Geographical disparities in infant mortality in the rural areas of China: a descriptive study, 2010-2018.

BACKGROUND: The infant mortality rate (IMR) is considered a basic measure of public health for countries around the world. The specific aim of our study was to provide an updated description of infant mortality rate among different regions in rural China, and assess the trends and causes of the IMR geographical disparities. METHODS: Data were collected from China's Under-5 Child Mortality Surveillance System(U5CMSS). The annual number of deaths and causes of death were adjusted using a 3-year moving average underreporting rate based on annual national data quality control results. The average annual decline rate (AADR) and the relative risk (RR) of the IMR and cause-specific infant mortality were calculated by Poisson regression and the Cochran-Mantel-Haenszel method. Data analysis was completed by SAS software. RESULTS: There was an apparent decrease in infant mortality in rural China from 2010 to 2018, at the AADR of 11.0% (95%CI 9.6-12.4), 11.2% (95%CI 10.3-12.1) and 6.6% (95%CI 6.0-7.3) in the eastern, central and western rural areas, respectively. The IMR was highest in the western rural area, followed by the central and eastern rural areas. Compared with the eastern rural area, the RR of infant mortality in the central rural area remained at 1.4-1.6 and increased from 2.4 (95%CI 2.3-2.6) in 2010-2012 to 3.1 (95% CI 2.9-3.4) in 2016-2018 in the western rural area. Pneumonia, preterm birth /LBW and birth asphyxia were the leading causes of infant deaths in the western rural area. Mortality rates of these three causes fell significantly in 2010-2018 but contributed to a higher proportion of deaths in the western rural area than in the central and western rural ares. CONCLUSIONS: Our study indicated that the infant mortality rate dropped significantly from 2010 to 2018, however, geographical disparities of IMR in rural China are still persist. Therefore, there is an urgent need for public health programmes and policy interventions for infants in western rural China.

Atypically larger variability of resource allocation accounts for visual working memory deficits in schizophrenia.

Working memory (WM) deficits have been widely documented in schizophrenia (SZ), and almost all existing studies attributed the deficits to decreased capacity as compared to healthy control (HC) subjects. Recent developments in WM research suggest that other components, such as precision, also mediate behavioral performance. It remains unclear how different WM components jointly contribute to deficits in schizophrenia. We measured the performance of 60 SZ (31 females) and 61 HC (29 females) in a classical delay-estimation visual working memory (VWM) task and evaluated several influential computational models proposed in basic science of VWM to disentangle the effect of various memory components. We show that the model assuming variable precision (VP) across items and trials is the best model to explain the performance of both groups. According to the VP model, SZ exhibited abnormally larger variability of allocating memory resources rather than resources or capacity per se. Finally, individual differences in the resource allocation variability predicted variation of symptom severity in SZ, highlighting its functional relevance to schizophrenic pathology. This finding was further verified using distinct visual features and subject cohorts. These results provide an alternative view instead of the widely accepted decreased-capacity theory and highlight the key role of elevated resource allocation variability in generating atypical VWM behavior in schizophrenia. Our findings also shed new light on the utility of Bayesian observer models to characterize mechanisms of mental deficits in clinical neuroscience.

Analysis of influencing factors of visual working memory in young adult patients with schizophrenia.

