Preparation and evaluation of sirolimus sustained release tablets based on mesoporous silicon loaded self-microemulsion / 药学学报

Sirolimus self-microemulsion-mesoporous silicon sustained release tablets were prepared in order to improve the dissolution of the insoluble drug sirolimus and reduce its side effects. Firstly, sirolimus self-microemulsion was prepared and cured with mesoporous silicon. Secondly, the suitable excipients were selected according to the appearance, hardness and in vitro release rate. The sustained-release tablets with hydroxypropyl methylcellulose (HPMC) as skeleton material were prepared by powder direct pressing method, and the formulation was optimized by central composite design-response surface method to investigate the drug release in vitro. Finally, the pharmacokinetics was carried out in beagle dogs using the commercial sirolimus tablets as references. The final formulation of sustained-release tablets is as follows: 162 mg of sirolimus self-microemulsion-mesoporous silica (1∶1, w/w), 80 mg of HPMC K4M and 80 mg of carboxymethyl starch sodium, the microcrystalline cellulose is 168 mg. The results of in vitro release test showed that the self-made sustained-release tablets released slowly within 12 h, which conformed to the Ritger-Peppas model. The in vivo test results showed that compared with the commercial sirolimus tablets, the Cmax of the sustained-release tablets decreased by 49.47%, the Tmax of the sustained-release tablets was prolonged by 5.1 times, and the relative bioavailability was 105.81%. Sirolimus self-microemulsion-mesoporous silicon sustained-release tablets have good sustained-release effects in vitro and in vivo, which provides a reference for the solubilization of other insoluble drugs and the research and development of sustained-release preparations. Animal experiments and welfare processes were reviewed and approved by the Animal Ethics Committee of the 900TH Hospital of the Joint Logistics support Force.

Nomogram for predicting overall survival in children with neuroblastoma based on SEER database

Purpose@#This study was performed to establish and validate a nomogram for predicting the overall survival in children with neuroblastoma. @*Methods@#The latest clinical data of neuroblastoma in Surveillance, Epidemiology, and End Results (SEER) database was extracted from 2000 to 2016. The cases included were randomly divided into training and validation cohorts. The survival curves were drawn with a Kaplan-Meier estimator to investigate the influences of certain single factors on overall survival. Also, least absolute shrinkage and selection operator regression was applied to further select the prognostic variables for neuroblastoma. Additionally, receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the accuracy of the nomogram. @*Results@#In total, 1,262 patients were collected and 8 independent prognostic factors were achieved, including patients’ age, sex, race, tumor grade, radiotherapy, chemotherapy, tumor site, and tumor size. Then we constructed a nomogram by using the data of the training cohort with 886 cases. Subsequently, the nomogram was validated internally and externally with 886 and 376 cases, respectively. The internal validation revealed that the area under the curves (AUC) of ROC curves of 1-, 3-, and 5-year overall survival were 0.69, 0.78, and 0.81, respectively. Accordingly, the external validation also showed that the AUC of 1-, 3-, and 5-year overall survival were all ≥0.69. Both methods of validation demonstrated that the predictive calibration curves were consistent with standard curves. @*Conclusion@#The nomogram possess the potential to be a new tool in predicting the survival rate of neuroblastoma patients.

Nomogram for predicting overall survival in children with neuroblastoma based on SEER database

Purpose@#This study was performed to establish and validate a nomogram for predicting the overall survival in children with neuroblastoma. @*Methods@#The latest clinical data of neuroblastoma in Surveillance, Epidemiology, and End Results (SEER) database was extracted from 2000 to 2016. The cases included were randomly divided into training and validation cohorts. The survival curves were drawn with a Kaplan-Meier estimator to investigate the influences of certain single factors on overall survival. Also, least absolute shrinkage and selection operator regression was applied to further select the prognostic variables for neuroblastoma. Additionally, receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the accuracy of the nomogram. @*Results@#In total, 1,262 patients were collected and 8 independent prognostic factors were achieved, including patients’ age, sex, race, tumor grade, radiotherapy, chemotherapy, tumor site, and tumor size. Then we constructed a nomogram by using the data of the training cohort with 886 cases. Subsequently, the nomogram was validated internally and externally with 886 and 376 cases, respectively. The internal validation revealed that the area under the curves (AUC) of ROC curves of 1-, 3-, and 5-year overall survival were 0.69, 0.78, and 0.81, respectively. Accordingly, the external validation also showed that the AUC of 1-, 3-, and 5-year overall survival were all ≥0.69. Both methods of validation demonstrated that the predictive calibration curves were consistent with standard curves. @*Conclusion@#The nomogram possess the potential to be a new tool in predicting the survival rate of neuroblastoma patients.

