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OBJECTIVE To investigate the effectiveness of a circulating tumor cell (CTC)-based classifier in stratifying stage IB lung adenocarcinoma (LUAD). SUMMARY BACKGROUND DATA Stage IB LUADs have an approximately 70% 5-year survival rate. The clinical application of adjuvant chemotherapy (ACT) is controversial due to inconsistent results in a series of trials and few useful guide biomarkers. Thus, there is a pressing need for robust biomarkers to stratify stage IB patients to define which group would most likely benefit from ACT. METHODS 212 stage IB LUAD patients were enrolled and were divided into three independent cohorts. The aptamer-modified NanoVelcro system was used to enrich the CTCs. RESULTS A cutoff of < 4 or ≥ 4 CTCs as the optimal prognostic threshold for stage IB LUAD was generated to stratify the patients in a 70-patient cohort into low-risk and high-risk groups. Patients with ≥ 4 CTCs in the training cohort had shorter progression-free survival (PFS, P < 0.0001) and overall survival (OS, P < 0.0001) than patients with < 4 CTCs. CTC number remained the strongest predictor of PFS and OS even in a multivariate analysis including other clinicopathological parameters. Furthermore, a nomogram based on the CTC count was developed to predict the 3-year and 5-year survival in the training cohort and performed well in the other two validation cohorts (C-index: 0.862, 0.853 and 0.877). CONCLUSION The presence of ≥ 4 CTCs can define a high-risk subgroup, providing a new strategy to make optimal clinical decisions for stage IB LUAD.

Dapagliflozin (DAPA) exerts cardioprotective effects in non-diabetic patients. Nonetheless, the protective mechanism remains unknown. This study aims to evaluate the performance of DAPA on cardiac function and remodeling as well as its potential mechanism in mice with myocardial infarction (MI). Here, a MI mice model was established. One week after MI, mice were treated with saline or DAPA (1.5 mg/kg/day) for 4 weeks. At the end of this study, echocardiography was performed to assess cardiac structure and function. Myocardial apoptosis was analyzed by Western blot and immunofluorescence. Inflammatory cytokines and cardiac fibrosis were analyzed by real-time PCR and Masson's trichrome stain, respectively. Results showed that DAPA improved cardiac structure and function, attenuated cardiac fibrosis, and inhibited inflammatory cytokines and myocardial apoptosis. Moreover, the inhibition of PI3K/AKT/mTOR pathway might be related to the cardioprotective role of DAPA. These findings reveal that dapagliflozin is a potential therapeutic agent for MI patients without diabetes.

Background. Global longitudinal strain (GLS) can be assessed by speckle tracking echocardiography (STE) to express the degree of cardiac fibrosis. Qianyangyuyin (QYYY) granules can effectively improve GLS in hypertensive patients. Using a hypertensive rat model, we carried out speckle tracking echocardiography to validate the effect of QYYY in diminishing LV remodeling. Methods. We randomly divided 16 spontaneously hypertensive rats (SHRs) into SHR, SHR + valsartan (SHR + V), SHR + low-dose QYYY (SHR + QL), and SHR + high-dose QYYY (SHR + QH) groups, with four rats in each group. Another group of 4 Wistar-Kyoto (WKY) rats were selected into a normal control (WKY) group. At the 8th week, conventional echocardiographic parameters were measured by GE Vivid E95 ultrasound (12S probe, 10–12 MHz) and GLS by speckle tracking echocardiography with EchoPAC (version 203) software. HE and Masson’s trichrome staining were performed to detect the cardiomyocyte width and collagen volume fraction after rat sacrifice. Collagen I, α-SMA, S100A4, TGF-β, Smad 3, MYH6, and MYH7 were further analyzed by Western blot. Results. The absolute values of GLS significantly increased in the SHR + QH group compared to the SHR group, while the CVF and CW values significantly decreased. In addition, Collagen I, α-SMA, S100A4, TGF-β, Smad3, MYH7, and MYH7/MYH6 ratio remarkably reduced in the SHR + QH group. The value of GLS could be repetitively measured and positively correlated with the collagen volume fraction of the myocardium and the cardiomyocyte width of the left ventricular free wall. Conclusions. GLS is a reliable indicator to evaluate the therapeutic effect on left ventricular remodeling in hypertension. QYYY granules can inhibit the development of cardiac fibrosis in the hypertensive rat model.

Objective: To observe the clinical effect of Jianpi Liqi Decoction on diabetic gastroparesis. Methods: 80 patients were randomly divided into 2 groups, Treatment and control groups, 40 cases per group, The treatment group used Jianpi Liqi recipe, One dose a day, Take it twice, Six times a week, For 4 weeks; Control group with mosapride citrate, 5 mg, each Three times a day, Take continuously for 4 weeks. Observe the two groups before treatment ,2 weeks after treatment ,4 weeks after treatment, Subjective symptoms (early satiety, abdominal distention, upper abdomen burning, upper abdomen pain) score; Before and after treatment, The contents of FBG,2 hPG, HbA1c, TC, GAS, MLT in the two groups. Results: The scores of early satiety, abdominal distention, burning sensation of upper abdomen and pain of upper abdomen were decreased, Intra-group comparisons, Differences were statistically significant (P

