Background/Aims: Distal mean nocturnal baseline impedance (MNBI) measuring via pH-impedance may be valuable in diagnosing patients with suspected laryngopharyngeal reflux (LPR). However, its wide adoption is hindered by cost and invasiveness. This study investigates whether baseline impedance measured during high-resolution impedance manometry (HRIM-BI) can predict pathological MNBI. Methods: A cross-sectional study in Taiwan included 74 subjects suspected of LPR, who underwent HRIM (MMS) and pH-impedance testing (Diversatek), after stopping proton pump inhibitors for more than 7 days. Subjects with grade C or D esophagitis or Barrett’s esophagus were excluded. The cohort was divided into 2 groups: those with concomitant typical reflux symptoms (CTRS, n = 28) and those with isolated LPR symptoms (ILPRS, n = 46). HRIM-BI measurements focused on both distal and proximal esophagi. Pathological MNBI was identified as values below 2065 Ω, measured 3 cm above the lower esophageal sphincter. Results: In all subjects, distal HRIM-BI values correlated weakly with distal MNBI(r = 0.34-0.39, P < 0.005). However, in patients with ILPRS, distal HRIM-BI corelated moderately with distal MNBI(r = 0.43-0.48, P < 0.005). The areas under the receiver operating characteristic curve was 0.78 (P = 0.001) with a sensitivity of 0.83 and a specificity of 0.68. No correlation exists between distal HRIM-BI and distal MNBI in patients with CTRS, and between proximal HRIM-BI and proximal MNBI in both groups. Conclusions Distal HRIM-BI from HRIM may potentially predict pathological MNBI in patients with ILPRS, but not in those with CTRS. Future outcome studies linked to the metric are warranted.

Background/Aims: Distal mean nocturnal baseline impedance (MNBI) measuring via pH-impedance may be valuable in diagnosing patients with suspected laryngopharyngeal reflux (LPR). However, its wide adoption is hindered by cost and invasiveness. This study investigates whether baseline impedance measured during high-resolution impedance manometry (HRIM-BI) can predict pathological MNBI. Methods: A cross-sectional study in Taiwan included 74 subjects suspected of LPR, who underwent HRIM (MMS) and pH-impedance testing (Diversatek), after stopping proton pump inhibitors for more than 7 days. Subjects with grade C or D esophagitis or Barrett’s esophagus were excluded. The cohort was divided into 2 groups: those with concomitant typical reflux symptoms (CTRS, n = 28) and those with isolated LPR symptoms (ILPRS, n = 46). HRIM-BI measurements focused on both distal and proximal esophagi. Pathological MNBI was identified as values below 2065 Ω, measured 3 cm above the lower esophageal sphincter. Results: In all subjects, distal HRIM-BI values correlated weakly with distal MNBI(r = 0.34-0.39, P < 0.005). However, in patients with ILPRS, distal HRIM-BI corelated moderately with distal MNBI(r = 0.43-0.48, P < 0.005). The areas under the receiver operating characteristic curve was 0.78 (P = 0.001) with a sensitivity of 0.83 and a specificity of 0.68. No correlation exists between distal HRIM-BI and distal MNBI in patients with CTRS, and between proximal HRIM-BI and proximal MNBI in both groups. Conclusions Distal HRIM-BI from HRIM may potentially predict pathological MNBI in patients with ILPRS, but not in those with CTRS. Future outcome studies linked to the metric are warranted.

