1.Characteristic volatile organic compounds in exhaled breath of coal workers' pneumoconiosis patients by thermal desorption gas chromatography-mass spectrometry
Yazhen HE ; Chunguang DING ; Junyun WANG ; Yuzhen FENG ; Fangda PENG ; Gaisheng LIU ; Fan YANG ; Chunmin ZHANG ; Rui GAO ; Qingyu MENG ; Zhijun WU ; Jingguang FAN
Journal of Environmental and Occupational Medicine 2025;42(5):571-577
Background Coal workers' pneumoconiosis is a serious occupational disease in China. Exhaled volatile organic compounds (VOCs) can serve as the "breath fingerprint" of internal pathological processes, which provides a theoretical basis for exhaled VOCs to be used as potential non-invasive biomarkers for early diagnosis of coal workers' pneumoconiosis. Objective To screen out the characteristic VOCs and important characteristic VOCs of exhaled air in patients with coal workers' pneumoconiosis, and to explore the potential of these VOCs as biomarkers for early non-invasive diagnosis of the disease. Methods In this study, 27 VOCs in the exhaled breath of 22 patients with stage I coal workers' pneumoconiosis, 77 workers exposed to dust, and 92 healthy controls were quantitatively detected by thermal desorption gas chromatography-mass spectrometry (TD-GC-MS). Substances with P<0.05 in univariate analysis and variable importance projection (VIP) >1 in supervised orthogonal partial least squares discriminant analysis (OPLS-DA) model were selected as the characteristic VOCs for early diagnosis of coal workers' pneumoconiosis. Age was included in the LASSO regression model as a covariate to screen out important characteristic VOCs, and the diagnostic performance was evaluated by receiver operating characteristic (ROC) curve. Spearman correlation was further used to explore the correlation between important characteristic VOCs and clinical lung function indicators. Results Through univariate analysis and OPLS-DA modeling, 8 VOCs were selected, including 2-methylpentane, 3-methylpentane, n-hexane, methylcyclopentane, n-heptane, methylcyclohexane, 4-methyl-2-pentanone, and 2-hexanone, in exhaled breath of patients with coal workers' pneumoconiosis. The concentrations of 4 VOCs, including 3-methylpentane, n-hexane, 4-methyl-2-pentanone, and 2-hexanone, showed a decreasing trend with the increase of dust exposure years. By LASSO regression, the important characteristic VOCs of the coal workers' pneumoconiosis group and the dust exposure group were n-hexane, methylcyclohexane and 4-methyl-2-pentanone, and the important characteristic VOCs of the coal workers' pneumoconiosis group and the healthy group were 2-methyl-pentane and 4-methyl-2-pentanone. The ROC analysis showed that the area under the curve (AUC) of n-hexane, methylcyclohexane, and 4-methyl-2-pentanone were 0.969, 0.909, and 0.956, respectively, and the AUC of combined diagnosis was 0.988 and its Youden index was 0.961, suggesting that these results can serve as a valuable reference for further research on early diagnosis. The Correlation analysis found that there was a positive correlation between n-hexane and lung function indicators in the important characteristic VOCs, indicating that it could indirectly reflect the obstruction of lung function ventilation, further proving that important characteristic VOCs have the potential to monitor lung function decline. Conclusion Three important characteristic VOCs selected in this study have the potential to be used as non-invasive biomarkers for early diagnosis and disease monitoring of coal workers' pneumoconiosis, and are worthy of further study and verification.
