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Lung segmentation using computed tomography (CT) images is important for diagnosing various lung diseases. Currently, no lung segmentation method has been developed for assessing the CT images of preschool children, which may differ from those of adults due to (1) presence of artifacts caused by the shaking of children, (2) loss of a localized lung area due to a failure to hold their breath, and (3) a smaller CT chest area, compared with adults. To solve these unique problems, this study developed an automatic lung segmentation method by combining traditional imaging methods with ResUnet using the CT images of 60 children, aged 0-6 years. First, the CT images were cropped and zoomed through ecological operations to concentrate the segmentation task on the chest area. Then, a ResUnet model was used to improve the loss for lung segmentation, and case-based connected domain operations were performed to filter the segmentation results and improve segmentation accuracy. The proposed method demonstrated promising segmentation results on a test set of 12 cases, with average accuracy, Dice, precision, and recall of 0.9479, 0.9678, 0.9711, and 0.9715, respectively, which achieved the best performance relative to the other six models. This study shows that the proposed method can achieve good segmentation results in CT of preschool children, laying a good foundation for the diagnosis of children’s lung diseases.

Background Different techniques have been reported to prevent perineal lacerations, but the effects of the use of lubricant have been unclear and is still subject of debate. Objective To assess the effect of lubricants on reducing perineal trauma during vaginal delivery. Search strategy PubMed, Embase, the Cochrane Library, CINAHL, China National Knowledge Infrastructure (CNKI), China Biology Medicine disc (CBM), WanFang databases, ClinicalTrials.gov in 25 June 2021. Selection criteria Randomized controlled trials published in English or Chinese that compared the vaginal application of lubricant with standard care in women with cephalic presentation at vaginal delivery were included . Data collection and analysis Two independent reviewers selected eligible trials and extracted data on perineal trauma, duration of the second-stage labor, postpartum hemorrhage and Apgar score for meta-analysis. Main results Nineteen trials enrolling 5445 pregnant women were included. Compared with standard care, women using lubricants had a lower incidence of perineal trauma (RR 0.84, 95%CI 0.76 to 0.93), second-degree perineal laceration (RR 0.72, 95%CI 0.64 to 0.82) and episiotomy (RR 0.77, 95%CI 0.62 to 0.96), had a shorter duration of the second-stage labor (MD -13.72 minutes, 95%CI -22.68 to -4.77). Subgroup analysis indicated that women with obstetric gel had a shorter duration of the second-stage (MD -16.9 minutes, 95%CI -27.03 to -6.78 vs MD -8.38 minutes, 95%CI -11.11 to -5.65; P interaction=0.02) when compared with liquid wax. Conclusions Compared with standard care, lubricants could reduce the incidence of perineal trauma, especially second-degree perineal laceration, and shorten the duration of the second-stage labor.

Background and Aims. Diagnosing pediatric intussusception from ultrasound images can be a difficult task in many primary care hospitals that lack experienced radiologists. To address this challenge, this study developed an artificial intelligence- (AI-) based system for automatic detection of “concentric circles” signs on ultrasound images, thereby improving the efficiency and accuracy of pediatric intussusception diagnosis. Methods. A total of 440 cases (373 pediatric intussusception and 67 normal cases) were retrospectively collected from Children’s Hospital affiliated to Zhejiang University School of Medicine from January 2020 to December 2020. An improved Faster RCNN deep learning framework was used to detect “concentric circle” signs. Finally, independent validation set was used to evaluate the performance of the developed AI tool. Results. The data of pediatric intussusception were divided into a training set and validation set according to the ratio of 8 : 2, with training set (298 pediatric intussusception) and validation set (75 pediatric intussusception and 67 normal cases). In the “concentric circle” detection model, the detection rate, recall, specificity, and F 1 score assessed by the validation set were 92.8%, 95.0%, 92.2%, and 86.4%, respectively. Pediatric intussusception was classified by “concentric circle” signs, and the accuracy, recall, specificity, and F 1 score were 93.0%, 92.0%, 94.1%, and 93.2% on the validation set, respectively. Conclusion. The model established in this paper can realize the automatic detection of “concentric circle” signs in the ultrasound images of abdominal intussusception in children; the AI tool can improve the diagnosis speed of pediatric intussusception. It is necessary to further develop an artificial intelligence system for real-time detection of “concentric circles” in ultrasound images for the judgment of children with intussusception.

