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Background Gut dysbacteriosis has been reported as one of the etiologies for irritable bowel syndrome (IBS). However, the association between gut microbiota and IBS is still inconclusive. Method A paired-sample study was designed by retrieving original multicenter 16 s-rRNA data of IBS patients and healthy controls from the GMrepo database. The propensity score matching (PSM) algorithm was applied to reduce confounding bias. The differential analysis of microbiota composition was performed at different taxonomic levels. The co-occurrence network was established. Subgroup analysis was performed to identify specific microbial compositions in different IBS subtypes. Results A total of 1522 amplicon samples were initially enrolled. After PSM, 708 individuals (354 IBS and 354 healthy controls) were eligible for further analysis. A total of 1,160 genera were identified. We identified significantly changed taxa in IBS groups (IBS-enriched: the families Enterobacteriaceae , Moraxellaceae and Sphingobacteriaceae ; the genera Streptococcus , Bacillus , Enterocloster , Sphingobacterium , Holdemania and Acinetobacter . IBS-depleted: the phyla Firmicutes , Euryarchaeota , Cyanobacteria , Acidobacteria and Lentisphaerae ; the families Bifidobacteriaceae , Ruminococcaceae , Methanobacteriaceae and the other 25 families; the genera Faecalibacterium , Bifidobacterium and other 68 genera). The co-occurrence network identified three hub genera and six hub species (including Faecalibacterium prausnitzii ) that may be involved in IBS pathophysiology. Strong positive interactions were identified among the Bifidobacterium longum , Bifidobacterium breve and Bifidobacterium adolescentis in the Bifidobacterium community. Conclusion This study provides quantitative analysis and visualization of the interaction between the gut microbiota and IBS. The identification of key species should be further validated to evaluate their causal relationships with the pathogenesis of IBS.

Alzheimer’s disease (AD) is the first most common neurodegenerative disease. Despite a large amount of research, the pathogenetic mechanism of AD has not yet been clarified. The two hallmarks of the pathology of AD are the extracellular senile plaques (SPs) of aggregated amyloid-beta (Aβ) peptide and the accumulation of the intracellular microtubule-associated protein tau into fibrillar aggregates. Heat shock proteins (HSPs) play a key role in preventing protein misfolding and aggregation, and Hsp90 can be viewed as a ubiquitous molecular chaperone potentially involved in AD pathogenesis. A role of Hsp90 regulates the activity of the transcription factor heat shock factor-1 (HSF-1), the master regulator of the heat shock response. In AD, Hsp90 inhibitors may redirect neuronal aggregate formation, and protect against protein toxicity by activation of HSF-1 and the subsequent induction of heat shock proteins, such as Hsp70. Therefore, we review here to further discuss the recent advances and challenges in targeting Hsp90 for AD therapy.

Chongqing is one of the five provinces in China that has the highest incidence of acute hemorrhagic conjunctivitis (AHC). Data of AHC cases from 2004 to 2018 were obtained from National Notifiable Diseases Reporting Information System (NNDRIS). Descriptive statistical methods were used to analyze the epidemiological characteristics; incidence maps were used to reflect incidence trends in each district; spatial autocorrelation was used to identify hotspot regions and spatiotemporal patterns of AHC outbreaks; spatiotemporal scan were conducted to identify AHC clusters. A total of 30,686 cases were reported with an annual incidence of 7.04 per 100,000. The incidence rates were high in 2007 and 2014, and large epidemics were observed in 2010 with the seasonal peak in September. Individuals aged 10–19 years, males, students and farmers were the prime high-risk groups. Except for 2012 and 2013, the spatial distribution of AHC did not exhibit significant global spatial autocorrelation. Local indicators of spatial association showed that the high-risk regions are Chengkou and Wuxi. The spatiotemporal scan indicated that all clusters occurred in September 2010, and the high-incidence clusters were mainly distributed in the northeast of Chongqing. The results could assist public health agencies to consider effective preventive measures based on epidemiological factors and spatiotemporal clusters in different regions.

Background Hand-foot-and-mouth disease (HFMD) is considered to be self-limited, however, severe HFMD is a deadly threat for children worldwide, therefore, it is essential to define the clinical and epidemiologic characteristics of children with severe HFMD and identify the risk factors of death. Methods Between 2013 and 2018, children who diagnosed with severe HFMD from Chongqing, China were enrolled in this population-based study. A total of 459 severe HFMD children cases were identified during the study period, including 415 survivors and 44 fatal cases. Demographic, geographical, epidemiological and clinical data of the cases were acquired and analyzed. Results Risk factors of the death because of severe HFMD children included female, aged 1 ~ 3 years, enterovirus 71 infection, falling ill in winter, more than one children in home, being taken care of by grandparents, the caregivers’ education not more than 9 years, having fever more than 3 days, consciousness disorders, general weakness, vomiting, general weakness, abnormal pupillary light reflex, repeated cough, tachypnea, moist rales, white frothy sputum, pink frothy sputum, and cyanosis on lips or the whole body, tachycardia, arrhythmia, cold limbs, pale complexion, weakened pulse. (all p  < 0.05). Spatial-temporal analysis detected high-value clusters, the most likely cluster located at rural countries in the northern parts of Chongqing, from January, 2015 to July, 2017. ( p  < 0.01). Besides, some urban districts were also found high incidence of severe HFMD cases according to the incidence maps. Conclusions The detection of clinical risk factors and the temporal, spatial and socio-demographic distribution epidemiological characteristics of severe HFMD contribute to the timely diagnosis and intervention, the results of this study can be the reference of further clinical and public health practice.

