OBJECTIVE To clarify the roles and functions of full-time pharmacists in the management of early-phase clinical trials of antineoplastic drugs， and to provide theoretical and practical support for their transformation from traditional drug managers to multi-dimensional roles in clinical research. METHODS Combined with relevant regulations such as the Good Clinical Practice （GCP） （2020 Edition）， and based on the clinical practice experience of the Phase Ⅰ Clinical Ward in our hospital， this study systematically sorted out full-time pharmacists’ roles and functions in early-phase clinical trials of antineoplastic drugs， and explored the core challenges and optimization pathways for role transformation and capacity-building of domestic full-time clinical trial pharmacists. RESULTS & CONCLUSIONS Full-time pharmacists assumed multiple roles in early-phase clinical trials of antineoplastic drugs， including providing pharmaceutical support for protocol design， implementing whole-process standardized management of clinical trial drugs， ensuring medication safety for clinical trial subjects/participants， conducting quality control throughout the clinical trial process， and serving as a bridge for interdisciplinary collaboration and communication. Currently， there are challenges in this field in China， such as unclear roles， an imperfect capacity building system， and insufficient regulatory support. This paper proposes that by establishing a standardized role framework， clarifying the core responsibilities and authorities of full-time pharmacists， and leveraging cutting-edge technologies to provide comprehensive support for their roles， so as to fully harness their pharmaceutical expertise and contribute to the standardization and efficiency of the antineoplastic new drug development process.

Objective To evaluate the efficacy and safety of a combination therapy regimen comprising stereotactic body radiation therapy (SBRT) combined with liposomal irinotecan, camrelizumab, and anti-angiogenic therapy (CAP) in patients with advanced bone and soft tissue sarcomas. Methods This study is a prospective subgroup analysis of the multicenter, open-label, single-arm phase Ⅱ CAP trial (NCT04569916), which enrolled 60 patients with advanced solid tumors who had progressed after standard therapy between November 2020 and February 2023, including 11 patients with advanced bone and soft tissue sarcomas. All patients received sequential liposomal irinotecan within 48 hours after stereotactic body radiotherapy (SBRT), followed by maintenance therapy with camrelizumab and an anti-angiogenic agent until disease progression or intolerable toxicity. The primary efficacy endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results In the bone and soft tissue sarcoma subgroup (n=11), three patients achieved partial response (PR), five had stable disease (SD), and three experienced disease progression (PD). ORR was 27.3%, and DCR was 72.7%. mPFS was 5.8 months (95%CI: 2.2-10.3), and mOS not reached. Regarding safety, adverse reactions primarily included bone marrow suppression, fatigue, and gastrointestinal reactions, indicating overall manageable toxicity. Conclusion As a subgroup analysis of the CAP study, this research suggests that radiotherapy combined with liposomal irinotecan, camrelizumab, and anti-angiogenic therapy demonstrates certain efficacy in advanced bone and soft tissue sarcomas that have failed multiple lines of treatment, with overall manageable adverse reactions. Future studies should expand the sample size.

It is proposed that although allergic rhinitis manifests primarily in the nasal orifices， its root lies in deficiency of the lung and spleen and insecurity of the lung defensive qi， while deficiency of healthy qi with latent pathogen， triggering by external stimuli， and constraint of defensive yang constitute the key pathogenesis. The onset of disease is not caused solely by newly contracted external pathogens. Rather， on the basis of insecurity of the lung-defense qi， external stimuli such as wind-cold and abnormal qi， dust mites， pollen， and sudden climatic changes， activate the latent pathogen， resulting in constraint of defensive yang， disharmony between nutritive and defensive qi， impaired diffusion of lung qi， failure to contain body fluids， and dysfunction of the nasal orifices. The disease progression can be summarized as following steps， deficiency of healthy qi with latent pathogen， activation by external stimuli， constraint of defensive yang， dysfunction of the nasal orifices， incomplete elimination of the pathogen and incomplete recovery of healthy qi. The general therapeutic principle is to consolidate the defensive qi and vent the latent pathogen while regulating the lung and nasal orifices simultaneously. The empirical prescription Xingui Fangzhi Decoction （辛桂防芷汤） is used as the basic formula and modified dynamically according to the attack and remission stages. During the attack stage， treatment focuses on dispelling wind and cold， regulating defensive qi， and venting the latent pathogen； during the remission stage， it emphasizes supplementing qi， consolidating the defensive exterior， and reinforcing the spleen to resolve the latent pathogen.

