Improvement of hepatic fibrosis after tenofovir disoproxil fumarate switching to tenofovir alafenamide for three years

BACKGROUND Both tenofovir alafenamide(TAF)and tenofovir disoproxil fumarate(TDF)are the first-line treatments for chronic hepatitis B(CHB).We have showed switching from TDF to TAF for 96 weeks resulted in further alanine aminotransferase(ALT)improvement,but data remain lacking on the long-term benefits of TDF switching to TAF on hepatic fibrosis.AIM To assess the benefits of TDF switching to TAF for 3 years on ALT,aspartate aminotransferase(AST),and hepatic fibrosis improvement in patients with CHB.METHODS A single center retrospective study on 53 patients with CHB who were initially treated with TDF,then switched to TAF to determine dynamic patterns of ALT,AST,AST to platelet ratio index(APRI),fibrosis-4(FIB-4)scores,and shear wave elastography(SWE)reading improvement at switching week 144,and the associated factors.RESULTS The mean age was 55(28-80);45.3%,males;15.1%,clinical cirrhosis;mean baseline ALT,24.8;AST,25.7 U/L;APRI,0.37;and FIB-4,1.66.After 144 weeks TDF switching to TAF,mean ALT and AST were reduced to 19.7 and 21,respectively.From baseline to switching week 144,the rates of ALT and AST<35(male)/25(female)and<30(male)/19(female)were persistently increased;hepatic fibrosis was also improved by APRI<0.5,from 79.2%to 96.2%;FIB-4<1.45,from 52.8%to 58.5%,respectively;mean APRI was reduced to 0.27;FIB-4,to 1.38;and mean SWE reading,from 7.05 to 6.30 kPa after a mean of 109 weeks switching.The renal function was stable and the frequency of patients with glomerular filtration rate>60 mL/min was increased from 86.5%at baseline to 88.2%at switching week 144.CONCLUSION Our data confirmed that switching from TDF to TAF for 3 years results in not only persistent ALT/AST improvement,but also hepatic fibrosis improvement by APRI,FIB-4 scores,as well as SWE reading,the important clinical benefits of long-term hepatitis B virus antiviral treatment with TAF.

Treatment with dimethyl fumarate ameliorates liver ischemia/reperfusion injury

To investigate the hypothesis that treatment with dimethyl fumarate (DMF) may ameliorate liver ischemia/reperfusion injury (I/RI). METHODSRats were divided into 3 groups: sham, control (CTL), and DMF. DMF (25 mg/kg, twice/d) was orally administered for 2 d before the procedure. The CTL and DMF rats were subjected to ischemia for 1 h and reperfusion for 2 h. The serum alanine aminotransferase (ALT) and malondialdehyde (MDA) levels, adenosine triphosphate (ATP), NO × metabolites, anti-oxidant enzyme expression level, anti-inflammatory effect, and anti-apoptotic effect were determined. RESULTSHistological tissue damage was significantly reduced in the DMF group (Suzuki scores: sham: 0 ± 0; CTL: 9.3 ± 0.5; DMF: 2.5 ± 1.2; sham vs CTL, P < 0.0001; CTL vs DMF, P < 0.0001). This effect was associated with significantly lower serum ALT (DMF 5026 ± 2305 U/L vs CTL 10592 ± 1152 U/L, P = 0.04) and MDA (DMF 18.2 ± 1.4 μmol/L vs CTL 26.0 ± 1.0 μmol/L, P = 0.0009). DMF effectively improved the ATP content (DMF 20.3 ± 0.4 nmol/mg vs CTL 18.3 ± 0.6 nmol/mg, P = 0.02), myeloperoxidase activity (DMF 7.8 ± 0.4 mU/mL vs CTL 6.0 ± 0.5 mU/mL, P = 0.01) and level of endothelial nitric oxide synthase expression (DMF 0.38 ± 0.05-fold vs 0.17 ± 0.06-fold, P = 0.02). The higher expression levels of anti-oxidant enzymes (catalase and glutamate-cysteine ligase modifier subunit and lower levels of key inflammatory mediators (nuclear factor-kappa B and cyclooxygenase-2 were confirmed in the DMF group. CONCLUSIONDMF improved the liver function and the anti-oxidant and inflammation status following I/RI. Treatment with DMF could be a promising strategy in patients with liver I/RI.

