1.Research Progress on Pathogenesis of Osteoporosis and Intervention of Traditional Chinese Medicine: A Review
Xiaoyun ZHANG ; Hao ZENG ; Zhengpeng LI ; Yueping CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):311-320
Osteoporosis (OP) is a metabolic disorder characterized by microstructural deterioration of bone and increased bone fragility due to reduced bone mass, which can cause the development of bone-related diseases. This condition imposes significant economic and psychological burdens on patients. While modern medicine has extensively researched the pathogenesis of OP, it remains incompletely understood. Current clinical management primarily relies on anti-resorptive drugs and synthetic metabolic agents. However, long-term use of some medications may yield suboptimal therapeutic outcomes and lead to severe adverse reactions. Given the necessity for prolonged or lifelong treatment for OP, there is a critical need to identify highly effective, safe, and cost-effective pharmaceutical interventions. In light of evolving disease management paradigms and recent advancements in OP research, traditional Chinese medicine has demonstrated emerging advantages in addressing this condition. Through literature review, this study delves into the pathogenesis of OP from five perspectives: hormonal dysregulation, autophagy, ferroptosis, oxidative stress, and intestinal flora alteration. Furthermore, it summarizes the therapeutic efficacy and specific mechanisms of traditional Chinese medicine monomers and compound formulas against OP through regulating hormone levels, interfering with autophagy, inhibiting ferroptosis, counteract oxidative stress,and maintain intestinal flora balance. These multifaceted insights are expected to provide theoretical reference and guide future clinical traditional Chinese medicine approaches for preventing and managing OP.
2.Progress of Clinical Research on Trop2 in Solid Tumors
Cancer Research on Prevention and Treatment 2025;52(1):79-86
Trophoblast cell surface antigen 2 (Trop2) is a glycoprotein that is barely expressed in normal tissues but highly expressed in malignant tumors; it is remarkably associated with poor prognosis. Various targeted therapeutics against Trop2, such as anti-Trop2 antibodies and antibody-drug conjugate drugs targeting Trop2, have been developed, and some therapeutics have been approved or are in clinical trials for cancer treatment. In this review, we comprehensively discuss the gene structure, mechanism of action, clinical research, drug development, and other aspects of Trop2 to provide references for the clinical development of effective and safe Trop2-targeting drugs.
3.Astrocyte FGF7/FGFR2 autocrine signaling mediates neuroinflammation and promotes MPTP-induced degeneration of dopaminergic neurons.
Xin SUN ; Yueping WANG ; Yajie ZHANG ; Ruixue HAN ; Min WANG ; Jing ZHANG ; Ting SUN ; Yang LIU ; Gang HU ; Lei CAO ; Ming LU
Acta Pharmaceutica Sinica B 2025;15(9):4730-4750
Reactive astrocytes, which exhibit a correlation with the degeneration of dopaminergic neurons, are present in a considerable number during the progression of Parkinson's disease (PD). However, the underlying factors shaping astrocyte reactivity and neuroinflammation in PD remain inadequately elucidated. Here, we demonstrate that fibroblast growth factor 7 (FGF7)/FGF receptor 2 (FGFR2) autocrine signaling intensifies astrocyte reactivity and inflammation. Genetic deletion of Arrb2, β-Arrestin2 encoding gene, led to escalated astrocyte reactivity in MPTP-treated mice, which was further substantiated in astrocyte-specific Arrb2 knockdown mice. RNA sequencing profiling of Arrb2 knockout astrocytes identified Fgf7 as a critical effector of astrocyte reactivity. Subsequently, conditional knockdown of Fgf7 and its receptor Fgfr2 in astrocytes elicited advantageous effects for MPTP-treated mice by restraining the inflammatory phenotypic transition of reactive astrocytes. Furthermore, deletion of astrocytic Fgf7 mitigated MPTP-induced pathology in Arrb2 knockout mice. Mechanistically, STAT1 was distinguished as the transcription factor suppressing Fgf7 expression, while β-Arrestin2 counteracted the proteasomal degradation of STAT1 by binding to RNF220, an E3 ubiquitin ligase for STAT1. More importantly, selectively engaging dopamine D2 receptor (Drd2)/β-Arrestin2-biased signaling using the agonist UNC9995 exhibited therapeutic potential in MPTP-treated mice via moderation of astrocytic FGF7 production, thereby restoring balance in astrocyte reactivity. Collectively, our study bridges a crucial knowledge gap by elucidating the novel functions of FGF family members within the central nervous system, particularly within the context of PD. The autocrine signaling of FGF7/FGFR2 represents a novel mechanism and a potential druggable target for modulating astrocyte-derived inflammation.
