Structural basis for the killing of human beta cells by CD8(+) T cells in type 1 diabetes.

The structural characteristics of the engagement of major histocompatibility complex (MHC) class II-restricted self antigens by autoreactive T cell antigen receptors (TCRs) is established, but how autoimmune TCRs interact with complexes of self peptide and MHC class I has been unclear. Here we examined how CD8(+) T cells kill human islet beta cells in type 1 diabetes via recognition of a human leukocyte antigen HLA-A*0201-restricted glucose-sensitive preproinsulin peptide by the autoreactive TCR 1E6. Rigid 'lock-and-key' binding underpinned the 1E6-HLA-A*0201-peptide interaction, whereby 1E6 docked similarly to most MHC class I-restricted TCRs. However, this interaction was extraordinarily weak because of limited contacts with MHC class I. TCR binding was highly peptide centric, dominated by two residues of the complementarity-determining region 3 (CDR3) loops that acted as an 'aromatic-cap' over the complex of peptide and MHC class I (pMHCI). Thus, highly focused peptide-centric interactions associated with suboptimal TCR-pMHCI binding affinities might lead to thymic escape and potential CD8(+) T cell-mediated autoreactivity.

A Prediction Model for Prolonged Hospital Length of Stay (ProLOS) in Coronavirus Disease 2019 (COVID-19) Patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the normalization of COVID-19 globally, it is crucial to construct a prediction model that enables clinicians to identify patients at risk for ProLOS based on demographics and serum inflammatory biomarkers. METHODS: The study included hospitalized patients with a confirmed diagnosis of COVID-19. These patients were randomly grouped into a training (80%) and a test (20%) cohort. The LASSO regression and ten-fold cross-validation method were applied to filter variables. The training cohort utilized multifactorial logistic regression analyses to identify the independent factors of ProLOS in COVID-19 patients. A 4-variable nomogram was created for clinical use. ROC curves were plotted, and the area under the curve (AUC) was calculated to evaluate the model's discrimination; calibration analysis was planned to assess the validity of the nomogram, and decision curve analysis (DCA) was used to evaluate the clinical usefulness of the model. RESULTS: The results showed that among 310 patients with COVID-19, 80 had extended hospitalization (80/310). Four independent risk factors for COVID-19 patients were identified: age, coexisting chronic respiratory diseases, white blood cell count (WBC), and serum albumin (ALB). A nomogram based on these variables was created. The AUC in the training cohort was 0.808 (95% CI: 0.75 - 0.8671), and the AUC in the test cohort was 0.815 (95% CI: 0.7031 - 0.9282). The model demonstrates good calibration and can be used with threshold probabilities ranging from 0% to 100% to obtain clinical net benefits. CONCLUSIONS: A predictive model has been created to accurately predict whether the hospitalization duration of COVID-19 patients will be prolonged. This model incorporates serum WBC, ALB levels, age, and the presence of chronic respiratory system diseases.

Association between garden work and risk of incident dementia in an older population in China: a national cohort study.

OBJECTIVES: Evidence on the association between garden work and risk of incident dementia in the older Chinese population is limited. This study aimed to explore the association between the frequency of garden work and risk of incident dementia in an older population in China. STUDY DESIGN: This was a national cohort study. METHODS: This study analysed data from 8676 participants (median age: 86 years) from the Chinese Longitudinal Healthy Longevity Survey. Cox proportional hazard models were used to assess the association between the frequency of garden work and risk of incident dementia using hazard ratios (HRs) and 95% confidence intervals (CIs). Multiplicative and additive interaction effects were calculated between the frequency of garden work and age, sex or residence on incident dementia; subgroup analyses of the association were also conducted by age, sex and residence. In addition, sensitivity analyses were performed to assess the robustness of the results. RESULTS: During 4.31 years (median) of follow-up, 633 participants developed dementia. Compared with participants who did not engage in garden work, the adjusted risk of incident dementia for those who regularly or almost daily engaged in garden work decreased by 28% (HR = 0.72, 95% CI: 0.57-0.93). An additive interaction effect between frequency of garden work and age on incident dementia was observed, with subgroup analyses demonstrating similar statistically significant associations among participants aged ≥85 years, women and city or town residents. Sensitivity analyses were consistent with the primary analysis in the present study. CONCLUSIONS: Frequent engagement in garden work may be associated with a reduced risk of dementia and may be an effective measure to prevent incident dementia in the older population in China.

[Design of an improved percutaneous transhepatic cholangio drainage tube based on MRCP imaging data].

