1.Modulation of colonic DNA methyltransferase by mild moxibustion and electroacupuncture in ulcerative colitis TET2 knockout mice
Gege FENG ; Yue ZHANG ; Huangan WU ; Lu ZHU ; Hongxiao XU ; Zhe MA ; Yan HUANG
Digital Chinese Medicine 2025;8(1):100-110
Objective:
To investigate the mechanism of in alleviating colonic mucosal inflammation in ten-eleven translocation (TET) protein 2 gene knockout (TET2-/-) mice with ulcerative colitis (UC) by regulating DNA methyltransferase (DNMT) and DNA hydroxymethylase.
Methods:
Male specific pathogen-free (SPF) grade C57BL/6J wild-type (WT) mice (n = 8) and TET2-/- mice (n = 20) were used to establish UC models by freely drinking 3% dextran sulfate sodium solution for 7 d. After UC model validation through histopathological examination in two mice from each type, the remaining mice were divided into four groups (n = 6 in each group): WT model (WT + UC), TET2-/- model (TET2-/- + UC), TET2-/- mild moxibustion (TET2-/- + MM), and TET2-/- electroacupuncture (TET2-/- + EA) groups. TET2-/- + MM group received mild moxibustion on Tianshu (ST25) and Qihai (CV6) for 10 min daily for 7 d. The TET2-/- + EA group also applied electroacupuncture (1 mA, 2/100 Hz) at the same acupoints for 10 min daily for 7 d. The disease activity index (DAI) scores of each group of mice were accessed daily. The colon lengths of mice in groups were measured following intervention. The pathological changes in the colon tissues were observed with hematoxylin and eosin (HE) staining. The concentrations of interleukin (IL)-6, C-C motif chemokine 17 (CCL17), and C-X-C motif chemokine ligand 10 (CXCL10) in serum were detected by enzyme-linked immunosorbent assay (ELISA). The expression of DNMT proteins (DNMT1, DNMT3A, and DNMT3B) in the colon tissues was detected by immunohistochemistry. The expression of 5-methylcytosine (5-mC), 5-hydroxymethylcytosine (5-hmC), histone deacetylase 2 (HDAC2), and DNA hydroxymethylase family proteins (TET 1 and TET3) was detected using immunofluorescence, which also determined the co-localization of TET1 and IL-6 protein.
Results:
Compared with WT + UC group, TET2-/- + UC group exhibited significantly higher DAI scores and shorter colon lengths (P < 0.01). Both mild moxibustion and electroacupuncture significantly decreased DAI scores and ameliorated colon shortening in TET2-/- mice (P < 0.001). Histopathological scores of TET2-/- + UC mice were significantly higher than those of WT + UC group (P < 0.001) and were significantly reduced after both mild moxibustion and electroacupuncture interventions (P < 0.001). Serum levels of IL-6, CCL17, and CXCL10 were significantly elevated in TET2-/- + UC group compared with WT + UC group (P < 0.001). Mild moxibustion significantly reduced IL-6, CCL17, and CXCL10 levels (P < 0.001, P < 0.001, and P < 0.01, respectively), while electroacupuncture also significantly reduced IL-6, CCL17, and CXCL10 levels (P < 0.05, P < 0.01, and P < 0.01, respectively). TET2-/- + UC mice showed increased expression levels of DNMT1, DNMT3A , DNMT3B, and 5-mC (P < 0.05, P < 0.01 and P < 0.001, respectively), with decreased expression levels of TET1, TET3, 5-hmC, and HDAC2 (P < 0.001). Mild moxibustion significantly reduced DNMT1, DNMT3B, and 5-mC levels (P < 0.05, P < 0.01, and P < 0.001, respectively), while increasing expression levels of TET1, TET3, 5-hmC, and HDAC2 (P < 0.001, P < 0.001, P < 0.05, and P < 0.001, respectively). Electroacupuncture significantly decreased 5-mC and DNMT3B levels (P < 0.001 and P < 0.01, respectively) and increased 5-hmC and HDAC2 levels (P < 0.05 and P < 0.001, respectively), but did not significantly affect TET1 and TET3 expression (P > 0.05). Compared with TET2-/- + MM group, TET2-/- + EA group showed significantly higher 5-mC expression (P < 0.001). TET2-/- + UC group exhibited markedly increased IL-6 expression and higher co-localization of TET1 and IL-6 in mucosal epithelium, whereas minimal IL-6 expression was observed in the other groups.
