Occult breast cancer is a rare disease with the primary symptom of enlarged ipsilateral axillary lymph node. At present,it is still difficult to diagnose occult breast cancer. The diagnosis is based on the core needle biopsy and following immunohistochemical staining for the enlarged lymph nodes. If the results support,the diagnosis can be confirmed after the exclusion of other primary tumors. The standard treatment of occult breast cancer is still the mastectomy and axillary lymph node dissection. Neoadjuvant chemotherapy is an independent factor affecting the prognosis,which is also recommended before the oper-ation. Chemotherapy,radiotherapy and endocrine therapy could be chosen based on immunohistochemical results after surgical treatment. The prognosis of occult breast cancer is similar to the other types of breast cancer at the same staging.

Objective To investigate the early alterations of neurometabolites in the splenium of corpus callosum by proton magnetic resonance spectroscopy (~1H-MRS) in patients with diffuse axonal injury (DAI) at early stage and their prognostic value. Methods Twenty-one patients with DAI underwent 1H-MRS examination in the splenium of corpus callosum 2 to 14 d after injury, the neurometabolite alterations were evaluated and compared with those of 10 healthy subjects (normal controls). Logistic regression analysis was performed to explore the correlation among neurometabolite alterations, clinical indexes and Glasgow outcome scale (GOS) six months after injury. Results There was a significant decrease in NAA/Cr and NAA/Cho and increase in Cho/Cr in the splenium of corpus callosum in patients with DAI as compared with control group (P<0.05), and these trends tended to be more evident with the increase of injury severity. NAA/Cr and NAA/Cho in patients with poor outcomes were lower than those in patients with good outcomes (P<0.05). NAA/Cr, NAA/Cho and Cho/Cr predicted long-term outcome with 89% accuracy, and the combination with GOS provided the predictive accuracy of 94%. Conclusion ~1H-MRS examination in the splenium of corpus callosum at early stage of DAI can depict brain injury severity, and is useful in predicting outcomes.

Objective To observe the spatiotemporal characteristics of the micro-structural injury in a rat model of diffuse axonal injury (DAI) and quantitatively assess the axonal injury severity in the vulnerable areas. Methods The 7.0 T MRI was performed in rats in DAI group (n =20) and control group ( n = 15 ) to synthesize the diffusion tensor imaging ( DTI) parameter map and calculate the parameter value of the vulnerable areas. Immunohistochemistry was used to detect β-APP expression in the vulnerable areas and the IPP software to quantitatively assess the axonal injury severity. Results Compared with the control group, FA and AD maps showed local signal defection or reduction in the corpus callosum and their values decreased significantly in the brain stem and corpus callosum in the DAI group (P ＜0.01 ). The integrated optical density (IOD) value of the vulnerable areas in the DAI group was significantly higher than that of the control group ( P ＜ 0. 01 ) , with the highest level in the brain stem (P＜0.05). The normalized FA, AD and ADC in the vulnerable areas were correlated negatively with the IOD (P ＜ 0.05). Conclusion DTI can detect invisible micro-structural injury in the vulnerable areas and quantitatively assess the axonal injury severity in vivo in the early stage.

Objective To investigate the brain metabolic changes and evaluate their spatial distributions after traumatic axonal injury (TAI)in rats by using proton magnetic resonance spectroscopy(1H-MRS).Methods The TAI model was made by subjecting the head of the rats to the linear and angular accelerations.The multi-voxel MRS was employed to detect the tissue metabolic state at the levels of hippocampus-caudate and pons prior to injury and at 24 hours after injury.The alterations of NAA/Cr,NAA/Cho and Cho/Cr values as well as the spatial distribution of NAA/Cr reduction were accessed. Immunohistochemical staining for β-APP was used to observe the injured axons. Results A siguificantdecrease in NAA/Cr and NAA/Cho(P<0.05)and subtle increase in Cho/Cr(P>0.05)were observed in rats at 24 hours after TAI in comparison to the pre-injury levels.Notable decrease in NAA/Cr value was observed in the areas including the brain stem,hippocampus,internal capsule,corpus callosum and thalamus,where axonal injuries were confirmed by the histological examination. Conclusion Metabolic imbalances Occur in the brains of rats with TAI.with notable changes in the brain stem and the hippocampus.

