Mechanical pain is one of the most common causes of clinical pain, but there remains a lack of effective treatment for debilitating mechanical and chronic forms of neuropathic pain. Recently, neurotoxin GsMTx4, a selective mechanosensitive (MS) channel inhibitor, has been found to be effective, while the underlying mechanism remains elusive. Here, with multiple rodent pain models, we demonstrated that a GsMTx4-based 17-residue peptide, which we call P10581, was able to reduce mechanical hyperalgesia and neuropathic pain. The analgesic effects of P10581 can be as strong as morphine but is not toxic in animal models. The anti-hyperalgesic effect of the peptide was resistant to naloxone (an μ-opioid receptor antagonist) and showed no side effects of morphine, including tolerance, motor impairment, and conditioned place preference. Pharmacological inhibition of TRPV4 by P10581 in a heterogeneous expression system, combined with the use of Trpv4 knockout mice indicates that TRPV4 channels may act as the potential target for the analgesic effect of P10581. Our study identified a potential drug for curing mechanical pain and exposed its mechanism.

Resistance to poly adenosine diphosphate (ADP)-ribose polymerase inhibitor (PARPi) presents a considerable obstacle in the treatment of ovarian cancer. F-box and tryptophan-aspartic (WD) repeat domain containing 11 (FBXW11) modulates the ubiquitination of growth-and invasion-related factors in lung cancer, colorectal cancer, and osteosarcoma. The function of FBXW11 in PARPi therapy is still ambiguous. In this study, RNA sequencing (RNA-seq) showed that FBXW11 expression was raised in ovarian cancer cells that had been treated with PARPi. FBXW11 was abnormally expressed at low levels in high-grade serous ovarian cancer (HGSOC) tissues, and low levels of FBXW11 were associated with shorter overall survival (OS) and progression-free survival (PFS) in HGSOC patients. Overexpressing FBXW11 made ovarian cancer more sensitive to PARPi, while knocking down FBXW11 made it less sensitive. The four-dimensional (4D) label-free quantitative proteomic analysis revealed that FBXW11 targeted S100 calcium binding protein A11 (S100A11) and promoted its degradation through ubiquitination. The increased degradation of S100A11 led to less efficient DNA damage repair, which in turn contributed to increased PARPi-induced DNA damage. The role of FBXW11 in promoting PARPi sensitivity was also confirmed in xenograft mouse models. In summary, our study confirms that FBXW11 promotes the susceptibility of ovarian cancer cells to PARPi via affecting S100A11-mediated DNA damage repair.

Objective:To investigate the value of biparametric-MRI (bpMRI) based peritumoral radiomics for preoperative prediction of extraprostatic extension (EPE) in prostate cancer (PCa).Methods:In this cross-sectional study, consecutive bpMRI of patients undergoing prostatectomy for PCa were retrospectively collected from the First Medical Center (center 1) and the Third Medical Center (center 2) of Chinese PLA General Hospital. A total of 274 patients were finally enrolled. Patients at center 1 from January 2020 to December 2022 were randomly divided into a training set (149 cases) and an internal validation set (63 cases) by stratified random sampling. Patients at center 2 from January 2023 to March 2024 were assigned to the external test set (62 cases). Patients were categorized into EPE-positive group and EPE-negative group according to pathological assessment postoperatively. In the training set, there were 49 cases in EPE-positive group and 100 cases in EPE-negative group. In the internal validation set, there were 26 cases in EPE-positive group and 37 cases in EPE-negative group. In the external test set, there were 22 cases in EPE-positive group and 40 cases in EPE-negative group. Axial T 2WI and apparent diffusion coefficient (ADC) images were manually annotated to obtain index lesion regions of interest (ROIs), with the peritumoral ROIs subsequently delineated by semi-automatic segmentation technique. Radiomics features were extracted from intra-tumoral, peri-tumoral, and intra-tumoral plus peri-tumoral ROIs. The training set data was employed to select and optimize features to build the radiomics models. The logistic regression analysis was used to develop radiomics, clinical, and integrated models. The predictive performance was assessed by the area under the receiver operating characteristic curve (AUC) in the external test set, and compared by the DeLong test. The sensitivity and specificity were compared by the exact McNemar test. Results:In the external test set, the peri-tumoral radiomics model based on bpMRI showed the highest performance in evaluating EPE, with an AUC of 0.739 (95% CI 0.611-0.842), which was identified as the optimal radiomics model. EPE grade ( OR=6.151, 95% CI 3.371-11.226, P<0.001) was incorporated into the clinical model, with an AUC of 0.780 (95% CI 0.657-0.875) in the external test set. The integrated model had an AUC of 0.817 (95% CI 0.698-0.904) in the external test set. There was no statistically significant difference in comparisons of AUCs among the three models (all P>0.05). The sensitivity of the integrated model (68.2%) showed no significant difference from those of the clinical model and the optimal radiomics model (77.3% and 86.4%, respectively; P=0.500 and P=0.289). However, the specificity of the integrated model (85.0%) was significantly higher than those of the clinical model (67.5%, P=0.016) and the optimal radiomics model (50.0%, P<0.001). Conclusion:A bpMRI-based peritumoral radiomics integrating clinical model demonstrates high performance for preoperative prediction of EPE in PCa.

