Search

The recently developed European Society for Radiotherapy and Oncology (ESTRO)/European Organization for Research and Treatment of Cancer (EORTC) oligometastatic disease (OMD) classification has not been validated in terms of its prognostic significance. This study stratified patients from the phase II SABR-5 trial based on ESTRO/EORTC criteria and compared progression-free survival (PFS) and overall survival (OS) to determine the prognostic significance of the classification scheme.The SABR-5 trial was a single arm phase II study conducted at the 6 regional cancer centers across British Columbia (BC), Canada, where SABR for oligometastases was only offered on trial. Patients with up to 5 oligometastases (total or not controlled by prior treatment and including induced OMD) underwent SABR to all lesions. Patients were 18 years of age or older, Eastern Cooperative Oncology Group 0 to 2, and life expectancy ≥6 months. PFS and OS were calculated using the Kaplan-Meier method and differences between OMD groups were assessed with log-rank tests. Univariable and multivariable analyses were performed using Cox regression modeling.Between November 2016 and July 2020, 381 patients underwent SABR on trial. Median follow-up was 27 months (interquartile range, 18-36). The most frequent OMD group was de novo OMD (69%), followed by repeat (16%) and induced (13%). OMD groups differed significantly in PFS (P.001) but not OS (P = .069). The OMD classification was an independent predictor of both PFS (P = .005) and OS (P = .002). Of the 5 classification factors, only chronicity (synchronous, hazard ratio, 0.52; P = .027) and oligoprogression (hazard ratio, 2.05; P = .004) were independently prognostic for OS.In this large prospective cohort, the ESTRO/EORTC classification was an independent predictor of PFS and OS and should be used to identify specific patient groups for clinical trials. In this trial population, the prognostic power is largely attributable to chronicity and oligoprogression. Simplification of the framework may be possible in the future and allow for greater ease of use; however, further data on underrepresented OMD groups and histologies will be required.

ImportancePatient-submitted images vary considerably in quality and usefulness. Studies that characterize patient-submitted images in a real-life setting are lacking.ObjectiveTo evaluate the quality and perceived usefulness of patient-submitted images as determined by dermatologists and characterize agreement of their responses.Design, Setting, and ParticipantsThis survey study included patient images submitted to the Department of Dermatology at Duke University (Durham, North Carolina) between August 1, 2018, and December 31, 2019. From a total pool of 1200 images, 10 dermatologists evaluated 200 or 400 images each, with every image being evaluated by 3 dermatologists. Data analysis occurred during the year leading up to the article being written.Main Outcomes and MeasuresThe primary outcomes were the responses to 2 questions and were analyzed using frequency counts and interrater agreement (Fleiss κ) to assess image quality and perceived usefulness. We performed a random-effects logistic regression model to investigate factors associated with evaluators’ decision-making comfort. We hypothesized that most images would be of low quality and perceived usefulness, and that interrater agreement would be poor.ResultsA total of 259 of 2915 patient-submitted images (8.9%) did not depict a skin condition at all. The final analysis comprised 3600 unique image evaluations. Dermatologist evaluators indicated that 1985 images (55.1%) were useful for medical decision-making and 2239 (62.2%) were of sufficient quality. Interrater agreement for a given image’s diagnostic categorization was fair to substantial (κ range, 0.36-0.64), while agreement on image quality (κ range, 0.35-0.47) and perceived usefulness (κ range, 0.29-0.38) were fair to moderate. Senior faculty had higher odds of feeling comfortable with medical decision-making than junior faculty (odds ratio [OR], 3.68; 95% CI, 2.9-4.66; P P P = .01) compared with inflammatory skin conditions and that were in focus (OR, 5.56; 95% CI, 4.63-6.67; P Conclusions and RelevanceIn this survey study including 10 dermatologists, a slight majority of patient-submitted images were judged to be of adequate quality and perceived usefulness. Fair agreement between dermatologists was found regarding image quality and perceived usefulness, suggesting that store-and-forward teledermatology initiatives should consider a physician’s individual experiences and comfort level. The study results suggest that images are most likely to be useful when they are in focus and reviewed by experienced attending physicians for wound surveillance, but dermatologists may be burdened by irrelevant or unsuitable images.

