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.

ObjectiveTo develop a nomogram-based risk prediction model for chronic obstructive pulmonary disease (COPD) incidence among the community-dwelling population aged 40 years old and above, so as to provide targeted references for the screening and prevention of COPD. MethodsBased on a natural population cohort in suburban Shanghai, a total of 3 381 randomly selected participants aged ≥40 years underwent pulmonary function tests between July and October 2021. Cox stepwise regression analysis was used to develop overall and gender-specific risk prediction models, along with the construction of corresponding risk nomograms. Model predictive performance was evaluated using the C-indice, area under the curve (AUC) values, and Brier score. Stability was assessed through 10-fold cross-validation and sensitivity analysis. ResultsA total of 3 019 participants were included, with a median follow-up duration of 4.6 years. The COPD incidence density was 17.22 per 1 000 person-years, significantly higher in males (32.04/1 000 person-years) than that in females (7.38/1 000 person-years) (P<0.001). The overall risk prediction model included the variables such as gender, age, education level, BMI, smoking, passive smoking, and respiratory comorbidities. The male-specific model incorporated the variables such as age, BMI, respiratory comorbidities, and smoking, while the female-specific model included age, marital status, respiratory comorbidities, and pulmonary tuberculosis history. The C-indices for the overall, male-specific, and female-specific models were 0.829, 0.749, and 0.807, respectively. The 5-year AUC values were 0.785, 0.658, and 0.811, with Brier scores of 0.103, 0.176, and 0.059, respectively. Both 10-fold cross-validated C-indices and sensitivity analysis (excluding participants with a follow-up duration of <6 months) yielded C-indices were above 0.740. ConclusionThis study developed concise and practical overall and gender-specific COPD risk prediction models and corresponding nomograms. The models demonstrated robust performance in predicting COPD incidence, providing a valuable reference for identifying high-risk populations and formulating targeted screening and personalized management strategies.

BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

OBJECTIVE: To explore the association between acupuncture during controlled ovarian hyperstimulation (COH) and the live birth rate (LBR) using different propensity score methods. METHODS: In this retrospective cohort study, eligible women who underwent a COH were divided into acupuncture and non-acupuncture groups. The primary outcome was LBR, as determined by propensity score matching (PSM). LBR was defined as the delivery of one or more living infants that reached a gestational age over 28 weeks after embryo transfer. The propensity score model encompassed 16 confounding variables. To validate the results, sensitivity analyses were conducted using three additional propensity score methods: propensity score adjustment, inverse probability weighting (IPW), and IPW with a "doubly robust" estimator. RESULTS: The primary cohort encompassed 9751 patients (1830 [18.76%] in the acupuncture group and 7921 [81.23%] in the non-acupuncture group). Following 1:1 PSM, a higher LBR was found in the acupuncture cohort (41.4% [755/1824] vs 36.4% [664/1824], with an odds ratio of 1.23 [95% confidence interval, 1.08-1.41]). Three additional propensity score methods produced essentially similar results. The risk of serious adverse events did not significantly differ between the two groups. CONCLUSION This retrospective study revealed an association between acupuncture and an increased LBR among patients undergoing COH, and that acupuncture is a safe and valuable treatment option. Please cite this article as: Zheng XY, Jiang ZY, Li YT, Li CL, Zhu H, Yu Z, Yu SY, Yang LL, Tang SY, Lü XY, Liang FR, Yang J. Association between acupuncture and live birth rates after fresh embryo transfer: A cohort study based on different propensity score methods. J Integr Med. 2025; 23(5):528-536.
Humans ; Female ; Propensity Score ; Embryo Transfer ; Adult ; Acupuncture Therapy ; Retrospective Studies ; Pregnancy ; Live Birth ; Birth Rate ; Cohort Studies

