Objective:To investigate the clinical characteristics and genetic etiology of a child with Cortical dysplasia, complex, with other brain malformations 4 (CDCBM4) and epilepsy due to a TUBG1 gene variant. Methods:A child diagnosed with CDCBM4 and epilepsy at the Children′s Medical Center of the Affiliated Hospital of Guangdong Medical University in May 2024 was selected as the study subject. Clinical data were retrospectively analyzed. Peripheral venous blood samples were collected from the child and her parents for genomic DNA extraction. Trio-based whole-exome sequencing (WES) was performed, and candidate variants were validated by Sanger sequencing. According to the Standards and Guidelines for the Interpretation of Sequence Variants established by the American College of Medical Genetics and Genomics (ACMG), candidate variants were classified for pathogenicity. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Guangdong Medical University (Ethics No.: PJ2021-097).Results:The child, a 4-month-old female infant, had no special facial features, normal limb muscle strength, and increased muscle tone of infantile onset, with generalized tonic-clonic seizures as the main manifestation. During seizures, she exhibited head retroflexion, tightly closed eyes, and tonic convulsions of the limbs, occurring approximately 2-3 times per day. Electroencephalogram suggested bilateral anterior predominant medium-to-high amplitude 7-8 Hz mixed rhythm discharges. Head MRI revealed ventricular system dilatation and pachygyria. Trio-WES results indicated that the child has harbored a TUBG1 gene variant of c. 776C>T (p.Ser259Leu). Sanger sequencing verification showed that neither of her parents had carried the same variant, confirming it as de novo in origin. According to the ACMG guidelines, the variant was rated as pathogenic (PS2+ PS3+ PM2_Supporting+ PP3). Combining the child′s clinical phenotype, the child was diagnosed as CDCBM4 with epilepsy. Conclusion:Children with CDCBM4 and epilepsy due to TUBG1 gene variants may show pachygyria or agyria and commonly present with intellectual and motor developmental delays and seizure disorders of variable severity. The heterozygous TUBG1 c. 776C>T (p.Ser259Leu) variant is likely the genetic etiology underlying this disorder. The results of this study has expanded the mutational spectrum of the TUBG1 gene associated with CDCBM4 and epilepsy.

OBJECTIVE: To investigate the clinical characteristics and genetic etiology of a child with Cortical dysplasia, complex, with other brain malformations 4 (CDCBM4) and epilepsy due to a TUBG1 gene variant. METHODS: A child diagnosed with CDCBM4 and epilepsy at the Children's Medical Center of the Affiliated Hospital of Guangdong Medical University in May 2024 was selected as the study subject. Clinical data were retrospectively analyzed. Peripheral venous blood samples were collected from the child and her parents for genomic DNA extraction. Trio-based whole-exome sequencing (WES) was performed, and candidate variants were validated by Sanger sequencing. According to the Standards and Guidelines for the Interpretation of Sequence Variants established by the American College of Medical Genetics and Genomics (ACMG), candidate variants were classified for pathogenicity. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Guangdong Medical University (Ethics No.: PJ2021-097). RESULTS: The child, a 4-month-old female infant, had no special facial features, normal limb muscle strength, and increased muscle tone of infantile onset, with generalized tonic-clonic seizures as the main manifestation. During seizures, she exhibited head retroflexion, tightly closed eyes, and tonic convulsions of the limbs, occurring approximately 2-3 times per day. Electroencephalogram suggested bilateral anterior predominant medium-to-high amplitude 7-8 Hz mixed rhythm discharges. Head MRI revealed ventricular system dilatation and pachygyria. Trio-WES results indicated that the child has harbored a TUBG1 gene variant of c.776C>T (p.Ser259Leu). Sanger sequencing verification showed that neither of her parents had carried the same variant, confirming it as de novo in origin. According to the ACMG guidelines, the variant was rated as pathogenic (PS2+PS3+PM2_Supporting+PP3). Combining the child's clinical phenotype, the child was diagnosed as CDCBM4 with epilepsy. CONCLUSION Children with CDCBM4 and epilepsy due to TUBG1 gene variants may show pachygyria or agyria and commonly present with intellectual and motor developmental delays and seizure disorders of variable severity. The heterozygous TUBG1 c.776C>T (p.Ser259Leu) variant is likely the genetic etiology underlying this disorder. The results of this study has expanded the mutational spectrum of the TUBG1 gene associated with CDCBM4 and epilepsy.
Humans ; Female ; Epilepsy/genetics* ; Malformations of Cortical Development/genetics* ; Infant ; Phenotype ; Exome Sequencing ; Microtubule-Associated Proteins/genetics*

