Objective To explore the risk factors for vancomycin-related acute kidney injury(VA-AKI)in elderly patients.Methods Clinical data of elderly inpatients who used vancomycin at the Inner Mongolia Autonomous Region People's Hospital from January 2021 to June 2024 were retrospectively collected.The incidence of VA-AKI and the situation of treatment drug monitoring(TDM)were statistically analyzed.LASSO regression was used for feature selection,and this process was repeated 10,000 times.In each iteration,75％of the training samples were randomly selected,and the frequency of each feature being selected was counted.Finally,the features with higher frequency in multiple iterations were selected for model training.The data were divided into training set and test set at an 8∶2 ratio.Four machine learning prediction models,including Logistic regression,random forest,extreme gradient boosting(XGBoost),and support vector machine(SVM),were established.The accuracy and area under the receiver operating characteristic curve(AUC)of the above prediction models were calculated in the test set.The minimum depth distribution was used to visualize the importance of the characteristics of the model.Results A total of 305 elderly patients receiving vancomycin were included,among which 49 cases(16.07％)developed VA-AKI.LASSO regression analysis selected 7 characteristic variables to build 4 machine learning models,and finally selected the random forest model as the risk prediction model.The random forest model has an AUC value of 0.91,an accuracy of 0.89,an accuracy of 0.88,a recall rate of 0.98,and an F1 value of 0.93.The predictor importance ranking was in order of post-treatment creatinine level,C-reactive protein(CRP),albumin(Alb),respiratory failure,cardiac insufficiency,trough concentration time,and dose.Conclusion Post-treatment creatinine level,respiratory weakness,trough concentration time,cardiac insufficiency,Alb,CRP,and dosage were the risk factors for VA-AKI.The random forest model is the most effective in predicting the risk of VA-AKI in elderly patients,providing a reference for rational use of vancomycin in elderly patients.

Objective To explore the risk factors for vancomycin-related acute kidney injury(VA-AKI)in elderly patients.Methods Clinical data of elderly inpatients who used vancomycin at the Inner Mongolia Autonomous Region People's Hospital from January 2021 to June 2024 were retrospectively collected.The incidence of VA-AKI and the situation of treatment drug monitoring(TDM)were statistically analyzed.LASSO regression was used for feature selection,and this process was repeated 10,000 times.In each iteration,75％of the training samples were randomly selected,and the frequency of each feature being selected was counted.Finally,the features with higher frequency in multiple iterations were selected for model training.The data were divided into training set and test set at an 8∶2 ratio.Four machine learning prediction models,including Logistic regression,random forest,extreme gradient boosting(XGBoost),and support vector machine(SVM),were established.The accuracy and area under the receiver operating characteristic curve(AUC)of the above prediction models were calculated in the test set.The minimum depth distribution was used to visualize the importance of the characteristics of the model.Results A total of 305 elderly patients receiving vancomycin were included,among which 49 cases(16.07％)developed VA-AKI.LASSO regression analysis selected 7 characteristic variables to build 4 machine learning models,and finally selected the random forest model as the risk prediction model.The random forest model has an AUC value of 0.91,an accuracy of 0.89,an accuracy of 0.88,a recall rate of 0.98,and an F1 value of 0.93.The predictor importance ranking was in order of post-treatment creatinine level,C-reactive protein(CRP),albumin(Alb),respiratory failure,cardiac insufficiency,trough concentration time,and dose.Conclusion Post-treatment creatinine level,respiratory weakness,trough concentration time,cardiac insufficiency,Alb,CRP,and dosage were the risk factors for VA-AKI.The random forest model is the most effective in predicting the risk of VA-AKI in elderly patients,providing a reference for rational use of vancomycin in elderly patients.