Background/Aims: Distal mean nocturnal baseline impedance (MNBI) measuring via pH-impedance may be valuable in diagnosing patients with suspected laryngopharyngeal reflux (LPR). However, its wide adoption is hindered by cost and invasiveness. This study investigates whether baseline impedance measured during high-resolution impedance manometry (HRIM-BI) can predict pathological MNBI. Methods: A cross-sectional study in Taiwan included 74 subjects suspected of LPR, who underwent HRIM (MMS) and pH-impedance testing (Diversatek), after stopping proton pump inhibitors for more than 7 days. Subjects with grade C or D esophagitis or Barrett’s esophagus were excluded. The cohort was divided into 2 groups: those with concomitant typical reflux symptoms (CTRS, n = 28) and those with isolated LPR symptoms (ILPRS, n = 46). HRIM-BI measurements focused on both distal and proximal esophagi. Pathological MNBI was identified as values below 2065 Ω, measured 3 cm above the lower esophageal sphincter. Results: In all subjects, distal HRIM-BI values correlated weakly with distal MNBI(r = 0.34-0.39, P < 0.005). However, in patients with ILPRS, distal HRIM-BI corelated moderately with distal MNBI(r = 0.43-0.48, P < 0.005). The areas under the receiver operating characteristic curve was 0.78 (P = 0.001) with a sensitivity of 0.83 and a specificity of 0.68. No correlation exists between distal HRIM-BI and distal MNBI in patients with CTRS, and between proximal HRIM-BI and proximal MNBI in both groups. Conclusions Distal HRIM-BI from HRIM may potentially predict pathological MNBI in patients with ILPRS, but not in those with CTRS. Future outcome studies linked to the metric are warranted.

The aim of this study is to investigate whether β-hydroxybutyrate(BHB)impaired the mitochondrial function of dairy cow monocytes through the peroxisome proliferator-activated re-ceptor γ coactivator 1 alpha(PGC-1α)signaling pathway.According to the clinical symptoms and the concentration of BHB in whole blood,the tail vein blood of 12 healthy cows(BHB＜1.2 mmol/L)and 12 clinical ketotic cows(CK,BHB＞3.0 mmol/L)was collected.In vivo,after isolation and purification of CD14+monocytes,the intracellular mitochondrial membrane potential was detected by flow cytometry.The protein abundance of oxidative phosphorylation complex cytochrome c oxi-dase subunit Ⅰ(CO Ⅰ),CO Ⅱ,CO Ⅲ,COⅣ,CO Ⅴ,PGC-1 α,mitochondrial transcription factor A(TFAM)and nuclear respiratory factor 1(NFR1)were determined by Western blot.In vitro,CD14+monocytes were co-cultured with 3.0 mmol/L BHB for 0,6,12,24 h.Flow cytometry was applied for intracellular mitochondrial membrane potential detection,and determination the protein abundance of PGC-1α,TFAM and NFR1 by Western blot.The results showed that compared with control group,the mitochondrial membrane potential in CD14+monocytes of ketotic cows was sig-nificantly increased,and the protein abundance of CO Ⅰ,CO Ⅱ,CO Ⅲ,CO Ⅳ,CO Ⅴ PGC-1α,TFAM,and NRF1 in CD14+monocytes of ketotic cows were significantly decreased.Compared with 0 h,the mitochondrial membrane potential of CD14+monocytes was significantly increased after BHB treatment for 6,12,24 h,and the protein abundance of PGC-1α,TFAM and NRF1 were significantly decreased.The results indicated that BHB induced mitochondrial dysfunction in CD14+monocytes of ketotic cows by inhibiting PGC-1α signaling pathway.Therefore,the PGC-1αsignaling pathway may be a preventive and therapeutic target to the mitochondrial dysfunction of monocytes in ketotic cows caused by BHB.

The aim of this study was to investigate whether β-hydroxybutyric acid(BHB)inhibits the phagocytic function of CD14+monocytes in dairy cows through the ROS(reactive oxygen spe-cies)-NLRP3(NOD-like receptor thermal protein domain associated protein 3)pathway.CD14+monocytes in the blood of postpartum healthy cows were extracted,and 3 mmol/L BHB was added after transfection of small interfering RNA targeting NLRP3(si-NLRP3).Monocytes were pre-treated with 10 nmol/L NLRP3 inhibitor MCC950(CP-456773)or 10 mmol/L ROS scavenger N-acetyl cysteine(NAC),and then was treated with 3 mmol/L BHB for 24 h.The protein abundance of NLRP3 was detected by Western blot and the phagocytosis of monocytes was determined by flow cytometry and immunofluorescence.The results showed that compared with the si-Control+BHB group,the phagocytic function of monocytes in the si-NLRP3+BHB treatment group was significantly increased,while the protein abundance of NLRP3 was significantly decreased.Com-pared with DMSO+BHB group,the phagocytic function of monocytes in MCC950+BHB group was significantly increased.In addition,compared with DMSO+BHB group,the protein abundance of NLRP3 in monocytes was significantly decreased in MCC950+BHB group.Compared with the PBS+BHB group,the phagocytosis of monocytes was significantly increased after the addition of ROS scavenger NAC,while the protein abundance of NLRP3 was significantly decreased.These results indicated that BHB inhibited the phagocytosis of CD14+monocytes in cows via the ROS-NLRP3 pathway.Therefore,regulating the activation of NLRP3 inflammasome may be an effective method to improve the decrease of monocyte phagocytosis in perinatal dairy cows.

