Activation of GPR81 by lactate drives tumour-induced cachexia.

Cachexia affects 50-80% of patients with cancer and accounts for 20% of cancer-related death, but the underlying mechanism driving cachexia remains elusive. Here we show that circulating lactate levels positively correlate with the degree of body weight loss in male and female patients suffering from cancer cachexia, as well as in clinically relevant mouse models. Lactate infusion per se is sufficient to trigger a cachectic phenotype in tumour-free mice in a dose-dependent manner. Furthermore, we demonstrate that adipose-specific G-protein-coupled receptor (GPR)81 ablation, similarly to global GPR81 deficiency, ameliorates lactate-induced or tumour-induced adipose and muscle wasting in male mice, revealing adipose GPR81 as the major mediator of the catabolic effects of lactate. Mechanistically, lactate/GPR81-induced cachexia occurs independently of the well-established protein kinase A catabolic pathway, but it is mediated by a signalling cascade sequentially activating Gi-Gßγ-RhoA/ROCK1-p38. These findings highlight the therapeutic potential of targeting GPR81 for the treatment of this life-threatening complication of cancer.

Change and pathological significance of glycogen content in oral squamous cell carcinoma and oral submucous fibrosis.

OBJECTIVE: This study aimed to investigate the change and pathological significance of glycogen content in oral squamous cell carcinoma (OSCC) and oral submucous fibrosis (OSF). METHODS AND MATERIALS: 13 normal oral mucosa (NOM), 12 OSF mucosa, and 35 pairs of OSCC tissues and their corresponding adjacent mucosa tissues (AT) were collected from Xiangya Hospital for PAS staining to detect glycogen. Transcriptome sequencing data from OSCC were used to compare glycogen metabolism gene expression differences. Kaplan-Meier method was conducted to estimate Recurrence-free survival (RFS). RESULTS: Glycogen levels were lower in OSF than in NOM and lower in OSCC than in AT. Transcriptome sequencing data analysis showed the expression of most glycogenolysis genes was increased and the expression of glycogen synthesis genes including PPP1R3C and GBE1 was decreased in OSCC tissues. High glycogen level was correlated with poor prognosis in OSCC patients under the background of OSF. CONCLUSION: Glycogen may be used as a potential diagnostic biomolecule for OSF and OSCC, as well as a potential prognostic factor for OSCC in the context of OSF.

Prognostic analysis of cT1-3N1M0 breast cancer patients who have responded to neoadjuvant therapy undergoing various axillary surgery and breast surgery based on propensity score matching and competitive risk model.

Background: Sentinel lymph node biopsy (SLNB) in breast cancer patients with positive clinical axillary lymph nodes (cN1+) remains a topic of controversy. The aim of this study is to assess the influence of various axillary and breast surgery approaches on the survival of cN1+ breast cancer patients who have responded positively to neoadjuvant therapy (NAT). Methods: Patients diagnosed with pathologically confirmed invasive ductal carcinoma of breast between 2010 and 2020 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. To mitigate confounding bias, propensity score matching (PSM) analysis was employed. Prognostic factors for both overall survival (OS) and breast cancer-specific survival (BCSS) were evaluated through COX regression risk analysis. Survival curves were generated using the Kaplan-Meier method. Furthermore, cumulative incidence and independent prognostic factors were assessed using a competing risk model. Results: The PSM analysis matched 4,890 patients. Overall survival (OS) and BCSS were slightly worse in the axillary lymph node dissection (ALND) group (HR = 1.10, 95% CI 0.91-1.31, p = 0.322 vs. HR = 1.06, 95% CI 0.87-1.29, p = 0.545). The mastectomy (MAST) group exhibited significantly worse OS and BCSS outcomes (HR = 1.25, 95% CI 1.04-1.50, p = 0.018 vs. HR = 1.37, 95% CI 1.12-1.68, p = 0.002). The combination of different axillary and breast surgery did not significantly affect OS (p = 0.083) but did have a significant impact on BCSS (p = 0.019). Competing risk model analysis revealed no significant difference in the cumulative incidence of breast cancer-specific death (BCSD) in the axillary surgery group (Grey's test, p = 0.232), but it showed a higher cumulative incidence of BCSD in the MAST group (Grey's test, p = 0.001). Multivariate analysis demonstrated that age ≥ 70 years, black race, T3 stage, ER-negative expression, HER2-negative expression, and MAST were independent prognostic risk factors for both OS and BCSS (all p < 0.05). Conclusion: For cN1+ breast cancer patients who respond positive to NAT, the optimal surgical approach is combining breast-conserving surgery (BCS) with SLNB. This procedure improves quality of life and long-term survival outcomes.

