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The heat shock protein 90 (Hsp90) protein family is a cluster of highly conserved molecules that play an important role in maintaining cellular homeostasis. Hsp90 and its co-chaperones regulate a variety of pathways and cellular functions, such as cell growth, cell cycle control and apoptosis. Hsp90 is closely associated with the occurrence and development of tumors and other diseases, making it an attractive target for cancer therapeutics. Inhibition of Hsp90 expression can affect multiple oncogenic pathways simultaneously. Most Hsp90 small molecule inhibitors are in clinical trials due to their low efficacy, toxicity or drug resistance, but they have obvious synergistic anti-tumor effect when used with histone deacetylase (HDAC) inhibitors, tubulin inhibitors or topoisomerase II (Topo II) inhibitors. To address this issue, the design of Hsp90 dual-target inhibitors can improve efficacy and reduce drug resistance, making it an effective tumor treatment strategy. In this paper, the domain and biological function of Hsp90 are briefly introduced, and the design, discovery and structure-activity relationship of Hsp90 dual inhibitors are discussed, in order to provide reference for the discovery of novel Hsp90 dual inhibitors and clinical drug research from the perspective of medicinal chemistry.
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Gallbladder carcinoma,a relatively rare malignancy within the biliary tract,presents a grave prognosis primarily due to asymptomatic early stages leading to advanced stage diagnosis and the absence of efficacious treatment options.Research has identified chronic inflammation,predom-inantly caused by gallstones,as a critical etiological factor.While surgical intervention offers potential curative outcomes in early stages,the majority of cases are identified too late for optimal surgical outcomes.Chemotherapy and targeted therapy,despite offering new therapeutic avenues,have not significantly improved overall survival rates.Thus,understanding the pathogenesis of gallbladder cancer,especially its association with key genetic and molecular pathways,is imperative for devising novel therapeutic strategies.This review delineates the epidemiology,pathogenesis,current treat-ment modalities,and research advancements in gallbladder cancer,aiming to provide innovative in-sights for clinical management and guide future research endeavors.
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【Objective】 To investigate the clinical features and prognostic factors of elderly patients with localized renal cell carcinoma after operation. 【Methods】 Clinical data of all elderly patients (60-100 years old) with localized renal cell carcinoma who underwent primary tumor resection during 2004 and 2017 in United States National Cancer Institute (SEER) database were collected.The clinical features, surgical methods and prognosis were analyzed.According to the surgical methods, the patients were divided into partial nephrectomy (PN) group and radical nephrectomy (RN) group.The effects of the two surgical methods on the prognosis were compared. 【Results】 A total of 20 348 patients were included.The median survival time was 164 months, and the 3-, 5- and 10-year cumulative overall survival rates were 91.1%, 84.2% and 64.4%, respectively.Multivariate Cox analysis showed that age, sex, race, histological grade, T stage and surgical method were independent prognostic factors for overall survival (P0.05). 【Conclusion】 Old age, male, black, non-chromophobe cell carcinoma, low degree of differentiation, high T stage of tumor and RN are independent risk factors for the prognosis of elderly patients with localized renal cell carcinoma.PN is the main treatment method and has remarkable therapeutic effects.
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To study the chemical constituents and their biological activities in the rhizomes of Curcuma phaeocaulis, silica gel column chromatography, reverse medium pressure liquid chromatography, preparative thin layer chromatography, and semi-preparative high performance liquid chromatography were used for isolation and purification and modern spectroscopic methods were used to determine the structure of the isolated compound. Moreover, the effect of the compound on the proliferation of HUVECs was determined by the MTT assay. A new elemane-type sesquiterpenoid glycoside was isolated from the n-butanol soluble fraction of 95% ethanolic extract of the rhizomes of Curcuma phaeocaulis. Its structure was identified as (1Z)-2-hydroxy-curzerenone 2-O-β-D-glucoside. It showed no inhibitory effect on the proliferation of HUVECs.
