Study on improvement mechanism of caudatin on liver injury in rats / 中国药房

OBJECTIVE To investigate the improvement mechanism of caudatin on liver injury of rats. METHODS SD rats were randomly divided into blank group， model group， caudatin low-dose and high-dose groups （25， 50 mg/kg）， with 6 rats in each group. Diethylnitrosamine （DEN） was injected intraperitoneally three times per week for eight weeks to establish liver injury model of rats. At 5th week of modeling， the rats received relevant medicine or 0.5% sodium carboxymethylcellulose intragastrically for 4 weeks. The levels of liver function indexes [alanine transaminase （ALT）， aspartate transaminase （AST）， total protein （TP） and total bilirubin （TBI）] and inflammatory factors [interleukin （IL-6）， tumor necrosis factor α （TNF-α）， IL-1β] in serum were detected； the histopathological morphological changes of rat liver were observed； the positive protein expressions of nuclear factor κB （NF-κB） and 78 kDa glucose regulatory protein （Grp78） in liver tissue were also determined； the expressions of endoplasmic reticulum stress-related protein Grp78， C/EBP homologous protein （CHOP）， activating transcription factor 6 （ATF6） and inositol requiring enzyme 1α （IRE1α） and the level of protein kinase R-like endoplasmic reticulum kinase robertluoyi@126.com （PERK） in liver tissue were detected. RESULTS Compared with blank group， serum levels of ALT， AST， TBI， IL-6， TNF-α and IL-1β and positive expressions of NF-κB and Grp78 in liver tissue as well as protein expressions of Grp78， CHOP， ATF6 and IRE1α， PERK protein phosphorylation level were all increased significantly in model group （P＜0.05）， while the serum level of TP was decreased significantly （P＜0.05）. The disordered structure of liver lobule， swollen liver cells， unclear intercellular boundary were observed and accompanied by inflammatory cell infiltration. Compared with model group， most of the above indexes were significantly reversed in caudatin groups （P＜0.05）； the structure of hepatic lobule was relatively complete and clear， the cells were arranged orderly， and the infiltration of inflammatory cells was also reduced. CONCLUSIONS Caudatin has a significant improvement effect against DEN-induced liver injury in rats， the mechanism of which may be associated with inhibiting endoplasmic reticulum stress and inflammatory reaction.

Effect of Arntl on T cell development and anti-infection function in mice / 西安交通大学学报(医学版)

【Objective】 To evaluate the effect of Arntl on T cell development and T cell-mediated anti-viral immunity. 【Methods】 ArntlF/FCD4cre+(KO) in mice was constructed to delete Arntl gene specifically in T cells. We examined the percentage and number of T cell subsets in the thymus and spleen by flow cytometry (FCM). At day 8 after lymphocytic choriomeningitis virus (LCMV) infection, the proportions of T cell subsets, virus-specific CD8+ T cells and IFN-γ secreting T cells were analyzed. The viral load in the spleen was measured using qPCR. Naive CD4+ T cells (CD4+CD25-CD44-CD62L+) were sorted by flow cytometry to perform T helper cell differentiation in vitro. 【Results】 The percentage and number of T cells in the thymus and spleen of KO mice showed no significant change compared with those in the control group (ArntlF/FCD4cre- mice, WT) (P>0.05). Acute LCMV infection did not cause observable changes in effector T cell proportion in the spleen of KO mice compared to that in WT mice (P>0.05), but KO mice showed a higher proportion of IFN-γ secreting T cells (P<0.05) and better virus clearance (P<0.05). In addition, naive CD4+ T cells from KO mice were more prone to differentiate into Th1 cells in vitro (P<0.05). 【Conclusion】 Arntl deletion in T cells does not affect T cell development, but enhances their ability to defend against viral infection by promoting Th1 cell differentiation and response.

