Objective To establish an animal model and evaluation system for lymph node metastasis of breast cancer.Methods A total of 60 female BALB/c mice(6～8 weeks old)were subjected,and then 6 models of lymph node metastasis(n=10)were constructed through injection at different parts in the mice with cell suspension of 4T1 breast cancer cells.Transgenic mice(n=5)of mouse mammary tumor virus-polyoma middle T antigen(MMTV-PyMT)were employed and served as model of spontaneous tumor metastasis.Then the advantages and disadvantages of different lymph node metastasis models were comprehensively evaluated from multiple aspects,such as operability,histomorphology and pathological detection,tumor growth rate and mouse survival.Results Among the 7 metastasis models,4 models of lymph node metastasis were successfully established.Among them,the PyMT mouse spontaneous tumorigenesis model showed the best clinical reproduction,with a tumorigenesis rate of up to 100％,but had a disadvantage of poor experimental standardization.The hind paw-popliteal lymph node model had the fastest lymph node metastasis,easy operation and high repeatability,and a tumorigenesis rate of 100％,indicating its suitable for lymph node metastasis related research.The thigh subcutaneous-inguinal lymph node model also successfully simulated lymph node metastasis,with simple operation and high repeatability,a tumorigenesis rate of up to 100％,but its metastasis time was slightly longer than the hind paw-popliteal lymph node model.The inguinal lymph node-contralateral lymph node model was also a successful lymph node metastasis model,but with difficult operation,only 50％tumor-bearing rate,and poor repeatability.Lymph node metastasis model was not successfully established in the other 3 tumor-bearing models(under the tongue-internal jugular scapular tongue muscle lymph node model,bone marrow-inguinal lymph node model and right upper back skin-axillary lymph node model)in a short time,with no tumor cells observed in the pathological sections.Conclusion Through the comprehensive comparison of multiple models,mouse hind paw-popliteal lymph node model is the most suitable for conducting related research.

The tumor immune microenvironment (TIME) is broadly composed of various immune cells, and its heterogeneity is characterized by both immune cells and stromal cells. During the course of tumor formation and progression and anti-tumor treatment, the composition of the TIME becomes heterogeneous. Such immunological heterogeneity is not only present between populations but also exists on temporal and spatial scales. Owing to the existence of TIME, clinical outcomes can differ when a similar treatment strategy is provided to patients. Therefore, a comprehensive assessment of TIME heterogeneity is essential for developing precise and effective therapies. Facilitated by advanced technologies, it is possible to understand the complexity and diversity of the TIME and its influence on therapy responses. In this review, we discuss the potential reasons for TIME heterogeneity and the current approaches used to explore it. We also summarize clinical intervention strategies based on associated mechanisms or targets to control immunological heterogeneity.

To summarize the nursing experience of an adolescent with early repolarization syndrome who had implanted a subcutaneous implantable cardioverter defibrillator(ICD)and experiences frequent ventricular fibrillation.The main nursing care were as follows:recognizing a ventricular fibrillation attack and emergency care;risk prevention and handling in transportation;prevention of iatrogenic infection and strengthening protective isolation;promoting the recovery of brain function;personalized health education;pre-hospital first aid skills training for families.After careful treatment and nursing,the patient did not recur arrhythmia,and heart function had improved significantly,and the pulmonary inflammation disappeared.No medical-acquired infections occurred during hospitalization.The patient's motor ability and language expression ability recovered to the baseline,and was discharged on the 20th day of admission.A month after discharge,the patient recovered well and could study and live normally.

