Functional prediction of the potential NGLY1 mutations associated with rare disease CDG.

Genetic diseases are currently diagnosed by functional mutations. However, only some mutations are associated with disease. It is necessary to establish a quick prediction model for clinical screening. Pathogenic mutations in NGLY1 cause a rare autosomal recessive disease known as congenital disorder of deglycosylation (NGLY1-CDDG). Although NGLY1-CDDG can be diagnosed through gene sequencing, clinical relevance of a detected mutation in NGLY1 needs to be further confirmed. In this study, taken NGLY1-CDDG as an example, a comprehensive and practical predictive model for pathogenic mutations on NGLY1 through an NGLY1/Glycopeptide complex model was constructed, the binding sites of NGLY1 and glycopeptides were simulated, and an in vitro enzymatic assay system was established to facilitate quick clinical decisions for NGLY1-CDDG patients. The docking model covers 42 % of reported NGLY1-CDDG missense mutations (5/12). All reported mutations were subjected to in vitro enzymatic assay in which 18 mutations were dysfunctional (18/30). In addition, a full spectrum of functional R328 mutations was assayed and 11 mutations were dysfunctional (11/19). In this study, a model of NGLY1 and glycopeptides was built for potential functional mutations in NGLY1. In addition, the effect of potential regulatory compounds, including N-acetyl-l-cysteine and dithiothreitol, on NGLY1 was examined. The established in vitro assay may serve as a standard protocol to facilitate rapid diagnosis of all mutations in NGLY1-CDDG. This method could also be applied as a comprehensive and practical predictive model for the other rare genetic diseases.

Identification and characterization of emGalaseE, a ß-1,4 galactosidase from Elizabethkingia meningoseptica, and its application on living cell surface.

The biological function of terminal galactose on glycoprotein is an open field of research. Although progress had being made on enzymes that can remove the terminal galactose on glycoproteins, there is a lack of report on galactosidases that can work directly on living cells. In this study, a unique beta 1,4 galactosidase was isolated from Elizabethkingia meningoseptica (Em). It exhibited favorable stability at various temperatures (4-37 °C) and pH (5-8) levels and can remove ß-1, 4 linked galactoses directly from glycoproteins. Using Alanine scanning, we found that two acidic residues (Glu-468, and Glu-531) in the predicted active pocket are critical for galactosidase activity. In addition, we also demonstrated that it could cleave galactose residues present on living cell surface. As this enzyme has a potential application for living cell glycan editing, we named it emGalaseE or glycan-editing galactosidase I (csgeGalaseI). In summary, our findings lay the groundwork for further investigation by presenting a simple and effective approach for the removal of galactose moieties from cell surface.

A Natural Compound Containing a Disaccharide Structure of Glucose and Rhamnose Identified as Potential N-Glycanase 1 (NGLY1) Inhibitors.

N-glycanase 1 (NGLY1) is an essential enzyme involved in the deglycosylation of misfolded glycoproteins through the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, which could hydrolyze N-glycan from N-glycoprotein or N-glycopeptide in the cytosol. Recent studies indicated that NGLY1 inhibition is a potential novel drug target for antiviral therapy. In this study, structure-based virtual analysis was applied to screen candidate NGLY1 inhibitors from 2960 natural compounds. Three natural compounds, Poliumoside, Soyasaponin Bb, and Saikosaponin B2 showed significantly inhibitory activity of NGLY1, isolated from traditional heat-clearing and detoxifying Chinese herbs. Furthermore, the core structural motif of the three NGLY1 inhibitors was a disaccharide structure with glucose and rhamnose, which might exert its action by binding to important active sites of NGLY1, such as Lys238 and Trp244. In traditional Chinese medicine, many compounds containing this disaccharide structure probably targeted NGLY1. This study unveiled the leading compound of NGLY1 inhibitors with its core structure, which could guide future drug development.

Characterization and Molecular Mechanism of Aminoglycoside-6-Adenyl Transferase Associated with Aminoglycoside Resistance from Elizabethkingia meningoseptica.

