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Abstract Objectives We aimed to explore the heterogeneity and differentiation trajectories of epithelial cells and NK/T-cells in Laryngeal Squamous Cell Carcinoma (LSCC). Methods We downloaded the GSE150321 data set containing LSCC01 and LSCC02 samples single cell RNA data from Gene Expression Omnibus. The UMAP analysis was performed to identify the cell subpopulations and cell locations of subpopulations. Seurat package was used to analyze the differential expression of genes. The function of differential expression genes was analyzed using DAVID database. The monocle2 package was used to analyze differentiation trajectories. We used the CellChat package to observe the signaling pathways and ligand-receptor pairs for epithelial cells and NK/T-cells. Results All the LSCC cells were divided into 16 subpopulation that included 7 epithelial cell subsets, 3 T-cell subsets. The function analysis indicated that epithelial cells and NK/T-cells mainly participated in different process, such as cell cycle, immune response, and cell migration. Then, the results of differentiation trajectory indicated that the ability of migration, and the activation of the immune system increases, while the ability of apoptosis, and glucose metabolic process decreases as pseudotime. Migration-related epithelial cells act on all T-cells via the CNTN2-CNTN2 ligand-receptor pair, which suggested that CNTN2 might be an important biomarker for regulating migration of epithelial cells. Conclusions Our study characterized the heterogeneity of LSCC, which provided novel insights into LSCC and identified a new mechanism and target for clinical LSCC threapies. Evidence IV.
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Epilepsy is a chronic nervous system disease, which affects more than 70 million people all over the world. Although more than 30 kinds of antiepileptic drugs (AEDs) have been on the market, about one third of the patients with epilepsy fail to respond to medical treatment, who become drug-resistant epilepsy patients. Identifying the mechanism and developing effective treatment methods for drug-resistant epilepsy have become a hot area in the field of epilepsy research. This review discussed resent advance on the pathogenesis of drug-resistant epilepsy from the transporter hypothesis, neural network hypothesis and target hypothesis, and we also summarized the existing potential treatment methods and research progress of drug-resistant epilepsy, such as surgical resection, deep brain stimulation, ketogenic diet, precise treatment, and traditional Chinese medicine treatment. Our review may provide useful clues for the mechanisms research and clinical treatments of drug-resistant epilepsy.
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OBJECTIVE To prepare the nanoporous flower-shaped lactose (FL)-loaded curcumin (Cur) solid lipid nanoparticles (SLN) inhalation powder (Cur-SLN-FL), and to investigate its inhibition effect on LPS-induced apoptosis of BEAS- 2B cells. METHODS Using different kinds (lactose, sucrose, mannitol, trehalose) and different amounts (2%, 3%, 5%) of freeze-dried protectants as objects, the suspension of Cur-SLN was micronized by freeze-drying technology into lyophilized powder, which was then mixed with FL and sieved by a 200-mesh sieve to obtain Cur-SLN-FL. The physicochemical properties of Cur-SLN-FL was characterized by scanning electron microscopy and laser particle size analyzer. Using BEAS-2B cells cultured in vitro as objects, LPS-induced apoptosis and the changes of mitochondrial membrane potential after treatment of Cur-SLN-FL were detected by Annexin Ⅴ/PI double staining method and JC-1 kit. RESULTS With 3% trehalose as Cur-SLN freeze-dried protective agent, the freeze-dried powder obtained was compact and full in shape, did not shrink and collapse, and was uniform in color and light-yellow powder, which could be completely dissolved in 30 s. When FL and Cur-SLN freeze-dried powder were mixed at a ratio of 1∶2, it had a higher deposition rate of secondary distribution ([ 40.92±0.02)%]. SEM results showed that Cur-SLN-FL had a flower-shaped appearance with an average particle size of (4.95±0.57) μm and an aerodynamic particle size of (4.03±0.40) μm. The critical relative humidity of Cur-SLN-FL was about 54%, and the evacuation rate was (90.34 ± 1.21)%; the quantity of fine particles that could be inhaled by Cur-SLN-FL in the 2-7 receiving discs was (47.5±0.7)%, and the measured aerodynamic particle size was (4.33±0.08) μm. The LD50 of Cur-SLN-FL to BEAS-2B cells was 5.809 mg/mL. The apoptosis rate of model cells was significantly reduced after treatment of Cur-SLN-FL, and the mitochondrial membrane potential was significantly increased (P<0.05). CONCLUSIONS The preparation process of Cur-SLN-FL is simple and feasible. Cur-SLN-FL can improve LPS-induced apoptosis of BEAS-2B cells, and this effect is related to the regulation of mitochondrial membrane potential.
