1.The regulatory role of tissue-resident memory T cells in chronic liver diseases and associated therapeutic targets
Jin LIN ; Yu ZENG ; Zhanfei TIAN ; Xiaoli FAN
Journal of Clinical Hepatology 2025;41(5):975-982
Tissue-resident memory T cells (TRM cells) are a subset of memory T cells that reside in tissues, exhibit tissue specificity, and do not recirculate. When potential hazards threaten the liver, such as pathogen invasion (bacteria, viruses, etc.) and excessive autoimmune responses, TRM cells are essential as the first line of immune defense, playing an important role in viral hepatitis, autoimmune liver disease, metabolic dysfunction-associated fatty liver disease, liver cirrhosis, and liver transplantation. Here, we present the immunophenotypes of TRM cells in the liver and their surface markers and transcriptional profiles, aiming to clarify the role of TRM cells in chronic liver diseases and explore their potential function as therapeutic targets in immunotherapy.
2.Discovery of a potential hematologic malignancies therapy: Selective and potent HDAC7 PROTAC degrader targeting non-enzymatic function.
Yuheng JIN ; Xuxin QI ; Xiaoli YU ; Xirui CHENG ; Boya CHEN ; Mingfei WU ; Jingyu ZHANG ; Hao YIN ; Yang LU ; Yihui ZHOU ; Ao PANG ; Yushen LIN ; Li JIANG ; Qiuqiu SHI ; Shuangshuang GENG ; Yubo ZHOU ; Xiaojun YAO ; Linjie LI ; Haiting DUAN ; Jinxin CHE ; Ji CAO ; Qiaojun HE ; Xiaowu DONG
Acta Pharmaceutica Sinica B 2025;15(3):1659-1679
HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.
3.Expert consensus on pulpotomy in the management of mature permanent teeth with pulpitis.
Lu ZHANG ; Chen LIN ; Zhuo CHEN ; Lin YUE ; Qing YU ; Benxiang HOU ; Junqi LING ; Jingping LIANG ; Xi WEI ; Wenxia CHEN ; Lihong QIU ; Jiyao LI ; Yumei NIU ; Zhengmei LIN ; Lei CHENG ; Wenxi HE ; Xiaoyan WANG ; Dingming HUANG ; Zhengwei HUANG ; Weidong NIU ; Qi ZHANG ; Chen ZHANG ; Deqin YANG ; Jinhua YU ; Jin ZHAO ; Yihuai PAN ; Jingzhi MA ; Shuli DENG ; Xiaoli XIE ; Xiuping MENG ; Jian YANG ; Xuedong ZHOU ; Zhi CHEN
International Journal of Oral Science 2025;17(1):4-4
Pulpotomy, which belongs to vital pulp therapy, has become a strategy for managing pulpitis in recent decades. This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing long-term patient-centered outcomes. Pulpotomy is categorized into partial pulpotomy (PP), the removal of a partial segment of the coronal pulp tissue, and full pulpotomy (FP), the removal of whole coronal pulp, which is followed by applying the biomaterials onto the remaining pulp tissue and ultimately restoring the tooth. Procedural decisions for the amount of pulp tissue removal or retention depend on the diagnostic of pulp vitality, the overall treatment plan, the patient's general health status, and pulp inflammation reassessment during operation. This statement represents the consensus of an expert committee convened by the Society of Cariology and Endodontics, Chinese Stomatological Association. It addresses the current evidence to support the application of pulpotomy as a potential alternative to root canal treatment (RCT) on mature permanent teeth with pulpitis from a biological basis, the development of capping biomaterial, and the diagnostic considerations to evidence-based medicine. This expert statement intends to provide a clinical protocol of pulpotomy, which facilitates practitioners in choosing the optimal procedure and increasing their confidence in this rapidly evolving field.
Humans
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Calcium Compounds/therapeutic use*
;
Consensus
;
Dental Pulp
;
Dentition, Permanent
;
Oxides/therapeutic use*
;
Pulpitis/therapy*
;
Pulpotomy/standards*
4.Expert consensus on intentional tooth replantation.
