1.The multi-center mid-term clinical outcomes of combined complete preservation of chordal structure mitral valve replacement with total anatomic complete arterial myocardial revascularization for coronary patients with moderate-to-severe or severe ischemic mitral regurgitation
Ke GUO ; Xujun CHEN ; Baoshi ZHENG ; Chao SHI ; Keli HUANG ; Yong CAO ; Chengquan LIAO ; Jingwei CHEN ; Yu LIN ; Chengxin LIU ; Quansheng CAO ; Lin SHEN ; Zhendong WANG
Chinese Journal of Surgery 2025;63(1):58-67
Objective:To evaluate the clinical outcomes of combined complete preservation of chordal structure mitral valve replacement (C-MVR) with total anatomical arterial myocardial revascularization (TACR) in coronary patients with moderate-to-severe or severe ischemic mitral regurgitation (IMR).Methods:This is a retrospective multi-center case series study. Data were retrospectively collected from 127 patients with coronary artery disease with moderate to severe or severe IMR who received TACR with C-MVR from July 2015 to April 2024 in 13 hospitals in China. There were 90 males and 37 females, aged (56.5±10.7) years (range: 33 to 74 years). Perioperative data and follow-up data including left ventricular ejection fraction, left ventricular end-diastolic diameter, and patency rate of arterial grafts of patients were collected. Comparisons were made using paired sample t-test or χ2 test. Results:In this cohort of 127 patients, 67 underwent concurrent tricuspid valve repair. During surgery, 113 grafts of the left internal mammary artery (LIMA), 127 grafts of the left radial artery, 80 grafts of the right radial artery, and 110 grafts of the right internal mammary artery (RIMA) were harvested. The number of the distal anastomosis was 4.2±0.4 (range: 3 to 5). The aortic cross-clamp time and cardiopulmonary bypass time were (97.5±23.4) minutes (range: 90 to 161 minutes) and (145.4±19.2) minutes (range: 101 to 210 minutes), respectively. There was one operative death. Intraoperative placement of an intra-aortic balloon pump was performed in 21 patients to improve the left ventricular ejection. No sternal ischemic occurred. All patients completed follow-up, with a mean follow-up period of (64.3±7.5) months (range: 4 to 110 months). No major cerebrovascular events occurred during the follow-up period, and all patients survived. Left ventricular ejection fraction improved postoperatively (55.0%±5.3% vs. 41.0%±15.3%, t=17.23, P<0.01). The proportion of patients with New York Heart Association functional class ≤2 increased postoperatively (23.6% (30/127) vs. 87.3% (110/126), χ2=103.77, P<0.01). The proportion of patients with Canadian Cardiovascular Society Angina Classification ≤3 decreased postoperatively (4.8% (6/126) vs. 78.7% (100/127), χ2=142.19, P<0.01). The left ventricular end-diastolic diameter decreased postoperatively ((5.70±4.50) cm vs. (6.10±0.23) cm, t=12.15, P<0.01). Coronary multi-detector computed tomography angiography (MDCTA) follow-up was conducted for (60.5±11.7) months (range: 6 to 109 months) postoperatively. MDCTA confirmed the patency rates of the grafts: 96.4% (108/112) for the LIMA grafts, 88.9% (112/126) for the left radial artery grafts, 93.7% (74/79) for the right radial artery grafts, and 90.9% (100/110) for the free RIMA grafts. No significant differences in graft patency rates were observed between the arterial grafts ( χ2=5.24, P=0.155). Conclusion:The results of this multi-centre study demonstrate satisfactory mid-term results of C-MVR with TACR for the treatment of coronary artery disease with moderate to severe or severe IMR.
