1.Protective effect of the active component DMDD from Averrhoa carambola root on myocardial injury in diabetic mice and its correlation with the NCOA4/FTH1/ATG8 axis
Yongxin CHEN ; Yuxuan LI ; Kailei GU ; Jiajun YOU ; Xiaohan SUN ; Jing MA ; Yanping ZHOU ; Xiaojie WEI
China Pharmacy 2026;37(9):1141-1147
OBJECTIVE To investigate the protective effect of 2-dodecyl-6-methoxy-2,5-diene-1,4-cyclohexanedione (DMDD), an active component from Averrhoa carambola root, on myocardial injury in diabetic mice based on the nuclear receptor coactivator 4/ferritin heavy chain 1/autophagy-related protein 8 (NCOA4/FTH1/ATG8) axis. METHODS The successfully modeled diabetic mice were randomly divided into model group and DMDD low-, medium-, and high-dose (12.5, 25, 50 mg/kg) groups, while an additional non-modeled control group was established, with 6 mice in each group. Each group received the corresponding drug solution or an equal volume of normal saline intragastically once daily for 21 consecutive days. After the administration, the levels of fasting blood glucose (FBG), serum lactate dehydrogenase (LDH), and creatine kinase isoenzyme MB (CK-MB) were measured. Myocardial pathological changes, degree of fibrosis, and myocardial cell ultrastructure were observed. Myocardial cell death index and NCOA4 protein positive index were detected. The protein expression levels of NCOA4, FTH1, ATG8, solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) in cardiac tissue were measured. RESULTS Compared with model group, each DMDD group showed significant alleviation of cardiac pathological injury and varying degrees of improvement in the myocardial cell ultrastructure. The FBG and serum LDH and CK-MB levels, the myocardial cell death index and NCOA4 protein positive index,the protein expression levels of NCOA4, FTH1, and ATG8 in cardiac tissue were significantly decreased ( P <0.001), while the protein expression levels of SLC7A11 and GPX4 were significantly increased ( P <0.001). CONCLUSIONS DMDD can reduce blood glucose levels, alleviate myocardial histopathological injury, and inhibit cell death in diabetic mice. The mechanism is associated with inhibiting excessive activation of the NCOA4/FTH1/ATG8 axis and reducing ferritinophagy.
2.Effect of Heat-Sensitive Moxibustion on Apoptosis of Gastric Mucosal Tissue in Chronic Atrophic Gastritis Model Rats:Based on PI3K/Akt Signaling Pathway
Qi ZHANG ; Yanping ZHOU ; Qide WANG ; Shujuan CHEN ; Yu SUN ; Fang LI ; Hongbin GONG ; Mingjun XIE ; Hui LIU ; Haifeng ZHANG
Journal of Traditional Chinese Medicine 2026;67(15):1650-1658
ObjectiveTo investigate the potential mechanism of heat-sensitive moxibustion on chronic atrophic gastritis (CAG) through the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. MethodsFifty-eight SD rats were randomly divided into blank group (n=14) and modeling group (n=44). Rats in the blank group were fed routinely, while the rats in the modeling group received drinking water containing 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) at a concentration of 140 μg/ml, combined with irregular fasting and feeding for 12 weeks to establish CAG model. After successful modeling, the rats were randomly divided into model group (n=10), inhibitor group (n=10) and moxibustion group (n=20). After 40 minutes of suspended moxibustion at "Zhongwan" (CV 12) daily, the rats in the moxibustion group were divided into heat-sensitive moxibustion group (n=10) and non-heat-sensitive moxibustion group (n=9) according to the change of tail temperature during moxibustion. The inhibitor group was bound for 40 minutes daily, and then administered with PI3K/Akt signaling pathway inhibitor, rapamycin solution, by gavage at a dose of 1 mg/kg. The model group received intragastric administration of 1 ml/kg normal saline after 40 minutes of restraint stress each day. All interventions were administered once daily for 28 consecutive days, while the blank group received no intervention. After the intervention finished, the body weight of rats in each group was compared. HE staining was used to observe the histopathological changes of gastric mucosa. The apoptosis-positive rate of gastric mucosal cells was detected by TUNEL assay. Immunohistochemistry was performed to determine the protein levels of matric metalloproteinase-7 (MMP7), vascular endothelial