1.TGF-β1-engineered Biomimetic Platelet Nanoparticles for Targeted Therapy of Ischemic Stroke
Li-Qi CHEN ; Tian-Fang KANG ; Guo-Jun HUANG ; Ting YIN ; Ai-Qing MA ; Lin-Tao CAI ; Hong PAN
Progress in Biochemistry and Biophysics 2026;53(3):697-710
ObjectivePost-ischemic acute inflammation and the subsequent persistent dysregulation of the immune microenvironment represent major pathological drivers that aggravate neuronal injury and severely restrict functional recovery following ischemic stroke. Although current reperfusion therapies partially restore blood flow, they fail to effectively modulate the secondary inflammatory cascade and oxidative stress, which remain critical barriers to neurological restoration. To address this challenge, this study aimed to engineer and systematically evaluate a biomimetic nanosystem composed of transforming growth factor-β1 (TGF-β1)-loaded platelet membrane-camouflaged lipid nanoparticles (PLP). This nanosystem was designed to achieve dual lesion-targeted delivery and immune microenvironment remodeling. By verifying its spatiotemporal accumulation, anti-inflammatory activity, and neuroprotective efficacy, we sought to establish an integrated therapeutic strategy that simultaneously enables lesion targeting, immune regulation, and functional recovery after ischemic injury. MethodsThe physicochemical properties of PLP, including hydrodynamic particle size, zeta potential, structural stability, and morphology, were characterized using dynamic light scattering, zeta potential analysis, and transmission electron microscopy. The preservation of platelet membrane-derived adhesion and immunoregulatory proteins was confirmed by SDS-PAGE through comparative analysis of protein band profiles between PLP and native platelet membranes. The in vitro biological activities of PLP were evaluated using two complementary cellular models. LPS-induced M1-polarized RAW264.7 macrophages were employed to assess inflammatory modulation, while oxygen glucose deprivation/reperfusion (OGD/R)-induced BV2 microglial cells and SH-SY5Y neuronal cells were utilized to investigate neuroinflammatory regulation and neuronal protection. For in vivo validation, a transient middle cerebral artery occlusion (tMCAO) mouse model was established to mimic ischemia-reperfusion injury. The spatiotemporal biodistribution and lesion-targeting capability of the PLP were monitored through live fluorescence imaging. Therapeutic efficacy was comprehensively evaluated by triphenyltetrazolium chloride (TTC) staining, glial fibrillary acidic protein (GFAP) immunofluorescence analysis, body weight monitoring, and neurological severity score (NSS) assessment. ResultsPLP nanoparticles displayed a uniform spherical morphology, nanoscale particle size distribution, and stable negative surface charge, indicating favorable colloidal stability and circulation potential. SDS-PAGE results confirmed the effective retention of key platelet membrane proteins associated with endothelial adhesion, immune evasion, and inflammatory regulation, demonstrating the successful biomimetic construction. Optimal therapeutic concentrations were determined in OGD/R-induced BV2 cells, where PLP exhibited excellent cytocompatibility and anti-inflammatory activity.In vitro experiments demonstrated that PLP significantly inhibited the polarization of RAW264.7 macrophages toward the pro-inflammatory M1 phenotype and markedly reduced neuronal apoptosis under ischemia-reperfusion conditions. In vivo fluorescence imaging revealed that PLP rapidly accumulated in the ischemic brain hemisphere and maintained prolonged retention for up to 7 d, suggesting enhanced lesion-specific targeting and sustained drug release. Compared with control group, PLP treatment significantly reduced cerebral infarct volume, attenuated reactive astrogliosis, improved weight recovery, and accelerated neurological functional restoration, as reflected by significantly improved NSS scores. ConclusionThis study establishes a multifunctional biomimetic nanoplatform that integrates platelet membrane-mediated active targeting with the anti-inflammatory, antioxidative, and neuroprotective properties of TGF-β1. The PLP system enables rapid lesion homing and long-term retention while synergistically regulating the post-stroke inflammatory microenvironment by suppressing pro-inflammatory immune activation, reducing neuronal apoptosis, and limiting excessive astrocyte reactivity. Importantly, this study proposes a conceptually therapeutic paradigm that combines targeted delivery with immune microenvironment remodeling to achieve comprehensive neurovascular protection. These findings provide strong experimental evidence supporting the translational potential of biomimetic nanotherapeutics as next-generation precision interventions for ischemic stroke.