本文报道1例耳硬化症合并残存镫骨动脉病例。患者，女，14岁，因“双耳听力逐渐降低1年”入院。根据患者纯音测听、盖莱试验和颞骨薄层CT检查结果，考虑诊断为双侧耳硬化症。在全身麻醉下行左侧人工镫骨手术时，在镫骨底板表面约中线处见一细小血管通过，穿过镫骨足弓下方，与镫骨底板长轴相垂直，进入面神经水平段骨管。患者3周后复查听力，左耳听力较术前提高，无搏动性耳鸣、面瘫、眩晕等并发症，对手术效果满意。.

In this case series, ustekinumab therapy demonstrated efficacy in some patients with severe hidradenitis suppurativa previously treated with adalimumab and/or infliximab. Larger prospective studies are needed to evaluate ustekinumab as a treatment option for recalcitrant hidradenitis suppurativa.

Sarcopenia refers to age-related loss of skeletal muscle mass. SARC-F is a screening tool for sarcopenia with high specificity and relatively good overall diagnostic accuracy but with low sensitivity. This study evaluated the diagnostic utility of SARC-F and its three modified versions (SARC-CalF, SARC-F+AC, and SARC-CalF+AC) for screening sarcopenia in community-dwelling older adults.Diagnostic accuracy study.We screened sarcopenia of older adults (age ≥ 60 years) in three communities in 2020. The participants' information and anthropometric measurements were collected, respectively.The updated consensuses of AWGS2019 and the EWGSOP2 were applied as the reference standards. we performed sensitivity/specificity analyses and estimated the areas under the receiver operating characteristic curves (AUCs) of the four scales.The prevalence of sarcopenia was 26.4% and 12.5% based on the AWGS2019 and EWGSOP2 criteria, respectively. The sensitivities/specificities of SARC-F, SARC-CalF, SARC-F+AC, and SARC-CalF+AC were 12.26%/95.59%, 47.17%/91.53%, 82.08%/68.47%, and 75.47%/83.73%, respectively, using the AWGS2019 criteria. Further, the corresponding AUCs of SARC-F, SARC-CalF, SARC-F+AC, and SARC-CalF+AC were 0.650 (95% confidence interval [CI]: 0.601-0.697), 0.811 (95% CI: 0.769-0.848), 0.801 (95% CI: 0.759-0.839), and 0.848 (95% CI: 0.809-0.881), respectively. Using the EWGSOP2 criteria, the sensitivities/specificities of SARC-F, SARC-CalF, SARC-F+AC, and SARC-CalF+AC were 20.00%/95.44%, 56.00%/86.61%, 70.00%/81.20%, and 80.00%/74.93%, respectively. The AUCs of SARC-F, SARC-CalF, SARC-F+AC, and SARC-CalF+AC were 0.706 (95% CI: 0.659-0.750), 0.799 (95% CI: 0.756-0.837), 0.815 (95% CI: 0.774-0.852), and 0.834 (95% CI: 0.794-0.869), respectively.The modified versions of SARC-F+AC and SARC-CalF+AC, which have superior sensitivity, can be used to screen sarcopenia in community-dwelling older adults. SARC-CalF+AC had the highest overall diagnostic accuracy for screening sarcopenia among community-dwelling older adults.

To investigate the feasibility of establishment of ultrasound radiomics-based models for classification of hepatic echinococcosis, so as to provide insights into precision ultrasound diagnosis of hepatic echinococcosis.The ultrasonographic images were retrospectively collected from 200 patients with hepatic echinococcosis in Shiqu County, Ganzi Tibetan Autonomous Prefecture, Sichuan Province in October 2014, and the regions of interest were plotted in ultrasonographic images of hepatic echinococcosis lesions. The ultrasound radiomics features of hepatic echinococcosis were extracted with 25 methods, and screened using pre-selection and the least absolute shrinkage and selection operator. Then, all ultrasonographic images were randomly assigned into the training and independent test sets according to the type of lesions at a ratio of 7:3. Machine learning models for classification of hepatic echinococcosis were created based on two classifiers, including kernel logistic regression (KLR) and medium Gaussian support vector machine (MGSVM). The receiver operating characteristic (ROC) curves were plotted, and the sensitivity, specificity and areas under the curves (AUC) of the created machine learning models for classification of hepatic echinococcosis were calculated.A total of 5 005 ultrasound radiomics features were extracted from 200 patients with hepatic echinococcosis using 25 methods, and 36 optimal radiomics features were screened through feature selection, based on which two machine learning models were created, including KLR and MGSVM. ROC curve analysis showed that MGS-VM presented a higher efficacy for hepatic echinococcosis classification than KLR in the training set, with a sensitivity of 0.82, a specificity of 0.78 and AUC of 0.88, while KLR presented a higher efficacy for hepatic echinococcosis classification than MGSVM in the independent test set, with a sensitivity of 0.82, a specificity of 0.72 and AUC of 0.86, respectively.Ultrasound radiomics-based machine learning models are feasible for hepatic echinococcosis classification.

