Degradation of methotrexate by UV/peroxymonosulfate:Kinetics,effect of operational parameters and mechanism

Methotrexate(MTX)is one of the most consumed anti-cancer drugs in the pharmaceutical market around the world.The widespread occurrence of MTX in aquatic environment through hospital effluent has attracted increasing concern due to its potential to induce water pollution.In the present study,the degradation of MTX in aqueous medium was investigated by UV-activated peroxymonosulfate(PMS).A significant improvement in degradation rate by increasing UV intensity and PMS concentration while the decrease in degradation efficiency with the increase of solution p H and initial concentration of MTX was observed.The proposed UV/PMS process could achieve more than 90%MTX degradation in 30 min with a good mineralization degree(65%).A pseudofirst order kinetic model was employed and successfully predicted the degradation of MTX.The effect of other operational parameters such as the initial concentration of the targeted compound,dosage of oxidant(PMS),solution p H and UV intensity on the degradation rate were investigated.At the last,the main transform intermediates were identified using LC–MS and possible degradation pathways were proposed.The results show that UV/PMS can be used as an efficient technology to treat pharmaceuticals such as methotrexate containing water and wastewater.

Conservative management of cervical pregnancy with intramuscular administration of methotrexate and KCl injection: Case report and review of the literature

We report the case of a cervical pregnancy successfully treated with intramuscular injection of methotrexate(MTX) and intramniotic administration of potassium chloride. A 41-year-old woman was admitted to our Department with the suspicion of ectopic pregnancy. Transvaginal ultrasound revealed empty endometrialcavity, gestational sac within the cervical canal and embryonic echo measuring crown rump length 1.5 mm. Serum beta human chorionic gonadotropine(β-HCG) was measured 28590 IU/L. No cardiac activity was detected. The diagnosis of a cervical pregnancy was made. Patient was treated with intramuscular administration of methotrexate(50 mg/m2) in combination with ultrasoundguided intramniotic injection of KCl(2 meq/mL). Gradual decrease of β-HCG levels as well as ultrasound observation of collapsed gestational sac was observed. No curettage was necessitated. Patient was discharged on day 10 th and was set in follow-up on a weekly basis. β-HCG values were measured < 10 IU/L on 56 th day after MTX administration. Intramuscular administration of MTX may be effective in treatment of cervical pregnancy without additional interventional measures.

Temporal profiles of synaptic plasticity-related signals in adult mouse hippocampus with methotrexate treatment

Methotrexate, which is used to treat many malignancies and autoimmune diseases, affects brain functions including hippocampal-dependent memory function. However, the precise mechanisms underlying methotrexate-induced hippocampal dysfunction are poorly understood. To evaluate temporal changes in synaptic plasticity-related signals, the expression and activity of N-methyI-D-aspartic acid receptor 1, calcium/calmodulin-dependent protein kinase II, extracellular signal-regulated kinase 1/2, cAMP responsive element-binding protein, glutamate receptor 1, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor were examined in the hippocampi of adult C57BL/6 mice after methotrexate （40 mg/kg） intraperitoneal injection. Western blot analysis showed biphasic changes in synaptic plasticity-related signals in adult hippocampi following methotrexate treatment. N-methyI-D-aspartic acid receptor 1, calcium/calmodulin-dependent protein kinase II, and glutamate receptor 1 were acutely activated during the early phase （1 day post-injection）, while extracellular signal-regulated kinase 1/2 and cAMP responsive element-binding protein activation showed biphasic increases during the eady （1 day post-injection） and late phases （7-14 days post-injection）. Brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression increased significantly during the late phase （7-14 days post-injection）. Therefore, methotrexate treatment affects synaptic plasticity-related signals in the adult mouse hippocampus, suggesting that changes in synaptic plasticity-related signals may be associated with neuronal survival and plasticity-related cellular remodeling.

