OBJECTIVE: To explore the genetic etiology of 46 Chinese pedigrees affected with Hereditary multiple exostoses (HME) and provide genetic counseling and reproductive intervention. METHODS: Whole-exome sequencing and Sanger sequencing were carried out on 87 patients from the 46 pedigrees to analyze the variants of EXT1 and EXT2 genes. Pathogenicity of the variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP). Prenatal diagnosis and preimplantation genetic testing (PGT) were provided for couples with identified pathogenic mutations. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: LL-SC-SG-2014-010). RESULTS: In total 17 and 22 pathogenic variants were respectively identified in the EXT1 and EXT2 genes, among which 5 EXT1 and 12 EXT2 variants were unreported previously. Three patients with no family history were found to harbor de novo variants of the EXT1 gene. Twenty nine couples had opted for PGT or underwent prenatal diagnosis following natural conception, and 17 healthy babies were born. CONCLUSION This study has clarified the genetic etiology of 45 HME pedigrees and identified 17 novel variants, which has enriched the mutational spectrum of the EXT1 and EXT2 genes. Reproductive intervention through PGT and prenatal diagnosis have prevented the recurrence of HME in these families.
Humans ; Female ; Male ; Pedigree ; Exostoses, Multiple Hereditary/diagnosis* ; N-Acetylglucosaminyltransferases/genetics* ; Adult ; Exostosin 1 ; Asian People/genetics* ; Genetic Testing ; Exostosin 2 ; Mutation ; China ; Prenatal Diagnosis ; Pregnancy ; Genetic Counseling ; Preimplantation Diagnosis ; Exome Sequencing ; East Asian People

Objective:To investigate the use of computed tomography (CT) and magnetic resonance imaging (MRI) in diagnosing primary retroperitoneal tumors.Methods:The study included 100 patients suspected of having primary retroperitoneal tumors, who were admitted to Xidian Group Hospital between February 2017 and February 2023. All patients underwent pathological biopsy, with the pathological diagnosis serving as the "gold standard." Additionally, each patient underwent both CT and MRI examinations. The diagnostic value of CT and MRI alone or in combination for primary retroperitoneal tumors was compared. Receiver operating characteristic curve was used to analyze the diagnostic efficacy of CT and MRI alone or in combination for primary retroperitoneal tumors.Results:Among the 100 patients with suspected primary retroperitoneal tumors, 90 were pathologically diagnosed with primary retroperitoneal tumors. These included 21 cases of liposarcoma, 18 of schwannoma, 17 of malignant lymphoma, 14 of malignant fibrous histiocytoma, 12 of leiomyoma, and 8 of lipoma. CT confirmed 81 positive cases, MRI confirmed 83 positive cases, and the combined CT and MRI diagnosis identified 89 cases as positive. Receiver operating characteristic curve analysis revealed that the sensitivity and specificity of the combined CT and MRI diagnosis for primary retroperitoneal tumors were 98.9% and 90.0%, respectively, with an area under the curve of 0.944, which was superior to that of either CT or MRI alone.Conclusions:CT and MRI play a crucial role in the diagnosis of primary retroperitoneal tumors. The combined use of these two imaging techniques significantly improves both the sensitivity and specificity of diagnosis.