Conclusion
Mild moxibustion and electroacupuncture significantly ameliorate colonic inflammation exacerbated by TET2 deficiency in UC mice via epigenetic modulation. Distinct mechanisms exist between the two interventions: mild moxibustion regulates both DNMT and hydroxymethylase, whereas electroacupuncture primarily affects DNMT.
2.Analysis of the monitoring results of radiation health technical service quality in Jiangxi Province, 2022-2024
Zhe HUANG ; Ning ZHOU ; Lingling GUO ; Zhongwen XU ; Lei DENG
Chinese Journal of Radiological Health 2025;34(3):390-394
Objective To access the current situation of the service capacity of radiation health technical service institutions in Jiangxi Province, analyze the existing problems of these institutions, and provide a scientific basis for standardizing the management of such institutions and improving their service capability. Methods A total of 11 radiation health technical service institutions in Jiangxi Province in the National Occupational Health Technical Service Organization Management Information System were selected as the monitoring objects. During the period from 2022 to 2024, 5-6 technical service institutions were selected each year and comprehensively evaluated and inspected using a checklist formulated by the state. Results Among the 16 quality monitoring results of 11 institutions, 2 (12.5%) were rated as excellent, 12 (75%) as qualified, and 2 (12.5%) as unqualified. The risk level assessment identified 7 (43.75%) high-risk institutions, 9 (56.25%) medium-risk institutions, and 0 (0%) low-risk institutions. Conclusion The overall service capacity of radiation health technical service institutions in Jiangxi Province needs to be improved. Notably, institutions within the health system, such as centers for disease control and prevention, show significant shortcomings in both on-site and laboratory testing capabilities.
3.Effect of chelerythrine on migration,invasion,and epithelial-mesenchymal transition of human ovarian cancer SKOV3 cells
Jia ZHOU ; Zhidong QIU ; Zhe LIN ; Guangfu LYU ; Jiaming XU ; He LIN ; Kexin WANG ; Yuchen WANG ; Xiaowei HUANG
Journal of Jilin University(Medicine Edition) 2024;50(1):25-32
Objective:To discuss the inhibitory effect of chelerythrine(CHE)on the migration,invasion,and epithelial-mesenchymal transition(EMT)of the human ovarian cancer SKOV3 cells,and to clarify the associated mechanism.Methods:The SKOV3 cells were cultured in vitro and divided into control group and 2.5,5.0,10.0,20.0,and 40.0 μmol·L-1 CHE groups.Methylthiazolydiphenyl-tetrazolium(MTT)assay was used to detect the inhibitory rates of proliferation of the cells in various groups.The SKOV3 cells were cultured in vitro and divided into control group,transforming growth factor-β1(TGF-β1)group,TGF-β1+5 μmol·L-1 CHE group,and TGF-β1+10 μmol·L-1 CHE group.Cell scratch assay was used to detect the migration rates of the cells in various groups;Transwell chamber assay was used to detect the numbers of migration and invasion cells in various groups;Western blotting method was used to detect the expression levels of E-cadherin,N-cadherin,and Vimentin proteins in the cells in various groups;immunofluorescence staining method was used to detect the fluorescence intensities of E-cadherin and N-cadherin in the cells in various groups.Results:The MTT assay results showed that compared with control group,the inhibitory rates of proliferation of the cells in 5.0,10.0,20.0,and 40.0 μmol·L-1 CHE groups were significantly increased(P<0.05 or P<0.01).The cell scratch assay results showed that compared with control group,the migration rate of the cells in TGF-β1 group was increased(P<0.01);compared with TGF-β1 group,the migration rates of the cells in TGF-β1+5 μmol·L-1 CHE group and TGF-β1+10 μmol·L-1 CHE group were significantly decreased(P<0.01).The Transwell chamber assay results showed that compared with control group,the numbers of migration and invasion cells in TGF-β1 group were significantly increased(P<0.05);compared with TGF-β1 group,the numbers of migration and invasion cells in TGF-β1+5 μmo·l L-1 CHE group and TGF-β1+10 μmo·l L-1 CHE group were significantly decreased(P<0.01).The Western blotting results showed that compared with control