1.Mechanism of Herbal Cake-separated Moxibustion in Improving Neuroimmune Inflammation in Rats with Chronic Fatigue Syndrome by Interfering TLR4/MyD88/NF-κB Pathway
Chuntao ZHAI ; Yawei HOU ; Linjuan SHI ; Yixiao WANG ; Wei LI ; Yuefeng TIAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):140-149
ObjectiveTo explore the mechanism of herbal cake-separated moxibustion using the classical formula Xiaoyaosan in alleviating neuroimmune inflammatory responses in chronic fatigue syndrome (CFS) rats, based on the regulation of the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear transcription factor-κB (NF-κB) signaling pathway. MethodsFifty SPF-grade SD rats aged 6-8 weeks were randomly divided into five groups: Normal group, model group, sham herbal cake moxibustion group, Chinese medicine intragastric administration group, and herbal cake-separated moxibustion group, with 10 rats in each group. Except for the normal group, all other groups underwent a 21-day modeling process, followed by behavioral testing. The herbal cake-separated moxibustion and sham herbal cake moxibustion groups received interventions at the Shenque (CV8), Guanyuan (CV4), Zusanli (ST36), and Qimen (LR14) acupoints. The Chinese medicine intragastric administration group was treated with a Xiaoyaosan suspension via gavage. Behavioral tests were conducted after 10 days of continuous intervention. Serum levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α), as well as hippocampal levels of IL-1β, IL-6, TNF-α, and NF-κB, were detected by enzyme-linked immunosorbent assay (ELISA). Morphological changes in the hippocampus were observed using hematoxylin-eosin (HE) staining. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect mRNA expression levels of TLR4, MyD88, and NF-κB in the hippocampus. Western blot analysis was performed to detect the relative expression levels of TLR4, MyD88, NF-κB, and p65 proteins in the hippocampus. ResultsCompared with the normal group, the model group showed a significant decrease in upright times during the open field test (P<0.01), as well as significant reductions in total movement distance, resting time, and center region duration (P<0.01). In the tail suspension test, immobility time increased (P<0.01), and struggle times decreased (P<0.01). Serum and hippocampal levels of IL-1β, IL-6, and TNF-α, as well as hippocampal NF-κB levels and TLR4, MyD88, and NF-κB mRNA expression, were significantly elevated (P<0.01). After treatment, compared with the model group, the total movement distance and upright times in the open field test were significantly increased in all treatment groups (P<0.01), while resting time and center region duration were notably prolonged (P<0.05, P<0.01). Immobility time in the tail suspension test was significantly shortened (P<0.01), and struggle times significantly increased (P<0.05). Serum and hippocampal levels of IL-1β, IL-6, TNF-α, hippocampal NF-κB levels, and TLR4 and NF-κB mRNA expression were significantly reduced (P<0.05, P<0.01). Compared with the sham herbal cake moxibustion group, the herbal cake-separated moxibustion group showed a significant extension in center region duration during the open field test (P<0.05) and a significant increase in upright times (P<0.01). In the tail suspension test, immobility time was reduced (P<0.01), and struggle times increased (P<0.01). Serum TNF-α levels in the Chinese medicine intragastric administration group were significantly reduced (P<0.01), while serum IL-6 levels, as well as hippocampal levels of IL-1β, TNF-α, NF-κB, and TLR4, MyD88, and NF-κB mRNA expression, were significantly decreased in both the Chinese medicine intragastric administration group and the herbal cake-separated moxibustion group (P<0.05, P<0.01). Compared with the Chinese medicine intragastric administration group, the herbal cake-separated moxibustion group exhibited significantly increased upright times in the open field test (P<0.01). In the tail suspension test, immobility time was reduced (P<0.01), and struggle times increased (P<0.01). Serum IL-1β, hippocampal TNF-α levels, and TLR4, MyD88, and NF-κB mRNA expression were significantly decreased (P<0.05, P<0.01). ConclusionHerbal cake-separated moxibustion effectively improves fatigue and memory function in CFS rats, regulates neuroimmune inflammatory responses, and its mechanism may be related to the modulation of the TLR4/MyD88/NF-κB signaling pathway.
