In order to promote the optional subjects' function in perfecting knowledge structure and developing students'personalities,through analyses of the results of 830 classmates' selection of optional subjects,we know in detail the contents,objective and the factors for which students hope to increase and select optional subjects.Thus suggestions for enhancing the construction and management of optional subjects have been put forward: transforming conception,nailing down the study purpose,increasing optional subjects and establishing the leading teachers' system of optional subjects.

The 25th Congress of the European Hematological Society (EHA) was held in the form of a virtual edition from June 11 to 21, 2020, which focused on the significance of the detection of MYD88 and CXCR4 mutations in Waldenstr?m macroglobulinemia (WM) patients by using circulating free DNA (cfDNA), as well as the clinical results of Bruton tyrosine kinase inhibitors and treatment regimen including rituximab in the front-line and relapsed WM patients.

Objective: To explored the effect and related mechanism of miRNA-21 on hydrogen peroxide-induced C-kit⁺ cardiac stem cells apoptosis. Methods: C-kit⁺ cardiac stem cells were isolated from SD rats by the methods of enzyme digestion and magnetic bead. Cells were divided into the following experimental groups: (1) negative control mimics (NCM)group: cells were transfected with negative control miRNA-21 mimics for 48 hours; (2)mimics group: cells were transfected with miRNA-21 mimics for 48 hours; (3) NCM+ H₂O₂ group: negative control miRNA-21 mimics were transfected into cells for 48 hours and then treated with 100 μmol H₂O₂ for 2 hours; (4)mimics+ H₂O₂ group: miRNA-21 mimics were transfected into cells for 48 hours and then treated with 100 μmol H₂O₂ for 2 hours. mRNA of miRNA-21 was detected by RT-PCR. The apoptosis rate of C-kit⁺ cardiac stem cells was determined using the annexin V-FITC/PI staining assay. Western blot was employed to measure the expression of apoptosis related proteins(Caspase-3, Bax, and Bcl-2). Results: (1) Compared with the NCM group, the mRNA expression level of miRNA-21 was significantly up-regulated in mimics group, while obviously down-regulated in NCM+ H₂O₂ group(all P<0.05). Compared with the mimics group, the mRNA expression levels of miRNA-21 in mimics+ H₂O₂ group was significantly downregulated (P<0.05), but remarkably upregulated compared with the NCM+ H₂O₂ group(P<0.05). (2) Flow cytometry results indicated that the early apoptosis rates were similar between the NCM group and mimics group ((4.57±3.45)% vs. (5.13±3.21)%, P>0.05). Compared with the NCM group, the early apoptosis rates were remarkably increased ((79.07±5.75)% vs.(4.57±3.45)%, P<0.05) in NCM+ H₂O₂ group. Compared with the mimics group, the early apoptosis was significantly up-regulated in the mimics+ H₂O₂ group ((30.27±1.36)% vs.(5.13±3.21)%, P<0.05), which were further down-regulated in mimics+ H₂O₂ group compared with the NCM+ H₂O₂ group ((30.27±1.36)% vs.(79.07±5.75)%, P<0.05). (3) Western blot results showed similar protein expression of Caspase-3, Bax and Bcl-2 between NCM group and mimics group(all P>0.05). Compared with the NCM group, the Caspase-3 and Bax protein expression was significantly increased in NCM+ H₂O₂ group (all P<0.05), but the protein expression level of Bcl-2 was similar between the 2 groups(P>0.05). The Caspase-3 and Bax protein expression was markedly decreased, while Bcl-2 apparently increased in the mimics+ H₂O₂ group compared with the NCM+ H₂O₂ group(all P<0.05). Conclusion Overexpression of miRNA-21 protects the C-kit⁺ cardiac stem cells from apoptosis caused by oxidative stress through downregulating proapoptotic and upregulating the antiapoptotic proteins.

