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 differences in acute intestinal injury and regulatory mechanisms in mice following carbon ion FLASH radiotherapy (FLASH-RT) and conventional dose rate radiotherapy (CONV-RT).Methods:Healthy C57BL/6J mice were randomly divided into three groups: control group, FLASH-RT group (100 Gy/s), and CONV-RT group (0.1 Gy/s), with 9 mice in each group. All mice received carbon ion whole abdominal radiotherapy. DNA double-strand breaks (DSB) and cell proliferation were evaluated by measuring the expression of phosphorylated histone H2AX (γ-H2AX) and nuclear-associated antigen 67 (Ki67) using immunohistochemistry; apoptosis was analyzed using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL); transcriptome sequencing was used to analyze the differences in molecular pathways between FLASH-RT and CONV-RT.Results:Compared with the CONV-RT group, the FLASH-RT group showed significantly reduced intestinal γ-H2AX signal at 3 h after radiotherapy ( t=3.80, P<0.01), significantly increased expression of Ki67 at the base of intestinal crypts at 6 h after radiotherapy ( t=4.30, P<0.001), and a significantly decreased number of TUNEL-positive cells at 12 h after radiotherapy ( t=3.08, P<0.01). Transcriptome sequencing analysis showed that FLASH-RT specifically activated the insulin-like growth factor (IGF) pathway, avoiding the excessive activation of CONV-RT-induced nuclear factor-κB and B cell receptor inflammatory pathways as well as the inhibition of energy metabolism. Conclusions:Compared with CONV-RT, carbon ion FLASH-RT can reduce DSB damage, preserve the proliferative activity of intestinal stem cells, activate the IGF pathway, and regulate inflammatory, immune, and metabolic pathways, thereby significantly alleviating acute intestinal epithelial injury. Specifically, the regulation of repair pathways mediated by reduced DSB and the inhibition of inflammatory pathways are potential protective mechanisms for normal tissues.

Objective:To investigate the differences in acute intestinal injury and regulatory mechanisms in mice following carbon ion FLASH radiotherapy (FLASH-RT) and conventional dose rate radiotherapy (CONV-RT).Methods:Healthy C57BL/6J mice were randomly divided into three groups: control group, FLASH-RT group (100 Gy/s), and CONV-RT group (0.1 Gy/s), with 9 mice in each group. All mice received carbon ion whole abdominal radiotherapy. DNA double-strand breaks (DSB) and cell proliferation were evaluated by measuring the expression of phosphorylated histone H2AX (γ-H2AX) and nuclear-associated antigen 67 (Ki67) using immunohistochemistry; apoptosis was analyzed using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL); transcriptome sequencing was used to analyze the differences in molecular pathways between FLASH-RT and CONV-RT.Results:Compared with the CONV-RT group, the FLASH-RT group showed significantly reduced intestinal γ-H2AX signal at 3 h after radiotherapy ( t=3.80, P<0.01), significantly increased expression of Ki67 at the base of intestinal crypts at 6 h after radiotherapy ( t=4.30, P<0.001), and a significantly decreased number of TUNEL-positive cells at 12 h after radiotherapy ( t=3.08, P<0.01). Transcriptome sequencing analysis showed that FLASH-RT specifically activated the insulin-like growth factor (IGF) pathway, avoiding the excessive activation of CONV-RT-induced nuclear factor-κB and B cell receptor inflammatory pathways as well as the inhibition of energy metabolism. Conclusions:Compared with CONV-RT, carbon ion FLASH-RT can reduce DSB damage, preserve the proliferative activity of intestinal stem cells, activate the IGF pathway, and regulate inflammatory, immune, and metabolic pathways, thereby significantly alleviating acute intestinal epithelial injury. Specifically, the regulation of repair pathways mediated by reduced DSB and the inhibition of inflammatory pathways are potential protective mechanisms for normal tissues.

