Purpose: The aim of this study is to determine the impact of solute carrier family 3 member 2 (SLC3A2) on the malignant phenotype of gliomas and its role in regulating ferroptosis sensitivity. Materials and Methods: The malignant phenotype of glioma was assessed by cell proliferation assay, colony formation assay, EdU assay, wound healing, and Transwell experiments. We further validated the impact of reduced SLC3A2 expression on the sensitivity to ferroptosis in glioma cells through Cell Counting Kit-8 assays, flow cytometry, western blotting, and transmission electron microscopy. Western blot was used to explore how SLC3A2 affects glioma sensitivity to ferroptosis through the AKT/NF-E2-related factor 2 (NRF2)/glutathione peroxidase 4 (GPX4) axis. By establishing a subcutaneous xenograft tumor model in BALB/c-nude mice, we investigated the growth of tumors following the knockout of SLC3A2 in glioma cells. Results: Downregulation of SLC3A2 suppressed the malignant phenotype of glioma by blocking the cell cycle and epithelial-mesenchymal transition processes. On the other hand, loss of SLC3A2 not only downregulated SLC7A11 but also prevented the activation of the AKT/NRF2/GPX4 axis. These lead to increased accumulation of reactive oxygen species and lipid peroxides, ultimately enhancing the susceptibility of glioma to ferroptosis. Conclusion Our findings suggest that SLC3A2 is an oncogene in gliomas, promoting their occurrence and development. It plays a critical role in ferroptosis resistance through the AKT/NRF2/GPX4 axis.

BACKGROUND:Intertrochanteric femoral fractures are the main type of fragility fracture in the elderly,and proximal femoral nail antirotation is the preferred surgical option,but the factors associated with postoperative internal fixation failure are controversial.OBJECTIVE:A new"three-column"classification of intertrochanteric femoral fractures was proposed by evaluating patients'imaging data preoperatively and analyzing its interaction with postoperative internal fixation failure.A risk prediction model was developed and validated by using numerical algorithms,which facilitates clinicians to identify and intervene in high-risk patients preoperatively.METHODS:Patients with intertrochanteric femur fractures in Sanshui Branch of Foshan Hospital of Traditional Chinese Medicine between June 2012 and June 2022 were selected.The patients were divided into the internal fixation failure group and the internal fixation maintenance group according to whether they had internal fixation failure after surgery.According to the preoperative radiographs,the proximal femur was divided into three columns:the medial column,the lateral column,and the middle column.Each column had different subgroups.The relationship between the morphological characteristics of the"three columns"and the failure of proximal femoral nail antirotation internal fixation was analyzed,and the independent risk factors for internal fixation failure were screened out by single and then multifactorial logistic regression analyses.A risk prediction model was constructed according to the independent risk factors using R language software.The Bootstrap method was used to resample 1 000 times.The area under the curve,calibration curve,and clinical decision curve were used to evaluate the differentiation,calibration ability,and clinical application value of the model.The Youden index was used to determine the optimal risk cut-off value of the prediction model,according to which the patients were divided into high and low risk groups.The stability and extensibility of the model were evaluated according to the accuracy of its risk prediction ability.RESULTS AND CONCLUSION:(1)The four independent risk factors for postoperative internal fixation failure after surgery were predicted using the"three-column"typing system:medial column(comminuted fracture of the lesser trochanter and femoral talar)[odds ratio=5.385,95％CI(1.961,14.782),P=0.001],medial column(chimney type)[odds ratio=2.893,95％CI(1.167,7.173),P=0.022],lateral column(lateral wall thickness＜20.5 mm)[odds ratio=2.804,95％CI(1.078,7.297),P=0.035]and lateral column(lateral wall fracture)[odds ratio=4.278,95％CI(1.670,10.959),P=0.012].(2)The constructed risk prediction model showed good discrimination and accuracy[area under the receiver operating characteristic curve=0.852,95％CI(0.837,0.922)].The calibration curve showed good agreement between the model-predicted risk and the actual risk of occurrence.(3)The clinical decision curve suggested that the model had good clinical applicability when the risk threshold probability was in the range of 0.2-0.82.The risk probability of 28％was the optimal threshold for risk stratification of the model,and the predictive performance of the model was better in patients with different risk groups.(4)The"three-column"typing system constructs a predictive model to calculate the risk probability of postoperative internal fixation failure in patients with intertrochanteric femoral fractures.This method is accurate,simple,and easy to apply clinically,and can be used as a digital tool to guide personalized clinical treatment.