Traditional diagnostic strategies are unable to accurately discriminate between patients with poor and satisfied prognosis in colon cancer. Therefore, it is urgently recommended to identify new biomarkers in favor of better selection of patients at higher risk of recurrence or poor outcomes, with the aim of early intervention or avoiding overtreatment.The weighted gene correlation network analysis (WGCNA), together with the proportion of tumor infiltrating immune cells, were employed to screen the key module related to immune infiltration. Using these genes among the key module, a predictive signature was generated via LASSO and multi-Cox regression method. Moreover, a novel nomogram was further developed by combining important clinical parameters and the predictive signature.Genes among the green module, indicating the highest correlation with regulatory T cells (Tregs), were incorporated into the establishment of predictive model. Then, a Tregs-related risk signature (TRRS) consisting of four genes (NRG1, TEX11, OVOL3 and FCRL2) was established, which performed well in predicting the mortality risk of colon cancer in both internal and external validation groups (p=0.004 for TCGA training set, p=0.016 for TCGA testing set and p=0.03 for GSE39582 dataset). Combining TNM stage and age, we developed a nomogram for 1-, 3-, 5-year OS, presenting a more reliable predictive performance in survival based on the receiver operating characteristic (ROC) curves and calibration curves (3-year AUC: 0.83 and 0.74 in the TCGA and GEO database, respectively).We constructed a four-gene signature for predicting the prognosis of patients with colon cancer, and further developed the nomogram together with TNM stage and age to improve the predictive efficacy.

OBJECTIVE: To compare a new thermosensitive recombinant human amelogenin (rhAm) carrier and traditional propylene glycol alginate (PGA) carrier for their characteristics, antibacterial activity, and biocompatibility with human periodontal membrane fibroblasts. METHODS: PGA-rhAm was prepared by mixing 3.3% PGA and rhAm, and CS-βGP-rhAm was prepared by mixing 2% chitosan (CS) with rhAm and then with 60% β-sodium glycerophosphate solution (βGP) as the crosslinking agent. The biophysical properties of the prepared carriers were characterized, and their antibacterial activity was assessed by observing Staphylococcus aureus growth. The biocompatibility of the carriers was evaluated in human periodontal membrane fibroblasts (hPDLFs) using CCK8 assay and scratch test, and mRNA and protein expressions of osteogenic genes of the cells incubated with the carriers were detected using RT-qPCR and Western blotting; osteogenic differentiation of the cells was detected using alkaline phosphatase staining. RESULTS: PGA-rhAm had a viscosity value of 3.262±0.055 Pa.s. CS-βGP-rhAm had a solidification capacity of 6 min at 37 ℃ with a pH value close to that of the oral cavity and a swelling rate of about 90%. CS-β GP-rhAm maintained sustained release of rhAm for over 2 weeks with a self-degradation time over 3 weeks. CS-βGPrhAm more effectively inhibited the growth of S. aureus than rhAm-loaded PGA. While PGA did not obviously affect the proliferation of hPDLFs, both CS-βGP and CS-βGP-rhAm significantly promoted the cell proliferation(P < 0.001). Scratch test showed that after rhAm loading, both CS-βGP and PGA promoted cell migration (P < 0.01). CS-βGP-rhAm significantly enhanced the mRNA expressions of RUNX2 and OCN mRNA level and the protein expressions of Ki67, RUNX2, collagen I, and β-catenin (P < 0.05); PGA-rhAm only enhanced RUNX2 (P < 0.05) and OCN (P < 0.01) mRNA expressions without significant effects on the protein expressions. Alkaline phosphatase staining results showed that CS-βGP, but not PGA, promoted osteogenic differentiation of hPDLFs. CONCLUSION: CS-βGP carrier is capable of sustained release of rhAm, inhibiting the growth of S. aureus, and improving the biological activity of hPDLFs without affecting the bioactivity of rhAm after drug loading.