The Electrocatalytic Activity of Bare Pyrolytic Graphite and Single Wall Carbon Nanotube Modified Glassy Carbon Sensors Is Same for the Quantification of Bisoprolol Fumarate

A comparison of voltammetric behavior of bisoprolol fumarate (BF) at edge and basal plane pyrolytic graphite electrodes (EPPGE/BPPGE) has been made with single wall carbon nanotube modified glassy carbon. The electrochemical properties are investigated exercising the cyclic voltammetry and square wave voltammetry (SWV). Enhanced peak current associated with bisoprolol fumarate oxidation at EPPGE is due to its better electron transfer property. Quantification of bisoprolol fumarate was carried out at pH 7.2 at both the pyrolytic graphite electrodes. Well-defined peak has been observed at ~ 792 and 954 mV at EPPGE and BPPGE respectively for bisoprolol fumarate oxidation. The detection limit is found to be 2.8 × 10–7 M and 7.3 × 10–7 M for EPPGE and BPPGE respectively. A comparison of common quantification parameters for bisoprolol at carbon nanotube modified glassy carbon electrode and bare BPPGE and EPPGE has been made and it is observed that carbon naotube modified glassy carbon exhibits sensitivity and detection limit close to that observed at bare basal plane pyrolytic graphite electrode. The method developed is applicable for determination of bisoprolol fumarate in pharmaceutical preparations and real samples.

Fumarate hydratase inactivation in renal tumors: HIF1α, NRF2, and "cryptic targets" of transcription factors

Biallelic inactivation of fumarate hydratase (FH) causes type 2 papillary renal cell carcinoma (PRCC2), uterine fibroids, and cutaneous leimyomas, a condition known as hereditary leiomyomatosis and renal cell cancer (HLRCC). The most direct effect of FH inactivation is intracellular fumarate accumulation. A majority of studies on FH inactivation over the past decade have focused on the theory that intracellular fumarate stabilizes hypoxia-inducible factor 1α (HIF1A) through competitive inhibition of HIF prolyl hydroxylases. Recently, a competing theory that intracellular fumarate activates nuclear factor (erythroid-derived 2)-like 2 (NRF2) through post-translational modification of its negative regulator. Kelch-like ECH-associated protein 1 (KEAP1) has emerged from a computational modeling study and mouse model studies. This review dissects the origin of these two governing theories and highlights the presence of chromatin-structure-regulated targets of transcription factors, which we refer to as "cryptic targets" of transcription factors. One such cryptic target is heme oxygenase I (HMOX1), the expression of which is known to be modulated by the gene product of SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 (SMARCA4, also known as BRG1).

Effect of dimethyl fumarate on rats with chronic pancreatitis

Objective:To discuss the effect of dimethyl fumarate(DMF) on rats with L-arginine induced chronic pancreatitis(CP).Methods:Male Wistar rats were given DMF treatment(25 mg/kg) by oral lavage method;then Wistar rats were given the intraperitoneal injection of L-arginine for 5times(250 mg/100 kg,twice per time,each interval of 1 h) for building of CP model.Rats were divided into control group,CP group,DMF group and CP+DMF group.Rats in CP+DMF group were given the oral intragastric administration of DMF(25 mg/kg),while rats in control group and CP group were given the equal volume of normal saline.The weight of rats was evaluated and the intraperitoneal glucose tolerance test was performed(IPGTT,2 g/kg).The islet of rats was isolated and then flow cytometry was employed to evaluate the quality and activity of islets.Meanwhile,the histology of non-endocrine tissues and levels of myeloperoxidase(MPO) and malondialdchyde(MDA) were detected.Results:Compared with control group,the weight of rats in CP group was significantly reduced at week 2,4 and 6;the blood glucose significantly increased,AUC increased,the histopathological scores of pancreatic atrophy,acinar injury,edema and cellular infiltration increased,levels of MDA and MPO increased,the islet equivalent and islet activity decreased at 0.30,60,120 and 180 min.Compared with CP group,the weight of rats in CP+DMF group significantly increased at week 2,4 and 6;the blood glucose significantly decreased.AUC decreased,the histopathological scores of pancreatic atrophy,acinar injury,edema and cellular infiltration decreased,levels of MDA and MPO decreased,the islet equivalent and islet activity increased at 0,30.60,120 and 180 min.Conclusions:DMF treatment can improve CP induced by L-argininc and islet function in rats.

