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Objective To explore the antimicrobial resistance of carbapenem-resistant Klebsiella pneumoniae(CRKP)isolated from blood and the related risk factors for infection in patients.Methods Clinical data of 383 KP-infected patients from whose blood Klebsiella pneumoniae(KP)were isolated during hospitalization period in a hos-pital from January 2018 to December 2021 were retrospectively analyzed.Patients were divided into CRKP group(n=114)and non-CRKP group(n=269)based on antimicrobial resistance.According to the prognosis,114 patients in the CRKP group were subdivided into the death group(n=30)and the survival group(n=84).General informa-tion,underlying diseases,antimicrobial use,and infection outcomes of two groups of patients were compared,and risk factors for infection and death after infection were analyzed.Results The resistance rates of KP to tigecycline and compound sulfamethoxazole showed upward trends,with statistically significant differences(both P=0.008).The CRKP group had higher resistance rates to amikacin,aztreonam,compound sulfamethoxazole,ciprofloxacin,cefepime,cefoperazone/sulbactam,piperacillin/tazobactam,tigecycline,ceftazidime,tobramycin,and levofloxacin,as well as higher in-hospital mortality than the non-CRKP group,with statistically significant differences(all P＜0.05).Acute pancreatitis prior to infection(OR=16.564,P＜0.001),hypoalbuminemia(OR=8.588,P＜0.001),stay in in-tensive care unit prior to infection(OR=2.733,P=0.017),blood transfusion(OR=3.968,P=0.001),broncho-scopy(OR=5.194,P=0.014),surgery within 30 days prior to infection(OR=2.603,P=0.010),and treatment with carbapenems(OR=2.663,P=0.011)were independent risk factors for the development of CRKP blood-stream infection(BSI).Cardiac insufficiency before infection(OR=11.094,P=0.001),combined with pulmonary infection(OR=20.801,P=0.010),septic shock(OR=9.783,P=0.002),disturbance of consciousness(OR=11.648,P=0.001),and receiving glucocorticoid treatment(OR=5.333,P=0.018)were independent risk factors for mortality in patients with CRKP BSI.Conclusion The resistance rate of KP from BSI to tigecycline and com-pound sulfamethoxazole presents upward trend.Underlying diseases,invasive procedures,and carbapenem treat-ment are closely related to CRKP BSI.Cardiac insufficiency,pulmonary infection,septic shock,disturbance of con-sciousness,and glucocorticoid treatment can lead to death of patients with CRKP BSI.
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Objective To investigate the effect of brachial plexus block on stress response in patients who underwent shoulder arthroscopic surgery.Methods A total of 150 patients with shoulder arthritis who underwent shoulder arthroscopic surgery in the Shanghai Fifth People's Hospital,Fudan University from December 2021 to December 2022 were selected as the study subjects.All patients were divided into the control group and the observation group by random number table method,with 75 cases in each group.Patients in the control group were given general anesthesia,while patients in the observation group were given brachial plexus block on the basis of the control group.The mean arterial pressure(MAP),heart rate(HR),norepinephrine(NE),cortisol(Cor)before operation(T0),10 minutes after operation(T1),30 minutes after operation(T2),at the end of operation(T3)and 30 minutes after extubation(T4)of the two groups were compared.The transforming growth factor-β1(TGF-β1),tumor necrosis factor-α(TNF-α),C-reactive protein(CRP)before and 3 days after operation of the two groups were compared.The visual analogue scale(VAS)scores at postoperative wakefulness and 6,12 and 24 hours after operation of the two groups were compared.Results Compared with T0,the levels of MAP and HR at T1,T2,T3,and T4 in the observation group and the control group were obviously decreased(P<0.01),the levels of NE and Cor were obviously increased(P<0.01),while the levels of MAP,HR,NE,and Cor at T1,T2,T3,and T4 in the observation group were obviously lower than those in the control group(P<0.01).The levels of TGF-β1,TNF-α,and CRP 3 days after operation in the observation group and the control group were obviously increased compared with those before operation (P<0. 01), and the above indicators after operation in the observation group were obviously lower than those in the control group (P<0. 01). The VAS scores at postoperative wakefulness and 6, 12 and 24 hours after operation in the observation group were obviously lower than those in the control group (P<0. 01). Conclusion Ultrasound-guided brachial plexus block by interscalene approach can ensure the stability of the vital signs of patients with shoulder arthritis during shoulder arthroscopic surgery, alleviate pain, reduce stress, and reduce inflammatory response.
