OBJECTIVE: To prepare decellularized nerve grafts from alpha-1, 3-galactosyltransferase (GGTA1) gene-edited pigs and explore their biocompatibility for xenotransplantation. METHODS: The sciatic nerves from wild-type pigs and GGTA1 gene-edited pigs were obtained and underwent decellularization. The alpha-galactosidase (α-gal) content in the sciatic nerves of GGTA1 gene-edited pigs was detected by using IB4 fluorescence staining and ELISA method to verify the knockout status of the GGTA1 gene, and using human sciatic nerve as a control. HE staining and scanning electron microscopy observation were used to observe the structure of the nerve samples. Immunofluorescence staining and DNA content determination were used to evaluate the degree of decellularization of the nerve samples. Fourteen nude mice were taken, and subcutaneous capsules were prepared on both sides of the spine. Decellularized nerve samples of wild-type pigs ( n=7) and GGTA1 gene-edited pigs ( n=7) were randomly implanted in the subcutaneous capsules. Blood was drawn at 1, 3, 5, and 7 days after implantation to detect neutrophil counting. RESULTS: IB4 fluorescence staining and ELISA detection showed that GGTA1 gene was successfully knocked out in the nerves of GGTA1 gene-edited pigs. HE staining showed that the structure of the decellularized nerve from GGTA1 gene-edited pigs was well preserved; the nerve basement membrane tube structure was visible under scanning electron microscopy; no cell nuclei was observed, and the extracellular matrix components was retained in the nerve grafts by immunofluorescence staining; and the DNA content was significantly reduced when compared with the normal nerves ( P<0.05). In vivo experiments showed that the number of neutrophils in the two groups were similar at 1, 3, and 7 days after implantation, with no significant difference ( P>0.05); only at 5 days, the number of neutrophils was significantly lower in the GGTA1 gene-edited pigs than in the wild-type pigs ( P<0.05). CONCLUSION The decellularized nerve grafts from GGTA1 gene-edited pigs have well-preserved nerve structure, complete decellularization, retain the natural nerve basement membrane tube structure and components, and low immune response after xenotransplantation through in vitro experiments.
Animals ; Transplantation, Heterologous ; Galactosyltransferases/genetics* ; Sciatic Nerve/immunology* ; Swine ; Tissue Engineering/methods* ; Humans ; Graft Rejection/prevention & control* ; Gene Editing ; Mice ; Mice, Nude ; Heterografts/immunology* ; Animals, Genetically Modified ; Tissue Scaffolds ; Decellularized Extracellular Matrix

Immune checkpoint blockade therapy has demonstrated remarkable efficacy in treating various malignancies; however, its clinical application remains challenged by low response rates and immune-related adverse events. Immunoglobulin superfamily member 11 (IGSF11), an inhibitory immune checkpoint molecule, serves as a specific ligand for the V-domain immunoglobulin suppressor of T cell activation (VISTA). Through the IGSF11/VISTA axis, it suppresses T cell function and represents a promising novel target for cancer immunotherapy. IGSF11 is widely expressed across multiple tumor types, though its regulatory mechanisms vary depending on the malignancy. Studies have confirmed that blocking the IGSF11-VISTA interaction or specifically inhibiting IGSF11 exerts antitumor effects. While IGSF11 is closely associated with patient prognosis, its prognostic significance differs among cancer types. This review systematically summarizes the structural characteristics of IGSF11, its regulatory mechanisms, interaction with VISTA, and functional role within the tumor microenvironment.
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Humans ; Immunotherapy ; Neoplasms/metabolism* ; B7 Antigens/chemistry* ; Animals ; Molecular Targeted Therapy ; Tumor Microenvironment

