Deep Learning Radiomics Model of Dynamic Contrast-Enhanced MRI for Evaluating Vessels Encapsulating Tumor Clusters and Prognosis in Hepatocellular Carcinoma.

BACKGROUND: Vessels encapsulating tumor cluster (VETC) is a critical prognostic factor and therapeutic predictor of hepatocellular carcinoma (HCC). However, noninvasive evaluation of VETC remains challenging. PURPOSE: To develop and validate a deep learning radiomic (DLR) model of dynamic contrast-enhanced MRI (DCE-MRI) for the preoperative discrimination of VETC and prognosis of HCC. STUDY TYPE: Retrospective. POPULATION: A total of 221 patients with histologically confirmed HCC and stratified this cohort into training set (n = 154) and time-independent validation set (n = 67). FIELD STRENGTH/SEQUENCE: A 1.5 T and 3.0 T; DCE imaging with T1-weighted three-dimensional fast spoiled gradient echo. ASSESSMENT: Histological specimens were used to evaluate VETC status. VETC+ cases had a visible pattern (≥5% tumor area), while cases without any pattern were VETC-. The regions of intratumor and peritumor were segmented manually in the arterial, portal-venous and delayed phase (AP, PP, and DP, respectively) of DCE-MRI and reproducibility of segmentation was evaluated. Deep neural network and machine learning (ML) classifiers (logistic regression, decision tree, random forest, SVM, KNN, and Bayes) were used to develop nine DLR, 54 ML and clinical-radiological (CR) models based on AP, PP, and DP of DCE-MRI for evaluating VETC status and association with recurrence. STATISTICAL TESTS: The Fleiss kappa, intraclass correlation coefficient, receiver operating characteristic curve, area under the curve (AUC), Delong test and Kaplan-Meier survival analysis. P value <0.05 was considered as statistical significance. RESULTS: Pathological VETC+ were confirmed in 68 patients (training set: 46, validation set: 22). In the validation set, DLR model based on peritumor PP (peri-PP) phase had the best performance (AUC: 0.844) in comparison to CR (AUC: 0.591) and ML (AUC: 0.672) models. Significant differences in recurrence rates between peri-PP DLR model-predicted VETC+ and VETC- status were found. DATA CONCLUSIONS: The DLR model provides a noninvasive method to discriminate VETC status and prognosis of HCC patients preoperatively. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 2.

CircRNA-ST6GALNAC6 increases the sensitivity of bladder cancer cells to erastin-induced ferroptosis by regulating the HSPB1/P38 axis.

Previous studies have demonstrated that circST6GALNAC6 is a tumor suppressor in bladder cancer. However, the role of circST6GALNAC6 in ferroptosis remains unclear. In the current study, ferroptosis was induced in bladder cancer cells by erastin. Functional experiments showed that overexpression of circST6GALNAC6 promoted ferroptosis of bladder cancer cells in vitro and in vivo. Mechanistic studies revealed that circST6GALNAC6 bound to the N-terminus of small heat shock protein 1 (HSPB1) and thus blocked the erastin-induced phosphorylation of HSPB1 at the Ser-15 site, a phosphorylation site in the protective response to ferroptosis stress. In addition, protein kinase C inhibited circST6GALNAC6-induced ferroptosis by increasing the overall phosphorylation level of HSPB1, further demonstrating the role of phosphorylation activation of HSPB1 in resistance to ferroptosis. Finally, the involvement of the HSPB1/p38 MAPK pathway in the downstream signal transduction of circST6GALNAC6 in bladder cancer ferroptosis regulation was determined. The regulatory mechanism of ferroptosis sensitivity dependent on circST6GALNAC6 expression levels in bladder cancer was revealed as circRNA regulation of various protein functions. CircST6GALNAC6 inhibits HSPB1 and promotes cell ferroptosis by occupying the phosphorylation site (Ser-15) of HSBP1 and activating the P38 MAPK signaling pathway. Therefore, enhancing the expression of circST6GALNAC6 to promote ferroptosis or using circST6GALNAC6 as a biomarker of ferroptosis sensitivity is of considerable importance to the development and application of ferroptosis intervention methods in bladder cancer.