Regulation of glycose and lipid metabolism and application based on the colloidal nutrition science properties of konjac glucomannan: A comprehensive review.

The physicochemical properties of dietary fiber in the gastrointestinal tract, such as hydration properties, adsorption properties, rheological properties, have an important influence on the physiological process of host digestion and absorption, leading to the differences in satiety and glucose and lipid metabolisms. Based on the diversified physicochemical properties of konjac glucomannan (KGM), it is meaningful to review the relationship of structural characteristics, physicochemical properties and glycose and lipid metabolism. Firstly, this paper bypassed the category of intestinal microbes, and explained the potential of dietary fiber in regulating glucose and lipid metabolism during nutrient digestion and absorption from the perspective of colloidal nutrition. Secondly, the modification methods of KGM to regulate its physicochemical properties were discussed and the relationship between KGM's molecular structure types and glycose and lipid metabolism were summarized. Finally, based on the characteristics of KGM, the application of KGM in the main material and ingredients of fat reduction food was reviewed. We hope this work could provide theoretical basis for the study of dietary fiber colloid nutrition science.

Prognostic value of coagulation markers in patients with colorectal caner: A prospective study.

Background and Aims: The occurrence, growth, and metastasis of colorectal cancer (CRC) are connected to the hypercoagulable state of blood (CRC). This study aimed to identify significant coagulation factors to predict metastasis and prognosis of CRC. Methods: Thrombomodulin (TM), thrombin-antithrombin complex (TAT), α2-plasmininhibitor-plasmin complex (PIC), and tissue plasminogen activator-inhibitor complex (t-PAIC) were detected by chemiluminescence immunoassay using Sysmex HISCL5000 automated analyzers. The Sysmex CS 5100 automatic blood coagulation analyzer was used to detect d-dimer (DD), fibrin degradation product (FDP), prothrombin time (PT), thrombin time (TT), international normalized ratio (INR), fibrinogen (Fbg), and activated partial thromboplastin time (APTT). Area under the curve (AUC) and the receiver operating characteristic curve (ROC) were used to assess the diagnostic efficacy of markers. Kaplan-Meier analysis was used to calculate survival probabilities. Independent prognostic factors and the nomogram were developed using single-factor and multifactor cox regression analysis model. Results: The following indicators (TM, TAT, PIC, t-PAIC, DD, FDP, PT, INR, APTT, and Fbg) were markedly higher in CRC patients than in healthy controls, and they were higher in the metastasis (M) group than in the nonmetastasis (NM) group. The combination "TAT + PIC + DD + FDP + Fbg" can distinguish M from NM with exceptional sensitivity and specificity. Patients with CRC who had high levels of TAT, PIC, DD, FDP, Fbg, TM, tPAIC, PT, and INR had significantly shorter survival. Conclusion: The prognosis of CRC patients can be predicted by coagulation indicators. The independent predictive variables for overall survival were found to be TM and DD. To forecast CRC patient survival, a nomogram was created.

E2F3/5/8 serve as potential prognostic biomarkers and new therapeutic direction for human bladder cancer.

