BACKGROUND: Concurrent chemo-radiotherapy (CCRT) is the standard treatment for locally advanced cervical cancer (LACC), but there are still many patients who suffer tumor recurrence. However, valuable predictors of treatment outcomes remain limited. This study aimed to assess the value of the serum immune biomarkers to predict the prognosis. METHODS: We reviewed cervical cancer patients treated with CCRT between January 2014 and May 2018 at Peking Union Medical College Hospital. The systemic immune inflammation index (SII), systemic inflammation response index (SIRI), and lactate dehydrogenase (LDH) were calculated using blood samples. The relationship between immune markers and the treatment outcome was analyzed. The area under the receiver operating characteristic (ROC) curve was used to evaluate the predictive efficiency. The Cox proportional hazards model and log-rank were used to predict overall survival (OS) and disease-free survival (DFS). RESULTS: This study included 667 patients. Among them, 195 (29.2%) patients were defined as treatment failure, including 127 (19.0%) patients with pelvic failure, 94 (14.1%) distant failure, and 25 (3.7%) concurrent pelvic and distant failure. It revealed that the tumor stage, size, metastatic lymph nodes (MLNs), and serum immune biomarkers, such as SII, SIRI, and LDH, were significantly related to treatment outcomes. We demonstrated that the optimal cut-off of the SII, SIRI, and LDH were 970.4 × 10 9 /L, 1.3 × 10 9 /L, and 207.52 U/L, respectively. Importantly, this study presented that LDH level had the highest OR (OR = 4.2; 95% CI [2.3-10.8]). Furthermore, the OS and DFS for patients with pre-SII ≥970.5 × 10 9 /L were significantly worse than those with pre-SII <970.5 × 10 9 /L. Similarly, pre-SIRI ≥1.25 × 10 9 /L and pre-LDH ≥207.5 U/L were related to poor survival outcomes. CONCLUSIONS This study demonstrated that the baseline SII, SIRI, and LDH levels can be used to accurately and effectively predict the treatment outcomes after CCRT and long-term prognosis. Our results may offer additional prognostic information in clinical, which helps to detect the potential recurrent metastasis in time.
Humans ; Female ; Uterine Cervical Neoplasms/drug therapy* ; Middle Aged ; Adult ; Aged ; Chemoradiotherapy/methods* ; L-Lactate Dehydrogenase/blood* ; Treatment Outcome ; Disease-Free Survival ; Prognosis ; ROC Curve ; Biomarkers, Tumor/blood* ; Proportional Hazards Models

Neutrophils, as the most abundant immune cells in the human body, possess the inherent ability to rapidly migrate to sites of inflammation and infection. Novel drug delivery systems leveraging neutrophils capitalize on their natural targeting and phagocytic capabilities to achieve precise drug delivery. Efficient drug loading into neutrophils within neutrophil-based delivery systems can be achieved through physical adsorption, chemical conjugation, and phagocytosis. Design strategies emphasize carrier selection and targeting ligand design to enhance delivery precision. Compared to traditional drug delivery systems, neutrophil-based systems offer significant advantages, including excellent biocompatibility and strong tissue penetration. These properties can significantly improve drug bioavailability and reduce adverse reactions associated with non-target tissue accumulation. However, these systems also face several challenges that require resolution, such as difficulties in cell collection and preservation, the need for stability optimization, challenges in large-scale production, and a lengthy clinical translation cycle. In disease treatment applications, neutrophil-based drug delivery systems enable precise delivery of anti-cancer drugs to tumor sites, potentially disrupting immunosuppression of the tumor microenvironment and enhancing therapeutic efficacy. For brain diseases, their unique ability to cross the blood-brain barrier facilitates effective drug delivery. In chronic inflammatory diseases, neutrophil-based systems can precisely deliver anti-inflammatory agents to mitigate inflammation. Performance enhancements for neutrophil-based systems can be achieved by the development of novel nanomaterials and optimization of targeting ligand affinity, thereby improving the accuracy and efficiency of drug delivery. This review comprehensively explores the design strategies, advantages, challenges, and future directions of neutrophil-based drug delivery systems. It summarizes research progress in disease treatment applica-tions, aiming to offer key insights for the development of novel drug delivery systems and advance precision medicine and targeted therapy.
Humans ; Drug Delivery Systems/methods* ; Neutrophils ; Phagocytosis ; Drug Carriers ; Blood-Brain Barrier ; Neoplasms/drug therapy*