Overexpression of PDE4D in mouse liver is sufficient to trigger NAFLD and hypertension in a CD36-TGF-ß1 pathway: therapeutic role of roflumilast.

Emerging evidence has shown that nonalcoholic fatty liver disease (NAFLD) may be both a consequence and a cause of hypertension. Recent studies have demonstrated that phosphodiesterase 4 (PDE4)-cAMP signaling represents a pathway relevant to the pathophysiology of metabolic disorders. This study aims to investigate the impact and the underlying mechanism of PDE4 in the pathogenesis of NAFLD and its associated hypertension. Here we demonstrated that high-fat-diet (HFD) fed mice developed NAFLD and hypertension, with an associated increase in hepatic PDE4D expression, which can be prevented and even reversed by PDE4 inhibitor roflumilast. Furthermore, we demonstrated that hepatic overexpression of PDE4D drove significant hepatic steatosis and elevation of blood pressure. Mechanistically, PDE4D activated fatty acid translocase CD36 signaling which facilitates hepatic lipid deposition, resulting in TGF-ß1 production by hepatocytes and excessive TGF-ß1 signaling in vessels and consequent hypertension. Specific silencing of TGF-ß1 in hepatocytes by siRNA using poly (ß-amino ester) nanoparticles significantly normalized hepatic PDE4D overexpression-activated TGF-ß1 signaling in vessels and hypertension. Together, the conclusions indicated that PDE4D plays an important role in the pathogenesis of NAFLD and associated hypertension via activation of CD36-TGF-ß1 signaling in the liver. PDE4 inhibitor such as roflumilast, which is clinically approved for chronic obstructive pulmonary disease (COPD) treatment, has the potential to be used as a preventive or therapeutic drug against NAFLD and associated hypertension in the future.

Merging Reagent Modulation and Remote Anchimeric Assistance for Glycosylation: Highly Stereoselective Synthesis of α-Glycans up to a 30-mer.

The efficient synthesis of long, branched, and complex carbohydrates containing multiple 1,2-cis glycosidic linkages is a long-standing challenge. Here, we report a merging reagent modulation and 6-O-levulinoyl remote anchimeric assistance glycosylation strategy, which is successfully applied to the first highly stereoselective synthesis of the branched Dendrobium Huoshanense glycans and the linear Longan glycans containing up to 30 contiguous 1,2-cis glucosidic bonds. DFT calculations shed light on the origin of the much higher stereoselectivities of 1,2-cis glucosylation with 6-O-levulinoyl group than 6-O-acetyl or 6-O-benzoyl groups. Orthogonal one-pot glycosylation strategy based on glycosyl ortho-alkynylbenzoates and ortho-(1-phenylvinyl)benzoates has been demonstrated in the efficient synthesis of complex glycans, precluding such issues as aglycon transfer inherent to orthogonal one-pot synthesis based on thioglycosides.

Serum omentin-1 level in patients with benign prostatic hyperplasia.

BACKGROUD: To evaluate the relationship between omentin-1 and benign prostatic hyperplasia (BPH). BPH is the most common urological disease in elderly men worldwide. Lower serum omentin-1 levels were reported to be negatively associated with the incidence of inflammation, diabetes, obesity and metabolic syndrome, which all play a role in the development of BPH. To the best of our knowledge, the relationship between omentin-1 and BPH has not been investigated previously. METHODS: A total of 70 males participated in this study, including forty patients diagnosed with BPH and thirty healthy males. The anthropometric measurements and the biochemical parameters were measured in this study. We evaluated serum omentin-1 levels and the correlation with those data. We also test the gene expression of IL-8, IL-18 in BPH group using the TURP tissues. RESULTS: The serum omentin-1 levels were lower in the BPH patients than in the control group (27.95 ± 4.18 versus 32.03 ± 5.46, p < 0.001). The general characteristics and biochemical parameters were investigated, and a negative correlation was found between serum omentin-1 levels and BMI in the BPH group (r = - 0.391, p = 0.013) as well as the whole group (r = - 0.457, p < 0.001). Multiple-factor binary regression analysis revealed that serum omentin-1was a protective factor of BPH development. Furthermore, lower serum omentin-1 levels were associated with higher mRNA expression of IL-8 or IL-18 in the BPH group. CONCLUSION: Omentin-1 may suppress the development of BPH and Lower serum omentin-1 levels in BPH patients might associated with higher prostate volume and higher IL-8 and IL-18 expression levels in their prostatic cells.