High-dose methotrexate and zanubrutinib combination therapy for primary central nervous system lymphoma

In this editorial I comment on the article,published in the current issue of the World Journal of Clinical Oncology.Primary central nervous system lymphoma(PCNSL)is a disease of elderly and immunocompromised patients.The authors reported clinical results of 19 patients with PCNSL treated with zanubrutinib/high dose methotrexate(HD-MTX)until disease progression.They demonstrated that the combination of zanubrutinib with HD-MTX led to a marked clinical response and tolerability among these patients.They also observed that cerebrospinal fluid liquid biopsy to detect circulating tumor DNA may be a good option for evaluating treatment response and tumor burden in patients with PCNSL.PCNSL is a challenging disease for treatment as these patients present with different neurological states and comorbidities.Treatment has evolved over the years from whole brain radiotherapy to HD-MTX followed by autologous stem cell transplant.Gradually,treatment of patients with PCNSL is going to become individualized.

CHEMOTHERAPY FOR ADVANCED NASOPHARYNGEAL CARCINOMA WITH METHOTREXATE, VINCRISTINE, CISPLATIN AND ADRIAMYCIN

Objective: To evaluate the efficacy and toxicity of M-VCA (methortrexate 30 mg/m2, vincristine 2 mg, cisplatin 70 mg/m2, adriamycin 30 mg/m2) combination chemotherapy for advanced nasopharyngeal carcinoma. Methods: Thirty-five patients with advanced nasopharyngeal carcinoma, including 11 patients with untreated local advanced nasopharyngeal carcinoma and 24 patients with local-regional recurrent or metastatic nasopharyngeal carcinoma, received the chemotherapy of M-VCA. The cycle was repeated on day 22 for two cycles. All patients completed the chemotherapy courses. Results: The overall response rate was 75%, with untreated local advanced nasopharyngeal carcinomas 11/11(100%), local-regional recurrent nasopharyngeal carcinomas 12/18(67%), lung metastases 8/9(89%), bone metastases 5/9(56%), and liver metastases 1/2(50%). The main side effects included mild to moderate degree alopecia, nausea/vomiting, and neutropenia. Conclusion: M-VCA is well tolerated and has good efficacy for advanced nasopharyngeal carcinoma and is worth investigating further.

Dose-individualization Efficiently Maintains Sufficient Exposure to Methotrexate without Additional Toxicity in High-dose Methotrexate Regimens for Pediatric Acute Lymphoblastic Leukemia

Objective:Methotrexate(MTX)can be safely administered to most patients but may cause severe toxicity in others.This study aimed to summarize the characteristics of high-dose methotrexate(HD-MTX)chemotherapy and to evaluate whether the modified dose-adjustment program was able to improve the maintenance of sufficient MTX exposure levels while minimizing toxicities.Methods:We evaluated 1172 cycles of high-dose MTX chemotherapy from 294 patients who were treated according to the CCCG-ALL-2015 protocol(clinical trial number:ChiCTR-IPR-14005706)and analyzed the data of actual MTX dosage,MTX concentration,toxicity,and prognosis.We compared data between the dose-adjustment Program 1(fixed 20%reduction in dose)and the dose-adjustment Program 2(dose-individualization based on reassessment of the creatine clearance rate and the MTX concentration-monitoring point at 16 h),which were applied if the MTX clearance was delayed in the previous cycle.Results:The patients who used Program 2 had higher actual MTX infusion doses and infusion rates and were able to better maintain the MTX concentration at 44 h at the established target value than those on Program 1(P<0.001).No significant differences in toxicities were found between these two programs except that abnormal serum potassium levels and prolonged myelosuppression in intermediate-risk/high-risk patients were more frequently observed in patients using Program 2(P<0.001).No significant correlations were observed between the MTX dose,dose-adjustment programs,or MTX concentrations and relapse-free survival.Conclusion:Adjusting the MTX dose using Program 2 is more efficient for maintaining sufficient MTX exposure without significantly increasing the toxicity.

