1.Tumor Microenvironment Polyamines Inhibit T Cell Antitumor Activity
Yuan-Bao AI ; Xue-Mei HUANG ; Sen LIU
Progress in Biochemistry and Biophysics 2025;52(8):1986-1997
Tumor immunotherapy has emerged as the fourth major therapeutic modality, following surgery, radiotherapy, and chemotherapy. Unlike traditional treatments that primarily target tumor cells directly, immunotherapy harnesses the body’s immune system to recognize and eliminate cancer cells. Over the past decade, various immunotherapeutic strategies have been developed, including immune checkpoint inhibitors (ICIs), chimeric antigen receptor (CAR) T cell therapy, cancer vaccines, and cytokine-based therapies. However, the immunosuppressive tumor microenvironment (TME) poses a significant obstacle to the effectiveness of these treatments. Polyamines—including putrescine, spermidine, and spermine—are polycationic metabolites that often accumulate abnormally in the TME and act as critical immunoregulatory molecules. T cells play a central role in antitumor immunity, yet their function is frequently influenced by immunoregulatory factors within the TME. Elevated polyamine levels in the TME have been implicated in dampening antitumor T cell responses, thereby facilitating tumor immune evasion. Polyamines in the TME originate from both tumor cells and tumor-associated immune cells. Tumor cells often overexpress the oncogene Myc, which drives the upregulation of polyamine biosynthetic enzymes, resulting in excessive intracellular polyamine production. Additionally, M2-polarized tumor-associated macrophages (M2-TAMs) contribute to polyamine accumulation by upregulating arginase-I (Arg-I), an enzyme that catalyzes the conversion of arginine into ornithine—a key precursor in the polyamine biosynthetic pathway. These combined sources lead to sustained polyamine enrichment in the TME, contributing to immune dysfunction and supporting tumor progression. Moreover, polyamines indirectly affect T cell activity by modulating macrophage polarization and directly suppress tumor cell apoptosis, further promoting an immunosuppressive environment. This review highlights the multifaceted roles of polyamines in modulating tumor-infiltrating T cell function, with a particular focus on their influence on CD4+ T cell differentiation,CD8+ T cell cytotoxicity, and immune checkpoint molecule expression. Recent studies suggest that polyamines suppress CD4+ T cell activation and differentiation by modulating the MAPK/ERK signaling pathway. Additionally, polyamines can impair T cell receptor (TCR) signaling and promote immune evasion through the upregulation of PD-L1 expression on tumor cells. These effects collectively contribute to weakened antitumor T cell responses. Polyamine blocking therapy (PBT), which primarily targets polyamine biosynthesis and transport, has emerged as a novel adjunctive immunotherapeutic strategy in cancer treatment. By reducing polyamine levels in the TME, PBT restores T cell effector functions and alleviates immunosuppression. Notably, studies have demonstrated that combining PBT with ICIs produces synergistic antitumor effects and may overcome resistance to ICI monotherapy. Although research has revealed the inhibitory effects of polyamines on T cell immune function, the underlying regulatory mechanisms remain to be fully elucidated. Moreover, due to compensatory mechanisms employed by tumor cells to maintain polyamine homeostasis, multi-targeted approaches may be necessary to achieve safe and effective therapeutic outcomes. Future PBT strategies may benefit from the integration of multi-omics technologies and the development of nanocarrier-based drug delivery systems, which could collectively enhance their specificity, efficacy, and applicability in cancer immunotherapy. This review systematically elucidates the immunomodulatory effects of polyamines on T cell function within the TME and provides theoretical support and novel insights for the advancement of tumor immunotherapeutic strategies.
