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Objective To analyze the effect and molecular mechanism of phellodendron amurense in the treatment of liver injury based on network pharmacology,and to verify the relevant prediction targets and the protective effect of phellodendron amurense extract-Phellodendron amurense polysaccharide on immune liver injury through mice.Methods TCMSP and Swiss target prediction databases were used to retrieve and screen phellodendron amurenses active components and action targets,and then obtain disease-related targets on GeneCards and OMIM websites,and take compounds and disease intersection targets for protein interaction.Analysis,GO biological function and KEGG signaling pathway enrichment analysis,followed by molecular docking of compounds and key target proteins,and finally established a mouse liver injury model induced by Daodou protein A(Con A)to explore the mechanism of phellodendron amurense extract in the treatment of liver injury.Results 37 active ingredients were screened.The key targets for their treatment were tumor necrosis factor α(TNF-α),serine/threonine protein kinase 1(AKT1),signal transduction and transcription activation factor 3(STAT3),epidermal growth factor receptor(EGFR)anditin.Enzyme 3(CASP3)and other enrichment analysis showed that phellodendron amurense might play a protective role in protecting the liver through molecular mechanisms such as positive regulation of MAPK cas-cade reaction,oxidative stress response and regulatory PI3K-Akt signaling pathway,lipid and atherosclerosis.Ani-mal experiments had found that the gastric treatment of phellodendron amurense polysaccharide could improve the activity of superoxide dismutase(SOD)and catalase(CAT)in liver tissue,reduce the levels of serum alkaline phosphatase(ALP),aspartate aminotransferase(AST)and malonaldehyde(MDA)in liver tissue,and regulate serum inflammatory factor while the expression of intercitin(IL)-6,IL-1 β,tumor necrosis factor α(TNF-α),ac-tivated the expression of transforming growth factor β1(TGF-β1),and reduced TNF-α mRNA expression in liver tissue.Conclusion Phellodendron amurense can intervene in lipid and atherosclerosis pathways by acting on tar-gets such as TNF-α,AKT1,STAT3,EGFR and CASP3 to reduce oxidative stress and inflammatory reactions and achieve liver protection.
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Purpose@#Chemotherapy has been the primary treatment for patients with B-cell acute lymphoblastic leukemia (B-ALL). However, there are still patients who are not sensitive to chemotherapy, including those with refractory/relapse (R/R) disease and those experiencing minimal residual disease (MRD) re-emergence. Chimeric antigen receptor-T lymphocytes (CAR-T) therapy may provide a new treatment option for these patients. @*Materials and Methods@#Our institution conducted a single-arm prospective clinical trial (ChiCTR-OPN-17013507) using CAR-T-19 to treat R/R B-ALL and MRD re-emergent patients. One hundred and fifteen patients, aged 1-25 years (median age, 8 years), were enrolled, including 67 R/R and 48 MRD re-emergent CD19-positive B-ALL patients. @*Results@#All patients achieved morphologic complete remission (CR), and within 1 month after infusion, 111 out of 115 (96.5%) patients achieved MRD-negative CR. With a median follow-up time of 48.4 months, the estimated 4-year leukemia-free survival (LFS) rate and overall survival (OS) rate were 68.7%±4.5% and 70.7%±4.3%, respectively. There were no significant differences in long-term efficacy observed among patients with different disease statuses before infusion (4-year OS: MRD re-emergence vs. R/R B-ALL, 70.6%±6.6% vs. 66.5%±6.1%, p=0.755; 4-year LFS: MRD re-emergence vs. R/R B-ALL, 67.3%±7.0% vs. 63.8%±6.2%, p=0.704). R/R B-ALL patients bridging to transplantation after CAR-T treatment had a superior OS and LFS compared to those who did not. However, for MRD re-emergent patients, there was no significant difference in OS and LFS, regardless of whether they underwent hematopoietic stem cell transplantation or not. @*Conclusion@#CD19 CAR-T therapy effectively and safely cures both R/R B-ALL and MRD re-emergent patients.
