IL-33 and its receptor ST2 play crucial roles in tissue repair and homeostasis. However, their involvement in optic neuropathy due to trauma and glaucoma remains unclear. Here, we report that IL-33 and ST2 were highly expressed in the mouse optic nerve and retina. Deletion of IL-33 or ST2 exacerbated retinal ganglion cell (RGC) loss, retinal thinning, and nerve fiber degeneration following optic nerve (ON) injury. This heightened retinal neurodegeneration correlated with increased neurotoxic astrocytes in Il33^-/- mice. In vitro, rIL-33 mitigated the neurotoxic astrocyte phenotype and reduced the expression of pro-inflammatory factors, thereby alleviating the RGC death induced by neurotoxic astrocyte-conditioned medium in retinal explants. Exogenous IL-33 treatment improved RGC survival in Il33^-/- and WT mice after ON injury, but not in ST2^-/- mice. Our findings highlight the role of the IL-33/ST2 axis in modulating reactive astrocyte function and providing neuroprotection for RGCs following ON injury.
Animals ; Interleukin-33/genetics* ; Interleukin-1 Receptor-Like 1 Protein/genetics* ; Optic Nerve Injuries/pathology* ; Retinal Ganglion Cells/pathology* ; Astrocytes/pathology* ; Mice ; Mice, Knockout ; Mice, Inbred C57BL ; Neuroprotection/physiology*

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Objective To investigate the capacity of low-intensity pulsed ultrasound(LIPUS)for promoting osteogenic differentiation of senescent bone marrow mesenchymal stem cell(BMMSC)in mice,also the potential mechanism of involving myocardin-related transcription factor-A(MRTF-A)during this process.Methods Five aged mice received LIPUS irradiation on the left femur for eight weeks.Micro CT and HE staining were employed to evaluate bone status of bilateral femur.Bone marrow cells were isolated from mouse long bones,BMMSC were cultured,and the cells were divided into H2O2+LIPUS group,H2O2 group and control group.Mouse BMMSC were subjected to H2O2 for 3 days,followed by reactive oxygen species fluorescence staining and senescence-associated β-galactosidase staining to assess cellular senescence.Immunofluorescence and phalloidin staining were performed to examine MRTF-A distribution and cytoskeletal status.Based on H2O2-induced senescence model,MRTF-A nuclear translocation inhibitor CCG-100602 was applied,and the cells were further divided into H2O2+CCG-100602+LIPUS group,H2O2+CCG-100602 group,H2O2+LIPUS group and H2O2 group.Immunofluorescence staining was used to assess MRTF-A distribution.Alkaline phosphatase(ALP)and alizarin red staining were conducted to evaluate osteogenic differentiation capacity.Results LIPUS resulted in increased trabecular bone in the left femur of aged mice compared to the right femur,with increased bone volume to total volume and trabecular number and decreased trabecular spacing(both P＜0.05).Compared with H2O2 group,H2O2+LIPUS group showed increased nuclear expression of MRTF-A and increased intracellular rigid actin filament density.The nuclear expression of MRTF-A in H2O2+CCG-100602+LIPUS group was significantly lower than that in H2O2+LIPUS group.Compared with the H2O2+CCG-100602+LIPUS group and H2O2 group,the ALP and alizarin red staining positive areas in H2O2+LIPUS group were significantly larger.Conclusion LIPUS could improve osteoporosis in aged mice.Nuclear translocation of MRTF-A was a key regulator to LIPUS for promoting osteogenic differentiation of senescent BMMSC.

