ObjectiveAutoimmune thyroiditis （AIT） is a complex and immune-mediated disorder， with no established treatment protocol. Both Western and traditional Chinese medicine （TCM） focus on the pathogenesis and treatment of AIT. This study evaluated the clinical consistency of existing AIT animal models based on the diagnostic criteria of both Western and TCM， using a novel evaluation method. Additionally， it proposed recommendations and future prospects for improving these models. MethodsA comprehensive literature review was conducted on existing AIT animal models， using databases and the diagnostic criteria of both Western and TCM. Core and accompanying symptoms of these models were scored based on the diagnostic criteria of both Western and TCM， and clinical consistency was assessed. ResultsMice are the primary experimental animals used in AIT modeling. Modeling methods include vaccine immunization， iodine induction， heterologous thyroid antigen immunization， and a combination of high iodine water and antigen immunization. The average consistency of clinical syndromes based on TCM and Western medicine is 40%， 60%， 54%， and 63%， with the highest consistency observed in the combined high iodine water and antigen immunization model. Pathological models based on TCM are less common， with the liver-stagnation-spleen-deficiency rat model showing high clinical consistency. While most models are designed according to Western medical theory， meeting the surface and structural effectiveness criteria of Western medicine. However， there is a lack of fine-tuning and clear differentiation of TCM syndromes. ConclusionCurrent AIT syndrome-disease combination animal models primarily reflect the pathological features of Western medicine， with limited integration of TCM syndromes. Future research should aim to combine the syndrome characteristics of TCM with the pathological features of Western medicine， creating multi-factor and dynamic syndrome-disease models. Such models would better facilitate an experimental platform that conforms to the theories of TCM， providing more comprehensive support and guidance for the pathogenesis and treatment strategies of AIT.

G protein-coupled receptor kinase 2 (GRK2) participates in the phosphorylation and desensitization of G protein-coupled receptor (GPCR), impacting various biological processes such as inflammation and cell proliferation. Dysregulated expression and activity of GRK2 have been reported in multiple cells in rheumatoid arthritis (RA). However, whether and how GRK2 regulates synovial hyperplasia and fibroblast-like synoviocytes (FLSs) proliferation is poorly understood. In this study, we investigated the regulation of GRK2 and its biological function in RA. We found that GRK2 transmembrane activity was increased in FLSs of RA patients and collagen-induced arthritis (CIA) rats. Additionally, we noted a positive correlation between high GRK2 expression on the cell membrane and serological markers associated with RA and CIA. Immunoprecipitation-mass spectrometry and pull-down analyses revealed tumor necrosis factor receptor-associated factor 2 (TRAF2) as a novel substrate of GRK2. Furthermore, surface plasmon resonance (SPR) and molecular docking assays determined that the C-terminus of GRK2 binds to the C-terminus of TRAF2 at the Gln340 residue. GRK2 knockdown and the GRK2 inhibitor CP-25 attenuated synovial hyperplasia and FLS proliferation in CIA both in vitro and in vivo by decreasing GRK2 membrane expression and activity. Mechanistically, increased GRK2 transmembrane activity contributed to the recruitment of TRAF2 on the cell membrane, promoting GRK2-TRAF2 interactions that facilitate the recruitment of the E3 ubiquitin ligase TRIM47 to TRAF2. This enhanced TRAF2 Lys63 polyubiquitylation and induced nuclear factor (NF)-κB activation, leading to synovial hyperplasia and abnormal proliferation of FLSs. Our study provides a mechanistic and preclinical rationale for further evaluation of GRK2 as a therapeutic target for RA.

Programmed cell death 1 ligand 1 (PD-L1) is an important immunosuppressive molecule, which inhibits the function of T cells and other immune cells by binding to the receptor programmed cell death-1. The PD-L1 expression disorder plays an important role in the occurrence, development, and treatment of sepsis or other inflammatory diseases, and has become an important target for the treatment of these diseases. Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cells with multiple differentiation potential. In recent years, MSCs have been found to have a strong immunosuppressive ability and are used to treat various inflammatory insults caused by hyperimmune diseases. Moreover, PD-L1 is deeply involved in the immunosuppressive events of MSCs and plays an important role in the treatment of various diseases. In this review, we will summarize the main regulatory mechanism of PD-L1 expression, and discuss various biological functions of PD-L1 in the immune regulation of MSCs.