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OBJECTIVE@#To explore the consistency of flow cytometry (FCM) method and polymerase chain reaction (PCR) technique in the detection of minimal residual disease (MRD) at different treatment stages in pediatric patients with TCF3/PBX1+ B-cell acute lymphoblastic leukemia (B-ALL) and the correlations between the detection results and prognosis.@*METHODS@#The clinical data of 64 newly diagnosed pediatric patients with TCF3/PBX1+ B-ALL admitted to the Department of Pediatrics of Peking University People's Hospital from January 2005 to December 2017 were retrospectively analyzed. FCM and PCR methods were used to monitor the MRD level in bone marrow samples from 64 children during the same period of treatment on d33 and d90 respectively, and the detection results were analyzed.@*RESULTS@#There were 37 males and 27 females in the 64 patients, with a median age of 8 years(range 0.8 to 16 years). The complete remission (CR) rate after the first cycle of induction chemotherapy was 98.4% (62/63), with overall CR rate of 100%. 12 patients experienced recurrence, with a median recurrence time of 16.9 (5.3-46.3) months. The median follow-up time of the 64 patients was 77.2 (1.0-184.8) months , and the 5-year overall survival (OS) rate and event-free survival (EFS) rate were 82.8%±4.7% and 75.0%±5.4%, respectively. On d90, the concordance rate of the MRD results from the two methods was 98.4%, and the related kappa value was 0.792 (P < 0.001), which were significantly higher than those on d33. After induction chemotherapy (d33), the 5-year EFS rate of MRD-FCM- group (79.3%±5.3%) was significantly better than that of MRD-FCM+ group (40.0%±21.9%) (P =0.028), there were no significant differences in the 5-year OS rate and EFS rate between MRD-PCR+ group and MRD-PCR- group, and the 5-year EFS rate of MRD-FCM-/PCR- group (85.4%±5.5%) was significantly better than that of MRD-FCM+/PCR+ group (40.0 %±21.9%) (P =0.026).@*CONCLUSION@#In children with TCF3/PBX1+ B-ALL, the MRD results detected by FCM and PCR methods show good consistency, especially in consolidation therapy period (d90). The MRD level at the end of induction therapy (d33) is an important factor affecting the long-term prognosis, especially the MRD results detected by FCM method, which is significantly associated with prognosis.
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Male , Female , Child , Humans , Infant , Child, Preschool , Adolescent , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Neoplasm, Residual/diagnosis , Clinical Relevance , Retrospective Studies , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , Prognosis , Burkitt Lymphoma , Basic Helix-Loop-Helix Transcription Factors/therapeutic useالملخص
OBJECTIVE To explore the improvement effect and potential mechanism of total flavonoids from Alpinia zerumbet on gastric mucosa injury induced by absolute ethanol through microRNA-146a-5p (miR-146a-5p). METHODS Using human gastric mucosa GES-1 cells as objects, the acute gastric ulcer model was established by absolute ethanol; based on the investigation of the effects of different concentrations of total flavonoids from A. zerumbet on cell activity and the selection of action concentration, the relative expression level of miR-146a-5p in GES-1 cells was detected, the protein expressions of tumor necrosis factor (TNF) receptor-associated factor 6(TRAF6), nuclear factor-κB p65 (NF-κB p65) and TNF-α were detected, and the levels of interleukin- 1β (IL-1β), IL-6 and prostaglandin E2 (PGE2) in cell supernatant were determined. The targeting relationship between miR-146a- 5p and TRAF6 was verified; the effects of overexpressed miR-146a-5p and TRAF6 knockdown on the levels of IL-1β, IL-6 and PEG2 in supernatant of model cells as well as the effects of miR-146a-5p knockdown on anti-gastric ulcer effect of total flavonoids from A. zerumbet were observed. RESULTS Compared with the blank group, the relative expression of miR-146a-5p in cells and the level of PGE2 in cell supernatant were decreased significantly in the model group (P<0.01), while the protein expressions of TRAF6, NF-κB p65 and TNF-α in cells and the levels of IL-1β and IL-6 in cell supernatant were increased significantly (P< 0.01). Compared with the model group, the relative expression of miR-146a-5p in cells and the level of PGE2 in cell supernatant were increased significantly in model+A. zerumbet total flavonoids (60 mg/L) group (P<0.01), while the protein expressions of TRAF6, NF-κB p65 and TNF-α in cells and 82260767) the levels of IL-1β and IL-6 in cell supernatant were decreased significantly (P<0.05 or P<0.01). There was a targeted relationship and a negative correlation between miR-146a-5p E-mail:3113836821@qq.com and TRAF6. After overexpression of miR-146a-5p or TRAF6 knockdown, the levels of IL-1β and IL-6 were decreased significantly in cell supernatant, while the level of PGE2 was increased significantly (P<0.05). After miR-146a-5p knockdown, the levels of IL-1β and IL-6 in cell supernatant and the protein expression of TRAF6 in cells administered with total flavonoids of A. zerumbet were increased significantly, while the level of PGE2 was decreased significantly (P<0.05). CONCLUSIONS Total flavonoids of A. zerumbet can improve the gastric mucosa injury induced by absolute ethanol. The mechanism may be related to up-regulating the expression of miR-146a-5p, inhibiting the expression of TRAF6, and further inhibiting the secretion of related inflammatory factors.
