Objective To explore the diagnosis of clinically suspicious von Willebrand disease(vWD)in a family and its pathogene-sis.Methods The pedigree information and the biological specimen were collected from the clinically suspected VWD patient and her family members(4 persons in total)in Peking University First Hospital.The levels of platelet count(PLT),activated partial thrombo-plastin time(APTT),vWF antigen(vWF:Ag),vWF activity(vWF:Ac)and FⅧ activity(FⅧ:C)were detected,and vWF risto-cetin cofactor(vWF:RCo)assay,ristocetin-induced platelet aggregation assay(RIPA)and vWF collagen binding(vWF:CB)assay were performed for phenotype diagnosis.The peripheral blood genomic DNAs were extracted from the proband and her family members to perform whole-exome sequencing for identifying the mutation of vWF gene,The mutation site was analyzed by using bioinformation tools to explore the pathogenesis of the proband.Results The APTT of proband(m 1)was slightly prolonged and her vWF:Ag,vWF:Ac,vWF:RCo and vWF:CB were significantly decreased.There was no obvious aggregation in RIPA assay(1.0 mg/mL and 1.25 mg/mL).In her father(Ⅱ3),APTT,FⅧ:C,vWF:Ag,vWF:Ac and vWF:CB were normal,but vWF:RCo was slightly decreased.In her mother(Ⅱ4),APTT,FⅧ:C,vWF:Ag,vWF:RCo and vWF:CB were all normal,but vWF:Ac significantly decreased.In her brother(Ⅲ2),APTT and FⅧ:C were normal,but vWF:Ag,vWF:Ac,vWF:RCo and vWF:CB were reduced to varying degrees.In all the family members(father,mother and brpther),no apparent aggregation in RIPA(1.0 mg/mL)was shown.Genetic analysis showed that the proband(Ⅲ1)carried a compound heterozygous mutation of vWF gene c.7288-9T＞G and c.1117C＞T,her father(Ⅱ3)carried vWF gene c.7288-9T＞G heterozygous mutation,and vWF gene c.1117C＞T heterozygous mutation was presented in both mother(Ⅱ4)and brother(Ⅲ2).Conclusion According to the results of laboratory tests,the proband was diagnosed as type 2A vWD.The hetero-zygous mutation in vWF gene c.1117C＞T and c.7288-9T＞G may be the molecular mechanism leading to type 2A vWD in the proband.

Aortic dissection (AD) is a life-threatening vascular disease due to the tearing of aortic intimal layer, leading to the formation of pseudocavity. Once the acute progression of dissection happens, serious complications such as rupture and stroke may occur. The current imaging examinations for AD are invasive and may cause adverse effects related to contrast medium, which cannot be used for large-scale screening of AD. The latest studies have found that metabolic processes and metabolites of lipids,saccarides and proteins are involved in the pathogenesis and development of AD. In this article, we review the research progress in the caracteristics of AD related metabolism,summarize changes of specific metabolites in AD,and explore the clinical implication of studies on AD related metaboliome..

【Objective】 To develop a prognosis model based on CT images using radiomics method for patients with osteonecrosis of the femoral head (ONFH) and to investigate the additional prediction value of the imaging features of the contralateral normal femoral head regions for the prognosis prediction. 【Methods】 A total of 51 patients were included in this retrospective study. All the patients had preoperative CT images. For each patient, two regions of interest (ROIs) were involved, including the osteonecrosis region and the contralateral normal femoral head region. A total of 968 radiomics features were extracted for each patient. We made both the univariate and multivariable analyses. Three models were developed based on the features of osteonecrosis region, contralateral normal femoral head region, and both regions. The 10 times of repeated random experiments were used for model construction and validation. The average performance of the 10 times of experiments was reported as the results. 【Results】 For the features of osteonecrosis region, 37 features showed significant predictive value, with the mean AUC value of 0.708 2±0.029 9. The AUC of the constructed prediction model was 0.911 0±0.029 4 and 0.688 6±0.089 3 for the training set and validation set, respectively. For the features of contralateral normal femoral head region, 14 features showed significant predictive value, with the mean AUC value of 0.703 6±0.006 9. The AUC value of the constructed model for the training set and validation set was 0.867 2±0.039 5 and 0.669 0±0.072 6, respectively. For the models developed based on combined features, the AUC value was higher than that of the models developed based on osteonecrosis region features (training set: 0.935 8±0.016 6 vs. validation set: 0.737 9±0.090 8). 【Conclusion】 We developed a novel CT images-based radiomics method to predict postoperative prognosis in patients with ONFH. Furthermore, the features of contralateral normal femoral head region has additional prediction value. Combining the imaging features of osteonecrosis region and contralateral normal femoral head region can obtain more accurate prediction of prognosis in patients with ONFH.