Objective: Quantified MRCP imaging data was used as a reference for design and preparation of a modified percutaneous transhepatic cholangio drainage (PTCD) tube. Methods: 3.0 T upper abdominal MR and MRCP imaging data of 2 300 patients treated from July 2015 to July 2020 at the Department of Radiology of the Affiliated Cancer Hospital of Zhengzhou University were screened and a total of 381 patients diagnosed with biliary duct structures were identified. Causative etiologies among these patients included pancreatic adenocarcinoma (pancreatic head), cholangiocarcinoma, ampullary carcinoma, as well as intrahepatic and/or extrahepatic bile duct dilation. An improved PTCD tube was designed based on MRCP quantification of left and right hepatic and common hepatic duct length. Results: In the setting of biliary obstruction caused by malignancy, the distance of the left hepatic duct from its origin to the point of left and right hepatic duct confluence was 15.9±3.8 mm, while the distance of the right hepatic duct from its origin to the point of left and right hepatic duct confluence was 12.4±3.2 mm; the length of the bile duct from its origin to the point of left and right hepatic duct confluence was 34.0±8.1 mm. The improved PTCD tube design incorporated an altered length of the drainage orifice. Conclusion: MRCP imaging of the biliary tract is effective for measuring biliary tract length in the setting of pathological dilation. Based on our biliary tract measurements, a modified PTCD tube was designed to more effectively meet drainage requirements and manage biliary obstruction caused by Bismuth-Corlette type Ⅱ and Ⅲ malignancies.

[Auxiliary diagnosis and prognosis evaluation of KIF4A, RAD51AP1 and CDKN3 in esophageal cancer].

To investigate the expression of mRNA in esophageal cancer (ESCA) tissues and its potential and diagnostic and prognostic value by high-throughput sequencing data. Using the Cancer Genome Atlas Program (TCGA) database in USA by integrative bioinformatics analysis methods, the gene expression profiles and clinical data of 173 patients with ECSA were collected. The mRNA expression levels in ESCA tissue and para-cancerous tissue samples were analyzed using DESeq2, edgeR and limma to screen the differentially expressed genes (DEGs). DEGs-related protein network diagrams were drawn. GO and KEGG function enrichment analysis were performed and the hub genes were screened and the survival analysis of hub genes was analyzed. Genes related to the prognosis of ESCA were selected and their prognostic value in ESCA was analyzed. Finally, the receiver operating characteristic curve was drawn to evaluate its diagnostic value. The results showed that using TCGA cancer data, a total of 620 up-regulated DEGs and 668 down-regulated DEGs with significant differential expression between ESCA and para-cancerous tissues were screened. DEGs were mainly involved in receptor complexes, ubiquitin ligase complexes, etc., playing GTPase activity, phospholipid binding, and other molecular functions, and participating in the regulation of intracellular substance transport, small molecule metabolism, and other biological processes. Protein functional enrichment analysis showed that these proteins were mainly enriched in the IL-17 signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway, Epstein-Barr virus infection, neutrophil extracellular trap formation, and other pathways involved in the formation and development process of ESCA. Survival analysis showed that the overall survival rate of ESCA patients with high expression of KIF4A, RAD51AP1, and CDKN3 was significantly shortened, and the difference was statistically significant (P<0.05). Furthermore, the areas under the curve (AUC) of KIF4A, RAD51AP1, and CDKN3 for diagnosing esophageal cancer were 0.956, 0.951 and 0.979, respectively, with sensitivities and specificities both exceeding 80%. Additionally, ROC results of the combined diagnostic model of these three genes showed an AUC of 0.979, with sensitivities and specificities of 0.914 and 1, respectively. This indicates that KIF4A, RAD51AP1 and CDKN3 have individual or combined auxiliary diagnostic value for ESCA. In conclusion, KIF4A, RAD51AP1 and CDKN3 have high diagnostic efficiency for ESCA, and their increased expression is closely related to the prognosis, suggesting that these three genes could be used as auxiliary diagnostic and prognostic factors for ESCA.

[Clinical efficacy of intraarticular vancomycin in preventing early periprosthetic joint infection after primary knee arthroplasty].

