OBJECTIVE:This study aims to evaluate the real-world effectiveness of 100 mg aspirin in preventing superimposed preeclampsia (PE) in pregnant women with chronic hypertension (CHTN). STUDY DESIGN:This retrospective cohort study included pregnant women with CHTN who began prenatal care before 20 weeks of gestation and delivered a singleton at Nanjing Drum Tower Hospital, affiliated with Nanjing University Medical School. The deliveries occurred between January 1, 2018, and May 1, 2025. The primary exposure was 100 mg/day aspirin initiated between 12 and 20 weeks of gestation, and the primary outcome was the incidence of superimposed PE. Secondary outcomes included PE delivery before 34 weeks, PE delivery before 37 weeks, preterm birth, postpartum hemorrhage, gestational diabetes mellitus, small for gestational age (SGA), and a composite of adverse neonatal outcomes. Multivariable logistic regression and inverse probability of treatment weighting (IPTW) were used to adjust for confounding factors. RESULTS:During the study period, 367 women met the inclusion criteria, with 111 in the aspirin group and 256 in the control group. After IPTW adjustment, baseline characteristics were comparable between the two groups. The incidence of superimposed PE was 34.6% in the aspirin group and 37.7% in the control group, with no statistically significant difference (weighted OR = 0.87, 95% CI: 0.49-1.54; p >0.05). In secondary outcomes, the incidence of SGA was significantly lower in the aspirin group both before and after IPTW adjustment (p<0.05); however, no significant differences were observed for other outcomes (p>0.05). Additionally, subgroup analyses showed no significant heterogeneity in aspirin effect when stratified by aspirin-related factors (initiation timing, adherence, and concurrent calcium supplementation) or CHTN-related factors (timing of diagnosis, blood pressure levels before 20 weeks of gestation, and use of antihypertensive medication within three months prior to conception or before 20 weeks) (p >0.05). CONCLUSION:Our study suggests that initiating 100 mg/day of aspirin between 12 and 20 weeks of gestation does not significantly reduce superimposed PE in women with CHTN; however, it significantly reduces the risk of SGA. Subgroup analyses also indicated that even initiation before 16 weeks did not provide additional preventive effect against PE.

Introduction: The epidural-related maternal fever (ERMF) induced by patient-controlled epidural analgesia (PCEA) remains unpredictable. Our objective is to develop ERMF prediction models using real-world data, aiming to identify pertinent contributing factors and support obstetricians in making personalized clinical decisions. Methods: Women who used patient-controlled epidural analgesia between October 2021 and March 2023 at a tertiary hospital in Jiangsu Province were retrospectively documented. The primary outcome was the occurrence of maternal fever associated with epidural use. We developed six machine learning (ML) models and assessed the area under curve (AUC) for characteristics of subjects' performance, calibration curves, and decision curve analyses. Results: A total of 1,492 women were enrolled, with 24.3% experiencing ERMF (362 cases). The AUC ratios between the logistic regression (LR) model and the stochastic gradient descent (SGD) models showed statistical significance (p < 0.05), while the differences between the other models were not statistically significant. In comparison to the SVM model, the LR model exhibited better calibration (Brier score: 0.193; calibration slope: 0.715; calibration intercept: 0.062). Consequently, the LR model was selected as the prediction model. Furthermore, the LR-based nomogram identified eight significant predictors of ERMF, including neutrophil percentage, first stage of labor, amniotic fluid contamination during membrane rupture, artificial rupture of membranes, chorioamnionitis, post-analgesic antimicrobials, pre-analgesic oxytocin, post-analgesic oxytocin, and dinoprostone suppositories. Conclusion: Optimally applying logistic regression models can enable rapid and straightforward identification of ERMF risk and the implementation of rational therapeutic measures, in contrast to machine learning models.

