Development and Validation of a Biparametric MRI Deep Learning Radiomics Model with Clinical Characteristics for Predicting Perineural Invasion in Patients with Prostate Cancer.

RATIONALE AND OBJECTIVES: Perineural invasion (PNI) is an important prognostic biomarker for prostate cancer (PCa). This study aimed to develop and validate a predictive model integrating biparametric MRI-based deep learning radiomics and clinical characteristics for the non-invasive prediction of PNI in patients with PCa. MATERIALS AND METHODS: In this prospective study, 557 PCa patients who underwent preoperative MRI and radical prostatectomy were recruited and randomly divided into the training and the validation cohorts at a ratio of 7:3. Clinical model for predicting PNI was constructed by univariate and multivariate regression analyses on various clinical indicators, followed by logistic regression. Radiomics and deep learning methods were used to develop different MRI-based radiomics and deep learning models. Subsequently, the clinical, radiomics, and deep learning signatures were combined to develop the integrated deep learning-radiomics-clinical model (DLRC). The performance of the models was assessed by plotting the receiver operating characteristic (ROC) curves and precision-recall (PR) curves, as well as calculating the area under the ROC and PR curves (ROC-AUC and PR-AUC). The calibration curve and decision curve were used to evaluate the model's goodness of fit and clinical benefit. RESULTS: The DLRC model demonstrated the highest performance in both the training and the validation cohorts, with ROC-AUCs of 0.914 and 0.848, respectively, and PR-AUCs of 0.948 and 0.926, respectively. The DLRC model showed good calibration and clinical benefit in both cohorts. CONCLUSION: The DLRC model, which integrated clinical, radiomics, and deep learning signatures, can serve as a robust tool for predicting PNI in patients with PCa, thus aiding in developing effective treatment strategies.

A nomogram based on LI-RADS features, clinical indicators and quantitative contrast-enhanced MRI parameters for predicting glypican-3 expression in hepatocellular carcinoma.

Purpose: Noninvasively assessing the tumor biology and microenvironment before treatment is greatly important, and glypican-3 (GPC-3) is a new-generation immunotherapy target for hepatocellular carcinoma (HCC). This study investigated the application value of a nomogram based on LI-RADS features, quantitative contrast-enhanced MRI parameters and clinical indicators in the noninvasive preoperative prediction of GPC-3 expression in HCC. Methods and materials: We retrospectively reviewed 127 patients with pathologically confirmed solitary HCC who underwent Gd-EOB-DTPA MRI examinations and related laboratory tests. Quantitative contrast-enhanced MRI parameters and clinical indicators were collected by an abdominal radiologist, and LI-RADS features were independently assessed and recorded by three trained intermediate- and senior-level radiologists. The pathological and immunohistochemical results of HCC were determined by two senior pathologists. All patients were divided into a training cohort (88 cases) and validation cohort (39 cases). Univariate analysis and multivariate logistic regression were performed to identify independent predictors of GPC-3 expression in HCC, and a nomogram model was established in the training cohort. The performance of the nomogram was assessed by the area under the receiver operating characteristic curve (AUC) and the calibration curve in the training cohort and validation cohort, respectively. Results: Blood products in mass, nodule-in-nodule architecture, mosaic architecture, contrast enhancement ratio (CER), transition phase lesion-liver parenchyma signal ratio (TP-LNR), and serum ferritin (Fer) were independent predictors of GPC-3 expression, with odds ratios (ORs) of 5.437, 10.682, 5.477, 11.788, 0.028, and 1.005, respectively. Nomogram based on LI-RADS features (blood products in mass, nodule-in-nodule architecture and mosaic architecture), quantitative contrast-enhanced MRI parameters (CER and TP-LNR) and clinical indicators (Fer) for predicting GPC-3 expression in HCC was established successfully. The nomogram showed good discrimination (AUC of 0.925 in the training cohort and 0.908 in the validation cohort) and favorable calibration. The diagnostic sensitivity and specificity were 76.9% and 92.3% in the training cohort, 76.8% and 93.8% in the validation cohort respectively. Conclusion: The nomogram constructed from LI-RADS features, quantitative contrast-enhanced MRI parameters and clinical indicators has high application value, can accurately predict GPC-3 expression in HCC and may help noninvasively identify potential patients for GPC-3 immunotherapy.