Objective: To investigate the clinical effect of intraarticular vancomycin on early periprosthetic joint infection (PJI) in knee arthroplasty and the incidence of postoperative complications. Methods: This is a retrospective cohort study. The clinical data of 1 867 patients who underwent primary knee arthroplasty at Department of Joint Surgery, the Affiliated Hospital of Qingdao University from April 2022 to June 2023 were retrospectively analysed, including total knee arthroplasty (TKA), robotic-assisted total knee arthroplasty (RA-TKA) and unicondylar knee arthroplasty (UKA). There were 687 males and 1 180 females, aged (68.0±11.2)years(range:45 to 87 years). Patients were divided into the vancomycin group and the control group according to whether or not intra-articular injection of 1 g of vancomycin powder dissolved in 30 ml of saline was performed after intraoperative joint capsule closure. In the vancomycin group, 925 patients were included, including 782 TKA, 27 RA-TKA and 116 UKA.In the control group, 942 patients were included, including 767 TKA, 99 RA-TKA and 76 UKA. Early PJI, wound complications, and vancomycin-related toxicity including acute renal collapse, ototoxicity, and allergic reactions were assessed within 3 months postoperatively. The data were compared using the independent sample t test, χ² test, and Fisher's exact probability method, as appropriate. Major Extremity Trauma Research Consortium (METRC). Results: No PJI was found in all patients in the vancomycin group.Five cases (0.7%,5/767) of early PJI were found in TKA patients in the control group, with a statistically significant difference (P=0.030); 1 case of early PJI was found in each RA-TKA and UKA patients, with non-significant difference compared with vancomycin group (all P>0.05). Two cases (0.3%,2/782) of incisional complications were found in TKA patients in the vancomycin group, and 4 cases (0.5%, 4/767) of incisional complications were found in TKA patients in the control group, with non-significant difference(P=0.449); no incisional complication was found in RA-TKA patients in the vancomycin group, and 1 case (1.0%,1/99) of incisional complications were found in RA-TKA patients in the control group, the difference was not statistically significant (P>0.05); no incisional complication was found in both groups of UKA patients.No vancomycin-related acute kidney injury, ototoxicity, or allergic reactions was observed in all patients. Conclusion: Intra-articular injection of 1 g of vancomycin suspension after arthrotomy closure during TKA maybe lower the risk of early PJI without increasing the risk of wound complication and vancomycin-associated systemic toxicity.

Mercury intoxication disrupts tonic signaling in B cells, and may promote autoimmunity due to abnormal phosphorylation of STIM-1 and other autoimmunity risk associated phosphoproteins involved in BCR signaling.

Epidemiological studies link exposure to mercury with autoimmune disease. Unfortunately, in spite of considerable effort, no generally accepted mechanistic understanding of how mercury functions with respect to the etiology of autoimmune disease is currently available. Nevertheless, autoimmune disease often arises because of defective B cell signaling. Because B cell signaling is dependent on phosphorylation cascades, in this report, we have focused on how mercury intoxication alters phosphorylation of B cell proteins in antigen-non stimulated (tonic) mouse (BALB/c) splenic B cells. Specifically, we utilized mass spectrometric techniques to conduct a comprehensive unbiased global analysis of the effect of inorganic mercury (Hg2+) on the entire B cell phosphoproteome. We found that the effects were pleotropic in the sense that large numbers of pathways were impacted. However, confirming our earlier work, we found that the B cell signaling pathway stood out from the rest, in that phosphoproteins which had sites which were affected by Hg2+, exhibited a much higher degree of connectivity, than components of other pathways. Further analysis showed that many of these BCR pathway proteins had been previously linked to autoimmune disease. Finally, dose response analysis of these BCR pathway proteins showed STIM1_S575, and NFAT2_S259 are the two most Hg2+ sensitive of these sites. Because STIM1_S575 controls the ability of STIM1 to regulate internal Ca2+, we speculate that STIM1 may be the initial point of disruption, where Hg2+ interferes with B cell signaling leading to systemic autoimmunity, with the molecular effects pleiotropically propagated throughout the cell by virtue of Ca2+ dysregulation.

The axial and sagittal CT values of the 7th thoracic vertebrae in screening for osteoporosis and osteopenia.

