1.Exploring Mechanism of Anti-atherosclerosis Effect of Huangqi Chifengtang Based on AMPK/PPARα Signaling Pathway and NLRP3 Inflammasome
Yuqin LIANG ; Jie LIU ; Chi ZHANG ; Pingping CHEN ; Fang LU ; Shumin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):131-139
ObjectiveTo explore the improving effect of Huangqi Chifengtang(HCT) on atherosclerosis(AS), and elucidate its mechanism in relation to adenosine monophosphate-activated protein kinase(AMPK)/peroxisome proliferator-activated receptor α(PPARα) signaling pathway and nucleotide-binding oligomerization domain(NOD)-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome. MethodsEight C57BL/6J mice were set as the normal group, and 32 ApoE-/- mice were randomly divided into the model group, the positive drug group(atorvastatin, 5 mg·kg-1·d-1), HCT low- and high-dose groups(1.95, 3.90 g·kg-1·d-1). ApoE-/- mice were fed with high-fat and high-cholesterol feed to establish an AS mouse model. After modeling, they were orally administered corresponding dose of drugs for 28 days, while the normal and model groups received an equal volume of physiological saline via oral gavage. Hematoxylin-eosin(HE) staining was used to observe the pathological status of the aorta and liver in mice, Biochemical testing and enzyme-linked immunosorbent assay(ELISA) were used to detect the levels of total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), alanine aminotransferase(ALT), aspartate aminotransferase(AST), C-reactive protein(CRP), interleukin(IL)-1β, IL-18 in the serum, as well as superoxide dismutase(SOD), malondialdehyde(MDA), and reduced glutathione(GSH) in the liver. Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) was used to measure the mRNA expression levels of NLRP3, apoptosis-associated speck-like protein(ASC), cysteinyl aspartate specific proteinase-1(Caspase-1), Toll-like receptor 4(TLR4) in the aorta, and fatty acid synthase(FAS), stearoyl-CoA desaturase 1(SCD1), PPARα, and carnitine palmitoyltransferase 1A(CPT1A) in the liver. Immunohistochemistry was used to determine the protein expressions of NLRP3, Caspase-1, and ASC in the aorta, and Western blot was used to measure the protein expressions of AMPK, p-AMPK, sterol regulatory element binding protein-1c(SREBP-1c), CPT1A, and FAS in the liver. ResultsCompared with the normal group, the model group showed a significant increase in lipid plaque deposition in the aorta and lipid accumulation in the liver, the levels of TC, TG, LDL-C, AST, ALT, IL-1β, IL-18 and CRP in the serum were significantly increased(P<0.01), and the mRNA and protein expressions of aortic TLR4, NLRP3, Caspase-1 and ASC were significantly upregulated(P<0.01). The levels of SOD and GSH in the liver were significantly reduced, while the level of MDA was significantly increased(P<0.01). The mRNA expressions of FAS and SCD1 in the liver were significantly downregulated, while the mRNA expressions of PPARα and CPT1A were significantly upregulated. The protein expressions of p-AMPK/AMPK and CPT1A in the liver were significantly reduced, while the expressions of SREBP-1c and FAS proteins were significantly increased(P<0.01). Compared with the model group, the low- and high-dose HCT groups showed significant improvements in aortic plaques and hepatic lipid deposition. The levels of TC, LDL-C, AST, IL-1β and IL-18 in the serum of the low-dose HCT group, as well as TC, TG, LDL-C, AST, ALT, IL-1β, IL-18 and CRP in the serum of the high-dose HCT group, were significantly reduced(P<0.01). The mRNA expressions of TLR4, NLRP3 and Caspase-1 in the aorta of the low-dose HCT group, as well as TLR4, NLRP3, Caspase-1 and ASC in the aorta of the high-dose HCT group, were significantly downregulated(P<0.01). The protein expressions of Caspase-1 and ASC in the aorta of the low-dose HCT group, as well as NLRP3, Caspase-1 and ASC in the high-dose HCT group, were significantly downregulated(P<0.01). The levels of SOD and GSH in the liver of the low- and high-dose HCT groups were significantly increased, while the level of MDA in the high-dose HCT group was significantly decreased(P<0.05, P<0.01). In the HCT-treated group, the mRNA expressions of FAS and SCD1 in the liver were significantly upregulated, while the mRNA expressions of PPARα and CPT1A were significantly downregulated, the protein expressions of p-AMPK/AMPK and CPT1A in the liver were significantly increased, while the protein expressions of SREBP-1c and FAS were significantly decreased(P<0.05, P<0.01). ConclusionHCT can improve lipid metabolism by activating the AMPK/PPARα pathway and inhibit NLRP3 inflammasome-mediated inflammatory responses, thereby reducing hepatic lipid deposition and AS plaque formation.