Graded and pan-neural disease phenotypes of Rett Syndrome linked with dosage of functional MeCP2

Rett syndrome (RTT) is a progressive neurodevelopmental disorder, mainly caused by mutations in MeCP2 and currently with no cure. We report here that neurons from R106W MeCP2 RTT human iPSCs as well as human embryonic stem cells after MeCP2 knockdown exhibit consistent and long-lasting impairment in maturation as indicated by impaired action potentials and passive membrane properties as well as reduced soma size and spine density. Moreover, RTT-inherent defects in neuronal maturation could be pan-neuronal and occurred in neurons with both dorsal and ventral forebrain features. Knockdown of MeCP2 led to more severe neuronal deficits as compared to RTT iPSC-derived neurons, which appeared to retain partial function. Strikingly, consistent deficits in nuclear size, dendritic complexity and circuitry-dependent spontaneous postsynaptic currents could only be observed in MeCP2 knockdown neurons but not RTT iPSC-derived neurons. Both neuron-intrinsic and circuitry-dependent deficits of MeCP2-deficient neurons could be fully or partially rescued by re-expression of wild type or T158M MeCP2, strengthening the dosage dependency of MeCP2 on disease phenotypes and also the partial function of the mutant. Our findings thus reveal stable neuronal maturation deficits and unexpectedly, graded sensitivities of neuron-inherent and neural transmission phenotypes towards the extent of MeCP2 deficiency, which is informative for future therapeutic development.

Prognostic Model for Survival and Recurrence in Patients with Early-Stage Cervical Cancer: A Korean Gynecologic Oncology Group Study (KGOG 1028) / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#We aimed to develop and validate individual prognostic models in a large cohort of cervical cancer patients that were primarily treated with radical hysterectomy. @*Materials and Methods@#We analyzed 1,441 patients with early-stage cervical cancer treated between 2000 and 2008 from the Korean Gynecologic Oncology Group multi-institutional cohort: a train cohort (n=788) and a test cohort (n=653). Models predicting the risk for overall survival (OS), disease- free survival (DFS), lymphatic recurrence and hematogenous recurrence were developed using Cox analysis and stepwise backward selection and best-model options. The prognostic performance of each model was assessed in an independent patient cohort. Model-classified risk groups were compared to groups based on traditional risk factors. @*Results@#Independent risk factors for OS, DFS, lymphatic recurrence, and hematogenous recurrence were identified for prediction model development. Different combinations of risk factors were shown for each outcome with best predictive value. In train cohort, area under the curve (AUC) at 2 and 5 years were 0.842/0.836 for recurrence, and 0.939/0.882 for OS. When applied to a test cohort, the model also showed accurate prediction result (AUC at 2 and 5 years were 0.799/0.723 for recurrence, and 0.844/0.806 for OS, respectively). The Kaplan-Meier plot by proposed model-classified risk groups showed more distinctive survival differences between each risk group. @*Conclusion@#We developed prognostic models for OS, DFS, lymphatic and hematogenous recurrence in patients with early-stage cervical cancer. Combining weighted clinicopathologic factors, the proposed model can give more individualized predictions in clinical practice.

Pretreatment Lymph Node Metastasis as a Prognostic Significance inCervical Cancer: Comparison between Disease Status / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Lymph node metastasis (LNM) is the most significant prognostic factor in cervical cancerthat was recently incorporated into the International Federation of Gynecology and Obstetrics(FIGO) staging system. This study was performed to evaluate whether the prognosticsignificance of LNM differs according to disease status. @*Materials and Methods@#Patients with FIGO stage IB or higher cervical cancer who had pretreatment computedtomography and/or magnetic resonance imaging studies as well as long-term follow-upwere enrolled in this retrospective study. The hazard ratio (HR) of Cox regression was usedto determine the prognostic significance of LNM. The HRs were compared between the differenttumor groups (based on stage, histology, tumor size, primary treatment, age, parametriuminvolvement, and lymphovascular space invasion). @*Results@#A total of 970 patients treated between January 1999 and December 2007 were included.The pretreatment LNM had prognostic significance in patients with stage IB1/IIA (HR forprogression-free survival 2.10, p=0.001; HR for overall survival 1.99, p=0.005). However,the significance gradually decreased or disappeared with advancing stages. Similarly, theprognostic significance of the pretreatment LNM decreased with advancing disease status,including old age, parametrial involvement or lymphovascular space involvement. In contrast,the tumor size was associated with the prognostic significance of LNM with advancingstatus. The significance of the clinical LNM did not reflect the significance of the clinicalstage. In contrast, the tumor size, parametrial involvement, and significance of the pathologicLNM reflected the clinical stage. @*Conclusion@#In patients with cervical cancer, pretreatment LNM on imaging has different clinical significancedepending on the tumor status.

