HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Objective: To analyze the frequency and investigate the causes of unexpected antibodies in D-negative blood donors. Methods: From January 2022 to December 2024, 3 768 D-negative blood donors sent to our laboratory were selected as research subjects. D-negative confirmation test and RhCE phenotype detection were applied by saline tube method and microcolumn gel indirect antiglobulin test (IAT), respectively. Antibody screening and identification were performed using the polybrene method and IAT column agglutination methods. Anti-D, anti-C and anti-G specificities were identified by a two-step adsorption-elution method, and the genotypes of D-negative samples were determined by RHD gene amplification, Sanger sequencing, and PacBio Single Molecule Real-Time (SMRT) sequencing. Results: Among D-negative donors, ccee and Ccee phenotypes accounted for the highest proportion, 55.68% (2 098/3 768) and 29.56% (1 114/3 768), respectively, while CcEE and CCEe phenotypes were the least, with one case detected in each, accounting for 0.03% (1/3 768). A total of 165 cases with D variant phenotype were detected, and the proportion of D variant was 4.38% (165/3 768) in the donors detected by D-negative confirmation test. Antibody screening positive blood donors were identified in 93 cases with a proportion of 2.47% (93/3 768). Antibody specificity was determined in 84 blood donors, and 9 samples showed no clear specificity. Anti-D was detected most frequently (n=68), in which 6 of them were detected having multiple antibodies, anti-D + anti-C (n=2), anti-D + anti-G(n=1), and anti-D + anti-E(n=3). The other antibodies detected were anti-E (n=1), anti-M(n=9), anti-P1 (n=3), anti-Le (n=1), and anti-HI(n=2). Fourteen cases were detected with anti-D in serological D-negative donors with C+ or E+ phenotype, in which three of them were DVI type 3 individuals and 11 cases were D negative individuals. Conclusion: The incidence of unexpected antibodies was higher in D-negative blood donors than in the total donors, with anti-D being the most common. The data provide insights for prevention and monitoring hemolytic disease of the fetus and newborn (HDFN) caused by anti-D. To ensure the safety of blood transfusion, routine unexpected antibody screening for RhD-negative blood donors is recommended to prevent the use of unexpected antibodies positive plasma in the clinic.

Objective:To serologically and genotypically analyze the pedigree of a case with a new allele c.175_176insGA of B el subtype and preliminarily explore the molecular mechanism of weak expression of glycosyltransferase B. Method:In the descriptive study,a 23-year-old male voluntary blood donor and his family members were selected for the study. The ABO and Le blood types of the proband and his family members was identified by the test tube method. The agglutination inhibition test was applied to detect the B and H antigens in saliva, and the Sanger sequencing and PacBio (Pacific Bioscience) third-generation haplotype sequencing were performed on the study subjects to identify genotypes. Finally, Expasy software were applied to amino acid translation of DNA sequences and prediction of protein length after gene alteration. ORF finder was applied to predict alternative start codons as well as open reading frames of mRNA, and protein expression mechanisms were analyzed.Results:The proband and her sister were B el subtype, her mother was AB el subtype, her father was normal O type, and all members of the family were Le(a+b+) phenotype. Sanger sequencing results showed that a new allele of c.175_176insGA was found in exon 4 of the proband, her mother, and her sister. Third-generation haplotype sequencing detected the haplotypes of the family members, which revealed that the proband was ABO*O.01.02/ABO*BEL.NEW (c.175_176insGA), the father was ABO*O.01.02/ABO*O.01.02, the mother was ABO*A1.02/ABO*BEL.NEW (c.175_176insGA), and the sister was ABO*O.01.02/ABO*BEL.NEW (c.175_176insGA). Analysis of the protein expression mechanism indicated that although the new allele of ABO*BEL.NEW was presumed to cause a frameshift mutation and result in a premature stop codon p.Asp59Glu*fs20 in exon 5, encoding an inactive glycosyltransferase, an alternative start codon could be utilized to initiate translation of B el subtype functional glycosyltransferase. Conclusion:Expression of the new allele of B el subtype is associated with the translation of B el subtype glycosyltransferase initiated by alternative start codons.

Purpose/Significance To construct a Chinese medical knowledge Q&A corpus dataset as a standardized evaluation bench-mark for large language models(LLMs)in the medical domain,so as to improve the accuracy and efficiency of LLMs in handling Chinese medical questions.Method/Process Chinese medical paper knowledge,medical terminology explanations and supplementary questions are acquired from the Chinese medical licensing examination,and open-source Chinese medical Q&A datasets are encompassed in the developed Q&A datasets.Result/Conclusion The Chinese medical knowledge Q&A corpus datasets enrich the sources of existing datasets and promote the objective and comprehensive quantitative evaluation of large models in the medical field.In the near future,additional data such as electronic medical records and those from online health communities will be used to strengthen the support of artificial intelli-gence for the Healthy China strategy.

Objective To explore the efficacy and safety of TACE combined with propranolol for treating giant infantile hepatic hemangioma(IHH).Methods Ten infants with giant IHH who underwent TACE combined with propranolol were retrospectively enrolled.The technical success rate,complications and recurrence were recorded.The therapeutic effect was evaluated according to clinical symptoms and changes of IHH volume before and 6 months after TACE.Results Totally 15 times of TACE were successfully performed in 10 infants,with technical success rate of 100%.Bleomycin-lipiodol emulsion+poly(vinyl alcohol)(PVA)+coil embolization were performed in 3 cases,while bleomycin-lipiodol emulsion+PVA embolization were performed in 7 cases.Complications of TACE included subcutaneous hematoma around the puncture site in 1 case and transient hypothermia within 24 h after TACE in 2 cases,all alleviated after symptomatic treatments.No other complication occurred.Six months after the last TACE,significantly effective was observed in 9 cases(9/10,90.00%),while effective was noticed in 1 case(1/10,10.00%),with total therapeutic effective rate of 100%.No serious complication such as gallbladder necrosis,liver necrosis,death,nor recurrence of hepatic hemangioma occurred during follow-up.Conclusion TACE combined with propranolol was effective and safe for treating giant IHH.