Pancreatic neuroendocrine neoplasms(pNENs)are rare and highly heterogeneous pancreatic tumors with insidious clinical manifestations.They have a high propensity for distant metastasis,with liver metastases being the most common,significantly impacting patient prognosis.Despite extensive research on treating pNEN with liver metastases in recent years,many controversies and gaps remain.With the advancement of multidisciplinary treatment approaches,therapeutic strategies for pNEN liver metastases have been continuously refined,encompassing surgical resection,local therapies(such as radiofrequency ablation and transarterial interventions),and systemic treatments(including chemotherapy,targeted therapy,immunotherapy,radionuclide therapy,and endocrine therapy).Combination therapy has become an emerging trend.Radical surgery remains the preferred option for resectable cases,while for inoperable or treatment-intolerant patients,a rational combination of local and systemic therapies can improve survival outcomes.Additionally,endocrine therapy is crucial in symptom relief and quality-of-life improvement for patients with functional pNEN.Multidisciplinary collaboration in formulating individualized treatment plans can significantly enhance patient prognosis.This review summarizes recent advancements in treating pNEN liver metastases,providing a reference for clinical decision-making.

BACKGROUND:Intertrochanteric femoral fractures are the main type of fragility fracture in the elderly,and proximal femoral nail antirotation is the preferred surgical option,but the factors associated with postoperative internal fixation failure are controversial.OBJECTIVE:A new"three-column"classification of intertrochanteric femoral fractures was proposed by evaluating patients'imaging data preoperatively and analyzing its interaction with postoperative internal fixation failure.A risk prediction model was developed and validated by using numerical algorithms,which facilitates clinicians to identify and intervene in high-risk patients preoperatively.METHODS:Patients with intertrochanteric femur fractures in Sanshui Branch of Foshan Hospital of Traditional Chinese Medicine between June 2012 and June 2022 were selected.The patients were divided into the internal fixation failure group and the internal fixation maintenance group according to whether they had internal fixation failure after surgery.According to the preoperative radiographs,the proximal femur was divided into three columns:the medial column,the lateral column,and the middle column.Each column had different subgroups.The relationship between the morphological characteristics of the"three columns"and the failure of proximal femoral nail antirotation internal fixation was analyzed,and the independent risk factors for internal fixation failure were screened out by single and then multifactorial logistic regression analyses.A risk prediction model was constructed according to the independent risk factors using R language software.The Bootstrap method was used to resample 1 000 times.The area under the curve,calibration curve,and clinical decision curve were used to evaluate the differentiation,calibration ability,and clinical application value of the model.The Youden index was used to determine the optimal risk cut-off value of the prediction model,according to which the patients were divided into high and low risk groups.The stability and extensibility of the model were evaluated according to the accuracy of its risk prediction ability.RESULTS AND CONCLUSION:(1)The four independent risk factors for postoperative internal fixation failure after surgery were predicted using the"three-column"typing system:medial column(comminuted fracture of the lesser trochanter and femoral talar)[odds ratio=5.385,95％CI(1.961,14.782),P=0.001],medial column(chimney type)[odds ratio=2.893,95％CI(1.167,7.173),P=0.022],lateral column(lateral wall thickness＜20.5 mm)[odds ratio=2.804,95％CI(1.078,7.297),P=0.035]and lateral column(lateral wall fracture)[odds ratio=4.278,95％CI(1.670,10.959),P=0.012].(2)The constructed risk prediction model showed good discrimination and accuracy[area under the receiver operating characteristic curve=0.852,95％CI(0.837,0.922)].The calibration curve showed good agreement between the model-predicted risk and the actual risk of occurrence.(3)The clinical decision curve suggested that the model had good clinical applicability when the risk threshold probability was in the range of 0.2-0.82.The risk probability of 28％was the optimal threshold for risk stratification of the model,and the predictive performance of the model was better in patients with different risk groups.(4)The"three-column"typing system constructs a predictive model to calculate the risk probability of postoperative internal fixation failure in patients with intertrochanteric femoral fractures.This method is accurate,simple,and easy to apply clinically,and can be used as a digital tool to guide personalized clinical treatment.