Impact of Angiotensin Receptor Blockers, Beta Blockers,Calcium Channel Blockers and Thiazide Diuretics on Survivalof Ovarian Cancer Patients / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#We investigated the impact of four types of antihypertensive medications, angiotensinreceptor blockers (ARBs), beta blockers (BBs; both selective and non-selective), calciumchannel blockers (CCBs), and thiazide diuretics (TDs) on survival outcomes in epithelial ovariancancer (EOC). @*Materials and Methods@#A single-institutional retrospective chart review of 878 patients with EOC was performed.Survival was compared according to use of the four antihypertensive medications duringprimary treatment. Propensity score matching (ratio 1:3) was performed to control possibleassociated covariates, such as age, International Federation of Gynecology and Obstetricsstage, residual status after primary debulking surgery, and co-morbidity. @*Results@#Among 878 patients, 56 patients (6.4%) were ARB users, 62 (7.1%) were BB users, 107(12.2%) were CCBs users and 32 (3.6%) used TDs. Median progression-free survival (PFS)for ARB, BB, and CCB users was 37.8, 27.2, and 23.6 months compared with 33.6 monthsfor non-users. ARB was associated with 35% decreased risk of disease progression (hazardratio [HR], 0.65; 95% confidence interval [CI], 0.42 to 0.99; p=0.046) in multivariate analysis.After propensity score matching, median PFS for ARB users was 37.8 months and ARBuse remained to be associated with lower recurrence rate in univariate (p=0.035) and multivariateanalysis (HR, 0.60; 95% CI, 0.39 to 0.93; p=0.022). @*Conclusion@#In this study, ARBs use during primary treatment is associated with lower recurrence in EOCpatients. However, CCBs, BBs, and TDs did not show beneficial impact.

Alkali extraction of Ganoderma lucidum β-glucan and its anti-tumor immune regulation / 药学学报

In this study, an immunostimulating particulate β-glucan was isolated from a hot alkaline extract of the fruiting bodies of Ganoderma lucidum. The optimum conditions of 8 hours treatment time, 1∶20 solid - liquid ratio and 55 ℃ for the alkaline extract process were obtained after investigating by single-factor experiments and Box-Benhnken design in terms of the Ganoderma lucidum particulate β-glucan (GLG) increment, and these conditions resulted in a GLG yield of 8.57%. The experimental protocol was approved by the Medical Laboratory Animal Ethics Committee of Jiangsu Provincial Academy of Chinese Medicine. The result showed that resident macrophages were effectively activated by GLG, such as with the up-regulation of co-stimulatory molecules, the secretion of cytokines and phagocytic uptake. GLG could also promote the proliferation of spleen lymphocytes in mice. In addition, IFN-γ production of spleen CD4+ T cells and cytotoxic T lymphocyte (CTL) responses were significantly enhanced on GLG orally treatment, which ultimately resulted in significantly decreased tumor burden. Taken together, these data suggest that GLG might act as an immune stimulator to exert antitumor effects.

Risk factors for nausea and vomiting after total hip arthroplasty in elderly patients / 中华麻醉学杂志

This study was a single-center large-sample case-control study.Data of 1 106 elderly patients who underwent unilateral total hip arthroplasty from June 2013 to May 2019 were collected, including items such as patient′s baseline characteristics, comorbidities, perioperative medication, intraoperative blood pressure, and postoperative outcomes.Patients were divided into postoperative nausea and vomiting(PONV)group and non-PONV group according to whether nausea and vomiting occurred within 24 h after operation.Logistic regression analysis was used to determine the risk factors for PONV.The incidence of PONV was 11.03%.Female, intraoperative use of dezocine, and intraoperative hypotension(duration>3 min or cumulative time>6 min)are independent risk factors for PONV, while femoral neck fractures and intraoperative use of dexamethasone are protective factors.

