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1.
Chinese Journal of Pediatrics ; (12): 49-54, 2024.
Artigo em Chinês | WPRIM | ID: wpr-1013248

RESUMO

Objective: To analyze the clinical characteristics and prognosis of patients with infant acute lymphoblastic leukemia (IALL). Methods: A retrospective cohort study.Clinical data, treatment and prognosis of 28 cases of IALL who have been treated at Beijing Children's Hospital, Capital Medical University and Baoding Children's Hospital from October 2013 to May 2023 were analyzed retrospectively. Based on the results of fluorescence in situ hybridization (FISH), all patients were divided into KMT2A gene rearrangement (KMT2A-R) positive group and KMT2A-R negative group. The prognosis of two groups were compared. Kaplan-Meier method and Log-Rank test were used to analyze the survival of the patients. Results: Among 28 cases of IALL, there were 10 males and 18 females, with the onset age of 10.9 (9.4,11.8) months. In terms of immune classification, 25 cases were B-ALL (89%), while the remaining 3 cases were T-ALL (11%). Most infant B-ALL showed pro-B lymphocyte phenotype (16/25,64%). A total of 22 cases (79%) obtained chromosome karyotype results, of which 7 were normal karyotypes, no complex karyotypes and 15 were abnormal karyotypes were found. Among abnormal karyotypes, there were 4 cases of t (9; 11), 2 cases of t (4; 11), 2 cases of t (11; 19), 1 case of t (1; 11) and 6 cases of other abnormal karyotypes. A total of 19 cases (68%) were positive for KMT2A-R detected by FISH. The KMT2A fusion gene was detected by real-time PCR in 16 cases (57%). A total of 24 patients completed standardized induction chemotherapy and were able to undergo efficacy evaluation, 23 cases (96%) achieved complete remission through induction chemotherapy, 4 cases (17%) died of relapse. The 5-year event free survival rate (EFS) was (46±13)%, and the 5-year overall survival rate (OS) was (73±10)%.The survival time was 31.3 (3.3, 62.5) months. There was no significant statistical difference in 5-year EFS ((46±14)% vs. (61±18)%) and 5-year OS ((64±13)% vs. (86±13)%) between the KMT2A-R positive group (15 cases) and the KMT2A-R negative group (9 cases) (χ2=1.88, 1.47, P=0.170, 0.224). Conclusions: Most IALL patients were accompanied by KMT2A-R. They had poor tolerance to traditional chemotherapy, the relapse rate during treatment was high and the prognosis was poor.


Assuntos
Masculino , Criança , Lactente , Feminino , Humanos , Estudos Retrospectivos , Hibridização in Situ Fluorescente , Prognóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Cariótipo Anormal , Recidiva
2.
Chinese journal of integrative medicine ; (12): 230-242, 2024.
Artigo em Inglês | WPRIM | ID: wpr-1010324

RESUMO

OBJECTIVE@#To examine the therapeutic effect of Fangji Fuling Decoction (FFD) on sepsis through network pharmacological analysis combined with in vitro and in vivo experiments.@*METHODS@#A sepsis mouse model was constructed through intraperitoneal injection of 20 mg/kg lipopolysaccharide (LPS). RAW264.7 cells were stimulated by 250 ng/mL LPS to establish an in vitro cell model. Network pharmacology analysis identified the key molecular pathway associated with FFD in sepsis. Through ectopic expression and depletion experiments, the effect of FFD on multiple organ damage in septic mice, as well as on cell proliferation and apoptosis in relation to the mitogen-activated protein kinase 14/Forkhead Box O 3A (MAPK14/FOXO3A) signaling pathway, was analyzed.@*RESULTS@#FFD reduced organ damage and inflammation in LPS-induced septic mice and suppressed LPS-induced macrophage apoptosis and inflammation in vitro (P<0.05). Network pharmacology analysis showed that FFD could regulate the MAPK14/FOXO signaling pathway during sepsis. As confirmed by in vitro cell experiments, FFD inhibited the MAPK14 signaling pathway or FOXO3A expression to relieve LPS-induced macrophage apoptosis and inflammation (P<0.05). Furthermore, FFD inhibited the MAPK14/FOXO3A signaling pathway to inhibit LPS-induced macrophage apoptosis in the lung tissue of septic mice (P<0.05).@*CONCLUSION@#FFD could ameliorate the LPS-induced inflammatory response in septic mice by inhibiting the MAPK14/FOXO3A signaling pathway.