Background ICP pregnant women have a unique profile of serum bile acid metabolism, thus the early and accurate identification of ICP patients is beneficial to early appropriate treatment and improvement of pregnancy outcomes. In this study, ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS/MS) was used to analyze the 15 types of serum bile acid profiles among patients with ICP in third trimester, patients with cholelithiasis, and patients with hepatitis B virus. The ICP diagnostic model established by partial least squares-discriminant analysis (PLS-DA) was used to screen the differential bile acids for clinical subtypes of ICP. 144 cases of ICP patients were involved in this study, and divided into four subgroups according to serum level of TBA, DBIL, and ALT. Results (1) The differential serum bile acid profiles of ICP group and normal pregnant women were DCA, TDCA, TCA, GDCA and GLCA. (2) The differential serum bile acid profiles of the ICP1 group (ICP with jaundice) and normal pregnant women were TCDCA, TCA, GCA, GCDCA, TUDCA and GUDCA. (3) The differential serum bile acid profiles of the ICP3 group (Hyperchoicemia of pregnancy) and normal pregnant group was GUDCA, LCA, GLCA, UDCA, TUDCA, CDCA, and TLCA (P 0.05). Conclusion Maternal serum bile acid profiles are useful to differentiate the four subtypes of ICP. ICP with jaundice could be an important predictor of adverse pregnancy outcomes of ICP.

Antigen-activated B cells diversify variable regions of B cell antigen receptors by somatic hypermutation in germinal centers (GCs). The positive selection of GC B cells that acquire high-affinity mutations enables antibody affinity maturation. In spite of considerable progress, the genomic states underlying this process remain to be elucidated. Single-cell RNA sequencing and topic modeling revealed increased expression of the oxidative phosphorylation (OXPHOS) module in GC B cells undergoing mitoses. Coupled analysis of somatic hypermutation in immunoglobulin heavy chain (Igh) variable gene regions showed that GC B cells acquiring higher-affinity mutations had further elevated expression of OXPHOS genes. Deletion of mitochondrial Cox10 in GC B cells resulted in reduced cell division and impaired positive selection. Correspondingly, augmentation of OXPHOS activity with oltipraz promoted affinity maturation. We propose that elevated OXPHOS activity promotes B cell clonal expansion and also positive selection by tuning cell division times. Xu and colleagues use single-cell transcriptomic analyses to uncover distinct expression dynamics of metabolic programs in germinal center B cells. Coupled analysis of transcriptional states and Igh variable sequences revealed that OXPHOS metabolism is enhanced in GC B cells undergoing positive selection. Their findings suggest BCR signaling tunes GC B cell metabolism to accelerate the cell cycle of positively selected GC B cells.

BACKGROUND: Hemodialysis (HD) can influence end-stage renal disease (ESRD) patients’ circulatory system. The present study aimed to evaluate the effect of volume depletion on left ventricular (LV) and left atrial (LA) function and determine the volume-independent parameters before and after HD in patients with ESRD. METHODS: Between January 2018 and January 2019, we recruited long-term HD patients (n=40, 51.0±16.4 years), excluding those with structural cardiac disease. Echocardiographic parameters, including LV and LA volumes, flow Doppler, pulsed tissue Doppler, and speckle tracking echocardiography (STE) before and after HD (within 24 h), were examined, and the values were compared. RESULTS: Following HD, alteration in LV end-systolic volume was not detected, whereas LV end-diastolic volume (90.18±23.91 vs. 84.21±23.54 mL, P=0.036) and LV ejection fraction (LVEF; 64.63%±6.56% vs. 62.84%±6.56%, P=0.049) decreased. Peak early diastolic trans-mitral flow velocity (E-wave; 82.22±20.13 vs. 72.43±18.32 cm/s, P

Compare the intraventricular hemodynamics of 60 females with systemic lupus erythematosus (SLE) and 61 healthy female controls, and determine cardiac function changes using vector flow mapping (VFM).To determine the effect of pulmonary artery pressure changes on left ventricular function, SLE patients were divided into a normal pulmonary artery pressure group (S1, n=24) and an elevated pulmonary artery pressure group (S2, n=36). The energy loss (EL) at each segment of the left ventricular chamber (total, basal, middle, and apical segments) during each period of the cardiac cycle (isovolumic contraction, rapid ejection, rapid filling, reduced filling, atrial contraction) was determined.The S1 group had significantly more vortices than the control group during the rapid ejection, rapid filling, and atrial contraction periods (p0.01), and the maximum vortex areas in the S1 and S2 groups were smaller than in the control group during rapid filling and atrial contraction periods (p0.05). Compared with the control group, the S2 group had greater EL during the systole and diastole periods (p0.01). EL in the S1 group was significantly greater than in the control group during systole (p0.01). During the rapid filling period, the EL was positively correlated with septal E' (r=0.784, p0.01), and during the atrial contraction period, EL was positively correlated with septal E/e' (r=0.812, p0.01) and A (r=0.715, p0.01).VFM of patients with SLE can comprehensively, rapidly, and efficiently evaluate changes of myocardial mechanics and intracardiac hemodynamics and provide quantitative analysis of complex intracardiac blood flow. Key points • Vector flow mapping (VFM) is a new non-invasive ultrasound technique that evaluates changes of myocardial mechanics and intracardiac hemodynamics, and provides quantitative analysis of complex intracardiac blood flow. • This study showed that vortex and energy loss may provide more sensitive detection of cardiac dysfunction than conventional echocardiographic indexes in patients with systemic lupus erythematosus.

