Objective:To construct univariate and multivariate relapse free survival (RFS) prediction models for breast cancer patients with diabetes mellitus type 2 (T2DM) and to compare and select the model with higher predictive performance.Methods:A total of 912 breast cancer patients treated at the First Affiliated Hospital of Dalian Medical University from January 2010 to December 2016 were included, of which 202 patients had T2DM and 710 patients did not. Kaplan-Meier survival curve was drawn based on whether patients had T2DM, and log-rank test was performed based on whether patients had T2DM. All patients were randomly divided into a training set ( n=640) and a validation set ( n=272) at a ratio of 7∶3. Univariate and multivariate Cox proportional risk regression models were used to analyze RFS in breast cancer patients with the survival package. The "rms" package was employed to construct univariate and multivariate RFS prediction models for breast cancer patients with T2DM. Clinical decision curves and calibration curves were used to validate the models. The receiver operator characteristic (ROC) curve was used to compare and analyze the prediction performance of the two models. Results:There were no statistically significant differences between the training set and the validation set patients in terms of age, T2DM, surgical approach, axillary management methods, T stage, N stage, molecular sub-type, estrogen receptor (ER) 1, ER2, progesterone receptor (PR) , ER and PR consistency, Ki67, human epidermal growth factor receptor 2 (HER2) (all P>0.05) . There was a statistically significant difference in histological grade ( χ2=7.59, P=0.022) . Survival analysis showed that the 5-year RFS rate was 83.7% in patients with T2DM and 92.3% in patients without T2DM ( χ2=16.61, P<0.001) . Univariate analysis revealed that age ( HR=1.04, 95% CI: 1.03-1.06, P<0.001) , T2DM ( HR=2.31, 95% CI: 1.49-3.55, P<0.001) , surgical approach ( HR=2.39, 95% CI: 1.20-4.77, P=0.013) , axillary management methods ( HR=2.62, 95% CI: 1.72-3.98, P<0.001) , T stage (T 2: HR=2.13, 95% CI: 1.36-3.31, P<0.001; T 3: HR=6.90, 95% CI: 3.35-14.22, P<0.001) , N stage (N 2: HR=3.87, 95% CI: 2.12-7.07, P<0.001; N 3: HR=8.61, 95% CI: 4.71-15.75, P<0.001) , molecular sub-type (Luminal B: HR=2.74, 95% CI: 1.17-6.36, P=0.019; HER2 +: HR=3.64, 95% CI: 1.38-9.58, P=0.009; TNBC: HR=4.40, 95% CI: 1.71-11.34, P=0.002) , ER1 (>10%: HR=0.57, 95% CI: 0.37-0.90, P=0.016) , ER2 ( HR=0.57, 95% CI: 0.37-0.89, P=0.015) , and PR ( HR=0.56, 95% CI: 0.37-0.86, P=0.008) were all factors influencing RFS in breast cancer patients. Multivariate analysis demonstrated that age ( HR=1.04, 95% CI: 1.02-1.06, P<0.001) , T2DM ( HR=1.82, 95% CI: 1.16-2.85, P=0.009) , T stage (T 2: HR=1.60, 95% CI: 1.01-2.54, P=0.046; T 3: HR=2.64, 95% CI: 1.22-5.72, P=0.014) , N stage (N 2: HR=3.72, 95% CI: 2.01-6.88, P<0.001; N 3: HR=5.34, 95% CI: 2.78-10.25, P<0.001) , and ER1 (>10%: HR=0.63, 95% CI: 0.39-0.99, P=0.046) were independent factors influencing RFS in breast cancer patients. Based on the 10 and 5 variables with P<0.05 in the univariate and multivariate analyses respectively, the nomograms of the univariate and multivariate prediction models were constructed to evaluate the influence of factors such as T2DM on the postoperative RFS of breast cancer patients. Clinical decision curves and calibration curves indicated that both models had high predictive value for RFS in breast cancer patients, and the predictive results were highly consistent with the actual observed results. ROC curve analysis showed that there was no statistically significant difference in the area under the curve (AUC) of the two models for predicting the RFS rates of breast cancer patients in the training set and validation set at 36, 60, and 84 months (all P>0.05) , indicating that the predictive efficacy of the two models was comparable. The multivariate model is more suitable for clinical application because it uses fewer variables. Conclusions:Breast cancer patients with T2DM have poorer prognosis. Age, T2DM, T stage, N stage, and ER1 are independent factors influencing postoperative RFS in breast cancer patients. The multi-factor prediction model of RFS in breast cancer patients based on T2DM is more suitable for clinical application due to its higher predictive efficacy and fewer variables.