ObjectiveTo evaluate the efficacy of three screening questionnaires for COPD in the community residents of Songjiang District， Shanghai， and to provide a basis for selecting COPD screening questionnaire and process that are more suitable. MethodsCommunity residents aged 40 years or over were randomly selected from the Shanghai Suburban Adult Cohort and Biobank for the study with screening questionnaires and spirometry. Questionnaires included the COPD screening questionnaire （COPD-SQ）， the COPD population screener （COPD-PS） and the revised COPD diagnostic questionnaire （revised-CDQ）. Evaluation of the efficacy of these questionnaires was based on the area under the receiver operating characteristic curve （AUC） of the subjects. DeLong test was used to compare the accuracy of different questionnaires； Z test was used to compare the accuracy of different cut-off values for the same questionnaire. ResultsAmong 3 184 community residents， a total of 259 （8.1%） COPD patients were screened by spirometry. AUC values of these 3 screening questionnaires were >0.7 indicating that they were reliable COPD screening tools. The sensitivity and specificity of the questionnaires at the recommended cut-off values were COPD-SQ （63.7% and 72.2%）， COPD-PS （12.0% and 96.1%）， and revised CDQ （78.8% and 52.7%）， with the COPD-SQ having the highest screening accuracy （AUC=0.754）. The optimal and recommended cut-off values for the three questionnaires differed in this population， but the difference in accuracy was statistically significant only for COPD-PS. The optimal cut-off values for the three questionnaires differed between male and female， and the sensitivity and accuracy of COPD-SQ and COPD-PS improved when lower cut-off values were used for women. The AUC was greater when two questionnaires were utilized simultaneously for screening， but the differences were not statistically significant. ConclusionThe COPD-SQ is recommended for primary COPD screening； a lower cut-off value for women should be considered. The COPD screening questionnaire needs to be further improved for the early diagnosis and treatment of COPD patients.

Objective To develop and validate a nomogram model for predicting the risk of kinesiophobia in patients after lung cancer surgery.Methods A total of 164 lung cancer patients who underwent surgery in a Grade ⅢA hospital in Xiamen were recruited from October 2022 to May 2023 in this study.Logistic regression was conducted to identify independent risk factors of kinesiophobia in patients who recieved lung cancer surgery.A Nomogram model was developed using R software for predicting the risk of kinesiophobia.The predictive performance of the model was assessed by calculating the receiver-operating-characteristics curve(ROC)and the area under curve(AUC).Results The incidence of postoperative kinesiophobia in lung cancer patients was at 44.51％.Logistic regression analysis showed that pain and fatigue were the risk factors for the occurrence of postoperative kinesiophobia in the patients(P<0.05)and self-efficacy was a protective factor(P<0.05).Validation of the Nomogram model showed that the ROC curve indicated an AUC of 0.888(95％CI 0.836-0.940)for predicting kenesiophobia in patients after lung cancer surgery and the calibration curve presented as a line with a slope close to 1.The Hosmer-Lemeshow goodnee-of-fit test showed that the model could accurately predict the risk of postoperative kinesiophobia in lung cancer patients(χ 2=1.931,P=0.983).Conclusion Self-efficacy,pain and fatigue are the influencing factors for the occurrence of postoperative kinesiophobia in the patients who received lung cancer surgery.The nomogram prediction model has good accuracy and discrimination,and it may assist the healthcare professionals to predict the occurrence of postoperative kinesiophobia in the patients after lung cancer surgery and take pertinent measures to minimise the incidence.

Objective To develop and validate a nomogram model for predicting the risk of kinesiophobia in patients after lung cancer surgery.Methods A total of 164 lung cancer patients who underwent surgery in a Grade ⅢA hospital in Xiamen were recruited from October 2022 to May 2023 in this study.Logistic regression was conducted to identify independent risk factors of kinesiophobia in patients who recieved lung cancer surgery.A Nomogram model was developed using R software for predicting the risk of kinesiophobia.The predictive performance of the model was assessed by calculating the receiver-operating-characteristics curve(ROC)and the area under curve(AUC).Results The incidence of postoperative kinesiophobia in lung cancer patients was at 44.51％.Logistic regression analysis showed that pain and fatigue were the risk factors for the occurrence of postoperative kinesiophobia in the patients(P<0.05)and self-efficacy was a protective factor(P<0.05).Validation of the Nomogram model showed that the ROC curve indicated an AUC of 0.888(95％CI 0.836-0.940)for predicting kenesiophobia in patients after lung cancer surgery and the calibration curve presented as a line with a slope close to 1.The Hosmer-Lemeshow goodnee-of-fit test showed that the model could accurately predict the risk of postoperative kinesiophobia in lung cancer patients(χ 2=1.931,P=0.983).Conclusion Self-efficacy,pain and fatigue are the influencing factors for the occurrence of postoperative kinesiophobia in the patients who received lung cancer surgery.The nomogram prediction model has good accuracy and discrimination,and it may assist the healthcare professionals to predict the occurrence of postoperative kinesiophobia in the patients after lung cancer surgery and take pertinent measures to minimise the incidence.