growth factor A (VEGFA) and epidermal growth factor receptor (EGFR) in gastric mucosa. The mRNA expression levels of PI3K, Akt and mammalian target of rapamycin (mTOR) in gastric mucosal tissues were detected by qPCR. The protein levels of phosphorylated Akt (p-Akt) and phosphorylated mTOR (p-mTOR) in rat gastric mucosal tissues were measured by Western Blotting. ResultsCompared to the blank group, rats in all other groups exhibited decreased body weight, significantly increased gastric mucosal cell apoptosis-positive rates, elevated protein levels of MMP7, VEGFA and EGFR in gastric mucosa, increased mRNA expression levels of PI3K, Akt and mTOR, and enhanced protein expression levels of p-Akt and p-mTOR (P<0.05 or P<0.01). Histopathological examination revealed thinning of the gastric mucosa, glandular disorganization and atrophy, accompanied by intestinal metaplasia.Compared to the model group, the heat-sensitive moxibustion group, the non-heat-sensitive moxibustion group and the inhibitor group all showed significant improvements in the above-mentioned indicators (P<0.05 or P<0.01). Compared to the heat-sensitive moxibustion group, the non-heat-sensitive moxibustion group and the inhibitor group exhibited increased positive rates of gastric mucosal cell apoptosis; the non-heat-sensitive moxibustion group showed increased protein levels of MMP7, VEGFA and EGFR, as well as mRNA expression levels of PI3K, Akt and mTOR, and protein expressions of p-Akt and p-mTOR; the inhibitor group exhibited elevated protein expression level of EGFR (P<0.05 or P<0.01). Histopathological examination showed that the gastric mucosal glands in the heat-sensitive moxibustion group were arranged more regularly, with an approximately normal structural appearance. ConclusionHeat-sensitive moxibustion can improve the body weight of CAG rats and repair gastric mucosal injury. Its therapeutic effects may be mediated by inhibiting excessive activation of gastric mucosal PI3K/Akt signaling pathway, thereby reducing gastric mucosal cell apoptosis.
3.Effect of Heat-Sensitive Moxibustion on Apoptosis of Gastric Mucosal Tissue in Chronic Atrophic Gastritis Model Rats:Based on PI3K/Akt Signaling Pathway
Qi ZHANG ; Yanping ZHOU ; Qide WANG ; Shujuan CHEN ; Yu SUN ; Fang LI ; Hongbin GONG ; Mingjun XIE ; Hui LIU ; Haifeng ZHANG
Journal of Traditional Chinese Medicine 2026;67(15):1650-1658
ObjectiveTo investigate the potential mechanism of heat-sensitive moxibustion on chronic atrophic gastritis (CAG) through the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. MethodsFifty-eight SD rats were randomly divided into blank group (n=14) and modeling group (n=44). Rats in the blank group were fed routinely, while the rats in the modeling group received drinking water containing 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) at a concentration of 140 μg/ml, combined with irregular fasting and feeding for 12 weeks to establish CAG model. After successful modeling, the rats were randomly divided into model group (n=10), inhibitor group (n=10) and moxibustion group (n=20). After 40 minutes of suspended moxibustion at "Zhongwan" (CV 12) daily, the rats in the moxibustion group were divided into heat-sensitive moxibustion group (n=10) and non-heat-sensitive moxibustion group (n=9) according to the change of tail temperature during moxibustion. The inhibitor group was bound for 40 minutes daily, and then administered with PI3K/Akt signaling pathway inhibitor, rapamycin solution, by gavage at a dose of 1 mg/kg. The model group received intragastric administration of 1 ml/kg normal saline after 40 minutes of restraint stress each day. All interventions were administered once daily for 28 consecutive days, while the blank group received no intervention. After the intervention finished, the body weight of rats in each group was compared. HE staining was used to observe the histopathological changes of gastric mucosa. The apoptosis-positive rate of gastric mucosal cells was detected by TUNEL assay. Immunohistochemistry was performed to determine the protein levels of matric metalloproteinase-7 (MMP7), vascular endothelial growth factor A (VEGFA) and epidermal growth factor receptor (EGFR) in gastric mucosa. The mRNA expression levels of PI3K, Akt and mammalian target of rapamycin (mTOR) in gastric mucosal