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Objective To study the diagnostic value of miR-571 for liver fibrosis by detecting miR-571 expression in the peripheral blood of patients with liver fibrosis.Methods From December 2022 to September 2023,40 patients with liver fibrosis,40 patients with chronic hepatitis,and 40 healthy controls were chosen as research subjects.The expression level of miR-571 in peripheral blood was detected using a real-time quantitative polymerase chain reaction,and the relative expression of miR-571 in each group was evaluated.The Spearman correlation method was utilized to examine the relationship between miR-571 and clinical detection indices.To assess the capacity of miR-571 and the multivariate diagnostic model to identify liver fibrosis,binary logistic regression was used to create a multivariate diagnostic model,and ROC curves were generated.Results The expression of miR-571 was significantly higher in the liver fibrosis group than in the healthy control and hepatitis groups,and the difference was statistically significant(P<0.001).The expression level of miR-571 was positively connected with ALT,APRI score,and FIB-4 index(r = 0.23,0.30,0.22,P<0.05)and negatively correlated with PLT(r =-0.19,P<0.05)according to Spearman correlation analysis.Logistic regression research revealed that miR-571 and the FIB-4 index were independent risk factors for liver fibrosis.The AUC for miR-571 to diagnose fibrosis was 0.91(95%CI:0.85～0.96),while the AUC for miR-571 paired with the FIB-4 index was 0.94(95%CI:0.90～0.98).Conclusion MiR-571 expression was shown to be considerably higher in the peripheral blood of hepatic fibrosis patients,and the combined FIB-4 index offers some clinical diagnostic value for hepatic fibrosis.
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Objective To investigate the sleep disorders and its effects on the changes in quality of life in patients with liver cancer from the hospital admission to 6 months after surgery and to analyse the correlation between the sleep disorder and quality of life.Methods A total of 214 patients who underwent surgery for liver cancer for the first time were included in the study.Demographic questionnaire,Pittsburgh sleep quality index(PSQI),and functional assessment of cancer therapy-hepatobiliary(FACT-Hep)were used for the investigation at admission and at 1,3 and 6 months after surgery.Multiple linear regression was employed to analyse the correlation between the sleep disorders at the admission and its effect on quality of life up to 6 months after surgery.Results Toally 214 patients finished the study at admission and 209 finished the study 1 month after surgery,and 208 finished the stuoly 3 months after surgery,and 205 patients finished the study 6 months after surgery.The scores of both of PSQI at admission and the quality of life at 6 months after surgery varied across the tested time points with a statistically significant difference(both P<0.001).The overall level of sleep disorder in the patients showed a characteristic pattern with initially increasing and then decreasing,and the quality of life presented a characteristic tendency of starting from high to low and then gradually increasing.It showed that the sleep disorder at admission was attributive to the poorer quality of life at 6 months after surgery.The hierarchical regression analysis showed that among the patients at BCLC Stage A,sleep disorder at admission was the influencing factor of the quality of life at 6 months after surgery.Conclusions The sleep disorder and quality of life in the patients who had surgical operations for hepatocellular carcinoma both changed dynamically from admission to the 6 months after surgery.The quality of life was poor in the patients with sleep disorder at admission.Therefore,medical staff should enhance the sleep management at admission,conduct dynamic assessment of the sleep disorder and quality of life of the patients,and then develop continuity nursing measures to improve the quality of life after surgery.
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Objective To prepare a nano drug(PFOB@Lip-MMC)with liposome as the carrier,liquid perfluorooc-tyl bromide(PFOB)as core and mitomycin C(MMC)loading on the liposome shell and study its inhibitory effect on the proliferation of human pterygium fibroblasts(HPFs).Methods The thin film dispersion-hydration ultrasonic method was used to prepare PFOB@Lip-MMC and detect its physical and chemical properties.Cell Counting Kit-8,Cam-PI cell viability staining and flow cytometry were employed to detect the impact of different concentrations of PFOB@Lip-MMC on the via-bility of HPFs.DiI fluorescence labeled PFOB@Lip-MMC was used to observe the permeability of the nano drug to HPFs under a laser confocal microscope.After establishing HPF inflammatory cell models,they were divided into the control group(with sterile phosphate-buffered saline solution added),PFOB@Lip group(with PFOB@Lip added),MMC group(with MMC added),PFOB@Lip-MMC group(with PFOB@Lip-MMC added)and normal group(with fresh culture medi-um added)according to the experimental requirements.After co-incubation for 24 h,flow cytometer was used to detect the apoptosis rate of inflammatory cells,and the gene expression levels of interleukin(IL)-1β,prostaglandin E2(PGE2),tumor necrosis factor(TNF)-α and vascular endothelial growth factor(VEGF)in cells were analyzed by PCR.Results The average particle size and Zeta potential of PFOB@Lip-MMC were(103.45±2.17)nm and(27.34±1.03)mV,respec-tively,and its entrapped efficiency and drug loading rate were(72.85±3.28)％and(34.27±2.04)％,respectively.The sustained-release MMC of drug-loaded nanospheres reached(78.34±2.92)％in vitro in a 24-hour ocular surface environ-ment.The biological safety of PFOB@Lip-MMC significantly improved compared to MMC.In terms of the DiI fluorescence labeled PFOB@Lip-MMC,after co-incubation with inflammatory HPFs for 2 h,DiI fluorescence labeling was diffusely dis-tributed in the cytoplasm of inflammatory HPFs.The apoptosis rate of inflammatory HPFs in the PFOB@Lip-MMC group[(77.23±4.93)％]was significantly higher than that in the MMC group[(51.62±3.28)％].The PCR examination results showed that the gene transcription levels of IL-1 β,PGE2,TNF-α and VEGF in other groups were significantly reduced com-pared to the control group and PFOB@Lip group,with the most significant decrease in the PFOB@Lip-MMC group(all P＜0.05).Conclusion In this study,a novel nano drug(PFOB@LIP-MMC)that inhibited the proliferation of HPFs was successfully synthesized,and its cytotoxicity was significantly reduced compared to the original drugs.It has good bio-compatibility and anti-inflammatory effects,providing a new treatment approach for reducing the recurrence rate after pte-rygium surgery.
