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【Objective】 To evaluate the predictive value of isoform [-2] proprostate-specific antigen, p2 PSA (p2PSA) and its derived indexes for prostate cancer in a Chinese cohort with PSA 4-20 ng/mL. 【Methods】 A total of 139 males scheduled for biopsy were enrolled in the prospective study from Nov.2021 to Jun.2022. The total PSA (tPSA), free PSA (fPSA), fPSA/tPSA (f/t) and p2PSA were collected, and the percentage of p2PSA(%p2PSA) and prostate health index(PHI) were calculated. The predictive value of p2PSA and its derived indexes were compared with traditional indexes with receiver operating characteristic (ROC) curve and Logistic analysis. 【Results】 Prostate cancer was found in 54 cases (38.8%). There were significant statistical differences in tPSA(10.68 vs.8.14, P=0.021), f/t(0.13 vs.0.16, P=0.006), p2PSA(30.25 vs.19.81, P<0.001), %p2PSA(21.52 vs.13.15, P<0.001) and PHI(64.3vs.38.2, P<0.001) between prostate cancer patients and non-prostate cancer patients. The area under the ROC curve (AUC) of tPSA, fPSA, %fPSA, p2PSA, %p2PSA and PHI were 0.63, 0.51, 0.63, 0.71, 0.73, and 0.80, respectively. The inclusion of %p2PSA and PHI significantly increased the prediction efficiency of the basic prediction model (AUCbase+PHI=0.81, AUCbase+%p2PSA=0.78, AUCbase=0.67). With 35 as the recommended cut-off value of PHI, the incidence of meaningless puncture was reduced by 25.8%(36/139). 【Conclusion】 The application of p2PSA and its derived indexes have good predictive value for patients with PSA 4-20 ng/mL. The combined detection of %p2PSA and PHI can significantly increase the detection efficiency of prostate cancer and reduce the incidence of meaningless prostate puncture by 25.8%.
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Objective:To observe the outcome of posterior staphyloma (PS) marginal retinal photocoagulation in pars plana vitrectomy (PPV) for high myopia macular hole retinal detachment eyes accompanied with PS.Methods:From January 2017 to June 2019, 49 patients (49 eyes) with high myopia macular hole retinal detachment accompanied with PS who were undergone PPV operation from Tianjin Eye Hospital were included in this study. There were 13 males (13 eyes) and 36 females (36 eyes). All patients underwent best corrected visual acuities (BCVA) and optical coherence tomography examinations. The standard logarithmic visual acuity chart was used for BCVA examination, and the visual acuity was converted to minimum resolution angle in logarithmic (logMAR) when recorded. The patients were randomly divided into two groups according to surgical options: conventional PPV with internal limiting membrane (ILM) peeling (group A, 24 eyes), PS marginal retinal photocoagulation in PPV with ILM peeling (group A, 25 eyes). The mean preoperative logMAR BCVA of group A and B were 1.87±0.28 and 1.80±0.37, the difference was not statistically significant ( t=0.604, P=0.551). The patients in the group A received 23G PPV, triamcinolone acetonide staining during the operation, the epiretinal membrane was peeled off, indocyanine green assisted staining, the posterior macular ILM was peeled off, and the peripheral retina was examined in detail during the operation. Areas with retinal degeneration were reinforced by laser photocoagulation, and the subretinal fluid was drained through the macular hole and filled with silicone oil. The eyes of the group B were subjected to retinal photocoagulation for 2 to 3 rows at the edge of the PS in addition to the usual surgical procedures. The average follow-up time was 8.34±3.21 months. Surgical outcome were estimated by the average number of operation, retinal reattachment rate, macular hole closure rate and BCVA. The χ2 test or Fisher exact probability was used to compare the count data. Independent sample t test was used to compare the measurement data. Results:Retinal reattachment was obtained in 17 eyes (70.8%, 17/24) and 24 eyes (96.0%, 24/25) in group A and B after first surgery respectively, the difference was statistically significant ( χ2=3.984, P=0.046). Final retinal reattachment was obtained in all 49 eyes. Final macular hole closure was in 15 eyes (62.5%, 15/24) and 19 eyes (76.0%, 19/25) in group A and B, respectively, the difference was not statistically significant ( χ2=1.051, P=0.305). The mean postoperative logMAR BCVA of group A (1.20±0.47) and B (1.08±0.39) were all improved than preoperative BCVA, the differences were all statistically significant ( t=2.899, 5.327; P=0.001, 0.000), the differences of mean postoperative logMAR BCVA between two groups was not statistically significant ( t=0.675, P=0.506). The mean number of operation of group A (2.63±0.88) was more than group B (2.08±0.28), the difference was statistically significant ( t=3.003, P=0.006). Conclusion:In comparison with conventional PPV, combined PS marginal retinal photocoagulation can improve retinal reattachment rate after first surgery, and reduce the number of reoperations.