With the advancement of China's healthcare reform,enhancing the capacity of primary healthcare services has become a pivotal task.Colorectal cancer,one of the most prevalent malignancies in China,highlights the critical importance of early screening and diagnosis to improve patient survival rates.This study,guided by the principles of Party building and Xi Jinping Thought on Socialism with Chinese Characteristics,examines the implementation and outcomes of a rural outreach program focused on colorectal cancer screening and diagnostic technologies.By promoting the dissemination of colorectal cancer screening initiatives,the paper aims to provide empirical evidence to support the deepening of primary-care services,foster high-quality ad-vancement of grassroots health services,and align with the national Healthy China Initiative,thereby more effectively safeguarding population health.

Objective:To investigate the characteristics of the endometrial microbiota in patients with varying degrees of intrauterine adhesion (IUA).Methods:This single-center cross-sectional observational study enrolled 115 patients with IUA who were treated at the Hysteroscopic Center of Fuxing Hospital, Capital Medical University, from May 2022 to October 2023. After quality control and data preprocessing, 81 samples met the inclusion criteria for analysis. Patients were grouped according to an established IUA scoring and grading system into mild IUA ( n=38) and moderate-to-severe IUA ( n=43). Endometrial tissue was collected under sterile conditions. Bacterial genomic DNA was extracted, the 16S rRNA V3-V4 region was amplified, and sequencing was performed on an Illumina platform. Differences in endometrial microbiota diversity and composition were compared between the two groups. Results:Patients with varying degrees of IUA exhibited comparable species richness, evenness and diversity of endometrial microbiota. At the phylum level, the endometrial microbiota across all subjects was predominantly composed of Proteobacteria, Firmicutes, Cyanobacteriota, Bacteroidota, and Actinobacteriota, with Proteobacteria (32.29%) and Firmicutes (23.82%) showing the highest mean relative abundances. At the genus level, Ralstonia (16.67%), Lactobacillus (13.45%), and Streptococcus (7.07%) were the most abundant genera. Group comparisons showed that the abundance of Ralstonia was higher in the mild IUA group, whereas Lactobacillus, Vibrio and Pseudoalteromonas were more abundant in the moderate-to-severe IUA group; however, these differences did not reach statistical significance (all P>0.05). LEfSe analysis further indicated that Lactobacillus, Vibrio, Pseudoalteromonas, Aeromonas, Ureaplasma and Acetobacterium were relatively enriched in the moderate-to-severe IUA group, while Geobacillus, Stomatobaculum and Fusicatenibacter were more abundant in the mild IUA group. Conclusion:The composition of the endometrial microbiota differs among patients with varying IUA severity. IUA progression may be associated with alterations in the endometrial microbiota; however, causal relationships and underlying mechanisms require further investigation.

Objective To establish a method for predicting the risk of endometrial cancer(EC)and endometrial atypical hyperplasia(AH)in women with postmenopausal bleeding(PMB)by collecting clinical data on routine medical history.Methods The clinical data of a total of 408 PMB patients admitted to Fuxing Hospital,Capital Medical University were consecutively collected in this retrospective study from December 2013 to December 2023.According to the results of endometrial pathology,patients were divided into case group and control group.EC and AH were included in the malignant group(case group)and the other endometrial pathologies were included in the non-malignant group(control group).Clinical data,including clinical history,high risk factors,and common gynecological ultrasound measurement indicators,were collected and studied by univariate and multivariate Logistic regression analysis.Results The mean age of 408 patients was(60.4±7.8)years.A total of 74 cases(18.1％)were in case group and 334 cases(81.9％)were in control group.Based on Logistic regression analysis,the best predictors of endometrial malignant lesions were selected to create a"LRDNT"(light bleeding,recurrent bleeding,diabetes,non-uniform echogenicity & thickness)model.LRDNT scores range from 0 to 22.The score of LRDNT ≥15 has the largest Yoden index,and the sensitivity to predict endometrial malignant lesions is 79.73％,the specificity is 80.84％,and the prediction accuracy is 80.64％.Conclusions The risk prediction model LRDNT,which combines clinical information and common gynecological ultrasound measurement indicators of PMB patients,can help clinicians classify patients at high and low risk of endometrial malignant lesions,and optimize the strategy of diagnosis and treatment.