Objective:To investigate the efficacy and safety of daratumumab-based regimens for the treatment of relapsed/refractory multiple myeloma (RRMM).Methods:A retrospective case series study was conducted. Thirty-seven RRMM patients treated with daratumumab-based regimens at Shanxi Bethune Hospital from January 2017 to November 2023 were selected, and their efficacy and adverse reactions were analyzed.Results:The median age [ M ( Q1, Q3)] of 37 RRMM patients was 62 (56, 68) years, the median number of previous treatment lines was 2 (1, 3.5) lines, 12 cases (32.4%) had extramedullary lesions, 12 cases (32.4%) had lactate dehydrogenase (LDH) ≥ 245 U/L, and 11 cases (29.7%) had previously received the third-line or more treatment. Among 27 patients who completed fluorescence in situ hybridization testing, 8 cases (29.6%) had high-risk cytogenetical changes. The median time from diagnosis to use of daratumumab was 23.1 (5.9, 52.0) months. The overall response rate (ORR) of 37 RRMM patients after treatment was 75.7% (28/37), with ORR of 88.0% (22/25) and 50.0% (6/12) for patients without and with extramedullary lesions, respectively, and the difference was statistically significant ( P = 0.036). The median follow-up time was 12.3 (4.6, 22.7) months, the median progression-free survival (PFS) time was 7.8 months (95% CI: 2.0- 13.7 months), and the median overall survival (OS) time was 22.4 months (95% CI: 17.5-29.5 months). The median PFS time for patients without and with extramedullary lesions was 11.8 and 4.2 months, and the median OS time was 23.5 and 8.3 months, respectively, and the differences in PFS and OS between the two were statistically significant (both P < 0.05); the median PFS time for patients with LDH ≥ 245 U/L and < 245 U/L was 6.5 and 11.9 months, and the median OS time was 30.2 and 12.1 months, respectively, and the differences in PFS and OS between the two were statistically significant (both P < 0.05). The incidence of non-hematological adverse reactions was 32.4% (12/37), with the most common being infusion-related adverse reactions (29.7%, 11/37), all of which were grade 1-2; the incidence of ≥ grade 3 hematological adverse reactions was 13.5% (5/37), with thrombocytopenia being the most common (8.1%, 3/37). Conclusions:The ORR of RRMM patients treated with daratumumab-based regimens is high, and the adverse reactions are tolerable.

