RNA aptamers with specific binding affinity to CD40 (CD40Apt) represents a promising antagonist of the CD40-CD40L signaling for thyroid-associated ophthalmopathy (TAO) treatment in mouse.

Thyroid-associated ophthalmopathy (TAO) is the most common autoimmune inflammatory diseases of the orbit. The CD40-CD40L pathway has been regarded as a potential molecular mechanism contributing to the development and progression of TAO, and RNA aptamers with specific binding affinity to CD40 (CD40Apt) represents a promising inhibitor of the CD40-CD40L signaling in TAO treatment. In this study, CD40Apt was confirmed to specifically recognize mouse CD40-positive ortibtal fibroblast. Mouse orbital fibroblasts were isolated from TAO mice model orbital tissues and validated. In TGF-ß-induced orbital fibroblast activation model in vitro, CD40Apt administration inhibited TGF-ß-induced cell viability, decreased TGF-ß-induced α-SMA, Collagen I, Timp-1, and vimentin levels, and suppressed TGF-ß-induced phosphorylation of Erk, p38, JNK, and NF-κB. In TAO mice model in vivo, CD40Apt caused no significant differences to the body weight of mice; furthermore, CD40Apt improved the eyelid broadening, ameliorated inflammatory infiltration and the hyperplasia in orbital muscle and adipose tissues in model mice. Concerning orbital fibroblast activation, CD40Apt reduced the levels of CD40, collagen I, TGF-ß, and α-SMA in orbital muscle and adipose tissues of model mice. Finally, CD40Apt administration significantly suppressed Erk, p38, JNK, and NF-κB phosphorylation. In conclusion, CD40Apt, specifically binds to CD40 proteins in their natural state on the cell surface with high affinity, could suppress mouse orbital fibroblast activation, therefore improving TAO in mice model through the CD40 and downstream signaling pathways. CD40Apt represents a promising antagonist of the CD40-CD40L signaling for TAO treatment.

New US capsule endoscopy for superficial and submucosal imaging of the esophagus: the first-in-human study.

BACKGROUND AND AIMS: EUS is essential in diagnosing and staging of esophageal subepithelial lesions and tumors. However, EUS is invasive, relies on highly trained endoscopists, and typically requires sedation. The newly developed US capsule endoscopy (USCE), which incorporates both white-light and US imaging modalities into a tethered capsule, is a minimally invasive method for obtaining superficial and submucosal information of the esophagus. This study aimed to assess the feasibility and safety of this USCE system. METHODS: Twenty participants were enrolled: 10 healthy volunteers and 10 patients with esophageal lesions indicated for EUS. Participants first underwent USCE and subsequently EUS within 48 hours. The primary outcome was the technical success rate of USCE. Secondary outcomes were safety, visualization of the esophagus, and comfort assessment. RESULTS: The technical success rate of USCE was 95% because 1 patient failed to swallow the capsule. No adverse events were observed. The esophagus was well visualized, and all lesions were detected under USCE optical mode in 19 participants. For healthy volunteers, the US images of normal esophageal walls were all characterized by differentiated 7-layer architecture under both USCE and EUS. For 9 patients, the features of esophageal lesions were recognized clearly under USCE, and presumptive diagnoses derived from USCE were all consistent with those from EUS. Most participants preferred USCE to EUS. CONCLUSIONS: The novel USCE is feasible and safe to observe the esophageal mucosa and acquire submucosal information, which has the potential to be widely used in the clinic. (Clinical trial registration number: NCT05054933.).

Enhanced Versatility in Thorium Removal: Mesoporous Silica-Coated Magnetic Nanoparticles Functionalized by Phenanthroline Diamide as a Selective Adsorbent.

In order to promote the sustainable development of nuclear energy through thorium (Th(IV)) recycling, we synthesized SiO2-coated magnetic functional nanocomposites (SiO2@Fe3O4) that were modified with 2,9-diamide-1,10-phenanthroline (DAPhen) to serve as an adsorbent for Th(IV) removal. SiO2@Fe3O4-DAPhen showed effective Th(IV) adsorption in both weakly and strongly acidic solutions. Owing to its porous structure that facilitated rapid adsorption kinetics, equilibrium was achieved within 5 and 0.5 min at pH 3 and 1 mol L-1 HNO3, respectively. In weakly acidic solutions, Th(IV) primarily formed chemical coordination bonds with DAPhen groups, while in strongly acidic solutions, the dominant interaction was electrostatic attraction. Density functional theory (DFT) calculations indicated that electrostatic attraction was weaker compared to chemical coordination, resulting in reduced diffusion resistance and consequently faster adsorption rates in strongly acidic solutions. Furthermore, SiO2@Fe3O4-DAPhen exhibited a high adsorption capacity for Th(IV); it removed Th(IV) through chelation and electrostatic attraction at pH 3 and 1 mol L-1 HNO3, with maximum adsorption capacities of 833.3 and 1465.7 mg g-1, respectively. SiO2@Fe3O4-DAPhen also demonstrated excellent tolerance to salinity, adsorption selectivity, and radiation resistance, thereby highlighting its practical potential for Th(IV) removal in diverse contaminated water sources. Hence, SiO2@Fe3O4-DAPhen represents a promising choice for the rapid and efficient removal of Th(IV).

