1.Working practices in eliminating the public health crisis caused by viral hepatitis in Hainan Province of China
Weihua LI ; Changfu XIONG ; Taifan CHEN ; Bin HE ; Dapeng YIN ; Xuexia ZENG ; Feng LIN ; Biyu CHEN ; Xiaomei ZENG ; Biao WU ; Juan JIANG ; Lu ZHONG ; Yuhui ZHANG
Journal of Clinical Hepatology 2025;41(2):228-233
In 2022, Hainan provincial government launched the project for the prevention and control of viral hepatitis with the goals of a hepatitis B screening rate of 90%, a diagnostic rate of 90%, and a treatment rate of 80% among people aged 18 years and above by the year 2025, and the main intervention measures include population-based prevention, case screening, antiviral therapy, and health management. As of December 31, 2024, a total of 6.875 million individuals in the general population had been screened for hepatitis B, with a screening rate of 95.6%. A total of 184 710 individuals with positive HBsAg were identified, among whom 156 772 were diagnosed through serological reexamination, resulting in a diagnostic rate of 84.9%. A total of 50 742 patients with chronic hepatitis B were identified, among whom 42 921 had hepatitis B-specific health records established for health management, with a file establishment rate of 84.6%. A total of 31 553 individuals received antiviral therapy, with a treatment rate of 62.2%. A total of 2.503 million individuals at a high risk of hepatitis C were screened, among whom 4 870 tested positive for HCV antibody and 3 858 underwent HCV RNA testing, resulting in a diagnostic rate of 79.2%, and 1 824 individuals with positive HCV RNA were identified, among whom 1 194 received antiviral therapy, with a treatment rate of 65.5%. In addition, 159 301 individuals with negative HBsAg and anti-HBs and an age of 20 — 40 years were inoculated with hepatitis B vaccine free of charge. Through the implementation of the project for the prevention and control of viral hepatitis, a large number of hepatitis patients have been identified, treated, and managed in the province within a short period of time, which significantly accelerates the efforts to eliminate the crisis of viral hepatitis.
2.Discovery of orally active and serine-targeting covalent inhibitors against hCES2A for ameliorating irinotecan-triggered gut toxicity.
Ya ZHANG ; Yufan FAN ; Yunqing SONG ; Guanghao ZHU ; Xinjuan LI ; Jian HUANG ; Xinrui GUO ; Changhai LUAN ; Dongning KANG ; Lu CHEN ; Zhangping XIAO ; Zhaobin GUO ; Hairong ZENG ; Dapeng CHEN ; Zhipei SANG ; Guangbo GE
Acta Pharmaceutica Sinica B 2025;15(10):5312-5326
Human carboxylesterase 2A (hCES2A) plays pivotal roles in prodrug activation and hydrolytic metabolism of ester-bearing chemicals. Targeted inhibition of intestinal hCES2A represents a feasible strategy to mitigate irinotecan-triggered gut toxicity (ITGT), but the orally active, selective, and efficacious hCES2A inhibitors are rarely reported. Here, a novel drug-like hCES2A inhibitor was developed via three rounds of structure-based drug design (SBDD) and structural optimization. Initially, donepezil was identified as a moderate hCES2A inhibitor from 2000 US Food and Drug Administration (FDA)-approved drugs. Following two rounds of SBDD and structural optimization, a donepezil derivative (B7) was identified as a strong reversible hCES2A inhibitor. Subsequently, nine B7 carbamates were rationally designed, synthesized and biologically assayed. Among all synthesized carbamates, C3 showed the most potent time-dependent inhibition on hCES2A (IC50 = 0.56 nmol/L), excellent specificity and favorable drug-like properties. C3 could covalently modify the catalytic serine of hCES2A with high selectivity, while this agent also showed favorable safety profiles, high intestinal exposure, and impressive effects for ameliorating ITGT in both human intestinal organoids and tumor-bearing mice. Collectively, this study showcases a rational strategy for developing drug-like and serine-targeting covalent inhibitors against target serine hydrolase(s), while C3 emerges as a promising orally active drug candidate for ameliorating ITGT.
3.Pharmacological modulation of mitochondrial function as novel strategies for treating intestinal inflammatory diseases and colorectal cancer.
