Transplantation of olfactory mucosa mesenchymal stromal cells repairs spinal cord injury by inducing microglial polarization.

STUDY DESIGN: Animal studies OBJECTIVES: To evaluate the therapeutic effect of olfactory mucosa mesenchymal stem cell (OM-MSCs) transplantation in mice with spinal cord injury (SCI) and to explore the mechanism by which OM-MSCs inhibit neuroinflammation and improve SCI. SETTING: Xiangya Hospital, Central South University; Affiliated Hospital of Guangdong Medical University. METHODS: Mice (C57BL/6, female, 6-week-old) were randomly divided into sham, SCI, and SCI + OM-MSC groups. The SCI mouse model was generated using Allen's method. OM-MSCs were immediately delivered to the lateral ventricle after SCI using stereotaxic brain injections. One day prior to injury and on days 1, 5, 7, 14, 21, and 28 post-injury, the Basso Mouse Scale and Rivlin inclined plate tests were performed. Inflammation and microglial polarization were evaluated using histological staining, immunofluorescence, and qRT-PCR. RESULTS: OM-MSCs originating from the neuroectoderm have great potential in the management of SCI owing to their immunomodulatory effects. OM-MSCs administration improved motor function, alleviated inflammation, promoted the transformation of the M1 phenotype of microglia into the M2 phenotype, facilitated axonal regeneration, and relieved spinal cord injury in SCI mice. CONCLUSIONS: OM-MSCs reduced the level of inflammation in the spinal cord tissue, protected neurons, and repaired spinal cord injury by regulating the M1/M2 polarization of microglia.

Weakly supervised video-based cardiac detection for hypertensive cardiomyopathy.

INTRODUCTION: Parameters, such as left ventricular ejection fraction, peak strain dispersion, global longitudinal strain, etc. are influential and clinically interpretable for detection of cardiac disease, while manual detection requires laborious steps and expertise. In this study, we evaluated a video-based deep learning method that merely depends on echocardiographic videos from four apical chamber views of hypertensive cardiomyopathy detection. METHODS: One hundred eighty-five hypertensive cardiomyopathy (HTCM) patients and 112 healthy normal controls (N) were enrolled in this diagnostic study. We collected 297 de-identified subjects' echo videos for training and testing of an end-to-end video-based pipeline of snippet proposal, snippet feature extraction by a three-dimensional (3-D) convolutional neural network (CNN), a weakly-supervised temporally correlated feature ensemble, and a final classification module. The snippet proposal step requires a preliminarily trained end-systole and end-diastole timing detection model to produce snippets that begin at end-diastole, and involve contraction and dilatation for a complete cardiac cycle. A domain adversarial neural network was introduced to systematically address the appearance variability of echo videos in terms of noise, blur, transducer depth, contrast, etc. to improve the generalization of deep learning algorithms. In contrast to previous image-based cardiac disease detection architectures, video-based approaches integrate spatial and temporal information better with a more powerful 3D convolutional operator. RESULTS: Our proposed model achieved accuracy (ACC) of 92%, area under receiver operating characteristic (ROC) curve (AUC) of 0.90, sensitivity(SEN) of 97%, and specificity (SPE) of 84% with respect to subjects for hypertensive cardiomyopathy detection in the test data set, and outperformed the corresponding 3D CNN (vanilla I3D: ACC (0.90), AUC (0.89), SEN (0.94), and SPE (0.84)). On the whole, the video-based methods remarkably appeared superior to the image-based methods, while few evaluation metrics of image-based methods exhibited to be more compelling (sensitivity of 93% and negative predictive value of 100% for the image-based methods (ES/ED and random)). CONCLUSION: The results supported the possibility of using end-to-end video-based deep learning method for the automated diagnosis of hypertensive cardiomyopathy in the field of echocardiography to augment and assist clinicians. TRIAL REGISTRATION: Current Controlled Trials ChiCTR1900025325, Aug, 24, 2019. Retrospectively registered.

