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 whether neoadjuvant therapy can improve the prognosis of patients with pancreatic cancer.Methods:A retrospective case-control study analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database on 12, 103 patients who underwent surgical treatment between January 1, 2010, and December 31, 2021. Patients were divided into the neoadjuvant therapy group ( n=3 276) and the upfront surgery group ( n=8 827) based on whether they received neoadjuvant treatment. The neoadjuvant therapy group included 2 342 patients receiving neoadjuvant chemotherapy and 934 patients receiving neoadjuvant chemoradiotherapy. The upfront surgery group consisted of 4 335 patients receiving adjuvant chemotherapy, 1 987 patients receiving adjuvant chemoradiotherapy, 63 patients receiving adjuvant radiotherapy, and 2 442 patients undergoing surgery alone. Propensity score matching was used to eliminate group differences and create a cohort with no statistical differences in other clinicopathological features except for the grouping variable. Variables such as age, gender, tumor location, race, population of residence, tumor diameter, household income, TNM stage, and information on radiotherapy and chemotherapy were used for 1∶1 case matching. T stage, N stage, and the use of radiotherapy or chemotherapy were matched exactly. After matching, 1 182 patients were included in each group: the neoadjuvant therapy group contained 1 155 patients receiving neoadjuvant chemoradiotherapy and 27 receiving neoadjuvant chemotherapy, while the upfront surgery group comprised 848 patients receiving adjuvant chemotherapy and 334 receiving adjuvant chemoradiotherapy. TNM staging was reported according to the 7th edition of the AJCC guidelines. The primary outcome was overall survival. Measurement data with skewed distributions were expressed as M( Q1, Q3), and intergroup comparisons were conducted using the Wilcoxon rank-sum test. Categorical data were compared using the chi-square test or the Fisher′s exact test. The Log-rank test and subgroup analyses to assess interactions between neoadjuvant therapy and subgroup in COX regression models were used to compare survival benefits across variables. Landmark analysis was performed to create segmented survival curves, studying the impact of neoadjuvant therapy on prognosis during different follow-up periods. Results:The neoadjuvant therapy group had a higher proportion of T 4 tumor involving celiac axis, superior mesenteric artery, and/or common hepatic artery compared to the upfront surgery group (14.7% vs 2.8%, P<0.001). Additionally, significant differences were observed between groups in terms of race, location, population of residence, age, tumor diameter, tumor stage, and adjuvant therapy regimen ( P<0.05). The median overall survival time in the neoadjuvant therapy group was 30 months, compared to 22 months in the upfront surgery group ( P<0.001). In the neoadjuvant therapy group, the median survival was 30 months for both neoadjuvant chemotherapy and chemoradiotherapy patients; in the upfront surgery group, it was 26 months for both adjuvant chemotherapy and chemoradiotherapy patients, 17 months for adjuvant radiotherapy patients, and 12 months for surgery-only patients. After propensity score matching, there were no differences in the distribution of clinical characteristics between groups ( P>0.05), and all patients in the matched cohort had received chemotherapy. The matched neoadjuvant therapy group had a longer median overall survival compared to the upfront surgery group (30 months vs 27 months, P<0.001). Subgroup interaction analysis revealed that T stage had a significant interaction with neoadjuvant therapy, both before (T 4 stage: HR=0.382, 95% CI: 0.319-0.458; T 2-T 3 stages: HR=0.696, 95% CI: 0.656-0.738; T 1 stage: HR=1.199, 95% CI: 0.867-1.657; interaction P<0.001) and after matching (T 4 stage: HR=0.581, 95% CI: 0.414-0.814; T 2-T 3 stages: HR=0.827, 95% CI: 0.734-0.931; T 1 stage: HR=1.320, 95% CI: 0.716-2.433; interaction P=0.043). Subgroup interaction analysis indicated that T 1 patients did not benefit from neoadjuvant therapy; survival curves plotted for matched T 1 patients showed no difference in survival between the neoadjuvant therapy group and the upfront surgery group ( P=0.323). Conversely, non-T 1 (T 2-T 4) stage patients showed significant survival benefits in both unmatched and matched cohorts ( P<0.001). Landmark analysis showing that the survival benefits occurred mainly in the early postoperative period of up to 3 years ( P<0.001), but there was no difference in overall survival between the neoadjuvant therapy group and the upfront surgery group of >3 years ( P>0.05). Patients with Arterial invasion (T 4 stage compared to T 1-T 3 stages) showed a similarly significant interaction with the benefit of neoadjuvant therapy in both the pre-matching cohort (interaction P<0.001) and the post-matching cohort (interaction P=0.037). Patients with T 4 stage disease in the neoadjuvant therapy group had longer overall survival compared to the upfront surgery group (median overall survival in pre-matching cohort: 30 months vs 13 months, P<0.001; median overall survival in post-matching cohort: 28 months vs 18 months, P=0.001). Among T 4 stage patients in the post-matching cohort, neoadjuvant therapy provided significant survival benefits during the early postoperative period of up to 3 years ( P=0.001). However, there was no difference in overall survival between the neoadjuvant therapy group and the direct surgery group beyond 3 years( P=0.729). Conclusions:The prognosis in the neoadjuvant therapy group was better than in the upfront surgery group. Propensity score matching and subgroup interaction analysis showed that non-T 1 and T 4 stage patients benefited more from neoadjuvant therapy, with benefits mainly seen in the early postoperative period (≤3 years).