2.Protective Effect of Xuebijing on Lung Injury in Rats with Severe Acute Pancreatitis by Blocking FPRs/NLRP3 Inflammatory Pathway
Guixian ZHANG ; Dawei LIU ; Xia LI ; Xijing LI ; Pengcheng SHI ; Zhiqiao FENG ; Jun CAI ; Wenhui ZONG ; Xiumei ZHAO ; Hongbin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):113-120
ObjectiveTo explore the therapeutic effect of Xuebijing injection (XBJ) on severe acute pancreatitis induced acute lung injury (SAP-ALI) by regulating formyl peptide receptors (FPRs)/nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammatory pathway. MethodsSixty rats were randomly divided into a sham group, a SAP-ALI model group, low-, medium-, and high-dose XBJ groups (4, 8, and 12 mL·kg-1), and a positive drug (BOC2, 0.2 mg·kg-1) group. For the sham group, the pancreas of rats was only gently flipped after laparotomy, and then the abdomen was closed, while for the remaining five groups, SAP-ALI rat models were established by retrograde injection of 5% sodium taurocholate (Na-Tc) via the biliopancreatic duct. XBJ and BOC2 were administered via intraperitoneal injection once daily for 3 d prior to modeling and 0.5 h after modeling. Blood was collected from the abdominal aorta 6 h after the completion of modeling, and the expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) in plasma was measured by enzyme-linked immunosorbent assay (ELISA). The amount of ascites was measured, and the dry-wet weight ratios of pancreatic and lung tissue were determined. Pancreatic and lung tissue was taken for hematoxylin-eosin (HE) staining to observe pathological changes and then scored. The protein expression levels of FPR1, FPR2, and NLRP3 in lung tissue were detected by the immunohistochemical method. Western blot was used to detect the expression of FPR1, FPR2, and NLRP3 in lung tissue. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of FPR1, FPR2, and NLRP3 in lung tissue. ResultsCompared with the sham group, the SAP-ALI model group showed significantly decreased dry-wet weight ratio of lung tissue (P<0.01), serious pathological changes of lung tissue, a significantly increased pathological score (P<0.01), and significantly increased protein and mRNA expression levels of FPR1, FPR2, and NLRP3 in lung tissue (P<0.01). After BOC2 intervention, the above detection indicators were significantly reversed (P<0.01). After treatment with XBJ, the groups of different XBJ doses achieved results consistent with BOC2 intervention. ConclusionXBJ can effectively improve the inflammatory response of the lungs in SAP-ALI rats and reduce damage. The mechanism may be related to inhibiting the expression of FPRs and NLRP3 in lung tissue, which thereby reduces IL-1β and simultaneously antagonize the release of inflammatory factors IL-6 and TNF-α.
3.Proteomics combined with bioinformatics analysis of protein markers of dry eye
Yanting YANG ; Yajun SHI ; Guang YANG ; Haiyang JI ; Jie LIU ; Jue HONG ; Dan ZHANG ; Xiaopeng MA
International Eye Science 2025;25(1):104-111
AIM:To analyze differential proteins associated with the pathogenesis of dry eye(DE)using bioinformatics methods, in order to reveal their potential molecular mechanisms.METHODS: Articles published in PubMed and EMBASE databases from the inception of the database to August 31, 2023, that used proteomic methods to detect protein expression in clinical samples of dry eye were searched. Differential proteins were selected and further analyzed using the STRING database and Cytoscape software for hub gene screening and module analysis. Protein-protein interaction(PPI)analysis, gene ontology(GO)functional annotation, and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were performed.RESULTS: A total of 21 articles were included, identifying 74 differentially expressed proteins. The most frequently occurring differential proteins were calgranulin A(SA1008), lipocalin-1(LCN1), lysozyme C(LYZ), mammaglobin-B(SCGB2A1), proline-rich protein 4(PRR4), transferrin(TF), and calgranulinB(S100A9). The top 10 hub genes were serum albumin(ALB), tumor necrosis factor(TNF), interleukin 6(IL6), IL1B, IL8, matrix metalloproteinase 9(MMP9), alpha-1-antitrypsin(SERPINA1), IL10, complement component 3(C3), and lactotransferrin(LTF). Module analysis suggested MMP9 and PRR4 as seed genes. KEGG analysis showed that differential proteins were mainly enriched in the IL17 signaling pathway(61.9%).CONCLUSION: The results reveal potential molecular targets and pathways for DE and confirm the association between the pathogenesis of DE and inflammation. Further in-depth research is needed to confirm the significance of these biomarkers in clinical practice.
