Background and Hypothesis Schizophrenia manifests large heterogeneities in either symptoms or brain abnormalities. However, the neurobiological basis of symptomatic diversity remains poorly understood. We hypothesized that schizophrenia’s diverse symptoms arise from the interplay of structural and functional alterations across multiple brain regions, rather than isolated abnormalities in a single area. Study Design A total of 495 schizophrenia patients and 507 healthy controls from 8 sites were recruited. Five symptomatic dimensions of schizophrenia patients were derived from the Positive and Negative Syndrome Scale. Multivariate canonical correlation analysis was introduced to identify symptom-related multimodal magnetic resonance imaging composite indicators (MRICIs) derived from gray matter volume, functional connectivity strength, and white matter fractional anisotropy. The intergroup differences in MRICIs were compared, and the paired-wise correlations between symptom dimensions and MRICIs were resolved. Finally, K-means clustering was used to identify the underlying biological subtypes of schizophrenia based on MRICIs. Study Results Canonical correlation analysis identified 15 MRICIs in schizophrenia that were specifically contributed by the neuroimaging measures of multiple regions, respectively. These MRICIs can effectively characterize the complexity of symptoms, showing correlations within and across symptom dimensions, and were consistent across both first-episode and chronic patients. Additionally, some of these indicators could moderately differentiate schizophrenia patients from healthy controls. K-means clustering identified 2 schizophrenia subtypes with distinct MRICI profiles and symptom severity. Conclusions Symptom-guided multimodal and multivariate MRICIs could decode the symptom heterogeneity of schizophrenia patients and might be considered as potential biomarkers for schizophrenia.

Schizophrenia is increasingly recognized as a heterogeneous disorder, and immune dysregulation may contribute to its variability. Recent evidence suggests biologically distinct inflammatory subtypes within schizophrenia. This review aims to identify inflammatory subgroups defined by peripheral inflammatory markers and examine whether these subgroups exhibit distinct biological or neuroimaging characteristics. To do this, we conducted a systematic search across PubMed, Web of Science, PsycINFO, and Scopus. Studies were included if they investigated the subgrouping of patients with schizophrenia based on peripheral inflammatory markers, including protein levels, gene expression, or immune-related epigenetic features. Twenty studies met the inclusion criteria, nine of which incorporated MRI to further characterize inflammation-related subgroups. Most studies employed data-driven clustering approaches to classify patients into high- and low-inflammation subtypes. High-inflammation subtypes were frequently associated with more severe symptoms, cognitive impairments, and pronounced brain structural changes. Although MRI modalities and outcomes varied, the literature suggests a potential association between inflammatory subtypes and structural or functional brain alterations. These findings emphasize the immunological heterogeneity of schizophrenia and support the potential of immunological stratification to uncover biologically meaningful subtypes, warranting further research into the underlying mechanisms and clinical applications.

The development of green hydrogen energy is crucial for achieving a low-carbon energy transition. Existing research has overlooked the practical demand for inter-regional hydrogen energy scheduling and the potential for future cost reductions in renewable energy-based hydrogen production. To address these gaps, this study establishes an optimization model for hydrogen energy distribution across seven regions in China, incorporating electricity prices, technological advancements, and hydrogen industry development trends. The results indicate a significant reduction in China's hydrogen production costs. By 2060, the average production cost will decrease to 8.94 CNY/kg. The share of hydrogen production in renewable energy will rise to 60 %-100 % by 2060, with PEM-based production accounting for 24 %-60 %. The carbon emission reduction potential of hydrogen energy production can reach 1040.5 Mt-1734.2 Mt by 2060. The Southwest region will become the primary exporter of hydrogen, contributing 36.9 % of the inter-regional hydrogen transmission. The South will be the largest importer, with hydrogen imports reaching 20.46 Mt by 2060. This study offers strategies to reduce renewable hydrogen costs, optimize production structures, and enhance transmission through technological innovation and market mechanisms, promoting efficient energy use and an integrated hydrogen network.

