BACKGROUND:silencing information regulatory 1(SIRT1)regulates the function of related proteins in chondrocytes in a deacetylated manner and participates in chondrocyte proliferation and differentiation,thereby promoting cartilage defect repair. OBJECTIVE:To screen for signaling pathways with unclear action status after SIRT1 gene knockdown in chondrocytes,as well as diseases or functions that produce changes using high-throughput technology. METHODS:ATDC5 chondrocytes from mice in logarithmic growth phase were divided into two groups:the cells were transfected with SIRT1 gene knockdown negative control lentivirus in control group and SIRT1 gene knockdown lentivirus in experimental group.GeneChip? Mouse Genome 430 2.0 Array was used to detect the mRNA expression at 72 hours after transfection.Applied bioinformatics technology was also used to screen for unclear activation or inhibition signaling pathways and their related factors.Moreover,enrichment of disease or function modules was analyzed. RESULTS AND CONCLUSION:After knocking down the SIRT1 gene,there were 245 signaling pathways with unclear activation or inhibition status in the mouse ATDC5 chondrocytes.According to the ranking of-Log(P-value),we reported the factors in the top 20 signaling pathways with unclear activation or inhibition status,including IGFBP4,TGFBR1,CTGF,COL4A5,LHX2,IL1RL1,and KLF6.According to the ranking of-Log(P-value),there were significant changes in 14 disease or function modules,including cellular growth and proliferation,organism survival,cell death and survival.According to the number of differentially expressed genes,there were significant changes in three disease or function modules,including organismal injury and abnormalities,cancer,and cell death and survival.According to the comprehensive ranking of-Log(P-value)and the number of differentially expressed genes,the disease or function module related to intrinsic immune response was significantly activated.

Objective To develop a multi-modal deep learning method for automatic classification of immune-mediated glomerular diseases based on images of optical microscopy(OM),immunofluorescence microscopy(IM),and transmission electron microscopy(TEM).Methods We retrospectively collected the pathological images from 273 patients and constructed a multi-modal multi-instance model for classification of 3 immune-mediated glomerular diseases,namely immunoglobulin A nephropathy(IgAN),membranous nephropathy(MN),and lupus nephritis(LN).This model adopts an instance-level multi-instance learning(I-MIL)method to select the TEM images for multi-modal feature fusion with the OM images and IM images of the same patient.By comparing this model with unimodal and bimodal models,we explored different combinations of the 3 modalities and the optimal methods for modal feature fusion.Results The multi-modal multi-instance model combining OM,IM,and TEM images had a disease classification accuracy of(88.34±2.12)%,superior to that of the optimal unimodal model[(87.08±4.25)%]and that of the optimal bimodal model[(87.92±3.06)%].Conclusion This multi-modal multi-instance model based on OM,IM,and TEM images can achieve automatic classification of immune-mediated glomerular diseases with a good classification accuracy.

MiR-138-5p is a microRNA that plays an important regulatory role in the pathogenesis of osteoarthritis.MiR-138-5p regulates various biological processes,including inflammation,cell apoptosis and proliferation,and matrix degradation in osteoarthritis,by modulating signaling pathways including nuclear factor-κB,Wnt/β-catenin,and phosphoinositide 3-kinase/AKT.This review summarizes the research progress regarding the mechanism of miR-138-5p in osteoarthritis.

Objective To develop a multi-modal deep learning method for automatic classification of immune-mediated glomerular diseases based on images of optical microscopy(OM),immunofluorescence microscopy(IM),and transmission electron microscopy(TEM).Methods We retrospectively collected the pathological images from 273 patients and constructed a multi-modal multi-instance model for classification of 3 immune-mediated glomerular diseases,namely immunoglobulin A nephropathy(IgAN),membranous nephropathy(MN),and lupus nephritis(LN).This model adopts an instance-level multi-instance learning(I-MIL)method to select the TEM images for multi-modal feature fusion with the OM images and IM images of the same patient.By comparing this model with unimodal and bimodal models,we explored different combinations of the 3 modalities and the optimal methods for modal feature fusion.Results The multi-modal multi-instance model combining OM,IM,and TEM images had a disease classification accuracy of(88.34±2.12)%,superior to that of the optimal unimodal model[(87.08±4.25)%]and that of the optimal bimodal model[(87.92±3.06)%].Conclusion This multi-modal multi-instance model based on OM,IM,and TEM images can achieve automatic classification of immune-mediated glomerular diseases with a good classification accuracy.

