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1.
Article in Chinese | WPRIM | ID: wpr-928622

ABSTRACT

OBJECTIVES@#To study the clinical features and fibroblast growth factor receptor 3 (FGFR3) gene mutations of children with achondroplasia (ACH) through an analysis of 17 cases.@*METHODS@#A retrospective analysis was performed on the clinical data and FGFR3 gene detection results of 17 children with ACH who were diagnosed from January 2009 to October 2021.@*RESULTS@#Of the 17 children with ACH, common clinical manifestations included disproportionate short stature (100%, 17/17), macrocephaly (100%, 17/17), trident hand (82%, 14/17), and genu varum (88%, 15/17). The common imaging findings were rhizomelic shortening of the long bones (100%, 17/17) and narrowing of the lumbar intervertebral space (88%, 15/17). Major complications included skeletal dysplasia (100%, 17/17), middle ear dysfunction (82%, 14/17), motor/language developmental delay (88%, 15/17), chronic pain (59%, 10/17), sleep apnea (53%, 9/17), obesity (41%, 7/17), foramen magnum stenosis (35%, 6/17), and hydrocephalus (24%, 4/17). All 17 children (100%) had FGFR3 mutations, among whom 13 had c.1138G>A hotspot mutations of the FGFR3 gene, 2 had c.1138G>C mutations of the FGFR3 gene, and 2 had unreported mutations, with c.1252C>T mutations of the FGFR3 gene in one child and c.445+2_445+5delTAGG mutations of the FGFR3 gene in the other child.@*CONCLUSIONS@#This study identifies the unreported mutation sites of the FGFR3 gene, which extends the gene mutation spectrum of ACH. ACH is a progressive disease requiring lifelong management through multidisciplinary collaboration.


Subject(s)
Achondroplasia/genetics , Child , Humans , Mutation , Osteochondrodysplasias/genetics , Receptor, Fibroblast Growth Factor, Type 3/genetics , Retrospective Studies
2.
Article in Chinese | WPRIM | ID: wpr-940419

ABSTRACT

ObjectiveBased on the protective effect of Dengzhan Shengmai capsules (DZSM) on chronic cerebral hypoperfusion (CCH), network pharmacology was employed to investigate the molecular mechanism. MethodCCH model was established by right common carotid artery ligation. The mice were divided into sham operation group, model group, ginaton group (48 mg·kg-1), DZSM low- and high-dose groups (0.040 5, 0.162 g·kg-1). The efficacy was evaluated by the Morris water maze test and open-field test. The underlying mechanism of DZSM for CCH was analyzed by network pharmacology and verified by molecular biology experiments. PubChem, GeneCards, Metascape and other databases were used for targets collection and enrichment analysis. Besides, the association of ingredients targets of DZSM with disease targets of CCH, core target network and chemical components-core targets-pathways network were constructed by STRING 11.0 and Cytoscape 3.7.1. ResultThe escape latency of CCH mice significantly shortened on the 3rd to 5th day after DZSM low-dose treatment, the crossing times, time spent in the target quadrant, movement distance and distance in the central region of CCH mice significantly increased after DZSM low-dose and high-dose treatment. The results of network pharmacology indicated that DZSM might play a key role by regulating inflammatory response, phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway, cytokine-cytokine receptor interaction, tumor necrosis factor (TNF) signaling pathway, blood circulation, angiogenesis, extracellular matrix and other related biological processes and pathways, and acting as targets such as interleukin-6 (IL-6), TNF, insulin-like growth factor 1 (IGF1), vascular endothelial growth factor A (VEGFA), epidermal growth factor (EGF). The results of biological experiments showed that DZSM could reduce the expression of IL-6 in brain tissue of CCH mice. ConclusionDZSM provides a protective effect during CCH, and its multi-component, multi-pathway, multi-target mechanism is also revealed, which provides a basis for further study of the mechanism.