Objective To analyze the risk factors of nosocomial infection among the patients in neuro-surgical ICU,and to construct the risk prediction model to provide reference for the prediction of nosocomial infection in neurosurgical ICU patients.Methods The clinical data of 280 patients admitted and treated in the neurosurgery ICU of this hospital from January 2021 to December 2022 were retrospectively analyzed.The pa-tients were divided into the infection group and non-infection group based on whether or not nosocomial infec-tion occurring,140 cases in each group.A total of 196 patients were extracted as the training set by a ratio of 7︰3 for constructing the model,while the remaining 84 patients served as the validation set for conducting the internal verification.The logistic regression was used to analyze the risk factors of nosocomial infection in the neurosurgery ICU patients,and a predictive model was established.The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive effect of the model.Results The multivariate logistic re-gression analysis indicated that old age,long surgery time,catheter use and glucocorticoids use were screened as the main risk factors of nosocomial infection occurrence in neurosurgery ICU patients.The nomogram mod-el was constructed based on the results of multivariate analysis,the area under the curve of training set and validation set were 0.796 and 0.875,respectively.The correcting model reflected good consistency between actual diagnosis and predictive diagnosis.Conclusion The model constructed in this study has the high predic-tive value for the nosocomial infection occurrence risk in the patients of the neurosurgery ICU.

Objective:To explore the expressions of long non-coding RNA LINC00673 and ISG15 protein in pancreatic cancer and their clinical significances.Methods:The clinical data of 57 patients diagnosed as pancreatic ductal carcinoma (PDAC) at the Affiliated Cancer Hospital of Xiangya Medical College of Central South University from January 2014 to December 2018 were retrospectively analyzed. The relative expressions of LINC00673 in pancreatic cancer tissues and paracancerous normal tissues (within 3 cm from the edge of cancer tissues) were examined by using quantificational reverse transcription-polymerase chain reaction (qRT-PCR). The ISG15 protein expressions in pancreatic cancer tissues and paracancerous normal tissues were examined by using immunohistochemistry. The difference in LINC00673 expression between ISG15 protein positive and negative patients was compared. The correlation between LINC00673 and ISG15 protein expressions in pancreatic cancer was analyzed by Spearman rank correlation analysis. Moreover, the correlations of LINC00673 and ISG15 protein expressions with clinical stage and pathological classification of pancreatic cancer patients were analyzed.Results:The positive expression of ISG15 protein in pancreatic cancer tissues was 40.4% (23/57), which was higher than that in paracancerous normal tissues [15.8% (9/57)] ( χ2 = 7.90, P = 0.004), and the relative expression of LINC00673 in pancreatic cancer tissues was 0.99±0.36, which was lower than that in paracancerous normal tissues (1.26±0.41) ( t = 4.80, P < 0.001). For 23 (40.4%) ISG15-positive patients and 34 (59.7%) ISG15-negative patients, the relative expression of LINC00673 was 0.77±0.46 and 0.45±0.27 ( P < 0.001). Spearman analysis showed that there was a correlation between LINC00673 and ISG15 protein expressions ( ρ = -0.429, P = 0.001). The relative expression of LINC00673 decreased in patients with low differentiated or undifferentiated tumor, vascular invasion and lymph node metastasis (all P < 0.05), but there was no correlation between LINC00673 expression and patients' age, tumor site, preoperative CA199 level, and TNM stage (all P > 0.05); ISG15 protein expression increased in patients with low differentiated or undifferentiated tumor, TNM stage Ⅲ-Ⅳ, vascular invasion and lymph node metastasis (all P < 0.05), but there was no correlation between ISG15 protein expression and patients' gender, age, tumor site, and preoperative CA199 level (all P > 0.05). Conclusions:The expression of LINC00673 in pancreatic cancer is related to vascular invasion, tumor differentiation degree and lymph node metastasis, and the expression of ISG15 in pancreatic cancer is related to vascular invasion, tumor differentiation degree, lymph node metastasis and TNM stage. The combined detection of LINC00673 and ISG15 protein could be a valuable prognostic indicator for pancreatic cancer. The therapies targeting LINC00673 and ISG15 protein signaling pathways are expected to be a potential option for immunotherapy of pancreatic cancer.