Schistosomiasis is a parasitic disease that seriously hinders socioeconomic developments and threatens public health security. To achieve the global elimination of schistosomiasis as a public health problem by 2030, WHO released the guideline on control and elimination of human schistosomiasis on February, 2022, with aims to provide evidence-based recommendations for schistosomiasis morbidity control, elimination of schistosomiasis as a public health problem, and ultimate interruption of schistosomiasis transmission in disease-endemic countries. Following concerted efforts for decades, great achievements have been obtained for schistosomiasis control in China where the disease was historically highly prevalent, and the country is moving towards schistosomiasis elimination. This article reviews the successful experiences from the national schistosmiasis control program in China, and summarizes their contributions to the formulation and implementation of the WHO guideline on control and elimination of human schistosomiasis. With the progress of the "Belt and Road" initiative, the world is looking forward to more China's solutions on schistosomiasis control.

On February 2022, WHO released the evidence-based guideline on control and elimination of human schistosomiasis, with aims to guide the elimination of schistosomiasis as a public health problem in disease-endemic countries by 2030 and promote the interruption of schistosomiasis transmission across the world. Based on the One Health concept, six evidence-based recommendations were proposed in this guideline. This article aims to analyze the feasibility of key aspects of this guideline in Chinese national schistosomiasis control program and illustrate the significance to guide the future actions for Chinese national schistosomiasis control program. Currently, the One Health concept has been embodied in the Chinese national schistosomiasis control program. Based on this new WHO guideline, the following recommendations are proposed for the national schistosomiasis control program of China: (1) improving the systematic framework building, facilitating the agreement of the cross-sectoral consensus, and building a high-level leadership group; (2) optimizing the current human and livestock treatments in the national schistosomiasis control program of China; (3) developing highly sensitive and specific diagnostics and the framework for verifying elimination of schistosomiasis; (4) accelerating the progress towards elimination of schistosomiasis and other parasitic diseases through integrating the national control programs for other parasitic diseases.

OBJECTIVE: To investigate the role of proline 4-hydroxylase Ⅱ (P4HA2) in the occurrence and progression of liver cancer. METHODS: GEPIA and Human Protein Atlas database were used to predict the expression of P4HA2 in hepatocellular carcinoma (HCC), and K-M plotter online database was used to analyze the relationship between P4HA2 expression and the prognosis of HCC. We also examined the expressions of P4HA2 in HCC cells and normal hepatocytes using qRT-PCR and Western blotting. With lentivirus-mediated RNA interference, P4HA2 expression was knocked down in hepatoma SNU-449 and Hep-3B cells, and the changes in cell proliferation, migration and invasion were assessed using cell counting kit-8 (CCK-8) assay, colony formation test, scratch test and Transwell assay. The changes in the expressions of epithelial-mesenchymal transition (EMT) and PI3K/Akt/mTOR signal pathway-related proteins were detected using Western blotting. RESULTS: Online database analysis showed that the expression of P4HA2 was significantly higher in HCC tissues than in normal liver tissues (P < 0.05). The expression levels of P4HA2 mRNA and protein were also significantly higher in HCC cell lines than in normal hepatocytes (P < 0.01). Lentivirus-mediated RNA interference of P4HA2 significantly lowered the expression levels of P4HA2 mRNA and protein in the hepatoma cells (P < 0.05) and caused obvious inhibition of cell proliferation, migration and invasion. P4HA2 knockdown significantly increased the expression of E-cadherin protein, lowered the expressions of N-cadherin and Snail, and obviously decreased the expressions of phosphorylated PI3K, AKT and mTOR (P < 0.05). CONCLUSION: P4HA2 enhances the proliferation, migration, invasion, and EMT of hepatoma cells by activating the PI3K/Akt/mTOR signaling pathway to promote the occurrence and progression of liver cancer.