OBJECTIVE: To investigate the clinical effect of prostatectomy combined with neoadjuvant endocrine therapy. METHODS: A total of 147 prostate cancer patients who were treated at the Hai'an People's Hospital from January 2019 to December 2023 were enrolled in the study. The patients were randomly divided into three groups using a random number table, with 49 cases in each group. The patients in control group 1 were treated with radical prostatectomy alone. Endocrine therapy was performed in control group 2. And the patients in observation group received radical prostatectomy combined with neoadjuvant endocrine therapy. Clinical indicators, improvement of prostate symptoms (measured by the IPSS), immune function (CD3+, CD4+, CD4+/CD8+ ratio), serum levels (PSA and vascular endothelial growth factor ［VEGF］), and complications were compared among the three groups. A one-year postoperative follow-up was conducted to monitor recurrence. RESULTS: After treatment, the patients in observation group had shorter operative time and lymph node dissection time, less intraoperative blood loss, and lower rate of positive surgical margins compared to control group 1. The IPSS score in the observation group was significantly lower than that in control group 1 and control group 2. The levels of CD3+, CD4+, and the CD4+/CD8+ ratio were higher in the observation group compared to the other two groups. The serum levels of PSA and VEGF were lower in the observation group. The incidence of complications in observation group was lower compared to both control groups. And the recurrence rate after one year was lower in the observation group than that in the other two groups. All differences were statistically significant (P<0.05). CONCLUSION The clinical indicators, immune function, levels of PSA and VEGF as well as postoperative complications can be improved through radical prostatectomy combined with neoadjuvant endocrine therapy.
Humans ; Male ; Prostatectomy ; Prostatic Neoplasms/drug therapy* ; Neoadjuvant Therapy ; Vascular Endothelial Growth Factor A/blood* ; Middle Aged ; Prostate-Specific Antigen/blood* ; Aged ; Treatment Outcome

OBJECTIVE: The aim of this study is to explore the clinical efficacy and safety of endocrinotherapy combined with Shenqi Pills on hormone-sensitive prostate cancer (HSPC). METHODS: Eighty patients who were diagnosed with HSPC and renal-yang deficiency at the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine and the Hospital of Traditional Chinese Medicine of Mayang Miao Autonomous County from 1st April 2021 to 30th April 2024 were randomly divided into 2 groups. The patients in the control group were treated with androgen deprivation therapy (ADT). And the patients in treatment group were treated with Shenqi Pills orally on the basis of the control group. The baseline data of the two groups were analyzed. After 36 months of treatment, the differences between the two groups were compared in terms of overall survival (OS), prostate-specific antigen (PSA) level, PSA response rate, Functional Assessment Scale for Prostate Cancer Therapy (FACT-P), Chinese medicine evidence scores, testosterone level and safety. RESULTS: A total of 80 study subjects were included in this study, including 42 cases in the treatment group and 38 cases in the control group. There was no statistical difference in the baseline data between the two groups before treatment (P>0.05). At the end of the observation period, a statistically significant difference in OS was found in the treatment group compared to the control group in the subgroup of patients with a disease duration ranged of 0-6 months (P<0.05). There was no statistically significant difference in PSA levels in the treatment group at 3 months (P>0.05). And the differences in the proportion of PSA50 (98.1% vs 91.4%), PSA90 (92.9% vs 84.6%) and the proportion of decrease in PSA (56.7% vs 33.8%) in the treatment group were found compared to those in the control group after 6 months of tre atment. After 12 months of treatment, the scores of FACT-4 and renal-yang deficiency in the treatment group were (95.28±7.93) and (15.73±5.70) respectively, compared to the scores in the control group (［85.46±10.12］ and ［18.20±4.27］ (P<0.05). However, there was no significant difference in serum testosterone (［0.60±0.24］ nmol/L vs ［1.09±2.10］ nmol/L) between the two groups (P>0.05). After 24 months of treatment, there were significant differences in in the FACT-4 total score (［97.95±7.54］ vs ［80.33±8.58］), renal-yang deficiency syndrome score (［14.64±5.15］ vs ［24.94±8.75］) between the treatment group and the control group (P<0.05). However, there was no significant difference in serum testosterone ( ［0.73±1.01］ nmol/L vs ［0.59±0.25］ nmol/L) between the two groups (P> 0.05). Better therapeutic results were showed in the treatment group in terms of total FACT-P score, physical situation score, social and family situation score, emotional state score, functional state score, additional score and renal-yang deficiency symptom score (P<0.05). After treatment, there was no serious adverse reaction in the course of treatment, and no obvious abnormality was found in the liver and kidney function of the patients from two groups. CONCLUSION Endocrinotherapy combined with Shenqi Pills is safe and effective in HSPC and can reduce the risk of death in HSPC patients, and the earlier the intervention, the longer the overall survival of the patients. In addition, this treatment regimen can increase the PSA response rate, improve patients' quality of life, and reduce the renal-yang deficiency syndrome score without the risk of elevating serum testosterone levels.
Humans ; Male ; Drugs, Chinese Herbal/therapeutic use* ; Prostatic Neoplasms/drug therapy* ; Androgen Antagonists/therapeutic use* ; Prostate-Specific Antigen/blood* ; Aged ; Middle Aged ; Treatment Outcome ; Testosterone