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Berberine(BBR),an isoquinoline alkaloid,has been found in many plants,such as Coptis chinensis Franch and Phellodendron chinense Schneid.Although BBR has a wide spectrum of pharmacological effects,its oral bioavailability is extremely low.In recent years,gut microbiota has emerged as a cynosure to un-derstand the mechanisms of action of herbal compounds.Numerous studies have demonstrated that due to its low bioavailability,BBR can interact with the gut microbiota,thereby exhibiting altered pharma-cological effects.However,no systematic and comprehensive review has summarized these interactions and their corresponding influences on pharmacological effects.Here,we describe the direct interactive relationships between BBR and gut microbiota,including regulation of gut microbiota composition and metabolism by BBR and metabolization of BBR by gut microbiota.In addition,the complex interactions between gut microbiota and BBR as well as the side effects and personalized use of BBR are discussed.Furthermore,we provide our viewpoint on future research directions regarding BBR and gut microbiota.This review not only helps to explain the mechanisms underlying BBR activity but also provides support for the rational use of BBR in clinical practice.
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Objective: To evaluate the effectiveness of mucosal flap combined with silicone keel for preventing and treating anterior commissure adhesion in canines and clinical cases. Methods: A prospective experiment was performed from November 2019 to June 2021. Twenty five canines were randomly divided into 5 groups(A, B, C, D, E). Group A, B, C, D received anterior commissure injury by CO2 laser, then separately treated with free mucosal flap-keel complex,intralaryngeal mucosal flap-keel complex, silicone keels and without treatment, group E didn't injure the vocal cord after intubation. The keel was removed after 2 weeks, the larynx was harvested after 4 weeks. The effectiveness of anterior commissure adhesion prevention was evaluated by manifestation under laryngoscope, standard vocal cord length and standard glottic area. A retrospective analysis was performed on sixteen patients with anterior commissure lesion, who underwent mucosal flap-keel technique in Huashan Hospital of Fudan University from January 2019 to January 2021 (10 cases with free mucosal flap-keel complex and 6 cases with intralaryngeal mucosal flap-keel complex). All the patients underwent evaluation of laryngeal function included manifestation under laryngoscope each month and voice analysis before and 3 month after surgery. SPSS 20.0 software was used for statistical analysis. Results: No surgery accident or complication happened in canines and patients. The standard vocal cord length and standard glottic area after 4 weeks in group B were significantly higher than those in group A, C, D (Hstandard vocal cord length=31.688, Hstandard glottic area=16.444, P<0.05). The standard vocal cord length and standard glottic area after 4 weeks in group A were also significantly higher than those in group C, D(Hstandard vocal cord length=20.936, Hstandard glottic area=11.786, P<0.05). The standard vocal cord length and standard glottic area after 4 weeks in group A, B, E were not significantly different to that before surgery(tA left standard vocal cord length=2.636, tA right standard vocal cord length=2.582, tB left standard vocal cord length=2.707, tB right standard vocal cord length=2.673, tE left standard vocal cord length=0.370, tE right standard vocal cord length=0.821, tA standard glottic area=2.731, tB standard glottic area=2.753, tE standard glottic area=-0.529, P>0.05). The standard vocal cord length and standard glottic area after 4 weeks in group C, D were significantly lower than those before surgery(tC left standard vocal cord length=16.137, tC right standard vocal cord length=13.984, tD left standard vocal cord length=11.903, tD right standard vocal cord length=14.587, tC standard glottic area=10.280, tD standard glottic area=22.974, P<0.05). During 6-18 months of follow-up in clinical patients, no one developed a glottic web. Three months after surgery, Jitter, Shimmer, noise to harmonic ratio(NHR), the maximum phonation time(MPT)in all patients were significantly different from preoperative(tintralaryngeal mucosal flap jitter=24.885, tintralaryngeal mucosal flap shimmer=22.643, tintralaryngeal mucosal flap NHR=6.202, tintralaryngeal mucosal flap MPT=-9.661, tfree mucosal flap jitter=25.459, tfree mucosal flap shimmer=18.683, tfree mucosal flap NHR=5.705, tfree mucosal flap MPT=-20.840, P<0.05). Conclusion: Mucosal flap combined with silicone keel is an effective technique for preventing and treating anterior commissure adhesion. The effect of pedicled intralaryngea lmucosal flap is better.