Objective:To analyze and validate the reliability and validity of the social skills improvement system-rating scales Chinese version (parent version) (SSIS-RS-C) in middle school students.Method:A total of 1 486 parents of middle school students were recruited according to the cluster sampling method.The social responsiveness scale and strengths and difficulties questionnaire were used as criterion validity tools.A retest was conducted one month later.SPSS 27.0 was used for descriptive statistics, item analysis, internal consistency test, test-retest reliability test and criterion validity test. AMOS 24.0 was used to perform confirmatory factor analysis .Results:Item analysis indicated significant positive correlations between each item and the subscales ( r=0.293-0.782, all P<0.01), with significant differences in scores between high and low groups ( t=10.079-37.038, all P<0.01).Confirmatory factor analysis supported a seven-factor structure for the social skills subscale(communication, cooperation, assertion, responsibility, empathy, engagement and self control) and a five-factor structure for the problem behavior subscale (externalizing, bullying, hyperactivity/inattention, internalizing and autism spectrum) of the SSIS-RS-C.There was a positive correlation between the social skills subscale and prosocial behavior ( r=0.637, P<0.001), and between the problem behavior subscale and social impairments and difficult behaviors ( r=0.765, 0.688, both P<0.001).The Cronbach's α coefficients for the total scale, social skills subscale and problem behavior subscale were 0.934, 0.972 and 0.963, respectively.The test-retest correlation coefficients for the total score and the two subscales were 0.665, 0.871 and 0.598, respectively (all P<0.001). Conclusion:The SSIS-RS-C demonstrated good reliability and validity in the Chinese adolescent population.

With the advancement of China's healthcare reform,enhancing the capacity of primary healthcare services has become a pivotal task.Colorectal cancer,one of the most prevalent malignancies in China,highlights the critical importance of early screening and diagnosis to improve patient survival rates.This study,guided by the principles of Party building and Xi Jinping Thought on Socialism with Chinese Characteristics,examines the implementation and outcomes of a rural outreach program focused on colorectal cancer screening and diagnostic technologies.By promoting the dissemination of colorectal cancer screening initiatives,the paper aims to provide empirical evidence to support the deepening of primary-care services,foster high-quality ad-vancement of grassroots health services,and align with the national Healthy China Initiative,thereby more effectively safeguarding population health.

Objective:To investigate the characteristics of the endometrial microbiota in patients with varying degrees of intrauterine adhesion (IUA).Methods:This single-center cross-sectional observational study enrolled 115 patients with IUA who were treated at the Hysteroscopic Center of Fuxing Hospital, Capital Medical University, from May 2022 to October 2023. After quality control and data preprocessing, 81 samples met the inclusion criteria for analysis. Patients were grouped according to an established IUA scoring and grading system into mild IUA ( n=38) and moderate-to-severe IUA ( n=43). Endometrial tissue was collected under sterile conditions. Bacterial genomic DNA was extracted, the 16S rRNA V3-V4 region was amplified, and sequencing was performed on an Illumina platform. Differences in endometrial microbiota diversity and composition were compared between the two groups. Results:Patients with varying degrees of IUA exhibited comparable species richness, evenness and diversity of endometrial microbiota. At the phylum level, the endometrial microbiota across all subjects was predominantly composed of Proteobacteria, Firmicutes, Cyanobacteriota, Bacteroidota, and Actinobacteriota, with Proteobacteria (32.29%) and Firmicutes (23.82%) showing the highest mean relative abundances. At the genus level, Ralstonia (16.67%), Lactobacillus (13.45%), and Streptococcus (7.07%) were the most abundant genera. Group comparisons showed that the abundance of Ralstonia was higher in the mild IUA group, whereas Lactobacillus, Vibrio and Pseudoalteromonas were more abundant in the moderate-to-severe IUA group; however, these differences did not reach statistical significance (all P>0.05). LEfSe analysis further indicated that Lactobacillus, Vibrio, Pseudoalteromonas, Aeromonas, Ureaplasma and Acetobacterium were relatively enriched in the moderate-to-severe IUA group, while Geobacillus, Stomatobaculum and Fusicatenibacter were more abundant in the mild IUA group. Conclusion:The composition of the endometrial microbiota differs among patients with varying IUA severity. IUA progression may be associated with alterations in the endometrial microbiota; however, causal relationships and underlying mechanisms require further investigation.