To summarize the nursing experience of a patient with schizophrenia complicated by severe neurodeptic malignant syndrome.Nursing points include:to emphasize monitoring of antipsychotic medications to detect the onset of neurodeptic malignant syndrome as early as possible;to leverage the multidisciplinary team for rapid initiation of acute phase management interventions;to combine multimodal cooling to help rewarm the patient;to implement the stepwise intervention program to promote recovery of bowel function;to emphasize family supportive therapy to restore social functioning;to continue case management by developing a multidisciplinary follow-up plan.After careful management and care by the multidisciplinary team,the patient was successfully discharged from the hospital after a total stay of 47 days.After 3 months of follow-up,the patient's daily life was basically back to normal.

Gyrus Cinguli ; Claustrum ; Cerebral Cortex ; Basal Ganglia ; Motor Activity ; Neural Pathways

Objective: To examine the patterning cropped and shaped mesh repair for perineal hernia after abdominoperineal excision (APE) in rectal cancer. Methods: The clinical data of 8 patients with perineal hernia after APE who accepted surgical treatment in the Department of Hepatopancreatobiliary and Hernia Surgery, the First Affiliated Hospital of Fujian Medical University from March 2017 to December 2022 were retrospectively reviewed. There were 3 males and 5 females, aged (67.6±7.2) years (range: 56 to 76 years). Eight patients developed a perineal mass at (11.3±2.9) months (range: 5 to 13 months) after APE. After surgical separation of adhesion and exposing the pelvic floor defect, a 15 cm×20 cm anti-adhesion mesh was fashioned as a three-dimensional pocket shape to fit the pelvic defect, then fixed to the promontory or sacrum and sutured to the pelvic sidewalls and the anterior peritoneum, while two side slender slings were tailored in front of the mesh and fixed on the pectineal ligament. Results: The repair of their perineal hernias went well, with an operating time of (240.6±48.8) minutes (range: 155 to 300 minutes). Five patients underwent laparotomy, 3 patients tried laparoscopic surgery first and then transferred to laparotomy combined with the perineal approach. Intraoperative bowel injury was observed in 3 patients. All patients did not have an intestinal fistula, bleeding occurred. No reoperation was performed and their preoperative symptoms improved significantly. The postoperative hospital stay was (13.5±2.9) days (range: 7 to 17 days) and two patients had postoperative ileus, which improved after conservative treatment. Two patients had a postoperative perineal hernia sac effusion, one of them underwent placement of a tube to puncture the hernia sac effusion due to infection, and continued irrigation and drainage. The postoperative follow-up was (34.8±14.0) months (range: 13 to 48 months), and 1 patient developed recurrence in the seventh postoperative month, no further surgery was performed. Conclusions: Surgical repair of the perineal hernia after APE can be preferred transabdominal approach, routine application of laparoscopy is not recommended, combined abdominoperineal approach can be considered if necessary. The perineal hernia after APE can be repaired safely and effectively using the described technique of patterning cropped and shaped mesh repair.
Male ; Female ; Humans ; Animals ; Herniorrhaphy/methods* ; Surgical Mesh ; Retrospective Studies ; Hernia, Abdominal/surgery* ; Hernia ; Rectal Neoplasms/surgery* ; Proctectomy ; Laparoscopy ; Perineum/surgery* ; Postoperative Complications ; Incisional Hernia/surgery* ; Hominidae

