1.N 6-Methyladenosine modification of circDcbld2 in Kupffer cells promotes hepatic fibrosis via targeting miR-144-3p/Et-1 axis.
Sai ZHU ; Xin CHEN ; Lijiao SUN ; Xiaofeng LI ; Yu CHEN ; Liangyun LI ; Xiaoguo SUO ; Chuanhui XU ; Minglu JI ; Jianan WANG ; Hua WANG ; Lei ZHANG ; Xiaoming MENG ; Cheng HUANG ; Jun LI
Acta Pharmaceutica Sinica B 2025;15(1):296-313
Kupffer cells (KCs), as residents and sentinels of the liver, are involved in the formation of hepatic fibrosis (HF). However, the biological functions of circular RNAs (circRNAs) in KCs to HF have not been determined. In this study, the expression levels of circRNAs, microRNAs, and messenger RNAs (mRNAs) in KCs from a mouse model of HF mice were investigated using microarray and circRNA-Seq analyses. circDcbld2 was identified as a candidate circRNA in HF, as evidenced by its up-regulation in KCs. Silver staining and mass spectrometry showed that Wtap and Igf2bp2 bind to cirDcbld2. The suppression of circDcbld2 expression decreased the KC inflammatory response and oxidative stress and inhibited hepatic stellate cell (HSCs) activation, attenuating mouse liver fibrogenesis. Mechanistically, Wtap mediated the N 6-methyladenosine (m6A) methylation of circDcbld2, and Igf2bp2 recognized m6A-modified circDcbld2 and increased its stability. circDcbld2 contributes to the occurrence of HF by binding miR-144-3p/Et-1 to regulate the inflammatory response and oxidative stress. These findings indicate that circDcbld2 functions via the m6A/circDcbld2/miR-144-3p/Et-1 axis and may act as a potential biomarker for HF treatment.
2.The PGAM5-NEK7 interaction is a therapeutic target for NLRP3 inflammasome activation in colitis.
Cheng-Long GAO ; Jinqian SONG ; Haojie WANG ; Qinghong SHANG ; Xin GUAN ; Gang XU ; Jiayang WU ; Dalei WU ; Yueqin ZHENG ; Xudong WU ; Feng ZHAO ; Xindong LIU ; Lei SHI ; Tao PANG
Acta Pharmaceutica Sinica B 2025;15(1):349-370
The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.
3.Obesity-driven oleoylcarnitine accumulation in tumor microenvironment promotes breast cancer metastasis-like phenotype.
Chao CHEN ; Hongxia ZHANG ; Lingling QI ; Haoqi LEI ; Xuefei FENG ; Yingjie CHEN ; Yuanyuan CHENG ; Defeng PANG ; Jufeng WAN ; Haiying XU ; Shifeng CAO ; Baofeng YANG ; Yan ZHANG ; Xin ZHAO
Acta Pharmaceutica Sinica B 2025;15(4):1974-1990
Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.
4.Anatomical Importance Between Neural Structure and Bony Landmark in Neuroventral Decompression for Posterior Endoscopic Cervical Discectomy
Xin WANG ; Tao HU ; Chaofan QIN ; Bo LEI ; Mingxin CHEN ; Ke MA ; Qingyan LONG ; Qingshuai YU ; Si CHENG ; Zhengjian YAN
Neurospine 2025;22(1):286-296
Objective:
This study aims to investigate the anatomical relationship among the nerve roots, intervertebral space, pedicles, and intradural rootlets of the cervical spine for improving operative outcomes and exploring neuroventral decompression approach in posterior endoscopic cervical discectomy (PECD).
Methods:
Cervical computed tomography myelography imaging data from January 2021 to May 2023 were collected, and the RadiAnt DICOM Viewer Software was employed to conduct multiplane reconstruction. The following parameters were recorded: width of nerve root (WN), nerve root-superior pedicle distance (NSPD), nerve root-inferior pedicle distance (NIPD), and the relationship between the intervertebral space and the nerve root (shoulder, anterior, and axillary). Additionally, the descending angles between the spinal cord and the ventral (VRA) and dorsal (DRA) rootlets were measured.