3.
Article in Chinese | WPRIM | ID: wpr-940294

ABSTRACT

ObjectiveOn the basis of determining the protective effect of berberine (BBR) on cerebral ischemia, crucial transcription factors (TFs) of BBR against cerebral ischemia was identified by using transcriptome and proteome sequencing. MethodThe model of middle cerebral artery occlusion (MCAO) was established by thread embolization. The sham operation group, model group, low-dose group of BBR (dose of 37.5 mg·kg-1·d-1) and high-dose group of BBR (75 mg·kg-1·d-1) were set up. The rats were killed after continuous intragastric administration for 7 days. The pharmacodynamics was evaluated by Longa score and cerebral infarction rate, and the expressions of inflammatory cytokines, such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α and monocyte chemotactic protein-1 (MCP-1) were measured by enzyme-linked immunosorbent assay (ELISA). Then, RNA-Seq technique was used to detect the differentially expressed genes (DEGs) before and after BBR intervention, and DAVID 6.8 was used for enrichment analysis of DEGs. CatTFREs technique was used to detect differential TFs before and after BBR intervention, and DAVID 6.8 and STRING 11.0 were used for enrichment analysis and TFs association analysis. Finally, by integrating the activity of TFs and the changes of downstream target genes, crucial TFs were identified and the related regulatory network was constructed by Cytoscape 3.7.1. ResultCompared with the sham operation group, the neurological impairment was significant in the model group (P<0.01), and compared with the model group, the low and high dose BBR groups could significantly reduce the neurological function damage (P<0.01) and decrease the rate of cerebral infarction (P<0.01). Transcriptome data analysis showed that BBR was involved in the recovery process after cerebral ischemia mainly by affecting cell adhesion, brain development, neuron migration, calcium signaling pathway, cyclic adenosine monophosphate (cAMP) signaling pathway, inflammatory response and other related functions and signaling pathways. Proteomic data analysis showed that the differentially expressed TFs after BBR intervention interfered with cerebral ischemia mainly by regulating cell differentiation, immune system process, cell proliferation and other biological processes. In addition, integration analysis of TFs and DEGs revealed that transcription factor CP2-like 1 (TFCP2L1), nuclear factor erythroid-2 like 1 (NFE2L1), neurogenic differentiation protein 6 (NeuroD6) and POU domain, class 2, transcription factor 1 (POU2F1) were crucial TFs against cerebral ischemia-reperfusion injury mediated by BBR. ConclusionBBR has obvious protective effect on cerebral ischemia-reperfusion injury and its crucial TFs include TFCP2L1, NFE2L1, NeuroD6 and POU2F1.

4.
Article in Chinese | WPRIM | ID: wpr-928168

ABSTRACT

Traditional Chinese medicine(TCM) carries the experience and theoretical knowledge of the ancients, and the use of "toxic" Chinese medicines is a major feature and advantage of TCM. "Toxic" Chinese medicines have unique clinical value and certain medication risk under the guidance of TCM theories such as compatibility for detoxification and treatment based on syndrome differentiation. In recent years, the safety events of Chinese medicines have occurred frequently, which has made the safety of Chinese medicine a public concern in China and abroad. However, limited by conventional cognitive laws and technical methods, basic research on toxicity of Chinese medicines fails to be combined with the clinical application. As a result, it is difficult to identify the clinical characteristics of, predict toxic and side effects of, or form a universal precise medication regimen for "toxic" Chinese medicines, which restricts the clinical application of them. In view of the problem that the toxicity of "toxic" Chinese medicines is difficult to be predicted and restricts the clinical application, the evidence-based research concept will provide new ideas for safe applcation of them in clinical practice. The integrated development of multiple disciplines and techniques in the field of big data and artificial intelligence will also promote the renewal and development of the research models for "toxic" Chinese medicines. Our team tried to propose the academic concept of evidence-based Chinese medicine toxicology and establish the data-intelligence research mode for "toxic" Chinese medicines and the intelligent risk prediction method for medicinal combination in the early stage, which provided methodological supports for solving the above problem. Thus, on the basis of summarizing the research status and problems of the clinical medication regimen of "toxic" Chinese medicines, our team took the evidence-based toxicology of TCM as the core concept, and tried to construct the multiple-evidence integrated evaluation and prediction method for "toxic" Chinese medicine, so as to guide the establishment of the non-toxic medication regimen of "toxic" Chinese medicines. Specifically, through the analysis of multivariate data obtained from the basic research, the evidence-based toxicology database of Chinese medicines and the individualized "toxicity-effect" intelligent prediction platform were built based on the disease-syndrome virtual patients, so as to identify the clinical characteristics and risks of "toxic" Chinese medicines and develop individualized medication regime. This study is expected to provide a methodological reference for the establishment of medication regimen and risk prevention strategy for "toxic" Chinese medicines. The method established in this study will bridge clinical research and basic research, enhance the transformation of the scientific connotation of attenuated compatibility, promote the development of evidence-based Chinese medicine toxicology, and ensure the clinical safety of "toxic" Chinese medicines.


Subject(s)
Artificial Intelligence , China , Drugs, Chinese Herbal/pharmacology , Humans , Medicine, Chinese Traditional , Research Design , Syndrome
5.
Article in Chinese | WPRIM | ID: wpr-906088

