ObjectiveTo evaluate the effect of time-related administration of methotrexate (MTX) on neural cell apoptosis in rats after spinal cord injury (SCI) so as to investigate its potential neuroprotective mechanism and appropriate administration time.
MethodA total of 120 male Sprague Dawley rats, 247-286 g in weight, were randomly divided into 4 groups (n=30) :sham group (group A), control group (group B), MTX treating group (group C), and MTX prophylaxis group (group D). The SCI model was established in the rats of groups B, C, and D by improved Allen method, and just laminectomy was performed in group A. MTX (0.5 mg/kg) was administered with tail vein injection at 1, 6, 12, 18, and 24 hours after injury in group C, and at 30 minutes before injury and at 6, 12, 18, and 24 hours after injury in group D; the equivalence saline was injected at 1, 6, 12, 18, and 24 hours after injury in groups A and B. Basso-Beattie-Bresnahan (BBB) score was used to evaluate the neural function at 1, 3, 7, 14, and 21 days after injury, HE staining to observe histological changes, immunohistochemical staining and TUNEL method to measure the expression of Caspase-3 and neural cells apoptosis, respectively.
ResultsTen rats died during the experiment in groups B, C, and D; 25 rats in each group were included into the experiments at last. BBB score of group A was significantly higher than that of groups B, C, and D at all time points after injury (P<0.05) . BBB score of groups C and D were significantly higher than that of group B at 3, 7, 14, and 21 days (P<0.05) , and BBB score of group D was significantly higher than that of group C at 3, 7, and 14 days (P<0.05) . The histological observation showed normal structure of spinal cord at all time points after injury in group A. While the degree of SCI in group D was lighter than that in groups B and C, and group C was lighter than group B. At 14 days after injury, the degree of SCI in groups B, C, and D tend to keep the same. The number of Caspase-3 and TUNEL positive cells of groups B, C, and D was significantly more than that of group A at all time points after injury (P<0.05) , group B was significantly more than groups C and D (P<0.05) . The number of Caspase-3 positive cells of group C was significantly more than that of group D at 3, 7, and 14 days (P<0.05) . While the number of TUNEL positive cells of group C was significantly more than that of group D at 3 and 7 days (P<0.05) . And the number of Caspase-3 positive cells and TUNEL positive cells was positively correlated in groups B, C, and D (P<0.05) at 1, 3, 7, 14, and 21 days after injury.
ConclusionsLow-dose MTX may effectively reduce the degree of the secondary injury of spinal cord by reducing the nerve cell apoptosis. Better effect can be obtained when MTX is used as prevent method than as a way of treatment.
Objective To analyze the effectiveness of conservative medical treatments for ectopic pregnancy (EP): methotrexate (MTX) + mifepristone + Ectopic Pregnancy II decoction (EP-II) vs. methotrexate + mifepristone. Methods A total of 95 patients with EP in Shenzhen Shajing Affiliated Hospital of Guangzhou Medical University from January 2009 to January 2011 were randomly divided into two groups: 45 patients in the experimental group were treated with MTX, mifepristone and EP II decoction, while the other 50 patients in the control group were treated with MTX and mifepristone. The effectiveness of the two groups was analyzed with SPSS 13.0 software. Results There were significant differences in the time of serum β-HCG return to normal (16.13±8.13 ds vs. 22.05±7.15 ds, Plt;0.05), time of EP mass absorption (30.46±7.56 ds vs. 39.99±18.26 ds, Plt;0.05) and tubal patency rate (80% vs. 75%, Plt;0.05) between the two groups. But there were no significant differences in effective rate (95.56%, 43/45 vs. 94%, 47/50, χ2=0.0809, Pgt;0.05) and side effects. Conclusion The combination of methotrexate, mifepristone and EP II decoction for ectopic pregnancy is more effective than mifepristone and methotrexate in coordinately killing the embryo, shortening the time of serum β-HCG return to normal and the time of EP mass absorption, and improving the function of oviducts.
We reported one case of MTX-induced aplastic anemia and reviewed related literature to investigate the mechanism of action of MTX, and summarize the clinical feature, diagnostic criteria, risk factor, and interventions. These were hoped to arouse the attention of clinicians and clinical pharmacists, in order to effectively prevent, diagnose, and treat MTX-induced aplastic anemia.