Subject(s)
Animals , Dogs , Humans , Free Tissue Flaps , Glottis , Laryngeal Neoplasms/surgery , Prospective Studies , Retrospective Studies , Vocal Cords/surgeryABSTRACT
OBJECTIVE@#To compare the clinical efficacy of initial periodontal therapy in periodontitis patients with or without type 2 diabetes mellitus and its correlation with white blood cell counts.@*METHODS@#In this study, 32 chronic periodontitis patients without systemic disease (CP group) and 27 chronic periodontitis patients with type 2 diabetes mellitus (CP+DM group) were enrolled. At admission, all the patients went through periodontal examination and fasting blood examination(baseline). Probing depth (PD), attachment loss (AL), bleeding index (BI), plaque index (PLI), white blood cells (WBC) counts and fasting blood glucose (FBG) were recorded respectively, while hemoglobin A1c (HbA1c) was recorded only in CP+DM group. After that, initial periodontal therapy was performed. All the tests were repeated 3 and 6 months after treatment. The changes of periodontal clinical indexes and WBC levels were compared between the two groups before and after treatment, and the correlation between WBC and periodontal clinical indexes and glucose metabolism indexes were analyzed by generalized linear mixed model.@*RESULTS@#At baseline, the periodontal inflammation and destruction were similar in CP and CP+DM group, but the WBC level was significantly higher in CP+DM groups [(6.01±1.26)×109/L vs. (7.14±1.99)×109/L, P=0.01]. After 3 and 6 months of initial periodontal therapy, the mean PD, AL, BI, and PLI in CP+DM and CP groups were significantly lower than the baseline, and the PD in CP+DM group was further decreased by 6 months compared with 3 months [(3.33±0.62) mm vs. (3.61±0.60) mm, P < 0.05]. However, none of these periodontal indexes showed significant difference between the two groups by 3 or 6 months. In CP+DM group, HbA1c at 3 months and 6 months were significantly lower than the baseline [(7.09±0.79)% vs. (7.64±1.16)%, P < 0.05; (7.06±0.78)% vs. (7.64±1.16)%, P < 0.05], and FBG was significantly lower than the baseline by 6 months [(7.35±1.14) mmol/L vs. (8.40±1.43) mmol/L, P < 0.05]. The WBC level in CP group was significantly lower than the baseline level by 3 months [(5.35±1.37)×109/L vs. (6.01±1.26)×109/L, P < 0.05], while that in CP+DM group was significantly lower than the baseline level by 6 months [(6.00±1.37)×109/L vs. (7.14±1.99)×109/L, P < 0.05]. The analysis of genera-lized linear mixed model showed that WBC level was significantly positively correlated with PD and FBG (P < 0.05).@*CONCLUSION@#Initial periodontal therapy can effectively improve the periodontal clinical status of patients with or without type 2 diabetes mellitus, and have benefits on glycemic control in diabetic patients. However, the response of periodontal indexes and WBC level to initial therapy were relatively delayed in diabetic patients. WBC plays an important role in the correlation between diabetes mellitus and periodontitis.
Subject(s)
Humans , Chronic Periodontitis/therapy , Diabetes Mellitus, Type 2/complications , Glycated Hemoglobin/analysis , Leukocytes/chemistry , Periodontal IndexABSTRACT
Two new neolignans and one new lignan (1-3) were obtained from the roots of Paeonia lactiflora. Their structures were unambiguously elucidated based on extensive spectroscopic analysis, single-crystal X-ray crystallography, and the calculated and experimental electronic circular dichroism (ECD) spectra. Compound 1 was a racemic mixture and successfully resolved into the anticipated enantiomers via chiral-phase HPLC. Compound 3 demonstrated moderate inhibitory activity against human carboxylesterase 2A1 (hCES2A1) with an IC50 value of 7.28 ± 0.94 μmol·-1.