Objective. Intrahepatic cholestasis of pregnancy (ICP) significantly impacts the maternal and fetal safety. Research on the role of clinical pharmacists in guiding drug therapy for this condition remains limited. This study aimed to evaluate the effectiveness of graded pharmaceutical care for women with intrahepatic cholestasis of pregnancy and to provide a theoretical foundation for clinical pharmacist services. Study Design. This study comprises a pre‐and‐post analysis of women with intrahepatic cholestasis of pregnancy (ICP) treated between December 2019 and June 2023 at a tertiary hospital in Jiangsu province. Each group consisted of 102 participants. The control group received standard treatment, while the guardianship group received graded pharmacological care provided by a clinical pharmacist. The effectiveness of pharmacological monitoring by clinical pharmacists was assessed by comparing and analyzing clinical outcome indicators, quality management indicators, safety indicators, and economic factors. Results. The guardianship group exhibited a noteworthy 12.8% reduction in combined adverse pregnancy outcome and more effective management of total prenatal bile acids compared to the control group (16.05 µmol/L vs. 22.85 µmol/L, P < 0.05). The guardianship group displayed superior rationalization of therapeutic drugs and medication duration (P < 0.05). The cost‐benefit analysis revealed a favorable economic impact concerning medication costs but did not indicate economic significance regarding total inpatient costs. Conclusion. The implementation of a graded pharmaceutical care model by a clinical pharmacist holds the potential to enhance outcomes for women experiencing intrahepatic cholestasis during pregnancy, mitigate adverse pregnancy results, optimize the rational utilization of therapeutic medications, and yield positive economic results.

IntroductionRecently, the rise of antibiotic resistance has prompted a reconsideration of tetracyclines. However, existing studies are inadequate in assessing the pediatric safety of this class of antibiotics. To address the gap, our study aims to comprehensively assess the safety of tetracyclines in children.MethodsAdverse event (AE) reports from January 2005 to September 2023 were obtained from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database, and reporting odds ratio (ROR) was performed to identify potential risk signals in children under 18 years old who were administered any of the three tetracyclines: doxycycline, minocycline, and tigecycline.ResultsA total of 1903 AE cases were included in our study: 782 for doxycycline, 981 for minocycline, and 140 for tigecycline. Doxycycline and tigecycline were predominantly associated with “general disorders and administration site conditions” and “gastrointestinal disorders,” while minocycline was more frequently linked to “skin and subcutaneous tissue disorders” and “gastrointestinal disorders.” Psychiatric risks predominantly included depression, suicidal ideation, and suicide attempt. In the category of skin and subcutaneous tissues, 30.88% of the minocycline-induced drug reaction with eosinophilia and systemic symptoms (DRESS) cases resulted in death, alongside a high occurrence of co-occurring AEs such as multiple organ dysfunction syndrome, Type 1 Diabetes Mellitus (T1DM), and autoimmune thyroiditis. As for the endocrine system, both doxycycline and minocycline were found to potentially increase the risk of thyroid dysfunction. For children under the age of 8, doxycycline was associated with tooth discoloration (N = 7, ROR = 20.11%, 95% CI: 9.48–42.67), although it remained unclear whether the discoloration was permanent.ConclusionOur findings indicated that for pediatric patients, the majority of results were in line with the prescribing information and previous studies, and minocycline tended to cause more frequent and severe AEs than doxycycline. However, it is noteworthy that exceptions were found for psychiatric disorders and thyroid dysfunction associated with doxycycline, which are not mentioned in its FDA prescribing information. Additionally, further safety studies on tigecycline are still needed for children. When prescribing tetracyclines to pediatric patients, a careful risk-benefit assessment is crucial.

目的 构建基于多维感官干预的产科重症监护室(sensory-maternity intensive care unit,S-MICU)护理模式,保障危重症产妇母婴安全,同时提供生理、心理状态调节方面的个性化护理,提高产科危重症护理服务质量.方法 通过对多维感官干预相关文献进行系统检索,形成最佳证据总结,并开展临床实施性研究,构建基于S-MICU护理模式.选取2021年2月至2021年8月南京大学医学院附属鼓楼医院MICU入组的48例危重症产妇作为对照组,使用产科重症监护室,采取常规护理方法;2021年9月至2022年3月入组的48例危重症产妇为试验组,在对照组基础上嵌入S-MICU护理模式干预方法.对比两组产妇的焦虑、疼痛、抑郁评分、睡眠质量、产妇自我效能以及MICU护士焦虑评分.结果 干预后,试验组相较于对照组其焦虑、抑郁评分降低,差异有统计学意义(P＜0.05);试验组产妇的睡眠质量、自我效能相较于对照组提升,且疼痛评分下降,差异有统计学意义(P＜0.05);此外,护士工作焦虑情绪得到相对缓解.结论 S-MICU护理模式的应用有利于调整危重症产妇的生理、心理状态,并提高其自我效能与生活质量,减轻了 MICU护士的工作压力与焦虑情绪,可为危重症产妇实施个体化护理,提供安全且舒适的住院体验.

