1. Effects of metabolites of eicosapentaenoic acid on promoting transdifferentiation of pancreatic OL cells into pancreatic β cells
Chao-Feng XING ; Min-Yi TANG ; Qi-Hua XU ; Shuai WANG ; Zong-Meng ZHANG ; Zi-Jian ZHAO ; Yun-Pin MU ; Fang-Hong LI
Chinese Pharmacological Bulletin 2024;40(1):31-38
Aim To investigate the role of metabolites of eicosapentaenoic acid (EPA) in promoting the transdifferentiation of pancreatic α cells to β cells. Methods Male C57BL/6J mice were injected intraperitoneally with 60 mg/kg streptozocin (STZ) for five consecutive days to establish a type 1 diabetes (T1DM) mouse model. After two weeks, they were randomly divided into model groups and 97% EPA diet intervention group, 75% fish oil (50% EPA +25% DHA) diet intervention group, and random blood glucose was detected every week; after the model expired, the regeneration of pancreatic β cells in mouse pancreas was observed by immunofluorescence staining. The islets of mice (obtained by crossing GCG
2.Identification of oxidative stress-related biomarkers in chronic rhinosinusitis with nasal polyps using WGCNA combined with machine learning algorithms
Ye YUAN ; Xueyun SHI ; Xinyi MA ; Xinyu XIE ; Changhua WU ; Liqiang ZHANG ; Xuezhong LI ; Pin WANG ; Xin FENG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2024;59(6):560-572
Objective:To identify diagnostic markers related to oxidative stress in chronic rhinosinusitis with nasal polyps (CRSwNP) by analyzing transcriptome sequencing data, and to investigate their roles in CRSwNP.Methods:Utilizing four CRSwNP sequencing datasets, differentially expressed genes (DEGs) analysis, weighted gene co-expression network analysis (WGCNA), and three machine learning methods for Hub gene selection were performed in this study. Subsequent validation was carried out using external datasets, as well as real-time quantitative polymerase chain reaction (Real-time qPCR), and immunofluorescence staining of clinical samples. Moreover, the diagnostic efficacy of the genes was assessed by receiver operating characteristic (ROC) curve, followed by functional and pathway enrichment analysis, immune-related analysis, and cell population localization. Additionally, a competing endogenous RNA (CeRNA) network was constructed to predict potential drug targets. Statistical analysis and plotting were conducted using SPSS 26.0 and Graphpad Prism9 software.Results:Through data analysis and clinical validation, CP, SERPINF1 and GSTO2 were identified among 4 138 DEGs as oxidative stress markers related to CRSwNP. Specifically, the expression of CP and SERPINF1 increased in CRSwNP, whereas that of GSTO2 decreased, with statistically significant differences ( P<0.05). Additionally, an area under the curve (AUC)>0.7 indicated their effectiveness as diagnostic indicators. Importantly, functional analysis indicated that these genes were mainly related to lipid metabolism, cell adhesion migration, and immunity. Single-cell data analysis revealed that SERPINF1 was mainly distributed in epithelial cells, stromal cells, and fibroblasts, while CP was primarily located in epithelial cells, and GSTO2 was minimally present in the epithelial cells and fibroblasts of nasal polyps. Consequently, a CeRNA regulatory network was constructed for the genes CP and GSTO2. This construction allowed for the prediction of potential drugs that could target CP. Conclusion:This study successfully identifies CP, SERPINF1 and GSTO2 as diagnostic and therapeutic markers related to oxidative stress in CRSwNP.