group,the expression level of E-cadherin protein in the cells in TGF-β1 group was significantly decreased(P<0.01),while the expression levels of N-cadherin and Vimentin proteins were increased(P<0.05 or P<0.01);compared with TGF-β1 group,the expression levels of E-cadherin protein in the cells in TGF-β1+5 μmol·L-1 CHE group and TGF-β1+10 μmol·L-1 CHE group were significantly increased(P<0.01),and the expression levels of N-cadherin and Vimentin proteins were significantly decreased(P<0.01).The immunofluorescence staining results showed that compared with control group,the fluorescence intensity of E-cadherin in the cells in TGF-β1 group was decreased,and the fluorescence intensity of N-cadherin was increased;compared with TGF-β1 group,the fluorescence intensities of E-cadherin in the cells in TGF-β 1+5 μmol·L-1 CHE group and TGF-β1+10 μmol·L-1 CHE group were significantly increased,and the fluorescence intensities of N-cadherin were decreased.Conclusion:CHE can inhibit the proliferation,migration,invasion,and EMT of the human ovarian cancer SKOV3 cells.
4.Study of the mechanism of acupuncture and moxibustion in protecting the intestinal mucosal barrier in DSS-induced UC rats based on the IL-9/IL-9R pathway
Yan HUANG ; Kexin SUN ; Jing XU ; Zhe MA ; Jimeng ZHAO ; Lingjie LI ; Chen ZHAO ; Ling YANG ; Feng LI ; Yanan LIU ; Yue ZHANG ; Luyi WU ; Rude HUANG
Journal of Acupuncture and Tuina Science 2024;22(2):91-103
Objective:To observe the effects of acupuncture and moxibustion on interleukin(IL)-9/IL-9 receptor(IL-9R)in the colon tissue of rats with ulcerative colitis(UC)and investigate the protective mechanism of acupuncture and moxibustion on the intestinal mucosal barrier in UC rats. Methods:Male Sprague-Dawley rats were randomly divided into a normal control(NC)group and a modeling group.UC models were prepared by giving 4%dextran sulfate sodium(DSS)water for 7 d.After the successful construction of the UC rat model,the modeling group was randomly divided into a UC group,a herb-insulated moxibustion(HM)group,and an electroacupuncture(EA)group.HM and EA interventions at bilateral Tianshu(ST25)were performed once a day for 7 d.Hematoxylin-eosin(HE)staining was used to observe the histopathological changes in the colon.The serum concentrations of IL-9,IL-6,IL-1β,and hemoglobin-H(HbH)were determined by enzyme-linked immunosorbent assay.The protein expression levels of IL-9,IL-9R,claudin-2,zonula occludens-1(ZO-1),and occludin in the colon tissue were measured by Western blotting or immuno-histochemistry.Immunofluorescence was used to detect the co-expression of PU.1 and CD4 with the IL-9 protein. Results:Compared with the NC group,the colon tissue of UC rats was severely damaged and ulcerated with congestion and edema,and the colonic histopathological score increased significantly(P<0.01).The serum HbH concentration decreased significantly(P<0.01),while the serum concentrations of IL-9,IL-6,and IL-1β increased(P<0.01).The protein expression of colonic ZO-1 and occludin decreased significantly(P<0.01),while the protein expression of colonic IL-9 and IL-9R increased(P<0.05).The positive co-expression levels of IL-9/PU.1 and IL-9/CD4 increased in the colon tissue(P<0.05).Compared with the UC group,the colonic mucosal structures were gradually repaired in both HM group and EA group,and healed ulcers could be observed,the colonic histopathological score decreased significantly(P<0.05).The serum concentration of HbH increased(P<0.01),while the serum concentrations of IL-9,IL-6,and IL-1β decreased(P<0.05).The protein expression levels of ZO-1 and occludin increased(P<0.05),while the protein expression levels of IL-9 and IL-9R decreased(P<0.01).The positive co-expression levels of IL-9/PU.1 and IL-9/CD4 decreased in the colon tissue(P<0.05). Conclusion:Both HM and EA can inhibit the protein expression levels of IL-9 and IL-9R in the UC colon by regulating the transcription factor PU.1,promote the repair of intestinal mucosal barrier,and down-regulate protein contents of proinflammatory factors IL-9,IL-6,and IL-1β in the serum,which may be one of the key mechanisms of acupuncture and moxibustion in reducing the inflammation of UC colonic mucosa and protecting the intestinal mucosal barrier.