Background Lentinan (LNT) is a complex fungal component that possesses effective antitumor and immunostimulating properties. However, there is a paucity of studies regarding the effects and mechanisms of LNT on type 1 diabetes. Objective In the current study, we investigated whether an intraperitoneal injection of LNT can diminish the risk of developing type 1 diabetes (T1D) in non-obese diabetic (NOD) mice and further examined possible mechanisms of LNT’s effects. Methods: Pre-diabetic female NOD mice 8 weeks of age, NOD mice with 140–160 mg/dL, 200–230 mg/dL or 350–450 mg/dL blood glucose levels were randomly divided into two groups and intraperitoneally injected with 5 mg/kg LNT or PBS every other day. Then, blood sugar levels, pancreas slices, spleen, PnLN and pancreas cells from treatment mice were examined. Results Our results demonstrated that low-dosage injections (5 mg/kg) of LNT significantly suppressed immunopathology in mice with autoimmune diabetes but increased the Foxp3+ regulatory T cells (Treg cells) proportion in mice. LNT treatment induced the production of Tregs in the spleen and PnLN cells of NOD mice in vitro. Furthermore, the adoptive transfer of Treg cells extracted from LNT-treated NOD mice confirmed that LNT induced Treg function in vivo and revealed an enhanced suppressive capacity as compared to the Tregs isolated from the control group. Conclusion LNT was capable of stimulating the production of Treg cells from naive CD4 + T cells, which implies that LNT exhibits therapeutic values as a tolerogenic adjuvant and may be used to reverse hyperglycaemia in the early and late stages of T1D.

目的 为临床选择妊娠期及产后抑郁症的药物治疗方案提供参考.方法 搜索妊娠期及产后抑郁症的药物治疗相关文献,归纳相关治疗方案及建议.结果 西酞普兰和舍曲林可用于治疗妊娠期抑郁症;帕罗西汀或氟西汀可能会增加心血管畸形的风险,应避免使用;帕罗西汀和舍曲林可用于母乳喂养,氟西汀和西酞普兰等应避免使用;对选择性5-羟色胺再摄取抑制剂治疗无效或不耐受的患者可考虑使用三环类抗抑郁药,如去甲替林、阿米替林和氯丙咪嗪.结论 妊娠期和产后药物的选用需进行个体化分析,建议使用最低有效剂量,此外应权衡治疗药物的利弊与治疗不充分的抑郁症带来的风险.

目的 探讨香菇多糖(lentinan,LNT)对高糖(glucose,HG)诱导人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVECs)损伤的干预作用和机制.方法 筛选HG诱导HUVEC损伤的最佳浓度后、给予不同浓度LNT治疗,检测HUVEC细胞活力、活性氧(ROS)、超氧化物歧化酶(SOD)、丙二醛(MDA)水平.MDC染色法测定HUVEC内自噬水平.PCR法检测自噬相关基有Beclin-1水平.West-ern blot法检测各组LC3、诱导型一氧化氮合酶(iNOS)表达和p38 MAPK磷酸化水平.结果 120 mmol·L-1的HG能引起适度的HUVEC损伤;LNT作用后可改善HG诱导的HUVEC细胞活力下降;缓解ROS增加;提高SOD水平,降低MDA水平;提高HUVEC内自噬水平;降低HUVEC内iNOS和p38 MAPK磷酸化蛋白表达.结论 LNT可改善HG诱导的HUVEC损伤,机制与调控ROS/p38 MAPK通路,增强自噬水平,改善胞内氧化应激有关.

