Survival of children with recurrent medulloblastoma undergoing sequential therapy: an analysis of 101 cases / 中国当代儿科杂志

OBJECTIVE@#To study the clinical features of children with recurrent medulloblastoma (MB) and treatment regimens.@*METHODS@#A retrospective analysis was performed on 101 children with recurrent MB who were admitted to the hospital from August 1, 2011 to July 31, 2017. The children were followed up to July 31, 2020. The Kaplan-Meier method was used for survival analysis. The Cox regression model was used for multivariate regression analysis.@*RESULTS@#Of the 101 children, 95 underwent remission induction therapy, among whom 51 had response, resulting in a response rate of 54%. The median overall survival (OS) time after recurrence was 13 months, and the 1-, 3-, and 5-year OS rates were 50.5%±5.0%, 19.8%±4.0%, and 10%±3.3% respectively. There was no significant difference in the 5-year OS rate between the children with different ages (< 3 years or 3-18 years), sexes, pathological types, or Change stages, between the children with or without radiotherapy before recurrence or re-irradiation after recurrence, and between the children with different times to recurrence (< 12 months or ≥ 12 months after surgery) (@*CONCLUSIONS@#As for the recurrence of MB, although remission induction therapy again can achieve remission, such children still have a short survival time. Only reoperation can significantly prolong survival time, and therefore, early reoperation can be considered to improve the outcome of children with recurrent MB.

MicroRNAs of bone marrow mesenchymal stem cell-derived exosomes regulate acute myeloid leukemia cell proliferation and apoptosis / 中华医学杂志(英文版)

BACKGROUND@#Acute myeloid leukemia (AML) is a malignant hematological disease, originating from hematopoiesis stem cell differentiation obstruction and clonal proliferation. New reagents or biologicals for the treatment of AML are urgently needed, and exosomes have been identified as candidate biomarkers for disease diagnosis and prognosis. This study aimed to investigate the effects of exosomes from bone marrow mesenchymal stem cells (BMSCs) on AML cells as well as the underlying microRNA (miRNA)-mediated mechanisms.@*METHODS@#Exosomes were isolated using a precipitation method, followed by validation using marker protein expression and nanoparticle tracking analysis. Differentially expressed miRNAs were identified by deep RNA sequencing and confirmed by quantitative real-time polymerase chain reaction (qPCR). Cell proliferation was assessed by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt method, and cell cycle progression and apoptosis were detected by flow cytometry. Functional gene expression was analyzed by qPCR and Western blotting (WB). Significant differences were determined using Student's t test or analysis of variance.@*RESULTS@#BMSCs-derived exosomes effectively suppressed cell proliferation (both P < 0.0001 at 10 and 20 μg/mL) and cell cycle progression (P < 0.01 at G0-G1 stage), and also significantly enhanced cell apoptosis (P < 0.001) in KG-1a cells. There were 1167 differentially expressed miRNAs obtained from BMSCs-derived exosomes compared with KG-1a cell-derived exosomes (P < 0.05). Knockdown of hsa-miR-124-5p in BMSCs abrogated the effects of BMSCs-derived exosomes in regulating KG-1a such as the change in cell proliferation (both P < 0.0001 vs. normal KG-1a cell [NC] at 48 and 72 h). KG-1a cells treated with BMSCs-derived exosomes suppressed expression of structural maintenance of chromosomes 4 (P < 0.001 vs. NC by qPCR and P < 0.0001 vs. NC by WB), which is associated with the progression of various cancers. This BMSCs-derived exosomes effect was significantly reversed with knockdown of hsa-miR-124-5p (P < 0.0001 vs. NC by WB).@*CONCLUSIONS@#BMSCs-derived exosomes suppress cell proliferation and cycle progression and promote cell apoptosis in KG-1a cells, likely acting through hsa-miR-124-5p. Our study establishes a basis for a BMSCs-derived exosomes-based AML treatment.