Objective: To investigate the risk factors for wheezing during infancy in preterm infants after discharge and to develop a nomogram model for predicting wheezing. Methods: A total of 329 preterm infants were selected for this study. The data were randomly divided into a training set (n = 232) and a validation set (n = 97) in a 7 ∶3 ratio. The training set was further divided into a wheezing group (n = 73) and a non⁃wheezing group (n = 159) based on the occurrence of wheezing. Logistic regression analysis was used to identify independent risk factors for wheezing , and the R software was used to construct and validate the predictive model. Results : Compared with the non⁃wheezing group , the wheezing group had significantly lower gestational age , higher rates of mechanical ventila⁃tion , neonatal pneumonia , patent ductus arteriosus within 1 week , pulmonary hypertension , and prolonged antibiot⁃ic use (P < 0. 05) . The independent risk factors for wheezing in preterm infants during infancy included gestational age ( OR : 0. 96 , 95% CI: 0. 95 - 0. 98) , mechanical ventilation ( OR : 11. 08 , 95% CI: 6. 36 - 19. 31) , duration of antibiotic use ( ≥1 week vs < 1 week , OR : 5. 31 , 95% CI: 3. 19 - 8. 84) , 25% tidal volume expiratory flow 22. 58) , neonatal pneumonia ( OR : 4. 79 , 95% CI: 2. 83 - 8. 10) , and frequency of respiratory infections in the first six months ( ≥3 times vs < 3 times , OR : 5. 18 , 95% CI: 3. 10 - 8. 67) ( P < 0. 05) . The areas under the ROC curve (AUC) for the training and validation sets were 0. 889 (95% CI:0. 844 - 0. 934) and 0. 959 (95% CI: 0. 923 - 0. 995 ) , respectively. The calibration curve showed good agreement with the ideal curve , and decision curve analysis demonstrated high net benefit for predicting wheezing. Conclusion The nomogram model based on independent risk factors for wheezing in preterm infants provides a high level of accuracy and may serve as a useful reference for clinical practice.

Objective:This study aimed to evaluate the prognostic factors of clinical and histopathological parameters,including age,gender,tumor stage,tumor grade,tumor differentiation,lymph node metastasis(LNM),tumor frequency,and tumor count,in patients undergoing radical cystectomy(RC)combined with Mainz Pouch Ⅱ bladder reconstruction.Methods:A total of 237 bladder cancer patients(198 male and 39 female)who underwent RC combined with Mainz Pouch Ⅱ bladder reconstruction without chemotherapy or radiotherapy,from January 2004 to January 2023,were included in this study.Kaplan-Meier and Cox regression analyses were performed to assess the impact of age,tumor grade,tumor stage,tumor differentiation,LNM,tumor frequency,and tumor count on 5-year overall survival(OS)and 5-year cancer-specific survival(CSS).Results:The mean age at diagnosis was 59.8 years,with 198 male and 39 female patients.The mean follow-up duration was 47.8 months.In univariate analysis,patients younger than 65 years had significantly higher 5-year OS and 5-year CSS compared to those aged≥65 years.Patients with urothelial carcinoma showed better 5-year OS than those with non-urothelial carcinoma.Additionally,tumor stage,tumor grade,and LNM were negatively associated with 5-year OS and 5-year CSS.On multivariate analysis,only tumor grade and LNM remained statistically significant(P<0.05).Conclusions:Tumor grade and LNM were identified as independent prognostic risk factors for 5-year OS and 5-year CSS following RC combined with Mainz PouchⅡ bladder reconstruction.Moreover,the application of RC combined with Mainz Pouch Ⅱ bladder reconstruction should consider the patient's preferences and physical condition.

Objective:This study aimed to evaluate the prognostic factors of clinical and histopathological parameters,including age,gender,tumor stage,tumor grade,tumor differentiation,lymph node metastasis(LNM),tumor frequency,and tumor count,in patients undergoing radical cystectomy(RC)combined with Mainz Pouch Ⅱ bladder reconstruction.Methods:A total of 237 bladder cancer patients(198 male and 39 female)who underwent RC combined with Mainz Pouch Ⅱ bladder reconstruction without chemotherapy or radiotherapy,from January 2004 to January 2023,were included in this study.Kaplan-Meier and Cox regression analyses were performed to assess the impact of age,tumor grade,tumor stage,tumor differentiation,LNM,tumor frequency,and tumor count on 5-year overall survival(OS)and 5-year cancer-specific survival(CSS).Results:The mean age at diagnosis was 59.8 years,with 198 male and 39 female patients.The mean follow-up duration was 47.8 months.In univariate analysis,patients younger than 65 years had significantly higher 5-year OS and 5-year CSS compared to those aged≥65 years.Patients with urothelial carcinoma showed better 5-year OS than those with non-urothelial carcinoma.Additionally,tumor stage,tumor grade,and LNM were negatively associated with 5-year OS and 5-year CSS.On multivariate analysis,only tumor grade and LNM remained statistically significant(P<0.05).Conclusions:Tumor grade and LNM were identified as independent prognostic risk factors for 5-year OS and 5-year CSS following RC combined with Mainz PouchⅡ bladder reconstruction.Moreover,the application of RC combined with Mainz Pouch Ⅱ bladder reconstruction should consider the patient's preferences and physical condition.