Objective:To develop a modified University of Wisconsin preservation solution (UW solution) containing α 2-adrenergic receptor agonists (dexmedetomidine) and noble gases (argon) and investigate its protective effect on the isolated amputated skeletal muscle of rats. Methods:Sixty male SD rats were selected to establish a hindlimb cold preservation/perfusion model and were divided into blank control group, hypothermic storage group, UW solution perfusion group, and modified UW solution perfusion group using a random number table, with 15 rats in each group. Simultaneously, a cold preservation model of rat skeletal muscle myoblasts (L6 cells) was established and the rats were also divided into four groups in the same way. Animal models were prepared in different ways: In the blank control group, the hindlimbs received no special treatment; In the hypothermic storage group, the amputated hindlimbs were stored in a dry centrifuge tube at 4℃ for 18 hours; In the UW solution perfusion group, the amputated hindlimbs were perfused with UW solution and then stored in a centrifuge tube containing UW solution at 4℃ for 18 hours; In the modified UW solution perfusion group, the amputated hindlimbs were perfused with modified UW solution (containing 0.1 nmol/L dexmedetomidine and 50% volume fraction of argon) and then stored in a centrifuge tube containing the modified UW solution at 4℃ for 18 hours. Cell models were treated as follows: In the blank control group, L6 cells were cultured under standard conditions; In the hypothermic storage group and UW solution group, L6 cells were treated with conventional culture medium or UW solution, stored in argon-filled sealed bags at 4℃ for 8 hours, and then rewarmed and cultured for 6 hours; In the modified UW solution group, L6 cells were treated with the modified solution, stored in argon-filled sealed bags at 4℃ for 8 hours, and then rewarmed and cultured for 6 hours. After sample collection, skeletal muscle morphology, tissue edema and ultrastructure features were assessed by HE staining, wet-to-dry weight ratio, and transmission electron microscopy, respectively. Additionally, L6 cell morphology was examined by light microscopy. L6 cell viability was determined by cell counting kit-8 (CCK-8) assay (expressed as absorbance A value). Expression levels of glutathione peroxidase 4 (GPX4) protein in both skeletal muscle tissue and L6 cells were evaluated by immunofluorescence staining and Western blot, respectively.Results:After 18 hours of in vitro preservation of rat isolated amputated limbs, the following results were obtained: (1) HE staining results showed that the muscle fiber morphology of the modified UW solution perfusion group was close to that of the blank control group. Moreover, the area ratio of skeletal muscle cells in the modified UW solution perfusion group was significantly higher than that in the hypothermic storage group and UW solution perfusion group ( P<0.05). (2) The wet-dry weight ratio results showed that there was no statistically significant difference among the modified UW solution perfusion group, the blank control group and UW solution group ( P>0.05), with significantly lower ratios in all three groups than that in the hypothermic storage group ( P<0.05). (3) Transmission electron microscopy results revealed that the modified UW solution perfusion group showed no statistically significant differences in ultrastructural metrics, including myofiber diameter, sarcomere length, mitochondrial short-axis/long-axis ratio, and mitochondrial cristae count, compared with those in the blank control group ( P>0.05), and performed significantly better than both the hypothermic storage group and UW solution perfusion group ( P<0.05). (4) Morphological observation of L6 cells showed that the cellular morphology was regular in the modified UW solution perfusion group, close to that in the blank control group, while it was severely damaged in the hypothermic storage group. Moreover, the cells were reduced in number and partially damaged in the UW solution group. The sequence of cell viability expressed as absorbance A value was blank control group >modified UW solution perfusion group > UW solution perfusion group > hypothermic storage group, with statistically significant differences among the four groups ( P<0.05). (5) Immunofluorescence staining showed that there was no statistically significant difference in fluorescence intensity of GPX4 protein expression between the modified UW solution perfusion group and blank control group ( P>0.05), while the fluorescence intensity was higher in the modified UW solution perfusion group than that in the hypothermic storage group and UW solution perfusion group ( P<0.05). Western blot analysis showed that the relative expression level of GPX4 in the modified UW solution group was significantly lower than that in the blank control group ( P<0.05), but higher than that in the hypothermic storage group and UW solution perfusion group ( P<0.05). Conclusion:The modified UW solution can stabilize the expression level of GPX4 protein, thereby inhibiting ferroptosis and alleviating cold preservation injury in both rat amputated isolated limb skeletal muscle tissue and L6 cells.

