1.Clinical Observation and Mechanism Study of Xu's Shenqi Yizhu Decoction Combined with Chemotherapy in the Treatment of Cancer-related Fatigue of Stagnated-toxin Spleen Deficiency Type in Postoperative Gastric Cancer Patients
Zhixiang SHEN ; Weimin LU ; Chuan SHI ; Mengwei YE ; Mengyuan LEI ; Ziyun LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):143-151
ObjectiveTo evaluate the clinical efficacy of Xu's Shenqiyizhu (SQYZ) decoction combined with chemotherapy in the treatment of cancer-related fatigue (CRF) of stagnated-toxin spleen deficiency type after gastric cancer surgery and explore its possible mechanism. MethodsFifty postoperative gastric cancer patients with CRF of stagnated-toxin spleen deficiency type were selected and randomly divided into an experimental group and a control group by using a random number table,with 25 cases in each group. The control group was treated with FLOT chemotherapy (50 mg·m-2 docetaxel (iv drip on day 1) + 85 mg·m-2 oxaliplatin (iv drip on day 1) + 200 mg·m-2 calcium folinate (iv drip on day 1) + 2 600 mg·m-2 fluorouracil (iv drip for 24 h on day 1),once every three weeks) and basic and symptomatic supportive treatment. The experimental group was treated with Xu's SQYZ decoction (decocted twice,200 mL taken orally twice a day) in addition to the treatment of the control group. One course of treatment lasted for three weeks,with a total of four courses conducted. Observation was performed on the piper fatigue scale (PFS) scores,karnofsky performance status (KPS) scores,European Organization for Research and Treatment of cancer quality of life questionnaire (EORTC QLQ-C30) scores,traditional Chinese medicine syndrome scores,and serum levels of tumor necrosis factor-α (TNF-α),interferon-γ (IFN-γ),and interleukin-6 (IL-6)detected via enzyme linked immunosorbent assay (ELISA) before and after treatment in the two groups. The safety test results before and after treatment for the two groups of patients,as well as the occurrence of adverse events during treatment, were recorded. Transcriptome sequencing data of peripheral blood samples from gastric adenocarcinoma patients and normal individuals were downloaded from the gene expression omnibus (GEO) database,and differentially expressed genes between the tumor and normal groups were identified. Differential gene enrichment analysis was made based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). The CRF relevance scores of genes were retrieved from the GeneCards database. Results① Compared with that before treatment,the total PFS score in the experimental group was significantly reduced (P<0.05). Compared with the control group after treatment,the experimental group showed significantly reduced total PFS score (P<0.05). ② Compared with that before treatment,the KPS score in the experimental group decreased significantly (P<0.05). Compared with the control group after treatment,the experimental group exhibited a significantly decreased KPS score (P<0.05). The experimental group demonstrated significantly increased functional scores (physical function,role function,emotional function,social function,and overall health) (P<0.05) and significantly reduced symptom scores (fatigue,shortness of breath,loss of appetite,constipation,and diarrhea) of the EORTC QLQ-C30 scale after treatment compared with before treatment. Compared with the control group after treatment,the experimental group presented significantly increased functional scores (physical function,emotional function,social function,and overall health) (P<0.05) and significantly reduced symptom scores (fatigue,nausea and vomiting,shortness of breath,loss of appetite,and diarrhea) of the EORTC QLQ-C30 scale (P<0.05). Compared with those before treatment,the traditional Chinese medicine syndrome scores (eating too little and poor digestion,fatigue and weakness,postprandial bloating,abnormal bowel movements,lassitude and weakness,and total score) in the experimental group were significantly reduced (P<0.05). Compared with the control group after treatment,the experimental group had significantly reduced traditional Chinese medicine syndrome scores (eating too little and poor digestion,fatigue and weakness,nausea and vomiting,and sallow complexion) (P<0.05), which indicated better efficacy in the experimental group than in the control group (χ2=7.996,P<0.05). The serum levels of TNF-α,IL-6,and IFN-γ were significantly correlated with each other (P<0.01). Compared with those before treatment,the levels of serum cytokines TNF-α,IL-6,and IFN-γ in the experimental group were significantly reduced (P<0.05). Compared with the control group after treatment,the experimental group showed significantly reduced serum levels of cytokines TNF-α,IL-6,and IFN-γ (P<0.05). ③ There were no significant intra-group and inter-group differences in the safety test results of the two groups before and after treatment. During the treatment period,there was no significant difference in the incidence of adverse reactions between the two groups of patients. ④ Compared with the normal group,the tumor group exhibited a total of 328 significantly up-regulated genes in the peripheral blood (P<0.05),and KEGG and GO analyses showed that they were significantly enriched in signaling pathways such as TNF (P<0.05). ⑤ TNF,IL6,IFNG, and other cytokine encoding genes may be key pathogenic genes for CRF. ConclusionXu's SQYZ decoction can alleviate symptoms such as fatigue in postoperative chemotherapy patients with gastric cancer and improve their functional status and quality of life. Its mechanism may be related to improving cytokine imbalance.