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Objective: To develop asolvent extraction-direct mercury analyzer method for determination of methylmercury in urine. Methods: After the urinehydrolyzesd by hydrobromic acid, methylmercury was extracted by tolueneand reverse-extracted from L-cysteine solution, it was then detectedbydirect mercuryanalyzer. Results: The linear range was 0.2-50.0 μg/L, and the related coefficient was 0.9999. The relative standard deviations (RSD) within the group were 5.04%-6.64%, and the RSD between the group were 5.65%-8.11 %. The average recovery efficiencies were 85.4%-95.5%. The detection limitation was 0.0482 μg/L and the quantification concentrations was 0.1607 μg/L. Conclusion: The method, which has low detection limit, high sensitivity, easy to operate, is stability for the determination of methylmercury in urine.
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Mercury , Methylmercury CompoundsABSTRACT
ObjectiveTo investigate the risk factors and construct a predictive model for severe myelosuppression due to chemotherapy in triple negative breast cancer (TNBC). MethodsPatients with TNBC who received anthracycline combined with cyclophosphamide sequential paclitaxel chemotherapy regimen at the Second Affiliated Hospital of Nanchang University from September 2, 2016 to September 2, 2021 were selected and assigned to severe myelosuppression group and no/mild myelosuppression group. The χ2 test and binary logistic regression were used to analyze the risk factors for severe myelosuppression due to chemotherapy and to develop a prediction model. Hosmer-Lemeshow test and receiver operating characteristic (ROC) curve were used to evaluate the predictive efficiency of the regression model. Kappa consistency test was used to verify the regression model externally. ResultsA total of 207 patients who met the inclusion were enrolled and 106 patients (51%) had severe myelosuppression. Binary logistic regression multivariate analysis showed that age 40 to 60 years (OR = 3.463, 95% CI: 1.144 to 10.486, P = 0.028), age >60 years (OR = 3.474, 95% CI: 1.004 to 12.020, P = 0.049), body mass index (BMI) 18.5 to 24.0 (OR = 1.445, 95% CI: 0.686 to 3.087, P = 0.328), BMI <18.5 (OR = 3.582, 95% CI: 1.260 to 10.182, P = 0.017), tumor TNM stage Ⅱ (OR = 1.698, 95% CI: 0.831 to 3.468, P = 0.146), tumor TNM stage Ⅲ (OR = 2.943, 95% CI: 1.199 to 7.227, P = 0.019), previous diabetes (OR = 2.441, 95% CI: 1.076 to 5.539, P = 0.033), low pre-treatment albumin level (OR = 2.759, 95% CI: 1.141 to 6.669, P = 0.024) and low pre-treatment lymphocytes (OR = 3.428, 95% CI: 1.689 to 6.958, P = 0.001) were independent risk factors for severe myelosuppression due to chemotherapy. The χ2 value for the logistic regression model Hosmer-Lemeshow test was 11.507, P= 0.175, the area under the ROC curve was 0.763, standard error 0.033, 95% CI: 0.698-0.828, P=0.000. External validation showed that the prediction model had a specificity of 88% and a sensitivity of 80%; the kappa value was 0.679, standard error 0.081, P=0.000. conclusionThis logistic regression model had high predictive efficacy and is useful for clinicians to predict whether patients with TNBC develop severe myelosuppression.