Objective To investigate the levels of γδ T cells and their subpopulations in bone marrow(BM)of patients with myelodysplastic syndrome(MDS),it aims to explore the immune deficiency status of BM microenvi-ronment in MDS patients.Methods BM samples were collected from MDS patients before and after treatment,as well as from normal donors.Multicolor flow cytometry was utilized to detect bone marrow γδ T cells and subpopulation levels.The changes of the T cell subsets after treatment were also analyzed.Results The levels of BM γδ T cells and follicular helper γδ T cells from MDS patients were significantly lower than those of normal donors(P<0.05).Among γδ T cells at different stages of differentiation,only the frequencies of na?ve γδ T cells from MDS patients decreased significantly(P = 0.037),and there was no significant difference observed about central memory,effector memory,and terminally differentiated γδ T cells in MDS patients compared to normal donors(P>0.05).Although there was a slight decrease in PD1+γδ T cells and an increase in TIM3+γδ T cells,these differences were not statistically significant(P>0.05).In patients who achieved a curative effect,the proportions of γδ T cells and naive γδ T cells increased significantly after treatment,and the effector memory γδ T cells decreased significantly after treatment(P<0.05).After treatment,85.71%(6/7)of MDS patients showed a decrease in γδ+TIM3+ T cell levels to varying degrees.Conclusions The levels of γδ T cells and their subpopulations in the BM microenvironment of patients with MDS exhibit varying degrees of abnormalities.However,in patients who receive effective treatment,these abnormal γδ T cells can recover.By detecting the levels of γδ T cells and subpopulations,we can gain insights into the immune deficiency status of MDS.This information might serve as an indicator to assess treatment efficacy and provide valuable insights for anti-tumor immunotherapy.

The National Medical Products Administration has authorized sodium oligomannate for treating mild-to-moderate Alzheimer's disease.In this study,an LC-MS/MS method was developed and validated to quantitate sodium oligomannate in different biomatrices.The plasma pharmacokinetics,tissue distri-bution,and excretion of sodium oligomannate in Sprague-Dawley rats and beagle dogs were system-atically investigated.Despite its complicated structural composition,the absorption,distribution,metabolism,and excretion profiles of the oligosaccharides in sodium oligomannate of different sizes and terminal derivatives were indiscriminate.Sodium oligomannate mainly crossed the gastrointestinal epithelium through paracellular transport following oral administration,with very low oral bioavail-ability in rats(0.6％-1.6％)and dogs(4.5％-9.3％).Absorbed sodium oligomannate mainly resided in circulating body fluids in free form with minimal distribution into erythrocytes and major tissues.So-dium oligomannate could penetrate the blood-cerebrospinal fluid(CSF)barrier of rats,showing a con-stant area under the concentration-time curve ratio(CSF/plasma)of approximately 5％.The cumulative urinary excretion of sodium oligomannate was commensurate with its oral bioavailability,supporting that excretion was predominantly renal,whereas no obvious biliary secretion was observed following a single oral dose to bile duct-cannulated rats.Moreover,only 33.7％(male)and 26.3％(female)of the oral dose were recovered in the rat excreta within 96 h following a single oral administration,suggesting that the intestinal flora may have ingested a portion of unabsorbed sodium oligomannate as a nutrient.

OBJECTIVE: To establish the in vivo traceable acute myeloid leukemia mice model with Luciferase-Expressing KG1a Cells. METHODS: KG1a cells with stable luciferase gene expression (called as KG1a-Luc cells) were constructed by lentivirus transfection, then sifted out by puromycin. Eighteen male NOD-SCID-IL2rg RESULTS: KG1a cells expressing luciferase stably were successfully obtained. The tumor luminescence wildly spread at day 17 captured by in vivo imaging. The KG1a-Luc tumor cells could be detected in the peripheral blood of the mice, with the average percentage of (16.27±6.66)%. The morphology and pathology result showed that KG1a-Luc cells infiltrate was detected in bone marrow, spleens and livers. The survival time of the KG1a-Luc mice was notably shorter as compared with those in the control group, the median survival time was 30.5 days (95%CI: 0.008-0.260). CONCLUSION The acute myeloid leukemia NOD-SCID-IL2rg
Animals ; Disease Models, Animal ; Interleukin Receptor Common gamma Subunit ; Leukemia, Myeloid, Acute ; Luciferases/genetics* ; Male ; Mice ; Mice, Inbred NOD ; Mice, SCID