Clinical effect of surgery combined with chemotherapy and radiotherapy in children with central primitive neuroectodermal tumor and prognostic analysis / 中国当代儿科杂志

OBJCTIVE@#To study the clinical effect of surgery combined with chemotherapy and radiotherapy in children with central primitive neuroectodermal tumor (cPNET), as well as the risks factors for poor prognosis.@*METHODS@#A retrospective analysis was performed for the clinical data of 42 children who were diagnosed with cPNET from June 2012 to September 2018.@*RESULTS@#The 42 children had a median overall survival (OS) time of 2.0 years and a median event-free survival (EFS) time of 1.3 years; the 1-, 3-, and 5-year OS rates were 76.2%±6.6%, 41.4%±8.7%, 37.3%±8.8% respectively, and the 1-, 3-, and 5-year EFS rates were 64.3%±7.4%, 32.7%±8.0%, 28.0%±8.1% respectively. The univariate analysis showed that there were significant differences in the OS and EFS rates among the children with different patterns of surgical resection, chemotherapy cycles, and risk grades (P<0.05), and there was also a significant difference in the OS rate between the children receiving radiotherapy and those not receiving radiotherapy (P<0.05). The multivariate Cox regression analysis showed that chemotherapy cycles and risk grade were independent influencing factors for EFS and OS rates (P<0.05). The EFS and OS rates increased with the increase in chemotherapy cycles and the reduction in risk grade.@*CONCLUSIONS@#Multimodality therapy with surgery, chemotherapy, and radiotherapy is an effective method for the treatment of cPNET in children. Early diagnosis and treatment and adherence to chemotherapy for as long as possible may improve EFS and OS rates.

Effect of bevacizumab in treatment of children with optic pathway glioma / 中国当代儿科杂志

OBJECTIVE@#To investigate the effect of bevacizumab in the treatment of children with optic pathway glioma (OPG).@*METHODS@#A retrospective analysis was performed for the clinical data of 30 children with OPG who underwent chemotherapy. According to whether bevacizumab was used, they were divided into conventional chemotherapy (carboplatin, vincristine and etoposide) group with 12 children and combined chemotherapy (bevacizumab, carboplatin, vincristine and etoposide) group with 18 children. The children were followed up to 6 months after chemotherapy, and the two groups were compared in terms of visual acuity and tumor size before and after chemotherapy and adverse reactions during chemotherapy.@*RESULTS@#The combined chemotherapy group had a significantly higher proportion of children achieving tumor regression than the conventional chemotherapy group (P0.05). No chemotherapy-related death was observed in either group.@*CONCLUSIONS@#Bevacizumab combined with conventional chemotherapy can effectively reduce tumor size. Compared with conventional chemotherapy, such combination does not increase adverse reactions and can thus become a new direction for the treatment of OPG in children.

Risk factors for recurrence within 2 years in children with medulloblastoma / 中国当代儿科杂志

OBJECTIVE@#To investigate the risk factors for recurrence of medulloblastoma (MB) within 2 years and their influence on progression-free survival (PFS).@*METHODS@#A retrospective analysis was performed for the clinical data of 123 children with MB who were admitted from January to December, 2017. According to the presence or absence of recurrence, they were divided into recurrence group with 30 children and non-recurrence group with 93 children. The risk factors for recurrence within 2 years were analyzed, and PFS was compared between the children with different risk factors.@*RESULTS@#Large-cell/anaplastic type and M stage were risk factors for MB recurrence within 2 years. The risk of recurrence in the children with M+ MB was 3.525 times that in those with M0 MB, and the risk of recurrence in the children with large-cell/anaplastic MB was 3.358 times that in those with classic MB (P<0.05). The survival analysis showed that the median PFS time was 20 months in the children with M+ MB, and the 20-month PFS rate was 50% ± 11% in the children with M+ MB and 81% ± 5% in those with M0 MB (P<0.05). The 20-month PFS rate was 80% ± 5% in the children with classic MB, 65% ± 10% in those with desmoplastic/nodular MB, 86% ± 13% in those with MB with extensible nodularity, and 36% ± 20% in those with large-cell/anaplastic MB (P<0.05).@*CONCLUSIONS@#Recurrence is an important influencing factor for the prognosis of MB, and M+ stage and large-cell/anaplastic MB are risk factors for recurrence. Children with such risk factors tend to have a low PFS rate.

