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Severe uterine injury is a major cause of endometrial scar formation and female infertility. Currently, the methods for accelerating injured uterine healing are still lacking. Genetic engineering modification of mesenchymal stem cells (MSCs) has been shown great promise in preclinical studies on regeneration. Here, we constructed a type of UC-MSCs with overexpressed bFGF (UC-MSCbFGF) and investigated the effects of the UC-MSCbFGF/scaffold on functional regeneration of the full-thickness defect uterus of the rat model. At day 7, 14, 30 after treatments, the rats were euthanized and the injured uterus were observed. The structural and functional change of uterine were assessed by hematoxylin and eosin (HE) staining, immunohistochemical staining and fertility experiment. The UC-MSCbFGF/scaffold group exhibited anti-inflammatory effect, and the number of CD45+ cell in the UC-MSCbFGF/scaffold group was significantly less than that in UC-MSCs/scaffold group and scaffold group, but higher than sham-operated group at day 7 post-mending. At day 14, the UC-MSCbFGF/scaffold group exhibited dramatically pro-angiogenesis efficacy compared with UC-MSCs/scaffold group and scaffold group. At day 30, the endometrial thickness, structure of myometrium and blood vessels in the UC-MSCbFGF/scaffold were better than those of the UC-MSCs/scaffold group and scaffold group, even close to sham-operated group. Implantation rate at injury region post-operation 30 days in the UC-MSCbFGF/scaffold group (8/16) was significantly higher than that in UC-MSCs/scaffold group (1/16) and scaffold group (0/16). Taken together, the UC-MSCbFGF/scaffold system suppressed local inflammation, promoted angiogenesis and accelerated regeneration of the defected uterine wall, and thereby greatly shortened the healing time of the injured uterus.

The acquisition of traditional wheat ear phenotypic parameters is labour intensive and subjective, and some trait parameters are difficult to measure, which greatly limits the progress of wheat ear research. To obtain the phenotypic parameters of wheat ears in batches at a low cost, this paper proposed a convenient and accurate method for extracting phenotypic parameters of wheat ears. First, three improvement directions were proposed based on the Mask Region-Convolutional Neural Network (Mask-RCNN) model. 1) To extract the multiscale features of wheat ears, a hierarchical residual link was constructed in a single residual block of the backbone network ResNet101 to obtain information on different sizes of receptive fields. 2) The feature pyramid network (FPN) was improved to increase the recognition accuracy of wheat ear edges through multiple two-way information flow sampling. 3) The mask evaluation mechanism was improved, specific network blocks were used to learn and predict the quality of the mask, and the detection of wheat ears and grains was performed by precise segmentation; an automatic extraction algorithm was designed for wheat ear phenotypic parameters based on the segmentation results to extract 22 phenotypic parameters. The experiments showed that the improved Mask-RCNN was superior to the existing model in the segmentation accuracy of wheat ears and grains; the parameters of wheat ear length, width, and number of grains extracted by the automatic extraction algorithm were close to the manual measurement values. This research meets the demand for automatic extraction of wheat ear phenotype data for large-scale quality testing and commercial breeding and has strong practicability.

Thin endometrium has been widely recognized as a critical cause of infertility, recurrent pregnancy loss, and placental abnormalities; however, access to effective treatment is a formidable challenge due to the rudimentary understanding of the pathogenesis of thin endometrium. Here, we profiled the transcriptomes of human endometrial cells at single-cell resolution to characterize cell types, their communications, and the underlying mechanism of endometrial growth in normal and thin endometrium during the proliferative phase. Stromal cells were the most abundant cell type in the endometrium, with a subpopulation of proliferating stromal cells whose cell cycle signaling pathways were compromised in thin endometrium. Both single-cell RNA sequencing and experimental verification revealed cellular senescence in the stroma and epithelium accompanied by collagen overdeposition around blood vessels. Moreover, decreased numbers of macrophages and natural killer cells further exacerbated endometrial thinness. In addition, our results uncovered aberrant SEMA3, EGF, PTN, and TWEAK signaling pathways as causes for the insufficient proliferation of the endometrium. Together, these data provide insight into therapeutic strategies for endometrial regeneration and growth to treat thin endometrium.