AIM: To study the effects of over-expression of tricarboxylic acid cycle intermediates transporter NaDC3 (high affinity sodium-dependent dicarboxylate transporter) on energy metabolism and ROS generation in human renal tubular cells. METHODS: Recombinant retrovirus vector containing NaDC3 gene was constructed and used for infecting human renal tubular epithelial cell HKC. Control vector containing Neo gene was also constructed and infected cells. Liquid scintillation method was used to determine the level of [~3H]-succinate (as a transport substrate of NaDC3) in the cells. Clark electrode method and reverse phase HPLC were used to detect oxygen consumption and ATP content intracellularly, respectively. Mitochondrial membrane potential and reactive oxygen species (ROS) content in HKC were determined with laser confocal microscope after treatment with fluorescent probe JC-1 and CM-H_2DCFDA, respectively. RESULTS: Western blotting analysis showed that the expression of NaDC3 protein in uninfected- and control vector-infected cells was at lower level. After infection with recombinant NaDC3 vector, expression level of NaDC3 protein in HKC cells was increased markedly. Transport assay revealed that the level of [~3H]-succinate in NaDC3-infected cells was noticeably increased. Oxygen consumption and ATP content in NaDC3-infected HKC were significantly higher than those in uninfected- and control vector-infected cells. Laser confocal analysis revealed that mitochondrial membrane potential and ROS level in NaDC3-infected HKC were increased, compared with uninfected- and control vector-infected cells. CONCLUSION: Over-expression of NaDC3 accelerates the speed rate of energy metabolism and increases intracellular ROS generation by transporting an overdose of tricarboxylic acid cycle intermediates in human renal tubular epithelial cells.

Objective:To optimize the injection protocol of contrast medium for contrast-enhanced MRA (CEMRA) of pulmonary artery and to evaluate the diagnostic value of CEMRA and pulmonary perfusion imaging (PPI) in an experimental model of acute pulmonary embolism. Methods:CEMRA and PPI were performed in 6 normal pigs with different doses of gadolinium contrast agent (5ml, 10ml, 15ml, 20ml and 25ml) at an injection rate of 3ml/s, and 3 pulmonary embolism models were injected with 20 ml contrast agent at 3 ml/s. DSA was also performed for comparison. Results:The signal intensities and the signal to noise ratios of the pulmonary arteries kept increasing with the dose increase of the contrast agent, but the best angio-pulmonary contrast dose was 10-15ml (0.25-0.375mmol/kg), while the optimal dose for PPI was 15-20ml (0.375-0.5mmol/kg). Although CEMRA demonstrated less obstructed pulmonary arteries than DSA (5/10 vs 8/10)did, it detected all obstructions when combined with PPI. The pulmonary infarction zones showed wedge-shaped perfusion defects on the PPI images, with the signal intensities lower than those of the normal areas (137.86±45.32 vs 330.14±46.52, P<0.001). Conclusion:It is suggested that the optimal dose of the contrast agent is 0.25mmol/kg to 0.375mmol/kg for CEMRA, and 0.375mmol/kg to 0.5mmol/kg for lung perfusion. CEMRA combined with PPI may be better than DSA in demonstrating pulmonary embolism.

Objective:To investigate the prognosis and related factors of ischemic cardiomyopathy.Methods:Clinical data of 271 patients with acute decompensated chronic heart failure admitted to the Cardiac Intensive Care Unit of Tianjin Chest Hospital from December 2019 to June 2022 were enrolled, including 135 cases with ischemic cardiomyopathy (ICM group) and 136 cases with non-ischemic cardiomyopathy (NICM group). Patients were followed up for 48 weeks; and the primary endpoint was all-cause death and/or readmission due to heart failure, the secondary end point was cardiogenic death. Kaplan-Meier survival curve was used to compare the difference in prognosis between the two groups. Univariate and multivariate Cox regression models were used to evaluate the factors influencing the primary and secondary end points of ischemic cardiomyopathy.Results:Compared with the NICM group, ICM group had higher proportion of patients with older age, fast pulse rate, high body mass index, comorbidities of hypertension, diabetes, chronic kidney disease, stroke or peripheral vascular disease; and greater left ventricular end-diastolic diameter, right ventricular end-diastolic anteroposterial diameter, pulmonary artery systolic blood pressure, and left ventricular ejection fraction (all P<0.05). Kaplan-Meier survival analysis showed that survival without primary endpoint (Log-rank P=0.009) and survival without secondary endpoint (Log-rank P=0.037) were lower in the ICM group than in the NICM group. Multivariate Cox regression analysis showed that elevated triglyceride (TG)/high density lipoprotein-cholesterol (HDL-C) ratio and elevated neutrophil percentage were independent risk factors for primary and secondary endpoint events in patients with ischemic cardiomyopathy. Conclusions:Patients with ischemic cardiomyopathy have lower survival rates than those with non-ischemic cardiomyopathy. High levels of TG/HDL-C ratio and neutrophil percentage are independent risk factors for poor prognosis in ischemic cardiomyopathy.