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@#AIM: To analyze the therapeutic effect of loratadine combined with diclofenac sodium eye drops in the treatment of allergic conjunctivitis, and the influence on tear film stability and tear-related indexes.<p>METHODS: A prospective study was conducted among 93 patients(186 eyes)with allergic conjunctivitis admitted to the hospital between January 2019 and January 2020. They were randomly divided into observation group(<i>n</i>=47, 94 eyes, treated with loratadine and diclofenac sodium eye drops)and control group(<i>n</i>=46, 48 eyes, treated with loratadine). All patients received 2wk of treatment. The improvement of ocular symptoms and signs after treatment was evaluated. Schirmer I test(SⅠt)and break up time(BUT)were used to evaluate the tear film stability. The height, depth and cross-sectional area of lacrimal rivus were measured by anterior segment related optical coherence tomography. Tear specimens were collected to detect changes in tear hyaluronic acid(HA), group ⅡA secretory phospholipase A2(sPLA2-Ⅱa and eosinophil cationic protein(ECP). The occurrence of adverse reactions was counted.<p>RESULTS: After 2wk of treatment, the scores of main symptoms and signs were reduced in the two groups(<i>P</i><0.05), and the observation group had lower scores than the control group(<i>P</i><0.05). SⅠt and BUT were increased in the two groups(<i>P</i><0.05), which were longer in the observation group than in the control group(<i>P</i><0.05). The height of lacrimal rivus increased, depth increased, and cross-sectional area were increased in the two groups(<i>P</i><0.05). Besides, the above indexes in observation group were higher than those in the control group(<i>P</i><0.05). Meanwhile, HA, ECP and sPLA2-Ⅱa were decreased in the two groups(<i>P</i><0.05), which were lower in the observation group than in the control group(<i>P</i><0.05). No significant differences were found between the 2 groups in the incidence of adverse reactions(12.8% <i>vs</i> 10.9%, <i>P</i>>0.05).<p>CONCLUSION: The overall effect of loratadine combined with diclofenac sodium eye drops is better than that of loratadine alone in the treatment of allergic conjunctivitis. The combined treatment can improve symptoms, signs and tear film stability, reduce inflammatory mediators in tears, and promote recovery of tear film function. Besides, it is safe and feasible.
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For rheumatoid arthritis， glucocorticoids or immunosuppressive agents are currently used in clinical treatment， but long-term use of these drugs has large side effect on humans， and immunosuppressive agents are expensive. To a certain extent， its wide application is limited. The treatment of rheumatoid arthritis with traditional Chinese medicine（TCM） has a long history and little toxic and side effect， but its specific mechanism of action needs further exploration. The process of autophagy is an active biological process in which cells themselves are stimulated by the outside world through intracellular signal transduction to maintain a stable internal environment. Its abnormality is involved in the occurrence of many diseases. At present， studies have shown that abnormal autophagy is closely related to the occurrence and development of rheumatoid arthritis， which can interfere with the pathological changes of RA pannus formation， synovial inflammation and bone destruction and affect the disease process. In recent years， many studies have found that traditional Chinese medicine and its active ingredients can affect the pathological development of rheumatoid arthritis by regulating autophagy. This article investigates the relevant literature on the intervention of rheumatoid arthritis by regulating autophagy through using TCM， with a view to providing new ideas for basic research， new drug development and clinical treatment of rheumatoid arthritis.
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OBJECTIVE@#Critical effective constituents were identified from Bufei Yishen formula (BYF), a traditional herbal compound and combined as effective-constituent compatibility (ECC) of BYF I, which may have potential bioactive equivalence to BYF.@*METHODS@#The active constituents of BYF were identified using four cellular models and categorised into Groups 1 (Bufeiqi), 2 (Bushen), 3 (Huatan) and 4 (Huoxue) according to Chinese medicinal theory. An orthogonal design and a combination method were used to determine the optimal ratios of effective constituents in each group and the ratios of "Groups 1 to 4" according to their pharmacological activity. We also comprehensively assessed bioactive equivalence between the BYF and the ECC of BYF I in a rat model of chronic obstructive pulmonary disease (COPD).@*RESULTS@#We identified 12 active constituents in BYF. The numbers of constituents in Groups 1 to 4 were 3, 2, 5 and 2, respectively. We identified the optimal ratios of effective constituents within each group. In Group 1, total ginsenosides:Astragalus polysaccharide:astragaloside IV ratio was 9:5:2. In Group 2, icariin:schisandrin B ratio was 100:12.5. In Group 3, nobiletin:hesperidin:peimine:peiminine:kaempferol ratio was 4:30:6.25:0:0. In Group 4, paeoniflorin:paeonol ratio was 4:1. An orthogonal design was then used to establish the optimal ratios of Group 1, Group 2, Group 3 and Group 4 in ECC of BYF I. The ratio for total ginsenosides:Astragalus polysaccharide:astragaloside IV:icariin:schisandrin B:nobiletin:hesperidin:peimine:paeoniflorin:paeonol was determined to be 22.5:12.5:5:100:12.5:4:30:6.25:25:6.25. A comprehensive evaluation confirmed that ECC of BYF I presented with bioactive equivalence to the original BYF.@*CONCLUSION@#Based on the ECC of traditional Chinese medicine formula method, the effective constituents of BYF were identified and combined in a fixed ratio as ECC of BYF I that was as effective as BYF itself in treating rats with COPD.
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Objective To study the relationship between atherogenic index of plasma ( AIP ) and renal impairment in male patients with gout. Methods A retrospective analysis of 821 male subjects was conducted to measure the relevant biochemical indicators and to calculate the AIP, endogenous creatinine-clearance rate (Ccr), and estimated glomerular filtration rate ( eGFR) . EpiData 3.1 software was used for data entry, SPSS21.0 was used for statistical analysis, and GraphPad Prism 6. 0 software was used for charts. Results Compared with control group, AIP, serum uric acid, triglyceride in gout group were significantly higher (all P<0.01), while eGFR and high density lipoprotein-cholesterol were significantly lower ( both P<0.05) . The composition ratio of renal function impairment in gout group was significantly higher (P<0.01). With the increase of AIP level, eGFR level decreased and serum creatinine level increased, but the overall difference was not statistically significant ( P>0.05) , while Ccr and serum uric acid levels gradually increased (P<0.05). Logistic regression analysis after adjusting for various confounding factors showed that AIP, triacylglycerol, and serum uric acid were risk factors for renal function damage in patients with gout (P<0.05), the relevant risk were 7.030, 1.291, 1.004 respectively, After adjusting corfounding factors, the associafions betwees triglyceride, serum uric acid and with renal function injury risk changed little, while AIP show more evident, the OR value increased from 2.629 to 6.265 and 7.030. Conclusions (1)AIP is closely related to the renal function damage of patients with gout. After adjusting various confounding factors, AIP can better reflect the renal function damage than other indicators, which is of great significance to predict the renal function damage of patients with gout. ( 2) That patients with gout with high uric acid level may suffer from renal atherosclerosis and have a higher risk of renal impairment. ( 3) Dynamic observation of AIP in gout patients is helpful for early identification of the risk of renal failure in such patients.