Assuntos
Camundongos , Animais , Proteína Quinase 14 Ativada por Mitógeno/metabolismo , Wolfiporia , Lipopolissacarídeos/farmacologia , Sepse/complicações , Transdução de Sinais , Inflamação/tratamento farmacológico , Radioisótopos de Oxigênio
3.
Chinese Journal of School Health ; (12): 606-611, 2023.
Artigo em Chinês | WPRIM | ID: wpr-972757

RESUMO

Objective@#To analyze the research status, hotspots and frontier progress of hypertension in children in English and Chinese literature, so as to provide reference for the early prevention of hypertension in children.@*Methods@#The Web of Science core collection database and CNKI database were searched to collect the literature related to the study of hypertension in children from 2000 to 2021, and the CiteSpace 5.8.R3 and VOSviewer 1.6.18 visualization tools were used to analyze the literature characteristics including publications, authors, regions, institutional cooperation, research hotspots and frontiers.@*Results@#A total of 22 687 English studies and 4 440 Chinese studies were finally included. According to the analysis results, the number of articles published on hypertension in children was on the rise. The published English articles were mainly University of Toronto and University of Colorado. The main publishing institution of Chinese articles was the First Affiliated Hospital of Peking University. The United States and China took the lead in the number of core journals published in the field of hypertension in children, the United States ranked first in terms of the influence of publications. Keyword co occurrence analysis showed that the high frequency keywords in the English literature included prevalence, risk, obesity, risk factor, body mass index, insulin resistance, overweight, metabolic syndrome, cardiovascular disease and mortality. Chinese high frequency keywords in the literature include obesity, risk factors, adiposis, influencing factors, overweight, prevalence, diabetes, treatment, health education and body mass index. The analysis of keywords showed that 25 burst terms were obtained separately in English and Chinese literature.@*Conclusion@#In recent years, the research interest on hypertension in children continues to grow and keeps updated, with the research scope expanding significantly, regarding obesity, diabetes and cardiovascular diseases.

4.
China Pharmacy ; (12): 2350-2355, 2023.
Artigo em Chinês | WPRIM | ID: wpr-996391

RESUMO

OBJECTIVE To investigate the effect and mechanism of α7 nicotinic acetylcholine receptor (α7nAChR) agonists PNU-282987 on cognitive function in temporal lobe epilepsy (TLE) model rats. METHODS Sixty rats were randomly divided into control group, model group, PNU-282987 group (3 mg/kg) and methyllycaconitine (MLA)+PNU-282987 group (6 mg/kg MLA+3 mg/kg PNU-282987), with 15 rats in each group. Except for control group, the TLE model was established in the other groups. After the model was successfully established, each group was given relevant medicine or normal saline intraperitoneally, once a day, for two consecutive weeks. The epilepsy attack of rats was observed and scored, and the duration of seizures was recorded; the cognitive function of rats was detected; pathological morphology of neurons in CA1 region was observed; the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1β in the hippocampus were detected; the positive expressions of ionized calcium-binding adapter molecule-1 (IBA-1), α7nAChR, nuclear factor-κB (NF-κB) p65, p-NF-κB p65 in the hippocampus were detected. RESULTS Compared with model group, the score and duration of seizures, the number of IBA-1 positive cells, the levels of TNF- α, IL-6 and IL-1β, the expressions of NF- κB p65 and p-NF- κB p65 protein decreased significantly in the hippocampus (P<0.05); the escape latency time was shortened significantly (P<0.05), the time spent in the original platform quadrant and times of crossing the platform increased significantly (P<0.05); neuronal damage in the CA1 region of the hippocampus was significantly reduced; the expression of α7nAChR protein increased significantly in hippocampus (P<0.05). Compared with PNU-282987 group, the above indexes of rats in MLA+PNU-282987 group were reversed significantly (P<0.05). CONCLUSIONS PNU-282987 could improve cognitive dysfunction in TLE model rats, and its mechanism may be associated with inhibiting microglia-mediated inflammatory response through α7nAChR/NF- κB signaling pathway, thus reducing hippocampal neuronal damage.