ABSTRACT

Objective:To explore the clinical effects of Xingshen Tongqiao Huoxue decoction in the treatment of dysphagia caused by cricopharyngeal achalasia (CPA) after cerebral infarction and its influence on neurotransmitters. Method:One hundred and fourteen eligible patients were randomly divided into a control group (56 cases) and a treatment group (58 cases). Patients in both groups received balloon catheter dilatation and rehabilitation training. In the observation group, the Tiandan Tongluo capsules were further orally taken, five capsales per time, three times per day. In the control group, the Xingshen Tongqiao Huoxue decoction was provided, one dose per day. The treatment lasted for four weeks. Following the videofluoroscopic swallow study (VFSS) and water-swallowing test (WST) before and after treatment, the swallowing quality of life questionnaire (SWAL-QOL), functional oral intake scale (FOIS) and National Institutes of Health Stroke Scale (NIHSS) scores were calculated. The serum brain-derived neurotrophic factor (BDNF), substance P (SP), dopamine (DA), 5-hydroxytryptamine (5-HT) and nerve growth factor (NGF) levels before and after treatment were detected, and the complications were recorded. Result:The clinical efficacy of the treatment group was superior to that of the control group (<italic>Z</italic>=2.079, <italic>P</italic><0.05). Both VFSS and WST findings in the treatment group were milder than those in the control group (<italic>Z</italic>=2.004, <italic>P</italic><0.05 and <italic>Z</italic>=1.973, <italic>P</italic><0.05). The VFSS, SWAL-QOL, and FOIS scores and the BDNF, DA, SP, 5-HT and NGF levels of the treatment group were elevated in contrast to those of the control group (<italic>P</italic><0.01), whereas the NIHSS score declined (<italic>P</italic><0.01). The complication rate in the treatment group was (8/58) 13.79%, significantly lower than (17/56) 30.36% in the control group (<italic>χ</italic><sup>2</sup>=4.565, <italic>P</italic><0.05). Conclusion:On the basis of balloon catheter dilatation and rehabilitation training, the Xingshen Tongqiao Huoxue decoction can significantly enhance the swallowing function, improve the quality of life, and reduce complications in patients with dysphagia caused by CPA after cerebral stroke.

6.
Article in Chinese | WPRIM | ID: wpr-879143

ABSTRACT

Pharmacology network was used to investigate the common key target and signaling pathway of Notoginseng Radix et Rhizoma in the protection against diabetic nephropathy(DN), diabetic encephalopathy(DE) and diabetic cardiomyopathy(DCM). The chemical components of Notoginseng Radix et Rhizoma were obtained through TCMSP database and literature mining, and SwissTargetPrediction database was used to predict potential targets of Notoginseng Radix et Rhizoma. The disease targets of DN, DE and DCM were obtained through OMIM and GeneCards databases. The overlapped targets of component targets and disease targets of DN, DE and DCM were obtained, and the network of "chemical component-target-disease" was established. The enriched GO and KEGG of the overlapped genes were investigated by using ClueGo plug-in with Cytoscape. At the same time, the PPI network was constructed through STRING database, and the common key targets for the treatment of three diseases by Notoginseng Radix et Rhizoma were obtained through topological parametric mathematical analysis by Cytoscape. A total of 166 chemical components and 835 component targets were screened out from Notoginseng Radix et Rhizoma. Briefly, 216, 194 and 230 disease targets of DN, DE and DCM were collected, respectively. And 54, 45 and 57 overlapped targets were identified when overlapping these disease targets with component targets of Notoginseng Radix et Rhizoma, respectively. Enrichment analysis indicated that the AGE-RAGE signaling pathway and FoxO signaling pathway were the common pathways in the protection of Notoginseng Radix et Rhizoma against DN, DE and DCM. Network analysis of the overlapped targets showed that TNF, STAT3, IL6, VEGFA, MAPK8, CASP3 and SIRT1 were identified as key targets of Notoginseng Radix et Rhizoma against DN, DE and DCM, the selected key targets were verified by literature review, and it was found that TNF, IL6, VEGFA, CASP3 and SIRT1 had been reported in the literature. In addition, there were the most compounds corresponding to the commom core target STAT3, indicating that more compounds in Notoginseng Radix et Rhizoma could regulate STAT3. This study indicated that Notoginseng Radix et Rhizoma potentially protected against DN, DE and DCM through regulating AGE-RAGE signaling pathway and FoxO signaling pathway and 7 common targets including TNF, STAT3, IL6, VEGFA, MAPK8, CASP3 and SIRT1. This study provided a reference for the research of "different diseases with same treatment" and also elucidated the potential mechanism of Notoginseng Radix et Rhizoma against DN, DE and DCM.


Subject(s)
Brain Diseases , Diabetes Mellitus , Diabetic Cardiomyopathies/genetics , Diabetic Nephropathies/genetics , Humans , Research Design , Signal Transduction
7.
Article in Chinese | WPRIM | ID: wpr-942424

ABSTRACT

Objective: To explore the clinical characteristics, intervention and treatment of tympanic osteoma at different locations. Methods: The medical history, audiological and imaging examination, operation and follow-up results of two patients with tympanic osteoma at different sites were reviewed and summarized. Furthermore, the clinical characteristics and interventions of 36 patients reported in literatures with tympanic osteomas were also summarized and analyzed. Results: Osteoma of the two patients collected in this study located at promontory and incus respectively;both of them presented with intact tympanum and conductive deafness, without obvious etiology or predisposing factor. Both of them underwent surgeries and the hearing improved significantly. For patient one, the ossicular chain was intact and restored to activity after removed the osteoma. For patient two, an artificial ossicle was implanted after removed the osteoma and incus. In the 36 patients reported in literatures, the average age was 26.5 years, and 39.47% of them located at promontory; in addition, the main symptoms of them were progressive hearing loss, tinnitus and ear stuffy. Conclusions: Patients with tympanic osteoma are characterized by conduction deafness with intact tympanic membrane, and the most common lesion is promontory. Hearing can be restored by excision of the osteoma and maintenance or reconstruction of the ossicle chain.


