1.Research progress on the mechanism of action of rosmarinic acid in the prevention of cardiovascular diseases
Ke CAI ; Sheng-ru HUANG ; Fang-fang GAO ; Xiu-juan PENG ; Sheng GUO ; Feng LIU ; Jin-ao DUAN ; Shu-lan SU
Acta Pharmaceutica Sinica 2025;60(1):12-21
With the rapid development of social economy and the continuous improvement of human living standard, the incidence, fatality and recurrence rates of cardiovascular disease (CVD) are increasing year by year, which seriously affects people's life and health. Conventional therapeutic drugs have limited improvement on the disability rate, so the search for new therapeutic drugs and action targets has become one of the hotspots of current research. In recent years, the therapeutic role of the natural compound rosmarinic acid (RA) in CVD has attracted much attention, which is capable of preventing CVD by modulating multiple signalling pathways and exerting physiological activities such as antioxidant, anti-apoptotic, anti-inflammatory, anti-platelet aggregation, as well as anti-coagulation and endothelial function protection. In this paper, the role of RA in the prevention of CVD is systematically sorted out, and its mechanism of action is summarised and analysed, with a view to providing a scientific basis and important support for the in-depth exploration of the prevention value of RA in CVD and its further development as a prevention drug.
2.Compilation Instructions for Expert Consensus on Clinical Application of Dieda Huoxue Capsules
Yuhang MENG ; Jinghua GAO ; Minshan FENG ; Quan JI ; Jin JIN ; Ting CHENG ; Yongyao LI ; Yuanyuan LI ; Xin CUI ; Yanming XIE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):177-183
The Compilation Instructions for Expert Consensus on Clinical Application of Dieda Huoxue capsules systematically expound the development methods and evidence-based basis of this consensus. In view of the weak clinical application evidence and ambiguous indications of Dieda Huoxue capsules, the Institute of Basic Research in Clinical Medicine of the China Academy of Chinese Medical Sciences and Wangjing Hospital took the lead and collaborated with 33 experts from 28 medical institutions nationwide. They strictly followed the World Health Organization (WHO) guideline-making norms and the Grading of Recommendations Assessment, Development and Evaluations (GRADE) evidence-grading system and completed the compilation through multidisciplinary cooperation. The workflow included constructing clinical questions (19 items were screened by the nominal group technique), retrieving evidence (from Chinese and English databases and grey literature), assessing safety (integrating drug monitoring data and clinical investigations), and forming recommendations and consensus suggestions (3 recommendations were reached via the GRADE grid method, and 16 consensus suggestions were reached by the majority vote rule). The results indicate that the consensus clearly states that this medicine (Dieda Huoxue capsules) is applicable to conditions like traumatic injury, blood stasis-induced pain, and sudden lumbar sprains. The recommended dose is 6 capsules each time, twice a day. Combining oral administration with external application can enhance the efficacy, and elderly patients should take the medicine at intervals. Safety monitoring suggests that it should be used with caution in people with a bleeding tendency and those with an allergic constitution. The compilation process involved three rounds of reviews by internal and external experts. Literature analysis, the Delphi method, and clinical applicability tests were employed to ensure methodological rigor. The compilation instructions comprehensively present key aspects such as project approval and registration, conflict-of-interest statements, and evidence evaluation through 12 appendices, providing methodological support for the clinical translation of the consensus. In the future, it will be continuously improved through a dynamic revision mechanism.