The clinicopathological significance of TOP2A expression in malignant peritoneal mesothelioma.

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare malignant tumor with a high mortality rate and extremely poor prognosis. TOP2A expression is associated with cell proliferation and cell cycle progression. We aimed to demonstrate the expression profile of TOP2A in MPM and its correlation with clinicopathological features. METHODS: Clinicopathological information from 100 MPM cases was collected at Beijing Shijitan Hospital, Capital Medical University. Immunohistochemistry (IHC) was performed to evaluate TOP2A levels. The associations between TOP2A levels and clinicopathological features or prognosis were analyzed. Clinical follow-up data were reviewed to determine correlations among the pathological prognostic factors using the Kaplan-Meier estimator and univariate/multivariate Cox proportional hazards regression models. RESULTS: Among the 100 MPM patients, there were 48 males and 52 females, with a median age of 54 years (range: 24-72 years). The cutoff curve was used to find the boundary value of the TOP2A-positive rate. TOP2A positive rate ≥ 11.97 % accounted for 48 % in tumor tissue. The TOP2A-positive rate was not associated with sex, age, asbestos exposure, peritoneal carcinomatosis index (PCI) score, or completeness of cytoreduction (CC) score in MPM. Univariate analysis revealed survival-related pathological parameters, including asbestos exposure, CA125, histological type, PCI score, CC score, Ki-67 index, and TOP2A positive rate. Multivariate analysis identified that asbestos exposure history, PCI score, Ki-67 proliferation index and TOP2A positive rate in tissue are independent prognostic factors. CONCLUSIONS: High expression of TOP2A is linked to better prognosis of MPM.

Construction of predictive ceRNA network and identification of the patterns of immune cells infiltrated in Graves' ophthalmopathy. / Gravesçœ¼ç— ä¸­é¢„æµ‹æ€§ceRNAç½‘ç»œçš„æž„å»ºåŠå ç–«ç»†èƒžæµ¸æ¶¦æ¨¡å¼çš„é‰´å®š.

OBJECTIVES: Graves' ophthalmopathy (GO) is a multifactorial disease, and the mechanism of non coding RNA interactions and inflammatory cell infiltration patterns are not fully understood. This study aims to construct a competing endogenous RNA (ceRNA) network for this disease and clarify the infiltration patterns of inflammatory cells in orbital tissue to further explore the pathogenesis of GO. METHODS: The differentially expressed genes were identified using the GEO2R analysis tool. The Kyoto encyclopedia of genes and genomes (KEGG) and gene ontology analysis were used to analyze differential genes. RNA interaction relationships were extracted from the RNA interactome database. Protein-protein interactions were identified using the STRING database and were visualized using Cytoscape. StarBase, miRcode, and DIANA-LncBase Experimental v.2 were used to construct ceRNA networks together with their interacted non-coding RNA. The CIBERSORT algorithm was used to detect the patterns of infiltrating immune cells in GO using R software. RESULTS: A total of 114 differentially expressed genes for GO and 121 pathways were detected using both the KEGG and gene ontology enrichment analysis. Four hub genes (SRSF6, DDX5, HNRNPC,and HNRNPM) were extracted from protein-protein interaction using cytoHubba in Cytoscape, 104 nodes and 142 edges were extracted, and a ceRNA network was identified (MALAT1-MIR21-DDX5). The results of immune cell analysis showed that in GO, the proportions of CD8+ T cells and CD4+ memory resting T cells were upregulated and downregulated, respectively. The proportion of CD4 memory resting T cells was positively correlated with the expression of MALAT1, MIR21, and DDX5. CONCLUSIONS: This study has constructed a ceRNA regulatory network (MALAT1-MIR21-DDX5) in GO orbital tissue, clarifying the downregulation of the proportion of CD4+ stationary memory T cells and their positive regulatory relationship with ceRNA components, further revealing the pathogenesis of GO.

Redundancy Reduction for Sensor Deployment in Prosthetic Socket: A Case Study.

The irregular pressure exerted by a prosthetic socket over the residual limb is one of the major factors that cause the discomfort of amputees using artificial limbs. By deploying the wearable sensors inside the socket, the interfacial pressure distribution can be studied to find the active regions and rectify the socket design. In this case study, a clustering-based analysis method is presented to evaluate the density and layout of these sensors, which aims to reduce the local redundancy of the sensor deployment. In particular, a Self-Organizing Map (SOM) and K-means algorithm are employed to find the clustering results of the sensor data, taking the pressure measurement of a predefined sensor placement as the input. Then, one suitable clustering result is selected to detect the layout redundancy from the input area. After that, the Pearson correlation coefficient (PCC) is used as a similarity metric to guide the removal of redundant sensors and generate a new sparser layout. The Jenson-Shannon Divergence (JSD) and the mean pressure are applied as posterior validation metrics that compare the pressure features before and after sensor removal. A case study of a clinical trial with two sensor strips is used to prove the utility of the clustering-based analysis method. The sensors on the posterior and medial regions are suggested to be reduced, and the main pressure features are kept. The proposed method can help sensor designers optimize sensor configurations for intra-socket measurements and thus assist the prosthetists in improving the socket fitting.

