1.Buqi-Tongluo Decoction inhibits osteoclastogenesis and alleviates bone loss in ovariectomized rats by attenuating NFATc1, MAPK, NF-κB signaling.
Yongxian LI ; Jinbo YUAN ; Wei DENG ; Haishan LI ; Yuewei LIN ; Jiamin YANG ; Kai CHEN ; Heng QIU ; Ziyi WANG ; Vincent KUEK ; Dongping WANG ; Zhen ZHANG ; Bin MAI ; Yang SHAO ; Pan KANG ; Qiuli QIN ; Jinglan LI ; Huizhi GUO ; Yanhuai MA ; Danqing GUO ; Guoye MO ; Yijing FANG ; Renxiang TAN ; Chenguang ZHAN ; Teng LIU ; Guoning GU ; Kai YUAN ; Yongchao TANG ; De LIANG ; Liangliang XU ; Jiake XU ; Shuncong ZHANG
Chinese Journal of Natural Medicines (English Ed.) 2025;23(1):90-101
Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals
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NFATC Transcription Factors/genetics*
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Drugs, Chinese Herbal/pharmacology*
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Ovariectomy
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Osteoclasts/metabolism*
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Female
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Osteogenesis/drug effects*
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Rats, Sprague-Dawley
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Rats
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NF-kappa B/genetics*
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Osteoporosis/genetics*
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Signal Transduction/drug effects*
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Bone Resorption/genetics*
;
Cell Differentiation/drug effects*
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Humans
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RANK Ligand/metabolism*
;
Mitogen-Activated Protein Kinases/genetics*
;
Transcription Factors
2.Ultrasonic morphological characteristics of superficial and deep thoracolumbar paraspinal muscles in patients with moderate adolescent idiopathic scoliosis
Shanshan ZHANG ; Yanjun WANG ; Zhiwei LIAN ; Yi XU ; Binbin YANG ; Qiuli LIANG ; Chuhuai WANG
Chinese Journal of Spine and Spinal Cord 2025;35(4):366-375
Objectives:To explore the morphological changes of the superficial and deep thoraolumbar paraspinal muscles on both convex and concave sides during rest and contraction states in patients with mod-erate adolescent idiopathic scoliosis(AIS),and their effects on scoliosis angle,to analyze the relations between scoliosis angle and the morphological changes of paraspinal muscles.Methods:21 AIS patients(thoracic Cobb angle 20°-45°,S-shaped with the main curve in thoracic segment,4 males and 17 females,aged 13.9±1.6 years old)treated in our hospital from July 2020 to December 2023 and 21 healthy subjects(7 males and 14 females,aged 14.6±1.4 years old)were prospectively enrolled.The morphological data of thoracolumbar paraspinal muscles were collected with musculoskeletal ultrasound,including the resting thickness and thick-ness during maximum voluntary isometric contraction(MVIC)of superficial erector spinae(ES)and multifidus(MF)muscles of AIS patients on both convex and concave sides(left and right sides of healthy controls).The differences in resting thickness,contraction thickness,change rate of contraction thickness,and total resting thickness and total contraction thickness(ES+MF)of superficial and deep thoracolumbar paravertebral muscles between the two groups were analyzed,and the structural characteristics of the thoracolumbar paravertebral muscles on the convex and concave sides of AIS were analyzed.The correlation between Cobb angle in tho-racolumbar segment and morphological indexes(resting thickness,contraction thickness change rates)of ES and MF muscles was analyzed,and the influence of scoliosis severity on the morphology of superficial and deep paravertebral muscle was further analyzed.Results:In AIS patients,the mean thoracic Cobb angle were 31.62°±7.68°,and mean lumbar Cobb angle were 19.52°±6.48°.Comparing with healthy controls,patients with AIS were significantly different in resting thickness,contraction thickness and thickness change rates of tho-racic paraspinal muscles on both convex and concave sides,and the resting thickness of ES in thoracic seg-ment on concave side was less than that on the convex side,which of MF was less