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Abstract Human embryonic stem cells and human induced pluripotent stem cells may be used to create 3D tissues called brain organoids. They duplicate the physiological and pathological characteristics of human brain tissue more faithfully in terms of both structure and function, and they more precisely resemble the morphology and cellular structure of the human embryonic brain. This makes them valuable models for both drug screening and in vitro studies on the development of the human brain and associated disorders. The technical breakthroughs enabled by brain organoids have a significant impact on the research of different brain regions, brain development and sickness, the connections between the brain and other tissues and organs, and brain evolution. This article discusses the development of brain organoids, their use in diabetes research, and their progress.

Abstract Background The prevalence of anxiety and depression symptoms among caretakers of children with atopic dermatitis (AD) and associated factors is unclear. The study was designed to explore anxiety and depression symptoms among caretakers of AD, and screen factors associated with anxiety and depression symptoms. Methods A total of 901 children with AD and their caretakers were continuously enrolled and interviewed at dermatology department of Capital Institute of Pediatrics, Beijing, China. Children’s medication was administered by their caretakers. Caretakers’ anxiety and depression symptoms were evaluated by Hamilton Depression Rating Scale-17 and Hamilton Depression Rating Scale, while medication compliance was evaluated and divided into poor ( 7 points) by Morisky Medication Adherence Scale. Multilevel ordered logistic regression was used to screen factors associated with caretakers’ anxiety and depression. Results Among caretakers, 41.5% had anxiety symptoms, 39.6% had depression symptoms, 51.4% have any of the two and 29.7% had both of the two. Factors associated with caretakers’ anxiety symptoms included longer duration of the illness (OR, 0.99, 95% CI 0.98–0.99) and taking care of children with severe AD (OR, 2.55, 95% CI 1.43–4.55). Factors associated with caretakers’ depression symptoms included higher educational level (OR, 0.56, 95% CI 0.39–0.80), taking care of children with moderate (OR, 2.01, 95% CI 1.15–3.50) and severe AD (OR, 3.99, 95% CI 2.10–7.59) and poor medication compliance (OR, 3.45, 95% CI 1.13–10.56). Conclusions Prevalence of anxiety and depression symptoms among caretakers of AD were high. Attention should be paid to caretakers of AD at higher risk for those psychological problems.

Abstract Background Recurrent tuberculosis (TB) contributes to the burden of TB. The study was designed to explore the time of diagnostic delay and risk of delay in patients with recurrent TB in China. Methods A total of 13,334 patients with new and recurrent TB registered in Yulin a city in China were included. The Kaplan-Meier survival curve was employed to estimate the median delay time. The mixed-effects survival model was used to identify the correlates associated with diagnostic delay. The outcome of interest in the model was"being diagnosed". Results We found that 6.5% of cases with TB were attributed to recurrence. The median delay time of recurrent TB cases (73 days) was more than twice as long as that of new TB (35 days). Individuals with recurrent TB had a higher risk of diagnostic delay than new TB (HR, 0.5, 95%CI, 0.5–0.6). Factors associated with diagnostic delay differed between new TB and recurrent TB cases. Immigrants (HR, 0.5, 95%CI, 0.3–0.9), cases notified by way of recommendation (HR, 0.6, 95%CI, 0.4–0.9) and diagnosed at TB dispensary (HR, 0.4, 95%CI, 0.3–0.6) were associated with a higher risk of a longer delay for recurrent TB cases. Conclusions The proportion of TB cases attributed to recurrence was high. Patients with recurrent TB had a longer delay time and a higher risk of diagnostic delay. Further interventions to improve diagnostic delay should focus on screening for TB in immigrants, improving public health services at the lowest healthcare level and update of TB diagnosis and management model.