[Effect of Isodon ternifolius-medicated serum on hepatic stellate cells based on TLR4/NF-κB/NLRP3 signaling pathway].

The present study aimed to investigate the inhibitory effect and mechanism of Isodon terricolous-medicated serum on lipopolysaccharide(LPS)-induced hepatic stellate cell(HSC) activation. LPS-induced HSCs were divided into a blank control group, an LPS model group, a colchicine-medicated serum group, an LPS + blank serum group, an I. terricolous-medicated serum group, a Toll-like receptor 4(TLR4) blocker group, and a TLR4 blocker + I. terricolous-medicated serum group. HSC proliferation was detected by methyl thiazolyl tetrazolium(MTT) assay. Enzyme-linked immunosorbent assay(ELISA) was used to measure type Ⅰ collagen(COL Ⅰ), COL Ⅲ, transforming growth factor-ß1(TGF-ß1), intercellular adhesion molecule-1(ICAM-1), α-smooth muscle actin(α-SMA), vascular cell adhesion molecule-1(VCAM-1), cysteinyl aspartate-specific proteinase-1(caspase-1), and monocyte chemotactic protein-1(MCP-1). Real-time PCR(RT-PCR) was used to detect mRNA expression of TLR4, IκBα, and NOD-like receptor thermal protein domain associated protein 3(NLRP3), nuclear factor-κB(NF-κB) p65, gasdermin D(GSDMD), and apoptosis-associated speck-like protein containing a CARD(ASC) in HSCs. Western blot(WB) was used to detect the protein levels of TLR4, p-IκBα, NF-κB p65, NLRP3, ASC, and GSDMD in HSCs. The results showed that I. terricolous-medicated serum could inhibit the proliferation activity of HSCs and inhibit the secretion of COL Ⅰ, COL Ⅲ, α-SMA, TGF-ß1, caspase-1, MCP-1, VCAM-1, and ICAM-1 in HSCs. Compared with the LPS model group, the I. terricolous-medicated serum group, the colchicine-medicated serum group, and the TLR4 blocker group showed down-regulated expression of p-IκBα, NLRP3, NF-κB p65, GSDMD, and ASC, and up-regulated expression of IκBα. Compared with the TLR4 blocker group, the TLR4 blocker + I. terricolous-medicated serum group showed decreased expression of TLR4, p-IκBα, NLRP3, NF-κB p65, GSDMD, and ASC, and increased expression of IκBα. In conclusion, I. terricolous-medicated serum down-regulates HSC activation by inhibiting the TLR4/NF-κB/NLRP3 signaling pathway.

Synergistic prognostic value of coronary distensibility index and fractional flow reserve based cCTA for major adverse cardiac events in patients with Coronary artery disease.

BACKGROUND: Coronary distensibility index (CDI), as an early predictor of cardiovascular diseases, has the potential to complement coronary computed tomography angiography (cCTA)-derived fractional flow reserve (CT-FFR) for predicting major adverse cardiac events (MACEs). Thus, the prognostic value of CT-FFR combined with CDI for MACEs is worth exploring. METHODS: Patients with a moderate or severe single left anterior descending coronary artery stenosis were included and underwent FFR and CDI analysis based on cCTA, followed up at least 1 year, and recorded MACEs. Multivariate logistic regression analysis was performed to determine independent predictors of MACEs. The area under of receiver operating characteristic (ROC) curve was used to evaluated evaluate the diagnostic performance of CT-FFR, CDI, and a combination of the two. RESULTS: All the vessel-specific data were from LAD. 150 patients were analysed. 55 (37%) patients experienced MACEs during follow-up. Patients with CT-FFR ≤ 0.8 had higher percentage of MACEs compared with CT-FFR > 0.8 (56.3% vs.7.3%, p < 0.05). Patients' CDI was significantly decreased in MACEs group compared with non-MACEs group (p < 0.05). Multivariate analysis revealed that diabetes (p = 0.025), triglyceride (p = 0.015), CT-FFR ≤ 0.80 (p = 0.038), and CDI (p < 0.001) are independent predictors of MACEs. According to ROC curve analysis, CT-FFR combined CDI showed incremental diagnostic performance over CT-FFR alone for prediction of MACEs (AUC = 0.831 vs. 0.656, p = 0.0002). CONCLUSION: Our study provides initial evidence that combining CDI with CT-FFR shows incremental discriminatory power for MACEs over CT-FFR alone, independent of clinical risk factors. Diabetes and triglyceride are also associated with MACEs.

