Yttrium-90 selective internal radiation therapy (⁹⁰Y-SIRT) is a treatment technique that delivers radioactive microspheres precisely to the arterial vascular bed of neoplasms, utilizing beta radiation to administer a high local dose of radiation to the neoplasm tissues. This technology has demonstrated significant efficacy in patients with unresectable pirmary liver cancers and liver metastases. This article systematically reviews the development history and clinical application status of ⁹⁰Y-SIRT in the treatment of liver cancer, and looks forward to future development directions.

OBJECTIVE: To evaluate the clinical significance of a hemizygous c.1042-10G>C variant of the SLC9A7 gene NM_001257291.2) previously identified in individuals with neurodevelopmental disorders, and to provide an evidence-based guidance for prenatal genetic counseling. METHODS: Four families presented at the Medical Genetics Center of Henan Provincial People's Hospital between December 2022 and July 2024 were included in this study. Phenotypic information and biological samples were collected from family members. Genomic DNA was extracted and subjected to whole-exome sequencing and copy number variation analysis to identify candidate pathogenic variants. Sanger sequencing was performed for familial co-segregation analysis. Reverse-transcription PCR was used to assess the RNA splicing pattern of the variant in peripheral blood samples. Quantitative PCR was employed to analyze the expression profiles of various SLC9A7 transcripts in fetal brain tissue and peripheral blood samples. Pathogenicity of the variant was classified based on guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of Henan Provincial People's Hospital (Ethics No.: 2021-171). RESULTS: Six hemizygous males carrying the SLC9A7 c.1042-10G>C variant were identified among the four families, which included three adult males and two male infants with normal phenotypes. Only one affected male from family 3 exhibited global developmental delay, short neck, webbed neck, ocular dysplasia, and congenital corneal leukoma. He also had a history of perinatal asphyxia and carried an additional hemizygous variant HUWE1 c.12283C>G. Reverse-transcription PCR showed no aberrant splicing in heterozygous or hemizygous carriers compared to healthy controls, suggesting that the variant does not affect RNA splicing. Quantitative PCR revealed that NM_001257291.2 is the predominant transcript expressed in fetal brain tissue and peripheral blood. CONCLUSION The SLC9A7 c.1042-10G>C variant does not alter RNA splicing and is present in multiple phenotypically normal males, which supported its classification as a benign variant.
Humans ; Male ; Female ; Genetic Counseling ; Pedigree ; Adult ; DNA Copy Number Variations/genetics* ; Sodium-Hydrogen Exchangers/genetics* ; Exome Sequencing

OBJECTIVE: To investigate the clinical phenotype and genetic characteristics of an infertile woman carrying a novel PADI6 gene variant. METHODS: An infertile woman who visited the Medical Genetics Center of Henan Provincial People's Hospital on April 29, 2024 was selected as the study subject. Clinical data of the proband and her family members were collected. Peripheral blood samples were obtained from the proband and her husband for genomic DNA extraction. Whole-exome sequencing (WES) was performed. Candidate variant was verified among the family members by Sanger sequencing. The pathogenicity of candidate variant was classified according to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants. Relevant literature on the pathogenic variants of the PADI6 gene was reviewed for genotype-phenotype correlation analysis. This study was approved by the Medical Ethics Committee of Henan Provincial People's Hospital (Ethics No.: 2021-171). RESULTS: The proband was a 35-year-old woman who underwent two oocyte retrieval cycles, yielding a total of five oocytes, with all embryos arrested at day 3 post-fertilization. WES identified a homozygous PADI6 variant, c.367+4_367+7del. In vitro splicing assay confirmed that this variant can cause skipping of exon 3, leading to a frameshift and alterations in the protein structure or premature termination of translation. Literature review identified 12 relevant publications, and the PADI6 c.367+4_367+7del was determined to be a novel variant. CONCLUSION The homozygous PADI6 c.367+4_367+7del variant probably underlay the pathogenesis of infertility in the proband.
Humans ; Female ; Infertility, Female/genetics* ; Adult ; Protein-Arginine Deiminase Type 6/genetics* ; Pedigree ; Exome Sequencing ; Mutation

In recent years,China has made great progress in basic nanomedicine,nanotoxicology and nanobiology research.Nanotechnology has been continuously applied in biomaterial and medical device,more and more medical devices applying nanomaterials are developed and manufactured.In order to gain more comprehension and accurate understanding of the research and industrial development in nanobiomaterial medical devices,this study reviewed the common nanomaterial in medical devices and the regulatory situation of nanomaterial medical devices at home and abroad,and discussed the current challenges in biological evaluation of nanomaterial medical devices,with a view to providing ideas for the safety evaluation and research of related products.

