[Objective] To investigate the influencing factors of immune-related thyroid dysfunction (irTD) treated with programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors and their impact on overall survival (OS) of cancer. [Methods] We enrolled 211 cancer patients treated with PD-1/PD-L1 inhibitors. Clinical differences between irTD groups were compared, and subgroup analysis was performed. Multifactor Logistic regression analysis was used to identify influencing factors of irTD, while survival analysis was used to explore the relationship between the occurrence of irTD and OS, and the log-rank test was used for comparison between groups. The multi-model COX regression analysis was used to evaluate the impact of irTD on OS. [Results] The incidence rate of irTD was 26.1%, with 13.3%, 10.0% and 2.8%, respectively for grade 1, grade 2, and grades 3-4, and the median time of occurrence was at week 9 (IQR: 5-25 weeks). Significant differences were observed between the irTD and non-irTD groups in terms of gender, smoking history, targeted therapy history, and baseline thyroid antibody status (P<0.05). In irTD patients, thyroglobulin antibody (TGAb) levels began to increase from week 3, remained above the baseline from week 6 to week 30, and then gradually declined to the baseline level after week 30. The change in thyroid microsomal antibody (TMAb) levels was less pronounced than that of TGAb. Subgroup analysis showed that patients with hyperthyroidism were younger at the time of initial immunotherapy than those with hypothyroidism (P<0.05) and had lower baseline TSH levels (P<0.05). Multifactor Logistic regression analysis revealed that patients with positive baseline thyroid antibodies had a 4.595-fold higher risk of developing irTD compared to those with negative antibodies (95% CI: 2.286-9.239, P<0.001). Survival analysis revealed that patients with irTD had a longer OS and the multi-model COX regression analysis revealed that after adjusting for factors such as age, gender, chemotherapy, tumor type and tumor metastasis status, patients with irTD had a significantly longer OS (HR=0.228, 95% CI: 0.079-0.656, P=0.006). [Conclusion] The severity of irTD was predominantly grades 1-2, with grades 3-4 being rare. Positive baseline thyroid antibodies were an independent risk factor for the development of irTD. Patients who develop irTD have a longer OS, which may be due to their stronger immune response.

Platelet is the key factor in hemostasis and coagulation,its potential in inflammatory response and immune response has been widely concerned in recent years.A growing number of studies indicate that tissue damage in inflammatory bowel disease is not only the result of dysregulated immune response,but also the active participation of various other cellular systems,and platelet might play an important role in intestinal mucosal inflammation and immunity.This article reviewed the abnormal changes and possible mechanisms of platelet in inflammatory bowel disease,and the prospects of platelet as a specific treatment target for inflammatory bowel disease.

Objective To observe the alterations in functional complexity of brain regions in autism spectrum disorder(ASD)patients and correlations with the predicted brain age.Methods Open brain resting-state functional MRI(rs-MRI)data of 93 ASD patients and 96 typically developing adolescents(healthy subjects)were downloaded.The functional complexity in brain regions were extracted with self-developed virtual digital brain software,and the alterations in functional complexity of brain regions in ASD patients and correlations with their ages were analyzed.Two networks were prospectively trained with data of 65 ASD patients and 67 healthy subjects as the training set to predict brain age,and the results were evaluated,and the predicting errors were compared using test set,i.e.the other 28 ASD patients and 29 healthy subjects.Results Compared to healthy subjects,on the basis of anatomical automatic labeling(AAL)atlas,ASD patients exhibited significantly reduced functional complexity based on Shannon entropy in the left precuneus,left cuneus and right parahippocampal gyrus.Conversely,functional complexity of ASD patients based on permutation entropy significantly increased in the left cuneus and right cerebellar Crus Ⅱ region.The left hippocampus showed reduced functional complexity based on Pearson correlation coefficient,while the left middle temporal gyrus showed increased functional complexity based on Pearson correlation coefficient.The functional complexity in brain regions of ASD patients were not closely correlated with ages(all|r|＜0.4).According to the trained fully connected network,the predicted brain ages of ASD patients and healthy subjects in test set were all lower than their physiological ages,but no significant difference was found between the prediction errors of ASD patients and healthy subjects(P=0.283).Conclusion Functional complexity changed in some brain region functions in ASD patients.The predicted brain ages of ASD patients based on the obtained fully connected network were on the low side,but not obviously affected by the alterations of functional complexity in brain regions.