5.Study on Traditional Chinese Medicine Syndrome Characteristics of 1676 Heart Failure Inpatients: A Cross-Sectional Survey Based on Real-World Electronic Medical Record Information
Yi DU ; Zheng LI ; Guanlin YANG ; Shuqi DONG ; Wenshuai HUANG ; Nanxing XIAN ; Puyu GUO ; Jiajie QI ; Bohang CHEN ; Xin XU ; Zhe ZHANG ; Yi YANG
Journal of Traditional Chinese Medicine 2024;65(3):299-307
ObjectiveTo analyse the clinical characteristics of different traditional Chinese medicine (TCM) syndromes in patients with heart failure based on information from electronic medical record. MethodsA cross-sectional study was conducted to collect clinical data of all inpatients with heart failure in the Department of Cardiology, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine from January 1, 2019 to December 31, 2020. A database of clinical TCM data was established to explore the characteristics of clinical data of basic information, syndromes and syndrome element types, and biochemical indexes. The distribution of TCM syndromes and syndrome elements in heart failure patients were also analysed, and the basic information and biochemical indexes of the patients with top 7 different TCM syndrome types were compared. ResultsA total of 1676 inpatients with heart fai-lure were included. The top 7 TCM syndromes of heart failure were syndrome of phlegm turbidity and blood stasis (477 cases, 28.46%), syndrome of qi deficiency and blood stasis (439 cases, 26.19%), syndrome of qi deficiency and blood stasis with water retention (274 cases, 16.35%), syndrome of yang deficiency with water retention (145 cases, 8.65%), syndrome of qi and yin deficiency (104 cases, 6.21%), syndrome of qi and yin deficiency with blood stasis (80 cases, 4.77%), syndrome of heart yang deficiency (59 cases, 3.52%). Among the 1676 patients, 6 syndrome elements accounted for more than 5%. Blood stasis accounted for the highest proportion of TCM syndrome element type (1292 cases, 77.09%), followed by qi deficiency (919 cases, 54.83%), phlegm (498 cases, 29.71%), water retention (434 cases, 25.89%), yang deficiency (215 cases, 12.82%) and yin deficiency (191 cases, 11.40%). Among the 1676 patients, 1308 cases of acute heart failure mainly showed syndrome of phlegm turbidity and blood stasis (386 cases, 29.51%), and 368 of chronic heart fai-lure mainly showed syndrome of qi deficiency and blood stasis (118 cases, 32.07%). Patients with syndrome of phlegm turbidity and blood stasis had the shortest disease duration of 0.3 months, while those with syndrome of heart yang deficiency had the longest disease duration of 15 months. The proportion of syndrome of phlegm turbidity and blood stasis was the highest in patients with heart failure combined with coronary artery disease, the proportion of syndrome of qi deficiency and blood stasis with water retention was the highest in patients with heart failure combined with atrial fibrillation, and the proportion of patients with syndrome of qi deficiency and blood stasis with water retention and syndrome of yang deficiency with water retention in those applying diuretics during the hospital stay was the highest with more than 86%. The different 7 TCM syndromes showed statistically difference in patients with complications including coronary artery disease, old myocardial infarction, atrial fibrillation, pre and post-admission medication usage including intravenous vasodilators, cardiac stimulants, diuretics, and level of blood chloride, blood urea, blood creatinine, blood bicarbonate, blood albumin, and blood total bilirubin (P<0.05). ConclusionThe most common TCM syndromes in patients with heart failure are syndrome of phlegm turbidity and blood stasis and syndrome of qi deficiency and blood stasis. Different TCM syndromes have different characteristics in gender, disease complications, medication before and after admission, and blood indexes.
