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.

Stem-leaf saponins from Panax notoginseng (SLSP) comprise numerous PPD-type saponins with diverse pharmacological properties; however, their role in Parkinson's disease (PD), characterized by microglia-mediated neuroinflammation, remains unclear. This study evaluated the effects of SLSP on suppressing microglia-driven neuroinflammation in experimental PD models, including the 1-methyl-4-phenylpyridinium (MPTP)-induced mouse model and lipopolysaccharide (LPS)-stimulated BV-2 microglia. Our findings revealed that SLSP mitigated behavioral impairments and excessive microglial activation in models of PD, including MPTP-treated mice. Additionally, SLSP inhibited the upregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) and attenuated the phosphorylation of PI3K, protein kinase B (AKT), nuclear factor-κB (NFκB), and inhibitor of NFκB protein α (IκBα) both in vivo and in vitro. Moreover, SLSP suppressed the production of inflammatory markers such as interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α) in LPS-stimulated BV-2 cells. Notably, the P2Y2R agonist partially reversed the inhibitory effects of SLSP in LPS-treated BV-2 cells. These results suggest that SLSP inhibit microglia-mediated neuroinflammation in experimental PD models, likely through the P2Y2R/PI3K/AKT/NFκB signaling pathway. These novel findings indicate that SLSP may offer therapeutic potential for PD by attenuating microglia-mediated neuroinflammation.
Animals ; Panax notoginseng/chemistry* ; Saponins/pharmacology* ; Microglia/immunology* ; Mice ; NF-kappa B/immunology* ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/immunology* ; Phosphatidylinositol 3-Kinases/genetics* ; Male ; Parkinson Disease/immunology* ; Mice, Inbred C57BL ; Disease Models, Animal ; Plant Leaves/chemistry* ; Neuroinflammatory Diseases/drug therapy* ; Humans

Objective To observe the effects of ultrasound-guided serratus anterior plane block(SAPB)for pain relief in the acute phase of rib fractures and its impact on early rehabilitation.Methods This study included 160 patients from Taizhou Central Hospital with unilateral rib fractures undergoing conservative treatment.The patients were randomly divided into two groups,with 80 patients in each group.Group A received flurbiprofen alone for pain relief,while Group B received ultrasound-guided SAPB combined with flurbiprofen.Numerical rating scale(NRS)before treatment and at 1h,6h,12h,24h,and 48h after treatment,additional analgesic use,adverse reactions,functional recovery parameters(including vital capacity,peak expiratory flow,and walking distance),and hospital stay duration were recorded and compared between the two groups.Results The pain scores in Group B were significantly lower than those in Group A at 1h,6h,and 12h after treatment(P＜0.01),with no significant differences at 24h and 48h(P＞0.05).The use of additional analgesics and adverse reactions were significantly less in Group B compared to Group A(P＜0.01).Group B patients had significantly higher vital capacity,peak expiratory flow,and walking distance(P＜0.01).Additionally,the average hospital stay in Group B was significantly shorter than that in Group A(P＜0.01).Conclusion Ultrasound-guided SAPB combined with flurbiprofen is significantly more effective than flurbiprofen alone for treating rib fracture patients.SAPB provides more effective pain control,faster functional recovery,and has a high safety profile.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.

Objective To investigate the value of CT radiomics models based on intranodal and perinodal in distinguishing pulmonary cryptococcosis(PC)from lung adenocarcinoma.Methods A total of 194 patients,including PC(n=94)and lung adenocarcinoma(n=100),confirmed by surgical or puncture pathology were analyzed retrospectively and randomly divided into training set and test set in a ratio of 7∶3.3D Slicer was used to delineate and extract the intranodal and perinodal volume of interest(VOI)radiomics features within a 5 mm range.The minimum redundancy maximum relevance(mRMR)and least absolute shrinkage and selection operator(LASSO)methods were used to dimensionality reduction.Statistically significant indicators were screened by one-way logistic regression and further incorporated into the multifactor logistic regression model.Support vector machine(SVM)was used to construct the intranodal image-based radiomics model,the perinodal image-based radiomics model,the intranodal-and-perinodal image-based radiomics model,and the combined model.The diagnostic efficacy of each model was evaluated by receiver operating characteristic(ROC)curve.Results In the test set,the area under the curve(AUC)of the clinical imaging model,the intranodal image-based radiomics model,the perinodal image-based radiomics model,the intranodal-and-perinodal image-based radiomics model,and the combined model were 0.84,0.88,0.85,0.90,and 0.94,respectively.Conclusion The combined model based on clinical imaging features,intranodal and perinodal radiomics features can improve the ability of differentiating PC from lung adenocarcinoma.