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Objective:In order to understand the difference of clinical efficacy between original TNF-α inhibitors (TNFi) and their biosimilars, Bayesian mesh Meta-analysis was compare Etanercept, Infliximab, Adalimumab with their biosimilars in the treatment of ankylosing spondylitis (AS).Methods:A systematic literature search was performed, using Ovid Biomedical, Embase, Cochrane Library, CNKI, Wanfang Database and Weipu Database (up to March 8, 2023 for all resources above), to search publications of randomized controlled trial (RCT) about all original and biosimilar TNFi for the treatment of AS in all language. Two reviewers independently identified the eligible trails, evaluated bias risk and extracted relevant data. Based on Bayesian network, data analysis of included studies was conducted using statistical software R3.6.1 and R Studio.Results:The results of the network meta-analysis showed that, no significant differences was observed among. Etanercept, Infliximab,Adalimumab, and their biosimilars for ASAS20 when Infliximab was compared with Etanercept [ OR (95% CI)=1.4 (0.54, 3.5)], placebo was compared with Etanercept [ OR (95% CI)=0.35 (0.17,0.67)], No significant differences were observed among Etanercept, Infliximab, Adalimumab, and their biosimilars for BASDAI, when Infliximab was compared with Ctanercept [ OR (95% CI)=-0.89 (-1.8, 0.081)], placebo was compared with Etanercept [ OR(95% CI)=1.7(0.86, 2.5)], No significant differences were observed among Etanercept, Infliximab, Adalimumab, and their biosimilars for BASFI, when Infliximab was compared with Etanercept [ OR(95% CI)=-0.46(-1.3, 0.47)], placebo was compared with Etanercept [ OR(95% CI)=1.6(0.8, 2.3)]. Conclusion:Etanercept, Infliximab, Adalimumab with their biosimilars are significantly superior to placebo and sulfasalazine in terms of ASAS20, BASDAI, BASFI, CRP, ESR. Limited evidence have shown that the efficacy of biological biosimilars are similar to that of their corresponding original drugs.
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Objective: To investigate the related factors associated with the structure of the gut microbial community in HIV infection/AIDS cases (HIV/AIDS) in Henan province. Methods: The convenience sampling method was used to select 122 cases who were receiving Antiviral Treatment (ART) or ART-naive in Henan. Whole blood and stool specimens were collected. Genomic DNA of stool samples was extracted, and the V3-V4 hypervariable regions of the 16S rRNA gene were sequenced using Illumina NovaSeq 6000 high-throughput sequencing system. The analysis was performed mainly at the genus level, and the 30 genera with the highest abundance were selected as a measure of the gut microbial community structure. The correlation between community structure and related factors was analyzed using redundancy analysis and Envfit function. Results: 122 cases were finally completed sequencing and analysis, the average BMI was (23.62±2.78) kg/m2 and the average age was (47±13) years. Among them, male accounted for 66.39% (81/122), and heterosexual transmission route constituted the largest ratio, accounting for 51.64% (63/122). 36 cases were treatment naive (29.51%, 36/122). The top five dominant genera of the total population (122 cases) were Prevotella, Roseburia, Megamonas, Bacteroides and Faecalibacterium and the top five dominant genera of the ART population (86 cases) were Prevotella, Megamonas, Bacteroides, Roseburia and Faecalibacterium. The top five dominant genera of the ART-naive population (36 cases) appeared as Prevotella, Faecalibacterium, Roseburia, Bacteroides and Megamonas. In the total population, ART (P<0.001) was the most significant factors of community structure. Other significant factors were: duration of diagnosis (P=0.009), viral load (P=0.022) and anti-HCV (P=0.018). ART was positively correlated with Megamonas and negatively correlated with Prevotella, Roseburia and Faecalibacterium, while the other three factors of duration of diagnosis, viral load and anti-HCV were positively correlated with Prevotella, Roseburia and Faecalibacterium and negatively correlated with Megamonas. In the ART-naive population, duration of diagnosis (P=0.003) were the factors significantly associated with community structure. Duration of diagnosis was positively correlated with Roseburia, Faecalibacterium, Megamonas and Prevotella and negatively correlated with Bacteroides. Conclusion: ART and duration of diagnosis were factors significantly associated with gut microbial community structure and had a significant impact on multiple high-abundance genera.
