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IntroductionAs a widely used traditional Chinese medicine with hot property, aconite can significantly promote energy metabolism. However, it is unclear whether the gut microbiota and bile acids contribute to the energy metabolism-promoting properties of aconite. The aim of this experiment was to verify whether the energy metabolism-promoting effect of aconite aqueous extract (AA) is related to gut microbiota and bile acid (BA) metabolism.MethodsThe effect of AA on energy metabolism in rats was detected based on body weight, body temperature, and adipose tissue by HE staining and immunohistochemistry. In addition, 16S rRNA high-throughput sequencing and targeted metabolomics were used to detect changes in gut microbiota and BA concentrations, respectively. Antibiotic treatment and fecal microbiota transplantation (FMT) were also performed to demonstrate the importance of gut microbiota.ResultsRats given AA experienced an increase in body temperature, a decrease in body weight, and an increase in BAT (brown adipose tissue) activity and browning of WAT (white adipose tissue). Sequencing analysis and targeted metabolomics indicated that AA modulated gut microbiota and BA metabolism. The energy metabolism promotion of AA was found to be mediated by gut microbiota, as demonstrated through antibiotic treatment and FMT. Moreover, the energy metabolism-promoting effect of aconite is associated with the bile acid receptor TGR5 (Takeda G-protein-coupled receptor 5)-UCP1 (uncoupling protein 1) signaling pathway.ConclusionThe energy metabolism-promoting effect of aconite is associated with gut microbiota and bile acid receptor TGR5-UCP1 signaling.

ObjectivesThis study aimed to compare the efficacy of pulsed radiofrequency (PRF) to dorsal root ganglia (DRG) in treating acute herpetic neuralgia (AHN) and postherpetic neuralgia (PHN) in the thoracic segment.MethodsA total of 243 patients with thoracic herpes zoster-related pain (AHN or PHN) from January 2020 to September 2022 were retrospectively analyzed. They were divided into two groups based on the timing of PRF after herpes zoster onset: an acute herpetic neuralgia group (within 90 days) and a postherpetic neuralgia group (more than 90 days). All patients were treated with PRF at the thoracic DRG. The Visual Analog Scale (VAS), the Athens Insomnia Scale (AIS), the Generalized Anxiety Disorder-7 items (GAD-7), and the Patient Health Questionnaire-9 items (PHQ-9) scores were assessed before and at 1 week, 1 month, 3 months, 6 months, and 12 months after surgery, and the results were then compared between the two groups.ResultsPostoperative scores of VAS, AIS, GAD-7, and PHQ-9 in both groups were significantly lower than preoperative scores (P < 0.001). From 1 month to 12 months after surgery, the AHN group showed significantly lower VAS, AIS, GAD-7, and PHQ-9 scores compared to the PHN group (P < 0.001). In the AHN group, there was a gradual improvement in these scores from 1 week to 12 months post-surgery. Conversely, the PHN group's scores began to worsen slowly from 1 week to 12 months post-surgery. Over time, the difference in scores between the two groups also increased gradually.ConclusionPRF to the DRG is an effective treatment for patients with AHN or PHN who do not respond well to conventional treatments. For AHN patients, PRF to the DRG significantly enhances early pain control, improves sleep and psychological status, and may even prevent the development of PHN.

Gut barrier is not only part of the digestive organ but also an important immunological organ for the hosts. The disruption of gut barrier can lead to various diseases such as obesity and colitis. In recent years, traditional Chinese medicine (TCM) has gained much attention for its rich clinical experiences enriched in thousands of years. After orally taken, TCM can interplay with gut microbiota. On one hand, TCM can modulate the composition and function of gut microbiota. On the other hand, gut microbiota can transform TCM compounds. The gut microbiota metabolites produced during the actions of these interplays exert noticeable pharmacological effects on the host especially gut barrier. Recently, a large number of studies have investigated the repairing and fortifying effects of TCM on gut barriers from the perspective of gut microbiota and its metabolites. However, no review has summarized the mechanism behand this beneficiary effects of TCM. In this review, we first briefly introduce the unique structure and specific function of gut barrier. Then, we summarize the interactions and relationship amidst gut microbiota, gut microbiota metabolites and TCM. Further, we summarize the regulative effects and mechanisms of TCM on gut barrier including physical barrier, chemical barrier, immunological barrier, and microbial barrier. At last, we discuss the effects of TCM on diseases that are associated gut barrier destruction such as ulcerative colitis and type 2 diabetes. Our review can provide insights into TCM, gut barrier and gut microbiota.

According to previous studies, the quality and fertilization rate of fresh sperm from boars of different ages were significantly different. However, the difference of freeze–thaw sperm quality and fertility in boars of different ages is unclear. In this study, boars of a Chinese native breed were assigned into two groups. Each group consisted of five boars aged aged either 2–3 years (young boars = YB) or 5–6 years (aging boars = AB) A total of 60 ejaculates for each group were collected and cryopreserved. Semen quality and in vitro fertility of post-thaw sperm was evaluated. The results showed that the concentration and motility of fresh sperm collected from AB were similar to YB, but their semen volume was higher than that in YB (p

BackgroundEarly neurological deterioration (END) is a frequent complication in patients with perforating artery territory infarction (PAI), leading to poorer outcomes. Therefore, we aimed to apply machine learning (ML) algorithms to predict the occurrence of END in PAI and investigate related risk factors.MethodsThis retrospective study analyzed a cohort of PAI patients, excluding those with severe stenosis of the parent artery. We included demographic characteristics, clinical features, laboratory data, and imaging variables. Recursive feature elimination with cross-validation (RFECV) was performed to identify critical features. Seven ML algorithms, namely logistic regression, random forest, adaptive boosting, gradient boosting decision tree, histogram-based gradient boosting, extreme gradient boosting, and category boosting, were developed to predict END in PAI patients using these critical features. We compared the accuracy of these models in predicting outcomes. Additionally, SHapley Additive exPlanations (SHAP) values were introduced to interpret the optimal model and assess the significance of input features.ResultsThe study enrolled 1,020 PAI patients with a mean age of 60.46 (range 49.11–71.81) years. Of these, 30.39% were women, and 129 (12.65%) experienced END. RFECV selected 13 critical features, including blood urea nitrogen (BUN), total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB), atrial fibrillation, loading dual antiplatelet therapy (DAPT), single antiplatelet therapy (SAPT), argatroban, the basal ganglia, the thalamus, the posterior choroidal arteries, maximal axial infarct diameter (measured at < 15 mm), and stroke subtype. The gradient-boosting decision tree had the highest area under the curve (0.914) among the seven ML algorithms. The SHAP analysis identified apoB as the most significant variable for END.ConclusionOur results suggest that ML algorithms, especially the gradient-boosting decision tree, are effective in predicting the occurrence of END in PAI patients.

BackgroundWe aim to evaluate the global, regional, and national burden of Uterine Cancer (UC) from 1990 to 2019.MethodsWe gathered UC data across 204 countries and regions for the period 1990-2019, utilizing the Global Burden of Disease Database (GBD) 2019 public dataset. Joinpoint regression analysis was employed to pinpoint the year of the most significant changes in global trends. To project the UC trajectory from 2020 to 2044, we applied the Nordpred analysis, extrapolating based on the average trend observed in the data. Furthermore, the Bayesian Age-Period-Cohort (BAPC) model with integrated nested Laplace approximations was implemented to confirm the stability of the Nordpred analysis predictions.ResultsGlobally, the age-standardized rate (ASR) of incidence for UC has increased from 1990 to 2019 with an Average Annual Percentage Change (AAPC) of 0.50%. The ASR for death has declined within the same period (AAPC: -0.8%). An increase in the ASR of incidence was observed across all Socio-demographic Index (SDI) regions, particularly in High SDI regions (AAPC: 1.12%), while the ASR for death decreased in all but the Low SDI regions. Over the past 30 years, the highest incidence rate was observed in individuals aged 55-59 (AAPC: 0.76%). Among 204 countries and regions, there was an increase in the ASR of incidence in 165 countries and an increase in the ASR of deaths in 77 countries. Our projections suggest that both the incidence and death rates for UC are likely to continue their decline from 2020 to 2044.ConclusionsUC has significantly impacted global health negatively, with its influence stemming from a range of factors including geographical location, age-related and racial disparities, and SDI.

Objective:This study aimed to explore the signal detection method for allergic reactions induced by inpatient iodixanol injection.Methods:A database of 3,719,217 hospitalized patients from 20 large Chinese general hospitals was processed and analyzed using the prescription sequence symmetry analysis (PSSA) method.Results:126,680 inpatients who used iodixanol and were concurrently treated with anti-allergic drugs were analyzed. In the medical records of these patients, only 32 had documented iodixanol allergies. Statistical analysis identified 22 drugs in 4 categories—calcium preparations, adrenergic/dopaminergic agents, glucocorticoids, and antihistamines—as marker drugs. With time intervals of 3, 7, and 28 days, the adjusted sequence ratios (aSRs) for all anti-allergics and the 4 categories were greater than 1. The 7-day aSRs were 2.12 (95% CI: 2.08–2.15), 1.70 (95% CI: 1.68–1.73), 3.85 (95% confidence interval [CI]: 3.75–2.30), 2.30 (95% CI: 2.26–2.35), and 1.95 (95% CI: 1.89–2.02), respectively. The proportions of adverse drug events indicated by each signal were as follows: all anti-allergics (2.92%–3%), calcium gluconate (0.19%–0.52%), adrenergic/dopaminergic agents (2.20%–3.37%), glucocorticoids (3.13%–3.76%), and antihistamines (1.05%–1.32%).Conclusion:This first multi-center Chinese inpatient database study detected iodixanol-induced allergy signals, revealing that reactions may be much higher than those in collected spontaneous reports. Iodixanol risk exposure was closer to actual pharmaceutical care findings. PSSA application with ≤7-day intervals appears better suited for monitoring late allergic reaction signals with these drugs.