OBJECTS: Human bladder cancer (BC) is the most common urogenital system malignancy. E2F transcription factors (E2Fs) have been reported to be involved in the growth of various cancers. However, the expression patterns, prognostic value and immune infiltration in the tumor microenvironment of the 8 E2Fs in BC have yet fully to be explored. METHODS AND STRATEGY: We investigated the differential expression of E2Fs in BC patients, the prognostic value and correlation with immune infiltration by analyzing a range of databases. RESULTS: We found that the mRNA expression levels of E2F1/2/3/4/5/7/8 were significantly higher in BC patients than that of control tissues. And the increased mRNA expression levels of all E2Fs were associated with tumor stage of BC. The survival analysis revealed that the elevated mRNA expression levels of E2F3/5/8 were significantly correlated with the overall survival (OS) of BC patients. And the genetic changes of E2Fs in BC patients were associated with shorter overall survival (OS) and progression-free survival (PFS). In addition, we revealed that the E2F3/5/8 expressions were closely correlated with tumor-infiltrating lymphocytes (TILs). CONCLUSIONS: E2F3/5/8 might serve as promising prognostic biomarkers and new therapeutic direction for BC patients.

A diagnostic model based on 18F-FDG PET/CT parameters in improving the differential diagnosis of invasive thymic epithelial tumors and anterior mediastinal lymphomas.

BACKGROUND: Accurately distinguishing between invasive thymic epithelial tumors (TETs) and anterior mediastinal lymphoma before surgery is crucial for subsequent treatment choices. But currently, the diagnosis of invasive TET is sometimes difficult to distinguish from anterior mediastinal lymphoma. OBJECTIVE: To assess the application of fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computer tomography (PET/CT) in the differential diagnosis of TETs and anterior mediastinal lymphomas. METHODS: 18F-FDG PET/CT images of 133 invasive TETs and anterior mediastinal lymphomas patients were retrospectively analyzed. In particular, the tumor's longest diameter and maximum standardized uptake value (SUVmax) were evaluated. The SUVmax and longest diameter values of the two groups were analyzed by using the receiver operating characteristic (ROC) curve to determine the optimal threshold and diagnostic efficiency. RESULTS: Age, myasthenia gravis, SUVmax and tumor longest diameter differed significantly between invasive TETs and anterior mediastinal lymphomas patients. The tumor location, calcification, relationship with adjacent vessels and distant metastasis differed significantly between the groups. The ROC analysis showed an AUC for SUVmax and tumor longest diameter of 0.841 and 0.737. Respectively, the cutoff values with the best diagnostic performance were 9.65 (sensitivity: 77.78%, specificity: 81.97%) and 6.65 (sensitivity: 80.56%, specificity: 62.30%) for SUVmax and tumor longest diameter. The diagnostic model of SUVmax, calcification, relationship with surrounding blood vessels, lymph node metastasis and lung metastasis in the highest AUC of 0.935 (sensitivity: 90.16%, specificity: 88.89%). In addition, we incorporated splenic involvement and metastatic sub-diaphragmatic lymph node into Model 2 as a new predictive model 3 for differential diagnosis and found a significant improvement in the diagnostic performance of Model 3. CONCLUSION: The diagnostic model composed of 18F-FDG PET parameters is improving the differential diagnosis of invasive TETs and anterior mediastinal lymphomas.

[Piriform sinus hamartoma in children: a case report and literature review].

Objective:To investigate the clinical manifestations and treatment of laryngopharynx hamartoma in children. Methods:The clinical data of a child with piriform sinus hamartoma treated in our hospital were analyzed retrospectively. The age, gender, clinical manifestations, auxiliary examination, location of the tumor and surgical methods were analyzed. Results:The patient had a good prognosis after surgery, and no tumor recurrence was found after 1 year of follow-up. Conclusion:Laryngopharynx hamartoma is rare in children. It should be considered in children with laryngeal dysfunction and upper airway obstruction. Complete resection of the tumor is the key to postoperative recurrence.

Improving diagnostic efficacy of primary prostate cancer with combined 99mTc-PSMA SPECT/CT and multiparametric-MRI and quantitative parameters.