Mechanisms of Akt3 gene knockout on neuropathic pain in mice with sciatic nerve ligation / 中华行为医学与脑科学杂志

Objective:To explore the mechanism of Akt3 gene knockout on neuropathic pain induced by sciatic nerve ligation.Methods:Twelve Akt3 knockout mice with SPF grade C57BL/6 mice as background were randomly divided into Akt3 gene knockout + Sham group (Akt3 -/-+ Sham, n=6)and Akt3 gene knockout + CCI group(Akt3 -/-+ CCI, n=6). Twelve wild type C57BL/6 mice were randomly divided into wild + Sham group (WT + Sham, n=6) and wild + CCI group (WT + CCI, n=6) by random number table. Chronic sciatic nerve ligation was used to make neuropathic pain model in CCI group, and sham group was subjected to sham operation. The paw withdrawal mechanical threshold (PWMT) was measured 1 day before operation and 7 days after CCI. Three mice were randomly killed in Sham group 7 days after modeling, and 3 mice in CCI group were killed at 7 days and 14 days respectively.The L3-5 spinal cord segment was taken. Akt3, phosphorylated Akt (p-Akt), GSK3β and phosphorylated NR2B (p-NR2B) were detected by Western blot. SPSS 21.0 software was used for statistical analysis. Results:Group time interaction effects of PWMT, the expression of protein Akt3, p-Akt, GSK3β, p-NR2B in spinal cord were significantly different ( F=16.667, 269.899, 26.651, 572.998, 37.836, P<0.01). Compared with the Akt3 -/-+ Sham group, the PWMT in Akt3 -/-+ CCI group was significantly lower((0.34±0.20)g, (1.18±0.11)g, P<0.01), and the expression of p-Akt((0.90±0.08), (0.51±0.06), P<0.01), GSK3β((0.74±0.04), (0.29±0.02), P<0.01) and p-NR2B((0.96±0.11), (0.71±0.04), P<0.05) in spinal cord increased. Compared with the WT+ CCI group, the PWMT of the Akt3 -/-+ CCI group was obviously lower((0.34±0.20)g , (0.49±0.12)g, P<0.05), and the expression of p-Akt((0.90±0.08), (1.02±0.17), P<0.05)decreased, and the expression of GSK3β((0.74±0.04), (0.57±0.09), P<0.01) and p-NR2B((0.96±0.11), (0.91±0.08), P<0.05) increased. Conclusion:After Akt3 gene knockout, the aggravation of neuropathic pain after sciatic nerve ligation may be related with the change of Akt/GSK3β/NR2B expression.

Effect of processing excipient suet oil on formation and absorption of baohuoside Ⅰ-bile salt self-assembled micelles / 中国中药杂志

The fried method with suet oil,which can strengthen the effect of Epimedium in warming kidney and enhancing Yang,has been widely used in the processing of Epimedium in traditional Chinese medicine. Based on the formation mechanism of Epimedium flavonoids self-assembled micelles in vivo,the synergistic mechanism of processing excipient suet oil was investigated in this paper from the perspective of pharmaceutics. Baohuoside Ⅰ,as representative component of processed Epimedium,was selected as model drug.Average size and zeta potential were measured and the morphology of micelles was observed under transmission electron microscopy. Caco-2 monolayer cell model,rat intestinal perfusion model and in vivo serum drug concentration method were established to investigate the effect of suet oil on the formation and absorption of the baohuosideⅠ bile salt self-assembled micelles. Baohuoside Ⅰ can form selfassembled micelles under the action of sodium deoxycholate. While,adding suet oil into the baohuoside Ⅰ-bile salt micelles( BSDOC) can make it form a more stable system with a smaller average size,higher Zeta potential,lower polydispersity index( PDI) value,significantly improved encapsulation efficiency and drug loading,indicating that suet oil could significantly improve the micelle formation in vivo. In addition,the permeability coefficient of baohuoside Ⅰ in Caco-2 monolayer cells and the four intestinal organs( duodenum,jejunum,ileum and colon) was increased and the oral bioavailability was also improved after adding the suet oil to BS-DOC.All the results demonstrated that the suet oil can promote the formation and absorption of baohuoside Ⅰ self-assembled micelles,so as to enhance its synergistic effects.