Objective:To explore the application effect of the modified presentation assimilation discussion combined with heuristic clinical medicine teaching in training of extracorporeal membrane oxygenation specialist nurses.Methods:The convenient sampling method was used to select 62 nurses who participated in training of extracorporeal membrane oxygenation specialist nurses in the Second Affiliated Hospital of Zhengzhou University from January to June 2023 as the research objects. A total of 30 nurses who participated in the 25th training session from January to March 2023 were selected as the control group, and 32 nurses who participated in the 26th training session from April to June 2023 were selected as the observation group. The control group received conventional training method, while the observation group received modified presentation assimilation discussion combined with heuristic clinical medicine teaching. The theoretical knowledge and operational skills of nurses, core competence of extracorporeal membrane oxygenation specialist nurses and training satisfaction were compared between the two groups after training.Results:After training, the scores of theoretical knowledge and operational skills, core competence of extracorporeal membrane oxygenation specialist nurses and training satisfaction in observation group were higher than those in control group, and the differences were statistically significant ( P<0.05) . Conclusions:The modified presentation assimilation discussion combined with heuristic clinical medicine teaching can improve the theoretical knowledge and operational skills of extracorporeal membrane oxygenation specialist nurses, and the nurses' training satisfaction is higher.

Objective:To investigate the outcome after laparoscopic radical surgery for colorectal cancer in patients over 80 years of age with preoperative combined type 2 diabetes (T2DM).Methods:Clinical data of 919 patients who underwent colorectal cancer laparoscopic resection surgery in Shaanxi Provincial People′s Hospital from January 2015 to January 2019 were retrospectively analyzed. The propensity score matching (PSM) method was used for 1∶1 matching of gender, ASA score, preoperative serum albumin level, body mass index(BMI), preoperative haemoglobin level, clinical tumour pathology TNM staging, tumour location, other medical comorbidities and history of abdominal surgery and finally group of 104 elderly diabetic patients aged ≥80 years with combined T2DM were successfully matched with another 104 non-elderly non-diabetic patients <80 years without combined diabetes group. (1) To compare the differences in operating time, intraoperative bleeding, number of intraoperative blood transfusions, number of lymph nodes dissected, number of ICU treatments, postoperative time to exhaustion and postoperative hospital stay, and postoperative adjuvant chemotherapy between the two groups after matching. (2)To observe the difference in major postoperative complications between the two groups. (3) Patients in both groups were observed for three years post-operative survival rate during the follow-up period. SPSS 25.0 statistical software was used for data analysis. The survival analysis was carried aut by the Kaplan-Meier curve method in parallel and the Log-Rank test.Results:Both groups were balanced in terms of baseline variable after PSM ( P>0.05). There was no difference between the two groups in terms of operative time, intraoperative bleeding, number of intraoperative blood transfusions, number of lymph nodes dissected, or time to postoperative evacuation ( P>0.05). There was a statistically significant difference between two groups in the number of people admitted to the ICU for treatment ( χ2=4.04, P=0.042), and ≥80 years diabetic group was higher. The difference in the incidence of postoperative complications between the two groups was not statistically significant [34.6% (36/104) vs 25.0% (26/104), χ2=2.30, P=0.130]; according to the Clavien-Dindo classification of postoperative complications, the incidence of Clavien-Dindo grade Ⅲ complications in the group ≥80 years with diabetes mellitus were was higher than that in the group <80 years without diabetes [12.5% (13/104) vs 4.8% (5/104), χ2=3.89, P=0.049]. For local surgical complications, the incidence of postoperative anastomotic leak was significantly higher in the ≥80 years diabetic group than in the <80 years non-diabetic group ( χ2=4.70, P=0.030), and the incidence of postoperative wound infection was no statistical significance in the two group. For non-surgical local complications, there was a statistically significant difference in pulmonary infection in the ≥80 years diabetic group compared to the <80 non-diabetic group ( χ2=4.68, P=0.031) and in acute coronary syndrome ( χ2=4.02, P=0.045). Compared with the <80 years non-diabetic group, patients in the ≥80 years diabetic group had significantly longer postoperative hospital stay [(13.3±4.4)d vs (9.2±3.2) d, t=3.41, P=0.019]. The difference in adjuvant chemotherapy after surgery between the two groups was not statistically significant (67.3% vs 76.0%, χ2=1.92, P=0.166). The survival rate at 3 years after surgery was not statistically significant in both groups [68.9% vs 74.2%, χ2=4.34, P=0.085]. Conclusions:The short-term and long-term outcomes of colorectal cancer in advanced age with type 2 diabetes are satisfactory. Adequate preoperative assessment of the patient's physical condition should be carried out, close intraoperative control of blood glucose, and close postoperative monitoring and regulation of blood glucose should be performed, except for patients with severe comorbidities and coexisting diseases that cannot tolerate surgery and advanced tumours that have lost their surgical significance.

