Objective : To investigate the role of enhancer of zeste homolog 2(EZH2)-trimethylated lysine 27 of histone H3(H3K27me3) axis in the dedifferentiation of thyroid cancer and its clinical value as a potential target for the treatment of anaplastic thyroid cancer(ATC). Methods : Immunohistochemical SP method was used to detect the expression of EZH2, H3K27me3, paired box gene 8(PAX8), thyroglobulin(TG) and thyroid transcription factor 1(TTF1) in ATC and papillary thyroid carcinoma(PTC) and their adjacent tissues. The relationship between EZH2 and thyroid differentiation markers(PAX8, TTF1, TG) was further analyzed by gene expression omnibus(GEO) database. ATC cell lines 8305C and BHT-101 were culturedin vitro. Real-time reverse transcription PCR(RT-qPCR) was used to detect the expression of thyroid differentiation markers(TTF1, PAX8) mRNA in ATC cell lines treated with EZH2 inhibitor(GSK126), and evaluate the potential therapeutic effect of GSK126in vitro. The effects of GSK126 and BRAF inhibitor vemurafenib on the proliferation of ATC cell lines were observed by cell proliferation assay. Results : The expression of EZH2 in ATC tissues was significantly higher than that in papillary thyroid carcinoma and adjacent tissues(P<0.05). The expression of H3K37me3 in ATC tissues was significantly lower than that in PTC tissues(P<0.05). EZH2 was negatively correlated with PAX8 and TG expression levels, but not with TTF1 expression level.In vitroexperiments, GSK126 could reverse the expression of thyroid differentiation markers PAX8 and TTF1 in ATC cell lines. GSK126 combined with BRAF inhibitor vemurafenib could significantly inhibit the growth of ATC cell lines. Conclusion The EZH2-H3K27me3 axis plays an important role in regulating thyroid specific markers, and the inhibition of EZH2 by small molecular compounds is a promising target for ATC treatment in the future.

Ribosome is an intracellular ribonucleoprotein particle that serves as the site of protein biosynthesis. Ribosomal dysfunction caused by mutations in genes encoding ribosomal proteins (RPs) and ribosome biogenesis factors (RBFs) can lead to a spectrum of diseases, collectively known as ribosomopathy. Phase separation is a thermodynamic process that produces multiple phases from a homogeneous mixture. The formation of membraneless organelles and intracellular structures, including ribosomes and nucleoli, cannot occur without the involvement of phase separation. Here, ribosome structure, biogenesis, and their relationship with ribosomopathy are systematically reviewed. The tissue specificity of ribosomopathy and the role of phase separation in ribosomopathy are particularly discussed, which may offer some clues for understanding the mechanisms of ribosomopathy. Then, some new ideas for the prevention, diagnosis, and treatment of ribosomopathy are provided.
Humans ; Ribosomes/physiology* ; Ribosomal Proteins/metabolism* ; Mutation ; Animals ; Cell Nucleolus/metabolism* ; Protein Biosynthesis ; Phase Separation

Objective:To explore the value of ultrasound imaging characteristics combined with clinical indicators in assessing the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC).Methods:A retrospective analysis was conducted for patients who underwent pancreatic contrast-enhanced ultrasound (CEUS) from September 2017 to October 2023 at Peking Union Medical College Hospital and were diagnosed with PDAC based on pathological findings. Various parameters were recorded, including CA19-9 levels, tumor size, location, morphologic features, echogenicity, presence of internal cystic components, dilatation of the main pancreatic duct, peripheral vascular invasion, CEUS characteristics, presence or absence of liver metastasis, and treatment methods. In April 2024, patient survival information was obtained through telephone follow-up or review of medical records. Based on the results of the cox regression model analysis, a nomogram model of the risk of death was developed. The receiver operating characteristic (ROC) curves were applied to evaluate the predictive efficacy of the model. The calibration curves were plotted to evaluate the accuracy of the model, and clinical decision curves were used to evaluate the clinical benefit of the model.Results:This study included a total of 207 patients with PDAC. As of April 2024, 71 patients were alive and 136 died, with a median survival time of 14 months (95% CI: 12 -17). Multivariate analysis confirmed that the elevated CA19-9 ( HR=1.689, 95% CI: 1.102-2.588), tumor size >4 cm ( HR=1.641, 95% CI: 1.159-2.322), taller-than-wide shapes ( HR=1.450, 95% CI: 1.019-2.065), incomplete hypo-enhancement ( HR=1.618, 95% CI: 1.100-2.380), and liver metastasis ( HR=1.687, 95% CI: 1.175-2.423) were independent risk factors for survival in patients with PDAC. A nomogram model was further constructed for 6-month, 12-month and 3-year survival of patients with PDAC. The areas under the ROC curve were 0.679, 0.705 and 0.815, respectively. The calibration curves suggested that the model was more accurate, and the clinical decision curves showed that the model had a better clinical benefit. Conclusion:The combined use of ultrasound imaging characteristics and clinical indicators could effectively predict the prognosis of PDAC patients. Specifically, tumor size >4 cm, taller-than-wide shapes, incomplete hypo-enhancement, elevated CA19-9, and the presence of liver metastasis are correlated with poorer survival outcomes. The nomogram model constructed on the basis of these factors can be used to assess the survival of patients with PDAC.