Effect of carnosol against proliferative activity of breast cancer cells and its estrogen receptor subtype's mediation and regulation mechanisms / 中国中药杂志

Carnosol has been proved to have anti-breast cancer effect in previous research. But its ER subtype's specific regulation and mediation mechanisms remain unclear. The aim of this study is to observe the effect of carnosol on cell proliferation and its estrogen receptor α and β's specific regulation and mediation mechanisms with ER positive breast cancer T47D cell. With estrogen receptor α and β antagonists MPP and PHTPP as tools, the MTT cell proliferation assay was performed to observe the effect of carnosol on T47D cell proliferation. The changes in the T47D cell proliferation cycle were detected by flow cytometry. The effect of carnosol on ERα and ERβ expressions of T47D cells was measured by Western blot. The findings showed that 1 x 10(-5)-1 x 10(-7) mol x L(-1) carnosol could significantly inhibit the T47D cell proliferation, which could be enhanced by MPP or weakened by PHTPP. Meanwhile, 1 x 10(-5) mol x L(-1) or 1 x 10(-6) mol x L(-1) carnosol could significantly increase ERα and ERβ expressions of T47D cells, and remarkably increase ERα/ERβ ratio. The results showed that carnosol showed the inhibitory effect on the proliferation of ER positive breast cancer cells through target cell ER, especially ERβ pathway. In the meantime, carnosol could regulate expressions and proportions of target cell ER subtype ERα and ERβ.

A clinical and pathological analysis of 22 cases of primary sclerosing cholangitis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To characterize the clinical, laboratory, imaging and pathological features of primary sclerosing cholangitis (PSC) and investigate the impact of ursodeoxycholic acid (UDCA) therapy on patient prognosis.</p><p><b>METHODS</b>The medical records of 22 patients diagnosed with PSC between 2002 and 2011 were retrospectively reviewed. The PSC diagnosis had been made in patients with suspect biochemical abnormalities following evaluation by magnetic resonance cholangiopancreatography (MRCP) and/or endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography (PTC). Fibrosis and inflammation were assessed by immunohistochemical analyses of tissue biopsies. Outcome of patients treated with UDCA (13-15 mg/kg/day, oral) were compared to that of patients without UDCA treatment by the X2 or corrected X2 tests.</p><p><b>RESULTS</b>Among the 22 PSC patients, the majority was male (n=15) and presented with fatigue, dark urine, and body weight loss (n=15). Four cases had ulcerative colitis. At admission, all 22 cases showed elevated levels of alkaline phosphatase[ALP: (348+/-184) U/L], 19 cases showed elevated alanine aminotransferase [ALT: (94.0+/-67.0) U/L] and aspartate aminotransferase [AST: (98.0+/-67.0) U/L], and 15 cases showed elevated levels of total bilirubin (99.0+/-115.0) mumol/L and direct bilirubin (74.4+/-92.4 mumol/L. ERCP examination showed segmental intrahepatic bile duct stenosis with expansion, and stiff and enlarged gallbladder bile ducts, but unclear findings for the common bile ducts and pancreatic ducts. MRCP showed beading of the intrahepatic bile duct, stiffness of the bile duct wall, and dilation of the common bile duct. Fibrosis and inflammation were observed in the bile ducts, along with hyperplasia and the typical features of "onion skin" fibrosis and fibrous obliterative cholangitis. Five of the 10 patients treated with UDCA improved, and seven of the 12 patients in the non-UDCA treatment group improved. There was no statistically significant difference in outcome between the groups (paired X2=0.333, corrected X2=0.083, P more than 0.05).</p><p><b>CONCLUSION</b>PSC patients were predominantly male and the common clinical manifestations were fatigue, dark urine, and body weight loss. At admission, serum biochemical indicators of cholangitis were increased significantly and subsequent imaging studies confirmed the suspected diagnosis by showing obvious characteristic changes. UDCA treatment did not significantly improve patient prognosis.</p>