Objective To evaluate the efficacy and safety of Leflunomide (LEF) in the treatment of Rheumatoid Arthritis (RA), so as to provide scientific proof for applying LEF in China. Methods Randomized controlled trials (RCTs) about the effect of LEF on patients with RA from January 1989 to January 2011 were searched from the following databases, CNKI, WanFang Data, MEDLINE, EMbase and CBM. After two reviewers independently screened the studies according to the inclusion and exclusion criteria, extracted the data and assessed the quality, the data were analyzed by RevMan 5.0 software. Results Among 3247 patients in 16 included RCTs, 1711 patients were in the LEF group, while the other 1536 patients were in the Methotrexate (MXT) group. The results of meta-analyses showed there was no significant difference in the efficacy between LEF and MXT (RR=1.03, 95%CI 0.94 to 1.11, Pgt;0.05), but a significant difference was found in the side reaction (RR=0.67, 95%CI 0.49 to 0.94, Plt;0.05). Conclusion Based on the current studies, Leflunomide is as effective as the commonly-used Methotrexate in the treatment of rheumatiod arthritis at present, much safer than Methotrexate, and thought as a safe and effective SAARD. For the quality restrictions of the included studies, more double blind RCTs with high quality are required to further assess the effects.
ObjectivesTo systematically review the efficacy and safety of iguratimod compared with methotrexate in the treatment of rheumatoid arthritis.MethodsPubMed, EMbase, The Cochrane Library, VIP, CBM, WanFang Data and CNKI databases were electronically searched to collect randomized controlled trials (RCTs) of the efficacy and safety of iguratimod compared with methotrexate in the treatment of rheumatoid arthritis from inception to June 2018. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies, then, meta-analysis was performed by using RevMan 5.3 software.ResultsA total of 10 RCTs involving 970 patients were included. The results of meta-analysis showed that: there was no statistical difference between iguratimod and methotrexate in ACR20 (RR=1.06, 95%CI 0.91 to 1.23, P=0.49), ACR50 (RR=0.93, 95%CI 0.73 to 1.19, P=0.55), ACR70 (RR=0.92, 95%CI 0.62 to 1.39, P=0.70), morning stiffness time (MD=0.45, 95%CI –0.26 to 1.16, P=0.22), tender joint count (MD=0.07, 95%CI –2.31 to 2.45, P=0.95), swollen joint count (MD=–0.30, 95%CI –1.44 to 0.84, P=0.61), health assessment questionnaire (MD=0.01, 95%CI –0.05 to 0.07, P=0.73) and the rate of adverse effects (RR=0.66, 95%CI 0.41 to 1.07, P=0.09). Meta-analysis of 2 RCTs using double-blind method showed that, iguratimod was superior to methotrexat in the patient (MD=4.11, 95%CI 0.11 to 8.10, P=0.04) and physician (MD=4.81, 95%CI 0.93 to 8.69, P=0.01) global assessment of disease activities.ConclusionsCurrent evidence shows that the efficacy and safety of iguratimod in the treatment of rheumatoid arthritis are similar to methotrexate. And iguratimod is superior in global assessment of disease activities by patients and doctors. Due to limited quality and quantity of the included studies, more high quality studies are required to verify above conclusions.
ObjectiveTo compare the cost-effectiveness of etanercept combined with methotrexate to methotrexate plus placebo in the treatment of rheumatoid arthritis and to provide references for clinical practice.MethodsDecision tree model was developed to estimate the cost-effectiveness from the perspective of the health care system by TreeAge Pro 2016 software. The cost-effectiveness of the two treatments were compared by incremental analysis, and the robustness of the results were analyzed by sensitivity analysis.ResultsThe cost of etanercept combined methotrexate group in one year duration was ￥212 692, the effective rate (ACR50) was 66.4%; the cost of methotrexate combined with placebo group in one year duration was ￥572, the effective rate (ACR50) was 40.6%. The incremental cost-effectiveness ratio of two groups was ￥818 000/person, and the sensitivity analysis showed that the results were robust.ConclusionEtanercept combined methotrexate is significant more effective than methotrexat. But the cost of etanercept combined methotrexate is too high to afford and is not economical compared to methotrexate.