BACKGROUND: Patients with schizophrenia have general cognitive impairments, and the impairment of working memory is considered to be the basis of cognitive impairments. The research on visual working memory, one of the subcomponents, is getting more and more attention. However, the influencing factors which cause the deficits of visual working memory in patients with schizophrenia have not been clearly explained. To provide evidence for cognitive impairment interventions, the present study explored the factors influencing the deficits of patients' visual working memory. AIM: The present study discussed the relevant factors influencing the visual working memory of patients with schizophrenia by measuring the accuracy of the visual working memory of patients with schizophrenia and healthy controls. METHODS: Colour-recall paradigm was employed to measure the accuracy of the visual working memory of 61 healthy controls and 61 patients who met the International Classification of Diseases, Tenth Revision diagnostic criteria for schizophrenia. The age range of subjects was 18-50. Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the Assessment of Negative Symptoms (SANS) were used to evaluate the patients' clinical symptoms. RESULTS: Compared with the healthy control group, the accuracy of visual working memory of patients with schizophrenia was significantly impaired (t=3.062, p=0.003). The accuracy of visual working memory of patients with schizophrenia was not related to age (r=0.023, p=0.860), the age of onset (r=-0.003, p=0.979), the duration of illness (r=-0.038, p=0.769), education level (r=-0.181, p=0.162), continuous working time before illness (r=-0.107, p=0.413) or the daily dose of antipsychotic drugs (r=0.062, p=0.635); however, it was positively related to the number of hospitalisations (r=0.471, p<0.001). The total score of Scale for the Assessment of Positive Symptoms (SAPS) was negatively related to the accuracy of visual working memory (r=-0.388, p=0.005), while the total score of Scale for the Assessment of Negative Symptoms (SANS) (r=0.416, p=0.001), the total score of diminished emotional expressiveness (r=0.352, p=0.005) and the total score of attention disorder (r=0.310, p=0.015) were positively related to the accuracy of visual working memory. Patients using a single drug and those using multiple drugs were compared with each other. They were not significantly different in age (t=0.010, p=0.992), the number of hospitalisations (t=0.656, p=0.514), the duration of illness (t=0.701, p=0.486), the total score of SANS (t=0.078, p=0.938), the total score of SAPS (t=1.815, p=0.079) and the daily dose of antipsychotic drugs (t=1.794, p=0.078). However, in order to explore whether single or combined drug use would affect the accuracy of visual working memory of patients with schizophrenia, the present study also compared these two groups' different S0 values of the accuracy of visual working memory. The results showed that the accuracy of visual working memory of patients with schizophrenia with combined drug use was significantly better than that of patients with single drug use (t=2.515, p=0.015, independent sample t-test). CONCLUSION: The present study indicates that the visual working memory of young adult patients with schizophrenia is impaired compared with the healthy people within the same age range. The impairment is more obvious in patients who have multiple hospitalisations and suffer from severe negative symptoms. The impairment in patients with more severe positive symptoms is not very obvious. Combined drug use is likely to alleviate the impairment.

Rosiglitazone, a peroxisome proliferator-activated receptor-γ agonist, attenuates airway inflammation by inhibiting the proliferation of effector T cells in a murine model of neutrophilic asthma.

An imbalanced Th17-mediated immune response contributes substantially to neutrophilic asthma. Studies have also demonstrated that peroxisome proliferator-activated receptor-γ (PPARγ) plays a critical role in inflammatory disease. However, the effect of PPARγ on airway inflammation in neutrophilic asthma remains unclear. In the current study, we evaluated the potential therapeutic role of rosiglitazone (RSG) in a new mouse model of asthma characterised by increased neutrophils rather than eosinophils. A co-culture system of DCs with CD4+ naïve T cells was established to evaluate the effects of RSG on T cell differentiation. After challenge with OVA, mice developed the typical pathophysiological features of asthma, including an increased number of neutrophils in the BALF and the up-regulation of IL-17. The numbers of Th17 cells and Th2 cells were also greatly elevated in the lungs. The administration of rosiglitazone reduced the pathophysiological features of asthma and decreased the up-regulated inflammatory mediators and cytokines. Furthermore, the cell viability in the co-culture system was markedly reduced by RSG. T-bet, Gata-3 and RORγt mRNA were down-regulated by RSG. These findings suggest that PPARγ is critical for airway inflammation during neutrophilic asthma, possibly due to its effect on Th cell proliferation and differentiation. These findings suggest that the therapeutic effect of rosiglitazone in neutrophilic asthma is partially due to the role of the PPARγ pathway in regulating T cell proliferation and differentiation.

Increased expression of herpesvirus entry mediator in 1,25-dihydroxyvitamin D3-treated mouse bone marrow-derived dendritic cells promotes the generation of CD4⁺CD25⁺Foxp3⁺ regulatory T cells.