Boya WANG ; Xinrui GUO ; Lanhui QIN ; Liheng HE ; Jingnan LI ; Xudong JIN ; Dapeng CHEN ; Guangbo GE
Journal of Pharmaceutical Analysis 2025;15(4):101074-101074
Inflammatory bowel disease (IBD) is a chronic and recurrent intestinal disease, and has become a major global health issue. Individuals with IBD face an elevated risk of developing colorectal cancer (CRC), and recent studies have indicated that mitochondrial dysfunction plays a pivotal role in the pathogenesis of both IBD and CRC. This review covers the pathogenesis of IBD and CRC, focusing on mitochondrial dysfunction, and explores pharmacological targets and strategies for addressing both conditions by modulating mitochondrial function. Additionally, recent advancements in the pharmacological modulation of mitochondrial dysfunction for treating IBD and CRC, encompassing mitochondrial damage, release of mitochondrial DNA (mtDNA), and impairment of mitophagy, are thoroughly summarized. The review also provides a systematic overview of natural compounds (such as flavonoids, alkaloids, and diterpenoids), Chinese medicines, and intestinal microbiota, which can alleviate IBD and attenuate the progression of CRC by modulating mitochondrial function. In the future, it will be imperative to develop more practical methodologies for real-time monitoring and accurate detection of mitochondrial function, which will greatly aid scientists in identifying more effective agents for treating IBD and CRC through modulation of mitochondrial function.
4.Signatures of proteomics and glycoproteomics revealed liraglutide ameliorates MASLD by regulating specific metabolic homeostasis in mice.
Yuxuan CHEN ; Chendong LIU ; Qian YANG ; Jingtao YANG ; He ZHANG ; Yong ZHANG ; Yanruyu FENG ; Jiaqi LIU ; Lian LI ; Dapeng LI
Journal of Pharmaceutical Analysis 2025;15(11):101273-101273
Liraglutide (Lira), a glucagon-like peptide-1 (GLP-1) receptor agonist approved for diabetes and obesity, has shown significant potential in treating metabolic dysfunction-associated steatotic liver disease (MASLD). However, its systematic molecular regulation and mechanisms remain underexplored. In this study, a mouse model of MASLD was developed using a high-fat diet (HFD), followed by Lira administration. Proteomics and glycoproteomics were analyzed using label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS), while potential molecular target analysis was conducted via quantitative real-time polymerase chain reaction (qPCR) and Western blotting. Our results revealed that Lira treatment significantly reduced liver weight and serum markers, including alanine aminotransferase (ALT) and others, with glycosylation changes playing a more significant role than overall protein expression. The glycoproteome identified 255 independent glycosylation sites, emphasizing the impact of Lira on amino acid, carbohydrate metabolism, and ferroptosis. Simultaneously, proteomic analysis highlighted its effects on lipid metabolism and fibrosis pathways. 21 signature molecules, including 7 proteins and 14 N-glycosylation sites (N-glycosites), were identified as potential targets. A Lira hydrogel formulation (Lira@fibrin (Fib) Gel) was developed to extend drug dosing intervals, offering enhanced therapeutic efficacy in managing chronic metabolic diseases. Our study demonstrated the importance of glycosylation regulation in the therapeutic effects of Lira on MASLD, identifying potential molecular targets and advancing its clinical application for MASLD treatment.