2.Development of a machine learning-based risk prediction model for mild cognitive impairment with spleen-kidney deficiency syndrome in the elderly.
Ya-Ting AI ; Shi ZHOU ; Ming WANG ; Tao-Yun ZHENG ; Hui HU ; Yun-Cui WANG ; Yu-Can LI ; Xiao-Tong WANG ; Peng-Jun ZHOU
Journal of Integrative Medicine 2025;23(4):390-397
OBJECTIVE:
As an age-related neurodegenerative disease, the prevalence of mild cognitive impairment (MCI) increases with age. Within the framework of traditional Chinese medicine, spleen-kidney deficiency syndrome (SKDS) is recognized as the most frequent MCI subtype. Due to the covert and gradual onset of MCI, in community settings it poses a significant challenge for patients and their families to discern between typical aging and pathological changes. There exists an urgent need to devise a preliminary diagnostic tool designed for community-residing older adults with MCI attributed to SKDS (MCI-SKDS).
METHODS:
This investigation enrolled 312 elderly individuals diagnosed with MCI, who were randomly distributed into training and test datasets at a 3:1 ratio. Five machine learning methods, including logistic regression (LR), decision tree (DT), naive Bayes (NB), support vector machine (SVM), and gradient boosting (GB), were used to build a diagnostic prediction model for MCI-SKDS. Accuracy, sensitivity, specificity, precision, F1 score, and area under the curve were used to evaluate model performance. Furthermore, the clinical applicability of the model was evaluated through decision curve analysis (DCA).
RESULTS:
The accuracy, precision, specificity and F1 score of the DT model performed best in the training set (test set), with scores of 0.904 (0.845), 0.875 (0.795), 0.973 (0.875) and 0.973 (0.875). The sensitivity of the training set (test set) of the SVM model performed best among the five models with a score of 0.865 (0.821). The area under the curve of all five models was greater than 0.9 for the training dataset and greater than 0.8 for the test dataset. The DCA of all models showed good clinical application value. The study identified ten indicators that were significant predictors of MCI-SKDS.
CONCLUSION
The risk prediction index derived from machine learning for the MCI-SKDS prediction model is simple and practical; the model demonstrates good predictive value and clinical applicability, and the DT model had the best performance. Please cite this article as: Ai YT, Zhou S, Wang M, Zheng TY, Hu H, Wang YC, Li YC, Wang XT, Zhou PJ. Development of a machine learning-based risk prediction model for mild cognitive impairment with spleen-kidney deficiency syndrome in the elderly. J Integr Med. 2025; 23(4): 390-397.
Humans
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Cognitive Dysfunction/diagnosis*
;
Aged
;
Male
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Female
;
Machine Learning
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Spleen
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Aged, 80 and over
;
Kidney
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Medicine, Chinese Traditional
3.Longitudinal Associations between Vitamin D Status and Systemic Inflammation Markers among Early Adolescents.
Ting TANG ; Xin Hui WANG ; Xue WEN ; Min LI ; Meng Yuan YUAN ; Yong Han LI ; Xiao Qin ZHONG ; Fang Biao TAO ; Pu Yu SU ; Xi Hua YU ; Geng Fu WANG
Biomedical and Environmental Sciences 2025;38(1):94-99
4.Application of Multi-Model Adaptive Statistical Iterative Reconstruction-Veo in Ultra-Low Dose Chest CT Examination of Children in Plateau Area.