The Involvement of Chronic Kidney Disease and Acute Kidney Injury in Disease Severity and Mortality in Patients with COVID-19: A Meta-Analysis.

BACKGROUND: A meta-analysis was performed to evaluate the association of chronic kidney disease (CKD) and acute kidney injury (AKI) with the clinical prognosis of patients with coronavirus disease 2019 (COVID-19). METHODS: The PubMed, EMBASE, Cochrane Library, medRxiv, Social Science Research Network, and Research Square databases (from December 1, 2019 to May 15, 2020) were searched to identify studies that reported the associations of CKD/AKI and disease severity/mortality. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated and meta-regression was performed. RESULTS: In total, 42 studies enrolling 8,932 participants were included in this meta-analysis. The quality of most included studies was moderate to high. Compared with patients without previously diagnosed CKD, those with CKD had a significantly increased risk of progressing to a severe condition (OR 2.31, 95% CI 1.64-3.24) or death (OR 5.11, 95% CI 3.36-7.77). Similarly, compared with patients without AKI, those with AKI had a significantly increased risk of progressing to a severe condition (OR 11.88, 95% CI 9.29-15.19) or death (OR 30.46, 95% CI 18.33-50.59). Compared with patients with previously diagnosed CKD, those with AKI were more likely to progress to a severe condition (pgroup < 0.001, I2 = 98.3%) and even to death (pgroup < 0.001, I2 = 96.5%). Age had a significant impact on the association between CKD and disease severity (p = 0.001) but had no impact on the associations between AKI and disease severity (p = 0.80), between CKD and mortality (p = 0.51), or between AKI and mortality (p = 0.86). Four important complications (cardiac injury, shock, acute respiratory distress syndrome, and liver injury) did not significantly affect the associations between CKD/AKI and disease severity/mortality, indicating that CKD/AKI may be independent clinical prognostic indicators for patients with COVID-19. CONCLUSIONS: In COVID-19 patients, CKD/AKI was associated with worse outcomes compared with those without CKD/AKI. AKI was associated with higher risks of severity and mortality than CKD.

Immunosuppressive treatment for primary membranous nephropathy in adults with nephrotic syndrome.