4.The cutting-edge progress of novel biomedicines in ovulatory dysfunction therapy.
Xuzhi LIANG ; Shiyu ZHANG ; Dahai LI ; Hao LIANG ; Yueping YAO ; Xiuhong XIA ; Hang YU ; Mingyang JIANG ; Ying YANG ; Ming GAO ; Lin LIAO ; Jiangtao FAN
Acta Pharmaceutica Sinica B 2025;15(10):5145-5166
Ovulatory dysfunction (OD) is one of the main causes of infertility in women of childbearing age, which not only affects their reproductive ability, but also physical and mental health. Traditional treatment strategies have limited efficacies, and the emergence of biomedicines provides a promising alternative solution via the strategies of combining engineered design with modern advanced technology. This review explores the pathophysiological characteristics and related induction mechanisms of OD, and evaluates the current cutting-edge advances in its treatments. It emphasizes the potentials of biomedicines strategies such as hydrogels, nanoparticles and extracellular vesicles in improving therapeutic precision and efficacy. By mimicking natural physiological processes, and achieving controlled drug release, these advanced drug carriers are expected to address the challenges in ovarian microenvironment reprogramming, tissue repair, and metabolic and immune regulation. Despite the promising progress, there are still challenges in terms of biomedical complexity, differences between animal models and human physiology, and the demand for intelligent drug carriers in the therapy of OD. Future researches are mainly dedicated to developing precise personalized biomedicines in OD therapy through interdisciplinary collaboration, promoting the development of reproductive regenerative medicine.
5.Scientific, transparent and applicable rankings of Chinese pathological guidelines and consensus published in the medical journals in 2022
Xiaohua SHI ; Shixian WANG ; Zhe WANG ; Jian WANG ; Zhihong ZHANG ; Yueping LIU ; Hongying ZHANG ; Hongwen GAO ; Xiaoyan ZHOU ; Qiu RAO ; Li LIANG ; Xiaohong YAO ; Dongge LIU ; Zhiyong LIANG
Chinese Journal of Pathology 2024;53(6):528-534
The STAR tool was used to evaluate and analyze the science, transparency, and applicability of Chinese pathology guidelines and consensus published in medical journals in 2022. There were a total of 18 pathology guidelines and consensuses published in 2022, including 1 guideline and 17 consensuses. The results showed that the guideline score was 21.83 points, lower than the overall guideline average (43.4 points). Consensus ratings scored an average of 27.87 points, on par with the overall consensus level (28.3 points). Areas that scored above the overall level were "conflict of interest" and "working groups", while areas that scored below the overall level were "proposals", "funding", "evidence", "consensus approaches" and "accessibility". To sum up, the formulation of pathology guidelines and consensuses in 2022 is not standardized, and the evidence retrieval process, evidence evaluation methods and grading criteria for recommendations on clinical issues are not provided in the formulation process; the process and method for reaching consensus are not provided, the plan is lacking, and registration is not carried out. It is therefore suggested that guidelines/consensus makers in the field of pathology should attach importance to evidence-based medical evidence, strictly follow guideline formulation methods and processes, further improve the scientific, applicable and transparent guidelines/consensuses in the field, and better provide support for clinicians and patients.
