Two cardenolide glycosides from the seed fairs of Asclepias curassavica and their cytotoxic activities / 中国天然药物

Two cardenolide glycosides, corotoxigenin 3-O-[β-D-glucopyranosyl-(1→4)-6-deoxy-β-D-glucopyranoside] (1) and coroglaucigenin 3-O-[β-D-glucopyranosyl-(1→4)-6-deoxy-β-D-glucopyranoside] (2), were isolated from the seed fairs of Asclepias curassavica. The structures of 1-2 were determined based on the combination of the analysis of their MS, NMR spectroscopic data and acid hydrolysis. The inhibitory effects of compounds 1 and 2 on human colorectal carcinoma cells (HCT116), non-small cell lung carcinoma cells (A549) and hepatic cancer cells (SMMC-7721) were evaluated. The results showed that both compounds 1 and 2 significantly inhibited the viability, proliferation, and migration of A549, HCT116 and SMMC-7721 cells, suggesting that compounds 1 and 2 can be applied in the treatment of lung, colon and liver cancers in clinical practice. This study may not only provide a scientific basis for clarifying the active ingredients in A. curassavica, but also help to understand its antitumor activity, which can promote the application of A. curassavica in clinical treatment of various cancers.

Network Meta-analysis of oral Chinese patent medicine for adjuvant treatment of primary liver cancer / 中国中药杂志

Network Meta-analysis was used to evaluate the efficacy and safety of different oral Chinese patent medicines combined with transcatheter arterial chemoembolization(TACE) in the treatment of primary liver cancer. Randomized controlled trials of oral Chinese patent medicines for primary liver cancer were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library and EMbase databases from inception to May 2020. According to the Cochrane recommendation standard, the quality of the included articles was evaluated, and the data were analyzed by RevMan, R software and GeMTC software. A total of 10 kinds of oral Chinese patent medicines and 68 RCTs were included. Network Meta-analysis results showed that: as compared with TACE alone, 10 kinds of oral Chinese patent medicines combined with TACE showed advantages in effective rate, 1-year survival rate, 2-year survival rate, KPS score improvement rate and reduced adverse reaction incidence. In the pairwise comparison of oral Chinese patent medicines, the results showed that Cidan Capsules were superior to Jinlong Capsules and Xihuang Pills in 1-year survival rate. According to the probabi-lity ranking results: Shenyi Capsules and Ganfule were more obvious in improving the effective rate; Cidan Capsules and Shenyi Capsules were more effective in improving the 1-year survival rate; Pingxiao Capsules and Shenyi Capsules had better efficacy in improving 2-year survival rate; Huaier Granules and Shenyi Capsules had better efficacy in improving the quality of life; Huisheng Oral Liquid and Ganfule were more effective in reducing the incidence of adverse reactions(such as nausea, vomiting and leukocytosis). The current evidence showed that oral Chinese patent medicine combined with TACE was superior to TACE alone in efficacy and safety. In terms of the effective rate, 1-year survival rate, 2-year survival rate, KPS score improvement rate and reduced adverse reaction incidence, the optimal treatment measures were Shenyi Capsules, Cidan Capsules, Pingxiao Capsules, Huaier Granules and Huisheng Oral Liquid in turn. However, due to the limitations of the research, the current level of evidence is not high, and clear conclusions and evi-dence strength still need to be further verified and improved by high-quality researches.

Systematic evaluation of Huaier Granules adjuvant treatment of primary liver cancer / 中国中药杂志