3.A preliminary study of the value of N-terminal pro-B-type natriuretic peptide in patients with end-stage heart failure implanted with magnetic fluid suspended left ventricular assist devices
Ze HOU ; Yuting LIU ; Xinyi WANG ; Yingnan YE ; Mengwei WANG ; Kegang JIA
Chinese Journal of Laboratory Medicine 2024;47(3):264-271
Objective:To investigate the changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and its role in predicting major adverse cardiac events (MACEs) in patients with end-stage heart failure (ESHF) before and after implanted a HeartCon left ventricular assist device (LVAD).Methods:The retrospective study included 30 ESHF patients [23 males and 7 females, aged 54.5 (40.8, 60.0) years], who were admitted to TEDA International Cardiovascular Disease Hospital from September 15, 2020 to June 20, 2023 to receive treatment with HeartCon LVAD implantation. Their clinical data were analyzed and NT-proBNP concentrations in their blood samples were measured preoperatively and during the follow-up period. Patients were followed regularly and MACEs, including cardiac death and rehospitalization for right heart failure, were recorded within 6 months of discharge; Logistic regression was used for prognostic analysis, and Receiver Operator Characteristic (ROC) curves were used to assess the adjunctive diagnostic value of NT-proBNP for poor prognosis in LVAD patients. The cut-off values for diagnosing poor prognosis by NT-proBNP were divided into two groups, and survival analysis was performed by Kaplan-Meier and tested by log rank; Cox regression was performed to analyze whether high levels of NT-proBNP at 6 months of follow-up wsa a risk factor for poor prognosis in patients with LVAD.Results:The median preoperative NT-proBNP level in 30 ESHF patients successfully implanted with HeartCon LVADs was 3 251.0 (1 544.5, 6 401.5) pg/ml. It decreased significantly 7 days postoperatively (3 251.0 vs. 1 815.0 pg/ml, P<0.05), and then the decreasing trend slowed. It decreased to 1 182.0 (620.0, 3 385.3) pg/ml on the 90th post-operative day. The preoperative NT-proBNP>3 251.0 pg/ml group had a longer postoperative hospital stay (47 d vs 33 d, Z=-2.138, P=0.032). Multivariate logistic regression analysis, only NT-proBNP at 7 days postoperatively was found to predict poor prognosis in LVAD patients, with an OR of 1.001 ( P=0.01); ROC curves were analyzed for the adjunctive diagnostic value of 7-day postoperative NT-proBNP levels for poor prognosis (cut-off value of 2 083.0 pg/ml), with an AUC of 0.833 ( P=0.002); The Kaplan-Meier survival analysis showed that the time to MACEs within 6 months was significantly shorter in the group with NT-proBNP>2 083.0 pg/mL on postoperative day 7 than in the group with NT-proBNP≤2 083.0 pg/ml (3.538±0.689 vs. 5.471±0.323 months, P=0.004); Cox regression analysis showed that the risk of MACEs was 4.25 times higher in the 7-day postoperative NT-proBNP>2 083.0 pg/ml group than in the NT-proBNP≤2 083.0 pg/ml group ( HR=4.25, P=0.035). Conclusions:The higher the preoperative NT-proBNP level, the longer the postoperative hospital stay in HeartCon LVAD patients. NT-proBNP levels decrease most significantly on postoperative day 7 and is a risk factor for MACEs. It may be used as a prognostic predictor in ESHF patients with implanted LVADs.