Subject(s)
Humans , Chromatography, High Pressure Liquid , Lignans/chemistry , Paeonia , Plant Roots/chemistry , StereoisomerismABSTRACT
Three new ursane-type triterpenoids, 3-oxours-12-en-20, 28-olide (1), 3β-hydroxyurs-12-en-20, 28-olide (2) and 3β-hydroxyurs-11, 13(18)-dien-20, 28-olide (3), were isolated from a potent anti-inflammatory and antibacterial fraction of the ethanolic extract of Rosmarinus officinalis. Their structures were elucidated by a combination of extensive 1D- and 2D-NMR experiments, MS data and comparisons with literature reports. Compounds 1-3 exhibited significantly inhibitory effects on nitric oxide production in lipopolysaccharide-activated mouse RAW264.7 macrophages, but no antibacterial activity was found at a concentration of 128 μg·mL-1.
Subject(s)
Animals , Mice , Drugs, Chinese Herbal/chemistry , Molecular Structure , Rosmarinus , Triterpenes/chemistryABSTRACT
Numerous studies have reported that the resistance of biofilm bacteria to antibiotics can be up to 10-1 000 fold higher than that of planktonic bacteria. Bacterial biofilms are reported to be responsible for more than 80% of human microbial infection, posing great challenges to the healthcare sector. Many studies have reported that plant extracts and their active ingredients can inhibit the formation and development of bacterial biofilms, including reducing biofilm biomass and the number of viable bacteria in biofilms, as well as eradicating mature biofilms. This review summarized the plant extracts and their active ingredients that are inhibitory to bacterial biofilms, and analyzed the underpinning mechanisms. This review may serve as a reference for the development of plant drugs to prevent and treat biofilm infections.
Subject(s)
Humans , Anti-Bacterial Agents/pharmacology , Bacteria , Biofilms , Plant Extracts/pharmacology , Quorum SensingABSTRACT
OBJECTIVE To observe the ther apeutic efficacy and safety of albumin-bound paclitaxel combined with oxaliplatin in the first-line treatment of advanced gastric cancer (GC). METHODS A total of 90 advanced unresectable GC patients were randomized into observation group and control group ,with 45 patients in each group. Control group was given oxaliplatin combined with tegafur ,and observation group was given albumin-bound paclitaxel combined with oxaliplatin. A chemotherapy cycle last for 21 days,and both groups received 6 cycles of chemotherapy ,and then the follow-up observation was conducted every 2 weeks. Short-term efficacy (after 2 chemotherapy cycles ),mid-term efficacy (after 6 chemotherapy cycles ),tumor marker,long-term efficacy (after follow-up ),quality of life ,the occurrence of ADRs were compared between 2 groups. RESULTS After 2 cycles of treatment ,objective remission rate (ORR)of observation group was significantly higher than that of control group (60.00% vs. 37.78%,P<0.05);there was no statistical significance in disease control rate between the two groups (P>0.05). After 6 chemotherapy cycles ,ORR of observation group was significantly higher than that of control group (55.56% vs. 31.11%,P<0.05);there was no statistical significance in disease control rate between the two groups (P>0.05);the levels of tumor markers [carcinoembryonic antigen , carbohydrate antigen (CA)724, CA199, CA242] in observation group were significantly lower than those of control group (P<0.05). After the follow-up period ,the median progression-free survival [ 8.78 (95%CI:6.94-11.01)months] and the median overall survival [ 13.02(95%CI:12.78-15.62)months] of observation group were significantly longer than those [ 6.99(95%CI:3.67-10.88)months and 10.42(95%CI:8.72-13.22)months] of control group (P< 0.05). The score of body dimension in the observation group was significantly higher than that in the control group (P<0.05). Except for peripheral neurotoxicity ,there was no significant difference in the incidence of ADR between 2 groups(P>0.05). CONCLUSIONS Albumin-bound paclitaxel combined with oxaliplatin has a good effect and safety in the first-line treatment of advanced unresectable GC.
