A multicenter study of the clinicopathological characteristics and a risk prediction model of early-stage breast cancer with hormone receptor-positive/human epidermal growth factor receptor 2-low expression / 中华医学杂志(英文版)

BACKGROUND@#In light of the significant clinical benefits of antibody-drug conjugates in clinical trials, the human epidermal growth factor receptor 2 (HER2)-low category in breast cancers has gained increasing attention. Therefore, we studied the clinicopathological characteristics of Chinese patients with hormone receptor (HR)-positive/HER2-low early-stage breast cancer and developed a recurrence risk prediction model.@*METHODS@#Female patients with HR-positive/HER2-low early-stage breast cancer treated in 29 hospitals of the Chinese Society of Breast Surgery (CSBrS) from Jan 2015 to Dec 2016 were enrolled. Their clinicopathological data and prognostic information were collected, and machine learning methods were used to analyze the prognostic factors.@*RESULTS@#In total, 25,096 patients were diagnosed with breast cancer in 29 hospitals of CSBrS from Jan 2015 to Dec 2016, and clinicopathological data for 6486 patients with HER2-low early-stage breast cancer were collected. Among them, 5629 patients (86.79%) were HR-positive. The median follow-up time was 57 months (4, 76 months); the 5-year disease-free survival (DFS) rate was 92.7%, and the 5-year overall survival (OS) rate was 97.7%. In total, 412 cases (7.31%) of metastasis were observed, and 124 (2.20%) patients died. Multivariate Cox regression analysis revealed that T stage, N stage, lymphovascular thrombosis, Ki-67 index, and prognostic stage were associated with recurrence and metastasis ( P <0.05). A recurrence risk prediction model was established using the random forest method and exhibited a sensitivity of 81.1%, specificity of 71.7%, positive predictive value of 74.1%, and negative predictive value of 79.2%.@*CONCLUSION@#Most of patients with HER2-low early-stage breast cancer were HR-positive, and patients had favorable outcome; tumor N stage, lymphovascular thrombosis, Ki-67 index, and tumor prognostic stage were prognostic factors. The HR-positive/HER2-low early-stage breast cancer recurrence prediction model established based on the random forest method has a good reference value for predicting 5-year recurrence events.@*REGISTRITATION@#ChiCTR.org.cn, ChiCTR2100046766.

The differences in clinical profiles and imaging features between liver cirrhosis combined with gastroesophageal varices type 2 and isolated gastric varices type 1 / 中华消化内镜杂志

Objective:To investigate the differences in clinical features and imaging findings of cirrhotic patients with fundic varices between gastroesophageal varices type 2 (GOV2) and isolated fundic varices type 1 (IGV1).Methods:Clinical and imaging data of cirrhotic patients with fundic varices treated in Union Hospital, Tonji Medical Colloge, of Huazhong University of Science and Technology from October 2013 to March 2021 were retrospectively analyzed.Results:A total of 210 patients were enrolled, including 139 patients of GOV2 (GOV2 group) and 71 patients of IGV1 (IGV1 group). Blood routine examination results showed that the median value of hemoglobin in GOV2 group was lower than that in IGV1 group(91.00 g/L VS 112.00 g/L, P<0.05). The incidence of portal hypertensive gastropathy (PHG) in GOV2 group was higher than that in IGV1 group [20.14% (28/139) VS 5.63% (4/71), P<0.05]. The incidence of peptic ulcer was lower in GOV2 group than that in IGV1 group [12.23% (17/139) VS 38.03% (27/71), P<0.05]. The median diameter of portal veins in GOV2 group was larger than that in IGV1 group (15.09 mm VS 12.85 mm, P<0.05), and the volume of gastric fundus varices in GOV2 group was smaller than that in IGV1 group (2.14 mL VS 10.00 mL, P<0.05). The proportion of afferent veins in left gastric vein in GOV2 group was higher than that in IGV1 group [98.43% (125/127) VS 77.78% (42/54), P<0.05], and the median diameter of left gastric vein in GOV2 group was larger than that in IGV1 group (5.58 mm VS 4.53 mm, P<0.05). The efferent vessels mainly included gastrorenal shunt and splenorenal shunt. The incidences of gastrorenal shunt [27.56% (35/127) VS 66.67% (36/54)] and splenirenal shunt [12.60% (16/127) VS 25.93% (14/54)] in GOV2 group were lower than those in IGV1 group ( both P<0.05). The incidences of venae parumbilicales vein [38.58% (49/127) VS 12.96% (7/54)] and retroperitoneal collateral shunt [30.71% (39/127) VS 11.11% (6/54)] in GOV2 group were higher than those in IGV1 group (both P<0.05). Conclusion:There is significant heterogeneity in clinical features and imaging findings between cirrhotic patients complicated with GOV2 and IGV1. Recognizing and understanding the differences between the two types of patients is beneficial to taking appropriate clinical measures and improving patient prognosis.