Identifying polyphenotype genes that simultaneously regulate important agronomic traits (e.g., plant height, yield, and disease resistance) is critical for developing novel high-quality crop varieties. Predicting the associations between genes and traits requires the organization and analysis of multi-dimensional scientific data. The existing methods for establishing the relationships between genomic data and phenotypic data can only elucidate the associations between genes and individual traits. However, there are relatively few methods for detecting elite polyphenotype genes. In this study, a knowledge graph for traits regulating-genes was constructed by collecting data from the PubMed database and eight other databases related to the staple food crops rice, maize, and wheat as well as the model plant Arabidopsis thaliana. On the basis of the knowledge graph, a model for predicting traits regulating-genes was constructed by combining the data attributes of the gene nodes and the topological relationship attributes of the gene nodes. Additionally, a scoring method for predicting the genes regulating specific traits was developed to screen for elite polyphenotype genes. A total of 125,591 nodes and 547,224 semantic relationships were included in the knowledge graph. The accuracy of the knowledge graph-based model for predicting traits regulating-genes was 0.89, the precision rate was 0.91, the recall rate was 0.96, and the F1 value was 0.94. Moreover, 4,447 polyphenotype genes for 31 trait combinations were identified, among which the rice polyphenotype gene IPA1 and the A. thaliana polyphenotype gene CUC2 were verified via a literature search. Furthermore, the wheat gene TraesCS5A02G275900 was revealed as a potential polyphenotype gene that will need to be further characterized. Meanwhile, the result of venn diagram analysis between the polyphenotype gene datasets (consists of genes that are predicted by our model) and the transcriptome gene datasets (consists of genes that were differential expression in response to disease, drought or salt) showed approximately 70% and 54% polyphenotype genes were identified in the transcriptome datasets of Arabidopsis and rice, respectively. The application of the model driven by knowledge graph for predicting traits regulating-genes represents a novel method for detecting elite polyphenotype genes.

AimThis research aimed to explore the causal impact of blood metabolites on oral cancer using a two-sample Mendelian randomization (MR) analysis. The study endeavored to identify potential biomarkers for oral cancer’s clinical management.Materials and methodsBased on the large individual-level datasets from UK Biobank as well as GWAS summary datasets, we first constructed genetic risk scores (GRSs) of 486 human blood metabolites and evaluated the effect on oral cancer. Various statistical methods, including inverse variance weighted (IVW), MR-Egger, and weighted median, among others, were employed to analyze the potential causal relationship between blood metabolites and oral cancer. The sensitivity analyses were conducted using Cochran’s Q tests, funnel plots, leave-one-out analyses, and MR-Egger intercept tests.Results29 metabolites met the stringent selection criteria. Out of these, 14 metabolites demonstrated a positive association with oral cancer risk, while 15 metabolites indicated a protective effect against oral cancer. The IVW-derived estimates were significant, and the results were consistent across different statistical methodologies. Both the Cochran Q test and the MR-Egger intercept test indicated no heterogeneity and pleiotropy.ConclusionThis MR study offers evidence of the role specific blood metabolites play in oral cancer, pinpointing several with potential risk or protective effects. These findings could be helpful for new diagnostic tools and treatments for oral cancer. While the results are promising, additional research is necessary to fully validate and refine these conclusions. This study serves as a foundational step towards more comprehensive understandings in the future.

BackgroundSarcopenia, a progressive loss of skeletal muscle mass and strength, needs to initially prevent in the twenties. Meanwhile, there is a lack of research on the effects of fat consumption on skeletal muscle mass and strength in adults aged 20–59. We aimed to assess associations between dietary fat intake and skeletal muscle mass, as measured by appendicular lean mass adjusted for body mass index (ALMBMI), and muscle strength, as represented by handgrip strength adjusted for body mass index (GSMAXBMI), among adults aged 20–59.MethodsDietary fat intake per kilogram of actual body weight was assessed using two 24h recalls, while ALM and GSMAX were measured using DXA and a handgrip dynamometer, respectively. A weighted multiple linear regression model was employed to analyze the association between dietary fat intake and skeletal muscle mass, utilizing data from the National Health and Nutrition Examination Survey spanning from 2011 to 2014. To assess the non-linear relationship and saturation value between dietary fat intake and skeletal muscle mass, a smooth curve fitting approach and a saturation effect analysis model were utilized.ResultsThe study comprised a total of 5356 subjects. After adjusting for confounding factors, there was a positive association observed between dietary fat intake and ALMBMI as well as GSMAXBMI. The relationship between dietary fat intake and ALMBMI showed an inverted U-shaped curve, as did the association with GSMAXBMI. Turning points were observed at 1.88 g/kg/d for total fat intake and ALMBMI, as well as at 1.64 g/kg/d for total fat intake and GSMAXBMI. Furthermore, turning points were still evident when stratifying by gender, age, protein intake, and physical activity. The turning points were lower in individuals with low protein intake(

Due to significant influence on the safety of marine structures, the interaction between extreme waves and structures is a crucial area of study in marine science. This paper focus on the verification of a solitary wave meshless SPH model and the application of the model on the interaction between solitary waves and semi-submersible structures. A solitary wave propagation model is established based on the SPH method combined with Rayleigh solitary wave theory, quintic kernel function, artificial viscosity, and Symplectic Method. The accuracy of the model is validated by comparing the calculated wave height with the theoretical value. The calculated results with relative particle spacing H0/d0 ≥ 20 are in good agreement with the analytical solution. The simulated solitary wave is also quite stable with a maximum L2 error 0.016. Therefore, the proposed SPH model can accurately simulate the propagation of the solitary waves. A case study on the interaction between solitary waves and semi-submersible platforms is conducted. The results show that the interaction between solitary waves and semi-submersible causes two double peaks with wave heights of 0.398 m and 0.410 m, respectively, induced by overtopping at the center of the platform. The wave transmission coefficient Kt is 0.880 due to that the solitary wave height reduces from 0.498 m to 0.438 m after the solitary wave propagates through the semi-submersible structure. In addition, the solitary wave induces significant vertical wave loads of the structure with a load amplitude of 0.688, while horizontal wave loads are relatively small with a load amplitude of 0.089. The solitary wave arrived the structure induces the upstream and downstream overtopping and forms a hydraulic jump leading to the complex flow field. The maximum velocity at the top and bottom of the structure is 2.2 m/s and 0.8 m/s respectively. Positive or negative vortex are formed at the bottom of the leading edge, top and downstream of the structure with the maximum intensity 28 s-1 and -40 s-1. In a word, the meshless SPH model can conveniently and accurately simulate the propagation of the solitary waves, and be applied to the investigation of the wave height, velocity, vorticity, wave load, and wave breaking of the interaction between solitary waves and structures in ocean engineering.

Long noncoding RNAs (lncRNAs) were important regulators affecting the cellular reprogramming process. Previous studies from our group have demonstrated that small molecule compounds can induce goat ear fibroblasts to reprogram into mammary epithelial cells with lactation function. In this study, we used lncRNA-Sequencing (lncRNA-seq) to analyze the lncRNA expression profile of cells before and after reprogramming (CK vs. 5i8 d). The results showed that a total of 3,970 candidate differential lncRNAs were detected, 1,170 annotated and 2,800 new lncRNAs. Compared to 0 d cells, 738 lncRNAs were significantly upregulated and 550 were significantly downregulated in 8 d cells. Heat maps of lncrnas and target genes with significant differences showed that the fate of cell lineages changed. Functional enrichment analysis revealed that these differently expressed (DE) lncRNAs target genes were mainly involved in signaling pathways related to reprogramming and mammary gland development, such as the Wnt signaling pathway, PI3K-Akt signaling pathway, arginine and proline metabolism, ECM-receptor interaction, and MAPK signaling pathway. The accuracy of sequencing was verified by real-time fluorescence quantification (RT-qPCR) of lncRNAs and key candidate genes, and it was also demonstrated that the phenotype and genes of the cells were changed. Therefore, this study offers a foundation for explaining the molecular mechanisms of lncRNAs in chemically induced mammary epithelial cells.

