OBJECTIVE To investigate the clinical characteristics of euglycemic diabetic ketoacidosis （euDKA） induced by empagliflozin， and provide references for safe medication. METHODS Case reports of euDKA induced by empagliflozin were retrieved and analyzed from PubMed， Web of Science， CNKI， and Wanfang Data. The Naranjo’s scale was adopted to assess the causal relationship between empagliflozin and euDKA. RESULTS A total of 29 patients were enrolled， including 16 males and 13 females，with a median age of 58 years. All patients were diagnosed with type 2 diabetes mellitus； 22 patients had at least one comorbidity. The median time to euDKA onset was 60 days after administration， and 7 cases occurred within 2 weeks of treatment. Perioperative periods，fasting，and low-carbohydrate or ketogenic diets were the main predisposing factors. Common presentations included nausea，vomiting， fatigue， tachypnea，and tachycardia. The causal relationship between empagliflozin and euDKA was assessed as “probable” in all cases. According to adverse reaction severity grading， 13 cases were grade 3 （severe） and 16 cases were grade 4 （life-threatening）. All patients discontinued empagliflozin and recovered after corresponding treatment. CONCLUSIONS euDKA is a serious adverse reaction to empagliflozin， which mostly occurs early in treatment. Perioperative periods， fasting， and ketogenic diets are prone to induce euDKA. Elderly patients and those with comorbidities are at higher risk. Risk assessment should be conducted before clinical administration； blood ketones and acid-base monitoring should be strengthened in the early medication period； withhold the drug before elective surgery， avoid prolonged fasting；upon diagnosis， discontinue empagliflozin and initiate intravenous insulin， provide fluid resuscitation promptly， and use other treatments to improve patient prognosis.

Objectives:To evaluate the hemodynamic impact of different bypass grafting methods on the left anterior descending(LAD)artery using computational fluid dynamics,providing a theoretical basis for optimizing coronary artery bypass grafting.Methods:A patient-specific 3D coronary model was constructed using SimVascular software,including an in-situ internal mammary artery graft(model 1)and three free grafts of varying diameters(model 2:2 mm internal mammary artery free graft;model 3 and model 4:3 mm and 4 mm great saphenous vein free grafts).The hemodynamic parameters of the native artery and grafts were compared among the four bypass grafting models.Results:All four bypass grafting models supply sufficient blood flow for the severely stenosed LAD.LAD flow was slightly lower in the model 1.Free internal mammary artery grafts showed higher flow and wall shear stress.4 mm great saphenous vein free grafts presented with maximum flow but lowest shear stress,3 mm great saphenous vein free grafts offered better hemodynamic stability.Conclusions:Computational fluid dynamics analysis indicates that free internal mammary grafts could provide superior hemodynamics,while larger grafts result in lower shear stress,which might affect long-term graft patency.These findings thus provide experimental evidences useful for optimizing LAD bypass strategies.

Objectives:To evaluate the hemodynamic impact of different bypass grafting methods on the left anterior descending(LAD)artery using computational fluid dynamics,providing a theoretical basis for optimizing coronary artery bypass grafting.Methods:A patient-specific 3D coronary model was constructed using SimVascular software,including an in-situ internal mammary artery graft(model 1)and three free grafts of varying diameters(model 2:2 mm internal mammary artery free graft;model 3 and model 4:3 mm and 4 mm great saphenous vein free grafts).The hemodynamic parameters of the native artery and grafts were compared among the four bypass grafting models.Results:All four bypass grafting models supply sufficient blood flow for the severely stenosed LAD.LAD flow was slightly lower in the model 1.Free internal mammary artery grafts showed higher flow and wall shear stress.4 mm great saphenous vein free grafts presented with maximum flow but lowest shear stress,3 mm great saphenous vein free grafts offered better hemodynamic stability.Conclusions:Computational fluid dynamics analysis indicates that free internal mammary grafts could provide superior hemodynamics,while larger grafts result in lower shear stress,which might affect long-term graft patency.These findings thus provide experimental evidences useful for optimizing LAD bypass strategies.