Expression of CAS in hepatocellular carcinoma tissues and its relationship with HBV infection / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To explore whether the cellular apoptosis susceptibility (CAS) protein could serve as a pathologic marker for HCC diagnosis and the roles of CAS expression in HBV infection associated HCC.</p><p><b>METHODS</b>The expression of CAS protein in HCC and its paracarcinoma tissues, non-tumor liver cirrhosis and hepatitis tissues were detected by immunohistochemistry. Meanwhile, HBsAg, HBcAg and HBV DNA in HCC tissues with HBV infection were examined by immunohistochemistry and in situ hybridization respectively.</p><p><b>RESULTS</b>The expression of CAS protein was significantly higher in HCC than in its paracarcinomas tissues (P < 0.01), and higher in paracarcinomas tissues than in non-tumor liver cirrhosis and hepatitis tissues (P < 0.01). Poorly differentiated tumors immunochemically stained stronger than moderately or well differentiated (P < 0.01). CAS protein expression was significantly higher in HBV-infected HCC tissues than that of in non-HBV infection (P < 0.01). Meanwhile, in HBV-infected HCC tissues, the staining intensity score of CAS protein in HBV DNA positive HCC tissues was significantly higher than HBV DNA negative tissues (P < 0.05).</p><p><b>CONCLUSIONS</b>Higher expression of CAS protein is found in HCC tissues,and the intensity of CAS protein expression is related closely to tumor differentiation. We suggested that CAS protein might serve as a marker for HCC diagnosis and differentiation estimation, and deduced that CAS might play an important role in the initiation of HBV infection associated HCC through upregulating expression of CAS.</p>

Clinical and pathological analysis of 100 cases of drug-induced liver injury / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the clinical and pathological features of drug-induced liver injury (DILI).</p><p><b>METHODS</b>Liver specimens were obtained through needle biopsies from 100 patients with DILI. The histological preparations of the specimens were stained with haematoxylin eosin, several histochemistry methods, and immunohistochemistry stains. The pathological changes of the livers were analyzed together with the patients's clinical data. The patients were divided into two groups, an acute DILI group (n=39) and a chronic DILI group (n=61), based on their clinical courses and histological changes in their livers. In the chronic DILI group, the clinical courses were longer than 6 months and/or fibrosis or cirrhosis occurred in their liver tissues.</p><p><b>RESULTS</b>Among our cases the leading cause of DILI was Chinese herb medicine, accounting for 21% of the 100 cases; steroids induced cases were 11% of the total. 78% of the patients presented elevated serum transaminases and/or jaundice. The degree of transaminases elevation and the frequency of jaundice happening in the acute group were significantly higher than those in the chronic group (P less than 0.05). The histopathological liver changes in these DILI cases included: (1) necrosis commonly occurred in acinar zone 3, (2) abundant neutrophil and/or eosinophil infiltrations, (3) hepatocytic and/or canalicular cholestasis with little or no inflammation, (4) microvesicular steatosis mixed with macrovesicular steatosis, and (5) presentation of epitheloid cell granuloma. There were no significant differences in liver histopathology between the acute and the chronic DILI groups, except that the fibrosis and the ductular proliferation were different.</p><p><b>CONCLUSION</b>DILI has become a notable liver disease in mainland China, and the use of Chinese herbal medicine must be improved, standardized and regulated more closely.</p>

Effect of Bacillus Bifidus Preparation on the Prevention of Gastrointestinal Side Effects in Children with Acute Lymphocyte Leukemia during High-Dose Methotrexate Chemotherapy / 实用儿科临床杂志

Objective To observe the effect of bacillus bifidus preparation on the prevention of gastrointestinal side effects in children with acute lymphocyte leukemia (ALL) during high-dose methotrexate (HD-MTX) chemotherapy.Methods One hundred and fifty-two ALL children were randomly assigned into 2 groups according to the suggestion of diagnosis and treatment of ALL in childhood.There were 76 patients in each group.In the treatment group,there were 46 male and 30 female,aged 2 to 13 years old (the median age was 8 years).While in the control group,there were 41 male and 35 female (the median age was 8.2 years).They were treated with the same chemotherapy schedule (HD-MTX),supportive therapies and infection preventive measures.ALL children in the treatment group were additionally given the bacillus bifidus preparation (one tablet for 2 to 6 years old,and two tablets for 7 to 15 years old,3 times daily),if their WBC was more than 2.0?109 L-1.Those in the control group were given vitamin B complex tablets (one tablet for 2 to 6 years old and two tablets for 7 to 15 years old,3 times daily).Results ALL children in treatment group had less diarrhea,abdominal pain,nausea and vomiting,or liver function impairment induced by chemotherapy than those in control group.However,the bacillus bifidus preparation had no significant effects on the symptoms of fever and oral mucosal erosions in the period of chemotherapy.Conclusion The bacillus bifidus preparation is clinically useful for the prevention of gastrointestinal side effects associated with HD-MTX chemotherapy.