Prediction of survival outcomes in patients with epithelial ovarian cancer using machine learning methods / 부인종양

OBJECTIVES: The aim of this study was to develop a new prognostic classification for epithelial ovarian cancer (EOC) patients using gradient boosting (GB) and to compare the accuracy of the prognostic model with the conventional statistical method. METHODS: Information of EOC patients from Samsung Medical Center (training cohort, n=1,128) was analyzed to optimize the prognostic model using GB. The performance of the final model was externally validated with patient information from Asan Medical Center (validation cohort, n=229). The area under the curve (AUC) by the GB model was compared to that of the conventional Cox proportional hazard regression analysis (CoxPHR) model. RESULTS: In the training cohort, the AUC of the GB model for predicting second year overall survival (OS), with the highest target value, was 0.830 (95% confidence interval [CI]=0.802–0.853). In the validation cohort, the GB model also showed high AUC of 0.843 (95% CI=0.833–0.853). In comparison, the conventional CoxPHR method showed lower AUC (0.668 (95% CI=0.617–0.719) for the training cohort and 0.597 (95% CI=0.474–0.719) for the validation cohort) compared to GB. New classification according to survival probability scores of the GB model identified four distinct prognostic subgroups that showed more discriminately classified prediction than the International Federation of Gynecology and Obstetrics staging system. CONCLUSION: Our novel GB-guided classification accurately identified the prognostic subgroups of patients with EOC and showed higher accuracy than the conventional method. This approach would be useful for accurate estimation of individual outcomes of EOC patients.

Unbiased transcriptomic analyses reveal distinct effects of immune deficiency in CNS function with and without injury

The mammalian central nervous system (CNS) is considered an immune privileged system as it is separated from the periphery by the blood brain barrier (BBB). Yet, immune functions have been postulated to heavily influence the functional state of the CNS, especially after injury or during neurodegeneration. There is controversy regarding whether adaptive immune responses are beneficial or detrimental to CNS injury repair. In this study, we utilized immunocompromised SCID mice and subjected them to spinal cord injury (SCI). We analyzed motor function, electrophysiology, histochemistry, and performed unbiased RNA-sequencing. SCID mice displayed improved CNS functional recovery compared to WT mice after SCI. Weighted gene-coexpression network analysis (WGCNA) of spinal cord transcriptomes revealed that SCID mice had reduced expression of immune function-related genes and heightened expression of neural transmission-related genes after SCI, which was confirmed by immunohistochemical analysis and was consistent with better functional recovery. Transcriptomic analyses also indicated heightened expression of neurotransmission-related genes before injury in SCID mice, suggesting that a steady state of immune-deficiency potentially led to CNS hyper-connectivity. Consequently, SCID mice without injury demonstrated worse performance in Morris water maze test. Taken together, not only reduced inflammation after injury but also dampened steady-state immune function without injury heightened the neurotransmission program, resulting in better or worse behavioral outcomes respectively. This study revealed the intricate relationship between immune and nervous systems, raising the possibility for therapeutic manipulation of neural function via immune modulation.

Prevalence and oncologic outcomes of BRCA1/2 mutation and variant of unknown significance in epithelial ovarian carcinoma patients in Korea

OBJECTIVE: BRCA mutational status is important in the management of ovarian cancer, but there is a lack of evidence supporting genetic testing in Asian populations. This study was performed to investigate the prevalence and prognostic outcomes of BRCA1/2 mutation and variant of unknown significance (VUS) in Korean patients diagnosed with epithelial ovarian cancer (EOC). METHODS: Among patients newly diagnosed with EOC between January 2007 and January 2017, those tested for germline BRCA1/2 mutation were studied, regardless of family history. Overall survival (OS) and progression-free survival (PFS) were compared between the patients with and without BRCA1/2 mutation and VUS. RESULTS: A total of 313 patients underwent BRCA testing: 88 patients had a BRCA1/2 mutation and 48 patients had a BRCA1/2 VUS (28.1% and 15.3%, respectively). There were no significant associations between BRCA1/2 mutation, BRCA1/2 wild-type, or BRCA1/2 VUS with age at diagnosis, histologic distribution, or residual disease status after primary cytoreductive surgery. BRCA1 mutation, including BRCA1 VUS, showed no difference in PFS or OS compared to BRCA1 wild-type. In contrast, BRCA2 mutation showed longer PFS than that of BRCA2 wild-type (P=0.04) or BRCA2 VUS (P=0.02). BRCA2 mutation, including BRCA2 VUS, did not show any difference in OS compared to BRCA2 wild-type. CONCLUSION: BRCA mutation and BRCA VUS had similar clinical characteristics and survival outcomes, except that BRCA2 mutation showed better PFS. The results of this study will help to understand the prognostic significance of BRCA mutation and VUS in Korean patients.