2.Randomized Double-blind Placebo-controlled Trial of Modified Zuojinwan Granules in Treating Reflux Esophagitis and Functional Dyspepsia with Same Syndrome with Disharmony Between Liver and Stomach
Guangming WANG ; Wanli LIU ; Lu YANG ; Hao WU ; Yuzhen HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(12):112-120
ObjectiveTo observe the clinical efficacy of modified Zuojinwan granules in treating reflux esophagitis (RE) and functional dyspepsia (FD) with the same syndrome with disharmony between liver and stomach). MethodA randomized double-blind placebo-controlled clinical trial was conducted to enroll 144 patients with disharmony between liver and stomach, including 72 patients with RE and 72 patients with FD. These patients were then randomly divided into observation and control groups, with 36 patients in each group. The observation group was given modified Zuojinwan granules orally, and the control group was given placebo granules orally. They both were treated with two packs each time, twice a day, for four weeks. The traditional Chinese medicine (TCM) syndrome scores, cerebrointestinal peptides [calcitonin gene-associated titanium (CGRP), vasoactive intestinal peptide (VIP), 5-hydroxytryptamine (5-HT), and substance P (SP)], inflammatory factors [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)], common gastrointestinal related hormones [gastrin (GAS) and motilin (MTL)], and other indicators in the two groups were compared before and after treatment, and the curative effect of TCM syndromes and the occurrence of adverse reactions were determined. At the same time, the changes in the above indicators and the curative effect of TCM syndromes in the two groups of patients with the same disease were analyzed. ResultAfter treatment, CGRP, VIP, 5-HT, SP, TNF-α, IL-6, GAS, MTL, and TCM syndrome scores in the observation group and control group were significantly improved (P<0.05). After treatment, the improvement of CGRP, VIP, 5-HT, SP, TNF-α, IL-6, GAS, MTL, and TCM syndrome scores in the observation group was better than that in the control group (P<0.05). After treatment, CGRP, VIP, 5-HT, SP, TNF-α, IL-6, GAS, MTL, and TCM syndrome scores in both groups of RE patients and FD patients were significantly improved (P<0.05). After treatment, the improvement of CGRP, VIP, 5-HT, SP, TNF-α, IL-6, GAS, MTL, and TCM syndrome scores in RE patients and FD patients in the observation group were better than that in the control group (P<0.05). In the observation group and the control group, the incidence of nausea, vomiting, fatigue, dry mouth, and other adverse reactions was lower, and there was no statistical significance. ConclusionModified Zuojinwan granules can effectively improve the TCM syndromes of disharmony between liver and stomach of RE and FD, brain and intestinal peptide, gastrointestinal hormone, and inflammatory factors and provide evidence for the clinical application of TCM theory of "treating different diseases with the same method".
3.Variation in renal function of type 2 diabetic rats undergoing aerobic exercise
Yuzhen WU ; Qing SUN ; Xia LIU ; Yu ZHOU ; Qiguan JIN
Chinese Journal of Tissue Engineering Research 2024;28(14):2145-2151
BACKGROUND:Type 2 diabetes is often accompanied by renal dysfunction.Increasing studies have shown that exercise can alleviate metabolic disorders and renal dysfunction in diabetic patients.However,the specific mechanism underlying the renal protective effect of exercise in patients with type 2 diabetes is rarely reported. OBJECTIVE:To investigate whether aerobic exercise can improve renal function in type 2 diabetic rats by inhibiting transforming growth factor β1/Notch1 pathway. METHODS:Male Sprague-Dawley rats were randomly divided into normal control group and diabetes model group.After successful modeling,they were randomly divided into diabetes control group and diabetes exercise group.Rats in the diabetes exercise group were subjected to an 8-week aerobic exercise.Samples were collected after exercise,and the relevant indexes of glucose and lipid metabolism and renal function were detected by automatic biochemical analyzer and ELISA.The microscopic structure of renal cortex was observed by electron microscope.ELISA and RT-PCR were used to detect the expression of related proteins and genes in rat kidney tissue. RESULTS AND CONCLUSION:Compared with the normal control group,fasting blood glucose,total cholesterol,and triglyceride levels and insulin resistance index were significantly increased in the diabetic control group(P<0.05).Aerobic exercise could significantly reduce fasting blood glucose and triglyceride levels(P<0.05).Compared with the normal control group,the diabetic control group had significantly increased contents of urinary microalbumin,serum urea nitrogen and serum creatinine(P<0.01),thickened renal basement membrane,mesangial matrix hyperplasia,accompanied by a certain degree of foot process fusion,and obvious lesion of the kidney.Aerobic exercise could significantly down-regulate the overexpressions of urinary microalbumin,serum urea nitrogen and serum creatinine in type 2 diabetic rats(P<0.01),and significantly improve the pathological changes of the kidney in diabetic rats.Compared with the normal control group,the protein and gene expression levels of transforming growth factor β1,Notch1,Jagged1 and Hes1 in rat kidney tissue were significantly increased in the diabetic control group(P<0.01).Aerobic exercise had a highly significant inhibitory effect on the overexpression of transforming growth factor β1,Notch1 and Jagged1 proteins and genes(P<0.01)and also significantly inhibited the overexpression of Hes1 protein(P<0.05).In conclusion,aerobic exercise can protect renal function and delay the pathological progression of the kidney in diabetic rats,which may be achieved by inhibiting the overexpression of transforming growth factor β1/Notch1 signaling pathway.