Xian-Tao WANG ; Rui-Ting BAI ; CIDANWANGJIU ; SUOLANGNIMA ; NIMAZHUOGA ; Bai-Yan SU
Acta Academiae Medicinae Sinicae 2025;47(1):29-34
Objective To explore the application value of multi-model adaptive statistical iterative reconstruction-Veo (ASiR-V) in ultra-low dose chest CT examination of children in the plateau area. Methods The children who underwent chest CT examination in Xizang Autonomous Region People's Hospital were enrolled in this study and assigned into two groups according to the scanning conditions.Group A underwent scanning at a tube voltage of 100 kV and ASiR-V 50% reconstruction,and group B underwent scanning at a tube voltage of 80 kV and ASiR-V 0 (Group B1) and ASiR-V 50% (Group B2) reconstruction.The image quality of each group was evaluated objectively and subjectively.The radiation dose and image quality were compared between groups. Results Groups A and B showed the volume CT dose indexes of (2.33±0.62) mGy and (0.86±0.01) mGy and the dose length products of (65.01±25.12) mGy·cm and (23.55±3.38) mGy·cm,respectively,which presented differences between groups (both P<0.001).The image noise in the bilateral upper and middle lung areas in group B2 was lower than that in group B1 but higher than that in group A (all P<0.001).There was no significant difference in image quality score of the lung window among groups (all P>0.05).Groups A,B1,and B2 had no significant differences in ascending aorta (P=0.538) or liver CT value (P=0.175) in the mediastinal window.The signal-to-noise ratios and contrast-to-noise ratios of ascending aorta and liver in group B2 were higher than those in group B1 (all P<0.001) and lower than those in group A (all P<0.05).The image quality score of the mediastinal window followed a descending order of group A>group B2>group B1 (all P<0.001)。Conclusion ASiR-V combined with low tube voltage can effectively reduce the radiation dose and guarantee the image quality of chest CT of children in the plateau area.
Humans
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Radiation Dosage
;
Tomography, X-Ray Computed/methods*
;
Child
;
Male
;
Female
;
Child, Preschool
;
Radiography, Thoracic/methods*
;
Infant
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Models, Statistical
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Image Processing, Computer-Assisted/methods*
5.Research and establishment of standards for traditional Chinese medicine sachet
Hailiang XIN ; Yiping JIANG ; Ting HAN ; Tao GUO ; Hua NIAN ; Xiaoqiang YUE
Journal of Pharmaceutical Practice and Service 2025;43(12):603-606
Objective Fragrant sachets are items with significant Chinese cultural characteristics and have multiple application values, with their medicinal value being an important aspect. Especially in recent years, with the successive outbreaks of SARS, MERS, COVID-19, the medicinal effect of traditional Chinese medicine sachets has been increasingly valued and widely used.However, there are no relevant standards for traditional Chinese medicine sachets at the national, industry, local, or organizational levels, which is not conducive to the healthy development of the industry. To establish standards for traditional Chinese medicine sachets to lead the development of the industry. Methods Based on the review of the current application status of traditional Chinese medicine sachets, a study on the quality standards of traditional Chinese medicine sachets was conducted through investigation and research, data collection, drafting of standard drafts, soliciting opinions, review and approval, and standard verification. Results The first group standard of traditional Chinese medicine sachet in China: Technological specification of traditional Chinese medicine sachet (powder core), which ensures the scientificity, progressiveness, rationality and practicability of the production of the standard of traditional Chinese medicine sachet. Conclusion The established group standard for traditional Chinese medicine sachets are practical, safe, reliable, and easy to implement, providing technical references for the inheritance and promotion of traditional Chinese medicine sachets.
6.The relationship between family function and anxiety/depression among medical college students:the mediating role of loneliness
Ying FENG ; Yujing TAO ; Haoqi LI ; Ting YU ; Weiwei CHANG ; Liying WEN
Journal of Shenyang Medical College 2025;27(4):359-363
Objective:To explore the relationship between medical students'family function and anxiety/depression,and the mediating role of loneliness in this relationship.Methods:A total of 577 medical students were surveyed using stratified cluster sampling.Questionnaires assessed family function,loneliness,anxiety,and depression.Spearman correlation analysis was used to examine the relationships among family function,loneliness,anxiety,and depression.The mediating effects were tested using SPSS 26.0 PROCESS program model 4.Results:Medical students'family function,loneliness,anxiety,and depression scores were 8.00(5.00,10.00),16.00(12.00,19.00),3.00(2.00,4.00),and 3.00(2.00,4.00),respectively.Spearman correlation analysis showed that family function was negatively correlated with loneliness(r=-0.337),anxiety(r=-0.237),and depression(r=-0.257)(all P<0.01).Loneliness was positively correlated with anxiety(r=0.394)and depression(r=0.392)(both P<0.01).Anxiety was positively correlated with depression(r=0.746,P<0.01).Family function negatively predicted anxiety(β=-0.118,P<0.01),depression(β=-0.105,P<0.01),and loneliness(β=-0.322,P<0.01).Loneliness positively predicted anxiety(β=0.348,P<0.01)and depression(β=0.346,P<0.01).Loneliness played a partial mediating role in the relationship of family function with anxiety and depression among medical students,with mediating effects of 49.0%and 43.2%,respectively.Conclusions:Family function not only directly affects medical students'anxiety and depression but also indirectly affects them by influencing loneliness.Therefore,improving medical students'family function can effectively reduce their loneliness,thereby helping to alleviate anxiety and depression.