Clinical symptoms and inflammatory markers cannot reliably distinguish the etiology of CAP, and chest radiographs have abundant information related with CAP. Hence, we developed a context-fusion convolution neural network (CNN) to explore the application of chest radiographs to distinguish the etiology of CAP in children. This retrospective study included 1769 cases of pediatric pneumonia (viral pneumonia, n = 487; bacterial pneumonia, n = 496; and mycoplasma pneumonia, n = 786). The chest radiographs of the first examination, C-reactive protein (CRP), and white blood cell (WBC) were collected for analysis. All patients were stochastically divided into training, validation, and test cohorts in a 7:1:2 ratio. Automatic lung segmentation and hand-crafted pneumonia lesion segmentation were performed, from which three image-based models including a full-lung model, a local-lesion model, and a context-fusion model were built; two clinical characteristics were used to build a clinical model, while a logistic regression model combined the best CNN model and two clinical characteristics. Our experiments showed that the context-fusion model which integrated the features of the full-lung and local-lesion had better performance than the full-lung model and local-lesion model. The context-fusion model had area under curves of 0.86, 0.88, and 0.93 in identifying viral, bacterial, and mycoplasma pneumonia on the test cohort respectively. The addition of clinical characteristics to the context-fusion model obtained slight improvement. Mycoplasma pneumonia was more easily identified compared with the other two types. Using chest radiographs, we developed a context-fusion CNN model with good performance for noninvasively diagnosing the etiology of community-acquired pneumonia in children, which would help improve early diagnosis and treatment.

Microstructural alterations of brain structure in haemophilic boys were found in our previous study.We investigated alterations of brain function in school-age boys with severe haemophilia A (HA) with resting-state functional magnetic resonance imaging (rs-fMRI).We obtained rs-fMRI scans from 24 boys with HA and 25 demographically matched healthy children. Spontaneous brain activity parameters were calculated. Graph theoretical analyses on rs-fMRI data at the global and regional levels were performed. Two-sample t tests were used to analyze differences, and correlation analyses identified relationships between altered neural properties and psychological characteristics.Children with severe HA showed small-worldness organization but with an increased efficiency and compactness in functional segregation. The whole brain showed an overtight connection pattern. At the regional level, significantly increased nodal efficiency in the salience network (SN), default mode network (DMN) and executive control network was found. Social Anxiety Scale for Children (SASC) scores were positively correlated with these alterations. Spontaneous brain activity alterations in regions including the cerebellum, frontal gyrus (orbital part), temporal gyrus and thalamus were observed; some of these regions have been closely related to social anxiety and family or social support.Our study is the first to evaluate the neurological functional changes in school-age boys with severe HA. Disruptions in topographic characteristics and abnormal activity were closely related to social conditions. These data could help us to understand early neurological alterations in haemophilic children, improve the traditional view of family support and strengthen normal school life at an early stage.

Depression disorder is accompanied by cognitive impairments. However, there is limited research focused on cognitive impairments and their neurological mechanism in adolescents with depression. The purpose of the current study is to illustrate the differences in brain activity patterns between depressed adolescents and healthy controls (HCs).A total of 72 adolescents with depression, as well as 74 HCs, were recruited. We utilized functional near-infrared spectroscopy (fNIRS) to monitor the concentrations of oxyhemoglobin (Oxy-Hb) in the brains of participants while they performed the verbal fluency task (VFT) to examine cognitive impairment in adolescents with depression.Our study demonstrated that adolescents with depression had significantly less cortical activation in the hemodynamic responses of Oxy-Hb at channels mainly located in the prefrontal cortex (PFC) than HCs during the 60-s task period (false discovery rate (FDR)-corrected p 0.05). The mean channel-to-channel connectivity was 0.400 for HCs (SD = 0.149) and 0.303 (SD = 0.138) for adolescents with depression, and the HC group had a higher mean channel-to-channel connectivity strength than the depression group (t = -15.586, p 0.001). For the patient group, we found significant negative correlations between HAMD scores and mean Oxy-Hb changes in Channel 38 (r = -0.33, p 0.01), Channel 39 (r = -0.34, p 0.01), Channel 41 (r = -0.25, p 0.05), Channel 42 (r = -0.28, p 0.05), and Channel 44 (r = -0.27, p 0.05), and these channels were mainly located in areas with little difference between groups.Our study provides neurological evidence about the executive function (EF) in depressed adolescents. Adolescents with depression exhibited an abnormal activation pattern and decreased task-related functional connectivity compared to HCs. The changed Oxy-Hb concentration of PFC during VFT was not sensitive to depression symptoms.