BackgroundSchizophrenia (SCZ) is a serious chronic mental disorder. Our previous case–control genetic association study has shown that microRNA-137 (miR-137) may only protect females against SCZ. Since estrogen, an important female sex hormone, exerts neuroprotective effects, the relationship between estrogen and miR-137 in the pathophysiology of SCZ was further studied in this study.MethodsGenotyping of single-nucleotide polymorphism rs1625579 of miR-137 gene in 1,004 SCZ patients and 896 healthy controls was conducted using the iMLDR assay. The effect of estradiol (E2) on the miR-137 expression was evaluated on the human mammary adenocarcinoma cell line (MCF-7) and the mouse hippocampal neuron cell line (HT22). The relationships between serum E2, prolactin (PRL), and peripheral blood miR-137 were investigated in 41 SCZ patients and 43 healthy controls. The miR-137 and other reference miRNAs were detected by real-time fluorescent quantitative reverse transcription-PCR.ResultsBased on the well-known SNP rs1625579, the distributions of protective genotypes and alleles of the miR-137 gene were not different between patients and healthy controls but were marginally significantly lower in female patients. E2 upregulated the expression of miR-137 to 2.83 and 1.81 times in MCF-7 and HT22 cells, respectively. Both serum E2 and blood miR-137 were significantly decreased or downregulated in SCZ patients, but they lacked expected positive correlations with each other in both patients and controls. When stratified by sex, blood miR-137 was negatively correlated with serum E2 in female patients. On the other hand, serum PRL was significantly increased in SCZ patients, and the female patients had the highest serum PRL level and a negative correlation between serum PRL and blood miR-137.ConclusionThe plausible SCZ-protective effect of miR-137 may be female specific, of which the underlying mechanism may be that E2 upregulates the expression of miR-137. This protective mechanism may also be abrogated by elevated PRL in female patients. These preliminary findings suggest a new genetic/environmental interaction mechanism for E2/miR-137 to protect normal females against SCZ and a novel E2/PRL/miR-137-related pathophysiology of female SCZ, implying some new antipsychotic ways for female patients in future.

Objective: To explore the risk factors of postpartum hemorrhage (PPH) in patients with pernicious placenta previa (PPP) and to develop and validate a clinical and imaging-based predictive model.Methods: A retrospective analysis was conducted on patients diagnosed surgically and pathologically with PPP between January 2018 and June 2022. All patients underwent PPP magnetic resonance imaging (MRI) and ultrasound scoring in the second trimester and before delivery, and were categorized into two groups according to PPH occurrence. The total imaging score and sub-item prediction models of the MRI risk score/ultrasound score were used to construct Models A and B/Models C and D. Models E and F were the total scores of the MRI combined with the ultrasound risk and sub-item prediction model scores. Model G was based on the subscores of MRI and ultrasound with the introduction of clinical data. Univariate logistic regression analysis and the logical least absolute shrinkage and selection operator (LASSO) model were used to construct models. The receiver operating characteristic curve andision curve analysis (DCA) were drawn, and the model with the strongest predictive ability and the best clinical effect was selected to construct a nomogram. Internal sampling was used to verify the prediction model’s consistency.Results: 158 patients were included and the predictive power and clinical benefit of Models B and D were better than those of Models A and C. The results of the area under the curve of Models B, D, E, F, and G showed that Model G was the best, which could reach 0.93. Compared with Model F, age, vaginal hemorrhage during pregnancy, and amniotic fluid volume were independent risk factors for PPH in patients with PPP (p < 0.05). We plotted the DCA of Models B, D, E, F, and G, which showed that Model G had better clinical benefits and that the slope of the calibration curve of Model G was approximately 45°.Conclusion: LASSO regression nomogram based on clinical risk factors and multiple conventional ultrasound plus MRI signs has a certain guiding significance for the personalized prediction of PPH in patients with PPP before delivery.

Introduction: The plasticity of cell identity allows cellular reprogramming that manipulates the lineage of cells to generate the target cell types, bringing new avenues for disease modeling and autologous tailored cell therapy. Previously, we had already successfully established a technical platform for inducing fibroblast reprogramming to chemically induced mammary epithelial cells (CiMECs) by small-molecule compounds. However, exactly how the molecular mechanism driving the lineage conversion remains unknown.Methods: We employ the RNA-sequencing technology to investigate the transcriptome event during the reprogramming process and reveal the molecular mechanisms for the fate acquisition of mammary lineage.Results: The multi-step reprogramming process first overcomes multiple barriers, including the inhibition of mesenchymal characteristics, pro-inflammatory and cell death signals, and then enters an intermediate plastic state. Subsequently, the hormone and mammary development genes were rapidly activated, leading to the acquisition of the mammary program together with upregulation of the milk protein synthesis signal. Moreover, the gene network analyses reveal the potential relationship between the TGF-β signaling pathway to mammary lineage activation, and the changes in the expression of these genes may play important roles in coordinating the reprogramming process.Conclusion: Together, these findings provide critical insights into the molecular route and mechanism triggered by small-molecule compounds that induce fibroblast reprogramming into the fate of mammary epithelial cells, and they also laid a foundation for the subsequent research on the development and differentiation of mammary epithelial cells and lactation.

PurposeTo evaluate the diagnostic efficacy of CapitalBio Mycobacterium real-time polymerase chain reaction assay (CapitalBio test) in spinal tuberculosis (STB). The value of histopathology combined with the CapitalBio test in diagnosing STB was also assessed.MethodsWe retrospectively analyzed the medical information of suspected STB. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of histopathology, CapitalBio test, and histopathology combined with CapitalBio test were calculated to evaluate their diagnostic efficacy compared with a composite reference standard.ResultsA total of 222 suspected STB patients were included in the study. The sensitivity, specificity, PPV, NPV, and AUC of histopathology for STB were recorded to be 62.0, 98.0, 97.4, 68.3%, and 0.80, respectively. The sensitivity, specificity, PPV, NPV, and AUC of the CapitalBio test were 75.2, 98.0, 97.9, 76.7%, and 0.87, respectively, while that of histopathology combined with the CapitalBio test was 81.0, 96.0, 96.1, 80.8%, and 0.89, respectively.ConclusionHistopathology and CapitalBio test exhibited high accuracy and are recommended in diagnosing STB. Histopathology combined with the CapitalBio test might give the best efficacy in STB diagnosis.

BackgroundBrain atrophy represents a final common pathway for pathological processes in patients with cerebral small vessel disease (CSVD) and is now recognized as a strong independent predictor of clinical status and progression. The mechanism underlying brain atrophy in patients with CSVD is not yet fully comprehended. This study aims to investigate the association of morphologic features of intracranial distal arteries (A2, M2, P2 and more distal) with different brain structures [gray matter volume (GMV), white matter volume (WMV), and cerebrospinal fluid volume (CSFV)]. Furthermore, we also examined whether a correlation existed between these cerebrovascular characteristics and GMV in different brain regions.MethodA total of 39 participants were eventually enrolled. The morphologic features of intracranial distal arteries based on TOF-MRA were extracted and quantified using the intracranial artery feature extraction technique (iCafe). The brain 3D-T1 images were segmented into gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) using the “Segment” tool in CAT12 for the voxel-based morphometry (VBM) analysis. Univariable and multivariable linear regression models were used to investigate the relationship between these cerebrovascular features and different brain structures. Partial correlation analysis with a one-tailed method was used to evaluate the relationship between these cerebrovascular features and GMV in different brain regions.ResultsOur findings indicate that both distal artery length and density were positively correlated with GM fraction in CSVD patients, regardless of whether univariable or multivariable linear regression analyses were performed. In addition, distal artery length (β = −0.428, p = 0.007) and density (β = −0.337, p = 0.036) were also found to be negative associated with CSF fraction, although this relationship disappeared after adjusting for potential confounders. Additional adjustment for the effect of WMHs volume did not change these results. In subgroup anasysis, we found that participants in the highest distal artery length tertile had significantly higher GM fraction and lower CSF fraction level than participants in the lowest distal artery length tertile. In partial correlation analysis, we also found that these cerebrovascular characteristics associated with regional GMV, especially subcortical nuclear.ConclusionThe morphologic features of intracranial distal arteries, including artery length, density and average tortuosity, measured from 3D-TOF MRA, are associated with generalized or focal atrophy indexes of CSVD.

Introduction: Aconite is a form of traditional Chinese medicine (TCM) that has been widely used to treat diarrhea for thousands of years. However, it is not clear whether the anti-diarrhea role of aconite aqueous extract (AA) is associated with regulation of the gut microbiota or with bile acid (BA) metabolism. This study aimed to confirm whether AA exerts its anti-diarrhea effects by regulating the gut microbiota and BA metabolism.Methods: The therapeutic effect of AA in a mouse model of diarrhea was measured based on analysis of body weight, fecal water content, diarrhea scores, intestinal propulsion rate, colonic pathology, and colonic immunohistochemistry. In addition, 16S rRNA high-throughput sequencing was conducted to analyze the effect of AA on the gut microbiota, and targeted metabolomics was employed to analyze the effect of AA on metabolism of BAs.Results: The results showed that treatment with AA reduced fecal water content and diarrhea scores, inhibited intestinal propulsion rate and pathological changes in the colon, and increased AQP3 and AQP4 content in the colon. In addition, AA was found to be capable of regulating the gut microbiota. Effects included increasing its richness (according to the ACE and Chao1 indices); altering the gut microbiota community structure (PCA, PCoA, and NMDS); increasing the relative abundance of norank_f_Muribaculaceae, Ruminococcus, Lachnospiraceae_NK4A136_group, Prevotellaceae_UCG-001, and norank_f_norank_o_Clostridia_UCG-014; and decreasing the relative abundance of Escherichia-Shigella, unclassified_f_Ruminococcaceae, Ruminococcus_torques_group, and Parasutterella. More importantly, AA significantly increased fecal TCA (a primary BA) and DCA, LCA, GDCA, dehydro-LCA, and 12-keto-LCA (secondary BAs), thus restoring BA homeostasis. Moreover, AA increased the ratios of DCA/CA, DCA/TCA, and LCA/CDCA and decreased the ratios of TLCA/LCA, GLCA/LCA, and TUDCA/UDCA.Conclusion: The anti-diarrhea effect of AA was associated with restoration of the gut microbiota and BA metabolism-related homeostasis. The results of this study provide insights into the application of AA and the treatment of diarrhea.

