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Malignant tumor is a serious threat to human life and health. The prevalence and mortality of malignancies in China are increasing year by year. Conquering cancer has become a difficult problem for human beings. Chemical drug therapy combined with molecular targeted therapy is a general and preferred anti-tumor clinical scheme， but the side effects and the drug resistance of cancer cells often hinder the efficacy. Therefore， it is of great significance to study the mechanism of drug resistance and the methods to reverse drug resistance. Chinese medicine has the characteristics of complex components， multiple targets， low toxicity， etc. A large number of experimental studies have demonstrated that the effective components or extracts of Chinese medicine can inhibit the proliferation， migration， and invasion of cancer cells， and induce apoptosis， autophagy， differentiation， and senescence. In clinical practice， Chinese medicine has been applied to the protection against ttumor， adjuvant treatment， and later consolidation. The research on Chinese medicine is expected to promote drug resistance reversal and cancer therapy. Studies have shown that the combination of Chinese medicine and chemotherapy can reverse drug resistance and increase efficacy， which has become the mainstream trend of cancer treatment. This study reviewed the mechanisms of the drug resistance of cancer cells induced by self-protective autophagy， gene mutation， high expression of enzymes， abnormal signaling pathways， and abnormal expression of RNA and protein， and summarized how compounds isolated from Chinese medicine， single drug and its extract， and classic anti-cancer prescription reversed the drug resistance to lay a solid foundation for the further investigation of the anti-tumor effect of Chinese medicine.
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ObjectiveTo investigate the effect of Draconis Sanguis petroleum ether fraction （DSPEF） on the proliferation， apoptosis， migration， and autophagy of human gastric cancer HGC-27 and MGC-803 cells， and preliminarily elucidate its molecular mechanism. MethodCell counting kit-8 （CCK-8） assay was used to detect the effect of DSPEF at different concentrations （0， 20， 40， 60， 80 mg·L-1） on the proliferation of HGC-27 and MGC-803 cells after 24， 48， 72 h. Hoechst staining and flow cytometry were used to explore the effects of DSPEF at different concentrations on the apoptosis and apoptosis rate of HGC-27 and MGC-803 cells after 48 h treatment， respectively. The wound healing assay and acridine orange staining were used to investigate the effects of DSPEF on the migration and autophagy of HGC-27 and MGC-803 cells， respectively. Western blot was used to detect the expression levels of signaling pathway-related proteins in HGC-27 and MGC-803 cells treated with DSPEF for 48 h. ResultCompared with the control group， DSPEF（30 mg·L-1） inhibited the proliferation and migration of HGC-27 and MGC-803 cells in a concentration- and time-dependent manner （P<0.05）， and induced the apoptosis （P<0.01） and autophagy of HGC-27 and MGC-803 cells. DSPEF （60 mg·L-1） down-regulated the protein levels of phosphorylated mammalian target of rapamycin （p-mTOR） （P<0.05， P<0.01） and down-regulated phospho-signal transducer and activator of transcription 3 （p-STAT3） in HGC-27 and MGC-803 cells （P<0.01）， suggesting that DSPEF presumedly inhibited the proliferation and migration of human gastric cancer HGC-27 and MGC-803 cells and induced their apoptosis and autophagy by inhibiting the mTOR/STAT3 signaling pathway. ConclusionThe down-regulation of the mTOR/STAT3 signaling pathway may be involved in the anti-gastric cancer effect of DSPEF. This study is expected to provide a reference for the investigation of the anti-tumor effect of Draconis Sanguis.