Malignant soft tissue tumors (STTs) are often mistaken for benign tumors, leading to inappropriate treatment including unplanned resection. Elastography, as a non-invasive measurement of tissue mechanical properties, makes use of the different soft tissue elasticity in diverse pathologies to generate information that can be used for diagnostic purposes. Elastography for STTs carries important information that is helpful in differentiating malignant and benign masses. The present study was undertaken to systematically review existing trials on the reliability of elastography in assessment of malignant STTs. A comprehensive literature exploration of the PubMed, EMbase and China National Knowledge Infrastructure databases was conducted for published articles involving the application of elastography in distinguishing malignant STTs. The diagnostic performance of elastography was evaluated with pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and area under the summary receiver operating characteristic curve. Publication bias was also evaluated. This meta-analysis enrolled 18 eligible studies with a total of 1420 patients. The overall number of reported STTs was 1569, of which 478 were classified as positive and 1091 as negative at elastography. The pooled sensitivity, specificity, positive likelihood ratio and negative likelihood ratio of elastography were 0.82 (95% confidence interval: 0.74-0.87), 0.80 (0.71-0.86), 3.99 (2.65-6.01) and 0.23 (0.15-0.34), respectively. The diagnostic odds ratio and area under the curve were 17.36 (8.28-36.38) and 0.88 (0.84-0.90), respectively (Glas et al. 2003). The results of meta-regression analysis revealed that the total number of patients and prevalence of malignant STTs were significant factors in sensitivity, and the year of publication, total number of patients and index test were significant factors affecting study heterogeneity for specificity (p0.05). No significant publication bias was observed. This meta-analysis indicates that ultrasound elastography achieves relatively good performance in discriminating between malignant and benign STTs. Nevertheless, further research is needed to verify this finding.

Circular RNAs (circRNAs) are increasingly gaining importance and attention due to their diverse potential functions and their value as diagnostic biomarkers (disease specific). This study aims to explore the novel mechanisms by which exosome-contained circRNAs promote tumor development and metastasis in TNBC. We identified increased circRNA circPSMA1 in TNBC cells, their exosomes, and serum exosomes samples from TNBC patients. The overexpression of circPSMA1 promoted TNBC cell proliferation, migration, and metastasis both in vitro and in vivo. Moreover, we investigated the tumor-infiltrating immune cells (TICs) or stromal components in immune microenvironment (IME), and identified the significant differences in the immune cells between TNBC and non-TNBC samples. Mechanistically, circPSMA1 acted as a “miRNAs sponge” to absorb miR-637; miR-637 inhibited TNBC cell migration and metastasis by directly targeted Akt1, which recognized as a key immune-related gene and affected downstream genes β-catenin and cyclin D1. Subsequent co-culture experiments also demonstrated that exosomes from TNBC carrying large amounts of circPSMA1 could transmit migration and proliferation capacity to recipient cells. Kaplan–Meier plots showed that high expression of Akt1 and low expression of mir-637 are highly correlated with poor prognosis in patients with lymph node metastasis of TNBC. Collectively, all these results reveal that circPSMA1 functions as a tumor promoter through the circPSMA1/miR-637/Akt1-β-catenin (cyclin D1) regulatory axis, which can facilitate the tumorigenesis, metastasis, and immunosuppression of TNBC. Our research proposes a fresh perspective on novel potential biomarkers and immune treatment strategies for TNBC.

Renin-angiotensin system (RAS) signaling has been implicated in the development of cancer. The new RAS ACE2/Ang-(1-7)/Mas axis antagonizes the classical ACE/Ang II/AT1R axis. Ang-(1-7) has pleiotropic roles in lung cancer including suppressing proliferation, angiogenesis, and metastasis. This research was designed to investigate the effect of Ang-(1-7) on tumor-associated angiogenesis in DDP-resistant lung cancer cell lines. We first established acquired DDP-resistant cell lines A549 (A549-DDP) and LLC (LLC-DDP). We next performed RT-qPCR, western blot, ELISA, tube formation, microvessel density detection, immunohistochemistry, and tumor formation assays. The results showed that the mRNA and protein levels of RAS components and vascular endothelial growth factor A (VEGFa) were lessened in the A549/LLC-DDP+Ang-(1-7) group compared with the A549/LLC-DDP group. This effect could be blocked by the MAS receptor antagonist A779. The data revealed that Ang-(1-7) could perform its antiangiogenic function by PI3K/AKT and MAPK pathways. Furthermore, the impact of Ang-(1-7) on tumor-associated angiogenesis has been confirmed in lung cancer xenograft model with acquired DDP resistance. These results provide a theoretical basis for designing therapeutic strategies for targeting Ang-(1-7) in the treatment of NSCLC.