4.To Investigate the Progression Mechanism of Breast Cancer in Mice Induced by Chronic Restraint Stress and the Regulatory Mechanism of Xiaoyaosan Based on TGF-β1/CD147 Signal
Yan LIU ; Gaoyuan LIU ; Mengwei PENG ; Luoyi KUANG ; Zilong LUO ; Tiezhu YANG ; Yaosong WU ; Yulong CHEN
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(4):934-943
Objective To investigate the progression of breast cancer in mice induced by chronic binding stress and the regulatory mechanism of Xiaoyao SAN based on TGF-β1/CD147 signal pathway.Methods 40 BABL/c mice were randomly divided into tumor group,model group,Xiaoyaosan group and Mifepristone group,and then 4T1 cell line was inoculated into the armpits of each group of mice.After Tumor formation,mice in all groups except tumor group were subjected to chronic restraint stress for 21 days.Meanwhile,mice in Xiaoyaosan and Mifepristone groups were gavaged with the corresponding drugs,and mice in the other two groups were gavaged with normal saline.After the modeling,the mice were sacrificed after anaesthesia.The weight and volume of the tumors and visceral index of the mice were measured.The contents of serum tumor markers(CA199,CEA,VEGF),serum neurotransmitters(DA and CORT),and inflammatory mediators(TGF-β1 and IL-10)in tumor tissues were detected by Elisa.The expressions of iNOS and Arg-1,the polarization markers of macrophages,and the expressions of CD147 and its downstream signaling molecules MMP2,MMP9 and VEGF in tumor tissues were all detected by immunohistochemistry and Western blot.Results Compared with tumor group,in model group,tumor weight and volume,serum CA199,CEA,VEGF,CORT content,tumor TGF-β1 and IL-10 content were significantly increased;visceral index and serum DA content were significantly reduced;the expression of M2-type polarization marker Arg-1 in tumor macrophages was significantly increased,while the expression of M1-type polarization marker iNOS was significantly decreased;the expressions of CD147 and its downstream signaling molecules MMP2,MMP9 and VEGF were significantly increased.Both Xiaoyaosan and mifepristone could effectively reverse the above changes.Conclusion The mechanism of chronic restraint stress promoting breast cancer progression in mice is related to the increased release of TGF-β1 from M2-type polarization of tumor-associated macrophages,which activates CD147 and its downstream related signals.Xiaoyaosan could relieve the M2-type polarization of macrophages caused by increased corticosterone under stress conditions,reduce the production of TGF-β1,inhibit CD147 and its downstream signal,and thus inhibit the progression of breast cancer caused by chronic restraint stress in mice.