6.Correlation between the level of NT-proBNP and cardiorespiratory fitness of individuals following acute high altitude exposure
Ping-Ping LI ; Xiao-Wei YE ; Jie YANG ; Zhe-Xue QIN ; Shi-Zhu BIAN ; Ji-Hang ZHANG ; Xu-Bin GAO ; Meng-Jia SUN ; Zhen LIU ; Hai-Lin LYU ; Qian-Yu JIA ; Yuan-Qi YANG ; Bing-Jie YANG ; Lan HUANG
Medical Journal of Chinese People's Liberation Army 2024;49(9):998-1003
Objective To investigate the correlation between the level of N-terminal pro-Brain natriuretic peptide(NT-proBNP)and cardiorespiratory fitness following acute exposure to high altitude.Methods Forty-six subjects were recruited from the Second Affiliated Hospital of Army Medical University in June 2022,including 19 males and 27 females.After completing cardiopulmonary exercise test(CPET),serological detection of myocardial cell-related markers,and multiple metabolites at a plain altitude(300 meters above sea level),all subjects flew to a high-altitude location(3900 meters above sea level).Biomarker testing and CPET were repeated on the second and third days after arrival at high altitude.Changes in serum biomarker and key CPET indicators before and after rapid ascent to high altitude were compared,and the correlation between serum levels of various myocardial cell-related markers and metabolites and high altitude cardiorespiratory fitness was analyzed.Results Compared with the plain altitude,there was a significant decrease in maximal oxygen uptake after rapid ascent to high altitude[(25.41±6.20)ml/(kg.min)vs.(30.17±5.01)ml/(kg.min),P<0.001].Serum levels of NT-proBNP,Epinephrine(E),plasma renin activity(PRA),angiotensin Ⅱ(Ang Ⅱ),angiotensin-converting enzyme 2(ACE2)and leptin(LEP)significantly increased,with all differences being statistically significant(P<0.05)after acute high altitude exposure.In contrast,no statistically significant differences were observed for creatine kinase MB(CK-MB),cardiac troponin I(cTnI),myoglobin(Myo)and norepinephrine(NE)(P>0.05).Correlation analysis showed a significant negative correlation between NT-proBNP at plain altitude(r=-0.768,P<0.001)and at high altitude(r=-0.791,P<0.001)with maximal oxygen uptake at high altitude.Multivariate linear regression analysis indicated that maximal oxygen uptake at plain altitude(t=2.069,P=0.045),NT-proBNP at plain altitude(t=-2.436,P=0.020)and at high altitude(t=-3.578,P=0.001)were independent influencing factors of cardiorespiratory fitness at high altitude.Conclusion Cardiorespiratory fitness significantly decreases after rapid ascent to high altitude,and the baseline NT-proBNP level at plain altitude is closely related to cardiorespiratory fitness at high altitude,making it a potential predictor indicator for high altitude cardiorespiratory fitness.