BackgroundSnail family transcriptional repressor 2 (SNAI2) is a transcription factor that induces epithelial to mesenchymal transition in neoplastic epithelial cells. It is closely related to the progression of various malignancies. However, the significance of SNAI2 in human pan-cancer is still largely unknown.MethodsThe Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE) databases were taken to examine the SNAI2 expression pattern in tissues and cancer cells. The link between SNAI2 gene expression levels and prognosis, as well as immune cell infiltration, was investigated using the Kaplan-Meier technique and Spearman correlation analysis. We also explored the expression and distribution of SNAI2 in various tumor tissues and cells by the THPA (Human Protein Atlas) database. We further investigated the relationship between SNAI2 expression levels and immunotherapy response in various clinical immunotherapy cohorts. Finally, the immunoblot was used to quantify the SNAI2 expression levels, and the proliferative and invasive ability of pancreatic cancer cells was determined by colony formation and transwell assays.ResultsWe discovered heterogeneity in SNAI2 expression in different tumor tissues and cancer cell lines by exploring public datasets. The genomic alteration of SNAI2 existed in most cancers. Also, SNAI2 exhibits prognosis predictive ability in various cancers. SNAI2 was significantly correlated with immune-activated hallmarks, cancer immune cell infiltrations, and immunoregulators. It’s worth noting that SNAI2 expression is significantly related to the effectiveness of clinical immunotherapy. SNAI2 expression was also found to have a high correlation with the DNA mismatch repair (MMR) genes and DNA methylation in many cancers. Finally, the knockdown of SNAI2 significantly weakened the proliferative and invasive ability of pancreatic cancer cells.ConclusionThese findings suggested that SNAI2 could be used as a biomarker in human pan-cancer to detect immune infiltration and poor prognosis, which provides a new idea for cancer treatment.

BackgroundAtractylodes macrocephala Koidz. (AM) is a functional food with strong ant-colitis activity. AM volatile oil (AVO) is the main active ingredient of AM. However, no study has investigated the improvement effect of AVO on ulcerative colitis (UC) and the bioactivity mechanism also remains unknown. Here, we investigated whether AVO has ameliorative activity on acute colitis mice and its mechanism from the perspective of gut microbiota.MethodsAcute UC was induced in C57BL/6 mice by dextran sulfate sodium and treated with the AVO. Body weight, colon length, colon tissue pathology, and so on were assessed. The gut microbiota composition was profiled using 16s rRNA sequencing and global metabolomic profiling of the feces was performed. The results showed that AVO can alleviate bloody diarrhea, colon damage, and colon inflammation in colitis mice. In addition, AVO decreased potentially harmful bacteria (Turicibacter, Parasutterella, and Erysipelatoclostridium) and enriched potentially beneficial bacteria (Enterorhabdus, Parvibacter, and Akkermansia). Metabolomics disclosed that AVO altered gut microbiota metabolism by regulating 56 gut microbiota metabolites involved in 102 KEGG pathways. Among these KEGG pathways, many metabolism pathways play an important role in maintaining intestine homeostasis, such as amino acid metabolism (especially tryptophan metabolism), bile acids metabolism, and retinol metabolism.ConclusionIn conclusion, our study indicated that AVO can be expected as novel prebiotics to treat ulcerative colitis, and modulating the composition and metabolism of gut microbiota may be its pharmacological mechanism.

BackgroundH-type hypertension has a high prevalence in China. However, the association of serum homocysteine levels with 1-year stroke recurrence in patients with acute ischemic stroke (AIS) and H-type hypertension has not been studied.MethodsA prospective cohort study of patients with AIS admitted to hospitals between January and December 2015 in Xi'an, China, was conducted. Serum homocysteine levels, demographic data, and other relevant information were collected from all patients upon admission. Stroke recurrences were routinely tracked at 1, 3, 6, and 12 months after discharge. The blood homocysteine level was studied as a continuous variable and tertiles (T1–T3). A multivariable Cox proportional hazard model and a two-piecewise linear regression model were utilized to evaluate the association and ascertain the threshold effect regarding the serum homocysteine level and 1-year stroke recurrence in patients with AIS and H-type hypertension.ResultsOverall, 951 patients with AIS and H-type hypertension were enrolled, of whom 61.1% were male. After adjusting for confounders, patients in T3 had a significantly increased risk of recurrent stroke within 1 year, compared with those in T1 as the reference (hazard ratio = 2.24, 95% confidence interval: 1.01–4.97, p = 0.047). Curve fitting showed that serum homocysteine levels were positively curvilinearly correlated with 1-year stroke recurrence. Threshold effect analysis showed that an optimal threshold of serum homocysteine level

To identify the genetic characteristics and local adaptation mechanism of the snail Neptunea cumingii in different sea areas of China, specimens from six coastal areas of the Yellow Sea and Bohai Sea were collected. Simplified genome technology was used to study the population genetic structure and genetic diversity level of N. cumingii and to infer the genetic variation pattern of environmental adaptation of this species. In total, 1992 discrete loci with high quality were obtained used for population genomics analysis. The observed heterozygosity was 0.1551–0.1612, and the expected heterozygosity was 0.1064–0.1117. Nucleotide diversity ranged from 0.1120 to 0.1241, and fixation index values ranged from −0.04683 to −0.02041. A total of 330 discrete loci were screened based on two fixation index values and a method associated with environmental factors. Functional annotation showed that the genes of discrete loci were involved in the three major functions of cell composition, biological process, and molecular function, including growth and development and cell metabolism and catalytic activity. These results suggested that different populations of N. cumingii had loci that may be related to local adaptation. The results of this study helped to clarify the level of genetic diversity and the germplasm genetic background of N. cumingii. They also provided information about the genetic mechanism of environmental adaptation of N. cumingii that can be applied to the restoration and management of N. cumingii resources.

The major enzyme encoded by the glucosinolate biosynthetic gene AOP2 is involved in catalyzing the conversion of glucoiberin (GIB) into sinigrin (SIN) in Brassicaceae crops. The AOP2 proteins have previously been identified in several Brassicaceae species, but not in Tumorous stem mustard. As per this research, the five identified members of the AOP2 family from the whole genome of Brassica juncea named BjuAOP2.1-BjuAOP2.5 were found to be evenly distributed on five chromosomes. The subcellular localization results implied that BjuAOP2 proteins were mainly concentrated in the cytoplasm. Phylogenetic analysis of the AOP2 proteins from the sequenced Brassicaceae species in BRAD showed that BjuAOP2 genes were more closely linked to Brassica carinata and Brassica rapa than Arabidopsis. In comparison with other Brassicaceae plants, the BjuAOP2 members were conserved in terms of gene structures, protein sequences, and motifs. The light response and hormone response elements were included in the BjuAOP2 genes’ cis-regulatory elements. The expression pattern of BjuAOP2 genes was influenced by the different stages of development and the type of tissue being examined. The BjuAOP2 proteins were used to perform the heterologous expression experiment. The results showed that all the five BjuAOP2 proteins can catalyze the conversion of GIB to SIN with different catalytic activity. These results provide the basis for further investigation of the functional study of BjuAOP2 in Tumorous stem mustard glucosinolate biosynthesis.

IntroductionTo investigate the major existing occupational hazards and to assess the occupational health risks for ferrous metal foundries (FMFs) in Ningbo, China.MethodsUnified questionnaires were formulated to investigate the information on the basic situations, occupational hazards, and occupational health management for 193 FMFs in Ningbo. Furthermore, we used the semi-quantitative risk assessment model, which was developed by the International Council on Mining and Metals (ICMM), to assess occupational health risks for 59 of 193 the FMFs.ResultsThe casting process of FMFs in Ningbo was mainly divided into sand casting and investment casting, and silica-dust and noise were the major occupational hazards in both sand casting and investment casting foundries. Silica-dust mainly occurred in industries with such work as sand handling, modeling, falling sand, and sand cleaning, with the median of the permissible concentration-time weighted average (PC-TWA) was 0.80, 1.15, 3.52, 0.83 mg/m3, respectively. The noise mainly existed in industries with such work as sand handling, core making, falling sand, sand cleaning, cutting and grinding, and smelting with median of PC-TWA was 81.72 dB(A), 82.93 dB(A), 90.75 dB(A), 80.18 dB(A), 90.05 dB(A), 82.70 dB(A), respectively. In addition, the results of the ICMM assessment model indicated that 100 and 98.7% of the jobs exposed to silica-dust and noise in 59 FMFs have an “intolerable risk” level of risks of causing pneumoconiosis and noise deaf, respectively.DiscussionThe hazard risk of silica-dust and noise is serious for FMFs in Ningbo. It is necessary to supervise enterprises to improve operating environmental conditions, accelerate the reduction of silica-dust and noise exposure risks, and promote the healthy and sustainable development of the foundry industry.