5.Study on the expression and prognostic value of uncoupling protein 2 and ubiquitin associated protein 2-like in non-small cell lung cancer
Ran AN ; Wei LIU ; Le SUN ; Dapeng ZHOU ; Xue LI
International Journal of Laboratory Medicine 2025;46(13):1542-1547
Objective To investigate the expression and prognostic value of uncoupling protein 2(UCP2)and ubiquitin associated protein 2-like(UBAP2L)in non-small cell lung cancer(NSCLC).Methods A total of 94 patients with NSCLC who received surgical treatment in a hospital from March 2019 to March 2021 were selected as the study objects.The expressions of UCP2 protein,UBAP2L protein,UCP2 mRNA and UBAP2L mRNA in cancer tissues and adjacent tissues of NSCLC patients were detected by real-time fluorescence quan-titative polymerase chain reaction and immunohistochemistry.The correlation between UCP2 mRNA and UBAP2L mRNA in NSCLC was analyzed by Pearson correlation.Kaplan-Meier curve was used to analyze the differences in survival rates of NSCLC patients with different UCP2 mRNA and UBAP2L mRNA expres-sions,and multivariate Cox regression was used to analyze the prognostic factors of NSCLC patients.Results The positive rate of UCP2 protein and UBAP2L protein in cancer tissues of NSCLC patients was higher than that in adjacent tissues,and the difference was statistically significant(P<0.05).The expressions of UCP2 mRNA and UBAP2L mRNA in cancer tissues of NSCLC patients were significantly higher than those in adjacent tissues,and the differences were statistically significant(P<0.05).There was a positive cor-relation between UCP2 mRNA and UBAP2L mRNA expression in NSCLC patients(r=0.721,P<0.001).The expression of UCP2 mRNA and UBAP2L mRNA in cancer tissues of NSCLC patients was related to TNM stage and lymph node metastasis.There was significant difference in 3-year survival rate between UCP2 mRNA high expression group and UCP2 mRNA low expression group(P<0.05).There was significant difference in 3-year survival rate between UBAP2L mRNA high expression group and UBAP2L mRNA low expression group(P<0.05).TNM stage Ⅲ A,lymph node metastasis,UCP2 mRNA high expression and UBAP2L mRNA high expression were risk factors for prognosis of NSCLC patients(P<0.05).Conclusion UCP2 protein,UBAP2L protein,UCP2 mRNA and UBAP2L mRNA are up-regulated in NSCLC patients,and UCP2 mRNA and UBAP2L mRNA are helpful to evaluate the survival prognosis of NSCLC patients.
6.The application of Doppler Ultrasound in the perioperative evaluation of patients with Moyamoya Disease
Dapeng DAI ; Hongwei ZHANG ; Aimin LI
International Journal of Cerebrovascular Diseases 2025;33(3):224-228
Moyamoya disease (MMD) is a chronic progressive cerebrovascular disease, and extracranial-intracranial revascularization is the most commonly treatment for MMD. With the continuous development of imaging techniques, the perioperative monitoring methods for MMD patients have gradually become more diverse. However, Doppler ultrasound still holds an important position due to its convenience and non-invasiveness. This article reviews the role of Doppler ultrasound in the perioperative assessment of patients with MMD.
7.Imaging predictors for hematoma expansion in patients with spontaneous intracerebral hemorrhage
Yuxian JIN ; Dapeng DAI ; Aimin LI
International Journal of Cerebrovascular Diseases 2025;33(7):539-544
Hematoma expansion (HE) in patients with spontaneous intracerebral hemorrhage (sICH) is often associated with neurological deterioration and poor prognosis. Early and accurate identification of patients at high risk for HE is crucial for guiding clinical practice. This article summarizes the imaging predictors for HE in patients with sICH, primarily focusing on non-enhanced CT and CT angiography, and briefly introduces various prediction models based on imaging features, in order to provide references for the clinical diagnosis and treatment of sICH.
8.Application progress of deep learning in chest low-dose computed tomography image denoising
Yunjian WU ; Dapeng YAO ; Ping GONG ; Xiaofeng LI
International Journal of Biomedical Engineering 2025;48(5):501-506
Chest low-dose computed tomography (LDCT) is a widely utilized modality for lung cancer screening and follow-up in high-risk populations, owing to its low radiation dose. However, the diagnostic accuracy of LDCT is significantly constrained by inherent limitations, including elevated image noise and reduced contrast resolution. The potential for deep learning technologies to address these challenges through data-driven LDCT image denoising approaches has been demonstrated. In this review, the advantages and limitations of deep learning models were introduced, including supervised, unsupervised, and self-supervised learning. The potential and challenges of these models in clinical applications were analyzed, thereby providing a reference for subsequent research and clinical practice.