BACKGROUND: Primary membranous nephropathy (PMN) is a common cause of nephrotic syndrome in adults. Without treatment, approximately 30% of patients will experience spontaneous remission and one third will have persistent proteinuria. Approximately one-third of patients progress toward end-stage kidney disease (ESKD) within 10 years. Immunosuppressive treatment aims to protect kidney function and is recommended for patients who do not show improvement of proteinuria by supportive therapy, and for patients with severe nephrotic syndrome at presentation due to the high risk of developing ESKD. The efficacy and safety of different immunosuppressive regimens are unclear. This is an update of a Cochrane review, first published in 2004 and updated in 2013. OBJECTIVES: The aim was to evaluate the safety and efficacy of different immunosuppressive treatments for adult patients with PMN and nephrotic syndrome. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 1 April 2021 with support from the Cochrane Kidney and Transplant Information Specialist using search terms relevant to this review. Studies in the Register were identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) investigating effects of immunosuppression in adults with PMN and nephrotic syndrome were included. DATA COLLECTION AND ANALYSIS: Study selection, data extraction, quality assessment, and data synthesis were performed using Cochrane-recommended methods. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: Sixty-five studies (3807 patients) were included. Most studies exhibited a high risk of bias for the domains, blinding of study personnel, participants and outcome assessors, and most studies were judged unclear for randomisation sequence generation and allocation concealment. Immunosuppressive treatment versus placebo/no treatment/non-immunosuppressive treatment In moderate certainty evidence, immunosuppressive treatment probably makes little or no difference to death, probably reduces the overall risk of ESKD (16 studies, 944 participants: RR 0.59, 95% CI 0.35 to 0.99; I² = 22%), probably increases total remission (complete and partial) (6 studies, 879 participants: RR 1.44, 95% CI 1.05 to 1.97; I² = 73%) and complete remission (16 studies, 879 participants: RR 1.70, 95% CI 1.05 to 2.75; I² = 43%), and probably decreases the number with doubling of serum creatinine (SCr) (9 studies, 447 participants: RR 0.46, 95% CI 0.26 to 0.80; I² = 21%). However, immunosuppressive treatment may increase the number of patients relapsing after complete or partial remission (3 studies, 148 participants): RR 1.73, 95% CI 1.05 to 2.86; I² = 0%) and may lead to a greater number experiencing temporary or permanent discontinuation/hospitalisation due to adverse events (18 studies, 927 participants: RR 5.33, 95% CI 2.19 to 12.98; I² = 0%). Immunosuppressive treatment has uncertain effects on infection and malignancy. Oral alkylating agents with or without steroids versus placebo/no treatment/steroids Oral alkylating agents with or without steroids had uncertain effects on death but may reduce the overall risk of ESKD (9 studies, 537 participants: RR 0.42, 95% CI 0.24 to 0.74; I² = 0%; low certainty evidence). Total (9 studies, 468 participants: RR 1.37, 95% CI 1.04 to 1.82; I² = 70%) and complete remission (8 studies, 432 participants: RR 2.12, 95% CI 1.33 to 3.38; I² = 37%) may increase, but had uncertain effects on the number of patients relapsing, and decreasing the number with doubling of SCr. Alkylating agents may be associated with a higher rate of adverse events leading to discontinuation or hospitalisation (8 studies 439 participants: RR 6.82, 95% CI 2.24 to 20.71; I² = 0%). Oral alkylating agents with or without steroids had uncertain effects on infection and malignancy. Calcineurin inhibitors (CNI) with or without steroids versus placebo/no treatment/supportive therapy/steroids We are uncertain whether CNI with or without steroids increased or decreased the risk of death or ESKD, increased or decreased total or complete remission, or reduced relapse after complete or partial remission (low to very low certainty evidence). CNI also had uncertain effects on decreasing the number with a doubling of SCr, temporary or permanent discontinuation or hospitalisation due to adverse events, infection, or malignancy. Calcineurin inhibitors (CNI) with or without steroids versus alkylating agents with or without steroids We are uncertain whether CNI with or without steroids increases or decreases the risk of death or ESKD. CNI with or without steroids may make little or no difference to total remission (10 studies, 538 participants: RR 1.01, 95% CI 0.89 to 1.15; I² = 53%; moderate certainty evidence) or complete remission (10 studies, 538 participants: RR 1.15, 95% CI 0.84 to 1.56; I² = 56%; low certainty evidence). CNI with or without steroids may increase relapse after complete or partial remission. CNI with or without steroids had uncertain effects on SCr increase, adverse events, infection, and malignancy. Other immunosuppressive treatments Other interventions included azathioprine, mizoribine, adrenocorticotropic hormone, traditional Chinese medicines, and monoclonal antibodies such as rituximab. There were insufficient data to draw conclusions on these treatments. AUTHORS' CONCLUSIONS: This updated review strengthened the evidence that immunosuppressive therapy is probably superior to non-immunosuppressive therapy in inducing remission and reducing the number of patients that progress to ESKD. However, these benefits need to be balanced against the side effects of immunosuppressive drugs. The number of included studies with high-quality design was relatively small and most studies did not have adequate follow-up. Clinicians should inform their patients of the lack of high-quality evidence. An alkylating agent (cyclophosphamide or chlorambucil) combined with a corticosteroid regimen had short- and long-term benefits, but this was associated with a higher rate of adverse events. CNI (tacrolimus and cyclosporin) showed equivalency with alkylating agents however, the certainty of this evidence remains low. Novel immunosuppressive treatments with the biologic rituximab or use of adrenocorticotropic hormone require further investigation and validation in large and high-quality RCTs.

Diagnostic thresholds and performance of noninvasive fibrosis scores are limited by age in patients with chronic hepatitis B.

AIM: We aimed at investigating the effects of age on the predictive performances of noninvasive fibrosis scores for significant fibrosis in patients with chronic hepatitis B (CHB). METHODS: A total of 496 CHB patients who underwent liver biopsy were stratified into four age groups: ≤30, 31 to 40, 41 to 50, and ≥51 years. Receiver operating characteristic curves were used to evaluate the diagnostic performance of aspartate aminotransferase to platelet ratio index (APRI), fibrosis score-4 (Fib-4) and γ-glutamyl transpeptidase to platelet ratio (GPR) in different age groups. RESULTS: The extent of fibrosis significantly increased with age, and the percentage of significant fibrosis (≥F2) was 21.3%, 29.0%, 38.5%, and 46.1%, respectively. All three scores displayed a moderate accuracy to diagnose significant fibrosis in overall patients. However, for patients with age ≤30 years, APRI, Fib-4, and GPR performed poorly with the AUROC of 0.567, 0.627 and 0.596, respectively. Furthermore, using the established cut-off values-1.45 for Fib-4, the sensitivity for significant fibrosis increased with age, from 14.8%, 38.1%, 74.5% to 97.87% in above age groups, respectively. To improve the diagnostic accuracy for significant fibrosis, the proposed low and high cut-off points for Fib-4 were 0.41 and 1.15 in ≤30 years, 0.8 and 1.59 in 31 to 40 years, 1.17 and 1.94 in 41 to 50 years, 1.76 and 3.10 in ≥ 51 years, respectively. CONCLUSIONS: Age may influence the diagnostic thresholds and performance of APRI, Fib-4, and GPR for significant fibrosis in patients with CHB. In particular, these scores performed poorly for identifying significant fibrosis in younger patients (≤30 years).

Detachable string magnetically controlled capsule endoscopy for complete viewing of the esophagus and stomach.