on the convex side than on the concave side(P<0.01).The contraction thickness of thoracic MF muscles on the convex and concave sides in S-type AIS patients was smaller than that in healthy controls(P<0.05),while the contraction thickness of thoracic ES muscles on the convex and concave side wasn't statistically different from that of healthy con-trols,and the contraction thickness change rate of ES muscles on the convex and MF on the concave side of thoracic segment in AIS patients was significantly decreased(P<0.05).There was no significant difference in the total resting thickness of thoracic(convex and concave)paravertebral muscles(ES+MF)between AIS patients and the corresponding segments(left and right)of control group(P>0.05),and there was no statistically signifi-cant difference in the total resting thickness of thoracic paravertebral muscle between the convex and concave sides of AIS patients(P>0.05).The total contraction thickness of thoracic paravertebral muscle(ES+MF)in AIS patients was lower than that in control group(P<0.05).Compared with the control group,the resting thickness,contraction thickness and thickness change rate of lumbar MF muscle on the convex and concave sides in AIS patients were significantly reduced(P<0.05),and the contraction thickness change rate of the lumbar ES muscle on the concave side was less than that of the control group(P<0.05).There were no significant differ-ences in resting thickness and contraction thickness between the convex and concave paravertebral muscles in AIS patients(P>0.05).The total resting thickness(ES+MF)and total contraction thickness(ES+MF)of lumbar(convex and concave)paraspinal muscles in AIS patients were lower than those in control group(P<0.05).There was a significant negative correlation between the Cobb angle of the main thoracic curve and the rest-ing thickness of the thoracic MF muscle on the concave and the change rate of the contraction thickness of the thoracic ES muscle on the convex in S-type AIS patients(r=-0.53/-0.45,P<0.05).There was no signifi-cant correlation between the Cobb angle of lumbar segment and the change rates of the resting thickness and contraction thickness of ES and MF muscles on both convex and concave sides(P>0.05).Conclusions:In pa-tients with moderate S-type AIS,there are different muscle morphological changes in the paraspinal muscles on both convex and concave sides of the main thoracic curve,and the concave paravertebral muscle is more affected by scoliosis;The contraction function of the bilateral deep core stabilizing muscles in the lumbar re-gion is markedly decreased.Different patterns of superficial and deep muscle atrophy and contractility decline may be a key cause of spinal movement disorder and scoliosis progression in AIS patients.
3.Development of an innovation-oriented curriculum indicator system for nursing science and technology innovation education
Hongli LI ; Yawen ZHANG ; Wen LI ; Yuhan LU ; Xinying YU ; Dong PANG ; Qian PENG ; Qiuli YAO ; Wei ZHANG ; Hong YANG
Chinese Journal of Modern Nursing 2025;31(34):4714-4719
Objective:To construct an indicator system for a nursing science and technology innovation curriculum guided by innovation competence, in order to provide a reference for cultivating innovation ability in nursing students.Methods:The overall research period was from March to December 2024. A nursing innovation curriculum indicator framework was initially developed through literature analysis and brainstorming. From October to December 2024, 19 experts from nine hospitals or universities across five provinces and cities were selected via purposive sampling to participate in two rounds of Delphi consultation. Revisions were made based on expert feedback.Results:Both rounds of expert consultation achieved a 100% response rate. The authority coefficient of the experts was 0.92. The final indicator system included four curriculum elements: course content, course objectives, teaching methods, and assessment, encompassing 14 first-level indicators and 40 second-level indicators.Conclusions:The innovation-oriented indicator system for nursing science and technology education demonstrates good scientific validity and reliability. It offers a foundational framework for advancing innovation-focused nursing education and curriculum design.