ObjectiveTo determine the epidemiological characteristics and distributions of measles in Baoshan District， Shanghai. MethodsThis study used the measles surveillance information and reporting system to collect reported cases of measles in Baoshan District in 2005‒2021 and then conducted descriptive epidemiological methods to determine the temporality using the concentration method. ResultsIn 2005‒2021， a total of 525 measles cases were reported in Baoshan District with an average annual reported incidence rate of 1.75/10⁵， showing an overall fluctuating downward trend and obvious seasonality. The cases concentrated in 30‒39 years of age （31.24%）， 20‒29 years （28.57%）， and under 5 years （16.57%）. Majority of them were workers （18.10%）， preschool children （16.19%）， and unemployed persons （12.76%）. The incidence was significantly higher in the central region than in the other two regions for workers， preschool children， and unemployed persons （χ²=54.515， P<0.001）. Spatially， the incidence was significantly higher in the north-central sub-districts than in the south （χ²=88.103， P<0.001）. Moreover， 33.14% of measles cases did not receive measles-containing vaccine （MCV）， while 53.90% of the cases remained unknown. Additionally， uptake rate of MCV in non-local residents was significantly lower than in local residents （χ²=14.422， P<0.001）. ConclusionThe measles incidence remains remarkably low in Baoshan District of Shanghai. Young and middle-aged populations in the north-central region are susceptible to measles. It is recommended to further strengthen measles surveillance， maintain high coverage of MCV among school-age children combined with catch-up immunization for at-risk populations， and improve health education.

OBJECTIVE: To investigate the clinical and prognostic characteristics of primary acute myeloid leukemia (AML) with 11q23/KMT2A rearrangements. METHODS: Clinical data of 90 patients with primary AML and 11q23/KMT2A rearrangements were analyzed retrospectively. RESULTS: By karyotyping analysis, 80 of the 90 patients had translocations involving 11q23/KMT2A, with t(9;11)(p22;q23), t(6;11)(q27;q23), t(10;11)(p12;q23) and t(11;19)(q23;p13) being the most common ones, while 10 cases were found to have non-translocation abnormalities. The overall complete remission (CR) rate was 75.6%, and patients with t(6;11) had lower CR rate compared with non-t(6;11) patients (47.1% vs. 82.2%, P = 0.005). After a median follow-up of 24.5 months, the patients receiving allo-hematopoietic stem cell transplantation (allo-HSCT) had significantly higher 3-year overall survival (OS) (80.3% vs. 16.6%, P < 0.001) and 3-year event-free survival (EFS) (73.5% vs. 16.3%, P < 0.001) compared with non-transplant patients. Patients with t(6;11) had the lowest 3-year OS (11.8% vs. 56.0%, P < 0.001) and 3-year EFS (5.9% vs. 53.8%, P < 0.001) compared with other type of abnormalities. No significant difference was noted in the survival between patients with t(9;11) and non-t(9;11) regardless whether they had received HSCT. CONCLUSION The clinical characteristics of primary AML with 11q23/KMT2A rearrangements are heterogeneous. Patients did not receive HSCT had poorer survival, particularly with the presence of t(6;11). Allo-HSCT could significantly improve the survival of such patients.
Humans ; Retrospective Studies ; Leukemia, Myeloid, Acute/therapy* ; Translocation, Genetic ; Gene Rearrangement ; Prognosis