Objective To explore and verify the active components of Dachengqi decoction in regulating autophagy and its mechanism of protecting the intestinal mucosal barrier through network pharmacology and animal experiments.Methods The chemical components and autophagy-related target points of Dachengqi decoction were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database Analysis Platform(TCMSP)and GeneCards databases.The intersection of the drug target points and disease target points was taken and analyzed.The Cytoscape 3.10.2 software's Network Analyzer tool was used to analyze the drug components and target points,and the core target points were screened out to construct a traditional Chinese medicine compound regulatory network.The drug active component target point-disease network model and protein-protein interaction(PPI)network were visualized.Then,30 C57BL/6J mice were randomly divided into the Dachengqi decoction group,the intestinal infection group,and the control group,with 10 mice in each group.The intestinal infection group was given 200 μL/d of Klebsiella pneumoniae strain by gavage for 5 consecutive days,with a colony count of 109 CFU/mL,to create an intestinal infection model.The control group was given 200 μL/d of sterile normal saline by gavage.The Dachengqi decoction group(drug composition:Rhubarb 12 g,Aurantii Fructus 12 g,Magnolia Officinalis 24 g,Mirabilite 9 g,the drugs were dissolved in boiling distilled water to make a 1 kg/L solution)was given by gavage at a dose of 8 g·kg-1·d-1 for 3 consecutive days,and then given Klebsiella pneumoniae by gavage for 5 consecutive days on the 4th day.Detection indicators and methods:after the experiment,the mice were sacrificed and the terminal ileum tissues were collected.The tissues were stained with hematoxylin-eosin(HE),and the pathological changes of the intestinal mucosa were observed under a light microscope;immunofluorescence staining was used to observe the positive expressions of junction proteins ZO-1,Claudin-2,light chain 3-Ⅱ(LC3-Ⅱ),and Beclin-1 and the intestinal mucosal autophagy;the mRNA expression levels of autophagy genes were determined by polymerase chain reaction(PCR).Results The intersection of the obtained drug targets and disease targets yielded 111 potential autophagy-related targets for drug treatment of diseases.Key targets included β2-adrenergic receptor(ADRB2),heme oxygenase-1(HO-1),etc.,and the signaling pathways involved included AMP-activated protein kinase(AMPK)pathway,mammalian target of rapamycin(mTOR)pathway,etc.Animal experiments confirmed that the intestinal mucosal barrier function in the Dachengqi decoction group was better than that in the intestinal infection group,and the positive expression of microtubule-associated protein 1 lingt chain 3-Ⅱ(LC3-Ⅱ)and autophagy gene Beclin1 was significantly higher than that in the intestinal infection group.Transcriptome sequencing results showed that the key genes associated with autophagy and oxidative stress included ADRB2,HO-1,etc.The mRNA expression levels of ADRB2 and HO-1 in the Dachengqi decoction group were significantly higher than those in the intestinal infection group[HO-1 mRNA expression(FPKM):11.20±0.80 vs.6.63±0.53,ADRB2 mRNA expression(FPKM):6.98±0.54 vs.3.98±0.32,both P<0.01],verifying some of the predictions from network pharmacology.Conclusions Dachengqi decoction regulates autophagy through multiple components,multiple targets and multiple pathways,protecting the intestinal mucosal barrier function and reducing the translocation of intestinal microbiota.This lays a certain foundation for further in-depth research on the mechanism of reducing intestinal bacterial translocation by Dachengqi decoction.

Rhinovirus (RV) has been reported as one of the main viral causes of human respiratory infections and has received increasing attention in recent years due to its strong association with various respiratory diseases. Studies have shown that RV not only causes the common cold but also plays a critical role in lower respiratory tract conditions such as bronchiolitis, pneumonia, and asthma. Notably, RV is implicated in both the onset and exacerbation of asthma. This review systematically summarizes a wide range of RV-associated respiratory diseases in the available literature. Although there are currently no specific antiviral therapies or vaccines targeting RV, advances in the development of polyvalent vaccines and antiviral drugs provide promising directions for future prevention and treatment. Clarifying the relationship between RV and diseases will provide strong support for optimizing treatment strategies and preventing and controlling respiratory diseases.