ObjectivesPromoting improvement in Infection Prevention and Control (IPC) is an important part of improving the quality of care. The influence of leadership attention and incentives on the self-perceived continuous improvement in IPC has drawn a lot of attention, but relevant academic research is still lacking. The objective of this study is to explore the effect of leadership attention on self-perceived continuous improvement in IPC among medical staff and its underlying mechanisms.MethodThe 3,512 medical staff from 239 health facilities in Hubei, China, were surveyed online during September 2020. Data on leadership attention, incentives, and improvement in Infection Prevention and Control were collected using self-administered questionnaires. Correlation analysis was used to analyze the relationship between leadership attention, incentives, and improvement in Infection Prevention and Control. Amos 24.0 was used to analyze the mediating role.ResultsThe scores of leadership attention, incentives and self-perceived continuous improvement in Infection Prevention and Control were all high. The score of leadership attention was the highest (4.67 ± 0.59), followed by self-perceived continuous improvement (4.62 ± 0.59) and incentives in Infection Prevention and Control (4.12 ± 0.83). Leadership attention positively affected self-perceived continuous improvement in Infection Prevention and Control (β = 0.85, 95% CI = [0.83, 0.87]). Moreover, incentives partially mediated the effect of leadership attention on self-perceived continuous improvement in Infection Prevention and Control among medical staff (β = 0.13, 95% CI = [0.12, 0.15]).ConclusionLeadership attention positively affects self-perceived continuous improvement in Infection Prevention and Control among medical staff, and incentives mediates this relationship. The present study has valuable implications for self-perceived continuous improvement in Infection Prevention and Control from the perspective of leadership attention and incentives.

Introduction: The molecular regulation mechanism of fat deposition in bovine and its improvement on beef quality are important research directions in the livestock industry. The research of molecular mechanisms that govern the regulation and differentiation of adipocytes may conduct to understand the mechanism of obesity, lipid disorders, and fat deposition. In the recent decade, small-molecule compounds have been widely used in reprogramming and transdifferentiation fields, which can promote the induction efficiency, replace exogenous genes, or even induce cell fate conversion alone. Furthermore, small-molecule compound induction is expected to be a novel approach to generate new cell types from somatic cells in vitro and in vivo.Methods: In this study, we established rapid chemically induced platform for transdifferentiation of bovine ear fibroblasts into adipocyte-like cells using a small-molecule cocktail (Repsox, VPA, TTNPB). The chemically induced adipocytes (CiADCs) were characterized by lipid staining, qRT-PCR and WB. Bovine natural adipocytes were used as positive control, and the expression of adipocyte-related marker genes in CiADCs were analyzed. Moreover, RNA-Seq explore the mechanism of RVB in the regulation of Bovine adipocyte transdifferentiation.Results: In this study, the chemically induced adipocytes (CiADCs) could be identified as early as day 6. The CiADCs appeared to be circular and rich of lipid droplets. The adipocyte-specific genes of LPL, PPARγ, IGF1, GPD1, C/EBPδ, ADIPOQ, PCK2, FAS, C/EBPβ, PPARGC1A, C/EBPα, and CFD were detected to be significantly upregulated in both CiADCs and natural adipocytes. Western blot analysis also confirmed the increase C/EBPα and PPARγ protein level in induced adipocytes (CiADCs-6d) treated with RVB. In addition, we also found that the signaling pathways (PPAR signaling pathway, PI3K-Akt signaling pathway, p53 signaling pathway, MAPK signaling pathway, and ECM-receptor interaction) regulated by the DEGs played a vital role in adipogenesis.Discussion: In the present study, a combination of small-molecule compounds RVB was used to transdifferentiate bovine ear fibroblasts into the chemically-induced adipocyte cells (CiADCs) that have a large number of lipid droplets. Importantly, the small-molecule cocktail significantly shortened the reprogramming turnaround time. The morphology of CiADCs is close to the “ring type” of natural differentiated adipocytes on sixth day. And, the CiADCs showed similar adipocyte-specific gene expression patterns to natural adipocytes. Furthermore, RVB increased protein expression of PPARγ and C/EBPα in the chemically-induced adipocytes (CiADCs-6d). Our findings reveal that the signaling pathways of C/EBPα and PPARγ play pivotal roles in this transdifferentiation process. In addition, we also found that the signaling pathways (PPAR signaling pathway, PI3K-Akt signaling pathway, p53 signaling pathway, MAPK signaling pathway, and ECM-receptor interaction) regulated by the DEGs played a vital role in adipogenesis. In general, this study provides valuable evidence to deepen our understanding of the molecular mechanism of small molecule cocktails in regulating adipogenesis.

BackgroundConcern about the risk of peripheral facial palsy (PFP) following vaccination is one reason for hesitancy in influenza vaccination. However, the association between the flu vaccine and PFP is still controversial, and further evidence is urgently needed.MethodsThis self-controlled case series study evaluated PFP risk following inactivated influenza vaccine in the elderly using a large linked database in Ningbo, China. Relative incidence ratios (RIRs) and 95% confidence intervals (CIs) estimated using conditional Poisson regression were utilized to determine whether the risk of PFP was increased after vaccination.ResultsThis study included 467 episodes, which occurred in 244 females and 220 males. One hundred twenty-four episodes happened within 1–91 days after vaccination, accounting for 26.7%. The adjusted RIRs within 1–30 days, 31–60 days, 61–91 days, and 1–91 days after influenza vaccination were 0.95 (95% CI 0.69–1.30), 1.08 (95% CI 0.78–1.49), 1.01 (95% CI 0.70–1.45), and 1.00 (95% CI 0.81–1.24), respectively. Similar results were found in subgroup analyses and sensitivity analyses.ConclusionsInfluenza vaccination does not increase PFP risk in the elderly population. This finding provides evidence to overcome concerns about facial paralysis after influenza vaccination.

BackgroundWe aimed to analyze the benign and malignant identification efficiency of CA125, HE4, risk of ovarian malignancy algorithm (ROMA), Copenhagen Index (CPH-I) in ovarian neoplasms and establish a nomogram to improve the preoperative evaluation value of ovarian neoplasms.MethodsA total of 3,042 patients with ovarian neoplasms were retrospectively classified according to postoperative pathological diagnosis [benign, n = 2389; epithelial ovarian cancer (EOC), n = 653]. The patients were randomly divided into training and test cohorts at a ratio of 7:3. Using CA125, HE4, ROMA, and CPH-I, Receiver operating characteristic (ROC) curves corresponding to different truncation values were calculated and compared, and optimal truncation values were selected. Clinical and imaging risk factors were calculated using univariate regression, and significant variables were selected for multivariate regression analysis combined with ROMA and CPH-I. Nomograms were constructed to predict the occurrence of EOC, and the accuracy was assessed by external validation.ResultsWhen the cutoff value of CA125, HE4, ROMA, and CPH-I was 100 U/ml, 70 pmol/L, 12.5/14.4% (premenopausal/postmenopausal) and 5%, respectively, the AUC was 0.674, 0.721, 0.750 and 0.769, respectively. From univariate regression, the clinical risk factors were older age, menopausal status, higher birth rate, hypertension, and diabetes; imaging risk factors were multilocular tumors, solid nodules, bilateral tumors, larger tumor diameter, and ascites. The AUC of the nomogram containing ROMA and CPH-I was 0.8914 and 0.9114, respectively, which was better than the prediction accuracies of CA125, HE4, ROMA, and CPH-I alone. The nomogram with CPH-I was significantly better than that with ROMA (P

Recent technological advances in micro-robotics have demonstrated their immense potential for biomedical applications. Emerging micro-robots have versatile sensing systems, flexible locomotion and dexterous manipulation capabilities that can significantly contribute to the healthcare system. Despite the appreciated and tangible benefits of medical micro-robotics, many challenges still remain. Here, we review the major challenges, current trends and significant achievements for developing versatile and intelligent micro-robotics with a focus on applications in early diagnosis and therapeutic interventions. We also consider some recent emerging micro-robotic technologies that employ synthetic biology to support a new generation of living micro-robots. We expect to inspire future development of micro-robots toward clinical translation by identifying the roadblocks that need to be overcome.

The interface-debonding defects of adhesive bonding structures may cause a reduction in bonding strength, which in turn affects the bonding quality of adhesive bonding samples. Hence, defect recognition in adhesive bonding structures is particularly important. In this study, a terahertz (THz) wave was used to analyze bonded structure samples, and a multi-feature fusion convolutional neural network (CNN) was used to identify the defect waveforms. The pooling method of the squeeze-and-excitation (SE) attention mechanism was optimized, defect feature weights were adaptively assigned, and feature fusion was conducted using automatic label net-works to segment the THz waveforms in the adhesive bonding area with fine granularity waveforms as an input to the multi-channel CNN. The results revealed that the speed of the THz waveform labeling with the automatic labeling network was 10 times higher than that with traditional methods, and the defect-recognition accuracy of the defect-recognition network constructed in this study was up to 99.28%. The F1-score was 99.73%, and the lowest pre-embedded defect recognition error rate of the generalization experiment samples was 0.27%.

We reported a general transition metal-free transformation to access C3-carbamoylated 2H-indazoles via visible light-induced oxidative decarboxylation coupling, in the presence of oxamic acids as the coupling sources, 4CzIPN as the photocatalyst, and Cs2CO3 as the base. The great application potential of this mild condition is highlighted by the late-stage modification of drugs, N-terminal modification of peptides, and the good antitumor activity of the novel desired product.