Objective:To identify prognostic factors associated with survival rates in patients with distal cholangiocarcinoma after radical surgery, and to construct a Nomogram prediction model based on these factors, as well as to perform internal validation of the model.Methods:A retrospective study was conducted on the clinical data of 162 patients (76 males and 86 females) with distal cholangiocarcinoma who underwent radical surgery at the Department of Hepatobiliary Surgery, Ningxia Medical University General Hospital from January 2011 to July 2019. The study used univariate and multivariate Cox regression analysis to identify independent risk factors and constructed a Nomogram prediction model using R software version 4.4.1. Additionally, the predictive accuracy of the model was evaluated through the C-index, the area under the receiver operating characteristic curve, and the calibration curve.Results:The median overall survival for the 162 patients was 18.4 months. The final multivariate Cox regression analysis revealed that the following factors were independent risk factors for poor postoperative prognosis in patients with distal cholangiocarcinoma: patient age [> 60 years, P = 0.004, hazard ratios ( HR) = 1.876], tumor diameter (> 2.0 cm, P < 0.001, HR = 0.174), tumor differentiation degree [moderately differentiated/moderately to highly differentiated/highly differentiated, P = 0.017, HR = 1.407], lymph node metastasis (Yes, P = 0.002, HR = 0.551), and vascular invasion (Yes, P = 0.025, HR = 1.329) (all P < 0.05). Based on these independent risk factors identified through statistical analysis, the C-index of the constructed nomogram prediction model was 0.793. The area under the receiver operating characteristic curve values for the model predicting postoperative 1-year, 3-year, and 5-year overall survival rates were 0.932, 0.771, and 0.758,respectively. Conclusions:Patient age, tumor diameter, tumor differentiation degree, lymph node metastasis, and vascular invasion are independent risk factors for poor postoperative prognosis in patients with distal cholangiocarcinoma. The final Nomogram prediction model demonstrates good predictive ability and has certain practical application potential.

Objective:To identify prognostic factors associated with survival rates in patients with distal cholangiocarcinoma after radical surgery, and to construct a Nomogram prediction model based on these factors, as well as to perform internal validation of the model.Methods:A retrospective study was conducted on the clinical data of 162 patients (76 males and 86 females) with distal cholangiocarcinoma who underwent radical surgery at the Department of Hepatobiliary Surgery, Ningxia Medical University General Hospital from January 2011 to July 2019. The study used univariate and multivariate Cox regression analysis to identify independent risk factors and constructed a Nomogram prediction model using R software version 4.4.1. Additionally, the predictive accuracy of the model was evaluated through the C-index, the area under the receiver operating characteristic curve, and the calibration curve.Results:The median overall survival for the 162 patients was 18.4 months. The final multivariate Cox regression analysis revealed that the following factors were independent risk factors for poor postoperative prognosis in patients with distal cholangiocarcinoma: patient age [> 60 years, P = 0.004, hazard ratios ( HR) = 1.876], tumor diameter (> 2.0 cm, P < 0.001, HR = 0.174), tumor differentiation degree [moderately differentiated/moderately to highly differentiated/highly differentiated, P = 0.017, HR = 1.407], lymph node metastasis (Yes, P = 0.002, HR = 0.551), and vascular invasion (Yes, P = 0.025, HR = 1.329) (all P < 0.05). Based on these independent risk factors identified through statistical analysis, the C-index of the constructed nomogram prediction model was 0.793. The area under the receiver operating characteristic curve values for the model predicting postoperative 1-year, 3-year, and 5-year overall survival rates were 0.932, 0.771, and 0.758,respectively. Conclusions:Patient age, tumor diameter, tumor differentiation degree, lymph node metastasis, and vascular invasion are independent risk factors for poor postoperative prognosis in patients with distal cholangiocarcinoma. The final Nomogram prediction model demonstrates good predictive ability and has certain practical application potential.

OBJECTIVE: To explore the molecular pathogenesis of a Chinese pedigree affected with inherited protein C (PC) deficiency. METHODS: The protein C activity (PC:A) and protein C antigen (PC:Ag) of the proband and his family members were determined by a chromogenic substrate method and enzyme-linked immunosorbent assay, respectively. The proband was subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing of other members of the pedigree. RESULTS: The PC:A and PC:Ag of proband were reduced to 15% and 11%, respectively. The above parameters of his parents and elder sister were also decreased to approximately 50% of reference values. Next generation sequencing has revealed that the proband has harbored a heterozygous c.572_574delAGA (p.Glu191_Lys192delinsGlu) variant in exon 7 and a missense c.752C>T (p.Ala251Val) variant in exon 8 of the PROC gene. His father was heterozygous for the c.572_574delAGA variant, while his mother and elder sister were heterozygous for the c.752C>T variant. According to the American College of Medical Genetics and Genomics Standards and Guidelines, the c.572_574delAGA (p.Glu191_Lys192 delinsGlu) variant was predicted to be likely pathogenic (PS1+PM4+PP3). c.752 C>T (p.Ala251Val) variant was also likely pathogenic (PS1+PM1+PP3). CONCLUSION The deletional variant of c.572_574delAGA (p.Glu191_Lys192delinsGlu) in exon 7 and missense variant c.752C>T (p.Ala251Val) in exon 8 of the PROC gene probably underlay the inherited protein C (PC) deficiency in this pedigree. Above finding has enriched the spectrum of PROC gene variants and provided a basis for genetic counseling for this pedigree.
Humans ; China ; Mutation ; Pedigree ; Protein C/genetics* ; Protein C Deficiency/genetics* ; Male ; Female

