Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

Objective To investigate the value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd-EOB-DTPA)enhanced MRI radiomics and signal intensity in hepatobiliary phase(HBP)in predicting the pathological differentiation degree of hep-atocellular carcinoma(HCC).Methods The clinical and imaging data of 224 patients pathologically confirmed with HCC were col-lected.All patients were randomly divided into test group(68 cases)and training group(156 cases)at a ratio of 7︰3.The ITK-SNAP software was used to delineate region of interest(ROI)on arterial phase(AP),portal venous phase(PVP)and HBP,the radiomics features of the tumor tissues were extracted and the radiomics models were established using the FAE software.Logistic regression analysis was used to determine the clinical independent predictors associated with the pathological differentiation degree of HCC and to construct clinical model and clinical-radiomics model.Receiver operating characteristic(ROC)curve was plotted for each model and the area under the curve(AUC)was calculated to compare the diagnostic efficacy of the models.Results Age,alpha-fetoprotein(AFP),and r-glutamyltransferase(r-GT)were independent risk factors for predicting the degree of pathological differentiation of HCC.The AUC of the clinical-radiomics model in the training group and test group were 0.825 and 0.779,respectively,which were higher than those of the radiomics model(0.812 and 0.771)and the clinical model(0.687 and 0.666).Conclusion Gd-EOB-DTPA enhanced MRI radiomics have certain value in predicting the degree of pathological differentiation of HCC,while the predictive value of the signal intensity on HBP and the signal intensity ratio(SIR)on HBP is limited.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Objective To investigate the value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd-EOB-DTPA)enhanced MRI radiomics and signal intensity in hepatobiliary phase(HBP)in predicting the pathological differentiation degree of hep-atocellular carcinoma(HCC).Methods The clinical and imaging data of 224 patients pathologically confirmed with HCC were col-lected.All patients were randomly divided into test group(68 cases)and training group(156 cases)at a ratio of 7︰3.The ITK-SNAP software was used to delineate region of interest(ROI)on arterial phase(AP),portal venous phase(PVP)and HBP,the radiomics features of the tumor tissues were extracted and the radiomics models were established using the FAE software.Logistic regression analysis was used to determine the clinical independent predictors associated with the pathological differentiation degree of HCC and to construct clinical model and clinical-radiomics model.Receiver operating characteristic(ROC)curve was plotted for each model and the area under the curve(AUC)was calculated to compare the diagnostic efficacy of the models.Results Age,alpha-fetoprotein(AFP),and r-glutamyltransferase(r-GT)were independent risk factors for predicting the degree of pathological differentiation of HCC.The AUC of the clinical-radiomics model in the training group and test group were 0.825 and 0.779,respectively,which were higher than those of the radiomics model(0.812 and 0.771)and the clinical model(0.687 and 0.666).Conclusion Gd-EOB-DTPA enhanced MRI radiomics have certain value in predicting the degree of pathological differentiation of HCC,while the predictive value of the signal intensity on HBP and the signal intensity ratio(SIR)on HBP is limited.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Objective:To explore the predictive value of 18F-FDG PET/CT in molecular subtyping of triple-negative breast cancer. Methods:A retrospective analysis was performed on the clinical and imaging data of 227 breast cancer patients who underwent 18F-FDG PET/CT examination in the Tianjin Medical University Cancer Institute & Hospital from January 1, 2010 to December 31, 2022. Based on the expression levels of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) in the primary breast cancer, the patients were categorized into two groups: triple-negative breast cancer (TNBC) and non-TNBC. Radiomic features were extracted from images of both groups, and a radiomic model was constructed to predict the molecular subtype of the TNBC groups. In addition, the clinical data, CT morphological features, and PET metabolic parameters of both groups were compared to determine the indicators with statistically significant differences and develop a comprehensive radiomic model combined with clinical characteristics. Results:Compared to the non-TNBC group, the TNBC groups exhibited more significant invasiveness in terms of tumor diameter, margins, ipsilateral axillary lymph node metastasis, invasion of neighboring skin or papillae, and PET metabolic parameters ( t = -3.19; χ2 = 7.30, 8.10, 5.34; t = 3.80, 3.30, 3.42, P < 0.05). The constructed 18F-FDG PET/CT radiomic model proved effective in predicting the molecular subtype of the TNBC group, and the receiver operating characteristic (ROC) curve showed an area under the curve (AUC) of 0.83 (95% CI 0.78-0.88), an accuracy of 75.9%, a sensitivity of 74.5%, and a specificity of 77.2%. In contrast, the constructed comprehensive radiomic model displayed an AUC of 0.86 (95% CI 0.81-0.90), an accuracy of 77.2%, a sensitivity of 78.6%, and a specificity of 75.9%. Conclusions:18F-FDG PET/CT plays an important role in predicting molecular subtypes of TNBC. The constructed radiomic model and comprehensive radiomic model can further enhance the prediction efficacy of PET metabolic parameters and accelerate the development of accurate treatment protocols in clinical practice, thus improving the prognosis of breast cancer.

Objective:To evaluate the efficacy and safety of unilateral adrenalectomy for treating primary bilateral macronodular adrenal hyperplasia (PBMAH) of different clinical types.Methods:The clinical and biochemical data of 54 patients with PBMAH who underwent unilateral adrenalectomy from May 2008 to March 2023 were retrospectively collected. Preoperative CT images of all patients showed enlarged bilateral adrenal glands with multiple nodules of " fused masses". Mean preoperative blood cortisol concentration at 8am was (21.5±7.7)μg/dl, urinary free cortisol concentration was (442.6±300.4)μg/24h, and mean 8am ACTH concentration was (6.4±2.3)pg/ml. Postoperative symptoms, BMI, blood pressure, mass diameter, cortisol and ACTH concentration were recorded and analyzed.Results:Compared with ordinary laparoscopic surgery, robot-assisted surgery showed shorter operation time [(115.4±22.1)min vs.(95.0±19.8)min, P=0.045]; less blood loss [(118.2±57.0)ml vs. (125.6±45.3)ml, P=0.441] and shorter hospitalization time [(5.2±0.9)day vs. (6.4±1.2)day, P=0.279]. Compared with laparoscopic surgery, open surgery showed longer operation time [(134 34.5) min vs. (104.3±20.1) min, P=0.035]; more blood loss [(305.5±85.2) ml vs. (122.5±44.3) ml, P=0.012] and longer hospitalization time[(10.4±3.2)day vs. (5.7±1.0) day, P=0.020]. The average follow-up time was (23.7±11.7) months. Sixteen cases biochemically relapsed, and the average relapse-free time was (25.4±13.4) month. Mean postoperative systolic blood pressure was (131.1±16.8)mmHg ( P=0.001) while diastolic blood pressure decreased to (82.2±11.1)mmHg ( P=0.002). Postsurgical average blood cortisol concentration decreased to (10.2±4.0)μg/dl ( P<0.01), while urine cortisol concentration decreased to (106.6±43.4)μg/24h( P<0.01). Average ACTH concentration increased to (12.6±4.1)pg/ml( P=0.005). Recurrent patients had higher preoperative blood and urine cortisol concentration(24.7±8.2)μg/dl( P=0.046), (522.8±234.2)μg/24h( P=0.028), and all of them underwent contralateral adrenalectomy. Conclusions:Unilateral adrenalectomy is safe and effective for treatment of PBMAH while part of patients biochemically relapsed. Subclinical patients were observed no recurrent cases after surgery. Recurrent patients have higher preoperative blood and urine cortisol levels and should undertake contralateral adrenalectomy and supplement corticosteroids for whole life.