A bispecific decoy receptor VEGFR-EGFR/Fc binding EGF-like ligands and VEGF shows potent antitumor efficacy.

Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) represent two clinically validated targets for a variety of human cancers, and dual inhibition of EGFR and VEGF(R) has demonstrated superior activity to single EGFR inhibitors. This study was to construct a novel bispecific decoy receptor VEGFR-EGFR/Fc that contains Fc portion of human IgG1 acted as molecular scaffold, and the immunoglobulin-like domain 1-3 of VEGFR1 and extracellular domain of EGFR fused to the N-terminal and C-terminal of Fc, respectively, aiming at capturing the EGF-like ligands and VEGF. ELISA showed that VEGFR-EGFR/Fc bound to EGF, TGF-α and VEGF with high affinity. It displayed potent proliferation inhibitory effects on human non-small-cell lung cancer A549 cells and human umbilical vein endothelial cells revealed by MTT assays. VEGFR-EGFR/Fc significantly inhibited cell invasion and migration demonstrated by wound healing assay and transwell assay. In vivo, VEGFR-EGFR/Fc showed remarkable growth inhibition on A549 xenografts. Cell apoptosis and inhibition of angiogenesis were also observed in xenograft tumour tissues. Mechanistically, VEGFR-EGFR/Fc pre-treatment blocked the phosphorylation of EGFR and VEGFR2 and resulted in a decrease in the downstream signalling molecules, AKT, p44/42MAPK and p38MAPK. These data suggest VEGFR-EGFR/Fc would be a promising candidate for cancer targeted therapy.

The Role of PSA Density among PI-RADS v2.1 Categories to Avoid an Unnecessary Transition Zone Biopsy in Patients with PSA 4-20 ng/mL.

OBJECTIVE: To evaluate the role of prostate-specific antigen density (PSAD) in different Prostate Imaging Reporting and Data System version 2.1 (PI-RADS v2.1) categories to avoid an unnecessary biopsy in transition zone (TZ) patients with PSA ranging from 4 to 20 ng/mL. MATERIALS AND METHODS: In this retrospective and single-center study, 333 biopsy-naïve patients with TZ lesions who underwent biparametric magnetic resonance imaging (bp-MRI) were analyzed from January 2016 to March 2020. Multivariate logistic regression analyses were performed to determine independent predictors of clinically significant prostate cancer (cs-PCa). The receiver operating characteristic (ROC) curve was used to compare diagnostic performance. RESULTS: PI-RADS v2.1 and PSAD were the independent predictors for TZ cs-PCa in patients with PSA 4-20 ng/mL. 0.9% (2/213), 10.0% (7/70), and 48.0% (24/50) of PI-RADS v2.1 score 1-2, 3, and 4-5 had TZ cs-PCa. However, for patients with PI-RADS v2.1 score 1-2, there were no obvious changes in the detection of TZ cs-PCa (0.8% (1/129), 1.3% (1/75), and 0.0% (0/9)) combining with different PSAD stratification (PSAD < 0.15, 0.15-0.29, and ≥0.30 ng/mL/mL). For patients with PI-RADS v2.1 score ≥ 3, the TZ cs-PCa detection rate significantly varied according to different PSAD stratification. A PI-RADS v2.1 score 3 and PSAD < 0.15 and 0.15-0.29 ng/mL/mL had 8.6% (3/35) and 3.7% (1/27) of TZ cs-PCa, while a PI-RADS v2.1 score 3 and PSAD ≥ 0.30 ng/mL/mL had a higher TZ cs-PCa detection rate (37.5% (3/8)). A PI-RADS v2.1 score 4-5 and PSAD <0.15 ng/mL/mL had no cs-PCa (0.0% (0/9)). In contrast, a PI-RADS v2.1 score 4-5 and PSAD 0.15-0.29 and ≥0.30 ng/mL/mL had the highest cs-PCa detection rate (50.0% (10/20), 66.7% (14/21)). It showed the highest AUC in the combination of PI-RADS v2.1 and PSAD (0.910), which was significantly higher than PI-RADS v2.1 (0.889, P = 0.039) or PSAD (0.803, P < 0.001). CONCLUSIONS: For TZ patients with PSA 4-20 ng/mL, PI-RADS v2.1 score ≤ 2 can avoid an unnecessary biopsy regardless of PSAD. PI-RADS v2.1 score ≥ 3 may avoid an unnecessary biopsy after combining with PSAD. PI-RADS v2.1 combined with PSAD could significantly improve diagnostic performance.