tissues were detected by qPCR. The protein levels of phosphorylated Akt (p-Akt) and phosphorylated mTOR (p-mTOR) in rat gastric mucosal tissues were measured by Western Blotting. ResultsCompared to the blank group, rats in all other groups exhibited decreased body weight, significantly increased gastric mucosal cell apoptosis-positive rates, elevated protein levels of MMP7, VEGFA and EGFR in gastric mucosa, increased mRNA expression levels of PI3K, Akt and mTOR, and enhanced protein expression levels of p-Akt and p-mTOR (P<0.05 or P<0.01). Histopathological examination revealed thinning of the gastric mucosa, glandular disorganization and atrophy, accompanied by intestinal metaplasia.Compared to the model group, the heat-sensitive moxibustion group, the non-heat-sensitive moxibustion group and the inhibitor group all showed significant improvements in the above-mentioned indicators (P<0.05 or P<0.01). Compared to the heat-sensitive moxibustion group, the non-heat-sensitive moxibustion group and the inhibitor group exhibited increased positive rates of gastric mucosal cell apoptosis; the non-heat-sensitive moxibustion group showed increased protein levels of MMP7, VEGFA and EGFR, as well as mRNA expression levels of PI3K, Akt and mTOR, and protein expressions of p-Akt and p-mTOR; the inhibitor group exhibited elevated protein expression level of EGFR (P<0.05 or P<0.01). Histopathological examination showed that the gastric mucosal glands in the heat-sensitive moxibustion group were arranged more regularly, with an approximately normal structural appearance. ConclusionHeat-sensitive moxibustion can improve the body weight of CAG rats and repair gastric mucosal injury. Its therapeutic effects may be mediated by inhibiting excessive activation of gastric mucosal PI3K/Akt signaling pathway, thereby reducing gastric mucosal cell apoptosis.
4.Influencing factors for the willingness to receive pneumococcal vaccine among middle-aged and elderly population in Zhejiang Province
XU Yanping ; YAN Xiaotong ; YAO Dingming ; XU Yue ; ZHANG Xuehai ; SUN Jie ; XU Jinhang
Journal of Preventive Medicine 2025;37(9):881-885
Objective:
To investigate the willingness to receive the pneumococcal vaccine and its influencing factors among middle-aged and elderly population in Zhejiang Province, so as to provide a basis for increasing the vaccination rate of pueumococcal among middle-aged and elderly population.
Methods:
From March to May 2024, a multi-stage random sampling method was employed to recruit residents aged ≥50 years from 35 counties (cities or districts) in Zhejiang Province. Data on basic information, knowledge of pneumonia, pneumococcal vaccine, and willingness to receive pneumococcal vaccine were collected through questionnaire surveys. A multivariable logistic regression model was used to analyze influencing factors for the willingness to receive pneumococcal vaccine among middle-aged and elderly population.
Results:
A total of 10 500 middle-aged and elderly population were surveyed. Among them, there were 5 202 males, accounting for 49.54%, and 5 298 females, accounting for 50.46%. The mean age was (65.11±9.05) years. Of the participants, 7 732 individuals were aware of pneumonia, accounting for 73.64%. A total of 1 724 individuals had received pneumococcal vaccine, corresponding to a vaccination rate of 16.42%. Furthermore, 5 138 participants expressed willingness to receive pneumococcal vaccine, with a willingness rate of 48.93%. The multivariable logistic regression analysis showed that middle-aged and elderly population aged ≥60 years (60-<70 years, OR=1.577, 95%CI: 1.433-1.736; ≥70 years, OR=2.110, 95%CI: 1.918-2.321), those with a history of chronic diseases (OR=1.250, 95%CI: 1.154-1.353), those who were recommended to receive the pneumonia vaccine by doctors (OR=4.896, 95%CI: 4.507-5.318), those who were aware of pneumonia (OR=1.460, 95%CI: 1.338-1.594), those who were aware that the elderly are prone to pneumonia (OR=1.490, 95%CI: 1.375-1.614), those who were aware of the causes of pneumonia (OR=1.559, 95%CI: 1.434-1.694), those who were aware that vaccination can prevent pneumonia (OR=2.196, 95%CI: 2.031-2.375), and those who were aware of the immunization schedule for pneumonia vaccine (OR=1.897, 95%CI: 1.683-2.124) had a higher willingness to receive pneumonia vaccine.