Subject(s)
Adult , Ear Ossicles/surgery , Ear, Middle/surgery , Hearing Loss, Conductive/surgery , Humans , Osteoma/surgery , Tympanic Membrane
8.
Chinese Journal of Cardiology ; (12): 894-899, 2021.
Article in Chinese | WPRIM | ID: wpr-941373

ABSTRACT

Objective: To summarize the efficacy of combined treatment strategy of mechanical circulation support devices and immunomodulation therapy for patients with fulminant myocarditis. Method: We retrospectively analyzed the clinical data and outcomes of 37 fulminant myocarditis patients complicating cardiogenic shock, who were hospitalized from October 2017 to December 2019 in our department. Patients received guideline therapy according to "Chinese expert consensus statement on clinical diagnosis and treatment of fulminant myocarditis in adults"issued by Chinese Society of Cardiology of Chinese Medical Association. Patients were divided into IABP group (n=19), ECMO group (n=5) and IABP+ECMO group (n=13) according to different mechanical circulation support regimen. The treatment effectiveness among various groups were compared. The major endpoint was in-hospital mortality. The duration and outcome of mechanical circulation support were also analyzed. Furthermore, relationships between baseline data, proportion of different treatments (including medicine treatment, temporary pacemaker and continuous renal replacement treatment, immunomodulation therapy) and clinical outcome were analyzed. Results: The age of the 37 patients in the cohort was (37.4±17.0) years, and there were 22 male among them. Immunomodulation therapy included glucocorticoid (methylprednisolone) and intravenous immunoglobin. At admission, blood pressure was (70.21±17.37)mmHg(1 mmHg=0.133 kPa),heart rate was(100±30)beat/minutes,there were 10 cases of Ⅲ° atrioventricular block and all received temporary pacemaker implantation, 12 cases of ventricular tachycardia and fibrillation,1 patient received temporary pacemaker implantation due to electronic storm, peak cardiac troponin I level was (18.61±9.55)μg/L, peak B type natriuretic peptide level was 1 670(518,3 410)ng/L,left ventricular ejection fraction (LVEF) was(32.3±10.4)%. Thirty-four out of the 37 patients survived and 3 patients died. Hospital duration was (22.7±8.2)days, LVEF was (50.1±10.5)% at discharge. Lactic acid level was significantly higher in IABP+ECMO group than in IABP group and ECMO group(P<0.001 or =0.005),LVEF was significantly lower in IABP+ECMO group than in IABP group(P=0.004),the proportion of ventilator usage was higher in IABO+ECMO group than in IABP group (P<0.05). Survival rate was similar among the three groups. Conclusion: Comprehensive treatment regimen with combined mechanical circulation support and immunomodulation therapy as the core strategies is effective in the treatment of fulminant myocarditis complicated with cardiogenic shock.


Subject(s)
Adult , Extracorporeal Membrane Oxygenation , Humans , Immunomodulation , Male , Middle Aged , Myocarditis/therapy , Retrospective Studies , Shock, Cardiogenic/therapy , Stroke Volume , Treatment Outcome , Ventricular Function, Left , Young Adult
9.
Acupuncture Research ; (6): 202-208, 2020.
Article in Chinese | WPRIM | ID: wpr-844181

ABSTRACT

OBJECTIVE: To explore the mechanism of electroacupuncture (EA) underlying improvement of cerebral infarction (CI) by investigating its influence on expression of cerebral Wnt7a, lymphoid enhancer factor-1 (LEF1), glycogen synthase kinase 3β(GSK-3β) and Dickkopf-1(DKK1) mRNA and proteins in CI rats. METHODS: A total of 280 male Wistar rats were randomly divided into blank control (n=10), sham-operation, model and EA groups,and 90 rats of the last 3 groups were further divided into 1, 3, 6, 9, 12 and 24 h, and 3, 7 and 12 d subgroups with 10 rats in each subgroup. The CI model was established by occlusion of the middle cerebral artery (MCAO). The sham-operation group received the same surgical operation but without thread embolus insertion. EA (2 Hz/15 Hz, 2 mA) was applied to "Shuigou" (GV26) for 20 min, once a day for 1, 3, 7 and 12 d, respectively. The neurological deficit was evaluated by using Neurological Severity Scores (NSS). The expression levels of Wnt7a,LEF1, GSK-3β and DKK1 mRNAs and proteins in the right ischemic brain tissues were detected by Quantative real-time PCR and Western blot, respectively. RESULTS: After MCAO, the NSS score was significantly increased in the model and EA groups relevant to the blank control and sham-operation groups (P0.05). CONCLUSION: EA of GV26 can significantly improve the neurological deficit symptoms in MCAO rats, which may be associated with its effects in up-regulating the expression of Wnt7a and LEF1 mRNAs and proteins, and in down-regulating the expression of GSK-3β and DKK1 mRNAs and proteins.