Cut-off period of subclassification and pathological features of severe hepatitis based on clinical and pathological analyses / 中华实验和临床病毒学杂志

<p><b>BACKGROUND</b>To explore the cut-off period of subclassification and pathological features of severe hepatitis (SH).</p><p><b>METHODS</b>Based on combined clinical and pathological analyses, the complete clinical and biopsy or autopsy liver tissues data from 196 cases of patients with severe hepatitis were investigated. Meanwhile, proliferative hepatocytes, cholangioepithelia and collagens were identified by a panel of monoclonal antibodies such as those against albumin, cytokeratin 18,19 and collagen I, III with immunohistochemical method.</p><p><b>RESULTS</b>The clinical and pathological analyses indicated the cut-off periods of acute, subacute and chronic SH (ASH,SSH and CSH) were (13.4+/-7.2) d, (77.4+/-69.3) d and (80.5+/-63.2) d, respectively. Among all SH cases, one case of ASH patient presented clinical manifestation and pathological changes of ASH for 21 days, however, one patient with SSH was demonstrated 12 day course by histological examination. The time of cut-off period between ASH and SSH in child cases was shorter than that in adult cases. Histologically, ASH liver tissues showed massive and/or submassive necrosis caused by one attack, with congestive sinusoid frameworks and proliferative cholangioepithelium-like hepatocytes, while SSH liver tissues presented combined fresh and old submassive or massive necrosis caused by multiple attacks, accompanied by obviously proliferative bile ducts and sinusoid framework collapse.However, the pathological changes of CSH showed ASH- or SSH-like lesions on the background of chronic liver injury.</p><p><b>CONCLUSION</b>Our data indicated that the cut-off period between ASH and SSH is in accordance with the Scheme of Viral Hepatitis Prevention and Therapy, China, published in 2000, but excluded a part of child SH cases. In our study, the authors found a few pathological features in ASH and SSH.</p>

Clinical pathology and pathogenesis of severe acute respiratory syndrome / 中华实验和临床病毒学杂志