Results:
The WN showed a gradual increase from C4 to C7, with measurements notably larger in men compared to women. The NSPD decreased gradually from the C2–3 to the C5–6 levels. However, the NIPD showed an opposite level-related change, notably larger than the NSPD at the C4–5, C5–6, and C7–T1 levels. Furthermore, significant differences in NIPD were observed between different age groups and genders. The incidence of the anterior type exhibited a gradual decrease from the C2–3 to the C5–6 levels. Conversely, the axillary type exhibited an opposite level-related change. Additionally, the VRA and DRA decreased as the level descended, with measurements significantly larger in females.
Conclusion
A prediction of the positional relationship between the intervertebral space and the nerve root is essential for the direct neuroventral decompression in PECD to avoid damaging the neural structures. The axillary route of the nerve root offers a safer and more effective pathway for performing direct neuroventral decompression compared to the shoulder approach.
5.Decision-making behavior in patients with depressive disorder and its relationship with depressive and anxiety symptoms
Yuxiang WANG ; Luoya ZHANG ; Maomao ZHANG ; Juan DENG ; Yanjie PENG ; Xiaotong CHENG ; Kezhi LIU ; Wei LEI ; Jing CHEN
Sichuan Mental Health 2025;38(1):22-27
BackgroundPatients with depressive disorder often exhibit impaired decision-making functions. However, the relationship between decision-making abilities and depressive and anxiety symptoms in these patients remains unclear. ObjectiveTo explore the characteristics of decision-making behavior in patients with depressive disorder, and to analyze its relationship with clinical symptoms. MethodsA total of 48 patients diagnosed with depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) were recruited from the Department of Psychosomatic Medicine of the Affiliated Hospital of Southwest Medical University from October 2020 to May 2023. Concurrently, 52 healthy individuals matched for age and gender were recruited from Luzhou as the control group. Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) were used for assessment, and decision-making behavior was evaluated using Probabilistic Reversal Learning (PRL) task. Indicators assessed included the number of trials to criterion, perseverative errors, win-stay rate and lose-shift rate. Spearman correlation analysis was used to assess the correlation between BDI and BAI scores and PRL task indicators. ResultsThe depression group showed a significantly higher lose-shift rate compared with the control group (t=3.684, P<0.01). There were no statistically significant differences between two groups in trials to criterion, perseverative errors and win-stay rate (t=0.329, 0.132, 0.609, P>0.05). In depression group, BDI and BAI scores were positively correlated with the win-stay rate(r=0.450, 0.398, P<0.01). ConclusionPatients with depressive disorder are more likely to change their decision-making strategies following negative outcomes. Furthermore, the severity of depressive and anxiety symptoms is associated with a greater propensity to maintain existing decisions after receiving positive feedback. [Funded by 2019 Joint Project of Luzhou Science and Technology Bureau-Southwest Medical University (number, 2019LZXNYDJ39]
6.Comprehensive evaluation of benign and malignant pulmonary nodules using combined biological testing and imaging assessment in 1 017 patients: A retrospective cohort study
Lei ZHANG ; Zihao LI ; Nan LI ; Jun CHENG ; Feng ZHANG ; Pinghui XIA ; Wang LÜ ; ; Jian HU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(01):60-66
Objective By combining biological detection and imaging evaluation, a clinical prediction model is constructed based on a large cohort to improve the accuracy of distinguishing between benign and malignant pulmonary nodules. Methods A retrospective analysis was conducted on the clinical data of the 32 627 patients with pulmonary nodules who underwent chest CT and testing for 7 types of lung cancer-related serum autoantibodies (7-AABs) at our hospital from January 2020 to April 2024. The univariate and multivariate logistic regression models were performed to screen independent risk factors for benign and malignant pulmonary nodules, based on which a nomogram model was established. The performance of the model was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Results A total of 1 017 patients with pulmonary nodules were included in the study. The training set consisted of 712 patients, including 291 males and 421 females, with a mean age of (58±12) years. The validation set included 305 patients, comprising 129 males and 176 females, with a mean age of (58±13) years. Univariate ROC curve analysis indicated that the combination of CT and 7-AABs testing achieved the highest area under the curve (AUC) value (0.794), surpassing the diagnostic efficacy of CT alone (AUC=0.667) or 7-AABs alone (AUC=0.514). Multivariate logistic regression analysis showed that radiological nodule diameter, nodule nature, and CT combined with 7-AABs detection were independent predictors, which were used to construct a nomogram prediction model. The AUC values for this model were 0.826 and 0.862 in the training and validation sets, respectively, demonstrating excellent performance in DCA. Conclusion The combination of 7-AABs with CT significantly enhances the accuracy of distinguishing between benign and malignant pulmonary nodules. The developed predictive model provides strong support for clinical decision-making and contributes to achieving precise diagnosis and treatment of pulmonary nodules.