4.Exploration of the pathogenesis and treatment of Cronkhite-Canada syndrome from the perspective of " endogenous toxins cause the disease"
Kunhan SU ; Yuzhen HUANG ; Wanli LIU
Journal of Beijing University of Traditional Chinese Medicine 2024;47(3):407-411
Cronkhite-Canada syndrome is a disease characterized by multiple polyps and changes in the ectoderm of the digestive tract, but its etiology and pathogenesis have not been completely elucidated. Endogenous toxins are a special class of intrinsic pathogenic factors, which are released upon visceral dysfunction and abnormal movement of qi and blood. Endogenous toxins can hide deeply in the body, they can enter the meridians and collaterals, and they can be mixed with phlegm and blood stasis. Endogenous toxins can damage the skin externally, corrode the internal organs, attack hands and feet, and damage the vital qi. The pathogenesis of Cronkhite-Canada syndrome can be understood from the perspective of " endogenous toxins cause the disease". Dampness-heat due to spleen deficiency and dampness toxin accumulation are the fundamental causes of Cronkhite-Canada syndrome. The mutual fusion of phlegm toxin and blood stasis toxin is the pathological essence of the diffuse growth of gastrointestinal polyps in Cronkhite-Canada syndrome. The internal toxin transformation process of "dampness toxin-phlegm stasis toxin-cancer toxin" may be a potential mechanism for the occurrence of cancer. The treatment of Cronkhite-Canada syndrome should be based on the principle of strengthening the spleen, removing dampness, and detoxification. Among them, strengthening the spleen is the foundation, removing dampness is the key, and detoxification is the core. The treatment of Cronkhite-Canada syndrome can be achieved through methods such as strengthening the spleen and infiltrating dampness, promoting diuresis and detoxification, resolving phlegm, and removing blood stasis. At the same time, correcting the patient's biased constitution should be used as an auxiliary treatment method, and treatment based on a combination of traditional Chinese and western medicine should be emphasized.
5.Effect of storage temperature and time on coagulation factor after cryoprecipitated antihemophilic factor melting
Yuan WANG ; Guoying LIU ; Dawei KONG ; Jianbin LI ; Xinli JIN ; Yuhong ZHANG ; Wenchao GE ; Lin CHENG ; Jiaxuan LIU ; Yuzhen LIU
Chinese Journal of Blood Transfusion 2024;37(4):425-430
【Objective】 To study and compare the effects of different storage temperature and time on coagulation factor after cryoprecipitated antihemophilic factor(CAF) melting, and to provide reference for the establishment of industry standards. 【Methods】 From June 2021 to May 2023, a total of 96 bags of CAF were sampled in 4 bags per month, and timely detected in the same month. After the CAF was melted in a 37℃ water bath, the mild to moderate lipemic blood was labeled. Each bag of CAF and two 50 mL transfer bags were divided into two bags and two groups of 20 mL each using a sterile adapter. One group was placed in a 4℃ refrigerator and the other in a 22℃ water bath for 0 h, 4 h, 8 h, 12 h, 24 h and 48 h. Then 2 mL of aseptic sample was taken separately and put into the test tube, and 1mL of sample and 3 mL of buffer were added into the other test tube with the sampling gun and mixed on the machine for testing. The experimental data of 60 bags without mild to moderate lipemic blood cryoprecipitation and coagulation factor were randomly selected and statistically analyzed by SPSS21.0. 【Results】 After melting, CAF was stored for 0 h, 4 h, 8 h, 12 h, 24 h and 48 h to detect the average content and growth rate of coagulation factor in the two groups: 1) Storage at 4℃, factor Ⅷ content was 118.62, 111.57(-5.95%), 105.51(-11.05%), 103.30(-12.92%), 94.35(-20.46%) and 83.25(-29.82%) IU/ bag, respectively; Storage at 22℃, the factor Ⅷ content was 118.62, 112.69(-5.00%), 111.41(-6.08%), 109.01(-8.10%), 101.55(-14.39%) and 92.75(-21.81%) IU/ bag, and the storage results of the two groups were compared. At 24 h at 4℃ and 48 h at 22℃, the content of factor Ⅷ had significant statistical significance(P<0.01), and when stored at 22℃, the decay rate of factor Ⅷ was slower; 2) When stored at 4℃, the content of factor V was 41.19, 41.31(0.29%), 40.52(-1.64%), 40.27(-2.23%), 39.05(-5.19%) and 36.99(-10.21%) IU/ bag, respectively; Stored at 22℃, the factor V content was 41.19, 41.71(1.25%), 42.54(3.28%), 41.94(1.80%), 39.21(-4.80%) and 35.64(-13.48%) IU/ bag, respectively. Comparison of storage results between the two groups showed that the content of factor V was statistically significant(P<0.05) and significantly significant(P<0.01) at 4℃48 h and 22℃48 h, respectively, and the decay rate of factor V was faster when stored at 22℃; 3) When stored at 4℃, the Fbg content was 268.86, 268.17(-0.26%), 262.46(-2.38%), 270.50(0.61%), 267.52(-0.50%) and 261.92(-2.58%) mg/ bag, respectively; Stored at 22℃, the Fbg content was 268.86, 265.86(-1.12%), 264.12(-1.77%), 265.89(-1.11%), 266.04(-1.05%) and 261.04(-2.91%) mg/ bag, respectively. There was no statistical significance between the 2 groups and the original 0 h content in each time period(P>0.05). 