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ObjectiveTo investigate effect of aqueous extract of Trametes robiniophila （TRM，Huaier） on autophagy of human prostate cancer VCaP cells and Lamin B1 expression， so as to uncover its role in the proliferation of VCaP cells. MethodThe inhibitory effect of 0， 2， 4， 6， 8， 10 g·L-1 TRM aqueous extract on the proliferation of human prostate cancer VCaP cells at different time points were determined by cell counting kit-8 （CCK-8） assay. Acridine orange staining was conducted for analyzing the effect of TRM aqueous extract on the formation of autolysosomes in VCaP cells. After medication， the expression of microtubule-associated protein Ⅰ light chain 3 （LC3）， autophagy-related protein 3 （Atg3）， autophagy-related protein 5 （Atg5）， and autophagy-related protein 7 （Atg7） in VCaP cells were detected by Western blot. The effect of TRM aqueous extract alone and its combination with autophagy inhibitor bafilomycin A1 on the proliferation of VCaP cells were assayed by CCK-8 assay. RNA interference technology was used to explore the role of Lamin B1 in anti-proliferation of VCaP cells by TRM. ResultCompared with the blank group， TRM aqueous extract inhibited the proliferation of human prostate cancer VCaP cells in a time- and concentration-dependent manner （P<0.01）. Acridine orange staining showed that TRM aqueous extract promoted the formation of autolysosomes in VCaP cells. As revealed by Western blotting， TRM aqueous extract up-regulated the expression levels of LC3-Ⅱ， Atg3， Atg5， and Atg7 in contrast to those in the blank group （P<0.05）. All these indicated that TRM aqueous extract induced the autophagy of VCaP cells. In addition， autophagy inhibition impaired the sensitivity of VCaP cells to TRM aqueous extract （P<0.05）. The comparison with the blank group showed that TRM aqueous extract inhibited Lamin B1 protein expression in VCaP cells （P<0.01）， which in turns weakened the sensitivity of VCaP cells to TRM aqueous extract. ConclusionTRM aqueous extract inhibited the proliferation of human prostate cancer VCaP cells possibly by inducing autography and down-regulating Lamin B1 expression. This study has provided a theoretical basis for the clinical application of TRM.
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ObjectiveProteoglycan TPG-1 isolated from Trametes robiniophila（Huaier） has proved to have anti-hepatoma activity， and this paper aims to explore the molecular mechanism. MethodHuman hepatoma SK-HEP-1 cells were treated with TPG-1 （0， 0.05， 0.1， 0.25， 0.5， 1 g·L-1）. Then cell survival was detected by methyl thiazolyl tetrazolium （MTT） and apoptosis by flow cytometry. In addition， expression of genes in SK-HEP-1 cells treated with or without TPG-1 was examined by DNA microarray to preliminarily explore the anti-hepatoma molecular mechanism of TPG-1. ResultTPG-1 inhibited the proliferation of SK-HEP-1 cells as compared with the blank group （P<0.01）. After treatment with 1 g·L-1 TPG-1 for 48 h， the apoptosis rate of SK-HEP-1 cells increased （P<0.01）， and TPG-1 promoted the cleavage of cysteinyl aspartate specific proteinase （Caspase）-3 and Caspase-7， the key mediators of apoptosis （P<0.01）. Additionally， TPG-1 （1 g·L-1） suppressed the migration of SK-HEP-1 cells （P<0.05）. A total of 971 differentially expressed genes （DEGs） were identified in SK-HEP-1 cells after treatment with TPG-1， with 486 up-regulated and 485 down-regulated. These DEGs were mainly involved in the Gene Ontology （GO） terms of interleukin-6 （IL-6） biosynthesis， antigen processing and presentation， superoxide dismutase activity， positive regulation of mitogen-activated protein kinase kinase kinase （MAPKKK） cascade， nature killer （NK） cell chemotaxis， and chemokine biosynthesis， and the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathways of nucleotide-binding oligomerization domain （NOD）-like receptor signaling pathway， apoptosis， Toll-like receptor signaling pathway， retinoic acid-inducible gene-Ⅰ （RIG-Ⅰ）-like receptor signaling pathway， T-cell receptor signaling pathway， and chemokine signaling pathway. Western blot results showed that TPG-1 （1 g·L-1） activated mitogen-activated protein kinase （MAPK） signaling pathway in SK-HEP-1 cells （P<0.01）. ConclusionProteoglycan TPG-1 inhibited the proliferation and migration， and induced apoptosis of human hepatoma SK-HEP-1 cells. Up-regulation of MAPK signaling pathway may be responsible for the growth inhibition of human hepatoma SK-HEP-1 cells by TPG-1.