Objective To investigate the status of management of iodinated contrast media(ICM)extravasation in Henan Province,as well as nurses' knowledge and influencing factors,in order to provide a basis for optimizing management strategies.Methods A self-designed questionnaire was applied,employing convenience sampling,to survey nursing administrators and nurses in the radiology departments of 55 tertiary hospitals across 16 regions of Henan Province,from December 2024 to January 2025.Multiple linear regression analysis was conducted to explore the factors influencing nurses' knowledge.Results A total of 55 nursing administrators and 64 nurses participated,with a valid questionnaire response rate of 100％.The survey results reveal that only 5.45％of radiology depart-ments utilized high-pressure central venous catheters,and 32.73％employed vascular visualization techniques.When setting the high-pressure injection speed for ICM,only 54.55％of radiology departments required an assessment of the type and model of intravenous access.Additionally,only 9.09％of radiology departments mandated an observa-tion for 2 to 4 hours following ICM extravasation.Furthermore,only 50.91％of radiology departments had estab-lished an information system for ICM use.The nurses' knowledge score regarding the prevention and management of ICM extravasation was(90.00±17.59),influenced by years of experience in radiology and professional titles(P＜0.05).Conclusion The prevention and management measures for ICM in radiology departments in Henan Province need further improvement.Nursing administrators should optimize management strategies,improve relevant training systems,and continuously enhance nurses' knowledge and practical abilities.