Objective:To investigate the clinical efficacy of qualitative and staging diagnosis of rectal tumors with dual contrast-enhanced ultrasonography and interventional biopsy.Methods:A total of 300 patients with rectal tumors who received treatment in The First People's Hospital of Huzhou from December 2019 to March 2022 were included in this study. All patients underwent dual contrast-enhanced ultrasonography and interventional biopsy followed by focus resection. Taking the postoperative histopathological test results as the gold standard, the efficacy of dual contrast-enhanced ultrasonography and interventional biopsy in the localization, qualitative analysis, and staging of rectal tumors was analyzed.Results:The compliance rate of dual contrast-enhanced ultrasonography and interventional biopsy in the localization of rectal tumors was 100%. The sensitivity, specificity, and accuracy of the dual contrast-enhanced ultrasonography and interventional biopsy for qualitative diagnosis of rectal tumors were 94.8%, 97.8%, and 96.7%, respectively. The Kappa value used for assessing agreement in the qualitative diagnosis of rectal tumors between dual contrast-enhanced ultrasonography and interventional biopsy and postoperative tissue pathological examination results was 0.947. The area under the curve plotted for qualitative diagnosis of rectal tumors was 0.974. The sensitivity, specificity, and sensitivity of dual contrast-enhanced ultrasonography and interventional biopsy for diagnosis of stage I-III rectal cancer were 94.1%-97.8%. The Kappa values used for assessing agreement in staging diagnosis of stage I-III rectal cancer between dual contrast-enhanced ultrasonography and interventional biopsy and postoperative tissue pathological examination results were 0.923, 0.912, and 0.927, respectively. The areas under the curve plotted for staging diagnosis of rectal cancer were 0.961, 0.955, and 0.970, respectively.Conclusion:Dual contrast-enhanced ultrasonography and interventional biopsy have a high efficacy in the localization, qualitative diagnosis, and staging diagnosis of rectal tumors.

Severe fever with thrombocytopenia syndrome virus (SFTSV), a member of the Phlebovirus genus from the Bunyaviridae family endemic to China, is the causative agent of life-threatening severe fever with thrombocytopenia syndrome (SFTS), which features high fever and hemorrhage. Similar to other negative-sense RNA viruses, SFTSV encodes a nucleocapsid protein (NP) that is essential for viral replication. NP facilitates viral RNA encapsidation and is responsible for the formation of ribonucleoprotein complex. However, recent studies have indicated that NP from Phlebovirus members behaves in inhomogeneous oligomerization states. In the present study, we report the crystal structure of SFTSV NP at 2.8 Å resolution and demonstrate the mechanism by which it processes a ringshaped hexameric form to accomplish RNA encapsidation. Key residues essential for oligomerization are identified through mutational analysis and identified to have a significant impact on RNA binding, which suggests that correct formation of highly ordered oligomers is a critical step in RNA encapsidation. The findings of this work provide new insights into the discovery of new antiviral reagents for Phlebovirus infection.
Binding Sites ; Crystallography, X-Ray ; Mutation ; Nucleocapsid Proteins ; chemistry ; genetics ; metabolism ; Phlebovirus ; metabolism ; Protein Binding ; Protein Multimerization ; Protein Structure, Quaternary ; RNA, Viral ; metabolism ; Recombinant Proteins ; biosynthesis ; chemistry ; genetics

The p53 signaling pathway works as a potent barrier to tumor progression. Two single nucleotide polymorphisms (SNPs) in the gene loci of p53 pathway, p53 codon 72 Arg72Pro and MDM2 SNP309 (T > G), have been shown to cause perturbation of p53 function, but the effect of the two SNPs on the risk of hepatocellular carcinoma (HCC) remains inconsistent. This study investigated the influence of combined p53 Arg72Pro and MDM2 SNP309 on the risk of developing HCC in patients with chronic hepatitis B virus infection, and evaluated the significance of the two combined SNPs on patient prognosis. In total, 350 HCC patients, 230 non-HCC patients, and 96 healthy controls were genotyped for the p53 Arg72Pro and MDM2 SNP309. The combined p53 Pro/Pro and MDM2 G/G genotype was significantly associated with HCC risk (P = 0.047). Multivariate analysis indicated that combined p53 Pro/Pro and MDM2 G/G genotype was an independent factor affecting recurrence and survival (P < 0.05). Patients with combined p53 Pro/Pro and MDM2 G/G genotypes had a poorer prognosis than other genotypes, P < 0.01 for both disease-free survival (DFS) and overall survival (OS). DFS and OS rates also differed significantly between Barcelona Clinic Liver Cancer (BCLC) stage A patients with combined p53 Pro/Pro and MDM2 G/G and other genotypes (P < 0.05). Thus, the combined p53 Pro/Pro and MDM2 G/G genotype is associated with increased risk of developing HCC and is an independent adverse prognostic indicator in early stage HCC.
Carcinoma, Hepatocellular ; diagnosis ; genetics ; surgery ; virology ; Carrier State ; virology ; Cohort Studies ; Female ; Genetic Predisposition to Disease ; genetics ; Hepatitis B virus ; physiology ; Humans ; Liver Neoplasms ; diagnosis ; genetics ; surgery ; virology ; Male ; Middle Aged ; Neoplasm Staging ; Polymorphism, Single Nucleotide ; Prognosis ; Proto-Oncogene Proteins c-mdm2 ; genetics ; Tumor Suppressor Protein p53 ; genetics