B-cell acute lymphoblastic leukemia(ALL)is a hematological malignancy.Blinatumomab,as a therapeutic target,targeting CD19,has demonstrated notable efficacy as a safe bridge to allogeneic hematopoietic stem cell transplantation(allo-HSCT)in patients with re-lapsed/refractory acute lymphoblastic leukemia(R/R B-ALL).In the treatment of newly diagnosed ALL,blinatumomab,when combined with chemotherapy or other immunotherapies,reduces toxicity while ensuring efficacy.Similarly,combining blinatumomab with second-or third-generation tyrosine kinase inhibitors(TKIs)for the treatment of Philadelphia chromosome--positive(Ph+)ALL holds promise for eliminating the need for subsequent allo-HSCT in patients.Disease relapse and long-term survival of patients are closely related to minimal residual dis-ease(MRD)at the conclusion of treatment,and blinatumomab contributes to enhancing the MRD conversion rate in patients with ALL,thus improving the long-term prognosis.This article comprehensively reviews the clinical trials and current progress of blinatumomab in various B-ALL patient groups.

Objective:To investigate the relation between rs2298771 genotype in voltage-gated sodium channels 1A ( SCN1A) polymorphism and antiepileptic drug (AED) response in children with epilepsy. Methods:Sixty-two children with epilepsy admitted to Department of Neurology, Zhangjiakou First Hospital from June 2022 to December 2023 were divided into AED response group and AED resistance group ( n=31) according to their response to AED. In addition, 31 children with pharyngitis or mild gastroenteritis admitted to Department of Pediatrics at the same period were selected as control group. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to analyze the rs2298771 genotype in SCN1A polymorphism, and differences in rs2298771 genotype and allele in SCN1A polymorphism were compared among the 3 groups. Relation between rs2298771 genotype in SCN1A polymorphism and AED response was analyzed. Multivariate Logistic regression was used to analyze the influencing factors for AED response in children with epilepsy. Results:(1) Significant differences in type of first seizure and AEDs were noted between AED response group and AED resistance group ( P<0.05); compared with the AED resistance group, the AED response group had significantly lower seizure frequency, significantly longer duration after last seizure, and statistically higher proportions of children with normal EEG or with one kind of AED ( P?0.05). (2) Compared with the control group and AED response group, the AED resistance group had significantly higher rs2298771 GC genotype and G allele, and statistically lower rs2298771 AA genotype and A allele in SCN1A polymorphism ( P?0.05). (3) In the AED response group, rs2298771 AA and AG genotype in SCN1A polymorphism were positively correlated with levetiracetam ( P?0.05); in AED resistance group, rs2298771 AG genotype in SCN1A polymorphism was positively correlated with topiramate and valproic acid ( P<0.05). (4) Multivariate Logistic regression analysis showed that duration after last seizure ( OR=3.249, 95% CI=1.097-9.621, P=0.033), rs2298771 genotype in SCN1A polymorphism ( OR=9.660, 95% CI=4.680-19.970, P=0.011) and seizure frequency ( OR=0.160, 95% CI=0.032-0.804, P=0.026) were independent influencing factors for AED response in children with epilepsy. Conclusion:Epilepsy children with shorter duration after last seizure, rs2298771 GG genotype in SCN1A polymorphism, and high seizure frequency are susceptible to AED resistance; especially, AG genotype is correlated with topiramate and valproic acid.

Objective To analyze the relationship of lipoprotein(a)[Lp(a)]with poor prognosis in chronic heart failure(CHF)patients aged over 80 years,and explore the influencing factors for poor prognosis in these patients.Methods A total of 135 over-80-year-old patients with acute de-compensated CHF admitted in Tianjin University Chest Hospital from June 2018 to August 2021 were enrolled in this study.With Lp(a)300 mg/L as the cut-off value,they were divided into higher Lp(a)group(73 cases)and lower Lp(a)group(62 cases).Their baseline clinical data and outcomes after 12 months of follow-up were collected.The primary endpoint was composite end-point including re-hospitalization due to CHF and/or all-cause mortality.Kaplan-Meier survival curve were plotted to compare the survival rates between the two groups.Logistic regression anal-ysis was employed to analyze the risk factors of poor prognosis in these patients.Results The higher Lp(a)group had larger proportion of chronic kidney disease and higher levels of homocys-teine,total cholesterol and low-density lipoprotein-cholesterol than the lower Lp(a)group(P＜0.05).Kaplan-Meier survival analysis showed that the lower group obtained significantly longer 1-year survival time without primary endpoint events than the higher group[9.8 months(95％CI:8.884-10.665)vs 8.2 months(95％CI:7.057-9.272),P＜0.05].Multivariate logistic regression analysis revealed that Lp(a)≥300 mg/L(OR=2.841,95％CI:1.133-7.092,P=0.026),female(OR=2.809,95％CI:1.111-7.092,P=0.029)and use of diuretic(OR=4.631,95％CI:1.103-19.443,P=0.036)were independent risk factors for primary endpoint events within 1 year.Con-clusion Lp(a)≥300 mg/L is an independent risk factor for re-hospitalization due to CHF and/or all-cause mortality in elderly CHF patients within 1 year after discharge.