In many fungi, the AreA GATA-type transcription factor mediates nitrogen catabolite repression affecting fungal development and, where applicable, virulence. Here, we investigated the functions of AreA in the fungal entomopathogen and plant endophyte

Due to the phenotypic similarities among different pediatric respiratory diseases with chronic cough, primary doctors often misdiagnose and the misuse of examinations is prevalent. In the pre-diagnosis stage, the patients' chief complaints and other information in the electronic medical record (EMR) provide a powerful reference for respiratory experts to make preliminary disease judgment and examination plan. In this paper, we proposed an intelligent prediagnosis system to predict disease diagnosis and recommend examinations based on EMR text.We examined the clinical notes of 178,293 children with chronic cough symptoms from retrospective EMR data. The dataset is split into 7:3 for training and testing. From the testing set, we also extract 5% of samples for validation. We proposed a medical-semantic-aware convolution neural network (MSCNN) framework that can accomplish two downstream tasks from the same medical language model through transfer learning. First, a medical language model based on the word2vec algorithm was built to generate embeddings for the text data. Then, text convolutional neural network (TextCNN) was used to build models for disease prediction and examination recommendation.We implemented 5 algorithms for disease prediction. In the disease prediction task, our algorithm outperformed the baseline methods on all metrics, with a top-1 accuracy (AC) of 0.68 and a top-3 AC of 0.923 on the testing set. By adding data enhancement, the top-3 AC reached 0.926. In the examination recommendation task, the overall AC on the testing set was 0.93 and the macro average (MA) F1-score was 0.88. The average area under the curve (AUC) on the training set was 0.97 while on the testing set it was 0.86.We constructed an intelligent prediagnosis system with an MSCNN framework that can predict diseases and make examination recommendations based on EMR data. Our approach achieved good results on a retrospective clinical dataset and thus has great potential for the application of automated diagnosis assist in clinical practice during pre-diagnosis stage, which will provide help for primary level doctors or doctors in basic-level hospitals. Due to the generality of the proposed framework, it can be straight forwardly extended to prediagnosis for other diseases.

Most women suffer from perineal trauma during childbirth, whether it is natural tears or episiotomy.To perform a systematic review and network meta-analysis investigating the effectiveness of different PFMT relevant strategies in the prevention of perineal trauma.PubMed, Embase, the Cochrane Library, CINAHL, CNKI, CBM, WANFANG DATABASE, and ClinicalTrials.gov were searched for citations published in any language from inception to 1 July 2021.Randomized controlled trials (RCTs) of PFMT relevant prevention strategies for preventing perineal trauma during childbirth.Data were independently extracted by two reviewers. Relative treatment effects were estimated using network meta-analysis (NMA).Of 12 632 citations searched, 21 RCTs were included. Comparing with usual care, "PFMT combine with perineal massage" and PFMT alone showed more superiority in intact perineum (RR = 5.37, 95% CI: 3.79 to 7.60, moderate certainty; RR = 2.58, 95% CI 1.34-4.97, moderate certainty, respectively), episiotomy (RR = 0.26, 95% CI 0.14-0.49, very low certainty; RR = 0.63, 95% CI 0.45-0.90, very low certainty, respectively), and OASIS (RR = 0.35, 95% CI 0.16-0.78, moderate certainty; RR = 0.49, 95% CI 0.28-0.85, high certainty, respectively). "PFMT combine with perineal massage" showed superiority in reducing perineal tear (RR = 0.41, 95% CI 0.20-0.85, moderate certainty).In view of the results, antenatal "PFMT combine with perineal massage" and PFMT were effective strategies for the prevention of perineal trauma.

Background: The treat-to-target (T2T) strategy is essential for patients with gout. However, the rate of T2T is low. This study aimed to explore doctor-led chronic disease management on the T2T of gout, survey the rate of T2T and assess the predictors associated with poor control of serum urate levels (SUA) in a large population of patients with gout receiving urate-lowering treatment (ULT). Methods: A multi-center, cross-sectional study was conducted. We surveyed the relevant information of outpatients who received ULT for more than six months using electronic questionnaires, including demographics, disease-related conditions, comorbid conditions, and management. The patients with gout were divided into the SUA > 360 µmol/L and ≤ 360 µmol/L, and the patient characteristics between the two groups were compared. We analyzed the predictors of SUA > 360 µmol/L and poor disease control.Results: We collected 425 (90.8% of the patients) valid questionnaires. There were significant differences in the gender, education level, regular visits, medication adherence, diabetes, economic burden and community doctor's help between the SUA > 360 µmol/L (n=311, 73.18%) and ≤ 360 µmol/L (n=114, 26.82%) groups. The predictors of SUA >360 µmol/L were general medication adherence (OR=2.35; 95% CI 1.17–4.77; p=0.016), poor medication adherence (OR=4.63; 95% CI 2.28–9.51; pConclusion: The T2T and well controlled rates were very low. The medication adherence, the community doctor’s help and gout popular science which was the doctor-led chronic gout management should be further improved to increase the T2T and well controlled rate.Trial registration: ChiCTR, ChiCTR2000034700, Registered 15 July 2020. http://www.chictr.org.cn/showproj.aspx?proj=55778