10.
Article in Chinese | WPRIM | ID: wpr-828037

ABSTRACT

To observe the efficacy of San'ao Decoction(SAD) in diffusing the lung and relieving asthma, and its intervention effect on the expression of transient receptor potential V2(TRPV2) during alleviating asthma, this study replicated an ovalbumin(OVA)-induced asthmatic mice model, and investigated the intervention effect of SAD on the airway inflammation and airway hyperresponsiveness. The regulatory mechanisms of SAD on the mRNA and protein expressions of TRPV2 in lung tissues and the levels of interleukin-4(IL-4),-10(IL-10), nerve growth factor(NGF), prostaglandin D_2(PGD_2) in bronchoalveolar lavage fluid(BALF) were discussed. Compared with the control group, the model group showed typical asthmatic phenotype, the level of eosinophils(EOS) in peripheral blood and BALF as well as the airway hyperresponsiveness were increased(P<0.01), and pathological damage in lung tissue was serious. The mRNA and protein expressions of TRPV2 in lung tissue were increased significantly, while the levels of IL-4, IL-10, NGF and PGD_2 in BALF were elevated(P<0.05,P<0.01). SAD could relieve bronchial asthma manifested as repaired lung patholo-gical changes(P<0.05), reduce the level of EOS in blood and BALF(P<0.05, P<0.01), and improve pulmonary resistance and lung compliance(P<0.05, P<0.01). SAD could also regulate the inflammatory cytokine levels of IL-4, IL-10, NGF, PGD_2 in BALF, and reduce the gene and protein expression of TRPV2 in the lung tissue(P<0.05, P<0.01). It is verified that SAD could reduce the lung inflammation, and improve lung function in asthmatic mice. The regulatory mechanism of SAD on asthma induced by OVA might be related to the regulation of TRPV2 expression and the induced decrease of Th2-related cytokines and neuropeptides, which provides the evidences for the treatment of asthma with SAD.


Subject(s)
Animals , Asthma , Bronchoalveolar Lavage Fluid , Calcium Channels , Disease Models, Animal , Drugs, Chinese Herbal , Lung , Mice , Mice, Inbred BALB C , Ovalbumin , TRPV Cation Channels
11.
Article in Chinese | WPRIM | ID: wpr-828017

ABSTRACT

Ischemic stroke is the most common form of stroke and one of the main diseases leading to death and disability in the world. Its pathological process is complex and changeable as a result of the interaction of multiple pathological links, such as oxidative stress, apoptosis and inflammation. Traditional Chinese medicine Notoginseng Radix et Rhizoma is the dried roots and rhizomes of Panax notoginseng. In clinic, it is mainly used for the treatment of diseases of cardio-cerebral system and vascular system. Recent studies have shown that total saponins of P. notoginseng, the main active ingredients of P. notoginseng against cerebral ischemia, are complex, and can interfere with the enzyme-promoted cascade reaction through multiple pathways, multiple links and multiple targets, so as to exert its physiological effect. Therefore, it has become a hotspot in studies for prevention and treatment of cerebral ischemia. At present, a great advance has been made in studies on the mechanism of anti-cerebral ischemia of P. notoginseng saponins, but more in-depth studies are needed because of its complex mechanism. Therefore, in this paper, a total of 165 kinds of P. notoginseng saponins were summarized, and simply divided into protopanaxadiol saponins(55 species), protopanaxadiol saponins(37 species) and special structural type saponins(73 species) according to their structural types, so as to provide reference for further studies of P. notoginseng saponins. In addition, the effect of P. notoginseng on cerebral ischemia is clear, but its mechanism remains to be further explored. This paper summarizes the mechanism of P. notoginseng saponins against cerebral ischemia in five aspects: antioxidant stress, reduction of apoptosis, reduction of inflammatory reaction, inhibition of calcium overload and protection of blood-brain barrier. Four kinds of drugs commonly used in the treatment of cerebral ischemia were summarized, in order to provide a theoretical basis for further development and utilization of P. notoginseng saponins in the treatment of cerebral ischemia.


Subject(s)
Brain Ischemia , Cerebral Infarction , Humans , Panax notoginseng , Rhizome , Saponins
12.
Journal of Medical Postgraduates ; (12): 720-725, 2020.
Article in Chinese | WPRIM | ID: wpr-822590