BACKGROUND:Psoralen has a strong anti-osteoporotic activity and may have a restorative effect on chemotherapy-induced osteoporosis. OBJECTIVE:To explore the restorative effect of psoralen on the osteogenic differentiation of bone marrow mesenchymal stem cells in mice inhibited by cyclophosphamide and its mechanism. METHODS:C57BL/6 mouse bone marrow mesenchymal stem cells were isolated and cultured.Effect of psoralen on viability of bone marrow mesenchymal stem cells was detected by MTT assay.Osteogenic induction combined with alkaline phosphatase staining was used to determine the optimal dose of psoralen to restore the osteogenic differentiation of bone marrow mesenchymal stem cells inhibited by cyclophosphamide.The mRNA expression levels of Runx2,alkaline phosphatase,Osteocalcin,osteoprotegerin,and Wnt/β-catenin signaling pathway-related genes Wnt1,Wnt4,Wnt10b,β-catenin,and c-MYC were measured by RT-qPCR at different time points under the intervention with psoralen.The protein expression of osteogenic specific transcription factor Runx2 and Wnt/β-catenin signaling pathway related genes Active β-catenin,DKK1,c-MYC,and Cyclin D1 was determined by western blot assay at different time points under the intervention with psoralen. RESULTS AND CONCLUSION:(1)There was no significant effect of different concentrations of psoralen on the viability of bone marrow mesenchymal stem cells.The best recovery of the inhibition of osteogenic differentiation of bone marrow mesenchymal stem cells caused by cyclophosphamide was under the intervention of psoralen at a concentration of 200 μmol/L.(2)Psoralen reversed the reduction in osteogenic differentiation marker genes Runx2,alkaline phosphatase,Osteocalcin and osteoprotegerin mRNA expression and Runx2 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(3)Psoralen reversed the decrease in Wnt/β-catenin pathway-related genes Wnt4,β-catenin,c-MYC mRNA and Active β-catenin,c-MYC,and Cyclin D1 protein expression and the increase in DKK1 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(4)The results showed that cyclophosphamide inhibited osteogenic differentiation of bone marrow mesenchymal stem cells in mice,and psoralen had a restorative effect on it.The best intervention effect was achieved at a concentration of 200 μmol/L psoralen,and this protective effect might be related to the activation of Wnt4/β-catenin signaling pathway by psoralen.

Objective To investigate the expression of YWHAQ protein in gastric adenocarcinoma tissues and its correlation with clinical pathological features and prognosis. Methods A total of 127 patients with gastric cancer who underwent radical surgery were enrolled. Clinical data and postoperative cancer tissue samples were collected from the patients. Immunohistochemistry was used to detect the protein expression of YWHAQ in gastric adenocarcinoma tissues. The relationship between YWHAQ expression and clinical pathological features and prognosis was analyzed. Bioinformatics prediction was performed to identify potential pathways regulated by YWHAQ in gastric adenocarcinoma. A protein-protein interaction network for YWHAQ was constructed using the STRING database. Results YWHAQ gene expression was significantly higher in gastric adenocarcinoma tissues than in normal tissues (P<0.05). The expression level of the YWHAQ protein was significantly correlated with age, tumor invasion depth, lymph node metastasis, and tumor stage (P<0.05). Kaplan-Meier survival analysis showed that patients with high YWHAQ expression had significantly poorer long-term survival than those with low expression (P<0.0001). Cox regression analysis revealed that high YWHAQ expression and distant metastasis were independent risk factors for gastric cancer (HR>1, P<0.05). Enrichment analysis indicated that YWHAQ positively regulated processes such as cell cycle, angiogenesis, and DNA damage repair. Conclusion YWHAQ is highly expressed in gastric adenocarcinoma tissues and may be associated with the occurrence, invasion, and metastasis of gastric adenocarcinoma. High YWHAQ expression and distant metastasis are independent risk factors for the prognosis of gastric adenocarcinoma patients.

We report a family with multiple endocrine neoplasia type 1(MEN1), in which the proband presented with primary amenorrhea and was diagnosed with both a pituitary prolactinoma and an ACTH-secreting adenoma. Genetic testing identified a heterozygous MEN1 gene c. 1449_1476del mutation in the proband, as well as in six additional family members, who exhibited variable clinical phenotypes. Following initial transsphenoidal pituitary surgery, the proband's symptoms and biochemical abnormalities persisted, with elevated ACTH and cortisol levels. Functional imaging using [ 68Ga]-DOTA-TATE PET/CT confirmed residual pituitary tumor tissue, and a second surgery resulted in biochemical remission.