5.Exploration of mouse model of breast cancer complicated with depression induced using 4T1 breast cancer cell inoculation combined with chronic restraint stress
Yan LIU ; Mengwei PENG ; Gaoyuan LIU ; Tiezhu YANG ; Wenxian ZHANG ; Yaosong WU ; Yulong CHEN
Chinese Journal of Comparative Medicine 2024;34(3):36-44,50
Objective To study the core behavioral symptoms,biological indicators,and pathological changes of a mouse model of breast cancer complicated with depression induced using 4T1 breast cancer cell inoculation combined with chronic restraint stress(CRS).Methods BABL/c mice were randomly divided into Control,Stress,Tumor,and stress combined with tumor(S+T)groups.Mice in the tumor and S+T groups were inoculated under the front legs with breast cancer 4T1 cells.After tumor formation,mice in the stress and S+T groups were subjected to CRS for 21 days.The body weight and food intake of each group were monitored during modeling.After the experiment,the occurrence of depression-like behavior of mice in each group was evaluated by sucrose preference test,open field test,elevated plus-maze test,and forced swimming test.After the mice were decapitated,the weights and volumes of the tumors were measured.Concentrations of serum tumor markers,including carbohydrate antigen(CA199),carcinoembryonic antigen(CEA),and vascular endothelial growth factor(VEGF),and related neurotransmitters,including 5-hydroxytryptamine(5-HT),norepinephrine(NE),and corticosterone(CORT),were determined using ELISA.HE staining was used to observe histopathological changes to the hippocampus and tumor.Results In S+T group mice,body weight and food intake were significantly decreased,tumor weight and volume were significantly increased,serum tumor marker(CA199,CEA,VEGF)levels were significantly increased,enthusiasm and desire to explore a new environment were reduced,stress and despair behaviors were significantly increased,and levels of the serum neurotransmitters 5-HT and NE and levels of CORT were significantly increased.In addition,the cell arrangement in the tumor tissue was loose,the amount of intercellular substance decreased,the pathological nuclear classification phase was increased,the arrangement and morphology of neurons in the CA3 region of the hippocampus were disordered,and there were obvious nuclear vacuolation-like changes.Conclusions A mouse model of breast cancer complicated with depression induced by 4T1 breast cancer cell inoculation combined with CRS showed the typical dual symptoms and biological indicators of breast cancer and depression and can be used as a good reference model for experimental studies of breast cancer complicated with depression.
6.Research progress on the use of Traditional Chinese Medicines to treat breast cancer-related depression and associated diseases
Mengwei PENG ; Yaosong WU ; Gaoyuan LIU ; Luoyi KUANG ; Zilong LUO ; Yulong CHEN ; Yan LIU
Chinese Journal of Comparative Medicine 2024;34(9):108-116
Pathological mood changes,mainly depression,occurring during the diagnosis and treatment of breast cancer are referred to as breast cancer-related depression(BCRD).Numerous epidemiological and clinical studies have confirmed that BCRD is a complex condition that is difficult to treat and has a poor prognosis.Most existing clinical treatments involve the use of postoperative chemotherapy for breast cancer,and antidepressant drugs,which treat breast cancer and depression as two independent diseases and have various disadvantages such as low efficiency and strong adverse reactions.Traditional Chinese Medicine(TCM)has a unique value in the prevention and treatment of BCRD via its ability to regulate multiple pathways and targets using multiple components at the same time.In this paper,we review the mechanism of BRCD and the therapeutic mechanisms of TCM from the aspects of neurological disorders,inflammatory immune response,and intestinal flora disorders,with a view to providing references for the clinical application and research of TCM in the treatment of BCRD.
7.Predictive value of FAR, CAR and PLR in hyperlipidemic acute pancreatitis
Qiaofang WANG ; Chaopeng MEI ; Yaodong SONG ; Yanna LIU ; Dejian LI ; Mengwei CUI ; Qianqian HE ; Huihui LI ; Haifeng WANG ; Changju ZHU
Chinese Journal of Emergency Medicine 2024;33(10):1376-1382