OBJECTIVE: Angiogenesis is a critical target for hepatocellular carcinoma (HCC) treatment. The previous studies indicated that Jiedu Fang (JDF) could inhibit hypoxia-induced angiogenesis through interleukin-8 (IL-8). Therefore, the present study further explores the mechanisms behind JDF's inhibition of HCC angiogenesis. METHODS: Angiogenesis was assessed with the capillary-like tube formation assay in vitro and the matrigel plug angiogenesis assay in vivo. A liver cancer-related gene set and genes associated with angiogenesis and the hypoxic microenvironment were analyzed using a bioinformatics platform. Real-time reverse transcription-polymerase chain reaction and Western blotting assays were used to assess the targeted mRNA and protein levels, respectively. The Transwell assay was used to assess the migration and invasion potential of EA.hy 926 cells. The orthotopic tumor xenograft model was established, and immunohistochemistry and immunofluorescence assays were used to detect cluster of differentiation 31 and angiopoietin 2 expression, while an enzyme-linked immunosorbent assay was used to detect vascular endothelial growth factor and IL-8 protein levels. RESULTS: In vitro and in vivo assays showed that IL-8 promoted angiogenesis, and JDF could antagonize this effect. Bioinformatics analysis indicated that aurora kinase A (Aurora A) was an important candidate, which can promote IL-8 expression through activation of signal transducer and activator of transcription 3 (STAT3). The overexpression of Aurora A increased IL-8 secretion and promoted HCC migration, invasion, and angiogenesis, which was partly inhibited by JDF. Such effects were validated by in vivo assays. Further validation using the STAT3 inhibitor S3I-201 demonstrated that STAT3 was regulated by Aurora A. CONCLUSION JDF exhibits efficacy in reducing hypoxia-induced angiogenesis in HCC through a mechanism involving the Aurora A/STAT3/IL-8 signaling pathway. Therefore, JDF holds promise as a potential therapeutic approach for targeting HCC angiogenesis. Please cite this article as: Zhong MF, Luo YJ, Guo YY, Xiang S, Lin WF. Jiedu Fang inhibits hypoxia-induced angiogenesis in hepatocellular carcinoma by targeting Aurora A/STAT3/IL-8 signaling pathway. J Integr Med. 2025; 23(6):683-693.
Carcinoma, Hepatocellular/blood supply* ; Humans ; STAT3 Transcription Factor/metabolism* ; Interleukin-8/metabolism* ; Liver Neoplasms/blood supply* ; Aurora Kinase A/metabolism* ; Neovascularization, Pathologic/drug therapy* ; Animals ; Signal Transduction/drug effects* ; Mice ; Drugs, Chinese Herbal/therapeutic use* ; Cell Line, Tumor ; Mice, Inbred BALB C ; Mice, Nude ; Angiogenesis

Both carcinoembryonic antigen and CA19-9 are considered as predictive markers of intestinal cancer recurrence and metastasis.In addition,CA19-9 elevation is considered as a predictive marker of connective tissue disease-related interstitial lung disease.The incidence of oxaliplatin and capecitabine-associated interstitial lung disease is low,and there is no report about CA19-9 as a predictive marker of oxaliplatin and capecitabine-associated interstitial lung disease.This paper reports a case of interstitial lung disease with CA19-9 elevation caused by oxaliplatin and capecitabine adjuvant therapy for ileocecal carcinoma.The change trend of serum carcinoembryonic antigen in this patient was consistent with tumor recurrence and metastasis,and that of serum CA19-9 was consistent with the severity of interstitial lung disease.Therefore,CA19-9 elevation after intestinal cancer surgery does not necessarily indicate the tumor recurrence and metastasis,and attention should be paid to the possibility of oxaliplatin and capecitabine-associated interstitial lung disease.
Humans ; CA-19-9 Antigen/blood* ; Capecitabine ; Cecal Neoplasms/drug therapy* ; Chemotherapy, Adjuvant ; Deoxycytidine/administration & dosage* ; Fluorouracil/administration & dosage* ; Lung Diseases, Interstitial/blood* ; Organoplatinum Compounds/administration & dosage* ; Oxaliplatin