3.Mechanisms and Molecular Networks of Hypoxia-regulated Tumor Cell Dormancy
Mao ZHAO ; Jin-Qiu FENG ; Ze-Qi GAO ; Ping WANG ; Jia FU
Progress in Biochemistry and Biophysics 2025;52(9):2267-2279
Dormant tumor cells constitute a population of cancer cells that reside in a non-proliferative or low-proliferative state, typically arrested in the G0/G1 phase and exhibiting minimal mitotic activity. These cells are commonly observed across multiple cancer types, including breast, lung, and ovarian cancers, and represent a central cellular component of minimal residual disease (MRD) following surgical resection of the primary tumor. Dormant cells are closely associated with long-term clinical latency and late-stage relapse. Due to their quiescent nature, dormant cells are intrinsically resistant to conventional therapies—such as chemotherapy and radiotherapy—that preferentially target rapidly dividing cells. In addition, they display enhanced anti-apoptotic capacity and immune evasion, rendering them particularly difficult to eradicate. More critically, in response to microenvironmental changes or activation of specific signaling pathways, dormant cells can re-enter the cell cycle and initiate metastatic outgrowth or tumor recurrence. This ability to escape dormancy underscores their clinical threat and positions their effective detection and elimination as a major challenge in contemporary cancer treatment. Hypoxia, a hallmark of the solid tumor microenvironment, has been widely recognized as a potent inducer of tumor cell dormancy. However, the molecular mechanisms by which tumor cells sense and respond to hypoxic stress—initiating the transition into dormancy—remain poorly defined. In particular, the lack of a systems-level understanding of the dynamic and multifactorial regulatory landscape has impeded the identification of actionable targets and constrained the development of effective therapeutic strategies. Accumulating evidence indicates that hypoxia-induced dormancy tumor cells are accompanied by a suite of adaptive phenotypes, including cell cycle arrest, global suppression of protein synthesis, metabolic reprogramming, autophagy activation, resistance to apoptosis, immune evasion, and therapy tolerance. These changes are orchestrated by multiple converging signaling pathways—such as PI3K-AKT-mTOR, Ras-Raf-MEK-ERK, and AMPK—that together constitute a highly dynamic and interconnected regulatory network. While individual pathways have been studied in depth, most investigations remain reductionist and fail to capture the temporal progression and network-level coordination underlying dormancy transitions. Systems biology offers a powerful framework to address this complexity. By integrating high-throughput multi-omics data—such as transcriptomics and proteomics—researchers can reconstruct global regulatory networks encompassing the key signaling axes involved in dormancy regulation. These networks facilitate the identification of core regulatory modules and elucidate functional interactions among key effectors. When combined with dynamic modeling approaches—such as ordinary differential equations—these frameworks enable the simulation of temporal behaviors of critical signaling nodes, including phosphorylated AMPK (p-AMPK), phosphorylated S6 (p-S6), and the p38/ERK activity ratio, providing insights into how their dynamic changes govern transitions between proliferation and dormancy. Beyond mapping trajectories from proliferation to dormancy and from shallow to deep dormancy, such dynamic regulatory models support topological analyses to identify central hubs and molecular switches. Key factors—such as NR2F1, mTORC1, ULK1, HIF-1α, and DYRK1A—have emerged as pivotal nodes within these networks and represent promising therapeutic targets. Constructing an integrative, systems-level regulatory framework—anchored in multi-pathway coordination, omics-layer integration, and dynamic modeling—is thus essential for decoding the architecture and progression of tumor dormancy. Such a framework not only advances mechanistic understanding but also lays the foundation for precision therapies targeting dormant tumor cells during the MRD phase, addressing a critical unmet need in cancer management.
4.Expression profile of mRNA sequencing for plasma exosomes among patients with latent tuberculosis infection and active tuberculosis
GAO Jin ; DU Xiaokang ; XIANG Haiyan ; FAN Chaoming ; CAI Chengsong ; PAN Feng
Journal of Preventive Medicine 2024;36(1):70-73, 77
Objective:
To analyse the expression of differential mRNA in the plasma exosomes in patients with latent tuberculosis infection (LTBI) and active tuberculosis (ATB) using high-throughput sequencing, so as to provide insights into differential diagnosis of LTBI and ATB.
Methods:
The plasma samples were collected from the patients treated at The Affiliated Hospital of Hangzhou Normal University, including 16 cases of LTBI and 21 cases of ATB. The exosomes were extracted by Invitrogen extracellular extracts purification kit, and the size and morphology of exosomes were observed by transmission electron microscope (TEM). The exosomes were identified by Western blotting. Total RNA was extracted from plasma exosomes using high-throughput sequencing, differential expression mRNA was identified, and gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed. Two differential mRNAs with the highest differential expression fold were selected, and five patients with ATB and three patients with LTBI were recruited for verification using real-time quantitative PCR.