The efficacy of platelet rich plasma on anterior cruciate ligament reconstruction: a systematic review and meta-analysis.

Anterior cruciate ligament (ACL) rupture is a common musculoskeletal injury, most frequently affecting young and physically active patients. Platelet-rich plasma (PRP) has been widely used in ACL reconstruction to augment the graft healing. However, high-level studies addressing its clinical efficacy could not reach a consensus. In this study, we assess the efficacy of PRP on pain relief, functional improvement along with radiological changes in patients who underwent ACL reconstruction. We performed comprehensive literature search and included 17 RCTs containing 970 participants who underwent ACL reconstruction. The combined data showed significant difference between PRP and control with regard to VAS score (MD: -1.12, 95% CI -1.92, -0.31; P = .007), subjective IKDC score (MD: 6.08, 95% CI 4.39, 7.77; P < .00001) and Lysholm score (MD: 8.49, 95% CI 1.63, 15.36; P = .02) by postoperative 6 months, but only pain reduction was deemed clinically important. At the end of one year's follow-up, no clinically meaningful improvement in VAS (MD: -0.47, P = .04), subjective IKDC score (MD: 3.99, P = .03), Lysholm score (MD: 2.30, P = .32), objective IKDC score (RR: 1.03, P = .09) and knee joint laxity (MD: 0.17, P = .28) was seen. In terms of radiological findings, about one-third of the studies favored PRP to facilitate the graft healing, improve the harvest site morbidity and prevent tunnel widening. In summary, moderate quality of evidence suggested that PRP could provide short-term but not long-term clinically important pain reduction.

Assembly and optical properties of 1D helical bundles induced by triphenylamine, side chains and solvents in crystals.

Two novel helical aromatic foldamer derivatives TPA-Q6(n-He) and TPA-Q6(i-Bu) were synthesized and characterized by introducing n-hexyloxy and isobutoxy side chains, respectively, and modifying quinoline amide foldamers with the triphenylamine (TPA) moiety at the N-terminus. X-ray single crystal diffraction analyses and theoretical calculations showed that the quinoline amide hexamer derivative TPA-Q6(i-Bu) enabled one-dimensional (1D) helical self-assembly in solids due to the synergistic interaction of the flexible π units of TPA, the steric hindrance of the alkyl groups, and methanol molecules. The chemical modification of the TPA end group significantly enhanced the fluorescence due to the intramolecular charge transfer. Steady-state fluorescence spectra and transient decay curves showed that TPA-Q6(i-Bu) forming a 1D helical assembly obviously exhibited a redshift of the emission wavelength and an increase of phosphorescence lifetimes in crystals compared with TPA-Q6(n-He) adopting the alternating insertion arrangement induced by the long alkyl chains. The results offered a new way to explore the intrinsic relationship among molecular structures, packing modes and optical properties for foldamers.

