托吡酯、丙戊酸钠预防幼鼠慢性癫痫脑损伤的实验研究

目的研究托吡酯、丙戊酸钠单药及联合用药对幼鼠慢性癫痫脑损伤的影响。方法将3～4周龄雄性Wistar大鼠60只随机分为5组，B、C、D、E组为慢性癫痫组，C、D、E组于戊四氮（PZT）腹腔注射后给予TPM40mg／kg、VPA200mg／kg、TPM40mg／kg＋VPA200mg／kg，A、B组给予等量的蒸馏水，连续用药2个月，观察癫痫发作后幼鼠的体重改变、行为学表现及海马组织病理形态学的变化检测血清神经元特异性烯醇化酶（NSE）水平，了解脑损伤的发生情况及药物的情况保护。结果①TPM使体重增长降低，VPA使体重增长增加；②TPM、VPA均使发作持续时间缩短（P〈0．05），联合用药组使发作持续的时间长（P〈005）；③TPM组、VPA组的NSE水平降低显著（P〈0．05）；④TPM组、VPA组神经元的退行性变和胶质细胞的反应性增生较阳性组减少。TPM＋VPA组神经元变性坏，胞浆浓缩，出现红色神经元。结论TPM、VPA单药均对癫痫脑损伤有保护作用，但2者联合可能削弱其单药的神经保护作用。     

丙戊酸钠与改良型无抽搐电休克治疗对氯氮平抵抗的难治性精神分裂症疗效和安全性比较

目的比较丙戊酸钠与改良型无抽搐电休克治疗（modified electroconvulsive therapy, MECT）对氯氮平抵抗的难治性精神分裂症（Clozapine-resistant schizophrenia, CRS）疗效和安全性的差异。方法本研究招募了90例CRS患者,进行为期8周随机对照试验,最终78例完成试验,脱落12例。将患者随机分为3组： (1) MECT联合氯氮平组(MC组)30例,完成28例、脱落2例;(2) 丙戊酸钠联合氯氮平组(VC组)30例,完成27例、脱落3例;（3） 维持原治疗组（对照组）30例,完成23例、脱落7例。采用阳性与阴性症状量表(The Positive and Negative Syndrome Scale, PANSS)评定临床疗效,采用血常规、血生化指标、体格检查及心电图评估安全性。结果在治疗4周和8周后MC组PANSS精神病理分和PANSS总分均较入组前显著下降（P<0.05）,而VC组和对照组均没有这种差异。PANSS阳性量表分和PANSS总分,干预与时间存在交互效应,简单效应分析发现只有PANSS总分存在组间差异。PANSS精神病理分存在组间差异（F=3.89,P=0.025）。同期组间对照比较发现治疗4周和8周的PANSS精神病理分以及治疗8周的PANSS总分减分幅度大于VC组和对照组（P<0.05）。3组间安全性比较差异无统计学意义(P均>0.05)。结论MECT联合治疗方案对CRS的疗效优于丙戊酸钠,且具有较好的安全性。     

A pilot study on the effects of early use of valproate sodium on neuroinflammation after traumatic brain injury北大核心CSCD