目的:研究接受自控硬膜外镇痛(PCEA)分娩的产妇发生硬膜外分娩镇痛相关产时发热(ERMF)的影响因素.方法:回顾分析2019年4月至2020年8月在南京大学医学院附属鼓楼医院接受PCEA分娩镇痛的387例产妇的临床资料.根据产妇是否发生ERMF分为2组:ERMF组(81例)、对照组(306例),比较两组间基本信息、妊娠合并症、产前用药、PCEA时宫口扩张、产时情况、视觉模拟评分法(VAS)的疼痛评估、满意度和新生儿Apgar评分,并进行二元logistic回归分析.结果:二元logistic分析显示,PCEA时宫口扩张程度小(OR=1.402,95％CI为1.049～1.874,P=0.022)是ERMF的危险因素,增加产妇ERMF发生风险.总产程时间短(OR=0.848,95％CI为0.785～0.915,P=0.000)、产前应用抗菌药物(OR=0.425,95％CI为0.238～0.760,P=0.004)、产前应用硫酸镁(OR=0.215,95％CI为0.060～0.766,P=0.018)是ERMF的保护因素,降低产妇ERMF的发生风险.ERMF的发生未影响产妇对PCEA分娩镇痛效果的满意度和新生儿Apgar评分(P>0.05).结论:ERMF的影响因素包括PCEA时宫口扩张程度、总产程、产前应用抗菌药物和硫酸镁.可据此对ERMF高危产妇进行初步预判,在产程中密切监测产妇体温,提前准备好母体和胎儿的处置措施,便于ERMF发生时的及时处理.

目的:探讨临床药师在经母口服地高辛治疗胎儿心动过速治疗过程中的作用.方法:临床药师参与1例胎儿心动过速孕妇的治疗全过程.根据患者妊娠31+6周、入院时胎心率230次/min的情况,临床药师针对经母口服地高辛治疗胎儿心动过速的安全性和血药浓度测定等问题向医师提出相关建议.因患者血钾值偏低,建议应用地高辛前先补钾,并建议地高辛的初始剂量为每12 h给药0.5 mg;在院7天时,患者地高辛血药浓度值升高明显,临床药师建议调整地高辛剂量至维持剂量(每12 h给药0.25 mg);在院11天时患者血钠值偏低,临床药师对其进行饮食指导;同时,临床药师向医、护、患交代地高辛不良反应的表现,对患者密切观察并进行用药宣教.结果:医师对临床药师的建议均采纳.患者于治疗13天后出院,出院时胎心率降至180次/min,母体地高辛血药浓度维持平稳,母胎均未发生药物不良反应.结论:妊娠期患者用药应兼顾母胎安全;临床药师协助医师制订用药策略、对患者进行药学监护和宣教,保障了胎儿心动过速治疗用药的有效性和安全性.

Objective To explore the clinical pharmacist participation in the treatment of pregnancy complicated with Clostridium difficile infection. Methods From the perspective of medications, clinical pharmacists followed evidence-based medical practice, combined pharmaceutical theory with clinical evidence and provided individualized pharmacy care in drug selection, dose adjustment, medication regime and liver protection treatment. Results Clinical pharmacists integrated into the treatment team to ensure the effectiveness and safety of medication in the patient with pregnancy. Conclusion The individualized pharmacy care improved the effectiveness of drug treatment.

Objective:To determine the concentration of hydroxychloroquine (HCQ) and its active metabolite deethylhydroxychloroquine (DHCQ) in breast milk of lactating patients with autoimmune disease. To observe the safety of hydroxychloroquine in lactation period, and to explore the factors that may affect HCQ and DHCQ concentration in the milk.Methods:Lactating patients with autoimmune disease who have taken HCQ for at least 6 months were included in our study. A new high performance liquid chromatography (HPLC) method was established to detect HCQ and DHCQ levels in breast milk. Milk samples were collected at different time points: before taking the drug (0 hours), and 2 hours, 4 hours, 6 hours after taking the drug. In addition, the genotype of cytochrome CYP3A4*1G, CYP3A5*3 and CYP2D6*10 which were related to HCQ metabolism were tested by dideoxy chain termination method. Visual acuity, hearing and growth status of the patients' infants were followed up on a regular basis. T-test, one-way ANOVA and Pearson's test were used for data analysis. Results:In 15 patients, the average concentration of HCQ and DHCQ in the milk of patients taking 200 mg/d were (520±261) ng/ml and (177±112) ng/ml, respectively. While the average concentration of HCQ and DHCQ in the milk of patients taking 400 mg/d were (1 036±374) ng/ml and (397±271) ng/ml, respectively. The peak of HCQ level for 11 patients was at 4 hour after taking the drug, while the others' were at 2 hour. The breast-fed infants did not show any abnormal symptoms of hearing, vision and growth. However, cytochrome gene polymorphism did not affect the peak of HCQ and DHCQ.Conclusion:The concentration of HCQ and DHCQ in breast milk is positively correlated to the dosage. The peak level of HCQ milk is 4 hours after taking the drug. The levels of HCQ and DHCQ at 6 hours are similar as those in the whole blood. It is suggested that patients who take HCQ can feed 4 hours after taking the drug to reduce the HCQ and its active metabolites being absorbed by infants. However, the impact of HCQ on infant safety and gene polymorphism of CYP on milk concentration among individuals needs to be further verified in large sample studies and long-term follow-up.