2.Mechanism of immunosuppression in rats by herb-partitioned moxibustion based on transcriptome sequencing technology
Yuefeng TIAN ; Luojie XIONG ; Huifang WANG ; Chuntao ZHAI ; Wei LI
Chinese Journal of Tissue Engineering Research 2025;29(5):978-988
BACKGROUND:Immunosuppression leads to impaired body immune function and aggravates the disease.Herb-partitioned moxibustion can effectively regulate immune function and improve immunity in the body,but its regulatory mechanism has not been elucidated. OBJECTIVE:To sequence immunosuppressed model rats treated with herb-partitioned moxibustion using bioinformatics techniques based on transcriptomics and to explore the mechanisms by which it regulates immunity. METHODS:Twenty-four Sprague-Dawley rats were randomly assigned to three groups:control,model,and herb-partitioned moxibustion groups,with eight rats in each group.The model and herb-partitioned moxibustion groups were subjected to establishment of an immune suppression model by intraperitoneal injection of cyclophosphamide at a dose of 35 mg/kg for 3 consecutive days.No interventions were administered to the control and model groups after modeling.In contrast,the herb-partitioned moxibustion group received moxibustion treatment at Zhongwan,Shenque,Guanyuan,and Zusanli acupoints using a combination of moxa and herbal cakes,once a day,for 10 consecutive days,with samples being collected the day after the end of the intervention.Peripheral blood was collected from all groups of rats to measure their white blood cell count.RNA-seq was performed on the Illumina sequencing platform,and differentially expressed genes were selected for bioinformatics analysis using the GO and KEGG databases. RESULTS AND CONCLUSION:Compared with the control group,the model group exhibited a significant decrease in white blood cell count(P<0.001).RNA-seq analysis identified 3 026 differentially expressed genes between the model and control groups,with 1 565 upregulated and 1 461 downregulated.There were 535 differentially expressed genes identified between the herb-partitioned moxibustion group and the model group,with 280 upregulated and 255 downregulated.The Venn diagram analysis revealed that 159 genes were downregulated in the model group compared with the control group.However,after moxibustion with herbal cakes,these genes were upregulated.Protein-protein interaction network analysis identified 10 core targets,including Oasl,Oas2,Isg15,Herc6,Mx2,Helz2,Mx1,Syk,Hspa1a,and Ret.According to GO and KEGG analyses,moxibustion with herbal cakes regulated the body through pathways related to immune response,viruses,angiogenesis,and the autoimmune system.To conclude,there is a significant association between herbal cake-separated moxibustion intervention and immune suppression targets,including Oasl,Oas2,Isg15,Herc6,Mx2,Helz2,and Mx1.The intervention exhibits regulatory effects in the pathways related to immune responses,viral activities,and angiogenesis.
3.Herbal Cake-separated Moxibustion Improves Cognitive Function in Rat Model of Chronic Fatigue Syndrome via PI3K/Beclin1 Signaling Pathway
Chuntao ZHAI ; Yawei HOU ; Linjuan SHI ; Yixiao WANG ; Yuefeng TIAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):149-158
ObjectiveTo explore the mechanism of moxibustion with the classical prescription Xiaoyaosan as the herbal cake in improving cognitive function in the rat model of chronic fatigue syndrome (CFS) by regulating autophagy via phosphatidylinosiol 3-kinase (PI3K)/autophagy key molecule yeast Atg6 homologue 1 (Beclin1) signaling pathway. MethodsFifty SPF-grade SD rats aged 6-8 weeks were randomly grouped as follows: control, model, sham cake-separated moxibustion, intragastric administration with Chinese herbs, and herbal cake-separated moxibustion, each with 10 rats. The other groups except the control group were subjected to modeling by exhaustive swimming and chronic restraint stress for 21 days, and the behavioral test was performed after modeling. Herbal cake-separated moxibustion and sham cake-separated moxibustion were carried out at Shenque (CV8), Guanyuan (CV4), Zusanli (ST36), and Qimen (LR14). The rats in the intragastric administration with Chinese herbs group were treated with Xiaoyaosan suspension by gavage. After continuous intervention for 10 days, rat behaviors were observed and the levels of interleukin (IL)-4, IL-10, blood urine nitrogen (BUN), and malondiadehyde (MDA) in the serum and hippocampal tissue of rats in each group were determined by enzyme-linked immunosorbent assay. The morphological changes of the hippocampal tissue were observed by hematoxylin-eosin staining. The relative mRNA and protein levels of PI3K and Beclin1 in the hippocampal tissue were determined by Real-time quantitative polymerase chain reaction (Real-time PCR) and Western blot, respectively. ResultsCompared with the normal group, the