ObjectiveAntibiotic resistance genes （ARGs） have received wide attention all over the world. The purpose of this study was to explore the bacterial community structure， the types and levels of antibiotic resistance genes in a water body in east China， and to compare and analyze the characteristics of microbial species distribution and antibiotic resistance gene distribution in various water environments. MethodsA total of 10 households in Haimen City， Jiangsu Province were selected and their surrounding water environment samples were collected. 21 water samples including river water （4）， Mingou water （9） and well water （8） were collected for metagenomics sequencing， assembled with MetaWRAP， annotated with CARD database， and analyzed with R software. ResultsIn various water bodies， the dominant bacteria phyla was Proteobacteria， the dominant bacteria genera were Deuterostomia， Pseudomonas， Flavobacteriales and Streptomycetaceae. The ARGs annotated were mainly composed of quinolones， aminoglycosides， macrolides and beta-lactams antibiotic resistance genes. The top four relative abundance of resistance genes were macB， RanA， evgS and TxR， The average absolute abundance and expression of resistance genes in well water and Mingou water were higher than those in river water. ConclusionMultiple ARGs are detected to varying degrees in well water， river water， and Mingou water bodies， and the expression of resistance genes in well water and Mingou water bodies is higher than that in river water bodies， possibly due to human production and living activities.

Objective:To investigate the expression of soluble T cell immunoglobulin and mucin domain-3 (Tim-3) in peripheral blood of patients with pancreatic cancer and its diagnostic value in combination with serum Carbohydrate antigen 19-9 (CA19-9) .Methods:106 newly diagnosed pancreatic cancer patients and 65 age and sex matched healthy individuals were enrolled. Tim-3 concentration was quantitatively determined by enzyme-linked immunosorbent assay (ELISA). According to the expression levels of soluble Tim-3 and serum CA19-9, a binary logistic regression model of receiver operating characteristic (ROC) curve was established to compare the diagnostic effects of serum CA19-9 and soluble Tim-3 alone or combined with the two tests.Results:The levels of soluble Tim-3 in the pancreatic cancer group were significantly higher than those in the healthy control group ( P<0.001). The expression level of soluble Tim-3 was significantly higher in patients with stage III-IV pancreatic cancer than in patients with stage I-II ( P=0.003). The AUC of soluble Tim-3 diagnosis for stage I-II pancreatic cancer was 0.856 (95%CI: 0.765 to 0.992 P<0.001), Serum CA19-9 The AUC used for the stage I-II pancreatic cancer diagnosis was 0.862 (95%CI: 0.772 to 0.926 P<0.001), The AUC for the combined diagnosis was 0.949 (95%CI: 0.880 - 0.985 P<0.001) ; In a healthy population and in patients with stage III-IV pancreatic cancer, the AUC of soluble T I I-IV pancreatic cancer in stage III was 0.927 (95%CI: 0.873 to 0.963 P<0.001), the AUC of serum CA19-9 used for the diagnosis of stage III-IV pancreatic cancer was 0.933 (95%CI: 0.881 to 0.968 P<0.001), the AUC for the combined diagnosis was 0.989 (95%CI: 0.956 to 0.999 P<0.001) . Conclusions:The combination of soluble Tim-3 and serum CA19-9 can improve the diagnostic rate of pancreatic cancer patients.

BACKGROUND: Acquired immune deficiency syndrome (AIDS)-related non-Hodgkin lymphoma (AR-NHL) is a high-risk factor for morbidity and mortality in patients with AIDS. This study aimed to determine the prognostic factors associated with overall survival (OS) and to develop a prognostic nomogram incorporating computed tomography imaging features in patients with acquired immune deficiency syndrome-related non-Hodgkin lymphoma (AR-NHL). METHODS: A total of 121 AR-NHL patients between July 2012 and November 2019 were retrospectively reviewed. Clinical and radiological independent predictors of OS were confirmed using multivariable Cox analysis. A prognostic nomogram was constructed based on the above clinical and radiological factors and then provided optimum accuracy in predicting OS. The predictive accuracy of the nomogram was determined by Harrell C-statistic. Kaplan-Meier survival analysis was used to determine median OS. The prognostic value of adjuvant therapy was evaluated in different subgroups. RESULTS: In the multivariate Cox regression analysis, involvement of mediastinal or hilar lymph nodes, liver, necrosis in the lesions, the treatment with chemotherapy, and the CD4 ≤100 cells/μL were independent risk factors for poor OS (all P < 0.050). The predictive nomogram based on Cox regression has good discrimination (Harrell C-index = 0.716) and good calibration (Hosmer-Lemeshow test, P = 0.620) in high- and low-risk groups. Only patients in the high-risk group who received adjuvant chemotherapy had a significantly better survival outcome. CONCLUSION A survival-predicting nomogram was developed in this study, which was effective in assessing the survival outcomes of patients with AR-NHL. Notably, decision-making of chemotherapy regimens and more frequent follow-up should be considered in the high-risk group determined by this model.
Acquired Immunodeficiency Syndrome ; Humans ; Lymphoma, Non-Hodgkin ; Neoplasm Staging ; Nomograms ; Prognosis ; Retrospective Studies