目的:分析临床药师在产科药学服务工作开展情况,了解产科用药咨询的特点,提高药学服务质量.方法:汇总鼓楼医院临床药师接受产科临床和门诊的用药咨询363例,对基本情况、咨询内容、问题类型和药物种类进行统计,通过帕累托法则进行分析.结果:在363例用药咨询中,咨询人员以医生为主,共212例(占58.40％);咨询问题主要来自产科住院病区(229例,占63.09％);咨询内容中药物对妊娠的影响所占比例最大;问题类型中妊娠期用药(200例,占55.10％)和哺乳期用药(34例,占9.37％)数量最多;抗微生物药物、电解质、维生素及营养类药物、消化系统药物、中成药等为咨询药物种类的主要因素.结论:临床药师在产科接受的用药咨询所涉及的各分类有鲜明的规律及差异,在药学服务中宜重点把握主要因素,为产科提供更优质的药学服务.

对妇科恶性肿瘤化疗防治恶心呕吐药物应用的合理性评价.收集本院妇科2018年4月接受化疗的住院患者病历111份,根据国内外肿瘤相关的恶心呕吐防治指南,分析应用防治恶心呕吐药物存在的问题.100例(90.09％)地塞米松(DXM)应用不合理;111例(100％)均应用5-羟色胺3受体拮抗剂,其中79例(71.17％)应用疗程不合理,17例(15.32％)超致吐风险级别用药,4例(3.60％)重复应用;104例(93.69％)无指征应用H2受体拮抗剂或质子泵抑制剂.化疗患者呕吐防治药物的应用存在不合理现象,建议加强医嘱审核,提高应用呕吐防治药物的合理性.

目的 调查南京大学医学院附属鼓楼医院应用鹿瓜多肽注射液的现状并进行合理性分析,为临床合理用药提供参考.方法 抽取南京大学医学院附属鼓楼医院2017年应用鹿瓜多肽注射液的出院病历,抽样点评其中667份,根据鹿瓜多肽注射液说明书及循证学依据,对鹿瓜多肽注射液临床应用的合理性进行回顾性分析.结果 鹿瓜多肽注射液临床应用的不合理率为58.47％,存在适应症不适宜(11.54％)、给药剂量不合理(2.10％)、溶媒体积偏小(52.47％)、疗程过长(10.64％)和配伍不合理(7.95％)的问题.结论 鹿瓜多肽注射液临床应用存在一些问题,建议加强药师医嘱审核和医师培训,促进临床合理用药,保证患者用药安全.