It is imminent to develop a new type of rapid COVID-19 detection method with high sensitivity. Here, we used novel red emission-enhanced carbon dot (CD)-based silica (RCS) spheres as the signals of lateral flow immunochromatography (LFI) to ultrasensitively detect novel severe acute respiratory syndrome coronavirus 2 nucleocapsid proteins (SARS-CoV-2 NPs). The red emission of CDs can be enhanced and enriched in silica spheres by a simple way. The amino ends of the N-β-(aminoethyl)-γ-aminopropyltrimethoxy anchor carboxyl-rich CDs and enhance the red emission, while the other end is embedded in the silica carrier. Then, the composite silica spheres werecoated with 3-(triethylsilyl) propylamine to protect the CDs, promote bioconjugation and obtain RCS spheres. The optimal emission peaks of the aqueous solution and the solid state of RCS spheres were at 634 nm and 638 nm, respectively, with quantum yields (QYs) of 48.5% and 35.7%, respectively. Their red emission has a wide excitation range (from the ultraviolet region to the red region), and the best excitation wavelength is about 580 nm. Two fluorescence detection modes of the RCS-LFI technology for the SARS-CoV-2 NP assay are available: the simple mode of observation under ultraviolet light has a sensitivity of 100 pg mL-1; the advanced mode of detection under a fluorescence microscope has a sensitivity of 10 pg mL-1. This assay also exhibits the advantages of fast detection speed, high specificity, and simple operation. In addition, the feasibility of this method in actual sample detection was verified in human serum by the standard-addition method, and the results show that the method has excellent practicability. We believe that this method will be a valuable supplement for the diagnosis of COVID-19.

Background: Some literature has studied the relationship between lignans intake and its metabolite, enterolactone, and breast cancer survival, but the results are far from consistent and conclusive. Therefore, we conducted a systematic review and meta-analysis in this situation. Methods: From its inception to August 2020, we conducted a comprehensive search of PubMed, Embase, Web of Science, and Cochrane Library databases. This study reported the correlation between lignans intake and serum enterolactone concentrations and prognosis of breast carcinoma. The total hazard ratios (HRs) and 95% confidence interval (95% CI) were estimated, comparing the highest versus the lowest category of lignans intake and serum enterolactone concentrations, using a fixed or random-effects effect model. Results: A total of 6 articles were included in reporting the all-cause mortality (ACM), breast cancer-specific mortality (BCSM), and recurrence of 2668, 1516, and 474 breast cancer patients in 18053 breast cancer patients. In postmenopausal women with breast cancer, lignans intake or enterolactone concentrations were associated with a reduced risk of all-cause mortality (maximum and minimum) (pooled HR = 0.73, 95% CI, 0.58-0.91), as was the association with breast cancer-specific mortality (maximum and minimum) (pooled HR = 0.72, 95% CI, 0.60, 0.87). Stratified analysis showed that exposure type and diagnosis time might be the sources of heterogeneity. In premenopausal women, the relationship seemed to be the opposite, showing an increased risk of all-cause mortality (maximum and minimum) in breast cancer patients (pooled HR = 1.57, 95% CI, 1.11-2.23). No significant association was found between lignans intake or enterolactone concentrations and breast cancer recurrence (pooled HR = 0.91, 95% CI, 0.69, 1.20). Conclusion: This study provides limited evidence that lignans intake and higher serum enterolactone concentrations in postmenopausal women are beneficial to breast cancer patients' prognosis. In premenopausal women, however, the relationship may be reversed.

Ginseng is usually consumed as a dietary supplement for health care in the normal state or prescribed as a herbal medicine in pathologic conditions. Although metabolic studies of ginseng are commonly performed on healthy organisms, the metabolic characteristics in pathologic organisms remain unexplored. This study aimed to uncover the difference in intestinal metabolism of ginseng between normal and cyclophosphamide-induced immunosuppressed rats and further discuss the potential mechanisms involved. Twelve Sprague-Dawley rats (6–8 weeks old) were randomly divided into two groups: the normal group (NG) and immunosuppressed group (ISG). Rats in the NG and ISG groups were intraperitoneally administered normal saline and cyclophosphamide injections (40 mg/kg) on the 1st, 2nd, 3rd and 10th days; on the 12th day, all rats were intragastrically administered ginseng water extract (900 mg/kg). The difference in intestinal metabolism of ginseng was compared using an ultra-high-performance liquid chromatography coupled with quadruple time-of-flight mass spectrometry-based metabolomics approach, and the diversities of gut microbiota were analyzed by 16S rRNA gene sequencing between the two groups. The intestinal metabolomic characteristics of ginseng were significantly different between the normal and immunosuppressed rats, with the ginsenoside F2 (F2), 20S-ginsenoside Rg3 (20(S)-Rg3), pseudo-ginsenoside Rt5 (Pseudo-Rt5), ginsenoside Rd (Rd), ginsenoside Rh1 (Rh1), 20S-ginsenoside Rg1 (20(S)-Rg1), ginsenoside compound K (CK), ginsenoside Rg2 (Rg2) and 20S-panaxatriol (S-PPT) more abundant in immunosuppressed ones (P

Resistance-nodulation-division (RND) efflux pumps are important determinants of multidrug resistance in Gram-negative bacteria. As one of the typical members of the RND superfamily, Escherichia coli OqxAB multidrug efflux pump confers resistance to antimicrobial agents, such as olaquindox and fluoroquinolone. In the present study, site-directed mutagenesis and antimicrobial susceptibility measurement assay were applied to identify the crucial residues within OqxB, the transporter component of the OqxAB efflux pump system. It was found that alanine substitution of proton translocation pathway residues D410, D411, and R976 resulted in a complete loss of the transport function. Further studies revealed that the charge property of these residues is important for proper function of OqxB. Alanine replacement of residues involved in substrate-binding domains, including V141, F180, Y330, and F626, exhibited different responses toward different antimicrobial agents. Conservative replacement of Y330, F626, and F180 with amino acids having similar aromatic ring structure resulted in full or partial recovery of the efflux function. Molecular docking analysis demonstrated that olaquindox may form hydrogen bonds with F626, Y330, and V141, whereas only Y330 and F180 may interact with ciprofloxacin, implicating the different roles played by these residues when transporting different kinds of substrates. Graphical Abstract [Figure: see text].