ABSTRACT

ObjectiveAt present, there are relatively few studies on the inhibitory effect of ursolic acid (UA) on the proliferation of thyroid cancer cells. This paper intends to explore the inhibitory effect and mechanism of ursolic acid on the proliferation of TPC-1 cells in thyroid papillary carcinoma.MethodsAfter adhering TPC-1 cells to the wall, the original medium was discarded and added ursolic acid medium without fetal bovine serum (0, 2, 4, 8, 16, 32 μmol/L, respectively, with 0 μmol/L as the control), and then the culture medium without cells was used as blank. The proliferation inhibition rate of TPC-1 cells was detected by CCK8 reagent at different times (24 h, 48 h); Flow cytometry was used to detect the apoptosis rate; JC1 kit was used to detect the changes of mitochondrial membrane potential (MMP) of TPC-1 cells after ursolic acid was applied; Fluorescent probe DCFH-DA was used to detect reactive oxygen species in TPC-1 cells after ursolic acid intervention; Flow cytometry was used to detect the protein expression of survivin and vascular endothelial growth factor (VEGF) in cells. RT-PCR assay detected the expression of survivin and VEGF mRNA in TPC-1 cells after the intervention of ursolic acid at different concentrations.ResultsThe inhibitory rate of 2, 4, 8, 16 and 32 mol/L ursolic acid on TPC-1 cells was significantly higher than that of 0 mol/L (P<0.01), and the inhibitory rate of 48 h ursolic acid on TPC-1 cells was significantly higher than that of 24 h (P<0.05). Therefore, the TPC-1 cell inhibition rate was positively correlated with ursolic acid concentration and the time (P<0.05). The apoptosis rates of 0 mol/L, 4 mol/L and 8 mol/L ursolic acid were (4.13±0.61)%, (6.53±0.65)% and (13.13±1.59)%, respectively. With the increase of the concentration, the apoptosis rate of TPC-1 cells increased gradually (P<0.05). The relative expression levels of survivin, VEGF protein and mRNA of 4 and 8 mol/L ursolic acid were significantly lower than those of 0 mol/L (P<0.05), and the expression levels of 8 mol/L ursolic acid was significantly lower than that of 4 mol/L (P<0.05).ConclusionUrsolic acid can effectively inhibit the proliferation and induce the apoptosis of TPC-1 cells, and its inhibitory induction pathway is related to the expression of survivin and VEGF in cells.

13.
Article in Chinese | WPRIM | ID: wpr-781465

ABSTRACT

OBJECTIVE@#To investigate the distribution of peripheral blood lymphocytes and natural killer (NK) cells, and its influence on the prognosis of patients with myelodysplastic syndromes (MDS).@*METHODS@#The lymphocytes proportion, absolute lymphocyte counts (ALC), NK cell proportion and absolute NK cell counts (ANKC) as well as the related data of 95 MDS patients diagnosed between 2013 and 2017 analyzed retrospectively. The correlation of ALC and ANKC with prognosis was also analyzed.@*RESULTS@#As compared with low ALC patients, MDS patients with ALC≥0.885×10/L had a higher overall response rate (66.7% vs 35.8%) (P<0.01). The ALC of effective patients after treatment significatitly increased in compaison of ALC at diagnosis. Multivariate analysis indicated that patients with ALC≥0.885×10/L had long overall survival (OS) time in comparison with patients with low level (16.4 vs 12.4 months) (P<0.05). The OS time of patients with ANKC≥0.110×10/L was shorter in comparison with patients with low level (10.9 vs 16.3 months) (P<0.01). Otherwise, blast, cytogenetic risks and treatment response were also independent risk factors of MDS (P<0.05). Revised International Prognostic Scoring System (IPSS-R) combined with ANKC could improve predictive accuracy of IPSS-R alone (AUC 0.718 vs 0.674) (P<0.05).@*CONCLUSION@#Lymphocytes and NK cells are important for the prognosis evaluation of MDS patients.

14.
Article in Chinese | WPRIM | ID: wpr-862678

ABSTRACT

Objective::Based on the protective effect of Guhong injection (GH) on cerebral ischemia, mechanism of GH against cerebral ischemia was identified using RNA-seq transcriptome and bioinformation analysis. Method::The model of middle cerebral artery occlusion (MCAO) was established through thread embolization. Sham group, model group, low-dose GH group (0.625 mL·kg-1·d-1), high-dose GH group (2.5 mL·kg-1·d-1), positive group (Ginaton, 8 mL·kg-1·d-1) were set up. Ludmila Belayev 12-point scoring method was applied to assess the protective effect of GH against MCAO-induced cerebral ischemia. And the differentially expressed genes after treatment with GH were identified by RNA-Seq technology. Enrichment analysis, cluster analysis and association analysis on disease targets of cerebral ischemia were carried out through such databases as DAVID, String and The Human Phenotype Ontology. Finally, the regulatory network was constructed by Cytoscape3.4.0. Result::Compared with the sham group, the neurological impairment was obvious in the model group (P<0.01), and the neurological impairment was alleviated in the GH group compared with the model group (P<0.05). RNA-Seq technology analysis showed that GH regulated genes involving such biological processes as cell apoptosis, inflammation, oxidative stress, toll-like signaling pathway and mitogen-activated protein kinase (MAPK) signaling pathway. Twenty disease targets and 64 MAPK signaling pathway genes were associated with differentially expressed genes after GH treatment, in which 23 genes were involved in apoptosis and inflammation. Conclusion::GH protected against cerebral ischemia in many ways, among which MAPK signaling pathway is an important way to exert its effect in inhibiting apoptosis and inflammation.

