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 investigate the differences and the immunocompatibility of wild-type (WT), four-gene modified (TKO/hCD55) and six-gene modified (TKO/hCD55/hCD46/hTBM) pig erythrocytes with human serum. Methods The blood samples were collected from 20 volunteers with different blood groups. WT, TKO/hCD55, TKO/hCD55/hCD46/hTBM pig erythrocytes, ABO-compatible (ABO-C) and ABO-incompatible (ABO-I) human erythrocytes were exposed to human serum of different blood groups, respectively. The blood agglutination and antigen-antibody binding levels (IgG, IgM) and complement-dependent cytotoxicity were detected. The immunocompatibility of two types of genetically modified pig erythrocytes with human serum was evaluated. Results No significant blood agglutination was observed in the ABO-C group. The blood agglutination levels in the WT and ABO-I groups were higher than those in the TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups (all P<0.001). The level of erythrocyte lysis in the WT group was higher than those in the ABO-C, TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups. The level of erythrocyte lysis in the ABO-I group was higher than those in the TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups (both P<0.01). The pig erythrocyte binding level with IgM and IgG in the TKO/hCD55 group was lower than those in the WT and ABO-I groups. The pig erythrocyte binding level with IgG and IgM in the TKO/hCD55/hCD46/hTBM group was lower than that in the WT group and pig erythrocyte binding level with IgG was lower than that in the ABO-I group (all P<0.05). Conclusions The immunocompatibility of genetically modified pig erythrocytes is better than that of wild-type pigs and close to that of ABO-C pigs. Humanized pig erythrocytes may be considered as a blood source when blood sources are extremely scarce.

Objective:To understand the epidemiological characteristics of human respiratory syncytial virus (HRSV) among acute respiratory infection (ARI) cases in 16 provinces of China from 2009 to 2023.Methods:The data of this study were collected from the ARI surveillance data from 16 provinces in China from 2009 to 2023, with a total of 28 278 ARI cases included in the study. The clinical specimens from ARI cases were screened for HRSV nucleic acid from 2009 to 2023, and differences in virus detection rates among cases of different age groups, regions, and months were analyzed.Results:A total of 28 278 ARI cases were enrolled from January 2009 to September 2023. The age of the cases ranged from<1 month to 112 years, and the age M ( Q1, Q3) was 3 years (1 year, 9 years). Among them, 3 062 cases were positive for HRSV nucleic acid, with a total detection rate of 10.83%. From 2009 to 2019, the detection rate of HRSV was 9.33%, and the virus was mainly prevalent in winter and spring. During the Corona Virus Disease 2019 (COVID-19) pandemic, the detection rate of HRSV fluctuated between 6.32% and 18.67%. There was no traditional winter epidemic peak of HRSV from the end of 2022 to the beginning of 2023, and an anti-seasonal epidemic of HRSV occurred from April to May 2023. About 87.95% (2 693/3 062) of positive cases were children under 5 years old, and the difference in the detection rate of HRSV among different age groups was statistically significant ( P<0.001), showing a decreasing trend of HRSV detection rate with the increase of age ( P<0.001). Among them, the HRSV detection rate (25.69%) was highest in children under 6 months. Compared with 2009-2019, the ranking of HRSV detection rates in different age groups changed from high to low between 2020 and 2023, with the age M (Q1, Q3) of HRSV positive cases increasing from 1 year (6 months, 3 years) to 2 years (11 months, 3 years). Conclusion:Through 15 years of continuous HRSV surveillance analysis, children under 5 years old, especially infants under 6 months old, are the main high-risk population for HRSV infection. During the COVID-19 pandemic, the prevalence and patterns of HRSV in China have changed.

Objective:To explore the effects and safety of saline mixed 1∶1 with contrast medium (mixed medium) and pure heparinized saline as alternative media for optimal Optical Coherence Tomography (OCT) guided percutaneous coronary intervention (PCI).Methods:This single-center, prospective cohort study enrolled patients who underwent PCI with OCT guidance for chronic stable angina or acute coronary syndrome at the Department of Cardiology, the Second Hospital of Jilin University from October 2021 to August 2022. The target vessels were examined using OCT with three different flushing media at the same anatomical positions: contrast agent, mixed medium, and pure heparinized saline. An independent observer analyzed all imaging results and evaluated the lumen imaging quality, using the proportion of the clear imaging field (CIF%) as a quantitative measure for analysis. The average luminal diameter was compared among different flushing media. The study also assessed the image quality of the luminal anatomical structures, lesion pathologies, and stents.Results:A total of 105 patients were enrolled in the study, including 110 target vessels. The age of the enrolled patients was (60.5±8.4) years, with 60 male patients (57.1%). OCT examinations were successfully completed using all three media, and no related complications were observed in any groups. The three flushing media presented with the same image quality in terms of depicting the lumen anatomical structures, lesion characteristics, and stent-related features. The mixed medium group achieved a comparable CIF% to the contrast group with both right and left coronary arteries (right coronary 100.0% (100.0%, 100.0%) vs. 100.0% (100.0%, 100.0%), P>0.05; left coronary 100.0% (95.9%, 100.0%) vs. 100.0% (100.0%, 100.0%), P>0.05). While the saline group reached a comparable CIF% to the contrast group with right coronary arteries (100.0% (97.6%, 100.0%) vs. 100.0% (95.9%, 100.0%), P>0.05) but showed a significantly lower CIF% with left coronary arteries (84.9% (75.9%, 93.4%) vs. 100.0% (100.0%, 100.0%), P<0.05). For the average diameter of the coronary lumen, there was no statistically significant difference between the mixed medium group and the saline group compared to the contrast group with both right and left coronary arteries ( P>0.05). Conclusions:A 1∶1 heparinized saline and contrast mixture can serve as a substitute flushing medium for OCT examination during PCI procedure. Pure saline can also yield good results in OCT examination of the right coronary artery, and both alternatives are safe for use as flushing medium in OCT imaging.