Effect of Recipes for Tonifying Kidney and Replenishing Qi on Learning and Memory-related Genes in Aged Rats / 中国实验方剂学杂志

Objective:To observe the effects of recipes for tonifying kidney and replenishing Qi, Zuoguiwan (ZG) and Yiqi Congming Tang(YQ) on memory capacity, expressions of learning and memory-related genes expression, and explore the changes in relevant epigenetic modification enzymes. Method:SD male rats with natural aging (24 months old) were used as animal models and randomly divided into aged control group, aged ZG group(12.12 g·kg-1), aged YQ group(10.18 g·kg-1), aged compound group(11.15 g·kg-1) and aged antagonist RU38486 group(5×10-3g·kg-1). Another 5 months old male SD rats were included as the young control group. Morris water maze method was used to observe the spatial learning and memory ability of the rats. The co-localizations of histone deacetylase 2 (HDAC2) and methyl CpG binding protein 2 (MeCP2) in hippocampus of rats in each group were observed by laser confocal microscope. The changes in expressions of glucocorticoid receptor (GR), synapsin1(Syn-1), HDAC2, and histone acetyltransferase 1(HAT1) proteins in hippocampus of each group were detected by Western blot, and mRNA expression of HDAC2 was detected by Real-time fluorescence quantitative polymerase Chain reaction (Real-time PCR). At the same time, the effects of ZG, YQ and compound decoction in alleviating the above-mentioned abnormal changes were observed. Result:Compared with the young control group(control group), the latency of the aged control group was significantly prolonged (PPPPPPPConclusion:ZG group, YQ group, and compound group can improve the spatial learning and memory abilities of aged rats by increasing the expression of learning-memory-associated protein GR and epigenetic modification enzyme HAT1, and reducing the expression of HDAC2 and the co-localization of HDAC2 protein and MeCP2 in the nucleus.

Prognostic factors for recurrence and survival in uterine leiomyosarcoma: Korean single center experience with 50 cases

OBJECTIVE: The aim of this study was to determine the possible prognostic factors in patients with uterine leiomyosarcoma (LMS). METHODS: This study retrospectively investigated 50 patients with uterine LMS treated at the Samsung Medical Center between 2001 and 2017. To analyze the prognostic significance of factors for recurrence-free survival (RFS), overall survival (OS), and survival after recurrence, the log-rank test and Cox proportional hazards model were used for univariate and multivariate analysis. RESULTS: Of the 50 patients, 30 (60.0%) experienced recurrence and 16 (32.0%) died within a median follow-up period of 21 (range, 3–99) months. Multivariate analysis revealed that older age, absence of residual tumor after surgery, lower mitotic count, and a history of adjuvant radiotherapy at first treatment were significantly associated with better RFS. Presence of residual tumor after surgery and severe nuclear atypia were associated with poor OS. In the analysis of survival after recurrence, hematogenous recurrence, severe nuclear atypia, and presence of residual tumor at primary surgery were significantly associated with worse prognosis. Notably, residual tumor status at primary surgery was associated with RFS, OS, and survival after recurrence. CONCLUSION: We demonstrated the possible prognostic factors for RFS, OS, and survival after recurrence for patients with LMS. These results may provide useful information for patients with LMS.