Zhengmei LIN ; Dingming HUANG ; Shuheng HUANG ; Zhi CHEN ; Qing YU ; Benxiang HOU ; Lihong QIU ; Wenxia CHEN ; Jiyao LI ; Xiaoyan WANG ; Zhengwei HUANG ; Jinhua YU ; Jin ZHAO ; Yihuai PAN ; Shuang PAN ; Deqin YANG ; Weidong NIU ; Qi ZHANG ; Shuli DENG ; Jingzhi MA ; Xiuping MENG ; Jian YANG ; Jiayuan WU ; Lan ZHANG ; Jin ZHANG ; Xiaoli XIE ; Jinpu CHU ; Kehua QUE ; Xuejun GE ; Xiaojing HUANG ; Zhe MA ; Lin YUE ; Xuedong ZHOU ; Junqi LING
International Journal of Oral Science 2025;17(1):16-16
Intentional tooth replantation (ITR) is an advanced treatment modality and the procedure of last resort for preserving teeth with inaccessible endodontic or resorptive lesions. ITR is defined as the deliberate extraction of a tooth; evaluation of the root surface, endodontic manipulation, and repair; and placement of the tooth back into its original socket. Case reports, case series, cohort studies, and randomized controlled trials have demonstrated the efficacy of ITR in the retention of natural teeth that are untreatable or difficult to manage with root canal treatment or endodontic microsurgery. However, variations in clinical protocols for ITR exist due to the empirical nature of the original protocols and rapid advancements in the field of oral biology and dental materials. This heterogeneity in protocols may cause confusion among dental practitioners; therefore, guidelines and considerations for ITR should be explicated. This expert consensus discusses the biological foundation of ITR, the available clinical protocols and current status of ITR in treating teeth with refractory apical periodontitis or anatomical aberration, and the main complications of this treatment, aiming to refine the clinical management of ITR in accordance with the progress of basic research and clinical studies; the findings suggest that ITR may become a more consistent evidence-based option in dental treatment.
Humans
;
Tooth Replantation/methods*
;
Consensus
;
Periapical Periodontitis/surgery*
5.Prognostic value of peripheral blood NLR and TrxR expression in ovarian cancer patients receiving immunotherapy
Qiumei JIN ; Xiaoli CAO ; Yifeng GU ; Xiaoxia ZHANG ; Yujie LI
International Journal of Laboratory Medicine 2025;46(6):714-718
Objective To investigate the prognostic value of peripheral blood neutrophil-lymphocyte ratio(NLR)and thioredoxin reductase(TrxR)in patients with ovarian cancer receiving immunotherapy.Methods A total of 109 patients with advanced ovarian cancer treated in the Tumor Hospital Affiliated to Nantong University from January 2021 to December 2021 were selected as the research objects.The levels of NLR and TrxR in peripheral blood before immunotherapy were detected,and the evaluation value of NLR and TrxR on short-term efficacy,progression-free survival(PFS)and overall survival(OS)in ovarian cancer pa-tients receiving immunotherapy was explored.Results The optimal cut-off values of TrxR and NLR were 4.97 U/mL and 2.49%,respectively.According to the optimal cut-off value of TrxR and NLR,the patients were divided into the high level of TrxR group(69 cases,≥4.97 U/mL)and the low level of TrxR group(40 cases,<4.97 U/mL),the high level of NLR group(72 cases,≥2.49%)and the low level of NLR group(37 cases,<2.49%).The objective response rate(ORR)of the high level of NLR group was lower than that of the low level NLR group(P<0.05),and the disease progression rate(DPR)was higher than that of the low NLR group(P<0.05).The high level of TrxR group had a significantly lower ORR and a significantly higher DPR than the low level of TrxR group(P<0.05).The median PFS and OS of the high level of NLR group were 15.0 months and 16.0 months,respectively.The median PFS and OS of the low level of NLR group were 19.0 months and 21.0 months,respectively.The median PFS and OS of the high level of TrxR group were 15.0 months and 17.0 months,respectively.The median PFS was 18.0 months and the median OS was 21.0 months in the low level of TrxR group.NLR and TrxR were the influencing factors of PFS and OS in pa-tients with ovarian cancer immunotherapy(P<0.05).Conclusion The levels of NLR and TrxR in peripheral blood can be used as important prognostic indicators for advanced ovarian cancer patients receiving immuno-therapy.The lower the levels of NLR and TrxR,the better the prognosis of ovarian cancer patients.