AIM: To evaluate the difference in computed tomography (CT) attenuation value of different planes of the 7th thoracic vertebra and investigate the efficacy of axial and sagittal vertebral CT measurements in predicting osteoporosis. MATERIALS AND METHODS: Patients who underwent routine chest CT and dual-energy X-ray absorptiometry (DXA) within 1 month were included in this retrospective study. The CT attenuation values of different planes were compared. Logistic regression and receiver operating characteristic (ROC) were used to analyse the difference of each plane in the diagnosis of osteoporosis. RESULTS: The study included 1,338 patients (mean age of 61.9±11.9; 54% female). The CT attenuation values decreased successively in the normal group, osteopenia group, and osteoporosis group. The paired t-test results showed that the mid-axial measurements were greater than mid-sagittal measurements, with a mean difference of 9 HU, the difference was statistically significant (p<0.001, 95% confidence interval [CI] = 7.8-10.1). For each one-unit reduction in mid-sagittal CT attenuation value, the risk of osteopenia or osteoporosis increased by 3.6%. To distinguish osteoporosis from non-osteoporosis (osteopenia + normal), the sensitivity was 90% and the specificity was 52.4% at the mid-sagittal threshold of 113.7 HU. CONCLUSIONS: The CT attenuation values of mid-sagittal plane have higher diagnostic efficacy than axial planes in predicting osteoporosis. For patients with a sagittal CT attenuation value of <113.7 HU in the T7, further DXA examination is warranted.

Development and multicenter validation of a novel radiomics-based model for identifying eosinophilic chronic rhinosinusitis with nasal polyps.

BACKGROUND: Reliable noninvasive methods are needed to identify endotypes of chronic rhinosinusitis with nasal polyps (CRSwNP) to facilitate personalized therapy. Previous computed tomography (CT) scoring system has limited and inconsistent performance in identifying eosinophilic CRSwNP. We aimed to develop and validate a radiomics-based model to identify eosinophilic CRSwNP. METHODS: Surgical patients with CRSwNP were recruited from Tongji Hospital and randomly divided into training (n = 232) and internal validation cohort (n = 61). Patients from two additional hospitals served as external validation cohort-1 (n = 84) and cohort-2 (n = 54), respectively. Data were collected from October 2013 to May 2021. Eosinophilic CRSwNP was determined by histological criterion. The least absolute shrinkage and selection operator and the logistic regression (LR) algorithm were used to develop a radiomics model. Univariate and multivariate LR were employed to build models based on CT scores, clinical characteristics, and the combination of radiological and clinical characteristics. Model performance was evaluated by assessing discrimination, calibration, and clinical utility. RESULTS: The radiomics model based on 10 radiomic features achieved an area under the curve (AUC) of 0.815 in the training cohort, significantly better than the CT score model based on ethmoid-to-maxillary sinus score ratio with an AUC of 0.655. The combination of radiomic features and blood eosinophil count had a further improved performance, achieving an AUC of 0.903. The performance of these models was confirmed in all validation cohorts with satisfying predictive calibration and clinical application value. CONCLUSIONS: A CT radiomics-based model is promising to identify eosinophilic CRSwNP. This radiomics-based method may provide novel insights in solving other clinical concerns, such as guiding personalized treatment and predicting prognosis in patients with CRSwNP.

[Infiltration and significance of M1 macrophage in breast cancer: an analysis of METABRIC database and clinical validation].

Objective: To investigate the differences of immune microenvironment between stage T1N3 and stage T3N0 breast cancer patients and explore the relationship between M1 macrophage infiltration and lymph node metastasis in breast cancer. Methods: Clinical information and RNA-sequencing (RNA-Seq) expression data of stage T1N3 (n=9) and stage T3N0 (n=11) breast cancer patients were extracted from Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases. Using CIBERSORT, the proportions of 22 types of immune cells were calculated, and then the differences of immune cell infiltration between stage T1N3 and T3N0 patients were compared. From 2011 to 2022, pathologic specimens were collected from breast cancer patients who underwent curative resection at the Cancer Hospital, Chinese Academy of Medical Sciences, including 77 at stage T1N3 and 58 at stage T3N0.The METABRIC database analysis results were verified by examining the density of M1 macrophages in tissues using dual-staining immunohistochemistry. Results: METABRIC data analysis showed M1 macrophage was the highest proportion, 15.85% in stage T1N3 breast cancer; M2 macrophage was the highest proportion, 13.07% in stage T3N0 breast cancer.M1 macrophage proportions were statistically different between patients with stage T1N3 and stage T3N0 (P=0.010). The dual-staining immunohistochemistry analysis of breast cancer tissues showed M1 macrophage density (median) of 62.0 and 38.0 cells/mm(2) for stage T1N3 and T3N0, respectively. The difference was statistically significant (P=0.002). Conclusion: The density of M1 macrophages is notably higher in stage T1N3 patients and is associated with lymph node metastasis.

[The expression of Plakoglobin in residual cancer after neoadjuvant chemotherapy for breast cancer and its prognostic impact on patients].