OBJECTIVE:Female patients with obsessive-compulsive disorder (OCD) exhibit more severe psychopathological symptoms, yet their underlying neural correlates remain unclear. This study aimed to determine OCD-specific sex differences in brain structure and examine whether these differences are associated with the greater psychopathological burden observed in female patients. METHODS:Structural MRI data and symptom severity assessments were obtained from 147 unmedicated OCD patients (69 females) and 98 demographically matched healthy controls (HC; 46 females). RESULTS:Female patients with OCD showed significantly higher levels of OCD symptom severity, depression and anxiety symptoms than male patients. A significant interaction effect between group and sex on cortical complexity in the right paracentral lobule was identified, indicating that sex differences in this brain region differed significantly between OCD and HC groups. More specifically, female patients with OCD showed lower cortical complexity in the right paracentral lobule than male patients, whereas in the HC group, females exhibited higher cortical complexity than males. In the OCD group, lower cortical complexity was related to greater depression and anxiety symptoms and showed an indirect serial association with OCD symptom severity via anxiety. CONCLUSIONS:This study identified an OCD-specific brain morphometric basis of sex differences and suggested a potential pathway through which morphometric features in this region may be associated with greater OCD symptom severity in females via anxiety.

Childhood trauma serves as a significant environmental risk factor for the onset of schizophrenia, and through complex biological programming mechanisms, it increases the susceptibility of individuals to neurodevelopmental abnormalities. Anhedonia, as one of the core negative symptoms of schizophrenia, is characterized by a persistent decline in the ability to respond to pleasurable stimuli, severely affecting the social functions and long-term prognosis of patients. Recent studies have revealed that the abnormal activation of immune-inflammatory pathways may serve as a crucial intermediary link connecting childhood trauma exposure with the pathophysiological process of anhedonia in schizophrenia. Childhood trauma can lead to a systemic low-grade chronic inflammatory state by continuously activating stress- and metabolism-related physiological pathways, which in turn causes a series of immune disorders, such as elevated pro-inflammatory factors, suppressed anti-inflammatory functions, and abnormal activation of neuroimmune cells. These changes may further mediate the occurrence and development of anhedonia by affecting neural functions and circuits. This review summarizes and analyzes current research progress, systematically elaborates the impact of childhood trauma on the immune system and the potential mechanisms of anhedonia in schizophrenia, and focuses on analyzing the correlation between the two and the mediating role of immune-inflammatory factors.

OBJECTIVE:Facial fractures can be disabling injuries, leading to long-term functional, aesthetic, and psychological impairments. Comprehensive assessment of their disease burden in China is essential for informed health policy and prevention strategies. METHODS:Data regarding facial fractures in China from 1990 to 2021 were extracted from the Global Burden of Disease study (GBD) 2021 database. Incidence, prevalence, and years lived with disability (YLDs) were estimated using DisMod-MR 2.1, a Bayesian meta-regression modeling tool. Estimates were presented as numbers and rates, with comparisons to global averages and socio-demographic index (SDI) quintiles, and stratified by sex, age, cause, and year. RESULTS:In 2021, China recorded 1.19 million new cases and 18,744.38 YLDs from facial fractures. Although age-standardized rates of incidence, prevalence, and YLDs in China remained below global and high-SDI quintile, a notable upward trend emerged after 2010. The age-standardized incidence rate was approximately twice as high in males as in females, with peaks among children under 5 years, young adults aged 20-24 years, and a steep increase after age 70. Falls, road injuries, mechanical forces, and interpersonal violence accounted for 90% of new facial fracture cases. Since 2010, a trend reversal has occurred as fall-related facial fractures have risen markedly, in contrast to the declining trend observed for the other three causes. CONCLUSION:These findings underscore the need for targeted interventions, including fall prevention as well as injury control strategies aimed at young males, to address the rising facial fracture burden in China.