Objective:To investigate the role of microRNA-709(miR-709)in erythroid development and its correlation with multiple hematological diseases.Methods:The expression of miR-709 in multiple tissues of mice was detected by qRT-PCR;The expression of miR-709 and other miRNAs in day-14.5 fetal liver cells from mouse embryos was detected by transcriptome microarray analysis;The expression of miR-709 in nucleated red blood cells derived from bone marrow and spleen,and in peripheral blood erythrocytes of mice was detected by magnetic bead sorting combined with qRT-PCR;The expression of miR-709 during erythroid differentiation of murine erythroleukemia(MEL)cells was analyzed by cell culture and qRT-PCR;The expression of miR-709 during erythroid lineage differentiation of mouse erythroid precursor cells derived from fetal livers was analyzed by magnetic bead sorting,flow cytometry,cell culture and qRT-PCR;The expression of miR-709 in peripheral blood of patients with different hematological diseases was measured by qRT-PCR.Results:Among the various tissues examined in mice,miR-709 exhibited the highest expression in peripheral blood,followed by high expression levels in muscle,bone marrow,and liver;In day-14.5 fetal liver cells from mouse embryos,miR-709 was highly expressed,significantly surpassing miR-451,which was most highly expressed in mature red blood cells;In nucleated red blood cells derived from mouse bone marrow and spleen,the expression of miR-709 was higher than that of miR-451,whereas the opposite pattern was observed in peripheral blood;During the differentiation of erythroid precursor cells derived from mouse embryonic liver,the expression level of miR-709 first increased and then decreased;During the differentiation of MEL cells,the expression of miR-709 gradually increased;Compared with the healthy controls,patients with myelodysplastic syndrome(MDS),α-thalassemia and β-thalassemia expressed lower levels of miR-709 in peripheral blood;while the expression of miR-709 in patients with infectious hemolytic anemia(IHA)was higher than that in healthy controls.Conclusion:miR-709 is highly expressed in the early stage of erythropoiesis and exhibits dynamic changes during erythroid development,potentially playing an important role.It is also differentially expressed in different hematological diseases,which is expected to serve as a promising biomarker and therapeutic target in the clinical diagnosis and treatment of hematological diseases.

Objective:To investigate the role of microRNA-709(miR-709)in erythroid development and its correlation with multiple hematological diseases.Methods:The expression of miR-709 in multiple tissues of mice was detected by qRT-PCR;The expression of miR-709 and other miRNAs in day-14.5 fetal liver cells from mouse embryos was detected by transcriptome microarray analysis;The expression of miR-709 in nucleated red blood cells derived from bone marrow and spleen,and in peripheral blood erythrocytes of mice was detected by magnetic bead sorting combined with qRT-PCR;The expression of miR-709 during erythroid differentiation of murine erythroleukemia(MEL)cells was analyzed by cell culture and qRT-PCR;The expression of miR-709 during erythroid lineage differentiation of mouse erythroid precursor cells derived from fetal livers was analyzed by magnetic bead sorting,flow cytometry,cell culture and qRT-PCR;The expression of miR-709 in peripheral blood of patients with different hematological diseases was measured by qRT-PCR.Results:Among the various tissues examined in mice,miR-709 exhibited the highest expression in peripheral blood,followed by high expression levels in muscle,bone marrow,and liver;In day-14.5 fetal liver cells from mouse embryos,miR-709 was highly expressed,significantly surpassing miR-451,which was most highly expressed in mature red blood cells;In nucleated red blood cells derived from mouse bone marrow and spleen,the expression of miR-709 was higher than that of miR-451,whereas the opposite pattern was observed in peripheral blood;During the differentiation of erythroid precursor cells derived from mouse embryonic liver,the expression level of miR-709 first increased and then decreased;During the differentiation of MEL cells,the expression of miR-709 gradually increased;Compared with the healthy controls,patients with myelodysplastic syndrome(MDS),α-thalassemia and β-thalassemia expressed lower levels of miR-709 in peripheral blood;while the expression of miR-709 in patients with infectious hemolytic anemia(IHA)was higher than that in healthy controls.Conclusion:miR-709 is highly expressed in the early stage of erythropoiesis and exhibits dynamic changes during erythroid development,potentially playing an important role.It is also differentially expressed in different hematological diseases,which is expected to serve as a promising biomarker and therapeutic target in the clinical diagnosis and treatment of hematological diseases.