6.Research on the clinical characteristics and prognosis of children with chronic myeloid leukemia in the blast phase
Fangyuan ZHENG ; Aidong LU ; Yueping JIA ; Yingxi ZUO ; Huimin ZENG ; Qian JIANG ; Leping ZHANG
Chinese Journal of Hematology 2024;45(10):931-936
Objective:To explore the clinical characteristics and prognosis of children with chronic myeloid leukemia in the blast phase (CML-BP) .Methods:The clinical characteristics, treatment measures, and survival outcomes of 28 children with CML-BP were analyzed in our hospital from January 2008 to November 2022.Results:The male to female ratio of the 28 children with CML-BP was 1.15∶1. The median age of diagnosis of CML-BP was 10 years, and the median follow-up time was 79 months. During the diagnosis of CML, four children were in the BP, one was in the accelerated phase (AP) and 23 children were in the chronic phase (CP). Among the 23 children with CML-CP, 75% had progressed directly from CP to BP without experiencing the AP. Among the children diagnosed with CML-BP, 71.4% were classified as chronic myeloid leukemia lymphoid blast phase (CML-LBP), 25.0% belonged to the chronic myeloid leukemia myeloid blast phase (CML-MBP), and 3.6% belonged to the chronic myeloid leukemia mixed phenotype acute leukemia (CML-MPAL). Treatment with hemaopoietic stem cell transplantation (HSCT) after tyosine kinase inhibitor (TKI) combined with chemotherapy was administered to 19 children, two children received HSCT after TKI alone, and seven children received TKI combined with chemotherapy but without HSCT. The 5-year overall survival of the 28 children with CML-BP was 59.3%.Conclusion:The direct progression of BP from CP is greater in children with CML-BP compared with adults, and the overall prognosis of children with CML-BP is poor.
7.Analysis of predictive effect of European treatment and outcome study long term survival score on survival outcomes in children with chronic myeloid leukemia of chronic phase
Fangyuan ZHENG ; Ruizhe DENG ; Aidong LU ; Yueping JIA ; Huimin ZENG ; Leping ZHANG ; Qian JIANG
Chinese Journal of Pediatrics 2024;62(10):956-961
Objective:To explore the predictive effect of European treatment and outcome study long term survival (ELTS) score on survival outcomes in chronic myeloid leukemia of chronic phase (CML-CP) children.Methods:A single-center retrospective cohort study was conducted. Clinical data of 216 children with CML-CP in Peking University People′s Hospital from January 2010 to December 2023 were analyzed. Children were divided into low, intermediate and high-risk groups according to ELTS score. The survival outcomes and prognostic factors were analyzed. Kaplan-Meier method and Log-Rank test were used for survival analysis.Cox regression model was applied for analysis of prognostic factors.Results:Among the 216 children with CML-CP, there were 122 males and 94 females, with the diagnosis age of 11.0 (8.0, 14.7) years. The follow-up time was 77 (57, 99) months. According to ELTS score, 145, 52, and 19 children were classified as low, intermediate and high-risk group. For the low-risk and intermediate/high-risk groups, the 6-year failure-free survival (FFS) rates were (83.0±3.1)% and (64.6±5.7)%, the 6-year progression-free survival (PFS) rates were (91.4±2.3)% and (78.7±4.8)%, and the 6-year event-free survival (EFS) rates were (80.8±3.3)% and (64.2±5.7)%, with statistically significant difference ( χ2=9.45, 7.16, 7.40, P=0.002, 0.007, 0.007), respectively.The 6-year overall survival (OS) rates were (98.5±1.0)% and (95.6±2.4)%, without statistically significant difference ( χ2=0.35, P=0.550). Multivariate analysis showed that ELTS score was an independent prognostic factor or tendency for FFS ( HR=1.97, 95% CI 1.11-3.49), PFS ( HR=2.95, 95% CI 1.18-7.39), and no independent prognostic factor for EFS and OS were found. Conclusions:ELTS score at diagnosis can help stratify the risk of children with CML-CP. The children in intermediate/high-risk group are more likely to have treatment failure, disease progression than those in low-risk group, but the predictive ability of ELTS score for OS is limited.