Perioperative Use of Methotrexate and Tumor Necrosis Factor α Inhibitors Combination Therapy Is Not Likely to Increase Post-Operative Infection Rate in the National Veterans Health Administration Administrative Databases

Objective: The aim of the study is to assess the risk of post-operative outcome in rheumatoid arthritis (RA) patients continuing versus stopping combination therapy of methotrexate (MTX) and hydroxychloroquine (HCQ) or tumor necrosis factor α inhibitors (TNF) prior to surgery. Methods: Using the United States Veterans Affairs (VA) databases, we identified surgical procedures in a 17-year cohort of RA patients. Among those patients, those on MTX + HCQ or MTX + TNF were identified. Post-operative outcome variables include infection, length of post-operative hospital stay and death. Results: We identified a total of 29,708 surgeries in RA patients. Among them, we identified the most recent elective surgeries without pre-operative infection in 16,174 patients. There were 783 and 550 patients on MTX + HCQ and MTX + TNF, respectively. The rates of post-op infection were 5% and 4% for the MTX + HCQ and MTX + TNF continuing medication groups, respectively, similar to the general RA population (5%). Sensitivity analyses at various time points of discontinuation combination therapies prior to surgery did not show significant change in terms of infection. Conclusions: The prevalence of adverse outcome is low. The proportion of post-operative infection in continuing and discontinuing medicine groups is similar for both MTX + HCQ and MTX + TNF. While we were unable to formally compare proportions of post-operative infection among the two groups, these preliminary findings do not support the hypothesis that continuing either MTX + TNF or MTX + HCQ combination during perioperative period increases post-operative infection compared with discontinuation prior to therapy.

Status of Renal and Liver Function in Rheumatoid Arthritis (RA) Patients of Chattogram, Bangladesh Treated with Methotrexate (MTX)

Rheumatoid Arthritis (RA) is a chronic autoimmune disorder that is usually manifested as inflammation in multiple joints and several extra-articular symptoms, involving the liver, kidney, eye, skin, blood, blood vessels, heart, lungs, nervous system, and other organs. Methotrexate (MTX) is the anchor drug that treats RA. As renal and liver abnormalities are more common during disease conditions as well as during the treatment period, we tried to find out if there is any impact of MTX in these organs during the treatment of RA patients. Once the disease complications are developed, it is quite difficult to reverse the disease, and treatment in this situation is not very effective. Consequently, patients suffer a lot. So, early evaluation of renal and liver function is essential for the treatment of RA patients and it might also help prevent different complications which are usually very frequently observed. This was a cross-sectional study. A total of 150 RA patients treated with MTX were evaluated for the study where female and male respondents were 115 and 35 respectively. In this study, we found that 82% of RA patients had creatinine levels ≤ 1.1 mg/dL although the normal range of serum creatinine is below 1.4 mg/dL. Usually, a 15% increase in Serum creatinine level from the baseline is considered renal impairment. We found 4% of such cases. Moreover, 2% of RA patients had creatinine levels above the normal range of 1.4 mg/dL and those patients were hypertensive as well. So, a total (4 + 2 = 6)% had renal impairments. Among them, 5% had diabetes mellitus. On the other hand, the ultrasonogram (USG) of RA patients with kidney disease showed signs of renal parenchymal disease and 3% of RA patients having renal problems whose serum creatinine level was within the normal range showed signs of chronic kidney disease (CKD). On the other hand, 2% of RA patients showed signs of hepatic parenchymal disease. In this study, 69% of RA patients had ALT levels ≤ 50 mg/dL, 23% had 50 - 100 mg/dL, and 5% had 101 - 150 mg/dL. The remaining 3% of RA patients had ALT levels above 150 mg/dL. All those patients with ALT levels above 100 mg/dL used Nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly. Different parameters of liver and renal function should be monitored strongly in RA patients treated with MTX and NSAIDs. MTX should not be given for a prolonged period without monitoring renal and liver function. As MTX, Diabetes Mellitus, Hypertension, etc., may cause renal complications, we could not concretely conclude which one is the actual causative agent.