【Conclusion】 After CAF melting, coagulation factor decreased with the extension of storage time, especially the decrease of factor Ⅷ, followed by factor V, while Fbg basically unchanged. Comparison between the two groups showed that, factor Ⅷ decay rate is slower, factor V decay rate is faster of storage at 22℃. CAF should be transfused as soon as possible after melting. If the delay is unavoidable, for the delay time less than 12 h, storage at 4℃ is recommended, fot the delay time more than 12 h and less than 24 h, storage at 22℃ is recommended.
6.Effect of oxaliplatin on the activation of hepatic stellate cells and its mechanism
Cunkai WANG ; Yijun WANG ; Dandan WANG ; Xiaoli XIE ; Hongyu LIU ; Yun BAI ; Huiqing JIANG ; Yuzhen WANG
Journal of Clinical Hepatology 2024;40(6):1142-1148
Objective To investigate the effect of oxaliplatin on the activation of hepatic stellate cells(HSCs),as well as the association of oxaliplatin with microRNA-30a-5p and autophagy.Methods HSC-LX2 cells were cultured and divided into groups according to the following three protocols:control group,PDGF treatment group,oxaliplatin treatment group,oxaliplatin+PDGF treatment group;control group,microRNA-30a-5p transfection group,PDGF treatment group,microRNA-30a-5p transfection+PDGF treatment group;control group,3-MA group,microRNA-30a-5p inhibitor group,microRNA-30a-5p inhibitor+3-MA group.Western Blot was used to measure the expression of HSC activation-related proteins(Collagen-I and alpha-smooth muscle actin[α-SMA])and HSC autophagy-related proteins(Beclin-1,P62,and LC3B);LysoTracker staining and immunofluorescence assay were used to measure the expression of LC3B autophagosomes;RT-PCR was used to measure the expression level of microRNA-30a-5p;bioinformatics techniques were used to predict the potential targets of microRNA-30a-5p in HSCs.The independent-samples t test was used for comparison of normally distributed continuous data between two groups;a one-way analysis of variance was used for comparison between multiple groups,and the least significant difference t-test was used for further comparison between two groups.Results After the cells were treated with oxaliplatin,RT-PCR results showed that the oxaliplatin treatment group had a significantly higher expression level of microRNA-30a-5p than the control group(P<0.01);Western Blot showed that the oxaliplatin treatment group had significant reductions in the expression levels of the HSC activation-related proteins α-SMA and Collagen-Ⅰ and the autophagy-related proteins Beclin 1 and LC3BⅡ/Ⅰ(all P<0.001);immunofluorescence assay showed that the oxaliplatin treatment group had a significantly lower number of autophagosomes than the control group(P<0.05).After HSC-LX2 cells were transfected with microRNA-30a-5p mimic,compared with the control group,the microRNA-30a-5p mimic group had significant reductions in the expression levels of the autophagy-related proteins Beclin 1 and LC3BⅡ/Ⅰ(P<0.05)and the HSC activation-related protein Collagen-Ⅰ(P<0.001);after HSC-LX2 cells were transfected with microRNA-30a-5p inhibitor,Western Blot showed that compared with the control group,the microRNA-30a-5p inhibitor group had significant increases in the expression levels of the HSC activation-related proteins Collagen-Ⅰ and α-SMA and the autophagy-related protein Beclin 1(t=2.41,2.32,and 4.57,all P<0.05).Western Blot showed that compared with the control group,the microRNA-30a-5p inhibitor group had significant increases in the expression levels of the HSC autophagy-related protein Beclin 1 and the HSC activation-related protein α-SMA(both P<0.05),and after the treatment with the autophagy inhibitor 3-MA,there were no significant differences in the expression of these proteins between the two groups(P>0.05).The bioinformatics analysis using TargetScan,PicTar,and miRanda databases showed that the autophagy-related protein Beclin-1 might be a potential target of miRNA-30a-5p.Conclusion Oxaliplatin can inhibit the activation of HSCs by upregulating the expression of microRNA-30a-5p,which provides new ideas and a new target for the treatment of liver fibrosis.