Aberrant activation of NLRP3 inflammasome in colonic macrophages strongly associates with the occurrence and progression of ulcerative colitis. Although targeting NLRP3 inflammasome has been considered to be a potential therapy, the underlying mechanism through which pathway the intestinal inflammation is modulated remains controversial. By focusing on the flavonoid lonicerin, one of the most abundant constituents existed in a long historical anti-inflammatory and anti-infectious herb

Objective:To explore the relationships between serum lipids, CA153 level and breast cancer incidence and clinicopathological features of patients.Methods:A total of 198 patients with breast cancer diagnosed and treated at Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School were enrolled as the case group, and 198 healthy women were selected with 1∶1 age pairing as controls. Five milliliters of fasting venous blood was collected to measure serum lipids levels in all subjects and CA153 levels in breast cancer patients. The difference of serum lipids levels between the two groups was compared. Logistic regression model was used to analyze the risk factors of breast cancer. For 165 breast cancer patients who did not receive neoadjuvant chemotherapy, independent sample t-test was used to compare serum lipids and CA153 levels in breast cancer patients with different pathological features, and Pearson correlation analysis was used to calculate the correlation between variables and CA153. Results:The triglyceride (TG) levels in the case group and the control group were (1.22±0.73) mmol/L and (1.06±0.52) mmol/L respectively, and the difference was statistically significant ( t=2.559, P=0.011); the total cholesterol (TC) levels were (4.47±0.86) mmol/L and (4.99±0.80) mmol/L respectively, and the difference was statistically significant ( t=-6.228, P<0.001); the high-density lipoprotein cholesterol (HDL-C) levels were (1.32±0.34) mmol/L and (1.53±0.38) mmol/L respectively, and the difference was statistically significant ( t=-5.913, P<0.001). Higher TC and HDL-C levels were independent protective factors for breast cancer ( OR=0.350, P<0.001; OR=0.531, P=0.013). The TC levels in lymph node positive and lymph node negative patients were (4.36±0.73) mmol/L and (4.67±0.83) mmol/L respectively, and the difference was statistically significant ( t=-2.518, P=0.013); low-density lipoprotein cholesterol (LDL-C) levels were (2.53±0.58) mmol/L and (2.77±0.70) mmol/L respectively, and the difference was statistically significant ( t=-2.312, P=0.022). The TC levels in patients with stage Ⅰ and stage Ⅱ/Ⅲ were (4.90±0.89) mmol/L and (4.46±0.76) mmol/L respectively, and the difference was statistically significant ( t=2.855, P=0.005); LDL-C levels were (2.95±0.71) mmol/L and (2.60±0.63) mmol/L respectively, and the difference was statistically significant ( t=2.705, P=0.008). The level of CA153 in triple-negative breast cancer patients [(14.94±7.45) U/ml] was significantly higher than that in non-triple-negative breast cancer patients [(11.96±5.96) U/ml], and the difference was statistically significant ( t=2.359, P=0.020). The level of CA153 was positively correlated with the level of TG ( r=0.167, P=0.032). Conclusion:Dyslipidemia is associated with an increased risk of breast cancer. The levels of serum lipids vary among patients with different lymph node status and tumor stages. CA153 level is positively correlated with TG level to some extent.

