Effect of deuteration on the single dose pharmacokinetic properties and postoperative analgesic activity of methadone

Although methadone is effective in the management of acute pain, the complexity of its absorption-distribution-metabolism-excretion profile limits its use as an opioid of choice for perioperative analgesia. Because deuteration is known to improve the pharmacokinetic, pharmacodynamic and toxicological properties of some drugs, here we characterized the single dose pharmacokinetic properties and post-operative analgesic efficacy of d₉-methadone.The pharmacokinetic profiles of d₉-methadone and methadone administered intravenously to CD-1 male mice revealed that deuteration leads to a 5.7- and 4.4-fold increase in the area under the time-concentration curve and maximum concentration in plasma, respectively, as well as reduction in clearance (0.9 ± 0.3 L/h/kg vs 4.7 ± 0.8 L/h/kg). The lower brain-to-plasma ratio of d₉-methadone compared to that of methadone (0.35 ± 0.12 vs 2.05 ± 0.62) suggested that deuteration decreases the transfer of the drug across the blood-brain barrier. The estimated LD₅₀ value for a single intravenous dose of d₉-methadone was 2.1-fold higher than that for methadone. Moreover, d₉-methadone outperformed methadone in the efficacy against postoperative pain by primarily activating peripheral opioid receptors. Collectively, these data suggest that the replacement of three hydrogen atoms in three methyl groups of methadone altered its pharmacokinetic properties, improved safety, and enhanced its analgesic efficacy.     

妊娠糖尿病患者血清、脐血及胎盘组织中 Visfatin和 Chemerin的表达与胰岛素抵抗发生机制的研究

目的　探讨妊娠糖尿病（ gestational diabetes mellitus，GDM）患者血清、脐血及胎盘组织中的内脏脂肪组织（Visfatin）、脂肪因子趋化素（ Chemerin）的表达变化及与患者发生胰岛素抵抗的关系。方法　选取阜阳市人民医院 2018年 12月～ 2020年 4月妊娠分娩的 GDM孕妇 100例作为 GDM组、糖耐量正常孕妇 100例作为 NGT组。统计分析两组的一般资料、血糖指标、血脂指标，检测两组研究对象血清、脐血、胎盘组织中的 Visfatin，Chemerin表达水平，分析 Visfatin，Chemerin表达与胰岛素抵抗指数（ HOMA-IR）的相关性；通过重组慢病毒载体构建 Visfatin， Chemerin过表达的 3T3-L1脂肪细胞，分析 Visfatin，Chemerin过表达对 3T3-L1脂肪细胞增殖、葡萄糖消耗量、 Akt及 pAkt蛋白表达的影响。结果　GDM 组的 FPG(5.84±0.52mmol/L)，Fins(18.96±3.75μU/ml)，HbA1c(6.42%±0.89%)， HOMA-IR(2.48±0.66)，TC(5.22±0.57mmol/L)和 TG(2.41±0.43mmol/L)测定值均高于 NGT组 (4.61±0.40mmol/L，     

Risk factors and a simple scoring system for predicting bowel resection in infants with NEC

Background and aimsWe intended to investigate the predictors for bowel resection in infants with necrotizing enterocolitis (NEC). We further developed a scoring system for better predicting bowel resection.MethodsA total of 207 infants who underwent surgical management at Children's Hospital, Chongqing Medical University between April 2008 and December 2020 were identified for the following investigation. Bowel resection was reviewed among the infants who underwent the procedure. Potential parameters related to bowel resection were explored using a multiple logistic regression method, and then a scoring system was developed.ResultsAmong the 207 patients who underwent operative intervention that were reviewed, 109 infants underwent bowel resection. Multivariate logistic regression analysis showed that birth weight, hypotension, neutropenia, pneumoperitoneum, acidosis, and intestinal wall thickness were predictors related to the occurrence of bowel resection. A 6-point scoring system was further developed based on the obtained total coefficient, and the infants could be divided into low-, moderate- and high-risk groups according to cut values of 7 and 13.ConclusionThe results of this study demonstrated that severe NEC features and low birth weight were associated with bowel resection. The risk scoring system could accurately separate infants that were suspected to have bowel loss during surgery.     