2.Impact of Wenyang lishui formula on ventricular remodeling in rats with pulmonary hypertension-induced right heart failure
Sijian FENG ; Yan HUANG ; Aimin XING ; Mei YUAN ; Yafang LIU ; Weiming WANG
China Pharmacy 2025;36(20):2531-2536
OBJECTIVE To discuss the impact of Wenyang lishui formula on ventricular remodeling in rats with pulmonary hypertension-induced right heart failure (RHF) based on the Hippo/Yes-associated protein (YAP) signaling pathway. METHODS Ten rats were randomly selected as the control group. The remaining 63 rats were given a single intraperitoneal injection of monocrotaline to establish the pulmonary hypertension-induced RHF model. The 50 rats that successfully underwent the model establishment were randomly divided into the RHF group, low-dose group of Wenyang lishui formula (4.25 g/kg), high-dose group of the Wenyang lishui formula (17.00 g/kg), furosemide group (20 mg/kg), and high-dose group of Wenyang lishui formula+ Hippo/YAP signaling pathway activator group (17.00 g/kg of Δ Wenyang lishui formula+16 mg/kg of PY-60), with 10 rats in each group. The rats in each group were given the corresponding drug solution or normal saline by gavage or/andtail vein injection, once a day, for 4 consecutive weeks. During the experiment, the general conditions of the rats in each group were observed; after the last administration, the right ventricular diameter, right atrial diameter, end-diastolic volume, pulmonary artery blood flow acceleration time (PAAT) and its ratio to ejection time (ET) (PAAT/ET), pulmonary artery pressure and its ratio to pulmonary arterial flow velocity (pulmonary artery pressure/velocity) were measured. The plasma levels of brain natriuretic peptide and angiotensin Ⅱ (Ang Ⅱ) were detected. The pathological changes of the right ventricular tissue were observed, and the collagen volume fraction, the phosphorylation levels of the large tumor suppressor 1/2 (LATS1/2) and YAP, and the protein expression of the transcriptional coactivator of PDZ-binding motif (TAZ) were also detected. RESULTS Compared with the RHF group, the rats in Wenyang lishui formula low-dose and high-dose groups showed improved hair color, movement, diet, and mental state. The atrophy of right ventricular myocardial cells, the increase of inflammatory cells, collagen deposition, and hypertrophy of myocardial fibers were significantly alleviated. The right ventricular internal diameter, right atrial internal diameter, end-diastolic volume, pulmonary artery pressure, pulmonary artery pressure/velocity, the plasma levels of brain natriuretic peptide and AngⅡ , collagen volume fraction, the phosphorylation level of YAP and protein expression of TAZ were significantly decreased, while the PAAT, PAAT/ET and the phosphorylation level of LATS1/2 were significantly increased (P<0.05). PY-60 could significantly reverse the improvement effects of high-dose Wenyang lishui formula on the above quantitative indicators (P< 0.05). CONCLUSIONS Wenyang lishui formula can restore the right heart function of pulmonary hypertension-induced RHF rats, reduce their pulmonary artery pressure, alleviate the pathological changes in their cardiac tissues, and the above effects may be related to the activation of Hippo expression and the inhibition of YAP phosphorylation.
3.Expression of brain-derived neurotrophic factor in hippocampal tissue of central obese mice induced by sodium glutamate
Peng-Juan CAO ; Jia-Yuan TANG ; Mei-Zi YANG ; Yuan-Yuan LI ; Li-Ting HUANG ; Wen-Wen MENG ; Yong-Jun JIN ; Jian-Xun MO
The Chinese Journal of Clinical Pharmacology 2024;40(15):2227-2230
Objective To explore whether the cognitive function of central obese mice is decreased by affecting the expression of brain-derived neurotrophic factor(BDNF)in hippocampus.Methods Healthy mice at the neonatal stage were divided into normal group and model group at random.To obtain the obese models,model group mice were injected at cervical subcutaneous with 10%L-monosodium glutamate(MSG;3 mg·g-1·d-1)for 5 days.The normal group was injected with the same dose of 0.9%NaCl.In addition,mice were removed according to the requirements.Finally,we got 8 mice in each group.The following parameters were compared:body weight,Lee's index and levels of the serum lipid.The BDNF expression levels in hippocampal tissue were measured using western blotting.Results At the 8th weekend,the body weight of the model and normal groups was(49.01±2.47)and(41.27±3.28)g;the Lee's indexes were(357.14±9.24)and(330.15±7.37)g1/3·cm-1;triglyceride levels were(1.37±0.52)and(0.73±0.31)mmol·L-1;total cholesterol levels were(2.98±0.18)and(1.98±0.30)mmol·L-1;low-density lipoprotein levels were(0.31±0.03)and(0.24±0.02)mmol·L-1;high-density lipoprotein levels were(2.70±0.15)and(1.98±0.40)mmol·L-1;the differences were statistically significant(P<0.05,P<0.01),which were consistent with the characteristics of the central obesity model.The BDNF protein expression levels in the hippocampus of the model and normal groups were 6.02 x 104±626.53 and 7.04 x 104±1 440.81,which has statistically significant(P<0.01).Conclusion The cognitive function of central obese mice may be decreased by down-regulating the expression of BDNF in hippocampus.