The aim of the study was to explore the risk factors of ovarian hyperstimulation in patients undergoing long-acting gonadotropin-releasing hormone (GnRH) agonist protocol in follicular phase of ovulation induction therapy and to establish a predictive model.A total of 1289 patients who received Long-acting GnRH agonist protocol in follicular phase for ovulation induction in the Fujian Provincial Maternity and Child Health Hospital from July 1, 2018, to July 31, 2019, were selected. Among them, 33 patients developed moderate/severe ovarian hyperstimulation syndrome. The relevant indicators of the two groups were followed up for comparison, and Lasso regression was used to screen independent risk factors and construct a nomogram prediction model. A receiver operating characteristic (ROC) curve and calibration curve were used to evaluate the discrimination and calibration of the prediction model.Univariate analysis suggested that the woman's age, basal antral follicle number (AFC), total gonadotropin (Gn) dose, Gn starting dose, basal estradiol (E2) level, basal anti-Müllerian hormone (AMH) value, number of follicles obtained, Gn start day E2, the difference in follicle-stimulating hormone (FSH) value and Gn starting day were statistically significant. Significant indicators of univariate analysis and clinical significance were included in the Lasso regression model, and AFC, woman's age, polycystic ovary syndrome, Gn starting dose and number of follicles obtained were finally screened as final predictors. The ROC curve indicated that the area under the curve (AUC) was 0.812.Ovarian hyperstimulation caused by long-acting GnRH agonist protocol in follicular phase for ovulation stimulation has a certain predictability. Paying attention to the patient's age, AFC, Gn starting dose, number of follicles obtained, and whether PCOS is evident may lead to early detection of ovarian hyperstimulation syndrome, which has clinical guiding significance.

AIM To explore the activation of necroptosis triggered by Enterococcus faecalis in human osteoblastic MG63 cells and provide new insights into the pathogenesis of refractory apical periodontitis. METHODOLOGY The viability of MG63 cells exposed to live E. faecalis was investigated using the cell counting kit-8 assay. The relative expressions of specific markers for necroptosis, namely p-RIPK3 and p-MLKL, were determined by western blotting. Cells pretreated with necrosulfonamide and GSK'872, which are specific inhibitors for MLKL and RIPK3, respectively, were then subjected to lactate dehydrogenase (LDH) cytotoxicity assay, flow cytometry analysis and Hoechst 33342/PI double fluorescence staining. Lentiviral-delivered short hairpin RNA (shRNA) targeting MLKL was employed to further confirm the activation of necroptosis in MG63 cells infected with E. faecalis. Transmission electron microscopy was additionally used to observe the morphological characteristics. Statistical analysis was conducted using Student's t-tests or one-way ANOVA followed by the Student-Newman-Keuls test. RESULTS The infection with E. faecalis significantly inhibited the viability of MG63 cells in a multiplicity of infection- and infection time-dependent manners (P

Pulp and periapical diseases are common and frequently occurring diseases of which diagnosis and treatment must be dealt with by the dental clinicians. The diagnostic techniques of these diseases include evaluation of pulp vitality, measurement of pulp blood circulation and analysis and judgment of root canal anatomy. With the continuous emergence of digital and imaging technologies, the correct application of these technologies in clinic will help clinicians improve their abilities in diagnosis and treatment of related diseases. The present article summarizes and reviews the progress of assistant technology for diagnosing dental pulp and periapical diseases in recent years and puts forward some suggestions for its application.牙髓及根尖周疾病是口腔临床诊疗中的常见病和多发病，这类疾病的诊断技术涵盖了牙髓活力状态检测、牙髓血运状况测定以及根管解剖形态分析和判断。数字化技术和影像技术不断涌现并快速发展，将这些技术正确应用于牙体牙髓临床诊疗中，将有助于提高口腔临床医师对相关疾病的正确诊断率。本文就近年牙髓诊断辅助技术的进展作一总结、回顾，并提出应用建议。.

Whether tumor mutational burden (TMB), which refers to the total number of somatic or acquired mutations per million bases in a particular region of the tumor genome, can serve as a predictive biomarker of immune checkpoint inhibitor (ICI) therapy for colon cancer remains unclear. Hereby, we retrospectively investigated the differentially expressed genes (DEGs) based on the level of TMB and tried to established a risk score model as a novel biomarker. The DNA mutation data were retrieved from the Masked Somatic Mutation in Genomic Data Commons data portal of the Cancer Genome Atlas, where the RNA sequencing data, clinical information, and survival outcomes of patients were downloaded. Patients with incomplete clinical information were excluded. The immune score and stromal score were calculated to investigate immune infiltration. The patients were grouped into TMB-high group and the TMB-low group based on the median value of TMB. An immune relevant gene set was obtained from the Immunology Database and Analysis Portal to identify immune-related DEGs. The Cox proportional hazard model and nomogram were applied to establish the risk model. In results: the TMB value was associated with age (p≤0.001), clinical stage (p≤0.001), N stage (p≤0.001), M stage (p=0.003), and immune score (p≤0.001). Twenty-nine immune-related DEGs were identified as enriched in immune response-related function or pathway and tumorigenesis signaling. Nine of 29 were determined to establish a riskScore model. The riskScore suggested a positive relationship with the TMB value (p=0.033), immune score (p≤0.001), and tumor immune dysfunction and exclusion (TIDE) (p=0.002) and presented an independent prognostic factor (p≤0.001, HR=1.04), which predicted the overall survival with good specificity. We concluded that the combination of TMB with transcriptome expression has a predictive and prognostic value for patients treated with ICIs.