Purpose: Elizabethkingia meningoseptica (EM) is a multi-drug-resistant bacterium of global concern for its role in nosocomial infection and is generally resistant to aminoglycoside antibiotics. In the whole genome of an EM strain (FMS-007), an aminoglycoside-6-adenyl transferase gene (ant(6)FMS-007) was predicted. This study aimed to characterize the biochemical function of ANT(6)FMS-007 and analyze the relationship between genotype and phenotype of ant(6) in clinical EM isolates, so as to provide evidence for clinical precision drug use. This study could establish a method for the verification of known or unknown functionally resistant genes. Methods: A total of 42 EM clinical isolates were collected from clinical departments during 2015-2023. The phenotype of aminoglycoside antibiotics was analyzed by broth microdilution (BMD) and Kirby-Bauer (K-B) methods. The whole-length ant(6) from EM clinical isolates was analyzed by polymerase chain reaction (PCR) and sequencing. The biochemical function of predictive ANT(6)FMS-007 from the FMS-007 whole genome was identified by 3D plate experiment and mass spectrometry analysis. Candidate active sites were predicted by multi-species sequence alignment and molecular docking, and other important sites were identified in the comparison of ant(6) genotypes and phenotypes of EM clinical isolates. Drug susceptibility test was used to verify the function of these sites. Results: The predictive ANT(6)FMS-007 protein could inactivate STR by modifying STR with ATP to form STR-AMP. Four active sites (Asp-38, Asp-42, Lys-95, and Lys-213) of ANT(6)FMS-007 were identified. Thirty-one EM clinical isolates (74%) carried the ant(6) gene. Eight EM clinical isolates containing the ant(6) gene had MIC values (<=32µg/mL) lower by at least 16-fold than FMS-007 (512µg/mL) for STR, and N59H and K204Q were the common mutations in the ant(6) gene. Conclusion: This assay verified the biochemical function of the predictive gene ant(6)FMS-007 and could provide an alternative method to study resistant gene function in multi-drug-resistant bacteria. The inconsistency between genotype and phenotype of resistant genes indicated that the combination of resistance gene detection and functional analysis could better provide precision medicine for clinical use.

Identification and characterization of an α-1,3 mannosidase from Elizabethkingia meningoseptica and its potential attenuation impact on allergy associated with cross-reactive carbohydrate determinant.

Core α-1,3 mannose is structurally near the core xylose and core fucose on core pentasaccharide from plant and insect glycoproteins. Mannosidase is a useful tool for characterization the role of core α-1,3 mannose in the composition of glycan related epitope, especially for those epitopes in which core xylose and core fucose are involved. Through functional genomic analysis, we identified a glycoprotein α-1,3 mannosidase and named it MA3. We used MA3 to treat allergen horseradish peroxidase (HRP) and phospholipase A2 (PLA2) separately. The results showed that after MA3 removed α-1,3 mannose on HRP, the reactivity of HRP with anti-core xylose polyclonal antibody almost disappeared. And the reactivity of MA3-treated PLA2 with anti-core fucose polyclonal antibody decreased partially. In addition, when PLA2 was conducted enzyme digestion by MA3, the reactivity between PLA2 and allergic patients' sera diminished. These results demonstrated that α-1,3 mannose was an critical component of glycan related epitope.

[Vitamins and Immune System Health].

Keeping the immune system healthy forms an effective way to fight infections. Past experience has shown that, in addition to effective interventions including vaccination, drug therapy, and non-pharmaceutical intervention (NPI), dietary nutrition and mental health are also key factors in maintaining immune system health and combating emerging and sudden outbreaks of infections. As the main dietary nutrients, vitamins are active regulators of the immune response and exert a critical impact on the immunity of the human body. Vitamin deficiency causes increased levels of inflammation and decreased immunity, which usually starts in the oral tissues. Appropriate vitamin supplementation can help the body optimize immune function, enhance oral immunity, and reduce the negative impact of pathogen infection on the human body, which makes it a feasible, effective, and universally applicable anti-infection solution. This review focuses on the immunomodulatory effects of vitamin A, B, C, D, and E and proposes that an omics-based new systemic approach will lead to a breakthrough of the limitations in traditional single-factor single-pathway research and provide the direction for the basic and applied research of vitamin immune regulation and anti-infection in all aspects.

Single Cell Raman Spectroscopy Deuterium Isotope Probing for Rapid Antimicrobial Susceptibility Test of Elizabethkingia spp.

Nosocomial infection by multi-drug resistance Elizabethkingia spp. is an emerging concern with severe clinical consequences, particularly in immunocompromised individuals and infants. Efficient control of this infection requires quick and reliable methods to determine the appropriate drugs for treatment. In this study, a total of 31 Elizabethkingia spp., including two standard strains (ATCC 13253 and FMS-007) and 29 clinical isolates obtained from hospitals in China were subjected to single cell Raman spectroscopy analysis coupled with deuterium probing (single cell Raman-DIP). The results demonstrated that single cell Raman-DIP could determine antimicrobial susceptibility of Elizabethkingia spp. in 4 h, only one third of the time required by standard broth microdilution method. The method could be integrated into current clinical protocol for sepsis and halve the report time. The study also confirmed that minocycline and levofloxacin are the first-line antimicrobials for Elizabethkingia spp. infection.