5.
Chinese Journal of Postgraduates of Medicine ; (36): 633-638, 2023.
Artigo em Chinês | WPRIM | ID: wpr-991070

RESUMO

Objective:To investigate the predictive value of anticardiolipin antibody (ACA) and D-dimer (D-D) combined with risk assessment profile for thromboembolism (RAPT) for deep vein thrombosis (DVT) in elderly postoperative patients with intertrochanteric fracture of femur (IFF).Methods:The clinical data of 123 elderly patients with IFF in Suzhou Hospital Affiliated to Anhui Medical University from January 2019 to March 2022 were retrospectively analyzed. All patients underwent closed reduction intramedullary nail fixation. The patients were divided into DVT group (27 cases) and non-DVT group (96 cases) according to the presence or absence of DVT 7 d after surgery. Before surgery and 3, 5 d after operation, the ACA was detected by enzyme-linked immunosorbent assay, the D-D was detected by automatic coagulation analyzer, and RAPT was performed. The correlation among ACA, D-D and RAPT was analyzed by Spearman method. Multivariate Logistic regression was used to analyze the independent risk factors of DVT in elderly postoperative patients with IFF. Receiver operating characteristic (ROC) curve was used to analyze the efficacy of ACA, D-D and RAPT in predicting DVT in elderly postoperative patients with IFF. The incidences of postoperative DVT in patients with different ACA, D-D and RAPT patients were compared.Results:There were no statistical difference in ACA, D-D and RAPT before operation between the two groups ( P>0.05); the ACA, D-D and RAPT 3 and 5 d after operation in DVT group were significantly higher than those in the non-DVT group, 3 d after operation: (12.44 ± 3.25) × 10 3 RU/L vs. (8.67 ± 2.81) × 10 3 RU/L, (7.29 ± 1.49) mg/L vs. (4.70 ± 1.23) mg/L and (9.79 ± 1.15) scores vs. (9.21 ± 1.32) scores; 5 d after operation: (10.28 ± 2.16) × 10 3 RU/L vs. (6.45 ± 2.04) × 10 3 RU/L, (5.49 ± 1.26) mg/L vs. (3.63 ± 1.05) mg/L and (9.57 ± 1.08) scores vs. (9.12 ± 0.70) scores, and there were statistical differences ( P<0.01 or <0.05). Since ACA, D-D and RAPT in the two groups all reached their peak 3 d after operation, this time point was selected for analysis. Three days after operation, Pearson correlation analysis result showed that ACA and D-D were positively correlated with RAPT ( r = 0.635 and 0.630, P<0.01), and ACA was positively correlated with D-D ( r = 0.657, P<0.01). ROC curve analysis result showed that the area under the curve (AUC) of ACA and D-D combined RAPT 3 d after operation in predicting DVT in elderly postoperative patients with IFF was greater than that predicted by the 3 indexes alone (0.982 vs. 0.894, 0.870 and 0.868), the optimal cut-off values were 11.48 × 10 3 RU/L, 6.75 mg/L and 9 scores. According to the optimal cut-off value of ROC curve analysis at 3 d after operation, the patients were divided into ACA low expression (≤11.48 × 10 3 RU/L, 92 cases) and ACA high expression (>11.48 × 10 3 RU/L, 31 cases), D-D low expression (≤6.75 mg/L, 99 cases) and D-D high expression (>6.75 mg/L, 24 cases), low RAPT (≤9 scores, 93 cases) and high RAPT (>9 scores, 30 cases). The incidences of postoperative DVT in patients with ACA high expression, D-D high expression and high RAPT were significantly higher than those in patients with ACA low expression, D-D low expression and low RAPT: 43.39% (15/31) vs. 13.04% (12/92), 54.17% (13/24) vs. 14.14% (14/99) and 53.33% (16/30) vs. 11.83% (11/93), and there were statistical differences ( χ2 = 16.91, 18.06 and 22.81; P<0.01). After controlling for diabetes and other factors, multivariate Logistic regression analysis result showed that ACA, D-D and RAPT 3 d after operation were independent risk factors for DVT in elderly postoperative patients with IFF ( OR = 2.156, 2.276 and 6.106; 95% CI 1.356 to 3.429, 1.240 to 4.177 and 1.564 to 23.840; P<0.01). Conclusions:The ACA, D-D combined with RAPT can improve the predictive value of DVT in elderly postoperative patients with IFF, which has important reference significance for taking timely and effective intervention measures in early clinical stage.

6.
Chinese Journal of Digestive Surgery ; (12): 933-937, 2023.
Artigo em Chinês | WPRIM | ID: wpr-990716

RESUMO

As a special mode of tumor metastasis, perineural invasion has been paid more and more attention. It is closely related to prognosis, recurrence and metastasis of tumor after surgery. As the most common malignancy of the biliary tract, perineural invasion is also an inde-pendent prognostic risk factor for gallbladder cancer due to its anatomical location, lymphatic reflux, blood perfusion and innervation. However, there are few studies on perineural invasion in gallbla-dder cancer, especially on its mechanism. By analyzing the general situation and recent progress of perineural invasion in gallbladder cancer, the authors mainly introduce the perineural invasion mechanism, perineural invasion rate of gallbladder cancer, relationship between perineural invasion and the clinical pathologic characteristic, the correlation with the prognosis, relationship with surgi-cal procedures and postoperative adjuvant therapy.