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Objective:To compare the effects and multi-organ intervention of tripterygium glycosides(TG) tablet from Hunan Qianjin Xieli (QJ) and Zhejiang Deende (DED) on type Ⅱ collagen-induced arthritis (CIA) in rats. Method:The 72 SD rats were randomly divided into normal group, model group, QJ TG clinical group 2 times, 6 times equivalent dose group (QJ-TG 0.018, 0.054 g·kg-1), derende TG clinical group 2 times, 6 times equivalent dose group (DED-TG 0.018, 0.054 g·kg-1). The intragastric administration was started on the day after the first immunization, once a day. After the second immunization, the symptoms such as redness and swelling of joints were observed, and the clinical score of arthritis were evaluated. The materials were taken for pathological examination of the inflammatory joints on the 21th and 42th day. The concentration of alkaline phosphatase(ALP), alanine aminotransferase(ALT), aspartate aminotransferase(AST), gamma-glutamyltransferase(GGT), total bilirubin(TBIL), creatinine(CRE) and urea(UREA) in serum were detected by enzymatic assay. The rate of sperm deformity, testicular and ovarian tissue damage in the rat epididymis was assessed. Result:TG from two manufacturers attenuated the inflammation, redness, swelling and deformity of joints in CIA rats, reduced the clinical score and incidence of arthritis in CIA rats. Meanwhile, it also exhibited obvious reduction in all pathological features such as joint synovitis, pannus, cartilage erosion and bone destruction. There were significant differences between the QJ-TG high and low dose groups and the DED-TG high dose group compared with the model group (PP-1 group had a significant inhibitory effect on the clinical scores on the 15th and 18th days than the QJ-TG same dose group (P-1 dose of DED-TG, the white blood cell count and spleen index were significantly increased.At the same time, two different manufacturers of TG had no effect on body weight, organ index, digestive system, liver and kidney function, liver and kidney pathology of CIA model rats. QJ-TG and DED-TG all significantly increased the rate of male rats sperm malformation and significant damage to testicular seminiferous tubules and the toxicity increased with the increase of dose and time. while the mole reproductive toxicity of DED-TG was higher than that of QJ-TG at the same dose. In the DED-TG 0.054 g·kg-1 and QJ-TG 0.054 g·kg-1 group, there were only the reduction of vascular distribution in the ovarian tissue and the reduction of the corpus luteum, and no other toxic effects were observed. Conclusion:Two manufacturers TG2 times (0.018 g·kg-1) and 6 times (0.054 g·kg-1) clinical equivalent dose can delay the onset of CIA in rats, reduce the clinical score of arthritis, improve the pathological changes of joints, but have a certain degree of male reproductive toxicity. The high-dose DED-TG is more toxic than the QJ-TG.
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Objective@#To study the relationship between atherogenic index of plasma (AIP)and renal impairment in male patients with gout.@*Methods@#A retrospective analysis of 821 male subjects was conducted to measure the relevant biochemical indicators and to calculate the AIP, endogenous creatinine-clearance rate (Ccr), and estimated glomerular filtration rate (eGFR). EpiData 3.1 software was used for data entry, SPSS21.0 was used for statistical analysis, and GraphPad Prism 6.0 software was used for charts.@*Results@#Compared with control group, AIP, serum uric acid, triglyceride in gout group were significantly higher (all P<0.01), while eGFR and high density lipoprotein-cholesterol were significantly lower (both P<0.05). The composition ratio of renal function impairment in gout group was significantly higher (P<0.01). With the increase of AIP level, eGFR level decreased and serum creatinine level increased, but the overall difference was not statistically significant (P>0.05), while Ccr and serum uric acid levels gradually increased (P<0.05). Logistic regression analysis after adjusting for various confounding factors showed that AIP, triglyceride, and serum uric acid were risk factors for renal function damage in patients with gout (P<0.05), the relevant risk were 7.030, 1.291, 1.004 respectively. After adjusting confounding factors, the associations between triglyceride, serum uric acid and renal function injury risk changed little, while AIP showed more evident, the OR value increased from 2.629 to 6.265 and 7.030.@*Conclusions@#(1)AIP is closely related to the renal function damage of patients with gout. After adjusting various confounding factors, AIP can better reflect the renal function damage than other indicators, which is of great significance to predict the renal function damage of patients with gout. (2)That patients with gout with high uric acid level may suffer from renal atherosclerosis and have a higher risk of renal impairment. (3)Dynamic observation of AIP in gout patients is helpful for early identification of the risk of renal failure in such patients.