Deep Learning-Based Classification for Melanoma Detection Using XceptionNet.

Skin cancer is one of the most common types of cancer in the world, accounting for at least 40% of all cancers. Melanoma is considered as the 19th most commonly occurring cancer among the other cancers in the human society, such that about 300,000 new cases were found in 2018. While cancer diagnosis is based on interventional methods such as surgery, radiotherapy, and chemotherapy, studies show that the use of new computer technologies such as image processing mechanisms in processes related to early diagnosis of this cancer can help the physicians heal this cancer. This paper proposes an automatic method for diagnosis of skin cancer from dermoscopy images. The proposed model is based on an improved XceptionNet, which utilized swish activation function and depthwise separable convolutions. This system shows an improvement in the classification accuracy of the network compared to the original Xception and other dome architectures. Simulations of the proposed method are compared with some other related skin cancer diagnosis state-of-the-art solutions, and the results show that the suggested method achieves higher accuracy compared to the other comparative methods.

Clinicopathological study of the polypoidal lesions of polypoidal choroidal vasculopathy.

PURPOSE: To investigate the pathogenic features of the polypoidal lesions from the specimens of polypoidal choroidal vasculopathy extracted from human subjects. METHODS: Seven specimens of polypoidal lesions extracted from five eyes of six patients (mean age, 60.16 ± 10.41 years) of polypoidal choroidal vasculopathy were examined. The polypoidal lesions were obtained by surgical excision. Thereafter, a histopathological analysis of the specimens was performed. RESULTS: The polypoidal lesions were oval nodules located underneath the retinal pigment epithelium. A pathological study of the lesions revealed that Bruch's membrane schisis was observed in all specimens and they were all located in the Bruch's membrane. The Bruch's membrane schisis and serosanguineous materials constituted the main structure of the lesions in five of the seven specimens, with small vessels being observed in two specimens. One specimen was composed of two polypoidal lesions of different characteristics, and one specimen had a neovessel membrane complex with several polypoidal lesions. Inflammatory cells and blood vessels were observed in the polypoidal lesion of the specimen with neovessel membrane complex. CONCLUSION: Polypoidal lesions of polypoidal choroidal vasculopathy are abnormalities of the Bruch's membrane. The lesions are characterized by the Bruch's membrane schisis, which is filled with serosanguineous materials. The lesions are progressive and may contain inflammatory cells and blood vessels.

Dual targeted delivery of statins and nucleic acids by chitosan-based nanoparticles for enhanced antiatherosclerotic efficacy.

Cardiovascular disease caused by atherosclerosis is a leading cause of morbidity and mortality worldwide. Owing to the synergistic regulation of cholesterol metabolism and lesion inflammation, the simultaneous administration of statins and nucleic acids is expected to alleviate atherosclerosis. In this work, we prepared atorvastatin- and galactose-modified trimethyl chitosan nanoparticles (GTANPs) with dual targeting to hepatocytes and lesional macrophages for encapsulating Baf60a siRNA (siBaf60a) and anti-miR-33 pDNA (pAnti-miR-33), attaining the effective codelivery of statins and nucleic acids. We demonstrated that GTANPs/siBaf60a and GTANPs/pAnti-miR-33 had in vitro antiinflammatory and lipid regulating efficacy. In ApoE-knockout atherosclerotic mice, intravenously injected GTANPs/siBaf60a synergistically reduced the plasma cholesterol and atherosclerotic plaque area; more importantly, orally delivered GTANPs/pAnti-miR-33 synergistically increased the levels of plasma high-density lipoprotein cholesterol (HDL-C) and antiinflammatory cytokines, resulting in a satisfactory antiatherosclerotic outcome. Our results suggest that codelivery of statins and nucleic acids provides a promising strategy for the treatment of atherosclerosis.

A Method for Optimal Detection of Lung Cancer Based on Deep Learning Optimized by Marine Predators Algorithm.