7.Progress in quality management and control of donor organ procurement in foreign countries
Lyu JIN ; Xiaoli FAN ; Qifa YE
Organ Transplantation 2024;15(2):191-199
Since the 20th century, organ transplantation has become a breakthrough technology to effectively save the lives of patients with end-stage organ failure, which has significantly enhanced the quality of life of patients. Organ donation is an important source of organ transplantation. Improving the quality of donor organ procurement is the key to promote the translation of donor organs and improve the prognosis of organ transplantation recipients. The United States, Spain and other countries have put forward a series of policies and standards in the quality management and control of donor organ procurement and achieved positive results. In this article, related concepts of medical quality management and control, advanced strategies and models of international donor organ procurement quality management, and quality control measures of Organ Procurement Organization, donors and donor organs were reviewed, aiming to provide reference for establishing a quality management and control system of donor organs with "Chinese characteristics" and advancing high-speed and high-quality development of donor organ procurement.
8.Influencing factors for the prognosis of patients with drug-induced liver injury and establishment of a nomogram model
Shimei WANG ; Shuai JIN ; Junru LI ; Na WANG ; Yan CHEN ; Ying CUI ; Mingming MA ; Xiaoli HU
Journal of Clinical Hepatology 2024;40(3):562-567
ObjectiveTo investigate the influencing factors for the clinical outcome of patients with drug-induced liver injury (DILI), and to establish a nomogram prediction model for validation. MethodsA retrospective analysis was performed for the general information and laboratory data of 188 patients with DILI who were admitted to Heilongjiang Provincial Hospital Affiliated to Harbin Institute of Technology from January 2017 to December 2022, and according to their clinical outcome, they were divided into good outcome group with 146 patients and poor outcome group with 42 patients. The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. Univariate and multivariate Logistic regression analyses were used to investigate the independent influencing factors for the clinical outcome of DILI patients. R Studio 4.1.2 software was used to establish a nomogram model, and calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to perform internal validation. ResultsThe univariate Logistic regression analysis showed that liver biopsy for the diagnosis of DILI, platelet count, cholinesterase, albumin, prothrombin time activity, IgM, and IgG were associated with adverse outcomes in patients with DILI. The multivariate Logistic regression analysis showed that liver biopsy for the diagnosis of DILI (odds ratio [OR]=0.072, 95% confidence interval [CI]: 0.022 — 0.213, P<0.001), clinical classification (OR=0.463, 95%CI: 0.213 — 0.926, P=0.039), alanine aminotransferase (OR=0.999, 95%CI: 0.998 — 1.000, P=0.025), prothrombin time activity (OR=0.973, 95%CI: 0.952 — 0.993, P=0.011), and IgM (OR=1.456, 95%CI: 1.082 — 2.021, P=0.015) were independent influencing factors for clinical outcome in patients with DILI. The nomogram prediction model was established, and after validation, the calibration curve was close to the reference curve. The area under the ROC curve was 0.829, and the DCA curve showed that the model had good net clinical benefit. ConclusionThe nomogram prediction model established in this study has good clinical calibration, discriminative ability, and application value in evaluating the clinical outcome of patients with DILI.