Valproic acid (VPA) exposure during pregnancy leads to a higher risk of autism spectrum disorder (ASD) susceptibility in offspring. Human dorsal forebrain organoids were used to recapitulate course of cortical neurogenesis in the developing human brain. Combining morphological characterization with massive parallel RNA sequencing (RNA-seq) on organoids to analyze the pathogenic effects caused by VPA exposure and critical signaling pathway. We found that VPA exposure in organoids caused a reduction in the size and impairment in the proliferation and expansion of neural progenitor cells (NPCs) in a dose-dependent manner. VPA exposure typically decreased the production of outer radial glia-like cells (oRGs), a subtype of NPCs contributing to mammalian neocortical expansion and delayed their fate toward upper-layer neurons. Transcriptomics analysis revealed that VPA exposure influenced ASD risk gene expression in organoids, which markedly overlapped with irregulated genes in brains or organoids originating from ASD patients. We also identified that VPA-mediated Wnt/β-catenin signaling pathway activation is essential for sustaining cortical neurogenesis and oRGs output. Taken together, our study establishes the use of dorsal forebrain organoids as an effective platform for modeling VPA-induced teratogenic pathways involved in the cortical neurogenesis and oRGs output, which might contribute to ASD pathogenesis in the developing brain.

Tight sandstone gas reservoir of Shaximiao formation in Jinqiu Gas field has the advantages of wide distribution and abundant resources. Due to its low porosity, low permeability and strong spatial heterogeneity, this reservoir puts forward high requirements for sweet spot identification, cluster design and hydraulic fracture morphology prediction. Since the conventional stimulation methods can not meet the requirement of economy, the geological-engineering integration model is established. This optimization model of multiple subjects could layout the relationship among engineering characteristics, hydraulic fracture shape and well productivity. Based on the simulation results, key controlling factors are identified and optimized. And the customized stimulation strategies are recommended for different reservoir quality and different channel sand. Through application of these methods, the average test well productivity in the target field increased from 50,500 cubic meter per day to 434,300 cubic meter per day, and it lay a solid foundation for the efficient development of tight gas in central Sichuan Basin.

As a novel origin of adipocytes, the superficial fascia, a typical soft connective tissue, has abundant adipocytes and preadipocytes, accompanied by numerous mast cells. Blood vessels pass through the fascia to form a network structure. The more reasonable statistical analysis methods can provide a new method for in-depth study of soft connective tissue by clarifying the spatial distribution relation between cells (point structure) and blood vessels (linear structure). This study adopted the Guidolin et al. statistical analysis methods used by epidemiology and ecology to quantitatively analyze the distribution pattern and correlations among blood vessels, adipocytes, and mast cells. Image-processing software and self-written computer programs were used to analyze images of whole-mounted fascia, and the relevant data were measured automatically. Voronoi’s analysis revealed that the vascular network was non-uniformly distributed. In fascia with average area of 3.75 cm2, quantitative histological analysis revealed 81.16% of mast cells and 74.74% of adipocytes distributed within 60 μm of blood vessels. A Spearman’s correlation coefficient (rs) of >0.7 showed the co-distribution of the two types of cells under different areas. Ridge regression analysis further revealed the spatial correlation among blood vessels, adipocytes and mast cells. The combination of classical epidemiological analysis and extended computer program analysis can better analyze the spatial distribution relation between cells and vessels and should provide an effective analysis method for study of the histology and morphology of fascia and related connective tissues.

ObjectiveA 2-dose varicella vaccine immunization strategy has been implemented in many cities in China, but there is few evidence on a long-term evaluation of the efficacy of the 2-dose varicella vaccine from China. This study aims to assess the long-term vaccine efficacy of the two doses varicella vaccine and analysis of its influencing factors.MethodsA retrospective study was carried out in 837,144 children born between 2011 and 2017 in Ningbo, Easten China. The logistic regression was performed to estimate varicella vaccine effectiveness (VE).ResultsThe overall VE of 2 doses of varicella vaccine compared without the vaccine was 90.31% (89.24–91.26%), and the overall incremental VE of 2 doses of varicella vaccine compared to the 1-dose was 64.71% (59.92–68.93%). Moreover, the varicella vaccination age of the second dose and the interval between 2 doses were both associated with VE. The VE compared to that without the vaccine in children vaccinated at

Mammary epithelial cells are the only cells of mammary glands with lactation capacity. They are closely related to mammary development and milk yield. Our earlier studies showed that the transformation of goat fibroblasts into induced mammary epithelial cells (iMECs) was closely correlated with SMAD3 overexpression. Therefore, we further explored the role of SMAD3 on iMECs reprogramming in this study. The SMAD3 gene was overexpressed in goat ear fibroblasts using the tetracycline-induced expression method. The outcomes demonstrated that goat ear fibroblasts can be converted into iMECs by overexpressing the SMAD3 gene. In contrast, it was discovered that SMAD3 downregulation by RNA interference significantly decrease the reprogramming efficiency of iMECs. These results show that SMAD3 plays a key regulatory role in the reprogramming of iMECs. Surprisingly, we also found a parabolic relationship between SMAD3 expression level and iMECs reprogramming efficiency, and that the reprogramming efficiency was maximum when the addition of doxycycline concentration was 5 μg/ml. In light of this, our findings may offer new perspectives on the regulatory mechanism governing mammary epithelial cell fate in goats as well as a fresh approach to studying mammary development and differentiation in vitro.

BackgroundNomogram, a visual clinical predictive model, provides a scientific basis for clinical decision making. Herein, we investigated 20 years of nomogram research responses, focusing on current and future trends and analytical challenges.MethodsWe mined data of scientific literature from the Core Collection of Web of Science, searching for the original articles with title “Nomogram*/Parton Table*/Parton Nomogram*”, published within January 1st, 2000 to December 30th, 2021. Data records were validated using HistCite Version and analyzed with a transformable statistical method, the Bibliometrix 3.0 package of R Studio.ResultsIn total, 4,176 original articles written by 19,158 authors were included from 915 sources. Annually, Nomogram publications are continually produced, which have rapidly grown since 2018. China published the most articles; however, its total citations ranked second after the United States. Both total citations and average article citations in the United States rank first globally, and a high degree of cooperation exists between countries. Frontiers in Oncology published the most papers (238); this number has grown rapidly since 2019. Journal of Urology had the highest H-index, with an average increase in publications over the past 20 years. Most research topics were tumor-related, among which tumor risk prediction and prognostic evaluation were the main contents. Research on prognostic assessment is more published and advanced, while risk prediction and diagnosis have good developmental prospects. Furthermore, nomogram of the urinary system has been highly developed. Following advancements in nomogram modeling, it has recently been applied to non-oncological subjects.ConclusionThis bibliometric analysis provides a comprehensive overview of the current nomogram status, which could enable better understanding of its development over the years, and provide global researchers a comprehensive analysis and structured information to help identify hot spots and gaps in future research.

Diabetic cardiomyopathy (DCM) is a prevalent complication in patients with diabetes, resulting in high morbidity and mortality. However, the molecular mechanisms of diabetic cardiomyopathy have yet to be fully elucidated. In this study, we investigated a novel target, NOX1, an isoform of superoxide-producing NADPH oxidase with key functional involvement in the pathophysiology of DCM. The DCM rat model was established by a high-fat diet combined with streptozotocin injections. DCM rats elicited myocardial fibrosis exacerbation, which was accompanied by a marked elevation of NOX1 expression in cardiac tissue. In particular, a specific NOX1 inhibitor, ML171, effectively decreased myocardial fibrosis and protected against cardiac dysfunction in DCM rats. Rat neonatal cardiac fibroblasts were incubated with high glucose (HG, 33 mM) as an in vitro model of DCM. We also observed that the expression of NOX1 was upregulated in HG-cultured cardiac fibroblasts. Silencing of NOX1 was found to attenuate myocardial fibrosis and oxidative stress in HG-induced cardiac fibroblasts. Furthermore, the upregulation of NOX1 by hyperglycemia induced activation of the TLR2/NF-κB pathway both in vitro and in vivo, whereas these effects were significantly attenuated with NOX1 gene silencing and further enhanced with NOX1 gene overexpression. In summary, we demonstrated that NOX1 induced activation of the TLR2/NF-κB pathway and increased reactive oxygen species production accumulation, which ultimately increased myocardial fibrosis and deteriorated cardiac function in diabetic cardiomyopathy. Our study revealed that NOX1 was a potential therapeutic target for DCM.

Background: Due to limited time windows and technical requirements, only a small percentage of patients can receive reperfusion therapy for acute ischemic stroke (AIS). Previous studies have shown that LongShengZhi (LSZ) capsule can improve neurological outcomes in patients after AIS, yet those results have not been finally verified through rigorous randomized controlled trials. Thus, this trial was designed to further clarify the efficacy and safety of LSZ capsule for patients with AIS.Methods: LSZ capsule on Functional Recovery after Acute Ischemic Stroke (LONGAN) trial is a prospective, multicenter, randomized, placebo-controlled, double-blind, parallel-group, superiority trial that enrolls patients from stroke and rehabilitation units in China. We will enroll 1,376 patients aged 18 years or older with AIS within 7 days of symptom onset and a National Institute of Health Stroke Scale (NIHSS) score of 4–15. Eligible patients will be randomized to receive either 2 g LSZ capsules three times a day or placebo LSZ capsules for 90 days. The primary outcome is the proportion of patients with favorable outcomes, as measured by the modified Rankin Scale (mRS) 90 days after randomization. The main safety outcome is the proportion of severe adverse events.Conclusion: This study will be the first randomized, double-blind trial to evaluate the efficacy and safety of LSZ capsule in patients with AIS. In order to improve the transparency and reproducibility of the trial, the data will be analyzed in accordance with this pre-specified plan for statistical analysis to reduce bias due to selective analysis and reporting. This trial aims to provide high-quality evidence for the efficacy and safety of LSZ capsule for AIS.