7.Research progress on antimicrobial materials modified root canal sealers
MA Jinyi ; LI Bolei ; CHENG Lei
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(3):237-243
Endodontic and periapical lesions are prevalent infectious diseases primarily caused by bacteria and their metabolic byproducts. The most widely used treatment method today is root canal therapy, which aims to remove infectious substances from the root canal. Root canal sealers can fill areas that core filling materials cannot reach, effectively reducing the risk of reinfection through their antimicrobial properties thus improving the success rate of root canal treatment. Various strategies have been employed to enhance the antimicrobial efficacy of root canal sealers through different mechanisms such as mechanical interlocking or chemical bonding. These strategies include antibiotic modification, quaternary ammonium compounds modification, nanoparticle modification, and others. Overall, antimicrobial modification strategies are increasingly diverse, and their effectiveness in enhancing the antimicrobial properties of sealers is beyond doubt. Root canal sealers modified with quaternary ammonium compounds and nanoparticles have shown certain advantages in antibiofilm activity and have potential clinical prospects. However, whether these modified materials have long-term antimicrobial effects, whether they can perform similarly in vivo as they do in vitro, and their biocompatibility are issues that still need to be addressed. In the future, the preparation of root canal sealers with ideal multidimensional properties will require further long-term and in-depth exploration.
8.In Vitro and in vivo Component Identification of Danshenyin Based on UPLC-Q-TOF-MS/MS
Sitong ZHANG ; Xianrun HU ; Wenkang LIU ; Jinchun LEI ; Xuemei CHENG ; Xiaojun WU ; Wansheng CHEN ; Manlin LI ; Changhong WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):175-183
ObjectiveTo elucidate the chemical composition of Danshenyin and its blood components in rats after oral administration. MethodsUltra performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS) coupled with PeakView 1.2 software was used to systematically characterize and identify the components of Danshenyin aqueous extract and its migratory components in rat blood after oral administration based on the retention time, quasi-molecular ion peaks, secondary fragmentation ions, and literature reports, and a preliminary compounds identification of Salviae Miltiorrhizae Radix et Rhizoma aqueous extract, the co-decoction of Santali Albi Lignum and Amomi Fructus was carried out to attribute the chemical constituents of the aqueous extract of Danshenyin. ResultsA total of 73 compounds, including 21 phenolic acids, 23 diterpenes, 6 flavonoids, 7 organic acids, 3 volatile oils and 13 others, were identified from the aqueous extract of Danshenyin. And 36 prototypes and 15 metabolites were identified in rat plasma, the major metabolic pathways included reduction, hydration, hydroxylation, demethylation, methylation, sulfation and others, these metabolites were mainly derived from tanshinones and salvianolic acids. ConclusionThe main blood components of the aqueous extract of Danshenyin are salvianolic acids and tanshinones, which may be the material basis of the efficacy. This study can provide reference for pharmacological research, quality control, and clinical application of Danshenyin.