The aim of this study is to investigate whether β-hydroxybutyrate(BHB)impaired the mitochondrial function of dairy cow monocytes through the peroxisome proliferator-activated re-ceptor γ coactivator 1 alpha(PGC-1α)signaling pathway.According to the clinical symptoms and the concentration of BHB in whole blood,the tail vein blood of 12 healthy cows(BHB＜1.2 mmol/L)and 12 clinical ketotic cows(CK,BHB＞3.0 mmol/L)was collected.In vivo,after isolation and purification of CD14+monocytes,the intracellular mitochondrial membrane potential was detected by flow cytometry.The protein abundance of oxidative phosphorylation complex cytochrome c oxi-dase subunit Ⅰ(CO Ⅰ),CO Ⅱ,CO Ⅲ,COⅣ,CO Ⅴ,PGC-1 α,mitochondrial transcription factor A(TFAM)and nuclear respiratory factor 1(NFR1)were determined by Western blot.In vitro,CD14+monocytes were co-cultured with 3.0 mmol/L BHB for 0,6,12,24 h.Flow cytometry was applied for intracellular mitochondrial membrane potential detection,and determination the protein abundance of PGC-1α,TFAM and NFR1 by Western blot.The results showed that compared with control group,the mitochondrial membrane potential in CD14+monocytes of ketotic cows was sig-nificantly increased,and the protein abundance of CO Ⅰ,CO Ⅱ,CO Ⅲ,CO Ⅳ,CO Ⅴ PGC-1α,TFAM,and NRF1 in CD14+monocytes of ketotic cows were significantly decreased.Compared with 0 h,the mitochondrial membrane potential of CD14+monocytes was significantly increased after BHB treatment for 6,12,24 h,and the protein abundance of PGC-1α,TFAM and NRF1 were significantly decreased.The results indicated that BHB induced mitochondrial dysfunction in CD14+monocytes of ketotic cows by inhibiting PGC-1α signaling pathway.Therefore,the PGC-1αsignaling pathway may be a preventive and therapeutic target to the mitochondrial dysfunction of monocytes in ketotic cows caused by BHB.

The aim of this study was to investigate whether β-hydroxybutyric acid(BHB)inhibits the phagocytic function of CD14+monocytes in dairy cows through the ROS(reactive oxygen spe-cies)-NLRP3(NOD-like receptor thermal protein domain associated protein 3)pathway.CD14+monocytes in the blood of postpartum healthy cows were extracted,and 3 mmol/L BHB was added after transfection of small interfering RNA targeting NLRP3(si-NLRP3).Monocytes were pre-treated with 10 nmol/L NLRP3 inhibitor MCC950(CP-456773)or 10 mmol/L ROS scavenger N-acetyl cysteine(NAC),and then was treated with 3 mmol/L BHB for 24 h.The protein abundance of NLRP3 was detected by Western blot and the phagocytosis of monocytes was determined by flow cytometry and immunofluorescence.The results showed that compared with the si-Control+BHB group,the phagocytic function of monocytes in the si-NLRP3+BHB treatment group was significantly increased,while the protein abundance of NLRP3 was significantly decreased.Com-pared with DMSO+BHB group,the phagocytic function of monocytes in MCC950+BHB group was significantly increased.In addition,compared with DMSO+BHB group,the protein abundance of NLRP3 in monocytes was significantly decreased in MCC950+BHB group.Compared with the PBS+BHB group,the phagocytosis of monocytes was significantly increased after the addition of ROS scavenger NAC,while the protein abundance of NLRP3 was significantly decreased.These results indicated that BHB inhibited the phagocytosis of CD14+monocytes in cows via the ROS-NLRP3 pathway.Therefore,regulating the activation of NLRP3 inflammasome may be an effective method to improve the decrease of monocyte phagocytosis in perinatal dairy cows.