Objective To evaluate the efficacy and toxicity of methotrexate (MTX) in the treatment of ankylosing spondylitis (AS). Methods Randomized controlled trials (RCTs) were identified from CENTRAL (The Cochrane Library Issue 4, 2005); MEDLINE (1966 to November 2005); EMBASE (1980 to November 2005); CINAHL (1982 to November 2005). The quality of included trials was evaluated. Data were extracted by two reviewers independently using a specially designed extraction form. The Cochrane Collaboration’s RevMan 4.2 software was used for data analysis. Results Three trials involving 116 patients were included. One 12-month trial compared naproxen plus MTX with naproxen alone. Two 24-week trials compared different doses of MTX with placebo. No statistically significant differences were found for the primary outcome measures of physical function, pain, spinal mobility, peripheral joints/entheses pain, swelling and tenderness, changes in spine radiographs and patient and physician global assessment. The response rate in one trial showed statistically significant benefits of 36% in the MTX group compared with the placebo group (RR 3.18, 95% CI 1.03 to 9.79). This response rate was a composite index including assessment of morning stiffness, physical well-being, Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), health assessment questionnaire for spondyloarthropathies (HAQ-S), and physician and patient global assessment. However, no single outcome showed a statistically significant difference between the MTX and placebo groups when endpoint results were compared. Therefore, this benefit of MTX was questionable. No serious side effects were reported in these studies. Conclusions There is no enough evidence to show any benefit of MTX in the treatment of AS. High quality randomized controlled trials of longer duration and with larger sample size are needed to clarify the effect of MTX on AS.
Primary vitreoretinal lymphoma (PVRL) represents the most prevalent subtype of primary intraocular lymphoma, predominantly exhibiting diffuse large B-cell lymphoma histopathology. This malignancy is characterized by poor prognosis and frequent central nervous system involvement. Current therapeutic strategies for PVRL are diverse, including local chemotherapy, systemic chemotherapy, targeted therapy, and autologous stem cell transplantation, yet marked by significant therapeutic heterogeneity and lack of standardized protocols. In recent years, clinical advancements have been achieved with local therapies (e.g., intravitreal methotrexate and rituximab and systemic treatments (e.g., Bruton's tyrosine kinase inhibitors). However, the absence of standardized treatment protocols remains a significant clinical challenge. Recent years have witnessed notable progress in both local and systemic treatment modalities. Nevertheless, existing evidence is primarily derived from small-scale retrospective studies with inherent limitations, including suboptimal study designs, therapeutic heterogeneity, and insufficient patient stratification. These constraints have hindered the establishment of evidence-based treatment consensus. Future research should focus on conducting multicenter prospective studies, establishing international collaborative networks, and implementing long-term follow-up protocols to facilitate precision medicine approaches. Concurrent exploration of novel therapeutic targets and pharmacological agents is imperative to transform PVRL management from empirical practice to evidence-based personalized medicine, ultimately improving clinical outcomes.
ObjectiveTo compare the curative effect of three therapeutic strategies for cesarean scar pregnancy (CSP).
MethodsBetween January 2009 and December 2013, 208 patients with CSP underwent intramuscular methotrexate alone (group A, n=72), transvaginal ultrasound monitoring after embryo sac strangulation after injection of methotrexate (group B, n=70) and uterine arterial chemoembolization therapy monitoring after hysteroscopy surgery (group C, n=66). We studied their clinical data retrospectively. The preoperative treatment interval, the hospitalization days, intraoperative bleeding, time of blood β-HCG to normal level and hospitalization costs were compared between the groups.
ResultsThe preoperative treatment interval, hospitalization days, intraoperative bleeding, and time of blood β-HCG to normal level of group C were significantly better than those of group A and B (P<0.05), while the hospitalization cost of the three groups were not statistically signficant (P>0.05).
ConclusionAs a treatment for CSP, uterine artery chemoembolization is a safe and effective method, and it has the advantages of short hospitalization time, less intraoperative bleeding and high fertility preservation. It is worth application in clinical medicine.
Objective To investigate the effectiveness, safety and cost-effectiveness of leflunomide for rheumatoid arthritis, and formulate an evidence-based treatment plan for a patient with rheumatoid arthritis. Methods We searched the ACP Journal Club, The Cochrane Library (Issue 2, 2007) and MEDLINE (1990 to 2007), and critically appraised the available evidence. Results The available Level A (high quality) evidence showed that the efficacy and adverse events of leflunomide were comparable to those of methotrexate. The total cost of treating patients with leflunomide was significantly higher when compared to methotrexate. The combination of leflunomide and methotrexate in patients with active rheumatoid arthritis unresponsive to methotrexate monotherapy was less costly and more effective than the strategy excluding leflunomide. Given the current evidence, together with our clinical experience and the patient’s preference, methotrexate was administered to the patient. There was an inadequate response after 6 months of treatment. And then, adding leflunomide to methotrexate attained a remarkable response 3 months later. The patient is still being followed up. Conclusion treatment with leflunomide and methotrexate in RA patients can improve the clinical outcomes. Long-term efficacy and toxicity remain to be established.