Objective:To explore the distribution variation of ultrasound-detected inflammatory lesions with clinical signs in patients with psoriatic arthritis (PsA).Methods:This was based on the Peking University First Hospital Psoriatic Arthritis (PKUPsA) cohort. Patients enrolled from January 2019 to June 2024 were inchuded, patients with complete data of physical examination and ultrasonographic evaluations of 62 joints in the hand and foot. The ultrasound-detected inflammatory lesions including synovitis, tenosynovitis, enthesitis, and soft tissue inflammation were compared with joint tenderness/swelling. The χ2 test was employed to analyze differences between groups. Results:A total of 7 440 joints in 120 PsA patients were included. Overall, the proportion of joints with clinical signs (tenderness or swelling) was higher than those with ultrasound-detected inflammatory lesions [9.14%(680/7 440) vs. 7.93%(590/7 440), χ2=1 245.928, P<0.001], with more tenderness joints than swelling joints [7.72%(574/7 440) vs. 6.14%(457/7 440), χ2=3 264.45, P<0.001]. Clinical signs were primarily observed in hand proximal interphalangeal (PIP), distal interphalangeal (DIP), wrist and ankle joints, mostly in DIP2 joints [19.58%(47/240)]. Ultrasound-detected inflammatory lesions were predominantly found in metatarsophalangeal (MTP), wrist, and ankle joints, mostly in MTP2 joints (18.75%, 45/240). Clinical signs were more prevalent than ultrasound-detected inflammatory lesions in hand PIP1-3, PIP5, DIP2, and DIP5 joints ( P<0.05), whereas more frequent ultrasound-detected inflammatory lesions than clinical tenderness/swelling were in MTP1-4 joints ( P<0.05). Among ultrasound-detected inflammatory lesions, synovitis in MTP2 joints (18.75%, 45/240), tenosynovitis in ankle joints (10.00%, 24/240), enthesitis in hand DIP2 joints (8.75%, 21/240), and soft tissue inflammation in MTP4 joints (2.50%, 6/240) most commonly observed. Dactylitis was more frequently observed in toes than in fingers, with the fourth toe most commonly affected(16.67%, 40/240). Ultrasound-detected inflammatory lesions were observed in 72.37%(55/240) of fingers/toes with clinical dactylitis, mainly presenting as synovitis, tenosynovitis, or combinations of these. Conclusion:PsA exhibits significant heterogeneity in the inflammatory lesions across different joints and lesion types. The discrepancies between clinical findings and ultrasonic inflammatory changes highlight the limitations of physical examination in fully capturing the pathological features of PsA. As a critical tool for PsA evaluation, ultrasonography offers distinct advantages in detecting subclinical inflammation and differentiating inflammatory from non-inflammatory lesions.

Objective To explore the value of CT radiomics analysis in predicting the curative effect of extracorporeal shock wave lithotripsy(ESWL)in ureteral calculus(UC)patients.Methods A total of 126 UC patients who underwent ESWL from January 2018 to December 2023 were selected,and randomly divided into training group and validation group at a ratio of 7∶3.Forty-five UC patients from January 2024 to September 2024 were selected as external validation group and divided into two groups according to whether the residual stones were less than 4 mm after operation.There were 81 cases in the successful lithotripsy group and 45 cases in the failed lithotripsy group.The 3D Slicer software was used to outline the stone layer by layer to obtain region of interest(ROI),and 851 radiomics features were extracted.After the observer consistency test,maximum relevance and minimum redundancy(mRMR)algorithm and least absolute shrinkage and selection operator(LASSO),the radiomics features were selected,and the logistic regression model was established.The diagnostic efficiency of the model was analyzed by receiver operating characteristic(ROC)curve.Results The six optimal features were obtained from the radiomics features.The combined clinical-radiomics model showed the best prediction efficiency with area under the curve(AUC)of 0.908,0.906 and 0.908 in the training,validation and external validation groups respectively.Conclusion CT radiomics model can be used to predict the curative effect of UC patients after ESWL,and provide a basis for assisting UC patients in individualized treatment.

