1.Effectiveness and safety of augmentative plating technique in managing nonunion following intramedullary nailing of long bones in the lower extremity: A systematic review and meta-analysis.
Cong-Xiao FU ; Hao GAO ; Jun REN ; Hu WANG ; Shuai-Kun LU ; Guo-Liang WANG ; Zhen-Feng ZHU ; Yun-Yan LIU ; Wen LUO ; Yong ZHANG ; Yun-Fei ZHANG
Chinese Journal of Traumatology 2025;28(3):164-174
PURPOSE:
To methodically assess the effectiveness of augmentative plating (AP) and exchange nailing (EN) in managing nonunion following intramedullary nailing for long bone fractures of the lower extremity.
METHODS:
PubMed, EMBASE, Web of Science, and the Cochrane Library were searched to gather clinical studies regarding the use of AP and EN techniques in the treatment of nonunion following intramedullary nailing of lower extremity long bones. The search was conducted up until May 2023. The original studies underwent an independent assessment of their quality, a process conducted utilizing the Newcastle-Ottawa scale. Data were retrieved from these studies, and meta-analysis was executed utilizing Review Manager 5.3.
RESULTS:
This meta-analysis included 8 studies involving 661 participants, with 305 in the AP group and 356 in the EN group. The results of the meta-analysis demonstrated that the AP group exhibited a higher rate of union (odds ratio: 8.61, 95% confidence intervals (CI): 4.12 - 17.99, p < 0.001), shorter union time (standardized mean difference (SMD): -1.08, 95% CI: -1.79 - -0.37, p = 0.003), reduced duration of the surgical procedure (SMD: -0.56, 95% CI: -0.93 - -0.19, p = 0.003), less bleeding (SMD: -1.5, 95% CI: -2.81 - -0.18, p = 0.03), and a lower incidence of complications (relative risk: -0.17, 95% CI: -0.27 - -0.06, p = 0.001). In the subgroup analysis, the time for union in the AP group in nonisthmal and isthmal nonunion of lower extremity long bones was shorter compared to the EN group (nonisthmal SMD: -1.94, 95% CI: -3.28 - -0.61, p < 0.001; isthmal SMD: -1.08, 95% CI: -1.64 - -0.52, p = 0.002).
CONCLUSION
In the treatment of nonunion in diaphyseal fractures of the long bones in the lower extremity, the AP approach is superior to EN, both intraoperatively (with reduced duration of the surgical procedure and diminished blood loss) and postoperatively (with an elevated union rate, shorter union time, and lower incidence of complications). Specifically, in the management of nonunion of lower extremity long bones with non-isthmal and isthmal intramedullary nails, AP demonstrated shorter union time in comparison to EN.
Humans
;
Bone Nails/adverse effects*
;
Bone Plates/adverse effects*
;
Femoral Fractures/surgery*
;
Fracture Fixation, Intramedullary/methods*
;
Fractures, Ununited/surgery*
;
Lower Extremity/injuries*
2.Progress in diagnosis and treatment of RAS-related autoimmune lymphoproliferative disorder.
Jia-Ning REN ; Yang WAN ; Xiao-Fan ZHU
Chinese Journal of Contemporary Pediatrics 2025;27(9):1149-1155
RAS-associated autoimmune lymphoproliferative disorder (RALD) is a rare congenital immunodeficiency disorder caused by somatic mutations in NRAS or KRAS. Its main pathological feature is immune dysregulation-induced hematologic destruction, presenting with symptoms resembling autoimmune diseases. RALD exhibits significant clinical heterogeneity, with manifestations including autoimmune phenomena, hepatosplenomegaly, lymphadenopathy, monocytosis, and increased susceptibility to infections. Owing to its rarity and its unclear nature, a standardized therapeutic regimen for RALD is currently lacking. This review summarizes the latest advances in the pathogenesis, clinical manifestations, differential diagnosis, and treatment of RALD, aiming to provide new insights and reference for the understanding and management of this disorder.
Humans
;
Lymphoproliferative Disorders/etiology*
;
Autoimmune Diseases/etiology*
;
Autoimmune Lymphoproliferative Syndrome/genetics*
;
GTP Phosphohydrolases/genetics*
;
Proto-Oncogene Proteins p21(ras)/genetics*
;
Mutation
;
Membrane Proteins
3.Avatrombopag for platelet engraftment after allogeneic hematopoietic stem cell transplantation in children: a retrospective clinical study.
Xin WANG ; Yuan-Yuan REN ; Xia CHEN ; Chao-Qian JIANG ; Ran-Ran ZHANG ; Xiao-Yan ZHANG ; Li-Peng LIU ; Yu-Mei CHEN ; Li ZHANG ; Yao ZOU ; Fang LIU ; Xiao-Juan CHEN ; Wen-Yu YANG ; Xiao-Fan ZHU ; Ye GUO
Chinese Journal of Contemporary Pediatrics 2025;27(10):1233-1239
OBJECTIVES:
To evaluate the efficacy and safety of avatrombopag in promoting platelet engraftment after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children, compared with recombinant human thrombopoietin (rhTPO).
