科研成果

Abstract：Gestational diabetes mellitus (GDM) reflects metabolic dysregulation that becomes clinically apparent during pregnancy and shares key pathophysiological features with broader forms of diabetes. Gut microbiome-host metabolic interactions may contribute to this process, yet their role in early pregnancy remains incompletely understood. In this prospective nested case-control study within the Tongji-Huaxi-Shuangliu Birth Cohort, 784 pregnant women, including 222 who developed GDM, underwent first-trimester gut metagenomic and plasma lipidomic profiling. Cross-omics analyses were performed to identify microbiome-lipid associations and potential mediation patterns. Women who later developed GDM showed reduced gut microbial diversity and altered microbial profiles in early pregnancy. We identified 26 microbial species associated with GDM risk, with seven species, including Ruminococcus bicirculans (R. bicirculans), showing concordant associations in external type 2 diabetes populations. Microbial pathways related to fatty acid and lipid biosynthesis were enriched in women at higher risk. Plasma lipidomics revealed widespread alterations, particularly among glycosphingolipid-related metabolites. Integrated analyses suggested that lipidomic variation statistically accounted for part of the microbiome-GDM association. A class-level dihexosylceramide feature, DHC 24:1, consistent with lactosylceramide-related metabolites, emerged as a potential mediator and was prioritized for exploratory follow-up. Experimental analyses provided functional support for a microbiome-lipid-host interaction axis. R. bicirculans promoted lactosylceramide 24:1 production in vitro, bacterial colonization and metabolite administration improved insulin tolerance in vivo, and lactosylceramide 24:1 modulated insulin-stimulated AKT signaling dynamics in hepatocytes. These findings identify a gut microbiome-lipid axis associated with metabolic dysregulation in pregnancy and suggest a potential mechanism linking microbial metabolism to host insulin signaling.

Abstract：

Background: Hypertensive disorders of pregnancy (HDP) are leading causes of maternal and fetal morbidity and mortality. Although lower grip strength has been linked to higher cardiovascular risk in the general population, evidence on its relationship with HDP remains limited. We aimed to prospectively investigate this association in a large cohort of pregnant women.

Methods: Between March 2017 and January 2020, 6802 pregnant women (mean age ± standard deviation: 26.6 ± 3.7 years) enrolled in the Tongji-Huaxi-Shuangliu Birth Cohort were included in this analysis. Grip strength was measured in early pregnancy (mean gestational week ± standard deviation: 10.3 ± 2.0 weeks) and assessed in three ways: absolute grip strength (AGS) and two relative indices (AGS normalized to body mass index or body weight). Logistic regression models were used to assess the associations between grip strength and the risk of HDP (gestational hypertension or preeclampsia). Multiple blood biomarkers (blood lipids, leptin, adiponectin, C-reactive protein, C-peptide, glycated hemoglobin, and homeostatic model assessment of insulin resistance) were measured among 638 women at enrollment.

Results: A total of 180 women developed HDP during pregnancy. The adjusted odds ratios (95% confidence intervals) of HDP across increasing quartiles of AGS in early pregnancy were 1.00 (reference), 0.93 (0.63-1.35), 0.67 (0.44-1.00), and 0.35 (0.21-0.56). Odds ratios across quartiles of two relative grip strength (RGS) indices showed similar patterns. Restricted cubic spline analyses indicated a nonlinear association between AGS and HDP risk ( P for nonlinearity = 0.014). The risk plateaued at lower AGS levels but showed a linear inverse association above a threshold of 18.1 kg. In contrast, the two relative measures showed linear associations with HDP risk ( P for nonlinearity ≥0.164). Additionally, higher RGS was generally correlated with favorable metabolic profiles (e.g., lower levels of low-density lipoprotein cholesterol, triglycerides, and C-reactive protein).

Conclusion: Grip strength in early pregnancy was inversely associated with the risk of HDP, and RGS may serve as a simple and useful measure for risk stratification.