Objective:To understand the epidemiological characteristics of human respiratory syncytial virus (HRSV) among acute respiratory infection (ARI) cases in 16 provinces of China from 2009 to 2023.Methods:The data of this study were collected from the ARI surveillance data from 16 provinces in China from 2009 to 2023, with a total of 28 278 ARI cases included in the study. The clinical specimens from ARI cases were screened for HRSV nucleic acid from 2009 to 2023, and differences in virus detection rates among cases of different age groups, regions, and months were analyzed.Results:A total of 28 278 ARI cases were enrolled from January 2009 to September 2023. The age of the cases ranged from<1 month to 112 years, and the age M ( Q1, Q3) was 3 years (1 year, 9 years). Among them, 3 062 cases were positive for HRSV nucleic acid, with a total detection rate of 10.83%. From 2009 to 2019, the detection rate of HRSV was 9.33%, and the virus was mainly prevalent in winter and spring. During the Corona Virus Disease 2019 (COVID-19) pandemic, the detection rate of HRSV fluctuated between 6.32% and 18.67%. There was no traditional winter epidemic peak of HRSV from the end of 2022 to the beginning of 2023, and an anti-seasonal epidemic of HRSV occurred from April to May 2023. About 87.95% (2 693/3 062) of positive cases were children under 5 years old, and the difference in the detection rate of HRSV among different age groups was statistically significant ( P<0.001), showing a decreasing trend of HRSV detection rate with the increase of age ( P<0.001). Among them, the HRSV detection rate (25.69%) was highest in children under 6 months. Compared with 2009-2019, the ranking of HRSV detection rates in different age groups changed from high to low between 2020 and 2023, with the age M (Q1, Q3) of HRSV positive cases increasing from 1 year (6 months, 3 years) to 2 years (11 months, 3 years). Conclusion:Through 15 years of continuous HRSV surveillance analysis, children under 5 years old, especially infants under 6 months old, are the main high-risk population for HRSV infection. During the COVID-19 pandemic, the prevalence and patterns of HRSV in China have changed.

Objective To screen ischemia and hypoxiarelated genes(IAHRGs)after spinal cord injury(SCI)and analyze their immune infiltration patterns by bioinformatics methods.Methods The expression profiles of SCI-related GSE5296,GSE47681 and GSE217797 were downloaded from the Gene Expression Omnibus(GEO)database,where GSE5296,GSE47681 samples were used as the test set and GSE217797 samples as the validation set,and the differentially expressed genes(DEGs)between SCI and healthy samples were obtained.IAHRGs were screened in GeneCards and MSigDB databases.The intersection of DEGs and IAHRGs yielded ischemic and hypoxia related differentially expressed genes(IAHRDEGs).Based on the IAHRDEGs,the key genes were jointly screened by LASSO model and SVM analysis.The key genes were subjected to logistic regression analysis and a diagnostic model was constructed.The diagnostic ability of the diagnostic model was analyzed by Nomogram and the column line graph of Logistic predictive values was plotted.The diagnostic value of the diagnostic model and key genes for SCI was evaluated using the receiver operating characteristics(ROC).Immune cell infiltration patterns of the disease were analyzed using the CIBERSORT tool.Results A total of 388 IAHRGs were screened,313 differentially expressed genes were detected between SCI and healthy samples,among which 312 were up-regulated and 1 was down-regulated.A sum of 27 up-regulated IAHRDEGs genes were obtained.Five key genes related to ischemia and hypoxia after SCI(Abca1,Caspl,Lpl,Procr,Tnfrsf1a)were screened by LASSO model and SVM analysis based on IAHRDEGs.Nomogram analysis confirms the effect of logistics diagnosis model.ROC curve analysis showed that Casp1,Lpl and Tnfrsf1a had higher diagnostic efficacy(AUC＞0.9),followed by Abca1 and Procr(AUC:0.7～0.9),and the logistics linear predictors had the best diagnostic effect(AUC=0.964).CIBERSORT analysis showed that five key genes were associated with the infiltration of eight types of immune cells(neutrophil cells,B cells naive,plasma cells,M0 macrophage,T cells CD4 naive,T cells CD4 follicular,Th17 cells,and NK resting).Conclusion The five key genes of Abcal,Caspl,Lpl,Procr,and Tnfrsfla,may be closely related to ischemic-hypoxic pathogenesis after SCI,and can be used as candidate molecular markers for the diagnosis and treatment after SCI.