Objective To observe the value of diffusion-weighted imaging(DWI)parameters for evaluating grade of gliomas.Methods Totally 116 patients with glioma were retrospectively enrolled and divided into low-grade group(Ⅰ—Ⅱ,n=66)and high-grade group(Ⅲ—Ⅳ,n=50)according to 2000 WHO tumor grading criteria.Clinical and DWI data,including Ki-67 labeling index(LI),apparent diffusion coefficient(ADC),exponential ADC(EADC)and relative ADC(rADC)were compared between groups.The correlations of ADC,EADC and rADC with Ki-67 LI were explored,and the efficacy of above indexes for evaluating grade of glioma was analyzed.Results Significant differences of Ki-67 LI,ADC,EADC and rADC were found between groups(all P＜0.05).ADC and rADC of glioma were negatively correlated(r=-0.565,-0.625,both P＜0.05),while EADC was positively correlated with Ki-67 LI(r=0.587,P＜0.05).ADC,EADC,rADC and Ki-67 LI were all impact factors of grade of glioma(all P＜0.05),with the area under the curve of 0.768,0.802,0.788 and 0.793,respectively,and AUC of the combination of the four was 0.874,significantly higher than each index alone(all P＜0.05).Conclusion ADC,EADC and rADC were helpful for evaluating grade of glioma.Combining with Ki-67 LI could further improve diagnostic efficacy.

Objective:To investigate the correlation between pathological features at the positive margins and biochemical re-currence after radical prostatectomy for prostate cancer.Methods:From June 2014 to December 2019,a total of 200 patients with organ-confined prostate cancer who underwent radical prostatectomy were included in this study by the method of case matching(1:1).One hundred patients with positive surgical margin and 100 with negative surgical margin were enrolled in this study.All patients did not receive any adjuvant treatment after surgery with a clinical stage of T2/N0.BCR-free survival was estimated using the Kaplan-Meier method.An optimal cutoff for the PSM length which differentiated risk for BCR was identified by Classification and Regression Tree analysis(CART).Cox proportional hazards regression model was used to assess the association between variables and BCR-free surviv-al.Results:A total of 200 patients were included in this study,and 177 patients with pT2 stage were pathological after operation.The median follow-up time of this group of patients was 32.8 months ranged from 5.6 to 80.5 months.A total of 28 cases of biochemi-cal recurrence were found through PSA follow-up after surgery,including 6 cases(6.0％)in the negative margin group and 22 cases(22.0％)in the positive margin group.The result of Kaplan Meier survival curve analysis showed that the non biochemical recurrence survival time of the negative margin group was longer than that of the positive margin group(log rank x2=9.336,P=0.003).It was found that the length of positive margin≥1 mm in the positive margin group was positively correlated with postoperative biochemical re-currence.Multivariate Cox proportional hazards regression was used to identify that the highest Gleason score ≥8 and the length of pos-itive ≥ 1 mm were independent factors of postoperative biochemical recurrence in both the overall patients and the patients with positive margin.Conclusion:The patients with highest Gleason score ≥8 and the length of positive ≥1mm are at elevated risk for BCR.

Hemorrhagic shock is a common clinical emergency that can aggravate cell injury after resuscitation. Astrocytes are crucial for the survival of neurons because they regulate the surrounding ionic microenvironment of neurons. Although hemorrhagic shock and resuscitation (HSR) injury can impair cognition, it remains unclear how this insult directly affects astrocytes. In this study, we established an HSR model by bleeding and re-transfusion in mice. The social interaction test and new object recognition test were applied to evaluate post-operative cognitive changes, and the results suggest that mice experience cognitive impairment following exposure to HSR. In the HSR group, the power spectral density of β and γ oscillations decreased, and the coupling of the θ oscillation phase and γ oscillation amplitude was abnormal, which indicated abnormal neuronal oscillation and cognitive impairment after HSR exposure. In brief, cognitive impairment in mice is strongly correlated with Ca²⁺ signal strength in lateral septum astrocytes following HSR.
Animals ; Astrocytes/metabolism* ; Shock, Hemorrhagic/metabolism* ; Resuscitation/adverse effects* ; Male ; Mice ; Calcium Signaling/physiology* ; Mice, Inbred C57BL ; Septal Nuclei/metabolism* ; Cognitive Dysfunction/etiology* ; Disease Models, Animal ; Cognition Disorders/etiology*

