Objective To investigate the characteristics of immune exhaustion in sepsis and analyze its association with gut microbiota translocation.Methods A total of 130 mice were randomly divided into a cecal ligation and puncture(CLP)group(n=100)and a Sham group(n=30)Mouse model of sepsis was established with CLP procedure.Flow cytometry was used to analyze the proportions of peripheral blood CD4+T and CD8+T cells and programmed cell death protein 1(PD-1)positive T cell subsets in mice.Bacterial colonization in organs such as the heart,liver and kidneys was quantified by plating homogenates of the organs.Pathological changes in immune organs were observed with HE staining.The expression and localization of CD4?,CD8?,and PD-1?cells in immune organs were detected with immunohistochemical staining,and Image J software was employed for subsequent quantification of the number of the positive cells.Results HE staining demonstrated that immune organs exhibited varying degrees of pathological damages with disease progression.Compared with the Sham mice,the CLP mice exhibited significantly increased bacterial colonization in parenchymal organs and peripheral blood(P<0.05),notably in the liver,which showed the most severe infection.In the CLP group,the proportion of CD4+T lymphocytes in peripheral blood at days 1,3,and 5 postoperatively was decreased by 56%,70.57%,and 87.42%,respectively,when compared with the Sham group(P<0.001).The proportion of CD8+T lymphocytes was decreased by 48.33%relative to the Sham group only at day 5(P<0.001).In contrast,the proportion of CD4+T cell subsets expressing PD-1 was increased to 673.08,423.08,and 600 times that of the Sham group,respectively,at the same postoperative time points(P<0.001).Immunohistochemical results showed that,in the CLP group,the proportion of CD4+T cells in the thymus,spleen,and mesenteric lymph nodes was increased to 7.65,2.66,and 3.7 times that of the Sham group,respectively,at the early-stage peak(P<0.001),and then these proportions were decreased by 82.8%(P<0.001),41.9%(P<0.01),and 60.15%(P<0.001),respectively,at the late-stage trough when compared with the early-stage peak in the corresponding organs.The proportion of CD8+positive cells was increased in the early stage and then decreased insignificantly,while the proportion of PD-1+positive cells was increased continuously,and reached 6.24,13.9,and 20.96 times that of the Sham group at the peak in the thymus,spleen,and mesenteric lymph nodes respectively(P<0.001),with their expression regions showing a rough overlap with those of CD4+cells.Conclusion During sepsis,the inflammatory response can cause severe damage to immune organs and persistent exhaustion of CD4?T lymphocytes,leading to declined defenses against infection,which may be the main causes for exacerbated gut microbiota translocation and then systemic infection.

Objective: To investigate the clinicopathologic and molecular genetic characteristics, diagnosis, differential diagnosis, treatment and prognosis of histiocyte-rich rhabdomyoblastic tumor (HRRMT). Methods: The clinical data of two cases of HRRMT diagnosed in Fujian Provincial Hospital and Fujian University of Traditional Chinese Medicine Affiliated People's Hospital from 2020 to 2021 were collected. Histopathology and immunohistochemical (IHC) staining were used to assess morphological changes; the genetic changes were analyzed with next-generation sequencing. The relevant literature was reviewed. Results: Both cases showed well-defined solid nodules and soft masses. Microscopically, the tumors had a fibrous pseudocapsule with lymphocytic aggregation, and locally invaded the surrounding skeletal muscle tissue, and the tumor cells were fusiform to epithelioid with an intensive foamy histiocytic infiltrate. No necrosis or mitosis was observed. Immunophenotyping showed the tumor cells were positive for desmin, either one or both skeletal muscle markers (myogenin or MyoD1), and negative for h-caldesmon, ALK and SMA. The Ki-67 index was<5%. Using next-generation sequencing, one case was found to harbour KRAS (G12D) and MSH3 (Q470^*) mutations. Conclusions: HRRMT is a newly described skeletal muscle tumor with uncertain malignant potential. Its diagnosis and differential diagnosis depend on morphologic and IHC staining. No specific molecular genetics changes have been identified so far.
Biomarkers, Tumor/analysis* ; Diagnosis, Differential ; Histiocytes/pathology* ; Humans ; Molecular Biology ; Muscle Neoplasms/pathology* ; Prognosis

OBJECTIVE: To observe the analgesic effect of manipulation loading on chronic low back pain (CLBP) model rats and the expression of inflammatory factors in psoas major muscle tissue, and to explore the improvement of manipulation on local inflammatory microenvironment. METHODS: Thirty two SPF male SD rats weighing 340-360g were randomly divided into blank group, sham operation group, chronic low back pain model group and treatment group, with 8 rats in each group. In the model group, L RESULTS: There was no significant difference in PWT and PWL between the blank group and the sham operation group after modeling ( CONCLUSION Local massage loading has analgesic effect on CLBP rats, at the same time, it can inhibit the content of CGRP and NGF in psoas muscle tissue of CLBP rats, and improve the local inflammatory microenvironment.
Animals ; Calcitonin ; Calcitonin Gene-Related Peptide ; Low Back Pain/therapy* ; Male ; Nerve Growth Factor/genetics* ; Rats ; Rats, Sprague-Dawley

Objective::To observe the effect of compound Kushen injection on the expressions of transforming growth factor-β₁ (TGF-β₁), drosophila mothers against decapentaplegic protein 3 (Smad3), glycogen synthase kinase-3β (GSK-3β) and β-catenin mice models with radiation-induced pulmonary injury (RIPI), in order to explore its possible mechanism of action. Method::On XStrahl precision radiation research platform for small animals (SARRP), a single 20 Gy bilateral lung field irradiation was performed to establish a mice model of RIPI. Thirty-two mice were randomly divided into normal control group, model group, compound Kushen injection group and dexamethasone injection group. The normal control group and the model group were given an equal volume of 0.9%sodium chloride solution and injected intraperitoneally for 4 weeks. The pathology of lung tissue tissues was observed by using hematoxylin-eosin (HE) staining. Immunohistochemical(IHC) was used to detect the expressions of E-cadheren and Vimentin proteins in mice lung tissues.Real-time polymerase chain reaction (Real-time PCR) was used to detect the mRNA expressions of TGF-β₁, Smad3, GSK-3β and β-cateninin.Western blot was used to detect the protein expressions of TGF-β₁, Smad3, GSK-3β and β-cateninin. Result::Compared with the normal group, the pulmonary coefficient of the model group was significantly decreased (P<0.01). Inflammatory cell infiltration, pulmonary interstitial edema, congestion, destruction of alveolar structure and partial alveolar atrophy were observed in the lung tissues of the model group. Compared with the model group, in the compound Kushen injection group, the levels of infiltration of lung inflammatory cells and pulmonary interstitial lesions in mice, the expression of Vimentin in lung tissues (P<0.01), and the expressions of TGF-β₁, Smad3, GSK-3β and β-cateninin were significantly decreased (P<0.01), whereas the expression of E-cadheren was significantly increased (P<0.01). However, compared with the dexamethasone injection group, in the compound Kushen injection group, the pathological changes of lung tissues were similar, and the expression levels of E-cadheren, Vimentin, TGF-β₁, Smad3, GSK-3β and β-cateninin were not significantly different. Conclusion::Compound Kushen injection can alleviate pulmonary fibrosis of lung in the treatment of RIPI, and the mechanism may be associated with inhibiting the mRNA and protein expressions of TGF-β₁, Smad3, GSK-3β and β-catenin related to epithelial-mesenchymal transition(EMT), promoting the expression of E-cadheren, and inhibiting the expression of Vimentin, so as to inhibit the occurrence of EMT.