg-nancy rate and embryo implantation rate of frozen-thawed embryo transfer in patients with URIF,which may be a-chieved by promoting the distribution of peripheral blood lymphocytes to the direction of embryo implantation,es-pecially by down-regulating the percentage of CD3-CD16+CD56+.CsA has a certain application prospect in the field of assisted reproduction.

Mutations in myosin heavy chain 7(MYH7)and myosin binding protein C3(MYBPC3)genes encoding thick filaments are the main cause of hypertrophic cardiomyopathy(HCM),while a small part of HCM is caused by mutations of troponin C1,slow skeletal and cardiac type(TNNC1),troponin T2,cardiac type(TNNT2),troponin I3,cardiac type(TNNI3),actin alpha cardiac muscle 1(ACTC1),and tropomyosin 1(TPM1)genes encoding thin filaments.In this review,we mainly introduce the detailed mechanism and research status of HCM caused by mutations of the gene encoding cardiomyocyte sarcomere in the past few years,in order to provide reference for further study of the pathogenesis and treatment of HCM.