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OBJECTIVE To analyze the current research status and hotspots of traditional Chinese medicine (TCM) in the treatment of ulcerative colitis (UC) via bibliometrics method. METHODS The clinical, basic, and pharmacological research of TCM in the treatment of UC in the CNKI core journals database and Web of Science core collection database were searched from January 2013 to April 2023. The CiteSpace 6.1. R6 software was adopted to analyze the number of authors, institutions and keywords. What’s more, a visual map was plotted. RESULTS Overall, 1 060 Chinese articles and 555 English articles were included. In 2013-2023, the number of relevant research documents issued by TCM in the treatment of UC has shown a significant upward trend. Among the included literature, there are 59 core authors in Chinese and 33 core authors in English. A stable group centered on multiple key scholars has been formed. Chinese research hotspots focus on the experience of famous doctors, classical famous prescriptions, etc.; English research hotspots center on cells, expression, activation,signaling pathway, etc. The study of intestinal flora, inflammatory factors, and other mechanisms has attracted much attention in both Chinese and English literature. CONCLUSIONS In recent years, some progress has been made in the study of treating UC with TCM. In the future, the top-level design of clinical research protocols based on maintaining the characteristics of TCM should be strengthened. Moreover, the long- term efficacy evaluation of TCM in the treatment of UC should be emphasized, and new technologies such as metabolomics and protein sequencing should be actively adopted to explore the scientific connotation of TCM compatibility in treating diseases.
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BACKGROUND:As a bone replacement and filling material,calcium phosphate stone bone cement has good biocompatibility,bone conductivity,and other advantages,especially its better biodegradability compared to other calcium phosphate bone cements.It has important application value in bone repair.However,due to its limitations such as insufficient mechanical properties,fast solidification reaction,and poor injection performance,it is currently only suitable for the repair of non weight-bearing bone. OBJECTIVE:To explore the modification of brushite cements with bioactive ions(metal and non metal ions)to expand its application range. METHODS:The author used PubMed,ScienceDirect,CNKI,and WanFang to search the literature published between 2018 and 2023 with the search terms"metal ion,iron,copper,strontium,magnesium,zinc,non-metal ion,modification,bone,brushite cements"in Chinese and"metal ion,iron,Fe,copper,Cu,strontium,Sr,magnesium,Mg,zinc,Zn,non-metal ion,modification,bone,brushite cements"in English.After reading titles and abstracts,the articles were initially screened,and irrelevant and duplicate articles were excluded.Finally,64 articles were included for review. RESULTS AND CONCLUSION:(1)Bioactive ions affect the hydration process of calcium phosphate bone cement.Different ions are substituted by ions and incorporated into the crystal structure of calcium phosphate bone cement,changing the crystal morphology of the cement and causing changes in physical and chemical properties such as setting time,injectability,and compressive strength.(2)Ionic modified calcium phosphate bone cement produces different ion release effects due to different crystal structures.Different types of ions have properties such as promoting angiogenesis/osteogenesis,antibacterial,anti-tumor,etc.In addition,calcium phosphate bone cement has good biodegradability,which has great advantages for the performance of various ions.(3)The physicochemical properties of calcium phosphate bone cement modified with different ions are as follows:iron,copper,strontium,magnesium,zinc,silver,and cobalt can prolong the setting time.Strontium,and magnesium can improve injection performance.Copper,strontium,magnesium,silver and silicon can enhance compressive strength.The ions that can simultaneously improve the three physical and chemical properties of calcium phosphate bone cement include strontium and magnesium.Good physical and chemical properties are a prerequisite for clinical application,so improving the setting time,injectability,compressive strength,and other properties of calcium phosphate bone cement with ions is of great significance for the research and application of bone cement.(4)The biological properties of calcium phosphate bone cement modified with different ions are as follows:copper,strontium,magnesium,zinc,cobalt,lithium,selenium,and silicon have promoting angiogenesis/osteogenic effects.Iron,copper,magnesium,zinc,and silver have antibacterial properties.Magnesium ions have anti-inflammatory properties.Copper and selenium have anti-tumor properties.(5)In summary,magnesium ions can improve the setting time,injectability,and compressive strength of calcium phosphate bone cement,while also promoting neovascularization/osteogenesis,antibacterial properties,and have good application prospects for the treatment of bone defects with concurrent infections.In addition,copper also has anti-tumor properties,so copper ions have great potential in the treatment of bone defects caused by infections and tumors.However,relevant research is still in the basic research stage,and the effects of different ion doping concentrations and synthesis conditions on the physicochemical properties of calcium phosphate bone cement need to be further explored.At the same time,the impact of biological properties also needs to be studied and observed for a longer period of time.