Immune checkpoint inhibitors (ICIs) are widely used in clinic, and the incidence of rare adverse events are increasing. The aim of this paper is to better define the rare adverse effect of diabetes mellitus associated with ICIs. We report 2 cases of diabetes mellitus associated with ICIs. Literature review was conducted and we discussed the clinical presentation, potential mechanisms and suggestions for optimal management. Two patients were both elderly women, case 1 had increased blood glucose after 7 months of using Durvalumab, and cases 2 had diabetic ketoacidosis after 6 weeks of using Pembrolizumab. Both patients were administered exogenous insulin to control blood glucose. Case 1 has been treated with Durvalumab until now and case 2 discontinued using of Pembrolizumab. HLA genotypes and other factors may explain the risk factors of diabetes associated with ICIs in some individuals. Diabetes mellitus associated with ICIs is an uncommon but potentially life-threatening endocrine system adverse event, which requires doctors to be vigilant. The patients who use ICIs need to monitor blood glucose. If they have hyperglycemia, endocrinologists should be asked to assist in diagnosis and treatment.
.
Aged ; Blood Glucose ; Diabetes Mellitus/drug therapy* ; Female ; Humans ; Immune Checkpoint Inhibitors/adverse effects* ; Lung Neoplasms/drug therapy*

3.38, PLR >210, CA125 >365, advanced stage, suboptimal disease, serous type, and ascites were significant predictive factors for platinum resistance. However, only NLR >3.38 and advanced stage were independent predictive factors with an adjusted odds ratio of 1.880 and 3.333, respectively. Regarding factors associated with poor survival outcomes, only PLR >210 and advanced stage were independent factors, with a hazard ratio of 1.578 and 3.994, respectively.CONCLUSION: High NLR and advanced stage were potential independent predictive factors for platinum resistance, whereas high PLR and advanced stage were potential independent predictive factors for poor survival outcomes.]]>
Ascites ; Blood Platelets ; Drug Therapy ; Fallopian Tubes ; Female ; Humans ; Lymphocytes ; Medical Records ; Multivariate Analysis ; Neutrophils ; Odds Ratio ; Ovarian Neoplasms ; Platinum ; Prognosis ; Retrospective Studies ; ROC Curve

We aimed to evaluate the current nationwide trend, efficacy, safety, and quality of life (QoL) profiles of hormone treatment in real-world practice settings for prostate cancer (PCa) patients in Korea. A total of 292 men with any biopsy-proven PCa (TanyNanyMany) from 12 institutions in Korea were included in this multi-institutional, observational study of prospectively collected data. All luteinizing hormone-releasing hormone (LHRH) agonists were allowed to be investigational drugs. Efficacy was defined as (1) the rate of castration (serum testosterone ≤50 ng dl^-1) at 4-week visit and (2) breakthrough (serum testosterone >50 ng dl^-1 after castration). Safety assessments included routine examinations for potential adverse events, laboratory tests, blood pressure, body weight, and bone mineral density (BMD, at baseline and at the last follow-up visit). QoL was assessed using the Expanded Prostate Cancer Index Composite-26 (EPIC-26). The most common initial therapeutic regimen was LHRH agonist with anti-androgen (78.0%), and the most commonly used LHRH agonist for combination and monotherapy was leuprolide (64.0% for combination and 58.0% for monotherapy). The castration and breakthrough rates were 78.4% and 6.6%, respectively. The laboratory results related to dyslipidemia worsened after 4 weeks of hormone treatment. In addition, the mean BMD T-score was significantly lower at the last follow-up (mean: -1.950) compared to baseline (mean: -0.195). The mean total EPIC-26 score decreased from 84.8 (standard deviation [s.d.]: 12.2) to 78.3 (s.d.: 8.1), with significant deterioration only in the urinary domain (mean: 23.5 at baseline and 21.9 at the 4-week visit). These findings demonstrate the nationwide trend of current practice settings in hormone treatment for PCa in Korea.
Aged ; Androgen Antagonists/therapeutic use* ; Antineoplastic Agents, Hormonal/therapeutic use* ; Cholesterol/blood* ; Drug Therapy, Combination ; Humans ; Leuprolide/therapeutic use* ; Male ; Middle Aged ; Prostatic Neoplasms/pathology* ; Quality of Life ; Receptors, LHRH/agonists* ; Republic of Korea ; Testosterone/blood* ; Treatment Outcome ; Triglycerides/blood*