Objective:To explore the value of ultrasound imaging characteristics combined with clinical indicators in assessing the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC).Methods:A retrospective analysis was conducted for patients who underwent pancreatic contrast-enhanced ultrasound (CEUS) from September 2017 to October 2023 at Peking Union Medical College Hospital and were diagnosed with PDAC based on pathological findings. Various parameters were recorded, including CA19-9 levels, tumor size, location, morphologic features, echogenicity, presence of internal cystic components, dilatation of the main pancreatic duct, peripheral vascular invasion, CEUS characteristics, presence or absence of liver metastasis, and treatment methods. In April 2024, patient survival information was obtained through telephone follow-up or review of medical records. Based on the results of the cox regression model analysis, a nomogram model of the risk of death was developed. The receiver operating characteristic (ROC) curves were applied to evaluate the predictive efficacy of the model. The calibration curves were plotted to evaluate the accuracy of the model, and clinical decision curves were used to evaluate the clinical benefit of the model.Results:This study included a total of 207 patients with PDAC. As of April 2024, 71 patients were alive and 136 died, with a median survival time of 14 months (95% CI: 12 -17). Multivariate analysis confirmed that the elevated CA19-9 ( HR=1.689, 95% CI: 1.102-2.588), tumor size >4 cm ( HR=1.641, 95% CI: 1.159-2.322), taller-than-wide shapes ( HR=1.450, 95% CI: 1.019-2.065), incomplete hypo-enhancement ( HR=1.618, 95% CI: 1.100-2.380), and liver metastasis ( HR=1.687, 95% CI: 1.175-2.423) were independent risk factors for survival in patients with PDAC. A nomogram model was further constructed for 6-month, 12-month and 3-year survival of patients with PDAC. The areas under the ROC curve were 0.679, 0.705 and 0.815, respectively. The calibration curves suggested that the model was more accurate, and the clinical decision curves showed that the model had a better clinical benefit. Conclusion:The combined use of ultrasound imaging characteristics and clinical indicators could effectively predict the prognosis of PDAC patients. Specifically, tumor size >4 cm, taller-than-wide shapes, incomplete hypo-enhancement, elevated CA19-9, and the presence of liver metastasis are correlated with poorer survival outcomes. The nomogram model constructed on the basis of these factors can be used to assess the survival of patients with PDAC.

Objective:To study the distribution and antibiotics resistance of the main pathogens of neonatal purulent meningitis in different regions of China.Methods:A retrospective descriptive clinical epidemiological study was conducted in children with neonatal purulent meningitis which admitted to 18 tertiary hospitals in different regions of China between January 2015 to December 2019. The test results of blood and cerebrospinal fluid, and drug sensitivity test results of the main pathogens were collected. The distributions of pathogenic bacteria in children with neonatal purulent meningitis in preterm and term infants, early and late onset infants, in Zhejiang Province and other regions outside Zhejiang Province, and in Wenzhou region and other regions of Zhejiang Province were analyzed. The chi-square test was used for statistical analysis.Results:A total of 210 neonatal purulent meningitis cases were collected. The common pathogens were Escherichia coli ( E. coli)(41.4%(87/210)) and Streptococcus agalactiae ( S. agalactiae)(27.1%(57/210)). The proportion of Gram-negative bacteria in preterm infants (77.6%(45/58)) with neonatal purulent meningitis was higher than that in term infants (47.4%(72/152)), and the difference was statistically significant ( χ2=15.54, P=0.001). There were no significant differences in the constituent ratios of E. coli (36.5%(31/85) vs 44.8%(56/125)) and S. agalactiae (24.7%(21/85) vs 28.8%(36/125)) between early onset and late onset cases (both P>0.05). The most common pathogen was E. coli in different regions, with 46.7%(64/137) in Zhejiang Province and 31.5%(23/73) in other regions outside Zhejiang Province. In Zhejiang Province, S. agalactiae was detected in 49 out of 137 cases (35.8%), which was significantly higher than other regions outside Zhejiang Province (11.0%(8/73)). The proportions of Klebsiella pneumoniae, and coagulase-negative Staphylococcus in other regions outside Zhejiang Province (17.8%(13/73) and 16.4%(12/73)) were both higher than those in Zhejiang Province (2.9%(4/137) and 5.1%(7/137)). The differences were all statistically significant ( χ2=14.82, 12.26 and 7.43, respectively, all P<0.05). The proportion of Gram-positive bacteria in Wenzhou City (60.8%(31/51)) was higher than that in other regions in Zhejiang Province (38.4%(33/86)), and the difference was statistically significant ( χ2=6.46, P=0.011). E. coli was sensitive to meropenem (0/45), and 74.4%(32/43) of them were resistant to ampicillin. E. coli had different degrees of resistance to other common cephalosporins, among which, cefotaxime had the highest resistance rate of 41.8%(23/55), followed by ceftriaxone (32.4%(23/71)). S. agalactiae was sensitive to penicillin, vancomycin and linezolid. Conclusions:The composition ratios of pathogenic bacteria of neonatal purulent meningitis are different in different regions of China. The most common pathogen is E. coli, which is sensitive to meropenem, while it has different degrees of resistance to other common cephalosporins, especially to cefotaxime.