Accumulation of LDL/ox-LDL in the necrotic region participates in osteonecrosis of the femoral head: a pathological and in vitro study.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a common but intractable disease that appears to involve lipid metabolic disorders. Although numerous studies have demonstrated that high blood levels of low-density lipoprotein (LDL) are closely associated with ONFH, there is limited evidence to explain the pathological role of LDL. Pathological and in vitro studies were performed to investigate the role of disordered metabolism of LDL and oxidized LDL (ox-LDL) in the femoral head in the pathology of ONFH. METHODS: Nineteen femoral head specimens from patients with ONFH were obtained for immunohistochemistry analysis. Murine long-bone osteocyte Y4 cells were used to study the effects of LDL/ox-LDL on cell viability, apoptosis, and metabolism process of LDL/ox-LDL in osteocytes in normoxic and hypoxic environments. RESULTS: In the pathological specimens, marked accumulation of LDL/ox-LDL was observed in osteocytes/lacunae of necrotic regions compared with healthy regions. In vitro studies showed that ox-LDL, rather than LDL, reduced the viability and enhanced apoptosis of osteocytes. Pathological sections indicated that the accumulation of ox-LDL was significantly associated with impaired blood supply. Exposure to a hypoxic environment appeared to be a key factor leading to LDL/ox-LDL accumulation by enhancing internalisation and oxidation of LDL in osteocytes. CONCLUSIONS: The accumulation of LDL/ox-LDL in the necrotic region may contribute to the pathology of ONFH. These findings could provide new insights into the prevention and treatment of ONFH.

A novel homozygous variant in NLRP5 is associate with human early embryonic arrest in a consanguineous Chinese family.

Early embryonic arrest is one of the major causes of recurrent assisted reproduction failure. It is characterized by delayed embryonic development and failure to form viable eight-cell stage embryos on day 3 of an assisted reproduction cycle. A recent study reported that biallelic mutations in NLRP5 can cause early embryonic arrest. NLRP5 is a member of subcortical maternal complex, which plays a significant role in embryogenesis. In this study, we described a female in a consanguineous Chinese family who displayed clinical features of early embryonic arrest and identified a novel homozygous variant c.1061C>T (p.Pro354Leu) in NLRP5. This is the second report of the biallelic NLRP5 variant that associates with early embryonic arrest in humans, further confirming the role of NLRP5 variants in early embryonic arrest and expanding the spectrum of known pathogenic variants in NLRP5.

Monocyte Chemotactic Protein 1-Induced Protein 1 Is Highly Expressed in Inflammatory Bowel Disease and Negatively Regulates Neutrophil Activities.

Monocyte chemotactic protein 1-induced protein 1 (MCPIP-1) is highly expressed in activated immune cells and plays an important role in negatively regulating immune responses. However, its role in regulating neutrophil functions in the pathogenesis of inflammatory bowel disease (IBD) is still unclear. Here, we found that MCPIP-1 was markedly increased at both the transcriptional and translational levels in inflamed mucosa of IBD patients compared with healthy controls, which was mainly expressed in neutrophils. Interestingly, MG-132, a proteasome inhibitor reducing the degradation of MCPIP-1, further facilitated neutrophils to express MCPIP-1 in vitro. Importantly, MCPIP-1 markedly downregulated the production of ROS, MPO, and proinflammatory cytokines (e.g., interleukin-1ß, interleukin-6, tumor necrosis factor-α, interleukin-8, and interferon-γ) and suppressed the migration of IBD neutrophils. Consistently, the same functional changes were observed in neutrophils from mice with myeloid-targeted overexpression of MCPIP-1 as MG-132 did. Altogether, these findings suggest that MCPIP-1 plays a negative role in regulating neutrophil activities through suppressing the production of ROS, MPO, and proinflammatory cytokines and inhibiting the migration. MG-132 may partially modulate the function of neutrophils via the induction of MCPIP-1. Therefore, targeting MCPIP-1 or exogenous supplementation of MG-132 may provide a therapeutic approach in the treatment of IBD.

Anti-TNF-α Monoclonal Antibody Therapy Improves Anemia through Downregulating Hepatocyte Hepcidin Expression in Inflammatory Bowel Disease.