Macrophage fumarate hydratase restrains mtRNA-mediated interferon production

Metabolic rewiring underlies the effector functions of macrophages1-3,but the mechanisms involved remain incompletely defined.Here,using unbiased metabolomics and stable isotope-assisted tracing,we show that an inflammatory aspartate argininosuccinate shunt is induced following lipopolysaccharide stimulation.The shunt,supported by increased argininosuccinate synthase(ASS1)expression,also leads to increased cytosolic fumarate levels and fumarate-mediated protein succination.Pharmacological inhibition and genetic ablation of the tricarboxylic acid cycle enzyme fumarate hydratase(FH)further increases intracellular fumarate levels.

Effects of Ferrous Fumarate on Growth Performance,Blood Biochemical Parameters and Trace Elements of Oncorhynchus mykiss

[ Objective] The study aimed to discuss the effects of ferrous fumarate on growth performance, blood biochemical parameters and content of trace element of Oncorhynchus mykiss. [ Method ] Juvenile rainbow trout with an initial weight of （89.2 ±0.2） g were fed with the basal fodder supplemented with different levels of ferrous fumarate （0, 20, 40, 80,160 and 480 mg/kg iron） for 60 d, and the six groups were named DO, D20, D40, D80, D160 and D480, wherein DO was as the control group, actually containing 62.60, 79.50, 99.60, 139.30, 215.20 and 538.40 mg/kg iron respectively. [ Result] The growth performance of juvenile rainbow trout was not affected by different dietary iron levels obviously （ P 〉 0.05）. With the increase of dietary iron level, hemoglobin （Hb） content and number of red blood cells（RBC） rose firstly and then leveled off. No significance was found in hematocrit （Hct） among the six groups （P 〉0.05）. Iron content in the whole body, vertebrae and muscle increased significantly with the improvement of dietary iron level（ P 〈0.05）, and iron concentration in the liver increased firstly and then leveled off in groups from D40 to D480. No significant difference in zinc content of the whole body was found among the six groups （ P〉0.05）, while zinc content in the vertebrae and muscle in control group was significantly higher than that of other groups （ P〈0.05）, and zinc concentration in the liver in groups DO and 1320 was significantly higher than that of other groups （ P 〈0.05）. Copper content in the whole body increased significantly with the increase of dietary iron level （P 〈 0.05 ）, while no significant difference was observed in the vertebrae （ P 〉0.05）, and copper concentration in the muscle in control group was significantly lower than that of other groups （ P 〈0.05）. Serum lysozyme （LZM） activity of group DO was significantly lower than that of other groups （ P 〈 0.05） except for group D480 （ P 〉 0.05）. Catalase （CAT） activity of serum enhanced significantly （ P 〈 0.05） from DO to EH0 and then decreased obviously （P 〈0.05）. [ Conclusion] Based on hemoglobin and iron content in the liver, the broken-line model analysis showed that the dietary iron level provided by ferrous fumarate for juvenile rainbow trout was estimated to be 99.8 and 100.4 mg/kg respectively in the experiment.

Aqueous Diels-Alder Reactions of Cyclopentadicnc with Symmetric Diester of Fumarate or Maleate

Symmetric, diesters of cis- or trans- bicyclo[2,2,1]hept-5-ene-2,3-dicarboxylate were prepared by aqueous Diels-Alder reaction of cyclopentadiene with symmetric diester of fumarate or maleate.

Determination of Bisoprolol Fumarate by Fluorescence Quenching Method

[Objectives]To establish a new method for indirect determination of bisoprolol fumarate based on fluorescence quenching technology.[Methods]In ammonia water and ammonium chloride buffer solution at pH=9.2,whenλexcitation=277 nm andλemission=596 nm,with the increase of CCu2+,the fluorescence signal intensity of bisoprolol fumarate weakened,and the difference between the fluorescence intensity of bisoprolol fumarate itself and the fluorescence intensity of the test solution after the quencher Cu2+was added(ΔF)and Cbisoprolol fumarate showed a good linear relationship.[Results]In the range of 15.39-76.93μg/mL,ΔF=146.7 Cbisoprolol fumarate+482.1,r=0.9988,and the detection limit is 0.1391μg/mL.[Conclusions]The fluorescence quenching method has been applied to the determination of actual samples with a recovery rate of 99.9%and an RSD of 2.7%.The results are satisfactory.