Synthesis of trisaccharide repeating unit of fucosylated chondroitin sulfate.

We described the chemical synthesis of a sulfated trisaccharide repeating unit of fucosylated chondroitin sulfate (FCS), which has significant anticoagulant activity. Well-functionalized monosaccharides were readily prepared, and highly efficient glycosylations using a common activator (NIS/TfOH) were also presented. The synthesized trisaccharide 4 could be used to extend oligosaccharide sequences.

Ground Control Point-Free Unmanned Aerial Vehicle-Based Photogrammetry for Volume Estimation of Stockpiles Carried on Barges.

In this study, an approach using ground control point-free unmanned aerial vehicle (UAV)-based photogrammetry is proposed to estimate the volume of stockpiles carried on barges in a dynamic environment. Compared with similar studies regarding UAVs, an indirect absolute orientation based on the geometry of the vessel is used to establish a custom-built framework that can provide a unified reference instead of prerequisite ground control points (GCPs). To ensure sufficient overlap and reduce manual intervention, the stereo images are extracted from a UAV video for aerial triangulation. The region of interest is defined to exclude the area of water in all UAV images using a simple linear iterative clustering algorithm, which segments the UAV images into superpixels and helps to improve the accuracy of image matching. Structure-from-motion is used to recover three-dimensional geometry from the overlapping images without assistance of exterior parameters obtained from the airborne global positioning system and inertial measurement unit. Then, the semi-global matching algorithm is used to generate stockpile-covered and stockpile-free surface models. These models are oriented into a custom-built framework established by the known distance, such as the length and width of the vessel, and they do not require GCPs for coordinate transformation. Lastly, the volume of a stockpile is estimated by multiplying the height difference between the stockpile-covered and stockpile-free surface models by the size of the grid that is defined using the resolution of these models. Results show that a relatively small deviation of approximately ±2% between the volume estimated by UAV photogrammetry and the volume calculated by traditional manual measurement was obtained. Therefore, the proposed approach can be considered the better solution for the volume measurement of stockpiles carried on barges in a dynamic environment because UAV-based photogrammetry not only attains superior density and spatial object accuracy but also remarkably reduces data collection time.

Self-assembled nanoparticles of reduction-sensitive poly (lactic-co-glycolic acid)-conjugated chondroitin sulfate A for doxorubicin delivery: preparation, characterization and evaluation.

In this study, reduction-sensitive self-assembled polymer nanoparticles based on poly (lactic-co-glycolic acid) (PLGA) and chondroitin sulfate A (CSA) were developed and characterized. PLGA was conjugated with CSA via a disulfide linkage (PLGA-ss-CSA). The critical micelle concentration (CMC) of PLGA-ss-CSA conjugate is 3.5 µg/mL. The anticancer drug doxorubicin (DOX) was chosen as a model drug, and was effectively encapsulated into the nanoparticles (PLGA-ss-CSA/DOX) with high loading efficiency of 15.1%. The cumulative release of DOX from reduction-sensitive nanoparticles was only 34.8% over 96 h in phosphate buffered saline (PBS, pH 7.4). However, in the presence of 20 mM glutathione-containing PBS environment, DOX release was notably accelerated and almost complete from the reduction-sensitive nanoparticles up to 96 h. Moreover, efficient intracellular DOX release of PLGA-ss-CSA/DOX nanoparticles was confirmed by CLSM assay in A549 cells. In vitro cytotoxicity study showed that the half inhibitory concentrations of PLGA-ss-CSA/DOX nanoparticles and free DOX against A549 cells were 1.141 and 1.825 µg/mL, respectively. Therefore, PLGA-ss-CSA/DOX nanoparticles enhanced the cytotoxicity of DOX in vitro. These results suggested that PLGA-ss-CSA nanoparticles could be a promising carrier for drug delivery.