Objective:To explore the influence of multidisciplinary treatment (MDT) on clinical staging and diagnosis and treatment strategies for rectal cancer.Methods:A retrospective case series study was conducted. The clinical data of 142 rectal cancer patients who underwent surgical treatment in Shanxi Provincial People's Hospital from March 2021 to December 2021 were retrospectively analyzed. According to whether to implement MDT or not, all patients were divided into MDT group (68 cases) and non-MDT group (74 cases). Relevant clinical data including patients' basic information (gender, age, etc.), TNM staging, whether to receive neoadjuvant radiotherapy and chemotherapy or not, surgical methods, R0 resection rate of both groups were compared. The implementation methods and the effects of MDT for patients were summarized.Results:There were statistically significant differences in the proportion of clinical N staging at initial diagnosis, whether to receive neoadjuvant radiotherapy and chemotherapy or not of both groups (all P < 0.05). The overall agreement rate of clinical T staging at initial diagnosis and pathological T staging was 67.6% (46/68), 50.0% (37/74), respectively in the MDT group and the non-MDT group, and the difference was statistically significant ( χ2 = 4.54, P = 0.033). The overall agreement rate of N staging at initial diagnosis and pathological N staging was 50.0% (34/68), 54.1% (40/74), respectively in the MDT group and the non-MDT group, and the difference was not statistically significant ( χ2 = 0.23, P = 0.629). The treatment rate of neoadjuvant radiotherapy and chemotherapy was 57.4% (39/68) and 4.1% (3/74), respectively in the MDT group and the non-MDT group, and the difference was statistically significant ( χ2 = 48.33, P < 0.001). The R0 resection rate in both the MDT group and non-MDT group was 100.0%, and no tumor tissue was found at the upper, lower, and circumferential margins. Conclusions:MDT could provide more accurate clinical staging and more effective diagnosis and treatment opinions for patients, and provide reliable guidance for the treatment selections.

Objective:To compare hamstring tendon graft (HTG), ligament advanced reinforcement system (LARS), and mixed HTG & LARS ligament in reconstruction of posterior cruciate ligament (PCL).Methods:A retrospective study was conducted to analyze the 59 patients with PCL rupture who had been admitted to Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University for arthroscopic PCL reconstruction between January 2018 and August 2021. The patients were divided into 3 groups: in the HTG group of 21 cases [14 males and 7 females aged (37.8±12.6) years], PCL was reconstructed by HTG; in the LARS group of 20 cases [12 males and 8 females aged (34.3±9.1) years], PCL was reconstructed by LARS; in the mixed group of 18 cases [13 males and 5 females aged (33.2±8.3) years], PCL was reconstructed by the mixed HTG & LARS ligament. The 3 groups were compared in terms of Lysholm knee score, International Knee Documentation Committee (IKDC) score, and laxity disparity between bilateral knees at 1 and 2 years after surgery.Results:There was no statistically significant difference in the preoperative general data between the 3 groups, indicating comparability ( P>0.05). One year after surgery, the mixed group had a significantly higher IKDC score [(90.0±6.5) points] than the HTG group [(78.1±5.7) points] and the LARS group [(84.1±7.3) points], and a significantly higher Lysholm score [(88.9±5.5) points] and a significantly smaller laxity disparity between bilateral knees [(2.8±1.7) mm] than the HTG group [(81.8±4.6) points, (4.7±2.4) mm] ( P<0.05). Two years after surgery, the mixed group had a Lysholm score of (93.0±4.5) points, a IKDC score of (92.5±5.7) points, and a laxity disparity between bilateral knees of (2.3±1.8) mm, all significantly better than those in the HTG group [(88.5±5.5) points, (82.7±5.7) points, and (4.2±2.5) mm] and in the LARS group [(89.0±5.2) points, (86.5±7.3) points, and (3.8±2.2) mm] ( P<0.05). In all the 3 groups, the knee function scores and laxity disparities between bilateral knees at 1 and 2 years after surgery were significantly improved compared with the preoperative values ( P<0.05). Conclusions:Satisfactory clinical outcomes can be obtained after arthroscopic PCL reconstruction using HTG, LARS or the mixed HTG & LARS ligament. However, the mixed ligament as a graft can achieve better clinical efficacy than the other two grafts.