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OBJECTIVE To investigate the improvement effects of sinomenine (Sin) on non-alcoholic steatohepatitis (NASH) and its potential mechanism. METHODS Male C57BL/6J mice were randomly divided into standard chow diet (SCD) group, high- fat diet (HFD) group, Sin low-dose group (Sin-L group, 50 mg/kg), and Sin high-dose group (Sin-H group, 100 mg/kg), with 6 mice in each group. The mice of SCD groups were fed with SCD, and other groups were given HFD for consecutive 24 weeks to establish NASH model. Since 17th week, the mice in each drug group were given corresponding drug solutions intragastrically, once a day, for 8 consecutive weeks. After the last medication, the body weight and liver weight of mice were determined, and liver indexes were calculated. The contents of total cholesterol (TC) and triglyceride (TG) in liver tissue, the serum contents of aspartate aminotransferase (AST), alanine aminotransferase (ALT), interleukin-1β (IL-1β) and IL-18 were all determined. Hepatic steatosis and fibrosis were observed, and hepatic lipid droplets were located. The expressions of IL-18 and IL-1β mRNA, inflammation-related proteins (IL-1β, cleaved-IL-1β), fibrosis-related proteins [collagen Ⅰ (Col-Ⅰ), α-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF)], and pathway-related protein [adenosine monophosphate-activated protein kinase (AMPK), phosphorylated AMPK (p-AMPK), Yes-associated protein (YAP), phosphorylated YAP (p-YAP)] were all determined. HepG2 human liver cancer cells were selected as subjects and divided into control group, oleic acid (OA) group, Sin 50 μmol/L group, Sin 100 μmol/L group, OA+Sin 50 μmol/L group and OA+Sin 100 μmol/L group. After 24 hours of treatment, the accumulation of lipid droplets was observed, and the expressions of pathway-related proteins were detected.RESULTS Compared to HFD group, hepatic steatosis, zengcheng@gdpu.edu.cn fibrotic lesions and lipid droplet accumulation were all alleviated in Sin groups; body weight, liver weight, liver indexes, the contents of AST, ALT, IL-1β, IL-18 in serum and TG, TC in liver tissue, the mRNA expressions of IL-1β and IL-18, and the expressions of cleaved-IL-1β and fibrosis-related proteins all decreased significantly (P<0.01); the protein expression of IL-1β, and the phosphorylation levels of AMPK and YAP proteins significantly increased (P<0.01). Compared with OA group, the lipid droplet accumulation of cells in OA+Sin groups significantly decreased, while the phosphorylation levels of AMPK and YAP proteins significantly increased (P<0.05). CONCLUSIONS Sin can ameliorate the inflammation, lipid deposition and fibrosis of liver tissue in mice, the mechanism of which may be associated with activating the AMPK signaling pathway and promoting YAP phosphorylation.
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The present study observed the regulatory effect of total flavonoids of Ziziphora clinopodioides on autophagy and the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathways in ApoE~(-/-) mice and explored the mechanism of total flavonoids of Z. clinopodioides against atherosclerosis(AS). ApoE~(-/-) mice were fed on a high-fat diet for eight weeks to induce an AS model. The model mice were randomly divided into a model group, a positive control group, and low-, medium-and high-dose groups of total flavonoids of Z. clinopodioides, while C57BL/6J mice fed on a common diet were assigned to the blank group. The serum and aorta samples were collected after intragastric administration for 12 weeks, and the serum levels of total cholesterol(TC), triglyceride(TG), low density lipoprotein-cholesterol(LDL-C), and high density lipoprotein-cholesterol(HDL-C) were detected by an automatic biochemical analyzer. The serum expression levels of intercellular adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1), matrix metalloproteinase-2(MMP-2), and matrix metalloprotei-nase-9(MMP-9) were detected by enzyme-linked immunosorbent assay(ELISA). Oil red O staining was used to observe the aortic plaque area in mice. Hematoxylin-eosin(HE) staining was used to observe the aortic plaque and pathological changes in mice. The expression of P62 and LC3 in the aorta was detected by the immunofluorescence method. The protein expression of LC3Ⅱ/Ⅰ, Beclin-1, P62, p-PI3K, p-Akt, and p-mTOR in the aorta of mice was detected by Western blot. The results showed that compared with the blank group, the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2 and MMP-9 in the model group were significantly increased(P<0.01 or P<0.05), the content of HDL-C was decreased(P<0.05), intra-aortic plaque area was enlarged(P<0.01), the expression of LC3 in the aorta was significantly down-regulated, P62 expression was up-regulated(P<0.01 or P<0.05), the expressions of LC3Ⅱ/Ⅰ and Beclin-1 in the aortic lysate were significantly down-regulated, and the expressions of p-PI3K, p-Akt, p-mTOR and P62 were significantly increased(P<0.01). The medium-and high-dose groups of total flavonoids of Z. clinopodioides could reduce the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2, and MMP-9 in AS model mice(P<0.01 or P<0.05), and increase the content of HDL-C(P<0.01 or P<0.05). The aortic plaque area of mice after middle and high doses of total flavonoids of Z. clinopodioides was significantly reduced(P<0.01), the content of foam cells decrease, and the narrowing of the lumen decreased. The total flavonoids of Z. clinopodioides significantly increased the expression of LC3 in the aorta and the expression of LC3Ⅱ/Ⅰ and Beclin-1 in the lysate, and decreased the expression of P62 in the aorta and the expression of p-PI3K, p-Akt, p-mTOR and P62 in the lysate(P<0.01 or P<0.05). The results showed that the total flavonoids of Z. clinopodioides could improve the content of blood lipids and inflammatory factors, and reduce the generation of foam cells and plaques in aortic tissue, and the mechanism may be related to the regulation of PI3K/Akt/mTOR signaling pathway.