2.Effect of Jianpi Qinghua Granules on Blood Glucose Fluctuations and Skeletal Muscle Mass and Function in Newly Diagnosed Overweight/Obese Type 2 Diabetes Patients with Qi-Yin Deficiency Syndrome
Yuan CHEN ; Qiuyue GUO ; Yanyan XIAO ; Hao LU ; Chi CHEN ; Junfei XU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):218-224
ObjectiveTo investigate the effects of Jianpi Qinghua granules on blood glucose fluctuations in patients with newly diagnosed overweight/obese type 2 diabetes mellitus (T2DM) and Qi-Yin deficiency syndrome from the perspective of skeletal muscle mass and function, while providing new insights for the treatment of diabetes. MethodsThis study employed a randomized, double-blind, placebo-controlled design. A total of 110 newly diagnosed overweight/obese T2DM patients meeting the inclusion criteria were randomly assigned to either the traditional Chinese medicine (TCM) group (54 cases) or the control group (56 cases). Patients in the TCM group received Jianpi Qinghua Granules, while those in the control group received a placebo. Both groups underwent dietary and exercise guidance. After 12 weeks of intervention, blood glucose fluctuations were assessed using the following parameters: time in the target blood glucose range (TIR), mean daily blood glucose (MBG), standard deviation of mean daily blood glucose (SDBG), mean amplitude of glycemic excursions (MAGE), coefficient of variation of blood glucose (CV), glycated hemoglobin (HbA1c) achievement rate, fasting plasma glucose (FPG), and 2 hour postprandial glucose (2 hPG). Skeletal muscle mass was measured by dual-energy X-ray absorptiometry (DXA), while skeletal muscle function was evaluated using a handheld dynamometer for distal muscle strength and a 5-time sit-to-stand test for lower limb function. Additionally, pancreatic islet function and TCM syndrome scores were analyzed. ResultsNo significant differences were observed in baseline data between the two groups before intervention, ensuring comparability. After treatment, compared to the control group, the TCM group showed a significant increase in TIR (P<0.01). While the SDBG and CV decreased, and MBG and MAGE increased in the TCM group, these differences were not statistically significant. Notably, the TCM group exhibited significant reductions in 2 hPG (P<0.01) and HbA1c (P<0.05), though the decrease in FPG was not statistically significant. The HbA1c achievement rate in the TCM group was significantly higher than that in the control group (χ2=45.498, P<0.01). In terms of skeletal muscle mass and function, the TCM group demonstrated a significant increase in handgrip strength (P<0.01) and a significant reduction in the 5-time sit-to-stand duration (P<0.05). However, although body fat percentage increased, leading to a decrease in skeletal muscle mass and the ratio of skeletal muscle to fat, these changes were not statistically significant. For pancreatic islet function, the TCM group showed significant reductions in fasting insulin (FINS) and homeostasis model assessment of insulin resistance (HOMA-IR) (P<0.01). Additionally, the TCM syndrome score in the TCM group was significantly reduced (P<0.01). ConclusionJianpi Qinghua granules may reduce blood glucose fluctuations in newly diagnosed overweight/obese T2DM patients with Qi-Yin deficiency syndrome by enhancing skeletal muscle function, improving pancreatic islet function, and ameliorating related TCM syndromes.
