Objective To explore the influencing factors of immune-associated thyroid dysfunction caused by sintilimab treatment in solid tumors and construct a prediction model.Methods Medical records of patients diagnosed with solid tumors and treated with sintilimab at Peking University People's Hospital(Xizhimen Campus,Tongzhou Campus,Shijiazhuang Campus)from January 2023 to September 2024 were collected to explore the influencing factors that caused immune-related thyroid dysfunction using univariate and multifactorial binary logistic regression analyses and to establish a prediction model.The predictive effect of the model was assessed using the receiver operating characteristic(ROC)curve.Results A total of 120 patients were included,and 33 presented with immune-related thyroid dysfunction.Multifactorial logistic regression analysis revealed that thyroid-stimulating hormone(TSH)[OR=2.470,95%CI=(1.279,4.771)]and treatment cycles[OR=1.298,95%CI=(1.117,1.509)]were independent risk factors for the occurrence of immune-associated thyroid dysfunction,and the difference was statistically significant(P＜0.05).The area under the ROC curve was(0.897±0.043)[95%CI=(0.813,0.981)],the Yoden index was 0.703,and the model prediction accuracy was 86.5%.Conclusion The risk of immune-related thyroid dysfunction caused by sintilimab is high,and TSH and treatment cycle are the influencing factors,and the constructed model has certain predictive value and is of reference significance.

Objective To explore the influencing factors of immune-associated thyroid dysfunction caused by sintilimab treatment in solid tumors and construct a prediction model.Methods Medical records of patients diagnosed with solid tumors and treated with sintilimab at Peking University People's Hospital(Xizhimen Campus,Tongzhou Campus,Shijiazhuang Campus)from January 2023 to September 2024 were collected to explore the influencing factors that caused immune-related thyroid dysfunction using univariate and multifactorial binary logistic regression analyses and to establish a prediction model.The predictive effect of the model was assessed using the receiver operating characteristic(ROC)curve.Results A total of 120 patients were included,and 33 presented with immune-related thyroid dysfunction.Multifactorial logistic regression analysis revealed that thyroid-stimulating hormone(TSH)[OR=2.470,95%CI=(1.279,4.771)]and treatment cycles[OR=1.298,95%CI=(1.117,1.509)]were independent risk factors for the occurrence of immune-associated thyroid dysfunction,and the difference was statistically significant(P＜0.05).The area under the ROC curve was(0.897±0.043)[95%CI=(0.813,0.981)],the Yoden index was 0.703,and the model prediction accuracy was 86.5%.Conclusion The risk of immune-related thyroid dysfunction caused by sintilimab is high,and TSH and treatment cycle are the influencing factors,and the constructed model has certain predictive value and is of reference significance.

BACKGROUND:Temporomandibular joint osteoarthritis is a common oral disease with a high incidence.However,temporomandibular joint osteoarthritis is not easy to be detected in the early stage,and it is difficult to obtain clinical pathological specimens,so it is difficult to carry out related research.The application of digital 3D printing technology to animal models of Temporomandibular joint osteoarthritis increases the consistency of the animal models,thus promoting the study of temporomandibular joint osteoarthritis. OBJECTIVE:To establish a standardized animal model of temporomandibular joint osteoarthritis using novel digital technology. METHODS:According to the different modeling methods of unilateral anterior crossbite,30 female Sprague-Dawley rats were randomly divided into traditional model group,digital model group,and control group(n=10 per group).Cartilage specimens of the condyles were collected at 4 and 8 weeks after modeling.The apparent morphology was observed by stereoscopic microscope.The pathological morphology was observed by hematoxylin-eosin staining and Safranin O/fast green staining.Changes in the expression of interleukin-1β and tumor necrosis factor-α were observed by ELISA,and changes in the expression of aggrecan,type Ⅱ collagen and matrix metalloproteinase-13 were observed by immunohistochemical staining. RESULTS AND CONCLUSION:Different degrees of degeneration were observed in the digital and traditional model groups.The body mass of rats in both the model groups decreased during the 1st week after intervention and subsequently demonstrated growth trend and were significantly lower than that in the control group.The results of stereoscopic microscope showed that at 4 and 8 weeks after modeling,the deformation and defect degree of the digital model group was significantly higher than that of the traditional model group.At these two time points,the Osteoarthritis Research Society International scores of the digital model group and the traditional model group were higher than those of the control group,and the Osteoarthritis Research Society International score of the digital model group was higher than that of the traditional model group(P＜0.05).Histopathological observation showed that the modified Mankin score and Osteoarthritis Research Society International score of the two model groups were significantly higher than those of the control group of the same age at 4 and 8 weeks after modeling(P＜0.05).Immunohistochemical staining results showed that at two time points,compared with the control group of the same age,the expression of aggrecan and type Ⅱ collagen decreased in the traditional model group and the digital model group,while the expression of matrix metalloproteinase 13 increased(P＜0.05).ELISA results showed that the expression levels of inflammatory factors interleukin-1β and tumor necrosis factor-α in the traditional and digital model groups were higher than those in the control group at 8 weeks,and the expression levels of interleukin-1β and tumor necrosis factor-α in the digital model group were higher than those in the traditional model group(P＜0.05).To conclude,the personalized metal tube designed and produced by 3D printing technology can quickly guide the osteoarthritis-like lesions of the temporomandibular joint without repeated trial and adjustment,which is reproducible and suitable for promotion and application.