Abstract Background The relationship between frailty and dementia is unclear and there are very few population-based studies regarding this issue in China. The purpose of this study is to estimate the association between frailty and incident dementia in China, and to explore different effects of frailty established by three definitions of frailty on dementia incidence. Methods A five-year prospective cohort study was carried out in 2022 participants aged 65 years and over in urban and rural sites in Beijing, China. The participants were interviewed by trained community primary health care workers from 2004 to 2009. Frailty was defined using modified Fried frailty phenotype, physical frailty definition, and multidimensional frailty definition. Dementia was diagnosed using the 10/66 dementia criterion for calculating cumulative incidence. Both competing risk regression models and Cox proportional hazards models were applied to examine the associations between frailty at baseline and five-year cumulative incidence of dementia. Results At the end of follow-up the five-year cumulative incidence rates of dementia with frailty and without frailty defined by the modified Fried frailty were 21.0% and 9.6%, those defined by the physical frailty were 19.9% and 9.0%, and those defined by the multidimensional frailty were 22.8% and 8.9%, respectively. Compared with non-frail participants, frail people had a higher risk of incident dementia using multidimensional frailty definition after adjusting covariates based on competing risk regression model (HR = 1.47, 95% CI 1.01~2.17) and Cox proportional hazards model (HR = 1.56, 95% CI 1.07~2.26). The association between frailty and incident dementia was statistically significant in participants in the upper three quartiles of age (aged 68 years and over) using the multidimensional frailty definition based on the competing risk regression model (HR = 1.61, 95% CI 1.06~2.43) and Cox proportional hazard model (HR = 1.76, 95% CI 1.19~2.61). Conclusions Multidimensional frailty may play an inherent role in incident dementia, especially in the people aged over 68, which is significant for distinguishing high risk people and determining secondary prevention strategies for dementia patients.

Abstract Background With great changes over the past 10 years in China, especially the rapid economic development, population mobility, urbanization and aging, dynamic change on risk of delay, to our knowledge, has not been well studied in China. The study was to explore risk of delay in diagnosis of new pulmonary tuberculosis (PTB) and dynamic changes in risk of delay in Northwest China. Methods From January 1, 2008 to December 31, 2017, a total of 13,603 people with new PTB registered in Yulin city of Shaanxi province were included. The median delay time was estimated by Kaplan-Meier survival curve. Time delay curves of year-, gender-year-, age-year- and smear-year specific were examined using log-rank test. Two-level mixed-effects survival model was used to calculate the hazard ratio (HR) and 95% confidence interval (95%CI) for factors associated with diagnostic delay. Time delay was defined as time interval between the onset of PTB symptoms and being diagnosed. The outcome variable of interest was defined as “being diagnosed” in survival analysis. Results The 10-year delay time was 33 days (Interquartile Range, 16–65). Annual median delay time gradually decreased from 60 days to 33 days during the past 10 years. The probability that individuals were diagnosed since onset of PTB symptoms increased by 1.29 times in 2017 when compared to 2008. Female (Hazard Ratio (HR), 95%CI, 0.95(0.91–0.99)), age>45 years (HR, 95%CI, 0.87(0.82–0.93)) and smear positive (HR, 95%CI, 0.86(0.78–0.95)) were associated with increased risk of diagnostic delay over 10-year timespan. However, Age>45 years and smear positive showed trend to be protective factors in the past 5 years. Conclusions Time and risk of delay in diagnosis of new PTB had declined over the past 10 years. However, more attentions should be paid to the fact that female still suffered from higher risk of diagnostic delay. We noted a potential reversal in traditional risk factors such as age>45 and smear positive. Those dynamic changes deserved further attention.

Abstract Background Blood transcriptomics can be used for confirmation of tuberculosis diagnosis or sputumless triage, and a comparison of their practical diagnostic accuracy is needed to assess their usefulness. In this study, we investigated potential biomarkers to improve our understanding of the pathogenesis of active pulmonary tuberculosis (PTB) using bioinformatics methods. Methods Differentially expressed genes (DEGs) were analyzed between PTB and healthy controls (HCs) based on two microarray datasets. Pathways and functional annotation of DEGs were identified and ten hub genes were selected. They were further analyzed and selected, then verified with an independent sample set. Finally, their diagnostic power was further evaluated between PTB and HCs or other diseases. Results 62 DEGs mostly related to type I IFN pathway, IFN-γ-mediated pathway, etc. in GO term and immune process, and especially RIG-I-like receptor pathway were acquired. Among them, OAS1, IFIT1 and IFIT3 were upregulated and were the main risk factors for predicting PTB, with adjusted risk ratios of 1.36, 3.10, and 1.32, respectively. These results further verified that peripheral blood mRNA expression levels of OAS1, IFIT1 and IFIT3 were significantly higher in PTB patients than HCs (all P