Objective To explore the value of nomogram of hepatocellular carcinoma(HCC)ultrasonic feature regression model for predicting microvascular invasion(MVI).Methods A total of 400 HCC patients(432 lesions)confirmed by pathology were retrospectively collected and divided into training set and validation set at the ratio of 7∶3.There were 280 cases(302 lesions)in training set,including 160 cases(172 lesions)of MVI(+)and 120 cases(130 lesions)of MVI(—),while 120 cases(130 lesions)in validation set,including 70 cases(76 lesions)of MVI(+)and 50 cases(54 lesions)of MVI(-).Univariate and multivariate logistic regression analyses were performed to analyze ultrasonic manifestations of HCC.The independent predictors of MVI of HCC were screened out,and a regression model and nomogram were established,and the efficacy,calibration and clinical value of the nomogram for predicting MVI of HCC were evaluated.Results The maximum diameter of HCC(OR=2.564),margin regular or not(OR=0.412),internal echo uniform or not(OR=1.875),the presence or absence of capsule(OR=0.305)and Adler blood flow grade(OR=3.502)were all independent predictors of MVI of HCC(all P＜0.05).The sensitivity,specificity,accuracy and the area under the curve(AUC)of the nomogram for predicting MVI of HCC in training set was 84.88％,81.05％,83.11％and 0.950,respectively,while in validation set was 78.95％,77.78％,78.46％and 0.910,respectively.Calibration curve and decision curve analysis indicated that this nomogram had good calibration and high clinical net benefit in both training and validation sets.Conclusion Nomogram of ultrasound feature regression model could be used to effectively predict MVI of HCC.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To investigate the relationship between serum orexin-A(OXA)and aspartate amin-otransferase(AST)levels and the disease severity and prognosis in patients with acute ischemic stroke(AIS).Methods A total of 167 AIS patients(AIS group)treated at Hebei Provincial People's Hospital from January 2021 to January 2024 and 84 healthy individuals undergoing physical examinations(control group)were selected as the research objects.AIS patients were categorized by severity into mild AIS group[National Institutes of Health Stroke Scale(NIHSS)score＜5,42 cases],moderate AIS group(NIHSS score 5—＜16,56 cases),moderate-to-severe AIS group(NIHSS score 16—＜21,36 cases),and severe AIS group(NIHSS score ≥21,33 cases).Based on 3-month prognosis(modified Rankin scale),patients were divided into poor prognosis group(＞2 grade,54 cases)and good prognosis group(≤2 grade,113 cases).Spearman correlation analysis was used to assess the relationship between NIHSS scores and serum OXA and AST levels in AIS pa-tients.Multivariate unconditional Logistic regression was used to determine the relationship between serum OXA and AST levels and the prognosis of AIS patients.Receiver operating characteristic(ROC)curve was used to analyze the predictive efficacy of serum OXA and AST levels for prognosis.Results Compared with the control group,serum OXA level in the AIS group was lower,while AST level was higher(P＜0.05).Ser-um OXA level progressively decreased,and AST level progressively increased across the mild,moderate,mod-erately severe,and severe AIS groups(P＜0.05).NIHSS score was negatively correlated with serum OXA level and positively correlated with AST level in AIS patients(P＜0.05).High OXA level was an independent protective factor for poor prognosis in AIS patients,while high AST level was an independent risk factor(P＜0.05).The area under the curve(AUC)of the combined assessment of serum OXA and AST levels in predic-ting poor prognosis in AIS patients was 0.873,which was greater than the AUC of OXA(0.793)and AST(0.770)alone(P＜0.05).Conclusion In AIS patients,lower serum OXA level and higher AST level are as-sociated with disease severity and poor prognosis.The combined evaluation of serum OXA and AST levels has higher predictive value for AIS prognosis.

Objective To investigate the correlations of serum levels of platelet activation com-plex-1(PAC-1)and soluble tumor necrosis factor-like weak inducer of apoptosis(sTWEAK)with neu-rological deficit and clinical prognosis in patients with acute cerebral infarction(ACI).Methods A total of 170 ACI patients(ACI group)and 85 healthy volunteers(control group)were enrolled in this study.Based on severity of neurological deficit assessed by the National Institutes of Health Stroke Scale(NIHSS)score,ACI patients were divided into of mild neurological deficit group(43 cases),moderate neurological deficit group(57 cases),moderate-to-severe neurological deficit group(37 cases),and severe neurological deficit group(33 cases).Additionally,based on the 6-month fol-low-up prognosis,ACI patients were divided into 51 cases of poor prognosis group and 119 cases of good prognosis group.Enzyme-linked immunosorbent assay was used to measure serum levels of PAC-1 and sTWEAK.Spearman correlation analysis was performed to evaluate their correlations with NIHSS scores in ACI patients.Multivariate unconditional Logistic regression analysis was conducted to determine their relationships with clinical prognosis.Receiver operating characteristic curves were used to explore their evaluation efficacy for poor clinical prognosis.Results Serum levels of PAC-1 and sTWEAK were significantly higher in the ACI group than in the control group(P＜0.05).Ser-um levels of PAC-1 and sTWEAK increased sequentially in the mild,moderate,moderate-to-severe,and severe neurological deficit groups(P＜0.05).Spearman correlation analysis showed that serum levels of PAC-1 and sTWEAK were positively correlated with NIHSS scores in ACI patients(rs=0.715 and 0.706,respectively;P＜0.001).Multivariate unconditional Logistic regression analysis revealed that older age,higher NIHSS score,larger infarct volume,higher PAC-1 level,and higher sTWEAK level were independent risk factors for poor prognosis in ACI patients(P＜0.05).The ar-ea under the curve for the combined assessment of serum PAC-1 and sTWEAK levels for poor clini-cal prognosis in ACI patients was 0.895,which was greater than the areas under the curve for the individual assessments(0.792 and 0.786,respectively;P＜0.05).Conclusion Elevated serum levels of PAC-1 and sTWEAK are closely related to increased neurological deficit and poor clinical prognosis in ACI patients.The combined detection of these two markers has high evaluation efficacy for clinical prognosis in ACI patients.