Purpose: This prospective study aimed to evaluate the difference between 99mTc-PSMA single-photon emission computed tomography (SPECT)/CT and multiparametric magnetic resonance imaging (mpMRI) in the detection of primary prostate cancer (PCa). Materials and methods: Fifty-six men with suspected PCa between October 2019 and November 2022 were prospectively enrolled in this study. The median age of the patients was 70 years (range, 29-87 years). Patients were divided into high-(Gleason score>7, n=31), medium- (Gleason score=7, n=6) and low-risk groups (Gleason score < 7, n=6). All patients underwent 99mTc-PSMA SPECT/CT and mpMRI at an average interval of 3 days (range, 1-7 days). The maximum standardized uptake value (SUVmax), the minimum apparent diffusion coefficient (ADCmin), and their ratio (SUVmax/ADCmin) were used as imaging parameters to distinguish benign from malignant prostatic lesions. Results: Of the 56 patients, 12 were pathologically diagnosed with a benign disease, and 44 were diagnosed with PCa. 99mTc-PSMA SPECT/CT and mpMRI showed no significant difference in the detection of primary PCa (kappa =0.401, P=0.002), with sensitivities of 97.7% (43/44) and 90.9% (40/44), specificities of 75.0% (9/12) and 75.0% (9/12), and AUC of 97.4% and 95.1%, respectively. The AUC of SUVmax/ADCmin was better than those of SUVmax or ADCmin alone. When SUVmax/ADCmin in the prostatic lesion was >7.0×103, the lesion was more likely to be malignant. When SUVmax/ADCmin in the prostatic lesion is >27.0×103, the PCa patient may have lymph node and bone metastases. SUVmax was positively correlated with the Gleason score (r=0.61, P=0.008), whereas ADCmin was negatively correlated with the Gleason score (r=-0.35, P=0.023). SUVmax/ADCmin was positively correlated with the Gleason score (r=0.59, P=0.023). SUVmax/ADCmin was the main predictor of the high-risk group, with an optimal cut-off value of 15.0×103. Conclusions: The combination of 99mTc-PSMA SPECT/CT and mpMRI can improve the diagnostic efficacy for PCa compared with either modality alone; SUVmax/ADCmin is a valuable differential diagnostic imaging parameter.

Spectral CT imaging versus conventional CT post-processing technique in differentiating malignant and benign renal tumors.

OBJECTIVE: Quantitative comparison of the diagnostic value of spectral CT imaging and conventional CT post-processing technique in differentiating malignant and benign renal tumors. METHODS: A total of 209 patients with renal tumors who had undergone CT enhancement were assigned to three groups-clear cell renal cell carcinoma (ccRCC, n = 106), non-ccRCC (n = 60), and benign renal tumor (n = 43) groups. Parametric CT enhancement of each tumor based on spectral CT and conventional CT was performed using in-house software, and the iodine concentration, water content, slope, and density values among the three groups were compared. The receiver operating characteristic (ROC) curve analysis was performed to determine the optimum diagnostic thresholds, the area under the ROC curve (AUC), sensitivity, specificity, and accuracy of the above parameters. RESULTS: The iodine concentration, slope, and density values were higher in the ccRCCs group compared to the non-ccRCCs and benign renal tumor groups (p < 0.05). Moreover, the iodine concentration, slope, and density values were higher in benign renal tumors compared to non-ccRCCs (p < 0.05). According to the ROC curve analysis, iodine concentration presented the highest diagnostic efficacy in differentiating ccRCCs/non-ccRCCs from benign renal tumors. The pairwise comparisons of the ROC curves and the diagnostic efficacies revealed that ROI-based CT enhancement was worse than the spectral CT imaging analysis in terms of density (p < 0.05). CONCLUSION: Iodine concentration presented the highest diagnostic efficacy in differentiating ccRCCs/non-ccRCCs from benign renal tumors. ADVANCES IN KNOWLEDGE: 1. The iodine concentration, slope, and density values were higher for the ccRCCs compared to non-ccRCCs and benign renal tumors.2. Iodine concentration presented the highest diagnostic efficacy in differentiating ccRCCs/non-ccRCCs from benign renal tumors.3. Spectral CT imaging analysis performed better than conventional CT in differentiating malignant and benign renal tumors.