To systematically evaluate the efficacy and safety of Huaier Granules in the adjuvant treatment of primary liver cancer. The databases of CNKI, Wanfang, VIP, CBMdisc, PubMed, Cochrane Library and EMbase were searched by computer to screen out the randomized controlled trial on Huaier Granules combined with Western medicine in the treatment of primary liver cancer from the establishment of the databases to January 2020. Data extraction and quality evaluation were conducted for the included literature. Meta-analysis was conducted with RevMan 5.3 software, and evidence quality evaluation was conducted for the outcomes by GRADE profiler software. A total of 24 articles were included, with a total sample size of 2 664 cases. Meta-analysis showed that as compared with Western medicine alone, Huaier Granules combined with Western medicine could improve the objective remission rate(RR=1.38, 95%CI[1.26, 1.51], P<0.000 01), disease control rate(RR=1.29, 95%CI[1.10, 1.52], P=0.002) and 6-month survival rate(RR=1.20, 95%CI[1.10, 1.32], P<0.000 1), 1-year survival rate(RR=1.39, 95%CI[1.23, 1.58], P<0.000 01), 2-year survival rate(RR=1.95, 95%CI[1.28, 2.96], P=0.002), KPS score(MD=17.15, 95%CI[6.47, 27.83], P=0.002) and the improvement rate of KPS score(RR=2.02, 95%CI[1.47, 2.77], P<0.000 1), AFP decline rate(RR=1.40, 95%CI[1.20, 1.62], P<0.000 1), CD3~+(MD=17.34, 95%CI[9.28, 25.40], P<0.000 1), CD4~+(MD=8.62, 95%CI[1.59, 15.64], P=0.02), CD8~+(MD=1.95, 95%CI[-3.93, 7.82], P=0.52), CD4~+/CD8~+(MD=0.42, 95%CI[-0.33, 1.17], P=0.27); reduce the level of AFP(MD=-71.57, 95%CI[-80.42,-62.72], P<0.000 01), recurrence rate(RR=0.76, 95%CI[0.67, 0.85], P<0.000 01), and incidence of adverse reactions(RR=0.60, 95%CI[0.41, 0.89], P=0.01) in patients with primary liver cancer. According to the GRADE system, the evidence for outcome measures was low to very low. The results show that Huaier Granules have certain efficacy and high safety in adjuvant treatment of primary liver cancer, but its effect in reducing adverse reactions and improve immunity remains to be verified. Due to the poor quality of the included studies and evidences, the conclusions still need to be further verified by multi-center, large sample, and randomized double-blind controlled studies.

Expression of CCR7 and Tim-3 in Childhood Patients with Acute Lymphoblastic Leukemia and Their Predictive Value for Prognosis / 中国实验血液学杂志

OBJECTIVE@#To analyze the expression of CCR7 and Tim-3 in childhood patients with acute lymphoblastic leukemia (ALL) and their predictive value for prognosis.@*METHODS@#Eighty-six newly diagnosed ALL childhood patients from January 2007 to January 2017 treated in our hospital were selected. The expression level of CCR7 and Tim-3 in bone marrow isolated cells of ALL patients were detected by flow cytometry, all the patients were divided into the recurrence group and non-recurrence group according to the follow-up results, the differences in the expressions of CCR7, Tim-3 between the two groups were compared. The correlation between the expression of CCR7 , Tim-3 and the clinicopathologic features of ALL patients were analyzed, the predictive value of CCR7 and Tim-3 for the prognosis of newly ALL patients were evaluated by ROC curve, and the relationship between serum CCR7, Tim-3 and prognosis were analyzed.@*RESULTS@#The expression levels of CCR7 and Tim-3 in recurrence group were significantly higher than those in non-recurrence group(P0.05). The exogenous infiltration rate of patients with high expression of CCR7 and Tim-3 was significantly higher than those in low expression group (P<005). The high expression rate 76.9% of Tim-3 in patients with T-ALL was significantly higher than that of B-ALL patients with Tim-3 high expression rate 45.2% (P<0.05). The median OS of patients with CCR7 level ≥45.97% and <45.97% were 9.3 months and 13.6 months respectively(P=0.004), and the Tim-3≥53.54% and Tim-3<53.54% were 9.1 months and 13.6 months respectively(P=0.001). The results of Cox's multi-factor regression analysis showed that CCR7 level(HR=1.024, 95 CI 1.001-1.049) and Tim-3 level (HR=1.879, 95 CI 1.183- 2.985) were the independent risk factors that affect the OS in ALL patients(P<0.05).@*CONCLUSION@#The expression of CCR7 and Tim-3 in bone marrow isolated cells of ALL patients shows good predictive value for prognosis, and the combination of CCR7 and Tim-3 can improve the sensitivity of the detection, the higher expression of CCR7 and Tim-3 can be used as potential indexes in prognosis evaluate.