Emerging evidence demonstrates the important role of circular RNAs (circRNAs) in regulating pathological processes in various diseases including organ fibrosis. Endometrium fibrosis is the leading cause of uterine infertility, but the role of circRNAs in its pathogenesis is largely unknown. Here, we provide the evidence that upregulation of circPTPN12 in endometrial epithelial cells (EECs) of fibrotic endometrium functions as endogenous sponge of miR-21–5 p to inhibit miR-21–5 p expression and activity, which in turn results in upregulation of ΔNp63α to induce the epithelial mesenchymal transition (EMT) of EECs (EEC–EMT). In a mouse model of endometrium fibrosis, circPTPN12 appears to be a cofactor of driving EEC–EMT and administration of miR-21–5 p could reverse this process and improve endometrial fibrosis. Our findings revealed that the dysfunction of circPTPN12/miR-21–5 p/∆Np63α pathway contributed to the pathogenesis of endometrial fibrosis.

Emerging evidence demonstrates the important role of circular RNAs (circRNAs) in regulating pathological processes in various diseases including organ fibrosis. Endometrium fibrosis is the leading cause of uterine infertility, but the role of circRNAs in its pathogenesis is largely unknown. Here, we provide the evidence that upregulation of circPTPN12 in endometrial epithelial cells (EECs) of fibrotic endometrium functions as endogenous sponge of miR-21-5p to inhibit miR-21-5p expression and activity, which in turn results in upregulation of ΔNp63α to induce the epithelial mesenchymal transition (EMT) of EECs (EEC-EMT). In a mouse model of endometrium fibrosis, circPTPN12 appears to be a cofactor of driving EEC-EMT. Our findings reveal the novel mechanism in the pathogenesis of endometrium fibrosis and the potential therapeutic strategy for endometrium fibrosis via targeting circPTPN12/miR-21-5p/ΔNp63α pathway.

Background: A comprehensive geriatric assessment (CGA) of elderly patients is useful for detecting the patients' vulnerabilities. Exercise and early rehabilitation, nutritional intervention, traditional Chinese medicine (TCM), standardized medication guidance and patient education can, separately, improve and even reverse the physical frailty status. However, the effect of combining a CGA and multi-disciplinary management on frailty in elderly patients remains unclear. The present study assessed the effects of a CGA and multi-disciplinary management on elderly patients with frailty in China.Methods: In this study, 320 inpatients with frailty ≥70 years old will be randomly divided into an intervention group and a control group. The intervention group will be given routine management, a CGA and multi-disciplinary management involving rehabilitation exercise, diet adjustment, multi-drug evaluation, acupoint massage in TCM and patient education for 12 months, and the control group will be followed up with routine management for basic diseases. The primary outcomes are the Fried phenotype and short physical performance battery (SPPB). The secondary outcomes are the clinical frailty scale (CFS), non-elective hospital readmission, basic activities of daily living (BADL), 5­level european quality of life 5 dimensions index (EQ-5D), nutrition risk screening-2002 (NRS-2002), medical insurance expenses, fall events and all-cause mortality. In addition, a cost-effectiveness study will be carried out. Discussion: This paper outlines the protocol for a randomized, single-blind, parallel multi-center clinical study. This protocol, if beneficial, will demonstrate the interaction of various intervention strategies, will help improve elderly frailty patients, and will be useful for clinicians, nurses, policymakers, public health authorities and the general population.Trial registration: Chinese Clinical Trials Register, ChiCTR1900022623. Registered on 19 April 2019, http://www.chictr.org.cn/showproj.aspx?proj=38141.

Intrauterine adhesions (IUAs), the leading cause of uterine infertility, are characterized by endometrial fibrosis. The management of IUA is challenging because the pathogenesis of the disease largely unknown. In this study, we demonstrate that the mRNA and protein levels of high mobility group AT-hook 2 (HMGA2) were increased by nearly 3-fold (P

Epithelial homeostasis plays an essential role in maintaining endometrial function. But the epithelial role in endometrial fibrosis has been less studied. Previously, we showed that ectopic expression of ΔNp63α is associated with fibrosis process and epithelial dysfunction in endometria of patients with intrauterine adhesions (IUAs). Since ΔNp63α is profoundly involved in maintaining the epithelial homeostasis, we hereby focused on its roles in regulating the function and phenotype of endometrial epithelial cells (EECs) in context of endometrial fibrosis. We identified a typical type 2 epithelial-to-mesenchymal transition (EMT) in EECs from IUA patients and this process was induced by the forced expression of ΔNp63α in EECs. In transcriptomic analysis, we found that diverse signaling pathways regulated by ΔNp63α were involved in pro-EMT. We demonstrated that the DUSP4/GSK-3β/SNAI1 pathway was critical in transducing the pro-EMT signals initiated by ΔNp63α, while bFGF reversed ΔNp63α-induced EMT and endometrial fibrosis both in vitro and in vivo by blocking DUSP4/GSK3β/SNAI1 pathway. Taken together, our findings are important to understand the molecular mechanisms of endometrial fibrosis and to provide potential therapeutic targets.

