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.

[Purpose]To analyze the incidence and mortality rates of female breast cancer in Henan Province in 2020 and the trends from 2010 to 2020.[Methods]Breast cancer incidence and mor-tality data stratified by urban and rural areas and age groups were collected from Henan Provincial tumor registry,and the province's household population statistics were used.The crude incidence/mortality rate,age-standardized incidence/mortality rate by Chinese standard population(ASIRC/ASMRC)and world standard population(ASIRW/ASMRW),cumulative rate(0～74 year old)were calculated.The annual percentage change(APC),average annual percentage change(AAPC)and 95％confidence interval(CI)were calculated using Joinpoint software to analyze the trends of the incidence and mortality from 2010 to 2020.[Results]In 2020,24 744 new cases and 4 989 deaths of female breast cancer were documented in Henan Province,with a crude incidence rate of 46.96/105,ASIRC of 38.43/105 and ASIRW of 35.71/105;a crude mortality rate of 9.47/105,ASMRC of 6.80/105 and ASMRW of 6.72/105,respectively.The above indicators in urban areas were signifi-cantly higher than those in rural areas.The highest incidence was observed in the age group of 50～54 years old,while the highest mortality reached in the age group of 85 years old and above.From 2010 to 2020,the overall incidence of female breast cancer showed a slow upward trend(AAPC=2.09％,95％CI:0.62％～3.58％,P=0.010),while the mortality rate exhibited a signif-icant downward trend(AAPC=-3.49％,95％CI:-5.62％～-1.30％,P=0.005).[Conclusion]The incidence and mortality rates of female breast cancer in Henan Province are still at a high level,and corresponding preventive measures and control strategies are needed to effectively reduce the health hazards of breast cancer to women.

Objective:To investigate the role of microRNA-25-5p (miR-25-5p) in melanogenesis, and to explore its underlying mechanisms.Methods:Target genes of miR-25-5p were predicted using the TargetScan database. The interaction between miR-25-5p and the 3' untranslated region (3' UTR) of the RAB11B gene (a member of RAS oncogene family) was validated through a dual-luciferase reporter assay. Post-inflammatory hyperpigmentation (PIH) models were established in female C57BL/6J mice (6 - 8 weeks old) and female brown guinea pigs (4 - 6 weeks old) through daily broadband ultraviolet B (UVB) irradiation on the dorsal skin of the mouse ear or shaved dorsal skin of guinea pigs, while untreated mice and untreated dorsal skin areas of guinea pigs served as control groups. During modeling, these experimental animals received intradermal injections of a miR-25-5p agomir or a miR control agomir. Changes in skin pigmentation were observed, and skin tissue samples were harvested for further analysis after modeling. Melanin content in skin tissues was evaluated using Masson-Fontana staining. Expression of RAB11B and tyrosinase (TYR) in skin tissues was determined using immunohistochemical staining and quantitative real-time PCR (qPCR). Primary human melanocytes were isolated from discarded normal foreskin tissues of healthy males after circumcision. Both primary human melanocytes and human MNT1 melanoma cells were transfected with miR-25-5p mimics or miR control mimics. Relative expression levels of miR-25-5p and RAB11B mRNA were quantified by qPCR using the 2 -ΔΔCt calculation method. In MNT1 cells, miR-25-5p and RAB11B were co-overexpressed to assess their effect on the mRNA expression of RAB11B and TYR. Statistical analysis was conducted using t test or one-way analysis of variance followed by Tukey's post hoc test for multiple comparisons. Results:The bioinformatic prediction and dual-luciferase reporter assay confirmed a binding site for miR-25-5p in the 3′ UTR of the RAB11B gene. In both animal models, the treatment with the miR-25-5p agomir significantly reduced local skin pigmentation compared to the control groups; Masson-Fontana staining showed a marked decrease in the density of melanin granules in the epidermis and dermis in the miR-25-5p agomir groups compared with the miR control agomir groups (mice: 0.050 ± 0.005 vs. 0.087 ± 0.008; guinea pigs: 0.067 ± 0.015 vs. 0.110 ± 0.013; both P < 0.05). Immunohistochemical staining revealed significantly lower expression of RAB11B in mouse skin tissues in the miR-25-5p agomir group than in those in the miR control agomir group (both P < 0.05). qPCR revealed significantly lower mRNA expression of RAB11B and TYR in skin tissues of guinea pigs in the miR-25-5p agomir group than in those in the miR control agomir group (both P < 0.05). Similarly, RAB11B mRNA expression significantly decreased in the miR-25-5p mimics group compared with the miR control mimics group in primary human melanocytes and MNT1 cells (both P < 0.05). In human MNT1 melanoma cells, miR-25-5p overexpression could suppress TYR mRNA expression, whereas co-overexpression of miR-25-5p and RAB11B could reverse this suppression. Conclusion:Overexpression of miR-25-5p could alleviate UVB-induced post-inflammatory hyperpigmentation and inhibit melanogenesis, likely by targeted suppression of RAB11B expression.

The paper reports a 32-year-old female acute myeloid leukemia patient who developed graft-versus-host disease after paternal hematopoietic stem cell transplantation, which subsequently led to renal thrombotic microangiopathy. She subsequently required a kidney transplant from the same donor 5 years later due to renal failure. Considering that both the bone marrow and kidney were from the same donor and the recovery of renal function was favorable, immunosuppressive therapy was discontinued after a short course of anti-rejection treatment, with maintained stable kidney function. This case suggests that under the condition of high chimerism, allogeneic hematopoietic stem cell transplantation and kidney transplantation from the same donor can achieve immune tolerance, potentially improving solid organ transplantation success rate. The findings provide a novel therapeutic approach for solid organ transplantation following allogeneic hematopoietic stem cell transplantation.