3.Molecular Characterization Network of Dampness-heat Syndrome in Patients with Chronic Hepatitis B Complicated by Glucose Metabolism Disorder Based on Shadowless Scleral Imaging and Metabolomics Technology
Caiying HE ; Hang ZHOU ; Yanqi CHI ; Baixue LI ; Liang HUANG ; Zhu CHEN ; Dafeng LIU ; Dong WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(14):271-285
ObjectiveThis paper aims to conduct the feature analysis and correlation analysis on the ocular collateral features and differential metabolites in patients with chronic hepatitis B (CHB) complicated by glucose metabolism disorder (GMD),particularly those with the damp-heat syndrome type,by integrating shadowless scleral imaging and metabolomics technologies. MethodsA total of 313 patients were recruited from the Hepatology and Endocrinology Outpatient Departments of Public Health Clinical Center of Chengdu according to the inclusion/exclusion criteria,and they were divided into a CHB group and a CHB complicated by GMD groups (damp-heat syndrome group and non-damp-heat syndrome group). All patients underwent high-definition ocular image acquisition and feature extraction using an intelligent analysis system for shadowless scleral imaging to analyze the differences in the counting of morphological feature scores of ocular collaterals among groups. By using a digital sampling method,24 patients from each group were randomly selected,along with 20 healthy volunteers,for untargeted metabolomic analysis of peripheral serum. Differential metabolites were identified,statistically analyzed,and subjected to potential biomarker analysis and pathway enrichment. Spearman method was performed to conduct the correlation analysis on the differential ocular collateral features and differential metabolites,followed by correlation network construction. ResultsCompared with those in the CHB group,patients with CHB complicated by GMD showed significant changes in ocular collateral feature scores such as "hillock","blood vessels",and "pale dusky coloration" (P<0.05). In comparison with those in the healthy group,metabolites including N-acetylglucosamine,acetylhomoserine,and myo-inositol (AUC>0.7) were identified as potential biomarkers for the disease. Compared with those in the CHB complicated by GMD group with non-damp-heat syndrome,patients with damp-heat syndrome exhibited significant changes in feature scores of "plaques","yellow coloration","spleen",and "gallbladder" (P<0.05). In comparison with those in the healthy group,metabolites such as O2′-4a-cyclic tetrahydrobiopterin,theobromine,xanthurenic acid,and L-glutamic acid 5-phosphate (AUC>0.7) were identified as potential biomarkers for the damp-heat syndrome type. The Spearman correlation analysis reveals weak to moderate linear correlations between the differential scleral collateral features and metabolites. By constructing a "disease-syndrome" network of ocular diagnosis and metabolites,"xanthurenic acid-gallbladder" and "theobromine-plaque/yellow coloration" were identified as specific molecular-phenotypic correlated biomarker clusters for CHB complicated by GMD with dampness-heat syndrome. ConclusionPatients with CHB complicated by GMD demonstrate differential ocular diagnostic features and serum metabolites corresponding to disease states and dampness-heat syndrome. These objective biomarkers can guide both clinical syndrome differentiation and medication. The macro-micro integration based on ocular feature clusters and potential metabolic biomarkers offers an innovative approach to a combined traditional Chinese and Western medicine diagnosis and treatment model for this disease.
4.Value of different noninvasive diagnostic models in the diagnosis of esophageal and gastric varices with significant portal hypertension in compensated hepatitis B cirrhosis
Cheng LIU ; Jiayi ZENG ; Mengbing FANG ; Zhiheng CHEN ; Bei GUI ; Fengming ZHAO ; Jingkai YUAN ; Chaozhen ZHANG ; Meijie SHI ; Yubao XIE ; Xiaoling CHI ; Huanming XIAO
Journal of Clinical Hepatology 2025;41(2):263-268