7.
Chinese Journal of Digestive Surgery ; (12): 866-872, 2023.
Artigo em Chinês | WPRIM | ID: wpr-990708

RESUMO

Objective:To investigate the influencing factors of textbook outcomes in liver surgery (TOLS) after radical resection of gallbladder carcinoma.Methods:The retrospective case-control study was conducted. The clinicopathological data of 530 patients who underwent radical resection of gallbladder carcinoma in 15 medical centers, including the First Affiliated Hospital of Army Medical University et al, from January 2014 to January 2020 were collected. There were 209 males and 321 females, aged (61±10)years. Patients underwent radical resection of gallbladder carcinoma, including cholecystectomy, hepatectomy, invasive bile duct resection, and lymph node dissection. Observation indicators: (1) situations of TOLS; (2) influencing factors of TOLS. Measure-ment data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the Mann-Whitney U test. The univariate analysis was conducted using the corresponding statistical methods based on data type, and variables with P<0.10 were included in multivariate analysis. Multivariate analysis was conducted using the Logistic stepwise regression model. Results:(1) Situations of TOLS. All 530 patients underwent radical resection of gallbladder carcinoma, and there were 498 cases achieving R 0 resection, 508 cases without ≥grade 2 intra-operative adverse events, 456 cases without postoperative grade B and grade C biliary leakage, 513 cases without postoperative grade B and grade C liver failure, 395 cases without severe com-plications within postoperative 90 days, 501 cases did not being re-admission caused by severe com-plications within postoperative 90 days. Of the 530 patients, 54.53%(289/530) of patients achieved postoperative TOLS, while 45.47%(241/530) of patients did not achieve postoperative TOLS. (2) Influencing factors of TOLS. Results of multivariate analysis showed that American Society of Anesthesiologists classification >grade Ⅱ, preoperative jaundice, T staging as T3?T4 stage, N staging as N2 stage, liver resection as right hemi-hepatectomy, and neoadjuvant therapy were independent factors influencing TOLS in patients undergoing radical resection of gallbladder carcinoma ( odds ratio=2.65, 1.87, 5.67, 5.65, 2.55, 3.34, 95% confidence interval as 1.22?5.72, 1.18?2.95, 2.51?12.82, 2.83?11.27, 1.41?4.63, 1.88?5.92, P<0.05). Conclusion:American Society of Anesthesiologists classification >grade Ⅱ, preoperative jaundice, T staging as T3?T4 stage, N staging as N2 stage, liver resection as right hemi-hepatectomy, and neoadjuvant therapy are independent factors influencing TOLS in patients undergoing radical resection of gallbladder carcinoma.

8.
Journal of Clinical Hepatology ; (12): 457-462, 2023.
Artigo em Chinês | WPRIM | ID: wpr-964815

RESUMO

Hepatic alveolar echinococcosis (HAE) is a parasitic disease caused by Echinococcus multilocularis infection and has wide distribution and great harm in China. At present, ultrasound, CT, and MRI are the main radiological examination methods for HAE, with certain limitations in preoperative diagnosis and evaluation. This article introduces the guiding effect of three-dimensional visualization technique and its derivative technologies in the accurate diagnosis and preoperative evaluation of HAE, so as to provide help for the clinical diagnosis and treatment of HAE in the future.

9.
Acta Academiae Medicinae Sinicae ; (6): 783-788, 2023.
Artigo em Chinês | WPRIM | ID: wpr-1008132

RESUMO

Objective To explore the inhibitory effects and mechanisms of benzodiazepines on Helicobacter pylori (Hp).Methods The Hp international standard strain ATCC43504 was treated with benzodiazepines diazepam,midazolam,and remimazolam,respectively.The treatments with amoxicillin and clarithromycin were taken as the positive controls,and that with water for injection as the negative control.The inhibition zone of each drug was measured by the disk diffusion method.The minimum inhibitory concentration(MIC)and minimum bactericidal concentration(MBC)of each drug against Hp were determined.Hp suspension was configured and treated with diazepam and midazolam,respectively.The bacterial suspension without drug added was used as the control group.The concentration of K+ in each bacterial suspension was measured by an automatic biochemical analyzer before drug intervention(T0)and 1(T1),2(T2),3(T3),4(T4),5(T5),6(T6),and 7 h(T7)after intervention.Hp urease was extracted and treated with 1/2 MIC diazepam,1 MIC diazepam,2 MIC diazepam,1/2 MIC midazolam,1 MIC midazolam,2 MIC midazolam,1 mg/ml acetohydroxamic acid,and water for injection,respectively.The time required for the rise from pH 6.8 to pH 7.7 in each group was determined by the phenol red coloring method.Results The inhibition zones of diazepam,midazolam,remimazolam,amoxicillin,clarithromycin,and water for injection against Hp were 52.3,42.7,6.0,72.3,60.8,and 6.0 mm,respectively.Diazepam and midazolam showed the MIC of 12.5 μg/ml and 25.0 μg/ml and the MBC of 25 μg/ml and 50 μg/ml,respectively,to Hp.The concentrations of K+ in the diazepam,midazolam,and control groups increased during T1-T7 compared with those at T0(all P<0.01).The concentration of K+ in diazepam and midazolam groups during T1-T4 was higher than that in the control group(all P<0.01).The time of inhibiting urease activity in the 1/2 MIC diazepam,1 MIC diazepam,2 MIC diazepam,1/2 MIC midazolam,1 MIC midazolam,and 2 MIC midazolam groups was(39.86±5.11),(36.52±6.65),(38.58±4.83),(39.25±6.19),(36.36±4.61),and(35.81±6.18)min,respectively,which were shorter than that in the acetohydroxamic acid group(all P<0.01)and had no significance differences from that in the water for injection group(all P>0.05).Conclusion Diazepam and midazolam exerted inhibitory effects on Hp,which may be related to the cleavage of Hp cells rather than inhibiting urease.