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Objective To evaluate the relationship between diabetic nephropathy(DN)and diabetic retinopathy(DR)in patients with type 2 diabetes mellitus(T2DM)based on imaging and clinical testing data.Methods Totally 600 T2DM patients who visited the First People's Hospital of Ziyang from March 2021 to December 2022 were included.The fundus photography and fundus fluorescein angiography were performed on all these patients and their age,gender,T2DM duration,cardiovascular diseases,cerebrovascular disease,hypertension,smoking history,drinking history,body mass in-dex,systolic blood pressure,diastolic blood pressure and other clinical data were collected.The levels of fasting blood glu-cose(FPG),triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),low-density lipo-protein cholesterol(LDL-C),glycosylated hemoglobin(HbA1c),24 h urinary albumin(UAlb),urinary albumin to creati-nine ratio(ACR),serum creatinine(Scr)and blood urea nitrogen(BUN)were measured.Logistic regression was used to analyze the risk factors associated with DR.DR staging was performed according to fundus images,and the convolutional neural network(CNN)algorithm was used as an image analysis method to explore the correlation between DR and DN based on emission computed tomography(ECT)and clinical testing data.Results The average lesion area rates of DR and DN detected by the CNN in the non-DR,mild-non-proliferative DR(NPDR),moderate-NPDR,severe-NPDR and pro-liferative DR(PDR)groups were higher than those obtained by the traditional algorithm(TCM).As DR worsened,the Scr,BUN,24 h UAlb and ACR gradually increased.Besides,the incidence of DN in the non-DR,mild-NPDR,moderate-NPDR,severe-NPDR and PDR groups was 1.67％,8.83％,16.16％,22.16％and 30.83％,respectively.Logistic regression analysis showed that the duration of T2DM,smoking history,HbA1c,TC,TG,HDL-C,LDL-C,24 h UAlb,Scr,BUN,ACR and glomerular filtration rate(GFR)were independent risk factors for DR.Renal dynamic ECT analysis demonstrated that with the aggravation of DR,renal blood flow perfusion gradually decreased,resulting in diminished renal filtration.Conclusion The application of CCN in the early stage DR and DN image analysis of T2DM patients will improve the diag-nosis accuracy of DR and DN lesion area.The DN is worsening as the aggravation of DR.
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Dental pulp stem cells (DPSC) are pluripotent stem cells with high differentiation potential isolated from dental pulp. Using DPSC for vascular regeneration may be a good option. Hypoxia inducible factor-1α (HIF-1α) is an upstream gene of vascular endothelial growth factor (VEGF), and the small ubiquitin like protease 1 (SENP1) can reverse the small ubiquitin like (SUMO) modification of HIF-1α. Through the regulation of SENP1/HIF-1α, good vascular regeneration characteristics have been demonstrated in many in vitro and in vivo experiments. The SENP1/HIF-1α signaling axis has varying degrees of promoting and inhibiting effects on many solid tumors. Although there is relatively little literature on the role of the SENP1/HIF-1α signaling axis in dental pulp stem cells, it can be determined that SENP1/HIF-1α plays an important role in the angiogenesis of dental pulp stem cells. This article will elucidate the SENP1/HIF-1α signaling pathway and its mechanism of promoting vascular differentiation of DPSC.
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Polystyrene nanoplastics (PS-NPs) are widely used in industry, pharmaceutical and consumer packaging materials, and medical products. The biological health impacts of PS-NPs are receiving increasing attention. Therefore, it is necessary to conduct a literature review of in vitro and in vivo experimental studies from a biological mechanism perspective. Based on the latest research results at home and abroad, this review introduced the characteristics and cell internalization of PS-NPs in cytotoxicity experiments, and summarized the effects of PS-NPs on cytotoxic targets such as mitochondria, lysosomes, proteins, and DNA. In addition, the influencing factors of the health effects of PS-NPs were analyzed from the aspects of physical and chemical properties and cell types. Finally, by discussing the current research hotspots of cytotoxicity mechanism and biological effects, it was anticipated to provide a reference for the health risk management and biological safety assessment of PS-NPs.