Objective:To utilize routinely available clinical parameters to uncover the clinical features of different clusters in patients with chronic rhinosinusitis with nasal polyp (CRSwNP) through unsupervised clustering analysis.Methods:The clinical data from 155 CRSwNP patients undergoing nasal endoscopic surgery at Renmin Hospital of Wuhan University from 2021 to 2023 were prospectively collected, including 112 males and 43 females, aged from 7 to 87 years. Unsupervised clustering analysis was conducted using various clinical parameters, including age, gender, smoking and drinking history, local eosinophil (EOS) and neutrophil (NEU) counts, comorbid allergic rhinitis (AR), comorbid asthma, recurrence status, serum-specific IgE, total IgE, cytokine levels, peripheral blood EOS count and percentage, Lund-Mackay CT score, the ratio of CT scores for the maxillary sinus and ethmoid sinus (E/M ratio), visual analogue scale (VAS) score, Lund-Kennedy endoscopic score, and other common clinical indicators to elucidate the clinical characteristics of each cluster. Statistical analysis was conducted using GraphPad Prism 9.5 software.Results:Hierarchical clustering analysis identified four main clusters (Cluster A1-A4), showcasing distinct characteristics such as mild nasal polyps with higher peripheral blood cytokines levels, nasal polyps accompanied by allergies and asthma, a subtype of nasal polyps with high recurrence rates dominated by neutrophils, and nasal polyps with high eosinophil levels. Further subset clustering revealed two clusters of mild polyps (Cluster B1-B2) featuring high cytokine expression and comorbid AR; and two clusters of severe polyps (Cluster B3-B4) presented with severe symptoms, high Lund-Mackay CT score, and high Lund-Kennedy endoscopic score. Variations between Cluster B3 and B4 included symptom complexity, the degree of eosinophil infiltration, and the probability of comorbid asthma. Further clustering analysis for eosinophilic nasal polyps revealed a cluster characterized by highly neutrophilic infiltration and recurrent nasal polyps. The comprehensive analysis of multi-index correlations demonstrated valuable insights into the relationships between common clinical parameters of nasal polyps, providing valuable information for a deeper understanding of the pathogenesis of CRSwNP.Conclusion:The clustering analysis in this study categorizes CRSwNP patients into different clusters based on clinical features and disease outcomes, providing a new perspective for more precise clinical treatment strategies.