Objective:To investigate the use of computed tomography (CT) and magnetic resonance imaging (MRI) in diagnosing primary retroperitoneal tumors.Methods:The study included 100 patients suspected of having primary retroperitoneal tumors, who were admitted to Xidian Group Hospital between February 2017 and February 2023. All patients underwent pathological biopsy, with the pathological diagnosis serving as the "gold standard." Additionally, each patient underwent both CT and MRI examinations. The diagnostic value of CT and MRI alone or in combination for primary retroperitoneal tumors was compared. Receiver operating characteristic curve was used to analyze the diagnostic efficacy of CT and MRI alone or in combination for primary retroperitoneal tumors.Results:Among the 100 patients with suspected primary retroperitoneal tumors, 90 were pathologically diagnosed with primary retroperitoneal tumors. These included 21 cases of liposarcoma, 18 of schwannoma, 17 of malignant lymphoma, 14 of malignant fibrous histiocytoma, 12 of leiomyoma, and 8 of lipoma. CT confirmed 81 positive cases, MRI confirmed 83 positive cases, and the combined CT and MRI diagnosis identified 89 cases as positive. Receiver operating characteristic curve analysis revealed that the sensitivity and specificity of the combined CT and MRI diagnosis for primary retroperitoneal tumors were 98.9% and 90.0%, respectively, with an area under the curve of 0.944, which was superior to that of either CT or MRI alone.Conclusions:CT and MRI play a crucial role in the diagnosis of primary retroperitoneal tumors. The combined use of these two imaging techniques significantly improves both the sensitivity and specificity of diagnosis.

Objective:To carry out cytogenetic and molecular genetic analysis for two infertile patients carrying rare small supernumerary marker chromosomes (sSMC).Methods:Two infertile patients who received reproductive and genetic counseling at CITIC Xiangya Reproductive and Genetic Hospital on October 31, 2018 and May 10, 2021, respectively were selected as the study subjects. The origin of sSMCs was determined by conventional G banding, fluorescence in situ hybridization (FISH) and copy number variation sequencing (CNV-seq). Microdissection combined with high-throughput whole genome sequencing (MicroSeq) was carried out to determine the fragment size and genomic information of their sSMCs. Results:For patient 1, G-banded karyotyping and FISH revealed that he has a karyotype of mos47, XY, del(16)(p10p12), + mar[65]/46, XY, del(16)(p10p12)[6]/48, XY, del(16)(p10p12), + 2mar[3].ish mar(Tel 16p-, Tel 16q-, CEP 16-, WCP 16+ ). CNV analysis has yielded a result of arr[GRCh37]16p12.1p11.2(24999364_33597595)×1[0.25]. MicroSeq revealed that his sSMC has contained the region of chromosome 16 between 24979733 and 34023115 (GRCh37). For patient 2, karyotyping and reverse FISH revealed that she has a karyotype of mos 47, XX, + mar[37]/46, XX[23].rev ish CEN5, and CNV analysis has yielded a result of seq[GRCh37]dup(5)(p12q11.2)chr5: g(45120001_56000000)dup[0.8]. MicroSeq results revealed that her sSMC has contained the region of chromosome 5 between 45132364 and 55967870(GRCh37). After genetic counseling, both couples had opted in vitro fertilization (IVF) treatment and preimplantation genetic testing (PGT). Conclusion:For individuals harboring sSMCs, it is vital to delineate the origin and structural characteristics of the sSMCs for their genetic counseling and reproductive guidance. Preimplantation genetic testing after microdissection combined with high-throughput whole genome sequencing (MicroSeq-PGT) can provide an alternative treatment for carrier couples with a high genetic risk.