BackgroundBladder cancer (BCa) is a commonly diagnosed malignancy worldwide that has poor survival depending on its intrinsic biologic aggressiveness and a peculiar radio- and chemoresistance features. Gaining a better understanding of tumorigenesis and developing new diagnosis and treatment strategies for BCa is important for improving BCa clinical outcome. SLC25 family member 21 (SLC25A21), a carrier transporting C5-C7 oxodicarboxylates, has been reported to contribute to oxoadipate acidemia. However, the potential role of SLC25A21 in cancer remains absolutely unknown.MethodsThe expression levels of SLC25A21 in BCa and normal tissues were examined by real-time PCR and immunohistochemistry. Gain-of- and loss-of-function experiments were performed to detect the biological functions of SLC25A21 in vitro and in vivo by CCK-8 assay, plate colony formation assay, cell migration, invasion assay and experimental animal models. The subcellular distribution of substrate mediated by SLC25A21, mitochondrial membrane potential and ROS production were assessed to explore the potential mechanism of SLC25A21 in BCa.ResultsWe found that the expression of SLC25A21 was downregulated in BCa tissues compared to normal tissues. A significant positive correlation between decreased SLC25A21 expression and poor prognosis was observed in BCa patients. Overexpression of SLC25A21 significantly inhibited cell proliferation, migration and invasion and induced apoptosis in vitro. Moreover, the enhanced SLC25A21 expression significantly suppressed tumor growth in a xenograft mouse model. Furthermore, we revealed that SLC25A21 suppressed BCa growth by inducing the efflux of mitochondrial α-KG to the cytosol, decreasing to against oxidative stress, and activating the ROS-mediated mitochondrion-dependent apoptosis pathway.ConclusionsOur findings provide the first link between SLC25A21 expression and BCa and demonstrate that SLC25A21 acts as a crucial suppressor in BCa progression, which may help to provide new targets for BCa intervention.

The SARS-CoV-2 virus emerged in December 2019 and then spread rapidly worldwide, particularly to China, Japan, and South Korea. Scientists are endeavoring to find antivirals specific to the virus. Several drugs such as chloroquine, arbidol, remdesivir, and favipiravir are currently undergoing clinical studies to test their efficacy and safety in the treatment of coronavirus disease 2019 (COVID-19) in China; some promising results have been achieved thus far. This article summarizes agents with potential efficacy against SARS-CoV-2.

In this note, the norm bounds and convex properties of special operator matrices ~H(m)n and ~S(m)n are investigated. When Hilbert space K is infinite dimensional, we firstly show that ~H(m)n = ~H(m)n+1 and ~S(m) n = ~S(m)n+1, for m, n = 1,2,.... Then we get that ~H(m) n is a convex and compact set in the ?* topology. Moreover, some norm bounds for ~H(m) n and ~S(m)n are given.

Renal cell carcinoma (RCC) is the third most common urological cancer with highly metastatic potential. MAGI1 plays an important role in stabilization of the adherens junctions and has been confirmed to suppress invasiveness and metastasis in multiple cancers in clinic. However, its expression and anti-metastatic ability in RCC are still unclear. In this study, we demonstrated that MAGI1 was markedly decreased in the RCC and indicated poor survival. Furthermore, we found that MAGI1 suppressed the invasion and migration of human RCC cells. Mechanistic investigations revealed that MAGI1 stabilized the PTEN/MAGI1/β-catenin complex to inhibit β-catenin signaling pathway. Moreover, MAGI1 was targeted by miR-520h which was transcriptionally activated by c-Myb. Collectively, our findings suggested that MAGI1mediated tumor metastasis through c-Myb/miR-520h/MAGI1 signaling pathway in RCC.

Metarhizium robertsii is an insect pathogen as well as an endophyte, and can antagonize the phytopathogen, Fusarium solani during bean colonization. However, plant immune responses to endophytic colonization by Metarhizium are largely unknown. We applied comprehensive plant hormone analysis, transcriptional expression and stomatal size analysis in order to examine plant immune responses to colonization by Metarhizium and/or Fusarium. The total amount of abscisic acid (ABA) and ABA metabolites decreased significantly in bean leaves by plant roots colonized by M. robertsii and increased significantly with F. solani compared to the un-inoculated control bean plant. Concomitantly, in comparison to the un-inoculated bean, root colonization by Metarhizium resulted in increased stomatal size in leaves and reduced stomatal size with Fusarium. Meanwhile, expression of plant immunity genes was repressed by Metarhizium and, alternately, triggered by Fusarium compared to the un-inoculated plant. Furthermore, exogenous application of ABA resulted in reduction of bean root colonization by Metarhizium but increased colonization by Fusarium compared to the control without ABA application. Our study suggested that ABA plays a central role in differential responses to endophytic colonization by Metarhizium and pathogenic colonization by Fusarium and, we also observed concomitant differences in stomatal size and expression of plant immunity genes.