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Adult , Humans , Male , Middle Aged , Acquired Immunodeficiency Syndrome/epidemiology , Gastrointestinal Microbiome/genetics , HIV Infections/epidemiology , Microbiota , RNA, Ribosomal, 16S/geneticsالملخص
OBJECTIVE@#To propose a new method for mining complexes in dynamic protein network using spatiotemporal convolution neural network.@*METHODS@#The edge strength, node strength and edge existence probability are defined for modeling of the dynamic protein network. Based on the time series information and structure information on the graph, two convolution operators were designed using Hilbert-Huang transform, attention mechanism and residual connection technology to represent and learn the characteristics of the proteins in the network, and the dynamic protein network characteristic map was constructed. Finally, spectral clustering was used to identify the protein complexes.@*RESULTS@#The simulation results on several public biological datasets showed that the F value of the proposed algorithm exceeded 90% on DIP dataset and MIPS dataset. Compared with 4 other recognition algorithms (DPCMNE, GE-CFI, VGAE and NOCD), the proposed algorithm improved the recognition efficiency by 34.5%, 28.7%, 25.4% and 17.6%, respectively.@*CONCLUSION@#The application of deep learning technology can improve the efficiency in analysis of dynamic protein networks.
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Algorithms , Cluster Analysis , Computer Simulation , Neural Networks, Computer , Research Designالملخص
Neuroscientists have emphasized visceral influences on consciousness and attention, but the potential neurophysiological pathways remain under exploration. Here, we found two neurophysiological pathways of heart-brain interaction based on the relationship between oxygen-transport by red blood cells (RBCs) and consciousness/attention. To this end, we collected a dataset based on the routine physical examination, the breaking continuous flash suppression (b-CFS) paradigm, and an attention network test (ANT) in 140 immigrants under the hypoxic Tibetan environment. We combined electroencephalography and multilevel mediation analysis to investigate the relationship between RBC properties and consciousness/attention. The results showed that RBC function, via two independent neurophysiological pathways, not only triggered interoceptive re-representations in the insula and awareness connected to orienting attention but also induced an immune response corresponding to consciousness and executive control. Importantly, consciousness played a fundamental role in executive function which might be associated with the level of perceived stress. These results indicated the important role of oxygen-transport in heart-brain interactions, in which the related stress response affected consciousness and executive control. The findings provide new insights into the neurophysiological schema of heart-brain interactions.
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Humans , Awareness , Brain , Consciousness , Oxygen , Visual Perceptionالملخص
Objective:To analyze the effects of espO gene knockout on the biological characteristics of enterhemorrhagic Escherichia coli (EHEC). Methods:Two-step methods mediated by the suicide plasmid pCVD442-Δ espO and plasmid pTrc99a were used to construct the espO gene-deleted strain (Δ espO) and the complemented mutant (CΔ espO), respectively. HeLa cells were infected with different EHEC strains to analyze the biological functions and lethal effects of espO gene during infection. Results:PCR, electrophoresis and gene sequencing showed that the Δ espO and CΔ espO mutants were successfully constructed. Compared with the wild-type strain, neither the Δ espO nor CΔ espO mutant showed significant difference in growth rate, indicating that the espO gene had no influence on the growth and replication of EHEC. Furthermore, EspO could activate the tumor necrosis factor receptor (TNF)-induced NF-κB signaling pathway, while the effector protein NleB could inhibit the process. EspO could not inhibit the death of HeLa cells induced by TNF or TNF-related apoptosis-inducing ligand (TRAIL) after EHEC infection. Conclusions:In this study, we successfully constructed the espO gene-deleted and complemented mutants of EHEC and preliminarily analyzed the interaction between espO gene and host cells and the effects of espO gene on cell apoptosis during infection, which provided reference for further research on the in vitro biochemical activity and in vivo pathogenic roles of EspO.