4.Clinical Efficacy of Modified Huangqi Chifengtang in Treatment of IgA Nephropathy Patients and Exploration of Dose-effect Relationship of Astragali Radix
Xiujie SHI ; Meiying CHANG ; Yue SHI ; Ziyan ZHANG ; Yifan ZHANG ; Qi ZHANG ; Hangyu DUAN ; Jing LIU ; Mingming ZHAO ; Yuan SI ; Yu ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):9-16
ObjectiveTo explore the dose-effect relationship and safety of high, medium, and low doses of raw Astragali Radix in the modified Huangqi Chifengtang (MHCD) for treating proteinuria in immunoglobulin A (IgA) nephropathy, and to provide scientific evidence for the clinical use of high-dose Astragali Radix in the treatment of proteinuria in IgA nephropathy. MethodsA total of 120 patients with IgA nephropathy, diagnosed with Qi deficiency and blood stasis combined with wind pathogen and heat toxicity, were randomly divided into a control group and three treatment groups. The control group received telmisartan combined with a Chinese medicine placebo, while the treatment groups were given telmisartan combined with MHCD containing different doses of raw Astragali Radix (60, 30, 15 g). Each group contained 30 patients, and the treatment period was 12 weeks. Changes in 24-hour urinary protein (24 hUTP), traditional Chinese medicine (TCM) syndrome scores, effective rate, and renal function were observed before and after treatment. Safety was assessed by monitoring liver function and blood routine. ResultsAfter 12 weeks of treatment, 24 hUTP significantly decreased in the high, medium, and low-dose groups, as well as the control group (P<0.05, P<0.01). The TCM syndrome scores in the high, medium, and low-dose groups also significantly decreased (P<0.01). Comparisons between groups showed that the 24 hUTP in the high-dose group was significantly lower than in the medium, low-dose, and control groups (P<0.05, P<0.01), and the 24 hUTP in the medium-dose group was significantly lower than in the control group (P<0.05). The TCM syndrome scores in the high and medium-dose groups were significantly lower than in the low-dose and control groups (P<0.05, P<0.01). The total effective rates for proteinuria in the high, medium, low-dose, and control groups were 92.59% (25/27), 85.19% (23/27), 60.71% (17/28), and 57.14% (16/28), respectively. The effective rates in the high and medium-dose groups were significantly higher than in the low-dose and control groups (χ2=13.185, P<0.05, P<0.01). The effective rates for TCM syndrome scores in the high, medium, low-dose, and control groups were 88.89% (24/27), 81.48% (22/27), 71.43% (20/28), and 46.43% (13/28), respectively. The efficacy of TCM syndrome scores in the high and medium-dose groups was significantly higher than in the control group (χ2=14.053, P<0.01). Compared with pre-treatment values, there was no statistically significant difference in eGFR and serum creatinine in the high and medium-dose groups. However, eGFR significantly decreased in the low-dose and control groups after treatment (P<0.05), and serum creatinine levels increased significantly in the control group (P<0.05). No statistically significant differences were observed in urea nitrogen, uric acid, albumin, total cholesterol, triglycerides, liver function, and blood routine before and after treatment in any group. ConclusionThere is a dose-effect relationship in the treatment of IgA nephropathy with high, medium, and low doses of raw Astragali Radix in MHCD. The high-dose group exhibited the best therapeutic effect and good safety profile.