Pre-Formulation Development of Lamivudine 300 mg and Tenofovir Disoproxil Fumarate (TDF) 300 mg Fixed Dose Combination Tablets

Introduction: In this study, physical and chemical characteristics of Lamivudine, Tenofovir Disoproxil Fumarate (TDF) and potential excipients were systematically followed and documented [1]. Objective: The objective of this scientific work was to carry out pre-formulation studies including compatibility studies on Lamivudine and Tenofovir Disoproxil Fumarate with their potential excipients prior a direct compression process [2]. Methodology: The interaction was studied in three set of environments namely uncontrolled room conditions for Zone VI b (30°C ± 2°C), oven conditions in which the oven was set at 50°C and accelerated climatic conditions in which a climatic chamber was set at 40°C ± 2°C/75% ± 5% Relative Humidity (RH %). Sample preparation was done by mixing the amount of formulation excipients to active substances at a ratio of 1:10, whereas active substance to another active substance at a ratio of 1:1, active substance to coating materials at 1:4, coating materials to the whole set of excipients 1:4. The whole set of samples was geometrically mixed and triturated by mortar and pestle to very fine uniform powder to ensure homogeneity of the mixture. HPLC analytical method was used for simultaneous quantitative determination of lamivudine and tenofovir disoproxil fumarate. Transmittance of the mixture was determined by Near Infra-Red (NIR) technique. Results: The amount of Lamivudine as on day 0 was comparable to day 90 for in all tested conditions (Room, Oven and Climatic Chamber), whereas for Tenofovir Disoproxil Fumarate only the amount of the drug at Room (30°C ± 2°C) was comparable to results on day 90. A significant drop of amount of Tenofovir Disoproxil Fumarate (TDF) exposed to moisture (Climatic chamber at 40°C ± 2°C/75% ± 5% Relative Humidity (RH %)) and temperature of 50°C was observed. Colour change was observed for samples subjected to moisture (Climatic chamber at 40°C ± 2°C/75% ± 5% Relative Humidity (RH %)) and as well picked up in the NIR region 400 to 1500 cm-1 (Finger print region) by a significant shift in Transmittance. Conclusion: It can be concluded that microcrystalline cellulose, cross linked sodium carboxymethyl cellulose, magnesium stearate and sodium carbxymethyl cellulose can be compressed together with Lamivudine and Tenofovir Disoproxil Fumarate (TDF) to produce a pharmaceutically acceptable solid dosage form, tablet. The produced tablets should be packed in moisture and light protective containers as Tenofovir Disoproxil Fumarate (TDF) has diester linkages which can be hydrolysed into the active drug Tenofovir in the presence of moisture.

Protective effect and mechanism of clemastine fumarate on acute lung injury in mice with intestinal ischemia-reperfusion

Objective:To evaluate the protective effect and mechanism of clemastine fumarate(CLE)on acute lung injury(ALI)in intestinal ischemia-reperfusion(I/R)mice.Methods:Twenty-four SPF Balb/c mice were randomly divided into sham operation group(sham group),ischemia-reperfusion group(I/R group),and clemastine fumarate pretreatment group(I/R+C group).In the I/R group,an intestinal ischemia-reperfusion model was established(ischemia for 40 minutes,reperfusion for 2 hours).In the I/R+C group,CLE 5 mg/kg was intraperitoneally injected before the operation.Lung tissue morphology was observed and scored by HE staining;and the ratios of wet weight to dry weight(W/D)were recorded.the levels of MDA,SOD,GSH-px,NF-κB and TNF-αin lung tissue of each group were determined by ELISA;Western blot method was used to determine the expression of TLR4 protein in lung tissue.Results:Compared with the Sham group,the I/R group had significantly higher lung tissue injury score and wet/dry ratio(P<0.05),increased lung tissue MDA level(P<0.05),decreased SOD and GSH-px levels(P<0.05),and increased NF-κB and TNF-αlevels,the expression of TLR4 protein in lung tissue increased(P<0.05);compared with the I/R group,the lung tissue injury score and wet/dry ratio of the I/R+C group decreased(P<0.05),the level of MDA in lung tissue decreased(P<0.05),the levels of SOD and GSH-px increased(P<0.05),and the levels of NF-κB and TNF-毩decreased(P<0.05),the expression of TLR4 protein in lung tissue decreased(P<0.05).Conclusion:Clemastine fumarate can alleviate acute lung injury after intestinal ischemia-reperfusion in mice,and the mechanism may be related to the inhibition of oxidative stress and inflammatory response in lung tissue.