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The aim of this paper was to compare the properties of Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets from dose-effect-toxicity on type Ⅱ collagen-induced arthritis( CIA) in rats. SD rats were randomly divided into eight groups,including normal group,model group,Tripterygium Glycosides Tablets groups( 1 times equivalent dose 0.009 g·kg-1,4 times equivalent dose 0.036 g·kg-1,16 times equivalent dose 0.144 g·kg-1),Tripterygium wilfordii Tablets groups( 1 times equivalent dose 0.007 5 mg·kg-1,4 times equivalent dose 0.030 mg·kg-1,16 times equivalent dose 0.120 mg·kg-1). Beginning on the first immunization,Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets administered intraperitoneally once a day. After the second immunization,the symptoms such as redness and swelling of joints were observed,and the clinical score and incidence of arthritis were evaluated. HE and Masson staining were used to examine the histopathological changes of joints. The expression level of anti-type Ⅱ collagen antibody Ig G in serum was detected by ELISA,routine testing of blood components,the concentration of ALP( alkaline phosphatase),ALT( alanine aminotransferase),AST( aspartate aminotransferase),GGT( gamma-glutamyltransferase),TBi L( total bilirubin),CRE( creatinine) and UREA( urea) in serum were detected by enzymatic assay. The rate of sperm deformity in the epididymis was evaluated under light microscope. The extent of damage to the testis and ovarian tissue was assessed by HE staining. Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets attenuated the inflammation,redness,swelling and deformity of joints and reduced the clinical score and incidence of arthritis in CIA rats. Meanwhile,it also exhibited obvious reduction in all pathological features such as joint synovitis,pannus,cartilage erosion and bone destruction. Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets reduced Ig G in a dose-dependent manner,and Tripterygium Glycosides Tablets is better than Tripterygium wilfordii Tablets( P<0.05 or P<0.01). The high doses of Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets could significantly increase the organ coefficient of liver and spleen and reduced RBC and HGB in CIA rats( P<0.01),and severity leading to death. Gastric mucosal injury and morphological changes of liver and kidney were not observed in CIA rats of Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets treatment group. The 4 and 16 times doses of Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets could significantly increase serum ALT,GGT and decrease CRE( P<0.05 or P<0.01). Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets could increase the sperm deformity rate and damage the testicular seminiferous tubules of CIA male rats. Severity increased with dose and time increasing. The effect of Tripterygium Glycosides Tablets( 16 times) is more significant than Tripterygium wilfordii Tablets( 16 times). Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets significantly delayed onset of arthritis and inhibited the paw edema and arthritic score. Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets also caused male reproductive damage,high dose affected hematopoiesis,and maximum dose leading to death. Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets all depended on dose-effect-toxicity manner. Anti-arthritis effect of Tripterygium Glycosides Tablets is better than Tripterygium wilfordii Tablets,but the toxicity of Tripterygium Glycosides Tablets maximum dose is more obvious. The relevant conclusions of our study will provide experimental references for clinical rational use of drugs,and further clinical studies are needed to confirm our conclusions.
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Animais , Masculino , Ratos , Artrite Experimental , Tratamento Farmacológico , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas , Toxicidade , Glicosídeos , Toxicidade , Distribuição Aleatória , Ratos Sprague-Dawley , Comprimidos , Tripterygium , ToxicidadeRESUMO
To systematically review the improvement effects of Tripterygium Glycosides Tables( TGT) alone or in combination with methotrexate( MTX) on the clinical signs and symptoms of rheumatoid arthritis( RA),and provide a basis for the rational use of TGT in clinic,in the current study,six literature databases including CNKI,Wan Fang,VIP,PubMed,EMbase,and Cochrane Library,were systematically searched,according to the inclusion and exclusion criteria. Review Manager 5.3 software was used to input the literatures,and we assessed the risk bias on the level of outcome indicators for each included literature. A total of 18 literatures were included,and the classification results showed that: compared with MTX,TGT alone can reduce the number of joint swelling( MD =0. 18,95%CI[-1.06,1.42],P = 0.78) and joint tenderness( MD =-0.06,95% CI[-1.69,1.56],P = 0.94) in RA patients with the same effect as MTX. In terms of drug combination,TGT combined with MTX had an advantage over MTX alone in lessening the morning stiffness time( MD = 18. 24,95% CI[12. 64,23. 84],P < 0. 000 01) of RA,joint tenderness( MD = 2. 65,95% CI[1. 85,3. 44],P<0.000 01) and joint swelling( MD = 3.01,95% CI[2.09,3.39],P< 0.000 01). In conclusion,this Meta-analysis suggest that TGT alone was superior to MTX in improving joint swelling and tenderness in RA patients,TGT combined with MTX may improve the clinical manifestation of RA patients better than MTX alone.
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Humanos , Antirreumáticos , Usos Terapêuticos , Artrite Reumatoide , Tratamento Farmacológico , Quimioterapia Combinada , Medicamentos de Ervas Chinesas , Usos Terapêuticos , Glicosídeos , Usos Terapêuticos , Metotrexato , Usos Terapêuticos , Comprimidos , Resultado do Tratamento , Tripterygium , QuímicaRESUMO
The aim of this study was to systematically evaluate the clinical efficacy of Tripterysium Glycosides Tablets( TGT) alone or in combination with methotrexate( MTX) in the treatment of rheumatoid arthritis( RA) based on the laboratory index criteria and to provide a basis for the clinical application of TGT against RA. Six databases including CNKI,Wan Fang,VIP,PubMed,EMbase and Cochrane were retrieved for randomized controlled trials( RCT) about TGT alone or combination with MTX in the treatment of RA.Then risk assessment tools were used for quality evaluation of the studies,and data extraction and analysis were conducted by using Rev Man 5.3 software for Meta-analysis. A total of 1 709 articles were retrieved,and finally 25 studies were included,with a total sample size of 2 507 cases. Meta-analysis results showed that between TGT alone and TGT alone,MDESR=-2. 66,95%CI[-8.17,2.86],P = 0.35; MDCRP=-2.38,95%CI[-9.01,4.24],P = 0.48; between TGT combined with MTX and MTX alone,MDESR= 8.74,95%CI[6.72,10.76],P<0.000 01; MDCRP= 5.37,95%CI[3.71,7.03],P<0.000 01; SMDRF= 1.05,95%CI[0.51,1.60],P = 0.000 1.The effect of TGT on decreasing CRP and ESR in RA patients was similar to the MTX. In addition,TGT combined with MTX were more effective in decreasing CRP,ESR,RF than MTX alone. However,due to the potential bias in the included studies,more and high-quality randomized controlled trials would be needed to improve the level of evidence.