Anti-angiogenic agents combined with immunotherapy for advanced non-small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: Anti-angiogenic agents could enhance tumor immunity response, and anti-angiogenesis plus immunotherapy has become a novel treatment option for advanced non-small cell lung cancer (NSCLC). The efficacy of this combination therapy remains controversial and obscure. AIM: We conducted a meta-analysis to evaluate the clinical efficacy and safety of this therapeutic strategy in patients with advanced NSCLC and provide more guidance for treating NSCLC clinically. METHODS: A systematic literature search was performed in PubMed, Embase, Web of Science, CNKI, and Wanfang databases to identify relevant studies published up to December 2021. The primary endpoint was the objective response rate (ORR). Second endpoints were progression-free survival (PFS), overall survival (OS), and grade ≥3 AEs adverse events (AEs). The sensitivity analysis was conducted to confirm the stability of the results. STATA 15.0 was utilized for all pooled analyses. RESULTS: Eleven studies were eventually included in the meta-analysis, involving 533 patients with advanced NSCLC. The pooled ORR rate was 27% (95% CI 18% to 35%; I2 =84.2%; p<0.001), while the pooled median PFS and OS was 5.84 months (95% CI 4.66 to 7.03 months; I2=78.4%; p<0.001) and 14.20 months (95% CI 11.08 to 17.32 months; I2=82.2%; p=0.001), respectively. Most common grade ≥3 AEs included hypertension, hand-foot syndrome, diarrhea, adrenal insufficiency, hyponatremia, proteinuria, rash, thrombocytopenia, and fatigue. CONCLUSION: Anti-angiogenesis combined with immunotherapy demonstrated satisfactory antitumor activity and an acceptable toxicity profile in patients with advanced NSCLC. The pooled results of our meta-analysis provided further evidence supporting the favorable efficacy and safety of this therapeutic strategy.

Traditional Chinese medication for oral submucous fibrosis: A systematic review and network meta-analysis of randomized controlled trials.

OBJECTIVE: The purpose of this study was to investigate the effectiveness of various drug therapy methods for treating oral submucous fibrosis (OSF) in terms of increasing mouth opening, reducing VAS score, decreasing lesion area, minimizing side effects, and determining effective proportion. METHOD: A database search was conducted. Only randomized clinical trials were included, and Cochrane checklist was used for assessing the risk of bias. Stata.17 software was employed and effective treatment ranking was used. RESULTS: Thirty-one RCT studies, with a total of 2986 patients, were included in the period of 2010-2022. The combination of oral Chinese herbal medicine formulas (OC) and intralesional Salvia miltiorrhiza (ISM) was found to be the most effective treatment in improving mouth opening. For reducing the burning pain, the combination of intralesional steroids (IS) and oral Salvia miltiorrhiza (OSM) was found to be more effective than the others. In terms of lesion area, IS combined with OC was more effective than the others. IS combined with ISM had the highest effective proportion while having the lowest incidence of side effects which mentioned the incidence of side effects. CONCLUSION: This study indicates that OC and SM can be employed by clinicians for treating OSF effectively.

Diffusion-weighted and diffusion kurtosis imaging analysis of microstructural differences in clear cell renal cell carcinoma: a comparative study.