Objective:To construct a non-invasive predictive model for liver fibrosis in HBeAg positive chronic hepatitis B (CHB) patients with alanine aminotransferase (ALT) lower than 2 upper limit of normal (ULN).Methods:The clinical data of 279 HBeAg positive CHB patients with ALT<2×ULN admitted in Zhejiang Provincial People’s Hospital from October 2014 to December 2020 were retrospectively analyzed. According to the pathological results of liver biopsy, there were 117 cases of mild liver fibrosis (S0-S1) and 162 cases of significant liver fibrosis (S2-S4). The independent predictors of liver fibrosis were analyzed by multivariate logistic regression analysis and a noninvasive predictive model was constructed. The model for predicting the severity of liver fibrosis was evaluated by receiver operating characteristic curve (ROC).Results:Multivariate logistic regression analysis showed that age, prothrombin time (PT), aspartate aminotransferase (AST), anti-HBc and HBV DNA were independent predictors of liver fibrosis ( OR=1.055, 1.365, 1.027, 1.231, 0.763, all P<0.05). The area under the ROC curve (AUR) of the model was 0.772 (95% CI: 0.716-0.828, P<0.05), the sensitivity and specificity for the diagnosis of significant liver fibrosis were 79.5% and 70.9% at the cut-off value of 0.504. The AUC of APRI model and FIB-4 index model for assessing significant liver fibrosis in CHB patients with HBeAg-positive and ALT<2×ULN were 0.720 and 0.671, respectively, which were lower than that of the current model (all P<0.05). Conclusion:The noninvasive predictive model constructed in this study has a high diagnostic value for evaluating the severity of liver fibrosis in CHB patients with HBeAg positive and ALT<2×ULN.

Objective:To evaluate the role of hsa_circ_0081596 in oxygen-glucose deprivation and restoration (OGD/R) injury to human neurons. Methods:SK-N-SH cells were cultured and the cells within 5 generations were divided into 4 groups ( n=20 each) using a random number table method: control group (group C), OGD/R group (group O), OGD/R+ siRNA group (group S) and OGD/R+ siRNA negative control group (group I). The cells in C group were cultured under normal conditions of 37 ℃ and 5% CO 2.The cells in group O were placed in 6- or 96-well plates until they were completely attached to the wall, and then subjected to oxygen-glucose deprivation for 4 h, followed by restoration of oxygen-glucose for 24 h. In group S and group I, the cells were transfected with hsa_circ_0081596 siRNA and its negative control, respectively, and 72 h later OGD/R model was established.The expression of hsa_circ_0081596 and mitochondrial fission protein 1 (Fis1) mRNA was detected using quantitative real-time polymerase chain reaction.The expression of Fis1 was determined by Western blot, the cell survival rate was determined by CCK-8 assay and the apoptosis rate was determined by flow cytometry. Results:Compared with group C, the expression of hsa_circ_0081596, Fis1 and its mRNA was significantly up-regulated, the cell survival rate was decreased, and the apoptosis rate was increased in group O ( P<0.05). Compared with group O, the expression of hsa_circ_0081596 and Fis1 was significantly down-regulated, the cell survival rate was increased and the apoptosis rate was decreased in group S, and the expression of hsa_circ_0081596 and Fis1 was significantly up-regulated, the cell survival rate was decreased and the apoptosis rate was increased in group I ( P>0.05). Conclusion:hsa_circ_0081596 is involved in the pathophysiological mechanism of OGD/R through up-regulating the expression of Fis1 in human neurons.