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OBJECTIVE@#To observe the effects of acupuncture on swallowing function and quality of life for patients with dysphagia in Parkinson's disease (PD).@*METHODS@#A total of 60 patients of PD with dysphagia were randomly divided into an observation group (30 cases, 2 cases dropped off) and a control group (30 cases, 3 cases dropped off). The control group was given conventional medication therapy and rehabilitation training. On the basis of the treatment as the control group, the observation group was given acupuncture at Fengfu (GV 16), Baihui (GV 20), Shenting (GV 24), Yintang (GV 24+), Yansanzhen and bilateral Fengchi (GB 20), 30 min each time, once a day, 6 times a week for 4 weeks. Before and after treatment, the Kubota water swallowing test, standardized swallowing assessment (SSA) and swallowing quality of life (SWAL-QOL) were used to evaluate the swallowing function and quality of life of the two groups.@*RESULTS@#After treatment, the Kubota water swallowing test grade, SSA scores in the two groups were decreased compared with those before treatment (P<0.05, P<0.001)，the SWAL-QOL scores were increased compared with those before treatment (P<0.001); in the observation group，the Kubota water swallowing test grade and SSA score were lower than those in the control group (P<0.05)，the SWAL-QOL score was higher than that in the control group (P<0.001).@*CONCLUSION@#On the basis of conventional medication therapy and rehabilitation training，acupuncture could improve the swallowing function and quality of life for patients of PD with dysphagia.
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Humanos , Trastornos de Deglución/terapia , Deglución , Calidad de Vida , Enfermedad de Parkinson/terapia , Terapia por Acupuntura , AguaRESUMEN
OBJECTIVE@#To evaluate the value of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) for assessing disease activity in patients with rheumatoid arthritis (RA) treated with tofacitinib.@*METHODS@#This retrospective study was conducted among 98 RA patients in active stage treated with tofacitinib in Third Xiangya Hospital and 100 healthy control subjects from the Health Management Center of the hospital from 2019 to 2021. We collected blood samples from all the participants for measurement of erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and other blood parameters 1 month before and 6 months after tofacitinib treatment. We further evaluated PLR and NLR before and after tofacitinib treatment in the RA patients, and analyzed their correlations with RA disease activity.@*RESULTS@#PLR and NLR increased significantly in RA patients as compared with the healthy controls. In the RA patients, PLR and NLR were positively correlated with the levels of hs- CRP, ESR, IL- 6, Disease Activity Score of 28 joints-ESR (DAS28-ESR), anti-cyclic citrullinated peptide (CCP), and rheumatoid factor (RF) before and after tofacitinib treatment. Tofacitinib treatment for 6 months significantly decreased hs-CRP, ESR, IL-6, CCP, RF and DAS28-ESR levels in the RA patients.@*CONCLUSION@#NLR and PLR can be useful biomarkers for assessing disease activity in RA patients treated with tofacitinib.
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Humanos , Neutrófilos , Estudios Retrospectivos , Proteína C-Reactiva/análisis , Interleucina-6/metabolismo , Artritis Reumatoide , LinfocitosRESUMEN
Purpose To investigate the clinicopathological and molecular genetic features of oncocytic carcinoma of the thy-roid(OCA).Methods The clinicopathological and immuno-histochemical data of 25 patients with oncocytic carcinoma of the thyroid were retrospectively reviewed.Genetic features were determined by fluorescence quantitative PCR.Results The male to female ratio of the 25 patients was 1 ∶ 1.8,and the aver-age age was 49 years.The tumor was confined to the thyroid gland.Of the 22 cases with a single nodule,5 cases were ill-de-marcated and 3 cases were multiple nodular lesions.The average size was 2.7 centimeter in diameter.Cytologically,the tumor cells were arranged in detached clusters with abundant eosino-philic and granular cytoplasm and hyperchromatic nuclei with prominent nucleoli.Histologically,the oncocytic tumor cells mainly arranged in trabecular and solid architecture.Capsular,blood and lymphoid vascular invasion could be observed in a cer-tain extent.Among 25 cases of OCA,8 cases were minimally in-vasive,14 cases were encapsulated angio-invasive and 3 cases were widely invasive.Positive immunoreaction with TTF-1,thy-roglobulin and CD56 supported the thyroid epithelial origination of the tumour.One recurrent case was found to have cervical lymph node metastasis,and another case was presented with bone metastasis,which was determined to harbor TERT promoter mu-tation(C228T)in each case.Different point mutation of RAS gene was determined in 2 cases(8%),respectively.Conclu-sion Oncocytic carcinoma of the thyroid shows typical eosino-philic and granular cytoplasm,immunohistochemical staining is helpful in differential diagnosis with other oncocytic lesions.It lacks BRAF-like mutation.Low frequency of RAS mutations could be found.Rare TERT promoter mutation has significant mutation with clinical behavior of OCA.