OBJECTIVE: To investigate the evaluation value of preoperative peripheral blood lymphocyte-to-monocyte ratio (LMR) on the prognosis of patients with stage III colon cancer undergoing radical resection and postoperative adjuvant chemotherapy. METHODS: Electronic medical record were retrospectively retrived for stage III colon cancer patients who underwent radical surgery at Sun Yat-sen University Cancer Center from December 2007 to December 2013. Inclusion criteria were pathologically comfirmed colon adenocarcinoma, complete clinicopathological data, and postoperative XELOX (oxaliplatin + capecitabine) chemotherapy with follow-up of at least 3 months. Patients with neoadjuvant anti-tumor therapy, infectious disease, other malignant tumors and death of non-tumor causes within 3 months after operation were excluded. A total of 258 patients were included in this retrospective cohort study, including 146 males and 112 females with median age of 55 (22 to 85) years. Tumors of 100(38.8%) patients were located in the right hemicolon, and of 158 (61.2%) in the left hemicolon. Tumors of 194(75.2%) patients were highly and moderately differentiated, and of 64 (24.8%) were poorly differentiated. According to the TNM tumor pathological stage of AJCC 7th edition, 196 (76.0%) patients were stage IIIA to IIIB, and 62(24.0%) patients were stage IIIC. The median preoperative CEA was 3.8 (0.3 to 287.5) μg /L and the median cycle of the adjuvant chemotherapy was 6 (1 to 8). The cut-off value of preoperative LMR in prediction of 3-year overall survival (OS) outcome was determined by receiver operating characteristic (ROC) curve analysis. All patients were divided into low LMR group and high LMR group according to the critical value. Clinicopathological characteristics between the two groups were compared by using chi-square test or Fisher's exact test as appropriate. The 3-year disease-free survival and overall survival rate were estimated with the Kaplan-Meier method, and differences between two groups were assessed with the log-rank test. Univariate and multivariate analyses were performed through Cox regression model. RESULTS: ROC curve showed that the cut-off value of preoperative LMR in predicting 3-year overall survival was 4.29. Then 143 patients were divided into low LMR group (LMR<4.29) and 115 patients into high LMR group (LMR ≥ 4.29). Compared with high LMR group, the low LMR group presented higher proportions of male [62.2%(89/143) vs. 50.4%(58/115), χ²=4.167, P=0.041], right hemicolon cancer [44.8% (64/143) vs. 31.3% (36/115), χ²=4.858, P=0.028], and the largest tumor diameter>4 cm [60.1% (86/143) vs. 33.0% (38/115), χ²=18.748, P<0.001]. During a median follow-up of 46.0 (range, 3.0 to 74.0) months, 3-year disease-free survival rate was 83.8% in high LMR group and 78.9% in low LMR group, which was not significantly different (P=0.210). While 3-year overall survival rate in low LMR group was significant lower than that in high LMR group (86.6% vs. 97.2%, P=0.018). Univariate analysis revealed that preoperative low LMR (HR=2.841, 95%CI: 1.146 to 7.043, P=0.024), right hemicolon cancer (HR=2.865, 95%CI: 1.312 to 6.258, P=0.008) and postoperative adjuvant chemotherapy≥6 cycles (HR=0.420, 95%CI: 0.188 to 0.935, P=0.034) were the risk factors for poor overall survival. Multivariate analysis identified that preoperative low LMR (HR=2.550, 95%CI: 1.024 to 6.347, P=0.004) and right hemicolon cancer (HR=2.611, 95%CI: 1.191 to 5.723, P=0.017) were the independent risk factors for overall survival. CONCLUSIONS Preoperative peripheral blood LMR level represents an effective prognostic predictor for patients with stage III colon cancer receiving radical therapy. Low LMR indicates the poor prognosis and such patients require aggressive postoperative treatment strategy.
Adenocarcinoma ; blood ; drug therapy ; surgery ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; Chemotherapy, Adjuvant ; Colonic Neoplasms ; blood ; drug therapy ; surgery ; therapy ; Female ; Humans ; Kaplan-Meier Estimate ; Leukocyte Count ; methods ; Lymphocytes ; Male ; Middle Aged ; Monocytes ; Preoperative Care ; Prognosis ; Retrospective Studies ; Young Adult