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective To observe the value of diffusion-weighted imaging(DWI)parameters for evaluating grade of gliomas.Methods Totally 116 patients with glioma were retrospectively enrolled and divided into low-grade group(Ⅰ—Ⅱ,n=66)and high-grade group(Ⅲ—Ⅳ,n=50)according to 2000 WHO tumor grading criteria.Clinical and DWI data,including Ki-67 labeling index(LI),apparent diffusion coefficient(ADC),exponential ADC(EADC)and relative ADC(rADC)were compared between groups.The correlations of ADC,EADC and rADC with Ki-67 LI were explored,and the efficacy of above indexes for evaluating grade of glioma was analyzed.Results Significant differences of Ki-67 LI,ADC,EADC and rADC were found between groups(all P＜0.05).ADC and rADC of glioma were negatively correlated(r=-0.565,-0.625,both P＜0.05),while EADC was positively correlated with Ki-67 LI(r=0.587,P＜0.05).ADC,EADC,rADC and Ki-67 LI were all impact factors of grade of glioma(all P＜0.05),with the area under the curve of 0.768,0.802,0.788 and 0.793,respectively,and AUC of the combination of the four was 0.874,significantly higher than each index alone(all P＜0.05).Conclusion ADC,EADC and rADC were helpful for evaluating grade of glioma.Combining with Ki-67 LI could further improve diagnostic efficacy.

Objective:To investigate the risk factors for patients with hypertriglyceridemia-related acute pancreatitis (HTG-AP) developing into severe acute pancreatitis or experiencing organ failure.Methods:This retrospective cohort study collected clinical data from 2 429 patients diagnosed with acute pancreatitis from five hospitals in China between January 2019 and December 2023 using a pre-designed data collection form. The cohort included 1 516 males and 913 females,with an age of (50.2±16.5)years(range: 11 to 99 years). Among them,353 patients (16.1%) had HTG-AP,while 1 846 (83.9%) had non-HTG-AP. HTG-AP was defined as serum triglyceride levels>500 mg/dl with other etiologies excluded. Intergroup comparisons were performed using t-tests,Mann-Whitney U test or χ2 tests,respectively. Univariate and multivariate logistic regression analyses were conducted to assess risk factors for severe acute pancreatitis after adjusting for potential confounders,and a predictive model was developed and validated. Results:Compared with other etiologies,HTG-AP patients had a higher risk of progressing to SAP ( OR=1.415,95% CI: 0.866 to 2.312, P=0.017) and organ failure ( OR=1.256,95% CI: 1.015 to 1.554, P=0.036). Among HTG-AP patients,risk factors for SAP included body mass index ( OR=1.856,95% CI: 1.742 to 1.987, P=0.033),fasting blood glucose ( OR=1.128,95% CI: 1.036 to 1.229, P=0.006),white blood cell count( OR=1.162,95% CI: 1.055 to 1.281, P=0.002),and the presence of pleural effusion ( OR=13.151,95% CI: 4.330 to 19.946, P<0.01). A nomogram prediction model for SAP in HTG-AP was constructed based on these risk factors,demonstrating good discriminative ability with area under the curve values of 0.877 in the training set and 0.894 in the validation set,along with satisfactory calibration. Conclusions:HTG-AP patients are at higher risk of developing SAP and organ failure. The risk prediction model incorporating body mass index,fasting blood glucose,white blood cell count,and pleural effusion shows good predictive value for SAP.