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To investigate the changes of bile acid(BA) levels in mice with sleep deprivation and the regulatory effect of Jiaotai Pills(JTP) on bile acid metabolism, this study established an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method for simultaneous determination of 23 BAs in mice. A total of 24 ICR mice were randomized into normal group, model group, and JTP group. Mice in the model group and JTP group were deprived of sleep at 20 h·d~(-1) by sleep deprivation apparatus for 8 consecutive days. Mice in the JTP group were given(ig, qd) JTP 3.3 g·kg~(-1) and those in the normal group and model group received(ig) the same volume of purified water. UPLC conditions are as follows: Waters ACQUITY UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 μm), gradient elution with the mobile phase of 0.1% formic acid in water-methanol. MS conditions are as below: negative-ion electrospray ionization, multiple reaction monitoring(MRM). Thereby, the content of 23 BAs in serum, liver, and ileum was determined and methodological investigation of the method was performed. The results showed that 23 BAs could be accurately determined within 15 min and the correlation coefficients were all higher than 0.99. The precision, accuracy, specificity, reproducibility, matrix effect, and recovery of BAs all met the requirement. The levels of BAs were significantly increased in the serum, liver, and ileum of sleep-deprived mice, but JTP can significantly reduce the levels. The UPLC-MS/MS method is simple, rapid, and accurate, which can be used for the determination of 23 BAs in biological samples, and JTP can adjust the elevated BA levels of sleep-deprived mice.
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Animals , Mice , Bile Acids and Salts , Chromatography, High Pressure Liquid , Chromatography, Liquid , Drugs, Chinese Herbal , Mice, Inbred ICR , Reproducibility of Results , Sleep , Tandem Mass Spectrometryالملخص
Objective:To identify new host substrate of SseK3 and study its biological function.Methods:A yeast two hybrid system (Y2H) was used to identify the potential binding proteins of SseK3 from the Hela cDNA library; the arginine N-acetylglucosamine (Arg-GlcNAc) modification of the substrate protein by SseK3 was detected by co-expression in 293T cells and in vitro activity test; the modification sites of the substrate protein by SseK3 were detected by point mutation; the effect of Arg-GlcNAc modification of the substrate protein on its interaction protein binding ability was detected by immunoprecipitation test. Results:Results of Y2H and gene sequencing showed that Snapin was a new substrate of SseK3. Snapin could be Arg-GlcNAc-modified by SseK3 in vivo and in vitro; the modification sites of Snapin were arginine 119 and arginine 120; Arg-GlcNAc-modified Snapin inhibited its binding with SNAP25. Conclusions:Snapin, a new host substrate protein of SseK3, was successfully screened in this study. The Arg-GlcNAc modification of Snapin by SseK3 was studied, and the effect of this modification on Snapin function was preliminarily studied, which provided theoretical basis for further understanding the function of Arg-GlcNAc modification of bacteria and the mechanism of action in the process of pathogen infection.
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OBJECTIVE:To explore the protective effect of Alpinia zerumbet extract on acute gastric ulcer model mice. METHODS:Totally 48 mice were collected and randomly divided into blank group ,model group ,positive group (Sanjiu weitai granules,20 mg/kg),A. zerumbet extract high-dose ,medium-dose and low-dose groups (2.34,1.17,0.59 g/kg,by crude drug ), with 8 mice in each group. They were given normal saline or relevant medicine intragastrically ,once a day ,for consecutive 7 d. Then,except for blank group ,other groups were given disposable intragastric administration of absolute ethanol 0.1 mL/10 g to establish acute gastric ulcer model. Another 48 mice were collected and grouped with same method ,and then given relevant medicine for consecutive 15 d. From the 10th day of administration ,except for blank group ,other groups were given intragastric administration of aspirin (20 mg/kg) for consecutive 6 d to establish acute gastric ulcer model. In ethanol induction model experiment,the formation of gastric ulcer and the index of gastric ulcer were observed in each group ;HE staining was used to observe the pathological changes of gastric tissue ;the levels of gastrin (GAS)in serum ,and the levels of SOD ,MDA and NO in gastric tissue were determined by ELISA. In the aspirin induced model experiment ,the formation of gastric ulcer and the index of gastric ulcer were observed and measured by the same method ;the levels of GAS ,TNF-α,IL-1β in serum,and the levels of PGE2 and COX- 2 in gastric tissue were determined by ELISA. RESULTS :Compared with model group ,obvious ulcer lesions were found in gastric tissue of rats in model group ;the levels of GAS ,TNF-α,IL-1β in serum,and MDA ,NO in gastric tissue were increased significantly , while the levels of SOD , PGE2, (No.QZYY-2019- COX-2 in gastric tissue were decreased si gnificantly(P<0.05 063). Compared with model group ,the degree of gastric lesions in administration groups was alleviated to some extent;gastric ulcer index was decreased to some extent , mail:997845460@qq.com while the levels of the above indexes in serum and gastric tissue were improved in varying degrees , with statistical 制。E-mail:672863283@qq.com significance in most indexes (P<0.05 or P<0.01). CONCLUSIONS:A. zerumbet extract exerts its protective effect on absolute ethanol and a spirin-induced acute gastric ulcer model mice,the mechanism of which may be relieving gastric mucosal injury through inhibiting oxidative stress and inflammatory response.