model group showed reduced crossings, shortened residence time in the target quadrant, and prolonged average escape latency on days 1, 2, 3, and 4 (P<0.01) in the Morris water maze test. In the new object recognition test, the model group showed decreased recognition index of exploration time and recognition index of exploration times (P<0.01), lowered levels of IL-4 and IL-10 and elevated levels of BUN and MDA in the serum and hippocampus (P<0.01), and down-regulated mRNA and protein levels of PI3K and Beclin1 (P<0.01). After treatment, compared with the model group, each treatment group showed increased crossings, prolonged residence time in the target quadrant, and shortened average escape latency on days 1, 2, 3, and 4 (P<0.05, P<0.01). In addition, the treatment elevated the levels of IL-4 and IL-10 and lowered the levels of BUN and MDA in the serum and hippocampus (P<0.05, P<0.01), and up-regulated the mRNA and protein levels of PI3K and Beclin1 (P<0.05, P<0.01). Compared with the sham cake-separated moxibustion group, the herbal cake-separated moxibustion group and the intragastric administration with Chinese herbs group showed increased crossings, prolonged residence time in the target quadrant (P<0.05), elevated level of IL-4, lowered level of MDA, and up-regulated relative mRNA and protein levels of PI3K and Beclin1 in the hippocampus (P<0.05, P<0.01). The serum levels of MDA and BUN in the intragastric administration with Chinese herbs group were significantly decreased. The average escape latency of the herbal cake-separated moxibustion group was significantly shortened on days 2 and 3 (P<0.05, P<0.01). In addition, this group showed elevated serum level of IL-4, lowered serum level of MDA, and declined BUN level in the hippocampus (P<0.05, P<0.01). Compared with the intragastric administration with Chinese herbs group, the herbal cake-separated moxibustion group presented risen serum level of IL-4 and up-regulated mRNA level of Beclin1 (P<0.05) and relative protein levels of PI3K and Beclin1 (P<0.05, P<0.01). ConclusionHerbal cake-separated moxibustion can effectively alleviate fatigue and improve the memory, reduce inflammatory response and oxidative stress, and decrease autophagy of hippocampal neurons in CFS rats by regulating the PI3K/Beclin1 signaling pathway.
4.Herbal Cake-separated Moxibustion Improves Cognitive Function in Rat Model of Chronic Fatigue Syndrome via PI3K/Beclin1 Signaling Pathway
Chuntao ZHAI ; Yawei HOU ; Linjuan SHI ; Yixiao WANG ; Yuefeng TIAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):149-158
ObjectiveTo explore the mechanism of moxibustion with the classical prescription Xiaoyaosan as the herbal cake in improving cognitive function in the rat model of chronic fatigue syndrome (CFS) by regulating autophagy via phosphatidylinosiol 3-kinase (PI3K)/autophagy key molecule yeast Atg6 homologue 1 (Beclin1) signaling pathway. MethodsFifty SPF-grade SD rats aged 6-8 weeks were randomly grouped as follows: control, model, sham cake-separated moxibustion, intragastric administration with Chinese herbs, and herbal cake-separated moxibustion, each with 10 rats. The other groups except the control group were subjected to modeling by exhaustive swimming and chronic restraint stress for 21 days, and the behavioral test was performed after modeling. Herbal cake-separated moxibustion and sham cake-separated moxibustion were carried out at Shenque (CV8), Guanyuan (CV4), Zusanli (ST36), and Qimen (LR14). The rats in the intragastric administration with Chinese herbs group were treated with Xiaoyaosan suspension by gavage. After continuous intervention for 10 days, rat behaviors were observed and the levels of interleukin (IL)-4, IL-10, blood urine nitrogen (BUN), and malondiadehyde (MDA) in the serum and hippocampal tissue of rats in each group were determined by enzyme-linked immunosorbent assay. The morphological changes of the hippocampal tissue were observed by hematoxylin-eosin staining. The relative mRNA and protein levels of PI3K and Beclin1 in the hippocampal tissue were determined by Real-time quantitative polymerase chain reaction (Real-time PCR) and Western blot, respectively. ResultsCompared with the normal group, the model group showed reduced crossings, shortened residence time in the target quadrant, and prolonged average escape latency on days 1, 2, 3, and 4 (P<0.01) in the Morris water maze test. In the new object recognition test, the model group showed decreased recognition index of exploration time and recognition index of exploration times (P<0.01), lowered levels of IL-4 and IL-10 and elevated levels of BUN and MDA in the serum and hippocampus (P<0.01), and down-regulated mRNA and protein levels of PI3K and Beclin1 (P<0.01). After treatment, compared with the model group, each treatment group showed increased crossings, prolonged residence time in the target