15.
Article in English | WPRIM | ID: wpr-773408

ABSTRACT

OBJECTIVE@#To investigate the molecular mechanisms of the adverse effects of exposure to sulfamonomethoxin (SMM) in pregnancy on the neurobehavioral development of male offspring.@*METHODS@#Pregnant mice were randomly divided into four groups: control- (normal saline), low- [10 mg/(kg•day)], middle- [50 mg/(kg•day)], and high-dose [200 mg/(kg•day)] groups, which received SMM by gavage daily during gestational days 1-18. We measured the levels of short-chain fatty acids (SCFAs) in feces from dams and male pups. Furthermore, we analyzed the mRNA and protein levels of genes involved in the mammalian target of rapamycin (mTOR) pathway in the hippocampus of male pups by RT-PCR or Western blotting.@*RESULTS@#Fecal SCFA concentrations were significantly decreased in dams. Moreover, the production of individual fecal SCFAs was unbalanced, with a tendency for an increased level of total fecal SCFAs in male pups on postnatal day (PND) 22 and 56. Furthermore, the phosphatidylinositol 3-kinase (PI3k)/protein kinase B (AKT)/mTOR or mTOR/ribosomal protein S6 kinase 1 (S6K1)/4EBP1 signaling pathway was continuously upregulated until PND 56 in male offspring. In addition, the expression of Sepiapterin Reductase (SPR), a potential target of mTOR, was inhibited.@*CONCLUSION@#In utero exposure to SMM, persistent upregulation of the hippocampal mTOR pathway related to dysfunction of the gut (SCFA)-brain axis may contribute to cognitive deficits in male offspring.


Subject(s)
Alcohol Oxidoreductases , Metabolism , Animals , Anti-Infective Agents , Toxicity , Fatty Acids, Volatile , Feces , Chemistry , Female , Hippocampus , Metabolism , Male , Memory , Mice, Inbred ICR , Pregnancy , Prenatal Exposure Delayed Effects , Sulfamonomethoxine , Toxicity , TOR Serine-Threonine Kinases , Metabolism
16.
Article in Chinese | WPRIM | ID: wpr-773120

ABSTRACT

Chemical constituents of the Fufang Huangbai Ye( FFHB) were analyzed and identified by UPLC-ESI-LTQ-OrbitrapMS. The analysis was performed on an Waters HSS T3 reverse phase column( 2. 1 mm×100 mm,1. 8 μm). The mobile phase consisting of 0. 1% aqueous formic acid( A) and acetonitrile( B) was used with gradient elution,and the flow rate was 0. 3 mL·min~(-1).Based on the information of the accurate mass,the multistage fragment ions,the mass spectrometric data of the standard substance and the relative reference literature,the structure of the chemical constituents in FFHB were identified. Based on the identified compounds,network pharmacology study,including target prediction,functional enrichment,and molecular docking was applied to screen out the main active substances for treatment of diabetes foot and explore the potential mechanism. The results showed that a total of 138 compounds were identified,including 28 alkaloids,16 flavonoids,11 phenylethanoid glycosides,9 cycloolefins,11 cyclohexylethanol derivatives,28 phenolic acids and derivatives,3 lignans,4 terpenes,28 volatile oils and the others. Further,36 active substances for diabetes foot were screened out,and the functional enrichment showed the potential mechanism of FFHB were mainly seven functional items including inflammatory response,growth factor activity. This study combining the UPLC-LTQ-Orbitrap-MS technology and the network pharmacology provide a useful reference and basis for active compounds,quality control markers and the pharmacological mechanism of FFHB for diabetic foot treatment.


Subject(s)
Chromatography, High Pressure Liquid , Diabetic Foot , Drug Therapy , Drugs, Chinese Herbal , Pharmacology , Humans , Mass Spectrometry , Molecular Docking Simulation , Phytochemicals , Pharmacology
17.
Article in Chinese | WPRIM | ID: wpr-775927

ABSTRACT

OBJECTIVE@#To select the optimized treatment plan of acupuncture for lateral femoral cutaneous neuritis by using multiple indexes decision-making method based on the clinical evidence.@*METHODS@#The randomized control trials (RCTs) regarding acupuncture for lateral femoral cutaneous neuritis in the CNKI database, CBM database, WANFANG database, VIP database, PubMed, Cochrane Library and Embase published before December 31, 2017 were comprehensively collected. The modified Jadad scale was used to evaluate the quality of the RCTs. Then the evaluation indexes were selected and the dimensions of evaluation indexes were standardized by using extreme difference transformation method. The weight of each index was determined by using relative comparison method and the standardized matrix was weighted. Thus, the ideal solution and the negative ideal solution were obtained, and the relatively degree of each treatment plan to the ideal solution was calculated to propose the optimized plan of acupuncture for lateral femoral cutaneous neuritis.@*RESULTS@#A total of 18 RCTs were included, the optimized plan of acupuncture for lateral femoral cutaneous neuritis was using thin fire needle to rapidly prick the abnormal skin region with fast needle insertion-withdrawal technique; the fire needle was applied repeatedly; intensive pricking to form a treatment area; the treatment was given once every 5 days.@*CONCLUSION@#Based on the current clinical evidence, the optimized plan of acupuncture for lateral femoral cutaneous neuritis is using thin fire needle to prick the abnormal skin region; the multiple methods of plum-blossom needling met the characteristic of lateral femoral cutaneous neuritis and is suitable for clinical selection. The main acupoints are points in the abnormal skin area or the acupoints in the foot- meridian and foot- meridian, combined with lumbar Jiaji (EX-B2) points.


