1.Emerging role of Jumonji domain-containing protein D3 in inflammatory diseases
Li XIANG ; Chen RU-YI ; Shi JIN-JIN ; Li CHANG-YUN ; Liu YAN-JUN ; Gao CHANG ; Gao MING-RONG ; Zhang SHUN ; Lu JIAN-FEI ; Cao JIA-FENG ; Yang GUAN-JUN ; Chen JIONG
Journal of Pharmaceutical Analysis 2024;14(9):1282-1300
Jumonji domain-containing protein D3(JMJD3)is a 2-oxoglutarate-dependent dioxygenase that specif-ically removes transcriptional repression marks di-and tri-methylated groups from lysine 27 on histone 3(H3K27me2/3).The erasure of these marks leads to the activation of some associated genes,thereby influencing various biological processes,such as development,differentiation,and immune response.However,comprehensive descriptions regarding the relationship between JMJD3 and inflammation are lacking.Here,we provide a comprehensive overview of JMJD3,including its structure,functions,and involvement in inflammatory pathways.In addition,we summarize the evidence supporting JMJD3's role in several inflammatory diseases,as well as the potential therapeutic applications of JMJD3 inhibitors.Additionally,we also discuss the challenges and opportunities associated with investigating the functions of JMJD3 and developing targeted inhibitors and propose feasible solutions to provide valuable insights into the functional exploration and discovery of potential drugs targeting JMJD3 for inflammatory diseases.
2.Risk factors for bronchopulmonary dysplasia in twin preterm infants:a multicenter study
Yu-Wei FAN ; Yi-Jia ZHANG ; He-Mei WEN ; Hong YAN ; Wei SHEN ; Yue-Qin DING ; Yun-Feng LONG ; Zhi-Gang ZHANG ; Gui-Fang LI ; Hong JIANG ; Hong-Ping RAO ; Jian-Wu QIU ; Xian WEI ; Ya-Yu ZHANG ; Ji-Bin ZENG ; Chang-Liang ZHAO ; Wei-Peng XU ; Fan WANG ; Li YUAN ; Xiu-Fang YANG ; Wei LI ; Ni-Yang LIN ; Qian CHEN ; Chang-Shun XIA ; Xin-Qi ZHONG ; Qi-Liang CUI
Chinese Journal of Contemporary Pediatrics 2024;26(6):611-618
Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.
3.Study on bioequivalence evaluation of Pemirolast potassium tablets in Chinese healthy volunteers on an empty stomach/after meals
Yi-Ming MA ; Wang HU ; Feng ZHANG ; Wen ZHANG ; Sheng-Long ZHAO ; Yang CAO ; Jing XIE ; Huan ZHOU ; Shun-Wang HUANG
Chinese Pharmacological Bulletin 2024;40(6):1075-1081
Aim To compare the pharmacokinetics of pemirolast potassium tablets in healthy subjects in Chi-na under single fasting and postprandial conditions,and to evaluate the bioequivalence of the test prepara-tion(T)and the reference preparation(R).Methods A randomized,open-ended,single-dose,two-cycle,double-cross bioequivalence trial design was adopted,and 26 and 30 subjects were enrolled in the fasting group and the postprandial group,respectively,and 10 mg of the test preparation and the reference preparation were taken in the fasting or postprandial state each cy-cle,and venous blood was collected at the designed time points before and after the administration cycle.The concentration of pemirolast potassium in plasma was determined by LC-MS/MS method,and the phar-macokinetic parameters were calculated with PhoenixTM WinNonlin ?(8.3)software,and the bioequivalence analysis of the two preparations was performed.Re-sults The t1/2 of the test preparation and the reference preparation was(4.44±0.91)h and(4.49±0.93)h,respectively;the median tmax was(1.96±1.29)h and(2.18±1.25)h,respectively;the Cmax was(867.12±205.56)μg·L-1 and(863.35±172.03)μg·L-1,respectively;the AUC0-t was(5 513.23±1463.67)h·μg·L-1 and(5 661.32±1 628.65)h·μg·L-1,respectively;AUC0_∞ was(5 699.81±1477.68)h·μg·L-1 and(5 849.44±1 644.75)h·μg·L-1,respectively.The statistical results of the 90%confidence intervals of the main pharmacokinetic parameters Cmax,AUC0-t,and AUC0-∞ was 92.49%~107.53%,94.71%~100.67%and 95.28%~100.27%,respectively,all of which were within the range of 80.00%~125.00%,and the safety of the tested preparation and the reference preparation was good when taken orally on an empty stomach.The t1/2 of single oral administration after prandial administra-tion of the tested preparation and the reference prepara-tion was(4.46±0.78)and(4.51±0.84)h,respec-tively;the median tmax was(3.08±1.36)h and(3.28±1.28)h,respectively;the Cmax was(683.83±111.87)μg·L-1 and(689.77±110.24)μg·L-1,respectively;the AUC0-t was(5 695.99±1566.05)h·μg·L-1 and(5 773.60±1 551.04)h·μg·L-1,respectively;the AUC0-∞ was(5 914.06±1 551.86)h·μg·L-1 and(5 967.30±1552.89)h·μg·L-1,respectively.The 90%confi-dence interval of Cmax,AUC0-t,and AUC0-∞ was 93.56%~104.69%,96.43%~100.83%,and 97.29%~101.14%,respectively,which was in the range of 80.00%~125.00%,and the safety of the tested preparation and the reference preparation was good after meals.Conclusion In the state of fasting and postprandial single oral administration,the two kinds of pemirolast potassium tablets have good bio-equivalence.