Weakly supervised instance segmentation (WSIS) provides a promising way to address instance segmentation in the absence of sufficient labeled data for training. Previous attempts on WSIS usually follow a proposal-based paradigm, critical to which is the proposal scoring strategy. These works mostly rely on certain heuristic strategies for proposal scoring, which largely hampers the sustainable advances concerning WSIS. Towards this end, this paper introduces a novel framework for weakly supervised instance segmentation, called Weakly Supervised R-CNN (WS-RCNN). The basic idea is to deploy a deep network to learn to score proposals, under the special setting of weak supervision. To tackle the key issue of acquiring proposal-level pseudo labels for model training, we propose a so-called Attention-Guided Pseudo Labeling (AGPL) strategy, which leverages the local maximal (peaks) in image-level attention maps and the spatial relationship among peaks and proposals to infer pseudo labels. We also suggest a novel training loss, called Entropic OpenSet Loss, to handle background proposals more effectively so as to further improve the robustness. Comprehensive experiments on two standard benchmarking datasets demonstrate that the proposed WS-RCNN can outperform the state-of-the-art by a large margin, with an improvement of 11.6% on PASCAL VOC 2012 and 10.7% on MS COCO 2014 in terms of mAP50, which indicates that learning-based proposal scoring and the proposed WS-RCNN framework might be a promising way towards WSIS.

Background Mumps is classified as a class C infection disease in China, and the Chongqing area has one of the highest incidence rates in the country. We aimed to establish a prediction model for mumps in Chongqing and analyze its seasonality, which is important for risk analysis and allocation of resources in the health sector. Methods Data on incidence of mumps from January 2004 to December 2018 were obtained from Chongqing Municipal Bureau of Disease Control and Prevention. The incidence of mumps from 2004 to 2017 was fitted using a seasonal autoregressive comprehensive moving average (SARIMA) model. The root mean square error (RMSE) and mean absolute percentage error (MAPE) were used to compare the goodness of fit of the models. The 2018 incidence data were used for validation. Results From 2004 to 2018, a total of 159,181 cases (93,655 males and 65,526 females) of mumps were reported in Chongqing, with significantly more men than women. The age group of 0–19 years old accounted for 92.41% of all reported cases, and students made up the largest proportion (62.83%), followed by scattered children and children in kindergarten. The SARIMA(2, 1, 1) × (0, 1, 1) 12 was the best fit model, RMSE and MAPE were 0.9950 and 39.8396%, respectively. Conclusion Based on the study findings, the incidence of mumps in Chongqing has an obvious seasonal trend, and SARIMA(2, 1, 1) × (0, 1, 1) 12 model can also predict the incidence of mumps well. The SARIMA model of time series analysis is a feasible and simple method for predicting mumps in Chongqing.

Background The induction of labour is an increasingly common procedure in the obstetrics field. Various methods have been used to induce labour, among which balloon catheters play an important role. Whether the specifically designed double-balloon catheter is better than the single-balloon device in terms of efficacy, efficiency, safety and patient satisfaction remains controversial. Identifying even small differences between these two devices could be useful to guide clinical practices, to further explore their mechanisms, and to promote a better understanding of the optimal methods for inducing labour. Methods Using the population, intervention, comparison, outcomes and study designs (PICOS) principle, we searched the PubMed, EMBASE, OVID, SCI, CENTRAL, ClinicalTrial.gov , and CDSR databases to identify relevant randomised controlled trials (RCTs) from inception through February 14, 2018. The primary outcome was the caesarean delivery rate, and the secondary outcomes focused on efficacy, efficiency, safety, and patient satisfaction. The relative risks or mean differences, including their 95% confidence intervals, were calculated using fixed-effects or random-effects models. All statistical analyses were completed with RevMan version 5.3. Results From a total of 1326 articles, 7 RCTs involving 1159 women were included. There were no significant differences in primary outcomes (RR, 0.88 [0.65, 1.2]; p -value, 0.43) or secondary outcomes identified between single- and double-balloon catheters. However, heterogeneity existed for some aspects. Conclusion Both kinds of balloon catheter have similar levels of efficacy, efficiency, safety and patient satisfaction; however, the single-balloon method is considered to be more cost-effective.