Bovine Serum Albumin (BSA) Microspheres Containing Methotrexate (MTX) I.Pharmaceutical Aspects

Microspheres Ⅰ,Ⅱ and Ⅲ were produced by emulsion technique.Microsphere I was solidified by glutaraldehyde crosslinking,microsphere Ⅱ was solidified by glutaraldehyde crosslinking and further treated with glycine solution and microsphere Illwas solidified by heating denaturation only.The results showed that the microsphere diameter produced by cross[inking was bigger than that prepared by heating.The microsphere Ⅱ had higher hydrophilicity than Microsphere I had.The methotrexate (MTX) contents in microspheres Ⅰ and Ⅱ were 2.73±0.053%,2.87±0.119% respectively. microsphere Ⅲ was only blank microspheres with MTX adsorbed on their surfaces.In vitro release studies,microspheres I and I have maintained sustained release of MTX till the next day,it was found that the drug releases from microspheres Ⅰ and Ⅱ were governed by Higuchi diffusion law.

Analytical methodologies for determination of methotrexate and its metabolites in pharmaceutical,biological and environmental samples

Methotrexate(MTX)is a folate antagonist drug used for several diseases,such as cancers,various malignancies,rheumatoid arthritis(RA)and inflammatory bowel disease.Due to its structural features,including the presence of two carboxylic acid groups and its low native fluorescence,there are some challenges to develop analytical methods for its determination.MTX is metabolized to 7-hydroxymethotrexate(7-OH-MTX),2,4-diamino-N10-methylpteroic acid(DAMPA),and the active MTX polyglutamates(MTXPGs)in the liver,intestine,and red blood cells(RBCs),respectively.Additionally,the drug has a narrow therapeutic range;hence,its therapeutic drug monitoring(TDM)is necessary to regulate the pharmacokinetics of the drug and to decrease the risk of toxicity.Due to environmental toxicity of MTX;its sensitive,fast and low cost determination in workplace environments is of great interest.A large number of methodologies including high performance liquid chromatography equipped with UVevisible,fluorescence,or electrochemical detection,liquid chromatography-mass spectroscopy,capillary electrophoresis,UVevisible spectrophotometry,and electrochemical methods have been developed for the quantitation of MTX and its metabolites in pharmaceutical,biological,and environmental samples.This paper will attempt to review several published methodologies and the instrumental conditions,which have been applied to measure MTX and its metabolites within the last decade.

Risk of liver disease in methotrexate treated patients

Methotrexate is the first line drug treatment for anumber of rheumatic and non-rheumatic diseases. It is effective in controlling disease activity and preventing disease-related damage, and significantly cheaper than many alternatives. Use in rheumatoid arthritis infers a significant morbidity and mortality benefit. Methotrexate is generally well tolerated but can cause symptomatic adverse events. Multiple serious adverse events have been attributed to methotrexate, based largely on older reports using high or daily doses, and subsequent case reports and circumstantial evidence. The risk with modern dosing regimens: Lower doses, weekly schedules, and concomitant folic acid is less clear. Clarification and dissemination of the actual risk is crucial so appropriate judgements can be made for patients who may benefit from this treatment. Methotrexate has been associated with a range of liver related adverse events ranging from asymptomatic transaminase elevations to fibrosis and fatal hepatic necrosis. Concern over potential liver toxicity has resulted in treatment avoidance, cessation, or recommendations for investigations which may be costly, invasive and unwarranted. Modern laboratory monitoring of liver blood tests may also influence the risk of more serious complications. The majority of present day studies report an approximate doubling of the relative risk of elevated transaminases in methotrexate treated patients but no increased risk of symptomatic or severe liver related adverse events. In this article we will review the evidence around methotrexate and liver related adverse events.