Objective:To preliminarily investigate the risk factors for distant metastasis and prognosis, and construct a prognostic nomogram in T 4 stage pancreatic cancer. Methods:A retrospective case-control study was conducted using data from the Surveillance, Epidemiology, and End Results (SEER) database for pancreatic patients from January 1, 2010, to December 31, 2021. Based on whether the tumor invaded the celiac axis, superior mesenteric artery, and/or common hepatic artery, 38 759 patients were divided into an arterial invasion group (T 4 stage, n=7 471) and a non-arterial invasion group (non-T 4 stage, n=31 288). Clinical and pathological data, including demographic characteristics, treatment information, and tumor data were collected. The primary outcome was overall survival. Categorical data were expressed as numbers (percentages), and intergroup comparisons were made using the chi-square test. Survival benefits were measured using the Log-Rank test. A multivariate logistic model was used to identify high-risk factors for metastasis in T 4 stage pancreatic cancer. Patients were randomly divided into training ( n=5 232) and validation ( n=2 239) sets at a 7∶3 ratio. A nomogram model was created based on independent prognostic factors from the multivariate Cox regression analysis, and the model′s predictive ability was evaluated using the C-index and calibration curves. Results:The overall metastasis rate in the arterial invasion group was higher than that in the non-arterial invasion group (32.8% vs 29.0%, P<0.001), with fewer patients showing no metastasis or single-organ metastasis (86.3% vs 89.7%, P<0.001) and higher rates of lung metastasis ( P<0.001), distant lymph node metastasis ( P<0.001), and other metastases excluding liver, lung, brain, bone, and distant lymph node metastases ( P<0.001). However, no significant difference was found between groups for liver, brain, or bone metastasis rates ( P>0.05). Surgical rates for T 4 stage patients were significantly lower than for non-T 4 stage patients (all patients: 10.7% vs 38.4%, P<0.001; M 0 stage patients: 15.0% vs 52.4%, P<0.001; M 1 stage patients: 2.1% vs 4.1%, P<0.001). Additionally, significant differences were observed in age, race, radiotherapy, chemotherapy, tumor location, tumor size, and tumor stage ( P<0.05). The median survival for patients with arterial invasion was 8 months, significantly lower than the 10-month median survival for non-arterial invasion patients ( P<0.001). The median survival for surgical patients with arterial invasion was 22 months, lower than the 24-month median for non-T 4 stage patients underwent surgery ( P<0.001) but significantly higher than for patients without surgery (T 4 stage patients without surgery: 8 months, P<0.001; non-T 4 stage patients without surgery: 6 months, P<0.001). For lymph node metastasis, patients with or without positive local lymph node metastasis had similar overall survival ( P>0.05). However, Patients with distant lymph node metastasis had significantly lower overall survival than that in patients without distant lymph node metastasis ( P<0.001). The multivariate logistic model indicated that tumor location in the body and tail ( OR=2.591, 95% CI: 2.343-2.867), positive regional lymph nodes ( OR=2.033, 95% CI: 1.836-2.252), and age <70 years old ( OR=1.183, 95% CI: 1.067-1.312) were risk factors for distant metastasis in arterial invasion patients. The multivariate Cox model showed that surgery ( HR=0.451, 95% CI: 0.405-0.503), radiotherapy ( HR=0.729, 95% CI: 0.677-0.784), chemotherapy ( HR=0.277, 95% CI: 0.258-0.297), tumor location in the body and tail ( HR=0.928, 95% CI: 0.874-0.985), and household income ≥$80, 000 ( HR=0.908, 95% CI: 0.853-0.968) were independent protective factors for prognosis in arterial invasion patients. Living in areas with a population ≤1 million ( HR=1.109, 95% CI: 1.044-1.178), age ≥70 years old ( HR=1.220, 95% CI: 1.150-1.296), larger tumor size (>2 cm but ≤4 cm: HR=1.124, 95% CI: 0.954-1.323; >4 cm: HR=1.310, 95% CI: 1.114-1.541), and having a metastatic burden (lung metastasis: HR=1.049, 95% CI: 0.869-1.267; distant lymph node metastasis: HR=1.179, 95% CI: 0.910-1.527; bone metastasis: HR=1.419, 95% CI: 0.854-2.359; brain or other metastasis: HR=1.519, 95% CI: 1.350-1.709; liver metastasis: HR=1.737, 95% CI: 1.600-1.886; two types of metastasis: HR=1.913, 95% CI: 1.689-2.168; three or more types: HR=2.436, 95% CI: 1.947-3.048) were independent risk factors for prognosis. The nomogram based on these prognostic factors had a C-index of 0.749 in the training set and 0.745 in the validation set; calibration curves in both sets were near the 45° line. Conclusions:High metastasis rates and low surgery rates are characteristic of pancreatic cancer with arterial invasion. Investigating the risk factors for distant metastasis and developing a prognostic nomogram incorporating metastatic burden hold significant clinical value for T 4 stage pancreatic cancer.