Objective To explore the value of CT radiomics analysis in predicting the curative effect of extracorporeal shock wave lithotripsy(ESWL)in ureteral calculus(UC)patients.Methods A total of 126 UC patients who underwent ESWL from January 2018 to December 2023 were selected,and randomly divided into training group and validation group at a ratio of 7∶3.Forty-five UC patients from January 2024 to September 2024 were selected as external validation group and divided into two groups according to whether the residual stones were less than 4 mm after operation.There were 81 cases in the successful lithotripsy group and 45 cases in the failed lithotripsy group.The 3D Slicer software was used to outline the stone layer by layer to obtain region of interest(ROI),and 851 radiomics features were extracted.After the observer consistency test,maximum relevance and minimum redundancy(mRMR)algorithm and least absolute shrinkage and selection operator(LASSO),the radiomics features were selected,and the logistic regression model was established.The diagnostic efficiency of the model was analyzed by receiver operating characteristic(ROC)curve.Results The six optimal features were obtained from the radiomics features.The combined clinical-radiomics model showed the best prediction efficiency with area under the curve(AUC)of 0.908,0.906 and 0.908 in the training,validation and external validation groups respectively.Conclusion CT radiomics model can be used to predict the curative effect of UC patients after ESWL,and provide a basis for assisting UC patients in individualized treatment.

Objective To explore and verify the active components of Dachengqi decoction in regulating autophagy and its mechanism of protecting the intestinal mucosal barrier through network pharmacology and animal experiments.Methods The chemical components and autophagy-related target points of Dachengqi decoction were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database Analysis Platform(TCMSP)and GeneCards databases.The intersection of the drug target points and disease target points was taken and analyzed.The Cytoscape 3.10.2 software's Network Analyzer tool was used to analyze the drug components and target points,and the core target points were screened out to construct a traditional Chinese medicine compound regulatory network.The drug active component target point-disease network model and protein-protein interaction(PPI)network were visualized.Then,30 C57BL/6J mice were randomly divided into the Dachengqi decoction group,the intestinal infection group,and the control group,with 10 mice in each group.The intestinal infection group was given 200 μL/d of Klebsiella pneumoniae strain by gavage for 5 consecutive days,with a colony count of 109 CFU/mL,to create an intestinal infection model.The control group was given 200 μL/d of sterile normal saline by gavage.The Dachengqi decoction group(drug composition:Rhubarb 12 g,Aurantii Fructus 12 g,Magnolia Officinalis 24 g,Mirabilite 9 g,the drugs were dissolved in boiling distilled water to make a 1 kg/L solution)was given by gavage at a dose of 8 g·kg-1·d-1 for 3 consecutive days,and then given Klebsiella pneumoniae by gavage for 5 consecutive days on the 4th day.Detection indicators and methods:after the experiment,the mice were sacrificed and the terminal ileum tissues were collected.The tissues were stained with hematoxylin-eosin(HE),and the pathological changes of the intestinal mucosa were observed under a light microscope;immunofluorescence staining was used to observe the positive expressions of junction proteins ZO-1,Claudin-2,light chain 3-Ⅱ(LC3-Ⅱ),and Beclin-1 and the intestinal mucosal autophagy;the mRNA expression levels of autophagy genes were determined by polymerase chain reaction(PCR).Results The intersection of the obtained drug targets and disease targets yielded 111 potential autophagy-related targets for drug treatment of diseases.Key targets included β2-adrenergic receptor(ADRB2),heme oxygenase-1(HO-1),etc.,and the signaling pathways involved included AMP-activated protein kinase(AMPK)pathway,mammalian target of rapamycin(mTOR)pathway,etc.Animal experiments confirmed that the intestinal mucosal barrier function in the Dachengqi decoction group was better than that in the intestinal infection group,and the positive expression of microtubule-associated protein 1 lingt chain 3-Ⅱ(LC3-Ⅱ)and autophagy gene Beclin1 was significantly higher than that in the intestinal infection group.Transcriptome sequencing results showed that the key genes associated with autophagy and oxidative stress included ADRB2,HO-1,etc.The mRNA expression levels of ADRB2 and HO-1 in the Dachengqi decoction group were significantly higher than those in the intestinal infection group[HO-1 mRNA expression(FPKM):11.20±0.80 vs.6.63±0.53,ADRB2 mRNA expression(FPKM):6.98±0.54 vs.3.98±0.32,both P<0.01],verifying some of the predictions from network pharmacology.Conclusions Dachengqi decoction regulates autophagy through multiple components,multiple targets and multiple pathways,protecting the intestinal mucosal barrier function and reducing the translocation of intestinal microbiota.This lays a certain foundation for further in-depth research on the mechanism of reducing intestinal bacterial translocation by Dachengqi decoction.