3.Clinical efficacy of full surgical area closure technique in percutaneous co-axial large-channel endo-scopic lumbar interbody fusion in the treatment of degenerative lumbar spondylolisthesis
Junlin LIU ; Qiang YU ; Pin FENG
Chinese Journal of Spine and Spinal Cord 2024;34(6):576-584
Objectives:To explore the application value of percutaneous co-axial large-channel endoscopic lumbar interbody fusion(PLE-LIF)combined with full surgical area closure technique(FSAC)in the treatment of degenerative lumbar spondylolisthesis.Methods:A retrospective analysis was conducted on 83 patients with single-segment degenerative lumbar spondylolisthesis who underwent PLE-LIF in our hospital from January 2020 to January 2023.Among the patients,46 received FSAC treatment during operation(FSAC group),and 37 patients did not receive FSAC treatment(N-FSAC group).Both groups of patients were comparable in gen-eral information such as gender,age,course of illness,and length of hospital stay(P>0.05).The two groups of patients were followed up for l year.The operative time and complications of the two groups of patients were recorded.Both groups of patients were followed up regularly for 1 year.The visual analogue scale(VAS)for low back pain and lower limb pain was recorded on ld before surgery,3d after surgery,at 3 months and 1 year after surgery,in addition,the Oswestry disability index(ODI)on 1d before surgery,at 3 months and 1 year after surgery was recorded.X-ray examination was performed at 3 months after operation,and Meyerding grading was used to evaluate the reduction of spondylolisthesis.CT examination was performed at 1 year after operation,and Brantigan criteria were used to evaluate the intervertebral fusion.Results:The operative time in the FSAC group was shorter than that in the N-FSAC group(118.9±10.6min vs 130.6±16.3min,P<0.05).The VAS for low back pain and lower limb pain and ODI at each postoperative time point in the two groups were significantly lower than those before surgery(P<0.05),and there was no statistically significant difference between the two groups at each time point(P>0.05).Two cases of lower limb numbness occurred in the N-FSAC group,while none occurred in the FSAC group;There were 4 cases and 1 case of neuroedema pain in the N-FSAC group and FSAC group,respectively;1 case in each group respectively had cage displacement,and there was no internal fixation loosening,infection,or dural sac tear in both groups.The incidence rate of intraoperative complications in the N-FSAC group was higher than that in the FSAC group(18.9%vs 4.3%)(P<0.05).One year after surgery,the degree of slippage in both groups of patients improved significantly compared to the conditions before operation(P<0.05),and there was no significant difference between the two groups(P>0.05);Intervertebral fusion occurred in 42 cases in the FSAC group,and 34 cases in the N-FSAC group,and no statistically significant difference was there in the fusion rate(91.3%vs 91.9%)and intervertebral fusion grading between the two groups(P<0.05).Conclusions:PEL-LIF combined with FSAC can shorten the operative time and improve safety in treating single-segment degenerative lumbar spondylolisthesis.
4.Artificial intelligence predicts direct-acting antivirals failure among hepatitis C virus patients: A nationwide hepatitis C virus registry program
Ming-Ying LU ; Chung-Feng HUANG ; Chao-Hung HUNG ; Chi‐Ming TAI ; Lein-Ray MO ; Hsing-Tao KUO ; Kuo-Chih TSENG ; Ching-Chu LO ; Ming-Jong BAIR ; Szu-Jen WANG ; Jee-Fu HUANG ; Ming-Lun YEH ; Chun-Ting CHEN ; Ming-Chang TSAI ; Chien-Wei HUANG ; Pei-Lun LEE ; Tzeng-Hue YANG ; Yi-Hsiang HUANG ; Lee-Won CHONG ; Chien-Lin CHEN ; Chi-Chieh YANG ; Sheng‐Shun YANG ; Pin-Nan CHENG ; Tsai-Yuan HSIEH ; Jui-Ting HU ; Wen-Chih WU ; Chien-Yu CHENG ; Guei-Ying CHEN ; Guo-Xiong ZHOU ; Wei-Lun TSAI ; Chien-Neng KAO ; Chih-Lang LIN ; Chia-Chi WANG ; Ta-Ya LIN ; Chih‐Lin LIN ; Wei-Wen SU ; Tzong-Hsi LEE ; Te-Sheng CHANG ; Chun-Jen LIU ; Chia-Yen DAI ; Jia-Horng KAO ; Han-Chieh LIN ; Wan-Long CHUANG ; Cheng-Yuan PENG ; Chun-Wei- TSAI ; Chi-Yi CHEN ; Ming-Lung YU ;
Clinical and Molecular Hepatology 2024;30(1):64-79
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.