The COVID-19 swept across the countries and regions all over the world in the past one year. The marketing of an effective and safe COVID-19 vaccine is expected to control the spread of the disease. A placebo-controlled field efficacy trial is generally considered in the pivotal study of COVID-19 vaccine to observe whether it is able to reduce the incidence rate of the disease effectively. This paper is to introduce and discuss the considerations in study design and the choice of endpoint, statistical evaluation methods, primary estimand choosing and the strategies to various intercurrent events in the COVID-19 efficacy trials.新型冠状病毒肺炎出现以来，席卷了全球各个国家和地区，安全且有效的新型冠状病毒肺炎疫苗是控制新型冠状病毒肺炎疫情最有效手段之一。新型冠状病毒肺炎疫苗的关键性临床研究通常采用安慰剂对照的保护效力试验，以观察疫苗是否可以有效降低疾病的发病率。本文即将对新冠疫苗保护效力临床试验中研究设计和研究终点的考量、统计学评价方法、主要估计目标的选择以及针对不同伴发事件的解决策略等进行介绍和探讨。.

OBJECTIVE: Bietti crystalline dystrophy (BCD) is a rare degenerative eye disease caused by mutations in the CYP4V2 gene, and Cyp4v3 is the murine ortholog to CYP4V2. To better understand the molecular pathogenesis of this disease and to explore the potential treatment we have established a Cyp4v3 knock-out mouse model. METHODS: Cyp4v3(-/-) mice were generated by clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 in embryonic stem cells of C57BL/6J mice. Ocular morphologic characteristics were evaluated via fundus imaging, histologic analysis of rods and cones via immunofluorescence, and phalloidin stain to observe retinal pigment epithelium (RPE) in whole-mounts, electroretinogram (ERG) was also conducted to examine the retinal function. RESULTS: The characteristic features of BCD recurred in the Cyp4v3(-/-) mice, including retinal crystalline deposits, atrophy and degeneration of RPE cells, and ERG amplitude decline of dark and light adapted a- and b- wave; however, the immunofluorescence stain of rod and cone cells did not show obvious differences when compared with the wild type (WT) mice. In the early stage of the disease, no crystal-like deposits were found in the fundus, ERG detection of the retinal function did not find a significant decline, and the morphological structure and quantity of the neural retina and RPE did not change significantly. Crystalline deposits occurred and converged when the Cyp4v3(-/-) mice at the end of 6 months, and the deposits disappeared when the Cyp4v3(-/-) mice at the end of 12 months. The ERG amplitude started to decline when the Cyp4v3(-/-) mice at the end of 6 months and deteriorated at the end of 12 months. The RPE cells of the 12-month old Cyp4v3(-/-) mice showed irregular shape by phalloidin staining of F-actin. The Cyp4v3(-/-) mice behaved normally and were viable and fertile when maintained under specific pathogen-free (SPF) housing conditions. CONCLUSION: Just like BCD patients, the disease progress of Cyp4v3(-/-) mouse is correlated with the age, which provides a good model for pathogenesis and gene therapy study in the future. The atrophy and degeneration of RPE take the lead in progressing of the disease, but the mechanism is not clear yet.

儿童中枢神经系统神经免疫疾病是一组复杂的、病理生理学机制和临床表现具有明显异质性的疾病，包括脱髓鞘、炎症性、围感染性和感染后免疫调节紊乱疾病。近年来，随着对这些疾病的分子机制和检测技术的不断深入研究，针对这些免疫功能障碍关键分子的分子诊断和生物治疗技术得到迅速发展，这些疾病的预后有了很大改善。因此儿科医生需要及时掌握和应用这些新进展，提高诊断及治疗水平。.