Calpain 6 inhibits autophagy in inflammatory environments: A preliminary study on myoblasts and a chronic kidney disease rat model.

A non­classical calpain, calpain 6 (CAPN6), can inhibit skeletal muscle differentiation and regeneration. In the present study, the role of CAPN6 in the regulation of the autophagy of myoblasts in vitro was investigated. The underlying molecular events and the CAPN6 level in atrophic skeletal muscle in a rat model of chronic kidney disease (CKD) were also investigated. In vitro, CAPN6 was overexpressed, or knocked down, in rat L6 myoblasts to assess autophagy and related gene expression and co­localization. Subsequently, myoblasts were treated with a mixture of cytokines, and relative gene expression and autophagy were assessed. A rat model of CKD for muscle atrophy was established, and blood chemical level and the expression of CAPN6 in muscle were assessed. The data revealed that the knockdown of CAPN6 in rat myoblasts resulted in increased microtubule­associated protein 1 light chain 3 (LC3) levels, while its overexpression decreased LC3 levels and impaired autophagy. Additionally, it was observed that the co­localization of mammalian target of rapamycin (mTOR) and lysosomal­associated membrane protein 1 (LAMP1), a lysosomal marker, proteins was increased. In addition, mTOR, Raptor and α­tubulin (a marker of microtubules) increased in the CAPN6 overexpression group. However, inflammatory cytokines, such as interleukin (IL)­6, tumor necrosis factor (TNF)­α, interferon (INF)­Î³ and lipopolysaccharides upregulated CAPN6 expression, inhibited L6 myoblast autophagy and stabilized mTOR activity. Furthermore, the animal model successfully mimicked human disease as regards an increase in body weight, and a reduction in muscle mass, cross­sectional area and blood biomarker concentrations; a slight increase in CAPN6 mRNA and protein levels in muscles was observed. Finally, the data of the present study suggested that CAPN6 reduced autophagy via the maintenance of mTOR signaling, which may play a role in CKD­related muscle atrophy. However, future studies are required to determine whether CAPN6 may be used as an intervention target for CKD­related skeletal muscle atrophy.

Diagnostic Accuracy and Interobserver Agreement of PI-RADS Version 2 and Version 2.1 for the Detection of Transition Zone Prostate Cancers.