4.Research and determination of related substances in flumazenil
Xue-yan MIAO ; Yuan YANG ; Si-si LU ; Jin-mei MO ; Lin-kai HUANG ; Jia-jun WEI ; Yi-ping GU
Acta Pharmaceutica Sinica 2024;59(6):1765-1772
A high performance liquid chromatography (HPLC) method utilizing correction factors was established for the quantitative detection of related substances in flumazenil. Separation was achieved using an Agilent Pursuit XRs C18 column (250 mm × 4.6 mm, 5 μm) with an isocratic elution of dilute phosphoric acid, methanol, and tetrahydrofuran as the mobile phases. Correction factors calculated from a standard curve method were applied to determine the impurity content. The quantification of impurities in flumazenil was conducted using both external standard and correction factor methods, followed by validation and comparison of the two. For the identification of degradation products, a forced degradation approach was employed to prepare a flumazenil degradation solution, and the resulting impurities were confirmed by LC-MS analysis. The separation of flumazenil and its impurities was found to be efficient. The limits of quantification for impurities A, B, D, and E were established at 0.169 9, 0.314 7, 0.143 9, and 0.270 8 ng, respectively, with the limits of detection at 0.055 8, 0.096 9, 0.048 8, and 0.089 0 ng. These impurities demonstrated a strong linear relationship across the concentration ranges of 0.034 9-7.847 0, 0.038 7-8.710 7, 0.034 6-7.794 1, and 0.032 4-7.292 8 µg·mL-1, respectively (
5.Clinical Diseases Responding Specifically to Traditional Chinese Medicine:Chronic Prostatitis
Zhan QIN ; Mei MO ; Chaoba HE ; Liguo GENG ; Bin WANG ; Jisheng WANG ; Kecheng LI ; Nianwen HUANG ; Zhiming HONG ; Shaoying YUAN ; Xiaoxiao ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):152-158
Chronic prostatitis is a common and frequently occurring disease in male clinics. Due to the diverse symptoms, complex etiology, unclear mechanisms, and recurrent episodes of chronic prostatitis, Western medicine often faces the challenge of limited treatment options and unsatisfactory outcomes. In order to fully leverage the unique advantages of traditional Chinese medicine (TCM) in the treatment of chronic prostatitis, the China Association of Chinese Medicine organized a discussion among experts from the fields of TCM urology, Western urology, and related pharmacy. The experts focused on the advancements in the understanding of chronic prostatitis in modern medicine, various theories on the etiology, pathogenesis, and treatment of chronic prostatitis in TCM, entry points from interdisciplinary fields, the role and advantages of TCM in the comprehensive management of chronic prostatitis, and research into mechanisms related to chronic prostatitis. After discussions, the experts concluded that chronic prostatitis is one of the diseases where TCM has a distinct advantage. TCM can effectively improve the clinical syndromes of chronic prostatitis, including urinary issues, social psychology, organ specificity, infection, nervous system problems, pain and discomfort, sexual dysfunction, etc., and can enhance the quality of life. For patients with chronic prostatitis who cannot tolerate or may not accept the adverse effects of Western medicine, as well as for those with non-inflammatory chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), those with pain as the primary symptom, those with urinary tract symptoms, those with coexisting anxiety and depression, and those with abnormal semen liquefaction, TCM-based treatment can be the main approach. Currently, the optimal diagnosis and treatment strategy for chronic prostatitis has not yet been established, and further research from perspectives such as clinical epidemiology, evidence-based medicine, and molecular biology is needed. Both TCM and Western medicine should integrate their respective strengths, clarify the role and advantages of TCM interventions based on mutual reference, and improve the diagnosis and treatment standards for chronic prostatitis in China.