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 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.

Objectives:To investigate the protective effect of nicotinamide adenine dinucleotide (NAD?) against noise-induced cochlear damage and preliminarily explore its underlying transcriptional and metabolic regulatory mechanisms.Methods:During the study period (January 2023-February 2025), an oxidative stress model was established using House Ear Institute-organ of Corti 1 (HEI-OC1) cells, and cell viability was assessed using the Cell Counting Kit-8 (CCK8) assay. Flow cytometry was employed to analyze cell apoptosis. A mouse model of noise-induced hearing loss was developed, and the mice were divided into three groups: a noise-exposed saline group, a noise-exposed NAD? intervention group, and a noise-free control group. Hearing protection effects were evaluated by auditory brainstem response (ABR) and immunofluorescence. Metabolomics and transcriptomics were used to analyze the regulatory effects of NAD +on transcription and metabolism in mouse cochlea. Enzyme-linked immunosorbent assay, quantitative real-time PCR, and western blot were used to verify the differential transcription and metabolic molecules and their functions. Data were statistically analyzed with GraphPad Prism 9.3.0. Results:NAD +at concentrations ranging from 10-80 μM effectively restored cell viability and reduced apoptosis induced by H?O? in HEI-OC1 cells. NAD? intervention significantly improved 16-32 kHz ABR thresholds after noise exposure ( P<0.05), reduced outer hair cell loss rates ( P<0.05), and attenuated ribbon synapse damage ( P<0.000 1). Metabolomics analysis revealed a significant downregulation in the glycerophospholipid metabolism pathway, with decreased levels of lysophosphatidic acid (LPA) and its related metabolites. ELISA results showed that LPA levels in the NAD? intervention group were significantly lower ( P<0.05). LPA inhibitor (ATX inhibitor 1) exhibited a cell protective effect similar to that of NAD?. Transcriptomics analysis indicated a significant upregulation of key genes related to potassium ion channels, such as Kcnq4. qPCR and Western blot further confirmed the significant upregulation of Kcnq4 and its encoded protein in the NAD? intervention group ( P<0.05). In the presence of the KCNQ4 inhibitor (ML252), the protective effect of NAD? was inhibited. Conclusions:NAD? exerts effective protective effects against noise-induced cochlear injury. Its protective mechanism may be closely related to the inhibition of LPA metabolic pathway and the up-regulation of KCNQ4 channel function.

Objective To investigate the role of autophagy involving the protein kinase B/sterol regulatory element binding protein 1(Akt/SREBP-1)signaling pathway in diabetic retinopathy(DR).Methods DR rat models were estab-lished via the intraperitoneal injection of streptozotocin.Rats were randomized into control(normal rats)and DM-DR groups(DR rats).The expression of autophagy-related proteins(autophagy markers LC3-Ⅱ and LC3-Ⅰ,autophagy specific substrate p62,and autophagy-related protein Beclin1)in rat retinas was compared between the two groups.Rats were di-vided into control B(normal rats injected with 1 μL saline),DR(DR rats injected with 1 μL saline),DR+si-NC(DR rats injected with 1 μL of the negative control siRNA),and DR+si-SREBP-1 groups(DR rats injected with 1 μL of the SREBP-1 siRNA).All interventions were given 1 day before modeling and 8 weeks after modeling.Akt/SREBP-1 expression and retinal ganglion cell(RGC)survival were compared among groups.R28 rat retinal precursor cells were classified into con-trol C(normal glucose,24 h),HG(high glucose,24 h),HG+si-NC(si-NC transfection+high glucose,24 h),and HG+si-SREBP-1 groups(si-SREBP-1 transfection+high glucose,24 h).The expression of autophagy-related proteins and au-tophagosome-lysosome fusion were compared among groups.Western blot and immunofluorescence were used to examine the expression of Akt,SREBP-1 and autophagy-related proteins.Results The relative expression of Beclin1 and p62 pro-teins and the LC3-Ⅱ/Ⅰ ratio in the DM-DR group were significantly higher than those in the control group 1 and 8 weeks after modeling(all P＜0.001).Compared with the control B group,the DR group exhibited elevated SREBP-1 and reduced Akt protein levels 1 and 8 weeks after modeling(all P＜0.01).RGC counts in the DR and DR+si-NC groups were significantly lower than those in the control B group(P＜0.001).The RGC count in the DR+si-SREBP-1 group was significantly higher than that in the DR+si-NC group(P＜0.001).Compared with those in the control C group,the Beclin1 and p62 protein levels and the LC3-Ⅱ/Ⅰ ratio were increased in the HG and HG+si-NC groups(all P＜0.01).Compared with those in the HG+si-NC group,the Beclin1 and p62 protein levels and the LC3-Ⅱ/Ⅰ ratio were reduced in the HG+si-SREBP-1 group(all P＜0.05).The HG and HG+si-NC groups showed significantly more LC3B/LAMP1 dual-positive puncta than the control C group(P＜0.001).The HG+si-SREBP-1 group showed significantly less LC3B/LAMP1 dual-positive puncta than the HG+si-NC group(P＜0.001).Conclusion SREBP-1 knockdown enhances autophagic flux in early DR to attenuate RGC loss.Thus,the Akt/SREBP-1 axis represents a promising therapeutic target for DR.