4.Construction of an automatic optic disc and cup segmentation and cup-to-disc ratio calculation system for ocular fundus image and its application in glaucoma screening
Xiaoxuan LYU ; Yang YANG ; Jiani ZHAO ; Qiuli YU ; Cheng WAN
Chinese Journal of Experimental Ophthalmology 2025;43(11):1007-1016
Objective:To develop a deep learning-based automated analysis system for precise segmentation of the optic cup and disc in fundus images and automatic measurement of the vertical cup-to-disc ratio (CDR) for early risk assessment and screening of chronic glaucoma.Methods:The proposed automated system comprised three modules: a dual coding-attention U-net (DCoAtUNet) segmentation network for optic cup and disc segmentation, a conditional random field (CRF) post-processing module, and a CDR measurement and glaucoma screening module based on the segmentation results.The system was designed to enhance boundary detection accuracy and measurement stability and its performance was evaluated on the publicly available Drishti-GS dataset.The dataset was divided into a training set and a test set in a 1∶1 ratio.Dice coefficient and intersection over union (IoU) were used to quantify segmentation accuracy and regional consistency, while accaracy, precision, recall, and F1-score were employed to assess glaucoma screening performance.Results:The DCoAtUNet combined with CRF post-processing achieved Dice coefficients of 0.976 0 for the optic disc and 0.908 1 for the optic cup, with corresponding IoU values of 0.953 4 and 0.837 9, demonstrating high segmentation precision and stability in boundary identification and region overlap.In glaucoma screening, the system achieved an accuracy of 0.843 1, precision of 0.840 9, recall of 0.973 7, and F1-score of 0.902 4, indicating good diagnostic sensitivity and accuracy.Conclusions:By integrating high-precision segmentation and automated measurement strategies, the DCoAtUNet+ CRF model significantly improves the accuracy and stability of CDR evaluation.It effectively assists in identifying high-risk individuals during early glaucoma screening and shows strong potential for clinical application in computer-aided diagnosis workflows.
5.Development of an innovation-oriented curriculum indicator system for nursing science and technology innovation education
Hongli LI ; Yawen ZHANG ; Wen LI ; Yuhan LU ; Xinying YU ; Dong PANG ; Qian PENG ; Qiuli YAO ; Wei ZHANG ; Hong YANG
Chinese Journal of Modern Nursing 2025;31(34):4714-4719
Objective:To construct an indicator system for a nursing science and technology innovation curriculum guided by innovation competence, in order to provide a reference for cultivating innovation ability in nursing students.Methods:The overall research period was from March to December 2024. A nursing innovation curriculum indicator framework was initially developed through literature analysis and brainstorming. From October to December 2024, 19 experts from nine hospitals or universities across five provinces and cities were selected via purposive sampling to participate in two rounds of Delphi consultation. Revisions were made based on expert feedback.Results:Both rounds of expert consultation achieved a 100% response rate. The authority coefficient of the experts was 0.92. The final indicator system included four curriculum elements: course content, course objectives, teaching methods, and assessment, encompassing 14 first-level indicators and 40 second-level indicators.Conclusions:The innovation-oriented indicator system for nursing science and technology education demonstrates good scientific validity and reliability. It offers a foundational framework for advancing innovation-focused nursing education and curriculum design.
6.Construction of an automatic optic disc and cup segmentation and cup-to-disc ratio calculation system for ocular fundus image and its application in glaucoma screening
Xiaoxuan LYU ; Yang YANG ; Jiani ZHAO ; Qiuli YU ; Cheng WAN
Chinese Journal of Experimental Ophthalmology 2025;43(11):1007-1016
Objective:To develop a deep learning-based automated analysis system for precise segmentation of the optic cup and disc in fundus images and automatic measurement of the vertical cup-to-disc ratio (CDR) for early risk assessment and screening of chronic glaucoma.Methods:The proposed automated system comprised three modules: a dual coding-attention U-net (DCoAtUNet) segmentation network for optic cup and disc segmentation, a conditional random field (CRF) post-processing module, and a CDR measurement and glaucoma screening module based on the segmentation results.The system was designed to enhance boundary detection accuracy and measurement stability and its performance was evaluated on the publicly available Drishti-GS dataset.The dataset was divided into a training set and a test set in a 1∶1 ratio.Dice coefficient and intersection over union (IoU) were used to quantify segmentation accuracy and regional consistency, while accaracy, precision, recall, and F1-score were employed to assess glaucoma screening performance.Results:The DCoAtUNet combined with CRF post-processing achieved Dice coefficients of 0.976 0 for the optic disc and 0.908 1 for the optic cup, with corresponding IoU values of 0.953 4 and 0.837 9, demonstrating high segmentation precision and stability in boundary identification and region overlap.In glaucoma screening, the system achieved an accuracy of 0.843 1, precision of 0.840 9, recall of 0.973 7, and F1-score of 0.902 4, indicating good diagnostic sensitivity and accuracy.Conclusions:By integrating high-precision segmentation and automated measurement strategies, the DCoAtUNet+ CRF model significantly improves the accuracy and stability of CDR evaluation.It effectively assists in identifying high-risk individuals during early glaucoma screening and shows strong potential for clinical application in computer-aided diagnosis workflows.