Fetal electrocardiogram (ECG) signals provide important clinical information for early diagnosis and intervention of fetal abnormalities. In this paper, we propose a new method for fetal ECG signal extraction and analysis. Firstly, an improved fast independent component analysis method and singular value decomposition algorithm are combined to extract high-quality fetal ECG signals and solve the waveform missing problem. Secondly, a novel convolutional neural network model is applied to identify the QRS complex waves of fetal ECG signals and effectively solve the waveform overlap problem. Finally, high quality extraction of fetal ECG signals and intelligent recognition of fetal QRS complex waves are achieved. The method proposed in this paper was validated with the data from the PhysioNet computing in cardiology challenge 2013 database of the Complex Physiological Signals Research Resource Network. The results show that the average sensitivity and positive prediction values of the extraction algorithm are 98.21% and 99.52%, respectively, and the average sensitivity and positive prediction values of the QRS complex waves recognition algorithm are 94.14% and 95.80%, respectively, which are better than those of other research results. In conclusion, the algorithm and model proposed in this paper have some practical significance and may provide a theoretical basis for clinical medical decision making in the future.
Algorithms ; Neural Networks, Computer ; Electrocardiography ; Databases, Factual ; Fetus

Purpose: Cavernous nerve injury induced erectile dysfunction (ED) is a refractory complication with high incidence in person under radical prostatectomy. Studies have shown that relaxin-2 (RLX-2) plays a vital role of endothelial protection, vasodilation, anti-fibrosis and neuroprotection in a variety of diseases. However, whether penile cavernous erection can benefit from RLX-2 remains unknown. The purpose of the experiment was to explore the effects of RLX-2 on ED in the rat suffering with bilateral cavernous nerve injury (BCNI). Materials and Methods: The rats were divided into three groups: Sham group was underwent sham operation, BCNI+RLX group or BCNI group was underwent bilateral cavernous nerve crush and then randomly treated with RLX-2 (0.4 mg/kg/d) or saline by continuous administration using a subcutaneously implanted micro pump for 4 weeks respectively. Then, erectile function was evaluated by electrical stimulation of cavernous nerves. Cavernous nerves and penile tissues and were collected for histological evaluation. Results: Erectile function of rats with BCNI was partially improved after RLX-2 treatment. The BCNI group had lower expression of relaxin family peptide receptor (RXFP) 1, p-AKT/AKT, p-eNOS/eNOS ratios than sham operation rats, but RLX-2 could partially reversed these changes. Histologically, the BCNI+RLX group had a significant effect on preservation of neurofilament, neuronal glial antigen 2 of penile tissue and nNOS of cavernous nerves when compared with BCNI group. RLX-2 could inhibited the lever of BCNI induced corporal fibrosis and apoptosis via regulating TGFβ1-Smad2/3-CTGF pathway and the expression of Bax/Bcl-2 ratio, caspase3. Conclusions RLX-2 could improve erectile function of BCNI rats by protecting cavernous nerve and endothelial function and suppressing corporal fibrosis and apoptosis via RXFP1 and AKT/eNOS pathway. Our findings may provide a promising treatment for refractory BCNI induced ED.

Objective:To explore the reasons for revision of tumor prosthesis of knee joint and summarize the experience of revision surgery.Methods:We conducted a retrospective study of 33 patients who underwent revision surgery for tumor prosthesis of knee joint in Tianjin Hospital and the 960th Hospital of the People's Liberation Army Hospital from June 2004 to June 2018. There were 25 male and 8 female patients, the mean age was 45±13.1 years (range 19-64 years) at the time of revision. Histological diagnosis was giant cell tumor in 17 patients, osteosarcoma in 9 patients, malignant fibrous histiocytoma in 3 patients and one for each of chondrosarcoma, peripheral schwannoma, ligamentoid fibroma and bone metastases. The reasons for revision were aseptic loosening in 23 cases, dislocation, stem breakage and periprosthetic fracture in 2 cases, infection in 3 cases, and local recurrence in 1 case. The general outcome, oncological outcome, reasons for prosthesis revision, postoperative limb function, and complications were summarized.Results:The median follow-up of the 33 patients was 48.0 (24.0, 107.0) months. The most common reason for revision was aseptic loosening (88%, 29/33), followed by infection (9%, 3/33) and local recurrence (3%, 1/33). The MSTS of 32 patients with survival more than 1 year was 24.28±4.74 points (range 9-30 points), which was statistically different from preoperative 11.78±5.23 points (range 4-21 points) ( t=10.02, P<0.001). The postoperative median TESS score of 32 patients with survival more than 1 year was 86.67(80.00, 91.67) points, and the preoperative median score was 56.0(43.17, 65.33) points, which was statistically significant ( Z=6.78, P<0.001). Postoperative complications occurred in 12 patients, most commonly mechanical problems (15%, 5/33) and infection (15%, 5/33), followed by local recurrence (6%, 2/33), with an overall complication rate of 36% (12/33). Conclusion:The main reason for revision of tumor prosthesis of knee joint is aseptic loosening. Revision surgery can achieve ideal postoperative function and should be the first choice for failure of prosthesis after initial replacement.

