Objective:To analyze the MYH9 gene sequence of a patient with hereditary thrombocytopenia and diffuse large B-cell lymphoma and his family members,and to explore the relationship between MYH9 gene and tumors.Methods:Peripheral blood samples were collected from the patients and their family members for complete blood count analysis.The platelet morphology was observed under microscope.The MYH9 gene sequence was analyzed by Whole Exon Sequencing and Sanger Sequencing.Results:The mutation site c.279C＞A:p.(Asn93Lys)in exon 2 of the MYH9 gene were found in patient and his family members,both presenting as thrombocytopenia.The platelet count was significantly increased after the administration of Avatrombopag.Conclusion:A novel mutation of MYH9 was found in this study,and the case was sensitive to Avatrombopag,by exploring the relationship between the MYH9 gene and tumors,suggesting that the MYH9 gene may be associated with the development of diffuse large B-cell lymphoma.

Objective:To investigate the effect of piperlongumine(PL)on the proliferation and ferroptosis of human adriamycin-resistant chronic myeloid leukemia K562/ADR cells,and to explore its possible molecular mechanism.Methods:CCK-8 assay was used to detect the effect of PL on the survival rate of K562/ADR cells and to screen the appropriate drug concentration.After K562/ADR cells were treated with low,medium and high concentrations of PL(2,4,and 6 μmol/L),EdU proliferation assay and plate colony formation assay were used to detect cell proliferation and colony formation ability.CCK-8 assay was used to detect the effects of different inhibitors(Fer-1,Z-VAD,Nec-1)combined with PL on cell proliferation.The intracellular Fe2+,ROS,malondialdehyde(MDA)and glutathine(GSH)contents were respectively detected by iron ion colorimetry,DCFH-DA fluorescent probe,MDA and GSH kits.RT-qPCR and Western blot were respectively used to detect the expression level of GPX4 mRNA and protein in cells.Bioinformatics websites predicted miRNA that could target and regulate GPX4.RT-qPCR was used to detect the effects of different concentrations of PL on the expression levels of the predicted miRNA.Dual luciferase gene reporter assay was used to verify the targeting relationship between miR-214-3p and GPX4.After treating cells with PL or PL+miR-214-3p inhibitor,the Fe2+,ROS,MDA,GSH centents and GPX4 protein expression levels in cells were detected.Results:PL inhibited K562/ADR cell proliferation in a concentration-dependent manner(r=0.979).Compared with the blank control group,the survival rate,EdU positive cells rate in low,medium and high concentration PL groups were significantly decreased(P＜0.01).Compared with the PL group alone,the survival rate of cells in the Z-VAD+PL group was increased slightly(P＜0.05).The cell survival rate was significantly increased in medium or high concentration PL+Fer-1 group(P＜0.01).Compared with blank control group,ROS expression level in low concentration PL group was slightly increased(P＜0.05),and GSH content was slightly decreased(P＜0.05).In medium and high concentration PL groups,the contents of Fe2+,ROS and MDA were significantly increased(P＜0.01),while the contents of GSH,expression of GPX4 mRNA and protein were significantly decreased(P＜0.01).Bioinformatics prediction and double luciferase reporter gene experiment confirmed the targeting relationship between GPX4 and miR-214-3p.Compared with the blank control group,the expression level of miR-214-3p in cells of medium and high concentration PL groups was significantly increased(P＜0.01).Compared with PL group alone,the intracellular Fe2+,ROS and MDA contents in PL+miR-214-3p inhibitor group were all decreased(P＜0.01),while GSH content and GPX4 protein expression levels were significantly increased(P＜0.01).Conclusion:Medium and high concentrations of PL can inhibit the proliferation of K562/ADR cells by inducing ferroptosis,which is related to the regulation of miR-214-3p/GPX4 pathway.

Objective:Invasive pulmonary mucormycosis(PM)is a rare but highly lethal opportunistic infection.COVID-19 associated mucormycosis(CAM)is difficult to diagnose,often leading to misdiagnosis or missed diagnosis,and has poor treatment outcomes.This study reports a case of successfully treated CAM and explores optimized diagnostic and therapeutic strategies.Methods:A retrospective analysis of the diagnosis and treatment process in a 50-year-old female patient with COVID-19 associated with diabetic ketoacidosis(DKA)and invasive pulmonary mucormycosis was conducted.Combined with a literature review,the therapeutic efficacy of local bronchoscopic instillation in conjunction with systemic treatment using liposomal Amphotericin B(L-AmB)was specifically evaluated.Results:The patient was rapidly diagnosed with Rhizopus microsporus infection through metagenomic next-generation sequencing(mNGS).She subsequently received antifungal treatment with intravenous L-AmB combined with local bronchoscopic instillation.After treatment,the patient was significantly improved,with imaging studies showing gradual absorption of the lesions.Follow-up at six months revealed no recurrence.A literature review suggests that early diagnosis and multimodal therapy are key to improving survival rates in patients with CAM.Conclusion:mNGS can significantly improve the early diagnosis rate of CAM.The combination of local and systemic treatment with L-AmB is valuable in improving prognosis.Early diagnosis,multimodal antifungal therapy,and individualized management are key to increasing the survival rate of patients with CAM.