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OBJECTIVE@#To evaluate the value of capsule endoscopy in children with small intestinal diseases with hematochezia as the chief complaint.@*METHODS@#A retrospective analysis was performed on the clinical data and capsule endoscopy findings of 93 children with hematochezia who were admitted to Children's Hospital of Fudan University from May 2015 to January 2019 and underwent capsule endoscopy. According to the capsule endoscopy findings of the jejunum and the ileum, they were divided into a positive lesion group with 39 patients and a negative lesion group with 54 patients. Related clinical data and the features of lesion on capsule endoscopy were analyzed for the two groups.@*RESULTS@#There were no significant differences in age, sex, duration of capsule endoscopy, gastric transit time, and small intestinal transit time between the positive lesion and negative lesion groups (P>0.05). The positive lesion group had a significantly lower level of hemoglobin than the negative lesion group (P<0.05). Hemoglobin level was negatively correlated with the rate of positive lesions on capsule endoscopy (r=-0.342, P=0.001). Among the 39 patients with positive lesions on capsule endoscopy, the detection of Meckel's diverticulum was the highest (41%), followed by inflammatory bowel disease (21%).@*CONCLUSIONS@#Capsule endoscopy has a certain value in detecting small intestinal diseases, especially diseases in the jejunum and the ileum, in children with lower gastrointestinal hemorrhage.
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Child , Humans , Capsule Endoscopy , Gastrointestinal Hemorrhage , Intestinal Diseases , Jejunum , Meckel Diverticulum , Retrospective Studiesالملخص
OBJECTIVE@#To explore the clinical-biological characteristics and prognosis of pediatric pro-B cell acute lymphoblastic leukemia (pro-B-ALL).@*METHODS@#A total of 64 patients aged less than 18 years old with pro-BALL were enrolled. Clinical characteristics, therapeutic effect and prognostic factors were retrospectively analyzed.@*RESULTS@#Pro-B-ALL occurred in 6.23% (64/1 028) of pediatric ALL. Among the 64 patients, 35 were male and 29 were female. The median age was 7.0 years (range 0.4-16.0 years) at diagnosis, of which 39% and 6% were ≥ 10 years old and < 1 year old respectively. The median WBC count was 25.5×10@*CONCLUSIONS@#Pediatric pro-B ALL is a heterogeneous disease with clinical and biological diversity. Biological characteristics, such as immunological markers, genetic alterations, and MRD at 3 months after chemotherapy may be important factors for the long-term prognosis.
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Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Antigens, CD/genetics , Disease-Free Survival , Histone-Lysine N-Methyltransferase/genetics , Myeloid-Lymphoid Leukemia Protein/genetics , Neoplasm, Residual/diagnosis , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Prognosis , Retrospective Studiesالملخص
Objective::To evaluate theclinical efficacy of Zhiwei pills combined with Hperadication programme for gastritis with liver and stomach Qi stagnation syndrome caused by helicobacter pylori (Hp) and to investigate its effect on antioxidant stress. Method::One hundred and sixty patients were randomly divided into control group (80 cases) and observation group (80 cases) by random number table. Patients in control group gotHperadication programme, and esomeprazole magnesium enteric-coated tablets, 20 mg/time, 1 time/day. Bismuth potassium citrate tablets, 0.3 g/time, 2 times/days. Amoxicillin capsules, 1.0 g/time, 2 times/days. Furazolidone tablets, 0.1 g/time, 2 times/days, all for 14 days. Based on the treatment in control group, the patients in observation group additionally got Zhiwei pills, 6 g/time, 3 times/day. The course of treatment was 8 weeks in both groups. After treatment, eradication of Hp was detected. Before and after treatment, scores of liver and stomach Qi stagnation syndrome were graded. After treatment, patients received gastroscopy and pathological review, and patient report outcome indicators (PRO) both before and after treatment were discussed. The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-8, oxidative dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were detected both before and after treatment. Result::Negative conversion rate of Hp was(70/75) 93.33% in observation group, higher than(58/71) 81.69% in control group (P<0.05). In the analysis of rank sum test, effect of traditional Chinese medical(TCM) syndrome in observation group was better than that in control group (Z=2.183, P<0.05), and clinical efficacy was also better than that in control group (Z=2.175, P<0.05). Scores of liver and stomach Qi stagnation syndrome and total PRO score in observation group were all lower than those in control group (P<0.01). Levels of TNF-α, IL-1β, IL-8 and MDA were lower than those in control group (P<0.01), while levels of SOD and GSH-Px were higher than those in control group (P<0.01). Conclusion::Zhiwei pills combined with Hperadication programme can improve the eradication rate of Hp, alleviate clinical symptoms, improve the quality of life of patients, inhibit inflammatory reaction and anti-oxidative stress, and improve the curative effect and clinical efficacy of TCM syndromes in the treatment of gastritis with liver and stomach Qi stagnation syndrome, so it is worth for further study and use.