5-Fluorouracil (5-FU) is widely used as a chemotherapeutic drug for the treatment of cancer but it has toxic side effects. It can induce severe intestinal damage and even lead to death. The purpose of this study was to investigate whether milk fermented with Lactobacillus rhamnosus FLRH93 could alleviate intestinal damage induced by 5-FU. The results of injury intervention in a mouse model showed that milk fermented with Lb. rhamnosus FLRH93 significantly ameliorated intestinal injury caused by 5-FU. The results of hematoxylin and eosin staining showed that mice fed Lb. rhamnosus FLRH93 preserved the villus/crypt ratio and reduced the loss of goblet cells in ileum sections of 5-FU-treated animal. Further, administration of fermented milk upregulated expression of Bcl-2 in the intestinal tract and downregulated the expression of NLRP3, thus reducing the production of inflammatory factors interleukin 1-β and tumor necrosis factor-α. The survival rate of mice treated with fermented milk was twice that of mice not fed fermented milk after continuous oral administration of 5-FU. In conclusion, Lb. rhamnosus FLRH93 has positive effects on body injury and could be used to prevent intestinal damage caused by cancer chemotherapy.

Uranium (VI), as a toxic contaminant, is a potential detriment to human health and environmental safety. In this experiment, carboxymethyl cellulose/Ca-rectorite composite material (Ca-REC/CMC) was prepared by crosslinking reaction to remove U(VI) from the liquid. The crystal structure was detected by X-ray diffraction (XRD) and surface structure and morphology of the materials were investigated by scanning electron microscopy (SEM). The surface functional groups of prepared materials were detected by Fourier transform infrared spectroscopy (FT-IR). The adsorption capacity of Ca-REC/CMC improved obviously after being modified by CMC. The adsorption capacity of Ca-REC/CMC was closely related to ionic strength and pH. According to thermodynamic parameter calculation, the adsorption process was endothermic and spontaneous. Adsorption isotherms could be depicted perfectly by the Langmuir model. Ca-REC/CMC maintained stability and regeneration after recycling six times. The adsorption mechanism, including electrostatic interactions and ionic interaction, was investigated by the X-ray photoelectron spectroscopy (XPS). Ca-REC/CMC is considered as remarkable potential material for removing U(VI) from the water environment.

Purpose Axillary lymph node (ALN) involvement is an important prognostic factor of early invasive breast cancer. The objective of this study was to establish simple nomograms for predicting ALN involvement based on ultrasound (US) characteristics and evaluate the predictive value of US in the detection of ALN involvement. Patients and methods A total of 1328 patients with cT1-2N0 breast cancer by physical exam were retrospectively analyzed. Univariate analysis was used for the comparison of variables, and multivariate analysis was performed by binary logistic regression analysis. The R software was used to establish simple nomograms based on the US characteristics alone. The receiver operating characteristic (ROC) curves of the prediction model and the verification group were drawn, and the area under the curve (AUC) was calculated to evaluate the discrimination of the prediction model. A calibration curve was plotted to assess the nomogram predictions vs the actual observations of the ALN metastasis rate and axillary tumor burden rate. Results The ALN metastasis rates of the training group and the validation group were 35.1% and 34.1%, respectively. Multivariate analysis showed that molecular subtype, lymphovascular invasion, mass descriptors (size, margin, microcalcification and blood flow signal) and LN descriptors (shape, cortical thickness and long-to-short ratio) were independent impact factors in early breast cancer. The AUC of ALN metastasis rate of prediction model based on US features was 0.802, the AUC of high tumor burden rate was 0.873, and the AUC of external validation group was 0.731 and 0.802, respectively. The calibration curve of the nomogram showed that the nomogram predictions are consistent with the actual metastasis rate and the high tumor burden rate. The results showed that preoperative US had a sensitivity of 59.4% and a specificity of 88.9% for predicting the ALN metastasis rate. Conclusion The successfully established nomograms based on US characteristics to predict ALN metastasis rate and high axillary tumor burden rate in early breast cancer can achieve individual prediction. Compared with other nomogram predictions, it is more intuitive, and can help clinical decision-making; thus, it should be promoted. However, at this time US features alone are insufficient to replace sentinel lymph node biopsy.