Background: No prior studies have assessed the role of cognitive impairment and physical frailty in elderly inpatients with cardiovascular disease (CVD). We aimed to assess the utility of a combination developed using the mini-mental state examination (MMSE) + clock drawing test (CDT) and the Fried phenotype for predicting non-elective hospital readmission or death within 6-month in elderly inpatients with CVD. Methods : A single center prospective cohort was conducted between September 2018 and February 2019. Inpatients aged 65 years or older were recruited. All enrolled patients received a comprehensive geriatric assessment during hospitalization. The Kaplan-Meier curves were used to estimate the cumulative incidence of events. The multivariate Cox regression model was used to analyze the association between frailty and cognitive status and the non-elective hospital readmission or death. Results : A total of 542 patients were included; and a total of 113 patients (20.9%) died or were readmitted at 6-month. Overall 20% screened positive for cognitive impairment, including 8% were cognitive impairment combined with physical frailty, which were more older, more common in women and non-married group, had a lower education and a higher risk of malnutrition. Frail participants with normal (hazard ratio [HR]:1.73, 95% confidence intervals [CI]:1.06-2.82, P=0.028) and impaired cognition (HR:2.50, 95% CI:1.27-4.91, P=0.008) had a higher risk of non-elective hospital readmission or death than robust patients, after adjustment for age, sex, education level, marital status, the presence of diabetes mellitus, heart failure, and previous stroke. Conclusions : The presence of physical frailty and cognitive frailty were powerful predictors of non-elective hospital readmission or death in elderly inpatients with CVD, and taking cognitive impairment into account in the frailty model may allow better prediction of adverse outcomes of frailty in the short time. Trial registration: ChiCTR1800017204; date of registration: 07/18/2018.

Assessing liver fibrosis with chronic hepatitis B (CHB) in patients is quite important. Some non-invasive approaches for evaluating liver fibrosis include blood tests and ultrasound elastography. How to effectively combine multiple methods to improve the diagnostic performance remains a challenging problem. The main goal of this paper is to assess and stage liver fibrosis in CHB using feature selection and machine learning methods based on multimodal data. Popular machine learning approaches (e.g., support vector machine (SVM)) and feature selection (FS) were explored to stage the CHB. 16 volunteers and 92 patients with CHB were investigated for liver fibrosis staging based on transient elastography (TE) and acoustical radiation force impulse imaging (ARFI) data. The accuracy of the staging result using FS and a SVM classifier was an accuracy of 90.68% for significant fibrosis (≥F2) and an accuracy of 93.52% for cirrhosis (F4), respectively. The proposed method also increased the sensitivity, specificity, and area under curve (AUC) values for both significant fibrosis and cirrhosis diagnosis, which is very promising for staging liver fibrosis from multimodal information. It outperforms any single method and their linear combination and also achieves a state-of-the-art performance.

Purpose – The purpose of this paper is to make research on causing mechanism of meteorological disaster as well as the components of meteorological disaster system and their semantic relationships. It has important practical significance due to the urgent need of further providing support for pre-assessment of influences of disastrous weather/climate events and promoting the level of emergency management. Design/methodology/approach – This paper analyses the occurrence regulations and components of meteorological disasters and proposes the concept of meta-action. Ontology modelling method is adopted to describe the components and relationships among different parts comprising meteorological disaster system, and semantic web rule language is selected to identify the implicit relationships among the domain knowledge explicitly defined in ontology model. Besides, a case is studied to elaborate how to provide logic and semantic information support for comprehensive risk assessment of disastrous weather/climate events based on rule-based ontology reasoning method. It proves that ontology modelling and reasoning method is effective in providing decision makings. Findings – This paper provides deep analyses about causing mechanisms of meteorological disasters, and implements information fusion of the components of meteorological disaster system and acquisition of potential semantic relations among ontology components and their individuals. Originality/value – In this paper, on the basis of analysing the disaster-causing mechanisms, the meteorological disaster ontology (MDO) model is proposed by using the ontology modelling and reasoning method. MDO can be applied to provide decision makings for meteorological departments.