7.Ability of artificial intelligence system to predict invasion depth and differentiation status of early gastric cancer: performance in single-center and multi-center videos
Ting YANG ; Zehua DONG ; Xiao TAO ; Lianlian WU ; Honggang YU
Chinese Journal of Digestive Endoscopy 2025;42(6):452-461
Objective:To evaluate the ability of ENDOANGEL artificial intelligence system to predict invasion depth and differentiation status of early gastric cancer using more diverse multi-center videos, and to test the performance of the new system upgraded from ENDOANGEL.Methods:Based on the completed 2020 man-machine competition for early gastric cancer diagnosis using single-center videos, the second man-machine competition was conducted in 2022, involving 30 endoscopists from 30 hospitals across 10 Chinese provinces. A multi-center video cohort was retrospectively collected from 12 institutions in 8 provinces/municipalities in China. The study proceeded in 3 stages. First, the ENDOANGEL was re-tested on multi-center videos, its performance on single and multi-center videos was compared, then the ENDOANGEL was upgraded to ENDOANGEL-2022. Second, the second man-machine competition was conducted between ENDOANGEL-2022 and 30 endoscopists using multi-center videos, and the performance between ENDOANGEL-2022, ENDOANGEL and endoscopists on multi-center videos were compared. Third, the ENDOANGEL-2022 was re-tested on the single-center videos previously collected in 2020, its performance on single and multi-center videos was also compared.Results:Compared with the performance on single-center videos, the sensitivity of ENDOANGEL for predicting submucosal invasion of early gastric cancer decreased significantly [18.18% (2/11) VS 70.00% (7/10), P=0.030], but demonstrated comparable ability to predict undifferentiated type of early gastric cancer ( P>0.05). On multi-center videos, in the respect of predicting submucosal invasion of early gastric cancer, the sensitivity of ENDOANGEL-2022 was higher than that of ENDOANGEL [40.00% (4/10) VS 18.18% (2/11), P=0.361], but inferior to that of 30 endoscopists [40.00% VS 52.04% (95% CI: 43.70%-60.38%), P<0.001]. The specificity of ENDOANGEL-2022 was lower than that of ENDOANGEL [82.86% (29/35) VS 100.00% (34/34), χ2=4.41, P=0.036] and higher than that of 30 endoscopists [82.86% VS 68.97% (95% CI: 60.83%-77.11%), P=0.018], the accuracy of ENDOANGEL-2022 was lower than that of ENDOANGEL [73.33% (33/45) VS 80.00% (36/45), χ2=0.56, P=0.455] and higher than that of 30 endoscopists [73.33% VS 65.30% (95% CI: 60.61%-69.99%), P=0.018]. In the respect of predicting undifferentiated type of early gastric cancer, the sensitivity of ENDOANGEL-2022 was higher than that of ENDOANGEL [71.43% (5/7) VS 57.14% (4/7), P>0.999] and 30 endoscopists [71.43% VS 63.11% (95% CI: 55.58%-70.64%), P=0.031], the specificity of ENDOANGEL-2022 was lower than that of ENDOANGEL [76.32% (29/38) VS 78.95% (30/38), χ2=0.08, P=0.783] and higher than that of 30 endoscopists [76.32% VS 65.27% (95% CI: 59.10%-71.44%), P=0.004],the accuracy of ENDOANGEL-2022 was similar to that of ENDOANGEL [75.56% (34/45) VS 75.56% (34/45), χ2=0.00, P>0.999] and higher than that of 30 endoscopists [75.56% VS 65.10% (95% CI: 59.96%- 70.24%), P<0.001]. Compared with performance in single center videos, the sensitivity [40.00% VS 60.00%(6/10), P=0.656], specificity [82.86% VS 93.75% (15/16), χ2=0.37, P=0.542] and accuracy [73.33% VS 80.77% (21/26), χ2=0.50, P=0.479] of ENDOANGEL-2022 for predicting submucosal invasion of early gastric cancer decreased; in predicting undifferentiated type of early gastric cancer, the sensitivity of ENDOANGEL-2022 increased [71.43% VS 37.50% (3/8), P=0.315], while the specificity [76.32% VS 100.00% (18/18), χ2=3.48, P=0.062] and accuracy [75.56% VS 80.77% (21/26), χ2=0.26, P=0.612] decreased. Conclusion:Multi-center cases introduce greater heterogeneity that may reduce artificial intelligence prediction accuracy, but the artificial intelligence system still outperforms endoscopists.