9.Analysis of Cardiac Reverse Remodeling After Transcatheter Edge-to-edge Repair of Mitral Regurgitation due to Various Etiologies and Experience of Echocardiography Application
Zhiling LUO ; Xiaoli DONG ; Qiuzhe GUO ; Yuanzheng WANG ; Jin LI ; Yunfei ZHOU ; Shuanglan YU ; Da ZHU ; Shouzheng WANG ; Xiangbin PAN
Chinese Circulation Journal 2024;39(3):234-241
Objectives:To evaluate the valvular and cardiac function,cardiac reverse remodeling at 6-month after transcatheter edge-to-edge repair(TEER)for patients with functional and degenerative mitral valve regurgitation,and summarize the experience of echocardiography application. Methods:The clinical data of 93 patients with moderate to severe mitral regurgitation(MR)treated with TEER and completed 6-month follow-up in Yunnan Fuwai Cardiovascular Hospital from July 2022 to February 2023 were retrospectively analyzed.Patients were divided into functional mitral regurgitation(FMR)and degenerative mitral regurgitation(DMR)groups according to MR etiology.The valve characteristic parameters,as well as valvular function,chamber volume and cardiac functional parameters before and at 6 months after operation were compared.The key points of echocardiography application were summarized. Results:Among all patients,71 were FMR and 22 were DMR.There were differences in valve structure between the two groups.Mitral TEER were successfully accomplished and all patients completed 6-month follow-up.The key points of echocardiography application included:valve structure analysis,atrial septal puncture location,device delivery process monitoring and image optimization during clamping process.The mitral regurgitation grade and NYHA grade were significantly improved in all patients at 6 months after TEER(P<0.05),and the mean mitral valve pressure gradient was higher than that before operation(P<0.05).Left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV)and left atrial volume index in FMR group were significantly decreased(P<0.05),while left ventricular and left atrial volume in DMR group remained unchanged(P>0.05).There were no significant changes in left ventricular ejection fraction and left ventricular global strain in both groups during the observation period(P>0.05).The changes of LVEDV and LVESV before and after operation were more significant in FMR group than those in DMR group(P<0.05). Conclusions:Mitral TEER can reduce the degree of regurgitation and improve cardiac function in the early postoperative period for moderate and severe MR patients with different etiologies.There are differences in preoperative valve structure and postoperative cardiac reverse remodeling between FMR and DMR patients.Echocardiography is an important imaging technique for the evaluation and monitoring process before,during and post mitral TEER.
10.Value of ultrasound gray ratio analysis in monitoring intracranial basal ganglia of neonates with hyperbilirubinemia
Wei FENG ; Jin YAN ; Xiaoli YI ; Ya MA
Chinese Journal of Ultrasonography 2024;33(3):247-251
Objective:To investigate the value of cranial ultrasound (CUS) globus pallidus to putamen gray ratio(G/P) in monitoring basal ganglia of neonatal hyperbilirubinemia.Methods:A retrospective analysis was performed on the CUS, magnetic resonance imaging (MRI, 46 cases) and clinical data of 69 neonates hospitalized in the Department of Neonatology of Children′s Hospital Affiliated to Capital Institute of Pediatrics from June 2022 to June 2023. UpToDate calculator was used to calculate the reference thresholds of phototherapy for each child, combined with the 342 μmol/L node value, the children were divided into control group, mild to moderate hyperbilirubinemia group and severe hyperbilirubinemia group; RadiAnt DICOM Viewer software was used to measure the ultrasound gray values of bilateral globus pallidus and putamen, and the ratio CUS (G/P) was calculated; MRI post-processing workstation was used to read T1 signal values of bilateral globus pallidus and putamen, and the ratio MRI (G/P) was calculated. The correlations between CUS (G/P) and total serum bilirubin (TSB)/ phototherapy threshold and TSB/ albumin ratio were analyzed; the consistency of CUS (G/P) and MRI (G/P) was analyzed; the difference of CUS (G/P) among control group, light-moderate hyperbilirubinemia group and severe hyperbilirubinemia group was compared.Results:①CUS (G/P) was positively correlated with TSB/ phototherapy threshold and TSB/albumin ( rs=0.721, 0.600, all P<0.001). ②CUS (G/P) value was consistent with MRI (G/P) value (τ=0.743, P<0.05). ③CUS(G/P) value increased sequentially in the control group, mild-moderate hyperbilirubinemia group, and severe hyperbilirubinemia group, and the differences between each two groups were statistically significant (all P<0.05). Conclusions:CUS (G/P) has dose-response relationship with TSB, diagnostic agreement with MRI (G/P) value, and shows differences in different levels of bilirubin, and can be used to monitor intracranial basal ganglia in neonatal hyperbilirubinemia.

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