Cerebral edema is characterized by fluid accumulation, and the glymphatic system (GS) plays a pivotal role in regulating fluid transport. Using the Tenecteplase system, magnesium salt of salvianolic acid B/ginsenoside Rg1 (SalB/Rg1) was injected intravenously into mice 4.5 h after middle cerebral artery occlusion and once every 24 h for the following 72 h. GS function was assessed by Evans blue imaging, near-infrared fluorescence region II (NIR-II) imaging, and magnetic resonance imaging (MRI). SalB/Rg1 had significant effects on reducing the infarct volume and hemorrhagic transformation score, improving neurobehavioral function, and protecting tissue structure, especially inhibiting cerebral edema. Meanwhile, the influx/efflux drainage of GS was enhanced by SalB/Rg1 according to NIR-II imaging and MRI. SalB/Rg1 inhibited matrix metalloproteinase-9 (MMP-9) activity, reduced cleaved β-dystroglycan (β-DG), and stabilized aquaporin-4 (AQP4) polarity, which was verified by colocalization with CD31. Our findings indicated that SalB/Rg1 treatment enhances GS function and attenuates cerebral edema, accompanying the regulation of the MMP9/β-DG/AQP4 pathway.
Animals ; Ginsenosides/administration & dosage* ; Brain Edema/etiology* ; Male ; Benzofurans/administration & dosage* ; Glymphatic System/diagnostic imaging* ; Mice ; Infarction, Middle Cerebral Artery/drug therapy* ; Aquaporin 4/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Matrix Metalloproteinase 9/metabolism* ; Neuroprotective Agents/pharmacology* ; Depsides

The advancement of medical technology has led to significant progress in the research of standardized surgical procedures for colorectal cancer, resulting in enhanced treatment regimens from preoperative to postoperative stages. Standardized surgical procedures are crucial for improving patient survival rates, reducing recurrence rates, minimizing complications, and improving quality of life. This article summarizes the latest research results on the classification, surgical methods, and adjuvant therapy of colorectal cancer surgery; analyzes and explores standardized surgical treatment strategies; and aims to provide reference and guidance for the clinical management of colorectal cancer.

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

Currently, the management of domestic laboratory developed test (LDT) is still in the exploration stage, and new plans and ideas need to be investigated that are suitable for our national development. By analyzing encountered issues, combining the actual needs of the government, healthcare reform, and patients, this article proposes that "promoting healthy development of LDT projects and focusing on the organic combination of patients′ interest protection and innovation support" is an important direction for LDT management, around which the new idea for LDT project management is proposed, that is, LDT management model targeting product registration. The core of this management model is to target product registration and to ensure low service fees for patients and continuous real-time data monitoring. Benefit and risk analysis demonstrate that this management model can to a larger extent balance the realistic demands of patients, medical institutions, in vitro diagnostics companies, and government management departments, which benefits promoting the perfection and development of LDT projects in our country.

Objective:To analyze the clinical features of MDA5 antibody positive dermatomyositis (MDA5-DM) and to provide evidence for early diagnosis and treatment.Methods:From March 2019 to June 2021, 272 patients with anti-MDA5-DM from the Nanjing Medical University myositis-associated interstitial lung disease cohort were enrolled, with 76 patients with anti-synthetase syndrome (ASS) as the control group. The clinical characteristics and the occurrence of interstitial lung disease were analyzed. T-test was used for normally distributed and variance-homogeneous independent samples, Mann-Whitney U test for non-normally distributed data, and chi-square test or Fisher′s exact test for dichotomous variables. Results:Among the 272 anti-MDA5-DM patients, 88.6% (241/272) developed interstitial lung disease (ILD), and 33.8% (92/272) developed rapidly progressive ILD (RP-ILD). The six-month all-cause mortality rate of anti-MDA5-DM patients was 16.9% (46/272), and it was as high as 47.8% (44/92) for those with RP-ILD. Compared with ASS patients, anti-MDA5-DM patients had a significantly higher proportion of males, arthritis, Gottron's sign, heliotrope rash, V-sign, periungual erythema, and skin ulcers ( P<0.05). The levels of ALT, AST, and ferritin were significantly increased ( P<0.05). Compared with non-RP-ILD patients, RP-ILD patients had a significantly higher proportion of males [35.9%(33/92) vs. 23.3%(42/180), χ2=4.79, P=0.029], higher levels of LDH [387 (276, 547) U/L vs. 310 (245, 400) U/L, Z=-3.67, P<0.001], ESR [45.5 (29.25, 63.25) mm/1 h vs. 31.2 (20, 51) mm/1 h, Z=-3.71, P<0.001], CRP [10.9 (4.1, 25.2) mg/L vs. 4.54 (2.58, 9.08) mg/L, Z=-4.97, P<0.001], ferritin [1 340 (650, 2 000) ng/ml vs. 556 (203, 1 186) ng/ml, Z=-4.40, P<0.001], and a higher proportion of anti-Ro52 antibody and anti-MDA5 antibody co-positivity [87.0%(80/92) vs. 52.2%(94/180), χ2=31.87, P<0.001]. Conclusion:Anti-MDA5-DM patients are prone to develop RP-ILD and have poor prognosis.

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.

Aluminum adjuvants (Alum), approved by the US Food and Drug Administration, have been extensively used in vaccines containing recombinant antigens, subunits of pathogens, or toxins for almost a century. While Alums typically elicit strong humoral immune responses, their ability to induce cellular and mucosal immunity is limited. As an alternative, layered double hydroxide (LDH), a widely used antacid, has emerged as a novel class of potent nano-aluminum adjuvants (NanoAlum), demonstrating advantageous physicochemical properties, biocompatibility and adjuvanticity in both humoral and cellular immune responses. In this review, we summarize and compare the advantages and disadvantages of Alum and NanoAlum in these properties and their performance as adjuvants. Moreover, we propose the key features for ideal adjuvants and demonstrate that LDH NanoAlum is a promising candidate by summarizing its current progress in immunotherapeutic cancer treatments. Finally, we conclude the review by offering our integrated perspectives about the remaining challenges and future directions for NanoAlum's application in preclinical/clinical settings.

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