BACKGROUND: Esophageal capsule endoscopy is reported to be insufficiently accurate to replace esophagogastroduodenoscopy (EGD) because the passage of the capsule through the esophagus is passive and precludes a thorough investigation. We developed a modified capsule endoscopy technique, called detachable string magnetically controlled capsule endoscopy (DS-MCE), and performed a pilot study to assess the feasibility and safety of this novel technique. METHODS: 4 healthy volunteers and 21 patients with suspected esophageal disease first underwent DS-MCE followed by EGD within 1 week. Outcomes included technical success of DS-MCE, adverse events, discomfort, and diagnostic accuracy. RESULTS: DS-MCE was successfully carried out in all 25 participants. No adverse events were observed. Mean overall discomfort score during DS-MCE was 0.96 (range 0 - 3). DS-MCE diagnoses were in accordance with EGD in all 25 participants. The per-patient sensitivity of DS-MCE for esophageal disease detection was 100 %. The accuracy of DS-MCE for grading esophageal varices and reflux esophagitis were 66.7 % and 100 %, respectively. CONCLUSIONS: DS-MCE was a feasible, safe, and well-tolerated method for viewing the esophagus and proceeding with gastric examination after string detachment.

MOF Capacitates Cyclodextrin to Mega-Load Mode for High-Efficient Delivery of Valsartan.

PURPOSE: To investigate the mechanism of enhancing solubility and bioavailability of water-insoluble drug, valsartan (VAL), with being mega-loaded by cyclodextrin metal organic framework (CD-MOF). METHODS: VAL was successfully mega-loaded into CD-MOF by magnetic agitation of VAL in ethanolic solution. Characterizations including powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), synchrotron radiation-based Fourier transform-infrared spectroscopy (SR-FTIR) 13C solid-state nuclear magnetic resonance spectroscopy ( 13C SS-NMR), nitrogen gas adsorption, and small-angle X-ray scattering (SAXS) were carried out to confirm the mechanism and incorporation behavior of VAL in CD-MOF. Ball milling process combined with molecular modeling was also used to confirm the mechanism. Improvement of bioavailability in vivo was confirmed by pharmacokinetic experiment in beagles. RESULTS: As a carrier with payload 150% higher than conventional CD complexation, CD-MOF included molecules of VAL as complexations in the chambers of (γ-CD)2, and nanoclusters in the confined spherical cages of (γ-CD)6 confirmed by SAXS and 13C SS-NMR. Ball milling combined with molecular modeling inferred that the reduced release rate of the milled CD-MOF with ultrahigh drug payload was mainly due to the partial aggregation of the VAL nanoclusters. The molecules of VAL as nanoclusters in the cages of (γ-CD)6 are critical in dramatically improving the apparent solubility (39.5-fold) and oral bioavailability (1.9-fold) of VAL in contrast to γ-CD inclusion. CONCLUSIONS: The new understanding of drug nanoclusters in CD-MOF will help to design more efficient drug delivery systems using CD-MOF carrier with nanocavities.

Predictive Capabilities of Three Widely Used Pathology Classification Systems and a Simplified Classification (Beijing Classification) in Primary IgA Nephropathy.

BACKGROUND/AIMS: Several pathological classification systems were commonly used in clinical practice to predict the prognosis of IgA nephropathy (IgAN). However, how prognostic value differs between these systems is unclear. The aim of this study was to compare the Lee grade, the Oxford classification, and the Haas classification and to find a simplified classification. METHODS: We retrospectively analyzed IgAN cases diagnosed between January 2002 and December 2007. The endpoints were progression to end-stage renal disease (ESRD) or a ≥50% decline in estimated glomerular filtration rate (eGFR). The predictive capabilities were evaluated by comparing the ability of discrimination (continuous net reclassification) and calibration (Akaike information criterion [AIC]). RESULTS: A total of 412 IgAN patients were included in the study. The average follow-up period was 80.62 ± 23.63 months. A total of 44 (10.68%) patients progressed to ESRD, and 70 (16.99%) patients showed a ≥50% decline in eGFR. All multivariate Cox regression models had limited power for high AIC values. The prognostic values of the Lee grade and the Oxford classification were higher than those of models containing only established baseline clinical indicators for progression to ESRD or a ≥50% decline in eGFR (Lee grade 0.50, 95% CI 0.21-0.74; Oxford classification 0.48, 95% CI 0.28-0.71). The prognostic value of the Haas classification was lower than that of the other pathological classification systems for progression to ESRD or a ≥50% decline in eGFR (Lee grade 0.53, 95% CI 0.23-0.92; Oxford classification 0.59, 95% CI 0.10-0.74). The prognostic value of hierarchical classification (Beijing classification) using M and T lesion was similar to the Oxford classification. CONCLUSIONS: Both the Lee grade and the Oxford classification showed incremental prognostic values beyond established baseline clinical indicators. The Haas classification was slightly inferior to the Lee grade and the Oxford classification. The hierarchical classification (Beijing classification) using less pathological parameters does not lose predictive efficiency.

Magnetic Steering of Capsule Endoscopy Improves Small Bowel Capsule Endoscopy Completion Rate.