ObjectiveTo investigate the value of different noninvasive diagnostic models in the diagnosis of esophageal and gastric varices since there is a high risk of esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension, and to provide a basis for the early diagnosis of esophageal and gastric varices. MethodsA total of 108 patients with significant portal hypertension due to compensated hepatitis B cirrhosis who attended Guangdong Provincial Hospital of Traditional Chinese Medicine from November 2017 to November 2023 were enrolled, and according to the presence or absence of esophageal and gastric varices under gastroscopy, they were divided into esophageal and gastric varices group (GOV group) and non-esophageal and gastric varices group (NGOV group). Related data were collected, including age, sex, imaging findings, and laboratory markers. The chi-square test was used for comparison of categorical data between groups; the least significant difference t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. The receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of five scoring models, i.e., fibrosis-4 (FIB-4), LOK index, LPRI, aspartate aminotransferase-to-platelet ratio index (APRI), and aspartate aminotransferase/alanine aminotransferase ratio (AAR). The binary logistic regression method was used to establish a combined model, and the area under the ROC curve (AUC) was compared between the combined model and each scoring model used alone. The Delong test was used to compare the AUC value between any two noninvasive diagnostic models. ResultsThere were 55 patients in the GOV group and 53 patients in the NGOV group. Compared with the NGOV group, the GOV group had a significantly higher age (52.64±1.44 years vs 47.96±1.68 years, t=0.453, P<0.05) and significantly lower levels of alanine aminotransferase [42.00 (24.00 — 17.00) U/L vs 82.00 (46.00 — 271.00) U/L, Z=-3.065, P<0.05], aspartate aminotransferase [44.00 (32.00 — 96.00) U/L vs 62.00 (42.50 — 154.50) U/L,Z=-2.351, P<0.05], and platelet count [100.00 (69.00 — 120.00)×109/L vs 119.00 (108.50 — 140.50)×109/L, Z=-3.667, P<0.05]. The ROC curve analysis showed that FIB-4, LOK index, LPRI, and AAR used alone had an accuracy of 0.667, 0.681, 0.730, and 0.639, respectively, in the diagnosis of esophageal and gastric varices (all P<0.05), and the positive diagnostic rates of GOV were 69.97%, 65.28%, 67.33%, and 58.86%, respectively, with no significant differences in AUC values (all P>0.05), while APRI used alone had no diagnostic value (P>0.05). A combined model (LAF) was established based on the binary logistic regression analysis and had an AUC of 0.805 and a positive diagnostic rate of GOV of 75.80%, with a significantly higher AUC than FIB-4, LOK index, LPRI, and AAR used alone (Z=-2.773,-2.479,-2.206, and-2.672, all P<0.05). ConclusionFIB-4, LOK index, LPRI, and AAR have a similar diagnostic value for esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension, and APRI alone has no diagnostic value. The combined model LAF had the best diagnostic efficacy, which provides a certain reference for clinical promotion and application.
5.Effect of Serum Containing Zhenwutang on Apoptosis of Myocardial Mast Cells and Mitochondrial Autophagy
Wei TANG ; Meiqun ZHENG ; Xiaolin WANG ; Zhiyong CHEN ; Chi CHE ; Zongqiong LU ; Jiashuai GUO ; Xiaomei ZOU ; Lili XU ; Lin LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):11-21
ObjectiveTo explore the effect of serum containing Zhenwutang on myocardial mast cell apoptosis induced by angiotensin Ⅱ (AngⅡ) and the mechanism of the correlation between apoptosis and mitochondrial autophagy. MethodsIn this experiment, AngⅡ and serum containing Zhenwutang with different concentrations were used to interfere with H9C2 cardiomyocytes for 24 h, and the survival rate of H9C2 cardiomyocytes was detected by cell counting kit-8 (CCK-8) to screen the optimal concentration for the experiment. Enzyme-linked immunosorbent assay (ELISA) was used to detect the content of B-type natriuretic peptide (BNP) in cell culture supernatant, and immunofluorescence was used to detect the cell surface area to verify the construction of the myocardial mast cell model. Subsequently, the experiment was divided into a blank group (20% blank serum), a model group (20% blank serum + 5×10-5 mol·L-1 AngⅡ), low-, medium-, and high-dose (5%, 10% and 20%) serum containing Zhenwutang groups, an autophagy inhibitor group (1×10-4 mol·L-1 3-MA), and autophagy inducer group (1×10-7 mol·L-1 rapamycin). The apoptosis level of H9C2 cells and the changes of mitochondrial membrane potential were detected by flow cytometry. The lysosomal probe (Lyso Tracker) and mitochondrial probe (Mito Tracker) co-localization was employed to detect autophagy. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect Caspase-3, Caspase-9, B-cell lymphoma 2 (Bcl-2), Bcl-2-related X protein (Bax), and cytochrome C (Cyt C) in apoptosis-related pathways and the relative mRNA expression of ubiquitin ligase (Parkin), phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1), and p62 protein in mitochondrial autophagy-related pathways. Western blot was used to detect cleaved Caspase-3, cleaved Caspase-9, Bax, Bcl-2, and Cyt C in apoptosis-related pathways, phosphorylated ubiquitin ligase (p-Parkin), phosphorylated PTEN-induced kinase 1 (p-PINK1), p62, and Bcl-2 homology domain protein Beclin1 in mitochondrial autophagy-related pathways, and the change of microtubule-associated protein 1 light chain 3 (LC3) Ⅱ/Ⅰ ratio. ResultsCCK-8 showed that when the concentration of AngⅡ was 5×10-5 mol·L-1, the cell activity was the lowest, and there was no cytotoxicity. At this concentration, the surface area of cardiomyocytes was significantly increased (P<0.01), and the content of BNP in the supernatant of culture medium was significantly increased (P<0.05). Therefore, AngⅡ with a concentration of 5×10-5 mol·L-1 was selected for the subsequent modeling of myocardial mast cells. Compared with the blank group, the model group and the autophagy inhibitor 3-MA group had a significantly increased apoptosis rate (P<0.01) and significantly decreased mitochondrial membrane potential (P<0.01). The results of immunofluorescence co-localization showed that compared with the blank group, the model group had a significantly decreased number of red and green fluorescence spots. The results of Real-time PCR showed that compared with that in the blank group, the relative mRNA expression of Bax, Caspase-3, Caspase-9, Cyt C, and p62 in the model group was significantly up-regulated (P<0.01), while the relative mRNA expression of Bcl-2, Parkin, and PINK1 was significantly down-regulated (P<0.01). In addition, the relative protein expression of Bax, cleaved Caspase-3, cleaved Caspase-9, Cyt C, and p62 was significantly up-regulated (P<0.01). The LC3Ⅱ/Ⅰ was significantly decreased, and the relative protein expression of Bcl-2, p-Parkin, p-PINK1, and Beclin1 was significantly down-regulated (P<0.01). Compared with the model group, the serum containing Zhenwutang groups and the autophagy inducer group had significantly decreased apoptosis rate (P<0.01), and the decrease ratio of mitochondrial membrane potential is significantly lowered (P<0.01) in a dose-dependent manner. Additionally, both red and green fluorescence spots became more in these groups. In the 3-MA group, the number of red and green fluorescence spots decreased significantly. The relative mRNA expression of Bax, Caspase-3, Caspase-9, Cyt C, and p62 was significantly down-regulated (P<0.05, P<0.01), while that of Bcl-2, Parkin, and PINK1 was significantly up-regulated (P<0.01). In the serum containing Zhenwutang groups, the relative protein expression levels of Bax, cleaved Caspase-3, cleaved Caspase-9, Cyt C, and p62 were significantly down-regulated (P<0.05,P<0.01). The LC3Ⅱ/Ⅰ was significantly increased, and the relative protein expression levels of Bcl-2, p-Parkin, p-PINK1, and Beclin1 were significantly up-regulated (P<0.01). ConclusionThe serum containing Zhenwutang can reduce the apoptosis of myocardial mast cells and increase mitochondrial autophagy. This is related to the inhibition of intracellular Bax/Bcl-2/Caspase-3 apoptosis pathway and regulation of Parkin/PINK1 mitochondrial autophagy pathway.
6.Predicting Clinically Significant Prostate Cancer Using Urine Metabolomics via Liquid Chromatography Mass Spectrometry
Chung-Hsin CHEN ; Hsiang-Po HUANG ; Kai-Hsiung CHANG ; Ming-Shyue LEE ; Cheng-Fan LEE ; Chih-Yu LIN ; Yuan Chi LIN ; William J. HUANG ; Chun-Hou LIAO ; Chih-Chin YU ; Shiu-Dong CHUNG ; Yao-Chou TSAI ; Chia-Chang WU ; Chen-Hsun HO ; Pei-Wen HSIAO ; Yeong-Shiau PU ;
The World Journal of Men's Health 2025;43(2):376-386
Purpose:
Biomarkers predicting clinically significant prostate cancer (sPC) before biopsy are currently lacking. This study aimed to develop a non-invasive urine test to predict sPC in at-risk men using urinary metabolomic profiles.
