Background::In the clinic, practitioners encounter many patients with an abnormal pattern of dense punctate magnetic resonance imaging (MRI) signal in the basal ganglia, a phenomenon known as "cheese sign". This sign is reported as common in cerebrovascular diseases, dementia, and old age. Recently, cheese sign has been speculated to consist of dense perivascular space (PVS). This study aimed to assess the lesion types of cheese sign and analyze the correlation between this sign and vascular disease risk factors.Methods::A total of 812 patients from Peking Union Medical College Hospital (PUMCH) dementia cohort were enrolled. We analyzed the relationship between cheese sign and vascular risk. For assessing cheese sign and defining its degree, the abnormal punctate signals were classified into basal ganglia hyperintensity (BGH), PVS, lacunae/infarctions and microbleeds, and counted separately. Each type of lesion was rated on a four-level scale, and then the sum was calculated; this total was defined as the cheese sign score. Fazekas and Age-Related White Matter Changes (ARWMC) scores were used to evaluate the paraventricular, deep, and subcortical gray/white matter hyperintensities.Results::A total of 118 patients (14.5%) in this dementia cohort were found to have cheese sign. Age (odds ratio [OR]: 1.090, 95% confidence interval [CI]: 1.064-1.120, P <0.001), hypertension (OR: 1.828, 95% CI: 1.123-2.983, P = 0.014), and stroke (OR: 1.901, 95% CI: 1.092-3.259, P = 0.025) were risk factors for cheese sign. There was no significant relationship between diabetes, hyperlipidemia, and cheese sign. The main components of cheese sign were BGH, PVS, and lacunae/infarction. The proportion of PVS increased with cheese sign severity. Conclusions::The risk factors for cheese sign were hypertension, age, and stroke. Cheese sign consists of BGH, PVS, and lacunae/infarction.

Objective:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.

The ApoE gene is a genetic risk determinant for sporadic Alzheimer′s disease (AD). The ApoEε4 allele increases the risk of developing AD relative to the common ApoEε3 allele, whereas the ApoEε2 allele decreases the risk of developing the disease. The 3 alleles encode ApoE2, ApoE3, and ApoE4 protein isoforms, respectively. ApoE4 contributes to the pathogenesis of AD by regulating β-amyloid protein, tau protein, transactive response DNA-binding protein-43, neuroinflammation, and cerebral vascular function. The pathways associated with ApoE also offer new opportunities for the treatment of AD. In addition, studies have shown that ApoE4 also plays a toxic role in other neurological disorders. This article described the biological characteristics of ApoE, as well as the impact of ApoE4 on AD and related dementias, aiming to enhance clinical doctors′ understanding of the involvement of ApoE4 in the pathogenesis of AD and related dementia.

Nanobodies (Nbs), the unique single-domain antibodies discovered in the species of Camelidae and sharks, are also known as the variable domain of the heavy chain of heavy-chain antibody (VHH). They offer strong antigen targeting and binding capabilities and overcome the drawbacks such as large size, low stability, high immunogenicity, and slow clearance of conventional antibodies. Nbs can be boosted by bioconjugation with toxins, enzymes, radioactive nucleotides, fluorophores, and other functional groups, demonstrating potential applications in the diagnosis and treatment of human and animal diseases. This article introduces the structures and characteristics of Nbs, the construction and screening of Nb libraries, and the strategies for affinity maturation and then reviews the current applications of Nbs in diagnosis and treatment, providing a reference for the development of diagnostic reagents and clinical therapies for infectious diseases.
Single-Domain Antibodies/chemistry* ; Animals ; Humans ; Camelidae/immunology*

Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers. However, the lack of druggable inhibitors restricts its therapeutic proof of concept. In the present work, we optimized a natural importin-β1 inhibitor DD1 to afford an improved analog DD1-Br with better tolerability (>25 folds) and oral bioavailability. DD1-Br inhibited the survival of castration-resistant prostate cancer (CRPC) cells with sub-nanomolar potency and completely prevented tumor growth in resistant CRPC models both in monotherapy (0.5 mg/kg) and in enzalutamide-combination therapy. Mechanistic study revealed that by targeting importin-β1, DD1-Br markedly inhibited the nuclear accumulation of multiple CRPC drivers, particularly AR-V7, a main contributor to enzalutamide resistance, leading to the integral suppression of downstream oncogenic signaling. This study provides a promising lead for CRPC and demonstrates the potential of overcoming drug resistance in advanced CRPC via targeting importin-β1.