PI3K-Akt/LKB1-AMPK-mTOR-p70S6K/4EBP1 signaling pathways participate in the regulation of testis development and spermatogenesis: An update / 中华男科学杂志

Male infertility is closely associated with spermatogenesis disorders triggered by aberrant gene expression or abnormal signaling pathways in the testis. The mammalian target of rapamycin (mTOR) is a central regulator of cell metabolism, playing an important role in regulating cell proliferation, differentiation, translation, actin polymerization, cycle progression, energy metabolism, autophagy, and other cellular activities. PI3K-Akt and LKB1-AMPK, the two well-defined classic signal transduction pathways, regulate the expressions of mTOR and its downstream p70S6K/4EBP1 through different molecular pathways. Recent studies show that mTOR-p70S6K/4EBP1 signaling participates in the regulation of the proliferation and differentiation of testicular cells and spermatogenesis. This review focuses on the role of PI3K-Akt/LKB1- AMPK-mTOR signaling cascades in testis development and spermatogenesis, providing some new perspectives for the studies of the molecular mechanism underlying male sterility.

Immunophenotypes and gene mutations in colorectal precancerous lesions and adenocarcinoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To analyze immunophenotypes and gene mutations of colorectal precancerous lesions and adenocarcinoma, and to compare the difference of carcinogenetic mechanisms between the two precancerous lesions.</p><p><b>METHODS</b>Fifty-three cases of colorectal serrated lesions including 30 hyperplastic polyps, 20 sessile serrated adenomas (SSA) and 3 mixed polyps were collected from January 2006 to June 2012.Forty-five cases of traditional adenomas and 50 cases of colorectal adenocarcinomas were also recruited. Thirty hyperplastic polyps, 20 cases of SSA, 3 mixed polyps and 45 traditional adenomas were investigated by immunohistochemistry for the expression of DNA mismatch repair (MMR) proteins (MLH1, MSH2 and MSH6) and DNA methyltransferase MGMT. Mutations of KRAS, BRAF and PIK3CA genes in 10 cases of SSAs, 10 traditional adenomas, 1 mixed polyps and 50 colorectal adenocarcinomas were analyzed by PCR followed by direct Sanger sequencing.</p><p><b>RESULTS</b>(1) Only 3 cases of hyperplastic polyps lost MLH1 expression, and none of SSAs or traditional adenomas showed loss of MLH1. The negative expression rates of MSH2, MSH6 and MGMT in hyperplastic polyps and SSA were significantly higher than those of traditional adenomas. (2) KRAS mutation was found in 5/10 cases of SSAs, 5/10 traditional adenomas and 1/1 mixed polyps. (3) Colorectal adenocarcinomas harbored the mutations of KRAS (48%, 24/50), BRAF (6%, 3/50) and PIK3CA (4%, 2/50).</p><p><b>CONCLUSIONS</b>Immunophenotypic and gene mutation profiles are different between colorectal serrated lesion and traditional adenoma. Alterations of MMR and MGMT expression play important roles in the pathogenesis of "serrated neoplasm". KRAS mutation is a significant genetic change in the early phase of colorectal carcinogenesis.</p>