Background: Pernicious placenta previa (PPP) is one of the most dangerous complications in pregnancy after cesarean section, with high perinatal mortality. This study aimed to develop a nomogram to predict postpartum hemorrhage in patients with PPP.Methods: A total of 246 patients with confirmed PPP at Shengjing Hospital of China Medical University from January 2018 to December 2021 were included. Patients were divided into to two cohorts depending on a postpartum blood loss of > 1000 ml (n = 146) or ≤ 1000 ml (n = 100). Lasso regression analysis was performed on the risk factors screened by univariate analysis to screen out the final risk factors affecting postpartum hemorrhage. Based on the final risk factors, a Nomogram prediction model with excellent performance was constructed using Logistic regression. A nomogram was constructed with further screening of the selected risk factors of postpartum hemorrhage in PPP. A second nomogram based only on the total ultrasonic risk score was constructed. Decision curve analysis (DCA) was used to evaluate the clinical efficacy of the nomograms.Results: Older age, larger gestational age, larger neonatal birth weight, presence of gestational diabetes mellitus, larger amniotic fluid index, absence of gestational bleeding, and higher ultrasonic risk single score were selected to establish a nomogram for postpartum hemorrhage in PPP. The area under the curve of the nomogram constructed by Lasso regression analysis was higher than that of the ultrasonic total score alone (0.887 vs. 0.833). Additionally, DCA indicated better clinical efficacy in the former nomogram than in the later nomogram. Furthermore, internal verification of the nomogram constructed by Lasso regression analysis showed good agreement between predicted and actual values.Conclusion: A nomogram for postpartum hemorrhage in PPP was developed and validated to assist clinicians in evaluating postpartum hemorrhage. This nomogram was more accurate than using the ultrasonic score alone.

To better understand the ensiling characteristics of sorghum stalk, the dynamic changes of fermentation parameters, nutrient components and bacterial community of sorghum stalk silage were analyzed by intermittently sampling on day 0, 1, 3, 7, 14, 28, and 56 of ensiling duration. The results showed that high-moisture sorghum stalk was well preserved during ensiling fermentation, with the DM loss of 4.10% and the little difference between the nutrients of sorghum stalk before and after ensiling. The pH value of silage declined to its lowest value of 4.32 by Day 7 of ensiling, and other fermentation parameters kept steady since Day 28 of ensiling. The amplicon sequencing analysis revealed that the alpha diversity parameters of silage bacterial community including Shannon index, observed features, Pielou evenness and Faith PD gradually declined (P < 0.01) with ensiling duration. Principal coordinate analysis (PCoA) revealed that bacterial profiles of raw material would experience a succession becoming a quite different community during ensiling fermentation. Taxonomic classification revealed a total of 10 and 173 bacterial taxa at the phylum and genus level, respectively, as being detected with relative abundances higher than 0.01% and in at least half samples. LEfSe analysis revealed that 26 bacterial taxa were affected by sampling timepoint (P < 0.05 and LDA score > 4). When focusing on the dynamic trend of silage bacterial taxa, lactic acid bacteria successfully dominated in the bacterial community on Day 1 of ensiling, and the bacterial community almost came to a plateau by Day 28 of ensiling, with Lactobacillus and Leuconostoc as the dominant genera. In a word, the succession of fermentation parameters, nutrient components and bacterial community indicate a successful dominance establishment of LAB and a fast advent of fermentation plateau, suggesting that high-moisture sorghum stalk can be ensiled directly, but the pH of mature silage is a little high.

BackgroundThyroid hormones play a vital role in maintaining the homeostasis of the cardiovascular system. The FT3/FT4 ratio can be used to evaluate the rate of T4-to-T3 conversion, reflecting the peripheral sensitivity of thyroid hormones. There is no study to investigate its relationship with death and cardiovascular disease (CVD) in the general population.MethodsThis retrospective cohort study involved 8,018 participants with measured thyroid function and no prior thyroid disease who participated in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2012. Mortality status was determined by routine follow-up using the National Death Index through December 31, 2015.ResultsDuring a median of 87 months of follow-up, we observed 699 all-cause deaths, including 116 cardiovascular deaths. In multivariate adjusted models, higher free thyroxine (FT4) was linked to increased all-cause mortality (HR, 1.15 per SD; 95% CI, 1.09-1.22), cardiovascular mortality (HR, 1.18 per SD; 95% CI, 1.01-1.39), and CVD risk (HR, 1.17 per SD; 95% CI, 1.08-1.27). Higher free triiodothyronine (FT3) was linked to decreased all-cause mortality (HR 0.81 per SD; 95% CI, 0.70-0.93). Higher FT3/FT4 ratio was linked to decreased all-cause mortality (HR, 0.77 per SD; 95% CI, 0.69-0.85), cardiovascular mortality (HR, 0.79 per SD; 95% CI, 0.62-1.00), and CVD risk (HR, 0.82 per SD; 95% CI, 0.74-0.92). The FT3/FT4 ratio stratified findings were broadly consistent with the overall results.ConclusionsFT3, FT4, and the FT3/FT4 ratio were all independent predictors of all-cause death. FT4 and the FT3/FT4 ratio, but not FT3, were independent predictors of cardiovascular mortality and CVD risk. Along with FT3 and FT4, we should pay equal attention to the FT3/FT4 ratio in the general population.

Background: The value of multiple magnetic resonance imaging (MRI) signs in predicting pernicious placenta previa (PPP) with placenta accreta spectrum disorders (PAS) is still controversial. This study aimed to investigate the value of a self-made fetal magnetic resonance imaging scoring system in predicting the different types of PAS in pernicious placenta previa and its associated risk of bleeding.Methods: This retrospective study included 193 patients diagnosed with PPP based on MRI findings before delivery. Based on pathological and intraoperative findings, we divided patients into four groups: non-PAS, placental adhesion, placental implantation, and placenta percreta. Receiver operator characteristic curves of the MRI total score and placental implantation type were drawn using pROC packages in the R Studio environment, and cutoff values of each type were calculated, as well as diagnostic evaluation indexes, such as sensitivity, specificity, and the Youden index. Hemorrhage during surgery was compared between the groups.Results: The boundary value between the non-PAS and placental adhesion was 5.5, that between placental adhesion and placental implantation was 11.5, and that between placental implantation and placenta percreta was 15.5 points. The respective specificities were 0.700, 0.869, and 0.958, and the respective sensitivities were 0.994, 0.802, and 0.577. The Youden indices were 0.694, 0.671, and 0.535, respectively. The median (minimum, maximum) quantities of hemorrhage during the operation in the non-PAS, placental adhesion, placental implantation, and placenta percreta groups were 225 (100, 3700), 600 (200, 6000), 1500 (300, 7000), and 3000 (400, 6300) ml, respectively. Hemorrhage was significantly different between the four groups (p < 0.001).Conclusion: These results suggest that the proposed MRI scoring system could be an effective diagnostic tool for assessing PPP types and predicting the associated bleeding risk.

Background: Acute ischemic stroke (AIS) is a common cause of death and long-term disability worldwide. Recent trials of platelet-activating factor receptor antagonists (PAFRA) appeared to indicate that they could play a neuroprotective role in the treatment of AIS; therefore, we conducted a systematic literature review to evaluate the clinical efficacy and safety of PAFRA in patients with AIS.Methods: A systematic literature search was performed in seven electronic databases from inception to 11 March 2022. All randomized controlled trials (RCTs) in which patients were treated with PAFRA strategies within 7 days of stroke onset were included. Modified Rankin Scale (mRS) was selected as the primary outcome of this systematic review. The methodological quality of included studies was assessed based on the Cochrane Collaborations tool. The review protocol was previously registered (PROSPERO CRD42020182075).Results: Fifteen RCTs comprising a total of 3,907 participants were included in this study. The PAFRA-related compounds included natural preparations of terpenoids, flavonoids, and saponins, namely, ginkgo endoterpene diester meglumine (GEDM, seven RCTs), ginkgo biloba dropping pill (GBDP, one RCT), ginkgolide injection (GDI, four RCTs), hesperidin (HES, one RCT), ginsenoside Rd injection (GSRI, one RCT), and hydroxysafflor yellow A (HSYA, one RCT). All studies were conducted in China between 2017 and 2021, employing a two-arm parallel design with sample sizes ranging from 40 to 1,113. Eight studies (53.3%) provided no information on their method of randomization, and only two studies (13.3%) utilized the double-blind design. Treatment was associated with improved clinical outcomes for (1) GEDM, GDI, and GBDP in patients treated with conventional treatment (CM) [GEDM + CM for AIS on mRS: MDmRS = −0.42, 95% CI (−0.47, −0.37), five trials, p < 0.00001; GEDM + CM for AIS on NIHSS: MDNIHSS = −1.02, 95% CI (−1.51, −0.52), four trials, p < 0.0001]; (2) GEDM and GDI in patients treated with neuroprotective agent (NPA) [GEDM + NPA + CM for AIS on mRS: MDmRS = −0.40, 95% CI (−0.54, −0.26), p < 0.00001; GEDM + NPA + CM for AIS on NIHSS: MDNIHSS = −3.93, 95%CI (−7.72, −0.14), p = 0.04]; (3) GBDP in patients treated with CM; (4) GDI and GSRI in patients treated with IV rt-PA therapy (IVT); and (5) HSYA in patients compared with Dengzhan Xixin injection (DZXXI). No access to improved clinical outcome was associated with HES in patients treated with IVT. Seven RCTs reported adverse events (AEs) but found that taking PAFRA-related preparations was not associated with an increased incidence of AEs.Conclusions: This systematic review not only makes an important contribution to the existing body of current evidence but also lays a well-conducted basis for providing opinions and recommendation on the evaluation of PAFRA-based medicine, which could also highlight the need for well-designed clinical trials of PAFRA for AIS to increase the quality of available evidence. Further research is required, using standardized functional outcome measures for AIS, adequate blinding and suitable comparator groups reflecting current best practice.