Objective:To explore the risk factors of venous leg ulcers (VLU) in patients with deep venous thrombosis (DVT) of central type.Methods:Using the convenient sampling, 268 patients with lower limb DVT of central type who were treated in the Vascular Surgery of Henan Provincial People's Hospital from January 2020 to January 2021 were selected for analysis. Patients were divided into a case group ( n=56) and a control group ( n=212) based on whether VLU occurred. Clinical factors were compared between the two groups. The risk factors for VLU in patients with lower limb DVT of central type were determined using univariate analysis and multivariate Logistic regression. A prediction model was constructed. The performance of the prediction model was evaluated using the Hosmer-Lemeshow test of goodness of fit and the area under the receiver operating characteristic (ROC) curve. Results:Univariate analysis showed that there were statistical differences between the two groups in terms of age, body mass index, smoking, alcohol consumption, work style, hypertension, deep venous reflux of the lower limbs, history of lower limb DVT, fracture history, Morisky Medication Adherence Scale scores, post-thrombotic syndrome, family history of lower limb varicose veins and family history of lower limb DVT ( P<0.05) . Multivariate Logistic regression analysis showed that age>60 years old, smoking cigarettes every day, post-thrombotic syndrome, hypertension and deep venous reflux were independent risk factors for VLU in patients with lower limb DVT ( P<0.05) . The area under the ROC curve of the risk prediction model for VLU in patients with lower limb DVT of central type was 0.972 (95% confidence interval was 0.945 to 0.988) . Conclusions:Age>60 years old, smoking cigarettes every day, post-thrombotic syndrome, hypertension, and deep venous reflux are independent risk factors for VLU in patients with lower limb DVT of central type. Nurses should provide prevention and treatment measures for the risk factors of VLU in patients with lower limb DVT of central type so as to reduce the incidence of VLU.

Objective:To explore the distribution of serum TRAb IgG subtypes in patients with thyroid-associated ophthalmopathy(TAO) at different stages and its value in assessing TAO activity.Methods:Forty-three patients with TAO, 30 patients with Graves′ disease (GD group), 19 patients with Hashimoto′s thyroiditis (HT group), and 50 healthy subjects (NC group)admitted to the First Affiliated Hospital of Zhengzhou University were collected from August 2018 to February 2019. According to the clinical activity score (CAS), the patients with TAO were further divided into the active period group (AP group, CAS≥3 points, 22 cases) and the inactive period group (IP group, CAS<3 points, 21 cases). The basic clinical data of subjects in each group were collected. The serum concentrations of FT 3, FT 4, TSH, thyroperoxidase antibody (TPOAb), thyroglobulin antibody (TgAb), and thyroid-stimulating hormone receptor antibody (TRAb) were detected by chemiluminescence immunoassay and the binding rate in percentage (B) of serum TRAb IgG and IgG subtypes were detected by ELISA. The positive rate in each group and relative content of positive samples were compared. Results:(1)Compared with HT group, the positive rates of IgG1 and IgG2 in TAO group and GD group were significantly decreased ( P<0.05). There was no significant difference in the relative content of positive TRAb IgG subtype among these disease groups ( P>0.05). (2)Compared with the IP group, IgG1(B) and the positive rates of IgG1 in the AP group were increased while IgG4(B) and the relative contents of IgG4 were reduced ( P<0.05). (3)IgG1(B)was positively correlated with TAO activity ( B=6.190, P=0.007), and higher IgG4(B)indicated more inclinations to the inactive period ( B=-16.390, P=0.052). (4) The area under the curve of receiver operating characteristic (ROC) for TAO developing into active period assessed by activity rate was 0.859 (95% CI 0.746-0.973, P<0.05). When the activity rate was 4.29, the Jordon index showed the largest, with sensitivity of 81.8% and specificity of 81.0%. Conclusions:Elevated levels of TRAb IgG1 in the patients with TAO indicate a tendency to active period, while elevated levels of TRAb IgG4 indicate a tendency to inactive period. The activity rate can provide a reference for assessing whether TAO is active or not.