Objective:To investigate the value of fibrinogen to albumin ratio (FAR), creatinine to albumin ratio (CAR) and platelet to lymphocyte ratio (PLR) in predicting the poor prognosis of hyperlipidemic acute pancreatitis (HLAP).Methods:Clinical data of HLAP patients admitted to the hospital from January 2021 to January and December 2023 were retrospectively collected. According to the prognosis, the patients were divided into two groups: good prognosis group and poor prognosis group.The independent risk factors of HLAP in different prognostic groups were obtained by multivariate Logistic regression analysis. Receiver operating characteristic (ROC) curves were plotted to evaluate the prognostic value of FAR, CAR and PLR alone and in combination.Results:A total of 118 patients with HLAP were included, including 69 patients with good prognosis and 49 patients with poor prognosis.The difference of heart rate, lymphocyte, triglyceride, albumin, creatinine, urea nitrogen, blood calcium, blood glucose, C-reactive protein, procalcitonin, fibrinogen, FAR, CAR, PLR, Bedside indicator of acute pancreatitis Severity score, Acute Physiology and Chronic Health status score, hospitalization time assessment between the two groups was statistically significant ( P<0.05). Multivariate Logistic regression analysis showed that FAR (odds ratio ( OR) = 25.949, 95% confidence interval (95% CI):3.190 ~ 211.080, P = 0.002), CAR ( OR = 1.453, 95% CI:1.095 ~ 1.928, P = 0.010) and PLR ( OR = 1.005, 95% CI: 1.001 ~ 1.009, P = 0.020) were independent risk factors for poor prognosis in HLAP patients. ROC curve analysis showed that the area under the ROC curve (AUC) of FAR, CAR and PLR to predict poor prognosis of HLAP patients were 0.823, 0.781 and 0.652, respectively.The AUC of FAR combined with CAR, FAR combined with PLR and CAR combined with PLR were 0.840, 0.845 and 0.849, respectively.The combined ability of FAR, CAR and PLR to predict poor prognosis in HLAP patients was (AUC=0.875,95% CI:0.814 ~ 0.937). When the cut-off value was 0.387, the sensitivity was 83.7%, and the specificity was 79.7%. Conclusions:The prognostic value of FAR, CAR and PLR in HLAP patients is better than that of single or pairwise combination.
8.Clinicopathological characteristics analysis of 20 cases of head and neck spindle cell squamous cell carcinoma
Ming HAN ; Mengwei XU ; Li SHI ; Yingmei WANG ; Yixiong LIU ; Wanni XU ; Yuqiao XU
Chinese Journal of Clinical Oncology 2023;50(22):1147-1152
Objective:To investigate the clinicopathological features,immunophenotype,and prognosis of head and neck spindle cell squamous cell carcinoma(SCSCC)to improve the understanding and diagnosis of this tumor.Methods:Clinicopathological data collected from January 2012 to December 2022 at the First Affiliated Hospital,Air Force Military Medical University from 20 patients with head and neck SCSCC were retrospectively reviewed for histological morphology and immunophenotype.In situ and fluorescence in situ hybridization were performed to detect EBV-encoded ribonucleic acid(EBER)status and MDM2 gene amplification,respectively.Results:The median age among the 20 SCSCC cases was 67 years with a male-to-female ratio of 4∶1.Tumor locations were laryngeal(35.0%)and sinonasal(30.0%).SCSCC presented as polypoid or exogenous growths(61.5%),often with surface ulceration(90.0%).Histologically,sarcomatoid growth pat-terns were exhibited in 75.0%of the patients(n=15),while the remainder showed granular tissue-like or angiosarcomatoid patterns.Most tumors(65.0%)displayed components of conventional squamous cell carcinomas,with a predominant occurrence of high to moderate dif-ferentiation(91.7%).In terms of immunohistochemistry,AE1/AE3 was expressed in 83.3%(15/18)of cases,while p63 and p40 expression rates were 62.5%and 66.7%,respectively.All cases were negative for EBER.The Ki-67 proliferation index ranged 10%-70%.Overall,33.3%(1/3)of the cases showed MDM2 gene amplification.Among these,the median follow-up time for 18 patients was 18.3 months(range:1-92 months),with 6 survivors and 12 deaths.Conclusions:Head and neck SCSCC is more prevalent among elderly male smokers,predominantly exhibits a polypoid growth pattern,and does not display human papillomavirus or Epstein-Barr virus infection.Diagnosis requires a compre-hensive evaluation of clinical and pathological features and immunophenotype.Surgical resection is the primary treatment method.