9.Mendelian randomization and bioinformatics analysis of the disulfidoptosis core gene SLC7A11 in clear cell renal cell carcinoma
Zifeng LI ; Bohong CHEN ; Haoxiang HUANG ; Cong FENG ; Jin ZENG ; Wei CHEN ; Dapeng WU
Journal of Modern Urology 2024;29(5):459-465,475
Objective To investigate the role of solute carrier family 7 member 11(SLC7A11)in the pathogenesis and progression of clear cell renal cell carcinoma(ccRCC)and its prognostic significance.Methods Mendelian randomization analysis was employed to identify genes causally associated with the risk of ccRCC.The expression patterns and prognostic relevance of SLC7A11 were assessed using RNA sequencing data and clinical information obtained from the UCSC Xcna pan-cancer cohort.Gene set enrichment analysis(GSEA)was conducted using data from The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma(TCGA-KIRC)dataset(training set).A prognostic model based on SLC7A11 was then developed using stepwise Cox regression and validated externally in the E-MTAB-1980 cohort(validation set).Results Elevated level of SLC7A11 was associated with an increased risk of ccRCC(HR=1.27,95%CI:1.15-1.40,P<0.001).SLC7A11 was overexpressed in various tumors and correlated with higher T stage and poorer survival(P<0.05).GSEA demonstrated that SLC7A11 was enriched in pathways related to proliferation and metastasis,including E2F and epithelial-to-mesenchymal transition signaling pathways.Moreover,the SLC7A11 prognostic model exhibited robust predictive performance in both the training set(1-,3-,and 5-year AUC=0.78,0.73,0.71,respectively)and the external validation set(1-,3-,and 5-year AUC=0.70,0.71,0.72,respectively).Conclusion SLC7A11 can be a potential biomarker and therapeutic target for ccRCC,offering novel perspectives for precision medicine.
10.Comparing the prognostic value of 3 diagnostic criteria of bronchopulmonary dysplasia in preterm infants
Xin WANG ; Jing GUO ; Yanyan WU ; Yangke LU ; Dapeng LIU ; Mingchao LI ; Rui LI ; Yingyuan WANG ; Wenqing KANG
Chinese Journal of Pediatrics 2024;62(1):36-42
Objective:To compare the prognostic value of 3 diagnostic criteria of bronchopulmonary dysplasia (BPD) in preterm infants with gestational age<32 weeks.Methods:The retrospective cohort study was conducted to collect the clinical data of 285 preterm infants with BPD admitted to the Department of Neonatology, Children′s Hospital Affiliated to Zhengzhou University from January 2019 to September 2021, who were followed up regularly after discharge. The primary composite adverse outcome was defined as death or severe respiratory morbidity from 36 weeks of corrected gestational age to 18 months of corrected age, and the secondary composite adverse outcome was defined as death or neurodevelopmental impairment. According to the primary or secondary composite adverse outcomes, the preterm infants were divided into the adverse prognosis group and the non-adverse prognosis group. The 2001 National Institute of Child Health and Human Development (NICHD) criteria, 2018 NICHD criteria, and 2019 Neonatal Research Network (NRN) criteria were used to diagnose and grade BPD in preterm infants. Chi-square test, Logistic regression analysis, receiver operating characteristic (ROC) curve and Delong test were used to analyze the prognostic value of the 3 diagnostic criteria.Results:The 285 preterm infants had a gestational age of 29.4 (28.1, 30.6) weeks and birth weight of 1 230 (1 000, 1 465) g, including 167 males (58.6%). Among 285 premature infants who completed follow-up, the primary composite adverse outcome occurred in 124 preterm infants (43.5%), and the secondary composite adverse outcome occurred in 40 preterm infants (14.0%). Multivariate Logistic regression analysis showed that severe BPD according to the 2001 NICHD criteria, gradeⅡand Ⅲ BPD according to the 2018 NICHD criteria and grade 2 and 3 BPD according to the 2019 NRN criteria were all risk factors for primary composite adverse outcomes (all P<0.05). ROC curve showed that the area under the curve (AUC) of the 2018 NICHD criteria and 2019 NRN criteria were both higher than that of the 2001 NICHD criteria (0.70 and 0.70 vs. 0.61, Z=4.49 and 3.35, both P<0.001), but there was no significant difference between the 2018 NICHD and 2019 NRN criteria ( Z=0.38, P=0.702). Multivariate Logistic regression analysis showed that the secondary composite adverse outcomes were all associated with grade Ⅲ BPD according to the 2018 NICHD criteria and grade 3 BPD according to the 2019 NRN criteria (both P<0.05). ROC curve showed that the AUC of the 2018 NICHD criteria and 2019 NRN criteria were both higher than that of the 2001 NICHD criteria (0.71 and 0.71 vs. 0.58, Z=2.93 and 3.67, both P<0.001), but there was no statistically significant difference between the 2018 NICHD and 2019 NRN criteria ( Z=0.02, P=0.984). Conclusion:The 2018 NICHD and 2019 NRN criteria demonstrate good and comparable predictive value for the primary and secondary composite adverse outcomes in preterm infants with BPD, surpassing the predictive efficacy of the 2001 NICHD criteria.

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