When initiating urate-lowering therapy, using anti-inflammatory prophylaxis therapy for at least 3 to 6 months is strongly recommended. Previous studies have found that zhengqing fengtongning sustained-release tablets (sinomenine) can improve inflammation in the acute phase of gout; however, the efficacy of urate-lowering therapy in reducing frequency of acute flares still needs to be investigated. The aim of the present study is to explore the efficacy and safety of sinomenine for prophylaxis of acute flares when initiating urate-lowering therapy.This randomized, placebo-controlled, double-blinded trial will include a total of 210 gout patients who meet the study criteria. The patients will be randomized (1:1) to the test group and the control group. The intervention is planned to be performed for 12 weeks with a follow-up of 12 weeks. All patients would be administered febuxostat (40 mg/d) and concomitant anti-inflammatory prophylaxis therapy. Sinomenine and colchicine placebo are administered in the sinomenine group, sinomenine placebo and colchicine are administered in the colchicine group. The primary outcome is the rate of acute gout flares in subjects within 12 weeks of the treatment period. The secondary outcomes include the times of acute gout flares and the duration of each acute flares within 12 weeks; the compliance rate in patients whose UA levels ≤6.0 mg/dL (360 μmol/L) at the weekend of 2nd, 4th, 8th, and 12th week in each group; the proportion of patients with ≥1 and ≥2 gout flares within 12 weeks; average visual analogue scale/score pain score during gout flares; and the oral dose of etoricoxib will be used to control the onset of acute flares within 12 weeks.The Institutional Medical Ethics Committee have approved the trial protocol. We plan to publish the results of this study in a peer-reviewed journal.ChiCTR, ChiCTR2100045114, Registered 8 April 2021 http://www.chictr.org.cn/showproj.aspx?proj=124688.

Background: Bladder cancer (BCa) is a commonly diagnosed malignancy worldwide that has poor survival depending on its intrinsic biologic aggressiveness and a peculiar radio- and chemoresistance features. Gaining a better understanding of tumorigenesis and developing new diagnosis and treatment strategies for BCa is important for improving BCa clinical outcome. SLC25 family member 21 (SLC25A21), a carrier transporting C5-C7 oxodicarboxylates, has been reported to contribute to oxoadipate acidemia. However, the potential role of SLC25A21 in cancer remains absolutely unknown. Methods: The expression levels of SLC25A21 in BCa and normal tissues were examined by real-time PCR and immunohistochemistry. Gain-of- and loss-of-function experiments were performed to detect the biological functions of SLC25A21 in vitro and in vivo by CCK-8 assay, plate colony formation assay, cell migration, invasion assay and experimental animal models. The subcellular distribution of substrate mediated by SLC25A21, mitochondrial membrane potential and ROS production were assessed to explore the potential mechanism of SLC25A21 in BCa.Results: We found that the expression of SLC25A21 was downregulated in BCa tissues compared to normal tissues. A significant positive correlation between decreased SLC25A21 expression and poor prognosis was observed in BCa patients. Overexpression of SLC25A21 significantly inhibited cell proliferation, migration and invasion and induced apoptosis in vitro. Moreover, the enhanced SLC25A21 expression significantly suppressed tumor growth in a xenograft mouse model. Furthermore, we revealed that SLC25A21 suppressed BCa growth by inducing the efflux of mitochondrial α-KG to the cytosol, decreasing to against oxidative stress, and activating the ROS-mediated mitochondrion-dependent apoptosis pathway. Conclusions: Our findings provide the first link between SLC25A21 expression and BCa and demonstrate that SLC25A21 acts as a crucial suppressor in BCa progression, which may help to provide new targets for BCa intervention.