quadrant, and shortened average escape latency on days 1, 2, 3, and 4 (P<0.05, P<0.01). In addition, the treatment elevated the levels of IL-4 and IL-10 and lowered the levels of BUN and MDA in the serum and hippocampus (P<0.05, P<0.01), and up-regulated the mRNA and protein levels of PI3K and Beclin1 (P<0.05, P<0.01). Compared with the sham cake-separated moxibustion group, the herbal cake-separated moxibustion group and the intragastric administration with Chinese herbs group showed increased crossings, prolonged residence time in the target quadrant (P<0.05), elevated level of IL-4, lowered level of MDA, and up-regulated relative mRNA and protein levels of PI3K and Beclin1 in the hippocampus (P<0.05, P<0.01). The serum levels of MDA and BUN in the intragastric administration with Chinese herbs group were significantly decreased. The average escape latency of the herbal cake-separated moxibustion group was significantly shortened on days 2 and 3 (P<0.05, P<0.01). In addition, this group showed elevated serum level of IL-4, lowered serum level of MDA, and declined BUN level in the hippocampus (P<0.05, P<0.01). Compared with the intragastric administration with Chinese herbs group, the herbal cake-separated moxibustion group presented risen serum level of IL-4 and up-regulated mRNA level of Beclin1 (P<0.05) and relative protein levels of PI3K and Beclin1 (P<0.05, P<0.01). ConclusionHerbal cake-separated moxibustion can effectively alleviate fatigue and improve the memory, reduce inflammatory response and oxidative stress, and decrease autophagy of hippocampal neurons in CFS rats by regulating the PI3K/Beclin1 signaling pathway.
5.Active surveillance of drug safety and influential factors in pediatric patients with Mycoplasma pneumoniae pneumonia
Yuefeng WANG ; Qiang GAO ; Ke QIN
China Pharmacy 2025;36(22):2838-2844
OBJECTIVE To analyze adverse drug reactions (ADRs) in pediatric patients with Mycoplasma pneumoniae pneumonia (MPP), and investigate the influential factors associated with the occurrence of ADRs. METHODS Clinical records of pediatric patients with MPP in Xinxiang Central Hospital (hereinafter referred to as “our hospital”) from Oct. 1st, 2023 to Sept. 30th, 2024 collected from the Hospital Information System were retrospectively reviewed using the global trigger tool (GTT). The positive triggers were further reviewed to confirm the occurrence of ADRs, and the characteristics of those ADRs were analyzed. The children were divided into the ADR group and the non-ADR group. Univariate analysis and multivariate Logistic regression analysis were performed to investigate the potential influential factors for ADRs in MPP children. RESULTS A total of 1 325 MPP children were included. Out of 24 designed triggers, 14 were positive, with a positive trigger rate of 58.3%. There were 1 301 positive trigger cases, involving 846 pediatric patients. After assessment, 399 cases of ADRs were identified in 372 pediatric patients, yielding a positive predictive value of triggers at 30.7%. The main types of ADRs were abnormal blood cells (230 cases, 57.6%), skin and its appendages damage (78 cases, 19.5%), and gastrointestinal system damage (42 cases, 10.5%), which predominantly occurred 4 days or more, within 2-3 days and within 2-3 days after medication, respectively. They were more prevalent in pediatric patients aged>3-10 years (295 cases, 79.3%). The major categories of drugs associated with ADRs included intravenous corticosteroids (209 cases), cephalosporins (180 cases), macrolides (38 cases), tetracyclines (28 cases) and traditional Chinese medicine (TCM) injections (28 cases). These ADR reports were classified into 3 types: 1 serious case, 394 general cases and 4 new cases. In terms of causality assessment, 1 case was assessed as certain, 19 cases as probable, and 379 cases as possible. In terms of ADR outcomes, 151 cases fully recovered, while the outcomes for 248 cases remained unknown. Univariate analysis and multivariate Logistic regression analysis revealed that a history of allergies [OR=5.231, 95%CI (2.004, 13.656), P<0.05], the number of medications used [OR=1.064, 95%CI (1.027, 1.103), P<0.05], and intravenous corticosteroid administration [OR=3.223, 95%CI (2.341, 4.437), P<0.05] were independent risk factors of ADRs in pediatric patients with MPP. The use of azithromycin [OR=0.544, 95%CI (0.376, 0.786), P<0.05] was identified as an independent protective factor against the occurrence of ADRs in pediatric patients with MPP. CONCLUSIONS Children with MPP in our hospital exhibit a higher incidence of ADRs, primarily involving abnormal blood cells, skin and its appendages damage, and gastrointestinal system damage. A history of allergies, the number of medications used, intravenous corticosteroid administration, and the use of azithromycin are associated with the occurrence of ADR in MPP pediatric patients.