Assuntos
Midazolam , Helicobacter pylori , Urease , Claritromicina/farmacologia , Benzodiazepinas/farmacologia , Diazepam/farmacologia , Amoxicilina , Água , Antibacterianos/farmacologia
10.
Acta Pharmaceutica Sinica ; (12): 1988-1999, 2023.
Artigo em Chinês | WPRIM | ID: wpr-999119

RESUMO

Cardiovascular disease (CVD) is a major contributor to patient deaths worldwide, and its pathogenesis is complex and mortality rates are increasing every year. Numerous researches have shown that the gut microbiota and its metabolites were closely associated with the development of CVD, and gut microbiota was expected to be a potential new target for the treatment of CVD. Traditional Chinese medicine (TCM), characterized by its multi-component, multi-target and integrity, can play a therapeutic role in CVD by regulating the gut microbiota, which has obvious advantages in stabilizing the disease, improving heart function and enhancing quality of life, and is an ideal intestinal microecological regulator. Therefore, this review will mainly discuss the intimate association of gut microbiota and its metabolites with CVD, and the therapeutic strategies of TCM targeting gut microbiota to improve CVD, including regulating the composition of gut microbiota, protecting the intestinal mucosal barrier, influencing the intestinal immune function and modulating the metabolites of gut microbiota, in order to provide a reference for the research of TCM targeting gut microbiota for CVD.

11.
Chinese Pharmacological Bulletin ; (12): 1853-1858, 2023.
Artigo em Chinês | WPRIM | ID: wpr-1013696

RESUMO

Aim To investigate the effects of IL-33/ST2 signal regulation by osteomortin on immune function and sodium channel in otitis media rats. Methods Fifty SD rats were randomly divided into NO group (normal rats with gavage of normal saline), MO group (model rats with gavage of normal saline), OS group (model rats with gavage of 40 mg • kg-

12.
Chinese Pharmacological Bulletin ; (12): 1840-1846, 2023.
Artigo em Chinês | WPRIM | ID: wpr-1013689

RESUMO

Aim To investigate the protective effect of baicalin on renal fibrosis in rats with diabetic nephrop- III (Col- III) athy (DN) and to investigate its mechanism of action. Methods A rat model of diabetic nephropathy was constructed. The rats were randomly divided into control group, model group, baicalin low dose group, baicalin medium dose group, baicalin high dose group and metformin group, with 10 rats in each group. Except for the control group, all rats in each group were fed with streptozotocin 65 mg • kg -

13.
Chinese Journal of Hematology ; (12): 642-648, 2023.
Artigo em Chinês | WPRIM | ID: wpr-1012206

RESUMO

Objective: To explore the prognostic factors of extracellular NK/T cell lymphoma (ENKTL) treated with pegaspargase/L-asparaginase. Methods: The clinical data of 656 ENKTL patients diagnosed at 11 medical centers in the Huaihai Lymphoma Working Group from March 2014 to April 2021 were retrospectively analyzed. The patients were randomly divided into two groups: a training set (460 cases) and a validation set (196 cases) at 7∶3, and the prognostic factors of the patients were analyzed. A prognostic scoring system was established, and the predictive performance of different models was compared. Results: Patients' median age was 46 (34, 57) years, with 456 males (69.5% ) and 561 nasal involvement (85.5% ). 203 patients (30.9% ) received a chemotherapy regimen based on L-asparaginase combined with anthracyclines, and the 5-year overall survival rate of patients treated with P-GEMOX regimen (pegaspargase+gemcitabine+oxaliplatin) was better than those treated with SMILE regimen (methotrexate+dexamethasone+cyclophosphamide+L-asparaginase+etoposide) (85.9% vs 63.8% ; P=0.004). The results of multivariate analysis showed that gender, CA stage, the Eastern Cooperative Oncology Group performance status (ECOG PS) score, HGB, and EB virus DNA were independent influencing factors for the prognosis of ENKTL patients (P<0.05). In this study, the predictive performance of the prognostic factors is superior to the international prognostic index, Korean prognostic index, and prognostic index of natural killer lymphoma. Conclusion: Gender, CA stage, ECOG PS score, HGB, and EB virus DNA are prognostic factors for ENKTL patients treated with pegaspargase/L-asparaginase.