7.Analysis of gene characteristics and core genome characteristics of carbapenem-resistant Enterobacter cloacae in rural residents of Weifang City, Shandong Province
Ange WANG ; Shuang WANG ; Lu LIU ; Gaoxiang SUN ; Yuzhen CHEN ; Jiaxin QI ; Zengqiang KOU ; Zhenwang BI
Chinese Journal of Preventive Medicine 2024;58(1):48-55
Objective:To investigate the drug-resistant gene characteristics and core genome characteristics of carbapenem-resistant Enterobacter cloacae (CR-ECL) in rural residents of Weifang City, Shandong Province. Methods:Fecal samples were collected from rural community residents in Weifang City, Shandong Province in 2017. Drug-resistant strains were screened using a carbapenem-resistant enterobacter chromogenic medium. CR-ECL positive strains were acquired via Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry(MALDI-TOFMS) analysis. The antibiotic resistance phenotype of CR-ECL was determined using a microbroth dilution assay. Whole genome sequencing (WGS) and analysis were conducted, along with an examination of the immediate vicinity of the blaNDM gene and phylogenetic analysis of the strains. Results:A total of 628 fecal samples were collected and tested, of which 6 were CR-ECL positive (detection rate 0.96%), all exhibiting multiple drug resistance (MDR) phenotypes. Six CR-ECL strains had four MLST genotypes (ST), all of which carried multiple drug resistance genes ( blaNDM-1, blaNDM-5, etc.) and virulence genes ( acrA, acrB, entB, fepC, etc.). There were mobile genetic elements ISAba125, TN3-IS3000, TN3 and IS5 in the genetic environment surrounding the blaNDM gene. The phylogenetic tree showed that the multi-locus sequence typing of the core genome (cgMLST) was consistent with the single nucleotide polymorphism (SNPs) results. The cgMLST results showed that the allele differences between strains 2BC0101B and 2BC0251B, 2BG0561B and 2BI0221B were 2 and 1, respectively. The SNPs results showed that the above two pairs of bacteria also clustered together. It was found that the strains of chicken fecal samples in the National Center for Biotechnology Information (NCBI) database were located in the center of the evolutionary tree, and the local sequences could be traced back to American human sequences. Conclusion:Multidrug-resistant CR-ECL is detected in rural community residents in Weifang City, Shandong Province.