A new eudesmane type sesquiterpene from cultivated Clerodendranthus spicatus in Hainan / 中国中药杂志

Six compounds were isolated from the aerial part of cultivated Clerodendranthus spicatus in Hainan with various chromatographic techniques,and their structures were determined as:1-dehydroxy-1-oxo-rupestrinol(1),N-trans-feruloyltyramine(2),methyl 3,4-dihydroxyphenyllactate(3),caffein acid(4),methyl caffeate(5) and ethyl caffeate(6),via analysis of physicochemical properties and spectroscopic evidence.Compound 1 was a new compound,while compounds 2 and 3 were isolated from C.spicatus for the first time.Biological activity results showed that compounds 2-4 exhibited α-glucosidase inhibitory activity with different inhibition ratio.

Reflection on Optimizing the Internal Application Environment of Management Accounting in Public Hospitals / 中国卫生经济

As a direction of accounting development in the new period,management accounting could play an important role in public hospital management.At present,the public hospital had not yet established a perfect organizational structure and management model of management accounting,which lacked human resources management in the management accounting.The information construction lacked united planning resulted that management accounting was not effectively introduced into the links of hospital planning,strategy,control and evaluation.Through summarizing hospital value innovation mode,it promoted the integration of business and finance,established depended management accounting department,optimized the internal application environment of management accounting in public hospitals,promoted the management accounting construction of public hospitals,guarantee the value preservation of national assets and promoted the public welfare.

Metabonomics study on hepatoprotective effect of Schisandrae Chinensis Fructus based on UPLC-Q-TOF-MS / 中国中药杂志

To investigate the hepatoprotective effect of Schisandrae Chinensis Fructus (SCF) on CCl₄-induced liver injury, observe its effect on serum metabolites, explore its scientific connotation in liver preservation and find the biomarkers for hepatoprotective effect of SCF. Liver injury model was established by using CCl₄. The pathological sections of liver tissues were observed and the contents of alanine transaminase (ALT) and aspartate transaminase (AST) in serum were determined. The metabolic skills were adopted based on ultra performance liquid chromatography time-of-flight mass spectrometry (UPLC-Q-TOF-MS), principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) for screening and identification of biomarkers related to liver injury. The results showed the metabolites in blank group, model group and administration group could be easily distinguished, 50 differential compounds were identified and 7 possible metabolic pathways of liver protection were enriched. In this experiment, the hepatoprotective effect of SCF was verified, and the related metabolic pathways such as amino acid metabolism, vitamin metabolism and glycerophospholipid metabolism were discussed.

Relationship between serum level of caveolin-1 and early neurological deterioration in patients with acute cerebral infarction / 上海交通大学学报（医学版）

Objective·To investigate the relationship between serum level of caveolin-1 (Cav-1) and early neurological deterioration (END) in patients with acute cerebral infarction. Methods·A total of 126 consecutive patients with acute cerebral infarction were recruited from July 2016 to January 2017 in Department of Neurology, the First Affiliated Hospital of Chongqing Medical University. The serum Cav-1 levels of all patients were detected by enzyme-linked immunosorbent assay (ELISA) test. The neurological deficits were assessed by the National Institutes of Health Stroke Scale (NIHSS) and the Glasgow Coma Scale (GCS) at the same time. Compared with the admission baseline NIHSS score, if second motor NIHSS score increased ≥ 1 point or the total NIHSS score increased ≥ 2 points within 3 days after hospitalization, they were classified as END group, otherwise they were classified as non-END group. Multivariable Logistic regression analysis was used to examine the independent predictors of END in the patients. Receiver operating characteristic (ROC) curves were obtained to explore Cav-1 levels in predicting END. Results·Serum Cav-1 levels in END group were significantly higher than those in non-END group [(29.88±19.57) ng/mL vs (16.08±13.37) ng/mL, P=0.000]. Based on the ROC curves, the best cut-off point of serum Cav-1 for predicting END was 16.55 ng/mL. The sensitivity and specificity were 73.33％ and 74.07％, respectively. Multivariable Logistic regression analysis showed that Cav-1≥16.55 ng/mL remained an independent predictor of END (OR=4.936, 95％CI 1.608-15.155, P=0.005). Conclusion·Serum Cav-1 is an independent predictor of END in patients with acute cerebral infarction.