Objective:To explore the prognostic factors of primary plasma cell leukemia (pPCL) in the era of novel agents.Methods:The clinical data of 66 patients with pPCL treated at the Department of Haematology, Beijing Chao-Yang Hospital, Capital Medical University from 2011 to 2022 were retrospectively collected to analyze their prognostic factors.Results:Among the 66 patients with pPCL, the median age was 59 (range: 29-79) years. The median overall survival (OS) duration was 19.0 (95% CI 10.4-27.6) months, and the median progression-free survival (PFS) duration was 11.0 (95% CI 6.5-15.6) months. The median OS and PFS were significantly longer in patients with the best post-treatment response of very good partial remission (VGPR) or better than in patients with a response of partial remission (PR) or worse (median OS: 33.0 months vs 6.0 months, P<0.001; median PFS: 16.0 months vs 3.0 months, P<0.001). OS was significantly longer in patients who underwent autologous hematopoietic stem cell transplantation than in those who did not undergo transplantation (49.0 months vs 6.0 months, P=0.002), and there was a trend toward a longer PFS in patients who underwent transplantation than in those who did not undergo transplantation (19.0 months vs 8.0 months, P=0.299). The median OS and PFS were significantly longer in patients who received maintenance therapy than in those who did not receive maintenance therapy (median OS: 56.0 months vs 4.0 months, P<0.001; median PFS: 20.0 months vs 2.0 months, P<0.001). Multivariate analysis showed that hypercalcemia was an independent risk factor ( HR=3.204, 95% CI 1.068-9.610, P=0.038) for patients with pPCL, while receiving maintenance therapy ( HR=0.075, 95% CI 0.022-0.253, P<0.001) and post-treatment response of VGPR or better ( HR=0.175, 95% CI 0.048-0.638, P=0.008) were independent protective factors for patients with pPCL. Conclusions:In the era of novel agents, hypercalcemia, receiving maintenance therapy, and post-treatment response of VGPR or better are independent prognostic factors for pPCL.

Objective:To explore the value of multi-parametric MRI for thyroid gland in differentiating benign and malignant thyroid nodules.Methods:From December 2018 to May 2020, 78 patients with 91 post-surgically pathologically confirmed thyroid nodules were enrolled in Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. For each patient, the following MRI findings were obtained including the nodules′ location, size, shape, margin, signal intensity, cystic change, degree and pattern of contrast enhancement, involvement of surrounding structure, and ADC values. The time-intensity curve (TIC) were plotted and subtyped based on dynamic contrast enhancement MRI. The MRI findings between the benign and malignant thyroid nodules were compared using Mann-Whitney U test, χ 2 test or Fisher exact test. Multiple logistic regression analysis was used to select independent predictive variables and build a combined model, and the ROC curve was used to evaluate the diagnostic performance of each MRI finding and the combined model. Results:Between the benign and malignant thyroid nodules, the significant differences were found in size, shape, margin, presence of cystic changes, T 1WI signal intensity, ADC value, enhancement homogeneity, TIC subtypes and presence of thyroid capsule involvement ( P<0.05). Multivariate logistic analysis showed that ill-defined margin (OR=77.61), no presence of cystic changes (OR=36.11) and difference between TIC subtypes (OR=83.41) were independent predictive variables, and the area under the ROC curve (AUC) was 0.879, 0.788, and 0.751, respectively. The AUC, sensitivity and specificity of the combined model were 0.977, 0.986, and 0.904, respectively. Conclusions:Thyroid multi-parametric MRI derived findings can be used for the differential diagnosis of benign and malignant nodules. Combined with the independent risk factors with ill-defined margin, no presence of cystic changes, TIC of type plateau or washout, the diagnostic model has a higher diagnostic efficiency.