Objective To study the effect of early use of sodium valproate on neuroinflammation after traumatic brain injury (TBI). Methods A total of 45 children who visited in Xuzhou Children's Hospital Affiliated to Xuzhou Medical University from August 2021 to August 2022 were enrolled in this prospective study, among whom 15 healthy children served as the healthy control group, and 30 children with TBI were divided into a sodium valproate treatment group and a conventional treatment group using a random number table (n=15 each). The children in the sodium valproate treatment group were given sodium valproate in addition to conventional treatment, and those in the conventional group were given an equal volume of 5% glucose solution in addition to conventional treatment. The serum concentrations of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3), high-mobility group box 1 (HMGB1), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were measured in the healthy control group on the day of physical examination and in the children with TBI on days 1, 3, and 5 after admission. Glasgow Outcome Scale-Extended (GOS-E) score was evaluated for the children with TBI 2 months after discharge. Results Compared with the healthy control group, the children with TBI had significantly higher serum concentrations of NLRP3, HMGB1, TNF- α, and IL-1β on day 1 after admission (P<0.017). The concentration of NLRP3 on day 5 after admission was significantly higher than that on days 1 and 3 after admission in the children with TBI (P<0.017). On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of NLRP3 than the conventional treatment group (P<0.05). For the conventional treatment group, there was no significant difference in the concentration of HMGB1 on days 1, 3, and 5 after admission (P>0.017), while for the sodium valproate treatment group, the concentration of HMGB1 on day 5 after admission was significantly lower than that on days 1 and 3 after admission (P<0.017). On day 5 after admission, the sodium valproate treatment group had a significantly lower concentration of HMGB1 than the conventional treatment group (P<0.05). For the children with TBI, the concentration of TNF-α on day 1 after admission was significantly lower than that on days 3 and 5 after admission (P<0.017). On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of TNF-α than the conventional treatment group (P<0.05). The concentration of IL-1β on day 3 after admission was significantly lower than that on days 1 and 5 after admission (P<0.017) in the children with TBI. On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of IL-1β than the conventional treatment group (P<0.05). The GOS-E score was significantly higher in the sodium valproate treatment group than that in the conventional treatment group 2 months after discharge (P<0.05). Conclusions Early use of sodium valproate can reduce the release of neuroinflammatory factors and improve the prognosis of children with TBI. © 2023 Xiangya Hospital of CSU. All rights reserved.     

Increased circulating magnesium concentrations after Roux-en-Y gastric bypass surgery in patients with type 2 diabetes

Background

Low circulating magnesium concentrations predict cardiovascular and all-cause mortality in patients with type 2 diabetes (T2D). Epidemiologic and clinical studies have indicated lower extra- and intracellular magnesium concentrations in patients with diabetes.

离子色谱-抑制电导法测定硫酸镁钠钾口服用浓溶液中镁、钠、钾离子

目的 建立离子色谱–抑制电导法同时测定硫酸镁钠钾口服用浓溶液中镁、钠、钾离子的方法。方法 采用Dionex IonPac^TM CS12A色谱柱（250 mm×4 mm）,Dionex IonPac^TM CG12A保护柱（50 mm×4 mm）;以甲烷磺酸溶液为洗脱液,梯度洗脱,体积流量为1.0 mL/min,柱温30 ℃,检测池温度35 ℃,电导检测器,抑制器为Dionex CDRS 600 4 mm,电流值117 mA,进样体积为25 μL。结果 镁在0.72～1.08μg/mL、钠在12.80～19.20 μg/mL、钾在3.20～4.80 μg/mL线性关系良好,平均回收率分别为101.0%、100.7%、102.9%,RSD值分别为1.4%、1.4%、0.7%。结论 该方法简单、快速、准确,能够有效地控制硫酸镁钠钾口服用浓溶液中镁、钠、钾离子。     

硫酸镁和/或沙丁胺醇雾化吸入对哮喘患儿吸入乙酰胆碱激发后肺功能影响的随机对照研究

目的观察硫酸镁雾化能否改善哮喘患儿吸入乙酰胆碱激发后的肺功能,并与雾化吸入沙丁胺醇和硫酸镁＋沙丁胺醇进行比较。方法330例乙酰胆碱激发试验阳性的哮喘患儿随机分为3组,3组分别给予雾化吸入硫酸镁,沙丁胺醇,硫酸镁+沙丁胺醇,观察用药后2个时点（10 和20 min）第1秒用力呼气量（FEV1）、最大呼气流速(PEF）的肺功能指标。结果①3组患儿用药后2个时点的FEV1、PEF值均较激发值显著上升（P<0.05）,但3组2个时点的FEV1、PEF值两两比较差异无统计学意义（P>0.05）;②沙丁胺醇组及硫酸镁+沙丁胺醇组2个时点的FEV1、PEF值占预计值的百分比高于硫酸镁组（P<0.05）;③硫酸镁组和硫酸镁+沙丁胺醇组用药后20 min时点的FEV1及PEF值占预计值的百分比高于用药后10 min时点的百分比（P<0.05）。 结论硫酸镁雾化吸入能改善哮喘患儿吸入乙酰胆碱激发后的肺功能,但其效果不如单用沙丁胺醇;硫酸镁+沙丁胺醇联合应用不具有协同效应。     