Resistance to poly adenosine diphosphate(ADP)-ribose polymerase inhibitor(PARPi)presents a considerable obstacle in the treatment of ovarian cancer.F-box and tryptophan-aspartic(WD)repeat domain containing 11(FBXW11)modulates the ubiquitination of growth-and invasion-related factors in lung cancer,colorectal cancer,and osteosarcoma.The function of FBXW11 in PARPi therapy is still ambiguous.In this study,RNA sequencing(RNA-seq)showed that FBXW11 expression was raised in ovarian cancer cells that had been treated with PARPi.FBXW11 was abnormally expressed at low levels in high-grade serous ovarian cancer(HGSOC)tissues,and low levels of FBXW11 were associated with shorter overall survival(OS)and progression-free survival(PFS)in HGSOC patients.Overexpressing FBXW11 made ovarian cancer more sensitive to PARPi,while knocking down FBXW11 made it less sensitive.The four-dimensional(4D)label-free quantitative proteomic analysis revealed that FBXW11 targeted S100 calcium binding protein A11(S100A11)and promoted its degradation through ubiquiti-nation.The increased degradation of S100A11 led to less efficient DNA damage repair,which in turn contributed to increased PARPi-induced DNA damage.The role of FBXW11 in promoting PARPi sensitivity was also confirmed in xenograft mouse models.In summary,our study confirms that FBXW11 promotes the susceptibility of ovarian cancer cells to PARPi via affecting S10OA11-mediated DNA damage repair.

OBJECTIVE To explore the clinical efficacy of dapagliflozin for stable coronary heart disease combined with heart failure （HF）. METHODS A prospective study method was employed. A total of 158 patients with stable coronary heart disease and HF admitted to our hospital from January 1， 2023， to January 1， 2024， were enrolled. Using a random number table method， they were divided into dapagliflozin group （n＝76） and conventional treatment group （n＝82）. All patients received conventional treatment， including diuretic， aspirin， losartan， metoprolol and statins. Patients in the dapagliflozin group were additionally administered Dapagliflozin tablets at a dose of 10 mg once daily on top of the conventional treatment. The treatment duration was six months. The changes in left ventricular ejection fraction （LVEF）， left ventricular end-systolic diameter （LVESD）， left ventricular end-diastolic diameter （LVEDD）， fasting blood glucose， N-terminal pro-brain natriuretic peptide （NT-proBNP）， the number of angina attacks， the duration of angina attacks， and lipoprotein-associated phospholipase A2 before and after treatment were compared between the two groups. The occurrence of adverse reactions such as renal dysfunction， liver dysfunction， urinary system infections， new-onset dialysis， hypotension and hypoglycemia was evaluated in the two groups during treatment. RESULTS During the study， 16 patients were lost to follow-up. Ultimately， 70 patients in the dapagliflozin group and 72 patients in the conventional treatment group completed the study. Before treatment， there were no statistically significant differences in the aforementioned indicators between the two groups （P＞0.05）. Compared with before treatment， after treatment， both groups showed significant shortening in LVESD and LVEDD， significant increases in LVEF， significant reductions in NT-proBNP and lipoprotein-associated phospholipase A2 levels， and significant reductions in the number of angina attacks and the duration of angina attacks （P＜0.05）； the improvements in the dapagliflozin group were more significant than those in the conventional treatment group （P＜0.05）. There was no statistically significant difference between the two groups in fasting blood glucose levels and the incidence of the aforementioned adverse reactions （P＞0.05）. CONCLUSIONS Adding dapagliflozin to conventional treatment can shorten LVESD and LVEDD， increase LVEF levels， reduce NT-proBNP and lipoprotein-associated phospholipase A2 levels， and decrease the number and duration of angina attacks in patients with stable coronary heart disease combined with HF， thereby improving their cardiac function， and demonstrates good safety.