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Humanos , Antirreumáticos , Usos Terapêuticos , Artrite Reumatoide , Tratamento Farmacológico , Quimioterapia Combinada , Medicamentos de Ervas Chinesas , Usos Terapêuticos , Glicosídeos , Usos Terapêuticos , Metotrexato , Usos Terapêuticos , Ensaios Clínicos Controlados Aleatórios como Assunto , Comprimidos , Resultado do Tratamento , Tripterygium , QuímicaRESUMO
As a complex system, the topology of human's brain network has an important effect on further study of brain's structural and functional mechanism. Graph theory, a kind of sophisticated analytic strategies, is widely used for analyzing complex brain networks effectively and comparing difference of topological structure alteration in normal development and pathological condition. For the purpose of using this analysis methodology efficiently, it is necessary to develop graph-based visualization software. Thus, we developed VisConnectome, which displays analysis results of the brain network friendly and intuitively. It provides an original graphical user interface (GUI) including the tool window, tool bar and innovative double slider filter, brain region bar, runs in any Windows operating system and doesn't rely on any platform such as Matlab. When importing the user-defined script file that initializes the brain network, VisConnectome abstracts the brain network to the ball-and-stick model and render it. VisConnectome allows a series of visual operations, such as identifying nodes and connection, modifying properties of nodes and connection such as color and size with the color palette and size double slider, imaging the brain regions, filtering the brain network according to its size property in a specific domain as simplification and blending with the brain surface as a context of the brain network. Through experiment and analysis, we conclude that VisConnectome is an effective visualization software with high speed and quality, which helps researchers to visualize and compare the structural and functional brain networks flexibly.
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Humanos , Encéfalo , Fisiologia , Conectoma , SoftwareRESUMO
Tripterygium wilfordii is widely used in the treatment of rheumatism with curative effect. However,its toxicity and adverse reactions,especially the hepatotoxicity,rank the first in the herbs induced liver injury,is the key factors hindering its clinical application. This paper reviewed the literatures related to the hepatotoxicity of T. wilfordii in recent 20 years,and summarized the characteristic of hepatotoxicity induced by T. wilfordii,the factors causing liver injury,the mechanism of toxicity,and the measures to reduce toxicity. In animal experiments,the T. wilfordii induced-hepatotoxicity in physiological state was more serious than pathological state. The T. wilfordii induced-hepatotoxicity is related to various toxic components contained in it,but alkaloids are the most toxic one.Overdose and cumulative overdose are the lead causing of hepatotoxicity induced by T. wilfordii. The theory of oxidative stress is still an important mechanism of T. wilfordii induced-hepatotoxicity,and Nrf2,as a key regulatory enzyme of oxidative stress,has become an important target for drugs to against T. wilfordii induced-hepatotoxicity. Mitochondrial autophagy and liver hypersensitivity are new mechanisms of liver injury induced by T. wilfordii. The measures such as dosage control,drug compatibility and dosage form variations can help to reduce the hepatotoxicity induced by T. wilfordii. This paper clarified the current situation and shortcomings of safety research on T. wilfordii,so as to propose new research strategies and provide ideas for rational evaluation of safety and clinical safe drug use of T. wilfordii.
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Animais , Doença Hepática Induzida por Substâncias e Drogas , Medicamentos de Ervas Chinesas , Toxicidade , Tripterygium , ToxicidadeRESUMO
To observe the effect of Tripterygium Glycosides Tablets on angiogenesis of rats with type Ⅱ collagen-induced arthritis( CIA) and on the tube formation of human umbilical vein endothelial cells( HUVEC) in vitro. The HUVEC were induced by 20 μg·L-1 vascular endothelial growth factor( VEGF) in vitro,and were treated with 0. 1,1,10 mg·L-1 Tripterygium Glycosides Tablets continuously for 7 hours. The numbers of branches of tube formation were measured. SD rats were immunized to establish CIA. CIA rats were treated with 9,18,36 mg·kg-1·d-1 Tripterygium Glycosides Tablets for 42 days. Histopathological examination( HE) was performed to observe the vascular morphology and vascular density in the synovial membrane of the inflamed joints. Immunohistochemistry and immunofluorescence were performed to observe the expression of platelets-endothelial cell adhesion molecule( CD31) and αsmooth muscle actin( αSMA) in synovial membrane. Immunohistochemistry and Western blot were performed to observe the expression of hypoxia-inducible factors 1α( HIF1α) and angiotensin 1( Ang1) in the synovial tissue. The results showed that the numbers of branches of tube formation of HUVEC induced by VEGF were improved,and declined significantly after treated by Tripterygium Glycosides Tablets. Compared with the normal group,the vascular density,CD31 positive expression,CD31 +/αSMA-immature and total vascular positive expression in the synovial membrane of the model group were significantly increased,and so as HIF1α and Ang1 in the synovium. Tripterygium Glycosides Tablets reduced the synovial vascular density and inhibited the positive expression of CD31,CD31+/αSMA-immature blood vessels and total vascular,but has no effect on CD31+/αSMA+mature blood vessels. Tripterygium Glycosides Tablets also inhibited the expression of HIF1α and Ang1 in synovial membrane of inflammatory joints. Our results demonstrated that Tripterygium Glycosides Tablets could inhibit the angiogenesis of synovial tissue in CIA rats and the tube formation of HUVEC,which is related to the down-regulation of HIF1α/Ang1 signal axis.