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Although hemorrhage after endoscopic retrograde cholangiopancreatography （ERCP） is mostly mild and self－limited， sometimes blood transfusion and endoscopic hemostasis are still needed. However， rebleeding may occur after conventional endoscopic hemostasis and thus requires interventional vascular embolization or surgical intervention， which might significantly increase the risk of death associated with post－ERCP bleeding. This article discusses the risk factors for post－ERCP bleeding， including disease－specific factors， patient－related factors， and operation－related factors， and elaborates on different measures for the prevention and treatment of post－ERCP bleeding， so as to provide a reference for identifying the high－risk population for bleeding and developing precise surgical strategies in clinical practice.
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Aim To investigate whether Linggui Zhugan Decoction ( LGZGD) can inhibit ventricular remodeling and prevent heart failure in rats after myocardial infarction by regulating Nrf2/BNIP3 pathway. Methods The model of heart failure after myocardial infarction was established by left coronary artery ligation in rats. Two weeks after modeling, all rats were randomly divided into model group, LGZGD group, and captopril group. Meanwhile sham operation group was set up. The rats were given continuous intragastric administration with drug or distilled water for 28 days, once a day. The behavioral signs of rats in each group were observed. The cardiac function of rats in each group was examined by echocardiography. Serum BNP and NT-ProBNP content were detected by enzyme -linked immunoassay; The changes of myocardial his-topathological and collagen fibers in rats were detected using sirius staining. The contents of oxidative stress index including ROS, SOD in myocardial tissue of rats in each group were observed by DCFH-DA fluorescent probe and Enzyme-linked immunoassay. The ultra-structure of mitochondria was observed by transmission electron microscopy. Expressions of apoptotic proteins ( mitochondrial CytC, cytoplasmic CytC) were detected by Western blot. Expression of proteins related to the Nrf2/BNIP3 pathway were examined by immunofluorescence and Western blot. Results LGZGD could significantly improve the cardiac function of rats, reduce the contents of BNP and NT-ProBNP, inhibit the excessive deposition of collagen in myocardial interstiti-um, reduce ROS, increase the content of SOD, improve mitochondrial structure damage, up-regulate the expression of Nrf2 and nuclear translocation, and reduce the expression of BNIP3. Conclusions LGZGD can inhibit the ventricular remodeling and prevent the occurrence of heart failure after myocardial infarction. Its pharmacological effects are mainly related to regulating the Nrf2/BNIP3 pathway, activating Nrf2, promoting its nuclear transfer, and further down-regulating BNIP3, protecting mitochondrial function, and reducing cardiomyocyte apoptosis.
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ObjectiveTo observe the inhibitory effect of modified Xiao Xianxiongtang on epithelial-mesenchymal transition （EMT） of human gastric cancer MGC803 cells and its relationship with secretory glycoprotein Wnt/β-catenin pathway. MethodThe BALB/c nude mice were implanted with human gastric cancer MGC803 cell suspension in the heterotopic subcutaneous position for inducing tumor. After successful modeling， they were randomly divided into the model group， low-， medium-， and high-dose （16.0，32.0，and 64.0 g·kg-1） groups of modified Xiao Xianxiongtang， and capecitabine （400 mg·kg-1） group， with eight mice in each group， and gavaged with the corresponding drugs， once per day， for 28 consecutive days. Those in the capecitabine group received one-week discontinuation after every two weeks of treatment. The general state and body weight of the nude mice were observed， and the transplanted tumor volume was measured. After being killed， they were weighed and the tumor inhibition rate was calculated. Hematoxylin-eosin （HE） staining was carried out for observing the pathological changes in transplanted tumor tissues. The gene and protein expression levels of Wnt1 and β-catenin were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， followed by the determination of matrix metalloproteinase-9 （MMP-9）， vascular endothelial growth factor （VEGF）， N-cadherin， E-cadherin， Vimentin， and Snail protein expression by Western blot. The expression levels of cyclooxygenase 2 （COX2） and prostaglandin E2 （PGE2） were detected by enzyme-linked immunosorbent assay （ELISA）. ResultIt was found that the transplanted tumor in each group showed different growth trends with time， with the most obvious growth observed in the model group. Compared with the model group， the low-， medium-， and high-dose modified Xiao Xianxiongtang groups exhibited reduced tumor volume and slowed growth to varying degrees over time. After medication for days 7，14，21，and 28， the tumor volumes in the low- and high-dose modified Xiao Xianxiongtang groups and capecitabine group declined （P<0.05， P<0.01）， and that in the medium-dose Xiao Xianxiongtang group was also remarkably reduced after medication for days 14，21，and 28 （P<0.01）. Compared with the model group， the high-dose modified Xiao Xianxiongtang group and capecitabine group showed a significant reduction in the relative tumor volume after treatment for days 7，14，21，28 （P<0.01）， and the low- and medium-dose modified Xiao Xianxiongtang groups also presented with decreased relative tumor volume after treatment for days 14，21，28 （P<0.05， P<0.01）. Compared with the model group， the modified Xiao Xianxiongtang at low， medium， and high doses and capecitabine all increased the tumor inhibition rate to varying degrees （P<0.01）， down-regulated the mRNA and protein expression levels of Wnt1 and β-catenin in tumor tissue （P<0.05， P<0.01） and protein expression levels of MMP-9， VEGF， N-cadherin， Vimentin， and Snail （P<0.05， P<0.01）， up-regulated E-cadherin protein expression （P<0.05， P<0.01）， and reduced COX2 and PGE2 contents （P<0.05， P<0.01）. ConclusionModified Xiao Xianxiongtang inhibits the EMT of human gastric cancer MGC803 cell-transplanted tumor， which may be related to Wnt/β-catenin pathway.