6.Biocontrol Effect and Culture Condition Optimization of Trichoderma citrinoviride Strain Isolated from Rhizosphere of Atractylodes lancea
Kuo LI ; Sheng WANG ; Hongyang WANG ; Zheng PENG ; Xiuzhi GUO ; Tielin WANG ; Yuefeng WANG ; Lanping GUO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(15):192-199
ObjectiveRoot rot is one of the most serious diseases in the cultivation and production of Atractylodes lancea. Trichoderma spp. are effective in the biocontrol of root rot without causing environmental pollution. This study aims to isolate and study a Trichoderma strain capable preventing and controlling root rot from the rhizosphere of A. lancea and to solve the problem of disease prevention and control in the planting and production of A. lancea. MethodTrichoderma T2204 was isolated by the dilution-coating method and identified by ITS sequencing. The inhibitory activities of T2204 and its volatiles against two pathogenic fungal strains were examined by dual-culture and co-culture experiments. The biocontrol potential of T2204 on root rot of A. lancea and the effect of T2204 on the accumulation of medicinal compounds in the rhizosphere of A. lancea were investigated by pot experiments and GC-MS, respectively. In addition, the optimal medium, photoperiod, temperature, pH, and carbon and nitrogen sources for the culture of T2204 were explored. ResultThe Trichoderma isolate T2204 was identified as T. citrinoviride and had direct inhibitory effects on two highly pathogenic strains causing root rot. In the dual-culture experiments with the two pathogenic strains, T2204 showcased the inhibition rates of 77.90% and 76.80%, respectively. In the co-culture experiments with the two pathogenic strains, the volatile organic compounds produced by T2204 showed the inhibition rates of 57.11% and 81.11%, respectively. The pot experiments showed that the survival rate of A. lancea seedlings infected by root rot reached 100% after inoculation with T2204 and was only 50% in the case without inoculation of T2204. After 150 days of cultivation, the dry weight and atractylodin content of the rhizome of A. lancea plants treated with T2204 increased by 32% (P<0.05) and 11%, respectively, compared with the untreated group. The optimal conditions for the growth of T2204 were PDA or PSA medium, photoperiod of 12 h dark/12 h light, 25-30 °C, pH 5-6, carbon sources of glucose, D-fructose, soluble starch, and maltose, and the nitrogen sources of ammonium sulfate and ammonium dihydrogen phosphate. The optimal conditions for the sporulation of T2204 were PSA or CMA medium, photoperiod of 12 h dark/12 h light, 20-30 °C, pH 8, carbon source of sucrose, and nitrogen source of sodium nitrate. ConclusionT2204 could improve the growth and root rot resistance of A. lancea and promote the accumulation of medicinal compounds. The findings laid a foundation for the industrialized production and application of T2204 in the production of A. lancea in the future.