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Animais , Camundongos , Apolipoproteínas E , Aterosclerose/genética , Proteína Beclina-1 , LDL-Colesterol , Molécula 1 de Adesão Intercelular , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/metabolismo , Placa Aterosclerótica , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/genética , Molécula 1 de Adesão de Célula Vascular/genéticaRESUMO
The biomechanical stability of Zero-Profile anterior cervical interbody fusion cage(Zero-P)was introduced when used for anterior cervical discectomy and fusion(ACDF),and the efficacy of Zero-P was reviewed for treating cervical dege-nerative diseases such as single-and two-segment,intersegmental and multisegmental spondylotic cervical spondylolisthesis.The advantages of Zero-P were described in reducing the incidence rates of postoperative dysphagia and adjacent segment degeneration,and the disadvantages and countermeasures were put forward.References were provided for enhancing the efficacy of Zero-P for treating cervical degenerative diseases.[Chinese Medical Equipment Journal,2023,44(9):103-109]
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Objective:The purpose of quantitatively evaluating policies related to clinical specialties and exploring existing policy problems and paths to optimization is to provide a reference basis for the formulation and improvement of the policies.Methods:Text mining was conducted on the policies related to clinical specialties issued by the national and some provincial governments since the new medical reform in 2009.The PMC index model was used to construct a comprehensive evaluation system of policies containing 9 primary variables and 35 secondary variables.22 clinical specialty policies were selected for quantitative analysis.Results:Among the 22 clinical specialty policies,6 policies were good-type policies,14 were acceptable-type policies,2 were bad-type policies,and there were no excellent-type policies.The overall design of the policies related to clinical specialties is reasonable,but there is still room for improvement.Conclusion:The quality of China's clinical specialty policy text needs to be improved,and it is necessary to strengthen the top-level design,optimise the content of the objectives,focus on the balanced and sustainable development of the speciality,give full play to the role of demand-based policy tools,and enrich the incentives and constraints,in order to mobilise multi-principal participation in the construction of the clinical speciality enthusiasm.
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Thyroid-associated ophthalmopathy(TAO)is an autoimmune disease associated with thyroid dysfunction that can significantly impact quality of life, result in visual impairment and facial disfigurement. Traditional treatments are often unsatisfactory. Studies have shown that teprotumumab, a human monoclonal antibody that can inhibit insulin-like growth factor 1 receptor(IGF-1R), has become an emerging targeted drug for TAO. Although the drug has proven to be effective and relatively safe in the treatment of TAO, adverse reactions are worthy of attention of ophthalmologists with the continuous promotion of clinical application, including hearing impairment, hyperglycemia, diarrhea, muscle spasms, infusion reactions, cognitive decline, thyroid suppression, alopecia, nausea and fatigue. Teprotumumab was generally well tolerated, with most adverse events being mild or moderate in severity. This paper aims to review the adverse reactions and precautions of teprotumumab in the treatment of TAO.