[Value of magnetic resonance imaging for early diagnosis of prostatic carcinoma in central zone].

OBJECTIVE: To explore the magnetic resonance imaging (MRI) manifestations of early prostatic carcinoma (PCa) in central zone (CZ) . METHODS: A total of 284 cases of PCa were scanned by MRI while 24 cases of carcinoma in 28 PCa focus were in central zone. Their T1WI, T2WI, DWI and ADC value characteristics were analyzed respectively and the completeness of annular low signal between central and peripheral zones were observed. At the same time, 45 cases of PCa were located in peripheral zone (PZ) . Twenty cases of benign prostatic hyperplasia (BPH) were comparatively analyzed. All cases received a histological diagnosis. RESULTS: Most cases of early PCa in CZ demonstrated ill-defined margin, amorphous shape and equal signal intensity on T1WI, low signal intensity on T2WI and high signal intensity on DWI. The mean ADC value for PCa focus was (0.867 ± 0.074)×10(-3) mm(2)/s and PCa foci were enhanced slightly. In these cases, most annular low signals between CZ and PZ were destroyed. The difference of ADC values between PCa in CZ and PZ groups ((0.914 ± 0.066) ×10(-3) mm(2)/s ) had no statistic significance (P > 0.05) , but the ADC values between PCa and BPH in CZ groups ((1.517 ± 0.315) ×10(-3) mm(2)/s ) had statistically significant difference (P < 0.05). CONCLUSION: Some reliable diagnostic characteristics on MRI may be used for an early diagnosis of PCa in CZ.

Association of blood trihalomethane concentrations with diabetes mellitus in older adults in the US: a cross-sectional study of NHANES 2013-2018.

Background: Previous studies have demonstrated that there is a correlation between trihalomethanes and disease progression, such as allergic diseases. As we know, only few studies focused on the relationship between trihalomethanes and metabolic diseases, such as diabetes mellitus. Objective: The aim of this study was to further explore the associations between blood trihalomethane concentrations and diabetes mellitus in older adults in the US. Methods: Data were collected from the National Health and Nutrition Examination Study (NHANES) database in the survey cycle during 2013 to 2018, including 2,511 older adults in the US whose blood trihalomethane concentrations were measured, involving chloroform (TCM) and brominated trihalomethanes (Br-THMs). Br-THMs include bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM). Meanwhile, the concentration of total trihalomethanes (TTHMs) was also measured later. A multivariate logistic regression and restricted cubic spline were used to examine the relationship between blood THMs and diabetes mellitus. Meanwhile, we performed a subgroup analysis, which aims to explore the stability of this relationship in different subgroups. In order to further consider the impact of various disinfection by-products on diabetes, we also used weighted quantile sum (WQS). To explore the correlation in trihalomethanes, we plot a correlation heatmap. Results: Adjusting for potential confounders, we found that there was a significant negative association between chloroform and diabetes mellitus [Model 1 (adjusted for covariates including age, sex, and race, OR = 0.71; 95% CI: 0.50-1.02; p = 0.068; p for trend = 0.094); Model 2 (adjusted for all covariates, OR = 0.68; 95% CI: 0.48-0.96; p = 0.029; p for trend = 0.061)]. In the bromodichloromethane, we reached a conclusion that is similar to TCM [Model 1 (adjusted for covariates including age, sex, and race, OR = 0.54; 95% CI: 0.35-0.82; p = 0.005; p for trend = 0.002); Model 2 (adjusted for all covariates, OR = 0.54; 95% CI: 0.35-0.82; p = 0.003; p for trend = 0.002)]. Meanwhile, the restricted cubic spline curve also further confirms this result (p overall = 0.0027; p overall< 0.001). Based on the analysis in the subgroups, we found that the value p for interaction in the majority of subgroups is higher than 0.1. Trihalomethanes and diabetes were inversely associated, and in the WQS, chloroform and bromodichloromethane were found to be the major contributors to this relationship. In the correlation analysis, we found that most trihalomethanes have a weak correlation, except for TBM and TCM with a strong correlation. Conclusion: Our results in this study showed that blood chloroform, bromodichloromethane concentrations, and diabetes mellitus in older adults in the US are negatively correlated, suggesting that chloroform and bromodichloromethane can be protective factors for diabetes.