OBJECTIVE: To explore the clinical phenotype and genetic etiology of a child with Ehlers-Danlos syndrome, spondylodysplastic type 2 (EDSSPD2). METHODS: A child who was admitted to the Children's Medical Center of the Affiliated Hospital of Guangdong Medical University in July 2024 for "delayed motor development for 1 and a half year" was selected as the study subject. Clinical data of the child was collected, including medical history, family history, and results of auxiliary examinations. Peripheral venous blood samples were collected from the child and his two brothers and both parents. Genomic DNA was extracted from the child and his family members and subjected to whole-exome sequencing (WES) and copy number variation (CNV) analysis. Sanger sequencing was used to verify the parental origin of the candidate variants. Multiple protein function prediction software tools, including SIFT, PolyPhen-2, and REVEL, were used to assess the impact of candidate variants on the protein function. Based on protein database information from UniProt, a two dimensional structural schematic of the target protein was generated. The pathogenicity of the variants was classified based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Relevant literature on the B3GALT6 gene variants leading to EDSSPD2 was retrieved from CNKI, Wanfang Data Knowledge Service Platform, and PubMed databases. The procedures followed in this study were reviewed and approved by the Medical Ethics Committee of Affiliated Hospital of Guangdong Medical University (Ethics No.：PJ2021-097). RESULTS: The proband was a 2-year-old male with an onset in infancy. The main clinical manifestations included loose skin, scoliosis and kyphosis, generalized hypermobility of joints, and motor developmental delay. WES has revealed two compound heterozygous variants of the B3GALT6 gene (NM_080605.4): c.766C>T (p.Arg256Trp) and c.962G>A (p.Cys321Tyr). Sanger sequencing verification showed that the c.766C>T and c.962G>A variants were respectively derived from his phenotypically normal father and mother. Bioinformatics analysis showed that for the c.766C>T (p.Arg256Trp) variant, the Arg256 site is located within the galactosyltransferase catalytic domain (GalT domain) of the β3GalT6 protein. According to the ACMG guidelines, the c.766C>T variant was classified as a likely pathogenic (PS3+PM2_supporting+PM3+PP3), and the c.962G>A was classified as a variant of unknown significance (PM2_Supporting+PM3+PP3). By following the pre-set literature retrieval strategy, a total of 12 articles related to B3GALT6 gene variants were identified (11 English and 1 Chinese), which involved a total of 71 patients. Among these, 4 reports (involving 20 patients) involved B3GALT6 gene variants leading to EDSSPD2. Among the 18 live-born EDSSPD2 patients (including the proband in this study), common clinical manifestations have included scoliosis (88.9%, 16/18), generalized hypotonia (83.3%, 15/18), and soft and lax skin (66.7%, 12/18). Some patients already showed skeletal abnormalities on prenatal ultrasound scan (22.2%, 4/18), while a few presented with cervical instability (16.7%, 3/18). One child had deceased at 18 months of age due to hypoxia caused by tracheomalacia and tracheal compression due to scoliosis. Among the 23 reported EDSSPD2 related B3GALT6 variant sites, missense variants were the most common (78.3%, 18/23), followed by nonsense variants (21.7%, 5/23). CONCLUSION Above finding has enriched the clinical and mutational spectra of EDSSPD2. Early genetic testing has important clinical value for the diagnosis, differential diagnosis, and genetic counseling of this disease.
Humans ; Male ; Ehlers-Danlos Syndrome/genetics* ; Pedigree ; N-Acetylgalactosaminyltransferases/genetics* ; Asian People/genetics* ; DNA Copy Number Variations ; Exome Sequencing ; Female ; Child ; Child, Preschool ; Phenotype ; Mutation ; China ; East Asian People ; Galactosyltransferases