6.Identification and anti-inflammatory activity of chemical constituents and a pair of new monoterpenoid enantiomers from the fruits of Litsea cubeba
Mei-lin LU ; Wan-feng HUANG ; Yu-ming HE ; Bao-lin WANG ; Fu-hong YUAN ; Ting ZHANG ; Qi-ming PAN ; Xin-ya XU ; Jia HE ; Shan HAN ; Qin-qin WANG ; Shi-lin YANG ; Hong-wei GAO
Acta Pharmaceutica Sinica 2024;59(5):1348-1356
Eighteen compounds were isolated from the methanol extract of the fruits of
7.Clinical Observation on the FANG's Scalp Acupuncture Combined with Timing Auricular Point Pressing Therapy in the Treatment of Insomnia Patients with Maintenance Hemodialysis
Jin-Hua LU ; Yuan-Yuan REN ; Xiao-Jing ZHENG ; Shao-Mei ZHANG ; Xi-Yue HU ; Wei HUANG
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(3):671-677
Objective To observe the clinical efficacy of FANG's scalp acupuncture combined with timing auricular point pressing therapy in the treatment of insomnia patients with maintenance hemodialysis(MHD).Methods A total of 70 patients with insomnia on MHD were randomly divided into observation group and control group,with 35 patients in each group.Both groups were given conventional treatment,the control group was given oral use of Estazolam Tablets on the basis of conventional treatment,and the observation group was given FANG's scalp acupuncture combined with timing auricular point pressing therapy.Both groups were treated for a total of 4 weeks of treatment.After 1 month of treatment,the clinical efficacy of the two groups was evaluated,and the changes in the Pittsburgh Sleep Quality Index(PSQI)score and the Kidney Disease Quality of Life Short Form(KDQOL-SF)score,as well as the scores of the Hamilton Depression Scale(HAMD)and the Hamilton Anxiety Scale(HAMA),were observed in the patients of the two groups before and after treatment.The changes in hemoglobin(Hb),serum creatinine(Scr),and blood urea nitrogen(BUN)levels were compared before and after treatment between the two groups,and the safety of the two groups was evaluated.Results(1)After treatment,the PSQI and KDQOL-SF scores of patients in the two groups were significantly improved(P<0.05),and the observation group was significantly superior to the control group in improving PSQI and KDQOL-SF scores,and the difference was statistically significant(P<0.05).(2)After treatment,the HAMD and HAMA scores of patients in the two groups were significantly improved(P<0.05),and the observation group was significantly superior to the control group in improving HAMD and HAMA scores,and the differences were statistically significant(P<0.05).(3)After treatment,the Hb,Scr,BUN levels of patients in the two groups were significantly improved(P<0.05),and the observation group was significantly superior to the control group in improving Hb,Scr,BUN levels,and the differences were all statistically significant(P<0.05).(4)The total effective rate was 77.14%(27/35)in the observation group and 62.86%(22/35)in the control group.The efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P<0.05).(5)Comparison of the incidence of adverse reactions in the two groups of patients,the difference was not statistically significant(P>0.05).Conclusion FANG's scalp acupuncture combined with timing auricular point pressing therapy in the treatment of insomnia patients with MHD can effectively improve the sleep quality of patients and alleviate anxiety and depression,so as to improve the quality of life of patients,with remarkable efficacy.
8.Trends in antimicrobial use and hospital infection incidence among inpatients
Yiwen SUN ; Sijin YAN ; Feng LU ; Xiaofang FU ; Ruihong SHEN ; Yayun YUAN ; Bingchao CAI ; Ya YANG ; Mei HUANG ; Haiqun BAN
Shanghai Journal of Preventive Medicine 2024;36(5):491-496
ObjectiveTo understand the use of antibiotics in inpatients and the incidence and trend of hospital infections, to explore the implementation effect of comprehensive management measures, and to provide reference for hospitals to use antibiotics reasonably. MethodsBased on the hospital infection monitoring and management system, a retrospective analysis and comparison were conducted on the use of antibiotics, submission of microbial test samples, and incidence of hospital infections among inpatients in a tertiary hospital from 2012 to 2021. ResultsFrom 2012 to 2021, the use of antibiotics showed a downward trend, from 50.82% in 2012 to 41.29% in 2021. At the same time, the use rate of restricted and special antibiotics had also decreased, and the use rate of restricted and special antibiotics in patients without hospital infection was significantly lower than that in patients with hospital infection, and the microbial testing rate was also on the rise. The annual incidence rate of hospital infection was 0.69%‒1.92%, and the annual case-time prevalence rate was 0.79%‒2.17%. The annual average rate of the above two in 10 years was 1.18% and 1.34%, respectively. The results of the exponential smoothing model also showed that the utilization rate of antibiotics was decreasing and the incidence of nosocomial infection was stable. ConclusionLarge general hospitals took comprehensive management measures to strengthen the management of rational use of antibiotics, which led to a decline in the use rate of antibacterial drugs for inpatients and an increase in the rate of microbial examination. At the same time, the overall incidence of hospital infection was relatively stable, suggesting that the comprehensive management measures of antibacterial drugs in hospitals had achieved certain results. The current measures need to be optimized in the future to continuously improve the management level of rational use of antibacterial drugs.