Objective: To investigate the relationship between the expression levels of Plakoglobin protein in residual lesions after neoadjuvant chemotherapy (NAC) and the prognosis of breast cancer patients. Methods: Clinical and pathological data from 174 breast cancer patients who underwent surgery after receiving NAC at the Cancer Hospital of Chinese Academy of Medical Sciences from January 2009 to December 2017 were collected. The expression level of Plakoglobin in residual cancer lesions was evaluated by immunohistochemistry. The correlation between Plakoglobin expression level and clinicopathological features was analyzed. Survival analysis was performed using the Kaplan-Meier method, and Cox proportional hazard regression models were used for factor analysis. Results: Among the 174 patients, 140 had low expression of Plakoglobin, and 34 had high expression. The median disease-free survival (DFS) and overall survival (OS) in the Plakoglobin low expression group were 59.46 and 71.68 months, respectively, both of which were higher than those in the high expression group (36.58 and 47.26 months, respectively, both P<0.05). Univariate analysis showed that Plakoglobin expression, pathological N stage, lymphovascular invasion status, histological grade, Ki-67, and molecular subtypes were associated with OS (all P<0.05), while pathological N stage, histological grade, and Ki-67 were associated with DFS (all P<0.05). Multivariate analysis revealed that Plakoglobin expression (HR=2.438, 95% CI: 1.256-4.735, P=0.008) was an independent predictor for OS, and Ki-67 (HR=2.228, 95% CI: 1.316-3.773, P=0.003) was an independent predictor for DFS. Conclusion: In breast cancer patients with residual lesions after NAC, those with low Plakoglobin expression have relatively longer OS and Plakoglobin is an independent prognostic factor for OS.

[Analysis of risk factors for depth of invasion and angiolymphatic invasion for circumferential superficial esophageal squamous cell carcinoma and precancerous lesion].

Objective: To analyze clinicopathological features of circumferential superficial esophageal squamous cell carcinoma and precancerous lesions and investigate the risk factors for deep submucosal invasion and angiolymphatic invasion retrospectively. Methods: A total of 116 cases of esophageal squamous epithelial high-grade intraepithelial neoplasia or squamous cell carcinoma diagnosed by gastroscopy, biopsy pathology and endoscopic resection pathology during November 2013 to October 2021 were collected, and their clinicopathological features were analyzed. The independent risk factors of deep submucosal invasion and angiolymphatic invasion were analyzed by logistic regression model. Results: The multivariate logistic regression analysis showed that drinking history (OR=3.090, 95% CI: 1.165-8.200; P<0.05), The AB type of intrapapillary capillary loop (IPCL) (OR=11.215, 95% CI: 3.955-31.797; P<0.05) were the independent risk factors for the depth of invasion. The smoking history (OR=5.824, 95% CI: 1.704-19.899; P<0.05), the presence of avascular area (AVA) (OR=3.393, 95% CI: 1.285-12.072; P<0.05) were the independent factors for the angiolymphatic invasion. Conclusions: The risk of deep submucosal infiltration is greater for circumferential superficial esophageal squamous cell carcinoma patients with drinking history and IPCL type B2-B3 observed by magnifying endoscopy, while the risk of angiolymphatic invasion should be vigilant for circumferential superficial esophageal squamous cell carcinoma patients with smoking history and the presence of AVA observed by magnifying endoscopy. Ultrasound endoscopy combined with narrowband imagingand magnification endoscopy can improve the accuracy of preoperative assessment of the depth of infiltration of superficial squamous cell carcinoma and precancerous lesions and angiolymphaticinvasion in the whole perimeter of the esophagus, and help endoscopists to reasonably grasp the indications for endoscopic treatment.

[Clinical factors affecting the prognosis of lower gingival squamous cell carcinoma].