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Animais , Humanos , Ratos , Inibidores da Angiogênese , Farmacologia , Angiotensina I , Metabolismo , Artrite Experimental , Tratamento Farmacológico , Medicamentos de Ervas Chinesas , Farmacologia , Glicosídeos , Farmacologia , Células Endoteliais da Veia Umbilical Humana , Subunidade alfa do Fator 1 Induzível por Hipóxia , Metabolismo , Ratos Sprague-Dawley , Transdução de Sinais , Membrana Sinovial , Comprimidos , Tripterygium , Química , Fator A de Crescimento do Endotélio VascularRESUMO
The aim of this paper was to observe the toxic effect of Tripterygium Glycosides Tablets( TG) on the reproductive system of Ⅱ type collagen induced arthritis( CIA) male rats,and to explore the toxic mechanism preliminarily. Fifty SD rats were randomly divided into normal control group( Con),model group( CIA),Tripterygium Glycosides Tablets clinical equivalent dose groups of 1,2,4 times( 9,18,36 mg·kg-1),10 rats in each group,and were given by gavage once a day for 42 days after the first immunization.The organ indexes of uterine and ovarian were calculated on days 21 and 42. Histopathological and morphological changes of uterine and ovarian were observed under optical microscope. The concentration of estradiol( E2),follicle-stimulating hormone( FSH),luteinizing hormone( LH),17α-hydroxylase( CYP17 A1) and cytochrome P450 19 A1( CYP19 A1) in serum were detected by ELISA. Immunohistochemistry was used to observe the expression of Bax and Bcl-2 related proteins in the apoptosis pathway of uterus and ovary. The results showed that compared with the Con group,CIA group could reduce the number of uterine glands( P<0.05),but no significant changes were observed in other groups. Compared with the CIA group,there were no significant changes in the coefficients of uterus and ovary in the Tripterygium Glycosides Tablets groups. The number of uterine glands,total follicles in the ovary,mature follicles and corpus luteum,the distribution of blood vessels and mitochondria had a certain inhibitory trend,and also slightly increased the number of atresia follicles,but the histopathological quantitative indicators were not statistically different. Except that 2 times clinical dose of Tripterygium Glycosides Tablets could significantly reduce the content of CYP19 A1( P<0. 05) after 42 d administration,there were no significant changes in serum estrogen E2,FSH,LH and estrogen synthesis key enzymes CYP17 A1 in each administration group. Medium and high doses of Tripterygium Glycosides Tablets could increase the expression of apoptotic protein Bax in uterine and ovarian tissues( P<0. 05,P<0. 01),and all the administration groups could inhibit the expression of apoptotic inhibiting protein Bcl-2( P <0. 05,P<0. 01,P<0.001),42 d was more obvious than 21 d. In conclusion,4 times and less than 4 times Tripterygium Glycosides Tablets did not cause obvious toxicity and histopathological changes in the reproductive organs of CIA rats,but it could reduce the level of serum estrogen synthesis key enzyme CYP19 A1 and affect the content of apoptosis-related proteins Bax and Bcl-2 in uterus and ovary tissues. The relevant mechanism needs further study.
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Animais , Feminino , Ratos , Apoptose , Aromatase , Metabolismo , Artrite Experimental , Tratamento Farmacológico , Medicamentos de Ervas Chinesas , Farmacologia , Toxicidade , Genitália Feminina , Glicosídeos , Farmacologia , Toxicidade , Distribuição Aleatória , Ratos Sprague-Dawley , Comprimidos , Tripterygium , QuímicaRESUMO
To investigate the mechanism of n-butanol extract of Pulsatilla decoction (BAEB) against murine ulcerative colitis (UC) model induced by DSS combined with Candida albicans (CA) colonization, mice were randomly divided into normal control group, DSS group, DSS+CA group, BAEB high, medium and low dose group, and positive drug Mesalazine group. The general condition of mice was observed, fungal loads of murine intestinal contents were detected by plate method, colonic pathological change of mice was examined by HE staining. ASCA in serum and IL-6, IL-8, IL-1β, HBD-2, HBD-3 in colonic mucosa were detected by ELISA. The results showed that, compared with DSS group, the general condition and ASCA in serum had no obvious change for DSS+CA group, but the fungal loads in intestinal contents, the colonic pathological damage, and the levels of IL-6, IL-8, IL-1β, HBD-2, HBD-3 in colonic mucosa were greater than that of DSS group. High dose of BAEB group and Mesalazine group could improve the colonic pathology, decrease IL-6, IL-8, IL-1β, HBD-2, HBD-3 expression level. In conclusion, BAEB could effectively improve the UC symptoms in mice induced by DSS combined with CA colonization, and inhibit the inflammatory factors such as IL-6, imply that BAEB is of important value for the treatment of intestinal fungal-related colitis.