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Objective:To explore the role of denervation on kidney tubulointerstitial fibrosis(TIF)induced by ischemia reperfusion injury(IRI)via NF-E2-related factor-2 (Nrf2)/transforming growth factor-β(TGF-β)pathway in mice.Methods:C57BL/6 mice were randomized into four groups(n=12 each)of sham, kidney ischemia reperfusion(IR), RDN and RDN+ IR(DIR). At Days 1 and 7 post-reperfusion, kidney histology and fibrotic injury are observed after hematoxylin-eosin(HE)and Masson staining.α-SMA protein is detected by immunohistochemistry.The serum levels of blood urea nitrogen(BUN), creatinine(Cr)and neutrophil gelatinase-associated lipocalin(NGAL)are measured.And the contents of superoxide dismutase(SOD), malondialdehyde(MDA), interleukin 4(IL-4), interleukin 10(IL-10)and interleukin 13(IL-13)in kidney tissues are detected.Western blot is utilized for observing the expression levels of Nrf2, TGF-β and phospho-Smad3 protein in kidney tissues.Results:Compared with sham group, kidney histologic score, serum levels of BUN, Cr and NGAL and contents of MDA, IL-4, IL-10 and IL-13 in kidney tissues spiked while activity of SOD declined.Protein expressions of Nrf2, TGF-β and phospho-Smad3 rise in IR-1 and DIR-1 groups( P<0.05). Compared with IR-7 group, degree of fibrosis and levels of α-SMA, IL-4, IL-10 and IL-13 drop in DIR-7 group, Nrf2 protein expression increased and protein expressions of TGF-β and phospho-Smad3 decreased( P<0.05). Conclusions:Acute oxidative stress injury induced by IRI becomes aggravated after kidney denervation and initiates TIF.The long-term expression of TGF-β and phosphorylation of Smad3 are suppressed due to a continuous activation of Nrf2 pathway, thereby blunting the long-term TIF degree of kidney.
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The serine/threonine p21-activated kinases (PAKs), as main effectors of the Rho GTPases Cdc42 and Rac, represent a group of important molecular switches linking the complex cytoskeletal networks to broad neural activity. PAKs show wide expression in the brain, but they differ in specific cell types, brain regions, and developmental stages. PAKs play an essential and differential role in controlling neural cytoskeletal remodeling and are related to the development and fate of neurons as well as the structural and functional plasticity of dendritic spines. PAK-mediated actin signaling and interacting functional networks represent a common pathway frequently affected in multiple neurodevelopmental and neurodegenerative disorders. Considering specific small-molecule agonists and inhibitors for PAKs have been developed in cancer treatment, comprehensive knowledge about the role of PAKs in neural cytoskeletal remodeling will promote our understanding of the complex mechanisms underlying neurological diseases, which may also represent potential therapeutic targets of these diseases.
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Animais , Humanos , Citoesqueleto/genética , Doenças do Sistema Nervoso/genética , Neurônios/enzimologia , Transdução de Sinais , Quinases Ativadas por p21/metabolismoRESUMO
Objective:The standard treatment for inoperable locally advanced esophageal cancer is concurrent chemoradiotherapy, but the survival was not satisfied. Nituzumab is a humanized IgG monoclonal antibody against EGFR. The purpose of this study is to investigate the toxicity and efficacy of concurrent chemoradiotherapy combined with nituzumab for locally advanced esophageal cancer.Methods:We retrospectively reviewed the clinical data of locally advanced esophageal cancer who were treated with concurrent chemoradiotherapy combined with nituzumab in Peking University Cancer Hospital from June 2015 to June 2020. Kaplan- Meier method was used for analysis. Results:Thirty Patients were enrolled this study.After a median follow-up of 22.5 months, The objective response rate was 93%. The 1-year, 2-year, 3-year overall survival rates were 83%, 57% and 41%, with the progression-free survival rates 75%, 47% and 32%, with the local-recurrence free survival rates 83%, 53% and 37%, with the metastasis-free survival rates 75%, 51% and 36%, respectively.The incidence of grade≥3 hematological toxicity was 32%. There were 16% patients experiencing grade≥3 esophagitis.Conclusion:The preliminary result of concurrent chemoradiotherapy combined with nituzumab is effective and safe for patients with locally advanced esophageal cancer.
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Purpose@#Intrahepatic cholangiocarcinoma (ICC) is one of the most common liver primary tumors but its treatments are limited. Bioinformatics showed that the expression level of long non-coding RNA cancer-associated susceptibility 15 gene (CASC15) is correlated with ICC progression, but its functional mechanism remains unclear. @*Materials and Methods@#Tissues from ICC patients, tumor and adjacent tissue, were used for detection of the expression of CASC15. Clinical data were also collected for clinicopathologic and survival analysis. Short interfering RNA and lentiviral short hairpin RNA were used to knock down CASC15 and PRDX2 expression in ICC cell lines, for the analysis of changes of cell function and xenografts. RNA-pulldown and RNA immunoprecipitation assays were used to detect RNA-binding protein, PRDX2. Male nude mice were used for ICC xenografts, and livers were collected after 4 weeks for immunohistochemistry. @*Results@#CASC15 is highly expressed in ICC tissues and is related to higher TNM stage. Knockdown of CASC15 in ICC cells reduced cell proliferation, migration, invasiveness and increased apoptosis, and G1/S block. PRDX2 bound to CASC15. Knockdown of CASC15 decreased PRDX2 expression which was rescued by the inhibition of proteasome formation. Downregulation of PRDX2 resulted in G1/S block, reduced ICC cell invasion. Downregulation of CASC15 inhibited phosphoinositide 3-kinase (PI3K)/AKT/c-Myc pathway through downregulating of PRDX2 and overexpressed PRDX2 rescued the block. CASC15 knockout in ICC xenografts suppressed tumor development in vivo, decreased the expression of PRDX2 and Ki67 and inhibited PI3K/AKT pathway. @*Conclusion@#CASC15 promotes ICC possibly by targeting PRDX2 via the PI3K/AKT pathway, indicating poor prognosis and high degree of malignancy of ICC.