Anemia is one of the most common complications in patients with inflammatory bowel disease (IBD). Hepcidin as a key regulator of iron metabolism is pivotal in mediating the occurrence of anemia of chronic disease. Herein, we analyzed the levels of hepcidin in sera from IBD patients by enzyme-linked immunosorbent assay and investigated its potential role in regulating the anemia in IBD. We observed that the levels of serum hepcidin were increased in active IBD patients compared with those in remitted IBD patients and healthy controls and that serum hepcidin was associated with disease activity, CRP, and ESR, respectively. Importantly, we found that the increased levels of serum hepcidin were positively correlated with the severity of anemia and the imbalance of iron metabolism in anemic UC and CD patients. Proinflammatory factors (e.g., IL-6, IL-17, and TNF-α) were positively correlated with the concentrations of serum hepcidin in IBD patients. Interestingly, hepcidin was found to be decreased in patients with Crohn's disease after successful therapy with anti-TNF-α mAb (i.e., infliximab), indicating the underlying association between TNF-α and hepcidin expression. To investigate the specific mechanisms involved, we cultured LO2 and HepG2 cell lines in vitro under stimulation with TNF-α and observed that the levels of hepcidin mRNA were markedly upregulated in caspase-3/8- and NF-κB-dependent manners. Therefore, our data suggest that TNF-α stimulates the expression of hepcidin in IBD patients, resulting in aggravated anemia and that blockage of TNF-α or the caspase-3/8 and NF-κB pathways could downregulate hepcidin expression. This study provides inspiration for the therapy and management of anemia in IBD.

Clinical significance of soluble immunoglobulins A and G and their coated bacteria in feces of patients with inflammatory bowel disease.

BACKGROUND: Immunoglobulin A (IgA) and IgG are major components in human intestinal mucosal surface and sera, and IgA- or IgG-coated bacteria play a vital role in the intestinal homeostasis. However, the correlation of IgA, IgG and their coated bacteria with the clinical characteristics of inflammatory bowel disease (IBD) has not been fully clarified. METHODS: The levels of soluble IgA and IgG in sera and feces were detected by ELISA, and the percentage of IgA- and IgG-coated bacteria in feces was analyzed by flow cytometry. Crohn's disease activity index (CDAI) and Simple Endoscopic Score for Crohn's disease (SES-CD) for Crohn's disease (CD) or Mayo score and ulcerative colitis endoscopic index of severity (UCEIS) for ulcerative colitis (UC), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were used to evaluate the disease activity. RESULTS: 178 patients with CD, 75 patients with UC and 41 healthy donors were recruited in this study. We found that the concentrations of soluble IgA and IgG in feces of active IBD patients were significantly higher than those in healthy controls and that the levels of soluble IgA and IgG in feces from IBD patients were positively correlated with CRP, ESR, Mayo score, UCEIS, SES-CD, and CDAI, respectively. Moreover, we also observed that the percentage of IgA- and IgG-coated bacteria markedly increased in feces of IBD patients, especially in CD patients at the age of 17 to 40 years old, with terminal ileal lesions and perianal lesions, as well as from E2 UC patients, and was closely associated with disease activities. CONCLUSIONS: The levels of soluble IgA and IgG and the percentage of IgA- and IgG-coated bacteria strikingly increase in feces of IBD patients and correlate with disease activity.

Non-traumatic myositis ossificans circumscripta at elbow joint in a 9-year old child.

Myositis ossificans circumscripta (MOC) is a kind of self-localized, benign and tumor-like lesions often seen in adults, with approximately 75% of cases caused by trauma. We reported a case of non-traumatic MOC occurred at the elbow joint in a 9-year old child and it has been excised by surgery. After 18 months follow-up, a favorable outcome has been achieved with the Broberg-Morrey score of 100. We suggest that surgical resection should be done as soon as the diagnosis is confirmed.

Does serum calcium relate to different types of hip fracture? A retrospective study.

PURPOSE: To investigate the potential correlation between two different types of hip fractures and serum calcium levels. METHODS: We consecutively studied 101 cases of femoral neck fracture and 95 cases of femoral inter- trochanteric fracture between January 2011 and December 2013. Fasting blood samples were taken and serum calcium measurements were performed respectively in three periods: the time of admission, postoperation, and discharge. Creatinine, alkaline phosphatase and albumin were also analyzed. RESULTS: Considering the levels of serum calcium between two groups at the time of admission, post- operation and discharge, there was significant difference at admission and discharge (p <0.05), while there was no significant difference at the time of postoperation (p > 0.05). The magnitude of serum calcium fluctuation was larger in femoral neck group than femoral intertrochanteric group. Concerning alkaline phosphatase and albumin levels at admission, there was no significant difference between two groups (p > 0.05). CONCLUSION: The capability of reservation and restoration of serum calcium in patients with femoral neck fracture is better than that in patients with femoral intertrochanteric fracture. A low serum calcium level may be susceptible to femoral intertrochanteric fracture.