Tea consumption has been found to be associated with low incidence of inflammatory bowel disease in Asian countries. However, there is very limited knowledge of such potential protection and its underlying mechanism. Ripened Pu-erh tea (RPT) belongs to the variety of microbial fermented tea, but its function regarding anti-inflammation remains unclear. In the present study, we investigated the effects of RPT on dextran sulfate sodium (DSS)-induced colitis in mice. The results demonstrated that RPT significantly relieved the loss of body weight, disease severity and shortening of colon length, and remarkably inhibited the secretion of pro-inflammatory cytokines by lessening the infiltration of inflammatory cells. Furthermore, we found that RPT suppressed the activation of the NF-κB pathway and down-regulated the expression of HIF-1α. Thus, it was concluded that RPT attenuated the progress of colitis via suppressing the HIF-1α/NF-κB signaling pathways thus reducing inflammation. This suggests that RPT may be a potential anti-inflammatory nutraceutical for the prevention and treatment of colonic colitis.

Sensitive detection of severe fever with thrombocytopenia syndrome virus (SFTSV) by a point-of-care assay is of great significance for promoting clinical diagnosis. In this work, ultrasensitive det...

BackgroundCurrently, there are few effective therapeutic options for pancreatic cancer patients. Sortilin is a member of vps10p receptor family，reported in many types of cancers. However, the underlying mechanism and prognostic value of sortilin in pancreatic cancer are still unclear. ObjectiveUnderstand the expression of sortilin in pancreatic cancer, and analyze its mechanism that affects the occurrence and development of pancreatic cancer. MethodsA tissue microarray of 115 pancreatic cancer metastases was analyzed by immunohistochemistry. All data were analyzed by univariate analysis and multivariate analysis. Multivariate logistic regression analysis and the area under the receiver operating characteristic (ROC) curve were used to analyze the ability of sortilin in predicting pancreatic cancer. Next, survival analysis was performed to compare the survival time between high-risk and low-risk patients to validate the prognosis prediction efficacy of sortilin. The effects of sortilin on the invasion，metastasis and proliferation of pancreatic cancer cells were investigated both in vitro. investigate the anti-cancer effect of soritlin on human pancreatic cancer Capna1 and Bxpc3 cells, and its possible molecular mechanism. ResultsDifferential expression analysis of 115 tissue microarrays showed sortilin expression was up‐regulated in pancreatic cancer tissues,and it mainly comes from the nucleus. Sortilin expression in nucleus(SEIN) was only negatively correlated with N stage, Binary logistic regression model showed that SEIN is a good diagnostic marker for predicting pancreatic cancer and the accuracy of prediction is as high as 79.1 %. ROC curve analysis demonstrated a statistically significant diagnostic value of SEIN,and the diagnostic accuracy was 86.3%, The Youden Index was calculated to evaluate the diagnostic power, The cut-off value for SEIN in pancreatic cancer diagnosis was 0.85, with a sensitivity of 90.9% and a specificity of 68.3%. Univariate analysis showed that M stage(P=0.022), histological grade(P=0.021), clinic stage(P=0.030)and SEIN(P=0.039) were correlated with prognosis of pancreatic cancer patients, Multivariate regression analysis showed that M stage(P=0.036)and ESIN(P=0.004) were independent factors.The proliferation, invasion and migration of pancreatic cancer cells were inhibited in vitro by sortilin siRNA knockdown.it may have something to do with soritlin/P53/NFκB regulated the the proliferation function and sortilin/MMP9 regulated the invasion-promotion of pancreatic cancer cells. Conclusions These fndings demonstrated that the low expression of SEIN indicates better prognosis in pancreatic cancer and supplemented the effect mechanism of sortilin on pancreatic cancer cells. SEIN expression may serve as a potential diagnostic indicator of pancreatic cancer.

Background：Elevated serum total bile acid level is currently the main index for clinical diagnosis of intrahepatic cholestasis of pregnancy, but the use of TBA as a detection index has certain limitations. The early diagnosis of ICP and new treatment options still need to be further strengthened. Methods: Plasma samples were collected, and exosomes were isolated. Key differential proteins were screened by bioinformatics methods. ELISA method was used to detect the concentration of the key differential protein cluster in plasma samples, and the ROC curve was drawn to find out the best critical value. Results: There were 138 differentially expressed proteins between the ICP group and the normal group by quantitative analysis. Cluster protein was screened as a clinical validation index. The cluster protein concentration of plasma exosomes in the ICP group was significantly higher than that in the normal group (PConclusion: the plasma exosome cluster protein concentration of ICP pregnant women is significantly higher than that of normal pregnant women. When the plasma cluster protein concentration of pregnant women is more remarkable than 255.28ng/ml, ICP can be diagnosed. When the plasma cluster protein concentration of pregnant women is higher than 286.72ng/ml, ICP pregnant women are more likely to have a premature birth.

This study aimed to probe carcinogenic genes and pathways associated with Wilms' tumor (WT) onset and malignancy progression. After screening, three datasets acquired from the Gene Expression Omnibus database were analyzed. Differentially expressed genes (DEGs) were identified and GO functional enrichment, KEGG pathway enrichment and protein-protein interaction (PPI) were analyzed. The DEGs with top fold change values or top protein interaction scores were used to analyze overall survival based on the TARGET WT dataset. Together, 866 up-regulated genes in GDS1791, 585 up-regulated genes in GDS2010, and 277 down-regulated genes in GDS4802 were found, from which 46 key DEGs were selected for further analysis. In the PPI network, hub positions included COL5A1, COL4A1, ARPP21, SPARCL1, CD86, LY96 and PPP1R12B. The top DEGs (ARPP21, SYNPO, PRRC2B, PPP1R12B, EFCAB2 and LY96) were selected for survival analysis, and they consistently showed a significantly positive correlation with poor survival. Together, five key carcinogenic genes (SYNPO, PRRC2B, PPP1R12B, EFCAB2 and LY96) were highly associated with WT onset and patient survival. These risk genes, interaction networks and enrichments should improve our understanding of the complex molecular mechanisms in WT development and help clinical applications.

