ObjectiveTo investigate the clinicopathological features， molecular profile， treatment response， and prognosis of SMARCA4 （BRG-1） and SMARCB1 （INI-1）-deficient undifferentiated tumors of the digestive system， aiming to enhance the understanding of this rare and highly aggressive molecular subtype. MethodsThis study is a single-center retrospective analysis. We included 9 cases of malignant digestive system tumors with loss of BRG-1 expression and 3 cases with loss of INI-1 expression， all pathologically confirmed at Sun Yat-sen University Cancer Center between April 2022 and December 2025. By reviewing clinical data， histological morphology，immunohistochemistry and next-generation sequencing （NGS） results from partial cases， we systematically summarized their clinicopathological and molecular characteristics， treatment strategies， and survival outcomes. Results​ Among the 12 patients， 6 were male and 6 were female， with a median age of 62 （44-70） years. 9 cases exhibited SMARCA4 deficiency， and 3 cases exhibited SMARCB1 deficiency. Tumors originated in the stomach （5 cases）， colon （3 cases）， pancreas （1 case）， with the primary site unknown in 3 cases. The histology predominantly showed undifferentiated carcinoma， with 1 case of poorly differentiated carcinoma. The tumor cells were epithelioid with significant atypia. Epithelial markers （e.g. CKpan） were often lost or markedly decreased， while vimentin could be positive. All 9 cases tested for MMR status were mismatch repair proficient （pMMR）， and the Ki-67 proliferation index was high ［median 80% （60%-90%）］. A discordance was observed between IHC findings and NGS results in the 6 sequenced cases. The NGS profiling revealed frequent co-occurring mutations， including TP53， KRAS， and NRAS， with no germline mutations identified.The median follow-up time was 277 （55-867） days. 9 of the 12 patients presented with stage Ⅳ disease at the time of initial diagnosis. Among 3 newly diagnosed patients without metastasis who received treatment， 2 achieved prolonged recurrence-free survival. Patients with advanced disease at initial diagnosis primarily underwent platinum-based chemotherapy or combination regimens， yet their prognosis was generally poor， with a median overall survival of 60 （45-541） days， ranging from 16 to 867 days. Notably， several patients who received chemotherapy combined with targeted therapy and immunotherapy achieved extended survival. ConclusionSMARCA4/SMARCB1-deficient undifferentiated tumor of the digestive system is a distinct molecular subtype characterized by high aggressiveness and poor prognosis， predominantly affecting middle-aged and elderly individuals. Diagnosis relies on the immunohistochemical loss of BRG-1 or INI-1 proteins. While no standard of care currently exists， treatment often refers to regimens for adenocarcinoma of the primary site. Combined immunotherapy and targeted therapy may offer potential benefits， warranting further validation in large-scale prospective studies.

Objective To observe the value of 5.0T MRI in measuring the volumes of hippocampal formation(HF)subfields in healthy adults.Methods Cranial high-resolution TIWI were prospectively obtained in 23 healthy adult volunteers using 5.0T and 3.0T MR scanners,respectively.HF was divided into 38 subfields,and then the volume of each subfield was measured using FreeSurfer software.The volumes of HF subfield based on 5.0T and 3.0T MR T1WI were compared,and the correlations of the outcomes were analyzed.Results Significant differences of the volumes of bilateral hippocampal tails,left parasubiculum,left molecular layer of hippocampal head,left granular cell-molecular layer-dentate gyrus head,right granular cell-molecular layer-dentate gyrus body,left cornu Ammonis(CA)1 head,left CA3 head,left CA4 head,right fimbria of hippocampus and left hippocampus amygdala transition area were found between 5.0T and 3.0T T1WI(all P＜0.05).The volumes of HF subfields measured based on 5.0T and 3.0T T1WI were moderately to highly positively correlated(all r＞0.5,all P＜0.01).Conclusion 5.0T MRI could be used to measure the volume of HF subfield in adults.

Objective Most common infected bacteria were found to analyze their effects on clinical characteristics and 3-year outcome of patients with diabetic foot ulcer ( DFU ) . Methods Materials of cases with positive bacterial culture were selected from DFU patients. 203 cases were infected with the most common 6 strains of mono-bacteria, and 62 cases were infected with multi-bacteria. Data were grouped according to the most common 6 infected bacteria. The outcomes of healing, recurrence, amputation, cardiac events, cerebrovascular events and death were calculated of 3 years after hospitalization. Clinical characteristics of mono-and multi-infected groups and these 6 mono-bacterial infection groups, and risk factors to outcome were analyzed. Results No significant difference was found in baseline clinical characteristics, cardiac and cerebrovascular events, and death during follow-up between mono-and multi-infected groups. The most common 6 infected bacteria were staphylococcus aureus, pseudomonas aeruginosa, proteus, enterococcus faecalis, escherichia coli and klebsiella pneumoniae. Among these groups, there were no significant differences of baseline clinical characteristics and recurrence, cardiac and cerebrovascular events, and death except for the foot ulcer and foot ulcer related prognosis. In staphylococcus aureus infected group, severe lower extremity arterial disease (8.5％), Wagner grade 3-5 (48.9％), moderate and severe infection rate (34.0％) were significantly lower than other groups, and the healing rate ( 93. 6％) was higher than other groups ( all P<0.05). Severe lower extremity arterial disease, cardiac function grading over 3(NYHA), eGFR<60 ml·min-1· (1.73 m2)-1, duration of DFU over 30 days were the main risk factors for ulcers′healing. Wagner grade over 3 was main risk factor for minor amputation. Severe lower extremity arterial disease, Hb<90g/L were the main risk factors for major amputation. Cardiac function grading over 3 ( NYHA ) was main risk factor for cardiac events, and also for death. ALB<30 g/L was main risk factor for death (all P<0.05). Conclusion DFU patients infected with different strains of bacteria were significantly different in foot ulcer and healing rate, while not in cardiac and cerebrovascular events and death.