基于ADE优化的IPMSM全速域无传感器控制

为了实现内置式永磁同步电机(IPMSM)全速域的无传感器控制和切换速域的平滑过渡,提出了一种基于自适应差分进化(ADE)算法优化的复合控制方法。分别在零低速域、中高速域采用旋转高频电压注入法和滑模观测器法来对电机转速和转子位置进行估算,并在切换速域采用基于ADE算法的权重系数优化法来实现上述两种控制方法的平滑切换,从而实现IPMSM全速域无传感器控制。仿真结果表明:提出的复合控制方法能够实现电机全速域的无感控制和切换速域的平滑过渡,且具有良好的稳定性。

Use of methotrexate in inflammatory bowel disease in 2014: A User's Guide

Methotrexate has been used an immunomodulator in many autoimmune diseases,including inflammatory bowel disease. However,many physicians are unfamiliar or uncomfortable with its use in the management of inflammatory bowel disease. We summarize the data for use of methotrexate in common clinical scenarios:(1) steroid dependant Crohn's disease(CD);(2) maintenance of remission in steroid free CD;(3) azathioprine failures in CD;(4) in combination therapy with Anti-TNF agents in CD;(5) decreasing antibody formation to Anti-TNF therapy in CD;(6) management of fistulizing disease in CD; and(7) as well as induction and maintenance of remission in ulcerative colitis. An easy to use algorithm is provided for the busy clinician to access and safely prescribe methotrexate for their inflammatory bowel disease patients.

Cytoprotective effects of amifostine,ascorbic acid and N-acetylcysteine against methotrexate-induced hepatotoxicity in rats

AIM: To investigate the potential role of oxidative stress and the possible therapeutic effects of N-acetyl cysteine (NAC), amifostine (AMF) and ascorbic acid (ASC) in methotrexate (MTX)-induced hepatotoxicity.

Protective effects of Balanites aegyptiaca extract, melatonin and ursodeoxycholic acid against hepatotoxicity induced by methotrexate in male rats

Objective: To compare the degree of ameliorative effects of Melatonin(MEL), Ursodeoxycholic acid(UDCA) and Balanites aegyptiaca(BA) against hepatotoxicity induced by MTX for one month. Methods: Eighty adult male rats(Sprague Dawely) weighing(190±10g), were randomly divided into eight equal groups: Control, MTX, MEL, BA, UDCA, MTX+MEL, MTX+BA, MTX+UDCA. Liver function biomarker enzymes, liver tissue oxidative stress parameters, together with total antioxidant capacity and tumor necrosis factor(TNF-α) were determined. Histopathological and immunohistochemistry examinations for TNF-α were also done. Results: MTX showed significant increase in alanine transaminase(ALT), aspartate transaminase(AST), alkaline phosphatase(ALP), gamma glutamyl transferase(GGT), total and direct bilirubin, as well as TNF-α levels, oxidized glutathione(GSSG), malodialdehyde(MDA) and nitric oxide(NO). whereas, total protein, albumin, total antioxidant capacity, reduced glutathione(GSH), glutathione peroxidase(GPx), glutathione reductase(GR), glutathione S-transferase(GST), superoxide dismutase(SOD) and catalase(CAT) levels were significantly decreased in MTX treated group. These alterations were improved by MEL and BA treatment, whereas no improvement was noticed in UDCA treatment. Conclusions: BA may be as promising as MEL in the hepatoprotection against MTX toxicity through their antioxidant and radical scavenging activities. In addition, it is not recommended to co-administer UDCA with MTX as it enhanced inflammation and damage to the liver.