Treatment of Chronic Hepatitis B with Tenofovir Disoproxil Fumarate in Ivory Coast

Little data exist on patients treated with tenofovir in Sub-Saharan Africa. Objective: To describe the clinical and laboratory characteristics of patients with viral hepatitis B treated with tenofovir. Material and methods: A descriptive single-center retrospective study, on chronic viral hepatitis B mono-infected, followed in the hepatogastroenterology department of the University Hospital of Yopougon and treated with tenofovir from February 2012 to February 2015. The studied parameters were demographic, clinical, biochemical, serological, virological, abdominal ultrasound. Liver fibrosis was assessed either by liver biopsy or non-invasive tests. Results: 110 patients were treated with tenofovir disoproxil fumarate with a mean age of 40.4 years and a male predominance. Clinical examination revealed jaundice in 9% of cases, hepatomegaly in 7.3% of cases, splenomegaly in 9.1% of cases and ascites in 15.5% of cases. The AST averaged 77.3 IU/l, the ALT 76.8 IU/l, prothrombin rate at 76.6% , albumin level at 32.3 g/l, total bilirubin at 29.9 g/l, alpha fetoprotein rate at 15.3 ng/ml. HBe antigen was negative in 76.2% of cases. The average rate of DNA at baseline was 7.4 log10 IU/l. 27.5% was cirrhotic. The average time of starting treatment was 23.7 months. Conclusion: TDF is the first-line treatment for chronic hepatitis B in our country, because it is a well-tolerated, potent therapy with a high threshold for resistance development. Our study population had an average age of 40.4 years. Virological profile was dominated by HBe antigen negative patients and high viral load of HVB DNA. One third of patients were at the stage of cirrhosis. This treatment must be delivered free of charge in all the country hospitals, which is going to improve significantly the natural evolution of the disease and to decrease the incidence of the HCC.

Progress in the Study of Vonoprazan Fumarate vs. Proton Pump Inhibitors in the Treatment of Gastroesophageal Reflux Disease

Gastroesophageal reflux disease (GERD) is a common gastrointestinal disease, and proton pump inhibitors (PPIs) have been recommended as the first-line treatment for GERD. In recent years, studies on vonoprazan fumarate in the treatment of GERD have attracted widespread attention. In this paper, we review the research progress of vonoprazan fumarate and proton pump inhibitors in the treatment of GERD in recent years, and compare and analyze the efficacy, safety, tolerability, and advantages and disadvantages of long-term application of both. By reviewing the relevant literature, we found that vonoprazan fumarate has similar performance with proton pump inhibitors in terms of efficacy and safety, but has potential advantages in terms of tolerability and long-term application. Therefore, we believe that vonoprazan fumarate may become a new option for GERD treatment, helping clinicians to develop more appropriate treatment plans for patients and providing new ideas and directions for research in related fields.

欧洲药品评审局批准Aclidinium Bromide—Formoterol Fumarate Dihydrate复方制剂上市

欧洲药品评审局（EMA）于2014年11月19Et批准艾美罗（Almirall）公司的Aclidinium Bromide-Formoterol Fumarate Dihydrate（参考译名：阿地溴铵一富马酸福莫特罗，商品名：Duaklir Genuair、Brimica Genuair）粉雾剂上市，作为成人慢性阻塞性肺疾病（COPD）的维持治疗。