Gut microbiota, a group of microorganisms that live in the gastrointestinal tract, plays important roles in health and disease. One mechanism that gut microbiota in modulation of the functions of hosts is achieved through synthesizing and releasing a series of metabolites such as short-chain fatty acids. In recent years, increasing evidence has indicated that dietary compounds can interact with gut microbiota. On one hand, dietary compounds can modulate the composition and function of gut microbiota; on the other hand, gut microbiota can metabolize the dietary compounds. Although there are several reviews on gut microbiota and diets, there is no focused review on the effects of dietary compounds on gut microbiota-derived metabolites. In this review, we first briefly discussed the types of gut microbiota metabolites, their origins, and the reasons that dietary compounds can interact with gut microbiota. Then, focusing on gut microbiota-derived compounds, we discussed the effects of dietary compounds on gut microbiota-derived compounds and the following effects on health. Furthermore, we give our perspectives on the research direction of the related research fields. Understanding the roles of dietary compounds on gut microbiota-derived metabolites will expand our knowledge of how diets affect the host health and disease, thus eventually enable the personalized diets and nutrients.

Alzheimer's disease and epilepsy are common nervous system diseases in older adults, and their incidence rates tend to increase with age. Patients with mild cognitive impairment and Alzheimer's disease are more prone to have seizures. In patients older than 65 years, neurodegenerative conditions accounted for ~10% of all late-onset epilepsy cases, most of which are Alzheimer's disease. Epilepsy and seizure can occur in the early and late stages of Alzheimer's disease, leading to functional deterioration and behavioral alterations. Seizures promote amyloid-β and tau deposits, leading to neurodegenerative processes. Thus, there is a bi-directional association between Alzheimer's disease and epilepsy. Epilepsy is a risk factor for Alzheimer's disease and, in turn, Alzheimer's disease is an independent risk factor for developing epilepsy in old age. Many studies have evaluated the shared pathogenesis and clinical relevance of Alzheimer's disease and epilepsy. In this review, we discuss the clinical associations between Alzheimer's disease and epilepsy, including their incidence, clinical features, and electroencephalogram abnormalities. Clinical studies of the two disorders in recent years are summarized, and new antiepileptic drugs used for treating Alzheimer's disease are reviewed.

The ventrolateral prefrontal cortex (VLPFC) plays a pivotal role in cognitive reappraisal. Previous studies suggested a functional asymmetry of the bilateral VLPFC, but the evidence is still insufficient during cognitive reappraisal. In this study, we conducted an online single-pulse transcranial magnetic stimulation (spTMS) to investigate the causal and distinct roles of the left and right VLPFC in reappraisal. Participants were instructed to reappraise (down-regulate) or attend to pictures depicting social exclusion scenarios while the spTMS was applied over the left or right VLPFC of the participants’ brains. The results showed that spTMS of either the left or the right VLPFC would increase reappraisal difficulty. Meanwhile, the outcome of reappraisal (measured by self-reported negative feelings) significantly deteriorated when the right (but not the left) VLPFC was temporally interrupted by spTMS, while the verbal fluency during oral reporting of the reappraisal strategy was significantly reduced when the left VLPFC was interrupted by spTMS. Taken together, these findings provide causal evidence for the involvement of left and right VLPFC with distinct roles: while the left VLPFC is responsible for the linguistic especially semantic process of generating and selecting appraisals according to the goal of emotion regulation, the right VLPFC plays a critical role in inhibiting inappropriate negative emotions and thoughts generated by the effective scenarios. These findings deepen our understanding of the neurocognitive mechanism of emotion regulation.

BackgroundEnhanced recovery after surgery (ERAS), a new clinical surgical concept, has been applied in many surgical disciplines with good clinical results for the past 20 years. Bibliometric analysis is an effective method to quantitatively evaluate the academic productivity. This report aimed to perform a scientometric analysis of the ERAS research status and research hotspots.MethodsComprehensive scientific mapping analysis of a wide range of literature metadata using the scientometric tools, including the Bibliometrix R Package, Biblioshiny, and CiteSpace. Data were retrieved from the Web of Science Core Collection database of original articles from 2001 to 2020. Specific indicators and maps were analyzed to show the co-authorship, co-institute, co-country, co-citation, and international cooperation. Automatic literature screening, unsupervised cluster filtering, and topic cluster identification methods were used to display the conceptual framework and thematic evolution.ResultsA total of 1,403 research projects drafted by 6,966 authors and published in 413 sources were found. There was an exponential growth in the number of publications on ERAS. There were 709 collaborations between authors from different countries, and the US, China, and the UK had the greatest number of publications. The WORLD JOURNAL OF SURGERY, located in Bradford’s Law 1, had the highest number of published articles (n = 1,276; total citations = 3,193). CiteSpace network analysis revealed 15 highly correlated cluster ERAS studies, and the earliest study was on colonic surgery, and ERAS was recently applied in cardiac surgery. The etiology of ERAS is constantly evolving, with surgery and length of hospital as the main topics. Meta-analyses and perioperative care have tended to decline.ConclusionThis is the first scientometric analysis of ERAS to provide descriptive quantitative indicators. This can provide a better understanding of how the field has evolved over the past 20 years, help identify research trends, and provide insights and research directions for academic researchers, policymakers, and medical practitioners who want to collaborate in these areas in the future.

Ulcerative colitis (UC) is a chronic and recurrent inflammatory disorder in the gastrointestinal tract. Here, we examined the pharmacological effects of ginsenoside Rg1, a natural compound with low bioavailability, on the acute experimental colitis mice induced by dextran sulfate sodium (DSS) and explored underlying mechanisms. Acute UC was induced in C57BL/6 mice by 2.5% DSS for 7 days, meanwhile, 2 mg/10 g b.w. ginsenoside Rg1 was administrated to treat the mice. Body weight, colon length, colon tissue pathology, and colon tissue inflammatory cytokines were assessed. The composition structure of gut microbiota was profiled using 16s rRNA sequencing. Global metabolomic profiling of the feces was performed, and tryptophan and its metabolites in the serum were detected. The results showed that Rg1 significantly ameliorated DSS-induced colonic injury and colonic inflammation. In addition, Rg1 also partly reversed the imbalance of gut microbiota composition caused by DSS. Rg1 intervention can regulate various metabolic pathways of gut microbiota such as valine, leucine, and isoleucine biosynthesis and vitamin B6 metabolism and the most prominent metabolic alteration was tryptophan metabolism. DSS decreased the levels of tryptophan metabolites in the serum, including indole-3-carboxaldehyde, indole-3-lactic acid, 3-indolepropionic acid, and niacinamide and Rg1 can increase the levels of these metabolites. In conclusion, the study discovered that Rg1 can protect the intestinal barrier and alleviate colon inflammation in UC mice, and the underlying mechanism is closely related to the regulation of gut microbiota composition and microbial tryptophan metabolism.

BackgroundThe spread of COVID-19 poses a challenge for obstetrics and gynecology (O&G) residents. In order to improve the theoretical knowledge and practical skills of residents in epidemic prevention and control, reduce work pressure and improve professional skills, effective and sound training models are required to improve the protection of O&G residents from COVID-19.MethodA total of 38 standardized training O&G residents working in Shengjing Hospital of China Medical University in March 2020 was selected. They were randomly divided into intervention and control groups. The control group underwent a protection theory exposition according to the traditional training method, while the intervention group adopted a conceive–design–implement–operate (CDIO) mode, arranged training courses in combination with the O&G specialty, and completed four modules of CDIO. After the training, the theoretical knowledge and practical operation were assessed, and the work stress and occupational identity scales were assessed. The assessment results and scores of the two groups of residents were analyzed.ResultsCompared with the scores of the residents in the control group, the theoretical and technical scores of the residents in the intervention group significantly improved (P < 0.05). In the evaluation of organizational management, workload, interpersonal relationship, and doctor–patient relationship pressure, the scores of the intervention group were lower than those of the control group, with a statistical difference (P < 0.05). For the intervention group, the job stress and professional identity evaluation scores were significantly higher than those of the control group (P < 0.05).ConclusionThe CDIO model can effectively enhance the theoretical knowledge and practical skills of O&G residents in COVID-19 epidemic prevention protocols to reduce work pressure and improve professional identity. In addition, it provides new ideas, methods, and approaches for future clinical practice training.