Objective:To investigate the feasibility and reproducibility of using three-dimensional arterial spin labeling (3D-ASL) technique to evaluate the thyroid blood flow (TBF) in healthy adults and compare the difference in TBF between subjects with different gender and age.Methods:In this prospective study, 100 healthy adult subjects were enrolled from November 2018 to June 2019 in Chinese Academy of Medical Sciences Cancer Hospital, Shenzhen Hospital. All subjects received thyroid 3D-ASL MRI scanning, but several subjects were excluded from analysis for reasons including intolerance to examination ( n=1), overt artifacts ( n=11), abnormality detected in thyroid gland during conventional MRI ( n=15), resulting in 73 subjects included. Two attending radiologists independently evaluated the quality of ASL images and measured the TBF in upper, middle and lower poles of each lobe in thyroid gland bilaterally. Cohen’s Kappa was used to test the agreement in image quality between 2 radiologists, while intraclass correlation (ICC) analysis was implemented to evaluate the consistency in TBF measurements. Univariate variance analysis was used to compare the TBF in upper, middle and lower pole of thyroid gland unilaterally, and student t-test was performed to test the difference in TBF between two lobes, or in the same lobe but between different gender or age groups. Results:For image quality, 2 radiologists have good agreement (Kappa=0.753, P<0.001). In terms of TBF, consistency was moderate in the lower pole of left lobe between 2 radiologists (ICC=0.648, P<0.001), but good in the remaining parts of thyroid gland (all ICC>0.75, P<0.001). Unilaterally, TBF in the middle pole was significantly higher than those in the upper or lower pole ( P<0.001), but no significant difference was found between the upper and lower pole ( P>0.05). Regardless of upper, middle or lower pole, TBF in the right lobe was higher than the counterpart in the left lobe ( t=6.182, 6.294, 4.896, P<0.001). Between male subjects ( n=31) and female subjects ( n=42), no significant difference was found in the corresponding upper, middle or lower pole of thyroid lobe unilaterally ( P>0.05). As for age group, TBF in the middle pole of thyroid gland was higher in the middle age group (45-59 years old, n=12) than that in the young adult group (18-44 years old, n=61) ( t=3.868, P=0.003 for the left lobe, and t=2.647, P=0.022 for the right lobe), but no significant difference was found in the upper or lower pole of the unilateral thyroid lobe ( P>0.05). Conclusion:ASL can accurately measure blood flow perfusion in the thyroid gland with good reproducibility.

Objective:To retrospectively analyze the serological, virological, biochemical, liver histological status and clinical outcomes in HBeAg-negative chronic hepatitis B (CHB) patients with low HBV viral load, and to explore the necessity of antiviral therapy for these patients.Methods:A total of 99 HBeAg-negative CHB patients with HBV DNA level < 4 lg copies/ml who performed liver biopsy at the baseline were enrolled from the follow-up cohort. Among them, 23 cases received the second liver biopsy during follow-up. The relationships among the degree of inflammation and fibrosis of liver tissues, the status of HBsAg and HBcAg, age, gender, family history, HBV DNA load, serological markers and other indicators were analyzed. The pathological differences between two liver biopsy examinations were compared. The effect of nucleos(t)ide analogues (NAs) treatment on patient’s clinical outcomes were analyzed. For multivariate analysis, a binary logistic regression model was performed. Log-rank test was used to compare the cumulative incidence of hepatocellular carcinoma (HCC) in NAs-treated and non-NA streated patients.Results:Baseline liver histology status showed that 58.6% (58/99) patients had obvious liver tissue damage in their baseline liver tissue pathology (G≥2 and /or S≥2). Univariate logistic regression analysis showed that a liver cirrhosis (LC) family history, a HBsAg-positive family history, baseline alanine aminotransferase and aspartate aminotransferase levels were positively correlated factors for liver tissue damage. Multivariate logistic regression analysis showed that a LC family history was the main risk factor for liver tissue damage. Twenty-three cases had received a second liver biopsy after an interval of 4.5 years. In 10 untreated cases, the second liver biopsy results showed the rate of obvious liver tissue damage (G≥2 and/ or S≥2) increased from 50.0% to 90.0%. In the other 13 cases who received NAs treatment, the second liver biopsy showed improvement in liver histology, and the rate of obvious liver tissue damage decreased from 61.5% to 46.2%. The 5-year HCC cumulative incidence in non-NAs-treated patients was significantly higher than that of in NAs-treated patients (17.7% vs. 3.8%, P = 0.046). Conclusion:For most HBeAg-negative CHB patients with low viral load, liver tissue pathology result suggests that it meets the indications for antiviral therapy, especially in patients with a LC familial history. Without antiviral therapy, liver tissue damage for these patients will progressively worse with the high incidence of HCC. Therefore, it is suggested that antiviral therapy should be started as soon as possible for the HBeAg-negative CHB patients with low viral load regardless of the alanine aminotransferase level, especially in patients over 30 years-old with a LC or HCC family history.