Abstract：

Introduction
The regimen of rituximab we not determined based on evidence from pharmacokinetics. However, rituximab exhibited significant pharmacokinetic variability among different clinical populations, which might be a key factor influencing individual exposure and response to this monoclonal antibody. This systematic review aimed to analyze the traditional and population pharmacokinetics of rituximab and to investigate covariates influencing its pharmacokinetics.
Methods
A systematic search was conducted in three English databases (Medline, Embase, Cochrane Central Register of Controlled Trials) and two Chinese database (China National Knowledge Infrastructure and Wanfang Data). Traditional and population pharmacokinetics of rituximab conducted in humans were included. Study designs, population characteristics, pharmacokinetic parameters, and covariates were extracted. The ClinPK’s checklist was used to assess the reporting quality of the included studies. The PROSPERO registered ID was CRD420251085784.
Results
The systematic research yield 25 traditional pharmacokinetics studies and 26 population pharmacokinetics studies. The included studies mainly investigated the pharmacokinetics of rituximab in patients with non-Hodgkin’s lymphoma, rheumatoid arthritis, kidney disease and anti-neutrophil cytoplasmic antibody-associated vasculitis. Significant variability in pharmacokinetic parameters existed among different clinical populations as well as among different subjects encountering similar clinical conditions. Most (23, 88.5%) population pharmacokinetics studies used a two-compartment model to describe rituximab pharmacokinetics. However, the elimination kinetics were inconsistent including the first-order elimination, time-varying elimination and target-mediated drug disposition. Body size descriptors such as body surface area, body mass index and body weight were the most frequently observed significant covariates, which appeared in 17 studies. Other significant covariates included gender, basal CD19+/20+ count, tumor stage, baseline total metabolic tumor volume, anti-drug antibodies, disease progression, urinary protein to creatinine ratios and the number of rituximab treatment courses. In addition, the pharmacokinetic parameters of rituximab biosimilars were proved to be non-inferior to that of the originators. Compared with intravenous administration, subcutaneous administration with a specific dose of 1600 mg or 1400 mg could achieve non-inferior Ctrough in chronic lymphocytic leukemia and diffuse large B-cell lymphoma respectively.
Conclusion
This systematic review presented a comprehensive overview of rituximab’s pharmacokinetics across various clinical populations. It highlighted the complexity and variability of rituximab’s pharmacokinetics. Future research should place emphasis on the model informed precision dosing of rituximab based on pharmacokinetics and various influencing factors in clinical practice.

Abstract：Isolated congenital heart block (iCHB) is defined as atrioventricular block without structural cardiac defects, characterized by irreversible fibrosis of the cardiac conduction system. Maternal autoantibodies may elicit systemic exaggerated immune responses involving type I interferon (IFN) signalling cascade, yet peripheral circulating immunity in CHB pathogenesis remains poorly understood. To investigate this, we performed single-cell RNA sequencing (scRNA-seq), followed by differential expression gene (DEG) analysis, SCENIC analysis, pseudotime analysis and cell communication analysis, to characterize systemic immune alterations in foetuses with CHB treated with dexamethasone and validated key findings by real-time quantitative PCR (qPCR) and flow cytometry. Compared with controls, CHB foetuses exhibited a markedly activated inflammatory response involving both IFN and NF-κB pathways. Although monocytes showed significant changes in cellular proportions, upregulated DEGs and interferon-stimulated genes, prioritized cellular responses and enhanced intercellular interactions. Notably, THBS1+CD14+ monocytes had a pro-inflammatory phenotype with upregulated NLRP3 inflammasome-related genes and maturation toward a pro-inflammatory state, and Thbs1 conditional knockout mice showed reduced IL-1β levels in BMDMs. Additionally, dexamethasone-treated monocytes had downregulated SOD2 (anti-apoptotic) levels compared to controls, confirmed by qPCR, and flow cytometry verified that dexamethasone promoted monocyte apoptosis. In conclusion, the peripheral immune system in CHB is characterized by innate immune activation driven mainly by monocytes, along with systemic inflammation including IFN signalling. THBS1+/CD14+ monocytes represent a distinct proinflammatory phenotype potentially linked to NLRP3-mediated inflammatory responses.