BACKGROUND:The glymphatic system is essential for cerebral waste clearance. This study evaluated glymphatic function in major depressive disorder (MDD) and bipolar disorder (BD) by combining diffusion tensor imaging along the perivascular space (DTI-ALPS) and global blood‑oxygen-level-dependent (gBOLD)-cerebrospinal fluid (CSF) coupling, exploring associations with affective, sleep, and cognitive symptoms. METHODS:We recruited 52 MDD patients, 31 BD patients, and 52 healthy controls (HCs) for multimodal magnetic resonance imaging (MRI). Glymphatic function was assessed via DTI-ALPS and gBOLD-CSF coupling. Standardized scales evaluated depression, anxiety, sleep disturbances, cognition, and anhedonia. Inter-group comparisons, correlation, regression, mediation, and receiver operating characteristic (ROC) curve analysis were performed. RESULTS:MDD and BD patients exhibited significantly reduced DTI-ALPS indices and gBOLD-CSF coupling compared to HCs, with no significant differences between patient groups. Exploratory analyses indicated these indirect imaging markers were intercorrelated weakly but significantly. Additionally, modality-specific alterations correlated with cognitive decline and increased anhedonia in MDD, and poorer sleep in BD. ROC analysis showed the joint imaging model provided modest diagnostic performance for distinguishing patients from HCs, which improved when integrated with clinical variables. Furthermore, mediation analysis suggested gBOLD-CSF coupling statistically mediated the association between disease status and affective symptoms. CONCLUSIONS:Glymphatic impairment is a shared feature of MDD and BD. DTI-ALPS and gBOLD-CSF coupling serve as complementary, indirect biomarkers linked to core clinical features. While causal relationships remain to be elucidated, targeting glymphatic function may offer a novel therapeutic avenue for mood disorders.

Although copy number variants (CNVs) represent well-established genetic contributors to schizophrenia (SCZ), their role in bipolar disorder (BD), especially within non-European ancestries, has been inadequately explored. We evaluated the genome-wide load of rare CNVs, encompassing deletions and duplications, in a Han Chinese sample of 3915 BD cases and 7820 ethnically matched controls. We observed a marked overrepresentation of rare deletions in BD patients relative to controls, with affected genes showing enrichment in neural signaling and dosage-dependent networks, indicating that haploinsufficiency in neurodevelopmental loci could underlie a central etiological pathway in BD. Among the 12 previously reported CNV loci from European cohorts, only deletions at 3q29 and 15q11.2 exhibited robust associations with BD susceptibility in Han Chinese individuals. Through genome-wide, gene-centric CNV association testing, we uncovered novel BD-linked loci, including deletions spanning GLIS2 and PAM16 at 16p13.3, GRID2IP at 7p22.1, and CFLAR at 2q33.1, alongside a duplication affecting ZNF878 and ZNF844 at 19p13.2. These disrupted genes are chiefly implicated in neuronal maturation, synaptic modulation, and mitochondrial dynamics. This work delivers the most thorough delineation of BD-associated CNVs in Han Chinese to date, underscoring the imperative for ancestry-inclusive research to comprehensively unravel psychiatric genomics and unveiling fresh mechanistic perspectives on BD etiology.

Oocyte activation is essential for successful fertilization and subsequent embryonic development. However, only a few disease-causing genes have been associated with sperm-derived oocyte activation failure, and the underlying molecular mechanisms and therapeutic approaches remain largely unknown. Here, we identified pathogenic mutations in HNRNPR from three infertile patients whose partners repeatedly failed to achieve transferable embryos despite undergoing both in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Remarkably, artificial oocyte activation (AOA, Srcl₂) combined with ICSI successfully restored fertilization. Whole-exome sequencing revealed HNRNPR mutations shared among affected families. To establish causality, we generated a knock-in mouse model, in which males exhibited phenotypes consistent with those observed in patients. Mechanistically, ICSI with sperm from Hnrnpr -mutated mice was unable to induce normal calcium oscillations in oocytes, while spermatozoa from both humans and mice exhibited reduced expression and mislocalization of phospholipase C zeta (PLCζ). Further analyses demonstrated that hnRNPR regulates Plcz1 splicing in an m6A-dependent manner. Beyond Srcl₂ treatment, we also developed NusA-PLCζ to effectively restore oocyte activation. Collectively, these findings reveal a previously unrecognized molecular mechanism by which HNRNPR mutations cause sperm-borne oocyte activation failure and male infertility, while highlighting targeted therapeutic strategies to restore fertilization.