BACKGROUND: Vaccination has been shown effective in controlling the global coronavirus disease 2019 (COVID-19) pandemic and reducing severe cases. This study was to assess the flare and change in disease activity after COVID-19 vaccination in patients with stable rheumatoid arthritis (RA). METHODS: A prospective cohort of RA patients in remission or with low disease activity was divided into a vaccination group and a non-vaccination group based on their COVID-19 vaccination status. Each of them was examined every 3 to 6 months. In the vaccination group, disease activity was compared before and after vaccination. The rates of flare defined as disease activity scores based on 28-joint count (DAS28) >3.2 with ΔDAS28 ≥0.6 were compared between vaccination and non-vaccination groups. RESULTS: A total of 202 eligible RA patients were enrolled. Of these, 98 patients received no vaccine shot (non-vaccination group), and 104 patients received two doses of vaccine (vaccination group). The median time interval from pre-vaccination visit to the first immunization and from the second dose of vaccine to post-vaccination visit was 67 days and 83 days, respectively. The disease activity scores at pre-vaccination and post-vaccination visits in the vaccination group patients were similar. At enrollment, gender, RA disease course, seropositivity, and disease activity were comparable across the two groups. Flare was observed in five (4.8%) of the vaccination group patients and nine (9.2%) of the non-vaccination group patients at post-vaccination assessment ( P  = 0.221). In terms of safety, 29 (27.9%) patients experienced adverse events (AEs) after vaccination. No serious AEs occurred. CONCLUSIONS COVID-19 vaccinations had no significant effect on disease activity or risk of flare in RA patients in remission or with low disease activity. Patients with stable RA should be encouraged to receive the COVID-19 vaccination.
Humans ; Arthritis, Rheumatoid ; Cohort Studies ; COVID-19/prevention & control* ; COVID-19 Vaccines/adverse effects* ; East Asian People ; Prospective Studies ; Vaccination/adverse effects*

Objective:To analyze the molecular characteristics of hemagglutinin-neuraminidase (HN) gene of human parainfluenza virus type 3 (HPIV3) among the cases with acute respiratory tract infection (ARI) in Henan Province.Methods:Nasal/throat swab samples collected from patients with severe acute respiratory tract infection (SARI) in Luohe and patients with influenza-like illness (ILI) in Zhengzhou were used in this study. HPIV nucleic acids in the samples were detected using real-time fluorescent PCR. HPIV3-positive samples were subjected to RT-PCR for the amplification of HN genes and the sequences were analyzed with Sanger method. CExpress and MEGA7.0 software were used for sequences editing, evolution tree construction and gene sequence analysis.Results:A total of 374 throat swab samples collected form ARI cases in Luohe and Zhengzhou were tested and 20 (5.3%) of them were positive for HPIV3. Eighteen HPIV3 HN gene sequences were successfully amplified and all belonged to C3 subgroups, including 16 sequences of C3f genotype and two sequences of C3a genotype. The 18 HN gene sequences shared the homology of 97.6%-100.0% in nucleotide and 99.3%-100.0% in amino acid, but the differences between them and the prototype strain Wash/47885/57 were significant. There were 12 amino acid mutations shared by them, including four function-related mutations (H295Y, I391V, D556N and I53T). There were no significant differences in the nucleotide or amino acid sequences as compared with the epidemic strain of China/BCH4210A/2014.Conclusions:The C3f and C3a branches of HPIV3 were the epidemic genotypes in Henan Province in recent years and a local circulating prevalence might be established. Continuous and in-depth monitoring of HPIV3 C3 subtype would be of great significance for the prevention and control of HPIV3-associated diseases.

Objective To explore the relationship between carbohydrate sulfotransferase 6(CHST6)expression level and prognosis in glioma patients and construct prognosis model by using bioinformatics method.Methods To analyze the difference of CHST6 expression in glioma.The median CHST6 expression was divided into high and low expression groups.The prognostic differences between the groups were analyzed.The expression level of CHST6 and different clinical features were analyzed by Cox regression,and the prediction and improvement model was established,and the validity improvement was compared with the control model.Results A total of 1204 medical records were included in TCGA and CGGA databases.CHST6 was significantly up-regulated in glioma samples(TCGA vs.GTEx,Z= 2.457,P＜0.001;CGGA vs.GTEx,Z=4.800,P＜0.001),and was an independent prognostic factor for glioma together with age,WHO grade,IDH mutation status,and 1p19q co-deletion(Cox analysis β=0.02,SE=0.01,HR=1.02,95%CI:1.01～1.04,P=0.01;C-Index 0.885,95%CI:0.862～0.908),has higher predictive validity than the control model(Improved model vs.Control model:TCGA d=0.036±0.004,SE=0.002,P=0.007;CGGA d=0.087±0.004,SE=0.002,P=0.001).Conclusion The high expression of CHST6 may be a predictor of poor prognosis and abnormal immune function in glioma patients.