OBJECTIVE: To quantitatively compare the diagnostic values of conventional diffusion-weighted imaging (DWI) and diffusion kurtosis imaging (DKI) analysis of microstructural differences for clear cell renal cell carcinoma (CRCC). METHODS: A total of 108 patients with pathologically confirmed CRCC, including 38 Grade I, 37 Grade II, 18 Grade III and 15 Grade IV, were enrolled and divided into groups according to tumor grade [low grade (Ⅰ+Ⅱ, n = 75) and high grade (Ⅲ+Ⅳ, n = 33)]. Apparent diffusion coefficient (ADC), mean diffusivity (MD), mean kurtosis (MK), kurtosis anisotropy (KA) and radial kurtosis (RK) were performed. RESULTS: Both the ADC (r = -0.803) and MD (-0.867) values showed a negative correlation with tumor grading (p < 0.05) and MK (r = 0.812), KA (0.816) and RK (0.853) values a positive correlation with tumor grading (p < 0.05). Mean FA values showed no significant differences among CRCC grades (p > 0.05). ROC curve analyses showed that MD values had the highest diagnostic efficacy in differentiating low/high and Ⅱ/Ⅲ tumor grading. MD values gave AUC: 0.937 (0.896); sensitivity: 92.0% (86.5%); specificity: 78.8% (77.8%) and accuracy: 90.7% (87.3%). ADC performed worse than MD, MK, KA or RK (all p < 0.05) during pair-wise comparisons of ROC curves to show diagnostic efficacy. CONCLUSION: DKI analysis performs better than ADC in differentiating CRCC grading. ADVANCES IN KNOWLEDGE: Both the ADC and MD values correlated negatively with CRCC grading.The MK, KA and RK values correlated positively with CRCC grading.MD values had the highest diagnostic efficacy in differentiating low/high and Ⅱ/Ⅲ CRCC grading.

ELK1/KIFC1 axis promotes breast cancer cell proliferation by regulating glutathione metabolism.

BACKGROUND: KIFC1 exerts an important function in centrosome aggregation in breast cancer (BC) cells and a variety of other cancer cells, but its potential mechanisms in BC pathogenesis are yet fully elucidated. The aim of this study was to investigate the effects of KIFC1 on BC progression and its underlying mechanisms. METHODS: Expression of ELK1 and KIFC1 in BC was analyzed by The Cancer Genome Atlas database and quantitative real-time polymerase chain reaction. Cell proliferative capacity was examined by CCK-8 and colony formation assays, respectively. Glutathione (GSH)/glutathione disulfide (GSSG) ratio and GSH level were measured using the kit. Expression of GSH metabolism-related enzymes (G6PD, GCLM, and GCLC) was detected by western blot. Intracellular reactive oxygen species (ROS) levels were measured by the ROS Assay Kit. The transcription factor ELK1 upstream of KIFC1 was identified by hTFtarget, KnockTFv2 database and Pearson correlation. Their interaction was validated by dual-luciferase reporter assay and chromatin immunoprecipitation. RESULTS: This study demonstrated the upregulation of ELK1 and KIFC1 in BC and found that ELK1 could bind to the KIFC1 promoter to promote KIFC1 transcription. KIFC1 overexpression increased cell proliferation and intracellular GSH levels, while decreasing intracellular ROS levels. The addition of the GSH metabolism inhibitor BSO attenuated the promotion of BC cell proliferation induced by KIFC1 overexpression. In addition, KIFC1 overexpression reversed the inhibitory effect of knockdown of ELK1 on BC cell proliferation. CONCLUSION: ELK1 was a transcriptional factor of KIFC1. ELK1/KIFC1 axis reduced ROS level by increasing GSH synthesis, thus facilitating BC cell proliferation. Current observations suggest that ELK1/ KIFC1 may be a potential therapeutic target for BC treatment.

Associations between functional constipation and non-IgE-mediated food allergy in infants and children.