Three patients diagnosed with focal cortical dysplasia (FCD) in the First Hospital of Peking University from September to November 2020 were recruited in the study. Based on stereotactic electroencephalogram (SEEG) or electrocorticogram (ECoG) analysis to localize the seizure onset zone (SOZ), RNA sequencing (RNA-seq) analysis was performed for the SOZ and para-SOZ tissue obtained from surgery. The differentially expressed genes between SOZ and para-SOZ samples were analyzed by performing Go (Gene ontology) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis."Extracellular matrix"was significantly enriched, which included collagen synthesis genes (e.g., COL1A1)."Ether lipid metabolism"was enriched in the KEGG pathway enrichment analysis. These differences could be the potential biological markers for SOZ localization.本研究纳入2020年9—11月就诊于北京大学第一医院的脑局灶性皮质发育不良（FCD）患者共3例，利用立体定向脑电图（SEEG）或皮质脑电图（ECoG）确定致痫灶，留取患者手术标本中致痫灶及灶旁对照组织，进行RNA-seq测序，对差异表达基因进行Go分析及KEGG信号通路富集分析。差异表达基因中，编码细胞外基质，特别是胶原成分相关的基因如COL1A1等存在显著差异表达；KEGG分析提示差异表达基因主要富集于醚酯代谢相关信号通路。FCD患者中致痫灶和自身对照组织相比，细胞外基质合成（特别是胶原成分）及醚酯代谢等生物过程存在差异，可以作为潜在的致痫灶生物标记物。.

Objective: To study the optimal cut-off value of thyroglobulin measurement in a fine-needle aspiration (FNA-Tg) in diagnosing malignant lymph nodes and benign lymph nodes (LNs) according to the thyroid tissue status.Methods: A total of 517 LNs were aspirated: 401 preoperative LNs, 42 LNs after subtotal thyroidectomy and 74 suspected LNs after total thyroidectomy. The cut-off value of FNA-Tg was obtained from receiver operating characteristic (ROC) analysis. The cut-off value with the best diagnostic performance was then obtained by comparing different cut-off values from other studies.Results: LN FNA-Tg levels differed between preoperative and total thyroid disease (p < 0.001) and subtotal thyroidectomy and total thyroidectomy (p = 0.03), but not between preoperative and subtotal thyroidectomy (p = 1.00). Accordingly, those 443 LNs with preoperative and subtotal thyroidectomy were compared to those 74 without thyroid tissue. The optimal cut-off value in thyroid tissue group was 19.4 ng/ml and the area under the ROC curve (AUC) was 0.95 (95% CI 0.92–0.97). The optimal cut-off value in thyroid tissue absence group was 1.2 ng/ml and the AUC was 0.93 (0.85–0.98). After the analysis and comparison of multiple cut-off values, the optimal diagnostic performance was still found to be 19.4 ng/ml and 1.2 ng/ml.Conclusion: The influential factors of FNA-Tg are still controversial, and the optimal cut-off value of FNA-Tg can be determined based on the presence or absence of thyroid tissue. FNA-Tg can be used as an important auxiliary method for diagnosing cervical metastatic LNs of thyroid cancer.

Based on Yichang health big data platform, 850 608 patients from September 2018 to September 2019 were included in this study. According to the date of birth, the participants were divided into early childhood famine exposure group, fetal famine exposure group and non-famine exposure group. The incidence of adult herpes zoster (HZ) in Yichang city was analyzed, and the correlation between early life famine exposure and adult HZ was analyzed. In 2019, the crude incidence rate of adult HZ in Yichang was 6.83‰. The crude incidence rate of adult HZ in females (7.26‰) was higher than that in males (6.40‰). Compared with the non-famine exposure group, fetal famine exposure was associated with the incidence of adult HZ (基于宜昌健康大数据平台，纳入2018年9月至2019年9月期间的850 608例就诊患者为研究对象，根据出生日期将研究对象分为儿童早期饥荒暴露组、胎儿期饥荒暴露组和非饥荒暴露组，分析宜昌市成人带状疱疹（HZ）发病情况并分析生命早期饥荒暴露与成年HZ的相关性。2019年宜昌市城区成年HZ粗发病率6.83‰，女性（7.26‰）高于男性（6.40‰）。与非饥荒暴露组相比，胎儿期饥荒暴露与成年HZ发病相关（

转甲状腺素蛋白心脏淀粉样变（ATTR-CA）是由转甲状腺素蛋白发生异常解离并聚集在心肌间质所导致，其中野生型（ATTRwt）为无TTR基因突变者。由于该病临床表现缺乏特异性，易被漏诊、误诊。该文报道了1例初诊为肥厚型心肌病最终确诊为ATTRwt患者的诊治过程。.