Aim To investigate the protective effect of Siwu decoction(SWD)on immune injury induced by 60Coγ-rays in mice and the related mechanism.Meth-ods C57BL/6J mice were randomly divided into six groups:Control group(Control),Model group(Mod-el),Siwu decoction low-dose group(SWD-L),Siwu decoction medium-dose group(SWD-M),Siwu decoc-tion high-dose group(SWD-H)and resveratrol positive group(Resveratrol,Res).The drug was continued to be administered 11 days before and after irradiation,with a single whole-body irradiation of 4 Gy,and all in-dexes were detected three days after irradiation.The changes of peripheral blood and organ indexes were de-tected.Serum levels of cytokine interferon gamma(IFN-γ),interleukin-1 β(IL-1 β),IL-2,IL-4,IL-6,IL-10,IL-17,transforming growth factor-β(TGF-β),tumor necrosis factor(TNF)-α,and immunoglobulin A(IgA),IgG,IgM,and complement protein 3(C3),C4 content were detected by enzyme-linked immunosorbent assay(ELISA).B lymphocytes,T lymphocytes,NK cells in spleen and T lymphocytes in thymus were de-tected by flow cytometry.The pathological changes of spleen and thymus were analyzed by hematoxylin-eosin(HE)staining.The expression of Sirt 1 protein in spleen after radiation was detected by immunofluores-cence staining.The protein contents of Sirt1,PI3K,Akt,p-Akt and mTOR in spleen were detected by Western blot assay.Results SWD could significantly increase LYMPH％and reduce pathological injury of spleen and thymus.Flow cytometry showed that SWD could significantly increase the percentage of CD19+B lymphocytes in spleen,decrease the percentage of NK lymphocytes and the ratio of CD4+/CD8+in spleen and thymus.ELISA results showed that SWD signifi-cantly inhibited the expression of IL-1 β,IL-2,IL-6,IL-17,IFN-γ,TGF-β,TNF-α,and increased the content of anti-inflammatory factors IL-4 and IL-10.At the same time,SWD significantly inhibited the increase of IgA,IgG,IgM,C3 and C4 induced by radiation.The results of immunofluorescence staining and Western blot showed that SWD could decrease the expression of PI3K,Akt,p-Akt and mTOR protein,and enhance the expression of Sirt1 protein.Conclusions SWD has obvious preventive effect on immune damage induced by 60Co gamma radiation in mice.The mechanism may be related to Sirt1-PI3K-Akt-mTOR.

Objective To investigate the differences in demographic characteristics,reproductive health status,and the distribution of pregnancy-related diseases between couples conceived via assisted reproductive technology(ART)and naturally conceived couples,and to analyze the impact of ART treatment on the incidence of preterm birth(PTB)in singleton and twin and multiple pregnancies.Methods We conducted a retrospective analysis of the maternal and infant cohort data of Jing'an District from 2013 to 2020.Based on the conception method,the subjects were categorized into two groups:the ART group and the natural conception group.Chi-square test was applied to compare baseline characteristics and disease distributions differences between the two groups,and logistic regression models were used to evaluate the association between ART and the PTB risks.A causal mediation model was used to evaluate the mediating effect of twin and multiple pregnancy in the relationship between ART and PTB.Results A total of 117 717 parturients were included,6 265 in the ART group and 111 452 in the natural conception group.Compared with the natural conception group,couples in the ART group were significantly older and had a higher prevalence of reproductive system diseases.The incidences of diabetes and hypertensive disorders during pregnancy in ART parturient were 13.76%and 9.99%,respectively,which were significantly higher than 7.88%and 4.75%in the natural conception group(both P<0.001).The overall PTB rate in the ART group was 14.81%,higher than 5.35%in the natural conceptions group(P<0.001).The PTB rate in ART for singleton pregnancies in the ART group was 6.40%,higher than 4.83%in the natural conception group(P<0.001),while the PTB rate in ART for twin and multiple pregnancies in the ART group was 53.97%,lower than 60.42%in the natural conception group(P<0.05).Mediation analysis showed that 97.99%of the effect of ART on PTB was mediated by twin and multiple pregnancy,with ART increasing the PTB risk by 3.44 times through multiple pregnancy.Conclusion The overall PTB rate of ART recipients is higher than that of natural recipients,but ART does not increase the PTB risk in singleton and twin and multiple pregnancies.Twin and multiple pregnancy is the key mediating factor contributing to PTB in ART-conceived recipients.Compared with naturally conceived couples,ART conception couples own more advanced maternal age,and have higher risks of suffering gestational diabetes,gestational hypertension,and PTB.