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.Precirrhotic Primary Biliary Cholangitis with Portal Hypertension:Bile Duct Injury Correlate
Yi-Fan HU ; Shun-Xin LI ; Hong-Li LIU ; Zhi-Xiang DU ; Shuang-Shuang WANG ; Miao-Yang CHEN ; Li WANG ; Qing-Fang XIONG ; Yan-Dan ZHONG ; Du-Xian LIU ; Yong-Feng YANG
Gut and Liver 2024;18(5):867-876
Background/Aims:
The histological characteristics and natural history of precirrhotic primary biliary cholangitis (PBC) with portal hypertension (PH) are unclear. Our aim was to clarify the prevalence, risk factors, and histological characteristics of precirrhotic PBC patients with PH.
Methods:
This retrospective study compared the clinical features, histological characteristics, and response to ursodeoxycholic acid (UDCA) between the PH and non-PH groups of precirrhotic PBC patients.
Results:
Out of 165 precirrhotic PBC patients, 40 (24.2%) also had PH. According to histological stage 1, 2 and 3 disease, 5.3% (1/19), 17.3% (17/98), and 45.8% (22/48) of patients also had PH, respectively. Precirrhotic PBC with PH was significantly positively correlated with bile duct loss, degree of cytokeratin 7 positivity, and degree of fibrosis in the portal area, but significantly negatively correlated with lymphoid follicular aggregation. Compared to the non-PH group, patients in the PH group showed a higher prevalence of obliterative portal venopathy, incomplete septal fibrosis, portal tract abnormalities and non-zonal sinusoidal dilatation (p<0.05). In addition, patients with PH were more likely to present with symptoms of jaundice, ascites, epigastric discomfort, a poorer response to UDCA, and more decompensation events (p<0.05). High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values were risk factors for precirrhotic PBC with PH.
Conclusions
Approximately 24.2% of precirrhotic PBC patients have PH, which is histologically related to the injury of bile ducts. High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values are associated with increased risk of precirrhotic PBC with PH.
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.Effect of HCMV infection on immune reconstitution of CD8+T cells in children with allogeneic hematopoietic stem cell transplantation.
Ze WEI ; Shun Qiao FENG ; Xiao Yu YI ; Qin LUO ; Hai Jun DU ; Guo Yong MEI ; Rong LIU ; Hai Lan YAO ; Jun HAN
Chinese Journal of Preventive Medicine 2023;57(12):2095-2101
Objective: To investigate the risk factors for human cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation in children and the impact of human cytomegalovirus infection on post-transplant immune reconstitution. Methods: A Retrospective Co-Hort study design was used to include 81 children treated with allo-HSCT from January 2020 to March 2022 at the Department of Hematology, Capital Institute of Pediatrics, Beijing, China, and followed up for 1 year. Real-time quantitative PCR was used to detect positive detection of HCMV in children after allo-HSCT, multifactorial logistic regression modeling was used to analyze the risk factors leading to HCMV infection, and generalized estimating equation modeling was used to analyze the effect of HCMV infection on the T-cells of the children who received allo-HSCT. Results: The age M(Q1, Q3) of 81 children was 5.1 years (10 months, 13.8 years), and 50 (61.7%) were male. By the endpoint of follow-up, a total of 50 HCMV-positive cases were detected, with an HCMV detection rate of 61.7%; The results of multifactorial logistic regression modeling showed that children with grade 2-4 aGVHD had a higher risk of HCMV infection compared with grade 0-1 after transplantation [OR (95%CI) value: 2.735 (1.027-7.286)]. The results of generalized estimating equation modeling analysis showed that the number of CD3+T cells in HCMV-positive children after transplantation was higher than that in the HCMV-negative group [RR (95%CI) value: 1.34 (1.008-1.795)]; the ratio of CD4+T/CD8+T cells was smaller than that in the HCMV-negative group [RR (95%CI) value: 0.377 (0.202-0.704)]; the number of CD8+T cells was higher than that in the HCMV-negative group [RR (95%CI) value: 1.435 (1.025-2.061)]; the number of effector memory CD8+T cells was higher than that in the HCMV-negative group [RR (95%CI) value: 1.877 (1.089-3.236)]. Conclusion: Acute graft-versus-host disease may be a risk factor for HCMV infection in children after allo-HSCT; post-transplant HCMV infection promotes proliferation of memory CD8+T-cell populations and affects immune cell reconstitution.
Male
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Humans
;
Child
;
Female
;
Immune Reconstitution
;
Retrospective Studies
;
Cytomegalovirus Infections
;
Hematopoietic Stem Cell Transplantation/adverse effects*
;
CD8-Positive T-Lymphocytes
9.Effect of HCMV infection on immune reconstitution of CD8+T cells in children with allogeneic hematopoietic stem cell transplantation.