Blood glucose fluctuation leads to poor bone defect repair in patients with type 2 diabetes (T2DM). Strategies to safely and efficiently improve the bone regeneration disorder caused by blood glucose fluctuation are still a challenge. Neutral sphingophospholipase 2 (Smpd3) is downregulated in jawbone-derived bone marrow mesenchymal stem cells (BMSCs) from T2DM patients. Here, we investigated the effect of Smpd3 on the osteogenic differentiation of BMSCs and utilized exosomes from stem cells overexpressing Smpd3 as the main treatment based on the glucose responsiveness of phenylboronic acid-based polyvinyl alcohol crosslinkers and the protease degradability of gelatin nanoparticles. The combined loading of Smpd3-overexpressing stem cell-derived exosomes (Exos-Smpd3) and nanosilver ions (Ns) to construct a hydrogel delivery system (Exos-Smpd3@Ns) promoted osteogenesis and differentiation of BMSCs in a glucose-fluctuating environment, ectopic osteogenesis of BMSCs in a glucose-fluctuating environment and jawbone regeneration of diabetic dogs in vitro. Mechanistically, Smpd3 promoted the osteogenesis and differentiation of jawbone-derived BMSCs by activating autophagy in the jawbone and inhibiting macrophage polarization and oxidative stress caused by blood glucose fluctuations. These results reveal the role and mechanism of Smpd3 and the Smpd3 overexpression exosome delivery system in promoting BMSC function and bone regeneration under blood glucose fluctuations, providing a theoretical basis and candidate methods for the treatment of bone defects in T2DM patients.
Exosomes ; Animals ; Bone Regeneration/drug effects* ; Dogs ; Mesenchymal Stem Cells ; Humans ; Blood Glucose ; Cell Differentiation ; Osteogenesis/drug effects* ; Diabetes Mellitus, Type 2/therapy* ; Diabetes Mellitus, Experimental ; Cells, Cultured ; Hydrogels ; Male

Objective To explore the relationship between the expression of plectin and the migration of hepatocellular carcinoma(HCC)cells and to elucidate the molecular mechanisms by which plectin expression affects the migration of HCC cells.Methods First of all,Western blot was performed to determine the expression of plectin in normal hepatocytes and HCC cells.Secondly,a plectin-downregulated HCC cell strain was established and the control group(shNC group)and shPLEC group were set up.Each group was divided into a vehicle control group(shNC+DMSO group or shPLEC+DMSO group)and a F-actin cytoskeleton polymerization inducer Jasplakinolide group(shNC+Jasp group or shPLEC+Jasp group).Western blot was performed to determine the expression of plectin and epithelial-mesenchymal transition(EMT)-related proteins,including N-cadherin,vimentin,and E-cadherin.HCC cell migration was evaluated by Transwell assay.KEGG(Kyoto Encyclopedia of Genes and Genomes)was used to analyze the signaling pathways related to plectin gene.The polymerization of F-actin was analyzed by immunofluorescence assay.Results Compared with the normal hepatocytes,HCC cells showed high expression of plectin.Compared with those in the shNC group,the expression of plectin in the shPLEC group was decreased(P<0.05),the migration ability of HCC cells was weakened(P<0.05),and the EMT process was inhibited(with the expression of N-cadherin and vimentin being decreased and the expression of E-cadherin being increased)(P<0.05).KEGG analysis showed that the regulation of cytoskeletal F-actin was most closely associated with plectin and cytoskeletal F-actin depolymerized in the shPLEC group.After treatment with Jasplakinolide,an inducer of F-actin cytoskeleton polymerization,the migration ability of HCC cells in the shPLEC+Jasp group was enhanced compared with that of shPLEC+DMSO group(P<0.05)and the EMT process was restored(with the expression of N-cadherin and vimentin being increased and the expression of E-cadherin being decreased)(P<0.05).In addition,the polymerization of cytoskeletal F-actin in HCC cells was also restored.Conclusion Plectin is highly expressed in HCC cells.Plectin promotes the migration and the EMT of HCC cells through inducing F-actin polymerization.