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Objective:To explore the mechanism of action of Coptis chinensis in the treatment of dental caries using a network pharmacology approach and animal experiments. Methods:The active ingredients of C. chinensis and their targets were screened by the traditional Chinese medicine systems pharmacology (TCMSP) database and analysis platform, and the targets were searched online through the GeneCards database. The intersecting targets of C. chinensis and dental caries were screened at Venny 2.1, and the intersection targets were analyzed online for protein-protein interaction analysis and gene ontology (GO) and kyoto encyclopedia of genes and genomics (KEGG) enrichment. Then, Cytoscape was used to create a "component-target-pathway" network diagram. Rats were randomly divided into the model group and the C. chinensis group to establish a rat model of dental caries. Rats in the model group were repeatedly rubbed with a cotton ball soaked in 150 μl of 0.9% NaCl solution for 5 min, and rats in the C. chinensis group were repeatedly rubbed with a cotton ball soaked in C. chinensis (5.8 mg of C. chinensis in 150 μl of 0.9% NaCl solution) for 5 min. The two groups of rats were treated once a week for four consecutive weeks. The number of Streptococcus mutans colonies was counted, and serum serine/threonine protein kinase 1 (AKT1), JUN, interleukin-6 (IL-6), tumor necrosis factor (TNF), and B-cell lymphoma-2 (Bcl-2) were detected by enzyme immunoassay. Results:A total of 11 active ingredients in C. chinensis were found, which regulate multiple molecular pathways by intervening in 54 targets, thereby treating dental caries. Quercetin, berberine, flavodoxin, berberine infusion, and tetrahydroberberine were the core components, and AKT1, JUN, IL-6, TNF, and Bcl-2 were the core targets. GO analysis showed that BP mainly included cytokine activity, signaling receptor activator activity, signaling receptor modulator activity, cytokine receptor binding, and receptor ligand activity, etc.; and CC mainly included the response to lipopolysaccharides, the response to bacterial molecules, cellular responses to lipids, inflammatory responses, and negative regulation of cell population proliferation; MF mainly includes membrane rafts, membrane microregions, extracellular matrix, external encapsulated structures, and plasma membrane protein complexes, etc. KEGG analysis showed that advanced glycosylation end product-receptor for advanced glycosylation end products (AGE-RAGE), TNF, IL-17, Toll-like receptor, hypoxia-inducible factor-1 (HIF-1), mitogen-activated protein kinase (MAPK), nuclear factor-κB (NF-κB), epidermal growth factor receptor (EGFR), Janus kinase-signal transducer and activator of transcription (JAK-STAT), and phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) signaling pathways have been associated with C. chinensis treatment. The results of animal experiments showed that serum Bcl-2 protein expression increased and serum AKT1, JUN, IL-6, TNF, and other proteins decreased after the C. chinensis treatment. Conclusions:C. chinensis can be involved in regulating the targets of dental caries through multiple pathways, with good therapeutic effects and a wide range of mechanisms of action, and is expected to be an important component in the development of proprietary Chinese medicines for the treatment of dental caries.
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The hydrolysis of xylo-oligosaccharides catalyzed by β-xylosidase plays an important role in the degradation of lignocellulose. However, the enzyme is easily inhibited by its catalytic product xylose, which severely limits its application. Based on molecular docking, this paper studied the xylose affinity of Aspergillus niger β-xylosidase An-xyl, which was significantly differentially expressed in the fermentation medium of tea stalks, through cloning, expression and characterization. The synergistic degradation effect of this enzyme and cellulase on lignocellulose in tea stems was investigated. Molecular docking showed that the affinity of An-xyl to xylose was lower than that of Aspergillus oryzae β-xylosidase with poor xylose tolerance. The Ki value of xylose inhibition constant of recombinant-expressed An-xyl was 433.2 mmol/L, higher than that of most β-xylosidases of the GH3 family. The Km and Vmax towards pNPX were 3.6 mmol/L and 10 000 μmol/(min·mL), respectively. The optimum temperature of An-xyl was 65 ℃, the optimum pH was 4.0, 61% of the An-xyl activity could be retained upon treatment at 65 ℃ for 300 min, and 80% of the An-xyl activity could be retained upon treatment at pH 2.0-8.0 for 24 h. The hydrolysis of tea stem by An-xyl and cellulase produced 19.3% and 38.6% higher reducing sugar content at 2 h and 4 h, respectively, than that of using cellulase alone. This study showed that the An-xyl mined from differential expression exhibited high xylose tolerance and higher catalytic activity and stability, and could hydrolyze tea stem lignocellulose synergistically, which enriched the resource of β-xylosidase with high xylose tolerance, thus may facilitate the advanced experimental research and its application.
