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 investigate the DSA imaging characteristics and efficacy of interventional treatment for post-pancreaticoduodenectomy hemorrhage(PPH),and to analyze the factors influencing recurrent bleeding following successful interventional hemostasis.Methods Clinical data of patients who underwent interventional treatment for PPH between January 2013 and December 2022 were retrospectively analyzed.All patients underwent DSA examination,and interventional therapy was the primary treatment option for patients with positive findings.Statistical analysis was performed on DSA angiography manifestations,bleeding sites,success rate of interventional treatment and hemostasis effectiveness.Univariate and multivariate logistic regression analysis were used to analyze the independent risk factors for rebleeding after interventional treatment for PPH.Results A total of 139 patients with PPH were included in this study.All 139 patients underwent DSA examination,with a positive rate of 82.01％(114/139)in the first examination.Major angiographic manifestations included contrast agent extravasation,pseudoaneurysm,and disrupted vascular architecture;bleeding sites included gastroduodenal artery in 45 cases(39.47％),hepatic artery in 22 cases(19.30％),and superior mesenteric artery in 32 cases(28.07％).107 patients underwent interventional treatment(81 embolization and 26 stenting),with a success rate of 91.59％(98/107).The independent risk factors for recurrent bleeding after interventional treatment in patients with PPH included preoperative bleeding(P＜0.001)and pancreatic fistula(P=0.041).Conclusion Interventional procedures for PPH can be efficient in diagnosis and treatment,with a high success rate and effective hemostasis.However,it should be noted that some patients remain at risk of recurrent bleeding after successful interventional hemostasis.

Objective To explore the value of neutrophil extracellular trapping nets(neutrophil extracellular traps,NETs)in the diagnosis and monitoring of acute ischemic stroke(acute ischemic stroke,AIS).Methods From June 2023 to February 2024,63 patients newly diagnosed with AIS at the Ganmei Hospital Affiliated with Kunming Medical University were selected as the experimental group,and 58 non-AIS individuals matched in gender,age,and other characteristics were selected as the control group.The NETs levels of patients in the experimental group were detected before and 7-10 days after treatment,and general clinical data and related laboratory results were statistically analyzed.Results The experimental group showed significantly higher levels of NEUT,LYMPH,MONO,EO,FDP,D-dimer,and NETs compared to the control group(P<0.05).The NETs levels before treatment were significantly higher than those at 7～10 days after treatment and in the control group(P<0.05).The NETs levels 7～10 days after treatment were significantly higher than those in the control group(P<0.05).NEUT,MONO,FDP,D-dimer,and NIHSS scores were positively correlated with the pre-treatment NETs levels(P<0.05).Elevated serum NETs levels were associated with AIS risk factors(P<0.05).The combined diagnostic value of NEUT,D-dimer,and NETs for AIS was superior to other indicators.Conclusion NETs are highly expressed in the serum of patients with acute ischemic stroke,and serum NETs have certain value in the auxiliary diagnosis and monitoring of acute ischemic stroke.

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.

In recent years,significant progress has been made in diabetes research both domestically and internationally,new diagno-sis and treatment techniques and methods have been constantly emerging,and clinical research evidence has been continuously accu-mulated and updated.To keep pace with these important developments,the Diabetes Branch of the Chinese Medical Association has ac-tively organized experts to update the China Guidelines for the Prevention and Treatment of Diabetes.This update aims to provide a more comprehensive and scientific guide for diabetes prevention and treatment,greatly promote the standardized and integrated man-agement of diabetes by clinicians,and ensure that patients receive standardized and personalized treatment plans to improve therapeu-tic outcomes and quality of life.

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 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.

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.

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.