BACKGROUND: Capsule endoscopy is currently available as a noninvasive and effective diagnostic modality to identify small bowel abnormalities, with a completion rate to the cecum between 75.1 and 95.6%. A novel magnetically controlled capsule endoscopy (MCE) system could facilitate passage of the capsule through the pylorus, thereby reducing the gastric transit time (GTT). OBJECTIVE: We performed this study to determine whether magnetic steering could improve the capsule endoscopy completion rate (CECR) compared to standard protocol. METHODS: Patients referred for MCE in our center from June 2017 to November 2017 were prospectively enrolled. Magnetic steering of the capsule through the pylorus was performed after standard gastric examination. CECR, GTT, pyloric transit time (PTT), and rapid gastric transit (GTT ≤ 30 min) rate were compared with a historical control group enrolled from January 2017 to May 2017. RESULTS: CECR was significantly higher in the intervention group (n = 107) than control group (n = 120) (100% vs. 94.2%, P = 0.02), with a significantly shorter GTT (22.2 vs. 84.5 min, P < 0.001) and PTT (4.4 vs. 56.7 min, P < 0.001). Rapid gastric transit rate in the intervention group was significantly higher than the control group (58.9% vs. 15.0%, P < 0.001). There were no statistical differences in the diagnostic yields between the two groups. CONCLUSIONS: Magnetic steering of capsule endoscopy improves small bowel CECR by reducing GTT, adding further support to MCE as a practical tool for noninvasive examination of both the stomach and small bowel. Trial registration ClinicalTrials.gov, ID: NCT03482661.

Repetitive Position Change Improves Gastric Cleanliness for Magnetically Controlled Capsule Gastroscopy.

BACKGROUND AND AIMS: Good gastric preparation is essential for magnetically controlled capsule gastroscopy (MCCG) examination. This study aims to determine if repetitive position change after dimethicone premedication could further improve gastric cleanliness for MCCG. METHODS: Consecutive patients referred for MCCG in our center from May 7 to May 31, 2018 were prospectively enrolled and randomized to undergo repetitive position change for 15 min (position change group) or not (conventional group) after ingesting dimethicone. Primary outcome was gastric cleanliness score and secondary outcomes were detection rate of positive findings, number of lesions per patient, gastric examination time, and safety of MCCG. RESULTS: Totals of 43 and 40 were included in the position change and conventional groups, respectively. Gastric cleanliness score in the position change group was significantly higher than in the conventional group (21.2 ± 1.0 vs. 18.6 ± 2.0, P  < 0.001), as was the proportion of acceptable gastric cleanliness (gastric cleanliness score ≥ 18) (100% vs. 72.5%, P  < 0.001). There was no statistical difference in detection rate of positive findings between the two groups (27.9% vs. 27.5%, P  = 0.97). In the position change group, the gastric examination time was significantly reduced (13.2 ± 4.0 vs. 15.3 ± 5.1, P = 0.043). No adverse events were observed. CONCLUSIONS: Repetitive position change after dimethicone premedication significantly improves gastric cleanliness for MCCG examination. Clinical Trial Registration ClinicalTrials.gov, ID: NCT03514966.

Impact of magnetic steering on gastric transit time of a capsule endoscopy (with video).

BACKGROUNDS AND AIMS: Delayed gastric transit of the capsule may lead to incomplete small bowel examination, reducing the diagnostic yield. Thus, this study was designed to determine if magnetic steering could enhance capsule gastric emptying and mucosal visualization within the duodenum. METHODS: The intervention group comprised 100 patients undergoing magnetic-controlled capsule endoscopy between May to September 2017 in whom magnetic control was used to assist transpyloric passage of the capsule and duodenal inspection. A cohort of 100 patients who had undergone the procedure before May 2017 was randomly selected from the database as an historic control group in whom transpyloric movement of the capsule occurred spontaneously (without magnetic assistance). The difference in the pyloric transit time (PTT) and duodenal papilla detection rate (DPDR) between the 2 groups were compared, and related factors were also investigated. RESULTS: Transpyloric passage of the capsule under magnetic control was successfully performed in 59 patients (59%). Median PTT was greatly reduced in the intervention group from 58.38 minutes (range, 13.45-87.47) to 4.69 minutes (range, 1.56-55.00; P < .001), and DPDR was also greatly improved with magnetic steering (30.5% vs 9%, P < .001). Magnetic steering, male gender, and higher body mass index were independently associated with reduced gastric transit time and magnetic steering with an enhanced DPDR. CONCLUSIONS: Magnetic steering of the capsule can enhance gastric emptying of the capsule and may prove useful in nonobese and female patients who appeared to have longer gastric transit time and achieved a better DPDR than that under the action of peristalsis alone. (Clinical trial registration number: NCT03441945.).

Screening for gastric cancer with magnetically controlled capsule gastroscopy in asymptomatic individuals.