8.Study of the association between the chemokine CXCL5 and the onset of chronic atrophic gastritis and gas-tric precancerous lesions
Bei PEI ; Yi ZHANG ; Qin SUN ; Yueping JIN ; Xuejun LI
The Journal of Practical Medicine 2024;40(15):2098-2104
Objective To clarify the changes in CXCL5 in serum and gastric tissues of patients with chronic atrophic gastritis(CAG)and precancerous lesions of gastric cancer(PLGC)and to investigate the predictive value of CXCL5 for the diagnosis of CAG and PLGC.Methods This study enrolled 72 participants of CAG admitted to the Department of Splenology and Gastroenterology of the Second Affiliated Hospital of Anhui University of Chinese Medicine from June 2022 to June 2023,with gastroscopy and pathologically confirmed diagnosis,as well as 68 healthy participants who underwent gastroscopy in the same period at our department.We collected clinical information and laboratory results from all participants.The logistic regression analysis methods were used to identify the diagnostic value of serum CXCL5.Furthermore,in order to clarify the role of CXCL5 in the developent of CAG,a total of 15 patients each with CAG,intestinal metaplasia,and dysplasia treated at our hospital from June 2023 to December 2023,and 15 healthy participants were selected.The relationship between the expression of CXCL5 and the degree of clinicopathology was analysed in each group using ELISA,PCR,and immunohistochemistry staining to validate and assess the diagnostic efficacy of CXCL5.Results The study found that several factors were associated with CAG,including family history of tumours,smoking and alcohol consumption history,dietary regularity,Helicobacter pylori infection,the number of lesions,gastric function scores and CXCL5(P<0.05).The ROC curve had an AUC of 1.00 and a Youden index of 0.986,indicating excellent predictive ability.The ELISA results indicated a significantly higher serum CXCL5 expression level in the CAG,intestinal metaplasia,and dysplasia groups compared to the normal group.There was a positive correlation between the serum CXCL5 expression level and the degree of pathology.The PCR and immunohistochemistry staining results indicate that the mRNA and pro-tein expression levels of CXCL5 in gastric tissues of patient groups were significantly higher compared to the nor-mal group.Furthermore,the mRNA and protein expression levels of CXCL5 in gastric tissues were positively correlated with the degree of pathology.Conclusions The results indicate that CXCL5 is highly expressed in the serum and gastric tissues of patients with CAG and PLGC,and its expression level is positively correlated with the degree of pathology.Therefore,CXCL5 could serve as a predictive indicator and a potential therapeutic target for the diagnosis of CAG and PLGC.
9.Expression of GLIS3 protein in triple negative breast cancer and its influence on prognosis of patients
Chenhao LI ; Yueping LIU ; Chunxiao LI ; Guozhong CUI ; Xuchen HUANG ; Yi ZHANG ; Guoyu ZHANG ; Cuizhi GENG
Journal of Army Medical University 2024;46(13):1553-1560
Objective To observe the expression of GLIS3 in triple negative breast cancer(TNBC)and analyze its relationship with the prognosis of TNBC patients.Methods Bioinformatic analysis was applied to analyze the expression level of GLIS3 in Gene Expression Omnibus(GEO).Kaplan-Meier survival curve was plotted to evaluate the impact of GLIS3 expression on the survival rate of patients based on DNA chip data.A total of 125 patients pathologically diagnosed as TNBC in the Fourth Hospital of Hebei Medical University from January to December 2014 were enrolled by cluster random sampling.Among them,53 patients had complete tissue specimens,medical records and follow-up data.Immunohistochemical assay was used to detect the expression of GLIS3 in TNBC and adjacent tissues to tumors,while the relationships between GLIS3 protein expression in breast cancer tissues and clinicopathological parameters such as age,menstrual status,tumor size,clinical stage,histological grade,pathological type,axillary lymph node metastasis,vascular tumor thrombus,and expression of TP53 and Ki-67 were analyzed.Kaplan-Meier survival curve was plotted to analyze the effect of GLIS3 on the overall and disease-free survival of TNBC patients.Cox regression model was established to identify the risk factors impacting the prognosis of the patients.Results Analysis of GEO data showed that the expression of GLIS3 in TNBC was significantly higher than that in paracancer tissues(P<0.05).The expression of GLIS3 was notably higher in the TNBC tissue than the adjacent tissue to tumor(P<0.05).A marked augmentation of GLIS3 expression was observed in both the advanced and larger-sized tumors(P<0.05).Univariate analysis of Cox regression model revealed that lymph node metastasis,TNM stage and GLIS3 expression were all related to disease-free survival of TNBC patients(P<0.05).Univariate and multivariate analyses displayed that TNM stage was related to the overall survival of TNBC patients(P<0.05).The patients with high expression of GLIS3 had significant shorter disease-free survival time than those with low expression(P<0.05),but had no statistical difference in overall survival(P>0.05).Conclusion GLIS3 protein is highly expressed in TNBC tissues,and tumor size and TNM stage are correlated with its high expression.The high expression of GLIS3 suggests that the patients have poor prognosis and low disease-free survival rate.