Rhinovirus (RV) has been reported as one of the main viral causes of human respiratory infections and has received increasing attention in recent years due to its strong association with various respiratory diseases. Studies have shown that RV not only causes the common cold but also plays a critical role in lower respiratory tract conditions such as bronchiolitis, pneumonia, and asthma. Notably, RV is implicated in both the onset and exacerbation of asthma. This review systematically summarizes a wide range of RV-associated respiratory diseases in the available literature. Although there are currently no specific antiviral therapies or vaccines targeting RV, advances in the development of polyvalent vaccines and antiviral drugs provide promising directions for future prevention and treatment. Clarifying the relationship between RV and diseases will provide strong support for optimizing treatment strategies and preventing and controlling respiratory diseases.

Objective:To explore the distribution variation of ultrasound-detected inflammatory lesions with clinical signs in patients with psoriatic arthritis (PsA).Methods:This was based on the Peking University First Hospital Psoriatic Arthritis (PKUPsA) cohort. Patients enrolled from January 2019 to June 2024 were inchuded, patients with complete data of physical examination and ultrasonographic evaluations of 62 joints in the hand and foot. The ultrasound-detected inflammatory lesions including synovitis, tenosynovitis, enthesitis, and soft tissue inflammation were compared with joint tenderness/swelling. The χ2 test was employed to analyze differences between groups. Results:A total of 7 440 joints in 120 PsA patients were included. Overall, the proportion of joints with clinical signs (tenderness or swelling) was higher than those with ultrasound-detected inflammatory lesions [9.14%(680/7 440) vs. 7.93%(590/7 440), χ2=1 245.928, P<0.001], with more tenderness joints than swelling joints [7.72%(574/7 440) vs. 6.14%(457/7 440), χ2=3 264.45, P<0.001]. Clinical signs were primarily observed in hand proximal interphalangeal (PIP), distal interphalangeal (DIP), wrist and ankle joints, mostly in DIP2 joints [19.58%(47/240)]. Ultrasound-detected inflammatory lesions were predominantly found in metatarsophalangeal (MTP), wrist, and ankle joints, mostly in MTP2 joints (18.75%, 45/240). Clinical signs were more prevalent than ultrasound-detected inflammatory lesions in hand PIP1-3, PIP5, DIP2, and DIP5 joints ( P<0.05), whereas more frequent ultrasound-detected inflammatory lesions than clinical tenderness/swelling were in MTP1-4 joints ( P<0.05). Among ultrasound-detected inflammatory lesions, synovitis in MTP2 joints (18.75%, 45/240), tenosynovitis in ankle joints (10.00%, 24/240), enthesitis in hand DIP2 joints (8.75%, 21/240), and soft tissue inflammation in MTP4 joints (2.50%, 6/240) most commonly observed. Dactylitis was more frequently observed in toes than in fingers, with the fourth toe most commonly affected(16.67%, 40/240). Ultrasound-detected inflammatory lesions were observed in 72.37%(55/240) of fingers/toes with clinical dactylitis, mainly presenting as synovitis, tenosynovitis, or combinations of these. Conclusion:PsA exhibits significant heterogeneity in the inflammatory lesions across different joints and lesion types. The discrepancies between clinical findings and ultrasonic inflammatory changes highlight the limitations of physical examination in fully capturing the pathological features of PsA. As a critical tool for PsA evaluation, ultrasonography offers distinct advantages in detecting subclinical inflammation and differentiating inflammatory from non-inflammatory lesions.