Conclusions
The willingness of middle-aged and elderly population in Zhejiang Province to receive pneumonia vaccine is related to age, history of chronic diseases, awareness of pneumonia, and awareness of pneumonia vaccine. It is recommended to strengthen health education on pneumonia and pneumonia vaccine for middle-aged and elderly population, in order to increase the willingness to receive the vaccine and vaccination rate.
5.Effects of meropenem exposure and degradation levels on clinical efficacy in patients with purulent meningitis
Tongtong LI ; Jiantong SUN ; Xianglong CHEN ; Peng DENG ; Yanping XUE ; Yao XIAO ; Lijuan YANG ; Jinhui XU ; Yanxia YU ; Lian TANG
China Pharmacy 2025;36(24):3084-3090
OBJECTIVE To explore the effects of meropenem exposure and degradation levels on clinical efficacy in patients with purulent meningitis (PM). METHODS A total of 131 PM patients treated with meropenem at the Affiliated Suzhou Hospital of Nanjing Medical University from January 2022 to June 2025 were prospectively included. Relevant data were collected and divided into a cured group (91 cases) and a non-cured group (40 cases) based on the efficacy. High-performance liquid chromatography-tandem mass spectrometry was used to determine the concentration of meropenem and its open-loop metabolites. Risk factors that affect efficacy were screened, and their predictive power and correlation were evaluated by univariate analysis, and multivariate Logistic regression analysis, receiver operating characteristic (ROC) curves, and correlation analysis. RESULTS Univariate analysis showed that serum creatinine, creatinine clearance rate, minimum inhibitory concentration of meropenem ≥16 μg/mL, cerebrospinal fluid red blood cell count, cerebrospinal fluid white blood cell count, cerebrospinal fluid glucose content, blood trough concentration, blood open-loop metabolite concentration/trough concentration ratio, and intrathecal injection were all correlated with efficacy (P<0.05). The results of multiple Logistic regression analysis showed that serum creatinine blood open-loop metabolite concentration/trough concentration ratio, intrathecal injection, and cerebrospinal fluid glucose content were influencing factors for suboptimal anti-infective ltt efficacy (P<0.05). ROC curve analysis showed that when the blood open-loop metabolite concentration/trough concentration ratio was greater than 2.854 (AUC=0.647), serum creatinine was less than 59.5 μmol/L (AUC=0.647), and cerebrospinal fluid glucose content was less than 3.37 mmol/L (AUC=0.709), the risk of treatment failure significantly increased (P<0.05). Correlation analysis showed that the blood trough concentration of meropenem was positively correlated with the concentration of its open-loop metabolites (R 2=0.134 5, P<0.000 1). CONCLUSIONS Insufficient exposure level and rapid degradation of meropenem are key mechanisms affecting the anti-infective efficacy of PM. Elevated blood open-loop metabolite concentration/ trough concentration ratio, low serum creatinine level, lack of intrathecal injection, and low cerebrospinal fluid glucose content are independent risk factors for poor efficacy.
6.Clinical Observation on Ruanjian Sanjie Pills in the Treatment of Hepatitis B-Related Compensated Cirrhosis with Blood Stasis Blocking Collaterals Syndrome
Sichen LIU ; Jingbao HU ; Yanping LU ; Xiaoying YAO ; Henghui SUN ; Qinyan ZHU
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(3):600-605
Objective To observe the clinical efficacy of Ruanjian Sanjie Pills in the treatment of patients with hepatitis B-related cirrhosis in compensatory stage differentiated as blood stasis blocking collaterals syndrome.Methods A total of 80 cases of patients with hepatitis B-related cirrhosis in compensatory stage admitted to Bao'an Hospital of Chinese Medicine Affiliated to Guangzhou University of Chinese Medicine from January 2023 to April 2024 were randomly divided into the trial group and the control group,40 cases in each group.The control group was treated with oral administration of Entecavir for hepatitis B virus(HBV),and the trial group was treated with Ruanjian Sanjie Pills on the basis of treatment for the control group,the course of treatment covering one year.Before and after treatment,the two groups were observed in the changes of routine blood test indicators of white blood cell count(WBC)and platelet count(PLT),liver function indicators[albumin(ALB),total bilirubin(TBIL),alanine transaminase(ALT)and aspartate transaminase(AST)],prothrombin time(PT),liver stiffness measurement(LSM),and traditional Chinese medicine(TCM)syndrome scores.After treatment,the clinical efficacy and safety were evaluated.Results(1)There were three cases in the control group and four cases in the trial group fell off,and eventually 37 cases in the control group and 36 cases in the trial group were enrolled in the efficacy statistics.