Multivitamins co-intake can reduce the prevalence of kidney stones: a large-scale cross-sectional study.

BACKGROUND: This research aimed to explore the association between changes in the intake of common individual vitamins and combinations of vitamins and the prevalence of kidney calculi. METHODS: We used data from NHANES to investigate the association between nine common vitamins and kidney stone prevalence. Participants were clustered into several vitamin exposure patterns using an unsupervised K-means clustering method. We used logistic regression models and restrictive cubic spline curves to explore the influence of vitamins. RESULTS: The regression model exposed that compared to lower intake, high intake of vitamin B6 [Q4: OR (95% CI) = 0.76 (0.62, 0.93)], vitamin C [Q4: OR (95% CI) = 0.73 (0.59, 0.90)] and vitamin D [Q4: OR (95% CI) = 0.77 (0.64, 0.94)] individually exerted protective effects against the prevalence of kidney stones. Furthermore, the restrictive cubic spline analysis showed that the protective effect against the prevalence of kidney stones is enhanced as the take of vitamin B6 and vitamin D increased. Moreover, with the increase in vitamin C intake, its protective effect may turn into a risk factor. Regarding mixed exposure, Cluster 4 exhibited a significant protective effect against kidney stones compared with Cluster 1 [Model 3: OR (95% CI) = 0.79 (0.64, 0.98)]. CONCLUSIONS: Our research revealed that high levels of vitamin B6 and vitamin D intake were linked to a lower prevalence of kidney stone. With the gradual increase intake of vitamin C, the prevalence of kidney calculi decreased first and then increased. In addition, the co-exposure of nine vitamins is a protective factor for kidney stone disease.

Total synthesis of Lentinus giganteus glycans with antitumor activities via stereoselective α-glycosylation and orthogonal one-pot glycosylation strategies.

The accessibility to long, branched and complex glycans containing many 1,2-cis glycosidic linkages with precise structures remains a challenging task in chemical synthesis. Reported here is an efficient, stereoselective and orthogonal one-pot synthesis of a tetradecasaccharide and shorter sequences from Lentinus giganteus polysaccharides with antitumor activities. The synthetic strategy consists of: (1) newly developed merging reagent modulation and remote anchimeric assistance (RMRAA) α-(1→6)-galactosylation in a highly stereoselective manner, (2) DMF-modulated stereoselective α-(1→3)-glucosylation, (3) RMRAA stereoselective α-(1→6)-glucosylation, (4) several orthogonal one-pot glycosylations on the basis of N-phenyltrifluoroacetimidate (PTFAI) glycosylation, Yu glycosylation and ortho-(1-phenylvinyl)benzoate (PVB) glycosylation to streamline oligosaccharide synthesis, and (5) convergent [7 + 7] glycosylation for the final assembly of the target tetradecasaccharide. In particular, this new RMRAA α-galactosylation method has mild reaction conditions, broad substrate scopes and significantly shortened step counts for the heptasaccharide synthesis in comparison with 4,6-di-tert-butylsilyene (DTBS) directed α-galactosylation. Furthermore, DFT calculations shed light on the origins of remote anchimeric assistance effects (3,4-OBz > 3,4-OAc > 4-OBz > 3-OBz) of acyl groups.

Inflammatory Myofibroblastic Tumor of the Urinary Bladder: An 11-Year Retrospective Study From a Single Center.

