Objective:To investigate the steady-state mechanism of interconversion between the SMN1 and SMN2 genes in a normal population. Methods:Fluorescence PCR capillary electrophoresis was employed to assess gene conversion and copy number variation of SMN1 and SMN2 in a cohort of 1, 133 healthy individuals (including 256 males and 877 females) recruited between 2019 and 2023. This study was approved by the Ethics Committee of Henan Provincial People′s Hospital (Ethics No.: 2019-134). Results:No significant gender difference was observed in the single copy carrying rate of SMN1. The probability of conversion from SMN1 to SMN2 was determined to be 3.2% for females, 2.7% for males, and 3.1% for the overall population. The probability of conversion from SMN2 to SMN1 was found to be 5.5% for females, 6.3% for males, and 5.6% for the overall population. No statistically significant difference was found in the conversion probability between different genders ( P>0.05). Among the 99 cases of gene conversion, the SMN1 gene predominantly exhibited a copy number of 2 (97.0%), with the remainder having 3 copies (3%). The SMN2 gene primarily showed a copy number of 2 (72.7%), with the rest having 1 copy (27.3%). Conclusion:Gene conversion tends to normalize the copy numbers of both SMN1 and SMN2 genes towards 2. However, SMN1 exhibited a higher priority over SMN2, causing the copy numbers approaching two.

Objective:To analyze the genetic variant characteristics of primary immunodeficiency diseases (PID) in families from Henan Province.Methods:This study conducted a retrospective analysis of 19 PID pedigrees referred to the Prenatal Diagnosis Center at Henan Provincial People's Hospital between January 2016 and March 2024. Among the 19 families, 13 underwent prenatal diagnosis at our hospital, while the remaining six received genetic counseling based on third-party genetic testing reports (confirmed by our institution's laboratory). The clinical data from these families were analyzed, and descriptive statistical analysis was applied to the data.Results:Among the 19 PID families, there were seven cases of combined immunodeficiency, three immunodeficiency syndromes, three phagocyte deficiencies, three antibody-dominant immunodeficiencies, and three immunodysregulatory disorders, involving a total of 12 genes ( IL2RG, ADA, RAG2, STAT3, SMARCAL1, ATM, POLA1, CYBB, BTK, RAB27A, LRBA, IL10R). A total of 25 genetic variants were identified, including 11 novel variants not previously documented in the ClinVar and HGMD professional databases. The novel variants comprised: IL2RG gene mutations (Exon5_8del and c.903_904delinsCT leading to p.E302*), ADA gene mutation (c.884A>G resulting in p.D295G), RAG2 gene mutation (c.513dupA causing p.W172Mfs3), POLA1 gene mutation (c.25+5G>C), CYBB gene mutations (c.824G>A/p.G275D and c.472A>T/p.K158), BTK gene mutations (c.522_523insC/p.A175fs and c.142-2A>C), and RAB27A gene mutations (c.121delA/p.T41fs and c.272delA/p.D91fs). Among the 13 families undergoing prenatal diagnosis, genetic testing revealed that 11 fetuses carried wild-type genes, and these families elected to continue their pregnancies. One fetus exhibited identical genetic variants to the proband and received a clinical diagnosis consistent with the genetic disorder, while another fetus demonstrated chromosomal copy number variations. In both of these latter cases, the families opted for pregnancy termination. Conclusion:This study identified 11 unreported variants across seven genes, highlighting the need for further expansion of PID genetic variant databases.

OBJECTIVE: To investigate the steady-state mechanism of interconversion between the SMN1 and SMN2 genes in a normal population. METHODS: Fluorescence PCR capillary electrophoresis was employed to assess gene conversion and copy number variation of SMN1 and SMN2 in a cohort of 1,133 healthy individuals (including 256 males and 877 females) recruited between 2019 and 2023. This study was approved by the Ethics Committee of Henan Provincial People's Hospital (Ethics No.: 2019-134). RESULTS: No significant gender difference was observed in the single copy carrying rate of SMN1. The probability of conversion from SMN1 to SMN2 was determined to be 3.2% for females, 2.7% for males, and 3.1% for the overall population. The probability of conversion from SMN2 to SMN1 was found to be 5.5% for females, 6.3% for males, and 5.6% for the overall population. No statistically significant difference was found in the conversion probability between different genders (P > 0.05). Among the 99 cases of gene conversion, the SMN1 gene predominantly exhibited a copy number of 2 (97.0%), with the remainder having 3 copies (3%). The SMN2 gene primarily showed a copy number of 2 (72.7%), with the rest having 1 copy (27.3%). CONCLUSION Gene conversion tends to normalize the copy numbers of both SMN1 and SMN2 genes towards 2. However, SMN1 exhibited a higher priority over SMN2, causing the copy numbers approaching two.
Humans ; Male ; Female ; Survival of Motor Neuron 2 Protein/genetics* ; Survival of Motor Neuron 1 Protein/genetics* ; Gene Conversion ; DNA Copy Number Variations/genetics* ; Adult ; Middle Aged ; Gene Dosage