Blood glucose fluctuation leads to poor bone defect repair in patients with type 2 diabetes(T2DM).Strategies to safely and efficiently improve the bone regeneration disorder caused by blood glucose fluctuation are still a challenge.Neutral sphingophospholipase 2(Smpd3)is downregulated in jawbone-derived bone marrow mesenchymal stem cells(BMSCs)from T2DM patients.Here,we investigated the effect of Smpd3 on the osteogenic differentiation of BMSCs and utilized exosomes from stem cells overexpressing Smpd3 as the main treatment based on the glucose responsiveness of phenylboronic acid-based polyvinyl alcohol crosslinkers and the protease degradability of gelatin nanoparticles.The combined loading of Smpd3-overexpressing stem cell-derived exosomes(Exos-Smpd3)and nanosilver ions(Ns)to construct a hydrogel delivery system(Exos-Smpd3@Ns)promoted osteogenesis and differentiation of BMSCs in a glucose-fluctuating environment,ectopic osteogenesis of BMSCs in a glucose-fluctuating environment and jawbone regeneration of diabetic dogs in vitro.Mechanistically,Smpd3 promoted the osteogenesis and differentiation of jawbone-derived BMSCs by activating autophagy in the jawbone and inhibiting macrophage polarization and oxidative stress caused by blood glucose fluctuations.These results reveal the role and mechanism of Smpd3 and the Smpd3 overexpression exosome delivery system in promoting BMSC function and bone regeneration under blood glucose fluctuations,providing a theoretical basis and candidate methods for the treatment of bone defects in T2DM patients.

Objective:To investigate the efficacy of postmastectomy radiotherapy (PMRT) for human epidermal growth factor receptor 2 (HER2)-positive T 1-2N 1M 0 breast cancer in the context of HER2-targeted therapy. Methods:This study collected the clinical data of 105 female patients with HER2-positive T 1-2N 1M 0 breast cancer who underwent modified radical mastectomy in the First Affiliated Hospital of Bengbu Medical College from January 2013 to December 2019. Then, the clinical outcomes of these patients were observed, and the prognostic factors and the efficacy of PMRT were analyzed. Results:The median follow-up time was 50 months (ranging from 14 to 107 months), and the 5-year overall survival (OS), local-regional recurrence-free survival(LRFS), and disease-free survival (DFS) were 81.6%, 91.9%, and 76.2%, respectively. The multivariate analysis indicated that independent prognostic factors for OS and DFS include the age, pathologic grade, and tumor size; the independent risk factors for LRFS include positive lymph node ratio (LNR) and hormone receptor (HR) status; and the independent prognostic factor for DFS was PMRT (HR: 2.85, 95% CI: 1.10-8.80, P < 0.05). The subgroup analysis suggested that PMRT significantly improved the OS of various high-risk subgroups ( χ2=4.01-9.18, P < 0.05). However, the further stratified analysis indicated that PMRT only increased the OS of the patients who did not receive HER2-targeted therapy in various high-risk subgroups ( χ2=4.50-6.70, P < 0.05), while there was no statistical difference before and after PMRT for the individuals who received targeted treatment ( P > 0.05). Conclusions:PMRT is an independent prognostic factor for the DFS of patients with HER2-positive T 1-2N 1M 0 breast cancer who underwent modified radical mastectomy. PMRT can improve the OS of high-risk patients with ages < 45 years old, pathologic grade Ⅲ, tumor diameter ≥ 3 cm, LNR > 10%, and HR (-) who received no HER2-targeted therapy. However, the efficacy may be compromised to some extent in the context of the application of HER2-targeted therapy.