Subject(s)
Acupuncture Therapy , Humans , Meridians , Needles , Neuritis , Therapeutics , Randomized Controlled Trials as Topic
18.
Article in Chinese | WPRIM | ID: wpr-802355

ABSTRACT

The clinical value is the core factor for determining the products of Chinese patent medicines on the market. It is clear that defining the clinical positioning of Chinese patent medicines and maximizing their clinical efficacy and value are of great practical significance for each Chinese patent medicine. Precise clinical positioning not only requires systematic analysis and summarization of existing literature and clinical practice data, but also requires verification and proof from detailed experimental data, thus to provide scientific support for basic research. In this research, a three-dimensional integration strategy of " traditional Chinese medicine (TCM) theory-clinical practice-basic research" was proposed to play a vital role in clinical positioning and evaluation of Chinese patent medicines. Yixinshu capsule was taken as an example to discuss clinical positioning of Chinese patent medicines under the guidance of TCM theory. Based on the interpretation of the evolution of the pathogenesis of coronary heart disease (thoracic obstruction), combined with the core efficacy of the drug composition, the effect of Yixinshu capsule in benefiting Zongqi, calming midnd, improving blood circulation and eliminating blood stasis was identified, which was suitable for treatment for the recurrent episodes of angina pectoris, and emergency of symptoms of chronic heart failure. At the level of TCM theory, the clinical positioning of Yixinshu capsule was further defined, and the key points of in-depth research were proposed to provide reference for the mechanism research and clinical application of Yixinshu capsule. Based on the prescription and its score functions, precise analysis of clinical positioning of large varieties of TCM under the guidance of TCM theory, on the one hand will give full play to the value of TCM original knowledge and guide the basic research of Chinese patent medicines, on the other hand the research results will enrich, benefit and sublimate the TCM theory, and finally provide a critical paradigmatic for the clinical positioning of large varieties of TCM under the guidance of TCM theory.

19.
Article in Chinese | WPRIM | ID: wpr-802023

ABSTRACT

Quality marker(Q-marker) is a new concept and pattern for quality control of traditional Chinese medicine(TCM),which will lead the development direction for quality control of TCM.Among them,how to characterize the overall quality attribute of TCM and its biological effect,is a critical scientific problem in the study of Q-marker.In this paper,integrated pharmacology is utilized to screen out and confirm the Q-marker from the complex system of TCM,so as to solve the critical scientific problem.System biology in vivo is firstly applied to establish the correlation of chemical fingerprints of TCM,their metabolic fingerprints,network targets,biological effects and efficacy of TCM,which is used to preliminary screen out Q-marker of TCM.Following that,a pharmacological method in vitro,including intestinal absorption in vitro coupled with bioactivity assessment,is employed to simultaneously determine the absorbed doses of TCM and evaluate their biological activity.Furthermore,data mining is utilized to establish the exact quantitative mathematic model between Q-marker of TCM and bioactivity.Meanwhile,two representative examples,including Yuanhu Zhitong tablets,Xinsuning capsules,are introduced to identify Q-marker of TCM and establish their quality standards related with bioactivity,which will be beneficial to improve the level of quality control of TCM and ensure the effectiveness and safety of clinical applications.

20.
Article in Chinese | WPRIM | ID: wpr-843768

ABSTRACT

Objective: To study the effects of fenvalerate exposure during puberty on oxidative stress in rat testis. Methods: Fifty male Sprague-Dawley (SD) rats were randomly divided into the control group (corn oil), low dose group (0.02 mg/kg fenvalerate), moderate dose group (1 mg/kg fenvalerate), high dose group (50 mg/kg fenvalerate) and intervention group (50 mg/kg fenvalerate+100 mg/kg N-acetyl-L-cysteine), ten rats for each group, for two months by gavage at four weeks of age. Malondialdehyde (MDA) content, activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in testis and testicular tissue morphology were detected. Results: Compared with the control group, the rat body weight and activities of GSH-Px and SOD in testis were significantly decreased in high dose group while MDA content was increased (all P<0.05). Compared with the high dose group, MDA content was decreased and GSH-Px activity was increased in the intervention group (both P<0.05). The results of testicular histology showed that with the increasing exposure dose, the spermatogenic cells were arranged loosely, the number of layers was decreased and the inner diameter of seminiferous tubules was increased. Conclusion: Exposure to fenvalerate during puberty may induce oxidative damage in testis tissue of male rats.

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