OBJECTIVE: To analyze a Chinese pedigree affected with Non-syndromic autosomal recessive deafness type 12 (NFNB12), validate the function of candidate variants, and explore the underlying mechanisms. METHODS: A NFNB12 pedigree presented at Henan Provincial People's Hospital in February 2023 was selected as the study subject. Whole exome sequencing (WES) was carried out, and candidate variant was verified by Sanger sequencing of the pedigree members. Reverse transcription polymerase chain reaction (RT-PCR) was used to determine the level of mRNA transcription in the peripheral blood samples from the pedigree members, and protein expression was evaluated with Western blotting assay. This study was approved by Medical Ethics Committee of Henan Provincial People's Hospital (Ethics No.: 2019-134). RESULTS: WES analysis revealed that the proband has harbored homozygous c.6688delG (p.Ala2230Profs*4) variant of the CDH23 gene, for which both parents were identified as heterozygous carriers. RT-PCR analysis demonstrated the sole presence of the variant mRNA in the proband, and both the variant and wild-type mRNAs in both parents. Furthermore, Western blotting analysis indicated that the proband had exclusively expressed the truncated CDH23 protein, while both the normal and truncated forms of the protein were noted in her parents. CONCLUSION The c.6688delG (p.Ala2230Profs*4) variant of the CDH23 gene probably underlay the pathogenesis of NFNB12 in this pedigree. The loss of function of the CDH23 gene resulting from this variant is not related with nonsense-mediated mRNA decay, but rather production of a truncated protein. Above finding has not only enriched the mutational spectrum of the CDH23 gene and offered a method for investigating the function of its variants using peripheral blood samples, but also delineated the molecular basis for the loss of function, which has provided crucial evidence for genetic counseling and prenatal diagnosis for this family.
Humans ; Pedigree ; Male ; Female ; Asian People/genetics* ; Cadherins/genetics* ; Exome Sequencing ; Deafness/genetics* ; Mutation ; China ; Adult ; Cadherin Related Proteins ; Hearing Loss, Sensorineural/genetics* ; East Asian People

The key points of the update of the content related to colorectal cancer and anal cancer in the Chinese Anti-Cancer Association (CACA) Guidelines for Integrative Oncology 2025 Edition (hereinafter referred to as the CACA 2025 Guidelines) include 4 aspects. In terms of epidemiology, the latest data on the incidence and mortality of colorectal cancer in China have been updated, and the recommended screening age has been adjusted. In diagnosis, the application of enhanced MRI examination in diagnosis has been optimized, and the recommendation for peripheral blood microsatellite instability (MSI) detection has been added. In terms of treatment, in surgical treatment, the total mesorectal excision of the right colon, the safety of the Natural Orifice Specimen Extraction Surgery (NOSES) technique, the applicable range of robotic surgery, and the high-level evidence-based medical evidence of transanal total mesorectal excision (taTME) have been newly added, and the principles of surgical treatment have been added as well. In medical treatment, the role of circulating tumor DNA (ctDNA) in treatment decision-making has been supplemented. The application of dual immunotherapy in advanced patients has been recommended, and the application of third-line and subsequent-line treatments in advanced patients has been newly added. The guidelines improved the principle of preoperative neoadjuvant radiotherapy for rectal cancer, changed the indication of short-course radiotherapy, and added a variety of chemoradiotherapy combinations and recommendations for the timing of surgery. In addition, the follow-up programs for colorectal cancer and anal canal cancer are clarified, and nutritional therapy, traditional Chinese medicine rehabilitation therapy and nursing care for sequelae are emphasized, which provide more scientific and comprehensive guidance for the diagnosis and treatment of colorectal cancer and anal canal cancer.

The key points of the update of the content related to colorectal cancer and anal cancer in the Chinese Anti-Cancer Association (CACA) Guidelines for Integrative Oncology 2025 Edition (hereinafter referred to as the CACA 2025 Guidelines) include 4 aspects. In terms of epidemiology, the latest data on the incidence and mortality of colorectal cancer in China have been updated, and the recommended screening age has been adjusted. In diagnosis, the application of enhanced MRI examination in diagnosis has been optimized, and the recommendation for peripheral blood microsatellite instability (MSI) detection has been added. In terms of treatment, in surgical treatment, the total mesorectal excision of the right colon, the safety of the Natural Orifice Specimen Extraction Surgery (NOSES) technique, the applicable range of robotic surgery, and the high-level evidence-based medical evidence of transanal total mesorectal excision (taTME) have been newly added, and the principles of surgical treatment have been added as well. In medical treatment, the role of circulating tumor DNA (ctDNA) in treatment decision-making has been supplemented. The application of dual immunotherapy in advanced patients has been recommended, and the application of third-line and subsequent-line treatments in advanced patients has been newly added. The guidelines improved the principle of preoperative neoadjuvant radiotherapy for rectal cancer, changed the indication of short-course radiotherapy, and added a variety of chemoradiotherapy combinations and recommendations for the timing of surgery. In addition, the follow-up programs for colorectal cancer and anal canal cancer are clarified, and nutritional therapy, traditional Chinese medicine rehabilitation therapy and nursing care for sequelae are emphasized, which provide more scientific and comprehensive guidance for the diagnosis and treatment of colorectal cancer and anal canal cancer.