5.Metformin and statins reduce hepatocellular carcinoma risk in chronic hepatitis C patients with failed antiviral therapy
Pei-Chien TSAI ; Chung-Feng HUANG ; Ming-Lun YEH ; Meng-Hsuan HSIEH ; Hsing-Tao KUO ; Chao-Hung HUNG ; Kuo-Chih TSENG ; Hsueh-Chou LAI ; Cheng-Yuan PENG ; Jing-Houng WANG ; Jyh-Jou CHEN ; Pei-Lun LEE ; Rong-Nan CHIEN ; Chi-Chieh YANG ; Gin-Ho LO ; Jia-Horng KAO ; Chun-Jen LIU ; Chen-Hua LIU ; Sheng-Lei YAN ; Chun-Yen LIN ; Wei-Wen SU ; Cheng-Hsin CHU ; Chih-Jen CHEN ; Shui-Yi TUNG ; Chi‐Ming TAI ; Chih-Wen LIN ; Ching-Chu LO ; Pin-Nan CHENG ; Yen-Cheng CHIU ; Chia-Chi WANG ; Jin-Shiung CHENG ; Wei-Lun TSAI ; Han-Chieh LIN ; Yi-Hsiang HUANG ; Chi-Yi CHEN ; Jee-Fu HUANG ; Chia-Yen DAI ; Wan-Long CHUNG ; Ming-Jong BAIR ; Ming-Lung YU ;
Clinical and Molecular Hepatology 2024;30(3):468-486
Background/Aims:
Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients.
Methods:
We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development.
Results:
Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients.
Conclusions
Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.
6.Management of ulcerative colitis in Taiwan: consensus guideline of the Taiwan Society of Inflammatory Bowel Disease updated in 2023
Hsu-Heng YEN ; Jia-Feng WU ; Horng-Yuan WANG ; Ting-An CHANG ; Chung-Hsin CHANG ; Chen-Wang CHANG ; Te-Hsin CHAO ; Jen-Wei CHOU ; Yenn-Hwei CHOU ; Chiao-Hsiung CHUANG ; Wen-Hung HSU ; Tzu-Chi HSU ; Tien-Yu HUANG ; Tsung-I HUNG ; Puo-Hsien LE ; Chun-Che LIN ; Chun-Chi LIN ; Ching-Pin LIN ; Jen-Kou LIN ; Wei-Chen LIN ; Yen-Hsuan NI ; Ming-Jium SHIEH ; I-Lun SHIH ; Chia-Tung SHUN ; Tzung-Jiun TSAI ; Cheng-Yi WANG ; Meng-Tzu WENG ; Jau-Min WONG ; Deng-Chyang WU ; Shu-Chen WEI
Intestinal Research 2024;22(3):213-249
Ulcerative colitis (UC) is a chronic inflammation of the gastrointestinal tract and is characterized by alternating periods of inflammation and remission. Although UC incidence is lower in Taiwan than in Western countries, its impact remains considerable, demanding updated guidelines for addressing local healthcare challenges and patient needs. The revised guidelines employ international standards and recent research, emphasizing practical implementation within the Taiwanese healthcare system. Since the inception of the guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease has acknowledged the need for ongoing revisions to incorporate emerging therapeutic options and evolving disease management practices. This updated guideline aims to align UC management with local contexts, ensuring comprehensive and context-specific recommendations, thereby raising the standard of care for UC patients in Taiwan. By adapting and optimizing international protocols for local relevance, these efforts seek to enhance health outcomes for patients with UC.