Results:
The sequencing results of plasma exosomes showed that compared with ATB patients, 2 875 differentially expressed mRNAs were detected in exosomes of LTBI patients, of which 1 002 mRNAs were up-regulated and 1 873 mRNAs were down-regulated. The most significant differentially expressed downregulated and upregulated mRNA were M6PR and RGPD5, respectively. GO analysis and KEGG pathway analysis showed that differential mRNAs were enriched in protein serine kinase activity, rRNA binding molecular function, human cytomegalovirus infection, pancreatic cancer, endometrial cancer, insulin signaling pathway and FoxO signaling pathway. The real-time quantitative PCR showed that the expression of differential mRNA was consistent with sequencing. Compared with ATB patients, the relative expression level of M6PR in plasma exosomes in LTBI patients (0.954±0.212) was downregulated compared with that of ATB patients (2.168±0.226), while the relative expression level of RGPD5 (2.126±0.200) was upregulated compared with that of ATB patients (0.588±0.129) (both P<0.05).
Conclusions
There is a difference in mRNA expression of plasma exosomes between patients with LTBI and ATB. M6PR and RGPD5 may become markers for distinguishing plasma exosomes between LTBI and ATB.
5.Distribution of urinary tract pathogens and susceptibility to nenofloxacin and levofolxacin in patients with community-acquired urinary tract infection
Zhen DU ; Shan CHEN ; Liang CUI ; Huiling WU ; Zhan GAO ; Jin YANG ; Gang CUI ; Jiajing WANG ; Tiehuan SHU ; Ninghan FENG ; Ludong QIAO
Chinese Journal of Urology 2024;45(1):24-28
Objective:To investigate the distribution characteristics of urinary tract pathogens in patients with community-acquired urinary tract infection and their sensitivity to nenoxacin and levofloxacin.Methods:This prospective, multicenter clinical trial included patients with community-acquired urinary tract infection who were admitted to urological clinics at 9 clinical research centers from November 2021 to August 2022.Inclusion criteria: Patients aged 18-70 years with community-acquired acute uncomplicated cystitis(AUC), recurrent acute episodes of urinary tract infection(rUTI), and non-febrile complicated urinary tract infection(cUTI) with signs of urinary tract irritation and abnormal elevation of routine white blood cells in urine. Exclusion criteria: ①Patients who received effective antimicrobial therapy within 72 h before enrollment and lasted for more than 24 h. ②Fever (>37.3℃) or symptoms of upper urinary tract infection such as low back pain, tapping pain in the kidney area, etc. ③Indwelling urinary catheter. At the first visit, clean midstream urine samples were taken for bacterial culture, and the distribution characteristics of urinary pathogens of different types of urinary tract infections were analyzed. Extended spectrum β-lactamases (ESBLs) were measured for Gram-negative bacteria. The susceptibility of nenoxacin and levofloxacin to urinary tract pathogens was determined by disk diffusion method. Drug resistance rate, sensitivity rate were analyzed between different disease groups.Results:There were 404 enrolled patients from 9 hospitals, including 364 (90.1%) females and 40 (9.9%) males. A total of 177 strains of pathogenic bacteria were isolated, among which the highest proportion of Escherichia coli was 66.1% (117/177).Klebsiella pneumoniae was followed by 6.8% (12/177) and Streptococcus agalactis 5.1% (9/177). The bacterial spectrum distribution of AUC and rUTI were similar, and the proportions of Escherichia coli were 70.6% (85/119) and 65.9% (29/44), respectively. However, the proportions of Escherichia coli isolated from cUTI patients were only 28.6% (4/14) and Enterococcus faecalis 7.1%(1/14). The overall detection rate of ESBLs in Gram-negative bacteria was 30.9%(43/139). The sensitivity rate of nenoxacin was 74.6%(91/122), and the resistance rate was 25.4%(31/122). The overall sensitivity rate of levofloxacin was 44.9%(70/156) and the resistance rate was 36.5%(57/156). The rate of