OBJECTIVE: This study aims to investigate the mechanism of K (lysine) acetyltransferase 2A (KAT2A) regulation and control on the osteogenic differentiation of periodontal ligament stem cells (PDLSCs). METHODS: The expression levels of KAT2A in PDLSCs were compared from each generation of the normal (H-PDLSCs) and periodontitis tissues (P-PDLSCs). The influences of KAT2A gene interference on the osteogenic differentiation of PDLSCs were also detected. In addition, the influences of the KAT2A gene interference to the canonical Wnt pathway and ligands were detected. The upstream and down-stream relationships between KAT2A and canonical Wnt pathway were also determined. RESULTS: The decreased expression of KAT2A in PDLSCs from the inflammatory tissue in each generation was compared with that in PDLSCs from the healthy tissue, and the difference was statistically significant (P<0.05). When the KAT2A gene was disrupted, the osteogenesis ability of PDLSC was declined, and the difference was statistically significant (P<0.05). The canonical Wnt pathway was activated, and the antagonist Dickkopf-1 (DKK-1) was reduced. After the DKK-1 addition, the osteogenic differentiation of the disturbed PDLSCs was recovered, and KAT2A was unaffected. CONCLUSIONS The KAT2A expression in PDLSCs was decreased because of perio-dontitis. The classical Wnt pathway was activated to inhibit the osteogenic differentiation of the cells.
Acetyltransferases ; Cell Differentiation ; Cells, Cultured ; Histone Acetyltransferases ; metabolism ; Humans ; Lysine ; Osteogenesis ; Periodontal Ligament ; metabolism ; Periodontitis ; metabolism ; Stem Cells ; Wnt Signaling Pathway

Objective: To compare the osteogenic differentiation abilities of human bone marrow mesenchymal stem cells (hBMSCs) from different sources, and to provide basis for choosing a new source of seed cells in bone tissue engineering. Methods: Jaw bone-marrow-derived mesenchymal stem cells (JMMSCs) were isolated from orthognathic surgical sites and cultured by limited dilution for single cell clone. Long bone-marrow-derived mesenchymal stem cells (BMMSCs) were obtained from bone marrow of volunteers and isolated by density gradient centrifugation method. Flow cytometry was used to detect the surface markers of both cells. Osteogenic ability was assessed by PCR and Western Blot after osteogenic differentiation for the following molecules: Runx2, COL-1 and OCN. Alizarin red staining was used for determining the ability of cell mineralization after osteogenic differentiation. Results : The expressions of cell surface markers CD90 and CD105 were positive in both type of cells, while CD34, CD14 and CD45 were all negative. After 21 days of osteogenic induction, JMMSCs formed significantly more mineralized nodules than BMMSCs. After 7, 14, 21 days of osteogenic induction, JMMSCs expressed more osteogenic-related molecules than BMMSCs. Conclusion The osteogenic differentiation capacity and mineralization ability of JMMSCs are significantly higher than BMMSCs. Jaw bone might be a more suitable source of seed cells in bone tissue engineering compared with long bone.

Objective:To investigate the trait of exosomes serected by mesenchymal stem cells derived form orofacial bone(OMMSCs-Exo) and the communication between the exosomes and macrophages.Methods:OMMSCs were isolated from orthognathic surgical sites and cultured by limited dilution.Their cell surface markers were characterized by flow cytometry.the rate of colony formation and the differentiation potential of OMMSCs were evaluated.Exosomes were prepaired from the culture supernatants of OMMSCs(P4-P6).Transmission electron microscopy(TEM) and western blot were used to identify the exosomes.The expression of miRNAs associated with immunity such as miR-223 and miR-let-7c were determined by Real-time RT-PCR.Human peripheral blood mononuclear cells(PBMCs) were isolated from health donor and co-cultured with OMMSCs-Exo.After co-cultured for 24 h,the communication between exosomes and macrophages was tested using a confocal microscope.Results:Human OMMSCs were proved to have the characteristics of mesenchymal stem cells.The diameter of OMMSCs-Exo ranged from 40 to 160 nm.The OMMSCs-Exo expressed CD63 and CD81 and contained miRNAs associated with immune regulation such as miR223 and miR-let-7c.OMMSCs-Exo could be uptaken by macrophages.After co-culture of OMMSCs-Exo with marcrophages for 72 h,miR223 expression in macrophages increased.Conclusion:OMMSCs-Exo has the potential of immune regulation.