7.Diversity of the T Cell Receptor β Chain Complementarity-Determining Region 3 in Peripheral Blood of Typical Syndromes Cirrhosis of the Liver:An Analysis Based on Immune Repertoire Sequencing
Jia WANG ; Yuting HU ; Yuefeng GONG ; Jian ZHU ; Shibing SU ; Yiyu LU
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(7):1916-1924
Objective In this study,the diversity of the TCR β chain CDR3 in peripheral blood of patients with different typical Traditional Chinese Medicine(TCM)syndromes of liver cirrhosis was analyzed by immune repertoire sequencing,the material basis and regularity of the syndromes of liver cirrhosis was discussed.Methods 20 patients with cirrhosis,including liver and gallbladder damp heat(LGHD),liver depression and spleen deficiency(LDSD),and liver and kidney yin deficiency(LKYD)were enrolled into case group,and 10 healthy patients were used as the healthy control group.DNA was extracted from peripheral blood samples,and multiplex PCR amplification of TCR β chain CDR3 was performed,followed by high-throughput sequencing of the products to analyze the diversity of the TCR β chain CDR3.Results The nt sequence numbers unique to CDR3 and aa sequence numbers unique to CDR3 of LDSD between liver cirrhosis syndromes were less than LKYD(P<0.05).Clonality,Pielous,Shannon.Index and DE50 of LGHD and LKYD had significant differences(P<0.05)between two groups,as well as the frequency of multiple fragments in V and J regions and V-J gene recombination of LGHD vs.LDSD,LGHD vs.LKYD,and LKYD vs.LDSD,respectively(P<0.05).LGHD vs.LDSD,TRBV21-1,TRBV12-4,TRBV11-1 subtype and 7 pairs of V-J recombination have statistical differences(P<0.05).LGHD vs.LKYD,TRBV10-2,TRBV7-6,TRBV5-8 subtypes and 30 pairs of V-J recombination were statistically different(P<0.05).LDSD vs.LKYD,there were statistical differences between TRBJ1-5 subtype and 18 pairs of V-J recombination(P<0.05).Conclusions The present study was conducted to find that the diversity of TCR CDR3 in liver cirrhosis syndrome is significantly different and conforms to the regularity of syndrome from excess to deficiency by explore the immunological characteristics of different TCM syndromes of liver cirrhosis,and to provide new support for the objective basis of"combination of disease and TCM syndrome"and"diagnosis and treatment".We explored the different expression patterns and specificity of adaptive immune gene rearrangement in patients with different TCM syndromes to identify different expression patterns and specific markers of adaptive immune gene rearrangements of typical TCM syndromes in liver cirrhosis.
8.The Chinese guideline for management of snakebites
Lai RONGDE ; Yan SHIJIAO ; Wang SHIJUN ; Yang SHUQING ; Yan ZHANGREN ; Lan PIN ; Wang YONGGAO ; Li QI ; Wang JINLONG ; Wang WEI ; Ma YUEFENG ; Liang ZIJING ; Zhang JIANFENG ; Zhou NING ; Han XIAOTONG ; Zhang XINCHAO ; Zhang MAO ; Zhao XIAODONG ; Zhang GUOQIANG ; Zhu HUADONG ; Yu XUEZHONG ; Lyu CHUANZHU
World Journal of Emergency Medicine 2024;15(5):333-355
In 2009,the World Health Organization included snakebite on the list of neglected tropical diseases,acknowledging it as a common occupational hazard for farmers,plantation workers,and others,causing tens of thousands of deaths and chronic physical disabilities every year.This guideline aims to provide practical information to help clinical professionals evaluate and treat snakebite victims.These recommendations are based on clinical experience and clinical research evidence.This guideline focuses on the following topics:snake venom,clinical manifestations,auxiliary examination,diagnosis,treatments,and prevention.