Lung cancer is the uncontrolled growth of cells in the lung that are made up of two spongy organs located in the chest. These cells may penetrate outside the lungs in a process called metastasis and spread to tissues and organs in the body. In this paper, using image processing, deep learning, and metaheuristic, an optimal methodology is proposed for early detection of this cancer. Here, we design a new convolutional neural network for this purpose. Marine predators algorithm is also used for optimal arrangement and better network accuracy. The method finally applied to RIDER dataset, and the results are compared with some pretrained deep networks, including CNN ResNet-18, GoogLeNet, AlexNet, and VGG-19. Final results showed higher results of the proposed method toward the compared techniques. The results showed that the proposed MPA-based method with 93.4% accuracy, 98.4% sensitivity, and 97.1% specificity provides the highest efficiency with the least error (1.6) toward the other state of the art methods.

Evaluating the effectiveness of measures to control the novel coronavirus disease 2019 in Jilin Province, China.

BACKGROUND: Based on differences in populations and prevention and control measures, the spread of new coronary pneumonia in different countries and regions also differs. This study aimed to calculate the transmissibility of coronavirus disease 2019 (COVID-19), and to evaluate the effectiveness of measures to control the disease in Jilin Province, China. METHODS: The data of reported COVID-19 cases were collected, including imported and local cases from Jilin Province as of March 14, 2019. A Susceptible-Exposed-Infectious-Asymptomatic-Recovered/Removed (SEIAR) model was developed to fit the data, and the effective reproduction number (Reff) was calculated at different stages in the province. Finally, the effectiveness of the measures was assessed. RESULTS: A total of 97 COVID-19 infections were reported in Jilin Province, among which 45 were imported infections (including one asymptomatic infection) and 52 were local infections (including three asymptomatic infections). The model fit the reported data well (R2 = 0.593, P < 0.001). The Reff of COVID-19 before and after February 1, 2020 was 1.64 and 0.05, respectively. Without the intervention taken on February 1, 2020, the predicted cases would have reached a peak of 177,011 on October 22, 2020 (284 days from the first case). The projected number of cases until the end of the outbreak (on October 9, 2021) would have been 17,129,367, with a total attack rate of 63.66%. Based on the comparison between the predicted incidence of the model and the actual incidence, the comprehensive intervention measures implemented in Jilin Province on February 1 reduced the incidence of cases by 99.99%. Therefore, according to the current measures and implementation efforts, Jilin Province can achieve good control of the virus's spread. CONCLUSIONS: COVID-19 has a moderate transmissibility in Jilin Province, China. The interventions implemented in the province had proven effective; increasing social distancing and a rapid response by the prevention and control system will help control the spread of the disease.

Predictors of short-term outcomes related to central subfield foveal thickness after intravitreal bevacizumab for macular edema due to central retinal vein occlusion.

AIM: To investigate the predictive factors for short-term effects of intravitreal bevacizumab injections on central subfield foveal thickness (CSFT) in patients with macular edema (ME) secondary to central retinal vein occlusion (CRVO). METHODS: This was a retrospective study in 60 eyes treated with intravitreal bevacizumab injections for ME due to CRVO. Follow-up was three months. The Early Treatment Diabetic Retinopathy Study (ETDRS) score and CSFT measured by spectral-domain optical coherence tomography (SD-OCT) were used to observe the changes in best-corrected visual acuity (BCVA). Baseline BCVA, CSFT, age, CRVO duration and the presence of cystoid macular edema (CME) or subretinal fluid (SRF) were analyzed as potential predictive factors of the effects of intravitreal bevacizumab injections. RESULTS: BCVA improved from 0.9 logMAR at baseline to 0.6 logMAR at 3mo, which was associated with a significant reduction in CSFT from 721 µm to 392 µm 3mo after injection. About 50% of CME cases and more than 90% of SRF cases responded to treatment with a complete resolution at 3mo. Age (P=0.036) and low baseline CSFT (P=0.037) were associated with a good 3-month prognosis. Patients >60 years old achieved better CME resolution (P=0.031) and lower CSFT at 3mo (305 µm vs 474 µm, P=0.003). CONCLUSION: Intravitreal bevacizumab significantly improved visual acuity and CSFT in patients with CRVO after 3mo. Older age and lower baseline CSFT were good predictors of short-term CSFT outcomes. The retinal thickness response to bevacizumab might depend on the resolution of CME rather than SRF.

Synthesis of copper micro-rods with layered nano-structure by thermal decomposition of the coordination complex Cu(BTA)2.