Objective:To explore the combined predictive value of serum stromal cell-derived factor-1 (SDF-1), chitinase 3-like protein 1 (YKL-40), carbohydrate antigen 724 (CA724) and pepsinogen (PG) on recurrence after endoscopic submucosal dissection (ESD) in patients with early gastric cancer.Methods:96 patients with early gastric cancer admitted to Yan 'an Hospital of Traditional Chinese Medicine from August 2021 to August 2023 were retrospectively selected and enrolled into the study. According to the recurrence after ESD, they were divided into recurrence group (31 cases) and non-recurrence group (65 cases). The differences in baseline data, serum SDF-1, YKL-40, CA724 and PG levels were compared between groups. The correlation between serum SDF-1, YKL-40, CA724 and PG levels and clinical indicators of patients was analyzed. Normally distributed quantitative data were expressed as xˉ± s, and independent sample t test was used for inter-group comparison. Counting data were calculated as percentages, and χ2 test was used for inter-group comparison. Spearman method was used for correlation analysis. Multivariate logistics regression analysis was used to analyze the factors affecting postoperative recurrence. ROC curve was used to analyze the single and combined diagnostic value of each serum indicator on recurrence after ESD. Results:The number of well-differentiated cases in recurrence group (32.26%, 10/31) was lower than that in non-recurrence group (70.77%, 46/65), the difference was statistically significant ( χ2=12.81, P<0.001). The levels of SDF-1 [(160.57±16.49) μg/L], YKL-40 [(208.49±22.69) μg/L] and CA724 [(10.49±1.91) kU/L] of recurrence group were higher than non-recurrence group[(136.57±14.56) μg/L, (157.53±20.46) μg/L, (5.11±0.83) kU/L)], and the differences were statistically significant ( t=7.23, 11.01 and 19.29, respectively, all P<0.05), while the PGⅠ/PGⅡ [(2.87±0.57) μg/L] was lower than that in non-recurrence group [(4.18±0.76) μg/L], the difference was statistically significant( t=8.514, P<0.05). Correlation analysis showed that SDF-1, YKL-40 and CA724 were negatively correlated with the degree of differentiation ( r=-0.545, -0.415, -0.718, respectively, all P<0.05), and the PGⅠ/PGⅡ was positively correlated with the degree of differentiation ( r=0.687, P<0.05). Multivariate logistics regression analysis suggested that SDF-1 ( OR=8.191, 95% CI=1.483-45.246, P=0.016), YKL-40 ( OR=9.843, 95% CI=1.782-54.387, P=0.009), CA724 ( OR=10.386, 95% CI=2.053-52.506, P=0.005), PGⅠ/PGⅡ ( OR=0.108, 95% CI=0.028-0.417, P=0.001) and differentiation degree ( OR=0.421, 95% CI=0.219-0.810, P=0.010) were influencing factors of postoperative recurrence. ROC analysis results showed that the AUCs of SDF-1, YKL-40, CA724 and PGⅠ/PGⅡ in predicting postoperative recurrence of early gastric cancer patients were 0.857, 0.956, 0.945 and 0.910, sensitivities were 80.65%, 90.32%, 83.87% and 83.87%, specificities were 78.46%, 76.92%, 81.54% and 80.00%, respectively. The AUC, sensitivity and specificity of combined prediction were 0.986, 96.77% and 73.85%. Conclusion:The levels of serum SDF-1, YKL-40 and CA724 in patients with early gastric cancer recurrence after ESD are higher while the PGI/PGII is lower, and the above levels are relevant factors for postoperative recurrence and can be used as clinical reference indicators to predict recurrence after ESD.

Objective On the basis of systematically summarizing and organizing the existing standards of mineral drugs in traditional Chinese medicine,this study aims to construct the top-level framework of the mineral drug standard system and promote the standardization process of the mineral drug industry.Methods A comprehensive search and analysis of the standards for 87 kinds of mineral drugs were conducted on authoritative platforms such as the National Standard Information Public Service Platform,China Standard Service Network,and Traditional Chinese Medicine Standard and Guideline Information Service.By delving into the theoretical foundation and scientific methods,combined with practical research,this study uses analogy reference,systematic decomposition,and process analysis to design the top-level framework of the mineral drug standard system.Results Through comprehensive analysis and scientific design,this study summarizes the construction process and methods of the mineral drug standard system,clarifies the hierarchical structure and classification principles of the system,proposes the compilation path,and forms a standard system covering the entire industry chain of mineral drugs,including raw minerals,product categories,and circulation categories.Conclusion This study constructs a full industry chain process framework for the standard system of mineral drugs,providing a clear perspective for the research of mineral drugs.It can more comprehensively display the current state of development of mineral drug standards in our country,laying a foundation for the research on the standardization of mineral drugs.