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OBJECTIVE:To establish the eva luation criteria for the rationality of tumor nutritional standardized treatment ,and to provide reference for nutritional standardized treatment in tumer patients . METHODS :Based on domestic and foreign guidelines or expert consensus ,the rationality evaluation standard of tumor nutritional standardized treatmentwas formulated in our hospital (Bozhou Municipal People ’s Hospital ). 50 nutritional treatment medical records in our hospital from Jan. to Jun. 2019 were evaluated by weighted TOPSIS ;according to the evaluation results ,nutritional intervention was carried out ,and 50 nutritional treatment medical records (group B )from Aug. to Dec. 2019 were re-evaluated by the same method after intervention. RESULTS : The established evaluation criteria for the rationality of tumor nutritional standardized treatment in our hospital included 18 indicators,such as malnutrition diagnosis ,description of the nature of malnutrition ,nutrition screening and evaluation ,etc. After analysis ,the rational rate of nutritional treatment was only 18% in group A (Ci of ideal solution with 9 medical records≥0.6),and 78% in group B (Ci of ideal solution with59 medical records ≥0.6). There was statistical significance in the rationality of nutritional treatment before and after nutritional intervention (Ci≥0.6)(P<0.05). CONCLUSIONS :The established rational evaluation method of tumor nutritional standardized treatment is feasible ,and the evaluation results are intuitive and reasonable. Nutrition intervention is helpful to reduce the irrational rate of nutritional treatment.
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To systemically evaluate the efficacy and safety of sinomenine combined with methotrexate(SIN+MTX) in the treatment of rheumatoid arthritis(RA). Literature databases of Wanfang, CNKI, VIP, SinoMed, PubMed, Cochrane Library and Web of Science were retrieved comprehensively for relevant clinical trials. The literature retrieval time was from database establishment to February 4, 2020. The quality of literatures was assessed by the Cochrane Evaluation Handbook 5.1.0, and qualified literature was reviewed and analyzed by using the RevMan 5.3 statistical software. Twenty randomized controlled trials met the inclusion criteria, and were enrolled in the Meta-analysis. The results showed that SIN+MTX remarkably reduced DAS28(MD=-0.85, 95%CI[-1.03,-0.67], P<0.000 01), and improved total efficiency(P<0.000 01). SIN+MTX could inhibit swollen joint count(MD=-1.19, 95%CI[-1.75,-0.63], P<0.000 1), tender joint count(MD=-1.58, 95%CI[-2.89,-0.28], P=0.02) and reduce morning stiffness time(MD=-8.44, 95%CI[-11.82,-5.07], P<0.000 01) compared with control group. The results showed that SIN+MTX was equal to control group in grip strength(SMD=0.20,95%CI[-1.11,1.51],P=0.77). SIN+MTX remarkably alleviated the erythrocyte sedimentation rate(MD=-9.87, 95%CI[-14.52,-5.22], P<0.000 1), C-reactive protein(SMD=-0.30, 95%CI[-0.51,-0.09], P=0.005), and rheumatoid factor(MD=-11.23,95%CI[-13.81,-8.65],P<0.000 01). The frequency of adverse reactions were reduced compared with that in the control group(P<0.000 01). Current clinical studies demonstrate that the efficacy and safety of SIN+MTX in the treatment of RA were superior to control group. However, due to the low quality and quantity of the included studies, high-quality randomized controlled trials are necessary to support the clinical evidences.