BACKGROUND: The non-IgE-mediated food allergy (non-IgE-FA) is less prevalent than IgE-mediated food allergy, and their relationship with functional constipation (FC) needs to be clarified. METHODS: A total of 305 infants and children with constipation treated in the Department of Pediatric Gastroenterology, Children's Hospital of Nanjing Medical University, from July 2020 to December 2021 were included in this study. Four cases with organic lesions were excluded. Among 301 diagnosed with FC, according to ROME IV criteria, 81 cases with allergy-related indicators were further evaluated for food allergy by food-specific IgG antibody test, allergen- specific IgE antibody detection, skin prick test, and food avoidance and reintroduction. RESULTS: A total of 45 cases with FC were diagnosed with food allergy, and the incidence rate was 15%. Among the 45 patients, 35 cases (77.8%) had FC with non-IgE-FA. The main clinical symptoms or signs included anal fissure, abdominal pain, and pain during defecation. The most prevalent allergic foods were cow's milk, eggs, fish, and shrimp. Ten (22.2%) cases reported FC with mixed food allergy, including both non-IgE-mediated and IgE-mediated food allergy. This study focused on non-IgE-mediated food allergy-related FC. CONCLUSION: Our results showed that the incidence of food allergy in infants and children with FC was 15%, which was mainly mediated by non-IgE-FA. The main clinical symptoms or signs in these cases included anal fissure, abdominal pain, and pain during defecation, and the main allergens included milk, eggs, fish, and shrimp.

Efficacy of short-chain polypeptide-based EEN formulas in alleviating intestinal injury in children with Crohn's disease: a single-center study in China.

Short-chain polypeptides are composed of three to nine amino acids, which can be absorbed by the intestinal tract without digestive enzymes and ATP energy. Crohn's disease (CD) is a chronic non-specific disease derived from inflammation and damage of the gastrointestinal tract. In this study, we aim to investigate the effect of short-chain polypeptide-based exclusive enteral nutrition (EEN) formulas on intestinal injury in Chinese children with active CD. From January 2013 to January 2019, a total of 84 consecutive children with a diagnosis of Crohn's disease (CD) in the Department of Pediatric Gastroenterology, Children's Hospital of Nanjing Medical University, were divided into mild and moderate-to-severe active CD groups. Each group was further divided into two subgroups: drug group and short-chain polypeptide plus drug group. Tests were carried out on the levels of intestinal fatty acid binding protein (I-FABP) in the blood, fecal calprotectin (FC), and occludin protein in the intestinal mucosa 1 day before treatment and 8 weeks after treatment. Endoscopic and histopathological observations were detected to compare the changes in intestinal injury in children with active CD. After 8 weeks of treatment, the SES-CD scores and Chiu scores of the ileocecal area and terminal ileum of children with mild active CD and the ileocecal area of children with moderate-to-severe active CD in short-chain polypeptide plus drug group were significantly lower than those in the drug group. The OD value of occludin in the terminal ileum and ileocecal area of children with mild active CD and the ileocecal area of children with moderate-to-severe active CD after short-chain polypeptide-based EEN formulas and drug treatment was significantly higher than those in the drug group (p < 0.05). Meanwhile, the levels of FC and I-FABP were significantly decreased (p < 0.05). The results showed that short-chain polypeptide-based EEN formulas effectively alleviate intestinal injury in children with active CD.

Nomogram for predicting preoperative axillary lymph node status in male breast carcinoma: a SEER population-based study.

Background: Sentinel lymph node biopsy (SLNB) has been recommended as a replacement for axillary lymph node dissection (ALND) in male breast carcinoma (MBC) with clinical axillary lymph node-negative (ALN-negative) as in the case of female. However, the morbidity after SLNB may also have short-term or long-term complications. To avoid unnecessary surgery, building a model which is able to assess the risk of lymph node metastasis is vitally significant. Methods: A retrospective review of the clinical and pathology data were carried out for patients diagnosed with MBC between 2010 and 2018 from the Surveillance, Epidemiology, and End Results (SEER) database. The cohort was divided into training and validation cohorts. A logistic regression model was used to construct the nomogram in the training cohort and then verified in the validation cohort. The receiver operating characteristic (ROC) curve, C-index, and calibration were used to evaluate the predictive ability of the nomogram. Results: Overall, 2,610 patients diagnosed with MBC were included in the study, of which 1,740 were in the training cohort and 870 were in the validation cohort. Logistic regression analysis indicated age at diagnosis, tumor location, tumor stage, pathological type, and histologic grade, were significantly related to axillary lymph node metastasis (ALNM). The area under the curve (AUC) of the nomogram was 0.846 (95% CI: 0.825-0.867) and C-index was 0.848 (95% CI: 0.807-0.889), demonstrating a notable prediction performance. The calibration curve for the nomogram was plotted and the slope was close to 1. The prognostic value of the nomogram was further validated in the validation cohort, with an AUC of 0.848 (95% CI: 0.819-0.877). Conclusions: A nomogram to predict ALNM was successfully established, especially for those who were of advanced age at diagnosis, had small tumor size, displayed low malignancy, and showed clinical ALN-negative, to avoid unnecessary axillary operation. The quality of life for patients is enhanced without conceding the overall survival rate.