7.Management of Crohn’s disease in Taiwan: consensus guideline of the Taiwan Society of Inflammatory Bowel Disease updated in 2023
Jia-Feng WU ; Hsu-Heng YEN ; Horng-Yuan WANG ; Ting-An CHANG ; Chung-Hsin CHANG ; Chen-Wang CHANG ; Te-Hsin CHAO ; Jen-Wei CHOU ; Yenn-Hwei CHOU ; Chiao-Hsiung CHUANG ; Wen-Hung HSU ; Tzu-Chi HSU ; Tien-Yu HUANG ; Tsung-I HUNG ; Puo-Hsien LE ; Chun-Che LIN ; Chun-Chi LIN ; Ching-Pin LIN ; Jen-Kou LIN ; Wei-Chen LIN ; Yen-Hsuan NI ; Ming-Jium SHIEH ; I-Lun SHIH ; Chia-Tung SHUN ; Tzung-Jiun TSAI ; Cheng-Yi WANG ; Meng-Tzu WENG ; Jau-Min WONG ; Deng-Chyang WU ; Shu-Chen WEI
Intestinal Research 2024;22(3):250-285
Crohn’s disease (CD) is a chronic, fluctuating inflammatory condition that primarily affects the gastrointestinal tract. Although the incidence of CD in Taiwan is lower than that in Western countries, the severity of CD presentation appears to be similar between Asia and the West. This observation indicates the urgency for devising revised guidelines tailored to the unique reimbursement system, and patient requirements in Taiwan. The core objectives of these updated guidelines include the updated treatment choices and the integration of the treat-to-target strategy into CD management, promoting the achievement of deep remission to mitigate complications and enhance the overall quality of life. Given the diversity in disease prevalence, severity, insurance policies, and access to medical treatments in Taiwan, a customized approach is imperative for formulating these guidelines. Such tailored strategies ensure that international standards are not only adapted but also optimized to local contexts. Since the inception of its initial guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease (TSIBD) has acknowledged the importance of continuous revisions for incorporating new therapeutic options and evolving disease management practices. The latest update leverages international standards and recent research findings focused on practical implementation within the Taiwanese healthcare system.
8.Early Improvement in Interstitial Fluid Flow in Patients With Severe Carotid Stenosis After Angioplasty and Stenting
Chia-Hung WU ; Shih-Pin CHEN ; Chih-Ping CHUNG ; Kai-Wei YU ; Te-Ming LIN ; Chao-Bao LUO ; Jiing-Feng LIRNG ; I-Hui LEE ; Feng-Chi CHANG
Journal of Stroke 2024;26(3):415-424
Background:
and Purpose This study aimed to investigate early changes in interstitial fluid (ISF) flow in patients with severe carotid stenosis after carotid angioplasty and stenting (CAS).
Methods:
We prospectively recruited participants with carotid stenosis ≥80% undergoing CAS at our institute between October 2019 and March 2023. Magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI), and the Mini-Mental State Examination (MMSE) were performed 3 days before CAS. MRI with DTI and MMSE were conducted within 24 hours and 2 months after CAS, respectively. The diffusion tensor image analysis along the perivascular space (DTI-ALPS) index was calculated from the DTI data to determine the ISF status. Increments were defined as the ratio of the difference between post- and preprocedural values to preprocedural values.
Results:
In total, 102 participants (age: 67.1±8.9 years; stenosis: 89.5%±5.7%) with longitudinal data were evaluated. The DTI-ALPS index increased after CAS (0.85±0.15; 0.85 [0.22] vs. 0.86±0.14; 0.86 [0.21]; P=0.022), as did the MMSE score (25.9±3.7; 24.0 [4.0] vs. 26.9±3.4; 26.0 [3.0]; P<0.001). Positive correlations between increments in the DTI-ALPS index and MMSE score were found in all patients (rs=0.468; P<0.001).
Conclusion
An increased 24-hour post-CAS DTI-ALPS index suggests early improvement in ISF flow efficiency. The positive correlation between the 24-hour DTI-ALPS index and 2-month MMSE score increments suggests that early ISF flow improvement may contribute to long-term cognitive improvement after CAS.
9.Benefits and Risks of Preprepared Parenteral Nutrition for Early Amino Acid Administration in Premature Infants with Very Low Birth Weight
Pin-Chun CHEN ; Hsin-Chung HUANG ; Mei-Jy JENG ; Feng-Shiang CHENG
Pediatric Gastroenterology, Hepatology & Nutrition 2024;27(4):246-257
Purpose:
Administering early parenteral amino acids to very low birth weight (VLBW) premature infants (birth body weight [BBW]<1,500 g) is challenging due to factors such as holidays, cost, and access to sterile compounding facilities. Using advance-prepared parenteral nutrition (PN) may address this issue and should be evaluated for its safety and potential benefits.