7.Ultrasonic morphological characteristics of superficial and deep thoracolumbar paraspinal muscles in patients with moderate adolescent idiopathic scoliosis
Shanshan ZHANG ; Yanjun WANG ; Zhiwei LIAN ; Yi XU ; Binbin YANG ; Qiuli LIANG ; Chuhuai WANG
Chinese Journal of Spine and Spinal Cord 2025;35(4):366-375
Objectives:To explore the morphological changes of the superficial and deep thoraolumbar paraspinal muscles on both convex and concave sides during rest and contraction states in patients with mod-erate adolescent idiopathic scoliosis(AIS),and their effects on scoliosis angle,to analyze the relations between scoliosis angle and the morphological changes of paraspinal muscles.Methods:21 AIS patients(thoracic Cobb angle 20°-45°,S-shaped with the main curve in thoracic segment,4 males and 17 females,aged 13.9±1.6 years old)treated in our hospital from July 2020 to December 2023 and 21 healthy subjects(7 males and 14 females,aged 14.6±1.4 years old)were prospectively enrolled.The morphological data of thoracolumbar paraspinal muscles were collected with musculoskeletal ultrasound,including the resting thickness and thick-ness during maximum voluntary isometric contraction(MVIC)of superficial erector spinae(ES)and multifidus(MF)muscles of AIS patients on both convex and concave sides(left and right sides of healthy controls).The differences in resting thickness,contraction thickness,change rate of contraction thickness,and total resting thickness and total contraction thickness(ES+MF)of superficial and deep thoracolumbar paravertebral muscles between the two groups were analyzed,and the structural characteristics of the thoracolumbar paravertebral muscles on the convex and concave sides of AIS were analyzed.The correlation between Cobb angle in tho-racolumbar segment and morphological indexes(resting thickness,contraction thickness change rates)of ES and MF muscles was analyzed,and the influence of scoliosis severity on the morphology of superficial and deep paravertebral muscle was further analyzed.Results:In AIS patients,the mean thoracic Cobb angle were 31.62°±7.68°,and mean lumbar Cobb angle were 19.52°±6.48°.Comparing with healthy controls,patients with AIS were significantly different in resting thickness,contraction thickness and thickness change rates of tho-racic paraspinal muscles on both convex and concave sides,and the resting thickness of ES in thoracic seg-ment on concave side was less than that on the convex side,which of MF was less on the convex side than on the concave side(P<0.01).The contraction thickness of thoracic MF muscles on the convex and concave sides in S-type AIS patients was smaller than that in healthy controls(P<0.05),while the contraction thickness of thoracic ES muscles on the convex and concave side wasn't statistically different from that of healthy con-trols,and the contraction thickness change rate of ES muscles on the convex and MF on the concave side of thoracic segment in AIS patients was significantly decreased(P<0.05).There was no significant difference in the total resting thickness of thoracic(convex and concave)paravertebral muscles(ES+MF)between AIS patients and the corresponding segments(left and right)of control group(P>0.05),and there was no statistically signifi-cant difference in the total resting thickness of thoracic paravertebral muscle between the convex and concave sides of AIS patients(P>0.05).The total contraction thickness of thoracic paravertebral muscle(ES+MF)in AIS patients was lower than that in control group(P<0.05).Compared with the control group,the resting thickness,contraction thickness and thickness change rate of lumbar MF muscle on the convex and concave sides in AIS patients were significantly reduced(P<0.05),and the contraction thickness change rate of the lumbar ES muscle on the concave side was less than that of the control group(P<0.05).There were no significant differ-ences in resting thickness and contraction thickness between the convex and concave paravertebral muscles in AIS patients(P>0.05).The total resting thickness(ES+MF)and total contraction thickness(ES+MF)of lumbar(convex and concave)paraspinal muscles in AIS patients were lower than those in control group(P<0.05).There was a significant negative correlation between the Cobb angle of the main thoracic curve and the rest-ing thickness of the thoracic MF muscle on the concave and the change rate of the contraction thickness of the thoracic ES muscle on the convex in S-type AIS patients(r=-0.53/-0.45,P<0.05).There was no signifi-cant correlation between the Cobb angle of lumbar segment and the change rates of the resting thickness and contraction thickness of ES and MF muscles on both convex and concave sides(P>0.05).Conclusions:In pa-tients with moderate S-type AIS,there are different muscle morphological changes in the paraspinal muscles on both convex and concave sides of the main thoracic curve,and the concave paravertebral muscle is more affected by scoliosis;The contraction function of the bilateral deep core stabilizing muscles in the lumbar re-gion is markedly decreased.Different patterns of superficial and deep muscle atrophy and contractility decline may be a key cause of spinal movement disorder and scoliosis progression in AIS patients.