Prevalence and risk factors of methotrexate hepatoxicity in Asian patients with psoriasis

AIM: To establish the prevalence of liver fibrosis and to evaluate the possible risk factors for fibrosis and progression in Asian with psoriasis treated with methotrexate (MTX) based on liver histology. METHODS: Patients with psoriasis treated with MTX referred to the Department of Gastroenterology, Tan Tock Seng Hospital for liver biopsy were identified and retrospectively studied. Patient case notes and electronic records were retrieved from the hospital database and relevant data collated. Histological changes of liver biopsies were staged according to Roengik score. The factors assessed were age, gender, ethnicity, cumulative dose of MTX, presence of comorbid conditions such as diabetes, hypertension, hyperlipidemia, and ethanol use. We also assessed the histological change in those with multiple liver biopsies. Statistical analysis was performed using Stata V.9.2. RESULTS: There were altogether 59 patients (median age 50 years old, range 22-81 years old, male, 88%) with 98 biopsies liver biopsies; 6 normal [median cumulative dose (MCD), 2285 mg]; 62 gradeⅠ (MCD 2885 mg), 23 grade Ⅱ (MCD 1800 mg) and 7 grade Ⅲ (MCD 1500 mg). There was no grade Ⅳ or cirrhosis. The prevalence of liver fibrosis (grade Ⅲ) was 12%. Of the factors assessed, diabetes (P=0.001) and hypertension (P=0.003) were significant for fibrosis on univariate analysis but not on multivariate analysis. Of the 26 patients who had more than one biopsy (median 2, range 2-6), 57.7% (n=15) were stable, 34.6% (n=9) had progression and 7.7% (n=2) had regression of histological grades. On univariate analysis, nonChinese ethnicity (P=0.031), diabetes (P=0.018), and hyperlipidemia (P=0.011) were predictive of progression of grades, but these were not significant on multivariate analysis. CONCLUSION: Liver fibrosis in Asian psoriatic population on MTX is comparable to the West. Cumulative dose was not associated with liver fibrosis. Metabolic syndrome is important factors.

Methotrexate combined with methylprednisolone for the recovery of motor function and differential gene expression in rats with spinal cord injury

Methylprednisolone is a commonly used drug for the treatment of spinal cord injury, but high doses of methylprednisolone can increase the incidence of infectious diseases. Methotrexate has anti-inflammatory activity and immunosuppressive effects, and can reduce in- flammation after spinal cord injury. To analyze gene expression changes and the molecular mechanism of methotrexate combined with methylprednisolone in the treatment of spinal cord injury, a rat model of spinal cord contusion was prepared using the PinPointTM preci- sion cortical impactor technique. Rats were injected with methylprednisolone 30 mg/kg 30 minutes after injury, and then subcutaneously injected with 0.3 mg/kg methotrexate 1 day after injury, once a day, for 2 weeks. TreadScan gait analysis found that at 4 and 8 weeks after injury, methotrexate combined with methylprednisolone significantly improved hind limb swing time, stride time, minimum longitudinal deviation, instant speed, footprint area and regularity index. Solexa high-throughput sequencing was used to analyze differential gene ex- pression. Compared with methylprednisolone alone, differential expression of 316 genes was detected in injured spinal cord treated with methotrexate and methylprednisolone. The 275 up-regulated genes were mainly related to nerve recovery, anti-oxidative, anti-inflammatory and anti-apoptotic functions, while 41 down-regulated genes were mainly related to proinflammatory and pro-apoptotic functions. These results indicate that methotrexate combined with methylprednisolone exhibited better effects on inhibiting the activity of inflammatory cytokines and enhancing antioxidant and anti-apoptotic effects and thereby produced stronger neuroprotective effects than methotrexate alone. The 316 differentially expressed genes play an important role in the above processes.

Prediction of Response of Collagen-induced Arthritis Rats to Methotrexate： An ~1H-NMR-based Urine Metabolomic Analysis