OBJECTIVE: To define the clinical factors that influence local recurrence and survival in patients with lower gingival squamous cell carcinoma (LGSCC) and determine whether bone invasion is an independent prognostic factor for them. METHODS: A total of 104 patients with LGSCC hospitalized in Peking University Stomatology Hospital from June 2013 to December 2015 were enrolled in this retrospective study.All the patients were followed-up for more than 3 years.The degree of bone invasion was assessed using preoperative imaging data (CT and panoramic radiograph).The degree of bone invasion was divi-ded into four categories: no bone invasion, invasion of cortical bone, invasion of bone marrow cavity, and invasion of the mandibular canal.According to the central position of tumor, it was divided into two types: anterior mandibular invasion (anterior region of the mental foramen) and posterior mandibular invasion (posterior region of the mental foramen). RESULTS: of different invasion depth groups were compared using Mann-Whitney U test.P value < 0.05 was considered to be statistically significant.Kaplan-Meier survival analysis method was used to draw survival curve, and COX regression was used to explore the risk ratio (HR) and 95% confidence interval (CI) of prognostic factors of LGSCC. RESULTS: The follow-up results showed that the 1-, 3-, and 5-year survival rates of LGSCC in this group were 91%, 84%, 82%, respectively.32.7%(34/104) of patients had cervical lymph node metastasis.The cervical lymph node metastasis rate of the anterior segment of the mandible was 12.5%(2/16), and 36.4%(32/88) for the posterior segment of the mandible (P < 0.05).Univariate and multivariate COX analysis showed that the N stage and local recurrence were the prognostic factors of LGSCC patients (P < 0.05). CONCLUSION: As the degree of mandibular invasion increases, the prognosis of patients with mandibular gum cancer becomes worse.N stage and local recurrence are prognostic risk factors for LGSCC.The incidence of cervical lymph node metastasis for LGSCC is related to the primary tumor location.It is concluded that tumors located at the posterior of the mandible might be more prone to cervical lymph node metastasis than the anterior of the mandible.Thus various levels of cervical lymph node dissection strategies should be adopted for different sites of LGSCC.

[Correlation between gene polymorphisms of killer cell immunoglobulin-like receptors and their ligands and Graves' disease].

Objective: To explore the relationship between gene polymorphism of killer cell immunoglobulin-like receptor (KIR) and its ligand-specific human leukocyte antigen C (HLA-C) and Graves' disease (GD). Methods: Case-control study. A total of 118 unrelated GD patients (GD group) admitted to Shandong Provincial Hospital from January 2011 to December 2017 and 108 age-and sex-matched healthy controls (healthy control group) were included. The KIR genotype and its ligand HLA-C allele were detected by polymerase chain reaction sequence-specific primers (PCR-SSP). The distribution of KIR/HLA-C gene combination in GD patients and control population was analyzed to explore its association with the occurrence of GD. Results: In GD group, there were 29 males and 89 females, aged (38±14) years. In the healthy control group, there were 28 males and 80 females, aged (37±13) years. Compared with the healthy control group, the occurrence frequency of HLA-Cw01 was higher in GD group[36.4%(43/118) vs 18.5%(20/108), P=0.003], and the occurrence frequency of HLA-Cw03 and HLA-Cw06 was lower in GD group[11.9%(14/118) vs 39.8%(43/108), P<0.001; 9.3%(11/118) vs 18.5%(20/108), P=0.045]. The frequency of KIR2DL1/HLA-C2 gene combination in GD group was lower than that in control group [17.8%(21/118) vs 34.3%(37/108), P=0.005]. Logistic regression analysis showed that KIR2DL1/HLA-C2 gene combination was a protective factor for GD occurrence (OR=0.308, 95%CI: 0.126-0.752, P=0.010). Conclusions: The polymorphism of KIR/HLA-C gene is related to GD. The low expression of KIR2DL1/HLA-C2 in GD patients may be a protective factor for GD.

[Value of direct immunohistochemical staining in assisting intraoperative frozen diagnosis of bronchiolar adenoma].

Objective: To explore the feasibility and application value of intraoperative direct immunohistochemical (IHC) staining in improving the diagnosis accuracy in difficult cases of bronchiolar adenoma (BA). Methods: Nineteen cases with single or multiple pulmonary ground-glass nodules or solid nodules indicated by imaging in Cancer Hospital of Chinese Academy of Medical Sciences from January to July 2021 and with difficulty in differential diagnosis at frozen HE sections were selected. In the experimental group, direct IHC staining of cytokeratin 5/6 (CK5/6) and p63 was performed on frozen sections to assist the differentiation of BA from in situ/micro-invasive adenocarcinoma/adenocarcinoma/invasive mucinous adenocarcinoma. In the control group, two pathologists performed routine frozen HE section diagnosis on these 19 cases. The diagnostic results of paraffin sections were used as the gold standard. The sensitivity and specificity of BA diagnosis, consistency with paraffin diagnosis and time used for frozen diagnosis were compared between the experimental group and the control group. Results: The basal cells of BA were highlighted by CK5/6 and p63 staining. There were no basal cells in the in situ/microinvasive adenocarcinoma/adenocarcinoma/invasive mucinous adenocarcinoma. In the experimental group, the sensitivity and specificity with aid of direct IHC staining for BA were 100% and 86.7%, respectively, and the Kappa value of frozen and paraffin diagnosis was 0.732, and these were significantly higher than those in the control group (P<0.05). The average time consumption in the experimental group (32.4 min) was only 7 min longer than that in the control group (25.4 min). Conclusions: Direct IHC staining can improve the accuracy of BA diagnosis intraoperatively and reduce the risk of misdiagnosis, but require significantly longer time. Thus frozen direct IHC staining should be restricted to cases with difficulty in differentiating benign from malignant diseases, especially when the surgical modalities differ based on the frozen diagnosis.