Humans ; Encephalitis

OBJECTIVE: To investigate the clinical characteristics, treatment, and prognosis of seizures in children with acute lymphoblastic leukemia (ALL) during chemotherapy. METHODS: Children with ALL with seizures during chemotherapy admitted to the Department of Pediatrics, Peking University People's Hospital from January 2010 to March 2022 were retrospectively analyzed. Clinical data including the incidence of seizure, time at seizure onset, causes, management, and prognosis were collected retrospectively. RESULTS: A total of 932 children with ALL were admitted during the study period, of whom, 75 (8%) were complicated with seizures during the period of chemotherapy. There were 40 males and 35 females, with a median age of 7.5 (1-17) years, and 43 cases (57.3%) occurred within the first 2 months of chemotherapy. The underlying diseases were reversible posterior encephalopathy syndrome (n=15), cerebral hemorrhage (n=10, one of whom was complicated with venous sinus thrombosis), intrathecal or systemic methotrexate administration (n=11), brain abscess (n=7, fungal infection in 3 cases, and bacterial in 4), viral encephalitis (n=2), febrile seizure (n=7), hyponatremia (n=7), hypocalcemia (n=2), and unknown cause (n=14). Sixty-four children underwent neuroimaging examination after seizure occurrence, of whom 37 (57.8%) were abnormal. The electroencephalograhpy (EEG) was performed in 44 cases and was abnormal in 24 (54.4%). Fifty-five patients remained in long-term remission with regular chemotherapy, 8 patients received hematopoietic stem cell transplantation, 9 died and 3 lost to follow-up. Symptomatic epilepsy was diagnosed in 18 cases (24%), and was well controlled in 16 with over 1 year of seizure-free. Whereas 2 cases were refractory to anti-seizure medications. CONCLUSION Seizures are relatively common in children with ALL, most commonly due to reversible posterior encephalopathy syndrome, methotrexate-related neurotoxicity, and cerebral hemorrhage. Seizures occurred within 2 months of chemotherapy in most cases. Neuroimaging and EEG should be performed as soon as possible after the first seizure onset to identify the etiology and to improve the treatment regimen. Some cases developed symptomatic epilepsy, with a satisfactory outcome of seizure remission mostly after concurrent antiseizure medication therapy.
Adolescent ; Brain Diseases/complications* ; Cerebral Hemorrhage/complications* ; Child ; Electroencephalography ; Epilepsy/drug therapy* ; Female ; Humans ; Male ; Methotrexate/adverse effects* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Prognosis ; Retrospective Studies

OBJECTIVE: To investigate the efficacy and safety of VDZ (Vedolizumab) in the salvage treatment of glucocorticoid resistance to gastrointestinal graft-versus-host disease (GR-GI GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children. METHODS: The clinical data of 5 patients with refractory GI GVHD who received allo-HSCT in Wuhan Children's Hospital from December 2020 to December 2021 were retrospectively analyzed with VDZ salvage therapy. RESULTS: Among the 5 children with refractory GI GVHD, there were 1 male and 4 female, including 2 cases of extremely severe aplastic anemia, 1 case of acute myeloid leukemia (M2, high-risk), 1 case of fanconi anemia and 1 case of myelodysplastic syndrome. The median age of transplant recipients was 54.4 (12-164) months. The median treatment time from transplantation to VDZ was 1.4 (0.6-6.8) months. On average, 3.5 (2-5) doses of VDZ were received. After receiving treatment, 2 patients achieved a complete response (CR), 2 patients achieved a very good partial response (VGPR), 1 patient was non-responsive (NR) after a short-term partial response (PR). Compared with that before VDZ treatment, the amount of diarrhea, stool color, blood and traits of the children after medication were effectively improved. The median follow-up time was 9.3 (7.23-12.83) months. No disseminated or severe bacterial/fungal infections occurred during VDZ treatment and follow-up, and 2 children died of leukemia recurrence and pulmonary bronchiolitis obliterans. CONCLUSION VDZ salvage treatment of refractory GI GVHD in children has obvious short-term efficacy and good safety.
Child ; Humans ; Female ; Male ; Child, Preschool ; Salvage Therapy ; Glucocorticoids/therapeutic use* ; Retrospective Studies ; Graft vs Host Disease