ObjectivesThe Australian Government funded a nationwide diabetic retinopathy screening programme to improve visual outcomes for people with diabetes. This study examined the benefits and barriers of the programme, image interpretation pathways and assessed the characteristics of people who had their fundus photos graded by a telereading service which was available as a part of the programme.DesignMultimethod: survey and retrospective review of referral forms.SettingTwenty-two primary healthcare facilities from urban, regional, rural and remote areas of Australia, and one telereading service operated by a referral-only eye clinic in metropolitan Sydney, Australia.ParticipantsTwenty-seven primary healthcare workers out of 110 contacted completed a survey, and 145 patient referrals were reviewed.ResultsManifest qualitative content analysis showed that primary healthcare workers reported that the benefits of the screening programme included improved patient outcomes and increased awareness and knowledge of diabetic retinopathy. Barriers related to staffing issues and limited referral pathways. Image grading was performed by a variety of primary healthcare workers, with one responder indicating the utilisation of a diabetic retinopathy reading service. Of the people with fundus photos graded by the reading service, 26.2% were reported to have diabetes. Overall, 12.3% of eyes were diagnosed with diabetic retinopathy. Photo quality was rated as excellent in 46.2% of photos. Referral to an optometrist for diabetic retinopathy was recommended in 4.1% of cases, and to an ophthalmologist in 6.9% of cases.ConclusionsThis nationwide diabetic retinopathy screening programme was perceived to increase access to diabetic retinopathy screening in regional, rural and remote areas of Australia. The telereading service has diagnosed diabetic retinopathy and other ocular pathologies in images it has received. Key barriers, such as access to ophthalmologists and optometrists, must be overcome to improve visual outcomes.

Currently, the removal of iodized salt is carried out in high water iodine regions. The present situation of iodine nutrition and the prevalence of thyroid diseases in such regions have not been clearly elucidated. This study aimed to figure out these problems to help render effective measures for cases of abnormal iodine nutrition status. A cross-sectional study was carried out in four areas of Jining and Heze, Shandong Province, China, with different water iodine concentrations (WIC). In total, 1344 adults were enrolled in this study, and data related to their iodine nutrition, thyroid function, and thyroid ultrasonography were collected. Subjects were grouped according to WIC, urine iodine concentration (UIC), serum iodine concentration (SIC), and combined UIC and SIC for analysis. Iodine levels were in excess in the 100 μg/L ≤ WIC300 μg/L and WIC ≥ 300 μg/L areas. Compared with the control WIC group (10-100 μg/L), the WIC ≥ 300 μg/L group had a higher prevalence of thyroid autoimmunity (TAI, 21.25% vs. 13.19%, P 0.05), subclinical hypothyroidism (SH, 20.20% vs. 11.96%, P0.05), thyroid nodules (TN, 31.75% vs. 18.71%, P0.05), and thyroid dysfunction (23.62% vs. 12.26%, P0.05). Compared with the UIC control group (100-300 μg/L), high UIC group (≥ 800 μg/L) had a higher prevalence of TN (33.75% vs. 21.14%, P0.05) and thyroid dysfunction (25% vs. 14.47%, P0.05). Next, compared with the control SIC group (50-110 μg/L), high SIC group (≥ 110 μg/L) had a higher prevalence of TAI (33.80% vs. 14.47%, P0.05), SH (23.94% vs. 14.30%, P0.05), and thyroid dysfunction (33.80% vs. 15.29%, P0.05). Finally, subjects with the highest UIC and the highest SIC also had a higher prevalence of TAI (25.92% vs. 10.97%, P0.05), SH (23.45% vs. 10.97%, P0.05), TN (34.56% vs. 15.85%, P0.05), and thyroid dysfunction (27.16% vs. 13.41%, P0.05) than subjects with middle iodine levels. The iodine nutrition of subjects in the WIC ≥ 300 μg/L areas was still in excess after removing iodized salt from their diets. High levels of iodine also increased the prevalence of TAI, SH, TN, and thyroid dysfunction in those areas. Simply removing iodized salt may not be sufficient for high water iodine regions.