Objective    To evaluate the midterm effect of valve-sparing aortic root replacement (VSRR) on aortic root aneurysm and moderate to severe aortic regurgitation (AR). Methods    The clinical data of patients with aortic root aneurysm and moderate to severe AR undergoing VSRR and surviving from the operation from October 2013 to May 2020 were retrospectively analyzed. There were 31 males and 9 females, with an average age of 47.1±13.4 years. There were 30 patients with true aneurysm of aortic root and 10 patients with dissecting aneurysm of aortic root. There were 3 patients with bicuspid aortic valve, and 12 patients with Marfan syndrome. The AR measured by the echocardiogram was moderate in 18 patients and severe in 22 patients. The average diameter of aortic annulus was 27.0±3.9 mm, and the mean largest diameter of aortic sinus was 52.3±6.1 mm. Results    A total of 32 patients underwent David technique and 8 patients underwent Yacoub technique, and 10 patients underwent aortic cusp repair simultaneously. All 40 patients  completed the follow-up, and the follow-up period was 12-86 (45.7±18.9) months. During the period, 1 patient died of heart failure, 2 had reoperation due to new-onset Stanford B aortic dissection, and no patients had reoperation related to aortic valve. The postoperative New York Heart Association cardiac function classification (1.6±0.5 vs. 2.8±0.8), left ventricular end-diastolic dimension (52.2±7.8 mm vs. 61.4±10.6 mm) and left ventricular end-diastolic volume (136.0±58.8 mL vs. 193.3±83.9 mL) of the patients were significantly improved compared with preoperative ones (P<0.05). By echocardiography, 19 patients had no AR, 18 patients had mild AR, 3 patients had mild-moderate AR, and no patients had moderate or higher AR. Conclusion    In patients with aortic root aneurysm and moderate to severe AR, VSRR technique avoids prosthetic valves and anticoagulation-related complications, has lower rate of AR recurrence and reoperation, and improves the quality of life in the midterm period.

Lung cancers are the leading cause of cancer deaths worldwide and pose a grave threat to human life and health. Non-small cell lung cancer (NSCLC) is the most frequent malignancy occupying 80% of all lung cancer subtypes. Except for other mutations (

Objective    To evaluate the short and mid-term outcomes of valve repair in patients with insufficient bicuspid aortic valves (BAV). Methods    The clinical data of 27 consecutive patients with insufficient BAV undergoing valve repair in Shanghai Chest Hospital from September 2016 to January 2020 were retrospectively reviewed. There were 24 males and 3 females with a mean age of 38.5±14.6 years (range: 20-68 years). BAV of all patients was type 1 in Seviers' classification. There were 23 patients with left-right fusion and 4 patients with right-noncoronary fusion. There was aortic regurgitation in the patients measured by the echocardiogram, including moderate regurgitation in 3 patients, moderate-severe in 18 patients, and severe in 6 patients. The diameter of aortic annular base was 27.9±3.4 mm, and the largest diameter of aortic sinus was 39.9±7.6 mm. Left ventricular end diastolic diameter was 62.7±6.5 mm, and the volume was 197.9±53.6 mL. Results    All 27 patients completed the follow-up, and the mean time was 24.2±12.5 months (range: 12-51 months). No patient died or required aortic valve-related reoperation during the follow-up. The cardiac function of the patients significantly improved postoperatively (P<0.05). By echocardiography, 11 patients had no aortic regurgitation, 13 had mild aortic regurgitation, and 3 had moderate aortic regurgitation, and no patient had severe aortic regurgitation. Postoperative left ventricular end diastolic diameter and volume decreased, compared to preoperative ones (P<0.05). Conclusion    In patients with insufficient BAV, valve repair is safe and effective, and has excellent short and mid-term outcomes.