Methods:
We extracted data from medical records collected between July 2015 and August 2019. VLBW infants received PN for at least seven days and were split into two groups:the traditional group (n=30), which initially received a glucose solution and then PN on workdays, and the pre-preparation group (n=16), which received advance-prepared PN immediately upon admission to the neonatal intensive care unit.
Results:
The median BBWs of the traditional and pre-preparation groups were 1,180.0 vs. 1,210.0 g. In the initial two days, the pre-preparation group had a significantly higher amino acid intake (2.23 and 2.24 g/kg/d) than the traditional group (0 and 1.78 g/kg/d). The pre-preparation group exhibited greater head circumference growth ratio relative to birth (7th day: 1.21% vs. −3.57%, p=0.014; 21st day: 7.71% vs. 3.31%, p=0.017). No significant differences in metabolic tolerance were observed.
Conclusion
Advanced preparation of PN can be safely implemented in VLBW preterm infants, offering advantages such as early, higher amino acid intake and improved head circumference growth within the first 21 days post-birth. This strategy may serve as a viable alternative in settings where immediate provision of sterile compounding facilities is challenging.
10.Clinical characteristics of epileptic seizure in neurofibromatosis type 1 in 15 cases.
Fan WU ; Xin Na JI ; Meng Xiao SHEN ; Shuo FENG ; Li Na XIE ; Yan Yan GAO ; Shu Pin LI ; Ai Yun YANG ; Jian Hua WANG ; Qian CHEN ; Xue ZHANG
Chinese Journal of Pediatrics 2023;61(12):1124-1128
Objective: To summarize the clinical characteristics of epileptic seizure associated with neurofibromatosis type 1 (NF1). Methods: From January 2017 to July 2023 at Children's Hospital Capital Institute of Pediatrics, medical records of patients with both NF1 and epileptic seizure were reviewed in this case series study. The clinical characteristics, treatment and prognosis were analyzed retrospectively. Results: A total of 15 patients(12 boys and 3 girls) were collected. Café-au-lait macules were observed in all 15 patients. There were 6 patients with neurodevelopmental disorders and the main manifestations were intellectual disability or developmental delay. The age at the first epileptic seizure was 2.5 (1.2, 5.5) years. There were various seizure types, including generalized tonic-clonic seizures in 8 patients, focal motor seizures in 6 patients, epileptic spasm in 4 patients, tonic seizures in 1 patient, absence in 1 patient, generalized myoclonic seizure in 1 patient and focal to bilateral tonic-clonic seizure in 1 patient. Among 14 patients whose brain magnetic resonance imaging results were available, there were abnormal signals in corpus callosum, basal ganglia, thalamus or cerebellum in 6 patients, dilated ventricles of different degrees in 3 patients, blurred gray and white matter boundary in 2 patients, agenesis of corpus callosum in 1 patient and no obvious abnormalities in the other patients. Among 13 epilepsy patients, 8 were seizure-free with 1 or 2 antiseizure medications(ASM), 1 with drug resistant epilepsy was seizure-free after left temporal lobectomy, and the other 4 patients who have received 2 to 9 ASM had persistent seizures. One patient with complex febrile convulsion achieved seizure freedom after oral administration of diazepam on demand. One patient had only 1 unprovoked epileptic seizure and did not have another seizure without taking any ASM. Conclusions: The first epileptic seizure in NF1 patients usually occurs in infancy and early childhood, with the main seizure type of generalized tonic-clonic seizure and focal motor seizure. Some patients have intellectual disability or developmental delay. Most epilepsy patients achieve seizure freedom with ASM.
Male
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Female
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Humans
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Child, Preschool
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Child
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Neurofibromatosis 1/diagnosis*
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Retrospective Studies
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Intellectual Disability
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Electroencephalography
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Epilepsy/etiology*
;
Seizures/etiology*

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