BACKGROUND AND AIMS: Gastric cancer (GC) is the fourth most common cancer and the fourth leading cause of cancer death worldwide. In some Asian countries, screening EGD has greatly improved the survival rate. However, patients' discomfort and the need for sedation may limit adherence to screening programs. Previous studies have shown good tolerance and good agreement of magnetically controlled capsule gastroscopy (MCCG) with EGD. This study was designed to assess the application of MCCG in GC detection in an asymptomatic population. METHODS: In this observational cohort study, 3182 asymptomatic individuals undergoing MCCG in 99 participating medical examination centers from April to December 2016 were enrolled. Patients with ulcers and suspected malignancies were referred for gastroscopy and biopsy. The detection rate of GC and focal lesions were used to explore the application of MCCG in asymptomatic individuals. RESULTS: Seven patients (0.22%) were diagnosed with GC among the enrolled 3182 individuals, accounting for 0.74% (7/948) in patients over 50 years. No gender disparity was observed. EGD and biopsy confirmed adenocarcinoma in all cases of suspected malignancy. Benign polyps, gastric ulcers, and submucosal tumors were found in 10.4%, 4.9%, and 3.6% of patients, respectively. There was a trend for the prevalence of focal lesions to increase with age. MCCG examination proved to be safe. CONCLUSIONS: MCCG can detect cancer and benign lesions and is safe and clinically feasible in a large population. Studies of its role in a screening program should be considered.

One step hydrothermal synthesis of 3D CoS2@MoS2-NG for high performance supercapacitors.

A three-dimensional (3D) MoS2 coated CoS2-nitrogen doped graphene (NG) (CoS2@MoS2-NG) hybrid has been synthesized by a one step hydrothermal method as supercapacitor (SC) electrode material for the first time. Such a composite consists of NG embedded with stacked CoS2@MoS2 sheets. With a 3D skeleton, it prevents the agglomeration of CoS2@MoS2 nanoparticles, resulting in sound conductivity, rich porous structures and a large surface area. The results indicate that CoS2@MoS2-NG has higher specific capacitance (198 F g-1 at 1 A g-1), better rate performance (with about 56.57% from 1 to 16 A g-1) and an improved cycle stability (with about 96.97% after 1000 cycles). It is an ideal candidate for SC electrode materials.

Treatment of chronic kidney disease using a traditional Chinese medicine, Flos Abelmoschus manihot (Linnaeus) Medicus (Malvaceae).

The flowers of Abelmoschus manihot (Linnaeus) Medicus (Malvaceae; Flos A. manihot) have been used in China for many centuries as a traditional Chinese medicine for the treatment of chronic kidney disease. The Huangkui capsule is a single-plant drug extracted from the dry corolla of Flos A. manihot that has been approved by China's State Food and Drug Administration for the treatment of chronic glomerulonephritis. The purpose of this paper is to review briefly some of the past experiences in rapid filtration and to present more fully a few facts brought out in recent studies. The primary chemical constituents of Flos A. manihot are flavonoids. In vivo, the flavonoids can be transformed into glucuronide-sulphate conjugates, which are the major metabolites of Flos A. manihot and could contribute to the renoprotective effects in vivo. Flos A. manihot can ameliorate proteinuria, podocyte apoptosis, glomerulosclerosis and mesangial proliferation. The renoprotective effects of Flos A. manihot are related to inhibition of caspase-3 and caspase-8 overexpression, reduction of the infiltration of ED1(+) and ED3(+) macrophages, downregulation of oxidative stress, inhibition of the p38 mitogen-activated protein kinase and serine/threonine kinase pathways and suppression of transforming growth factor-ß1 and tumour necrosis factor-α expression. Recently, a multicentre randomized controlled trial demonstrated that Flos A. manihot was more effective than the angiotensin-receptor blocker losartan in reducing proteinuria in patients with primary glomerular disease. Because Flos A. manihot is generally preferred by Chinese patients and clinicians, high-quality trials to test the efficacy and safety of Flos A. manihot are urgently needed.

TRPM8 promotes aggressiveness of breast cancer cells by regulating EMT via activating AKT/GSK-3ß pathway.

Breast cancer already taken the first place of incidence in Chinese female cancer patients. TRPM8 is found to be over-expressed in breast cancer, but whether it promotes breast cancer aggressiveness remains unknown. In our study, TRPM8 was identified highly expressing in all the tested breast cancer cell lines including MCF-7, T47D, MDA-MB-231, BT549, SKBR3 and ZR-75-30, while it just could be detected in MCF-10A, the normal breast epithelial cell. Then four pairs of clinical samples were analyzed using Western blotting and the result showed that TRPM8 expression is higher in tumor tissues than in adjacent nontumor tissues. Subsequently, we established TRPM8 high-expressing MCF-7 cell line and TRPM8 knockout MDA-MB-231 cell line to explore expression status of cancer-related proteins. The Western blotting and immunofluorescence analysis outcomes demonstrated that TRPM8 might influence cancer cell metastasis by regulating the EMT phenotype via activating AKT/GSK-3ß pathway, and the hypothesis had been supported by cell function tests. All the results demonstrated that TRPM8 significantly up-expressed in breast cancer cells and promoted their metastasis by regulating EMT via activating AKT/GSK-3ß pathway, indicating TRPM8 gets the prospects of to be developed as medication or diagnostic indicator to be applied in clinical work.

Immunosuppressive treatment for idiopathic membranous nephropathy in adults with nephrotic syndrome.