Purpose To explore the cardioprotective effect of cang-ai volatile oil(CAVO)on rats with cardiac function impairment model under low-pressure and low-oxygen environment in Tibet Plateau based on 7.0T cardiovascular magnetic resonance(CMR)imaging.Materials and Methods Forty SD rats were randomly divided into the normal group,the high altitude model group,the CAVO-treated group and the rhodiola rosea-treated group,with 10 rats in each group.Except for the normal group,the rats in other groups were transferred from the plain(500 m above sea level)to the Tibet Plateau(4 250 m above sea level)for two months,and then administered with the corresponding drugs by gavage for 14 d.The left ventricle function was measured by using a 7.0T high-field strength CMR and myocardial strain was analysed by using tissue tracing technique.HE staining was used to observe the morphology of cardiomyocytes,Masson staining to observe interstitial fibrosis,wheat germ agglutinin staining to observe cardiomyocyte hypertrophy,and transmission electron microscopy to observe the morphological changes of mitochondria in each group.Serum levels of creatine kinase,creatine kinase isoenzyme,lactate dehydrogenase,cardiac troponin T,superoxide dismutase,malondialdehyde and glutathione peroxidase were detected.Intracellular reactive oxygen species levels were detected using flow cytometry.Results The left ventricular ejection fraction of rats in the CAVO-treated group was higher than that of the high altitude model group[(66.61±1.38)％vs.(60.94±3.21)％;t=3.969,P=0.032];meanwhile,the global circumferential strain of the left ventricle in the CAVO-treated group was higher than that of the high altitude model group(-25.68±1.30 vs.-22.84±1.17;t=3.967,P=0.003).HE,Masson and wheat germ agglutinin staining showed hypertrophy and necrosis as well as interstitial fibrosis and ultrastructural disruption of cardiomyocytes in the high altitude model group,which improved after CAVO treatment.The level of cardiac troponin T in the serum of rats with CAVO treatment group was significantly decreased compared with that of the high altitude model group[(314.03±20.05)pg/ml vs.(518.30±18.13)pg/ml;1=13.090,P=0.001].Conclusion CAVO treatment can reduce cardiac injury caused by low-pressure hypoxia in high altitude,and its effect can be detected dynamically and non-invasively by 7.0T high-field strength CMR.

Inflammatory bowel disease (IBD) is a chronic non ‑ specific intestinal inflammatory disease. Spondyloarthritis (SpA) is a chronic inflammatory disease that occurs in the axial skeleton and surrounding joints, and is one of the most common extraintestinal manifestations of IBD. The main pathophysiologic mechanism of IBD accompanied with SpA involves the "gut‑joint axis" hypothesis, and dysbiosis of gut flora plays a key role in explaining the pathologic connection of the "gut‑joint axis" in patients with IBD accompanied with SpA. This article reviewed the progress of research on gut flora and IBD accompanied with SpA.

Objectives:This study aimed to assess the efficacy and safety of bendamustine in combination with rituximab (BR regimen) for the treatment of newly diagnosed indolent B-cell non-Hodgkin's lymphoma (B-iNHL) and elderly mantle cell lymphoma (eMCL) .Methods:From December 1, 2020 to September 10, 2022, a multi-center prospective study was conducted across ten Grade A tertiary hospitals in Shandong Province, China. The BR regimen was administered to evaluate its efficacy and safety in newly diagnosed B-iNHL and eMCL patients, and all completed at least four cycles of induction therapy.Results:The 72 enrolled patients with B-iNHL or MCL were aged 24-74 years, with a median age of 55 years. Eastern Cooperative Oncology Group (ECOG) performance status scores of 0-1 were observed in 76.4% of patients, while 23.6% had scores of 2. Disease distribution included follicular lymphoma (FL) (51.4% ), marginal zone lymphoma (MZL) (33.3% ), eMCL (11.1% ), and the unknown subtype (4.2% ). According to the Ann Arbor staging system, 16.7% and 65.3% of patients were diagnosed with stage Ⅲ and stage Ⅳ lymphomas, respectively. Following four cycles of BR induction therapy, the overall response rate was 98.6%, with a complete response (CR) rate of 83.3% and a partial response (PR) rate of 15.3%. Only one eMCL patient experienced disease progression during treatment, and only one FL patient experienced a relapse. Even when evaluated using CT alone, the CR rate was 63.9%, considering the differences between PET/CT and CT assessments. The median follow-up duration was 11 months (range: 4-22), with a PFS rate of 96.8% and an OS rate of 100.0%. The main hematologic adverse reactions included grade 3-4 leukopenia (27.8%, with febrile neutropenia observed in 8.3% of patients), grade 3-4 lymphopenia (23.6% ), grade 3-4 anemia (5.6% ), and grade 3-4 thrombocytopenia (4.2% ). The main non-hematologic adverse reactions such as fatigue, nausea/vomiting, rash, and infections occurred in less than 20.0% of patients.Conclusion:Within the scope of this clinical trial conducted in China, the BR regimen demonstrated efficacy and safety in treating newly diagnosed B-iNHL and eMCL patients.

Objective:To construct a cognitive training program suitable for elderly patients with mild cognitive impairment based on horticultural therapy, so as to effectively slow down the cognitive decline of patients with mild cognitive impairment.Methods:Through searching the Chinese and English database literature of cognitive intervention from July 2000 to July 2020 and field visits to nursing homes, the draft intervention plan was formed. Two rounds of focus group interview were held to consult experts in cognitive impairment and geriatric care, etc., and to revise the intervention plan.Results:In the two rounds of focus group interview, the expert positive coefficient was 100%, the expert judgment basis was 0.84, the expert familiarity degree was 0.84, and the expert authority coefficient was 0.84. In the end, a 10-week cognitive intervention program targeting six cognitive domains -- "visuospatial/executive ability", "memory ability", "language ability", "attention ability", "abstract ability" and "naming ability" was formed, and the implementation steps of the program were improved.Conclusions:The construction process of cognitive training program for patients with mild cognitive impairment based on horticultural therapy theory is rigorous, scientific and feasible, and can be used to guide the cognitive training of patients with mild cognitive impairment.