Purpose: To share our experience in the diagnosis and treatment of an inflammatory myofibroblastic tumor of the urinary bladder (IMTUB). Materials and Methods: A database searches in the pathology archives by using the term "inflammatory myofibroblastic tumor" and" bladder" in our hospital department of pathology from 2010 to 2021. Patient characteristics, clinical features, histopathological results, immunohistochemical staining results, and treatment outcomes were reviewed. Results: Fourteen cases of IMTUB were retrieved. The mean age was 44.7 ± 18.9 years (range 12-74). Nine (64.3%) of the patients presented with hematuria, followed by seven (50%) with odynuria, five (35.7%) with urgent urination, and one (7.1%) with dysuria. Ten (71.4%) of the patients were treated with partial cystectomy (PC), three (21.4%) with transurethral resection of bladder tumor (TURBT), and one (7.1%) with radical cystectomy (RC). Histopathologically, eight (57.1%) had a compact spindle cell pattern. Anaplastic lymphoma kinase (ALK) staining was positive in six (75%) of 8 cases. During a mean follow-up period of 43.9 ± 38 months (range 3-117), a patient had recurrence within half a month. Then, the patient was treated with further TURBT surgery and had no recurrence within 6 months. Thirteen of the patients had no local recurrence or distant metastasis. Conclusion: Inflammatory myofibroblastic tumor of the urinary bladder (IMTUB) is clinically rare and has a good prognosis. The disease is mainly treated with surgery to remove the tumor completely. It can easily be misdiagnosed as bladder urothelial carcinoma, leiomyosarcoma, or rhabdomyosarcoma, which may result in overtreatment and poor quality of life of patients.

Self-delivery of metal-coordinated mitochondria protonophore uncoupler for O2-exhausting enhanced bioreductive therapy.

Mitochondrial uncouplers are capable of maximizing cell respiration to induce local hypoxia, which provides a promising target for bioreductive therapy. In this work, we develop a metal-coordinated mitochondria protonophore uncoupler (designated as Cu-BAQ) for O2-exhausting enhanced bioreductive therapy. In brief, carrier free Cu-BAQ is self-assembled by copper ion (Cu2+), mitochondria protonophore uncoupler (BAM15) and bioreductive drug (AQ4N), which possesses a favorable stability and an improved bioavailability. After intravenous administration, nanosized Cu-BAQ prefers to accumulate at tumor site for effective cellular uptake. Moreover, the Cu2+-coordinated nanomedicine of Cu-BAQ exhibits a glutathione (GSH) responsive drug release behavior and the released BAM15 could promote the mitochondria uncoupling to maximize the cell respiration. As a result, the excessive O2 consumption would induce local hypoxia to activate AQ4N for enhanced bioreductive therapy. In vivo investigations demonstrate that Cu-BAQ is able to regulate tumor hypoxia microenvironment and significantly inhibit tumor growth with a minimized side effect. This GSH-responsive self-delivery nanoplatform provides a new insight for the development of individualized biomedicine for hypoxic tumor precision therapy.

Direct Detection of Pulmonary Fibrosis by Near-Infrared-Responsive Biomimetic Platelets.

BACKGROUND: Pulmonary fibrosis (PF) is a fatal lung disease and affects over 5 million patients worldwide. Precise and early detection of PF is of pivotal importance to slow the disease progression. However, there are currently no effective tools to detect PF directly. PURPOSE: This study aimed to develop an imaging modality to detect PF directly. Excessive collagen deposition is the hallmark of PF. Herein, we developed a novel PF diagnostic agent, namely PVD (platelets-derived nanovesicles labeled with dye), by utilizing near-infrared (NIR)-responsive biomimetic platelets that specifically recognize collagen. METHODS: In brief, platelets membrane was extracted from purified platelets by freeze/thaw and formed to PVD nanovesicles via sonication and extrusion, when loaded with DiR dye. Red blood cells membrane loaded with DiR was prepared in the same way as PVD to form RVD as control. Collagen self-assembled on microplates was used as an in vitro collagen fibrils model and monocrotaline-induced rats were used as an in vivo PF model. RESULTS: We demonstrated that PVD, but not RVD nor other controls, could bind collagen both in vitro and in vivo, and directly detect pulmonary fibrosis in vivo and ex vivo at the early PF stage. CONCLUSION: Collectively, PVD is a versatile NIR-responsive probe for the direct visualization of collagen, and can be particularly helpful in direct detecting PF. To the best of our knowledge, PVD is the first report of a NIR probe for the direct detection of pulmonary fibrosis.