8.Screening of material basis for Rhei Radix et Rhizoma on improving human umbilical vein endothelial cell injury before and after carbonization based on spectrum-effect relationship
Ting ZHAI ; Li-tao LU ; Jiang-wei HE ; Ya-fei GUO ; Mei GUO ; Xin-yu ZHU
Chinese Traditional Patent Medicine 2025;47(7):2163-2171
AIM To screen the material basis for Rhei Radix et Rhizoma on improving human umbilical vein endothelial cell(HUVECs)injury before and after carbonization.METHODS The HPLC fingerprints were established,after which difference analysis was performed by orthogonal partial least squares discriminant analysis.The LPS-induced HUVECs injury model was established,then NO,MDA levels and SOD activity were detected.Gray correlation analysis and partial least squares regression were adopted in the investigation of spectrum-effect relationship,and active constituents were screened.RESULTS There were 22 and 20 common peaks in the fingerprints for 17 batches of raw products and carbonized products,respectively,along with the similarities of more than 0.8.Twelve main difference components were observable,among which gallic acid,5-hydroxymethylfurfural,catechin,aloe rhodopsin-8-O-β-D-glucoside,rhubarbic acid-8-O-β-D-glucoside and sennosides A were identified.The carbonized products demonstrated stronger effect on improving HUVECs injury than the raw product.The correlations of common peaks were more than 0.5 in the fingerprints for raw products and carbonized products,and peaks 3,5,11,12,15,19,23 exhibited significant effects on their efficacy(VIP values>1).CONCLUSION This accurate,reliable and reproducible method can provide a basis for clarifying the material basis for hemostatic efficacy of Rhei Radix et Rhizoma and its carbonized product.
9.Detection of TERT promoter C228T/C250T mutations by droplet digital PCR for predicting the postoperative recurrence of hepatocellular carcinoma
Nan HU ; Aizimuaji ZULIHUMAER ; Haiyang LI ; Yue LIU ; Changcheng TAO ; Ting XIAO ; Weiqi RONG
Chinese Journal of Hepatobiliary Surgery 2025;31(9):647-653
Objective:To investigate the predictive value of telomerase reverse transcriptase (TERT) promoter C228T/C250T mutations in tumor tissues of patients with hepatocellular carcinoma (HCC) for postoperative recurrence after hepatectomy.Methods:Clinical data of 66 patients with HCC who underwent curative surgical resection at the Cancer Hospital, Chinese Academy of Medical Sciences, between January 2013 and May 2016 were retrospectively analyzed, including 54 males and 12 females, aged (53.5±11.1) years. Tumor tissues were collected from all patients. Droplet digital ploymerase chain reation (ddPCR) was employed to detect the TERT promoter C228T/C250T mutations. Survival outcomes were estimated using the Kaplan-Meier method and compared by the log-rank test. Univariate and multivariate Cox regression were used to analyze the impact of TERT promoter C228T/C250T mutations on postoperative recurrence. The predictive performance of TERT mutations for postoperative recurrence was further assessed using receiver operating characteristic (ROC) curve analysis.Results:The prevalence of TERT C228T and C250T mutations in tumor tissues was 43.9% (29/66) and 3.0% (2/66), respectively. Patients were stratified into a TERT promoter mutation group ( n=31) and a non-mutation group ( n=35). Those harboring C228T/C250T mutations exhibited significantly lower recurrence-free survival compared with non-mutated cases ( χ2=10.10, P=0.002). Multivariate Cox regression analysis showed that TERT promoter C228T mutation ( HR=2.24, 95% CI: 1.18-4.25, P=0.013) and TERT promoter C228T/C250T mutations in tumor tissue ( HR=2.49, 95% CI: 1.31-4.75, P=0.006) were associated with an increased risk of postoperative recurrence in patients with HCC. ROC analysis demonstrated the predictive accuracy for recurrence, with an area under the curve of 0.68 (95% CI: 0.55-0.81) for TERT C228T mutation and 0.71 (95% CI: 0.58-0.84) for combined C228T/C250T mutations. Conclusion:TERT promoter C228T/C250T mutations in tumor tissues of HCC patients detected by ddPCR are risk factors for postoperative recurrence and may serve as indicators for predicting recurrence.