Auditory verbal hallucinations (AVHs), the experience of hearing voices in the absence of corresponding external stimuli, are widely attributed to failures of self-monitoring. However, theoretical models and empirical investigations have primarily localized the underlying dysfunction to abnormalities within auditory cortices. Recent studies have revealed that the motor system exerts predictive regulation over auditory processing, suggesting that AVHs are not merely an abnormal auditory processing but also involve distinct, functionally dissociable impairments in motor-to-sensory transformation. How these impairments dynamically manifest in motor-to-sensory neural circuits remains unclear. This review synthesizes recent findings on the functional interactions between motor and sensory systems and proposes a hierarchical neurobiological framework for predictive coding in AVHs across two dimensions: temporal precision and spatial circuit architecture. In the temporal dimension, mismatches between motor-based predictions and sensory feedback disrupt the precision of predictive coding and Bayesian inference, giving rise to three forms of predictive dysfunction: excessively weak predictive signals, excessively strong predictive signals, and impaired predictive updating. In the spatial dimension, we characterize the spatiotemporal disintegration of the frontal-temporal-thalamic circuit underlying AVHs, focusing on both circuit-level disruption and hierarchical computational misalignment between predictive and perceptual signals. By explicitly linking the temporal precision of predictive coding to the spatial architecture of sensorimotor circuits, this study provides a unified mechanistic framework that bridges cognitive, computational, neurobiological, and clinical perspectives on AVHs.

Interleukin-17 (IL-17) is a pleiotropic cytokine produced mainly by peripheral T helper 17 cells. Yet, the brain functions of IL-17 derived from central nervous cells remain poorly understood. Here, we find an aberrant IL-17A signaling in the cerebellum of Fmr1-KO mice, a well-established genetic model for autism spectrum disorder (ASD). Cerebellar IL-17A, derived exclusively from microglia, is essential for the regulation of social behaviors by maintaining neuronal excitability and selectively suppressing inhibitory neurotransmission of Purkinje cells (PCs) in the cerebellar Crus I, a brain region critically involved in social cognition. Specific downregulation of IL-17 receptor-mediated signaling in cerebellar PCs recapitulates ASD-like social deficits and repetitive behaviors. Notably, both direct administration of IL-17A and induction of IL-17A release from cerebellar microglia by poly(I:C) effectively restore PC excitability and ameliorate ASD-like symptoms. The findings uncover an indispensable role of microglia-derived IL-17A for cerebellar social processing and suggest potential therapeutic strategies targeting IL-17A signaling for ASD.

Background and Hypothesis Identifying generalizable brain imaging markers from large multi-center datasets remains challenging due to varying statistical aggregation approaches and p-hacking with increasing big data. We hypothesized that effect size (ES) inference surpasses P-value-based inference in reliably identifying core brain damage of schizophrenia, regardless of whether Mega- or Meta-analyses are used. Study Design We examined voxel-wise inter-group differences in gray matter volume (GMV) based on individual data from 976 schizophrenia patients and 801 healthy controls across 16 datasets, along with published coordinates data from 103 studies involving 5151 patients and 5438 controls, using Mega-analysis (Mega), Image-Based Meta-analysis (IBMA), and Coordinate-Based Meta-analysis (CBMA) under P-value and ES inference frameworks, respectively. We then compared the performances of different statistical aggregation (Mega, IBMA, and CBMA) and statistical inference (P-value and ES) strategies in revealing brain abnormalities in schizophrenia. Study Results P-value Mega identified significant GMV abnormalities in nearly all gray matter voxels (94.85%) with high sensitivity to sample size; in contrast, ES Mega detected core abnormalities in only 24.63% of voxels that had large ES and manifested higher resistance to sample size. ES IBMA and CBMA also demonstrated superior detection performance and were less affected by sample size than P-value ones. Finally, IBMA exhibited comparable performance with the Mega-analysis and superior performance than all types of CBMAs. Conclusions These results underscore the advantages of using ES inference in multi-center statistical aggregation and highlight the potential of IBMA for enhanced detection of brain structural abnormalities in schizophrenia.