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Humanos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Medicamentos de Ervas Chinesas/efeitos adversos , Metotrexato/efeitos adversos , MorfinanosRESUMO
Abstract Purpose To explore the role of all-trans retinoic acid (ATRA) in renal ischemia/reperfusion injury of diabetic rats. Methods Sixty adult male rats were randomly divided into 6 groups, including sham group (S group), ischemia-reperfusion group (I/R group), ischemia-reperfusion+ATRA group (A group), diabetic group (D group), diabetic ischemia-reperfusion group (DI/R group), diabetic ischemia-reperfusion +ATRA group (DA group). The levels of creatinine (Cr), cystatin C (Cys-C) and β2-microglobulin (β2-MG) were measured. Morphology of renal tissue was observed under light microscope. Results DJ-1, Nrf2, HO-1 and caspase-3 were detected by western blot. DJ-1, Nrf2, HO-1 and caspase-3 in I/R group, D group and DI/R group was higher than that in S group. Compared with I/R group, Nrf2 and HO-1 in A group was decreased, but caspase-3 was increased. However, Nrf2 in DA group was higher than that in DI/R group, HO-1 and caspase-3 in DA group were lower than that in DI/R group. Compared with group S, Cr, Cys-C and β2-MG in I/R group, A group, D group, and DI/R group were higher. Whereas the levels of Cr, Cys-C, β2-MG and renal injury score in DA group were lower than those in DI/R group. Conclusion ATRA has a protective effect on renal ischemia-reperfusion injury in diabetic rats, maybe relating to DJ/Nrf2 pathway.
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Animais , Masculino , Ratos , Tretinoína/uso terapêutico , Traumatismo por Reperfusão/prevenção & controle , Diabetes Mellitus Experimental/induzido quimicamente , Fator 2 Relacionado a NF-E2/uso terapêutico , Rim/efeitos dos fármacos , Tretinoína/farmacologia , Traumatismo por Reperfusão/patologia , Estreptozocina , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Fator 2 Relacionado a NF-E2/farmacologia , Rim/patologiaRESUMO
OBJECTIVE@#To evaluate the efficacy and safety of Chinese medicine (CM) improving pregnancy outcomes after surgery for endometriosis-associated infertility.@*METHODS@#A multicenter, randomized, double-blind placebo parallel controlled clinical trial was designed. A total of 202 patients who had laparoscopy for endometriosis-associated infertility with qi stagnation and blood stasis syndrome were included and randomly divided into the CM treatment group and placebo control group at a ratio of 1:1 using a central block randomization from May 2014 to September 2017, 101 patients in each group. The two groups received continuous intervention at 1-5 days after surgery, for 6 menstrual cycles. Before ovulation, the CM group was treated Huoxue Xiaoyi Granule (); after ovulation, Bushen Zhuyun Granule ( was involved. The control group was treated with placebo. Transvaginal ultrasonography was performed every menstrual cycle during the treatment, and female hormone levels in the follicular and luteal phases were measured during the 1st, 3rd and 6th menstrual cycles. The analysis was continued until pregnancy. The primary outcomes were clinical pregnancy rate and pregnancy outcome, and the secondary outcomes were follicular development and endometrial receptivity. Safety evaluations were performed before and after treatment.@*RESULTS@#(1) Clinical pregnancy and live birth rates: the clinical pregnancy and live birth rates of the CM group were significantly higher than those of the placebo group [44.6% (45/101) vs. 29.7% (30/101), 34.7% (35/101) vs. 20.8% (21/101), both P0.05).@*CONCLUSION@#Strategies for activating blood circulation-regulating Gan (Liver)-tonifying Shen (Kidney) sequential therapy can effectively improve the clinical pregnancy rate and live birth rate of endometriosis-associated infertility with qi stagnation and blood stasis after laparoscopy, improve follicular development, promote ovulation, improve endometrial receptivity, while being a safe treatment option. (Trial registration No. NCT02676713).
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Objective To study the biological properties of microRNA (miRNA) -21 expression in esophageal squamous cell carcinoma. Methods MiRNA-21 sense expression vector, miRNA-21 empty vector and miRNA-21 inhibitor were transfected and detected by fluorescence Real-time PCR. The normal cells of esophageal squamous cell carcinoma TE-1 were used as the control group, and the transfection result were detected. The cell proliferation activity was detected by cell counting kit-8(CCK-8), and the apoptosis ability was detected by flow cytometry. The invasion ability and migration ability of TE-1 cells were observed by Transwell chamber and scratch test. Changes in the sensitivity of TE-1 cells to radiotherapy were observed by colony formation experiments. The data were analyzed using SPSS 19. 0 software. Results The result of Real-time PCR showed that the expression level of miRNA-21 in TE-1 cells was significantly decreased after transfected with miRNA-21 inhibitor (P<0. 05). Compared with the normal cell growth group, positive control group and negative control group, the proliferation of TE-1 cells was reduced and apoptosis was accelerated after transfection with miRNA-21 inhibitor (P<0. 05). In addition, the ability of cell invasion and migration in the experimental inhibition group was decreased. Clone formation assays showed that inhibition of miRNA-21 expression significantly increased the sensitivity of TE-1 cells to radiation. Conclusion Down-regulation of miRNA-21 reduces the proliferation, invasion, migration and sensitivity of radiotherapy in esophageal squamous cell carcinoma TE-1 cells, and is a potential target for the future treatment of esophageal cancer.