Background: Restless legs syndrome (RLS), known as a kind of neurological disease, is prevalent but easy to be ignored. Studies have demonstrated that massage therapy can effectively reduce the symptoms of patients with RLS and improve their quality of life. However, the efficacy of massage therapy for RLS is still controversial. Therefore, this protocol aims to evaluate the reliability of massage therapy in treating RLS in a thorough way. Methods: We will search relevant randomized controlled trials from Chinese Biomedical Literature Database, Chongqing VIP, CNKI, Wanfang, Web of Science, Cochrane Library, PubMed, and EMBASE, when publication status and language are not considered and the time limit ends with September 6, 2020. Two experienced researchers will use RevMan V.5.3 software to perform the selection of literature, data collection, data analysis and synthesis separately. Besides, the quality of trials involved in this study will be measured with the Cochrane bias risk assessment tool. Results: This protocol will be applied to carry out a systematic evaluation of the massage therapy purposed to treat RLS for its effectiveness and safety. Conclusion: The review will provide a credible evidence suggesting whether massage therapy is a reliable intervention for RLS. INPLASY registration number: INPLASY202090038

Background: Nowadays, there are some randomized controlled trials (RCTs) to explore the effectiveness of drug therapy for bipolar disorder with anxiety disorders. However, due to lack of sufficient data, there are currently no good treatment recommendations. The purpose of this network meta-analysis is to compare the efficacy and safety of different drugs for bipolar disorder complicated with anxiety disorders to provide evidence to support clinical practice and guidelines development. Methods: A systematic literature search will be performed in the Cochrane Library, PubMed, EMBASE, and Web of Science from inception to July 2020. RCTs that compared the efficacy and safety of different drugs for bipolar disorder complicated with anxiety disorders will be included. Two reviewers will independently search and select the studies, extract the data, and assess the risk of bias. We will assess the risk of bias of included RCTs using the Cochrane risk of bias tool. The WinBUGS 1.4.3 software will be used to perform the network meta-analysis, and the result figures will be generated by STATA 15.0 software. In addition, we will use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) to assess the quality of evidence. Results: This study will systematically compare the efficacy and safety of different drugs for bipolar disorder complicated with anxiety disorders. The results of this network meta-analysis will be submitted to a peer-reviewed journal for publication. Conclusion: Our study will provide evidence for the drug therapy of patients with bipolar disorder complicated with anxiety disorders, and provide suggestions for clinical practice or guidelines. INPLASY registration number: INPLASY202070132.

Objective To investigate the preoperative psychological distress in the primary caregivers of glioma patients and its influencing factors and to determine the relationship between preoperative psychological states of glioma patients and their caregivers. Methods Using a mixed methods design, the caregivers of patients with malignant glioma were interviewed and completed questionnaires about anxiety/depression and family function during preoperative period. Results Caregivers of glioma patients had different types of psychological distress before surgery. A total of 46 caregivers (36.5 %) had preoperative psychological depression or anxiety symptom; 30 caregivers (23.8 %) had depression symptoms, 39 caregivers (31.0 %) had anxiety symptoms, and 23 (18.3 %) had both preoperative anxiety and depression symptoms. Female gender was an influential factor for both preoperative depression and anxiety symptoms in caregivers, surgical information was a risk factor for caregivers' preoperative depression symptoms and residence was a risk factor for caregivers' preoperative anxiety symptoms. The preoperative psychological states of patients was positively correlated with the preoperative anxiety and depression symptoms of caregivers. Conclusion The rural female caregivers are more likely to experience psychological distress before surgery, and the preoperative psychological states of patients was positively correlated with the psychological distress in caregivers.

Drugs that are specifically efficacious against SARS-CoV-2 have yet to be established. Chloroquine and hydroxychloroquine have garnered considerable attention for their potential to treat coronavirus disease 2019 (COVID-19). Increasing evidence obtained from completed clinical studies indicates the prospects for chloroquine/hydroxychloroquine to treat COVID-19. More randomized control clinical studies are warranted to determine the feasibility of these two drugs in treating COVID-19.

Metarhizium robertsii is a fungus with two lifestyles; it is a plant root symbiont and an insect pathogen. A spontaneously phenotypically degenerated strain of M. robertsii strain ARSEF 2575 (M. robertsii lc-2575; lc = low conidiation) showed a reduction in conidiation and fungal virulence after successive subculturing on agar medium. In order to recover conidiation, we experimentally passaged M. robertsii lc-2575 through plant (soldier bean and switchgrass) root or insect (Galleria mellonella) larvae. After five passages, the resultant strains had significantly increased conidial yields on agar and increased virulence in insect bioassays. Concomitantly, DNA methyltransferase, MrDIM-2 expression was downregulated in BR5 (a strain after 5 bean root passages) and isolates after switchgrass and insect passages. Bisulfite sequencing showed little difference in overall genomic DNA methylation levels (~ 0.37%) between M. robertsii lc-2575 and BR5. However, a finer comparison of the different methylated regions (DMRs) showed that DMRs of BR5 were more abundant in the intergenic regions (69.32%) compared with that of M. robertsii lc-2575 (33.33%). The addition of DNA methyltransferase inhibitor, 5-azacytidine, to agar supported the role of DNA methyltransferases and resulted in an increase in conidiation of M. robertsii lc-2575. Differential gene expression was observed in selected DMRs in BR5 when compared with M. robertsii lc-2575. Here we implicated epigenetic regulation in the recovery of conidiation through the effects of DNA methyltransferase and that plant passage could be used as a method to recover fungal conidiation and virulence in a phenotypically degenerated M. robertsii. KEY POINTS: • Passage of Metarhizium through plant root or insect results in increased conidiation. • DNA methyltransferase is downregulated after host passage. • Bisulfite sequencing identified potentially methylated genes involved in conidiation.