resistance of urinary tract pathogens to levofloxacin was 48.2% (27/56) in patients with previous urinary tract infection history, and 30.0% (30/100) in patients with no previous urinary tract infection history, the difference was statistically significant( P=0.023).The sensitivity rate of Gram-negative bacteria to nenofloxacin was 70.7% (65/92) and that to levofloxacin was 50.0% (46/92, P<0.001). The sensitivity of Gram-positive bacteria to nenofloxacin was 80.0% (16/20), and that to levofloxacin was 70.0% (14/20, P=0.009). Conclusions:The bacterial profile of out-patient community acquired urinary tract infection varies greatly according to different diseases. The proportion of Escherichia coli in AUC and rUTI patients is higher than that in cUTI. The detection rate of ESBLs in Gram-negative bacteria was lower than the domestic average.Patients with a history of urinary tract infection had a high risk of treatment failure with levofloxacin. The sensitivity of common urinary tract pathogens to nenofloxacin was higher than levofloxacin.
6.Analysis of oligoclonal bands detection results of 3 217 patients with neurological disorders
Zhenyu NIU ; Haiqiang JIN ; Hongjun HAO ; Yiming ZHENG ; Jing GUO ; Yan YAO ; Feng GAO ; Zhaoxia WANG
Chinese Journal of Laboratory Medicine 2024;47(1):57-64
Objective:To study positive rates and typing of oligoclonal bands (OCB) in patients with neurological disorders, and to reveal the clinical significance and applicational value of OCB test.Methods:A retrospective analysis was performed on the detection results of 3 217 patients with neurological disorders who undertook both serum and cerebrospinal fluid OCBs in the First Hospital of Peking University from January 2012 to August 2022. According to the final diagnosis, the patients were divided into 13 groups including multiple sclerosis (479 cases), neuromyelitis optica spectrum disorders (935 cases), autoimmune encephalitis (192 cases), viral encephalitis (94 cases), nervous system complication after HSCT (232 cases), Guillain-Barré syndrome (644 cases), chronic inflammatory demyelinating polyneuropathy (157 cases), etc. Cerebrospinal fluid and serum OCBs were detected using isoelectric focusing electrophoresis combining immunofixation, then classified into Ⅰ-Ⅴ types according to the morphology. Consequently, positive rates and types were analyzed for each group. χ2 test was used for comparison between groups. Results:The positive rates of cerebrospinal fluid OCB in multiple sclerosis, nervous system complication after hematopoietic stem cell transplantation (HSCT), autoimmune encephalitis, viral encephalitis, neuromyelitis optica spectrum disorders, Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy were respectively 66.8% (320/479), 48.7% (113/232), 46.4%(89/192), 19.1% (18/94), 17.6% (165/935), 9.9% (64/644), 5.1% (8/157). For patients with multiple sclerosis, neuromyelitis optica spectrum disorders, viral encephalitis, and autoimmune encephalitis, Type Ⅱ bands took the majority of cerebrospinal fluid OCB-positive cases with the rates of 94.1% (301/320), 78.7% (70/89), 77.8% (14/18), and 77.6% (128/165) respectively, indicating intrathecal IgG synthesis; for patients with nervous system complication after HSCT, Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy, type Ⅳ bands took the majority of cerebrospinal fluid OCB-positive cases with the rates of 94.7% (107/113), 82.8% (53/64) and 100% (8/8), indicating no obvious intrathecal IgG synthesis. The positive rates of cerebrospinal fluid oligoclonal bands were significantly different among all groups (χ 2=1 268.31, P<0.001). Conclusion:The positive rates of cerebrospinal fluid oligoclonal bands are different among different neurological disorders, in which the positive rate of cerebrospinal fluid OCB is higher with type Ⅱ bands as the majority type in multiple sclerosis, which indicates that the detection and typing of cerebrospinal fluid OCB are helpful for the diagnosis of various neurological diseases, especially for multiple sclerosis.