BACKGROUND. PI-RADS version 2.1 (v2.1) introduced a number of key changes to the assessment of transition zone (TZ) lesions. OBJECTIVE. The purpose of this study was to evaluate interobserver agreement and diagnostic accuracy for detecting TZ prostate cancer (PCa) and clinically significant PCa (csPCa) by use of PI-RADS v2 and PI-RADS v2.1 among radiologists with different levels of experience. METHODS. This retrospective study included 355 biopsy-naïve patients who from January 2017 to March 2020 underwent prostate MRI that showed a TZ lesion and underwent subsequent biopsy. PCa was diagnosed in 93 patients (International Society of Urological Pathology [ISUP] grade group 1, n = 34; ISUP grade group ≥ 2, n = 59) and non-cancerous lesions in 262 patients. Five radiologists with varying experience in prostate MRI scored lesions using PI-RADS v2 and PI-RADS v2.1 in sessions separated by at least 4 weeks. Interobserver agreement was evaluated with kappa and Kendall W statistics. ROC curve analysis was used to evaluate performance in detection of TZ PCa and csPCa. RESULTS. Interobserver agreement among all readers was higher for PI-RADS v2.1 than for PI-RADS v2 (mean weighted κ = 0.700 vs 0.622; Kendall W = 0.805 vs 0.728; p = .03). The pooled AUC values for detecting TZ PCa and csPCa were higher among all readers using PI-RADS v2.1 (0.866 vs 0.827 for TZ PCa; 0.929 vs 0.899 for TZ csPCa; p < .001). For detecting TZ PCa, the pooled sensitivity, specificity, and accuracy were 86.9%, 79.4%, and 75.4% among all readers for PI-RADS v2.1 compared with 79.4%, 71.8%, and 73.8% for PI-RADS v2. For detecting TZ csPCa, the pooled sensitivity, specificity, and accuracy were 84.8%, 90.9%, and 89.9% among all readers for PI-RADS v2.1 compared with 81.4%, 89.9%, and 88.5% for PI-RADS v2. Reader 1, who had the least experience, had the lowest sensitivity, specificity, and accuracy (78.0%, 89.2%, and 87.3%). Reader 5, who had the most experience, had the highest sensitivity, specificity, and accuracy (88.1%, 92.9%, and 92.1%) in detecting csPCa. CONCLUSION. PI-RADS v2.1 had better interobserver agreement and diagnostic accuracy than PI-RADS v2 for evaluating TZ lesions. Reader experience continues to affect the performance of prostate MRI interpretation with PI-RADS v2.1. CLINICAL IMPACT. PI-RADS v2.1 is more accurate and reproducible than PI-RADS v2 for the diagnosis of TZ PCa.

The Nutritional Status of Pediatric Patients with Single Ventricle Undergoing a Bidirectional Glenn Procedure.

Single ventricle (SV) physiology is associated with growth retardation in children. The nutritional status of pediatric patients with SV undergoing a bidirectional Glenn (BDG) procedure vitally affects the feasibility of the next operation stages. To explore the nutritional status and to identify specific anthropometric parameters relevant to short-term surgical outcomes in children with SV after the BDG procedure, this study included 151 patients who underwent the BDG procedure. Anthropometric assessments and Infant and Child Feeding Index (ICFI) scores were used to evaluate nutritional status. There was a significant statistical correlation between ICFI and malnutrition in both the height-for-age Z-score (HAZ) and weight-for-age Z-score (WAZ) groups (P < 0.05). The clinical data, including ventilation time, nosocomial infection presence, pressure injury presence, peritoneal dialysis status, and total intensive care unit days, after BDG surgery were significantly different among the HAZ groups (P < 0.05), while nosocomial infection was different among the WAZ groups (P < 0.05). Children after BDG procedure had a high incidence of malnutrition, in addition to disease factors, the type and frequency of dietary intake were also important factors leading to worse clinical outcomes during hospitalization. Therefore, it is vital to maintain an optimal nutritional status in infants with SV who are undergoing a series of surgical procedures.

Biparametric prostate MRI and clinical indicators predict clinically significant prostate cancer in men with "gray zone" PSA levels.

PURPOSE: To predict clinically significant prostate cancer (cs-PCa) by combining the Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) score based on biparametric magnetic resonance imaging (bp-MRI) and clinical indicators in men with prostate-specific antigen (PSA) levels in the gray zone of 4-10 ng/mL. METHOD: We retrospectively analyzed 364 patients with elevated PSA levels in the gray zone who had pathologically confirmed disease and had undergone MRI examinations from January 2015 to October 2019; a training group (n = 255) and validation group (n = 109) were randomly established. Multivariate logistic regression analysis of the training group was performed to identify the independent predictors for cs-PCa, thereby establishing a predictive model that was evaluated in the training and validation groups by analyzing the receiver operating characteristic (ROC) curve. RESULTS: In the training group, the PI-RADS v2 score and prostate volume (PV) were independent predictors of cs-PCa (P < 0.05). The prediction model comprising the PI-RADS v2 score and PV had a larger AUC than the other predictors alone in the training group. The diagnostic sensitivity and specificity of the prediction model were 84.1 % and 83.4 %, respectively. The prediction model was indicated to have better predictive performance in the validation group. CONCLUSIONS: The prediction model exhibits a satisfactory predictive value for cs-PCa in men with PSA levels in the gray zone. PI-RADS v2 is the strongest univariate predictor for the detection of cs-PCa in men with PSA in the gray zone, but combining this with the PV can provide superior predictive ability.