9.Gastrointestinal dysfunction in prognosis of liver cirrhotic patients with sepsis
Cai-Jun HAN ; Yuan HUANG ; Zheng-Xie WU ; Xing JIN ; Mei-Hua PIAO ; Hua JIN
Chinese Journal of Infection Control 2024;23(2):162-168
Objective To assess the value of acute gastrointestinal injury(AGI)and intestinal fatty acid-binding protein(I-FABP)in the prognosis of liver cirrhotic patients with sepsis.Methods Clinical data of 84 liver cirrhosis patients with sepsis who were admitted to the intensive care unit(ICU)of a hospital from September 2020 to March 2023 were analyzed retrospectively,and 41 patients with decompensated liver cirrhosis during the same period were selected as the control group.Serum I-FABP level in patients was determined with enzyme-linked immunosorbent assay(ELISA).Scores of the model of end-stage liver disease(MELD)and sequential organ failure assessment(SOFA)were calculated.AGI was evaluated based on medical records.30-day and 90-day survival was observed.Correlation among variables was analyzed by Spearman correlation.Risk factors for death in patients with liver cir-rhosis and sepsis was determined by multivariate Cox regression analysis.The optimal cut-off value was determined by receiver operating characteristic(ROC)curve,and the diagnostic efficacy was compared through the area under the ROC curve(AUC).Results Both AGI grading and I-FABP level in liver cirrhosis patients with sepsis were higher than those in the control group(both P<0.05).I-FABP level was correlated with procalcitonin(PCT),MELD,and SOFA scores in patients with liver cirrhosis and sepsis(all P<0.05).AGI grading was positively cor-related with SOFA score(P=0.038).The 30-day and 90-day mortality of patients in the liver cirrhosis with sepsis group were 25.0%(n=21)and 35.7%(n=30),respectively.Multivariate Cox regression analysis showed that baseline I-FABP and SOFA scores were independently correlated with 30-day and 90-day survival,and the I-FABP quartile showed good prognostic differentiation efficacy.ROC curve showed that I-FABP could significantly improve the predictive effect of SOFA score on the prognosis of patients.Conclusion AGI grading and I-FABP level in liver cirrhosis patients with sepsis are elevated significantly.Serum I-FABP is associated with the prognosis of patient and can improve the predictive efficacy of SOFA score for survival.
10.Effect of hand hygiene intervention on healthcare-associated case infection incidence from 2014 to 2022
Jia-Yan DING ; Rui-Hong SHEN ; Wen-Qin ZHOU ; Ya-Yun YUAN ; Mei HUANG ; Ya YANG ; Bing-Chao CAI ; Hai-Qun BAN ; Xiao-Fang FU
Chinese Journal of Infection Control 2024;23(2):208-213
Objective To observe the effect of multi-modal hand hygiene(HH)intervention on HH compliance,as well as the relationship between HH compliance and the healthcare-associated(HA)case infection incidence.Methods From 2014 to 2022,the infection control team in a tertiary first-class hospital implemented multi-modal HH intervention for health care workers(HCWs).The changing trend of HH monitoring data,the correlation be-tween HH compliance rate and HA case infection incidence were analyzed retrospectively.Results The consump-tion of HH products in the wards showed a stable upward trend;HH compliance rate increased from 64.98%in 2014 to 85.01%in 2022(P<0.001),and HA case infection incidence decreased from 1.21%to 0.83%(P<0.05).HH compliance rate was negatively correlated with HA case infection incidence(r=-0.369,P=0.027).HH compliance rates in different regions and job posts in each quarter were increased(P<0.001).For 5 different HH moments in each quarter,HH compliance rate fluctuated slightly before sterile manipulation and after touching patient;presented rising trend after touching surroundings around patient,and decreased before touching patient and after touching patient's body fluid since 2020(P<0.001).Conclusion Multi-modal HH intervention can im-prove the HH compliance of HCWs,improving their HH awareness is conducive to reducing HA case infection incidence.

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