9.Safety and efficacy of neoadjuvant chemotherapy combined with immunotherapy in 101 patients with muscle-invasive bladder cancer
Chaosheng GAN ; Tao LI ; Junjie FAN ; Zhangdong JIANG ; Guojing WANG ; Ke XU ; Qiyuan KANG ; Yangqingqing ZHOU ; Yuefeng DU ; Jinhai FAN ; Lei LI ; Dalin HE ; Kaijie WU
Journal of Modern Urology 2024;29(9):790-796
Objective To explore the safety and efficacy of neoadjuvant chemotherapy(NAC)combined with immunotherapy before radical cystectomy plus pelvic lymph nodes dissection(RC-PLND)for muscle-invasive bladder cancer(MIBC).Methods The clinical data of 101 patients with MIBC who underwent neoadjuvant therapy followed by RC-PLND in the Department of Urology,the First Affiliated Hospital of Xi'an Jiaotong University during Jan.2019 and Dec.2023 were retrospectively analyzed,including 71 patients(70.3%)who received NAC(NAC group)and 30(29.7%)who received NAC combined with immunotherapy(NAC combine immunotherapy group).The clinical and pathological data and adverse events during neoadjuvant therapy were compared.Logistic regression analysis was used to explore the independent predictors of pathological complete response(pCR)and pathological partial response(pPR).Results There were no significant differences in the baseline data between the two groups(P>0.05).However,the proportion of multiple tumors in patients receiving NAC before surgery was significantly higher than that in the NAC combined immunotherapy group(69.0%vs.46.7%,P=0.034).Compared with NAC group,NAC combined with immunotherapy group had significantly improved rate of pathological downstaging and pPR(60.6%vs.83.3%,P=0.026;45.1%vs.70.0%,P=0.022).Furthermore,the rate of pCR in patients undergoing NAC combined immunotherapy was higher than those undergoing NAC,but the difference was not significant(53.3%vs.33.8%,P=0.067).Logistic regression analysis revealed that clinical T-stage and tumor diameter were independent predictors of pCR and pPR(P<0.05).In addition,the most common adverse events during neoadjuvant therapy were anemia,decreased white blood cells,nausea,and vomiting,but most of them were grade 1-2 and could be relieved through symptomatic treatment.Conclusion NAC combined with immunotherapy is safe and effective,which can improve the rate of pathological downstaging,pPR and pCR,without increasing the incidence of adverse reactions.
10.Integrating proteomics and targeted metabolomics to reveal the material basis of liver-gallbladder damp-heat syndrome in chronic hepatitis B
LI Ni&rsquo ; ao ; GONG Yuefeng ; WANG Jia ; CHEN Qingqing ; SU Shibing ; ZHANG Hua ; LU Yiyu
Digital Chinese Medicine 2024;7(4):320-331
Methods:
CHB patients and healthy volunteers were enrolled from Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine between August 21, 2018 and December 31, 2020. They were divided into three groups: healthy group, LGDHS group, and latent syndrome (LP) group. Proteomic analysis using isobaric tags for relative and absolute quantitation (iTRAQ) was performed to identify differentially expressed proteins (DEPs). Metabolomic profiling via ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was applied to serum samples to detect differentially regulated metabolites (DMs). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment were employed to explore dysregulated pathways. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were utilized to visualize group separation and identify key metabolites and proteins contributing to LGDHS differentiation. Receiver operating characteristic (ROC) curve analysis evaluated the diagnostic performance of key biomarkers, while logistic regression models assessed their predictive accuracy. P values were corrected for multiple tests using the Benjamini-Hochberg method to control the false discovery rate (FDR). Validation of potential biomarkers was conducted using independent microarray data and real-time quantitative polymerase chain reaction (RT-qPCR).
Results:
A total of 150 participants were enrolled, including healthy group (n = 45), LGDHS group (n = 60), and LP group (n = 45). 254 DEPs from proteomics data and 72 DMs from metabolomic profiling were identified by PCA and OPLS-DA. DEPs were mainly enriched in immune and complement pathways, while DMs involved in amino acid and energy metabolism. The integrated analysis identified seven key biomarkers: α1-acid glycoprotein (ORM1), asparagine synthetase (ASNS), solute carrier family 27 member 5 (SLC27A5), glucosidase II alpha subunit (GANAB), hexokinase 2 (HK2), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), and maltase-glucoamylase (MGAM). Microarray validation confirmed the diagnostic potential of these genes, with area under the curve (AUC) values for ROC analysis ranging from 0.536 to 0.759. Among these, ORM1, ASNS, and SLC27A5 showed significant differential ability in differentiating LGDHS patients (P = 0.016, P = 0.035, and P < 0.001, respectively), with corresponding AUC of 0.749, 0.743, and 0.759, respectively. A logistic regression model incorporating these three genes demonstrated an AUC of 0.939, indicating a high discriminatory power for LGDHS. RT-qPCR further validated the differential expression of ORM1 and SLC27A5 between LGDHS and LP groups (P = 0.011 and P = 0.034, respectively), with ASNS showing a consistent trend in expression (P = 0.928).
Conclusion
This study integrates multi-omics approaches to uncover the molecular mechanisms underlying LGDHS in CHB. The identification of biomarkers ORM1, ASNS, and SLC27A5 offers a solid basis for the objective diagnosis of LGDHS, contributing to the standardization and modernization of TCM diagnostic practices.

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