Materials and Methods:
Urine samples from 934 at-risk subjects and 268 treatment-naïve PC patients were subjected to liquid chromatography/mass spectrophotometry (LC-MS)-based metabolomics profiling using both C18 and hydrophilic interaction liquid chromatography (HILIC) column analyses. Four models were constructed (training cohort [n=647]) and validated (validation cohort [n=344]) for different purposes. Model I differentiates PC from benign cases. Models II, III, and a Gleason score model (model GS) predict sPC that is defined as National Comprehensive Cancer Network (NCCN)-categorized favorable-intermediate risk group or higher (Model II), unfavorable-intermediate risk group or higher (Model III), and GS ≥7 PC (model GS), respectively. The metabolomic panels and predicting models were constructed using logistic regression and Akaike information criterion.
Results:
The best metabolomic panels from the HILIC column include 25, 27, 28 and 26 metabolites in Models I, II, III, and GS, respectively, with area under the curve (AUC) values ranging between 0.82 and 0.91 in the training cohort and between 0.77 and 0.86 in the validation cohort. The combination of the metabolomic panels and five baseline clinical factors that include serum prostate-specific antigen, age, family history of PC, previously negative biopsy, and abnormal digital rectal examination results significantly increased AUCs (range 0.88–0.91). At 90% sensitivity (validation cohort), 33%, 34%, 41%, and 36% of unnecessary biopsies were avoided in Models I, II, III, and GS, respectively. The above results were successfully validated using LC-MS with the C18 column.
Conclusions
Urinary metabolomic profiles with baseline clinical factors may accurately predict sPC in men with elevated risk before biopsy.
7.Intratesticular Testosterone and Its Precursors among Azoospermic Men: A Pilot Study
I-Shen HUANG ; Li-Hua LI ; Wei-Jen CHEN ; Chi-Chang JUAN ; William J. HUANG
The World Journal of Men's Health 2025;43(1):142-153
Purpose:
The study aimed to comprehensively analyze testosterone and precursor concentrations in the testicular interstitial fluid (TIF) of men with azoospermia, exploring their significance in the testicular microenvironment and their correlation with testicular sperm retrieval outcomes.
Materials and Methods:
We analyzed 37 TIF samples, including 5 from men with obstructive azoospermia (OA) and 32 from men with non-obstructive azoospermia (NOA). Liquid chromatography with tandem mass spectrometry quantified testosterone and precursor levels. Comparative assessments of the outcomes of testicular sperm retrieval were performed between the OA and NOA groups as well as among men with NOA.
Results:
Men with NOA who had not undergone hormone treatment exhibited significantly higher intratesticular concentrations of testosterone (median 1,528.1 vs. 207.5 ng/mL), androstenedione (median 10.6 vs. 1.9 ng/mL), and 17-OH progesterone (median 13.0 vs. 1.8 ng/mL) than men diagnosed with OA. Notably, in the subgroup of patients with NOA subjected to medical treatment, men with successful sperm retrieval had significantly reduced levels of androstenedione (median androstenedione 5.7 vs. 18.5 ng/mL, p=0.004). Upon a more detailed analysis of these men who underwent hormone manipulation treatment, the testosterone/androstenedione ratio (indicative of HSD17B3 enzyme activity) was markedly increased in men with successful sperm retrieval (median: 365.8 vs. 165.0, p=0.008) compared with individuals with NOA who had unsuccessful sperm recovery. Furthermore, within the subset of men with NOA who did not undergo medical treatment before microdissection testicular sperm extraction but achieved successful sperm retrieval, the ratio of 17-OH progesterone/progesterone (indicative of CYP17A1 activity) was substantially higher.
Conclusions
The study suggests distinct testosterone biosynthesis pathways in men with compromised spermatogenesis and those with normal spermatogenesis. Among NOA men with successful retrieval after hormone optimization therapy, there was decreased androstenedione and increased HSD17B3 enzyme activity. These findings have diagnostic and therapeutic implications for the future.
8.Effect of Anti-reflux Mucosal Ablation on Esophageal Motility in Patients With Gastroesophageal Reflux Disease: A Study Based on High-resolution Impedance Manometry
Chien-Chuan CHEN ; Chu-Kuang CHOU ; Ming-Ching YUAN ; Kun-Feng TSAI ; Jia-Feng WU ; Wei-Chi LIAO ; Han-Mo CHIU ; Hsiu-Po WANG ; Ming-Shiang WU ; Ping-Huei TSENG
Journal of Neurogastroenterology and Motility 2025;31(1):75-85
Background/Aims:
Anti-reflux mucosal ablation (ARMA) is a promising endoscopic intervention for proton pump inhibitor (PPI)-dependent gastroesophageal reflux disease (GERD). However, the effect of ARMA on esophageal motility remains unclear.