Ze WEI ; Shun Qiao FENG ; Xiao Yu YI ; Qin LUO ; Hai Jun DU ; Guo Yong MEI ; Rong LIU ; Hai Lan YAO ; Jun HAN
Chinese Journal of Preventive Medicine 2023;57(12):2095-2101
Objective: To investigate the risk factors for human cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation in children and the impact of human cytomegalovirus infection on post-transplant immune reconstitution. Methods: A Retrospective Co-Hort study design was used to include 81 children treated with allo-HSCT from January 2020 to March 2022 at the Department of Hematology, Capital Institute of Pediatrics, Beijing, China, and followed up for 1 year. Real-time quantitative PCR was used to detect positive detection of HCMV in children after allo-HSCT, multifactorial logistic regression modeling was used to analyze the risk factors leading to HCMV infection, and generalized estimating equation modeling was used to analyze the effect of HCMV infection on the T-cells of the children who received allo-HSCT. Results: The age M(Q1, Q3) of 81 children was 5.1 years (10 months, 13.8 years), and 50 (61.7%) were male. By the endpoint of follow-up, a total of 50 HCMV-positive cases were detected, with an HCMV detection rate of 61.7%; The results of multifactorial logistic regression modeling showed that children with grade 2-4 aGVHD had a higher risk of HCMV infection compared with grade 0-1 after transplantation [OR (95%CI) value: 2.735 (1.027-7.286)]. The results of generalized estimating equation modeling analysis showed that the number of CD3+T cells in HCMV-positive children after transplantation was higher than that in the HCMV-negative group [RR (95%CI) value: 1.34 (1.008-1.795)]; the ratio of CD4+T/CD8+T cells was smaller than that in the HCMV-negative group [RR (95%CI) value: 0.377 (0.202-0.704)]; the number of CD8+T cells was higher than that in the HCMV-negative group [RR (95%CI) value: 1.435 (1.025-2.061)]; the number of effector memory CD8+T cells was higher than that in the HCMV-negative group [RR (95%CI) value: 1.877 (1.089-3.236)]. Conclusion: Acute graft-versus-host disease may be a risk factor for HCMV infection in children after allo-HSCT; post-transplant HCMV infection promotes proliferation of memory CD8+T-cell populations and affects immune cell reconstitution.
Male
;
Humans
;
Child
;
Female
;
Immune Reconstitution
;
Retrospective Studies
;
Cytomegalovirus Infections
;
Hematopoietic Stem Cell Transplantation/adverse effects*
;
CD8-Positive T-Lymphocytes
10.Effect of laparoscopic surgery for pancreatic cancer after neoadjuvant chemotherapy.
Qi Feng ZHUO ; Meng Qi LIU ; Zheng LI ; Wen Sheng LIU ; Yi Hua SHI ; Wen Yan XU ; Shun Rong JI ; Xiao Wu XU ; Xian Jun YU
Chinese Journal of Surgery 2022;60(2):134-139
Objective: To evaluate the safety and feasibility of laparoscopic surgery after neoadjuvant chemotherapy for pancreatic cancer. Methods: Clinical data of 8 patients underwent laparoscopic surgery after neoadjuvant chemotherapy for pancreatic cancer at Fudan University Shanghai Cancer Center from September 2019 to June 2020 were reviewed retrospectively. There were 5 males and 3 females,aged from 47 to 72 years old. All patients underwent abdominal enhanced CT and PET-CT before operation to accurately evaluate the tumor stage and exclude distant metastasis. Results: Neoadjuvant chemotherapy with AG regimen(gemcitabine 1 000 mg/m2 and albumin bound paclitaxel 125 mg/m2) was received for 2 to 6 cycles before surgery. All 8 patients successfully completed the operation,including 5 cases of pancreaticoduodenectomy,2 cases of radical antegrade modular pancreatosplenectomy(RAMPS),and 1 case of total pancreatectomy. No conversion to laparotomy or laparoscopic assisted surgery. The operation time was 240 to 450 minutes,the blood loss was 100 to 500 ml,the postoperative length of stay was 10 to 16 days. During the follow-up period up to December 31, 2020, there was 1 case suffered grade B pancreatic leakage and abdominal infection. The numbers of resected lymph nodes were 9 to 31. All patients received R0 resection. The follow-up times were 4.5 to 9.5 months. One patient underwent RAMPS was diagnosed as liver metastasis after 2 months of the operation,and the other 7 patients still survived without tumor recurrence. Conclusion: Minimally invasive surgery of pancreatic cancer after neoadjuvant chemotherapy is safe and feasible in experienced pancreatic minimally invasive centers.
Aged
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China
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Female
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Humans
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Laparoscopy
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Male
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Middle Aged
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Neoadjuvant Therapy
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Neoplasm Recurrence, Local
;
Pancreatectomy
;
Pancreatic Neoplasms/surgery*
;
Positron Emission Tomography Computed Tomography
;
Retrospective Studies

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