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Aspergillus niger/genetics , Xylose/metabolism , Molecular Docking Simulation , Xylosidases/genetics , Cellulases , Tea , Hydrogen-Ion Concentration , Substrate SpecificityABSTRACT
Scopoletin is a coumarin compound with various biological activities including detumescence and analgesic, insecticidal, antibacterial and acaricidal effects. However, interference with scopolin and other components often leads to difficulties in purification of scopoletin with low extraction rates from plant resource. In this paper, heterologous expression of the gene encoding β-glucosidase An-bgl3 derived from Aspergillus niger were carried out. The expression product was purified and characterized with further structure-activity relationship between it and β-glucosidase analyzed. Subsequently, its ability for transforming scopolin from plant extract was studied. The results showed that the specific activity of the purified β-glucosidase An-bgl3 was 15.22 IU/mg, the apparent molecular weight was about 120 kDa. The optimum reaction temperature and pH were 55 ℃ and 4.0, respectively. Moreover, 10 mmol/L metal ions Fe2+ and Mn2+ increased the enzyme activity by 1.74-fold and 1.20-fold, respectively. A 10 mmol/L solution containing Tween-20, Tween-80 and Triton X-100 all inhibited the enzyme activity by 30%. The enzyme showed affinity towards scopolin and tolerated 10% methanol and 10% ethanol solution, respectively. The enzyme specifically hydrolyzed scopolin into scopoletin from the extract of Erycibe obtusifolia Benth with a 47.8% increase of scopoletin. This demonstrated that the β-glucosidase An-bgl3 from A. niger shows specificity on scopolin with good activities, thus providing an alternative method for increasing the extraction efficiency of scopoletin from plant material.
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Aspergillus niger/genetics , beta-Glucosidase/chemistry , Scopoletin , Polysorbates , CoumarinsABSTRACT
Irritable bowel syndrome (IBS) is a common refractory disease. Chinese medicine (CM) has remarkable efficacy and advantages on the treatment of IBS. This review summarized the articles focusing on the treatment of IBS with CM to sum up the latest treatment methods for IBS and the underlying mechanisms. Literature analysis showed that prescriptions, acupuncture, and moxibustion are the primary methods of CM treatment for IBS. The potential mechanism centers on the regulation of the enteric nervous system, the alleviation of visceral hypersensitivity, the stability of intestinal flora, and the regulation of the immune system.
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Humans , Irritable Bowel Syndrome/therapy , Medicine, Chinese Traditional , Acupuncture Therapy/methods , MoxibustionABSTRACT
This study aimed to investigate the therapeutic effect of Leonuri Herba aqueous decoction on primary dysmenorrhea(PD) and explore the underlying mechanism in conjunction with untargeted metabolomics. Forty adult female rats were randomly divi-ded into a normal group, a model control group, ibuprofen(0.12 g·kg~(-1)) group, and high-and low-dose Leonuri Herba aqueous decoction(5 and 2.5 g·kg~(-1)) groups, with eight rats in each group. The PD rat model was prepared using intramuscular injection of estradiol benzoate combined with intraperitoneal injection of pitocin. Drugs were administered by gavage from the 4th day of modeling for 7 d. After the last administration, pitocin was injected intraperitoneally, and the writhing latency and writhing times within 30 min were recorded. The uterine and ovarian coefficients were determined. Estradiol(E_2), progesterone(Prog), oxytocin(OT), cyclooxyge-nase 2(COX-2), prostaglandin E_2(PGE_2), prostaglandin F_(2α)(PGF_(2α)), and Ca~(2+) levels in uterine tissues were measured by ELISA and biochemical kits. Morphological changes in uterine and ovarian tissues were observed by hematoxylin-eosin(HE) staining. The protein expression of oxytocin receptor(OTR), prostaglandin E_2 receptor 3(EP3), and estrogen receptor alpha(ERα) in uterine tissues was detected by immunohistochemistry. The mRNA expression of OTR, PGE_2 receptors 1-4(EP1, EP2, EP3, and EP4), and PGF_(2α) receptor(FP) in uterine tissues was detected by quantitative real-time PCR. Untargeted metabolomics analysis was performed by ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(LC-QTOF-MS) technology to screen potential biomarkers and enrich metabolic pathways. The results showed that Leonuri Herba was able to significantly reduce the writhing times in PD rats(P<0.05 or P<0.01), significantly reduce the uterine and ovarian coefficients(P<0.01), and improve their histomorphology. After treatment with Leonuri Herba, PGE_2 content was significantly increased(P<0.05), COX-2, PGF_(2α) and Ca~(2+) content, and PGF_(2α)/PGE_2 was significantly decreased(P<0.05 or P<0.01), and OT content was decreased, while E_2 and Prog content tended to further increase in uterine tissues of PD rats. Correspondingly, OTR and EP3 protein expression was significantly downregulated(P<0.05 or P<0.01) and ERα protein expression was upregulated(P<0.05) in uterine tissues. The mRNA expression of FP and EP4 in uterine tissues was significantly downregulated(P<0.01), and the mRNA expression of EP1, EP3, and OTR showed a decreasing trend. The untargeted metabolomics results showed that 10 differential metabolites were restored in the plasma of PD rats after Leonuri Herba treatment. The results indicate that Leonuri Herba is effective in the prevention and treatment of PD, and the underlying mechanism may be attributed to the regulation of PGs synthesis and corresponding receptor binding.