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As a traditional Chinese medicine, Chinese dragon's blood has multiple effects, such as activating blood to remove blood stasis, softening and dispelling stagnation, astringent and hemostasis, clearing swelling and relieving pain, regulating menstruation and rectifying the blood, so it is called "an effective medicine of promoting blood circulation". It has been widely used clinically to treat a variety of diseases. With the further research on Chinese dragon's blood, its anti-tumor medicinal value is gradually emerging. Modern pharmacological studies have shown that Chinese dragon's blood exerts anti-tumor effects mainly by inhibiting cell proliferation, inducing apoptosis, inducing DNA damage and cell cycle arrest, inducing senescence and autophagy of tumor cells, inhibiting metastasis and angiogenesis, as well as reversing multidrug resistance. This article focuses on the research progress on anti-tumor effects of Chinese dragon's blood extract and its chemical components, with a view to provide new references for the in-depth research and reasonable utilization of Chinese dragon's blood.
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Female , China , Dracaena , Plant Extracts , Resins, PlantABSTRACT
Objective:To explore whether the 15-minute retention rate (R15) of indocyanine green (ICG) in the indocyanine green excretion test and the effective hepatic blood flow (EHBF) can predict the occurrence of mild hepatic encephalopathy (MHE).Methods:Using the convenience sampling method, we collected clinic data from 153 patients diagnosed with liver cirrhosis or liver failure from June 2019 to December 2019 in the Third Affiliated Hospital of Sun Yet-sen University in Guangzhou. We screened the MHE patients with the number connect test-A and the digital symbol test, and analyzed the clinical data. By taking different values for R15 and EHBF as cut-off points, the significance of the two factors in predicting MHE is explored respectively.Results:The incidence of MHE was 38.56% (59/153). Single factor analysis showed that the difference of Child-Pugh grade between the MHE group and the non-MHE group was statistically significant ( χ2 value was 7.606, P<0.05), while the differences between cirrhosis and liver failure diagnosis, fasting blood glucose, and serum creatinine were not statistically significant ( P>0.05). When most points between 0.11 and 0.61 were selected as normal and abnormal cut-off points of R15, R15 had statistical significance ( P<0.05) and when R15 selected 0.18, it was most significant (Fisher exact test P=0.00024). When most points between 0.08 and 0.76 were selected as normal abnormal cut-off points of EHBF, EHBF had statistical significance ( P<0.05) and when EHBF selected 0.25, it was most significant (Fisher exact test P=0.00022). Through Logistic stepwise regression analysis, the risk factors for MHE were R15 and EHBF. The ROC curve was used to illustrate the predictive effects of two factors on MHE. Conclusions:The incidence of MHE in patients with cirrhosis or liver failure is high. When R15≥0.18 or EHBF≤0.25 L/min, R15 and EHBF in indocyanine green excretion test can better predict the occurrence of MHE than Child-Pugh classification, and can be help to evaluate and manage patients in time.
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Objective To study the clinical features,diagnosis,treatment and genetic characteristics of chronic granulomatosis disease (CGD) in neonates,and to improve the understanding of CGD.Method Clinical manifestations and treatments of one patient with CGD and aspergillus infection in our hospital were analyzed.Key words including "infant","newborn","chronic granulomatous disease","lung abscess",and "aspergillus infection"were searched in Chinese medical databases,PubMed and Embase until 2018 September.The clinical features and genetic mutations of CGD reported in literature were summarized.Result The patient in our hospital was a full-term male infant naturally delivered with birth weight of 3 400 g.The onset of the disease was on the 19th day after birth,and the initial clinical manifestations included fever,cough,and then pulmonary abscess,diarrhea,recurrent skin infection,and aspergillus infection.Anti-infection and symptom-alleviating treatments were not effective,and weight gain was poor.Laboratory examination indicated bacterial and fungal infection.The neutrophil respiratory burst test was positive and indicated CGD.Hetero-zygotic frameshift mutation [c.1599-1602delAGTTt (p.V534Sfs* 12)] of CYBB gene 13 exon was detected and the diagnosis of CGD was confirmed.The mother carried the heterozygous mutation and the father didn't.Antifungal therapy was continued after the children got better and discharged from hospital.The patient was followed up until 3-month-old and his condition was stable.Our literature review revealed 28 reports including 108 cases of CGD infants,including 79 male cases (73.1％) and 21 female cases (19.4％).Most of the CGD infants (79/108,73.1％) had the onset within 2 weeks of life.The main clinical features included pneumonia/pulmonary abscess/pleural effusion (87.0％),diarrhea (58.3％),perianal abscess (35.2％),skin infection (53.7％),aspergillus infection (41.7％),and tuberculosis infection (26.9％).75 cases had positive neutrophil respiratory burst test (69.4％),and 95 cases were diagnosed using genetic tests (88.0％).Over 300 loci of the CYBB gene mutation had been reported contributing to the disease.28 cases had abnormal family history (25.9％),19 cases received hematopoietic stem cell transplantation (17.6％),41 cases had clinical improvement (38.0％),and 35 cases died (32.4％).Conclusion CGD is rare in neonatal period.The main clinical manifestations included recurrent infection with pathogens like aspergillus,tuberculosis and others.CGD can be diagnosed based on recurrent multiple bacterial or fungal infections,neutrophil respiratory burst test and gene tests.CGD should be considered among children with recurrent infections at early life stage,especially those with poor maternal history or positive family history.