Intravoxel incoherent motion diffusion-weighted imaging as a quantitative tool for evaluating disease activity in patients with axial spondyloarthritis.

AIM: To determine the correlations between four quantitative magnetic resonance imaging (MRI) parameters derived from intravoxel incoherent motion diffusion-weighted images (IVIM DWI) and the semi-quantitative Spondyloarthritis Research Consortium of Canada (SPARCC) score of the sacroiliac joint (SIJ) and five clinical activity indices in patients with axial spondyloarthritis (axSpA). AND METHODS: A total of 75 patients with axSpA and complete clinical activity indices and SIJ MRI were enrolled to this prospective study. Univariable and multivariable linear regression analyses were performed to evaluate correlations between MRI parameters and clinical activity indices after controlling for confounders. All data were further analysed using Pearson's correlation coefficients (r). RESULTS: Only pure diffusion coefficient (D) and incoherent perfusion related microcirculation (D∗) were found to be independently positively correlated with several clinical activity indices (all p<0.05). Positive correlations were observed between D and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), Patient Global Assessment (PGA), extent of influence of pain, with r of 0.605, 0.402, 0.319, and 0.485 (all p<0.0125). D∗ correlated positively with BASDAI, BASFI, and PGA (r=0.436, 0.356, 0.301, respectively; all p<0.0125). CONCLUSION: D and D∗ derived from IVIM DWI could be associated with some disease activity indices in patients with axSpA; apparent diffusion coefficient (ADC) and SPARCC scores were not correlated with these indices. IVIM DWI may be a useful tool for the quantitative assessment of disease activity in patients with axSpA.

Association between awareness of vulnerability and disaster preparedness in an infrastructure-resilient city: a population-based study.

OBJECTIVES: Factors associated with an individual's awareness of vulnerability can be modified by the infrastructure of a city. These factors may impact disaster preparedness among local populations in an infrastructure-resilient city, which further influences the health risks of various population subgroups. STUDY DESIGN: This was a population-based study. METHODS: Four population subgroups, which have previously been reported to be related to awareness of vulnerability (i.e. past experiences, sociodemographic deprivation, poor housing conditions and family medical needs), were analysed for their impacts on disaster preparedness. Validated population-based phone interviews (n = 856) were conducted in Hong Kong. Three types of disaster preparedness were studied: (1) physical preparedness; (2) social preparedness; and (3) education preparedness. RESULTS: Previous experience of social hazards, accidental hazards and epidemics increased disaster preparedness among the local population. Specifically, experiences of accidental hazards and social hazards were positively associated with physical preparedness (odds ratios 1.626, 95% confidence interval [95% CI] 1.215, 2.172) and 1.501 [95% CI 1.114, 2.024], respectively). However, experiences of natural hazards did not increase preparedness, even in Hong Kong, which is a city with high 'disaster resilience' because of its well-developed infrastructure. Moreover, individuals with a low educational level or low income had lower education preparedness, unmarried individuals had lower social preparedness, and poor housing conditions of non-private-housing households had negative associations with education preparedness. These findings partially align with local disaster responses to the 2018 Typhoon Mangkhut, the 2019 social unrest and the 2020 COVID-19 pandemic, all of which were observed after the 2018 survey reported in this study. CONCLUSIONS: Social and environmental interventions should be targeted to marginalised subpopulations through location-based community strategies to encourage increased environmental knowledge and participation in disaster preparedness activities.

Renal outcomes in Asian patients receiving oral anticoagulants for non-valvular atrial fibrillation.