富马酸二甲酯减轻帕金森病模型鼠神经损伤的作用机制

背景:帕金森病是一种特征为多巴胺能神经元进行性丢失的多因素神经系统疾病,富马酸二甲酯(dimethyl fumarate,DMF)在神经退行性疾病中具有强大的神经保护和免疫调节作用。目的:探究DMF对MPTP诱导的帕金森病小鼠模型的神经保护机制。方法:选取24只C57BL/6系小鼠,随机将其分为对照组、模型组及DMF低剂量和DMF高剂量组。除对照组外,其余各组小鼠腹腔注射MPTP 30 mg/kg,1次/d,连续注射5 d,建立帕金森病的动物模型。每次注射MPTP后间隔30 min给予小鼠灌胃,DMF低剂量组和DMF高剂量组每天分别灌胃DMF 30,50 mg/kg,1次/d,对照组和模型组灌同等剂量的生理盐水,连续灌胃7 d。通过行为学检测、Western Blot、氧化应激标志物检测和免疫组织化学染色等方法,分析DMF对MPTP诱导的帕金森病小鼠氧化应激和Keap1/Nrf2信号通路的调节作用,以及DMF对多巴胺神经元变性的保护机制。结果与结论:①与模型组比较,DMF低剂量组小鼠的运动迟缓和姿势平衡障碍得到明显改善(P<0.01),在DMF高剂量组中的改善更为显著(P<0.01)。②与对照组相比,模型组氧化应激标志物丙二醛明显升高,超氧化物歧化酶表达降低(P<0.01);与模型组相比,DMF低、高剂量组降低了丙二醛的产生,增加了超氧化物歧化酶的表达(P<0.01)。③模型组小鼠的中脑黑质多巴胺能神经元数目和酪氨酸羟化酶蛋白表达较对照组明显减少(P<0.01),而DMF低剂量组小鼠的黑质多巴胺能神经元数目和蛋白表达增多(P<0.01),DMF高剂量组改善更明显(P<0.01)。④模型组Keap1蛋白表达升高伴随Nrf2蛋白表达降低;与模型组相比,DMF组降低了Keap1蛋白表达且伴随Nrf2蛋白表达增多(P<0.01)。⑤结果说明,DMF对帕金森病小鼠黑质区Keap1/Nrf2通路有调控作用,且与剂量呈现正相关(P<0.01),推测DMF依赖于Keap1/Nrf2信号发挥神经元保护作用。

HPLC法测定富马酸伏诺拉生片中三种潜在基因毒性杂质的含量

目的建立高效液相色谱(HPLC)法测定富马酸伏诺拉生片中三种潜在基因毒性杂质的含量,并通过方法学验证该方法的可行性。方法采用色谱柱YMC-Pack ODS-AQ,以高氯酸钠溶液(pH 2.5)为流动相A,乙腈为流动相B,进行梯度洗脱,检测波长为265 nm,柱温为30℃,进样量为60μl。结果该方法专属性良好,三种潜在基因毒性杂质分别在0.01483~0.29662μg/ml、0.01479~0.29587μg/ml和0.01618~0.33944μg/ml浓度范围内线性关系良好,平均回收率分别为97.2%、98.3%、97.6%,相对标准偏差(RSD)分别为1.2%、1.6%、4.9%;使用该方法对国产和原研进口的富马酸伏诺拉生片进行检测,均未检出上述潜在基因毒性杂质。结论所建立的HPLC分析法简便、准确、易于操作,可用于富马酸伏诺拉生片潜在基因毒性杂质含量测定,并为其质量控制提供参考依据。

布地格福与茚达特罗格隆溴铵在稳定期慢阻肺患者中的疗效对比

目的:探究对比布地格福与茚达罗特格隆溴铵在稳定期慢性阻塞性肺疾病(COPD)患者中的疗效。方法:回顾性分析2020年5月—2023年9月上饶市立医院收治的80例稳定期COPD患者的病例资料,根据使用药物不同将患者分对照组(n=38,用茚达特罗格溴铵治疗)、观察组(n=42,用布地格福治疗)。比较两组临床疗效,治疗4、12周后的肺功能指标、炎症因子、血气指标,并记录治疗期间不良反应发生情况。结果:观察组临床总有效率明显高于对照组,差异有统计学意义(P<0.05);与治疗前比较,两组治疗4、12周后的用力肺活量(FVC)、第1秒用力呼气容积(FEV1)、最大呼气压(MEP)、动脉血氧分压(PaO_(2))均明显升高,且观察组均较对照组高,差异均有统计学意义(P<0.05);与治疗前比较,两组治疗4、12周后白介素(IL)-6、IL-8、肿瘤坏死因子(TNF)-α、动脉血二氧化碳分压(PaCO_(2))均明显降低,且观察组均较对照组低,差异均有统计学意义(P<0.05);观察组与对照组不良反应总发生率比较,差异无统计学意义(P>0.05)。结论:相较茚达特罗格隆溴铵,布地格福治疗稳定期COPD患者的效果好,可有效促进肺功能恢复,改善血气指标,减轻炎症反应,且具有良好安全性。