7.Evaluation of Potential Donors With Different Causes of Brain Death for Adult Heart Transplantation:a Bedside Echocardiographic Study
Xin SUN ; Jie LIU ; Zhongkai LIAO ; Kui XU ; Sheng LIU ; Jie HUANG ; Zhe ZHENG ; Hao WANG ; Zhenhui ZHU
Chinese Circulation Journal 2024;39(5):484-489
Objectives:To investigate the feasibility of using bedside echocardiography on the evaluation of potential donors with different causes of brain death for adult heart transplantation. Methods:Bedside echocardiographic and clinical data of consecutive potential donors for adult heart transplantation evaluated by the team of our institution from February 2018 to December 2020 were retrospectively analyzed.Based on different causes of brain death,the potential donors were divided into stroke(ischemic or hemorrhagic,n=398)and non-stroke(head trauma,brain tumor,anoxia,n=272)groups.The clinical and echocardiographic features were compared between the two groups.A total of 350 donors were assigned to our hospital by the China Organ Transplant Response System and met the inclusion criteria for donor selection.There were 195 cases in the stroke group and 155 in the non-stroke group.Retrieval operations were performed and the retrieval rate of hearts for transplantation in stroke donors was compared to that in non-stroke donors. Results:(1)Among the 670 potential heart donors,compared with the non-stroke group,donors in the stroke group were significantly older,had higher body mass index,larger left ventricular end-diastolic diameter,thicker interventricular septum,higher rates of echocardiographic abnormalities,higher prevalence of hypertension(all P<0.001).Among the 670 potential heart donors,17.5%(117 cases)did not meet the echo selection criteria,the common causes were left ventricular hypertrophy(59 cases,50.4%),left ventricular ejection fraction<50%(27 cases,23.1%),wall motion abnormalities(21 cases,17.9%),and left ventricular dilation(14 cases,12.0%).(2)Among the 350 donors who had met the selection criteria and assigned to our hospital by the China Organ Transplant Response System and underwent retrieval operation,70.3%(246 cases)were successfully procured,110 cases(44.7%)in the stroke group and 136 cases(55.3%)in the non-stroke group.The retrieval rate of stroke donors(110/195,56.4%)was lower compared with that of non-stroke(136/155,87.7%,P<0.001),104 cases(29.7%)were not retrieved,and the leading cause of unsuccessful organ retrieval was the occlusion of at least one major coronary artery(91 cases,87.5%). Conclusions:Bedside echocardiography is of great value as a screening tool for cardiac donors.Cardiac structures of the potential donor with stroke as the cause of brain death were different from those with non-stroke causes.The retrieval rate of stroke donors was lower than that of non-stroke donors,even if the initial criteria for donor selection were fulfilled.
8.Effect mechanism investigation of herb-partitioned moxibustion on relieving colon inflammation in Crohn disease rats based on neutrophil extracellular traps
Chi LU ; Jing XU ; Yuan LU ; Luyi WU ; Chunhui BAO ; Zhe MA ; Rui ZHONG ; Zhaoqin WANG ; Kexin SUN ; Handan ZHENG ; Zhijun WENG ; Yan HUANG ; Huangan WU ; Yanping YANG
Journal of Acupuncture and Tuina Science 2024;22(3):173-183
Objective:To explore the mechanism of herb-partitioned moxibustion in relieving rat intestinal inflammation by focusing on the neutrophil extracellular traps(NETs)in Crohn disease(CD)development. Methods:Rats were randomly divided into a normal group,a model group,a herb-partitioned moxibustion group,and a mesalazine group.The CD rat model was prepared with 2,4,6-trinitrobenzene sulfonic acid except for rats in the normal group.Rats in the normal group and model group did not receive any treatment but had the same fixation as the other groups.Rats in the herb-partitioned moxibustion group received herb-partitioned moxibustion at Qihai(CV6)and bilateral Tianshu(ST25).Rats in the mesalazine group received intragastric administration of mesalazine enteric-coated tablets.The general situation of rats in each group was recorded,and the histopathological changes in the colon were observed and scored by hematoxylin-eosin staining.The serum concentrations of NETs DNA(NETs-DNA),neutrophil elastase(NE)-DNA,and myeloperoxidase(MPO)-DNA were detected by ABC enzyme-linked immunosorbent assay,and the citrullinated histone 3(citH3),MPO,and NE protein and mRNA expression levels in rat colon tissue were observed by immunofluorescence and real-time quantitative polymerase chain reaction. Results:Compared with the normal group,the mucosal ulcer reached the muscularis,the epithelium was incomplete,the goblet cells decreased obviously with significant inflammatory cell infiltration in the colon;the colonic mucosa damage index(CMDI)score increased significantly(P<0.01);the serum NETs-DNA,NE-DNA,and MPO-DNA concentrations increased(P<0.05);the NE,citH3,and MPO protein and mRNA expression in the colonic tissue increased significantly in the model group(P<0.01 or P<0.05).Compared with the model group,the mucosal epithelium in the herb-partitioned moxibustion group and the mesalazine group was repaired and the goblet cells increased with a few infiltrating inflammatory cells in the colon;the CMDI score decreased(P<0.01);the serum NETs-DNA,NE-DNA,and MPO-DNA concentrations decreased(P<0.05);the NE,citH3,and MPO protein and mRNA expression in the colonic tissue was down-regulated(P<0.01 or P<0.05). Conclusion:Herb-partitioned moxibustion reduced the serum NETs complex and inhibited the protein and mRNA expression of NETs complex in the colon tissue,which may be one mechanism of herb-partitioned moxibustion in relieving colon mucosal inflammation in CD.