Objective: We aimed to investigate whether 2-[ 18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (2-[ 18F]FDG PET/CT) can aid in evaluating the risk of malignancy in ampullary tumors detected by endoscopy. Materials and Methods: This single-center retrospective cohort study analyzed 155 patients (79 male, 76 female; mean age, 65.7 ± 12.7 years) receiving 2-[ 18F]FDG PET/CT for endoscopy-detected ampullary tumors 5–87 days (median, 7 days) after the diagnostic endoscopy between June 2007 and December 2020. The final diagnosis was made based on histopathological findings. The PET imaging parameters were compared with clinical data and endoscopic features. A model to predict the risk of malignancy, based on PET, endoscopy, and clinical findings, was generated and validated using multivariable logistic regression analysis and an additional bootstrapping method. The final model was compared with standard endoscopy for the diagnosis of ampullary cancer using the DeLong test. Results: The mean tumor size was 17.1 ± 7.7 mm. Sixty-four (41.3%) tumors were benign, and 91 (58.7%) were malignant. Univariable analysis found that ampullary neoplasms with a blood-pool corrected peak standardized uptake value in earlyphase scan (SUVe) ≥ 1.7 were more likely to be malignant (odds ratio [OR], 16.06; 95% confidence interval [CI], 7.13–36.18;P < 0.001). Multivariable analysis identified the presence of jaundice (adjusted OR [aOR], 4.89; 95% CI, 1.80–13.33; P = 0.002), malignant traits in endoscopy (aOR, 6.80; 95% CI, 2.41–19.20; P < 0.001), SUVe ≥ 1.7 in PET (aOR, 5.43; 95% CI, 2.00–14.72; P < 0.001), and PET-detected nodal disease (aOR, 5.03; 95% CI, 1.16–21.86; P = 0.041) as independent predictors of malignancy. The model combining these four factors predicted ampullary cancers better than endoscopic diagnosis alone (area under the curve [AUC] and 95% CI: 0.925 [0.874–0.956] vs. 0.815 [0.732–0.873], P < 0.001). The model demonstrated an AUC of 0.921 (95% CI, 0.816–0.967) in candidates for endoscopic papillectomy. Conclusion Adding 2-[ 18F]FDG PET/CT to endoscopy can improve the diagnosis of ampullary cancer and may help refine therapeutic decision-making, particularly when contemplating endoscopic papillectomy.

Purpose: Numerous studies have produced conflicting findings regarding the efficacy of statins in prostate cancer treatment. Our objective was to examine the correlation between statin usage and clinical outcomes in Taiwanese men with de novo metastatic prostate cancer. Materials and Methods: We identified patients diagnosed with de novo metastatic prostate cancer from the Chang Gung Research Database spanning the years 2007 to 2020. To minimize confounding bias, we employed the inverse probability of treatment weighting (IPTW) method. Clinical outcomes were assessed using IPTW-adjusted Kaplan-Meier curves. Multivariate Cox proportional hazard regression analysis was utilized to evaluate the association between mortality and clinical factors. Results: The study cohort comprised 1,716 statin users and 276 non-users. Patients who used statins exhibited a longer median overall survival (85.4 months compared to 58.2 months; p=0.001) and cancer-specific survival (112.6 months compared to 75.7 months; p<0.001) compared to non-users. The median time to the development of castration-resistant status was similar between statin users and non-users (p=0.069). Multivariable Cox proportional hazards regression analysis, after IPTW adjustment, demonstrated that statin use was associated with improved overall survival. Conclusions Our study indicates that the use of statins following a de novo metastatic prostate cancer diagnosis enhances survival outcomes. However, statins did not appear to delay the onset of castration-resistant status. Further large-scale and long-term studies are warranted to investigate the biological effects of statins in men with prostate cancer.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.