Assuntos
Masculino , Humanos , Pessoa de Meia-Idade , Asparaginase/uso terapêutico , Prognóstico , Estudos Retrospectivos , Linfoma Extranodal de Células T-NK/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Etoposídeo , Ciclofosfamida , Metotrexato/uso terapêutico , DNA/uso terapêutico , Resultado do Tratamento
14.
Acta Pharmaceutica Sinica B ; (6): 4918-4933, 2023.
Artigo em Inglês | WPRIM | ID: wpr-1011221

RESUMO

As a novel and promising antitumor target, AXL plays an important role in tumor growth, metastasis, immunosuppression and drug resistance of various malignancies, which has attracted extensive research interest in recent years. In this study, by employing the structure-based drug design and bioisosterism strategies, we designed and synthesized in total 54 novel AXL inhibitors featuring a fused-pyrazolone carboxamide scaffold, of which up to 20 compounds exhibited excellent AXL kinase and BaF3/TEL-AXL cell viability inhibitions. Notably, compound 59 showed a desirable AXL kinase inhibitory activity (IC50: 3.5 nmol/L) as well as good kinase selectivity, and it effectively blocked the cellular AXL signaling. In turn, compound 59 could potently inhibit BaF3/TEL-AXL cell viability (IC50: 1.5 nmol/L) and significantly suppress GAS6/AXL-mediated cancer cell invasion, migration and wound healing at the nanomolar level. More importantly, compound 59 oral administration showed good pharmacokinetic profile and in vivo antitumor efficiency, in which we observed significant AXL phosphorylation suppression, and its antitumor efficacy at 20 mg/kg (qd) was comparable to that of BGB324 at 50 mg/kg (bid), the most advanced AXL inhibitor. Taken together, this work provided a valuable lead compound as a potential AXL inhibitor for the further antitumor drug development.

15.
Journal of Integrative Medicine ; (12): 543-549, 2023.
Artigo em Inglês | WPRIM | ID: wpr-1010968

RESUMO

BACKGROUND@#Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is an important occurrence in the natural history of idiopathic pulmonary fibrosis (IPF), associated with high hospitalization rates, high mortality and poor prognosis. At present, there is no effective treatment for AE-IPF. Chinese herbal medicine has some advantages in treating IPF, but its utility in AE-IPF is unclear.@*OBJECTIVE@#The treatment of AE-IPF with Kangxian Huanji Granule (KXHJ), a compound Chinese herbal medicine, lacks an evidence-based justification. This study explores the efficacy and safety of KXHJ in patients with AE-IPF.@*DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS@#We designed a randomized, double-blind, placebo-controlled, exploratory clinical trial. A total of 80 participants diagnosed with AE-IPF were randomly assigned to receive KXHJ or a matching placebo; the treatment included a 10 g dose, administered twice daily for 4 weeks, in addition to conventional treatment. Participants were followed up for 12 weeks after the treatment.@*MAIN OUTCOME MEASURES@#The primary endpoints were treatment failure rate and all-cause mortality. Secondary endpoints included the length of hospitalization, overall survival, acute exacerbation rate, intubation rate, the modified British Medical Research Council (mMRC) score, and the St George's Respiratory Questionnaire for IPF (SGRQ-I) score.@*RESULTS@#The rate of treatment failure at 4 weeks was lower in the intervention group compared to the control group (risk ratio [RR]: 0.22; 95% confidence interval [CI]: 0.051 to 0.965, P = 0.023). There was no significant difference in all-cause mortality at 16 weeks (RR: 0.75; 95% CI: 0.179 to 3.138; P > 0.999) or in the acute exacerbation rate during the 12-week follow-up period (RR: 0.69; 95% CI: 0.334 to 1.434; P = 0.317). The intervention group had a shorter length of hospitalization than the control group (mean difference [MD]: -3.30 days; 95% CI, -6.300 to -0.300; P = 0.032). Significant differences in the mean change from baseline in the mMRC (between-group difference: -0.67; 95% CI: -0.89 to -0.44; P < 0.001) and SGRQ-I score (between-group difference: -10.36; 95% CI: -16.483 to -4.228; P = 0.001) were observed after 4 weeks, and also in the mMRC (between-group difference: -0.67; 95% CI: -0.91 to -0.43; P < 0.001) and SGRQ-I (between-group difference: -10.28; 95% CI, -15.838 to -4.718; P < 0.001) at 16 weeks. The difference in the adverse events was not significant.@*CONCLUSION@#KXHJ appears to be effective and safe for AE-IPF and can be considered a complementary treatment in patients with AE-IPF. As a preliminary exploratory study, our results provide a basis for further clinical research.@*TRIAL REGISTRATION@#Chinese Clinical Trial Registry (ChiCTR1900026289). Please cite this article as: Li JS, Zhang HL, Guo W, Wang L, Zhang D, Zhao LM, Zhou M. Efficacy and safety of Kangxian Huanji Granule as adjunctive treatment in acute exacerbation of idiopathic pulmonary fibrosis: an exploratory randomized controlled trial. J Integr Med. 2023; 21(6): 543-549.