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Humans , Rats , Female , Animals , Estrogen Receptor alpha , Oxytocin , Dysmenorrhea/metabolism , Cyclooxygenase 2 , Dinoprostone , RNA, Messenger/metabolism , DinoprostABSTRACT
ObjectiveTo investigate the effect of Zhishi Xiebai Guizhitang (ZXGT) on isoproterenol (ISO)-induced myocardial infarction (MI) in rats through the tumor necrosis factor/nuclear factor-κB (TNF/NF-κB) signaling pathway. MethodForty-eight SD rats were randomly divided into control group (blank), model group, perindopril group (4 mg·kg-1), ZXGT group (24.4 g·kg-1), ZXGT +inhibitor group (ZXGT, 24.4 g·kg-1, TNF-α receptor inhibitor R7050, 5 mg·kg-1), and an inhibitor group (R7050, 5 mg·kg-1), with eight rats in each group. The rats in each group were orally administered with their respective drugs for 7 days. Additionally, in the ZXGT + inhibitor group and the inhibitor group, R7050 was injected intraperitoneally at a dose of 5 mg·kg-1 on the 6th and 7th days. Except for the control group, all other groups were given intraperitoneal injections of ISO for 2 consecutive days to induce MI in rats. On the 7th day of the experiment, the rats were anesthetized 30 min after ISO injection, and their electrocardiograms (ECGs) were recorded to observe ST-segment elevation. Small animal echocardiography was used to measure global longitudinal strain (GLS) and cardiac synchrony. Blood samples were collected from the abdominal aorta to measure the levels of serum cardiac troponin T (cTnT), creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β). Histopathological changes in myocardial tissue were observed using hematoxylin-eosin (HE) staining. Immunohistochemistry (IHC) was used to detect the expression of TNF-α, NF-κB p65, and p-NF-κB p65 proteins in myocardial tissue. Western blot was performed to measure the expression of tumor necrosis factor receptor 1 (TNFR1), tumor necrosis factor receptor-associated factor 2 (TRAF2), transforming growth factor-beta-activated kinase 1 (TAK1), NF-κB inhibitory protein alpha (IκBα), phosphorylated (p)-IκBα, NF-κB p65, and p-NF-κB p65 proteins in myocardial tissue. ResultCompared with the control group, the model group showed significant ST segment elevation on the ECG (P<0.01), increased GLS, and reduced cardiac synchrony on echocardiography (P<0.01). Histopathological examination revealed extensive myocardial necrosis. Furthermore, the serum levels of cTnT, CK-MB, LDH, TNF-α, and IL-1β were significantly increased (P<0.01), and the expression levels of TNF-α, TNFR1, TRAF2, TAK1, p-IκBα, and p-NF-κB p65 proteins in myocardial tissue were significantly elevated (P<0.01), while the expression level of IκBα was significantly decreased (P<0.01). Compared with the model group, the perindopril group, the ZXGT group, the ZXGT + inhibitor group, and the inhibitor group rats showed a significant reduction in ST-segment elevation on the ECG (P<0.05, P<0.01), improvement in GLS and cardiac synchrony (P<0.05, P<0.01), a decrease in the area of myocardial necrosis, and reduced serum levels of cTnT, CK-MB, LDH, TNF-α, and IL-1β (P<0.01). Additionally, the ZXGT group, the ZXGT + inhibitor group, and the inhibitor group downregulated the increased TNF-α, TNFR1, TRAF2, TAK1, p-IκBα, and p-NF-κB p65 protein expression levels and upregulated IκBα expression levels in the myocardial tissue (P<0.05, P<0.01). No significant differences were observed between the ZXGT group and the ZXGT + inhibitor group or the inhibitor group. ConclusionZXGT can protect against ISO-induced myocardial injury in rats and improve cardiac function, and its mechanism of action may be related to the regulation of the TNF/NF-κB signaling pathway.