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ObjectiveTo explore the guidance value of “treatment of disease in accordance with three conditions” theory in the prevention and treatment of corona virus disease 2019（COVID-19） based on the differences of syndromes and traditional Chinese medicine（TCM） treatments in COVID-19 patients from Xingtai Hospital of Chinese Medicine of Hebei province and Ruili Hospital of Chinese Medicine and Dai Medicine of Yunnan province and discuss its significance in the prevention and treatment of the unexpected acute infectious diseases. MethodDemographics data and clinical characteristics of COVID-19 patients from the two hospitals were collected retrospectively and analyzed by SPSS 18.0. The information on formulas was obtained from the hospital information system （HIS） of the two hospitals and analyzed by the big data intelligent processing and knowledge service system of Guangdong Hospital of Chinese Medicine for frequency statistics and association rules analysis. Heat map-hierarchical clustering analysis was used to explore the correlation between clinical characteristics and formulas. ResultA total of 175 patients with COVID-19 were included in this study. The 70 patients in Xingtai，dominated by young and middle-aged males，had clinical symptoms of fever， abnormal sweating，and fatigue. The main pathogenesis is stagnant cold-dampness in the exterior and impaired yin by depressed heat， with manifest cold， dampness， and deficiency syndromes. The therapeutic methods highlight relieving exterior syndrome and resolving dampness， accompanied by draining depressed heat. The core Chinese medicines used are Poria，Armeniacae Semen Amarum，Gypsum Fibrosum，Citri Reticulatae Pericarpium，and Pogostemonis Herba. By contrast，the 105 patients in Ruili， dominated by young females， had atypical clinical symptoms， and most of them were asymptomatic patients or mild cases. The main pathogenesis is dampness obstructing the lung and the stomach， with obvious dampness and heat syndromes. The therapeutic methods are mainly invigorating the spleen， resolving dampness， and dispersing Qi with light drugs. The core Chinese medicines used are Poria，Atractylodis Macrocephalae Rhizoma，Glycyrrhizae Radix et Rhizoma，Coicis Semen，Platycodonis Radix，Lonicerae Japonicae Flos， and Pogostemonis Herba. ConclusionThe differences in clinical characteristics， TCM syndromes， and medication of COVID-19 patients from the two places may result from different regions，population characteristics， and the time point of the COVID-19 outbreak. The “treatment of disease in accordance with three conditions” theory can help to understand the internal correlation and guide the treatments.
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ObjectiveTo explore the effect of Xiao Xianxiongtang （XXXT） on the transforming growth factor （TGF）-β1-induced invasion， metastasis， and epithelial-mesenchymal transition （EMT） of gastric cancer MGC-803 cells and the underlying mechanism. MethodThe molecular docking between XXXT and nuclear factor of activated T cells （NFAT） was performed by CB-DOCK （http：//clab.labshare.cn/cb-dock/）. The invasion and metastasis model of MGC-803 cells was established with 10 μg·L-1 TGF-β1. MGC-803 cells were classified into blank group， model group， 0.1 g·L-1 XXXT group， 0.2 g·L-1 XXXT group， and 0.4 g·L-1 XXXT group. For further clarifying the key role of Wnt5a/Ca2+/NFAT signaling pathway in the inhibition of XXXT on gastric cancer， MGC-803 cells were transfected with Wnt5a overexpression plasmid， and then the cells were classified into blank plasmid group， Wnt5a-OE group， blank plasmid + XXXT （0.4 g·L-1） group， and Wnt5a-OE + XXXT （0.4 g·L-1） group. Cell viability was determined by cell counting kit-8 （CCK-8） assay， cell invasion and migration ability by Transwell invasion assay and wound healing assay， expression of EMT-related proteins （E-cadherin， N-cadherin， Vimentin， Snail） and Wnt5a/Ca2+/NFAT signaling pathway-related key proteins ［Wnt5a， calcineurin （CaN）， NFAT1， and p-NFAT1］ by Western blot， and changes in intracellular Ca2+ concentration by immunofluorescence assay. ResultMolecular docking suggested that XXXT acted on Wnt5a/Ca2+/NFAT signaling pathway. XXXT （0.1， 0.2， 0.4 g·L-1） significantly promoted the loss of MGC-803 cell viability （P<0.05，P<0.01）. It inhibited cells from invading the transwell lower chamber and slowed down the healing of cell wounds in a dose-dependent manner （P<0.05， P<0.01）. Moreover， it promoted the expression of E-cadherin while suppressed the expression of N-cadherin， Vimentin， and Snail （P<0.05， P<0.01）. Further experiments showed that XXXT could inhibit the expression of Wnt5a， CaN， NFAT1， and p-NFAT1， and reduce the nuclear expression of NFAT1 and the transcription activity mediated by NFAT1， so as to reduce the cellular Ca2+ concentration （P<0.05， P<0.01）. XXXT can reverse the effect of Wnt5a （P<0.05， P<0.01）. ConclusionXXXT can attenuate the invasion， metastasis， and EMT of MGC-803 cells via the Wnt5a/Ca2+/NFAT pathway， thereby weakening the tumor-promoting effect of TGF-β1. In summary， XXXT may exert therapeutic effect on gastric cancer by regulating the invasion， metastasis， and EMT of gastric cancer cells.