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Objective::To evaluate the effects of Valeriana amurensis roots and rhizomes extract and its active constituents on the activities of six major cytochrome P450 (CYP450) enzymes in human liver microsomes. Method::Coumarin, bupropion, tolbutamide, omeprazole, dextromethorphan and testosterone were used as probe substrates for CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4, respectively. Taking their specific metabolites of hydroxylation or demethylation (7-hydroxycoumarin, hydroxybupropion, 4-hydroxytolbutamide, 5-hydroxyomeprazole, dextromethorphan, 6β-hydroxytestosterone) as indicators of enzyme activities. The analytical indexes were used to establish an in vitro model of human liver microsomes of Cocktail probe substrates. This method was applied to evaluate the effects of V. amurensis roots and rhizomes extract and its active constituents on human liver microsomal enzymes. Result::The V. amurensis roots and rhizomes extract had different inhibitory effects on CYP2B6, CYP2C9, CYP2D6 and CYP3A4, their half-inhibitory concentration (IC50) values were 87.49, 1.73, 68.29, 2.80 mg·L-1, respectively. Among the 9 lignans, (-)-massoniresinol-3α-O-β-D-glucopyranoside had a moderate inhibitory effect on CYP2A6 with an IC50 value of 8.51 μmol·L-1, 8, 8′-dihydroxypinoresinol-4, 4′-di-O-β-D-glucopyranoside had a moderate inhibitory effect on CYP2D6 with an IC50 value of 8.73 μmol·L-1, (+)-medioresinol-4, 4′-O-di-β-D-glucopyranoside had a moderate inhibitory effect on CYP2B6 and CYP2C9 with IC50 values of 5.41 μmol·L-1 and 8.20 μmol·L-1. Conclusion::The V. amurensis roots and rhizomes extract and its active constituents have inhibitory effects on liver CYP450 enzymes. Therefore, in the clinical study of new drugs, it is necessary to fully evaluate the risk of drug interactions caused by combination therapy.
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To analyze types of urinary calculi and patients' clinical characteristics, and to explore the strategies for prevention and treatment of urinary calculi. Methods: A total of 1 849 patients with urinary calculi were treated in the Department of Urology, the Third Xiangya Hospital of Central South University. The components were analyzed by infrared spectroscopy. The relationship between stone composition and clinical parameters was analyzed according to the clinical characteristics of the patients. Results: The proportion of calcium oxalate stone or uric acid stone in male (84.1% or 7.7%) was higher than that in female (78.4% or 4.2%). The older patients were more likely to be diagnosed as uric acid stone. The proportions of uric acid stone in patients <18 years old, 18-<41 years old, 41-<66 years old, and ≥66 years old were 0.0%, 1.6%, 6.6%, and 12.4%, respectively. There was no significant difference in the proportion of stones in patients with different BMI. There were no significant difference in the stone composition between the patients with or without urinary tract infection, hypertension or diabetes. The proportion of uric acid stones in patients with acidic urine was higher than the other types. The proportion of uric acid stones in patients with elevated creatinine (12.1%) was higher than that in the patients with normal creatinine (4.5%). Conclusion: Elderly patients, or patients with high uric acid and renal insufficiency are more prone to uric acid stones. Regulation of urinary pH may be an important strategy for preventing and treating urinary calculi in Hunan Province.