Purpose: Gastric cancer (GC) has high morbidity and mortality, the cure rate of surgical treatment and drug chemotherapy is not ideal. Therefore, development of new treatment strategies is necessary. We aimed to identify the mechanism underlying Sp1 regulation of GC progression. Methods: and Methods: The levels of Sp1, β-catenin, SET domain bifurcated 1 (SETDB1), and 15-hydroxyprostaglandin dehydrogenase (HPGD) were detected by quantitative reverse transcription polymerase chain reaction and western blot analysis. The targets of SETDB1 were predicted by AnimalTFDB, and dual-luciferase reporter assay was used for confirming the combination of Sp1, β-catenin, and SETDB1. HGC27 or AGS cells (1×10 6 cells/mouse) were injected into mice via the caudal vein for GC model establishment. The level of Ki67 was detected using immunohistochemistry, and hematoxylin and eosin staining was performed for evaluating tumor metastasis in mice with GC. Results: HPGD was inhibited, while the protein levels of Sp1, β-catenin, and SETDB1 were up-regulated in GC tissues and cell lines. HPGD overexpression or SETDB1 silencing inhibited the proliferation, invasion, and migration of GC cells, and Sp1 regulated the proliferation, invasion, and migration of GC cells in a β-catenin-dependent manner. Furthermore, HPGD served as a target of SETDB1, and it was negatively regulated by SETDB1; additionally, Sp1 and β-catenin bound to the SETDB1 promoter and negatively regulated HPGD expression. We proved that Sp1 regulated GC progression via the SETDB1/HPGD axis. Conclusions Our findings revealed that Sp1 transcriptionally inhibited HPGD via SETDB1 in a β-catenin-dependent manner and promoted the proliferation and metastasis of GC cells.

Objective::The effectiveness of statins in reducing atherosclerotic calcification remains controversial. The aim of this study was to confirm that simvastatin reduces atherosclerotic calcification and stabilizes plaque by restricting endoplasmic reticulum stress (ERS)-mediated apoptosis.Methods::Twenty-four 8-week-old male apolipoprotein E (ApoE) -/- mice (C57BL/6J genetic background) were selected and randomly divided into model ( n = 12) and simvastatin ( n = 12) groups. Twelve male C57BL/6J mice were selected as control group ( n = 12). The mice were adaptively fed for 2 weeks and were put on a high-fat diet thereafter. After 9 weeks, they were treated with simvastatin (20 mg/kg) or phosphate-buffered saline daily for 8 weeks. Aortic sinus samples were obtained from ApoE -/- and C57BL/6J mice for hematoxylin and eosin, von Kossa, alizarin Red S, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, and immunohistochemical staining after in vivo treatment with simvastatin. In addition, mouse vascular smooth muscle cells were analyzed after exposure to simvastatin in vitro.Results::Administration of simvastatin in vivo drastically attenuated the atherosclerosis, calcification, and apoptosis, and decreased the serum levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. The expression levels of glucose-regulated protein, 78 kDa (GRP78), C/EBP homologous protein (CHOP), and caspase 12 (CASP12) in the aortic sinus decreased in the simvastatin group compared with the model group. In vitro, simvastatin or simvastatin plus ERS inhibitor (taurine) attenuated calcification and apoptosis, and reduced the expression of ERS-related proteins GRP78, CHOP, and CASP12. Conclusion::Treatment with simvastatin suppressed atherosclerotic calcification. This effect may be mediated through the inhibition of ERS-related apoptosis.

Objective::The effectiveness of statins in reducing atherosclerotic calcification remains controversial. The aim of this study was to confirm that simvastatin reduces atherosclerotic calcification and stabilizes plaque by restricting endoplasmic reticulum stress (ERS)-mediated apoptosis.Methods::Twenty-four 8-week-old male apolipoprotein E (ApoE) -/- mice (C57BL/6J genetic background) were selected and randomly divided into model ( n = 12) and simvastatin ( n = 12) groups. Twelve male C57BL/6J mice were selected as control group ( n = 12). The mice were adaptively fed for 2 weeks and were put on a high-fat diet thereafter. After 9 weeks, they were treated with simvastatin (20 mg/kg) or phosphate-buffered saline daily for 8 weeks. Aortic sinus samples were obtained from ApoE -/- and C57BL/6J mice for hematoxylin and eosin, von Kossa, alizarin Red S, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, and immunohistochemical staining after in vivo treatment with simvastatin. In addition, mouse vascular smooth muscle cells were analyzed after exposure to simvastatin in vitro.Results::Administration of simvastatin in vivo drastically attenuated the atherosclerosis, calcification, and apoptosis, and decreased the serum levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. The expression levels of glucose-regulated protein, 78 kDa (GRP78), C/EBP homologous protein (CHOP), and caspase 12 (CASP12) in the aortic sinus decreased in the simvastatin group compared with the model group. In vitro, simvastatin or simvastatin plus ERS inhibitor (taurine) attenuated calcification and apoptosis, and reduced the expression of ERS-related proteins GRP78, CHOP, and CASP12. Conclusion::Treatment with simvastatin suppressed atherosclerotic calcification. This effect may be mediated through the inhibition of ERS-related apoptosis.