5.Effect of Acupuncture Combined with Bloodletting and Cupping on the Expression of Coagulation-Complement-Mast Cell Activation Axis-Related Factors in Patients with Chronic Spontaneous Urticaria:Randomize-controlled Study
Yuzhu DU ; Yuqiang XUE ; Xiang LIU ; Yu SHI ; Hongkun LI ; Wenshan LIU ; Zan TIAN ; Yutong HU ; Yanjun WANG
Journal of Traditional Chinese Medicine 2025;66(2):150-156
ObjectiveTo observe the clinical efficacy of acupuncture combined with bloodletting and cupping in the treatment of chronic spontaneous urticaria(CSU) and to explore its potential mechanisms of action. MethodsSeventy CSU patients were randomly divided into loratadine group and acupuncture + bloodletting group, with 35 patients in each group. The loratadine group received oral loratadine tablets, 10 mg once daily in the evening. The acupuncture + bloodletting group received acupuncture at Zhongwan (CV 12), Guanyuan (CV 4), Tianshu (ST 25), Zusanli (ST 36), Sanyinjiao (SP 6), Xuehai (SP 10), Quchi (LI 11), Hegu (LI 4), Taichong (LR 3), Baihui (GV 20), and Shenting (GV 24), once daily,along with bloodletting and cupping at Dazhui (GV 14) and Geshu (BL 17), every other day. Both groups were treated for 4 weeks. The 7-day urticaria activity score(UAS7) was assessed before and after the treatment, and levels of serum immunoglobulin E (IgE), interleukin-4 (IL-4), interleukin-5 (IL-5), eosinophil cationic protein (ECP), plasma tissue factor (TF), activated factor Ⅶ (FⅦa), prothrombin fragment 1+2 (F1+2), D-dimer (D-D) and complement component 5a (C5a) were detected. ResultsA total of 65 patients were included in the final analysis, 32 in the loratadine group and 33 in the acupuncture + bloodletting group. Before treatment, there was no significant difference in UAS7 score, serum IgE, IL-4, IL-5, ECP levels, or plasma TF, FⅦa, F1+2, D-D, C5a levels between groups (P> 0.05). After treatment, both groups showed significant reductions in UAS7 score, serum IgE, IL-4, IL-5, and plasma TF, FⅦa, F1+2, D-D, and C5a levels compared to those before treatment (P<0.01). However, after treatment, there was no significant difference in UAS7 score and serum ECP, IgE, IL-4, IL-5 levels between groups (P>0.05). The acupuncture + bloodletting group showed lower plasma TF, FⅦa, F1+2, D-D and C5a levels compared to the loratadine group (P<0.05 or P<0.01). ConclusionAcupuncture combined with bloodletting and cupping can effectively improve the skin symptoms of CSU patients and reduce the levels of inflammatory factors. The potential mechanism of action may involve the regulation of the coagulation-complement-mast cell activation axis, thereby inhibiting mast cell degranulation.
6.Fufang Kangjiaolv Capsules Treat Anxiety in Rat Model of Chronic Restraint Stress via Microbiota-gut-brain Axis
Wenxin FAN ; Tingyue JIANG ; Yu WANG ; Ge ZHANG ; Yifan LU ; Mengmeng LIU ; Jiayuan LI ; Renzhi MA ; Jinli SHI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):95-107
ObjectiveTo observe the intervention effect of Fufang Kangjiaolv capsules on anxiety-like behaviors in the rat model of chronic restraint stress (CRS) and explore the mechanism underlying the anti-anxiety effect via the microbiota-gut-brain axis. MethodsRats were assigned into blank, model, positive drug (diazepam, 1 mg·kg-1), and low-, medium-, and high-dose (0.75, 1.5, 3 g·kg-1, respectively) Fufang Kangjiaolv capsules groups. After 14 days of administration, the elevated plus maze test, open field test, light and dark box test, and marble burying test were performed. Hematoxylin-eosin staining was employed to observe the pathological changes in the hippocampus and colon of rats, and Nissl staining was conducted to observe the damage of hippocampal neurons. The gut microbiota was analyzed by 16S rRNA gene sequencing. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was employed to determine the mRNA levels of zonula occludens-1 (ZO-1) and occludin in the colon of rats. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in the colon, serum, and hippocampus were determined by enzyme-linked immunosorbent assay. Western blot was employed to determine the protein levels of ZO-1, occludin, nuclear factor-κB p65 (NF-κB p65) in the colon tissue and NF-κB p65 and brain-derived neurotrophic factor (BDNF) in the hippocampal tissue. ResultsCompared with the blank group, the model group showed reductions in the time and frequency ratio of rats entering the elevated plus maze, the time and frequency of rats entering the central area of the open field, the time of entering the open box, the times of passing through the light and dark box, and the number of unburied beads (P<0.05, P<0.01). Compared with the model group, Fufang Kangjiaolv capsules ameliorated the anxiety of the model rats to varying degrees, and the high-dose group had the best effect, with increases in the proportions of time and frequency of rats entering the open arm in the elevated plus maze (P<0.05), the number of rats entering the central area in the open field (P<0.05), the time of entering the open box, the times of passing through the light and dark boxes, and the number of unburied beads (P<0.01). Moreover, the high-dose group showed alleviated pathological damage of hippocampal neurons and colon. The results of 16S rRNA gene sequencing showed that the model group had increased relative abundance of Firmicutes, Deferribacterota, Romboutsia, and Phascolarctobacterium, while it had decreased relative abundance of Bavcteroidota and Lactobacillus. The drug administration groups showed increased relative abundance of Bavcteroidota, Bacteroides, norank f norank o Clostridia UCG-014, and Blautia and decreased relative abundance of Firmicutes and Deferribacterota. Compared with the blank group, the model group showed down-regulated protein and mRNA levels of ZO-1 and occludin in the colon (P<0.01), elevated levels of TNF-α, IL-6, and IL-β in the colon, serum, and hippocampus (P<0.01), up-regulated protein level of NF-κB p65 in the colon and hippocampus (P<0.01), and down-regulated protein level of BDNF in the hippocampus (P<0.05). Compared with the model group, high-dose Fufang Kangjiaolv capsules up-regulated the mRNA levels of ZO-1 and occludin in the colon (P<0.01), lowered the levels of TNF-α, IL-6, and IL-β in the colon, serum, and hippocampus (P<0.01), up-regulated the protein levels of ZO-1 (P<0.01) and occludin (P<0.05) in the colon, down-regulated the protein level of NF-κB p65 in the colon and hippocampus (P<0.05), and up-regulated the protein level of BDNF in the hippocampus. ConclusionFufang Kangjiaolv capsules can reduce the anxiety-like behaviors in the rat model of CRS by regulating the gut microbiota disturbance, up-regulating the expression of tight junction proteins in the colon, repairing intestinal mucosal mechanical barrier, and down-regulating NF-κB/BDNF signaling pathway, thereby reducing peripheral and central inflammation. This study proves the hypothesis that Fufang Kangjiaolv capsules play an anti-anxiety role via the microbiota-gut-brain axis, providing a new idea for further research.
7.Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis
Jian LIU ; Hongchun ZHANG ; Chengxiang WANG ; Hongsheng CUI ; Xia CUI ; Shunan ZHANG ; Daowen YANG ; Cuiling FENG ; Yubo GUO ; Zengtao SUN ; Huiyong ZHANG ; Guangxi LI ; Qing MIAO ; Sumei WANG ; Liqing SHI ; Hongjun YANG ; Ting LIU ; Fangbo ZHANG ; Sheng CHEN ; Wei CHEN ; Hai WANG ; Lin LIN ; Nini QU ; Lei WU ; Dengshan WU ; Yafeng LIU ; Wenyan ZHANG ; Yueying ZHANG ; Yongfen FAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):182-188
The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis (GS/CACM 337-2023) was released by the China Association of Chinese Medicine on December 13th, 2023. This expert consensus was developed by experts in methodology, pharmacy, and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine (CACM) and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine (pulmonary diseases) and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung, acute bronchitis, and acute attack of chronic bronchitis from the aspects of applicable populations, efficacy evaluation, usage, dosage, drug combination, and safety. It is expected to guide the rational drug use in medical and health institutions, give full play to the unique value of Qinbaohong Zhike oral liquid, and vigorously promote the inheritance and innovation of Chinese patent medicines.