8.Research progress of transcranial alternating current stimulation in the treatment of cognitive impairment in neuropsychiatric diseases
Xuelin ZHANG ; Qiuli YANG ; Xiaying SI ; Peishan HUANG ; Ke WANG ; Yi MIAO ; Qiangli DONG
Chinese Journal of Nervous and Mental Diseases 2024;50(1):43-48
Cognitive dysfunction is the impairment of higher brain functions.Cognitive impairment caused by neuropsychiatric diseases has caused serious impact on patients'quality of life and the outcome of the disease.The transcranial alternating current stimulation(tACS)improves cognitive function by modulating neural oscillations of specific frequencies,affecting the release of neurotransmitters such as serotonin and dopamine,and enhancing local and distal synchronization of brain networks.Specific frequencies of tACS can improve the cognitive impairment caused by Alzheimer disease(AD),schizophrenia,and depression,among which the gamma and theta frequencies of tACS have the most significant effects on cognitive function.tACS has high safety and low operational difficulty,and has great potential to improve cognitive function.
9.Construction of the clinical practice pathway for narrative medicine in traditional Chinese medicine
Zixu WANG ; Jingjing ZHAO ; Yipin LIU ; Jie LI ; Qiuli YANG ; Yongyan WANG
Chinese Medical Ethics 2024;37(11):1251-1262
Objective:To construct the clinical practice pathway for narrative medicine in traditional Chinese medicine(TCM),with a view to providing clinical practice guidelines for narrative medicine in TCM for frontline practitioners.Methods:Using the realistic literature review and the Nominal Group Technique(NGT),the paper systematically sorted out the practices of humanistic care in ancient Chinese medical books and famous medical cases,as well as constructed the first draft of the clinical practice pathway and details for narrative medicine in TCM.Subsequently,experts from multiple fields were invited to demonstrate by using the NGT.After in-depth discussion and collective voting,various operational modules,and their detailed rules and supporting tools were determined,thus completing the construction of the entire practical pathway.Results:A complete set of clinical practice pathways for narrative medicine in TCM had been established.It encompassed six core modules,including"start of diagnosis and treatment","communication of disease conditions","diagnosis and explanation","joint decision-making","end of diagnosis and treatment",and"reflection and summary".Besides,detailed operating rules and supporting tools were also provided.Conclusion:The clinical practice pathway for narrative medicine in TCM integrates the humanistic spirit of TCM,the core concepts of narrative medicine,and the communication skills of psychology,providing medical workers with standardized,procedural,and operationally flexible practice guidance,which helps both doctors and patients to better communicate,empathize,and make joint decisions throughout the entire process of diagnosis and treatment.