Efficacy and Safety of Probiotics Combined With Traditional Chinese Medicine for Ulcerative Colitis: A Systematic Review and Meta-Analysis.

Background: The combination of probiotics and traditional Chinese medicine (TCM) is a prospective therapy for ulcerative colitis (UC), and its efficacy and safety need to be urgently evaluated. Objective: This study aims to comprehensively assess the efficacy and safety of probiotics combined with TCM for the treatment of UC. Methods: The Pubmed, EMBASE, Cochrane library, China Academic Journals (CNKI), Wan-fang database, Chinese biomedical literature service system (CBM), and Chinese Science and Technology Journals (CQVIP) were searched. Subgroup analysis were designed in accordance with different control drugs, treatment courses, and types of probiotics. The Review Manager software (version 5.4.1) was utilized for statistical analysis. Results: 14 original studies containing 1,154 patients were analyzed and showed that probiotics with TCM was more effective than 5-aminosalicylic acid (5-ASA), probiotics or TCM used individually. Moreover, probiotics combined with TCM could inhibit the intestinal inflammation, reduce the recurrence rate and the incidence of adverse events. The subgroup analysis showed that a mixture of different probiotics was more effective than a single strain. Conclusion: It is suggested that probiotics combined with TCM could effectively control clinical symptoms, inhibit intestinal inflammatory response, and finally slow down the disease progress and reduce the disease recurrence with less adverse events. The mixture of different probiotics used in conjunction with individually tailored TCM is a potential clinical strategy for UC.

The application of Tong-fu therapeutic method on ulcerative colitis: A systematic review and meta-analysis for efficacy and safety of rhubarb-based therapy.

Background: Tong-fu therapeutic method (TFTM) is a traditional Chinese medicine treatment method for ulcerative colitis, which is a novel treatment strategies and have purgative effect. As the most representative medicinal of TFTM, Rhubarb has been reported to have a therapeutic impact on ulcerative colitis by regulating intestinal flora, anti-inflammation, and improving intestinal microcirculation. Although rhubarb has been widely used in Chinese medicine for the treatment of ulcerative colitis, the appropriate protocol is still demanded to its rational use in clinic, which promoted to evaluate the efficacy and safety for rhubarb-based therapy on ulcerative colitis. Method: Clinical trials were searched through PubMed, Cochrane Library, Web of Science, Excerpta Medica Database, Chinese National Knowledge Infrastructure, WAN FANG Database, Chinese Scientific Journal Database, and Chinese Biomedical Literature Database. The subgroup analyses were performed with three groups: medication, course of treatment, and route of administration. The statistical analyses were performed on Review Manager software (version 5.4.1). Results: A total of 2, 475 patients in 30 original studies were analyzed in this article. It was found that rhubarb-based therapy could increase clinical efficacy and reduce the recurrence rate. Subgroup analyses showed that rhubarb-based therapy was more effective than 5-aminosalicylic acid or sulfasalazine alone. In addition, the hypercoagulable state of ulcerative colitis could be ameliorated by decreasing platelet (PLT) and fibrinogen (FIB), and increasing prothrombin time (PT) significantly. Moreover, C-reaction protein (CRP), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8, and IL-1ß expression were significantly reduced, while IL-10 production was increased, which mediated the alleviation of intestinal inflammation stress. Conclusion: Rhubarb-based therapy could effectively improve ulcerative colitis. Of note, the rhubarb-based medicinal formulas combined with 5-ASA or SASP are more effective than the 5-ASA or SASP alone. In addition, although rhubarb has side effect, the results of our analysis showed that rhubarb-based therapy did not exhibit significant side effects. This means it has a high safety profile in clinical use. Moreover, the use of rhubarb-based therapy is recommend to use within 1-13 weeks or 3 months via administered orally or by enema, which is contributes to ensure the curative effect and avoid its toxic and side effects. As an important case of TFTM, rhubarb-based therapy provides evidence for the practical application of TFTM.