While heavy metals are established contributors to adverse health outcomes, evidence regarding trace element effects on maternal thyroid hormones and birth outcomes remains limited. This prospective study investigated effects of first-trimester exposure to seven trace elements, including vanadium(V), chromium (Cr), manganese (Mn), cobalt (Co), nickel (Ni), arsenic (As), and Se (selenium), on maternal third-trimester thyroid hormone levels and birth outcomes in Shanghai, China. Among 2069 enrolled pregnant women, 1351 with complete data were analyzed. Linear regression model, restricted cubic spline (RCS), and quantile g computation (QGC) were employed to assess element-outcome relationships. QGC analysis revealed that the increase in the element’s mixture was associated with the elevation of total triiodothyronine (TT3) (β = 0.026, 95

Background Gestational diabetes mellitus (GDM) is a metabolic disorder posing significant risks to maternal and infant health, with a lack of effective early screening markers. Therefore, identifying early screening biomarkers for GDM with higher sensitivity and specificity is urgently needed. Methods High-throughput sequencing was employed to screen for key circular RNAs (circRNAs), which were then evaluated using reverse transcription quantitative polymerase chain reaction. Logistic regression analysis was conducted to examine the relationship between clinical characteristics, circRNA expression, and adverse pregnancy outcomes. The diagnostic accuracy of circRNAs for early and mid-pregnancy GDM was assessed using receiver operating characteristic curves. Pearson correlation analysis was utilized to explore the relationship between circRNA levels and oral glucose tolerance test results. A predictive model for early GDM was established using logistic regression. Results Significant alterations in circRNA expression profiles were detected in GDM patients, with hsa_circ_0031560 and hsa_ circ_0000793 notably upregulated during the first and second trimesters. These circRNAs were associated with adverse pregnancy outcomes and effectively differentiated GDM patients, with second trimester cohorts achieving an area under the curve (AUC) of 0.836. In first trimester cohorts, these circRNAs identified potential GDM patients with AUCs of 0.832 and 0.765, respectively. The early GDM prediction model achieved an AUC of 0.904, validated in two independent cohorts. Conclusion Hsa_circ_0031560, hsa_circ_0000793, and the developed model serve as biomarkers for early prediction or mid-term diagnosis of GDM, offering clinical tools for early GDM screening.

BackgroundPatients with mental disorders often exhibit unique challenges in medication adherence, comprehension of drug information, and self-management abilities, underscoring the need for a specialized assessment tool to accurately reflect their medication literacy levels and support targeted clinical interventions.MethodsA stepwise, mixed-methods design was adopted to develop the Medication Literacy Assessment Scale. Preliminary items were generated through a comprehensive literature review and semi-structured interviews with 20 patients and 6 psychiatric professionals. Then, a two-round Delphi study was conducted to refine the scale based on expert consensus. Quantitative analysis of expert feedback guided the scale’s refinement, ensuring it effectively captures the unique aspects of medication literacy for patients with mental disorders in recovery.ResultsThe finalized Medication Literacy Assessment Scale for patients with mental disorders in recovery was developed, yielding 35 items across four dimensions: functional literacy (10 items), communicative literacy (6 items), critical literacy (11 items), and numeracy (8 items). Each dimension reflects essential aspects of medication literacy specific to this population, as identified through expert consensus.ConclusionThis study developed a preliminary, standardized tool for assessing medication literacy in patients with mental disorders during recovery, with the potential to identify individuals at risk of medication mismanagement and to enable targeted interventions and improved outcomes in China’s healthcare system. Although its psychometric properties have not yet been evaluated in this stage, future research will conduct empirical validation to establish its measurement reliability and validity.