<p><b>BACKGROUND</b>To explore the pathological features and pathogenesis of severe acute respiratory syndrome (SARS) to provide evidence for the clinical treatment and prevention of SARS.</p><p><b>METHODS</b>Pathological features of 2 cases of full autopsy and 4 cases of needle biopsy tissue samples from the patients who died from SARS were studied by light and electron microscopy. The distribution and quantity of lymphocyte subpopulations in the lungs and immune organs from SARS patients were analyzed by immunohistochemistry. The location and semi-quantitative analysis of SARS coronavirus in the tissue specimens were studied by electron microscopy, in situ hybridization and immunohistochemistry.</p><p><b>RESULTS</b>In total of 6 cases, diffuse alveolar damage and alveolar cell proliferation were common. The major pathological changes of 2 autopsy cases of SARS in lung tissues were acute pulmonary interstitial and alveolar exudative inflammation, and 2 autopsy and one biopsy lung tissues showed alveolar hyaline membrane formation. Terminal bronchiolar and alveolar desquamation of lung tissues in one autopsy and 2 biopsy cases were noted. Among 6 cases, 2 biopsy cases presented early pulmonary fibrosis and alveolar organization. Meanwhile, the immune organs, including lymph nodes and spleens from 2 autopsy cases of SARS whose disease courses were less than 12 days showed extensive hemorrhagic necrosis, reactive macrophage/histocyte proliferation, with relative depression of mononuclear and granulocytic clones in the bone marrows. However, spleen and bone marrow biopsy tissue samples from 4 dead SARS cases whose clinical course lasted from 21 to 40 days presented repairing changes. SARS coronaviruses were mainly identified in type I and II alveolar epithelia, macrophages, and endothelia; meanwhile, some renal tubular epithelial cells, cardiomyocytes, mucosal and crypt epithelial cells of gastrointestinal tracts, parenchymal cells in adrenal glands, lymphocytes, testicular epithelial cells and Leydig's cells were also detected by electron microscopy combined with in situ hybridization. The semi-quantitative analysis of lymphocyte subpopulations revealed that the proportion of CD8+ T lymphocytes were about 80% of the total infiltrative inflammatory cells in the pulmonary interstitium, with a few CD4+ lymphocytes CD3+, CD4+, CD8+ or CD20+ lymphocyte subpopulations were obviously decreased and there was imbalance in number and proportion, while CD57+, CD68+, S-100+ and HLA-DR+ cells were relatively increased in lymph nodes and spleens.</p><p><b>CONCLUSIONS</b>Histologically, the pulmonary changes could be divided into acute inflammatory exudative, terminal bronchiolar and alveolar desquamative and proliferative repair stages or types during the pathological process of SARS. SARS coronavirus was found in multi-target cells in vivo, which means that SARS coronavirus might cause multi-organ damages which were predominant in lungs. There were varying degrees of decrease and imbalance in number and proportion of lymphocyte subpopulations in the immune organs of the patients with SARS. However, these changes may be reversible. It was found that cellular immune responses were predominant in the lungs of SARS cases, which might play an important role in getting rid of coronaviruses in infected cells and inducing immune mediated injury.</p>

Clinical and pathological analysis on characteristics of primary biliary cirrhosis / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To explore the clinical and pathological features and the pathogenesis of primary biliary cirrhosis (PBC) in Chinese Mainland.</p><p><b>METHODS</b>30 PBC patients were divided into the early group (Scheuer stage I and II, 19 patients) and the late group (Scheuer stage III and IV, 11 patients). The data of clinics and serology were analyzed, and the pathological features of the liver tissues were characterized. The changes of dendritic cells (DCs) and hepatic stellate cells (HSCs) were studied by immunohistochemistry.</p><p><b>RESULTS</b>In all the PBC patients, the rate of the male to the female was 1 to 5, and the average age was 40.6 years. The mean levels of TBiL, ALP and GGT in the sera were (95.9+-88.5) micromol/L, (537.2+-339.2) U/L, and (582.0+-351.2) U/L, respectively. 73.3% patients showed AMA positive, and the level of GGT was positively correlated with the AMA level according to the result of statistical analysis (r=0.778, P=0.000). The symptoms of jaundice and hepatomegaly were presented more commonly in the late group than those in the early group (chi2=5.182, P<0.05; chi2=13.659, P<0.01, respectively). The main changes of morphology of PBC located in portal tracts. The liver tissues in the early stage of PBC showed the damage of bile ducts and obvious proliferation of small bile ducts. The granulomas, the lymphoid follicles and the foamy cells were found in the liver tissues of PBC (2/19 patients, 12/19 patients, and 10/19 patients in the early stage respectively, while 0/11 patients, 4/11 patients, and 3/11 patients in the late stage respectively). There was significant difference between the early stage and the late stage in presence of the lymphoid follicles and the foamy cells (t=4.489, P<0.05; t=4.019, P<0.05, respectively). The biliary pigmentary particles were mainly accumulated in the liver cells around the portal tracts in 90.0% PBC patients, and the accumulation of copper and iron increased, compared with that in normal specimens. The DCs and HSCs located mainly in the portal tracts, especially around the damaged bile ducts.</p><p><b>CONCLUSIONS</b>There are some clinical and pathological characteristics in the patients with PBC. The level of AMA has no direct relationship with the level of transaminase or bilirubin. The proliferated bile ductules may express the antigens which maybe the target of immune attack. As an antigen-presenting cell, DCs may play an important role in the pathogenesis of PBC.</p>