A multivariate analysis of acute severe cholangitis and the establishment and evaluation of a risk prediction scoring model / 临床肝胆病杂志

Objective To investigate the independent risk factors for acute severe cholangitis and related protective factors, and to construct a risk prediction scoring model for acute severe cholangitis. Methods A retrospective analysis was performed for the clinical data of 381 patients with acute cholangitis who were admitted to Department of Hepatobiliary Surgery, The 940th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, from January 2016 to July 2021, among whom there were 273 patients with non-severe cholangitis and 108 patients with severe cholangitis. Univariate and multivariate logistic regression analyses were used to screen out the independent risk factors for acute severe cholangitis and related protective factors, and then a logistic regression model was established. The receiver operating characteristic (ROC) curve was used to evaluate the discriminatory ability of the model, the calibration curve was used to evaluate the prediction accuracy of the model, and decision curve analysis (DCA) was used to evaluate the clinical value of the model. Moreover, the enhanced Bootstrap method was used to perform internal validation of the model and evaluate the performance of the model in internal validation. The model was visualized by the construction of Web calculator, nomogram, and scoring system. The two-independent-samples t test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. Results The univariate and multivariate logistic regression analyses showed that total bilirubin (TBil) (odds ratio [ OR ]=1.014, 95% confidence interval [ CI ]: 1.009-1.020, P < 0.001), percentage of neutrophils ( OR =1.128, 95% CI : 1.088-1.175, P < 0.001), and age ( OR =1.053, 95% CI : 1.027-1.082, P < 0.001) were independent risk factors, and albumin (Alb) ( OR =0.871, 95% CI : 0.817-0.924, P < 0.001) was a protective factor. The above independent risk factors and protective factor were included in the logistic regression analysis for model fitting, and the predictive model obtained had an area under the ROC curve (AUC) of 0.925 (95% CI : 0.897-0.952), with a specificity of 0.817 and a sensitivity of 0.935 at the optimal cut-off value of 0.245. The calibration curve showed that the predicted probability of the model was approximately equal to the actual probability, with a Brier value of 0.098, and the decision curve analysis showed that the model had a higher net income within the threshold probability interval of 0.1-0.9. Internal validation showed an AUC internal validation of 0.915 and a Brier value internal verification of 0.106. Conclusion TBil, percentage of neutrophils, and age are independent risk factors for acute severe cholangitis, while Alb is a protective factor. The established risk prediction scoring model has good discriminatory ability, calibration, and clinical value and can identify patients with acute severe cholangitis at an early stage, which provides a reference for subsequent diagnosis and treatment.

Multicenter study of the clinicopathological features and recurrence risk prediction model of early-stage breast cancer with low-positive human epidermal growth factor receptor 2 expression in China (Chinese Society of Breast Surgery 021) / 中华医学杂志(英文版)

BACKGROUND@#: Breast cancer with low-positive human epidermal growth factor receptor 2 (HER2) expression has triggered further refinement of evaluation criteria for HER2 expression. We studied the clinicopathological features of early-stage breast cancer with low-positive HER2 expression in China and analyzed prognostic factors.@*METHODS@#: Clinical and pathological data and prognostic information of patients with early-stage breast cancer with low-positive HER2 expression treated by the member units of the Chinese Society of Breast Surgery and Chinese Society of Surgery of Chinese Medical Association, from January 2015 to December 2016 were collected. The prognostic factors of these patients were analyzed.@*RESULTS@#: Twenty-nine hospitals provided valid cases. From 2015 to 2016, a total of 25,096 cases of early-stage breast cancer were treated, 7642 (30.5%) of which had low-positive HER2 expression and were included in the study. After ineligible cases were excluded, 6486 patients were included in the study. The median follow-up time was 57 months (4-76 months). The disease-free survival rate was 92.1% at 5 years, and the overall survival rate was 97.4% at 5 years. At the follow-up, 506 (7.8%) cases of metastasis and 167 (2.6%) deaths were noted. Multivariate Cox regression analysis showed that tumor stage, lymphvascular invasion, and the Ki67 index were related to recurrence and metastasis (P < 0.05). The recurrence risk prediction model was established using a machine learning model and showed that the area under the receiving operator characteristic curve was 0.815 (95% confidence interval: 0.750-0.880).@*CONCLUSIONS@#: Early-stage breast cancer patients with low-positive HER2 expression account for 30.5% of all patients. Tumor stage, lymphvascular invasion, and the Ki67 index are factors affecting prognosis. The recurrence prediction model for breast cancer with low-positive HER2 expression based on a machine learning model had a good clinical reference value for predicting the recurrence risk at 5 years.@*TRIAL REGISTRATION@#: ChiCTR.org.cn, ChiCTR2100046766.