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AIM: To evaluate the influence of slight eye movement during laser scanning on femtosecond laser precision of corneal ablation and postoperative refractive status in small incision lenticule extraction(SMILE). METHODS: Totally 32 patients(62 eyes)who underwent SMILE surgery in our hospital from January 2019 to March 2021 were included and divided into the movement group and the fixation group according to whether the eyeballs were slightly moved during the operation, and select patients with slightly moved monocular eyeballs for binocular pairing. The actual difference of absolute value of corneal absolute cutting error(ACE), astigmatism error(AE), absolute refractive error(ARE)and absolute visual error(AVE)was compared between the movement group and the fixation group and the two eyes of the patients with slight ocular movement in one eye at 1mo after surgery, and the surgical images were quantified to analyze the correlation between the amplitude of ocular movement and AE, and to compare the effects of the area, layer and direction of slight eye movement on ACE.RESULTS: There were no differences in all observed results between movement group and fixation group(P>0.05). Patients with slight movement of one eye had a difference in binocular AE(0.57±0.31D vs 0.33±0.27D, P<0.05), and the amplitude of movement was positively correlated with AE at 1mo after surgery(r=0.564, P<0.05). There was no statistical differences in ACE at 1mo after surgery in patients with slight ocular movement in different regions(central/peripheral), layers(upper/lower lens)and direction(nasal/temporal)(all P>0.05).CONCLUSION:The slight eye movement during laser scanning in SMILE has no significant influence on precision of corneal ablation. It mainly causes decentered ablation and the changes of corneal astigmatism, which has little effect on the spherical equivalent and visual acuity.
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In a continuing search for biological natural products with structure diversity from traditional Chinese herbs, five new sesquineolignans (1-5) were isolated from an ethyl acetate extract of the twigs of Litsea cubeba. Their structures were elucidated based on MS, 1D and 2D NMR spectroscopic data, as well as experimental electronic circular dichroism (ECD) spectra. Compounds 1-5 showed moderate inhibitory effects against LPS-induced NO production in RAW264.7 macrophages, with IC
Subject(s)
Litsea , Macrophages , Molecular StructureABSTRACT
Objective:In general, patients with seropositive rheumatoid arthritis (RA) are considered to show an aggressive disease course. However, the relationship between the two subgroups in disease severity is controversial. Our study is aimed to compare the clinical characteristics and prognosis of double-seropositive and seronegative RA in China through a real-world large scale study.Methods:RA patients who met the 1987 American College of Rheumatology (ACR) classification criteria or the 2010 ACR/European Anti-Rheumatism Alliance RA classification criteria, and who attended the 10 hospitals across the country from September 2015 to January 2020, were enrolled. According to the serological status, patients were divided into 4 subgroups [rheumatoid factor (RF)(-) anti-cyclic citrullinated peptide (CCP) antibody (-), RF(+), RF(+) anti-CCP antibody(+), anti-CCP antibody(+)] and compared the disease characteristics and treatment response. One-way analysis of variance was used for measurement data that conformed to normal distribution, Kruskal-Wallis H test was used for measurement data that did not conform to normal distribution; paired t test was used for comparison before and after treatment within the group if the data was normally distributed else paired rank sum test was used; χ2 test was used for count data. Results:① A total of 2 461 patients were included, including 1 813 RF(+) anti-CCP antibody(+) patients (73.67%), 129 RF(+) patients (5.24%), 245 RF(-) anti-CCP antibody(-) patients (9.96%), 74 anti-CCP antibody(+) patients (11.13%). ② Regardless of the CCP status, RF(+) patients had an early age of onset [RF(-) anti-CCP antibody(-) (51±14) years old, anti-CCP antibody(+) (50±15) years old, RF(+) anti-CCP antibody(+) (48±14) years old, RF(+)(48±13) years old, F=3.003, P=0.029], longer disease duration [RF(-) anti-CCP antibody(-) 50 (20, 126) months, anti-CCP antibody(+) 60(24, 150) months, RF(+) anti-CCP antibody(+) 89(35, 179) months, RF(+) 83(25, 160) months, H=22.001, P<0.01], more joint swelling counts (SJC) [RF(-) anti-CCP antibody(-) 2(0, 6), Anti-CCP antibody(+) 2(0, 5), RF(+) anti-CCP antibody(+) 2(0, 7), RF(+) 2(0, 6), H=8.939, P=0.03] and