Diagnostic value of carbohydrate antigen 50 in biliary tract cancer: A large-scale multicenter study.

BACKGROUND: To date, carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) have been widely used for the screening, diagnosis and prediction of biliary tract cancer (BTC) patients. However, few studies with large sample sizes of carbohydrate antigen 50 (CA50) were reported in BTC patients. METHODS: A total of 1121 patients from the Liver Cancer Clin-Bio Databank of Anhui Hepatobiliary Surgery Union between January 2017 and December 2022 were included in this study (673 in the training cohort and 448 in the validation cohort): among them, 458 with BTC, 178 with hepatocellular carcinoma (HCC), 23 with combined hepatocellular-cholangiocarcinoma, and 462 with nontumor patients. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were used to evaluate the diagnostic efficacy and clinical usefulness. RESULTS: ROC curves obtained by combining CA50, CA19-9, and AFP showed that the AUC value of the diagnostic MODEL 1 was 0.885 (95% CI 0.856-0.885, specificity 70.3%, and sensitivity 84.0%) in the training cohort and 0.879 (0.841-0.917, 76.7%, and 84.3%) in the validation cohort. In addition, comparing iCCA and HCC (235 in the training cohort, 157 in the validation cohort), the AUC values of the diagnostic MODEL 2 were 0.893 (95% CI 0.853-0.933, specificity 96%, and sensitivity 68.6%) in the training cohort and 0.872 (95% CI 0.818-0.927, 94.2%, and 64.6%) in the validation cohort. CONCLUSION: The model combining CA50, CA19-9, and AFP not only has good diagnostic value for BTC but also has good diagnostic value for distinguishing iCCA and HCC.

Tumour response following preoperative chemotherapy is affected by body mass index in patients with colorectal liver metastases.

BACKGROUND: Colorectal cancer is the third most prevalent malignancy globally and ranks second in cancer-related mortality, with the liver being the primary organ of metastasis. Preoperative chemotherapy is widely recommended for initially or potentially resectable colorectal liver metastases (CRLMs). Tumour pathological response serves as the most important and intuitive indicator for assessing the efficacy of chemotherapy. However, the postoperative pathological results reveal that a considerable number of patients exhibit a poor response to preoperative chemotherapy. Body mass index (BMI) is one of the factors affecting the tumorigenesis and progression of colorectal cancer as well as prognosis after various antitumour therapies. Several studies have indicated that overweight and obese patients with metastatic colorectal cancer experience worse prognoses than those with normal weight, particularly when receiving first-line chemotherapy regimens in combination with bevacizumab. AIM: To explore the predictive value of BMI regarding the pathologic response following preoperative chemotherapy for CRLMs. METHODS: A retrospective analysis was performed in 126 consecutive patients with CRLM who underwent hepatectomy following preoperative chemotherapy at four different hospitals from October 2019 to July 2023. Univariate and multivariate logistic regression models were applied to analyse potential predictors of tumour pathological response. The Kaplan-Meier method with log rank test was used to compare progression-free survival (PFS) between patients with high and low BMI. BMI < 24.0 kg/m2 was defined as low BMI, and tumour regression grade 1-2 was defined as complete tumour response. RESULTS: Low BMI was observed in 74 (58.7%) patients and complete tumour response was found in 27 (21.4%) patients. The rate of complete tumour response was significantly higher in patients with low BMI (29.7% vs 9.6%, P = 0.007). Multivariate analysis revealed that low BMI [odds ratio (OR) = 4.56, 95% confidence interval (CI): 1.42-14.63, P = 0.011], targeted therapy with bevacizumab (OR = 3.02, 95%CI: 1.10-8.33, P = 0.033), preoperative carcinoembryonic antigen level < 10 ng/mL (OR = 3.84, 95%CI: 1.19-12.44, P = 0.025) and severe sinusoidal dilatation (OR = 0.17, 95%CI: 0.03-0.90, P = 0.037) were independent predictive factors for complete tumour response. The low BMI group exhibited a significantly longer median PFS than the high BMI group (10.7 mo vs 4.7 mo, P = 0.011). CONCLUSION: In CRLM patients receiving preoperative chemotherapy, a low BMI may be associated with better tumour response and longer PFS.

Fermented calcium butyrate supplementation in post-peak laying hens improved ovarian function and tibia quality through the "gut-bone" axis.

The compromised egg quality and leg abnormality during the end of the laying cycle (after 40 weeks) have been leading to poor animal welfare and substantial economic losses. Therefore, the effects of fermented calcium (Ca) butyrate, produced by fermentation by Clostridium butyricum, on production, eggshell quality, and tibial property of hens were explored. A total of 192 Hy-line brown laying hens at 50-week-old were assigned to a basal diet or the basal diet with 300 mg/kg of the fermented Ca butyrate from 50 to 58 weeks of age. Each treatment had 6 replicates with 16 hens each. The diet supplemented with 300 mg/kg fermented Ca butyrate notably increased egg weight, ovarian follicle number, and eggshell strength (P = 0.072) as compared to the basal diet, which were associated with cytokine secretion, toll-like receptor signaling pathways, and intestinal immunity based on the RNA-seq data from the granulosa. Dietary Ca butyrate inclusion decreased the expression of ileal tumor necrosis factor-alpha and serum pro-inflammatory cytokine concentration, as well as increased the content of serum immunoglobulin A when compared to the basal diet (both P < 0.05). The birds that received fermented Ca butyrate diets exhibited higher villus height (P < 0.05) and upregulated expression of tight junction proteins, whereas it did not alter the composition of cecal microbiota (P > 0.05). In addition, the diet with fermented Ca butyrate reduced the number of osteoclasts in the proximal tibia and the level of C-terminal cross-linked telopeptide of type I collagen, a bone resorption marker (P < 0.05), whereas it tended to increase the concentration of the procollagen type I N-terminal propeptide that reflects bone formation marker in serum. Moreover, the layers fed fermented Ca butyrate diets possessed higher (P < 0.05) bone area and trabecular number of the proximal tibia, yield load, and ultimate load than those that consumed basal diets. Collectively, dietary fermented Ca butyrate supplementation in post-peak layer diets improved the ovarian function and tibia quality, which might be related to enhancing intestinal integrity and consequently decreasing inflammation mediated bone resorption.