[ Epidemiological Analysis of Imported Malaria in Shijiazhuang City from 2010 ].

Epidemiological analysis was performed on the 103 reported malaria cases during 2010-2014 in Shijiazhuang City. All the cases were imported from abroad, comprising 18（17.5%） cases of vivax malaria, 43 （41.7%） falciparum malaria, 2（1.9%） ovale malaria, 18（17.5%） cases with mixed infections， and 22（21.4%） unclassified cases. No significant seasonal variation in disease onset was observed. The male-to-female ratio was 33.3 : 1 and the cases were concentrated within 20-50 years. Africa was the main source of imported cases (92.2%).

Effect of Discharge Energy on Micro-Arc Oxidation Coating of Zirconium Alloy.

The micro-arc oxidation (MAO) technique was used to grow in situ oxidation coating on the surface of R60705 zirconium alloy in Na2SiO3, Na2EDTA, and NaOH electrolytes. The thickness, surface morphology, cross-section morphology, wear resistance, composition, and structure of the micro-arc oxidation coating were analyzed by an eddy current thickness measuring instrument, XPS, XRD, scanning electron microscopy, energy spectrometer, and wear testing machine. The corrosion resistance of the coating was characterized by a polarization curve and electrochemical impedance spectroscopy (EIS). The results show that, with the increase in frequency, the single-pulse discharge energy decreases continuously, and the coating thickness shows a decreasing trend, from the highest value of 152 µm at 400 Hz to the lowest value of 87.5 µm at 1000 Hz. The discharge pore size on the surface of the coating gradually decreases, and the wear resistance and corrosion resistance of the coating first increase and then decrease. The corrosion resistance is the best when the frequency is 400 Hz. At this time, the corrosion potential is -0.215 V, and the corrosion current density is 2.546 × 10-8 A·cm-2. The micro-arc oxidation coating of zirconium alloy is mainly composed of monoclinic zirconia (m-ZrO2) and tetragonal zirconia (t-ZrO2), in which the content of monoclinic zirconia is significantly more than that of tetragonal zirconia.

SIA: A sustainable inference attack framework in split learning.

Split learning is a widely recognized distributed learning framework suitable for joint training scenarios with limited computing resources. However, recent research indicates that the malicious server can achieve high-quality reconstruction of the client's data through feature space hijacking attacks, leading to severe privacy leakage concerns. In this paper, we further enhance this attack to enable efficient data reconstruction while maintaining acceptable performance on the main task. Another significant advantage of our attack framework lies in its ability to fool the state-of-the-art attack detection mechanism, thus minimizing the risk of attacker exposure and making sustainable attacks possible. Moreover, we adaptively refine and adjust the attack strategy, extending the data reconstruction attack for the first time to the more challenging scenario of vertically partitioned data in split learning. In addition, we introduce three training modes for the attack framework, allowing the attacker to choose according to their requirements freely. Finally, we conduct extensive experiments on three datasets and evaluate the attack performance of attack frameworks in different scenarios, parameter settings, and defense mechanisms. The results demonstrate our attack framework's effectiveness, invisibility, and generality. Our research comprehensively highlights the potential privacy risks associated with split learning and sounds the alarm for secure applications of split learning.

Few-shot segmentation framework for lung nodules via an optimized active contour model.