8.Establishment of Dual Fluorescent Labeled Human High Bone Metastasis Lung Adenocarcinoma Cell Line and Transcriptomic Characterization Analysis
LU YUE ; QIU RONG ; DENG YAN ; LIU XINGYU ; DU YUZHEN
Chinese Journal of Lung Cancer 2024;27(4):257-265
Background and objective Bone is a common site for metastasis in lung adenocarcinoma,but the mechanism behind lung adenocarcinoma bone metastasis is still unclear.And currently,there is a lack of easily traceable and stable lung adenocarcinoma bone metastasis cell models,which limits the research on the mechanism of lung adenocarcinoma bone metastasis.The establishment of human lung adenocarcinoma cell line that are highly metastatic to bone,labeled with green fluorescent proteins(GFP)and fireflies luciferase(LUC),along with transcriptomic characterization,would be beneficial for research on lung adenocarcinoma bone metastasis and provide new experimental methods.Methods The human lung ad-enocarcinoma cell line A549-GFP-LUC was injected into nude mice via the left ventricle to construct a bone metastasis model,and was domesticated in vivo for three consecutive times to obtain the human high bone metastasis lung adenocarcinoma cell line A549-GFP-LUC-BM3;cell counting kit-8(CCK-8),colony formation assay,scratch wound assays,Transwell assay and Western blot were used to compare the proliferation and invasion abilities of A549-GFP-LUC-BM3 with the parental cells.A549-GFP-LUC-BM3 cells and parental cells were further analyzed by transcriptomic sequencing.Results Human high-bone metastatic lung adenocarcinoma cells A549-GFP-LUC-BM3 was successfully established.Compared to parental cells,this cells exhibited a significantly higher incidence of bone metastasis and enhanced in vitro proliferation,migration,and invasion abilities.Transcriptomic sequencing results revealed that the A549-GFP-LUC-BM3 cell line had 2954 differentially expressed genes compared to the parental cells,with 1021 genes up-regulated and 1933 genes down-regulated.Gene Ontology(GO)functional enrichment analysis indicated that the differentially expressed genes were primarily localized in cellular components such as the cell periphery.The molecular functions identified as significantly enriched included signaling receptor activity,cal-cium ion binding,and extracellular matrix structural constituent.Additionally,the biological processes found to be enriched were cell adhesion and biological adhesion.The enrichment analysis conducted using the Kyoto Encyclopedia of Genes and Genomes(KEGG)revealed that the differentially expressed genes were primarily involved in the metabolism of xenobiot-ics by cytochrome P450,retinol metabolism,drug metabolism-cytochrome P450,cell adhesion molecules,steroid hormone biosynthesis,and the nuclear factor kappa B(NF-κB)signaling pathway.Conclusion The highly bone-metastatic human lung adenocarcinoma cell line with GFP and luciferase double labeling was successfully established.The biological behavior and transcriptome sequencing of the cell line suggest that it has a high bone-metastatic potential.
9.Comparison of Short-term Efficacy of Neoadjuvant Immunotherapy Combined with Chemotherapy and Surgery Alone for Locally Advanced Resectable Non-small Cell Lung Cancer
LI HAITIAN ; LIU QING ; LI BIN ; CHEN YUZHEN ; LIN JUNPING ; MENG YUQI ; FENG HAIMING ; ZHENG ZHIZHONG ; HUI YIMING
Chinese Journal of Lung Cancer 2024;27(6):421-430
Background and objective Lung cancer is the cancer with the highest incidence and mortality rates in China,and non-small cell lung cancer(NSCLC)accounts for 80%-85%of all malignant lung tumors.Currently,surgical treat-ment remains the primary treatment modality for lung cancer.In recent years,the effectiveness of immune checkpoint inhibi-tors for NSCLC has become a consensus,and neoadjuvant immunochemotherapy(nICT)has shown promising efficacy and safety in early to intermediate stage NSCLC.However,there are fewer studies related to nICT for locally advanced NSCLC.This study aims to evaluate the efficacy and safety of nICT therapy in locally advanced resectable NSCLC.Methods 85 con-firmed resectable stage ⅢA and ⅢB patients treated in the Department of Thoracic Surgery,Second Hospital of Lanzhou University,from January 2021 to April 2024,were divided into the nICT group(n=32)and the surgery alone group(n=53).Clinical baseline data,perioperative indicators,postoperative complications,imaging response rate,pathological response rate,incidence of adverse events,and quality of life were compared between the two groups.Results There were no statisti-cally significant differences in clinical baseline data between the two groups(P>0.05).Incidence of choosing thoracotomy was higher in the nICT group than in the surgery alone group(P=0.002).There were no significant differences in surgical time,intraoperative blood loss,number of dissected lymph nodes,duration of chest tube placement,postoperative hospital stay,and R0 resection rate between the two groups(P>0.05).The overall incidence of postoperative complications was 31.25%in the nICT group and 22.64%in the surgery alone group,with no statistically significant difference(P=0.380).In the nICT group,the objective response rate(ORR)was 84.38%,with 5 cases of complete response(CR)(15.63%),22 cases of partial response(PR)(68.75%),15 cases of pathological response rate(pCR)(46.88%),and 11 cases of major pathological reaponse(MPR)(34.38%).During nICT treatment,12 cases(37.50%)experienced grade 3 treatment-related adverse events,no death induced by adverse events or immune related adverse events.Moreover,the symptoms of the patients were improved after nICT treat-ment.Conclusion Neoadjuvant immunochemotherapy shows promising efficacy in locally advanced resectable NSCLC,with manageable treatment-related adverse events.It is a safe and feasible neoadjuvant treatment modality for locally advanced resectable NSCLC.