tender joint counts (TJC) [RF(-) anti-CCP antibody(-) 3(0, 8), anti-CCP antibody(+) 2(0, 6), RF(+) anti-CCP antibody(+) 3(1, 9), RF(+) 2(0, 8), H=11.341, P=0.01] and the morning stiff time was longer [RF(-) anti-CCP antibody(-) 30(0, 60) min, anti-CCP antibody(+) 20(0, 60) min, RF(+) anti-CCP antibody(+) 30(10, 60) min, RF(+) 30(10, 60) min, H=13.32, P<0.01]; ESR [RF(-) anti-CCP antibody(-) 17(9, 38) mm/1 h, anti-CCP antibody(+) 20(10, 35) mm/1 h, RF(+) anti-CCP antibody(+) 26(14, 45) mm/1 h, RF(+) 28(14, 50) mm/1 h, H=37.084, P<0.01] and CRP [RF(-) anti-CCP antibody(-) 2.3 (0.8, 15.9) mm/L, Anti-CCP antibody(+) 2.7(0.7, 12.1) mm/L, RF(+) anti-CCP antibody(+) 5.2(1.3, 17.2) mm/L, RF (+) 5.2(0.9, 16.2) mm/L, H=22.141, P<0.01] of the RF(+)patients were significantly higher than RF(-) patients, and RF(+) patients had higher disease severity(DAS28-ESR) [RF(-) anti-CCP antibody(-) (4.0±1.8), anti-CCP antibody(+) (3.8±1.6), RF(+) anti-CCP antibody(+) (4.3±1.8), RF(+) (4.1±1.7), F=7.269, P<0.01]. ③ The RF(+) anti-CCP antibody(+) patients were divided into 4 subgroups, and it was found that RF-H anti-CCP antibody-L patients had higher disease severity [RF-H anti-CCP antibody-H 4.3(2.9, 5.6), RF-L anti-CCP antibody-L 4.5(3.0, 5.7), RF-H anti-CCP antibody-L 4.9(3.1, 6.2), RF-L anti-CCP antibody-H 2.8(1.8, 3.9), H=20.374, P<0.01]. ④ After 3-month follow up, the clinical characteristics of the four groups were improved, but there was no significant difference in the improvement of the four groups, indicating that the RF and anti-CCP antibody status did not affect the remission within 3 months. Conclusion:Among RA patients, the disease activity of RA patients is closely related to RF and the RF(+) patients have more severe disease than RF(-) patients. Patients with higher RF titer also have more severe disease than that of patients with low RF titer. After 3 months of medication treatment, the antibody status does not affect the disease remission rate.
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OBJECTIVE@#To observe the clinical efficacy of allogeneic peripheral blood stem cell transplantation(allo-HSCT) on the treatment of adult acute leukemia patients, moreover, to establish and evaluate a Logistic model to predict the risk of relapse in adult acute leukemia patients after allo-HSCT.@*METHODS@#The clinical data of 145 adult acute leukemia patients treated by peripheral blood stem cell transplantation in the First Affiliated Hospital of Xi'an Jiaotong University from January 2010 to December 2019 was enrolled and analyzed retrospectively. Complications and survival of patients were observed. The relationship between patients' age, diagnosis, leukocyte count at onset, risk stratification, time of diagnosis to transplantation, HCT-CI, minimal residual disease pre-transplantation, donor-recipient sex relationship, HLA match degree, prophylaxis of graft versus host disease(GVHD), donor age, number of transfused mononuclear cells, CD34 positive cells, engraftment time, acute and chronic GVHD, CMV, EBV infection, and hemorrhagic cystitis and recurrence after transplantation were analyzed by logistic regression. Relapse prediction model was established and evaluated according to the results.@*RESULTS@#Among 145 acute leukemia patients, 81 with acute myeloid leukemia, 64 with acute lymphocytic leukemia, 18 with EBV infection, 2 with post-transplant lymphoproliferative disorder(PTLD), 85 with CMV, 26 with hemorrhagic cystitis, 65 patients developed acute GVHD, 51 patients developed chronic GVHD and 45 patients relapsed. The overall survival (OS) rates in one and three years were 86.4% and 61.8%, and the progress-free survival (PFS) rates in one and three years were 67.5% and 62.4%, respectively. There were significant differences in OS and PFS between relapsed and non-relapsed patients, as well as AML and ALL patients. Univariate analysis revealed that patient's age, risk stratification, time to transplantation, HCT-CI index, ATG based GVHD prophylaxis, minimal residual disease pre-transplantation, GVHD prophylaxis, and acute and chronic GVHD were associated with the relapse of disease, multivariate logistic regression analysis showed that pre-transplantation minimal residual disease showed positively correlation with relapse of the disease, while chronic GVHD showed negatively correlation.@*CONCLUSION@#The relapse rate of adult acute leukemia patients treated with allo-HSCT in our hospital is 31.0%, and OS of AML patients is better than ALL patients'. OS of relapsed patients is significantly lower than non-relapsed patients'. Pre-transplantation minimal residual disease is a risk factor of relapse. The risk of relapse is reduced in patients with chronic GVHD.