7.Research Progress in TCM for Prevention and Treatment of Precancerous Lesions of Gastric Cancer Based on Angiogenesis Microenvironment
Zhuangzhuang FENG ; Pengcheng DOU ; Ruiping SONG ; Xinyi CHEN ; Juan'e WANG ; Ruirui GAO ; Xiaolong WANG ; Jin SHU
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(1):180-184
The angiogenic microenvironment is a new blood vessel with different molecular and functional characteristics that sprouts on the original blood vessels through different mechanisms,which directly affects the process of tumor cell growth,proliferation,and migration and has an important impact on the occurrence and development of precancerous lesions of gastric cancer.Correa mode has shown that precancerous lesions of gastric cancer is the key pathological stage before the occurrence of gastric cancer,and it is of great significance to advance the prevention and treatment strategy to this stage.TCM believes that qi deficiency and blood stasis is the key pathogenesis of precancerous lesions of gastric cancer,and its basic treatment is to replenish qi and remove blood stasis,and based on the syndrome differentiation,drugs with the efficacy of nourishing yin and tonifying stomach,soothing the liver and regulating qi,resolving phlegm and dispersing lumps,and clearing heat and dampness for treatment.This article discussed the correlation between precancerous lesions of gastric cancer and angiogenic microenvironment and its regulatory pathways,and summarized the methods and mechanisms of TCM in the treatment of precancerous lesions of gastric cancer from the perspective of regulating angiogenic microenvironment-related pathways,in order to provide a reference for the treatment of precancerous lesions of gastric cancer with TCM.
8.The role of postoperative radiotherapy for central neurocytoma
Jiankun XU ; Yidong CHEN ; Leiming WANG ; Ying GAO ; Yongrui ZHAO ; Jin FENG ; Xiaoguang QIU
Chinese Journal of Radiation Oncology 2024;33(4):314-318
Objective:To evaluate clinical efficacy of adjuvant radiotherapy (RT) for central neurocytoma (CN) after surgical resection.Methods:Clinical data of 136 CN patients admitted to Beijing Tiantan Hospital and Xuanwu Hospital from January 2001 to December 2020 were retrospectively analyzed. Preliminary interventions consisted of craniotomy (gross total resection, subtotal resection and partial resection, the latter two belonging to incomplete resection) and postoperative radiotherapy. Three-dimensional conformal or intensity-modulated radiotherapy was adopted, with a median radiotherapy dose of 54 Gy. Post-recurrence treatment included salvage surgery and radiotherapy. The overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method. Univariate analysis was performed by log-rank test to evaluate the effect of each prognostic factor on OS and PFS. The effects of multiple prognostic factors on PFS and OS were assessed by Cox regression model.Results:The median age was 28 years (range: 6-66 years). The median follow-up was 94.5 months (12-237 months). Among all patients, 79 cases underwent total resection, and 68 of them received adjuvant radiotherapy. Thirty-eight patients underwent subtotal resection, and 37 of them were treated with adjuvant radiotherapy. Sixteen patients received partial resection and adjuvant radiotherapy. Three cases received biopsy and postoperative radiotherapy. Among all patients, 3 cases died, including 2 from tumor recurrence and 1 from postoperative complication. Eight patients had recurrences during follow-up. Among them, 7 patients had recurrences at the primary site,1 had tumor dissemination to the spinal cord. The 5- and 10-year OS rates were 98.5% and 96.8%, and the 5- and 10-year PFS rates were 95.3% and 91.6% for the in the entire cohort. In the gross total resection without radiotherapy group, the 5- and 10-year PFS rates were 90.9% and 90.9%, and 96.6% and 96.6% in the gross total resection + radiotherapy group ( P=0.338). The 5- and 10-year OS rates were 100% and 100% in the gross total resection without radiotherapy group, and 98.5% and 98.5% in the gross total resection + radiotherapy group ( P=0.693). The 10-year PFS rates between the gross total resection±radiotherapy group and the incomplete resection+radiotherapy group was 95.8% vs. 90.3% ( P=0.368), and the 10-year OS rate was 98.6% vs. 94.7% ( P=0.436). Multivariate analysis showed that tumor site, degree of surgical resection, adjuvant radiotherapy and age exerted no significant effects on PFS and OS. A total of 81 patients had late neurotoxicities, including 69 cases at grade 1, 9 cases at grade 2, and 3 cases at grade 3. And 64.2% (52/81 cases) of patients suffered from short-term memory impairment. Conclusions:Gross total resection alone yields high efficacy for CN. Postoperative radiotherapy is not required. Incomplete resection combined with postoperative adjuvant radiotherapy can achieve equivalent clinical efficacy to gross total resection.