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Objective To investigate the effect of Water-soluble total alkaloids of Yimucao Injection(YITA)on postpartum uterine involution.Methods A guinea pig abortion model was established by drug method.0.17 g·kg-1 YITA was intragastrically administered to record the amount of bleeding and the contents of E2 and P in serum of guinea pigs after delivery.The uterine coefficient was calculated and the contents of NO,ET-1 and Ca2+ in uterine tissue were measured.The isolated uterine model and the in vivo uterine model were prepared by guinea pigs.The former was given YITA 0.05,0.1 and 0.2 mg·mL-1,and the latter was intramuscularly injected with YITA 10,20 and 40 mg·kg-1.The changes of uterine smooth muscle(USM)contractile activity,frequency and tension were recorded by biological function test system.Results Intragastric administration of YITA could decrease the uterine coefficient(P<0.001),NO content in uterine tissue and serum P content in guinea pigs with medical abortion(P<0.01),significantly increased ET/NO ratio(P<0.001);it tended to increase Ca2+ content in uterine tissue(P<0.1).In the isolated USM test,50 and 100 mg·L-1 YITA significantly increased USM contractile activity in guinea pigs(P<0.05),and 200 mg·L-1 YITA significantly decreased USM contractile minimum in guinea pigs(P<0.05)in the in vivo USM contractile test,YITA enhanced USM contractile activity,and 40 mg·kg-1 YITA significantly increased USM contractile activity and frequency in guinea pigs(P<0.05);10 mg·kg-1 YITA significantly increased USM contractile frequency in guinea pigs(P<0.05)and tended to increase motility(P=0.0569<0.1);20 mg·kg-1 YITA tended to increase frequency(P=0.0898,0.0699 respectively,<0.1).Conclusion YITA has the effect of promoting uterine involution,and the mechanism is related to the regulation of ET/NO balance and the direct promotion of USM contraction.YITA is an effective substance for uterine contraction and hemostasis with leonurus injection in the treatment of postpartum hemorrhage and uterine involution.
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Objective To explore the therapeutic effect and toxicity of Croton tiglium L.(croton)oil on rats with cold accumulation constipation,and to clarify the toxic-effect relationship of croton oil in the treatment of cold accumulation constipation.Methods The rats were orally treated with 10%2℃activated carbon solution for 3 consecutive days to replicate the model of cold constipation.The rats were fed with croton oil on the fourth day,and then the time of first defecation and the number of defecations within 3 h were observed and recorded.HE staining was used to evaluate the general pathological conditions of the colon tissues of rats.The serum levels of interleukin(IL)-6,IL-10,tumor necrosis factor(TNF)-α,cyclooxygenase(COX)-2,macrophage inflammatory protein(MIP)-1,alanine aminotransferase(ALT),aspartate aminotransferase(AST),and total protein(TP)were detected.Immunohistochemistry was used to detect the expression of myeloid differentiation factor 88(MyD88)and nuclear transcription factor(NF)-κB P65 in colon tissues of rats.Results Croton oil could shorten the time of first defecation and increase the number of defecations within 3h in rats with cold accumulation constipation to varying degrees,and the 3.78,2.83,and 1.89 g·kg-1 croton oil group had significant statistical significance(P<0.05).HE staining results showed that compared with the model group,croton oil group could cause different degrees of inflammation and focal necrosis,goblet cell loss and lamina propria edema in the colon tissue of rats,and the 3.78 g·kg-1 croton oil group was the most serious in the colon tissue injury.In addition,compared with model group,croton oil group could increase the levels of COX-2,TNF-α and IL-6 in serum to varying degrees(P<0.05),and 3.78 g·kg-1 croton oil group had the most obvious effect.The level of MIP-1 in serum was increased in croton oil group,and the effect was significant in 3.78 g·kg-1 croton oil group(P<0.01).But croton oil group