Porous metallic copper was successfully prepared by a simple thermal decomposition strategy. A coordination compound of Cu(BTA)2 with the morphology of micro-rod crystal was synthesized as the precursor. The precursor to copper transformation was performed and annealed at 600°C with the shape preserved. The copper micro-rods are assembled from unique thin lamellar layers, each with the thickness of approximately 200 nm and nano-pores of approximately 20 to 100 nm. This morphology is highly related to the crystal structure of the precursor. The mechanism of the morphology formation is proposed, which would be able to offer a guideline toward porous metals with controllable macro/micro/nano-structures by the precursor crystal growth and design.

Changes following supplementation with lutein and zeaxanthin in retinal function in eyes with early age-related macular degeneration: a randomised, double-blind, placebo-controlled trial.

AIMS: To investigate functional and macular pigment (MP) changes in patients with early age-related macular degeneration (AMD) after multiple supplementation with lutein and zeaxanthin. METHODS: 112 patients with early AMD were randomly (1:1:1:1) assigned to receive 10 mg lutein, 20 mg lutein, lutein (10 mg)+zeaxanthin (10 mg), or placebo daily for 2 years. MP optical density (MPOD) was recorded at baseline, 48 weeks and 2 years. Retinal sensitivities were measured by multifocal electroretinogram for peak-to-trough amplitude (N1P1) at baseline and at 48 weeks, and in terms of microperimeter-determined mean retinal sensitivity (MRS) at 48 weeks and 2 years. RESULTS: Supplementation with lutein and zeaxanthin augmented MPOD significantly in active treatment groups (all p<0.05). N1P1 response densities showed significant increases in ring 1 and ring 2 after 48 weeks of supplementation, while no significant changes were seen in rings 3-6. Significant increases in MRS were detected after supplementation with either 10 or 20 mg lutein, whereas no such increases were seen in the placebo arm. CONCLUSIONS: Supplementation with lutein and/or zeaxanthin increases MPOD, and supplemental lutein enhances retinal sensitivity, in patients with early AMD. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT10528605.

Human influenza A(H7N9) virus infection associated with poultry farm, Northeastern China.

We report on a case of human infection with influenza A(H7N9) virus in Jilin Province in northeastern China. This case was associated with a poultry farm rather than a live bird market, which may point to a new focus for public health surveillance and interventions in this evolving outbreak.

Epidemiology of twin births in southeast China: 1993-2005.

Recently, there has been a significant increase in the rate of multiple births in most developed countries. However, few population-based studies have been conducted in China regarding the epidemiology of twin births in recent years. We performed a descriptive analysis of twin births from 1993 to 2005 using data from a population-based perinatal care program in southeast China. The twin birth rate in southeast China was 0.65%, and the twin birth rates from 1993 to 2005 fluctuated between 0.60% and 0.70%. During the three periods of 1993-1996, 1997-2000, and 2001-2005, the twin birth rate increased from 0.57% to 0.71% in urban areas (p = .005) and from 0.59% to 0.68% in mothers who had an education level of high school or higher (p = .046). After 2000, the twin birth rate of primiparae 30 years of age and older significantly increased from 0.72% to greater than 1.20%. We concluded that the twin birth rates in southeast China from 1993 to 2005 stayed constant in the overall population but increased in certain subgroups of women, presumably due to increased use of fertility treatment and the development of assisted reproductive technology.

Effect of lutein and zeaxanthin on macular pigment and visual function in patients with early age-related macular degeneration.

PURPOSE: To determine whether supplementation with lutein and zeaxanthin improves macular pigment and visual function in patients with early age-related macular degeneration (AMD). DESIGN: Randomized, double-masked, placebo-controlled trial. PARTICIPANTS: Participants with probable AMD who were 50 to 79 years of age were screened for study eligibility from the local communities. One hundred eight subjects with early AMD were recruited. INTERVENTION: Early AMD patients were assigned randomly to receive 10 mg/day lutein (n = 27), 20 mg/day lutein (n = 27), 10 mg/day lutein plus 10 mg/day zeaxanthin (n = 27); or placebo (n = 27) for 48 weeks. Macular pigment optical density (MPOD) and visual function variables were assessed at baseline, 24 weeks, and 48 weeks. MAIN OUTCOME MEASURES: The primary outcome was MPOD. Secondary outcomes were visual function variables including best-corrected visual acuity (BCVA), contrast sensitivity (CS), photorecovery time, and Amsler grid testing results. RESULTS: Macular pigment optical density increased significantly by a mean ± standard error of 0.076 ± 0.022 density unit in the 20-mg lutein group and 0.058 ± 0.027 density unit in the lutein and zeaxanthin group during 48 weeks. There was a significant dose-response effect for lutein supplementation, and the changes in MPOD from baseline to 48 weeks were correlated negatively with baseline MPOD in all active treatment groups (r = -0.56; P<0.001). At 48 weeks, a trend toward improvement was seen in BCVA, and there was a significant between-group difference in CS at 3 and 6 cycles/degree between the 20-mg lutein group and the placebo group. The increase in MPOD related positively to the reduction in the logarithm of the minimum angle of resolution BCVA (r = -0.31; P<0.01) and the increases in CS at 4 spatial frequencies (r ranging from 0.26 to 0.38; all P<0.05). CONCLUSIONS: Among patients with early AMD, supplementation with lutein and zeaxanthin improved macular pigment, which played a causative role in boosting visual function and might prevent the progression of AMD. Future studies are required to evaluate the effect of these carotenoids on the incidence of late AMD.