The role of key image notes in CT imaging study interpretation.

The objective of the study was to investigate the clinical effects of CT key image notes (KIN) in the interpretation of a CT image study. All experiments were approved by the ethics committee of the local district. Six experienced radiologists were equally divided into routine reporting (RR) group and KIN reporting (KIN) group. CT scans of each 100 consecutive cases before and after using KIN technique were randomly selected, and the reports were made by group RR and KIN, respectively. All the reports were again reviewed 3 months later by both groups. All the results with using or not using KIN were interpreted and reinterpreted after 3 months by six clinicians, who were experienced in picture archiving and communication system (PACS) applications and were equally divided into the clinical routine report group and the clinical KIN report group, respectively. The results were statistically analyzed; the time used in making a report, the re-reading time 3 months later, and the consistency of imaging interpretation were determined and compared between groups. After using KIN technique, the time used in making a report was significantly increased (8.77 ± 5.27 vs. 10.53 ± 5.71 min, P < 0.05), the re-reading time was decreased (5.23 ± 2.54 vs. 4.99 ± 1.70 min, P < 0.05), the clinical interpretation and reinterpretation time after 3 months were decreased, and the consistency of the interpretation, reinterpretation between different doctors in different time was markedly improved (P < 0.01). CT report with KIN technique in PACS can significantly improve the consistency of the interpretation and efficiency in routine clinical work.

Novel Insight Into the Role of Immune Dysregulation in Amyotrophic Lateral Sclerosis Based on Bioinformatic Analysis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of motor neurons. The causative pathogenic mechanisms in ALS remain unclear, limiting the development of treatment strategies. Neuroinflammation and immune dysregulation were involved in the disease onset and progression of several neurodegenerative disorders, including ALS. In this study, we carried out a bioinformatic analysis using publicly available datasets from Gene Expression Omnibus (GEO) to investigate the role of immune cells and genes alterations in ALS. Single-sample gene set enrichment analysis revealed that the infiltration of multiple types of immune cells, including macrophages, type-1/17 T helper cells, and activated CD4 + /CD8 + T cells, was higher in ALS patients than in controls. Weighted gene correlation network analysis identified immune genes associated with ALS. The Gene Ontology analysis revealed that receptor and cytokine activities were the most highly enriched terms. Pathway analysis showed that these genes were enriched not only in immune-related pathways, such as cytokine-cytokine receptor interaction, but also in PI3K-AKT and MAPK signaling pathways. Nineteen immune-related genes (C3AR1, CCR1, CCR5, CD86, CYBB, FCGR2B, FCGR3A, HCK, ITGB2, PTPRC, TLR1, TLR2, TLR7, TLR8, TYROBP, VCAM1, CD14, CTSS, and FCER1G) were identified as hub genes based on least absolute shrinkage and selection operator analysis. This gene signature could differentiate ALS patients from non-neurological controls (p < 0.001) and predict disease occurrence (AUC = 0.829 in training set; AUC = 0.862 in test set). In conclusion, our study provides potential biomarkers of ALS for disease diagnosis and therapeutic monitoring.

A One-Pot Synthesis of Glycans and Nucleosides Based on ortho-(1-Phenylvinyl)benzyl Glycosides.

One-pot synthesis of both glycans and nucleosides remains rare and challenging. Herein, we report a one-pot glycosylation strategy for glycans and nucleosides synthesis based on ortho-(1-phenylvinyl)benzyl glycosides, which has several advantages, including no aglycon transfers, no undesired interference of departing species, no unpleasant odor, and up to the construction of four different glycosidic linkages.