الموضوعات
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Age Factors , Body Mass Index , Calcium Oxalate , Creatinine , Urine , Hydrogen-Ion Concentration , Kidney Calculi , Chemistry , Therapeutics , Sex Factors , Spectrophotometry, Infrared , Uric Acid , Urinary Calculi , Chemistry , Therapeutics , Urineالملخص
Objective: To explore the clinical features and prognostic factors of Ph-positive and/or BCR-ABL positive acute lymphoblastic leukemia (Ph+ ALL) in children. Methods: The clinical data of 68 Ph+ ALL children who were treated at Peking University People's Hospital from December 2006 to December 2016 was retrospectively reviewed. Survival analysis were estimated by Kaplan-Meier method. Univariate analysis was estimated by Log-rank test and Chi-square, and multivariate analysis was estimated by Cox proportional hazards regression model. Results: In the 68 cases, the proportion of male to female was 2.1∶1, with a median age of 8 (1-16) years, and the median overall survival (OS) and disease free survival (DFS) were 16.8 months and 13.5 months, respectively. The early response rate to treatment was 43.9%, with myeloid-antigens-expression group lower than the non-expression group (29.6% vs 61.3%, χ2=5.814, P=0.020); The complete remission (CR) rate after one-course induction therapy was 86.2% (56/65), with good-response group higher than the poor-response group (100.0% vs 74.2%, χ2=6.680, P=0.003);The CR rate after induction in patients receiving imatinib plus chemotherapy was higher than the patients receiving chemotherapy only (94.9% vs 73.1%, χ2=5.185, P=0.024). The 2-and 5-year OS were (61.4±7.0)% and (50.8±8.1)%, respectively. The 2-and 5-year DFS were (54.6±6.8)% and (48.6±7.3)%, respectively. Univariate analysis showed that the initial WBC, LDH, spleen size, liver size, with-myeloid-antigens-expression, early response to treatment, MRD (BCR-ABL) after one-course induction, application of imatinib and different treatment options affected 2-year OS rate (all P<0.05). LDH, spleen size, liver size, with-myeloid-antigens-expression, early response to treatment, MRD (BCR-ABL) after one-course induction, application of imatinib and different treatment options affected 2-year DFS rate (all P<0.05). Multivariate prognostic analysis for OS (RR=45.7, 95% CI 1.4-1 528.2, P=0.033) and DFS (RR=52.3, 95% CI 1.6-1 725.9, P=0.026) showed that the spleen ≥ 3 cm was the independent risk factor. Conclusions: Pediatric Ph+ ALL is a special condition with unique clinical and biological features. The early response to treatment was poor in patients with myeloid-antigens-expression, which resulted in a low CR rate after one-course induction and the administration of imatinib can remarkably improve the CR rate. Initial spleen ≥ 3 cm is an independent prognostic factor. The efficacy of chemotherapy alone is poor, and imatinib combined with chemotherapy is applauded in the aim of improving outcomes.
الموضوعات
Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Antineoplastic Combined Chemotherapy Protocols , Benzamides , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Prognosis , Remission Induction , Retrospective Studies , Treatment Outcomeالملخص
<p><b>OBJECTIVE</b>To assess the efficacy and safety of bladder irrigation with amphotericin B for treatment of fungal infection in the urinary tract.</p><p><b>METHODS</b>All the available randomized controlled trials (published before March, 2018) examining bladder irrigation with amphotericin B for treatment of urinary tract fungal infection were searched in the Cochrane Central Register of Controlled Trials (Issue 12, 2017), PubMed, EMBase, Web of Knowledge Database, CNKI, CBM, Wanfang DATA and VIP information. Data were extracted from the selected trials for meta-analysis using RevMan 5.3 software.</p><p><b>RESULTS</b>A total of 96 studies were retrieved from the databases, and 9 trials involving 853 patients were included in the analysis. Meta-analysis results showed that compared with oral administration of fluconazole, bladder irrigation with amphotericin B was more effective in the treatment of fungal infection in the urinary tract (OR=1.66, 95%CI: 1.2-2.3, P=0.002) and was associated with less adverse reactions.</p><p><b>CONCLUSION</b>Bladder irrigation with amphotericin B can improve the curative effect of fungal infection in the urinary tract, but due to the small sample size of the included studies, this conclusion needs to be further validated by high-quality studies.</p>
الملخص
The study found that the presence of intestinal microbiota is not only important for the metabolism of essential nutrients in the body, but also plays a key role in the development of the body′s immune system in recent years. Partial microbiota, through natural selection and co-evolution with the host, forms symbiotic relationships with host microbes that are inseparable from host physiology in mice. Symbiotic flora affects the formation of the body′s immune system by affecting innate and adaptive immunity and the development of various regulatory mechanisms. The destruction of the microbial ecosystem in the intestine can lead to the occurrence of many diseases,especially those related to the immune system. Peripheral immune organs always receive a number of immune cells colonized by antigen stimulation. So,the intestinal flora plays an important role in maintaining the function of immune cells. This article will investigates the effects of mouse-related intestinal flora on peripheral immune organ function.