Aim To investigate the effect and potential mechanisms of tetramethylpyrazine(TMP)on athero-sclerotic plaques.Methods 43 ApoE-/-mice were used to establish the animal model of atherosclerosis(As)by high-fat diet for 8 weeks,3 of which were used for model outcome verification,and another 40 model mice were randomly divided into model group,TMP low dose(25 mg/kg)group,TMP medium dose(50 mg/kg)group,TMP high dose(100 mg/kg)group and atorvastatin(AT,2.6 mg/kg)group,with 8 mice in each group;another 8 C57BL/6J mice were set as control group.After gavaging administration for 8 weeks,the levels of total cholesterol(TC),triglyceride(TG),low density lipoprotein(LDL),high density lipoprotein(HDL)in the serum were detected by biochemical methods,and the As index was calculated.The levels of oxidized low density lipoprotein(ox-LDL),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),monocyte chemoattractant protein-1(MCP-1),intercellular adhesion molecule-1(ICAM-1)in serum were detected by ELISA method.The pathological changes of aorta was evaluated by HE staining.The aortic plaque formation was evaluated by oil red O staining,and the plaque area percentage was calculated.The aortic fibrosis was evaluated by Masson staining,and the collagen area percentage was calculated.The expression of monocyte macro-phage antibody-2(MOMA-2)and α-smooth muscle actin(α-SMA)in the aorta was detected by immunohistochemistry(IHC)method,and the plaque vulnerability index was calculated.The mRNA and protein expression of peroxisome pro-liferator-activated receptor γ(PPARγ),nuclear factor-κB p65(NF-κB p65)in aorta were detected by RT-qPCR or West-ern blot method.Results Compared with control group,the levels of TC,TG,LDL,ox-LDL,TNF-α,IL-1β,MCP-1,ICAM-1 in serum and As index of the mice were significantly increased in model group,while the level of HDL was sig-nificantly decreased(P＜0.05).The aorta showed pathological changes such as uneven thickening of the intima,accu-mulation of foam cells and fat cells,formation of a large number of plaques,lumen stenosis and infiltration of inflammatory cells;the percentage of aortic plaque area,percentage of collagen area,MOMA-2 and α-SMA positive area,plaque vulner-ability index were all significantly increased(P＜0.05).The mRNA and protein expression of PPARγ in aorta were sig-nificantly decreased,and the mRNA and protein expression of NF-κB p65 were significantly increased(P＜0.05).Com-pared with model group,the levels of TC,TG,LDL,ox-LDL,TNF-α,IL-1β,MCP-1,ICAM-1 in serum and As index of the mice were significantly decreased in the TMP medium,high dose group and AT group,the level of HDL was signifi-cantly increased(P＜0.05).The pathological changes of aorta were significantly improved.The plaque area percentage,collagen area percentage,MOMA-2 positive area percentage and plaque vulnerability index were significantly decreased,and the α-SMA positive area percentage was significantly increased(P＜0.05).The mRNA and protein ex-pression of PPARγ in aorta were significantly increased,the mRNA and protein expression of NF-κB p65 were significantly decreased(P＜0.05).Moreover,TMP exhibited a certain dose-dependent effect on various detection indicators(except MCP-1)in As mice.The regulatory effect of TMP high dose group on various detection indicators(except LDL and As index)in As mice was comparable or superior to those of AT group.Conclusion TMP can reduce the area of As plaque and improve the stability of vulnerable plaque in As mice,its mechanism may be related to regulating PPARγ/NF-κB signaling pathway,improving lipid metabolism and inhibiting inflammatory response.

Objective:To quantitatively evaluate the impact of hypothyroidism on renal function and address its underlying mechanisms using 99Tc m-diethylene triamine pentaacetic acid (DTPA) renal dynamic imaging. Methods:A total of 35 patients with differentiated thyroid cancer (12 males, 23 females, age (44.8±10.7) years), who were referred for radioiodine remnant ablation, were consecutively enrolled prospectively from October 2022 to October 2023 in Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. Serum examinations of thyroid- and renal function-relevant parameters and 99Tc m-DTPA renal dynamic imaging were performed before and 4 weeks after stopping taking levothyroxine ( L-T 4). Paired t test, Wilcoxon signed rank test and Wilcoxon rank sum test were used to analyze data. Results:After L-T 4 withdrawal, glomerular filtration rate (GFR) derived from renal dynamic imaging, estimated GFR (eGFR), and cystatin C level significantly decreased ((95.80±18.09) vs (89.86±15.58) ml/min; t=4.83, P<0.001; (108.27±18.39) vs (87.97±16.24) ml·min -1·1.73 m -2;t=9.37, P<0.001; (0.72±0.12) vs (0.64±0.15) mg/L; t=3.73, P=0.001). GFR decreased more robustly in male patients than in females (6.16(3.62, 14.89) vs 3.83(0.57, 8.25) ml/min; Z=-1.98, P=0.048). Additionally, 99Tc m-DTPA renal dynamic imaging revealed that the peak times of both left and right kidneys were significantly prolonged (3.03(2.53, 3.78) vs 3.04(2.53, 4.13) min; Z=-3.85, P<0.001; 3.14(2.46, 4.20) vs 3.50(2.74, 4.50) min; Z=-3.44, P=0.001), but the left and right renal half-excretion times remained stable ( Z values: -0.88, -0.48, P values: 0.381, 0.634). Conclusion:Based on the 99Tc m-DTPA renal dynamic imaging results, it can be demonstrated that hypothyroidism can lead to a significant decrease in renal function, and the possible reason might be the reduction in the blood perfusion of kidneys.