Objective? To investigate the effect of intervention theory based on timing theory on self-management behavior and medication compliance of patients with percutaneous coronary intervention (PCI). Methods? A total of 126 patients who underwent PCI in People＇s Hospital of He＇nan Province in 2018 were enrolled, including 67 who had PCI from April to June in 2018 in the experimental group and 59 who had PCI from January to March in 2018 in the control group. Patients in the control group received routine nursing intervention. The patients in the experimental group were treated with an intervention program based on timing theory. The Coronary Heart Disease Self-Management Scale and the Morisky Medication Adherence Questionnaire were used to compare the effects of the intervention. Results? After intervention, the scores of "daily life management(17.11±3.62)", "bad habit management(16.33±4.36)", "disease knowledge management(17.11±3.68)", "symptom management(14.25±4.15)", "first aid management(13.55±4.27)","treatment compliance management(11.13±3.62)" and "emotional cognitive management(15.69±4.25)" in the experimental group were higher than the control group with(14.57±3.69),(14.17±3.88),(14.36±3.56), (12.34±4.46),(10.41±3.89),(7.69±4.14),(13.23±4.32)respectively, and the differences were statistically significant (t=3.895, 2.921, 4.250, 2.489, 4.293, 4.976,3.217;P＜0.05). After the intervention, the scores of the medication adherence questionnaire in the experimental group was (6.35±1.12), and the control group was (5.92±1.17). The difference between the two groups was statistically significant (t=2.106, P=0.037). Conclusions? Timing theory can improve the self-management behavior and medication compliance of PCI patients, and can be applied in clinical practice.

OBJECTIVETo investigate the value of serum IgA/C3 ratio in the diagnosis of IgA nephropathy and explore its relationship with the clinicopathological features of the patients.

METHODSSixty-six patients with IgA nephropathy, 111 with other glomerular diseases, and 40 healthy control subjects without kidney disease were tested for serum IgA and C3 levels using CRM470 adjusted standardized immune turbidimetric method, and the IgA/C3 ratio was calculated. According to Oxford and Lee's classification criteria, we analyzed the pathological grades of the renal biopsy samples from patients with IgA nephropathy. The ROC curve was used to assess the value of serum IgA and IgA/C3 ratio in predicting IgA nephropathy.

RESULTSPatients with IgA nephropathy had an elevated serum IgA/C3 ratio than those with other glomerular diseases and the control subjects, with an area under the ROC curve of 0.776. An elevated serum IgA/C3 ratio was not found to significantly correlate with the pathological grade of renal biopsy samples in patients with IgA nephropathy.

CONCLUSIONIn the absence of renal biopsy findings, serum IgA/C3 ratio can help in the diagnosis of IgA nephropathy.

Biopsy ; Case-Control Studies ; Complement C3 ; analysis ; Glomerulonephritis, IGA ; blood ; diagnosis ; Humans ; Immunoglobulin A ; blood ; Kidney ; pathology

OBJECTIVETo compare the predictive value of liver enzymes and alcohol consumption for determining risk of type 2 diabetes (T2DM).

METHODSA cross-sectional study was conducted in Zhengzhou with a total of 2, 693 men.Participants' height, weight, and histories of smoking and drinking were recorded. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT) and blood glucose, as well as related metabolic indexes were detected.

RESULTSModerate daily alcohol consumption (more than 35 g ethanol/week and less than 140 g ethanol/week) decreased the risk of type 2 diabetes (OR =0.376, 95% CI:0.306 -0.463, P less than 0.05) but increased risk for higher levels of GGT and ALT (OR GGT =3.012, 95% CI:2.357-3.849, Pless than 0.01; ORALT =1.473, 95% CI:1.043-2.081, Pless than 0.05). In joint analyses of alcohol consumption and liver enzymes, the group of nondrinkers/light drinkers (less than or equal to 35 g ethanol/week) in the fourth quartile of GGT levels had the highest risk for type 2 diabetes (OR =12.219, 95% CI:6.217-24.016, P less than 0.01). The relationship of ALT and daily alcohol consumption with the risk of type 2 diabetes was almost the same as that of GGT (nondrinkers/light drinkers in the fourth quartile of ALT levels (OR =5.357, 95% CI:3.070-9.350, P less than 0.0 1).