INTRODUCTION: Patients with non-valvular atrial fibrillation (NVAF) may be prescribed warfarin or a non-vitamin K oral anticoagulant (NOAC). There is increasing evidence that NOACs are superior to warfarin in terms of renal function preservation. This study aimed to compare renal outcomes in Chinese patients with NVAF between patients receiving NOACs and patients receiving warfarin. METHODS: In total, 600 Chinese patients with NVAF receiving oral anticoagulant therapy were retrospectively identified from an administrative database. The renal outcomes (≥30% decline in estimated glomerular filtration rate [eGFR], doubling of serum creatinine, and kidney failure) were compared among four propensity-weighted treatment cohorts (warfarin, n=200; rivaroxaban, n=200; dabigatran, n=100; and apixaban, n=100). RESULTS: The mean follow-up period across all groups was 1000 ± 436 days. Compared with warfarin, the three NOACs (pooled for consideration as a single unit) had significantly lower risks of ≥30% decline in eGFR (hazard ratio [HR]=0.339; 95% confidence interval [CI]=0.276-0.417) and doubling of serum creatinine (HR=0.550; 95% CI=0.387-0.782). Dabigatran and rivaroxaban users both had lower risks of ≥30% decline in eGFR (both P<0.001) and doubling of serum creatinine (both P<0.05). Apixaban was only significantly associated with a lower risk of ≥30% decline in eGFR (P<0.001). CONCLUSIONS: Compared with warfarin, NOACs may be associated with a significantly lower risk of decline in renal function among Chinese patients with NVAF.

[The relationships between functional gastrointestinal diseases and psychological factors, diet and lifestyles: a network analysis].

Objective: To investigate the relationship between common functional gastrointestinal diseases symptoms with psychological factors, diet and lifestyles by using the network analysis method which has achieved great success in the field of psychology in recent years. Method: A questionnaire survey was conducted in two military units using the cluster sampling method during July 2020, and a total of 1 805 subjects were included. Functional gastrointestinal disease symptoms were evaluated with the Gastrointestinal Symptom Rating Scale (GSRS). The state, trait anxiety scale and stress response scale were used to evaluate the mental and psychological state by self-evaluation. R was used to build the network and calculate statistical parameters. Results: 1 486 of the 1 805 subjects (82.3%) had experienced functional gastrointestinal diseases symptoms within 2 weeks, but most of them were mild. Network analysis shows that there was a strong interaction between digestive system symptoms with different clinical manifestations (Spearman coefficient ranges 0.31-0.56). There was a clear relationship between functional gastrointestinal symptoms and mental and psychological factors (Spearman coefficient ranges 0.16-0.27), but there was no clear interaction with diet, age, education level, body mass index, etc. Functional gastrointestinal diseases symptoms were connected with mental and psychological factors through two nodes: stress and indigestion. The stability coefficient of node strength correlation was 0.75, indicating that the network was stable. Conclusions: The current study revealed the network structure and features of functional gastrointestinal diseases symptoms with mental and psychological factors. The key linking nodes provided potential interfering target for controlling functional gastrointestinal symptoms related to mental and psychological factors.

[A prospective cohort study of the influence of positive/negative effectivity on the mortality risk of the Chinese elderly].

OBJECTIVE: To explore the influence of positive/negative effectivity on the mortality risk of the Chinese elderly. METHODS: Using the latest four surveys data of Chinese longitudinal healthy longevity survey in 2008, 2012, and 2014, as well as 2018 and selecting 10 993 elderly people who were aged 65 and above as research objects, this paper compared the positive/negative effectivity status and differences of the elderly in different gender and age groups. And then this paper analyzed the effect of positive/negative effectivity on elderly people' s mortality risk by constructing Cox proportional hazards model. RESULTS: Compared with the female elderly, the male elderly had lower negative effectivity and higher positive effectivity. With the increase of age, the negative effectivity of the elderly increased, while the positive effectivity decreased. The results showed that after adjusting for the basic demographic characteristics, health status and living habits of the respondents in the baseline survey, in the positive effectivity dimension, "clean preference" (HR=0.922, 95%CI: 0.889-0.956), "autonomy" (HR=0.933, 95%CI: 0.914-0.952) and "sense of youth" (HR=0.948, 95%CI: 0.927-0.969), had a protective effect on the mortality risk of the elderly, while in the dimension of "open-minded view", there was no significant difference in the mortality risk of the elderly with different answers. In the negative effecti-vity dimension, "tension and fear" (HR=1.039, 95%CI: 1.014-1.065), "loneliness" (HR=1.053, 95%CI: 1.029-1.079) and "uselessness" had a harmful effect on the mortality risk of the elderly. The more positive effectivity, the lower the mortality risk of the elderly (HR=0.967, 95%CI: 0.956-0.978), while the more negative effectivity, the higher the mortality risk of the elderly (HR=1.024, 95%CI: 1.013-1.035). CONCLUSION: The negative effectivity of the elderly in all dimensions may increase the mortality risk of elderly people. We ought to dredge the negative emotions of the elderly in time. In the health promotion of the elderly, we should also pay attention to the encouragement of positive effectivity in all dimensions, which requires the joint efforts of families, communities and governments.