Over one half the patients with rheumatoid arthritis （RA） are being treated with methotrexate （MTX）. Although well proven, the efficacy of MTX varies in individual patients. This study examined the metabolic biomarkers that can be used to predict the therapeutic effect of MTX by using metabolomic analysis. Rats were immunized with collagen to rapidly cause collagen-induced arthritis （CIA） and then treated with 0.1 mg/kg MTX for 4 weeks. The clinical signs and the histopathological features of CIA were observed to evaluate the therapeutic effects. Urine samples of CIA rats were collected, and analyzed by using 600 M 1H-nuclear magnetic resonance （1H-NMR） for spectral binning after the therapy. The urine spectra were divided into spectral bins, and 20 endogenous metabolites were assigned by Chenomx Suite. Multivariate analyses were performed to identify the spectral pattern of endogenous metabolites related to MTX therapy. The results showed that the clustering of the spectra of the urine samples from the responsive rats （n=20） was different from that from the non-responsive rats （n=11）. Multivariate analysis showed difference in metabolic profiles between the responsive and non-responsive rats by using partial least squares-discrimination analysis （PLS-DA） （R2=0.812, Q2=0.604）. In targeted profiling, 13 endogenous metabolites （uric acid, taurine, histidine, methionine, glycine, etc.） were selected as putative biomarkers for predicting therapeutic response to MTX. It was suggested that 1H-NMR-based metabolomic analysis can be used to predict the therapeutic effect of MTX, and several metabolites were found to be related to the therapeutic effects of MTX.

化瘀杀胚汤联合甲氨蝶呤治疗异位妊娠的疗效及对TGF-β/Smad2/3蛋白水平和microRNA-30d-5p表达量的影响

【目的】探讨化瘀杀胚汤(由丹参、赤芍、桃仁、蜈蚣、紫草、天花粉、三七等中药组成)联合甲氨蝶呤治疗异位妊娠疗效及对患者TGF-β/Smad2/3蛋白水平和microRNA-30d-5p表达量的影响。【方法】将104例异位妊娠患者随机分为观察组和对照组,每组各52例。对照组给予甲氨蝶呤联合米非司酮治疗,观察组在对照组的基础上加用化瘀杀胚汤治疗,连续用药3 d并随访观察1个月。比较2组患者保守治疗成功率、血β人绒毛膜促性腺激素(β-HCG)水平恢复正常时间以及异位妊娠包块吸收时间、治疗后输卵管完全通畅率与不通畅率,观察2组保守治疗成功患者治疗前后血清TGF-β/Smad2/3蛋白水平和microRNA-30d-5p相对表达量的变化情况。【结果】(1)观察组的保守治疗成功率为94.23%(49/52),明显高于对照组的71.15%(37/52),差异有统计学意义(P<0.05)。(2)与对照组比较,观察组的血β-HCG恢复正常时间及包块吸收时间均明显缩短,差异均有统计学意义(P<0.01)。(3)观察组治疗后的输卵管完全通畅率为55.77%(29/52),明显高于对照组的21.15%(11/52);不通畅率为19.23%(10/52),明显低于对照组的59.62%(31/52),差异均有统计学意义(P<0.05或P<0.01)。(4)与治疗前比较,2组保守治疗成功患者治疗结束1个月后的TGF-β/Smad2/3蛋白水平和microRNA-30d-5p相对表达量均明显降低(P<0.05或P<0.01);与对照组比较,观察组治疗结束1个月后的TGF-β/Smad2/3蛋白水平和microRNA-30d-5p相对表达量均明显降低,差异均有统计学意义(P<0.01)。(5)2组患者的不良反应均以胃肠道不适为主,观察组的不良反应发生率为25.00%(13/52),明显低于对照组的46.15%(24/52),组间比较,差异有统计学意义(P<0.05)。【结论】化瘀杀胚汤联合甲氨蝶呤治疗异位妊娠,可有效提高药物保守治疗的成功率,有助于包块的吸收以及输卵管通畅,能有效降低患者的TGF-β/Smad2/3蛋白水平及microRNA-30d-5p的相对表达量,且药物安全性较高。

儿童维生素AD滴剂,这样吃才对

众所周知,维生素A、D对孩子的生长发育至关重要。而补充维生素A、D,最好选择专门的维生素AD制剂,比如维生素AD滴剂。但许多家长对其又不甚了解,有诸多疑问。以下,笔者将一一进行解答。