10.Long-term efficacy and prognosis of intensity-modulated chemoradiotherapy for patients with anal squamous cell carcinoma
Jinming SHI ; Ning LI ; Shulian WANG ; Yongwen SONG ; Yueping LIU ; Hui FANG ; Ningning LU ; Shunan QI ; Bo CHEN ; Yirui ZHAI ; Wenwen ZHANG ; Hao JING ; Ye-Xiong LI ; Yuan TANG ; Jing JIN
Chinese Journal of Radiation Oncology 2024;33(9):818-824
Objective:To analyze clinical efficacy of intensity-modulated chemoradiotherapy for patients with anal squamous cell carcinoma and identify prognostic factors.Methods:Clinical data of patients with anal squamous cell carcinoma who received intensity-modulated chemoradiotherapy in the Cancer Hospital of Chinese Academy of Medical Sciences from January 1, 2010 to January 1, 2022 were retrospectively analyzed. Regular follow-up was carried out. The main indexes included disease-free survival (DFS), locoregional failure-free survival (LRFFS) and overall survival (OS), and adverse reactions were recorded. The survival curve was delineated by Kaplan-Meier method and the influencing factors of survival were analyzed by Cox regression models.Results:A total of 65 patients were enrolled with 19 (29%) males and 46 (71%) females. According to the American Joint Committee on Cancer (AJCC) 7 th edition staging, there were 7 (11%), 28 (43%), 10 (15%), and 20 (31%) patients with stage I, II, IIIa, and IIIb, respectively. Before the chemoradiotherapy, 2 (3%) patients received chemotherapy and 12 (18%) patients received local resection. The median dose of radiotherapy was 54 Gy (range: 45-64 Gy) and the main concurrent chemotherapy regimen was capecitabine combined with cisplatin ( n=34, 52%). The completion rate of radiotherapy during concurrent chemoradiotherapy was 100%, and the chemotherapy completion rate was 88%. During the therapy, 5 patients (8%) were interrupted but completed concurrent chemoradiotherapy in full dose, and 8 patients (12%) reduced the dose of concurrent chemotherapy due to the toxicities. During the chemoradiotherapy, 15 cases (23%) experienced grade 3-4 leukopenia, and 17 cases (26%) experienced grade 3-4 radiation dermatitis. No treatment-related death occurred during the treatment. The median follow-up time was 50.4 months (range: 4.4-142.2 months), local recurrence occurred in 7 cases (11%), distant metastasis occurred in 3 cases (5%), and the 5-year DFS, LRFFS and OS rates were 78.8%, 86.5% and 85.1%, respectively. Cox univariate analysis indicated that T stage was significantly associated with DFS ( P=0.006), and tended to be associated with OS ( P=0.054). Conclusions:Intensity-modulated radiotherapy combined with concurrent chemotherapy is an effective treatment for anal squamous cell carcinoma, with tolerable acute toxicities. T stage is an influencing factor of DFS in anal squamous cell carcinoma patients.

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