Analysis of Folium Epimedium toxicity in combination with Radix Morindae Officinalis based on zebrafish toxicity/metabolism synchronization / 药学学报

Metabolic transformation in vivo is a critical approach in the study of toxicity, but real-time dynamic observation of the transformation is difficult. We proposed that zebrafish toxicity/metabolism synchronization may be used in the analysis of toxicity of Folium Epimedium (Yinyanghuo for Chinese, YYH) and the toxicity may be reduced by Radix Morindae Officinalis (Bajitian for Chinese, BJT). Healthy zebrafish embryos 1 day post fertilization (1 dpf) were exposed to different concentrations of YYH, total flavonoids of YYH (YTF), representative flavonoids (epimedin C and icariin) and their respective in combination with BJT. Death numbers of the embryos or larvals were counted during 1-5 days after dosing (2-6 dpf); embryonic micro-morphology of zebrafish (3 dpf) was observed and pictures were taken. The blank vehicle (0.4% DMSO) was used in the control group, and LC50 value of 2 to 6 dpf was calculated by SPSS16.0. A relative safe concentration was sampled every day to analyze the dynamic metabolites changes of major flavonoids of YYH. The results showed that epimedin A/B/C (EA/EB/EC) and icariin, the major flavonoids of YYH, were dynamically transformed into major metabolites of sagittatoside C (SC) and baohuoside I (BI) by zebrafish. BI was mainly derived from EA, EB and icariin. Neither original form nor their metabolite BI can cause zebrafish poisoning. SC was mainly derived from EC, and its accumulation was closely related to the toxicity of YYH, YTF and EC. After combination with BJT, the metabolism of EC was slowed down and the toxicity was alleviated. Zebrafish toxicity/metabolism synchronization revealed that the toxicity of EC of YYH was increased after metabolism into SC, which maybe the key potential poisonous factor of YYH, and BJT can reduce the toxicity by slowing down the metabolism rate of EC. The data provides new ideas and methods in the study of toxic substances in Chinese medicine and mechanism of detoxicity by combination.

Characterization of sediment of water extract of Guizhi decoction and its effect on relevant compound (fractions) in decoction / 中国中药杂志

In order to study the effect of sediment of water extract of Guizhi decoction on the stability, clarity and peaks area, and characterize the chemical composition of the sediments, HPLC and MS methods were established. Through comparison of the common peak areas and the turbidity value of water extract and filtrate, the sediments could greatly change the common peak areas of the decoction (for more than 5 times of the study standard); at the same time, the turbidity value of the decoction could increase by （38.66±1.57）% in 48 h [particularly by （24.54±1.68）% in 6 h]. The test indicated that the sediments had an effect on the stability and clarity under the test conditions in Guizhi decoction. The study confirmed that the sediments were mainly derived from Cassia twig, Paeonia lactiflora and Glycyrrhiza uralensis. On the basis of the reference information, the accurate molecular weight and fragment ion information provided by LC-MS were analyzed, the molecular formula of sediments components A-F were determined, and the possible structural information of components B, C, D and F were deduced. It was suggested that the multi-index, multi-target and multi-angle analysis could ensure the quality of traditional Chinese medicine and the effect of clinical medication. The study also suggested the effect of the sediments on clinical application and the preparation of traditional Chinese medicine.

Survival impact of low anterior resection in patients with epithelial ovarian cancer grossly confined to the pelvic cavity: a Korean multicenter study / 부인종양

OBJECTIVE: To evaluate survival impact of low anterior resection (LAR) in patients with epithelial ovarian cancer (EOC) grossly confined to the pelvis. METHODS: We retrospectively reviewed 397 patients who underwent primary staging surgery for treatment of 2014 International Federation of Gynecology and Obstetrics (FIGO) stage II–IIIA EOC: 116 (29.2%) IIA, 212 (53.4%) IIB, and 69 (17.4%) IIIA. Patients with grossly enlarged retroperitoneal lymph nodes positive for metastatic carcinoma were excluded. Of 92 patients (23.2%) with gross tumors at the rectosigmoid colon, 68 (73.9%) underwent tumorectomy and 24 (26.1%), LAR for rectosigmoid lesions. Survival outcomes between patients who underwent tumorectomy and LAR were compared using Kaplan-Meier curves. RESULTS: During the median follow-up of 55 months (range, 1–260), 141 (35.5%) recurrences and 81 (20.4%) deaths occurred. Age (52.8 vs. 54.5 years, p=0.552), optimal debulking (98.5% vs. 95.0%, p=0.405), histologic type (serous, 52.9% vs. 50.0%, p=0.804), FIGO stage (p=0.057), and platinum-based adjuvant chemotherapy ≥6 cycles (85.3% vs. 79.2%, p=0.485) were not different between groups. No significant difference in 5-year progression-free survival (PFS; 57.9% vs. 62.5%, p=0.767) and overall survival (OS; 84.7% vs. 63.8%, p=0.087), respectively, was noted between groups. Postoperative ileus was more frequent in patients subjected to LAR than those who were not (4/24 [16.7%] vs. 11/373 [2.9%], p=0.001). The 5-year PFS (60.3% vs. 57.9%, p=0.523) and OS (81.8% vs. 87.7%, p=0.912) between patients who underwent tumorectomy and those who did not were also similar. CONCLUSION: Survival benefit of LAR did not appear to be significant in EOC patients with grossly pelvis-confined tumors.