Improvement of retinal function in early age-related macular degeneration after lutein and zeaxanthin supplementation: a randomized, double-masked, placebo-controlled trial.

PURPOSE: To examine the effects of lutein and zeaxanthin supplementation on retinal function using multifocal electroretinograms (mfERG) in patients with early age-related macular degeneration (AMD). DESIGN: Randomized, double-masked, placebo-controlled trial. METHODS: One hundred eight subjects with early AMD were randomly assigned to receive 10 mg/d lutein (n = 27), 20 mg/d lutein (n = 27), 10 mg/d lutein plus 10 mg/d zeaxanthin (n = 27), or placebo (n = 27) for 48 weeks. Thirty-six age-matched controls without AMD were also enrolled to compare baseline data with early AMD patients. MfERG responses and macular pigment optical densities (MPODs) were recorded and analyzed at baseline and at 24 and 48 weeks. RESULTS: There were significant reductions in N1P1 response densities in ring 1 to ring 3 in early AMD patients compared with the controls (P < .05), whereas neither N1P1 response densities in ring 4 to ring 6 nor P1 peak latencies significantly changed. After 48-week supplementation, the N1P1 response densities showed significant increases in ring 1 for the 20 mg lutein group and for the lutein and zeaxanthin group, and in ring 2 for the 20 mg lutein group. The increases in MPOD related positively to the increases in N1P1 response density in ring 1 and ring 2 for nearly all active treatment groups. N1P1 response densities in ring 3 to ring 6 or P1 peak latencies in all rings did not change significantly in any group. CONCLUSION: Early functional abnormalities of the central retina in the early AMD patients could be improved by lutein and zeaxanthin supplementation. These improvements may be potentially attributed to the elevations in MPOD.

Secular trends of macrosomia in southeast China, 1994-2005.

BACKGROUND: The rate of macrosomia (birth weight≥4, 000 g) increased over the past four decades in many parts of the world. Macrosomia is associated not only with higher risks of maternal and neonatal complications but also with health risks in adulthood. We examined trends in neonatal macrosomia and large-for-gestational-age (LGA) births among singleton, live, term and postterm births (≥37 complete weeks' gestation) in southeast China from 1994 to 2005 and explored possible causes of the temporal trends. METHODS: Data from Perinatal Health Care Surveillance System in 12 cities and counties in southeast China were analyzed for trends in birth weight, neonatal macrosomia and LGA from 1994 to 2005. A total of 594, 472 singleton live births were included. We conducted multiple logistic regression analyses to relate these trends to changes in maternal and pregnancy characteristics. RESULTS: The rate of macrosomia rose from 6.00% in 1994 to 8.49% in 2000 and then levelled off to 7.83% in 2005. Similar trends were observed in mean birth weight. The incidence of LGA births increased continuously from 13.72% in 1994 to 18.08% in 2000, but the LGA rate remained relatively stable from 2002 to 2005. There was a decrease in gestational age and a significant increase in frequency of prelabor caesarean delivery from 1994 to 2005. In an adjusted multivariable model, the increase in LGA rate from 1994 to 2000 was associated with increasing net gestational weight gain, maternal age, maternal height and maternal education. But they didn't fully explain the increase. The trends of 2002-2005 LGA declined after adjusted for maternal and neonatal characteristics. CONCLUSIONS: In southeast China, the incidence of macrosomia increased from 1994 to 2000 was mainly related to increasing net gestational weight gain. The incidence of macrosomia has levelled off in recent years partly due to increasing use of prelabor caesarean delivery and earlier delivery and partly due to moderation of gestational weight gain.