富马酸二甲酯对Th17细胞体外分化调节作用的研究

目的:探讨富马酸二甲酯(DMF)对小鼠体外诱导分化的辅助性T细胞17(Th17)的抑制作用。方法:从C57BL/6J小鼠全身淋巴结和脾脏中获取淋巴细胞,采用免疫磁珠技术分选出Na?ve CD4+T细胞,在细胞因子作用下定向诱导分化为Th17细胞,建立Th17细胞体外诱导分化模型。实验分组设置为:对照组、5μmol/L DMF组、15μmol/L DMF组、25μmol/L DMF组。流式细胞术检测各组中Th17细胞的比率,qRT-PCR检测各组视黄酸受体相关孤儿受体γt(RORγt)、白细胞介素-17A(IL-17A)、白细胞介素-23受体(IL-23R)、粒细胞-巨噬细胞集落刺激因子(GM-CSF)、γ-干扰素(IFN-γ)、T辅助细胞分化转录因子(T-bet)和叉头框蛋白P3(FOXP3)m RNA的相对表达量,ELISA法检测各组IL-17A的蛋白表达量。结果:CD4+T细胞阳性分选率约为93%;流式细胞术检测结果显示,与对照组相比,DMF处理后Th17细胞比率显著降低,25μmol/L DMF组抑制作用最显著(t=5.227,P<0.01),且呈剂量依赖性,并且在25μmol/L DMF给药浓度下对细胞活性没有影响;qRT-PCR结果分析显示,25μmol/L DMF组中RORγt、IL-17A、IL-23R、GM-CSF和IFN-γ的mRNA相对表达量均低于对照组(t=4.061,P<0.05;t=4.701,P<0.01;t=19.18,P<0.000 1;t=19.18,P<0.05;t=2.870,P<0.05),而两组中T-bet和FOXP3 mRNA表达量差异无统计学意义(t=0.105、0.731 9,均P>0.05);ELISA法检测结果显示,与对照组相比,25μmol/L DMF组的IL-17A浓度显著降低(t=4.786,P<0.01)。结论:DMF可能通过抑制RORγt与IL-17A、IL-23R、GM-CSF、IFN-γ的表达,进而抑制Na?ve CD4+T细胞向Th17细胞分化的能力与Th17细胞的致病功能。

富马酸伏诺拉生联合阿莫西林治疗幽门螺杆菌感染的临床效果

目的观察富马酸伏诺拉生联合阿莫西林治疗幽门螺杆菌感染的临床效果。方法选取2023年1月—2024年1月临沂市中心医院收治的幽门螺杆菌感染患者62例,采用随机数字表法分为研究组和对照组,每组31例。对照组采用常规四联疗法治疗,研究组采用富马酸伏诺拉生联合阿莫西林治疗,2组均治疗1个月。比较2组临床疗效,治疗前后症状积分、炎性指标[白介素-2(IL-2)、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)、C反应蛋白(CRP)]水平,幽门螺杆菌根除率、复发率及不良反应。结果研究组总有效率(96.77%)高于对照组(80.65%)(χ^(2)=4.026,P=0.045)。治疗1个月后,2组上腹痛、反酸嗳气、恶心呕吐积分均低于治疗前,且研究组低于对照组(P<0.05或P<0.01);2组IL-2、TNF-α、IL-6及CRP水平均低于治疗前,且研究组低于对照组(P<0.01)。研究组幽门螺杆菌根除率为96.77%(30/31),高于对照组的80.65%(25/31)(χ^(2)=4.026,P=0.045);研究组疾病复发率为3.33%(1/30),低于对照组的28.00%(7/25)(χ^(2)=4.838,P=0.028)。研究组不良反应总发生率(3.23%)低于对照组(19.35%)(χ^(2)=4.026,P=0.045)。结论富马酸伏诺拉生联合阿莫西林治疗幽门螺杆菌感染的疗效较好,安全性较高,可改善患者症状,降低血清炎性指标,提升幽门螺杆菌根除率,降低疾病复发率。