A pedigree with familial acanthosis nigricans presenting with atypical clinical symptoms was reported. The 4-year-old female proband began to develop black patches on the neck and abdomen since the age of 1 year, which had gradually spread to the lips and front of the trunk in recent years. Reflectance confocal microscopy of the abdominal skin showed downward extension and twisting of dermal papillary rings with formation of gully-like structures, and moderately to highly refractive particles in the dermal papillary rings. The proband′s father and grandmother had similar medical history, but the pigmentation spontaneously subsided with age, leaving only local thickened skin lines. Peripheral blood samples were collected from the proband, her parents and grandmother, and panel-based targeted sequencing of peripheral blood DNA was performed for the proband. Sequencing showed a missense mutation c.1949A>C (p.Lys650Thr) in exon 14 of the FGFR3 gene in the proband, and Sanger sequencing confirmed the presence of this mutation in the proband and her father and grandmother. A diagnosis of familial acanthosis nigricans was made.

In order to train professionals in medical laboratory technology who are directly engaged in medical examination and medical laboratory work and who have strong practical ability and can adapt to the development of precision medicine, the reform of precise teaching for experiment is implemented. Through the precise stratification of experimental projects and knowledge points, the design of precise teaching activity and the construction of precise evaluation system for experiments, guided by precision medicine during the experimental process, the standardization and precision training of basic skills for students are strengthened in clinical laboratory test. The students can more well adapt to the needs of society for technical and innovative talent in the new period. The precise teaching for experiment will become one of the main characteristics of medical laboratory technology education in our school.

Objective:To investigate the current status and trend of disease burden of neoplasms in 1990 and 2016 for Beijing people.Methods:The incidence situation, deaths status and disease burden of neoplasms in Beijing were described by using the results of the global burden of diseases study 2016 (GBD 2016). The measurement index included incidence, death, years of life lost due to premature mortality (YLL), years lived with disability (YLD), and disability-adjusted years (DALY). Using the average world population from 2000 to 2025 as standard population to calculate the age-standardized incidence rate, mortality rate, DALY rate, YLL rate and YLD rate.Results:The age-standardized incidence rate of neoplasms in 2016 was 250.68 per 100 000, which increased by 30.03% than in 1990. The age-standardized mortality rate was 115.83 per 100 000, which decreased by 26.71% than in 1990. The DALY, YLL and YLD of neoplasms in 2016 were 671.2, 651.1 and 20.1 thousand person-years, respectively, which increased by 85.83%, 82.79% and 302.00% than those in 1990. The age-standardized DALY rate and YLL rate were 2 549.00 and 2 469.84 per 100 000, which decreased by 33.22% and 34.30% than those in 1990. The age-standardized YLD rate was 79.16 per 100 000, which increased by 37.17% than that in 1990. The male DALY, YLL and YLD in 2016 were 428.8, 417.8 and 11.0 thousand person-years, and female were 242.4, 233.3 and 9.1 thousand person-years, respectively.Among different neoplasms, the top three neoplasms of DALY and YLL were lung cancer, liver cancer, colon and rectum cancer, the top three of YLD were lung cancer, colon and rectum cancer, breast cancer. The topped group of disease burden of neoplasms was aged from 50 to 69 years old, the DALY of which was 323.6 thousand person-years, accounted for 48.21% of all DALY, and increased by 87.70% than that in 1990.Conclusions:The disease burden of neoplasms in Beijing is dominated by YLL, and the YLD increases rapidly. The burden is severe in the group of aged from 50 to 69 years old, and the male is severer than female. Lung cancer ranks the first of the disease burden of neoplasms. The DALY of colorectal cancer has increased. Comprehensive strategies should be promoted, including cultivating a good lifestyle and implementing prevention and control of neoplasm risk factors as early as teenage group, early screening of high-risk population, and enhancing the instruction of patients′ treatment and rehabilitation.