Subject(s)
Adult , Humans , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute/therapy , Peripheral Blood Stem Cell Transplantation , Recurrence , Retrospective Studies , Transplantation ConditioningABSTRACT
OBJECTIVE@#To analyze the risk factors affecting hemorrhagic cystitis(HC) after allogeneic hematopoietic stem cell transplantation(allo-HSCT).@*METHODS@#The clinical data of 153 patients underwent allogeneic hematopoietic stem cell transplantation in the First Affiliated Hospital of Xi'an Jiaotong University from January 2010 to December 2018 were selected and retrospectively analyzed. The incidence, median time and treatment outcome of HC should be observed. Multivariate analysis was used to observe the risk factors of HC in patients, including sex, age, diagnosis, disease status before transplantation, transplantation type, ATG and CTX in the pretreatment scheme, stem cell source, neutrophil and platelet implantation time; CMV, EBV and BKV infection, and acute graft-versus-host disease(aGVHD).@*RESULTS@#Among 153 patients underwent allogeneic hematopoietic stem cell transplantation, 25 (16.34%) patients had HC, the median occurance time was 31 days, all patients achieved complete remission after treatment, no bladder irritation and bladder contracture were left. The results of univariate and multivariate Logistic regression analysis showed that the type of transplantation, ATG, CMV viremia before treatment, aGVHD (r=1.036, 3.234, 3.298 and 2.817, respectively) were the independent risk factors of HC.@*CONCLUSION@#The urinary BKV detections in the patients with HC are positive, mainly occured during the period from day +13 to days +56. HLA haplotype, pretreatment including ATG, and CMV viremia, and aGVHD are the independent risk factors for HC after allo-HSCT.
Subject(s)
Humans , Cystitis/etiology , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation/adverse effects , Retrospective Studies , Risk FactorsABSTRACT
The present study explored the mechanism of Fagopyri Dibotryis Rhizoma(FDR) and its main active components in the treatment of acute lung injury(ALI) based on the network pharmacology and the in vitro experiments. The main active components of FDR were obtained from the TCMSP database and screened by oral bioavailability and drug-likeness. The related target proteins of FDR were retrieved from the PubChem database, and the target genes related to ALI were screened out from the GeneCards database. A protein-protein interaction(PPI) network of compound target proteins and ALI target genes was constructed using STRING 11.0. Ingenuity Pathway Analysis(IPA) platform was used to analyze the common pathways of the potential compound target proteins of FDR and ALI target genes, thereby predicting the key targets and potential signaling pathways of FDR for the treatment of ALI. Finally, the potential pathways and key targets were verified by the in vitro experiments of lipopolysaccharide-induced RAW264.7 cells intervened by epicatechin(EC), the active component of FDR. The results of network pharmacology showed that 15 potential active components such as EC, procyanidin B1, and luteolin presumedly functioned in the treatment of ALI through nuclear transcription factor-κB(NF-κB) signaling pathway, transforming growth factor-β(TGF-β) signaling pathway, and adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK) signaling pathway through key targets, such as RELA(P65). The results of in vitro experiments showed that 25 μmol·L~(-1) EC had no toxicity to cells and could inhibit the expression of the p65-phosphorylated protein in the NF-κB signaling pathway to down-regulate the expression of downstream inflammatory cytokines, including tumor necrosis factor-α(TNF-α), IL-1β and nitric oxide(NO), and up-regulate the expression of IL-10. These results suggested that the therapeutic efficacy of FDR on ALI was achieved by inhibiting the phosphorylation of p65 protein in the NF-κB signaling pathway and down-regulating the level of proinflammatory cytokines downstream of the signaling pathways.