Inflammatory breast cancer(IBC)is a rare but highly aggressive subtype of breast cancer characterized by rapid clinical progression and poor prognosis.Although it accounts for only 2%-4%of all breast cancer cases,it is responsible for 8%-10%of breast cancer-related mortality.The etiology of IBC is multifactorial,involving genetic,hormonal,environmental,and socioeconomic factors.Pathologically,IBC is marked by the presence of dermal lymphatic tumor emboli,and molecular subtypes are predominantly HER2-positive and triple-negative,indicating high tumor invasiveness.Diagnosis relies on characteristic clinical manifestations and histopathological confirmation,while imaging techniques such as MRI and PET/CT play important roles in evaluating disease extent and metastasis.Given that IBC is often diagnosed at a locally advanced or metastatic stage,there is currently no specific treatment protocol.Instead,management generally follows the treatment paradigm of non-IBC,emphasizing systemic therapy within a multidisciplinary framework.HER2-positive IBC benefits from chemotherapy combined with dual-targeted anti-HER2 therapy;triple-negative IBC may respond to immune checkpoint inhibitors;and CDK4/6 inhibitors show potential efficacy in hormone receptor-positive subtypes.Despite advancements,the prognosis remains poor,with a high risk of early recurrence and distant metastasis.Prognostic factors include lymph node involvement,molecular subtype,and response to neoadjuvant therapy.As research into the tumor microenvironment and molecular mechanisms deepens,targeted and individualized therapies hold promise for improving outcomes.This review summarizes the epidemiology,pathology,diagnostic criteria,treatment strategies,and prognostic factors of IBC,aiming to inform clinical practice and future research.

OBJECTIVE: EPF3 is a fibrinolysin monomer isolated and purified from Pheretima vulgaris Chen, an earthworm used in traditional Chinese medicine as Dilong for treating blood stasis syndrome. Its composition, anticoagulant and fibrinolytic activities, and relevant mechanisms have been confirmed through in vitro experiments. However, whether it has antithrombotic effects in vivo and can be absorbed by the gastrointestinal tract is unknown. This study evaluates the antithrombotic effect in zebrafish and investigates the gastrointestinal stability and intestinal absorption mechanism of this protein in vitro. METHODS: The antithrombotic effect of EPF3 in vivo was verified using the zebrafish thrombus model induced by arachidonic acid and FeCl₃. Then, the protein bands of EPF3 incubated with simulated gastric fluid (SGF), simulated intestinal fluid (SIF), and homogenate of Caco-2 cells (HC2C) were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to evaluate its gastrointestinal stability. Finally, the transport behavior and absorption mechanism of EPF3 were studied using Caco-2 cell monolayer. RESULTS: EPF3 could significantly enhance the returned blood volume and blood flow velocity in zebrafish with platelet aggregation thrombus induced by arachidonic acid. It could also prolong the formation time of tail artery thrombus and increase the blood flow velocity in zebrafish with vessel injury thrombus induced by FeCl₃. EPF3 was stable in SIF and HC2C and unstable in SGF. The permeability of EPF3 in Caco-2 monolayer was time-dependent and concentration-dependent. The efflux ratio was less than 1.2 during transport, and the transport behavior was not affected by inhibitors. EPF3 could reversibly reduce the expression of tight junction-related proteins, including zonula occludens-1, occludin, and claudin-1 in Caco-2 cells. CONCLUSION EPF3 could play a thrombolytic and antithrombotic role in zebrafish. It could be transported and absorbed into the intestine through cellular bypass pathway by opening the intestinal epithelium tight junction. This study provides a scientific explanation for the antithrombotic effect of earthworm and provides a basis for the feasibility of subsequent development of EPF3 as an antithrombotic enteric-soluble preparation. Please cite this article as: Zhong WL, Yang JQ, Liu H, Wu YL, Shen HJ, Li PY, Du SY. Antithrombotic effect in zebrafish of a fibrinolytic protein EPF3 from Dilong (Pheretima vulgaris Chen) and its transport mechanism in Caco-2 monolayer through cell bypass pathway. J Integr Med. 2025; 23(4): 415-428.
Animals ; Zebrafish ; Humans ; Caco-2 Cells ; Fibrinolytic Agents/pharmacology* ; Thrombosis/drug therapy* ; Intestinal Absorption

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.