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??Abstract??Objective To study the effectiveness of the antiepileptic lamotrigine ??LTG?? and the relationship between the plasma concentration and oral dosage?? co-medication and patients age. Methods Totally 111 epileptic patients were divided into 2 groups?? LTG monotherapy group ??n=58?? and LTG??VPA ??Valproate??VPA?? group ??n=53??. LTG??VPA group was divided into three subunits in terms of plasma concentration of VPA. LTG monotherapy group was divided into two subunits?? older ??7??18 y?? n=40?? and younger ??3????7 y?? n=18?? group. The dosage was then increased to target dose gradually. Blood specimens were collected more than one month after LTG target dose or when effective maintenance dosage was achieved. The serum concentrations of LTG and VPA were determined by high performance liquid chromatography. Results The effect of the LTG was 82.9%.VPA combination enhanced LTG blood concentration. The ratio of serum level and dose of LTG did not vary with the range of the serum concentration of VPA 0.28??0.62mol/L.In younger group the relativity between blood concentration of LTG and LTG maintaining dose didn’t exist. However?? there was a positive correlation in the older group. Conclusions When we prescribe LTG??we should consider epilepsy type?? co-medication and individual difference as a whole.Therefore TDM??therapeutic drug monitoring??TDM??is an essential tool to control seizure and avoid side effects.     

Maternal risk factors in the origin of isolated hypospadias: A population‐based case‐control study

The birth prevalence of hypospadias increased in Hungary during the last decades, thus the aim of this study was to analyze the possible role of maternal risk factors in the origin of isolated hypospadias (IHS). The incidence/prevalence of acute and chronic maternal diseases with related drug treatments were compared in the mothers of cases with IHS, population controls without defect and malformed controls affected with other isolated abnormalities in the population‐based Hungarian Case‐Control Surveillance of Congenital Abnormalities including 3038 cases with IHS, 24 814 population male controls without any defects and 11 096 malformed male controls with other isolated defect. Among exposures, prospective medically recorded chronic diseases and medically recorded or retrospective maternal information regarding acute diseases and drug treatments were evaluated in the study groups. Maternal epilepsy due to the treatment of valproate (odds ratio [OR] with 95% confidence interval [CI]: 1.97, 1.07–3.61) and cervical erosion (4.09, 1.84–9.12) were associated with a higher risk of IHS. In addition, there was an association of oral nystatin (1.94, 1.22–3.09), lynestrenol (26.66, 8.69–81.80) and ethynilestradiol (3.51, 1.61–7.67) treatments in the mothers of cases with a higher risk for IHS. In conclusion, maternal cervical erosion, valproate, nystatin, lynestrenol and ethynilestradiol associated with a higher risk for IHS.     

镁剂对大鼠蛛网膜下腔出血后血管内皮生长因子表达的影响

目的 观察硫酸镁对大鼠蛛网膜下腔出血(SAH)模型脑内内皮细胞生长因子(VEGF)的影响.方法 将96只SD大鼠随机分为SAH组、假手术组、SAH加镁组、假手术加镁组建立实验动物模型.分别于相应时间点采用免疫组化技术分析大鼠脑内VEGF分布情况.结果 假手术组和假手术加M镁组均可见到少量VEGF的表达,两者差异无显著性.在蛛网膜下腔出血组24 h明显表达,3 d表达强度进一步增高,7 d达高峰,14 d下降至正常.其阳性细胞主要分布在大脑皮层,基底节区、海马等部位也有较多.其细胞类型主要为神经细胞、胶质细胞、血管内皮细胞等.在SAH后的不同时间点免疫组织化学结果为:SAH加镁组大鼠VEGF的表达明显高于SAH组.结论 硫酸镁促进了VEGF的表达,其通过促进VEGF的表达参与了继发性脑损伤的保护机制.