Objective:To investigate the steady-state mechanism of interconversion between the SMN1 and SMN2 genes in a normal population. Methods:Fluorescence PCR capillary electrophoresis was employed to assess gene conversion and copy number variation of SMN1 and SMN2 in a cohort of 1, 133 healthy individuals (including 256 males and 877 females) recruited between 2019 and 2023. This study was approved by the Ethics Committee of Henan Provincial People′s Hospital (Ethics No.: 2019-134). Results:No significant gender difference was observed in the single copy carrying rate of SMN1. The probability of conversion from SMN1 to SMN2 was determined to be 3.2% for females, 2.7% for males, and 3.1% for the overall population. The probability of conversion from SMN2 to SMN1 was found to be 5.5% for females, 6.3% for males, and 5.6% for the overall population. No statistically significant difference was found in the conversion probability between different genders ( P>0.05). Among the 99 cases of gene conversion, the SMN1 gene predominantly exhibited a copy number of 2 (97.0%), with the remainder having 3 copies (3%). The SMN2 gene primarily showed a copy number of 2 (72.7%), with the rest having 1 copy (27.3%). Conclusion:Gene conversion tends to normalize the copy numbers of both SMN1 and SMN2 genes towards 2. However, SMN1 exhibited a higher priority over SMN2, causing the copy numbers approaching two.

Objective:To analyze the genetic variant characteristics of primary immunodeficiency diseases (PID) in families from Henan Province.Methods:This study conducted a retrospective analysis of 19 PID pedigrees referred to the Prenatal Diagnosis Center at Henan Provincial People's Hospital between January 2016 and March 2024. Among the 19 families, 13 underwent prenatal diagnosis at our hospital, while the remaining six received genetic counseling based on third-party genetic testing reports (confirmed by our institution's laboratory). The clinical data from these families were analyzed, and descriptive statistical analysis was applied to the data.Results:Among the 19 PID families, there were seven cases of combined immunodeficiency, three immunodeficiency syndromes, three phagocyte deficiencies, three antibody-dominant immunodeficiencies, and three immunodysregulatory disorders, involving a total of 12 genes ( IL2RG, ADA, RAG2, STAT3, SMARCAL1, ATM, POLA1, CYBB, BTK, RAB27A, LRBA, IL10R). A total of 25 genetic variants were identified, including 11 novel variants not previously documented in the ClinVar and HGMD professional databases. The novel variants comprised: IL2RG gene mutations (Exon5_8del and c.903_904delinsCT leading to p.E302*), ADA gene mutation (c.884A>G resulting in p.D295G), RAG2 gene mutation (c.513dupA causing p.W172Mfs3), POLA1 gene mutation (c.25+5G>C), CYBB gene mutations (c.824G>A/p.G275D and c.472A>T/p.K158), BTK gene mutations (c.522_523insC/p.A175fs and c.142-2A>C), and RAB27A gene mutations (c.121delA/p.T41fs and c.272delA/p.D91fs). Among the 13 families undergoing prenatal diagnosis, genetic testing revealed that 11 fetuses carried wild-type genes, and these families elected to continue their pregnancies. One fetus exhibited identical genetic variants to the proband and received a clinical diagnosis consistent with the genetic disorder, while another fetus demonstrated chromosomal copy number variations. In both of these latter cases, the families opted for pregnancy termination. Conclusion:This study identified 11 unreported variants across seven genes, highlighting the need for further expansion of PID genetic variant databases.

Objective To observe the value of deep learning model for automatically segmenting prostate on large-field T2WI based on integrated 68Ga-prostate specific membrane antigen(PSMA)PET/MRI.Methods Ninety male patients with prostate tumors who underwent 68Ga-PSMA PET/MRI were retrospectively enrolled and divided into training set(n=72)and validation set(n=18)at the ratio of 4∶1.Models were established based on 3D SegResNet and 3D Unet deep learning neural networks,respectively.Taken physicians'manual segmentation results as reference standards,the performances of models for segmenting the peripheral zone(PZ)and central zone(CZ)+transition zone(TZ)of prostate on large-field T2WI were evaluated.Results In both training and validation sets,the Dice similarity coefficient(DSC)of 3D SegResNet deep learning model for segmenting prostate on T 2WI were both higher than that of 3D Unet model(both P＜0.05),the 95％Hausdorff distance(HD95)of SegR esNet deep learning model for segmenting prostate CZ+TZ was lower than that of 3D Unet model(both P＜0.05),while DSC and HD95 of these 2 models for segmenting prostate CZ+TZ were superior to PZ(all P＜0.05).Conclusion 3D SegResNet deep learning model could be used to automatically segment prostate on large-field T2WI based on integrated 68Ga-PSMA PET/MRI.