Dendritic cells (DCs) can initiate immune responses or induce immune tolerance. 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] is a secosteroid hormone that can induce tolerogenic dendritic cells favoring the induction of regulatory T cells (Treg). The present study revealed a tolerogenic effect of 1,25(OH)2D3 on the phenotype and function of ovalbumin (OVA)­activated mouse bone marrow­derived DCs. Three inhibitory molecules associated with tolerogenic DCs, programmed death­ligand-1 (PD­L1), PD­L2 and herpesvirus entry mediator (HVEM) and the expression of co­stimulatory molecules (CD80, CD86 and CD40) on 1,25(OH)2D3­treated DCs were examined. The levels of interleukin (IL)­2, IL­6 and IL­10 secreted by 1,25(OH)2D3­treated DCs were analyzed. The capability of 1,25(OH)2D3­treated DCs to induce CD4+CD25+Foxp3+ Treg and the stimulation of allogeneic CD4+ T­cell proliferation in mixed lymphocyte reaction (MLR) was studied. 1,25(OH)2D3­treated DCs induced up to 21.0­fold upregulation of the HVEM expression and 4.1­fold enhancement of the HVEM expression upon activation with OVA [OVA­D3/immature (im)DCs]. PD­L1 was not affected by 1,25(OH)2D3­treated DCs and downregulated PD­L2 expression on 1,25(OH)2D3­treated DCs and OVA­D3/imDC. The expression of co­stimulatory molecules (CD80, CD86 and CD40) was downregulated in 1,25(OH)2D3­treated DCs and OVA­D3/imDC. Furthermore, 1,25(OH)2D3­treated DCs secreted much higher levels of IL­10, however lower levels of IL­2 and IL­6 compared with the activated control DCs. Together with this pattern of cytokines, 1,25(OH)2D3­treated DCs exhibited low allogeneic CD4+ T­cell stimulatory activity and a higher number of CD4+CD25+Foxp3+ cells in the MLR cultures but not in the activated control DCs. These findings indicate that 1,25(OH)2D3 possesses the immunosuppressive properties by upregulating the expression of the inhibitory molecules, HVEM, which may be therapeutically useful in controlling chronic immune and/or inflammatory diseases.

A role for WNT1-inducible signaling protein-1 in airway remodeling in a rat asthma model.

Over-expression of WISP1 has been described in multi-organ fibrosis and tissue remodeling. Moreover, it has recently been found that polymorphism of WISP1 gene is related with the change of lung function in asthmatic subjects. Therefore, we hypothesized that WISP1 might be closely linked to occurrence and development of asthmatic airway remodeling. Aim of this study was to examine the roles of WISP1 in an asthmatic model with airway remodeling and assess the specific effects of WISP1 on human lung fibroblast in vitro. Animal models were developed by challenged with ovalbumin. The levels of WISP1 expression in animal models were assessed by real-time PCR and immunohistochemistry. To examine the specific effects of WISP1 on airway remodeling, WISP1 was depleted by neutralizing α-WISP1 antibodies in vivo. Moreover, human lung fibroblast (HFL-1) was challenged with WISP1 in the presence and absence of SH-5 in vitro. Our study showed that OVA exposure increased the levels of WISP1 expression in a rat asthma model. WISP1 depletion could partially inhibit OVA-induced airway remodeling. In vitro, WISP1-treated HFL-1 cells presented abnormal proliferation and over-expression of Col1a1 and Fn1. However, WISP1-induced collagen release from HFL-1 cells could be attenuated by pretreatment with an Akt inhibitor. Moreover, the levels of p-Akt and p-GSK-3ß in WISP1-treated HFL-1 cells were also significantly elevated. In summary, WISP1 might initiate and perpetuate the pathological remodeling of asthma by inducing fibroblast proliferation and ECM deposition. The specific effects of WISP1 were likely due to activation of pulmonary Akt/GSK-3ß signaling.