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OBJECTIVE: To explore the protective effect of tea polyphenols and its mechanism in potassium dichromate(PD)-induced acute renal injury in mice. METHODS: The specific pathogen free weaned Kunming mice were divided into control group, model group and low-, middle-and high-dose tea polyphenols groups, with 12 mice in each group. Mice in the control group were given 0.9% sodium chloride solution, and mice in other four groups were given PD solution with 4.275 mg/kg body weight every morning by intragastric administration. Then, mice in the control group and model group were given 0.9% sodium chloride solution in the afternoon, while mice in the low-, middle-and high-dose tea polyphenols groups were given 0.3 mL tea polyphenols solution with a dose of 200, 400 or 600 mg/kg body weight, respectively by gavage, once a day for two consecutive weeks. The body mass of mice was weighed during the experiment. At the end of the experiment, the mice were sacrificed. The kidneys were removed and weighed. The kidney organ coefficients were calculated. The levels of urea nitrogen and creatinine in serum were determined by two-point method, the activities of catalase(CAT) and glutathione peroxidase(GSH-Px) in serum of mice were detected by colorimetry. The pathological change of kidney in mice was observed. RESULTS: The body weight of mice in the model group decreased(P<0.05), while the kidney mass, renal organ coefficient, serum levels of urea nitrogen and creatinine increased(all P<0.05), and the serum activities of CAT and GSH-Px decreased(all P<0.05) compared with the control group. The body weight of mice in the three tea polyphenols groups increased(all P<0.05), while the kidney mass, renal organ coefficient, urea nitrogen and creatinine levels in serum decreased(all P<0.05), and the activities of CAT and GSH-Px in serum increased with the increasing intervention dose of tea polyphenols(all P<0.05) compared with the model group. The change of acute renal injury was mainly caused by renal tubular injury in the model group. The pathological changes of renal tissue in the three tea polyphenols intervention groups were improved compared to that in the model group, and the improvement showed a dose-effect relationship with the intervention of tea polyphenols. CONCLUSION: Tea polyphenols have a protective effect on PD-induced acute renal injury with a dose-effect relationship. Its mechanism of action is related to the fact that tea polyphenols can reduce or reverse oxidative stress and inflammation in the kidney.
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This study aimed to assess whether chrysin(ChR) can inhibit epithelial-mesenchymal transition(EMT) of type Ⅱ alveolar epithelial cell and produce anti-pulmonary fibrosis effect by regulating the NF-κB/Twist 1 signaling pathway. Sixty rats were randomly divided into the control group, the bleomycin(BLC) group, BLC+ChR(50 mg·kg~(-1)) group and BLC+ChR(100 mg·kg~(-1)) group, with 15 rats in each group. The pulmonary fibrosis model was induced by intratracheal injection of BLC(7 500 U·kg~(-1)). Rats were orally administered with different doses of ChR after BLC injection for 28 days. The cells were divided into control group, TGF-β1 group(5 ng·mL~(-1)), and TGF-β1+ChR(1, 10, 100 μmol·L~(-1)) groups. The type Ⅱ alveolar epithelial cells were treated with TGF-β1 for 24 h, and then treated with TGF-β1 for 48 h in the presence or absence of different doses of ChR(1, 10 and 100 μmol·L~(-1)). The morphological changes and collagen deposition in lung tissues were analyzed by HE staining, Masson staining and immunohistochemistry. The mRNA and protein expression levels of collagen Ⅰ, E-cadherin, zonula occludens-1(ZO-1), vimentin, alpha smooth muscle actin(α-SMA), inhibitor of nuclear factor kappa B alpha(IκBα), nuclear factor-kappa B p65(NF-κB p65), phospho-NF-κB p65(p-p65) and Twist 1 in lung tissues and cells were detected by qPCR and Western blot, respectively. The animal experiment results showed that as compared with the BLC group, after administration of ChR for 28 days, bleomycin-induced pulmonary fibrosis in rats was significantly relieved, collagen Ⅰ expression in lung tissues was significantly reduced(P<0.05 or P<0.01), and EMT of alveolar epithelial cells was obviously inhibited [the expression levels of E-cadherin and ZO-1 were increased and the expression levels of vimentin and α-SMA were decreased(P<0.05 or P<0.01)], concomitantly with significantly reduced IκBα and p65 phosphorylation level in cytoplasm and decreased NF-κB p65 and Twist 1 expression in nucleus(P<0.05 or P<0.01). The cell experiment results showed that different doses of ChR(1, 10 and 100 μmol·L~(-1)) significantly reduced TGF-β1-induced collagen Ⅰ expression(P<0.05 or P<0.01), significantly inhibited EMT of type Ⅱ alveolar epithelial cells[the expression levels of E-cadherin and ZO-1 were increased and the expression levels of vimentin and α-SMA were decreased(P<0.05 or P<0.01)], and inhibited IκBα and p65 phosphorylation in cytoplasm and down-regulated NF-κB p65 and Twist 1 expression in nucleus induced by TGF-β1(P<0.05 or P<0.01). The results suggest that ChR can reverse EMT of type Ⅱ alveolar epithelial cell and alleviate pulmonary fibrosis in rats, and its mechanism may be associated with reducing IκBα phosphorylation and inhibiting NF-κB p65 phosphorylation and nuclear transfer, thus down-regulating Twist 1 expression.