Objective:To investigate the clinical characteristics and genetic etiology of a child with Cortical dysplasia, complex, with other brain malformations 4 (CDCBM4) and epilepsy due to a TUBG1 gene variant. Methods:A child diagnosed with CDCBM4 and epilepsy at the Children′s Medical Center of the Affiliated Hospital of Guangdong Medical University in May 2024 was selected as the study subject. Clinical data were retrospectively analyzed. Peripheral venous blood samples were collected from the child and her parents for genomic DNA extraction. Trio-based whole-exome sequencing (WES) was performed, and candidate variants were validated by Sanger sequencing. According to the Standards and Guidelines for the Interpretation of Sequence Variants established by the American College of Medical Genetics and Genomics (ACMG), candidate variants were classified for pathogenicity. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Guangdong Medical University (Ethics No.: PJ2021-097).Results:The child, a 4-month-old female infant, had no special facial features, normal limb muscle strength, and increased muscle tone of infantile onset, with generalized tonic-clonic seizures as the main manifestation. During seizures, she exhibited head retroflexion, tightly closed eyes, and tonic convulsions of the limbs, occurring approximately 2-3 times per day. Electroencephalogram suggested bilateral anterior predominant medium-to-high amplitude 7-8 Hz mixed rhythm discharges. Head MRI revealed ventricular system dilatation and pachygyria. Trio-WES results indicated that the child has harbored a TUBG1 gene variant of c. 776C>T (p.Ser259Leu). Sanger sequencing verification showed that neither of her parents had carried the same variant, confirming it as de novo in origin. According to the ACMG guidelines, the variant was rated as pathogenic (PS2+ PS3+ PM2_Supporting+ PP3). Combining the child′s clinical phenotype, the child was diagnosed as CDCBM4 with epilepsy. Conclusion:Children with CDCBM4 and epilepsy due to TUBG1 gene variants may show pachygyria or agyria and commonly present with intellectual and motor developmental delays and seizure disorders of variable severity. The heterozygous TUBG1 c. 776C>T (p.Ser259Leu) variant is likely the genetic etiology underlying this disorder. The results of this study has expanded the mutational spectrum of the TUBG1 gene associated with CDCBM4 and epilepsy.

Stem cells have been a hot spot in medical research for a long time and have unique advantages in tissue repair, diagnosis and treatment of diseases. With the development of regenerative medicine, stem cells have been widely studied and applied in reproductive medicine, such as improving ovarian function and repairing endometrial damage. These efforts are achieved primarily through the use of mesenchymal stem cells(MSCs) from a variety of sources. However, the application of stem cells also faces problems such as low cell retention rate and medical ethics. This article focuses on the research progress and clinical application of MSCs (not involving embryonic stem cells) in the field of female reproductive medicine.
Humans ; Female ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells ; Regenerative Medicine ; Signal Transduction

Objective:To investigate the feasibility of a novel in vitro fertilization (IVF) strategy with levonorgestrel intrauterine system (Mirena) in situ in infertility patients after successful conservative treatment of early well-differentiated endometrial adenocarcinoma (EC) and atypical endometrial hyperplasia (AEH). Methods:The clinical characteristics of infertility patients after a complete regression of previous EC and AEH who underwent IVF with a Mirena in situ from March 2018 to December 2019 in Center for Gynecological Endocrinology & Reproductive Medicine, Peking Union Medical College Hospital were retrospectively analyzed. These patients underwent one or more cycles to harvest at least 4 blastocysts cryopreserved, before removing the Mirena and re-evaluating the endometrium. Then the outcomes of frozen-thawed embryo transfer (FET) were commenced. Results:A total of 20 patients were included with a median age of 33 years. The complete regression of endometrial lesion was achieved at 4.3 months. Thirty-four IVF cycles were conducted in total, leading to a median oocytes retrieved of 8. We had attempted 21 embryo trasfer but only 14 cycles were effective, and 5 patients got clinical pregnancy and 2 patients had ongoing pregnancy.Conclusion:It is a supposedly practical way that IVF with the Mirena until pooling enough blastocysts before removing the device and initiating embryo trasfer for assisting reproduction and endometrial protection in patients after fertility-sparing treatment of EC or AEH.