Objective    To explore the relationship between obstructive sleep apnea-hypopnea syndrome (OSAHS) and aortic dissection (AD). Methods    Fifty three patients with AD diagnosed by CTA in our hospital from January 2016 to January 2018 were selected. All the patients with AD were scored by the STOP-BANG questionnaire. The patients who scored more than or equal to 3 received polysomnography (PSG) after surgical or conservative treatment, and according to whether the sleep apnea-hypopnea index was higher than or equal to 5. Fifty-three patients were divided into an OSAHS group and a non OSAHS group. Results    There were 18 patients with 17 males and 1 female at average age of 43.3±8.4 years in the OSAHS group, and 35 patients with 23 males and 12 females at average age of 56.6±12.9 years in the non OSAHS group. There was no statistical difference between the two groups in the Stanford classification of aortic dissection, the time of onset, personal history, the history of diabetes, coronary heart disease and hyperlipidemia, or post-treatment systolic/diastolic blood pressure before sleep (P>0.05). The age of patients in the OSAHS group was significantly less than that in the non OSAHS group (P<0.01), the proportion of men/women (P=0.021), weight (P<0.01), height (P=0.028), body mass index (P<0.01), and post-treatment systolic/diastolic blood pressure after waking up (P=0.028,P=0.044) in the OSAHS group were significantly higher than those in the non OSAHS group. In the OSAHS group, the proportion of previous hypertension was significantly higher than that in the non OSAHS group (P=0.042).   Conclusion    AD patients combined with OSAHS are mostly male patients. The number of young and high-fat people is significantly more than that in the non OSAHS group. OSAHS may be one of the risk factors for young, high-fat men with AD.

Objective To analyze the association of serum γ-glutamyl transpeptidase(γ-GT)level with carotid intima media thickness(IMT) in essential hypertension.Methods All the 300 essential hypertension patients and 70 healthy controls were from Ganzhou People′s Hospital.They were divided into healthy control group(70 cases),hypertension with out arteriosclerosis group(141 cases) and hypertension with arteriosclerosis group(159 cases) based on carotid IMT.Fasting blood glucose,serum lipid,routine laboratory tests,hepatic and renal function were detected by routine methods.The one-way analysis of variance and χ2-test were used to compared among the three groups,and the relationship of γ-GT with IMT was assessed by using the Spearman correlation coefficient,multiple linear regressions and Logistic regression analysis.Results The diastolic blood pressure,body mass index,fasting blood glucose,glomerular filtration rate and glycosylated hemoglobin had no differences among the three groups(P>0.05),but systolic pressure,triacylglycerol,total cholesterol,high density lipoprotein cholesterol,aspartate transaminase(AST),low density lipoprotein cholesterol alanine,transaminase(ALT) and γ-GT had significant differences among the three groups(P<0.05).Multiple linear regression analysis showed that the serum γ-GT(β=-0.345,95%CI was-0.005——0.511,P=0.036) was also negatively correlated with IMT,and Logistic regression analysis showed that γ-GT(OR=0.569,95%CI was 0.237-0.867,P=0.029)was a protective factor for atherosclerosis.Conclusion Our study demonstrated the level of γ-GT is negative with IMT among essential hypertension patients,and monitoring the changes of serum liver enzyme might has significant effect on the early detection of arteriosclerosis.

Objective To analyze the relationship and clinical meaning of serumglutamyl transpeptidase (GGT) level with left atrial diameter.Methods All the 320 essential hypertension patients from Ganzhou People′s Hospital were divided into normal left atrial group and enlarged left atrial group based on the size of left atrial diameter.Fasting blood glucose,serum lipid,routine laboratory tests,hepatic and renal function and blood pressure were measured by routine methods,and used for analyzing between groups.Results Among essential hypertension patients,the GGT level in enlarged left atrial group [(24.78±10.93)U/L] was lower than normal left atrial group[(35.23±12.46)U/L] (P=0.004).Multiple linear regression analysis showed that the serum GGT was negatively correlated with left atrial diameter (P=0.032),and logistic regression analysis showed that GGT was a protective factor for enlarged left atrial (OR=0.424,P=0.026).Conclusion Our study demonstrated the level of GGT was negatively with left atrial diameter among essential hypertension patients,and monitoring the changes of serum liver enzyme may has significant effect on the early detection of enlarged left atrial diameter.

Objective To explore the influence of citalopram on early recovery of motor function in patients with acute cortical infarction.Methods A total of 276 patients with acute cerebral infarction were randomly divided into observation group and control group,138 cases in each group.Patients in control group were treated with anti-platelet,blood lipid,protective nerve and rehabilitation therapy.The observation group was given citalopram hydrobromide tablets on the basis of control group.Results The incidence rate of depression in the observation group was 18.1％,which was significantly lower than 42.7％ in the control group (P ＜ 0.05).After treatment,HDRS score and NIHSS score in the observation group were significantly lower than the control group (P ＜ 0.05).In the observation group,after treatment of 30 days and 90 days,the increasing scores of hand motor function of FMA were 4.1 ± 1.0 points and 6.5 ± 2.5 points,which were significantly higher than 1.4 ± 0.7 points and 2.5 ± 1.5 points (P ＜ 0.05).After treatment of 30 days,the BI score of observation group was significantly higher than control group (P ＜ 0.05).Conclusion Early application of citalopram can effectively reduce the incidence rate of post-stroke depression in patients with acute cerebral infarction,promote the recovery of motor function and improve the quality of prognosis.