Assuntos
Humanos , Método Duplo-Cego , Medicamentos de Ervas Chinesas/uso terapêutico , Fibrose Pulmonar Idiopática/tratamento farmacológico , Resultado do Tratamento
16.
China Journal of Chinese Materia Medica ; (24): 3287-3293, 2023.
Artigo em Chinês | WPRIM | ID: wpr-981466

RESUMO

This paper aimed to study the chemical constituents from the root bark of Schisandra sphenanthera. Silica, Sephadex LH-20 and RP-HPLC were used to separate and purify the 80% ethanol extract of S. sphenanthera. Eleven compounds were identified by ~1H-NMR, ~(13)C-NMR, ESI-MS, etc., which were 2-[2-hydroxy-5-(3-hydroxypropyl)-3-methoxyphenyl]-propane-1,3-diol(1), threo-7-methoxyguaiacylglycerol(2),4-O-(2-hydroxy-1-hydroxymethylethyl)-dihydroconiferylalcohol(3), morusin(4), sanggenol A(5), sanggenon I(6), sanggenon N(7), leachianone G(8),(+)-catechin(9), epicatechin(10), and 7,4'-dimethoxyisoflavone(11). Among them, compound 1 was a new compound, and compounds 2-9 were isolated from S. sphenanthera for the first time. Compounds 2-11 were subjected to cell viability assay, and the results revealed that compounds 4 and 5 had potential cytotoxicity, and compound 4 also had potential antiviral activity.


Assuntos
Schisandra , Casca de Planta , Antivirais , Bioensaio , Catequina , Fenóis
17.
China Journal of Chinese Materia Medica ; (24): 2876-2895, 2023.
Artigo em Chinês | WPRIM | ID: wpr-981422

RESUMO

Microbial transformation is an efficient enzymatic approach for the structural modification of exogenous compounds to obtain derivatives. Compared with traditional chemical synthesis, the microbial transformation has in fact the undoubtable advantages of strong region-and stereo-selectivity, and a low environmental and economic impact on the production process, which can achieve the reactions challenging to chemical synthesis. Because microbes are equipped with a broad-spectrum of enzymes and therefore can metabolize various substrates, they are not only a significant route for obtaining novel active derivatives, but also an effective tool for mimicking mammal metabolism in vitro. Artemisinin, a sesquiterpene with a peroxy-bridged structure serving as the main active functional group, is a famous antimalarial agent discovered from Artemisia annua L. Some sesquiterpenoids, such as dihydroartemisinin, artemether, and arteether, have been developed on the basis of artemisinin, which have been successfully marketed and become the first-line antimalarial drugs recommended by WHO. As revealed by pharmacological studies, artemisinin and its derivatives have exhibited extensive biological activities, including antimalarial, antitumor, antiviral, anti-inflammatory, and immunomodulatory. As an efficient approach for structural modification, microbial transformation of artemisinin and its derivatives is an increasingly popular strategy that attracts considerable attention recently, and numerous novel derivatives have been discovered. Herein, this paper reviewed the microbial transformation of artemisinin and its artemisinin, including microbial strains, culture conditions, product isolation and yield, and biological activities, and summarized the advances in microbial transformation in obtaining active derivatives of artemisinin and the simulation of in vivo metabolism of drugs.