Pancreatic β‐cell death or dysfunction mediated by oxidative stress underlies the development and progression of diabetes mellitus ( DM ). In this study, we evaluated the effect of lentinan ( LNT ), an active ingredient purified from the bodies of Lentinus edodes , on pancreatic β‐cell apoptosis and dysfunction caused by streptozotocin ( STZ ) and the possible mechanisms implicated. The rat insulinoma cell line INS‐1 were pre‐treated with the indicated concentration of LNT for 30 min. and then incubated for 24 hrs with or without 0.5 mM STZ . We found that STZ treatment causes apoptosis of INS ‐1 cells by enhancement of intracellular reactive oxygen species ( ROS ) accumulation, inducible nitric oxide synthase ( iNOS ) expression and nitric oxide release and activation of the c‐jun N‐terminal kinase ( JNK ) and p38 mitogen‐activated protein kinase ( MAPK ) signalling pathways. However, LNT significantly increased cell viability and effectively attenuated STZ ‐induced ROS production, iNOS expression and nitric oxide release and the activation of JNK and p38 MAPK in a dose‐dependent manner in vitro . Moreover, LNT dose‐dependently prevented STZ ‐induced inhibition of insulin synthesis by blocking the activation of nuclear factor kappa beta and increasing the level of Pdx‐1 in INS ‐1 cells. Together these findings suggest that LNT could protect against pancreatic β‐cell apoptosis and dysfunction caused by STZ and therefore may be a potential pharmacological agent for preventing pancreatic β‐cell damage caused by oxidative stress associated with diabetes.

The pro-inflammatory profile of M1 macrophage accumulation in adipose tissue is a central event leading to the metabolic complications of obesity. However, the mechanisms by which M1 macrophages are enriched in adipose tissue during weight gain remain incompletely understood. Here, we investigated the effects of adipocyte-derived microvesicles (ADM) on modulating macrophage phenotype in mice and explored the involved molecular signalling pathways. We found that, compared with ADM from lean mice (SD ADM), ADM from obese mice (HFD ADM) significantly enhanced M1 marker expression. The quantitative RTPCR assay demonstrated that miR-155 was upregulated in both HFD ADM and HFD ADM-treated macrophages. By depleting miR155 expression in HFD ADM and increasing miR-155 level in SD ADM, we further illustrated that miR-155 in ADM-induced M1 macrophage polarization. Functionally, in contrast to SD ADM, HFD ADM significantly decreased the protein level of SOCS1, a proven miR-155 target, leading to activation of STAT1, and suppression of STAT6 signalling; these effects were reversed by silencing miR-155 in HFD ADM. Furthermore, the supernatant of bone marrow-derived macrophages pre-stimulated with miR-155-bearing ADM interfered with insulin signalling and insulin-induced glucose uptake in adipocytes. Collectively, these results provide the first evidence that M1 macrophage polarization can be mediated by miR-155-bearing ADM, which reciprocally regulates insulin signalling and glucose uptake in adipocytes. Our study reveals a novel mechanism through which obesity induces an imbalance in the M1-to-M2 macrophage ratio in adipose tissue, thus causing chronic inflammation and local insulin resistance.

BACKGROUND:Cytokines secreted by adipose tissue macrophages (ATMs) significantly alter adipocyte function, inducing inflammatory responses and decreasing insulin sensitivity. However, little relevant information is available regarding the role of microvesicles (MVs) derived from ATMs in macrophage-adipocyte crosstalk.METHODS:MVs were generated by stimulation of M1 or M2 phenotype THP-1 macrophages and incubated with human primary mature adipocytes and differentiated adipocytes. Subsequently, insulin-stimulated phosphorylation of Akt (pAkt) and glucose uptake were determined. Glucose transporter 4 (GLUT4) translocation and nuclear translocation of nuclear factor (NF)-kappa B were also analyzed in treated adipocytes.RESULTS:M1 macrophage-derived MVs (M1 MVs) significantly reduced protein abundance of insulin-induced Akt phosphorylation in human primary mature adipocytes and differentiated adipocytes, when compared with the same concentration of M2 macrophage-derived MVs (M2 MVs). In contrast to M2 MVs, which enhanced the insulin-induced glucose uptake measured by 2-NBDG, M1 MVs decreased this effect in treated adipocytes. M1 MVs treatment also brought about a significant increase in the nuclear translocation of nuclear factor (NF)-kappa B, coupled with a decrease in pAkt level and GLUT4 translocation compared with M2 MVs-treated adipocytes. These effects were reversed by BAY 11-7085, a NF- kappa B specific inhibitor.CONCLUSIONS:MVs derived from proinflammatory (M1) macrophages may, at least in part, contribute to the pathogenesis of obesity-induced insulin resistance, reducing insulin signal transduction and decreasing glucose uptake in human adipocytes, through NF-kappa B activation. Therefore, these MVs may be potential therapy candidates for the management of type 2 diabetes mellitus.