Objective:To systematically evaluate the clinical efficacy of programmed death-1 and programmed death ligand 1 (PD-1/PD-L1) inhibitors versus traditional first-line regimens for the treatment of solid tumors.Methods:Databases including PubMed, Embase and Cochrane Library were searched for literatures from the date of their establishment to October 2018 with the key words including "PD-1/PD-L1, solid tumors, melanoma, non-small cell lung cancer, renal cell carcinoma, immunotherapy" . The randomized controlled trial or non randomized controlled trial of high quality about PD-1/PD-L1 inhibitors and traditional fist-line regimens for the treatment of solid tumors were received and enrolled. Patients underwent PD-1/PD-L1 inhibitors immunotherapy were allocated into treatment group, patients underwent traditional first-line regimens treatment were allocated into control group. Two reviewers independently screened literatures, extracted data and assessed the risk of bias. Count data were described as odds ratio ( OR) and 95% confidence interval (95% CI). The heterogeneity of the studies included was analyzed using the I2 test. Funnel plot was used to test potential publication bias if the studies included≥5, and no test was needed if the studies included<5. Results:(1) Document retrieval: a total of 11 available randomized clinical trials were included. There were 5 161 patients, including 2 677 in the treatment group and 2 484 in the control group. (2) Results of Meta analysis. ① There was a significant difference in the objective response rate between the treatment group and the control group ( OR=4.49, 95% CI: 3.01-6.68, P<0.05). The bilateral symmetry was presented in the funnel plot based on the 9 studies, suggesting that publication bias had little influence on results of Meta analysis. ② There was no significant difference in the disease control rate between the treatment group and the control group ( OR=1.53, 95% CI: 1.01-2.32, P=0.05). The bilateral symmetry was presented in the funnel plot based on the 9 studies, suggesting that publication bias had little influence on results of Meta analysis. ③ There was a significant difference in disease stability rate between the treatment group and the control group ( OR=0.49, 95% CI: 0.33-0.73, P<0.05). The bilateral symmetry was presented in the funnel plot based on the 9 studies, suggesting that publication bias had little influence on results of Meta analysis. ④ There was no significant difference in disease progression rate between the treatment group and the control group ( OR=0.71, 95% CI: 0.45-1.15, P>0.05). The bilateral symmetry was presented in the funnel plot based on the 9 studies, suggesting that publication bias had little influence on results of Meta analysis. ⑤ There were significant differences in overall incidence of adverse events and incidence of adverse events not less than three levels between the treatment group and the control group ( OR=0.53, 0.54, 95% CI: 0.38-0.74, 0.31-0.93, P<0.05). The bilateral symmetry was presented in the funnel plot based on the 11 studies, suggesting that publication bias had little influence on results of Meta analysis. Conclusion:Compared with traditional first-line regimens treatment, PD-1/PD-L1 inhibitors immunotherapy can improve the objective response rate and decrease the incidence of adverse events.

In the original publication, the label of Fig. 2C should be read as "GFAP/lectin/DAPI" not "DMP1/GFAP/lectin/DAPI".

BACKGROUND: Advanced epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma had a high overall incidence of brain metastasis during the full course, and local brain radiotherapy combined with systemic targeted therapy may be a better strategy. This study aimed to identify the prognostic factors of EGFR-mutant brain-metastatic lung adenocarcinoma patients who received EGFR-tyrosine kinase inhibitors (EGFR-TKIs) in combination with gamma knife radiosurgery. METHODS: Retrospective analysis of EGFR-mutant lung adenocarcinoma patients with brain metastases which developed at initial diagnosis or during EGFR-TKIs treatment period were performed. Intracranial progression free survival (PFS) was statistically analyzed between different subgroups to find out the prognostic factors including gender, age, smoking history, extracranial metastasis, EGFR mutation type, size and number of intracranial lesions, carcino-embryonic antigen (CEA) level, lung-molGPA score and so on. RESULTS: A total of 74 EGFR-mutant brain-metastatic lung adenocarcinoma patients were enrolled in this study, with median intracranial PFS of 14.7 months. One-year intracranial-progression-free rate was 58.5%, and two-year rate was 22.2%. Univariate survival analysis showed that patients with lower CEA level at initial diagnosis (<10 ng/L)(16.9 months vs 12.6 months, P=0.012) and smaller intracranial lesions (<2 cm)(15.4 months vs 10.8 months, P=0.021) and higher lung-molGPA score (>3)(15 months vs 12.6 months, P=0.041) were prone to have a superior intracranial PFS. Multivariate analysis showed that CEA≥10 ng/mL and intracranial lesion≥2 cm were the independent risk factors of intracranial PFS. CONCLUSIONS EGFR-TKIs in combination with gamma knife radiosurgery was an efficient treatment option to control the cranial tumor lesion. CEA≥10 μg/L at initial diagnosis and intracranial lesion≥2 cm were the risk factors of EGFR-mutant brain-metastatic lung adenocarcinoma patients receiving EGFR-TKIs in combination with gamma knife radiosurgery.
Adenocarcinoma of Lung ; drug therapy ; pathology ; radiotherapy ; therapy ; Adult ; Aged ; Brain Neoplasms ; secondary ; Combined Modality Therapy ; ErbB Receptors ; antagonists & inhibitors ; genetics ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Prognosis ; Protein Kinase Inhibitors ; pharmacology ; therapeutic use ; Radiosurgery ; Retrospective Studies