Aim To investigate the effect and potential mechanisms of tetramethylpyrazine(TMP)on athero-sclerotic plaques.Methods 43 ApoE-/-mice were used to establish the animal model of atherosclerosis(As)by high-fat diet for 8 weeks,3 of which were used for model outcome verification,and another 40 model mice were randomly divided into model group,TMP low dose(25 mg/kg)group,TMP medium dose(50 mg/kg)group,TMP high dose(100 mg/kg)group and atorvastatin(AT,2.6 mg/kg)group,with 8 mice in each group;another 8 C57BL/6J mice were set as control group.After gavaging administration for 8 weeks,the levels of total cholesterol(TC),triglyceride(TG),low density lipoprotein(LDL),high density lipoprotein(HDL)in the serum were detected by biochemical methods,and the As index was calculated.The levels of oxidized low density lipoprotein(ox-LDL),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),monocyte chemoattractant protein-1(MCP-1),intercellular adhesion molecule-1(ICAM-1)in serum were detected by ELISA method.The pathological changes of aorta was evaluated by HE staining.The aortic plaque formation was evaluated by oil red O staining,and the plaque area percentage was calculated.The aortic fibrosis was evaluated by Masson staining,and the collagen area percentage was calculated.The expression of monocyte macro-phage antibody-2(MOMA-2)and α-smooth muscle actin(α-SMA)in the aorta was detected by immunohistochemistry(IHC)method,and the plaque vulnerability index was calculated.The mRNA and protein expression of peroxisome pro-liferator-activated receptor γ(PPARγ),nuclear factor-κB p65(NF-κB p65)in aorta were detected by RT-qPCR or West-ern blot method.Results Compared with control group,the levels of TC,TG,LDL,ox-LDL,TNF-α,IL-1β,MCP-1,ICAM-1 in serum and As index of the mice were significantly increased in model group,while the level of HDL was sig-nificantly decreased(P＜0.05).The aorta showed pathological changes such as uneven thickening of the intima,accu-mulation of foam cells and fat cells,formation of a large number of plaques,lumen stenosis and infiltration of inflammatory cells;the percentage of aortic plaque area,percentage of collagen area,MOMA-2 and α-SMA positive area,plaque vulner-ability index were all significantly increased(P＜0.05).The mRNA and protein expression of PPARγ in aorta were sig-nificantly decreased,and the mRNA and protein expression of NF-κB p65 were significantly increased(P＜0.05).Com-pared with model group,the levels of TC,TG,LDL,ox-LDL,TNF-α,IL-1β,MCP-1,ICAM-1 in serum and As index of the mice were significantly decreased in the TMP medium,high dose group and AT group,the level of HDL was signifi-cantly increased(P＜0.05).The pathological changes of aorta were significantly improved.The plaque area percentage,collagen area percentage,MOMA-2 positive area percentage and plaque vulnerability index were significantly decreased,and the α-SMA positive area percentage was significantly increased(P＜0.05).The mRNA and protein ex-pression of PPARγ in aorta were significantly increased,the mRNA and protein expression of NF-κB p65 were significantly decreased(P＜0.05).Moreover,TMP exhibited a certain dose-dependent effect on various detection indicators(except MCP-1)in As mice.The regulatory effect of TMP high dose group on various detection indicators(except LDL and As index)in As mice was comparable or superior to those of AT group.Conclusion TMP can reduce the area of As plaque and improve the stability of vulnerable plaque in As mice,its mechanism may be related to regulating PPARγ/NF-κB signaling pathway,improving lipid metabolism and inhibiting inflammatory response.

The phenomenon that the listener's reception,perception,and understanding of a sound are dis-turbed by an irrelevant sound is called the auditory masking effect.In the auditory masking effect,the human audi-tory nervous system is able to screen and extract target sounds from different sound sources based on different cues,and filter out unwanted masked sounds.The auditory masking effect is not a simple processing from separation to integration however it is,with a complex internal mechanism.Under energetic masking,acoustic information such as frequency and intensity of target and masher generates coding competition in the auditory periphery.Under infor-mational masking,target sound and masher competes with perceptive and cognitive information in the auditory cen-ter.Informational masking is the focus of masking research,but its mechanism is still controversial.This study studies the neural mechanism of informational masking effect from three factors,including similarity,uncertainty and intelligibility.