Objective:To investigate the feasibility of a novel in vitro fertilization (IVF) strategy with levonorgestrel intrauterine system (Mirena) in situ in infertility patients after successful conservative treatment of early well-differentiated endometrial adenocarcinoma (EC) and atypical endometrial hyperplasia (AEH). Methods:The clinical characteristics of infertility patients after a complete regression of previous EC and AEH who underwent IVF with a Mirena in situ from March 2018 to December 2019 in Center for Gynecological Endocrinology & Reproductive Medicine, Peking Union Medical College Hospital were retrospectively analyzed. These patients underwent one or more cycles to harvest at least 4 blastocysts cryopreserved, before removing the Mirena and re-evaluating the endometrium. Then the outcomes of frozen-thawed embryo transfer (FET) were commenced. Results:A total of 20 patients were included with a median age of 33 years. The complete regression of endometrial lesion was achieved at 4.3 months. Thirty-four IVF cycles were conducted in total, leading to a median oocytes retrieved of 8. We had attempted 21 embryo trasfer but only 14 cycles were effective, and 5 patients got clinical pregnancy and 2 patients had ongoing pregnancy.Conclusion:It is a supposedly practical way that IVF with the Mirena until pooling enough blastocysts before removing the device and initiating embryo trasfer for assisting reproduction and endometrial protection in patients after fertility-sparing treatment of EC or AEH.

Objective:To evaluate the oncologic outcomes of different laparoscopic radical hysterectomy.Methods:From January 2011 to December 2014, the laparoscopic operation cases of cervical cancer at stage Ⅰb1, Ⅰb2, Ⅱa1 and Ⅱa2, including the histologic subtypes of squamous-cell carcinoma, adenocarcinoma and adenosquamous carcinoma, were collected in five clinical centers. The data were divided into two groups according to the surgical procedures, that is, modified laparoscopic-vaginal radical hysterectomy (mLVRH) and total laparoscopic radical hysterectomy (TLRH). The overall survival rate (OS), disease-free survival rate (DFS) at 5 years were retrospectively analyzed in this study.Results:There were 674 cases in total, including 377 cases of mLVRH, 297 cases of TLRH. (1) The OS at 5 years: the mLVRH was 96.1% and the TLRH was 92.0%, and the mLVRH was higher than that of TLRH （ P=0.010）. Stratify analysis， including stage of disease （Ⅰb1 and Ⅱa1）， histologic subtypes （squamous-cell carcinoma, adenocarcinoma）， lymph node metastasis， revealed that, ① Stage of disease: in stage Ⅰb1, the OS at five years of mLVRH was higher than that in TLRH group （98.6% vs 93.6%, P=0.012）. In stage Ⅱa1, there was significant difference between the two groups, the OS at five years of mLVRH and TLRH were 93.6% and 77.6% （ P=0.007）. ② Histologic subtypes: for the OS at five years of squamous-cell carcinoma, mLVRH and TLRH were 96.1% and 92.3%, and there was significant difference （ P=0.046）； for adenocarcinoma, the OS at five years were 91.0% and 88.6%， and there was no difference between two groups （ P=0.230）. ③ Lymph node metastasis： the mLVRH and TLRH with lymph node metastasis, the OS at five years were 98.6% and 96.4%; the mLVRH and TLRH without lymph node metastasis, the OS at five years were 89.3% and 80.8%. There were no significant differences between the two groups,respectively ( P=0.156， P=0.093）. (2) The DFS at 5 years: there was no significant difference between mLVRH and TLRH (94.1% vs 90.9%, P=0.220). Stratify analysis for stage of disease, the mLVRH group was higher than that in the TLRH group in stage Ⅰb1 (97.0% vs 92.8%, P=0.039). However, for stage Ⅱa1, there was no significant difference between mLVRH and TLRH group （88.2% vs 75.8%, P=0.074）. Conclusions:The results of this retrospective study indicated that different laparoscopy surgical procedures had diverse oncologic outcomes. The OS at 5 years of the mLVRH is superior to the TLRH. The DFS at 5 years in Ⅰb1 stage, the mLVRH is higher than the TLRH. Therefore, the modified laparoscopy is still an alternative surgery for early cervical cancer patients when following the principle of no-tumor-exposure.

