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.

OBJECTIVE: To investigate possible associations between physical function assessment scales, such as Short Physical Performance Battery (SPPB) and Berg Balance Scale (BBS), with all-cause mortality in acute decompensated heart failure (ADHF) patients. METHODS: A total of 108 ADHF patients were analyzed from October 2020 to October 2022, and followed up to May 2023. The association between baseline clinical characteristics and all-cause mortality was analyzed by univariate Cox regression analysis, while for SPPB and BBS, univariate Cox regression analysis was followed by receiver operating characteristic curves, in which the area under the curve represented their predictive accuracy for all-cause mortality. Incremental predictive values for both physical function assessments were measured by calculating net reclassification index and integrated discrimination improvement scores. Optimal cut-off value for BBS was then identified using restricted cubic spline plots, and survival differences below and above that cut-off were compared using Kaplan-Meier survival curves and the log-rank test. The clinical utility of BBS was measured using decision curve analysis. RESULTS: For baseline characteristics, age, female, blood urea nitrogen, as well as statins, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, or angiotensin receptor-neprilysin inhibitors, were predictive for all-cause mortality for ADHF patients. With respect to SPPB and BBS, higher scores were associated with lower all-cause mortality rates for both assessments; similar area under the curves were measured for both (0.774 for SPPB and 0.776 for BBS). Furthermore, BBS ≤ 36.5 was associated with significantly higher mortality, which was still applicable even adjusting for confounding factors; BBS was also found to have great clinical utility under decision curve analysis. CONCLUSIONS BBS or SPPB could be used as tools to assess physical function in ageing ADHF patients, as well as prognosticate on all-cause mortality. Moreover, prioritizing the improvement of balance capabilities of ADHF patients in cardiac rehabilitation regimens could aid in lowering mortality risk.

OBJECTIVES: Increasing detection of low-risk papillary thyroid carcinoma (PTC) is associated with overdiagnosis and overtreatment. N6-methyladenosine (m⁶A)-mediated microRNA (miRNA) dysregulation plays a critical role in tumor metastasis and progression. However, the functional role of m⁶A-miRNAs in PTC remains unclear. This study aims to elucidate the regulatory mechanism of m⁶A-miR-139-5p expression in PTC, determine its association with PTC metastasis, and evaluate its potential as a diagnostic biomarker for PTC metastasis, thereby providing experimental evidence for precision diagnosis and therapy. METHODS: Expression profiles of m⁶A-miRNAs were compared between the The Cancer Genome Atlas (TCGA) and GSE130512 cohorts to identify metastasis-associated candidates. Clinical specimens from 13 metastasis and 18 non-metastasis PTC patients were analyzed to assess m⁶A-miR-139-5p expression and its correlation with metastasis. Functional experiments were conducted to investigate the effect of fat mass and obesity-associated protein (FTO) on pri-miR-139 methylation and processing, clarifying its regulatory role in miR-139-5p expression. In TPC-1 cells, MTT assays were performed to evaluate whether miR-139-5p overexpression could counteract FTO-mediated cell proliferation. Transwell invasion assays were used to determine the impact of miR-139-5p on PTC cell invasion, exploring whether it functions through the ZEB1/E-cadherin axis. RESULTS: By comparing TCGA and GSE130512 cohorts, it was found that circulating m⁶A-miR-139-5p could serve as a biological indicator for detecting PTC metastasis. Detection of 13 metastatic and 18 non-metastatic clinical specimens showed that FTO inhibited the processing of pri-miR-139 by reducing its methylation level, leading to the dysregulation of miR-139-5p in PTC (P<0.05). In TPC-1 cells, MTT assay showed that overexpression of miR-139-5p could partially reverse FTO overexpression-mediated cell proliferation (P<0.05). In addition, miR-139-5p inhibited the invasive ability of PTC cells by targeting the ZEB1/E-cadherin axis, while FTO overexpression could partially weaken this inhibitory effect. CONCLUSIONS Circulating miR-139-5p can be a potential marker for evaluating PTC metastasis. FTO affects the expression and function of miR-139-5p by regulating m⁶A modification of pri-miR-139, but its clinical value needs further verification.
Humans ; MicroRNAs/metabolism* ; Thyroid Cancer, Papillary/metabolism* ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/metabolism* ; Thyroid Neoplasms/metabolism* ; Cell Line, Tumor ; Neoplasm Metastasis ; Adenosine/genetics* ; Gene Expression Regulation, Neoplastic ; Female ; Male ; Cadherins/metabolism* ; Cell Proliferation ; Zinc Finger E-box-Binding Homeobox 1/genetics*