Subject(s)
Acute Lung Injury/genetics , Lipopolysaccharides , NF-kappa B/metabolism , Rhizome , Signal TransductionABSTRACT
The genus Chloranthus has 13 species and 5 varieties in China, which can be found in the southwest and northeast regions. Phytochemical studies on Chloranthus plants have reported a large amount of terpenoids, such as diterpenoids, sesquiterpenoids, and sesquiterpenoid dimers. Their anti-inflammation, anti-tumor, antifungal, antivirus, and neuroprotection activities have been confirmed by previous pharmacological research. Herein, research on the chemical constituents from Chloranthus plants and their biological activities over the five years was summarized to provide scientific basis for the further development and utilization of Chloranthus plants.
Subject(s)
Diterpenes , Phytochemicals/pharmacology , Plants , Sesquiterpenes/pharmacology , TerpenesABSTRACT
With repeated silica gel, octadecyl silica(ODS), and Sephadex LH-20 column chromatography, normal-phase and reverse-phase high performance liquid chromatography(HPLC), etc., a pair of new enantiomers and 5 known compounds were separated from the 95% ethanol extract of Chloranthus multistachys. These compounds were identified by the nuclear magnetic resonance spectroscopy(including 1 D-NMR and 2 D-NMR), single-crystal X-ray diffraction, circular dichroism(CD) spectroscopy, mass spectrometry(MS), and some other methods as(1R,4R,5R,8S,10R)-chloraeudolide H(1 a),(1S,4S,5S,8R,10S)-chloraeudolide H(1 b), hydroxyisogermafurenolide(2), 4α-hydroxy-5α,8β(H)-eudesm-7(11)-en-8,12-olide(3), chloraniolide A(4), chlorantene D(5), 4α,8β-dihydroxy-5α(H)-eudesm-7(11)-en-8,12-olide(6). Compounds 1 a and 1 b are a pair of new eudesmane-type sesquiterpene enantiomers, and compounds 2-4 were isolated from C. multistachys for the first time.
Subject(s)
Chromatography, High Pressure Liquid , Magnetic Resonance Spectroscopy , Mass Spectrometry , Molecular Structure , Sesquiterpenes , StereoisomerismABSTRACT
Trigonella foenum-graecum is an annual plant of the genus Trigonella in the Leguminosae family. It is widely distributed in China and has a long history of application. According to phytochemistry research, the seeds, stem, and leaves of this herb contain not only a variety of bioactive ingredients, including alkaloids, saponins, polysaccharides, flavonoids, and phenols, but also abundant nutrients such as unsaturated fatty acids and amino acids and various trace elements. Pharmacological studies have shown that both the extract of T. foenum-graecum and its chemical constituents exhibit hypoglycemic, hypolipidemic, antitumor, antioxidative, antimicro-bial, and hepatoprotective activities. This paper reviews the research progress on the chemical constituents and pharmacological effects of T. foenum-graecum, which may contribute to further development, application, and clinical research of this herb.
Subject(s)
Antioxidants/pharmacology , Hypoglycemic Agents , Plant Extracts/pharmacology , Seeds , TrigonellaABSTRACT
Eight sesquiterpenes were isolated and purified from the ethanol extract of Chloranthus henryi by column chromatographies over silica gel, ODS and Sephadex LH-20,and preparative HPLC. Their chemical structures were established by spectral data and physiochemical properties as(1S,6S,8S,10R)-8-ethoxy-10-methoxychlomultin C(1),tianmushanol(2),multistalide A(3),myrrhterpenoid N(4),1α,9α-dihydroxy-8,12-expoxy-eudesma-4,7,11-trien-6-one(5),4β,10α-aromadendranediol(6),oplopanone(7),10α-hydroxycadinan-4-en-3-one(8). Among them, compound(1) was a new compound, and compounds 2-8 were isolated from Chloranthus henryi for the first time.