[Epidemiological characteristics of acupuncturists who are sensitive to stimulation of moxa smoke: a face-to-face sectional survey based on 733 participants].

OBJECTIVE: To explore the epidemiologic characteristics of acupuncturists who are sensitive to stimulation of moxa smoke, which could provide further direction for safety protection of exerting moxibustion and to further verify the feasibility of internet survey. METHODS: A self-made questionnaire regarding body response to moxa smoke was established, which was used to conduct a face-to-face survey among acupuncturists who had performed long-term moxibustion. The Logistic regression model was used to analyze the factors affecting the stimulation response of acupuncturists and the epidemiological characteristics of acupuncturists was obtained. RESULTS: A total of 733 valid data was obtained. The multivariate Logistic regression analysis showed that the history of chronic respiratory disease was the main risk factor of stimulus response including cough, phlegm in the throat, asthma, dyspnea, shortness of breath and nasal dryness after exposure to moxa smoke (P<0.05, P<0.01). The risk of stimulus response such as cough, tearing and nasal dryness was higher in women than in men (P<0.05, P<0.01). The risk of dry eyes and eyes pain in smokers was higher than those in non-smokers (P<0.05). The risk of shortness of breath in those who were exposed to second-hand smoke was higher than those who were not exposed to second-hand smoke (P<0.05). The analysis of index trend line showed that the results of internet survey were similar to those of face-to-face survey. CONCLUSION: The stimulus response of acupuncturist after long-term exposure to moxa smoke is related to the history of chronic respiratory disease, being female, smoking or exposure of second-hand smoke, therefore more attention should be paid to those populations. In addition, the internet survey can be used for the epidemiological investigation of safety of moxa smoke.

Nrf2 participates in mechanisms for reducing the toxicity and enhancing the antitumour effect of Radix Tripterygium wilfordii to S180-bearing mice by herbal-processing technology.

Context: Radix Tripterygium wilfordii Hook. f. (Celastraceae) (LGT) has outstanding curative efficacy; however, side effects include high toxicity, particularly hepatotoxicity and nephrotoxicity. Objective: To investigate detoxification mechanisms of LGT through processing separately with each of these medicinal herbs including Flower Lonicera japonica Thunb. (Caprifoliaceae) (JYH), Radix Paeonia lactiflora Pall. (Ranunculaceae) (BS), Herba Lysimachia christinae Hance (Primulaceae) (JQC), Radix et Rhizoma Glycyrrhiza uralensis Fisch. (Fabaceae) (GC) and Seed Phaseolus radiatus L. (Fabaceae) (LD) in S180-bearing mice by involving nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Materials and methods: LGT raw and processed products were orally administered at 60 mg/kg to KM male mice inoculated with S180 tumour cells for 14 consecutive days, and blood, tumour, liver and kidney were taken to observe the detoxifying effects and biological mechanisms. Results: Herbal-processing technology significantly weakened hepatotoxicity and nephrotoxicity evoked by LGT with ED50 of the converted triptolide in each processed-herb product for serum alanine transaminase, aspartate transaminase, creatinine and urea nitrogen of 9.3, 16.6, 2.5 and 4.2 µg/kg, for liver glutathione, glutathione S-transferase, catalase, tumour necrosis factor-α and interleukin-10 of 114.9, 67.8, 134.1, 7.7, 4171.6 µg/kg, and for kidney 21.9, 20.5, 145.0, 529.7, 19.4 µg/kg, respectively. Moreover, herbal-processing technology promoted the accumulation of Nrf2 into the nucleus, and upregulated mRNA expression of Nrf2 and heme oxygenase-1. Additionally, herbal-processing technology enhanced the tumour inhibition rate with ED50 12.2 µg/kg. Discussion and conclusions: Herbal-processing technology improves the safety and effectiveness of LGT in cancer treatment, and future research may be focused on the Nrf2-related molecules.