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Objective To compare the expression of leukemia inhibitory factor (LIF), interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) in tissue and fluid samples from patients with endometriosis, and investigate whether LIF and IL-6 regulate VEGF in human endometriotic stromal cells (ESC). Methods The levels of VEGF, LIF, IL-6 in serum, peritoneal fluid of patients with and without endometriosis were measured by ELISA. The mRNA of these three factors in the ectopic and eutopic endometrial tissue and stromal cells were measured by real-time PCR. ESC derived from ovarian endometriomas were cultured using the method of primary cell culture with LIF and IL-6, and the level of VEGF mRNA and protein were measured by the method of real-time PCR and ELISA respectively.Results VEGF and IL-6 concentration were 1.2 and 1.3 times higher in the serum of patients with endometriosis than in the control group [(94±19) versus (78±17) ng/L; (45±14) versus (35±9) ng/L; all P<0.05]. VEGF and IL-6 concentration were 1.2 and 1.4 times higher in the peritoneal fluid of patients with endometriosis than in the control group [(110±25) versus (91±21) ng/L; (69±20) versus (49±15) ng/L; all P<0.05]. VEGF and IL-6 concentrations in peritoneal fluid of patients with endometriosis were 1.2 and 1.5 times higher than in serum (all P<0.01). VEGF, LIF and IL-6 mRNA expression were 2.2, 8.6, 44.7 times higher in ESC compared with the matching eutopic endometrial stromal cells (all P<0.01). LIF and IL-6 mRNA were 2.0 and 64.8 times higher in ectopic endometrial tissue than the matching eutopic endometrial tissue (all P<0.05).ESC cultured with LIF, IL-6 and LIF+IL-6 induce VEGF protein secretion [(106±18), (124±30), (140±27) ng/L] by 1.3 , 1.5 and 1.7 times (all P<0.05). Conclusion Overexpression of LIF and IL-6 may synergistically contribute to upregulation of VEGF in ESC and promote development of endometriosis.
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Background:@#Estradiol, as an important hormone in follicular development and endometrial receptivity, is closely related to clinical outcomes of fresh in vitro fertilization embryo transfer (IVF-ET) cycles. The aim of this retrospective study was to evaluate the association between elevated serum estradiol (E2) levels on the day of human chorionic gonadotrophin (hCG) administration and IVF-ET pregnancy and birth outcomes.@*Methods:@#A total of 1771 infertile patients with their first fresh IVF-ET cycles were analyzed retrospectively between January 2011 and January 2016 in Peking University First Hospital. Patients were categorized by serum E2 levels on the day of hCG administration into six groups: group 1 (serum E2 levels ≤ 1000 pg/mL, n = 205), group 2 (serum E2 levels 1001–2000 pg/mL, n = 457), group 3 (serum E2 levels 2001–3000 pg/mL, n = 425), group 4 (serum E2 levels 3001–4000 pg/mL, n = 310), group 5 (serum E2 levels 4001–5000 pg/mL, n = 237), and group 6 (serum E2 levels > 5000 pg/mL, n = 137). The retrieved oocyte and MII oocyte numbers and implantation and clinical pregnancy rates of the groups were compared as the first objective of the study. For the 360 women with singleton births among all patients, the area under the corresponding receiver operating characteristic curve (ROC curve) was calculated to assess the predictive value of the E2 change for the probability of low birth weight (LBW) infants as the second objective.@*Results:@#The retrieved oocyte and MII oocyte numbers and implantation and clinical pregnancy rates gradually increased from groups 1 to 5 but decreased in group 6. The parameters of group 1 were statistically worse than those of the other groups, from group 2 to group 6 (the number of retrieved oocytes, t = 13.096, t = 23.307, t = 23.086, t = 26.376, t = 19.636, P < 0.003; the number of retrieved MII oocytes, t = 10.856, t = 20.868, t = 21.874, t = 23.374, t = 19.092, P < 0.003; the implantation rate, χ2 = 12.179, χ2 = 22.239, χ2 = 23.993, χ2 = 23.344, χ2 = 16.758, P < 0.003; the clinical pregnancy rate, χ2 = 16.415, χ2 = 28.074, χ2 = 35.387, χ2 = 37.025, χ2 = 24.590, P < 0.003). ROC analysis revealed that when a serum peak E2 of 3148 pg/mL was used to predict LBW.@*Conclusions:@#The results indicate that serum E2 levels have a concentration-dependent effect on clinical outcomes. The optimal range of the E2 level during a fresh IVF-ET cycle is 1000 to 3148 pg/mL.