Preparation and evaluation of resveratrol-loaded mesoporous silica nanoparticles modified by amino / 中国药学杂志

OBJECTIVE: To prepare and evaluate resveratrol-loaded mesoporous silica nanoparticles modified by amino (NH2-MSN-RES) to improve the bioavailability of resveratrol. METHODS: Mesoporous silica nanoparticles modified by amino (NH2-MSN) were synthesized by the modified Stober method. The structure of the nanoparticles were analyzed and characterized by FT-IR, Malvern particle size analyzer, and TEM. By introducing the innovative preparation process of repeated saturated solution adsorbing method, RES was encapsulated into NH2-MSN in larger amount. Dialysis bag method was used to investigate the in vitro drug release characteristics and MTT method was used to investigate the cytotoxicity on Caco-2 cells. The transport ability of the carrier was investigated by the Caco-2 cells monolayer model. Finally, the pharmacokinetics of NH2-MSN-RES was studied in rats. RESULTS: The particle size distribution of NH2-MSN was uniform with an average value of (98.4±2.8) nm, and the Zeta potential was (13.2±1.8) mv. Within the scope of 0-20 μg·mL-1, NH2-MSN had no obvious toxicity on Caco-2 cells. After 8 times of repeated adsorption, the drug loading of NH2-MSN-RES reached up to (19.26±2.51)%. In the drug release experiment, the cumulative release quantity of NH2-MSN-RES was 73.3% within 48 h, indicating sustained-release characteristics. NH2-MSN-RES had good ability of transmembrane transport in the Caco-2 cell monolayer model, and the two-way apparent permeability coefficient (Papp) was much larger than the RES solution. In the pharmacokinetic study, RES solution complied with one-compartment model, whereas NH2-MSN-RES complied with two-compartment model, indicating that the carrier changed the pharmacokinetic characteristics of RES. The AUC0-∞ of NH2-MSN-RES was 2.58-fold of that of RES solution, what's more, the t1/2, tmax, and ρmax of NH2-MSN-RES were significantly greater than those of RES solution. CONCLUSION: NH2-MSN is synthesized by modified Stober method successfully. Repeated saturated solution adsorbing method could effectively improve the drug loading. NH2-MSN-RES improves the bioavailability of RES prominently. NH2-MSN will be a promising nano-material for oral drug delivery carrier.

Correlation of recurrent pregnancy loss with sperm parameters and sperm DNA fragmentation / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To evaluate and compare standard sperm parameters and sperm DNA fragmentation in seminal ejaculates from men whose partners had a history of recurrent pregnancy loss (RPL) and a control group of men who had recently established their fertility.</p><p><b>METHODS</b>Semen samples from 85 patients with a history of RPL and 20 men with proven fertility were analyzed according to World Health Organization guidelines. Sperm DNA fragmentation was detected by sperm chromatin dispersion test (SCD).</p><p><b>RESULTS</b>A significant difference (P< 0.05) was observed in sperm motility but not other parameters between the two groups. The mean number of sperm cells with fragmented DNA, represented as DNA fragmentation index, was significantly increased in the RPL group [(34.99± 14.62)%] compared with controls [(10.82± 4.80)%].</p><p><b>CONCLUSION</b>This study has indicated that sperm from men with a history of RPL have a higher incidence of DNA damage and poor motility compared with fertile males.</p>

Role of miR-124a methylation in patients with gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the DNA methylation status of the promoter region within the coding gene hsa-miR-124a in human gastric cancer tissue, and examine its association with the expression of Rb and CDK6 protein and clinicopathological factors.</p><p><b>METHODS</b>Methylation-specific PCR (MS-PCR) was used to detect the DNA methylation status of hsa-miR-124a in gastric cancer tissues and adjacent normal tissues from 30 patients. The expression of Rb and CDK6 protein within these tissues was examined using immunohistochemistry.</p><p><b>RESULTS</b>The overall methylation rate of gastric cancer tissues was 73.3%, which was significantly higher than that in the adjacent tissues(10.0%, P<0.05). The overall positive rates of Rb and CDK6 protein in gastric cancer tissues were 86.7% and 80.0%, respectively. DNA methylation of hsa-miR-124a was positively correlated with the expression of Rb and CDK6 proteins. Significant associations were found between hypermethylation of hsa-miR-124a and tumor size, differentiation, lymphatic metastasis, and invasion depth(P<0.01).</p><p><b>CONCLUSIONS</b>Hypermethylation of hsa-miR-124a is present in gastric cancer, and is associated with increased expression of CDK6 and Rb protein. These may be related to the proliferation and development of malignancy in the stomach.</p>