Establishment and evaluation of mouse models of hepatic sinusoidal obstruction syndrome induced by three pyrrolidine alkaloids / 中华消化杂志

Objective:To establish and evaluate acute hepatic sinusoidal obstruction syndrome (HSOS) mouse models induced by three pyrrolidine alkaloids (PAs) including monocrotaline (MCT), retrorsine (RTS) and senecionine (SEN).Methods:Forty-eight male C57 mice were divided into four groups, control group, MCT group, RTS group and SEN group, with 12 mice in each group, which were gavaged once with phosphate buffer saline (300 μL), MCT solution (800 mg/kg), RTS solution (100 mg/kg) and SEN solution (100 mg/kg), respectively. At 24 hours after gavage, the number of mortality and success modeling, liver function, and pathological changes of liver of four groups of mice were analyzed. One way analysis of variance, Bonferroni test and Chi-square test were used for statistical analysis.Results:At 24 hours after gavage, the number of dead mice of MCT group, RTS group and SEN group was zero, nine and zero, respectively; and the number of survival successfully modeled mice was nine, three and six, respectively; the difference of mortality among three groups was statistically significant ( χ2=21.734, P<0.05), and the difference of the number of success modeling was not statistically significant ( χ2=2.836, P>0.05). The alanine aminotransferase (ALT) levels of MCT group, RTS group and SEN group were (111.72±37.62), (562.97±242.42) and (3 891.40±1 009.44) U/L, respectively; aspartate transaminase (AST) levels were (156.96±64.95), (331.22±120.83) and (2 107.55±532.80) U/L, respectively; and total bilirubin (TBil) levels were (41.66±10.42), (79.43±18.45) and (120.80±17.44) μmol/L, respectively, which were all higher than those of the control group ((31.40±10.98) U/L, (34.66±13.00) U/L and (16.91±2.89) μmol/L, respectively); and the differences were statistically significant (Bonferroni test, all P<0.008 3). There were statistically significant differences in ALT and AST levels between MCT group and RTS group (Bonferroni test, both P<0.008 3), while there was no statistically significant difference in TBil level between two groups ( P>0.008 3). There was statistically significant difference in TBil level between MCT group and SEN group (Bonferroni test, P=0.002), however there were no statistically significant differences in ALT and AST levels between two groups (both P>0.008 3). There were statistically significant differences in ALT, AST and TBil levels between RTS group and SEN group (Bonferroni test, all P<0.008 3). The mouse liver tissues of all three groups showed coagulative necrosis of hepatocytes, subendothelial hemorrhage of central vein, the dilation of hepatic sinusoids, erythrocyte clogging in the space of disse, and destruction of normal lobular structure. In MCT and RTS groups, the main damages were hepatocyte necrosis, sinusoidal dilatation and congestion in zone 3 of the liver acinus, while in SEN group, which were hepatocyte necrosis and sinusoidal congestion in zone 1 and 2 of the liver acinus. The histological changes of mouse liver tissues of MCT group were moderate to severe, and those of RTS group and SEN group were all severe. Conclusions:Acute HSOS mouse models induced by three kinds of PA including MCT, RTS and SEN are successfully established, of which MCT is the most suifable choice.