Methods:
Twenty patients with PPI-dependent GERD receiving ARMA were prospectively enrolled. Comprehensive self-report symptom questionnaires, endoscopy, 24-hour impedance-pH monitoring, and high-resolution impedance manometry were performed and analyzed before and 3 months after ARMA.
Results:
All ARMA procedures were performed successfully. Symptom scores, including GerdQ (11.16 ± 2.67 to 9.11 ± 2.64, P = 0.026) and reflux symptom index (11.63 ± 5.62 to 6.11 ± 3.86, P = 0.001), improved significantly, while 13 patients (65%) reported discontinuation of PPI. Total acid exposure time (5.84 ± 4.63% to 2.83 ± 3.41%, P = 0.024) and number of reflux episodes (73.05 ± 19.34 to 37.55 ± 22.71, P < 0.001) decreased significantly after ARMA. Improved esophagogastric junction (EGJ) barrier function, including increased lower esophageal sphincter resting pressure (13.89 ± 10.78 mmHg to 21.68 ± 11.5 mmHg, P = 0.034), 4-second integrated relaxation pressure (5.75 ± 6.42 mmHg to 9.99 ± 5.89 mmHg, P = 0.020), and EGJ-contractile integral(16.42 ± 16.93 mmHg · cm to 31.95 ± 21.25 mmHg · cm, P = 0.016), were observed. Esophageal body contractility also increased significantly (distal contractile integral, 966.85 ± 845.84 mmHg · s · cm to 1198.8 ± 811.74 mmHg · s · cm, P = 0.023). Patients with symptom improvement had better pre-AMRA esophageal body contractility.
Conclusions
ARMA effectively improves symptoms and reflux burden, EGJ barrier function, and esophageal body contractility in patients with PPIdependent GERD during short-term evaluation. Longer follow-up to clarify the sustainability of ARMA is needed.
9.Baseline Impedance via Manometry Predicts Pathological Mean Nocturnal Baseline Impedance in Isolated Laryngopharyngeal Reflux Symptoms
Yen-Ching WANG ; Chen-Chi WANG ; Chun-Yi CHUANG ; Yung-An TSOU ; Yen-Chun PENG ; Chi-Sen CHANG ; Han-Chung LIEN
Journal of Neurogastroenterology and Motility 2025;31(1):63-74
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.
10.Unmet Need for Palliative Care in Pediatric Hematology/Oncology Populations
Yi-Lun WANG ; Wan-Ju LEE ; Tsung-Yen CHANG ; Shih-Hsiang CHEN ; Chia-Chi CHIU ; Yi-Wen HSIAO ; Yu-Chuan WEN ; Tang-Her JAING
Clinical Pediatric Hematology-Oncology 2025;32(1):19-22
Background:
Delivering a poor prognosis to patients and their families is critically challenging in pediatric populations. The application of palliative care (PC) provides a bridge between accepting the occurrence of mortality and offering lifelong support.However, little is known about the specifics of PC. This study aims to explore the unmet need for PC in pediatric populations.
Methods:
We retrospectively reviewed the medical records of mortality cases in the Department of Pediatric Hematology and Oncology at Chang Gung Memorial Hospital. Statistical tests, including Chi-square and Student’s t-tests, were applied to determine the differences between early and late intervention groups in terms of the timing of PC introduction.
Results:
During the study period, 41 patients were included. Their median age was 11.8 years (IQR, 7.6-15.9). The majority of the disease statuses were refractory or relapsing (R/R). The incidence of memento application was significantly higher in the early intervention group (47.6% vs. 10%, P=0.0081). Vital signs variations tended to be end-of-life (EoL) indicators in this study.
Conclusion
The early introduction of PC encourages families to accompany their beloved child. EoL signs in the pediatric population include vital sign variations. With the presence of relevant EoL signs, clinical physicians can apply PC earlier to meet the needs.

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