CKD autophagy activation and skeletal muscle atrophy-a preliminary study of mitophagy and inflammation.

BACKGROUND/OBJECTIVES: Long-lived proteins and organelles, such as mitochondria and the sarcoplasmic reticulum, are degraded by autophagy. However, the specific role of autophagy in chronic kidney disease (CKD) muscle atrophy is still undefined. SUBJECTS/METHODS: This was a cross-sectional study with 20 subjects and 11 controls. Autophagy induction was studied in human skeletal muscle biopsies from CKD patients and controls by comparing the cross-sectional areas of muscle fibers, protein, and mRNA expression of autophagy-related genes and the appearance of autophagosomes. RESULTS: The cross-sectional area of muscle fibers was decreased in CKD patients as compared with the control group. CKD was associated with activated autophagy and mitophagy, as measured by the elevated mRNA and protein expression of BNIP3, (microtubule-associated proteins 1 A/1B light chain 3, also MAP1LC3) LC3, p62, PINK1, and PARKIN in the skeletal muscle and isolated mitochondria of the CKD group. Electron microscopy and immunohistofluorescence analysis showed mitochondrial engulfment by autophagosomes. Mitophagy was further demonstrated by the colocalization of LC3 and p62 puncta with the mitochondrial outer membrane protein TOM20. In addition, degradative FOXO3 (Forkhead box O3) was activated and synthetic mTOR (mammalian target of rapamycin) was inhibited, whereas the upstream mediators VPS34 (class III PI3-kinase) and AKT (protein kinase B, PKB) were activated in CKD patients. CONCLUSIONS: Hyperactive autophagy and mitophagy may play important roles in CKD muscle atrophy. Autophagy was activated by FOXO3 translational factors in the skeletal muscle tissues of CKD patients, which maybe a new way of intervention for CKD muscle atrophy.

Detoxication mechanisms of Radix Tripterygium wilfordii via compatibility with Herba Lysimachia christinae in S180-bearing mice by involving Nrf2.

The combined administration between Radix Tripterygium wilfordii Hook F (LGT) and Herba Lysimachia christinae Hance (JQC) belongs to mutual detoxication compatibility of seven emotions in traditional Chinese medicine (TCM) theory. However, until now, the compatibility detoxication mechanisms remain unknown. The present study was undertaken to observe detoxication mechanisms of LGT through compatibility with JQC in tumor-bearing mice by involving NF-E2-related factor 2 (Nrf2)-mediated antioxidant defenses. In addition, influence of compatibility on antitumor activity was also investigated here. Our results demonstrated that compatibility with JQC administration significantly reversed LGT-elevated serum alanine/aspartate transaminase (ALT/AST) levels and alleviated hepatocytes' swelling or degeneration damage, and at the ratio 2/1 (LGT/JQC) produced the strongest detoxication effect. Besides, compatibility with JQC administration reversed not only LGT-elevated hepatic malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α) but also the LGT lowered GSH, glutathione-s transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and interleukin (IL)-10 levels. Furthermore, compatibility with JQC administration significantly up-regulated protein expression of Nrf2 and mRNA expression of it regulated downstream antioxidant genes such as heme oxygenase-1 (HO-1), NAD(P)H: quinone oxidoreductase-1 (NQO1), and glutamate cysteine ligase catalytic subunit (GCLC). In addition, compatibility with JQC further decreased LGT-decreased tumor weight and at the ratio 2/1 (LGT/JQC) also exerted the strongest synergistic effect. Collectively, through compatibility with JQC exerted detoxication effect on LGT-induced hepatotoxicity and the mechanisms could be at least partly attributed to up-regulation of Nrf2 and its downstream signals, thereby enhancing antioxidant defenses, and inhibiting lipid peroxidation, oxidative stress, and inflammation. Additionally, at the ratio 2/1 (LGT/JQC) exerted the strongest effects on both detoxication and synergism.