had no significant effect on serum IL-10 level of rats.The immunohistochemical results showed that the protein levels of MyD88 were increased in croton oil dose groups except 0.05 dose group,and there were significant differences in 3.78,2.83,and 1.89 g·kg-1 dose groups(P<0.05).The expression level of NF-κB p65 was enhanced in the colon of rats after croton oil treatment,and there was significant difference in 3.78 g·kg-1 croton oil group(P<0.05).In addition,compared with model group,croton dose groups had no changes in organ indexes of heart,spleen,lung,kidney and thymus(P>0.05),while liver organ indexes in1.89 and 0.94 g·kg-1 croton oil groups were significantly increased(P<0.05).The results of liver biochemical indexes showed that croton oil group did not increase the contents of ALT,AST,and TP in serum of rats,and the differences were not statistically significant(P>0.05).Conclusion Croton oil can exert a dose-dependent purgative effect at 3.78,2.83,and 1.89 g·kg-1,but it also induced colonic mucosal injury in rats by regulating the inflammatory response mediated by the MyD88/NF-κB pathway.At 0.94 and 0.47 g·kg-1,croton oil almost did not cause colon tissue injury in rats,but it had a weak purgative effect at this dose,suggesting that the best concentration range of croton oil in the treatment of cold accumulation constipation may be between 0.94 and 1.89 g·kg-1.
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Sodium dichloroacetate (DCA) is a small molecule drug usually administered orally. It has therapeutic effects against several diseases, such as metabolic syndrome, cardiovascular and cerebrovascular diseases, and several solid tumors. In this review, the research progresses of DCA in mechanism of action, pharmacological action and toxicological studies were summarized from the recent literatures on the pharmacological actions of DCA.
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Objective:To explore the effect of early clinical clerkship training in the early exposure to clinical practice of eight-year program medical students.Methods:Experimental control method was used in this study. A total of 120 eight-year program medical students in the third year of Batch 2014 to 2016 from the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology were selected as the research objects. The students of each grade were randomly selected by computer and divided into experimental group and control group, with 20 students in each group. Before early clinical exposure, the experimental group received 16 class hours of early clinical clerkship training, while the control group did not receive early clinical clerkship training. After the early clinical exposure, the clinical diagnosis and treatment ability of the two groups of students was compared. SPSS 24.0 software was used for t test. Results:The scores of medical history inquiry of experimental group and control group were [(17.45±1.96) points and (15.95±1.93) points; (18.30±1.03) points and (16.75±1.86) points; (17.95±1.36) points and (16.40±1.60) points, respectively]. The physical examination scores were [(17.75±1.65) points and (16.05±1.64) points; (17.85±1.18) points and (16.80±1.47) points; (18.25±1.16) points and (16.85±1.63) points, respectively]. The clinical judgment scores were [(18.15±1.42) points and (16.35±2.41) points; (18.20±1.24) points and (16.65±1.53) points; (18.35±1.35) points and (16.25±1.83) points, respectively]. Diagnosis and treatment scheme scores were [(17.15±1.57) points and (14.55±2.56) points; (17.30±1.42) points and (15.90±1.48) points; (17.80±1.06) points and (16.35±1.87) points, respectively]. The scores of communication skills were [(17.95±1.15) points and (17.00±1.19) points; (18.55±0.83) points and (17.45±1.50) points; (18.45±1.00) points and (17.45±1.23) points, respectively], with statistically significant differences (all P<0.05). Conclusion:The application of early clinical clerkship training in the early exposure to clinical practice of eight-year program medical students can improve the quality of students' clerkship.