9.Rapid health technology assessment of ulinastatin in the treatment of acute pancreatitis
Zihui ZHENG ; Zinan ZHAO ; Feng GAO ; Wenying LI ; Han YUAN ; Baige ZHANG ; Liping YANG ; Pengfei JIN
China Pharmacy 2024;35(21):2676-2683
OBJECTIVE To conduct rapid health technology assessment (HTA) of ulinastatin (UTI), and to evaluate the efficacy, safety and cost-effectiveness of UTI in the treatment of acute pancreatitis (AP). METHODS Retrieved from PubMed, Embase, the Cochrane Library, CNKI, Wanfang database, CBM and official websites of HTA institutions, the systematic review (SR)/meta-analysis, economic evaluation and HTA reports of UTI in the treatment of AP were collected from the inception to Apr. 2024. Two researchers independently conducted screening, quality evaluation and data extraction according to the admission and exclusion criteria, and descriptive analysis was adopted to analyze and summarize the data. RESULTS A total of 19 studies were included, involving 15 SR/meta-analysis and 4 economic studies, and no HTA report was retrieved. In the treatment of AP, UTI showed clear advantages over conventional treatment alone in terms of improving the overall effective rate, shortening the recovery time of amylase, reducing the time required to relieve abdominal pain and distension, lowering the mortality rate, and decreasing the average hospital stay. Compared to other positive drugs (carbendate mesylate, octreotide, somatostatin, etc.), its efficacy is similar, with a favorable safety profile. As far as the current research was concerned, UTI had obvious economic advantages over other positive drugs. CONCLUSIONS UTI is safe and effective in the treatment of AP, and has economic advantages.
10.Emerging role of Jumonji domain-containing protein D3 in inflammatory diseases
Li XIANG ; Chen RU-YI ; Shi JIN-JIN ; Li CHANG-YUN ; Liu YAN-JUN ; Gao CHANG ; Gao MING-RONG ; Zhang SHUN ; Lu JIAN-FEI ; Cao JIA-FENG ; Yang GUAN-JUN ; Chen JIONG
Journal of Pharmaceutical Analysis 2024;14(9):1282-1300
Jumonji domain-containing protein D3(JMJD3)is a 2-oxoglutarate-dependent dioxygenase that specif-ically removes transcriptional repression marks di-and tri-methylated groups from lysine 27 on histone 3(H3K27me2/3).The erasure of these marks leads to the activation of some associated genes,thereby influencing various biological processes,such as development,differentiation,and immune response.However,comprehensive descriptions regarding the relationship between JMJD3 and inflammation are lacking.Here,we provide a comprehensive overview of JMJD3,including its structure,functions,and involvement in inflammatory pathways.In addition,we summarize the evidence supporting JMJD3's role in several inflammatory diseases,as well as the potential therapeutic applications of JMJD3 inhibitors.Additionally,we also discuss the challenges and opportunities associated with investigating the functions of JMJD3 and developing targeted inhibitors and propose feasible solutions to provide valuable insights into the functional exploration and discovery of potential drugs targeting JMJD3 for inflammatory diseases.


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