Retrospective study of combination chemotherapy with etoposide and ifosfamide in patients with heavily pretreated recurrent or persistent epithelial ovarian cancer

OBJECTIVE: This retrospective study is to evaluate the efficacy and toxicity of combination chemotherapy with etoposide and ifosfamide (ETI) in the management of pretreated recurrent or persistent epithelial ovarian cancer (EOC). METHODS: Patients with recurrent or persistent EOC who had measurable disease and at least one chemotherapy regimen were to receive etoposide at a dose of 100 mg/m²/day intravenous (IV) on days 1 to 3 in combination with ifosfamide 1 g/m²/day IV on days 1 to 5, every 21 days. RESULTS: From August 2008 to August 2016, 66 patients were treated with ETI regimen. Most patients were heavily pretreated prior to ETI: 53 (80.3%) patients had received 3 or more chemotherapy regimens. The response rate (RR) of ETI chemotherapy was 18.2% and median duration of response was 6.8 months (range, 0–30). Median survival of all patients was 5 months at a median follow up of 7.2 months. Platinum-free interval (PFI) more than 6 months prior to ETI has statistically significant correlation with overall survival (OS; 9.2 vs. 5.6 months; P=0.029) and RR (34.5% vs. 5.4%; P < 0.010). However, treatment free interval before ETI, number of prior chemotherapy regimen, and optimality of primary surgery did not show significant difference for RR or OS. Grade 3 or 4 hematologic toxicities were observed in 7 cases (3%) of the 232 cycles of ETI. CONCLUSION: The ETI combination regimen shows comparatively low toxicity and modest activity in heavily pretreated recurrent or persistent EOC patients with more than 6 months of PFI after last platinum treatment.

Molecular Signature for Lymphatic Invasion Associated with Survival of Epithelial Ovarian Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We aimed to develop molecular classifier that can predict lymphatic invasion and their clinical significance in epithelial ovarian cancer (EOC) patients. MATERIALS AND METHODS: We analyzed gene expression (mRNA, methylated DNA) in data from The Cancer Genome Atlas. To identify molecular signatures for lymphatic invasion, we found differentially expressed genes. The performance of classifier was validated by receiver operating characteristics analysis, logistic regression, linear discriminant analysis (LDA), and support vector machine (SVM). We assessed prognostic role of classifier using random survival forest (RSF) model and pathway deregulation score (PDS). For external validation, we analyzed microarray data from 26 EOC samples of Samsung Medical Center and curatedOvarianData database. RESULTS: We identified 21 mRNAs, and seven methylated DNAs from primary EOC tissues that predicted lymphatic invasion and created prognostic models. The classifier predicted lymphatic invasion well, which was validated by logistic regression, LDA, and SVM algorithm (C-index of 0.90, 0.71, and 0.74 for mRNA and C-index of 0.64, 0.68, and 0.69 for DNA methylation). Using RSF model, incorporating molecular data with clinical variables improved prediction of progression-free survival compared with using only clinical variables (p < 0.001 and p=0.008). Similarly, PDS enabled us to classify patients into high-risk and low-risk group, which resulted in survival difference in mRNA profiles (log-rank p-value=0.011). In external validation, gene signature was well correlated with prediction of lymphatic invasion and patients' survival. CONCLUSION: Molecular signature model predicting lymphatic invasion was well performed and also associated with survival of EOC patients.