Aim To study the protective effect of the silibinin derivative Sil-1 on acute myocardial ischemia in SD rats and its mechanism of action.Methods Af-ter 18 hours of oxygen-glucose deprivation and treat-ment of H9c2 cells,the protective effect of Sil-1 on rat cardiomyocytes was examined.SD rats were treated 30 minutes before surgery,followed by 24 h ligation of the left anterior descending coronary artery.The cardiopro-tective effects of Sil-1 and its mechanisms for improving myocardial ischemic injury were investigated using pro-teomics technology.Results In vitro,compared with the control group,the activity of H9c2 cells in the mod-el group showed reduced cell viability,increased dead cells,elevated ROS and higher levels of LDH and in-flammatory cytokines TNF-α,IL-1β and IL-6 in the culture medium.Sil-1 could improve the above condi-tions to different degrees.In vivo,compared with the control group,rats in the model group showed signifi-cantly higher T waves on electrocardiogram,significant ischemic areas in the heart section,disorganized ar-rangement of cardiomyocytes,increased inflammatory factor infiltration and elevated CK,CK-MB,LDH and inflammatory factors TNF-α,IL-6 and IL-1β.Besides,NF-κB phosphorylation levels in myocardial tissue in-creased.Sil-1 improved the above conditions to varying degrees.The results of proteomics showed that 90 pro-teins were found between the control vs model group and the Sil-1 vs model group,and KEGG enrichment a-nalysis showed that MAPK,chemokines,VEGF and other signaling pathways were abundant.Western blot results showed that Sil-1 blocked the phosphorylation of ERK,JNK and p38 MAPK.Conclusions Sil-1 inhib-its the MAPK pathway by blocking the phosphorylation of JNK,ERK,and p38 MAPK,and achieves a protec-tive effect on rats with acute myocardial infarction.

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.

This article reports a child with cardioaciocutaneous syndrome (CFCS) caused by a rare microdeletion of chromosome 19p13.3, and a literature review is conducted. The child had unusual facies, short stature, delayed mental and motor development, macrocephaly, and cardiac abnormalities. Whole-exome sequencing identified a 1 040 kb heterozygous deletion in the 19p13.3 region of the child, which was rated as a "pathogenic variant". This is the first case of CFCS caused by a loss-of-function mutation reported in China, which enriches the genotype characteristics of CFCS. It is imperative to enhance the understanding of CFCS in children. Early identification based on its clinical manifestations should be pursued, and genetic testing should be performed to facilitate diagnosis.
Humans ; Chromosome Deletion ; Chromosomes, Human, Pair 19/genetics* ; Ectodermal Dysplasia/genetics* ; Facies ; Failure to Thrive/genetics* ; Heart Defects, Congenital/genetics*

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Temporomandibular joint (TMJ) disc displacement is one of the most significant subtypes of temporomandibular joint disorders, but its etiology and mechanism are poorly understood. In this study, we elucidated the mechanisms by which destruction of inflamed collagen fibrils induces alterations in the mechanical properties and positioning of the TMJ disc. By constructing a rat model of TMJ arthritis, we observed anteriorly dislocated TMJ discs with aggravated deformity in vivo from five weeks to six months after a local injection of Freund's complete adjuvant. By mimicking inflammatory conditions with interleukin-1 beta in vitro, we observed enhanced expression of collagen-synthesis markers in primary TMJ disc cells cultured in a conventional two-dimensional environment. In contrast, three-dimensional (3D)-cultivated disc cell sheets demonstrated the disordered assembly of inflamed collagen fibrils, inappropriate arrangement, and decreased Young's modulus. Mechanistically, inflammation-related activation of the nuclear factor kappa-B (NF-κB) pathway occurs during the progression of TMJ arthritis. NF-κB inhibition reduced the collagen fibril destruction in the inflamed disc cell sheets in vitro, and early NF-κB blockade alleviated collagen degeneration and dislocation of the TMJ discs in vivo. Therefore, the NF-κB pathway participates in the collagen remodeling in inflamed TMJ discs, offering a potential therapeutic target for disc displacement.
Animals ; NF-kappa B/metabolism* ; Temporomandibular Joint Disorders/pathology* ; Temporomandibular Joint Disc/metabolism* ; Rats ; Rats, Sprague-Dawley ; Disease Models, Animal ; Male ; Collagen/metabolism* ; Cells, Cultured ; Joint Dislocations/pathology* ; Interleukin-1beta ; Arthritis, Experimental