8.Prediction of pathological type of early lung adenocarcinoma using machine learning based on SHOX2 and RASSF1A methylation levels
Runqi HUANG ; Guangliang QIANG ; Yifei LIU ; Jiahai SHI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(01):67-72
Objective To explore the accuracy of machine learning algorithms based on SHOX2 and RASSF1A methylation levels in predicting early-stage lung adenocarcinoma pathological types. Methods A retrospective analysis was conducted on formalin-fixed paraffin-embedded (FFPE) specimens from patients who underwent lung tumor resection surgery at Affiliated Hospital of Nantong University from January 2021 to January 2023. Based on the pathological classification of the tumors, patients were divided into three groups: a benign tumor/adenocarcinoma in situ (BT/AIS) group, a minimally invasive adenocarcinoma (MIA) group, and an invasive adenocarcinoma (IA) group. The methylation levels of SHOX2 and RASSF1A in FFPE specimens were measured using the LungMe kit through methylation-specific PCR (MS-PCR). Using the methylation levels of SHOX2 and RASSF1A as predictive variables, various machine learning algorithms (including logistic regression, XGBoost, random forest, and naive Bayes) were employed to predict different lung adenocarcinoma pathological types. Results A total of 272 patients were included. The average ages of patients in the BT/AIS, MIA, and IA groups were 57.97, 61.31, and 63.84 years, respectively. The proportions of female patients were 55.38%, 61.11%, and 61.36%, respectively. In the early-stage lung adenocarcinoma prediction model established based on SHOX2 and RASSF1A methylation levels, the random forest and XGBoost models performed well in predicting each pathological type. The C-statistics of the random forest model for the BT/AIS, MIA, and IA groups were 0.71, 0.72, and 0.78, respectively. The C-statistics of the XGBoost model for the BT/AIS, MIA, and IA groups were 0.70, 0.75, and 0.77, respectively. The naive Bayes model only showed robust performance in the IA group, with a C-statistic of 0.73, indicating some predictive ability. The logistic regression model performed the worst among all groups, showing no predictive ability for any group. Through decision curve analysis, the random forest model demonstrated higher net benefit in predicting BT/AIS and MIA pathological types, indicating its potential value in clinical application. Conclusion Machine learning algorithms based on SHOX2 and RASSF1A methylation levels have high accuracy in predicting early-stage lung adenocarcinoma pathological types.
9.Design, synthesis and antifungal and antitumor activity research of novel Hsp90 inhibitors
Qiao SHI ; Guiyan HAN ; Junteng ZHANG ; Na LIU
Journal of Pharmaceutical Practice and Service 2025;43(3):124-135
Objective To design and synthesize novel Hsp90 inhibitors with dual functions of synergistically enhancing the antifungal activity of fluconazole (FLC) against drug-resistant fungi and anti-tumor activity based on the Hsp90 inhibitor Ganetespib. Methods The previous research found that Ganetespib had a good synergistic anti-resistant fungal activity with FLC, with a fractional inhibitory concentration index (FICI) of 0.023 to 0.039. In this study, structural modifications were made to Ganetespib by replacing its indole ring with a phenyl ring containing different substituents to design and synthesize a series of new compounds. The in vitro synergistic anti-resistant fungal activity against C. albicans 0304103 in combination with FLC, anti-tumor activity (against HEL, HL60 and A549 cells), and Hsp90α inhibition activity were determined to explore their structure-activity relationship and mechanism of action. Results The chemical structures of 19 new compounds were confirmed by 1H NMR, 13C NMR and HRMS. Most of the compounds exhibited strong Hsp90α inhibitory activity, good synergistic activity against drug-resistant fungi in combination with FLC and anti-tumor activity. The substitution of electron-donating groups on the benzene ring was beneficial to enhancing the synergistic activity against drug-resistant fungi in combination with FLC. Among them, compounds F3 and F5 showed excellent synergistic activity against drug-resistant fungi in combination with FLC (FICI were both 0.047) and anti-tumor activity (IC50 were 0.025 to 0.15 μmol/L and 0.021 to 0.23 μmol/L respectively), and could down-regulate the expression levels of drug resistance genes and efflux pump genes in fungi, inhibit the formation of fungal biofilms, and arrest the cell cycle of HEL cells at G0/G1 phase. Conclusion The novel Hsp90 inhibitors such as F3 and F5 could both effectively exert the dual activities of synergizing with FLC to combat drug-resistant fungi and fight against tumors, which provided a new idea for the development of new drugs with dual functions of synergizing with FLC to combat drug-resistant fungi and fight against tumors.
10.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.

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