Abstract：

Aim: We explored whether adherence to a combined healthy lifestyle was associated with the long-term risk of type 2 diabetes mellitus (T2DM) among women with prior gestational diabetes mellitus (GDM) or hypertensive disorders of pregnancy (HDP) and whether genetic susceptibility modified this association.
Methods: A total of 3,109 women aged 40-69 years with a history of GDM or HDP were included in the present study. All participants were selected from the UK Biobank. We constructed a combined lifestyle score based on six favorable lifestyle factors, including diet, smoking, alcohol consumption, physical activity, sleep, and body mass index. Scores ranged from 0 to 6, with higher scores reflecting a healthier lifestyle. We applied the Cox proportional hazards regression to evaluate the association between the combined lifestyle score and the risk of T2DM. We further examined the interplay between the polygenic risk score (PRS) and the combined lifestyle score regarding the development of T2DM.
Results: Compared with those scoring 0 points, participants with combined lifestyle scores of 2, 3, and ≥ 4 points had significantly lower risks of T2DM, with hazard ratios (95% confidence intervals) of 0.54 (0.32, 0.93), 0.37 (0.22, 0.64), and 0.29 (0.16, 0.53), respectively. A significant dose-response relationship was observed (P for trend < 0.001). However, there was no interaction between the PRS and combined lifestyle score for the risk of T2DM (P for interaction = 0.247).
Conclusions: For those with a history of GDM or HDP, a healthier combined lifestyle was associated with a dose-dependent reduction in T2DM risk. These inverse associations were consistent across strata of genetic susceptibility and other major participant characteristics.

Abstract：

Background: Reducing under-5 mortality remains a global health priority. Large language models (LLMs) are increasingly used by the public to access medical information. However, current evidence evaluating LLMs’ performance in public-facing child health communication is scarce.Methods: We selected the top five search terms related to each of the five leading causes of under-5 mortality (prematurity, pneumonia, birth asphyxia, malaria, and diarrhoea) using Google Trends, generating 25 representative public queries. Responses were collected from four LLMs (ChatGPT-4.0, Claude 3.5 Sonnet, Bing AI, and Gemini) and independently evaluated by four pediatricians. We used the DISCERN instrument for information reliability; 5-point Likert scales for accuracy, completeness, and comprehensibility; Flesch Reading Ease (FRE) and Flesch–Kincaid Grade Level (FKGL) indices for readability; and the Patient Education Materials Assessment Tool for Printable Materials (PEMAT-P) for understandability and actionability. Differences among models were evaluated with Kruskal–Wallis and ANOVA tests, with statistical significance set at p < 0.05.Results: We found significant performance variations among the four models across most evaluation metrics. Bing AI achieved the highest total DISCERN score (median 42) and the highest reliability subscore (Section A median 28). Claude consistently underperformed across multiple domains. Notably, readability was poor for all models, with high language complexity (mean FKGL score 12.4). Critically, actionability scores were near zero for all models on the PEMAT-P scale, reflecting a universal lack of clear and practical behavioral guidance.Conclusion: While LLMs can generally provide accurate health information, limitations in readability and actionability restrict their practical application in public health communication. Future development should prioritize language simplification and clearer behavioral guidance to enhance their value in public-facing child health communication.

Abstract：Dysregulated B cells are central to many hematologic malignancies and autoimmune diseases, but current B cell-targeted therapies often fail to translate binding into effective signaling. Here, we present CD20 EryPatch, a living dynamic cellular patch that co-opts natural erythrocyte processes of morphological and biological changes, enabling a dual mechanism of micrometer-scale mechanotransduction and phagocytic "tag-and-clear" for enhanced B cell depletion. CD20 EryPatches are designed to adhere to B cells and anchor on CD20 receptors across extensive cell surface areas. Their progressive discocyte-to-echinocyte transition provides deformability-driven traction, enabling localized, large-scale CD20 cross-linking that amplifies downstream apoptosis in target B cells. Concomitant biomarker alteration on CD20 EryPatch converts it into an "eat me" tag attached to the B cell, facilitating further clearance by initiating erythrophagocytosis. This approach proves more effective than standard CD20 monoclonal antibodies in models of B cell disorders, including non-Hodgkin lymphoma, systemic lupus erythematosus, and rheumatoid arthritis.