(2)After one year of treatment,the total effective rate of the trial group was 91.67%(33/36)and that of the control group was 67.57%(25/37),and the intergroup comparison(tested by chi-square test)showed that the therapeutic efficacy of the trial group was significantly superior to that of the control group(P<0.05).(3)After treatment,the routine blood test indicators of WBC and PLT in the trial group were increased compared with those before treatment(P<0.05),while the WBC and PLT in the control group did not change significantly(P>0.05).The post-treatment WBC and PLT in the trial group were significantly higher than those of the control group(P<0.05).(4)After treatment,the ALB of patients in the two groups was increased compared with that before treatment(P<0.05),and the PT value of patients in the two groups and the ALT of the trial group were decreased compared with those before treatment(P<0.05),but TBIL and AST of the two groups and ALT of the control group did not differ from those before treatment(P>0.05).The comparison between the two groups showed that the decrease of PT value in the trial group was significantly superior to that of the control group(P>0.05),but no statistically significant differences of ALT,AST,TBIL and ALB were shown between the two groups(P>0.05).(5)After treatment,the LSM of patients in the two groups was decreased compared with that before treatment(P<0.05),and the decrease in the trial group was significantly superior to that in the control group(P<0.05).(6)After treatment,the TCM syndrome scores of the two groups of patients were decreased compared with those before treatment(P<0.05),and the decrease in the trial group was significantly superior to that in the control group(P<0.05).(7)There were no significant adverse reactions or adverse events occurring in the two groups during the treatment.Conclusion Ruanjian Sanjie Pills can improve the clinical symptoms of patients with hepatitis B-related cirrhosis in the compensatory stage,improve the coagulation function,reduce the hardness of the liver,and slow down the process of cirrhosis,with satisfactory efficacy and good safety.
7.Consensus recommendation on Comprehensive Geriatric Assessment for elderly cancer patients from Peking Union Medical College Hospital
Qiumei WANG ; Xiaoyuan LI ; Lin KANG ; Xiaohong SUN ; Hailong LI ; Yanping DUAN ; Ying LIU ; Mei GUAN ; Lin ZHAO
Basic & Clinical Medicine 2025;45(9):1122-1131
In the context of an aging society,the number of elderly cancer patients is constantly increasing,and geriatric oncology has garnered significant attention in recent years.Given the heterogeneity in the health status of older patients,it has become increasingly important to provide individualized diagnosis,treatment,follow-up,and care.Thus,it must be emphasized the Comprehensive Geriatric Assessment(CGA)for elderly patients,which encompasses their physical function,nutritional status,cognitive function,emotional state,comorbidities,polypharmacy,social situation,and treatment preferences.This article provides consensus recommendations on CGA tools for elderly patients prior to anticancer treatment,offering valuable references and insights for clinical practice in China.
8.Quality Control and Analysis of Treatment for Hospitalized Cancer Patients:Interview and Medical Records Study from Nine Hospitals in Beijing
Liting LU ; Yanping ZHOU ; Xiang WANG ; Xiaoyuan LI ; Xiaorong HOU ; Lidong ZHU ; Xiaohong XU ; Guibin SUN ; Ziyuan WANG ; Jieshi ZHANG ; Lin ZHAO ; Yi BA
Medical Journal of Peking Union Medical College Hospital 2025;16(2):399-405
Objective To analyze the current quality of treatment for hospitalized cancer patients in Bei-jing,identify major issues in treatment practices,and propose improvements.Methods Nine hospitals in Beijing were selected for examination.Expert on-site interviews and medical record sampling were conducted.The"Bei-jing Cancer Diagnosis and Treatment Quality Control Checklist"was used to assess the hardware,management,anti-cancer drug therapy,radiation therapy,and surgical treatment during cancer treatment at these hospitals from January to October 2023.The relevant problems were analyzed.Results Among the nine hospitals,two(22.2%)were equipped with laminar flow rooms,and three(33.3%)had intravenous drug preparation centers.In terms of institutional management,seven