Nutritional outcomes in infants with food allergy after cardiac surgery.

BACKGROUND: Food allergy is a rapidly growing public health concern because of its increasing prevalence, as well as life-threatening potential. There is limited knowledge on the nutritional status for the pediatric congenital heart disease (CHD) patients with food allergy. OBJECTIVE: This study investigated both clinical and nutritional outcomes according to the CHD infants with food allergy. METHODS: Forty CHD infants with food allergy and 39 controls were recruited in Shanghai, China. The height and weight for age and weight for height were converted to z-scores to evaluate their effects on nutritional status before and after CHD operation. RESULTS: Cow's milk showed the most frequently sensitized food allergen. The WHZ in the ≥2 allergen group was different before operation and after operation (P = .040). The number of sensitized food allergens significantly correlated with the WHZ (r = -0.431, P = .001), WAZ (r = -0.465, P = .000), and HAZ (r = -0.287, P = .025). Infection and NT-BNP showing negative correlation with WHZ and WAZ of infants with food allergy. CONCLUSIONS: The increased number of sensitized food allergens is associated with negative effects on both short-term and long-term nutritional status in infants with CHD. Therefore, the meticulous and continuous evaluation and management of both growth and nutritional status should be considered in CHD patients with a high number of sensitized food allergens.

Effect of a low-protein diet supplemented with keto-acids on autophagy and inflammation in 5/6 nephrectomized rats.

Ketoacids (KA) are known to preserve muscle mass among patients with chronic kidney disease (CKD) on a low-protein diet (LPD). The present study was to compare the effects of KA supplemented diet therapy in autophagy and inflammation in CKD rats' skeletal muscle. Rats with 5/6 nephrectomy were randomly divided into three groups and fed with either 11 g/kg/day protein [normal-protein diet (NPD)], 3 g/kg/day protein (LPD) or 3 g/kg/day protein which including 5% protein plus 1% KA (LPD + KA) for 24 weeks. Sham-operated rats with NPD intake were used as control. LPD could improve body weight, gastrocnemius muscle mass, as well as gastrocnemius muscle cross-sectional area, with the effect being more obvious in the LPD + KA group. The autophagy marker LC3 (microtubule-associated protein 1 light chain 3), p62, Parkin and PTEN induced putative kinase 1 (PINK1) were significantly attenuate in LPD + KA group than LPD group. LPD + KA group had the lower total mtDNA (mitochondiral DNA) and cytosol mtDNA, NACHT-PYD-containing protein 3 (NALP3) inflammasome than LPD group, but its reactive oxygen species (ROS), caspase-1 and apoptosis-associated speck-like protein containing a CARD (ASC) level was higher. Immunoblotting showed IL-1ß (interleukin-1-beta) was lower in LPD and LPD + KA group than the NPD group, but IL-18 showed no significant difference among control and CKD group; toll-like receptor signalling-dependent IL-6 was higher in LPD + KA group than LPD group, but tumor necrosis factor-α (TNF-α) was not significantly changed between LPD + KA and LPD group. Systematic changes of the four cytokines were different from that of the tissue. Although LPD + KA could further ameliorate-activated autophagy than LPD, its effect on the activated inflammation state in CKD was not distinctly. Further study is still required to explore the method of ameliorating inflammation to provide new therapeutic approaches for CKD protein energy wasting (PEW).

Synthesis of gem-difluoromethylenated daidzein analogues and their inhibitory effect on U2OS cell cycle.

gem-Difluoromethylenated daidzein analogues 2 and 4 were obtained by the insertion reaction of difluorocarbene. A series of alkylated fluorine-containing daidzein analogues 3a-f and 5a-f were synthesized. All the compounds were tested for the inhibitory effect on U2OS cell cycle in vitro. The results showed that 7-octyloxy-3-(4-difluoromethoxyphenyl)-chromen-4-one 5d was the most active inhibitor.