9.Anatomical Importance Between Neural Structure and Bony Landmark in Neuroventral Decompression for Posterior Endoscopic Cervical Discectomy
Xin WANG ; Tao HU ; Chaofan QIN ; Bo LEI ; Mingxin CHEN ; Ke MA ; Qingyan LONG ; Qingshuai YU ; Si CHENG ; Zhengjian YAN
Neurospine 2025;22(1):286-296
Objective:
This study aims to investigate the anatomical relationship among the nerve roots, intervertebral space, pedicles, and intradural rootlets of the cervical spine for improving operative outcomes and exploring neuroventral decompression approach in posterior endoscopic cervical discectomy (PECD).
Methods:
Cervical computed tomography myelography imaging data from January 2021 to May 2023 were collected, and the RadiAnt DICOM Viewer Software was employed to conduct multiplane reconstruction. The following parameters were recorded: width of nerve root (WN), nerve root-superior pedicle distance (NSPD), nerve root-inferior pedicle distance (NIPD), and the relationship between the intervertebral space and the nerve root (shoulder, anterior, and axillary). Additionally, the descending angles between the spinal cord and the ventral (VRA) and dorsal (DRA) rootlets were measured.
Results:
The WN showed a gradual increase from C4 to C7, with measurements notably larger in men compared to women. The NSPD decreased gradually from the C2–3 to the C5–6 levels. However, the NIPD showed an opposite level-related change, notably larger than the NSPD at the C4–5, C5–6, and C7–T1 levels. Furthermore, significant differences in NIPD were observed between different age groups and genders. The incidence of the anterior type exhibited a gradual decrease from the C2–3 to the C5–6 levels. Conversely, the axillary type exhibited an opposite level-related change. Additionally, the VRA and DRA decreased as the level descended, with measurements significantly larger in females.
Conclusion
A prediction of the positional relationship between the intervertebral space and the nerve root is essential for the direct neuroventral decompression in PECD to avoid damaging the neural structures. The axillary route of the nerve root offers a safer and more effective pathway for performing direct neuroventral decompression compared to the shoulder approach.
10.Anatomical Importance Between Neural Structure and Bony Landmark in Neuroventral Decompression for Posterior Endoscopic Cervical Discectomy
Xin WANG ; Tao HU ; Chaofan QIN ; Bo LEI ; Mingxin CHEN ; Ke MA ; Qingyan LONG ; Qingshuai YU ; Si CHENG ; Zhengjian YAN
Neurospine 2025;22(1):286-296
Objective:
This study aims to investigate the anatomical relationship among the nerve roots, intervertebral space, pedicles, and intradural rootlets of the cervical spine for improving operative outcomes and exploring neuroventral decompression approach in posterior endoscopic cervical discectomy (PECD).
Methods:
Cervical computed tomography myelography imaging data from January 2021 to May 2023 were collected, and the RadiAnt DICOM Viewer Software was employed to conduct multiplane reconstruction. The following parameters were recorded: width of nerve root (WN), nerve root-superior pedicle distance (NSPD), nerve root-inferior pedicle distance (NIPD), and the relationship between the intervertebral space and the nerve root (shoulder, anterior, and axillary). Additionally, the descending angles between the spinal cord and the ventral (VRA) and dorsal (DRA) rootlets were measured.
Results:
The WN showed a gradual increase from C4 to C7, with measurements notably larger in men compared to women. The NSPD decreased gradually from the C2–3 to the C5–6 levels. However, the NIPD showed an opposite level-related change, notably larger than the NSPD at the C4–5, C5–6, and C7–T1 levels. Furthermore, significant differences in NIPD were observed between different age groups and genders. The incidence of the anterior type exhibited a gradual decrease from the C2–3 to the C5–6 levels. Conversely, the axillary type exhibited an opposite level-related change. Additionally, the VRA and DRA decreased as the level descended, with measurements significantly larger in females.
Conclusion
A prediction of the positional relationship between the intervertebral space and the nerve root is essential for the direct neuroventral decompression in PECD to avoid damaging the neural structures. The axillary route of the nerve root offers a safer and more effective pathway for performing direct neuroventral decompression compared to the shoulder approach.


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