Objective To observe the ultrasonic manifestations of abdominal pregnancy.Methods Ultrasonic and clinical data of 18 pregnant woman with abdominal pregnancy diagnosed by operation and pathology were retrospectively analyzed.Results Among 15 cases in first trimester,no preoperative ultrasonic diagnosis of abdominal pregnancy was obtained.Ultrasound showed no gestational sac in uterine cavity but mass in pelvic cavity,which located in the adnexal region in 8 cases,in the front and the post of uterus each in 2 cases,while in the adnexal region and the front of uterus in 1 case,in the post of the cervix in 1 case,and closed to uterine wall in 1 case,without obvious tubal echo around mass in all 15 cases.There were 2 cases of abdominal pregnancy in the second trimester,which were first diagnosed with ultrasound at 13+6 weeks and 21 weeks,with gestational sac located on the left side of uterus and behind the uterus,respectively.One case of abdominal pregnancy in the third trimester was first diagnosed with ultrasound at 35 4 weeks,with gestational sac located on the right side of uterus.Ultrasonic manifestations of the above three cases all showed gestational sac located outside the uterus without myometrium wrapping around the gestational sac nor placenta implanted in uterus,while echoes of fluid accumulation were detected around fetus.The ultrasonic diagnosis rate of abdominal pregnancy was 16.67％(3/18).Conclusion In the first trimester,if the ectopic pregnancy mass was large or the gestational sac located adjacent to the cervix,anterior or posterior to uterus and on the uterine wall,also no fallopian tube-like echo around the mass,the possibility of abdominal pregnancy should be considered.Ultrasonic manifestations of abdominal pregnancy in the second and third trimester present as gestational sac outside uterine cavity without wrapping uterine muscle layer around,no placenta implantation in uterine cavity,as well as echoes of fluid accumulation around fetus.Transabdominal combined with transvaginal ultrasound could improve diagnostic rate of abdominal pregnancy.

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:To analyze the differences in clinicopathological features between non-elderly and elderly patients with melanoma, and to identify risk factors for prognosis in elderly patients with melanoma.Methods:A retrospective analysis was conducted on clinical and pathological data collected from non-elderly (aged < 60 years) and elderly (aged ≥ 60 years) patients with melanoma, who were confirmedly diagnosed according to clinical manifestations and histopathological findings at the People's Hospital of Xinjiang Uygur Autonomous Region from January 2008 to December 2023. The differences in clinical and pathological characteristics between the two groups were analyzed using the chi-square test and Wilcoxon rank-sum test. Survival curves were estimated using the Kaplan-Meier method and log-rank test. The relationship between clinicopathological variables and overall survival was analyzed using a Cox regression model.Results:A total of 233 patients with cutaneous melanoma were included, with the age being 60.3 ± 14.7 years, and the number of patients was highest in the age group of 60 - 69 years. There were 102 cases (43.8%) in the < 60 years old group and 131 cases (56.2%) in the ≥ 60 years old group. Compared with the < 60 years old group, the ≥ 60 years old group showed a significant increase in the proportion of patients with active tumor-infiltrating lymphocytes ( P = 0.040), proportion of those with Ki-67 index ≥ 30% ( P = 0.010), and Charlson comorbidity index ( P = 0.002), but a significant decrease in the proportion of patients with BRAF/KIT/NRAS mutations ( P = 0.003), proportion of those receiving surgical treatment ( P = 0.034), and proportion of those receiving adjuvant therapy ( P = 0.042). There was a significant difference in the overall survival between the two groups (log-rank test, χ2 = 6.10, P = 0.014). The gender, metastasis status, presence or absence of ulceration, distant metastasis status, American Joint Committee on Cancer staging, Charlson comorbidity index, and Breslow thickness were important prognostic indicators affecting the overall survival in the elderly patients with melanoma. Multivariate Cox regression analysis showed that males ( P = 0.015, HR = 4.622, 95% CI: 1.352 - 15.798), presence of distant metastasis ( P = 0.013, HR = 9.844, 95% CI: 4.621 - 59.763), and Charlson comorbidity index ≥ 3 ( P = 0.038, HR = 3.149, 95% CI: 1.067 - 9.294) were independent risk factors affecting the overall survival in the elderly patients with melanoma. Conclusions:Compared with the non-elderly patients with melanoma, a higher Ki-67 index, a higher Charlson comorbidity index, less surgical treatment, and less adjuvant therapy were more common in the elderly patients with melanoma. Males, the presence of distant metastasis, and Charlson comorbidity index ≥ 3 appeared to be independent risk factors affecting the overall survival in the elderly patients with melanoma.

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*