Androgen receptor expression and association with clinicopathological features and prognosis in early stage triple-negative breast cancer / 国际外科学杂志

Objective@#To discuss the androgen receptor (AR) expresion and its association with clinicopathological features and prognosis in early stage triple-negative breast cancer patients (TNBC).@*Methods@#The present study retrospectively analyzed the clinic data of 1 018 patients with early-stage invasive breast cancer treated at the Breast Disease Center at Peking University First Hospital between January 2014 and December 2016, including 1 011 females and 7 males; the age range was 21 to 92 years, and the median age was 57 years. Patients with TNBC were enrolled, and divided into AR positive group and AR negative group according to the expression of AR.The clinicopathological features were analysed, including menopause status, pathological type, T staging, lymph node involvement, anatomic staging, prognostic staging, Ki-67 index, histological grade, vascular tumor thrombus and neuroinvation, and the correlation between the expression of AR and clinicopathological features, curative effect of neoadjuvant chemotherapy and prognosis were calculated. The Student’s t test was used to compare continuous data, the Pearson χ2 test or Fisher exact test was used to compare categorical variables, and the Mann-Whitney U test was used for quantitative data. The Kaplan-Meier method was used to analyze survival status, and comparisons between groups were calculated by the log-rank test.@*Results@#This study included 148 TNBC, accounting for 14.5% of all patients, in which all patients were females, and the median age was 55 years, ranging from 27 years to 75 years. The number of AR-positive TNBC was 59, accounted for 39.9% of all TNBC patients, and the numbers of AR-negative were 89, accounted for 60.1%. Ki-67 index, histological grade and prognostic stage were significantly different in AR-positive and AR-negative TNBC(P<0.05). There was no statistically significant difference between AR-positive TNBC and AR-negative TNBC in OS (98.3% vs 95.4%, P=0.830) or in DFS (91.4% vs 91.0%, P=0.812). Among TNBC who received neoadjuvant chemotherapy, AR-positive patients showed a lower pCR rate than AR-negative patients(χ2=4.381, P=0.046).@*Conclusions@#AR expression is associated with lower respond to neoadjuvant chemotherapy in TNBC. However, the association between AR expression and prognosis in TNBCs was still not clear.

Androgen receptor expression and association with clinicopathological features and prognosis in early stage triple-negative breast cancer / 国际外科学杂志

Objective To discuss the androgen receptor (AR expresion and its association with clinicopathological features and prognosis in early stage triple-negative breast cancer patients (TNBC).Methods The present study retrospectively analyzed the clinic data of 1 018 patients with early-stage invasive breast cancer treated at the Breast Disease Center at Peking University First Hospital between January 2014 and December 2016,including 1 011 females and 7 males;the age range was 21 to 92 years,and the median age was 57 years.Patients with TNBC were enrolled,and divided into AR positive group and AR negative group according to the expression of AR.The clinicopathological features were analysed,including menopause status,pathological type,T staging,lymph node involvement,anatomic staging,prognostic staging,Ki-67 index,histological grade,vascular tumor thrombus and neuroinvation,and the correlation between the expression of AR and clinicopathological features,curative effect of neoadjuvant chemotherapy and prognosis were calculated.The Student's t test was used to compare continuous data,the Pearsonx2 test or Fisher exact test was used to compare categorical variables,and the Mann-Whitney U test was used for quantitative data.The Kaplan-Meier method was used to analyze survival status,and comparisons between groups were calculated by the log-rank test.Results This study included 148 TNBC,accounting for 14.5％ of all patients,in which all patients were females,and the median age was 55 years,ranging from 27 years to 75 years.The number of AR-positive TNBC was 59,accounted for 39.9％ of all TNBC patients,and the numbers of AR-negative were 89,accounted for 60.1％.Ki-67 index,histological grade and prognostic stage were significantly different in AR-positive and AR-negative TNBC (P ＜ 0.05).There was no statistically significant difference between AR-positive TNBC and AR-negative TNBC in OS (98.3％ vs 95.4％,P =0.830) or in DFS (91.4％ vs 91.0％,P =0.812).Among TNBC who received neoadjuvant chemotherapy,AR-positive patients showed a lower pCR rate than AR-negative patients (x2 =4.381,P =0.046).Conclusions AR expression is associated with lower respond to neoadjuvant chemotherapy in TNBC.However,the association between AR expression and prognosis in TNBCs was still not clear.