Pancreatic neuroendocrine neoplasms(pNENs)are rare and highly heterogeneous pancreatic tumors with insidious clinical manifestations.They have a high propensity for distant metastasis,with liver metastases being the most common,significantly impacting patient prognosis.Despite extensive research on treating pNEN with liver metastases in recent years,many controversies and gaps remain.With the advancement of multidisciplinary treatment approaches,therapeutic strategies for pNEN liver metastases have been continuously refined,encompassing surgical resection,local therapies(such as radiofrequency ablation and transarterial interventions),and systemic treatments(including chemotherapy,targeted therapy,immunotherapy,radionuclide therapy,and endocrine therapy).Combination therapy has become an emerging trend.Radical surgery remains the preferred option for resectable cases,while for inoperable or treatment-intolerant patients,a rational combination of local and systemic therapies can improve survival outcomes.Additionally,endocrine therapy is crucial in symptom relief and quality-of-life improvement for patients with functional pNEN.Multidisciplinary collaboration in formulating individualized treatment plans can significantly enhance patient prognosis.This review summarizes recent advancements in treating pNEN liver metastases,providing a reference for clinical decision-making.

Objective To explore esomeprazole(EMZ)on acetaminophen(APAP)pharmacokinetics and intestinal microbial balance.Methods A total of 14 rats were randomly allocated into two groups,with 7 rats in each group:acetaminophen group(APAP group),and acetaminophen+esomeprazole combination group(APAP+EMZ group),respectively.Rats in the combination group were fed in the metabolic cage.Equivalent 3.6 mg·kg-1·d-1 esomeprazole was administered intragastrically to the combination group for 14 days;Similarly,an equal volume of 0.9％sodium chloride soution(NaCl)was fed to the APAP group for 14 days.During this period,fecal samples were collected from the rats before and after 14 days of EMZ administration for microbial 16S rRNA sequencing.On the 15th day,both the APAP group and APAP+EMZ groups were administratered an equivalent of 44.82 mg·kg-1 APAP by the same method after the regular EMZ administration.The concentrations of APAP in rat plasma were determined by the UPLC-MS/MS method.Main pharmacokinetic parameters were processed and compared using the software DAS 3.0.1 and SPSS 24.0.Results The pharmacokinetic parameter Cmax of APAP was significantly different between APAP group and APAP+EMZ group(P＜0.05).Compared with APAP group,Cmax increased by 120.38％in the APAP+EMZ group.The pharmacokinetic parameters(AUC(0-∞)、CL、t 1/2、tmax)of APAP showed no statistical differences between APAP group and APAP+EMZ group(P＞0.05).The results of 16SrRNA of intestinal flora showed that the abundance of Lactobacillus,Bacteroides,Clostridium,and Escherichia decreased compared with that before drug administration,while the abundance of Bifidobacterium increased.However,the relative abundance of the above flora showed no prominent differences before and after the EMZ intervention(P＞0.05).Conclusions This study showed that when combining EMZ with APAP,the relative abundance of those related flora,which may influence the β-Glucuronidase,all changed to some extent,but made no difference in statistics.The effect of EMZ on the Cmax of APAP was statistically significant.However,the use of EMZ for two weeks did not alter the other pharmacokinetics of APAP by affecting the gut microbiota.