Correction to: Expression profle of PU.1 in CD4+T cells from patients with systemic lupus erythematosus

Clinical and Experimental Medicine - A correction to this paper has been published: https://doi.org/10.1007/s10238-021-00731-x     

首诊缺血性脑卒中病人出院准备度与出院后生活质量的相关性研究

目的探讨首诊缺血性脑卒中病人的出院准备度与出院后生活质量之间的相关性。方法便利抽样选取首次诊断为缺血性脑卒中的符合纳入标准的210例病人作为研究对象，使用成人版出院准备度量表（RHDS）和简明健康调查问卷（SF-36）对病人出院前4 h的出院准备度和出院后1个月的生活质量进行问卷调查。结果首诊为缺血性脑卒中病人的出院准备度总均分为（7.69±0.70）分，与国内其他研究相比处于中等水平；3个维度中适应能力维度平均得分最高为（8.12±1.04）分，预期性支持维度平均得分最低为（7.26±0.88）分；单因素分析结果显示性别、月收入、文化程度是影响首诊缺血性脑卒中病人出院准备度的影响因素（P < 0.01）；多元逐步回归分析结果显示文化程度是影响病人出院准备度的显著影响因子（b=0.218，95%CI:0.072~0.216，P < 0.01），文化程度越高者出院准备度越高；出院后1个月的生活质量得分为（91.86±14.26）分，Pearson相关分析结果显示出院准备度与生活质量呈正相关关系（r=0.843，P < 0.05）。结论首诊缺血性脑卒中病人的出院准备度有待进一步提高，临床医护人员并根据病人的文化程度不同给予有针对性的临床干预，提高其出院准备度，从而改善病人出院后的生活质量。     

TOPSIS法和秩和比法模糊联合在基本公共卫生服务质量综合评价中的应用研究

背景国家基本公共卫生服务项目的开展是我国新医改的重要举措，自2009年国家基本公共卫生服务项目开展后，其服务经费与服务项目不断扩增，由于涉及指标较多，覆盖面较广，探寻科学、客观、全面的基本公共卫生服务综合评价方法十分必要。目的探索适宜的基本公共卫生服务质量综合评价方法，通过质量评价为调整相关政策和提高服务质量提供依据。方法2019年2—4月，采用多阶段立意抽样方式从Z省南部、中部和北部地区共选取24家社区卫生服务中心（乡镇卫生院）作为评价对象，记为机构A~X。采用逼近理想解排序法（TOPSIS法）、秩和比法及二者模糊联合的方法对24家社区卫生服务中心（乡镇卫生院）2018年基层医疗卫生机构基本公共卫生服务质量进行综合评价（参考2018年国家基本公共卫生服务项目选取12项评价指标）。结果在TOPSIS法评价中，Ci值排名前三名的为A（0.917 4）、C（0.875 9）和G（0.787 9），Ci值排名后三名的为I（0.414 2）、W（0.413 7）和N（0.407 7）。在秩和比法评价中，RSR值排名前三名的为A（0.890 6）、G（0.765 6）和C（0.711 8），RSR值排名后三名的为V（0.381 9）、W（0.362 8）和K（0.357 6）。根据模糊集理论，将W1Ci+W2RSR值进行排序，依据"择多原则"，排名前三名的分别为A、C和G，排名后三名的分别为I、K和W，这与TOPSIS法和秩和比法的评价结果基本一致。结论TOPSIS法和秩和比法模糊联合得到的评价结果及影响因素与其他研究结果相一致，并且两者联用能克服单一使用TOPSIS法或秩和比法的局限性，适宜在基本公共卫生服务质量评价中推广应用。     

Cervical cancer in Morocco: A systematic review

BackgroundThis systematic review aims to determine the epidemiological profile, etiology and risk factors, prevention, diagnosis, treatment, cost-effectiveness, survival, and quality of life related to cervical cancer in Morocco.MethodsThis study was conducted according to the recommendations of the "preferred reporting items for systematic reviews and meta-analysis." The PubMed, ScienceDirect, Springer, Web of Science data bases were used, as was Google Scholar for the grey literature. The review protocol was registered in the PROSPERO register (CRD42021235241).ResultsFifty studies were selected. The mean age was 49.31 ±6.3 years. HPV infection prevalence ranged from 13.30% to 76%, with a peak in HIV-positive women. Acceptability of the HPV vaccine was higher among parents (35% and 82%) than among adolescents (16.9% to 46.6%). Knowledge of the vaccine and its price are two key factors related to vaccine acceptability among parents. This systematic review highlights that the fact that few eligible women (not more than 11%) were participating in the cervical cancer screening program. Moroccan women's level of knowledge and awareness regarding cervical cancer screening was low, negatively impacting their use of such screening tools, as illustrated by the high percentage (mean 76.32% ± 17.21) of women who had never been screened for cervical cancer. Treatment was the most significant component of the global care budget (95.87%), with an annual cost of $13,027,609. Five-year overall survival ranged from 41.3% to 73.6%, with higher survival rates for patients diagnosed at an earlier stage (77.3–85% for stage I). Lastly, low quality of life was observed in women with tumors at an advanced stage who had received brachytherapy and lacked social support.ConclusionsSubjects that require further investigation include Moroccan women's knowledge, attitudes, and awareness, especially among those at high risk of developing cervical cancer, and its impact on their quality of life and survival.