Objective:To explore the diagnosis, surgical methods and therapeutic effect of primary duodenal malignant tumor.Methods:The clinical data of 116 patients with primary duodenal malignant tumor from January 2010 to December 2018 were retrospectively analyzed.Results:Among 116 patients, adenocarcinoma was in 74 cases, interstitial tumor was in 25 cases, carcinoid was in 9 cases, the others was in 8 cases. Before operation, duodenoscopy was performed in 107 cases, and CT examination was performed in 76 cases. There were 57 cases of pancreaticoduodenectomy, 15 cases of duodenal segmental resection, 13 cases of subtotal gastrectomy and duodenal bulbar resection, 13 cases of duodenal partial resection, and 18 cases of palliative short circuit operation. The total incidence of postoperative complication was 31.9% (37/116), including pancreatic fistula in 8 cases (grade B 5 cases, grade C 3 cases), biliary fistula in 6 cases, abdominal infection in 5 cases, pulmonary infection in 4 cases, intestinal fistula in 3 cases, delayed gastric emptying in 3 cases, and hemorrhage in 8 cases. Four cases (3.4%) died during the perioperative period. Single factor Cox regression analysis result showed that the postoperative survival time was related to the tumor differentiation degree, operation method, tumor infiltration degree and lymphatic metastasis ( P<0.05 or <0.01); multi-factor Cox regression analysis results showed that the operation method, tumor infiltration degree and lymphatic metastasis were the independent risk factors for the postoperative survival time of patients with primary duodenal malignant tumor ( P<0.05). The patients were followed up until June 2021, and 9 cases were lost to follow-up. Kaplan-Meier survival curve analysis result showed that the postoperative overall 1-,3- and 5-year survival rates were 82.11%, 57.56% and 33.11%, respectively. Conclusions:Adenocarcinoma is the main primary malignant tumor of duodenum. Duodenoscopy and CT are the main examination methods. Radical resection is the most effective treatment for primary duodenal malignant tumor, and pancreaticoduodenectomy is the first choice. Surgical method, tumor infiltration degree and lymphatic metastasis are the independent risk factors affecting the prognosis of patients.

Objective: To investigate the expression and clinical significance of exosomal miR-1231 in plasma of pancreatic cancer (PC) patients and pancreatic cancer cells. Methods: A total of 16 patients who were diagnosed with pancreatic cancer in Hunan Cancer Hospital were collected from April 2016 to August 2017. Meanwhile, 16 healthy volunteers were recruited as the healthy control group at the same period. The plasma exosomes were extracted, and the levels of miR-1231 were detected by qRT-PCR in PC and healthy control groups. Moreover, the clinicopathological significance of exosomal miR-1231 expression was analyzed. Furthermore, the expression of exosomal miR-1231 was detected in several pancreatic cancer cells (MIA PaCa-2, PANC-1, SW1990, AsPC-1 and BxPc-3) and two normal pancreatic epithelial cells (HPDE and human primary pancreatic epithelial cell). Results: qRT-PCR results showed that the expression level of miR-1231 in plasma exosomes of pancreatic cancer patients (1.06±0.46) was significantly lower than that in healthy controls (2.30±0.99; P<0.05). The levels of exosomal miR-1231 in patients with stage Ⅰ-Ⅱ (1.515±0.531), no distant metastasis (1.236±0.461) and no lymph node metastasis (1.337±0.522) were significantly higher than those with stage Ⅲ-Ⅳ (0.848±0.224), distant metastasis (0.757±0.278) and lymph node metastasis (0.838±0.261), respectively (P<0.05 for all). In addition, there were no correlation between exosomal miR-1231 expression and age, sex, smoking history, CA19-9 levels and tumor sites (P>0.05). Furthermore, the expression level of exosomal miR-1231 in pancreatic cancer cell lines (0.142±0.135) was significantly lower than that in normal epithelial cells (1.127±0.179; P<0.05). Conclusions The downregulation of exosomal miR-1231 in plasma of pancreatic cancer patients and pancreatic cancer cells suggests that it is related to the initiation and development of PC. It may be a new diagnostic and prognostic marker for PC.