Objective To develop and validate a machine learning model for predicting Pneumocystis jirovecii infection in patients with acquired immunodeficiency syndrome (AIDS). Methods Clinical data from 651 AIDS patients, including 93 with P. jirovecii coinfection, were retrospectively collected from our hospital information system. Five machine learning algorithms—logistic regression, decision tree (DT), k‐nearest neighbors (KNN), extreme gradient boosting (XGBoost), and support vector machine (SVM)—were used to build prediction models. Models were trained on 70% of the data and tested on the remaining 30%. Performance was evaluated using the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA). SHAP analysis was applied to interpret the contribution of each variable. Results Twenty‐six clinical variables including ethnicity, pneumonia, max temperature, average temperature, initial respiratory rate, max respiratory rate, max pulse, average pulse, hematocrit, percentage of lymphocytes, percentage of monocyte, absolute number of lymphocytes, absolute number of monocyte, hematocrit of platelet, aspartate aminotransferase, albumin, globulin, albumin/globulin ratio, total bilirubin, indirect bilirubin, glomerular filtration rate, uric acid, sodium, fibrinogen, lactate dehydrogenase, and initial CD4‐positive T‐cell count were identified as potentially related to P. jirovecii infection in AIDS patients. The machine learning model demonstrated good predictive performance in the training and test group. Conclusion The developed machine learning model effectively identifies AIDS patients at risk of P. jirovecii infection and may support early risk stratification and clinical decision‐making. External validation is needed to confirm its generalizability.

BackgroundActivating the Stimulator of Interferon Genes (STING) adaptor incites antitumor immunity against immunogenic tumors in mice, prompting clinical trials to test STING activators. However, STING signaling in the tumor microenvironment (TME) during development of Lewis lung carcinoma (LLC) suppresses antitumor immunity to promote tumor growth. We hypothesized that local immune balance favoring suppression of antitumor immunity also attenuates antitumor responses following STING activation. The purpose of this study was to evaluate how STING activation impacts antitumor responses in mice bearing LLC tumors.MethodsMice bearing established LLC tumors were treated with synthetic cyclic diadenyl monophosphate (CDA) to activate STING. Mice were monitored to assess LLC tumor growth, survival and protective antitumor immunity. Transcriptional and metabolic analyses were used to identify pathways responsive to CDA, and mice were co-treated with CDA and drugs that disrupt these pathways.ResultsCDA slowed LLC tumor growth but most CDA-treated mice (77%) succumbed to tumor growth. No evidence of tumor relapse was found in surviving CDA-treated mice at experimental end points but mice were not immune to LLC challenge. CDA induced rapid increase in immune regulatory pathways involving programmed death-1 (PD-1), indoleamine 2,3 dioxygenase (IDO) and cyclooxygenase-2 (COX2) in the TME. PD-1 blockade enhanced antitumor responses to CDA and increased mouse survival but mice did not eliminate primary tumor burdens. Two IDO inhibitor drugs had little or no beneficial effects on antitumor responses to CDA. A third IDO inhibitor drug synergized with CDA to enhance tumor control and survival but mice did not eliminate primary tumor burdens. In contrast, co-treatments with CDA and the COX2-selective inhibitor celecoxib controlled tumor growth, leading to uniform survival without relapse, and mice acquired resistance to LLC re-challenge and growth of distal tumors not exposed directly to CDA. Thus, mice co-treated with CDA and celecoxib acquired stable and systemic antitumor immunity.ConclusionsSTING activation incites potent antitumor responses and boosts local immune regulation to attenuate antitumor responses. Blocking STING-responsive regulatory pathways synergizes with CDA to enhance antitumor responses, particularly COX2 inhibition. Thus, therapy-induced resistance to STING may necessitate co-treatments to disrupt regulatory pathways responsive to STING in patients with cancer.

Hepatocellular carcinoma (HCC) is a frequently occurred malignancy worldwide with a high mortality. The treatment for HCC is still controversial. Emerging evidences have demonstrated that microRNAs (miRs) play a role in HCC. This study aims to investigate the effects of lentiviral‐mediated miRNA‐26b (miR‐26b) on the proliferation and metastasis of HCC cells. The normal hepatic cell line HL‐7702 and HCC cell lines HepG2 (without metastatic potential), SMMC‐7721 (with low metastatic potential) and MHCC97H (with high metastatic potential) were purchased for our experiment. The lentiviral‐mediated miR‐26b overexpression (miR‐26b‐LV) and low expression (sh‐miR‐26b) were constructed to transfect the cells. The miR‐26b expression and expressions of Karyopherin α‐2 (KPNA2), matrix metalloproteinase 1 (MMP‐1), MMP‐7 and MMP‐14 were determined by RT‐qPCR and western blot analysis. The proliferation and metastasis of transfected HCC cells were detected by MTT and Transwell assay respectively. The miR‐26b expressions were decreased significantly in MHCC97H cells. With lentiviral‐mediated miR‐26b overexpression, the proliferation and migration of HepG2, MHCC97H and SMMC‐7721 cells were decreased significantly. The RT‐qPCR and western blot analysis results revealed that the mRNA and protein expressions of KPNA2, MMP‐1, MMP‐7 and MMP‐14 were decreased by lentiviral‐mediated miR‐26b overexpression. All the above indexes in the HepG2, MHCC97H and SMMC‐7721 cells treated by sh‐miR‐26b exhibited opposite trends. These results show that overexpressed miR‐26b could inhibit the proliferation and metastasis of HCC cells significantly, which provides a novel target and theoretical foundation for the treatment of HCC.