Intravenous leiomyomatosis (IVL) is a rare neoplasm that is characterized by smooth muscle cell proliferation within venous vessels. The aim of this study is to investigate the clinicopathological features, immunophenotypes, and MED12 gene mutations in IVL. Nine cases of IVL from the Affiliated Hospital of Qingdao University were collected, and the clinicopathological features were reviewed. The immunohistochemical expressions of p16, phosphatase and tensin homolog deleted on chromosome 10 (PTEN), alpha thalassemia/mental retardation syndrome X-linked (ATRX), retinoblastoma 1 (RB1), fumarate hydratase (FH), and p53, were evaluated. The mutation status of MED12 gene exon 2 was detected by Sanger sequencing. All the 9 patients were women ranging from 32 to 58 years, and uterine leiomyomas were identified in 5 patients. Immunohistochemical staining showed that all IVL and leiomyoma samples were positive for estrogen receptor and progesterone receptor, but negative for CD34. IVL displayed similar immunostaining patterns with their uterine counterparts with focal p16 immunostaining. FH, PTEN, ATRX, and RB1 were variably positive, and p53 and Ki-67 positive rates were less than 5% in all cases. Two novel genetic variations at MED12 exon 2, a synonymous mutation c.141C>T (p.Asn47=), and an in-frame deletion mutation c.133_147del15 (p.Phe45_Pro49del) were identified in two IVL cases. One missense mutation c.131G>A (p.Gly44Asp) was identified in one uterine leiomyoma. The remaining 11 tumor samples (7 IVL cases and 4 uterine leiomyomas) showed no mutations at MED12 exon 2. Our results showed two novel MED12 mutations in IVL. The MED12 mutations are different between IVL and uterine leiomyoma. These findings indicate that IVL is a unique entity and different from uterine leiomyoma.

Cancer is a major public health issue in China, and effective anticancer drugs remain a huge unmet need. Generic drugs have long been the main products of pharmaceutical companies in China. In this decade, research on and development of innovative drugs has greatly advanced thanks to policy reforms and economic growth. Five innovative anticancer drugs - anlotinib, pyrotinib, fruquintinib, sintilimab, and toripalimab - that were developed by Chinese domestic pharmaceutical companies were approved by the National Medical Products Administration (NMPA) of China in 2018. Several novel anticancer drugs such as avitinib, flumatinib, zanubrutinib, and ensartinib may also receive approval for marketing in China in the near future. There are unprecedented opportunities for development of innovative drugs in China. In the future, innovative drug development in China is poised to shift from "me too" or "me better" drugs to "first-in-class" or "best-in-class" drugs.

Background : Post-stroke insomnia (PSI) is a serious problem which has significant adverse effects on the subsequent recovery of patients and the quality of their daily life. Massage is effective in improving the quality of sleep for stroke patients displaying no significant adverse reactions. Up to now, however, there are still no systematic studies conducted to provide compelling evidence for its effectiveness in treating PSI. Allowing for this, this project is purposed to make a thorough summary of the efficacy of massage therapy in treating PSI and the safety of this practice. Methods : Without considering the status of publication and language, a meticulous search will be conducted, covering the Web of Science, the Cochrane Library search, PubMed, EMBASE, Chinese biomedical literature database, Chongqing VIP Database for Chinese Technical Periodicals, China National Knowledge Infrastructure, and Wanfang. All randomized controlled trials of PSI will be retrieved. The deadline is set as October 23, 2020. The team will be comprised of 2 experienced researchers who will apply RevMan V.5.3 software to conduct literature selection, data collection, data analysis, and data synthesis, respectively. In addition, the Cochrane risk Assessment tool will be taken as the top choice to evaluate the quality of the trials involved in this study. Results : The effectiveness and safety of massage therapy intended for PSI will be subject to a systematic evaluation under this program. Conclusion : It will be substantiated in this review whether massage therapy is a reliable intervention for PSI by examining the evidence collected.

