2025年 · 第07卷第03期

Objective: To systematically study the mechanisms by which Yinzhihuang (YZH), a traditional Chinese medicine, ameliorates intrahepatic cholestasis of pregnancy (ICP), a liver disorder associated with significant maternal and fetal complications. Methods: This experimental study was conducted from January 2024 to August 2024, utilizing data from public databases (Traditional Chinese Medicine Systems Pharmacology, GeneCards, Online Mendelian Inheritance in Man, DisGeNET, Proteome Xchange) alongside in vitro cell culture experiments. Network pharmacology identified active components of YZH and potential therapeutic targets for ICP. Ultra-performance liquid chromatography–mass spectrometry characterized YZH oral liquid, and its effective doses were evaluated in taurocholic acid (TCA)-induced HTR-8/SVneo cells, an in vitro ICP model. ICP-related targets were gathered from multiple databases, and hub genes were selected through bioinformatics and previously identified differentially expressed proteins. Functional annotation and pathway enrichment analyses were conducted, with validation in TCA-induced cells treated with various YZH concentrations (0.1%–5.0%) compared to controls. Molecular docking confirmed predicted interactions. Results: Using network pharmacology, 104 active compounds and 241 potential targets of YZH were identified. Integration of multiple databases yielded 1897 YZH-related therapeutic targets and 3783 ICP-associated genes. Proteomic analysis identified 227 differentially expressed proteins, from which 10 hub genes were selected; among these, APOA2, COL1A1, and ADIPOQ were significantly upregulated in ICP samples. UPLC-ESI-MS/MS detected 2022 compounds, predominantly flavonoids (25.07%, 507/2022) and phenolic acids (14.44%, 292/2022). Molecular docking demonstrated strong binding affinities between several active compounds and the hub genes. In TCA-induced HTR-8/SVneo cells, 0.5% YZH treatment significantly enhanced cell viability and modulated hub gene expression, supporting a potential multi-target mechanism. Conclusion: This study systematically explored the active components and potential targets of YZH in ICP through network pharmacology, proteomics, and in vitro validation. The findings suggest that YZH may act via the PPAR signaling pathway by modulating genes such as PPARA, PPARG, ADIPOQ, and APOA2.

Objective: To validate and compare the performance of four risk stratification tools—the DEVI (Adverse Cardiac Events in Valvular Rheumatic Heart Disease in Pregnancy) score, Zwangerschap bij Aangeboren Hartafwijking (ZAHARA) score, Cardiac Disease in Pregnancy II (CARPREG II), and modified WHO (mWHO) classification—in predicting adverse cardiac events during pregnancy in women with valvular heart disease (VHD). Methods: This retrospective cohort study was conducted at Fernandez Hospital, a tertiary care referral center in Hyderabad, India, utilizing clinical data from pregnancies managed between January 2011 and December 2023. The primary outcome was the development of composite adverse cardiac events. Discriminative ability was assessed using the area under the receiver operating characteristic curve (AUC), calibration was evaluated via calibration plots, and clinical utility was determined by decision curve analysis (DCA). Categorical variables were reported as frequencies and percentages and continuous variables were presented as means with standard deviations or medians with interquartile ranges. Individual risk assessment was conducted using both the CARPREG II and DEVI risk stratification models, while the ZAHARA score was calculated by aggregating weighted parameters according to established scoring criteria. Results: The study enrolled 176 women and analyzed 205 pregnancies with adverse cardiac events in 19 pregnancies (9.3%). The DEVI score demonstrated superior discrimination (AUC = 0.846, 95% CI: 0.765-0.927, P < 0.001), followed by mWHO (AUC = 0.826, 95% CI: 0.736–0.917, P < 0.001), CARPREG II (AUC = 0.762, 95% CI: 0.652–0.872, P < 0.001), and ZAHARA (AUC = 0.716, 95% CI: 0.628–0.803, P < 0.001). Calibration plots revealed an overestimation of risk at higher probabilities for DEVI and CARPREG II. DCA indicated net clinical benefit for both tools at 10–30% threshold probabilities. Conclusion: The DEVI score showed the highest discriminative performance, though its calibration and clinical utility were comparable to CARPREG II. These findings support its use for risk stratification in pregnant women with VHD, particularly in resource-limited settings where rheumatic VHD predominates.