9.Intracranial activity of first-line immune checkpoint inhibitors combined with chemotherapy in advanced non-small cell lung cancer.
Zhe HUANG ; Fang WU ; Qinqin XU ; Lianxi SONG ; Xiangyu ZHANG ; Zhan WANG ; Li DENG ; Yongchang ZHANG ; Liang ZENG ; Nong YANG
Chinese Medical Journal 2023;136(12):1422-1429
BACKGROUND:
Immune checkpoint inhibitors (ICIs) are increasingly used as first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) harboring no actionable mutations; however, data on their efficacy among patients presenting with intracranial lesions are limited. This study aimed to explore the efficacy and safety of ICIs combined with chemotherapy in advanced NSCLC patients with measurable brain metastasis at initial diagnosis.
METHODS:
Our study retrospectively analyzed clinical data of a total of 211 patients diagnosed with driver gene mutation-negative advanced NSCLC with measurable, asymptomatic brain metastasis at baseline from Hunan Cancer Hospital between January 1, 2019 and September 30, 2021. The patients were stratified into two groups according to the first-line treatment regimen received: ICI combined with chemotherapy ( n = 102) or chemotherapy ( n = 109). Systemic and intracranial objective response rates (ORRs) and progression-free survival (PFS) were analyzed. Adverse events were also compared between the groups.
RESULTS:
Compared with the chemotherapy-based regimen, the ICI-containing regimen was associated with a significantly higher intracranial (44.1% [45/102] vs . 28.4% [31/109], χ2 = 5.620, P = 0.013) and systemic (49.0% [50/102] vs . 33.9% [37/109], χ2 = 4.942, P = 0.019) ORRs and longer intracranial (11.0 months vs . 7.0 months, P <0.001) and systemic (9.0 months vs . 5.0 months, P <0.001) PFS. Multivariable analysis consistently revealed an independent association between receiving ICI plus platinum-based chemotherapy as a first-line regimen and prolonged intracranial PFS (hazard ratio [HR] = 0.52, 95% confidence interval [CI]: 0.37-0.73, P <0.001) and systemic PFS (HR = 0.48, 95% CI: 0.35-0.66, P <0.001). No unexpected serious adverse effects were observed.
CONCLUSION:
Our study provides real-world clinical evidence that ICI combined with chemotherapy is a promising first-line treatment option for driver gene mutation-negative advanced NSCLC patients who present with brain metastasis at initial diagnosis.
CLINICAL TRIAL REGISTRATION
https://www.clinicaltrials.gov/ , OMESIA, NCT05129202.
Humans
;
Carcinoma, Non-Small-Cell Lung/genetics*
;
Lung Neoplasms/genetics*
;
Immune Checkpoint Inhibitors/therapeutic use*
;
Retrospective Studies
;
Brain Neoplasms/genetics*
10.Evaluation of metoprolol standard dosing pathway in Chinese patients with acute coronary syndrome: a prospective multicenter single-arm interventional study.
Xiao-Yun YIN ; Yun-Mei ZHANG ; Ai-Dong SHEN ; Jing-Ping WANG ; Zhe-Xun LIAN ; Yi-Bing SHAO ; Wen-Qi ZHANG ; Shu-Ying ZHANG ; Yang ZHENG ; Kang CHENG ; Biao XU ; Cheng-Xing SHEN ; Rong-Chong HUANG ; Jin-Cheng GUO ; Guo-Sheng FU ; Dong-Kai SHAN ; Dan-Dan LI ; Yun-Dai CHEN
Journal of Geriatric Cardiology 2023;20(4):256-267
OBJECTIVE:
To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS).
METHODS:
In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4.
RESULTS:
Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group.
CONCLUSIONS
In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable.

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