9. Effects and mechanism of dapagliflozin on myocardial injury in type 1 diabetes mice
Xuejiao ZHANG ; Jieting LIU ; Luxin LI ; Peijian CHEN ; Minglu DING ; Mengwei SUN ; Yanhui CHU ; Zhen ZHANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(3):257-265
AIM: To investigate the effect of dapagliflozin on myocardial injury in type 1 diabetes mice and its mechanism. METHODS: Normal C57BL / 6J male mice were randomly divided into normal control group (Control), diabetes cardiomyopathy group (DCM) and dapagliflozin group (DAPA). The model of diabetes was induced by streptozotocin (STZ) and given maintenance feed. DAPA group was given 10 mg · kg
10.Expression of soluble ST2 and its prognostic value in patients with heart failure and hypertension with ejection fraction retention
Yuting LIU ; Yuting GAO ; Ze HOU ; Mengwei WANG ; Xuejing HAN ; Hongxia TANG ; Kegang JIA
Chinese Journal of Laboratory Medicine 2023;46(12):1274-1280
Objective:To investigate the relationship between peripheral blood sST2 level and prognosis in patients with heart failure (HFpEF) complicated with hypertension with ejection fraction preservation.Methods:A total of 122 patients with HFpEF hospitalized in Teda International Cardiovascular Hospital and Baoding First Central Hospital from May 5, 2021 to March 9, 2023 were selected. According to whether they were combined with hypertension, they were divided into HFpEF combined with hypertension group (73 cases, 32 males, (67.56±12.06) years old). There were 41 females (70.61±9.95 years old) and 49 males (67.00±11.64 years old) in the HFpEF group alone. There were 24 female patients (70.12±7.49 years old). sST2 levels in peripheral blood were compared between the two groups.HFpEF patients with hypertension were grouped by hypertension grade and prognosis, and the difference of sST2 in different groups was compared. Logistic regression was used for multivariate analysis. ROC curve to evaluate the diagnostic value of sST2 in the poor prognosis of HFpEF patients with hypertension. Patients were followed up regularly and major adverse cardiac events were recorded within 6 months after discharge, including cardiogenic death and heart failure re-hospitalization. The critical value of poor prognosis diagnosed by sST2 was divided into two groups, survival analysis was performed by Kaplan-Meier,and the Log Rank test was performed. Cox regression analysis was performed to determine whether high levels of sST2 were a risk factor for poor prognosis after 6 months of follow-up.Results:There was no significant difference in sST2 in HFpEF combined with hypertension and HFpEF alone ( P>0.05). sST2 was higher in grade 2 and 3 than in grade 1 hypertension (23.83 ng/ml vs. 12.68 ng/ml, Z=-2.778, P=0.005; 22.54 ng/ml vs. 12.68 ng/ml, Z=-2.865, P=0.004); BNP was higher in grade 3 hypertension than in grade 1 hypertension (582.95 pg/ml vs. 154.50 pg/ml, Z=-2.101, P<0.05). sST2 and BNP were higher in the poor prognosis group than in the good prognosis group (30.10 ng/ml vs. 18.95 ng/ml, Z=-2.803; 685.00 pg/ml vs. 347.50 pg/ml, Z=-2.385), all P<0.05. Logistic regression analysis showed that sST2 was a risk factor for poor prognosis ( OR=1.045, P=0.013). The auxiliary diagnostic value of sST2 level in HFpEF patients with hypertension was analyzed by ROC curve (AUC was 0.721, P<0.05). The incidence of cardiac adverse events in sST2>29.12 group was higher than that in sST2≤29.12 group (44.00% vs. 14.58%), and the difference was statistically significant (χ 2=7.657, P=0.006). Kaplan-Meier survival analysis showed that the percentage of patients with no endpoint event in the sST2≤29.12 group was higher than that in the sST2>29.12 group ( P=0.003).Cox regression analysis showed that the risk of endpoint event in sST2>29.12 group was 3.879 times that in sST2≤29.12 group ( OR=3.879, P=0.011). Conclusions:sST2 level can be used as an indicator of poor prognosis in HFpEF patients with hypertension, and can be used to stratify the risk of HFpEF patients. High levels of sST2 are associated with major adverse cardiac events.

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