BACKGROUND: Accurate segmentation of lung nodules is crucial for the early diagnosis and treatment of lung cancer in clinical practice. However, the similarity between lung nodules and surrounding tissues has made their segmentation a longstanding challenge. PURPOSE: Existing deep learning and active contour models each have their limitations. This paper aims to integrate the strengths of both approaches while mitigating their respective shortcomings. METHODS: In this paper, we propose a few-shot segmentation framework that combines a deep neural network with an active contour model. We introduce heat kernel convolutions and high-order total variation into the active contour model and solve the challenging nonsmooth optimization problem using the alternating direction method of multipliers. Additionally, we use the presegmentation results obtained from training a deep neural network on a small sample set as the initial contours for our optimized active contour model, addressing the difficulty of manually setting the initial contours. RESULTS: We compared our proposed method with state-of-the-art methods for segmentation effectiveness using clinical computed tomography (CT) images acquired from two different hospitals and the publicly available LIDC dataset. The results demonstrate that our proposed method achieved outstanding segmentation performance according to both visual and quantitative indicators. CONCLUSION: Our approach utilizes the output of few-shot network training as prior information, avoiding the need to select the initial contour in the active contour model. Additionally, it provides mathematical interpretability to the deep learning, reducing its dependency on the quantity of training samples.

Development and validation of a novel therapeutic drug monitoring-based nomogram for prediction of primary endoscopic response to anti-TNF therapy in active Crohn's disease.

Background: Anti-tumor necrosis factor (TNF) monoclonal antibodies, especially infliximab (IFX) and adalimumab (ADA), are considered the first-line treatment for active Crohn's disease (CD). However, the predictive role of therapeutic drug monitoring (TDM) of serum anti-TNF in monitoring the treatment of inflammatory bowel disease (IBD) remains controversial. Objectives: To explore the correlation between serum anti-TNF levels and early endoscopic response in active CD using a TDM-based nomogram. Design: Cross-sectional study. Methods: The simplified endoscopic activity score for CD (SES-CD), Crohn's disease activity index (CDAI), laboratory parameters, and the serum trough levels of IFX and ADA were assessed. Results: The trough levels of IFX or ADA were significantly higher in patients with endoscopic response compared to non-responders in the development cohort (p < 0.001). The IFX and ADA levels showed a weak but significantly negative correlation with SES-CD (p < 0.001), CDAI (p < 0.001), and C-reactive protein (CRP) (p < 0.001) at week 14 post-IFX therapy in the development cohort. Furthermore, the receiver operating characteristic curve revealed that an optimal level of IFX (4.80 µg/mL) and ADA (8.80 µg/mL) exhibited the best performance in predicting endoscopic response. Concomitantly, we developed a novel nomogram prediction model based on the results of multivariate logistic regression analysis, which consisted of CRP, albumin (Alb), and anti-TNF trough levels at week 14. The nomogram showed significant discrimination and calibration for both IFX and ADA in the development cohort and performed well in the external validation cohort. Conclusion: This study demonstrates a robust association between serum concentrations of IFX, ADA, Alb, and CRP and primary endoscopic response in active CD patients. Importantly, the TDM- and laboratory marker-based nomogram may be used to evaluate the primary endoscopic response to anti-TNF therapy, especially for optimizing treatment strategies and switching therapy in CD patients.

Therapeutic drug monitoring-based nomogram predicts primary endoscopic response in Crohn's disease The present study established a therapeutic drug monitoring-based nomogram, which exhibits an exceptional predictive value, remarkable accuracy, and discrimination. This algorithmic nomogram holds the potential to enhance clinicians' comprehension of the underlying mechanisms contributing to individual patients' failure in achieving expected efficacy. Such approach is crucial for optimizing therapy options and facilitating biologic switching in refractory Crohn's disease.

Development and validation of a novel criterion of histologic healing in ulcerative colitis defined by inflammatory cell enumeration in lamina propria mucosa: A multicenter retrospective cohort in China.