One of the major challenges in treating Alzheimer's disease (AD) is its early diagnosis. Increasing data from clinical and animal research indicate that the retina may facilitate an early diagnosis of AD. However, a previous study on the 5xFAD (a fast AD model), showing retinal changes before those in the brain, has been questioned because of the involvement of the retinal degeneration allele Pde6brd1. Here, we tested in parallel, at 4 and 6 months of age, both the retinal and the brain structure and function in a 5xFAD mouse line that carries no mutation of rd1. In the three tested regions of the 5xFAD brain (hippocampus, visual cortex, and olfactory bulb), the Aβ plaques were more numerous than in wild-type (WT) littermates already at 4 months, but deterioration in the cognitive behavioral test and long-term potentiation (LTP) lagged behind, showing significant deterioration only at 6 months. Similarly in the retina, structural changes preceded functional decay. At 4 months, the retina was generally normal except for a thicker outer nuclear layer in the middle region than WT. At 6 months, the visual behavior (as seen by an optomotor test) was clearly impaired. While the full-field and pattern electroretinogram (ERG) responses were relatively normal, the light responses of the retinal ganglion cells (measured with multielectrode-array recording) were decreased. Structurally, the retina became abnormally thick with few more Aβ plaques and activated glia cells. In conclusion, the timeline of the degenerative processes in the retina and the brain is similar, supporting the use of non-invasive methods to test the retinal structure and function to reflect changes in the brain for early AD diagnosis.

Background: Functional dyspepsia (FD) is a gastrointestinal disorder associated with epigastric pain and fullness, with symptoms such as anxiety and depression. Electroacupuncture (EA) has emerged as a potential therapeutic strategy to treat FD via electrical stimulation at specific acupoints of the body and has previously been demonstrated to be effective in promoting gastric motility and attenuating the symptoms of FD. However, the mechanisms underlying the effect of EA remain elusive.Results: Herein, we constructed an in vivo model of FD in rats and performed EA on FD-induced rats. Preliminary bioinformatic analysis through RNA sequencing revealed that differentially expressed microRNAs exist between non-treated and EA-treated rats subjected to EA. Among them, miR-221-3p was associated with the target gene c-kit, the expression of which is closely linked to interstitial cells of Cajal (ICCs) and gap junction intercellular communication, factors critically implicated in gastrointestinal motility. We further proved that miR-221-3p overexpression aggravated FD, but EA downregulated miR-221-3p to alleviate the symptoms of FD. The mechanisms of action underlying the effect of EA involve an increase in c-kit+ ICCs, upregulation of stem cell factor and connexin 43, and enhanced Raf/Erk signaling.Conclusions: Our findings suggest that EA is an effective method of managing FD by regulating miR-221-3p, the c-kit/stem cell factor axis, and Raf/Erk signaling, reinforcing the strong role of gap junction intercellular communication in gastrointestinal motility.

Triple negative (TN) breast cancer is a subtype of breast cancer which is difficult for early detection and the prognosis is poor. In this paper, 910 benign and 934 malignant (110 TN and 824 NTN) B-mode breast ultrasound images were collected. A Resnet50 deep convolutional neural network was fine-tuned. The results showed that the averaged area under the receiver operating characteristic curve (AUC) of discriminating malignant from benign ones were 0.9789 (benign vs. TN), 0.9689 (benign vs. NTN). To discriminate TN from NTN breast cancer, the AUC was 0.9000, the accuracy was 88.89%, the sensitivity was 87.5%, and the specificity was 90.00%. It showed that the computer-aided system based on DCNN is expected to be a promising noninvasive clinical tool for ultrasound diagnosis of TN breast cancer.

The present study hypothesized that fumaric acid and succinic acid may exhibit therapeutic effects on gestational hypertension. During pregnancy, estrogen upregulates ten-eleven translocation 1 (TET1) expression, which subsequently increases calcium-activated potassium channel subunit β1 (KCNMB1) expression. KCNMB1 is associated with hypertension. Fumaric acid and succinic acid are understood to inhibit TET. Therefore, the present study investigated whether fumaric acid and succinic acid exhibit therapeutic effects on gestational hypertension and whether these effects are mediated by TET1 and KCNMB1. Nω-Nitro-L-arginine methyl ester hydrochloride was injected into rats to establish a gestational hypertension model. Dimethyl fumarate (DMF) and succinic acid were administrated into rats to treat gestational hypertension. Rats were divided into five groups: i) Control; ii) model; iii) DMF; iv) succinic acid; and v) DMF + succinic acid. Blood pressure was monitored by a noninvasive meter and urinary protein was determined using a urinary protein kit. Placenta pathology was examined by hematoxylin-eosin staining. Compared with the control group, urinary protein and blood pressure in the model group increased significantly. The placental cells in the control group were arranged orderly. However, in the model group, decidual cellular edema of placenta and vacuolar degeneration were observed, and the intervascular membrane was markedly thicker with plenty of fibrin deposition. These results indicate successful establishment of a gestational hypertension model. However, compared with the model group, urinary protein, blood pressure, edema, vacuoles and fibrin deposition were markedly reduced in the DMF, succinic acid and DMF + succinic acid groups. mRNA and protein levels of TET1 and KCNMB1 in placenta were evaluated by immunohistochemical analysis, reverse transcription-quantitative polymerase chain reaction and western blotting. The TET1 and KCNMB1 levels in the model group were markedly increased compared with those in the control group. However, compared with the model group, the expression levels were markedly downregulated in the DMF, succinic acid and DMF + succinic acid groups. In conclusion, fumaric acid and succinic acid may treat gestational hypertension by downregulating the expression of KCNMB1 and TET1.