Objective:To analyze the epidemic characteristics and trends of newly reported HIV-infected people among Chinese and Burmese in Dehong Dai and Jingpo Autonomous Prefecture (Dehong Prefecture) of Yunnan Province, China, from 2000 to 2023, and provide evidence for formμlating AIDS prevention and control measures for the Burmese living in Dehong.Methods:The data were obtained from the Chinese Disease Control and Prevention Information System. The distribution of HIV-infected people with different population characteristics was analyzed, and the Joinpoint regression model was used to analyze the temporal trend of crude detection rate in different genders, ethnicities, and ages.Results:From 2000 to 2023, 24 989 newly HIV infections were reported in Dehong Prefecture, of which 14 594 (58.4%) were Chinese and 10 395 (41.6%) were Burmese. Compared with Chinese, Burmese women (32.9%, 3 416/10 395), those aged 20-29 (40.9%, 4 248/10 395), and Jingpo people (26.7%, 2 773/10 395) accounted for a higher proportion. The new diagnosis rate of Chinese nationals increased from 1.0/10 000 in 2000 to 15.4/10 000 in 2004, and then showed a downward trend, falling to 1.2/10 000 in 2023. Among them, compared with other age groups, Dai and other ethnic groups and women, the new diagnosis rate among 20-49 age group, Jingpo and men were relatively higher, at 1.7/10 000, 2.3/10 000 and 1.3/10 000 respectively. Regarding the method of detection, the Chinese HIV-infected people were mainly detected by key population testing (35.7%), while the Burmese HIV-infected people by key population testing (28.9%) and physical examination for entry-exit personnel (25.3%). The transmission routes of both nationalities were mainly heterosexual transmission, but compared with Chinese HIV-infected persons, the proportion of Burmese infected persons through non-marital non-commercial transmission was relatively higher (66.4% vs. 60.6%). The proportion of Chinese nationals with a first CD4 +T lymphocyte (CD4) counts of <200 cells/μl (28.9%) was higher than that of Burmese nationals (19.8%). Conclusions:The rising trend of HIV infection among Chinese and Burmese people in Dehong Prefecture from 2000 to 2023 slowed down. The new diagnosis rate was higher in the 20-49 age group, Jingpo and men. Compared with Burmese HIV-infected people, the proportion of Chinese HIV-infected people with first CD4 counts <200 cells/μl was relatively higher. Comprehensive interventions should be further carried out for Myanmar nationals, and efforts should be made to expand testing for Chinese nationals.

This study aimed to analyze the impact of single nucleotide polymorphism (SNP) of ADCY3 (encoding adenylate cyclase 3) on the outcome of high-intensity interval training (HIIT) on body composition and screen genetic markers sensitive to HIIT in Chinese Han youth. A total of 237 non-regular exercise Han college students were recruited in a 12-week HIIT program, attending sessions 3 times a week. Before and after the HIIT program, their body composition was measured. DNA from the white blood cells was extracted and genotyped. PLINK (V1.09) software was used for quality control screening of SNPs loci, and a linear regression model was constructed to analyze the association between ADCY3 gene SNPs loci and body composition. ANOVA multiple comparisons (LSD) were performed to test the difference between groups, with the significance level set at 0.05. The results showed that: 1) A total of 22 SNPs loci were identified by the gene microarray scanning of ADCY3 gene, with 15 of them meeting the quality control criteria. The rs6753096 locus was associated with the training effect of HIIT on body composition; 2) The rs6753096 locus was not associated with pre-HIIT body composition; 3) Compared with volunteers with TT genotype, those with CT/CC genotype exhibited significant decrease in body mass index (BMI) and total body fat after training (P < 0.05); Male volunteers carrying the C allele had more significant training changes in skeletal muscle and lean body weight, while HIIT was more effective in decreasing body fat in female volunteers with CT/CC genotype; 4) The rs6753096 locus was significantly correlated with body fat sensitivity to HIIT (P = 0.0475), indicating that volunteers with CT/CC genotype were more sensitive to HIIT. In conclusion, 12-week HIIT program effectively improved the body composition of college students. The ADCY3 gene rs6753096 locus is not associated with pre-HIIT body composition, but it is associated with body composition sensitivity to HIIT, with individuals carrying CT/CC genotype showing greater responsiveness to HIIT.
Humans ; Adenylyl Cyclases/genetics* ; Male ; Female ; Body Composition/genetics* ; Polymorphism, Single Nucleotide ; Young Adult ; High-Intensity Interval Training/methods* ; Genotype ; Adult ; Adolescent