Objective:To analyze the short-term hospital-based transmission characteristics and gene variation of Carbapenem-Resistant Klebsiella pneumoniae (CRKP) by genome-wide technique to provide evidence for transmission control. Methods:The experimental strain was derived from all the CRKP isolated in Affiliated Hospital of North China University of Science and Technology from October 2022 to December 2023. Strain identification and drug susceptibility were tested with VITEK 2-Compact automatic bacterial identification drug susceptibility analyzer or disk method, and the results were interpreted through whole genome sequencing. The ST type, carbapenem resistance gene, virulence factor, and O serotype of the collected strains were analyzed.Results:Among the 115 strains of CRKP, 94 strains were isolated from the intensive care unit (ICU), accounting for 81.7%, and 21 strains were isolated from the non-intensive care unit (NICU), accounting for 18.3%. The 115 strains of CRKP can be divided into 11 ST types, of which ST11 type was the most (54.8%, 63/115), followed by ST15 type (22.6%, 26/115) and ST5492 type (15.7%, 18/115). Type ST5492 was a new clonal group in the region. The 115 strains of CRKP could be divided into 7 O serotypes, most of which were O2a type(32.2%,37/115), followed by O5 type(30.4%,35/115) and O1 type(27.8%,32/115). The resistance genes of carbapenem antibiotics showed that there were 107 strains carrying the blaKPC-2 gene, one strain with the blaNDM-1 gene, and one strain with both the blaKPC-2 and blaNDM-13 genes. Virulence genes were detected in 55 CRKP strains (47.8%, 55/115), among which six strains detected peg-344, iucA, iroB, rmpA, and rmpA2 virulence genes (5.2%, 6/115). Four virulence genes ( peg-344, iucA, rmpA, and rmpA2) were detected in 34 strains (29.6%, 34/115). Three virulence genes ( iucA, iroB and rmpA) were detected in two strains (1.7%, 2/115). Three virulence genes ( peg-344, iucA and rmpA) were detected in one strain (0.8%, 1/115). IucA and rmpA virulence genes were detected in 12 strains (10.4%, 12/115). KPC-2_ST11_O2a, KPC-2_ST15_O1 and KPC-2_ST5492_O5 were dominant clones, and their distribution was mainly in the intensive care unit. The whole genome sequence analysis showed that there were three dominant clones, among which ST11 clones were subdivided into three dominant O serotypes, all of which were mainly in the intensive care unit. Conclusion:The popular strain in the hospital of CRKP is a KPC-2_ST11 clone group carrying iucA, rmpA/rmpA2, with cross-department transmission and mutation. ST5492 is a newly-launched clone type. The intensive care unit of hvKP carrying five virulence genes, including peg-344, should be alert to the epidemic risk of CR-hvKP outbreak.

Objective:Exploring the diagnostic and therapeutic points of pectoralis minor muscle transection for the treatment of pectoralis minor syndrome, as well as the differences between pectoralis minor syndrome and thoracic outlet syndrome.Methods:A retrospective summary and analysis were conducted on the clinical data, surgical methods, and prognosis of patients with pectoralis minor syndrome who underwent thoracic and cardiovascular surgery at the Second Affiliated Hospital of Southwest Medical University from January 2012 to December 2022. The literature was reviewed, and the clinical data, surgical methods, and prognosis of thoracic outlet syndrome during the same period were combined to analyze the differences between pectoralis minor syndrome and thoracic outlet syndrome.Results:All patients underwent surgical resection of the pectoralis minor muscle, with significant pain relief, disappearance of clinical symptoms, no surgical complications, and a good prognosis.Conclusion:Pectoral muscle syndrome is a disease independent of thoracic outlet syndrome, with a high rate of missed diagnosis and misdiagnosis. Comprehensive preoperative pain localization and closed treatment, clear diagnosis, and cutting of the pectoralis minor muscle are effective methods for treating this disease.

Pathogenesis of immune thrombocytopenia(ITP)is complex,with a high reoccurence rate after first-line treatment and limited efficacy of second-line treatment,especially in refractory ITP,for which there is a lack of effective treatment.In recent years,it has been found that impaired function of mesenchymal stem cells(MSCs)is also involved in pathogenesis of ITP in addition to humoral and cellular immunity.Exogenous infusion of MSCs or endogenous restoration of immunomodulatory function of MSCs is expected to be an effective treatment strategy for ITP.Therefore,this article reviews biological characteristics and immunomodulatory effects of MSCs and their research progress in ITP,with aim of providing new ideas for further elucidating pathogenesis and exploring effective treatment options of ITP.