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Animales , Ratas , Células Epiteliales Alveolares/metabolismo , Transición Epitelial-Mesenquimal , Flavonoides , FN-kappa B/metabolismo , Transducción de Señal , Factor de Crecimiento Transformador beta1/genéticaRESUMEN
Hydroxytyrosol as one of natural anti-oxidants，extracted from the fruits and leaves of Olea europaea，is a natural polyphenol compound in the form of esters. Recently，considerable studies showed that hydroxytyrosol demonstrated intrinsic biological activity for metabolic syndromes， cardiovascular- and neurodegenerative-related diseases，and it was revealed to play the roles in the anti-activities of cancerous，inflammatory as well as depressing issues. In addition，hydroxytyrosol is an oleophilic and hydrophilic compound with high bioavailability and low cellular cytotoxicity. It could be absorbed by various tissues and could easily passe through blood brain barrier. Therefore，hydroxytyrosol was introduced as one of the key subjects targeted by innovative drug development. However，it has a short half-life in vivo and non-tissue specific，which lead to its limitation in clinical application， so further in-depth studies are still needed. The authors had a literature review of hydroxytyrosol，and summarized the basic properties of its pharmacokinetic，pharmacological effects and molecular mechanisms. This article mainly focused on it’s pharmacological activity and the mechanism involved in treating damages induced by the oxidative stress，in alleviating cardiovascular diseases and in inhibition of neurodegenerative diseases. In this article， its anti-inflammatory，anti-tumor，anti-depressant effects，other biological activities，and pharmacokinetics were also briefly reviewed. The authors put forward some personal thoughts on its future research direction，hoping to provide ideas and inspirations for the vast number of researchers，and provide references for its further development，research and application.
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Objective: To investigate the value of serum miR-133a in early diagnosis and the assessment of 30-day incidence of cardiovascular adverse events in patients with acute myocardial infarction (AMI). Methods: Ninety patients with acute chest pain within 6 h were included, and 63 cases of AMI, 13 cases of unstable angina pectoris (UAP) and 14 cases of control (chest pain of other causes) were finally diagnosed. The levels of troponin I (cTnI), creatine kinase MB (CK-MB) and myoglobin (Mb) were measured by electrochemical fluorescence. Quantitative real-time PCR (qPCR) was used to detect the expression of miR-133a in the serum of patients immediately after admission and 24 h after percutaneous coronary intervention (PCI). The Gensini score of patients who underwent coronary angiography was recorded. The incidence of cardiovascular adverse events was observed within 30 days. Spearman correlation analysis, multivariate Logistic regression analysis and receiver operator characteristic curve (ROC curve) were used to analyze the corresponding data. Results: The expression of miR-133a in the AMI group was significantly higher than that in the UAP group and the control group (both P<0.05). Spearman correlation analysis showed that the expression of miR-133a was positively correlated with cTnI, CK-MB, MB level and Gensini scores (all P<0.05). Multivariate Logistic regression analysis showed that miR-133a and the history of coronary heart disease were independent risk factors for AMI. ROC curve showed that the area under the curve (AUC) of miR-133a in the diagnosis of AMI was 0.816 (95% CI 0.716-0.917), and the AUC of 30 days cardiovascular adverse event was 0.700 (95% CI 0.535-0.865). Conclusion: The expression of miR-133a in patients with AMI is significantly increased, which is expected to be a biomarker for early diagnosis of AMI. The expression level of miR-133a in serum may be related to the severity of coronary artery disease and short-term prognosis.