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BACKGROUND:Three-dimensional (3D) printing technology is currently one of the most advanced industrial manufacturing technologies. The surgical template prepared based on the 3D printing technology is mainly made of resin, and a great improvement in its accuracy is required. However, the clinical application of the surgical template made of metal is rarely reported. OBJECTIVE:To evaluate the clinical value of 3D-printing implant template in the restoration of free-end missing teeth.METHODS:A prospective study was conducted in 64 enrolled patients with free end-tooth defects. All the patients were randomly assigned to receive traditional implant template (control group,n=32) or 3D-printing implant template (study group,n=32), and 3-6 months later, the patients were subjected to crown restoration. At 6 months after crown restoration, cone beam computed tomography was performed to compare the deviation of the implant tip and neck (including vertical, buccolingual, mesial-distal). Success rate and chewing rate were compared between the two groups at 6 months after crown restoration; patient satisfaction assessment was done and compared between the two groups at 1 year after crown restoration. RESULTS AND CONCLUSION:There were no significant differences between the two groups in the success rate and chewing rate (98.7％ vs. 95.6％; 97.4％ vs. 97.1％,P>0.05). The vertical, buccolingual, mesial-distal deviations of the implant tip were significantly lower in the study group than the control group (P<0.05), while there was no difference in the vertical and buccolingual deviations of the implant neck between the two groups (P>0.05), and the mesial-distal deviation of the implant neck was significantly lower in the study group than the control group (P<0.05). In addition, there was no difference in the patient satisfaction between the study and control groups (94％vs. 91％, P>0.05). To conclude, the 3D printing implant template can effectively reduce implant excursion based on the assurance of therapeutic efficacy and patient satisfaction, which is of great significance in the restoration of free-end tooth loss.
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Objective To raise awareness of the late-onset meningitis caused by group B streptococcus (GBS) which was homogenous to the maternal colonization.Methods The clinical data of late-onset GBS meningitis in neonates twins whose pathogens were homogenous to their maternal colonization were collected from Department of Neonatology,Guangzhou Women and Children's Medical Center.The general conditions,clinical symptoms,laboratory tests and drug treatment of the twins and their mother were retrospectively analyzed,and the GBS homology during inpatient care was tested.And the progress of the twins' condition was investigated by telephone follow-up.Results The mother had two pregnancies without prenatal GBS screening or intrapartum antimicrobial intervention for GBS,everything was normal during pregnancy and delivery.Twins were born through cesarean section.The elder sister was discharged with Linezolid taken orally after 167 days in hospital without convulsions,shaking or other discomfort.The elder sister was followed up for every 2 weeks,and in the last time of follow-up,cerebrospinal fluid white blood cell counts were 45 × 106/L,protein level was 1.52 g/L and Linezolid was withdrawn.The younger brother was discharged after 58 days in hospital with follow-up for every 2 weeks,and in the last time of follow-up,cerebrospinal fluid white blood cell counts were 30 × 106/L,protein level was 0.66 g/L.During the hospitalization and follow-up without convulsions and irritation,and the cranial magnetic resonance imaging of the twin brother was normal.Test results showed that the GBS bacteria strain for twins and their mother were all serotype Ⅲ.The possibility of the GBS homology was more than 90％.Conclusions The toxicity of serotype Ⅲ GBS strain was strong.More proactive precautions should be considered to apply for the mother whose first birth already had GBS infection.Early identification and intervention of infection risk factors would help optimize the anti-infection treatment program and reduce nerve system damage and other adverse outcomes caused by invasive GBS infection.