An analysis of 68 invasive lobular breast cancer cases in clinicopathological characteristics and the prognostic determinants / 中华外科杂志

Objective@#To study the clinicopathological characteristics and the prognostic determinants of the invasive lobular carcinoma breast cancer.@*Methods@#This was a retrospective single-center study of invasive lobular breast cancer cases diagnosed from January 2008 to December 2014 at Peking University First Hospital Breast Disease Center. The study enrolled 68 invasive lobular breast cancer patients, which represented 3.64% (68/1 870) of total invasive breast cancer. The median age of all selected patients was 46 years ranging from 36 to 83 years. All patients were restaged based on the 8th edition of AJCC cancer staging system and follow-up data including disease-free survival (DFS) and overall survival (OS) were analyzed to explore the prognostic determinants. The 5-year OS and DFS were calculated using Kaplan-Meier method; the significance of correlations between clinicopathological features and prognostic factors was estimated using log-rank test.@*Results@#There were significant differences in OS between patients with different anatomic stage, prognostic stage, lymph node metastasis, progesterone receptor (PR) expression, lymphvascular invasion and perineural invasion (χ2: 4.318 to 32.394, all P<0.05); significant differences in DFS were also observed between patients with different anatomic stage, prognostic stage, lymph node metastasis, PR expression, human epidermal growth factor receptor-2 expression, Ki-67 level, histological grade and lymphvascular invasion (χ2: 4.347 to 27.369, all P<0.05). Prognostic stages of 52.9% patients changed compared with anatomic stage, among which Luminal subtype mainly downstaged (22/30), however, triple negative subtype mainly upstaged (6/6).@*Conclusions@#Anatomic stage, prognostic stage, lymph node metastasis, PR expression, lymphvascular invasion are the prognostic factors of invasive lobular breast cancer. Regard to invasive lobular breast cancer patients, clinicians should pay close attention to the differences between prognostic stage and anatomic stage.

Expression of Aquaporin-4 in White Matter of Spinal Cord in Rats after Spinal Cord Contusion / 中国康复理论与实践

Objective To explore the expression of aquaporin (AQP)-4 in white matter of spinal cord after spinal cord contusion (SCC). Methods 88 adult Sprague-Dawley rats were assigned randomly to sham operation group and SCC group. The model was established by Al-len's method. BBB sore was used to assess the motor function of rats. The relative expression of AQP-4 mRNA was determined by Q-PCR technique. The localization of AQP-4 was observed by immunohistochemistry. Results BBB score showed motor dysfunction in SCC group, and it increased 7 and 14 days after SCC (t>5.061, P50.44, P<0.001), and increased on the 5th day (t=-3.968, P=0.001), and lasted until the 28th day (t=-4.227, P=0.001) compared with that on the 3rd day. The immunohistochemistry showed AQP-4 was located on the process of glial cell and vascular endothelial cells in white matter of spi-nal cord. Conclusion AQP-4 may play various roles at different stages in SCC.

Lentivirus-mediated inhibition of tumor necrosis factor-alpha effect in expression of Caspase-3 and Bcl-2 in spinal cord contusion rats / 实用医学杂志

Objective To explore the change of apoptosis factor Caspase-3 and Bcl-2 in the injured segment of rat with spinal cord injury after inhibiting lentivirus expression of inflammation factor TNF-α. To study the relationship between Caspase-3, Bcl-2, Bax and TNF-α in spinal cord injury. Mthods Spinal cord contusion model was prepared by Allen method. The relation between tumor necrosis factor alpha and Bcl-2, was predicted by the method of GeneMANIA bioinformatics. The RNA which was packaged by lentivirus constructed the RNA interference model of tumour necrosis factor alpha. After interference of tumor necrosis factor alpha, we used the method of QRT-PCR to assays the mRNA expression of Caspase-3 and Bcl-2 in spinal cord and detect of the localization of Caspase-3 and Bcl-2 by immunohistochemistry. Statistical analysis with SPSS17.0. Results SD rats had paraplegia and urinate retentaion because of spinal cord injury. The result of QRT-PCR showed that in the seventh day after SCC, the expression of Caspase-3 reduced significantly (P 0.05). Immunohistochemistry experiment results showed that Caspase-3 Bcl-2 and Bax immunoreactive cells were observed in the neurons and glial cells of both white matter and gray matter in the spinal cord. The results were the same with QRT-PCR.. Conclusion TNF-α in rats after SCC can effectively regulate the ratio of Bcl-2 and Bax , and then regulate the expression of Caspase-3 , which may affect the function of apoptosis and function recovery after spinal cord injury.