Objective:To investigate the effects of 3-methyladenine(3-MA)on extracellular matrix deposition in early diabetic nephropathy(DN)and its mechanism.Methods:A streptozotocin(STZ)-induced type 1 diabetes mouse model was used, and the mice were divided into vehicle control group, diabetes group(STZ group), 3-MA group, and chloroquine(CQ)group, 8 mice in each group. After 6 weeks of intervention, both kidneys were harvested, and the kidney-to-body weight ratio was recorded. Western blotting was performed to detect protein expressions of renal cortex fibronectin, α-smooth muscle actin(α-SMA), LC3, Beclin 1, p62, and vascular endothelial growth factor(VEGF). Immunohistochemistry was used to observe kidney fibronectin staining. Bioinformatics analysis was conducted on shared genes between diabetic nephropathy(DN)gene targets and 3-MA predicted gene targets.Results:Both 3-MA and CQ exhibited certain hypoglycemic effects in diabetic mice. Compared to the STZ group, the kidney-to-body weight ratio decreased in the 3-MA group( P<0.05). Western blotting showed that 3-MA reduced the expression of renal cortex matrix-related proteins fibronectin and α-SMA in diabetic mice( P<0.05 or P<0.01). Immunohistochemistry also revealed that 3-MA reduced fibronectin staining in the kidneys of diabetic mice. Both 3-MA and CQ inhibited the protein expression of renal cortex Beclin 1 in diabetic mice(both P<0.05), while 3-MA increased the expression of renal cortex p62( P<0.05). Bioinformatics analysis indicated a connection between shared genes of DN gene targets and 3-MA predicted gene targets with the VEGF signaling pathway. Western blotting results further showed that 3-MA reduced renal cortex VEGF expression in diabetic mice( P<0.01). Conclusion:3-MA can alleviate extracellular matrix deposition in the kidneys of early DN mice by inhibiting the VEGF signaling pathway.

OBJECTIVES: To establish a carbofuran intragastric administration death model in rabbits, and to observe the postmortem distribution and postmortem redistribution of carbofuran-7-phenyl glucuronic acid (Glu-7PH) in rabbits. METHODS: The postmortem distribution: Rabbits were given an administration of 1/2LD50, LD50, 2LD50 carbofuran. Dead rabbits were dissected immediately. Rabbits that had remained alive 2 hours were sacrificed by carbon dioxide (CO₂) inhalation and dissected immediately. The myocardium, cardiac blood, liver, spleen, lung, kidney, brain and right hindlimb muscle were collected. The postmortem redistribution: After giving an administration of 4LD50 carbofuran, the myocardium, cardiac blood, liver, spleen, lung, kidney, brain, and right hindlimb muscle were collected at 0, 12, 24, 48, and 72 h postmortem in supine position at 15 ℃ room temperature. The quantity of Glu-7PH was determined by LC-MS/MS. RESULTS: The postmortem distribution: Among the three dose groups, there were significant differences in the quantities of Glu-7PH in different tissues. The postmortem redistribution: There was no significant difference in the Glu-7PH quantities in cardiac blood, mycardium, spleen, kidney, brain and right hindlimb muscle, but there was a significant difference in the Glu-7PH quantities in the liver and lung. CONCLUSIONS The mycardium, cardiac blood, liver, lung, kidney, brain and hindlimb muscle of rabbits can be used as appropriate samples for Glu-7PH detection. However, it should be noted that Glu-7PH was redistributed postmortem in rabbit liver and lung.
Animals ; Rabbits ; Carbofuran ; Chromatography, Liquid ; Postmortem Changes ; Tandem Mass Spectrometry ; Autopsy