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BACKGROUND@#Estradiol, as an important hormone in follicular development and endometrial receptivity, is closely related to clinical outcomes of fresh in vitro fertilization embryo transfer (IVF-ET) cycles. The aim of this retrospective study was to evaluate the association between elevated serum estradiol (E2) levels on the day of human chorionic gonadotrophin (hCG) administration and IVF-ET pregnancy and birth outcomes.@*METHODS@#A total of 1771 infertile patients with their first fresh IVF-ET cycles were analyzed retrospectively between January 2011 and January 2016 in Peking University First Hospital. Patients were categorized by serum E2 levels on the day of hCG administration into six groups: group 1 (serum E2 levels ≤ 1000 pg/mL, n = 205), group 2 (serum E2 levels 1001-2000 pg/mL, n = 457), group 3 (serum E2 levels 2001-3000 pg/mL, n = 425), group 4 (serum E2 levels 3001-4000 pg/mL, n = 310), group 5 (serum E2 levels 4001-5000 pg/mL, n = 237), and group 6 (serum E2 levels > 5000 pg/mL, n = 137). The retrieved oocyte and MII oocyte numbers and implantation and clinical pregnancy rates of the groups were compared as the first objective of the study. For the 360 women with singleton births among all patients, the area under the corresponding receiver operating characteristic curve (ROC curve) was calculated to assess the predictive value of the E2 change for the probability of low birth weight (LBW) infants as the second objective.@*RESULTS@#The retrieved oocyte and MII oocyte numbers and implantation and clinical pregnancy rates gradually increased from groups 1 to 5 but decreased in group 6. The parameters of group 1 were statistically worse than those of the other groups, from group 2 to group 6 (the number of retrieved oocytes, t = 13.096, t = 23.307, t = 23.086, t = 26.376, t = 19.636, P < 0.003; the number of retrieved MII oocytes, t = 10.856, t = 20.868, t = 21.874, t = 23.374, t = 19.092, P < 0.003; the implantation rate, χ = 12.179, χ = 22.239, χ = 23.993, χ = 23.344, χ = 16.758, P < 0.003; the clinical pregnancy rate, χ = 16.415, χ = 28.074, χ = 35.387, χ = 37.025, χ = 24.590, P < 0.003). ROC analysis revealed that when a serum peak E2 of 3148 pg/mL was used to predict LBW.@*CONCLUSIONS@#The results indicate that serum E2 levels have a concentration-dependent effect on clinical outcomes. The optimal range of the E2 level during a fresh IVF-ET cycle is 1000 to 3148 pg/mL.
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Objective To evaluate the effect of tert-butylhydroquinone ( t-BHQ) on DJ-1∕nuclear factor erythroid 2-related factor 2 (Nrf2) pathway during renal ischemia-reperfusion (I∕R) in diabetic rats. Methods Forty SPF healthy adult male Sprague-Dawley rats, weighing 200-220 g, were divided into 4 groups (n=10 each) using a random number table method: control group (group C), diabetes mellitus group (group D), diabetes mellitus plus renal I∕R group (I∕R group) and t-BHQ group (group T). Diabe-tes mellitus was induced by intraperitoneal streptozotocin 60 mg∕kg and confirmed by fasting blood glucose level>16. 7 mmol∕L 72 h later. t-BHQ 50 mg∕kg was intraperitoneally injected in 3 times at an interval of 8 h starting from 24 h before surgery in group T, while the equal volume of normal saline was given instead in D and I∕R groups. Blood samples were collected from the apex of the heart at 24 h of reperfusion for deter-mination of serum creatinine (Cr), cystatin C (Cys C) and β2-microglobulin (β2-MG) concentrations. The rats were then sacrificed, and kidneys were removed for determination of pathological changes of kidneys (with a light microscope) and for detection of the expression of DJ-1, Nrf2 and heme oxygenase-1 (HO-1) in renal tissues (by Western blot). Results Compared with group C, the concentrations of serum Cr, Cys C and β2-MG and pathological scores were significantly increased, and the expression of DJ-1, Nrf2 and HO-1 was up-regulated in D, I∕R and T groups ( P<0. 05). Compared with group D and group I∕R, the concentrations of serum Cr, Cys C and β2-MG and pathological scores were significantly decreased, and the expression of DJ-1, Nrf2 and HO-1 was up-regulated in group T ( P<0. 05). Conclusion t-BHQ can at- tenuate renal I∕R injury by activating DJ-1∕Nrf2 pathway in diabetic rats.