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BACKGROUND@#Hyaluronic acid dermal fillers are composed of cross-linked viscoelastic particles with high biocompatibility. The performance of the fillers is determined by the viscoelastic properties of particles and the connecting force between particles. However, the relationships among the properties of fillers, the interaction of the gels and the surrounding tissue are not clear enough.METHOD: Four kinds of typical dermal filler were selected in this research to reveal the interaction between the gels and cells. A series of analytical tools was applied to characterize the structure and physicochemical properties of the gel, as well as observing their interaction with the surrounding tissues in vivo and discussing their internal mechanism.RESULT: The large particles internal the gel and the high rheological properties endow the Restylane2 with excellent support. However, these large-size particles have a significant impact on the metabolism of the local tissue surrounding the gel. Juvéderm3 present gel integrity with the high cohesiveness and superior support. The rational matching of large and small particles provides the Juvéderm3 with supporting capacity and excellent biological performance. Ifresh is characterized by small-size particles, moderate cohesiveness, good integrity, lower viscoelasticity and the superior cellular activity located the surrounding tissues. Cryohyaluron has high cohesion and medium particle size and it is prominent in cell behaviors involving localized tissues. Specific macroporous structure in the gel may facilitate the nutrients delivering and removing the waste. @*CONCLUSION@#It’s necessary to make the filler both sufficient support and biocompatibility through the rational matching of particle sizes and rheological properties. Gels with macroporous structured particle showed an advantage in this area by providing a space inside the particle.
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To analyze the changes of coagulation function in severe fever with thrombocytopenia syndrome (SFTS) and its relationship with thrombocytopenia, and to explore its value as an early predictor of the severity of SFTS. The clinical data of 428 SFTS patients (70 deaths and 358 survivors) admitted to the Department of Infectious Disease at Wuhan Union Hospital from January 2014 to July 2020 were retrospectively analyzed. The differences of coagulation parameters and disseminated intravascular coagulation (DIC) scores between the two groups were compared. The results showed that abnormal coagulation function was commonly presented in SFTS patients. Bleeding was more frequent in mortality group (41.4% vs. 26.5%). The D-dimer levels in mortality patients were significantly higher above normal range. Activated partial thrombin time (APTT) and thrombin time (TT) were significantly prolonged. The levels of prothrombin time (PT), TT, APTT, international standardized ratio (INR) and D-dimer between mortality group and survival group started to separate from day 5-6. The difference of fibrinogen (FIB) level developed on day 7-8, while platelet counts between the two groups were significant different from day 9-10. The mortality rate increased according to the increase of baseline DIC score. When DIC score reached 6, the mortality rate surged to 66.67%. Excessive platelet consumption is mediated by significant coagulation abnormalities during disease course, and coagulation parameters are more sensitive than platelet count as an early predictor of severe SFTS.
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A new compound was isolated from the 95% ethanolic extract of the rhizomes of Curcuma longa L. using silica gel column chromatography, medium pressure liquid chromatography, and semi-preparative high performance liquid chromatography. The structure and absolute configuration of the compound was elucidated by HR-ESI-MS, NMR, and electronic circular dichroism (ECD) calculations. It is a novel sesquiterpenoid, which is named as isoturmeronol B (1). The carbon skeleton of compound 1 is similar to that of bisabolane-type sesquiterpenoid. The only difference is that the methyl group at C-4 in bisabolene-type sesquiterpenoid is migrated to C-5 in compound 1. Besides, the anti-inflammatory and antioxidant activities of the compound 1 were evaluated. The results showed that 1 has no anti-inflammatory and antioxidant activities.
ABSTRACT
To investigate the chemical constituents of Anisodus tanguticus, silica gel column chromatography, Sephadex LH-20 column chromatography, preparative thin layer chromatography, and semi-preparative HPLC were used to separate and purify the chemical constituents from the extract of A. tanguticus. The planar structure of the isolated compound was identified by HRMS, IR, and 2D NMR experiments. The absolute configuration of the isolated compound was determined by a combination of NOESY, coupling constant, circular dichroism (CD), and transition metal chelate reagent dimolybdenum tetraacetate [Mo2(OAc)4]-induced circular dichroism (ICD) data analysis. A new compound of the anisotane-type sesquiterpene (1) was isolated, which was determined to be (1R,2S,3R,4R,6R,7R,9R)-anisotane-11(13)-ene-3,4,9-triol and named anisotanol F. This is the second report of anisotane-type sesquiterpene, which has previously been reported as a novel sesquiterpenoid skeleton by our research group. Furthermore, the cytotoxicity against HUVECs and inhibitory effect on NO release in LPS-induced RAW264.7 cells of compound 1 were investigated. However, the results showed that it was inactive. Compound 1 is a new compound isolated from A. tanguticus. It belongs to the unusual anisotane-type sesquiterpene. This result enriches the chemical composition of A. tanguticus.