Objective:To analyze the short-term hospital-based transmission characteristics and gene variation of Carbapenem-Resistant Klebsiella pneumoniae (CRKP) by genome-wide technique to provide evidence for transmission control. Methods:The experimental strain was derived from all the CRKP isolated in Affiliated Hospital of North China University of Science and Technology from October 2022 to December 2023. Strain identification and drug susceptibility were tested with VITEK 2-Compact automatic bacterial identification drug susceptibility analyzer or disk method, and the results were interpreted through whole genome sequencing. The ST type, carbapenem resistance gene, virulence factor, and O serotype of the collected strains were analyzed.Results:Among the 115 strains of CRKP, 94 strains were isolated from the intensive care unit (ICU), accounting for 81.7%, and 21 strains were isolated from the non-intensive care unit (NICU), accounting for 18.3%. The 115 strains of CRKP can be divided into 11 ST types, of which ST11 type was the most (54.8%, 63/115), followed by ST15 type (22.6%, 26/115) and ST5492 type (15.7%, 18/115). Type ST5492 was a new clonal group in the region. The 115 strains of CRKP could be divided into 7 O serotypes, most of which were O2a type(32.2%,37/115), followed by O5 type(30.4%,35/115) and O1 type(27.8%,32/115). The resistance genes of carbapenem antibiotics showed that there were 107 strains carrying the blaKPC-2 gene, one strain with the blaNDM-1 gene, and one strain with both the blaKPC-2 and blaNDM-13 genes. Virulence genes were detected in 55 CRKP strains (47.8%, 55/115), among which six strains detected peg-344, iucA, iroB, rmpA, and rmpA2 virulence genes (5.2%, 6/115). Four virulence genes ( peg-344, iucA, rmpA, and rmpA2) were detected in 34 strains (29.6%, 34/115). Three virulence genes ( iucA, iroB and rmpA) were detected in two strains (1.7%, 2/115). Three virulence genes ( peg-344, iucA and rmpA) were detected in one strain (0.8%, 1/115). IucA and rmpA virulence genes were detected in 12 strains (10.4%, 12/115). KPC-2_ST11_O2a, KPC-2_ST15_O1 and KPC-2_ST5492_O5 were dominant clones, and their distribution was mainly in the intensive care unit. The whole genome sequence analysis showed that there were three dominant clones, among which ST11 clones were subdivided into three dominant O serotypes, all of which were mainly in the intensive care unit. Conclusion:The popular strain in the hospital of CRKP is a KPC-2_ST11 clone group carrying iucA, rmpA/rmpA2, with cross-department transmission and mutation. ST5492 is a newly-launched clone type. The intensive care unit of hvKP carrying five virulence genes, including peg-344, should be alert to the epidemic risk of CR-hvKP outbreak.

Pathogenesis of immune thrombocytopenia(ITP)is complex,with a high reoccurence rate after first-line treatment and limited efficacy of second-line treatment,especially in refractory ITP,for which there is a lack of effective treatment.In recent years,it has been found that impaired function of mesenchymal stem cells(MSCs)is also involved in pathogenesis of ITP in addition to humoral and cellular immunity.Exogenous infusion of MSCs or endogenous restoration of immunomodulatory function of MSCs is expected to be an effective treatment strategy for ITP.Therefore,this article reviews biological characteristics and immunomodulatory effects of MSCs and their research progress in ITP,with aim of providing new ideas for further elucidating pathogenesis and exploring effective treatment options of ITP.

Objective To investigate the capacity of low-intensity pulsed ultrasound(LIPUS)for promoting osteogenic differentiation of senescent bone marrow mesenchymal stem cell(BMMSC)in mice,also the potential mechanism of involving myocardin-related transcription factor-A(MRTF-A)during this process.Methods Five aged mice received LIPUS irradiation on the left femur for eight weeks.Micro CT and HE staining were employed to evaluate bone status of bilateral femur.Bone marrow cells were isolated from mouse long bones,BMMSC were cultured,and the cells were divided into H2O2+LIPUS group,H2O2 group and control group.Mouse BMMSC were subjected to H2O2 for 3 days,followed by reactive oxygen species fluorescence staining and senescence-associated β-galactosidase staining to assess cellular senescence.Immunofluorescence and phalloidin staining were performed to examine MRTF-A distribution and cytoskeletal status.Based on H2O2-induced senescence model,MRTF-A nuclear translocation inhibitor CCG-100602 was applied,and the cells were further divided into H2O2+CCG-100602+LIPUS group,H2O2+CCG-100602 group,H2O2+LIPUS group and H2O2 group.Immunofluorescence staining was used to assess MRTF-A distribution.Alkaline phosphatase(ALP)and alizarin red staining were conducted to evaluate osteogenic differentiation capacity.Results LIPUS resulted in increased trabecular bone in the left femur of aged mice compared to the right femur,with increased bone volume to total volume and trabecular number and decreased trabecular spacing(both P＜0.05).Compared with H2O2 group,H2O2+LIPUS group showed increased nuclear expression of MRTF-A and increased intracellular rigid actin filament density.The nuclear expression of MRTF-A in H2O2+CCG-100602+LIPUS group was significantly lower than that in H2O2+LIPUS group.Compared with the H2O2+CCG-100602+LIPUS group and H2O2 group,the ALP and alizarin red staining positive areas in H2O2+LIPUS group were significantly larger.Conclusion LIPUS could improve osteoporosis in aged mice.Nuclear translocation of MRTF-A was a key regulator to LIPUS for promoting osteogenic differentiation of senescent BMMSC.