Aim We aimed to investigate the efficacy and safety of telbivudine (LdT) on the intervention of mother-to-child transmission (MTCT) in different trimesters of pregnant women with high viral loads. Methods In this prospective cohort study, 160 cases of mothers with high viral loads were included. Eighty-two subjects received 600 mg/day LdT therapy. Fifty of them started LdT therapy before the third trimester of gestation, including 17 cases before pregnancy, nine and 24 cases in the first and second trimesters of pregnancy, respectively. The other 32 cases started LdT in the third trimester of gestation. Control pregnant women (78 cases) did not take LdT therapy. MTCT rate was determined by hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA data of infants at the 51st week post-partum. Adverse events were also evaluated throughout the study. Results One hundred and sixty infants were born from 160 pregnant women. Both LdT-treated groups displayed a marked decline in HBV DNA levels from the beginning to delivery. Positive rate of serum HBsAg in infants born from the above two groups of mothers were 0% and 3.1%, respectively, which was significantly lower than that in the untreated controls (24.4%). The incidence of detectable HBV DNA levels was significantly lower in infants born to LdT-treated mothers than in the controls (16.7%) at the 51st week post-partum. No infant had birth defects. No severe adverse event or complication were observed in LdT-treated mothers or infants followed until the 51st week post-partum. Conclusion The earlier application of LdT during pregnancy, the better preventive effects it offered on MTCT.

AIM In this prospective study, we aimed to evaluate the efficacy and safety of tenofovir disoproxil fumarate (TDF) in Chinese chronic hepatitis B (CHB) patients after multiple nucleoside/nucleotide analog (NA) treatment failures. METHODS A total of 115 Chinese CHB patients with suboptimal response to two or more NA treatments were included in this study. All patients were changed to TDF (300 mg/day, oral administration) antiviral treatment for at least 72 weeks. Hepatitis B virus (HBV) polymerase (P) gene mutation screening for each patient was performed. In addition, virological, biochemical responses and estimated glomerular filtration rate (eGFR) of each patient at weeks 12, 24, 48 and 72 of TDF treatment were evaluated. RESULTS Seventy-six out of 115 patients had drug-resistance mutations (R(+) ), including 27 with adefovir (ADV)-associated mutations (35.5%) and 49 with lamivudine (LMV)-associated mutations (64.5%). For all included patients, complete viral response (CVR) of HBV DNA (

To investigate the combined diagnostic accuracy of acoustic radiation force impulse (ARFI), aspartate aminotransferase to platelet ratio index (APRI) and Forns index for a non-invasive assessment of liver fibrosis in patients with chronic hepatitis B (CHB).In this prospective study, 206 patients had CHB with liver fibrosis stages F0-F4 classified by METAVIR and 40 were healthy volunteers were measured by ARFI, APRI and Forns index separately or combined as indicated.ARFI, APRI or Forns index demonstrated a significant correlation with the histological stage (all P0.001). According to the AUROC of ARFI and APRI for evaluating fibrotic stages more than F2, ARFI showed an enhanced diagnostic accuracy than APRI (P0.05). The combined measurement of ARFI and APRI exhibited better accuracy than ARFI alone when evaluating ≥ F2 fibrotic stage (Z = 2.77, P = 0.006). Combination of ARFI, APRI and Forns index did not obviously improve the diagnostic accuracy compared to the combination of ARFI and APRI (Z = 0.958, P = 0.338).ARFI + APRI showed enhanced diagnostic accuracy than ARFI or APRI alone for significant liver fibrosis and ARFI + APRI + Forns index shows the same effect with ARFI + APRI.

We aimed to investigate the efficacy and safety of telbivudine (LdT) on the intervention of mother-to-child transmission (MTCT) in different trimesters of pregnant women with high viral loads.In this prospective cohort study, 160 cases of mothers with high viral loads were included. Eighty-two subjects received 600 mg/day LdT therapy. Fifty of them started LdT therapy before the third trimester of gestation, including 17 cases before pregnancy, nine and 24 cases in the first and second trimesters of pregnancy, respectively. The other 32 cases started LdT in the third trimester of gestation. Control pregnant women (78 cases) did not take LdT therapy. MTCT rate was determined by hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA data of infants at the 51st week post-partum. Adverse events were also evaluated throughout the study.One hundred and sixty infants were born from 160 pregnant women. Both LdT-treated groups displayed a marked decline in HBV DNA levels from the beginning to delivery. Positive rate of serum HBsAg in infants born from the above two groups of mothers were 0% and 3.1%, respectively, which was significantly lower than that in the untreated controls (24.4%). The incidence of detectable HBV DNA levels was significantly lower in infants born to LdT-treated mothers than in the controls (16.7%) at the 51st week post-partum. No infant had birth defects. No severe adverse event or complication were observed in LdT-treated mothers or infants followed until the 51st week post-partum.The earlier application of LdT during pregnancy, the better preventive effects it offered on MTCT.