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BACKGROUND AND PURPOSE: External counterpulsation (ECP) is a noninvasive method used to enhance cerebral perfusion by elevating the blood pressure in ischemic stroke. However, the response of the beat-to-beat blood pressure variability (BPV) in ischemic stroke patients during ECP remains unknown. METHODS: We enrolled recent ischemic stroke patients and healthy controls. Changes in the blood flow velocities in bilateral middle cerebral arteries and the continuous beat-to-beat blood pressure before, during, and after ECP were monitored. Power spectral analysis revealed that the BPV included oscillations at very low frequency (VLF; <0.04 Hz), low frequency (LF; 0.04-0.15 Hz), and high frequency (HF; 0.15-0.40 Hz), and the total power spectral density (TP; <0.40 Hz) and LF/HF ratio were calculated. RESULTS: We found that ECP significantly increased the systolic and diastolic blood pressures in both stroke patients and controls. ECP decreased markedly the systolic and diastolic BPVs at VLF and LF and the TP, and the diastolic BPV at HF when compared with baseline. The decreases in diastolic and systolic BPV reached 37.56% and 23.20%, respectively, at VLF, 21.15% and 12.19% at LF, 8.76% and 16.59% at HF, and 31.92% and 23.62% for the total TP in stroke patients, which did not differ from those in healthy controls. The change in flow velocity on the contralateral side was positively correlated with the total TP systolic BPV change induced by ECP (r=0.312, p=0.035). CONCLUSIONS: ECP reduces the beat-to-beat BPV when increasing the blood pressure and cerebral blood flow velocity in ischemic stroke patients. ECP might be able to improve the clinical outcome by decreasing the beat-to-beat BPV in stroke patients, and this should be explored further in future studies.
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Humanos , Velocidade do Fluxo Sanguíneo , Pressão Sanguínea , Circulação Cerebrovascular , Contrapulsação , Métodos , Artéria Cerebral Média , Perfusão , Acidente Vascular CerebralRESUMO
Previous studies showed that three methods for regulating and invigorating lung and kidney (lung invigorating and spleen strengthening, lung invigorating and kidney tonifying, and Qi supplementing and kidney nourishing) could regulate inflammatory signaling pathways of chronic obstructive pulmonary disease (COPD) in rats, so as to alleviate inflammation. In the present study, R-value comprehensive evaluation method was used to evaluate the comprehensive effect of three methods for regulating and invigorating lung and kidney on inflammatory signaling pathways. Rats were randomly divided into control, model, lung invigorating and spleen strengthening, lung invigorating and kidney tonifying, Qi supplementing and kidney nourishing and aminophylline groups. The COPD rat models were established by cigarette smoking combined with bacterial infection, and orally administered with drugs between the 9th and 20th week. Afterwards, efforts were made to observe the long-term effects between the drug withdrawal and the 32rd week and detect indicators in two batches in the 20th week and 32th week. Specifically, (1) Linking JAK/STAT signaling pathway: JAK2 mRNA, and protein expressions of STAT-1, STAT-3, STAT-5, JAK-2; (2) NF-kappaB signaling pathway: Smad2 mRNA and protein expressions of I-kappaB, NF-kappaB, TGF-beta1; (3) PPARgamma and antioxidant signaling pathway: SOD, PGE mRNA, PPARgamma protein. According to the results, 5 indicators in JAK/STAT pathway, 4 indicators in NF-kappaB pathway, and 3 indicators in PPARgamma pathway were significantly rectified by three methods for regulating and invigorating lung and kidney in between the 20th week and 32nd week. Between the 20th and 32nd week, the recipes for rectifying JAK/STAT pathway with intensity from high to low were recipes for lung invigorating and spleen strengthening, Qi supplementing and kidney nourishing, lung invigorating and kidney tonifying, aminophylline, particularly those for lung invigorating and spleen strengthening; The recipes for rectifying NF-kappaB pathway with intensity from high to low were recipes for lung invigorating and spleen strengthening, lung invigorating and kidney tonifying, Qi supplementing and kidney nourishing and aminophylline, particularly the first three types of drugs. The recipes for rectifying PPARgamma and antioxidant signaling pathway with intensity from high to low were recipes for lung invigorating and kidney tonifying, Qi supplementing and kidney nourishing, lung invigorating and spleen strengthening and aminophylline. Therefore, three methods for regulating and invigorating lung and kidney showed better long-term effects in regulating COPD lung inflammation signaling pathways. Specifically, recipe for lung invigorating and spleen strengthening showed a better effect in JAK/STAT and NF-kappaB pathways, while recipe for lung invigorating and kidney tonifying and Qi supplementing and kidney nourishing showed better effects in PPARgamma and antioxidant signaling pathways. In conclusion, R-value comprehensive evaluation method can evaluate the comprehensive effect of medicines and define the ranking of multiple drugs and their main targets.