Assuntos
Animais , Antimaláricos/farmacologia , Antivirais , Artemeter , Artemisininas , Mamíferos
18.
China Journal of Chinese Materia Medica ; (24): 1705-1710, 2023.
Artigo em Chinês | WPRIM | ID: wpr-981387

RESUMO

Novel drug discovery from the active ingredients of traditional Chinese medicine is the most distinctive feature and advantageous field of China, which has provided an unprecedented opportunity. However, there are still problems such as unclear functional substance basis, action targets and mechanism, which greatly hinder the clinical transformation of active ingredients in traditional Chinese medicine. Based on the analysis of the current status and progress of innovative drug research and development in China, this paper aimed to explore the prospect and difficulties of the development of natural active ingredients from traditional Chinese medicine, and to explore the efficient discovery of trace active ingredients in traditional Chinese medicine, and obtain drug candidates with novel chemical structure, unique target/mechanism and independent intellectual property rights, in order to provide a new strategy and a new model for the development of natural medicine with Chinese characteristics.


Assuntos
Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/química , Pesquisa , Descoberta de Drogas , China
19.
Chinese Medical Journal ; (24): 1680-1689, 2023.
Artigo em Inglês | WPRIM | ID: wpr-980933

RESUMO

BACKGROUND@#Textbook outcome (TO) can guide decision-making among patients and clinicians during preoperative patient selection and postoperative quality improvement. We explored the factors associated with achieving a TO for gallbladder carcinoma (GBC) after curative-intent resection and analyzed the effect of adjuvant chemotherapy (ACT) on TO and non-TO patients.@*METHODS@#A total of 540 patients who underwent curative-intent resection for GBC at the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi'an Jiaotong University from January 2011 to December 2020 were retrospectively analyzed. Multivariable logistic regression was used to investigate the factors associated with TO.@*RESULTS@#Among 540 patients with GBC who underwent curative-intent resection, 223 patients (41.3%) achieved a TO. The incidence of TO ranged from 19.0% to 51.0% across the study period, with a slightly increasing trend over the study period. The multivariate analysis showed that non-TO was an independent risk factor for prognosis among GBC patients after resection ( P = 0.003). Age ≤60 years ( P = 0.016), total bilirubin (TBIL) level ≤34.1 μmol/L ( P <0.001), well-differentiated tumor ( P = 0.008), no liver involvement ( P <0.001), and T1-2 stage disease ( P = 0.006) were independently associated with achieving a TO for GBC after resection. Before and after propensity score matching (PSM), the overall survival outcomes of non-TO GBC patients who received ACT and those who did not were statistically significant; ACT improved the prognosis of patients in the non-TO group ( P <0.05).@*CONCLUSION@#Achieving a TO is associated with a better long-term prognosis among GBC patients after curative-intent resection, and ACT can improve the prognosis of those with non-TO.


Assuntos
Humanos , Pessoa de Meia-Idade , Neoplasias da Vesícula Biliar/patologia , Estudos Retrospectivos , Prognóstico , Hepatectomia , Colecistectomia
20.
Chinese Acupuncture & Moxibustion ; (12): 843-853, 2023.
Artigo em Chinês | WPRIM | ID: wpr-980805

RESUMO

The efficacy on chronic obstructive pulmonary disease (COPD) at stable stage treated with different methods of acupuncture and moxibustion was evaluated using network Meta-analysis method. The articles of the randomized controlled trial (RCT) on stable COPD treated with acupuncture and moxibustion were searched electronically in CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Web of Science and Cochrane library. The search was conducted from the inception of the databases to March 20th, 2022. Data analysis was performed using R4.1.1, Stata16.0 and RevMan5.3 softwares. A total of 48 RCTs were included, involving 15 kinds of acupuncture and moxibustion interventions and a sample size of 3 900 cases. The results of network Meta-analysis showed that: ① For the forced expiratory volume in one second predicted (FEV1%), both the governor vessel moxibustion combined with conventional treatment (G+C therapy) and the yang-supplementing moxibustion combined with conventional treatment (Y+C therapy) obtained the better effect than that of the conventional treatment (P<0.05), and the G+C therapy was more effective compared with the thread-embedding therapy combined with conventional treatment (E+C therapy) and warm needling (P<0.05). ② Concerning to COPD assessment test (CAT) score, the results indicated that the Y+C therapy, and the mild moxibustion combined with conventional treatment (M+C therapy) were more effective when compared with the conventional treatment (P<0.05), and the effect of the Y+C therapy was better than that of the E+C therapy (P<0.05). ③ Regarding six-minute walking distance (6MWD), the effect of acupuncture combined with conventional treatment (A+C therapy) was better than that of either the E+C therapy or the conventional treatment (P<0.05). The effect of the G+C therapy was optimal for improving FEV1%, the Y+C therapy obtained the best effect for improving CAT score, and A+C therapy was the most effective for improving 6MWD. Due to the limitation of the quality and quantity of included studies, this conclusion needs to be further verified through high-quality RCT.


Assuntos
Humanos , Moxibustão , Metanálise em Rede , Terapia por Acupuntura , Bases de Dados Factuais , Doença Pulmonar Obstrutiva Crônica/terapia
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