Objective: To explore the application value of biochemical and immunological assembly line in emergency test by comparatively analyzing the changes in sample test process and turnaround time (TAT) in emergency test before and after installation of the assembly line. Methods: A retrospective study was performed with the run data of the emergency biochemical and immunodetection project in Department of Clinical Laboratory in Tongji Hospital Affiliated to Tongji University from July to September in 2017 and from July to September in 2018. (1)The changes in sample circulation mode and test process were compared in emergency test before and after installation of the assembly line.(2)The changes in TAT of sample test and distribution of time interval in emergency laboratory report were statistically analyzed before and after installation.(3)The number of samples tested between instruments and occurrence of instrument failure were statistically compared before and after installation. (4)Biosafety risk assessment was performed on the sample test process before and after installation to analyze the effects of the assembly line installation on biosafety control in emergency test. Results: (1) By applying the assembly line, the sample test process was well controlled and the workload for laboratorians was eased greatly through reduction of manual work.(2) Report TAT was remarkably shortened after installation compared to that before installation; the TAT of dry biochemistry and myocardial zymogram report in emergency test was shorted from 39 min and 48 min to 34 min and 42 min respectively, with a reduction of 12.82% an 12.50% compared to those before installation; the TAT of dry biochemistry and myocardial zymogram report in inpatient emergency was shorted from 37 min and 43 min to 29 min and 35 min respectively, with a reduction of 21.61% an 18.60% compared to those before installation; distribution of report TAT was comparatively analyzed, the percentage of reports in 0-30 min and 31-45 min increased remarkably compared to that before installation, the percentage of TAT of dry biochemistry report falling into 0-45 min increased to 74.58% and 85.66% after installation from 57.91% and 78.28% before installation, respectively in emergency and inpatient emergency. (3)For the model VITROS5600, the percentage of samples tested changed from 30.29% and 69.71% before installation to 47.63% and 52.37% after installation, respectively; for the model DXI800, the percentage of samples tested changed from 28.77% and 71.23% before installation to 53.49% and 46.51% after installation, respectively. After installation, there was a tendency of balance in the number of samples tested between instruments. Instrument failure was significantly reduced: for the model VITROS5600, the frequency of instrument failure decreased from 3.5 times a month/instrument before installation to 2 times a month/instrument after installation on average; for the model DXI800, the frequency of instrument failure decreased from 2.8 times a month/instrument before installation to 1.8 times a month/instrument after installation on average.(4) Installation of the assembly line lowered the risks biosafety events in sample test process in emergency test and the two risks of accidental contact with aerosol in sample tubes before detection and accidental contact with biological specimen due to overturning and spilling during detection were reduced from a high level before installation to a low level after installation. Conclusion In emergency test, biochemical and immunological assembly line is of certain value in process improvement, reduction of workload for laboratorians, improvement of work efficiency, TAT reduction and optimization, as well as control of biosafety conditions.

Objective:To explore the short-term prognostic factors for Guillain-Barré syndrome (GBS) in children.Methods:The clinical data of children with GBS from 24 hospitals in 10 provinces/municipalities/autonomous regions in southern China (south of Huaihe River) from January 1, 2013 to September 30, 2016 were retrospectively analyzed. The factors affecting the short-term prognoses of children were explored.Results:In these 78 children (50 males and 28 females), the average age was 9.53±5.44 years, and 19 were under 5 years old. Fifty children had history of prodromal events; 28 children had cranial nerve involvement, and 22 had autonomic nerve involvement. Five children needed assisted respiration, and one died during hospitalization. There was no statistically significant difference in percentage of children having poor short-term prognosis (scores of Hughes GBS disability scale≥3 at discharge) between children with different ages, children having different days from onset to admission, children with different clinical classifications or electrophysiological classifications, children with different treatment plans, children having presence or absence of prodromal events, children having presence or absence of cranial nerve involvement ( P>0.05). The proportion of children having poor short-term prognosis in children with autonomic nerve involvement was significantly higher than that of children without autonomic nerve involvement (31.8% vs. 10.7%, P<0.05). Conclusion:The short-term prognosis of children with autonomic nerve involvement is poor.