Objective:To identify the risk factors of cognitive dysfunction in patients with atrial fibrillation and to establish a risk prediction model.Methods:The convenience sampling method was used to evaluate 260 patients with atrial fibrillation who were hospitalized in the Department of Cardiology of the Affiliated Hospital of Jining Medical College from January to December 2020. The cognitive function of the patients was evaluated with the Montreal Cognitive Function Assessment Scale (MoCA). Univariate analysis was used to screen the independent variables that had influence on the occurrence of cognitive dysfunction, and the statistically significant variables were included in the multivariate Logistic regression model. According to the regression coefficients of statistically significant variables, a line map was drawn to construct the risk prediction model of cognitive dysfunction in patients with atrial fibrillation.Results:There were 209 cases with cognitive impairment and 51 cases without cognitive impairment. Univariate analysis showed that sex, age, smoking history, drinking history, education level, free thyroxine, hemoglobin, D-dimer and BMI ( χ2 values were 4.08-18.83, t values were -6.04-2.94, Z=-2.76) were significantly different between the patients with or without cognitive dysfunction. The results of multivariate Logistic regression analysis showed that age ( OR values were 1.13), education level ( OR=0.01-0.05), quit smoking history ( OR=0.36), drinking history ( OR=0.35) and free thyroxine( OR=1.14) had significantly statistical significance ( P<0.05). The area under ROC curve (AUC) = 0.878 and AUC>0.8, this model had good clinical prediction ability. Conclusions:The construction of cognitive dysfunction risk prediction model for patients with atrial fibrillation can prevent or intervene high risk factors in advance, facilitate clinical use, and provide data support for the improvement of cognitive function in patients with atrial fibrillation.

To investigate the relationship of biofilm-forming ability of (PA) with swimming motility, twitching motility and virulence gene distribution. A total of 192 clinical isolates of PA were collected consecutively. Microtiter plate method was used to evaluate the ability to form biofilm. The swimming and twitching motilities were detected by plate method. Polymerase chain reaction (PCR) was used to detect virulence genes. Of the 192 PA clinical isolates, 186 (96.9%) showed biofilm-forming ability. Among them, 36 isolates showed weak biofilm-forming ability, 84 exhibited moderate biofilm-forming ability and 66 showed strong biofilm-forming ability. The diameters of the swimming ring for PA with none biofilm-forming ability, weak biofilm-forming ability, moderate biofilm-forming ability, strong biofilm-forming ability were (9.12±6.76), (18.42±7.51), (19.10±4.77) and respectively. The diameters of the twitching ring for PA in above groups were (8.38±1.50), (17.21±7.42), (18.49±5.62) and respectively. The swimming motility and twitching motility of none biofilm-forming ability group were weaker than biofilm-forming ability groups (all <0.05). Among 192 PA strains, 163 were positive (84.9%), 40 were positive (20.8%), 183 were positive (95.3%), and 189 were positive (98.4%). The positive rate of PA virulence gene , and were different in strains with different biofilm-forming abilities (<0.05). The rate of in the strong biofilm-forming ability group was lower than that in the moderate biofilm-forming ability group (=9.293, <0.01) and the weak biofilm-forming ability group (=9.997, <0.01). The rate of in the strong biofilm-forming ability group was higher than that in the weak biofilm-forming ability group (=10.803, <0.01). Most clinical isolates of PA can form biofilm. Swimming and twitching motilities are related to the formation of biofilm, but not significantly related to strength of biofilm-forming ability. The virulence genes of type Ⅲ secretion system for PA may be related to the biofilm-forming ability.
Biofilms ; Humans ; Swimming ; Virulence/genetics*

Malignant tumors usually have no obvious clinical symptoms in the early stage. Most patients are already in the advanced stage when they are diagnosed. Some patients have lost the opportunity for operation, resulting in poor prognosis. Therefore, how to find the best therapeutic target for such patients and improve the prognosis of patients has gradually become the focus of scholar′s attention. Recently, Kruppel-like factor (KLF) is a transcriptional regulator that can bind to the target DNA, and its family plays an important role in the occurrence and development of malignant tumors. It has also been confirmed that the KLF family affects the proliferation, differentiation and migration of tumor cells, but the specific mechanism is still not fully elucidate. Consequently, in order to further explored the effect of the KLF family on tumors, this study intends to briefly review the roles and regulatory mechanisms of the KLF family in the cell proliferation, differentiation and migration of malignant tumors, hoping to provide new target for the biological treatment of tumors.