Self-reactive B cell progenitors are eliminated through central tolerance checkpoints, a process thought to be restricted to the bone marrow in mammals. Here, we identified a consecutive trajectory of B cell development in the meninges of mice and non-human primates. The meningeal B cells were located predominantly at the dural sinuses, where endothelial cells expressed essential niche factors to support B cell development. Parabiosis experiments together with lineage tracing showed that meningeal developing B cells were replenished continuously from hematopoietic stem cell (HSC)-derived progenitors via a circulation-independent route. Autoreactive immature B cells that recognized myelin oligodendrocyte glycoprotein (MOG), a central nervous system-specific antigen, were eliminated specifically from the meninges. Furthermore, genetic deletion of the Mog gene restored the self-reactive B cell population in the meninges. These findings identify the meninges as a distinct reservoir for B cell development, allowing in situ negative selection to ensure a locally non-self-reactive immune repertoire.

The random V(D)J recombination of immunoglobulins (Ig) loci often creates autoreactive B cell progenitors expressing self-recognized B-cell receptors (BCRs)1, which are eliminated or inactivated through an autoantigen-dependent central tolerance checkpoint to prevent autoimmune reactions2,3, a process thought to be restricted to the bone marrow (BM) in the adult mammals4. Here we report that early developing B cells are also present in the meninges of mice at all ages. Single cell RNA-sequencing (scRNA-seq) analysis revealed a consecutive trajectory of meningeal developing B cells in mice and non-human primates (NHPs). Parabiosis together with lineage tracing of hematopoietic stem cells (HSCs) showed that meningeal developing B cells are continuously replenished from the HSC-derived progenitors via a circulationindependent route. Importantly, autoreactive immature B cells which recognize myelin oligodendrocyte glycoprotein (MOG)5, a central nervous system (CNS)-specific antigen, are eliminated from the meninges but not BM. Furthermore, genetic deletion of MOG restored the self-reactive B cells in the meninges. Thus, we propose that meninges function as a unique reservoir for B cell development, allowing in situ negative selection of CNS-antigen-autoreactive B cells to ensure a local non-self-reactive immune repertoire.

ObjectivesTo explore the relationship between ultrasound (US) features and Ki-67 labeling index (LI) of soft tissue sarcoma (STS).MethodsForty-six patients with 47 STS lesions, between September 2014 and April 2020, were enrolled in the study. Point-biserial correlation analysis and Spearman’s correlation analysis were utilized to examining the relationship between the US features and the Ki-67 LI of STS. The differences of US features between high and low Ki-67 proliferation groups were statistically analyzed by independent t test, Wilcoxon rank-sum test, and Fisher’s exact test. The optimal cut-off points of US features revealing significant differences were estimated by the maximum Youden index.ResultsA moderate correlation between the vascular density grade and the Ki-67 LI (ρ = 0.409, P = 0.004) was found in this study. In addition, other ultrasound features were irrelevant to the Ki-67 LI. The cut-off for differentiating low- and high-proliferation groups was grade II according to the best Youden index. The area under receiver operating characteristic (ROC) curve was 0.74 (p = 0.011) with a sensitivity of 60.6% and specificity of 78.6%.ConclusionsOnly the vascular density grade of STS had a weak positive correlation with Ki-67 LI, and might be capable of predicting the proliferation of STS. Other ultrasonographic features of STS such as shape and tumor margin have no correlation with Ki-67 LI.

Objective The study objective was to enhance clinical skills among undergraduate students majoring in clinical medicine in performing physical examination by establishing a novel platform for peer assessment of clinical skills. Methods A total 126 Year 2012 students majoring in medicine and receiving traditional training were assigned to the control group, and 126 Year 2013 students receiving instruction via the peer assessment platform of clinical skills were allocated to the study group. Scores of the physical examination, paper exam, and peer assessment were compared using a t-test, and we performed linear correlation analysis of the data. Results Scores of the physical examination and peer assessment among Year 2013 students (the study group) were significantly higher than those in the control group. Paper exam scores in the study group were also significantly higher than those in the controls. The three assessment scores did not differ significantly according to sex. Conclusions The peer assessment platform can not only improve medical students’ skills and capabilities in physical examination, it can also enhance their theoretical knowledge of basic clinical principles. We determined that sex was not related to the assessment scores obtained by medical students.