hospitals(77.8%)had standardized anti-cancer drug prescription authority management,eight(88.9%)had complete emergency plans,and five(55.6%)had oncology specialist pharmacists.Regarding anti-cancer drug therapy,the areas with higher completion rates included pathology diag-nosis support(97.6%),routine pre-treatment examinations(96.3%),adverse reaction evaluation(92.7%),discharge summaries(95.1%),and admission records(91.5%).However,the accuracy of tumor staging before treatment(70.7%)and the evaluation of therapeutic efficacy after drug treatment(76.9%)needed improvement.The oncology specialty significantly outperformed the non-oncology specialty in terms of the accuracy rate of TNM staging(86.0%vs.46.9%,P<0.001),the completeness of informed consent forms(100%vs.68.8%,P<0.001),the completeness of drug indication evaluation(96.0%vs.78.1%,P=0.025),the completeness of admission medical history records(98.0%vs.81.3%,P=0.008),the rationality of drug dosage(96.0%vs.75.0%,P=0.005),the rationality of drug infusion time(100%vs.62.5%,P<0.001),and the rationality of the order of drug infusion(100%vs.87.5%,P=0.010).Although the quality of radiation therapy was high,the subsequent evaluation of therapeutic efficacy(39.3%)requires enhancement.In surgical treatment,the preoper-ative pathology diagnosis support rate(78.1%)and the accuracy of tumor staging(37.5%)were relatively low,indicating issues with incomplete preoperative evaluation and the absence of multidisciplinary discussions.Conclusions There remains significant room for improvement in the quality of cancer treatment in China.It is recommended to standardize tumor staging assessment processes,strengthen entry assessments for non-oncology departments,promote the implementation of multidisciplinary treatment models,and establish a multi-department collaborative management model.Continuous monitoring of cancer diagnosis and treatment quality indicators is es-sential to promote ongoing improvements in cancer treatment quality.
9.Effect of moxibustion at Shenque(CV8)and Guanyuan(CV4)on TRPV1 channel in spinal dorsal horn and hypothalamus of dysmenorrhea rats
Yanqiu SUN ; Yulei LIANG ; Di WANG ; Zhiguo ZHAO ; Liyun YANG ; Xuanping ZHANG ; Yan ZHANG ; Xuan ZHANG ; Yanxue XING ; Min ZHOU ; Xiaoyan WANG ; Xinhua LI ; Yanping YANG
Journal of Acupuncture and Tuina Science 2025;23(2):117-125
Objective:To investigate the effect of mild moxibustion on transient receptor potential vanilloid type 1(TRPV1)channel expression in primary dysmenorrhea(PD)rats and explore its mechanism in alleviating central pain sensitization.Methods:Thirty-two female non-pregnant Wistar rats were randomized into a blank group,a model group,a mild moxibustion group,and a capsazepine group,with 8 rats in each group.Except for the blank group,the other three groups used estradiol benzoate,ice-water bath,and oxytocin to establish the rat PD model of cold-dampness stagnation pattern.The interventions began on day 1 of modeling,once a day,and lasted 10 d.The mild moxibustion group received mild moxibustion at Shenque(CV8)and Guanyuan(CV4),20 min/time;in the capsazepine group,capsazepine was injected at a dose of 2 mg/(kg·bw).The abdominal pain threshold was measured 10-30 min after oxytocin injection on day 11;enzyme-linked immunosorbent assay was used to detect serum prostaglandin F2α(PGF2α)level;the expression of TRPV1,cluster of differentiation 11B(CD11B),and proto-oncogene c-Fos in the spinal dorsal horn and hypothalamus was detected by immunofluorescence and Western blotting.Results:Compared to the blank group,the model group showed a decreased pain threshold(P<0.05)and an increased serum PGF2α level with elevated TRPV1,CD11B,and c-Fos protein expression in the spinal dorsal horn and hypothalamus(P<0.05).Compared to the model group,both the mild moxibustion group and capsazepine group showed significantly increased pain thresholds(P<0.05),along with decreased serum PGF2α levels and reduced protein expression levels of TRPV1,CD11B,and c-Fos in the spinal dorsal horn and hypothalamus(P<0.05).Rat pain threshold in the capsazepine group was higher than that in the mild moxibustion group(P<0.05).Serum PGF2α level,the expression levels of CD11B and c-Fos proteins in the spinal dorsal horn,as well as TRPV1,CD11B,and c-Fos proteins in the hypothalamus of the capsazepine group were lower than those in the mild moxibustion group(P<0.05).Conclusion:Mild moxibustion at Shenque(CV8)and Guanyuan(CV4)may alleviate the central pain sensitization in PD rats by down-regulating TRPV1 channel expression in the spinal dorsal horn and hypothalamus,thus playing an analgesic effect.