The brain pericyte is a unique and indispensable part of the blood-brain barrier (BBB), and contributes to several pathological processes in traumatic brain injury (TBI). However, the cellular and molecular mechanisms by which pericytes are regulated in the damaged brain are largely unknown. Here, we show that the formation of neutrophil extracellular traps (NETs) induces the appearance of CD11b⁺ pericytes after TBI. These CD11b⁺ pericyte subsets are characterized by increased permeability and pro-inflammatory profiles compared to CD11b^- pericytes. Moreover, histones from NETs by Dectin-1 facilitate CD11b induction in brain pericytes in PKC-c-Jun dependent manner, resulting in neuroinflammation and BBB dysfunction after TBI. These data indicate that neutrophil-NET-pericyte and histone-Dectin-1-CD11b are possible mechanisms for the activation and dysfunction of pericytes. Targeting NETs formation and Dectin-1 are promising means of treating TBI.
Blood-Brain Barrier/metabolism* ; Brain/pathology* ; Brain Injuries, Traumatic/metabolism* ; Extracellular Traps/metabolism* ; Histones ; Humans ; Lectins, C-Type ; Pericytes/pathology*

Objective:To explore the application effect of the "combination of virtuality and actuality" practical teaching on Medical Imaging Equipment. Methods:The 2018 medical imaging technology students of Qiqihar Medical University were taken as the observation group, and the study adopted teaching method of "combination of virtuality and reality" in the practical teaching of Medical Imaging Equipment, including in-kind visit teaching (8 learning hours), experimental box circuit measurement teaching (20 learning hours) and virtual simulation teaching (16 learning hours). Besides, the 2017 medical imaging major students (control group) did not conduct virtual simulation teaching. The teaching effect and student achievement were compared between the two groups, and SPSS 17.0 was used to conduct t test and chi-square test. Results:There was significantly improvement in the practical performance of the students in the observation group compared with the control group ( t=6.44, P=0.007); the teaching satisfaction of the two groups was significantly improved ( χ2=5.25, P=0.022), and the teaching satisfaction degree was 100%. Conclusion:The teaching method of "combination of virtuality and reality" can effectively improve students' hands-on ability, strengthens their cognition of abstract principles, and solves the problems of equipment failure analysis, disassembly and installation of large-scale equipment that cannot be completed in physical teaching.

Macrophages are widely distributed immune cells that contribute to tissue homeostasis. Human THP-1 cells have been widely used in various macrophage-associated studies, especially those involving pro-inflammatory M1 and anti-inflammatory M2 phenotypes. However, the molecular characterization of four M2 subtypes (M2a, M2b, M2c, and M2d) derived from THP-1 has not been fully investigated. In this study, we systematically analyzed the protein expression profiles of human THP-1-derived macrophages (M0, M1, M2a, M2b, M2c, and M2d) using quantitative proteomics approaches. The commonly and specially regulated proteins of the four M2 subtypes and their potential biological functions were further investigated. The results showed that M2a and M2b, and M2c and M2d have very similar protein expression profiles. These data could serve as an important resource for studies of macrophages using THP-1 cells, and provide a reference to distinguish different M2 subtypes in macrophage-associated diseases for subsequent clinical research.
Humans ; Macrophages/metabolism* ; Phenotype ; Proteomics ; THP-1 Cells