Objective Cognitive dysfunction is a core symptom of depression and contributes significantly to functional and psychosocial impairment. However, pharmacotherapy has shown limited efficacy in alleviating these cognitive deficits. This study aimed to systematically evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) in improving cognitive impairments in patients with depression. Methods A literature search was conducted across PubMed, Embase, Web of Science, PsycINFO, and the Cochrane Library databases up to June 19, 2024. Studies were included if they met the following criteria: (1) participants were exclusively patients with unipolar depression, (2) both active rTMS and sham stimulation were administered in parallel groups, (3) sufficient data were available, and (4) the study design was a randomized controlled trial (RCT). Results A total of 15 studies met the inclusion criteria. The meta-analysis revealed no significant improvement in cognitive impairment with active rTMS compared to sham rTMS across multiple cognitive domains, including global cognitive function, attention, working memory, psychomotor speed, language, visuospatial ability, learning and memory, and executive function. Conclusion Current evidence suggests that rTMS does not demonstrate substantial efficacy in alleviating cognitive dysfunction in patients with depression. Future research should focus on elucidating the underlying mechanisms of rTMS efficacy and optimizing stimulation protocols, including the precise targeting of stimulation sites, as well as refining frequency, intensity, and duration parameters to better address cognitive impairment.

BACKGROUND:Women are particularly vulnerable to depression during pregnancy, which is one of the strongest risk factors for developing postpartum depression (PPD). Addressing antenatal depressive symptoms in these women is crucial for preventing PPD. However, little is known about the effectiveness of internet-based cognitive behavioral therapy (ICBT) in preventing PPD in this high-risk group. OBJECTIVE:This study aims to evaluate the short- and long-term effects of ICBT in preventing PPD among women with antenatal depressive symptoms. METHODS:Participants were screened for antenatal depressive symptoms using the Edinburgh Postnatal Depression Scale (EPDS) and randomly allocated (1:1) to either the ICBT group (receiving weekly online modules starting antenatally and continuing into early postpartum) or the control group (observed without treatment). Follow-up assessments were conducted up to 12 months postpartum, and data were analyzed using generalized estimating equations. The primary outcome was the prevalence of depressive symptoms at 6 weeks postpartum. A subgroup analysis based on the severity of antenatal depressive symptoms was also performed. The secondary outcomes included the long-term effects of ICBT on maternal depression, as well as its impact on anxiety, sleep quality, social support, parenting stress, co-parenting relationships, and infant development. RESULTS:Between August 2020 and September 2021, 300 pregnant individuals were recruited from 5 centers across China. No significant differences were observed in depressive symptoms at 6 weeks postpartum (P=.18) or at any longer-term follow-up time points (P=.18). However, a post hoc subgroup analysis showed that participants with antenatal EPDS scores of 10-12 in the ICBT group had a lower risk of developing depression during the first year postpartum (odds ratio 0.534, 95% CI 0.313-0.912; P=.02), but this was not observed for participants with more severe depression. Additionally, this subgroup demonstrated higher levels of co-parenting relationships (P=.02). CONCLUSIONS:Among individuals with antenatal depression, ICBT did not prevent the development of PPD. However, ICBT may be a preferable option for those with mild to moderate antenatal depressive symptoms. Future research is needed to explore modifications to ICBT to address more severe depressive symptoms. TRIAL REGISTRATION:Chinese Clinical Trial Registry ChiCTR2000033433; https://www.chictr.org.cn/showproj.html?proj=54482. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID):RR2-10.1186/s13063-022-06728-5.