BACKGROUND: Idiopathic membranous nephropathy (IMN) is the most common form of nephrotic syndrome in adults. The disease shows a benign or indolent course in the majority of patients, with a rate of spontaneous complete or partial remission of nephrotic syndrome as high as 30% or more. Despite this, 30% to 40% of patients progress toward end-stage kidney disease (ESKD) within five to 15 years. The efficacy and safety of immunosuppression for IMN with nephrotic syndrome are still controversial. This is an update of a Cochrane review first published in 2004. OBJECTIVES: The aim of this review was to evaluate the safety and efficacy of immunosuppressive treatments for adult patients with IMN and nephrotic syndrome. Moreover it was attempted to identify the best therapeutic regimen, when to start immunosuppression and whether the above therapies should be given to all adult patients at high risk of progression to ESKD or only restricted to those with impaired kidney function. SEARCH METHODS: We searched Cochrane Renal Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Chinese databases, reference lists of articles, and clinical trial registries to June 2014. We also contacted principal investigators of some of the studies for additional information. SELECTION CRITERIA: Randomised controlled trials (RCTs) investigating the effects of immunosuppression in adults with IMN and nephrotic syndrome. DATA COLLECTION AND ANALYSIS: Study selection, data extraction, quality assessment, and data synthesis were performed using the Cochrane-recommended methods. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes. MAIN RESULTS: Thirty nine studies with 1825 patients were included, 36 of these could be included in our meta-analyses. The data from two studies could not be extracted and one study was terminated due to poor accrual. Immunosuppression significantly reduced all-cause mortality or risk of ESKD ((15 studies, 791 patients): RR 0.58 (95% CI 0.36 to 0.95, P = 0.03) and risk of ESKD ((15 studies, 791 patients): RR 0.55, 95% CI 0.31 to 0.95, P = 0.03), increased complete or partial remission ((16 studies, 864 patients): RR 1.31, 95% CI 1.01 to 1.70, P = 0.04), and decreased proteinuria ((9 studies,(393 patients): MD -0.95 g/24 h, 95% CI -1.81 to -0.09, P = 0.03) at the end of follow-up (range 6 to 120 months). However this regimen was associated with more discontinuations or hospitalisations ((16 studies, 880 studies): RR 5.35, 95% CI 2.19 to 13.02), P = 0.0002). Combined corticosteroids and alkylating agents significantly reduced death or risk of ESKD ((8 studies, 448 patients): RR 0.44, 95% CI 0.26 to 0.75, P = 0.002) and ESKD ((8 studies, 448 patients): RR 0.45, 95% CI 0.25 to 0.81, P = 0.008), increased complete or partial remission ((7 studies, 422 patients): RR 1.46, 95% CI 1.13 to 1.89, P = 0.004) and complete remission ((7 studies, 422 patients): RR 2.32, 95% CI 1.61 to 3.32, P < 0.00001), and decreased proteinuria ((6 studies, 279 patients): MD -1.25 g/24 h, 95% CI -1.93 to -0.57, P = 0.0003) at the end of follow-up (range 9 to 120 months). In a population with an assumed risk of death or ESKD of 181/1000 patients, this regimen would be expected to reduce the number of patients experiencing death or ESKD to 80/1000 patients (range 47 to 136). In a population with an assumed complete or partial remission of 408/1000 patients, this regimen would be expected to increase the number of patients experiencing complete or partial remission to 596/1000 patients (range 462 to 772). However this combined regimen was associated with a significantly higher risk of discontinuation or hospitalisation due to adverse effects ((4 studies, 303 patients): RR 4.20, 95% CI 1.15 to 15.32, P = 0.03). Whether this combined therapy should be indicated in all adult patients at high risk of progression to ESKD or only restricted to those with deteriorating kidney function still remained unclear. Cyclophosphamide was safer than chlorambucil ((3 studies, 147 patients): RR 0.48, 95% CI 0.26 to 0.90, P = 0.02). There was no clear evidence to support the use of either corticosteroid or alkylating agent monotherapy. Cyclosporine and mycophenolate mofetil failed to show superiority over alkylating agents. Tacrolimus and adrenocorticotropic hormone significantly reduced proteinuria. The numbers of corresponding studies related to tacrolimus, mycophenolate mofetil, adrenocorticotropic hormone, azathioprine, mizoribine, and Tripterygium wilfordii are still too sparse to draw final conclusions. AUTHORS' CONCLUSIONS: In this update, a combined alkylating agent and corticosteroid regimen had short- and long-term benefits on adult IMN with nephrotic syndrome. Among alkylating agents, cyclophosphamide was safer than chlorambucil. This regimen was significantly associated with more withdrawals or hospitalisations. It should be emphasised that the number of included studies with high-quality design was relatively small and most of included studies did not have adequate follow-up and enough power to assess the prespecified definite endpoints. Although a six-month course of alternating monthly cycles of corticosteroids and cyclophosphamide was recommended by the KDIGO Clinical Practice Guideline 2012 as the initial therapy for adult IMN with nephrotic syndrome, clinicians should inform their patients of the lack of high-quality evidence for these benefits as well as the well-recognised adverse effects of this therapy. Cyclosporine or tacrolimus was recommended by the KDIGO Clinical Practice Guideline 2012 as the alternative regimen for adult IMN with nephrotic syndrome; however, there was no evidence that calcineurin inhibitors could alter the combined outcome of death or ESKD.