CONCLUSIONGGT, ALT and daily alcohol consumption were independently associated with risk of type 2 diabetes. Nondrinkers/light drinkers with the highest levels ofGGT orALT were at high risk of type 2 diabetes.

Alanine Transaminase ; Alcohol Drinking ; Aspartate Aminotransferases ; Blood Glucose ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2 ; Humans ; Liver ; Male ; Risk Factors ; Smoking ; gamma-Glutamyltransferase

To study the effects of forkhead transcription factor O1 (FoxO1) on the expression of type Ⅳ collagen and desmin in podocytes of diabetic rats.Streptozotocin-induced diabetic rats were divided into three groups:diabetic rats (DM group),rats transfected with blank lentiviral vectors (diabetes mellitus plus LV-pSC-GFP group,LV-NC group),and rats which were transfected with lentiviral vectors carrying constitutively active FoxO1 (diabetes mellitus plus LV-FoxO1-AAA group,LV-CA group).Rats which received an injection of diluent buffer served as normal control.At 2,4,and 8 weeks after transfection,the levels of urine albumin,blood glucose,blood urea nitrogen,and serum creatinine were measured.Realtime PCR and Western blotting were performed to measure the mRNA and protein levels of FoxO1,COL4A3,COL4A5,and desmin in the renal cortex.Moreover,light microscope and electron microscope were used to observe the structural changes in glomerulus and podocytes.Compared with LV-NC and DM group,in LV-CA group,there was a significant increase in the mRNA and protein levels of FoxO1,and a distinct decrease in the levels of urine albumin,blood urea nitrogen and serum creatinine of rats (except at the twoweek time point) (all P＜0.05),the mRNA and protein levels of COL4A3,COL4A5,and desmin were all decreased (all P＜0.05),and pathological changes in kidney were also improved.Upregulating the expression of FoxO1 by transfecting with constructed lentiviral vectors can definitely improve the abnormal expression of type Ⅳ collagen and desmin in podocytes of diabetic rats.

Objective To study the effect and mechanism of forkhead transcriptionfactor O1( FoxO1) on proliferation of rat mesangial cells(MCs) cultured under high glucose conditions. Methods Constructing lentiviral vectors of LV-CA-FoxO1 and LV-siRNA-FoxO1 were used to upregulate or downregulate FoxO1. Moreover, negative control LV-NC-FoxO1 was also constructed. Rat MCs were separately cultured in normal glucose(5. 6 mmol/ L, NG group), only high glucose(30 mmol/ L, HG0 group), LV-NC-FoxO1 with HG(HG1 group),LV-CA-FoxO1 with HG (HG2 group), and LV-siRNA-FoxO1 with HG(HG3 group) for 72 h. MTT assay and flow cytometrywas were used to analyze cell proliferation and cell cycle distribution. The expression of FoxO1, cyclin-dependent kinase inhibitor (p27), cyclinD1, and cyclin-dependent kinase 4( CDK4) were detected by QRT-PCR and Western blot. Results The MCs proliferation rate in HG0 group was faster than that in NG group. Besides, there were no statistical differences in FoxO1 expression and proliferation rate of MCs between HG0 group and HG1 group. Nevertheless, LV-CA-FoxO1 promoted cell cycle arrest at the G1 phase and attenuated proliferation rate, along with upregulation of FoxO1 and p27 and downregulation of cyclin D1 and CDK4 in HG2 group ( all P < 0. 05). Moreover, degradation of FoxO1 by LV-siRNA-FoxO1 stimulated hyperproliferation of MCs, associating with decline of p27 and increase of cyclin D1 and CDK4 in HG3 group(all P<0. 05). Conclusion The proliferation of MCs induced by high glucose is regulated by utilizing transgenic technology targeted and regulated FoxO1 expression and consequently through FoxO1 / p27 signaling pathway. These findings indicate that FoxO1 seems to be a new therapeutic target for early diabetic nephropathy.