10.Genetic analysis of three fetuses with small supernumerary marker chromosome derived from chromosome 15
Xiaoxian SUN ; Xiaohan ZHAO ; Jing TAO ; Ting LU ; Bowen ZHAO ; Hua JIN
Chinese Journal of Perinatal Medicine 2025;28(5):408-413
Objective:To investigate the genetic characteristics of fetuses carrying a small supernumerary marker chromosome (sSMC) derived from chromosome 15.Methods:This was a retrospective study involving three fetuses who were diagnosed with microdeletions or microduplications by non-invasive prenatal testing (NIPT) and confirmed to carry sSMC derived from chromosome 15 through prenatal diagnosis at the Center of Prenatal Diagnosis, Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University from June to October 2023. Clinical data, including NIPT results and ultrasound findings, were collected. Genetic tests for the fetuses and their parents were performed using genetic karyotype analysis, fluorescence in situ hybridization (FISH), and single nucleotide polymorphisms array (SNP-array). All data were analyzed using descriptive statistics. Results:(1) The mothers of the three fetuses were aged 36, 37, and 41 years, and all of them were multiparous with no family history of genetic disorders. The fetuses exhibited duplications of 8.80, 8.17, and 8.80 Mb in the 15q11.2q13.3 region, respectively. Amniotic fluid karyotyping revealed a 47,XN,+mar karyotype in all three cases. The abnormal sSMC contained two centromeres. One of them was pycnotic, deeply stained, but remained active, while the other was enlarged and formed a band, losing its activity. Both were pseudo-dicentric structures. (2) FISH was not performed on Fetus 1. FISH results for both Fetus 2 and Fetus 3 were ish idic(15)( D15Z1++, SNRPN++, PML-), indicating the presence of two copies of the D15Z1 and SNRPN probes on the sSMC, with no PML probe signal. The D15Z1 probe was located at both ends of the sSMC, while the SNRPN probe was near the center. (3) SNP-array results were arr[GRCh37] 15q11.2q13.2(22 770 422-31 098 691)×4 for Fetus 1, covering 29 OMIM genes including UBE3A and 38 protein-coding genes; arr[GRCh37] 15q11.2q13.3(22 770 422-32 915 723)×4 for Fetus 2, covering 36 OMIM genes including UBE3A and 50 protein-coding genes; and arr[GRCh37] 15q11.2q13.1 (22 770 422-28 560 664)×4 and arr[GRCh37] 15q13.1q13.3(29 009 041-32 444 043)×3 for Fetus 3, covering 24 OMIM genes including UBE3A and 20 protein-coding genes. Additionally, Fetus 3 had a 3.435 Mb duplication in 15q13.1q13.3, covering 11 OMIM genes including CHRNA7 and 20 protein-coding genes. (4) No significant abnormalities were found in the peripheral blood karyotyping for the parents of Fetus 1 or in the SNP-array analysis for the parents of Fetus 3. (5) All three families opted for pregnancy termination. There were no obvious abnormalities in the appearance of Fetus 1 and Fetus 3 after induction, while details of Fetus 2 were unavailable. Conclusion:The three fetuses carried a psu idic(15)(q13)-derived sSMC, leading to increased copy numbers in the 15q11q13 region.

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