Objective: To analyze fetal renal abnormality genetic features and the prenatal characteristics of the 17q12 microdeletion syndrome. Methods: This prospective cohort study examined prenatal ultrasound findings of renal abnormalities in pregnant women who underwent single nucleotide polymorphism (SNP) array or copy number variation sequencing (CNV-seq) testing on amniotic fluid or fetal tissue at Tianjin Central Obstetrics and Gynecology Hospital between January 2016 and August 2022. The study cohort comprised women with advanced maternal age, fetal ultrasound anomalies, high-risk non-invasive prenatal testing results, or suspected 17q12 microdeletion syndrome. Comprehensive clinical data, including maternal age, detailed ultrasound findings, and pregnancy outcomes, were systematically collected. SNP-array analysis was conducted using an Affymetrix CytoScan 750 K Array Chip to identify CNVs and loss of heterozygosity, while CNV-seq was performed on the Illumina HiSeq 2000 platform. Detected variants were classified according to the American College of Medical Genetics and Genomics guidelines. Statistical analyses were performed using SPSS version 27.0. Results: Abnormal renal development was identified in 141 patients, among whom 26 exhibited hyperechogenic kidneys (HCK). Of these, 12 cases were associated with 17q12 microdeletion syndrome, while the remaining 14 were linked to other chromosomal abnormalities. When excluding patients with HCK, those diagnosed with polycystic kidney disease demonstrated a higher prevalence of chromosomal abnormalities compared to those with multicystic dysplastic kidney and renal dysplasia. Although isolated conditions such as horseshoe kidney, hydronephrosis, ectopic kidney, and unilateral kidney typically presented with normal chromosomal findings, the incidence of chromosomal abnormalities increased when these conditions coexisted with other anomalies. A detailed analysis of the correlation between 17q12 microdeletion syndrome and HCK revealed that 12 out of the 14 patients diagnosed with 17q12 microdeletion syndrome exhibited HCK. Genetic testing confirmed the syndrome in seven patients, with five cases attributed to novel mutations and two cases resulting from inherited mutations. Conclusion: Fetal HCK was closely associated with the 17q12 microdeletion syndrome, and polycystic kidney disease showed a higher rate of chromosomal abnormalities. Chromosome test results were mostly normal in patients with other renal abnormalities, such as kidney dysplasia, horseshoe kidneys, hydronephrosis, kidney deficiency, and ectopic kidneys. Prenatal diagnosis is recommended, especially in cases of non-isolated fetal renal abnormalities. This study provides strong evidence supporting a link between fetal renal abnormalities and genetic syndromes.

Objective: To examine the impact of hypertensive disorders of pregnancy (HDP) on offspring metabolomics. Methods: We searched five databases: PubMed, Ovid Embase, MEDLINE, Web of Science, and China National Knowledge Infrastructure, and included studies that reported metabolomics among human offspring born to HDP-complicated pregnancies. Results: Database search yielded 4054 articles, and after full-text screening, ten observational studies met inclusion criteria. Half of the studies had a sample size of less than 100 and were all observational studies in preeclampsia (PE) and gestational hypertension.Neonates were the most focused group in all included studies. Offspring born to HDP-complicated pregnancies exhibited statistically significant variations in blood metabolomics compared to their counterparts, characterized by amino acids, lipids, carnitine, and others (e.g., 1α,25-(OH)2-D). Most studies reported a significant increase in differential metabolites of offspring born to HDP-complicated pregnancies. Four studies (n = 1109) measured lipids-related metabolites, and all consistently showed that offspring born to PE-complicated pregnancies had significantly higher concentrations than non-PE exposed offspring. Conclusion: The existing evidence suggests an intergenerational effect of HDP on offspring metabolomics. Long-term follow-up studies are needed to advance the health effects of related adverse health outcomes and inform the prevention of offspring’s health.

Fetal lingual lesion is a rare category of embryological anomalies, characterized by distinctive anatomical positioning, which may precipitate mechanical airway obstruction to unfavorable perinatal outcomes. There is a lack of comprehensive prenatal diagnostic strategies and effective treatments. This review has conducted a systematic literature overview of the clinical classification of fetal lingual anomalies, prenatal diagnosis, and perinatal treatment, including prenatal ultrasonography and magnetic resonance imaging, for optimizing perinatal care and obtaining an improved pregnancy outcome. Utilizing a multidisciplinary team framework, individualized peripartum management strategies are developed, contingent upon the presence or absence of airway compromise, with selective application of the ex-utero intrapartum treatment procedure as clinically warranted. By refining diagnostic accuracy and advancing therapeutic protocols, this review aims to elevate clinical management standards for congenital lingual lesions, thereby enhancing both short-term perinatal outcomes and long-term developmental prognoses.

Preterm birth (PTB), predominantly induced by intraamniotic inflammation, stands as the foremost contributor to neonatal morbidity and mortality globally. Fetal inflammatory response syndrome, stemming from the activation of the innate immune system, signifies the occurrence of funisitis or chorionic vasculitis. Maternal-fetal complications associated with infection-related PTB encompass maternal sepsis, fetal demise, neonatal sepsis, neonatal neurological impairment, and chronic lung disease. The inflammatory cascade is initiated when Toll-like receptors present on immune cells within the fetal membranes and the female reproductive tract encounter pathogen-associated molecular patterns derived from infectious agents. Subsequently, the nuclear factor kappa-light-chain-enhancer of activated B cells facilitates the transcription of cytokines. The accumulation of neutrophils compromises the tissue integrity of the fetal membranes, leading to membrane rupture via the secretion of matrix metalloproteinases. Elevated prostaglandin levels prompt uterine contractions and cervical remodeling, resulting in progressive cervical effacement and dilation, ultimately culminating in fetal delivery. The diagnosis of PTB should encompass three pivotal criteria: gestational age, uterine activity, and the consequences of that uterine activity. The diagnosis of chorioamnionitis is established through a combination of clinical manifestations, laboratory findings, identification of infectious microorganisms, and placental pathology. Fetal monitoring involves antenatal ultrasonography and non-stress testing. The management of infection-related PTB involves controlling and treating the infection, timing delivery to coincide with optimal fetal lung maturity, and optimizing outcomes for both the mother and neonate. Current preventive strategies for PTB primarily focus on inhibiting myometrial contractions that arise from the inflammatory cascade initiating PTB. An understanding of these pathways serves as the cornerstone for the development of therapeutic interventions aimed at preventing PTB.