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Animais , Humanos , Ratos , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Rim , Pulmão , Alergia e Imunologia , Metabolismo , NF-kappa B , Alergia e Imunologia , Doença Pulmonar Obstrutiva Crônica , Tratamento Farmacológico , Alergia e Imunologia , Metabolismo , Ratos Sprague-Dawley , Transdução de Sinais , Proteína Smad2 , Metabolismo , Fator de Crescimento Transformador beta1 , MetabolismoRESUMO
<p><b>OBJECTIVE</b>To evaluate the therapeutic and long-term effects of three methods for regulating and invigorating Fei-Shen [reinforcing Fei and invigorating Pi (RFIP), reinforcing Fei and invigorating Shen (RFIS), benefiting qi and nourishing Shen (BQNS)] on T lymphocyte subsets and CD4+ CD25+ in rats with chronic obstructive pulmonary disease (COPD).</p><p><b>METHODS</b>Totally 120 rats were randomly divided into the control group, the model group, the RFIP group, the RFIS group, the BQNS group, and the aminophylline group, 20 in each group. Except those in the control group, the rest rats were exposed to cigarette smoking and bacterial infection to prepare the COPD rat model. Rats in the RFIP group, the RFIS group, the BQNS group, and the aminophylline group were administrated with Bufei Jianpi Recipe, Bufei Yishen Recipe, Yiqi Zishen Recipe, and aminophylline from week 9 to 20. After rats were sacrificed at week 20 and 32, lung pathological impairments and the levels of T lymphocyte subsets (CD3+, CD4+, CD8+, CD4+ / CD8+) and CD4+ CD25+ in the peripheral blood and the bronchoalveolar lavage fluid (BALF) were detected.</p><p><b>RESULTS</b>At week 20 and 32, the impairments in the lungs were obvious in rats of the model group, while the levels of CD3+, CD4+, CD8+, and CD4+ CD25+ were significantly lower in the peripheral blood and the BALF in the model group than in the controls group (P < 0.05, P < 0.01), and they were higher in the four groups than in the model group (P < 0.05, P < 0.01). However, the levels of CD3+ and CD4+ in the peripheral blood and the BALF were higher in the three TCM-treated groups than in the aminophylline group (P < 0.05, P < 0.01). CD4+ in the peripheral blood in the RFIP group was higher than in the RFIS group and the BQNS group (P < 0.01). At week 20, the ratio of CD4+ /CD8+ was higher in the RFIP group than in the aminophylline group (P < 0.01). CD4+ was higher in the three TCM-treated groups than in the aminophylline group (P < 0.05, P < 0.01). At week 32, the ratio of CD4+ / CD+ in the three TCM- and aminophylline-treated groups was higher than that of the model group (P < 0.05). CD4+ in the RFIP group and the RFIS group was higher than that of the aminophylline group (P < 0.05, P < 0.01). Compared with that at week 20, the ratio of CD4+/CD8+ in the BALF group was significantly higher in the RFIP at week 32 (P < 0.05). The CD4+ CD25+ levels in the peripheral blood and BALF of the BQNS group was significantly lower (P < 0.05).</p><p><b>CONCLUSIONS</b>The efficacy and long-term effects of three methods for regulating and invigorating Fei-Shen might be possibly associated with regulating T lymphocyte subsets (CD3+, CD4+, CD8+, CD4+ / CD8+) and CD4+ CD25+ levels. Of them, RFIP showed significant effects in regulating CD4+ and CD4+ / CD8+ in the peripheral blood and BALF.</p>
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Animais , Feminino , Masculino , Ratos , Medicamentos de Ervas Chinesas , Usos Terapêuticos , Imunidade Celular , Fitoterapia , Métodos , Doença Pulmonar Obstrutiva Crônica , Tratamento Farmacológico , Alergia e Imunologia , Ratos Sprague-Dawley , Subpopulações de Linfócitos T , Alergia e ImunologiaRESUMO
<p><b>OBJECTIVE</b>To evaluate the impact and long-term effect of three prescriptions regulating and tonifying lung and kidney (prescription tonifying lung and spleen, prescription tonifying lung and kidney, and prescription tonifying Qi and kidney) on JAK/STAT signaling of COPD rats.</p><p><b>METHOD</b>Rats were randomly divided into the control group, the model group, the Bufeijianpi group, the Bufeiyishen group, the Yiqizishen group and the aminophyline group. The COPD rat model was established by smoke inhalations and bacterial infections. In the 9th week, the control group and the model group were administered with normal saline, while the remaining groups are orally given corresponding medicines. In the 20th and 32nd week, the rats were sacrificed in batches to observe the pathology in their lung tissues, protein expressions of JAK2, STAT1, STAT3, STAT5, and expressions of JAK2 and SOCS3 mRNA.</p><p><b>RESULT</b>In the 20th and 32nd week, protein expressions of JAK2 mRNA and phosphorylation-JAK2, STAT1, STAT3 and STAT5 in the model group were higher than the control group (P < 0.01), whereas the three traditional Chinese medicine (TCM) (Bufeijianpi, Bufeiyishen and Yiqizishen) groups and the aminophyline group were significantly lower (P < 0.05, P < 0.01). The expression of SOCS3 mRNA in the model group was higher than the control group (P < 0.01), whereas the level was notably higher in the three TCM groups and the aminophylline group (P < 0.01). The three TCM groups were remarkably higher than the aminophylline group (P < 0.05, P < 0.01). Compared with the figures in the 20th week, JAK2 mRNA and phosphorylation-JAK2, STAT3 and STAT5 were significantly lower in the Bufeijianpi group in the 32nd week (P < 0.05, P < 0.01), and so did phosphorylation-STAT3 in Bufeiyishen group (P < 0.01) and phosphorylation-STAT3 and STAT5 in the Yiqizishen group (P < 0.05, P < 0.01). However, the aminophylline group showed no significant difference in above indicators.</p><p><b>CONCLUSION</b>The three medicines regulating and tonifying lung and kidney can effectively relieve injury of lung tissues, and have long-term effect, which may be related to the regulation of JAK/ STAT signaling. Specifically, prescription tonifying lung and spleen shows good effect in reducing JAK2, STAT3 and STAT5, prescription tonifying lung and kidney shows good effect in reducing p-STAT3, and prescription tonifying Qi and kidney shows good effect in reducing p-STAT3 and p-STAT5.</p>