Background:Crohn's disease (CD) involves chronic intestinal inflammation, frequently requiring surgical intervention. CD patients undergoing surgery often undergo increased psychological stress. One of the outcomes of persistent stress is post-traumatic stress (PTS), a mental health concern associated with immune dysregulation and disease progression. However, research on PTS in CD patients following surgery is limited. Objectives:This study aims to explore the incidence and associated factors of PTS in CD patients after surgery. Design:A retrospective cross-sectional study. Methods:This retrospective cross-sectional study investigated 124 patients with CD who underwent surgery between September 2015 and July 2023. Online questionnaires, including the PTSD checklist, 5th edition (PCL-5), Crohn's and Colitis Knowledge Score, and Short Generic Patient Experience Questionnaire, were employed. The potential risk factors for PTS were evaluated through univariate and multivariate analyses. Results:Among sampled individuals, 44 patients (35.5%) were classified into the PTS group. The patients in the PTS group had a significant lower monthly income (27.3% vs 8.8%, p = 0.006), higher Harvey-Bradshaw Index score (3.82 ± 3.25 vs 2.31 ± 2.50, p = 0.009), more occurrence of perianal lesions (36.4% vs 20%, p = 0.047), higher ostomy (36.4% vs 20%, p = 0.047), and laparotomy rates (31.8% vs 15%, p = 0.028). Through logistic regression analysis, we identified postoperative complications and a history of multiple surgeries as independent risk factors for PTS (p = 0.002 and p = 0.019, respectively). Conclusion:PTS is common in CD patients requiring bowel resection and multiple surgeries, as well as other postoperative related factors, can invoke psychological and mental stress. These findings provide insights for formulating medical service strategies that prioritize patient mental health.

BACKGROUND:Gestational diabetes mellitus (GDM) affects millions of females and their children. Effective dietary strategies for early prevention are controversial. OBJECTIVES:This study aims to investigate whether an individualized nutritional intervention reduced GDM incidence in high-risk females. METHODS:A randomized trial was conducted at 3 tertiary hospitals in Shanghai, China. We randomly assigned (1:1) pregnant females in the first trimester who were identified to be at high risk of GDM by a prediction model to either an individualized nutritional intervention or usual care. The intervention consisted of 3 dietary consultations by dietitians based on Chinese dietary guidelines before the oral glucose tolerance test (OGTT) at 24-28 wk of gestation. The control group received usual care. All participants provided 3-d food records at each follow-up. The primary outcome was GDM incidence using the International Association of Diabetes and Pregnancy Study Group criteria. Key secondary outcomes were dietary alterations, gestational weight gain (GWG), maternal metabolic profile, perinatal and pregnancy outcomes. Intention-to-treat analyses were conducted. RESULTS:A total of 519 females were enrolled, of whom 261 were assigned to the intervention and 258 to usual care. GDM was diagnosed in 85/245 (34.7%) females in the intervention group compared with 89/244 (36.5%) in the control group [adjusted relative risk 0.91 (95% confidence interval: 0.73, 1.15), P = 0.44]. More females in the intervention group had an appropriate GWG than the control group [1.38 (1.06, 1.79)] and lower levels of fasting and 2-h insulin during the OGTT (P < 0.001). We observed a reduction in the rate of small for gestational age in the intervention group compared with the control group [0.11 (0.01, 0.80)] and neonatal hypoglycemia [0.14 (0.04, 0.57)]. CONCLUSIONS:Among females at risk of GDM, an individualized nutritional intervention based on Chinese dietary guidelines provided before the OGTT did not prevent GDM but helped to manage GWG appropriately and improved pregnancy outcomes. This trial was registered on 27 October, 2019, with initial participant enrollment on 5 May, 2020 at ChiCTR as 1900026963 (https://www.chictr.org.cn/searchproj.html?regno=1900026963).