10.Mechanism of Modified Si Junzitang and Shashen Maidong Tang in Improving Sensitivity of Cisplatin in EGFR-TKI Resistant Lung Adenocarcinoma Cells Based on Aerobic Glycolysis
Yanping WEN ; Yi JIANG ; Liping SHEN ; Haiwei XIAO ; Xiaofeng YANG ; Surui YUAN ; Lingshuang LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):39-46
ObjectiveTo investigate the mechanism of modified Si Junzitang and Shashen Maidong Tang [Yiqi Yangyin Jiedu prescription (YQYYJD)] in enhancing the sensitivity of cisplatin in epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)-resistant lung adenocarcinoma cells based on aerobic glycolysis. MethodsThe effects of different concentrations of YQYYJD (0, 2, 3, 4, 5, 6, 7, 8 g·L-1) and cisplatin (0, 3, 6, 9, 12, 15, 18, 21, 24, 27 mg·L-1) on the proliferation and activity of PC9/GR cells were detected by the cell counting kit-8 (CCK-8) assay after 24 hours of intervention. The half-maximal inhibitory concentration (IC50) for PC9/GR cells was calculated to determine the concentrations used in subsequent experiments. PC9/GR cells were divided into blank group (complete medium), YQYYJD group (5 g·L-1), cisplatin group (12 mg·L-1), and combined group (YQYYJD 5 g·L-1 + cisplatin 12 mg·L-1). After 24 hours of intervention, cell viability was measured using CCK-8 assay. Cell proliferation was assessed by colony formation assay, and cell migration was evaluated by scratch and Transwell assays. Glucose consumption, lactate production, and adenosine triphosphate (ATP) levels were measured by colorimetric assays. The expression levels of glycolysis-related proteins, including hexokinase 2 (HK2), phosphofructokinase P (PFKP), pyruvate kinase M2 (PKM2), lactate dehydrogenase A (LDHA), glucose transporter 1 (GLUT1), and monocarboxylate transporter 4 (MCT4), were determined by Western blot. ResultsBoth YQYYJD and cisplatin inhibited the viability of PC9/GR cells in a concentration-dependent manner. The IC50 of PC9/GR cells for YQYYJD and cisplatin were 5.15 g·L-1 and 12.91 mg·L-1, respectively. In terms of cell proliferation, compared with the blank group, the cell survival rate and the number of colonies formed in the YQYYJD group, cisplatin group, and combined group were significantly decreased (P<0.01). Compared with the YQYYJD and cisplatin groups, the combined group showed a further significant reduction in cell survival rate and colony formation (P<0.01). In terms of cell migration, compared with the blank group, the cell migration rate and the number of cells passing through the Transwell membrane in the YQYYJD group, cisplatin group, and combined group were significantly decreased (P<0.01). Compared with the YQYYJD and cisplatin groups, the combined group exhibited a further significant reduction in cell migration rate and the number of cells passing through the Transwell membrane (P<0.01). In terms of glycolysis, compared with the blank group, glucose consumption, lactate production, and ATP levels in the YQYYJD group, cisplatin group, and combined group were significantly decreased (P<0.01). Compared with the YQYYJD and cisplatin groups, the combined group showed a further significant reduction in glucose consumption, lactate production, and ATP levels (P<0.05). Compared with the blank group, the protein expression levels of HK2, PFKP, PKM2, and LDHA in the YQYYJD, cisplatin, and combined groups were significantly decreased (P<0.01). The combined group showed a further significant reduction in the expression levels of these proteins compared with the YQYYJD and cisplatin groups (P<0.01). No significant differences were observed in the protein expression levels of GLUT1 and MCT4 among the groups. ConclusionYQYYJD can synergistically inhibit the proliferation and migration of PC9/GR cells and enhance their sensitivity to cisplatin. The mechanism may be related to the downregulation of the expression of glycolysis-related rate-limiting enzymes, including HK2, PFKP, PKM2, and LDHA, thereby inhibiting glycolysis.


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