METHODS:
A retrospective analysis was conducted on 53 pediatric patients who underwent allo-HSCT at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences from April 2023 to August 2024. Based on medications used during the periengraftment period, patients were divided into two groups: the avatrombopag group (n=15) and the rhTPO group (n=38).
RESULTS:
At days 14, 30, and 60 post-transplant, platelet engraftment was achieved in 20% (3/15), 60% (9/15), and 93% (14/15) of patients in the avatrombopag group, and in 39% (15/38), 82% (31/38), and 97% (37/38) in the rhTPO group, respectively. There were no significant differences between the two groups in platelet engraftment rates at each time point, cumulative incidence of platelet engraftment, overall survival, and relapse-free survival (all P>0.05). Multivariable Cox proportional hazards analysis indicated that acute graft-versus-host disease was an independent risk factor for delayed platelet engraftment (P=0.043).
CONCLUSIONS
In children undergoing allo-HSCT, avatrombopag effectively promotes platelet engraftment, with efficacy and safety comparable to rhTPO, and represents a viable therapeutic option.
Humans
;
Retrospective Studies
;
Hematopoietic Stem Cell Transplantation/adverse effects*
;
Male
;
Female
;
Child
;
Child, Preschool
;
Infant
;
Adolescent
;
Transplantation, Homologous
;
Blood Platelets/drug effects*
;
Thiazoles/therapeutic use*
;
Thrombopoietin/therapeutic use*
;
Thiophenes
4.Wip1 Phosphatase Regulates Hematopoietic Function in Mouse Spleen.
Xiao-Ping REN ; Zhi-Lin CHANG ; Yi WANG ; Hui-Min ZHU ; Wen-Yan HE
Journal of Experimental Hematology 2025;33(5):1491-1498
OBJECTIVE:
To investigate the regulatory effect of Wip1 phosphatase on hematopoietic function in the mouse spleen.
METHODS:
Wip1 knockout mice were bred, and the effect of Wip1 deletion on the proportion and number of hematopoietic stem/progenitor cells, as well as their mature subsets in mouse spleen was detected by flow cytometry. The Proteome ProfilerTM antibody array was used to analyze the role of Wip1 deletion on the expression of inflammatory cytokines in CD45highCD11b+ myeloid cells sorted from mouse spleen.
RESULTS:
Wip1 deletion resulted in smaller size and significant reduction of cell number in the mouse spleen. The absolute numbers of hematopoietic stem/progenitor cells were decreased. Meanwhile, the absolute number of T and B lymphocytes also significantly declined. However, the proportion of erythroid progenitors and erythroid cells at various stage significantly increased, but the number of mature erythroid cells decreased. Furthermore, the myeloid cells and their subsets neutrophils, monocytes, CD45highCD11b+ and CD45lowCD11b+ were all reduced. CD45highCD11b+ myeloid cells displayed proinflammatory phenotype in the spleen.
CONCLUSION
Wip1 gene deletion impairs normal hematopoietic function in the mouse spleen, leading to a significant reduction of mature hematopoietic cells of various lineages, and proinflammatory phenotype in CD45highCD11b+ myeloid cells.
Animals
;
Mice
;
Spleen/cytology*
;
Mice, Knockout
;
Hematopoietic Stem Cells/cytology*
;
Myeloid Cells/cytology*
;
Protein Phosphatase 2C
;
Hematopoiesis
;
Flow Cytometry
5.A Novel Model of Traumatic Optic Neuropathy Under Direct Vision Through the Anterior Orbital Approach in Non-human Primates.
Zhi-Qiang XIAO ; Xiu HAN ; Xin REN ; Zeng-Qiang WANG ; Si-Qi CHEN ; Qiao-Feng ZHU ; Hai-Yang CHENG ; Yin-Tian LI ; Dan LIANG ; Xuan-Wei LIANG ; Ying XU ; Hui YANG
Neuroscience Bulletin 2025;41(5):911-916
6.Curcumae Rhizoma: An anti-cancer traditional Chinese medicine.