Dietary cinnamaldehyde with carvacrol or thymol improves the egg quality and intestinal health independent of gut microbiota in post-peak laying hens.

Essential oils have been proven to exert multiple effects on growth performance, production quality, and health status in poultry nutrition, which is dependent on the component and/or dose of essential oils. Diets with the optimal combination of essential oils might be able to improve the performance traits and welfare of laying hens. Therefore, this study was conducted to evaluate the effects of dietary essential oils, which are composed of cinnamaldehyde with carvacrol or thymol, on performance, egg quality, and intestinal health in post-peak laying hens. A total of 384, 50-week-old Hy-line brown laying hens were randomly divided into three groups with 8 replicates of 16 birds each: (1) a basal diet (Ctrl), (2) a basal diet with 100 mg/kg of essential oils consisting of 4.5% cinnamaldehyde with 13.5% carvacrol (CAR+CIN), and (3) a basal diet containing 100 mg/kg of essential oils composed of 4.5% cinnamaldehyde with 13.5% thymol (THY+CIN). The CAR+CIN diet increased the feed consumption from 52 to 55 weeks more than the Ctrl and the THY+CIN diet. Compared with the Ctrl group, the addition of essential oils decreased the dirty egg rate (P = 0.07) in the whole trial period. Regarding egg quality, the birds that received the CAR+CIN and THY+CIN diets increased the eggshell strength (P = 0.099) or Haugh unit (HU, p = 0.03) at 54 weeks, respectively. Supplementation of both CAR+CIN and THY+CIN diets significantly increased the ratio of villus height to crypt depth in the duodenum through increasing villus height and decreasing crypt depth as well as upregulated the mRNA abundances of duodenal occluding and cadherin (P < 0.05). However, the treatment with dietary essential oils did not notably change the proportion of cecal microbiota and bacterial diversity. This study suggested that dietary supplementation of cinnamaldehyde with carvacrol or thymol, the active components of essential oils, could promote egg quality in post-peak laying hens, which might be associated with improved intestinal development and barrier.

Combination of Cinnamaldehyde with Carvacrol or Thymol Improves the Mechanical Properties of Tibia in Post-Peak Laying Hens.

Roles of plant-derived cinnamaldehyde, carvacrol, and thymol in the gut and bone health of laying hens was evaluated in the present study. After acclimation for 2 weeks, a total 384 of 52-week-old laying hens were allocated into three groups for 6 weeks: (1) basal diet group (Ctrl), (2) combination of cinnamaldehyde with carvacrol group (CAR+CIN), and (3) blend of cinnamaldehyde with thymol (THY+CIN). The dietary essential oil level was 100 mg/kg. Each treatment group had eight replicate pens (16 birds/pen). The stiffness and ultimate load of the tibiae from both the CAR+CIN and THY+CIN groups were higher than that of the Ctrl group (p < 0.05), along with comparable tibia ash, calcium, and phosphorus content among groups. At the same time, the manipulation of essential oils upregulated the transcription abundances of intestinal barrier proteins to varying degrees, whereas the experimental treatment failed to affect the composition in phyla of cecal microbiota. When compared to the Ctrl group, birds fed the CAR+CIN and THY+CIN diet displayed decreased bone resorption markers, reduced interleukin-1 concentrations, and increased transforming growth factor beta levels in serum. These findings suggest that cinnamaldehyde with carvacrol or thymol in feed of hens could enhance intestinal barrier and improve the mechanical properties of tibiae through structural modelling but not increase the mineral density, which might be involved in suppressing inflammation-mediated bone resorption.

Paris Saponin II induced apoptosis via activation of autophagy in human lung cancer cells.

Paris Saponin II (PSII) has been shown anticancer activity against several cancer lines through the pro-apoptotic pathway. The aim of the study was to investigate the relationship between apoptosis and autophagy taking part in the anti-cancer mechanisms of PSII. In this study, PSII induced autophagy and apoptosis in dose- and time-dependent manners. Meanwhile, it induced autophagy as early as 2 h after exposure to 1 µM of PSII accompanying with apoptosis. Blockade of autophagy with chloroquine (CQ) attenuated apoptosis, while regulation of reactive oxygen species (ROS) by N-acetyl cysteine (NAC), gallic acid (GA) and H2O2 could not influence autophagy. In addition, PSII induced apoptosis via activation of autophagy, which might be associated with the activation of JNK and inhibition of PI3K/AKT/mTOR pathway. All in all, our research increased the understanding of the role of PSII regulating autophagy and apoptosis, which would hopefully provide prospective strategies for cancer therapy.