Brucellosis is a kind of animal epidemic disease that can be transmitted to human beings through skin, mucous membrane, digestive tract, respiratory tract and other ways. In recent years, the incidence of brucellosis has increased. Its pathogenesis is relatively complicated. In addition to bacteria, toxins and other factors, genetic susceptibility has gradually attracted the attention of scholars. In this paper, we summarized the previous reports and reviewed the relationship between interleukin gene polymorphism and susceptibility to brucellosis.

Brucellosis is an zoonosis, humans can be infected by Brucella through skin, mucous membrane, digestive tract, respiratory tract and so on. In the past, most of them recorded the infection of brucellosis from animal to human, but rarely reported the transmission of brucellosis between humans. This paper retrospectively reviews previous reports describing the spread of brucellosis between humans.

Objective:To investigate the therapeutic effect of modified Zhuyujingkang decoction combined with glucosamine sulfate on cervical spondylosis and its influence on the serum level of thromboxane B2(TBX 2). Methods:From June 2017 to June 2019, 82 patients with cervical spondylosis in the Maternal and Child Health Hospital of Zhoushan were selected, and they were divided into control group and observation group according to the random digital table method, with 41 cases in each group.The control group was treated with glucosamine sulfate, and the observation group was treated with modified Zhuyujingkang decoction on the basis of the control group.The course of treatment in both two groups was 4 weeks.The therapeutic effects of the two groups were compared.The changes of VAS, NDI and TBX 2 before and after treatment were compared. Results:The total effective rate of the observation group was 92.68%, which was higher than 70.73% of the control group(χ 2=6.609, P<0.05). After treatment, the VAS score of the observation group was (3.82±0.42)points, which was lower than (4.52±0.38)points of the control group( t=8.479, P<0.05). The NDI score of the observation group was (22.31±2.68)points, which was lower than (27.39±1.89)points of the control group( t=9.919, P<0.05). The serum level of TBX 2 in the observation group was (57.84±3.19)ng/L, which was lower than (65.74±2.48)ng/L in the control group( t=12.519, P<0.05). Conclusion:The therapeutic effect of modified Zhuyujingkang decoction combined with glucosamine sulfate on cervical spondylosis is good.It can reduce the pain, improve the related function of neck and shoulder, and reduce the level of TBX 2, which is worthy of clinical reference.

Objective To establish a test of autoantibody-panel for the diagnosis of autoimmune cerebellitis (AC) and determine the prevalence of AC in patients with cerebellar ataxia of unknown etiology.Methods Autoantibody screening tests with indirect immunofluorescence were performed in serum and cerebrospinal fluid (CSF) samples of 400 previously'idiopathic'Chinese patients with cerebral ataxia (inpatients and outpatients in Peking Union Medical College Hospital or referred from hospitals of Beijing Encephalitis Group from 2016 to 2018).Immunotherapy was given to autoantibody positive patients and the effectiveness of immunotherapy was assessed.Detailed AC autoantibodies panel included anti-glutamate decarboxylase 65 (GAD65) antibody,anti-Tr (delta notch-like epidermal growth factor-related receptor (DNER)) antibody,anti-zinc finger protein 4 (ZIC4) antibody,anti-inositol 1,4,5-trisphosphate receptor 1 (ITPR1) antibody,anti-homer protein homolog 3 (Homer 3) antibody,anti-neurochondrin (NCDN) antibody,anti-carbonic anhydrase-related protein (CARP) antibody and anti-Purkinje cell antibody 2 (PCA2) antibody.Results Eight out of 400 (2％) ataxia patients were positive for this AC panel tests,of whom two were positive for anti-GAD65 antibody,two for anti-Tr antibody,one for anti-PCA2 antibody,one for anti-Homer 3 antibody and two were positive for serum anti-NCDN antibody.Autoantibodies against ZIC4,ITPR1 and CARP were not detected in this cohort.Two of the eight ataxia patients also presented with limbic encephalitis,and only one anti-GAD antibody patient was screened with underlying small cell lung carcinoma (SCLC).All the eight patients received immunotherapy and four experienced partial response.Conclusions Autoimmune cerebellitis is the cause of acquired cerebellar ataxia.Tests of autoantibodies associated with AC have diagnostic value for paraneoplastic and non-paraneoplastic cerebellar ataxia.Immunotherapy may yield partial response in patients with AC.