Objective To study the changes of six sex hormones corresponding to the follicle growth during the normal menstrual cycle of Chinese women.Methods Thirty Chinese women with regular menstrual period and average age of (28.8±3.2) years were selected for the study by Peking Union Medical College Hospital in September,2010.Growth of follicles was monitored by using transvaginal sonography.Six sex hormones,including follicle-stimulating hormone (FSH),luteinizing hormone (LH),estradiol (E2),progesterone (P),testosterone (T),and prolactin (PRL) were measured by chemoluminescence immunoassay every day during a menstrual cycle.Nonparametric statistical analysis was used.ResultsMenstrual cycle of all the patients was in the range of 25 to 39 d,with mean of (29.5 ± 3.1) d.Length of follicular phase and luteal phase was 15.3 and 14.4 d,respectively.Number of days from antral follicle to emergence of dominant follicle,and from the latter to ovulation,was 6.2 and 8.9 d,respectively.Average diameter of preovulatory follicle was 19.33 mm.Both FSH and LH reached peak on the day before ovulation.P started to increase before ovulation and remained at a high plateau from 6th to 9th day after ovulation.Both PRL and T reached peak after ovulation,near the end of a menstrual cycle.Conclusions A small rise of LH and P emerges just 1 to 2 d before ovulation,indicating the maturing of follicle.PRL and T shows cyclic changes as follicle grows.Therefore,PRL and T levels should be measured in the early follicle phases in the clinical practice so that leading the impact of menstrual cycle minimal.

Objective To study the effects of electroacupuncture (EA) on the proliferation and differentiation of neural stem cells (NSCs),and to explore any effect of EA in neurological rehabilitation and its mechanism.Methods Middle cerebral artery occlusion (MCAO) was used to establish a model of cerebral infarction in 120 Wistar rats.They were then randomly divided into a treatment group and a control group,both of which were further subdivided into 1,3,7,14,21 and 28 day sub-groups with 10 in each sub-group.Bromodeoxyuridine (Brdu) was given at the 1st,2nd,6th,13th,20th and 27th day to detect any proliferation and differentiation of NSCs.After 7 days the motor function of the two groups was evaluated using a beam walking test.Rats were sacrificed at the different time points and Brdu labeled cells and nestin-positive cells were determined by immunohistochemistry.The level of basic fibroblast growth factor-2 (FGF-2) mRNA was determined by in-situ hybridization.The results were analyzed using a micro-image analysis system.Results The Brdu-labeled cell counts and nestin-positive cells were significantly different between the treatment and control groups at each time point.Motor function improved significantly in the treatment group with EA stimulation compared with the control group,but there was no significant difference between the 21 day and 28 day sub-groups in the treatment group.The expression levels of bFGF-2 mRNA were significantly different between the treatment and control groups at the early time points (up to the 14th day).Conclusions EA can promote proliferation of NSCs and increase the expression of FGF-2 mRNA,particularly early after cerebral infarction.It may be one of mechanisms of EA's effectiveness in treating ischemic stroke.