Middle East respiratory syndrome coronavirus (MERS-Co V) is a RNA virus causing serious harm to people. In order to investigate the codon usage characteristics and influence factors, codon preference and multivariate statistical analysis of MERS-Co V 9 gene sequences were performed by using Codon W, CUSP and SPSS software, getting the content of GC at three positions of codons, ENC (Effective number of codon)and RSCU(Relative synonymous codon usage)of all genes. In addition, the results were compared with Escherichia coli, yeast and human’s codon usage frequency. The results showed that GC3 content is significantly lower than GC1 and GC2content,and less than 50%.It indicates that the third position of codons prefers to A or T.ENC value is 50.59,which implies codon usage bias is a little slight in MERS-Co V genome. According to the neutral drawing analysis and ENC-plot analysis, codon bias is mainly affected by selection pressure in the MERS-Co V genome. It is found that codon usage frequency of MERS-Co V is more close to yeast, compared with other three kinds of biological codon usage frequency.Finally,19 codons are defined as the major preference codons in MERS-Co V. The results have a certain significance for MERS-Co V that selecting gene expression host system, contributing further to development of genetically engineered vaccine and therapeutic antibody.

MicroRNAs (miRNAs/miRs) offer great potential as biomarkers for the early detection and prognosis of cancer, and the discovery of miRNAs associated with gastric cancer is required. In the present study, the differences in the plasma expression levels of miR-141 between patients with gastric cancer and healthy controls, and the role of miR-141 in gastric cancer cell oncogenesis were investigated. A follow-up study of 164 patients with gastric cancer who underwent tumor resection was conducted, and comparisons with healthy control subjects were drawn. To investigate the biological functions of miR-141, a series of in vitro and in vivo assays were conducted, including proliferation, wound-healing and Transwell assays, and a xenograft tumor model. The results demonstrated that miR-141 expression was significantly decreased in tumor tissues compared with in healthy tissues (P

Clinical manifestation and survival rates published by different countries since 2008. (DOCX 19 kb)

Clinical manifestation and survival rates published by different countries since 2008. (DOCX 19 kb)

Figure S1. Survival analysis based on respiratory symptoms. Figure S2. Survival analysis based on organ involvement. (DOCX 550 kb)

Objective To investigate the effects and mechanisms of action of auricular electroacupuncture (AEA) on visceral pain induced by colorectal distension (CRD). Methods Twenty-nine female Sprague-Dawley rats were randomly divided into four groups: control; untreated CRD; CRD+AEA; and CRD+sham electroacupuncture (SEA). An electromyogram (EMG) was recorded for 120 min in the conscious state. After a 30 min baseline recording, CRD was performed in untreated CRD, AEA and SEA groups and lasted for 90 min. AEA and SEA were started at 30 min and lasted for 30 min. The EMG was recorded and analysed to evaluate the severity of visceral pain, indicated by the magnitude of the vasomotor response (VMR). mRNA expression of the 5-hydroxytryptamine 1a (5-HT1a) receptor was measured separately in the colon and raphe nuclei using real-time fluorescent quantitative PCR. Results No differences were seen in the baseline EMG among the four groups (p>0.05). During pre-stimulation, VMR magnitude in the CRD, AEA and SEA groups increased compared with that in the control group (p1a receptor in both the colon and raphe nuclei was lower in AEA but not SEA groups compared with the CRD group (pConclusions AEA can ameliorate CRD-induced visceral pain in rats, and increase mRNA expression of the 5-HT1a receptor peripherally (in the colon) and centrally (in the raphe nuclei), suggesting a serotonergic mechanism of action.

Background: Matrix metalloproteinase-2 (MMP-2), a member of the zinc-dependent metalloproteinase gene family, plays a vital role in cancer invasion, metastasis, and progression. This systematic review and meta-analysis aims to explore the clinical significance of MMP-2 expression in endometrial cancer. Methods: PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure databases were systematically searched up to September 30, 2017, supplemented by manual searches of bibliographies. Two reviewers independently identified articles, extracted data, assessed quality, and cross-checked the results. Meta-analysis was conducted to explore the difference in the positive rate of MMP-2 expression between patients with endometrial cancer and those with endometriosis or normal endometrium, and to investigate the associations of MMP-2 expression with clinicopathologic characteristics of patients with endometrial cancer. Weighted mean differences and risk ratios (RRs) with 95% confidence interval (CI) were calculated for continuous and dichotomous variables, respectively. Results: Totally 20 studies were selected for this systematic review and meta-analysis. Compared with those with endometriosis or normal endometria, the positive rate of MMP-2 expression is significantly higher in patients with endometrial cancer (RR = 2.31, 95% CI: 1.78–3.00, P