Yu LUO ; Lin ZHU ; Zhengyu REN ; Jian XIAO ; Erwei HAO ; Jiahong LU ; Jinmin ZHAO ; Chun YAO ; Yitao WANG ; Hua LUO
Chinese Herbal Medicines 2025;17(3):428-447
Curcumae Rhizoma, derived from the rhizome of Curcuma phaeocaulis, Curcuma kwangsiensis and Curcuma wenyujin, was called Ezhu in China. In the past, Curcumae Rhizoma extracts were obtained through water decoction or alternative methods, which showed significant anti-cancer effects. However, the mixed extracts contain various compound components of Curcumae Rhizoma, leading to an ambiguous mechanism of action for Curcumae Rhizoma extracts anti-cancer. Contemporary researchers have extracted the chemical components of Curcumae Rhizoma separately for experimental verification of its active ingredients in the anti-cancer field. Numerous studies demonstrated that curcumol, germacrone, β-elemene, and curcumin in Curcumae Rhizoma extracts have significant governing effects in anti-cancer activities. Pharmacological studies have shown that Curcumae Rhizoma suppresses cancer cell proliferation, invasion, and migration, triggering apoptosis and regulating cellular autophagy to achieve anticancer effects. Here, we summarized the research progress of Curcumae Rhizoma on anti-cancer effects from 2013 to 2022, aiming to explore the deeper molecular mechanisms of Curcumae Rhizoma's active components in cancer treatment.
7.Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells.
Yi WANG ; Xiao-Yu SUN ; Fang-Qi MA ; Ming-Ming REN ; Ruo-Han ZHAO ; Meng-Meng QIN ; Xiao-Hong ZHU ; Yan XU ; Ni-da CAO ; Yuan-Yuan CHEN ; Tian-Geng DONG ; Yong-Fu PAN ; Ai-Guang ZHAO
Journal of Integrative Medicine 2025;23(3):320-332
OBJECTIVE:
Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC.
METHODS:
For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC.
RESULTS:
Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway.
CONCLUSION
Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans
;
Flavonoids/therapeutic use*
;
Stomach Neoplasms/pathology*
;
Animals
;
Proto-Oncogene Proteins c-bcl-2/metabolism*
;
Cell Line, Tumor
;
Apoptosis/drug effects*
;
Cell Proliferation/drug effects*
;
Ubiquitination/drug effects*
;
Mice
;
Drug Synergism
;
Mice, Inbred BALB C
;
Mice, Nude
;
Xenograft Model Antitumor Assays
;
Flavones
8.NFKBIE: Novel Biomarkers for Diagnosis, Prognosis, and Immunity in Colorectal Cancer: Insights from Pan-cancer Analysis.
Chen Yang HOU ; Peng WANG ; Feng Xu YAN ; Yan Yan BO ; Zhen Peng ZHU ; Xi Ran WANG ; Shan LIU ; Dan Dan XU ; Jia Jia XIAO ; Jun XUE ; Fei GUO ; Qing Xue MENG ; Ren Sen RAN ; Wei Zheng LIANG
Biomedical and Environmental Sciences 2025;38(10):1320-1325
9.Elemene Antitumor Drugs Development Based on "Molecular Compatibility Theory" and Clinical Application: A Retrospective and Prospective Outlook.
Xiao-Ying JIANG ; Li-Ping SHI ; Jun-Long ZHU ; Ren-Ren BAI ; Tian XIE
Chinese journal of integrative medicine 2024;30(1):62-74
Elemene, derived from Curcuma wenyujin, one of the "8 famous genuine medicinal materials of Zhejiang province," exhibits remarkable antitumor activity. It has gained wide recognition in clinical practice for effectiveness on tumors. Dr. XIE Tian, introduced the innovative concept of "molecular compatibility theory" by combining Chinese medicine principles, specifically the "monarch, minister, assistant, and envoy" theory, with modern biomedical technology. This groundbreaking approach, along with a systematic analysis of Chinese medicine and modern biomedical knowledge, led to the development of elemene nanoliposome formulations. These novel formulations offer numerous advantages, including low toxicity, well-defined composition, synergistic effects on multiple targets, and excellent biocompatibility. Following the principles of the "molecular compatibility theory", further exploration of cancer treatment strategies and methods based on elemene was undertaken. This comprehensive review consolidates the current understanding of elemene's potential antitumor mechanisms, recent clinical investigations, advancements in drug delivery systems, and structural modifications. The ultimate goal of this review is to establish a solid theoretical foundation for researchers, empowering them to develop more effective antitumor drugs based on the principles of "molecular compatibility theory".
Humans
;
Retrospective Studies
;
Antineoplastic Agents/therapeutic use*
;
Neoplasms/drug therapy*
;
Drugs, Chinese Herbal/therapeutic use*
;
Sesquiterpenes/therapeutic use*
10.A novel TNKS/USP25 inhibitor blocks the Wnt pathway to overcome multi-drug resistance in TNKS-overexpressing colorectal cancer.
Hongrui ZHU ; Yamin GAO ; Liyun LIU ; Mengyu TAO ; Xiao LIN ; Yijia CHENG ; Yaoyao SHEN ; Haitao XUE ; Li GUAN ; Huimin ZHAO ; Li LIU ; Shuping WANG ; Fan YANG ; Yongjun ZHOU ; Hongze LIAO ; Fan SUN ; Houwen LIN
Acta Pharmaceutica Sinica B 2024;14(1):207-222
Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APCmin/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

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