Correlation of ¹⁸F-FDG uptake with tumor-proliferating antigen Ki-67 expression in aggressive lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the correlation between ¹⁸F-FDG uptake in positron emission tomography/computed tomography imaging and tumor-proliferating antigen Ki-67 expression in aggressive lymphoma.</p><p><b>METHODS</b>Data of ¹⁸F-FDG PET-CT imaging and immunohistochemical detection of Ki-67 expression of seventy-seven cases with initially diagnosed aggressive lymphoma were retrospectively analyzed. The intensity of ¹⁸F-FDG accumulation was determined by calculating the maximum standardized uptake value (SUVmax) and average standardized uptake value (SUVave). The average SUV at biopsy site (BxSUVave), SUVmax at biopsy site (BxSUVmax) and SUVmax at the highest tumor activity site of the body (BmSUVmax) were collected.</p><p><b>RESULTS</b>The BmSUVmax, BxSUVmax, and BxSUVave were 13.4 ± 6.8, 11.9 ± 6.8 and 7.3 ± 4.4, respectively,and Ki-67 was (61.2 ± 20.4)% in the 77 aggressive lymphomas. The BmSUVmax was significantly higher than the BxSUVmax or BxSUVave (P < 0.05). The BmSUVmax, BxSUVmax and BxSUVave were positively correlated with the Ki-67 expression in aggressive lymphoma (P < 0.05). A positive correlation was revealed between the BxSUVmax and BmSUVmax (P < 0.05), and between the BxSUVmax and BxSUVave (P < 0.05). No significant correlation was found between the BmSUVmax or BxSUVmax and the Ki-67 in DLBCL (P > 0.05). A positive correlation was observed between the BmSUVmax or BxSUVmax and the Ki-67 expression in NK/T cell lymphoma (P < 0.05).</p><p><b>CONCLUSION</b>The increasing trend of ¹⁸F-FDG uptake is correlated with the Ki-67 expression in aggressive lymphoma. The results of this study suggest that the metabolic information obtained by using BmSUVmax may help to compensate the limited sampling of histological examination at the biopsy site. Significant correlation in NK/T cell lymphoma suggests that the metabolic information from positron emission tomography-computed tomography may offer a useful parameter in the prognosis and management of this disease.</p>

Pulmonary-bronchus myelolipoma and review on extra-adrenal myelolipomas in Chinese literature / 中华医学杂志(英文版)

Extra-adrenal myelolipomas are extremely rare, especially in bronchus and lung. Up to now, only nine cases of intra pulmonary lesions have been reported all over the world. Here we describe a new discovered pulmonary-bronchus myelolipoma in a 53-year-old man, which is different from the previously reported ones. And we mainly comment on the pathology and diagnosis, comparing with the findings of the extra-adrenal cases reported in Chinese literature.

Morroniside inhibits H2O2-induced apoptosis in cultured nerve cells / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effects of morroniside on H2O2-induced apoptosis in nerve cells.</p><p><b>METHOD</b>Human neuroblastoma cell line SH-SY5Y cells were pre-incubaed with morroniside (1, 10, and 100 micromol x L(-1)) for 24 h prior to exposure to H2O2 (500 micromol x L(-1)) for 18 h. The activity of reactive SOD was measured by a biochemical assay. The expression of caspase-3, caspase-9, Bcl-2 and Bax was determined by Wastern blotting method.</p><p><b>RESULT</b>Pretreatment of the cells with morroniside (10 and 100 micromol x L(-1)) increasd SOD activity by 14% (P<0.01) and 11% (P<0.05) in comparison with cells exposed only to H2O2. Morroniside (1, 10, 100 micromol x L(-1)) lowered caspase-3 level by 31% (P<0.01), 103% (P<0.001) and 95% (P<0.001), decreased caspase-9 content by 71% (P<0.001), 132% (P<0.001) and 37% (P<0.05), and increasd Bcl-1 level by 88% (P<0.01), 121% (P<0.001) and 60% (P<0.01) respectively but no significant change occurred in Bax level in comparison with cells exposed only to H2O2.</p><p><b>CONCLUSION</b>Morroniside has neuroprotection effect against H2O2-induced oxidation injury in nerve cell.</p>