Objective:To compare acetyltransferase MORF level in periodontal ligament stem cells( PDLSCs) derived from healthy individuals ( H-PDLSCs) with those derived from the individuals with periodontitis ( P-PDLSCs ) . And to determine the effect of MORF on the osteogenic differentiation potential of PDLSCs. Methods: Human H-PDLSCs and P-PDLSCs were cultured and cloned with limited dilution method. H-PDLSCs were stimulated by LPS, TNF-α, IL-β and the mix of the 3 inflammatory factors to imitate inflammatory environment ( IP-PDLSCs ) . Quantitative RT-PCR and Western Blot were applied to examine different expression of MORF in H-PDLSCs and P-PDLSCs. Western Blot was applied to detect expression of MORF in IP-PDLSCs. Quantitative RT-PCR, Western Blot and alizarin red staining were applied to determine osteogenic differentiation potential of H-PDLSCs with MORF knock-down. Results:Quantitative RT-PCR and Western Blot showed lower expression of MORF in P-PDLSCs compared with H-PDLSCs( P<0. 05). Western Blot revealed lower expression of MORF in IP-PDLSCs. Quantitative RT-PCR, Western Blot and alizarin red stai-ning indicated osteogenic differentiation potential was inhibited in H-PDLSCs with MORF knockdown(P<0. 05). Conclusion: Peri-odontitis can suppress the expression of MORF in PDLSCs and inhibite the osteogenic differentiation potential of PDLSCs.

Objective:To compare the proliferation and osteogenic differentiation between human bone marrow mesenchymal stem cells from orofacial bone(OMMSCs)and those from long bone(BMMSCs).Methods:OMMSCs were isolated from orthognathic surgical sites and cultured by limited dilution.BMMSCs were obtained from bone marrow of volunteers and isolated by density gradient centrifugation method.The surface markers of the cells were detected by flowcytometry.Single-colony formation,CCK assay and cell circle analyses were conducted.Osteogenic differentiation ability was evaluated by ALP activity test and Alizarin red staining after osteogenic induction culture.Results:The cell surface markers STRO-1 and CD105 of both stem cells were positive,CD34,CD31 and CD45 were negative. OMMSCs generated significantly higher numbers of colonies than BMMSCs.In addition,OMMSCs had a higher proliferation rate and more cells in proliferative(S +G2 )stage than BMMSCs.After osteogenic induction for 3,5,7 and 10 d,OMMSCs showed higher levels of ALP activity.OMMSCs formed significantly more mineralized nodules than BMMSCs after 21-day ostogenic induction.Conclusion:The proliferation and osteogenic differentiation capacity of OMMSCs are higher than those of BMMSCs.

Objective To explore the distribution of pathogenic micro-organisms in the diabetic patients with foot infection,and to investigate the characteristics of the pathogen distribution and its relationship with the severity of diabetic foot ulcer( DFU ).Methods Ninety diabetic foot patients with positive culture of micro-organisms were classified into Wagner 1-5 grades according to the severity of DFU,which was ranked as mild,moderate,and severe infection based on the gradient of infection.The family,genus,and strain of micro-organisms were analyzed,and associated factors were discussed in regard to the kinds and severity of DFU and infection.Results With rising Wagner's grades and aggravating infection,the bacterial floras were transformed from gram-positive cocci( 61.1％ in Wagner 1 ) to gram-negative rods( 80.0％ in Wagner 5),at the same time,composite( 10.0％ to 28.6％ ) and opportunist ( 83.3％ to 100％ ) infections were increased.Wagner's grade,severity of infection,previous treatment,patients' age,control of blood glucose,course of DFU,etc,were all related to types of infection and opportunist infection ( P＜0.05 ).Conclusions Proportion of gram-negative bacilli with opportunist composite infection seems to increase in patients with severe DFU and severe infection requiring appropriate application of antibiotics.

Objective To investigate the effects of extracellular ATP on the recovery of motor function after spinal cord injury in rats.Methods Twenty healthy adult rats were randomly divided into two groups after contusion injury was performed by the weight drop method at T10 with Allen impactor.Group A(ATP group) and group B(control group) each had ten rats.At days 1,3,7,14 and 28 after injury,the recovery of motor function after spinal cord injury in rats was assessed with modified Tarlov scores and slanting board test.Results Modified Tarlov scores and slanting board test were better in group A than in group B after spinal cord injury in rats.Significant difference was found in modified Tarlov scores and slanting board test between the two groups at days 14 and 28 after injury(P