Diarrhea is a common and frequent disease in clinical practice.Many factors cause diarrhea,and numerous research method with animal models of diarrhea have been explored.Despite this,drugs for the treatment of diarrhea in clinical practice are limited,and some existing drugs are only suitable for diarrhea caused by a single factor.Therefore,the construction and selection of appropriate animal models of diarrhea are not only important for in-depth studies of the pathogenesis,but are also effective means for the clinical screening and evaluation of drugs for comprehensively preventing and treating diarrhea.This article reviews the literature on the establishment and evaluation of animal models of functional,bacterial,viral,and symptomatic diarrhea,as well as progress of therapeutic drug research,to provide a reference for animal experimental research into the prevention and treatment of diarrhea.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To evaluate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) combined with lenvatinib and tislelizumab in the treatment of unresectable intrahepatic cholangiocarcinoma (ICC).Methods:The clinical data of 12 patients with unresectable ICC who received HAIC combined with lenvatinib and tislelizumab in the First Affliated Hospital of Soochow University from October 2021 to April 2023 were retrospectively analyzed. HAIC included gemcitabine plus oxaliplatin; this regimen was combined with lenvatinib and tislelizumab within 3-7 days after its initial administration. Relevant laboratory examinations were performed before each cycle of HAIC, and enhanced computed tomography/magnetic resonance imaging examinations were performed every 6-9 weeks. Tumor response to treatment was evaluated using the modified Response Evaluation Criteria in Solid Tumors. The objective response rate, disease control rate, progression-free survival, overall survival, and treatment-related adverse reactions of patients with ICC were statistically analyzed.Results:The objective response rate to HAIC combined with lenvatinib and tislelizumab was 6/12; the disease control rate was 8/12; the median progression-free survival was 11.8 months; and the median overall survival was 14.2 months. Three patients had grade Ⅳ adverse reactions (increased alanine aminotransferase and aspartate aminotransferase thrombocytopenia), while three patients had grade Ⅲ adverse reactions (increased total bilirubin, alanine aminotransferase, and aspartate aminotransferase). The remaining patients had grade Ⅰ-Ⅱ adverse reactions. There were no serious complications related to interventional surgery.Conclusions:Use of HAIC (gemcitabine plus oxaliplatin) combined with lenvatinib and tislelizumab in the treatment of unresectable ICC may be safe and feasible. Preliminary clinical studies have shown that this combination can improve the survival and prognosis of patients with ICC.

Objective To explore the high-quality development path of tertiary public hospitals and provide scientific reference for deepening the reform of public hospitals.Methods Based on SPO theory,it constructed an analytical framework for the high-quality development of tertiary public hospitals,collected data of a quarterly monitoring in-dex for the performance assessment and high-quality development of tertiary public hospitals in a certain province in 2023,and analysed 73 tertiary public hospitals participating in the performance assessment as the object of analy-sis,and adopted the fuzzy-set Qualitative Comparative Analysis to explore different condition sets of high-quality de-velopment of tertiary public hospitals and reveal the path of high-quality development of public hospitals.Results High-quality development is the result of multi-factor interaction.Four configurations were identified to promote the high-quality development of tertiary public hospitals:service quality-technology-driven path,service quality-driven path,comprehensive service-driven path,and service quality-benefit-driven path.Quality safety and functional orientation were found to be the core elements in promoting high-quality development of public hospitals.Conclusion Hospitals at all levels should strengthen the guidance of party building,combine with the actual functional positioning,take quality and safety as the core,and optimize the combination conditions of technical level,personnel structure,service process,and cost control.It is essential to clarify the development strategy of hospitals,implement the dynamic concept,and realize the high-quality development of public hospitals.

Objective To explore the high-quality development path of tertiary public hospitals and provide scientific reference for deepening the reform of public hospitals.Methods Based on SPO theory,it constructed an analytical framework for the high-quality development of tertiary public hospitals,collected data of a quarterly monitoring in-dex for the performance assessment and high-quality development of tertiary public hospitals in a certain province in 2023,and analysed 73 tertiary public hospitals participating in the performance assessment as the object of analy-sis,and adopted the fuzzy-set Qualitative Comparative Analysis to explore different condition sets of high-quality de-velopment of tertiary public hospitals and reveal the path of high-quality development of public hospitals.Results High-quality development is the result of multi-factor interaction.Four configurations were identified to promote the high-quality development of tertiary public hospitals:service quality-technology-driven path,service quality-driven path,comprehensive service-driven path,and service quality-benefit-driven path.Quality safety and functional orientation were found to be the core elements in promoting high-quality development of public hospitals.Conclusion Hospitals at all levels should strengthen the guidance of party building,combine with the actual functional positioning,take quality and safety as the core,and optimize the combination conditions of technical level,personnel structure,service process,and cost control.It is essential to clarify the development strategy of hospitals,implement the dynamic concept,and realize the high-quality development of public hospitals.