Abstract：Maternal Hb and fetal growth change dynamically throughout pregnancy. We examined the associations of time-specific Hb levels and Hb trajectories with fetal biometrics and adverse birth outcomes. This prospective study included 6844 pregnant women (mean age 26·6 (SD 3·7) years) from the Tongji-Huaxi-Shuangliu Birth Cohort. Hb levels were measured at four periods: early (6–12 gestational weeks), middle (13–27), middle-late (28–32) and late pregnancy (33–37). Fetal biometrics were assessed by ultrasound from middle to late pregnancy. Birth outcomes were obtained from medical records, including small for gestational age (SGA), low birth weight (LBW) and preterm birth. Three Hb trajectories were identified: consistent decline (Trajectory 1), consistently low (Trajectory 2) and increase from middle-late pregnancy (Trajectory 3). Compared with Trajectory 1, Trajectory 3 was associated with lower estimated fetal weight (β, −0·54; 95 % CI −0·99, −0·09) and abdominal circumference (β, −0·21; 95 % CI −0·40, −0·01) in late pregnancy and higher umbilical artery resistance index across pregnancy (β, 0·65; 95 % CI 0·31, 1·00). Trajectory 3 was also associated with higher risk of LBW (OR, 1·57; 95 % CI 1·09, 2·26). In middle-late pregnancy, higher Hb (≥ 130 g/l) was associated with higher risks of LBW (OR, 2·26; 95 % CI 1·08, 4·25) and preterm birth (OR, 2·03; 95 % CI 1·12, 3·44) compared with the reference (110–129 g/l). Elevated maternal Hb from middle-late pregnancy onwards may be associated with lower fetal weight and increased risk of LBW. Dynamic monitoring of maternal Hb may facilitate targeted nutritional management in pregnant women.

Abstract：Mother-to-infant transmission of the bacteriome, virome, mycobiome, archaeome, and their mobile genetic elements has been recognised in nature as an important step for the infant to acquire and maintain a healthy early-life (from birth till age 3 years) microbiota. A comprehensive overview of other maternal multikingdom transmissions remains unavailable, except for that of the bacteriome. Associations between microorganisms and diseases throughout the human life span have been gradually discovered; however, whether these microorganisms are maternally derived and how they concomitantly interact with other microbial counterparts remain poorly understood. This Review first discusses the current understanding of maternal multikingdom transmissions, their contributions to the development of early-life microbiota, and the primary factors that influence the transmission processes. The clinical implications of the inherited microbiota on human health in early life have been emphasised upon next, along with highlighting of knowledge gaps that should be addressed in future research. Finally, interventions to restore typical vertical transmission or disturbed early-life microbiota have been discussed as potential therapeutic approaches.

Abstract：Pharmacy practice has profoundly shifted from product-centric dispensing to patient-centered, outcomes-oriented care, necessitating greater rigor, transparency, and efficiency in medication-related decisions. Concurrently, biomedical evidence is growing exponentially, while clinical care is becoming more complex due to multimorbidity, polypharmacy, and fragmented data. In this context, evidence-based pharmacy (EBP) has evolved from a toolkit for critical appraisal into a broader paradigm for generating, synthesizing, and translating evidence across diverse settings. This editorial synthesizes key developments in evidence-based pharmacy through narrative review of seminal works, authoritative guidelines, and representative recent studies, outlining EBP's trajectory from conceptual adoption to systemic integration, and subsequently examining its ongoing transformation in the era of intelligence, where real-world data and artificial intelligence (AI) are reshaping evidence production and clinical decision support.