Associations between functional constipation and non-IgE-mediated food allergy in infants and children

Background: The non-IgE-mediated food allergy (non-IgE-FA) is less prevalent than IgE-mediated food allergy, and their relationship with functional constipation (FC) needs to be clarified. Methods: A total of 305 infants and children with constipation treated in the Department of Pediatric Gastroenterology, Children’s Hospital of Nanjing Medical University, from July 2020 to December 2021 were included in this study. Four cases with organic lesions were excluded. Among 301 diagnosed with FC, according to ROME IV criteria, 81 cases with allergy-related indicators were further evaluated for food allergy by food-specific IgG antibody test, allergen- specific IgE antibody detection, skin prick test, and food avoidance and reintroduction. Results: A total of 45 cases with FC were diagnosed with food allergy, and the incidence rate was 15%. Among the 45 patients, 35 cases (77.8%) had FC with non-IgE-FA. The main clinical symptoms or signs included anal fissure, abdominal pain, and pain during defecation. The most prevalent allergic foods were cow’s milk, eggs, fish, and shrimp. Ten (22.2%) cases reported FC with mixed food allergy, including both non-IgE-mediated and IgE-mediated food allergy. This study focused on non-IgE-mediated food allergy–related FC. Conclusion: Our results showed that the incidence of food allergy in infants and children with FC was 15%, which was mainly mediated by non-IgE-FA. The main clinical symptoms or signs in these cases included anal fissure, abdominal pain, and pain during defecation, and the main allergens included milk, eggs, fish, and shrimp (AU)

Increased risk of cutaneous immune-related adverse events in patients treated with talimogene laherparepvec and immune checkpoint inhibitors: A multi-hospital cohort study.

BACKGROUND: Previous studies have shown that combining immune checkpoint inhibitors (ICIs) with talimogene laherparepvec (TVEC) may improve antitumor responses. However, the risk of developing cutaneous immune-related adverse events (cirAEs) in patients treated with ICI and TVEC has not been studied. OBJECTIVE: To evaluate the differences in cirAE development between patients treated with ICI alone and both ICI and TVEC (ICI + TVEC). METHODS: Patients with cutaneous malignancy receiving ICI with or without TVEC therapy at the Massachusetts General Brigham healthcare system were included. CirAE development, time from ICI initiation to cirAE, cirAE grade, cirAE morphology, and survival were analyzed. Pearson's χ2 test or Fisher's exact test for categorical variables and t test or Kruskal-Wallis test for continuous variables were used. To account for immortal time bias, we performed adjusted time-varying Cox proportional hazards modeling. RESULTS: The rate of cirAE development was 32.3% and 38.7% for ICI only and ICI + TVEC, respectively. After adjusting for covariates, ICI + TVEC was associated with a 2-fold increased risk of cirAE development (hazard ratio: 2.03, P = .006) compared to patients receiving ICI therapy alone. LIMITATIONS: The retrospective nature and limited sample size from a tertiary-level academic center. CONCLUSION: These findings underscore potential opportunities for dermatologists and oncologists in counseling and monitoring patients.