BACKGROUND: Histological healing is closely associated with improved long-term clinical outcomes and lowered relapses in patients with ulcerative colitis (UC). Here, we developed a novel diagnostic criterion for assessing histological healing in UC patients. METHODS: We conducted a retrospective cohort study in UC patients, whose treatment was iteratively optimized to achieve mucosal healing at Shanghai Tenth People's Hospital of Tongji University from January 2017 to May 2022. We identified an inflammatory cell enumeration index (ICEI) for assessing histological healing based on the proportions of eosinophils, CD177 + neutrophils, and CD40L + T cells in the colonic lamina propria under high power field (HPF), and the outcomes (risks of symptomatic relapses) of achieving histological remission vs . persistent histological inflammation using Kaplan-Meier curves. Intrareader reliability and inter-reader reliability were evaluated by each reader. The relationships to the changes in the Nancy index and the Geboes score were also assessed for responsiveness. The ICEI was further validated in a new cohort of UC patients from other nine university hospitals. RESULTS: We developed an ICEI for clinical diagnosis of histological healing, i.e., Y = 1.701X 1 + 0.758X 2 + 1.347X 3 - 7.745 (X 1 , X 2 , and X 3 represent the proportions of CD177 + neutrophils, eosinophils, and CD40L + T cells, respectively, in the colonic lamina propria under HPF). The receiver operating characteristics curve (ROC) analysis revealed that Y <-0.391 was the cutoff value for the diagnosis of histological healing and that an area under the curve (AUC) was 0.942 (95% confidence interval [CI]: 0.905-0.979) with a sensitivity of 92.5% and a specificity of 83.6% ( P  <0.001). The intraclass correlation coefficient (ICC) for the intrareader reliability was 0.855 (95% CI: 0.781-0.909), and ICEI had good inter-reader reliability of 0.832 (95% CI: 0.748-0.894). During an 18-month follow-up, patients with histological healing had a substantially better outcome compared with those with unachieved histological healing ( P  <0.001) using ICEI. During a 12-month follow-up from other nine hospitals, patients with histological healing also had a lower risk of relapse than patients with unachieved histological healing. CONCLUSIONS: ICEI can be used to predict histological healing and identify patients with a risk of relapse 12 months and 18 months after clinical therapy. Therefore, ICEI provides a promising, simplified approach to monitor histological healing and to predict the prognosis of UC. REGISTRATION: Chinese Clinical Trial Registry, No. ChiCTR2300077792.

Fruits and vegetables consumption and risk of non-Hodgkin's lymphoma: a meta-analysis of observational studies.

Epidemiologic evidence suggests that intakes of fruits and/or vegetables may play a role in the etiology of non-Hodgkin's lymphoma (NHL), but the findings are inconsistent. We aimed to assess fruits and/or vegetables intakes in relation to risk of NHL by a meta-analytic approach. We searched on PubMed database from January 1966 to September 2012 to indentify case-control and cohort studies. We used a random-effects model to compute summary risk estimates. For vegetables, the summary relative risks (RRs) of NHL for high versus low intake for case-control, cohort and all studies were 0.75 (95% CI, 0.60-0.94; N = 8), 0.90 (95% CI, 0.81-1.00; N = 5) and 0.81 (95%CI, 0.71-0.92; N = 13) ; and the corresponding RRs for intake of 1 serving per day were 0.88 (95% CI, 0.80-0.96; N = 8), 0.96 (95% CI, 0.92-1.00; N = 5) and 0.92 (95%CI, 0.87-0.96; N = 13). For fruits and vegetables combined, the summary RR for high versus low intake was 0.78 (95%CI, 0.66-0.92; N = 4), and for intake of 1 serving per day was 0.95 (95%CI, 0.91-1.00; N = 4). Regarding histological subtypes, vegetables intake was significantly inversely associated with diffuse large B-cell lymphoma and follicular lymphoma, but not small lymphocytic lymphoma/chronic lymphocytic leukemia (high vs. low intake, RR = 0.70, 0.70 and 1.01, respectively; N = 7, 7 and 10, respectively). Fruits intake was generally not associated with total NHL, or any histological subtypes. Our findings suggest that intakes of vegetables, and fruits and vegetables combined, but not fruits alone, significantly reduce risk of NHL.