10.Association between preconception oral microbiome and fetal overgrowth
Qiuli XIAO ; Xushan CAI ; Lifeng ZHANG ; Fengyun YANG ; Xingying LI ; An CHEN ; Huajun ZHENG ; Hong JIANG
Chinese Journal of Perinatal Medicine 2024;27(6):457-467
Objective:To analyze the association between the pre-pregnancy oral microbiota of women and fetal overgrowth, and the possible mechanisms involved.Methods:A nested case-control study design based on a pre-pregnancy cohort was used to select 51 mothers who delivered macrosomia and/or large-for-gestational-age (LGA) infants from the population recruited at the Maternal and Child Health Care Hospital of Jiading District in Shanghai from October 2016 to December 2021 as the case group. A control group was formed by selecting 204 mothers who delivered infants with normal birth weight and appropriate for gestational age during the same period, in a 1:4 ratio. The LGA subgroup consisted of 48 mothers who delivered LGA infants from the total population, and a corresponding control group of 192 was randomly selected from the remaining mothers who delivered non-LGA infants in a 1∶4 ratio for the LGA subgroup analysis. The 16S rRNA gene sequencing technique was utilized to detect pre-pregnancy saliva samples to compare the characteristics of the oral microbiota, differential microorganisms, and differential functional pathways between groups. Nonparametric Wilcoxon rank-sum tests, two independent samples t-tests, or Chi-square (or Fisher's exact) tests were used for statistical analysis. Factor analysis was conducted on the pre-pregnancy diet data of women, and the primary dietary pattern of each study subject was identified based on the highest score of the dietary pattern factors. For microbiota count data, α and β diversity indices were calculated using R and QIIME2 software, and the corresponding microbiota functional count data were acquired through PICRUSt2. Results:(1) General data: There was no significant difference in the time interval from pre-pregnancy sampling to pregnancy and from sampling to delivery between the two groups. In the case group, there were three cases of macrosomia and 48 cases (94.1%) of LGA. The corresponding control group for the LGA subgroup consisted of 192 cases. There were no significant differences in dietary patterns between the case group and the control group. (2) α diversity analysis: The species richness index of the case group was lower than that of the control group [(367.27±84.57) vs. (408.71±93.08), multivariate analysis, P=0.009], while no significant differences were found between the two groups in the Shannon and Simpson indices; the species richness index of the LGA subgroup was also lower than that of the corresponding control group [(371.04±83.92) vs. (408.04±94.21), multivariate analysis, P=0.033], with no significant differences in the Shannon and Simpson indices. (3) β diversity analysis: There was a statistically significant difference in the unweighted UniFrac distance of the oral microbiota between the case group and the control group ( R2=0.006, F=1.479, P=0.048). No significant differences were found in the β diversity indices of the oral microbiota between the LGA subgroup and the corresponding control group. (4) Differential microbiota analysis: There were 14 differential microbiotas from phylum to genus between the case group and the control group. At the genus level, members of the G1 genus of the Streptococcaceae were enriched in the case group, while the Lautropia, Dialister, Leptotrichia, and Rothia were enriched in the control group. In the LGA subgroup and its corresponding control group, there were 14 differential microbiota from phylum to genus; at the genus level, Leptotrichia, Rothia, G6 genus of the Saccharibacteria, and Selenomonas were enriched in the control group (all LDA value>2, and all P<0.05). (5) Differential functional analysis: In the case group, metabolic pathways such as nicotinate degradation [log 2 fold change ( FC)=3.510, q=0.005], de novo synthesis of pyrimidine nucleotides (log 2FC=0.078, q=0.005), and L-tyrosine degradation pathway (log 2FC=0.710, q=0.034) were enriched in the oral microbiota of women. In the LGA subgroup, compared to the corresponding control group, metabolic pathways related to nicotinate degradation were enriched in the oral microbiota (log 2FC=3.660, q=0.012). Conclusions:There are differences in the structure of the pre-pregnancy oral microbiota of mothers with overgrown fetuses compared to those with normally grown fetuses, and mothers of normally grown fetuses show higher diversity in their pre-pregnancy oral microbiota. The enrichment of certain pathogenic bacteria and the reduction of symbiotic bacteria in the pre-pregnancy oral microbiota are associated with fetal overgrowth, and this association may be mediated by functional pathways such as nicotinate degradation.

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