10.Antidepressant effects of Yuanzhi (Polygalae Radix) extract on chronic unpredictable mild stress-induced depression in rats: modulation of the NLRP3 inflammasome and NF-κB pathway
CHEN Yuzhen ; ZHAO Yongzhi ; ZHANG Yiwen ; CHEN Fang ; Iqbal Choudhary Muhammad ; LIU Xinmin ; JIANG Ning
Digital Chinese Medicine 2024;7(2):184-194
Objective:
To investigate the antidepressant effects of Yuanzhi (Polygalae Radix, PR) aqueous extract on chronic unpredictable mild stress (CUMS)-induced depression rat models and the underlying mechanisms.
Methods:
A total of 40 male Sprague Dawley (SD) rats were randomly divided into control, model, low dose of PR (PR-L, 0.5 g/kg), high dose of PR (PR-H, 1 g/kg), and fluoxetine (10 mg/kg) groups, with 8 rats in each group. Except for the rats in control group, those in the other four groups underwent CUMS-induced depression modeling. PR and fluoxetine were administered intragastrically once daily, 30 min prior to the CUMS procedure, for 14 consecutive days until the behavioral tests were performed. After CUMS modeling, the sucrose preference test (SPT), open field test (OFT), novelty-suppressed feeding test (NSFT), forced swim test (FST), and tail suspension test (TST) were employed to assess the pharmacological effects of PR on the mitigation of depressive-like behaviors in rat models. Additionally, the enzyme-linked immunosorbent assay (ELISA) was utilized to quantify the serum levels of tumor
necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in the rats. Western blot analysis was also conducted to evaluate the protein expression levels of nuclear factor kappa-B (NF-κB), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing caspase recruitment domain (ASC), and caspase-1 in the hippocampal tissues of the rats. Immunofluorescence staining was performed to observe the morphological changes in ionized calcium-binding adapter molecule 1positive (Iba-1+) cells in the dentate gyrus (DG) of rats with CUMS-induced depression.
Result:
(i) Treatment with PR-H and fluoxetine resulted in significant enhancements in both the total distance and time the rats moved during tests (P < 0.01 and P < 0.05, respectively). Post-administration of PR-H and fluoxetine also led to statistically significant increase in sucrose preference among rats (P < 0.05). Besides, PR-L, PR-H, and fluoxetine treatment markedly decreased the latency of ingestion (P < 0.05, P < 0.05, and P < 0.01, respectively). As observed from the FST, PR-L, PR-H, and fluoxetine presented antidepressant effects on rats with CUMS-induced depression, leading to the reduction in time of their immobility (P < 0.05, P < 0.01, and P < 0.01, respectively). The results of TST indicated reduced immobility time in rats receiving PR-H and fluoxetine treatment as well (P < 0.01). (ii) Rats in model group showed an increase in the levels of Iba-1+ microglia in their left and right brains in comparison with control group (P < 0.01). However, such increase was negated post PR treatment (P < 0.01). Treatment with PR-L, PR-H, and fluoxetine considerably reduced the levels of inflammatory factors (TNF-α, IL-1β, and IL-6, P < 0.01). In addition, treatment of PR-L and PR-H effectively counteracted the elevated levels of NLRP3, ASC, and caspase-1, and markedly down-regulated the expression levels of phosphorylated p65 (p-p65), COX-2, and iNOS in rats’ hippocampus (P < 0.01).
Conclusion
Collectively, these findings indicate that PR exerts an antidepressant effect on rats with CUMS-induced depression partially through the modulation of the NLRP3 and NF-κB signaling pathways.

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