1.Diagnostic Techniques and Risk Prediction for Cardiovascular-kidney-metabolic (CKM) Syndrome
Song HOU ; Lin-Shan ZHANG ; Xiu-Qin HONG ; Chi ZHANG ; Ying LIU ; Cai-Li ZHANG ; Yan ZHU ; Hai-Jun LIN ; Fu ZHANG ; Yu-Xiang YANG
Progress in Biochemistry and Biophysics 2025;52(10):2585-2601
Cardiovascular disease (CVD), chronic kidney disease (CKD), and metabolic disorders are the 3 major chronic diseases threatening human health, which are closely related and often coexist, significantly increasing the difficulty of disease management. In response, the American Heart Association (AHA) proposed a novel disease concept of “cardiovascular-kidney-metabolic (CKM) syndrome” in October 2023, which has triggered widespread concern about the co-treatment of heart and kidney diseases and the prevention and treatment of metabolic disorders around the world. This review posits that effectively managing CKM syndrome requires a new and multidimensional paradigm for diagnosis and risk prediction that integrates biological insights, advanced technology and social determinants of health (SDoH). We argue that the core pathological driver is a “metabolic toxic environment”, fueled by adipose tissue dysfunction and characterized by a vicious cycle of systemic inflammation and oxidative stress, which forms a common pathway to multi-organ injury. The at-risk population is defined not only by biological characteristics but also significantly impacted by adverse SDoH, which can elevate the risk of advanced CKM by a factor of 1.18 to 3.50, underscoring the critical need for equity in screening and care strategies. This review systematically charts the progression of diagnostic technologies. In diagnostics, we highlight a crucial shift from single-marker assessments to comprehensive multi-marker panels. The synergistic application of traditional biomarkers like NT-proBNP (reflecting cardiac stress) and UACR (indicating kidney damage) with emerging indicators such as systemic immune-inflammation index (SII) and Klotho protein facilitates a holistic evaluation of multi-organ health. Furthermore, this paper explores the pivotal role of non-invasive monitoring technologies in detecting subclinical disease. Techniques like multi-wavelength photoplethysmography (PPG) and impedance cardiography (ICG) provide a real-time window into microcirculatory and hemodynamic status, enabling the identification of early, often asymptomatic, functional abnormalities that precede overt organ failure. In imaging, progress is marked by a move towards precise, quantitative evaluation, exemplified by artificial intelligence-powered quantitative computed tomography (AI-QCT). By integrating AI-QCT with clinical risk factors, the predictive accuracy for cardiovascular events within 6 months significantly improves, with the area under the curve (AUC) increasing from 0.637 to 0.688, demonstrating its potential for reclassifying risk in CKM stage 3. In the domain of risk prediction, we trace the evolution from traditional statistical tools to next-generation models. The new PREVENT equation represents a major advancement by incorporating key kidney function markers (eGFR, UACR), which can enhance the detection rate of CKD in primary care by 20%-30%. However, we contend that the future lies in dynamic, machine learning-based models. Algorithms such as XGBoost have achieved an AUC of 0.82 for predicting 365-day cardiovascular events, while deep learning models like KFDeep have demonstrated exceptional performance in predicting kidney failure risk with an AUC of 0.946. Unlike static calculators, these AI-driven tools can process complex, multimodal data and continuously update risk profiles, paving the way for truly personalized and proactive medicine. In conclusion, this review advocates for a paradigm shift toward a holistic and technologically advanced framework for CKM management. Future efforts must focus on the deep integration of multimodal data, the development of novel AI-driven biomarkers, the implementation of refined SDoH-informed interventions, and the promotion of interdisciplinary collaboration to construct an efficient, equitable, and effective system for CKM screening and intervention.
2.Effects of astragalus angelica on apoptosis and expression of Bax and caspase-3/9 in rabbit chondrocytes after fresh osteochondral allograft
Wan-Tao DONG ; Pan YANG ; Xiu-Juan YANG ; Shi-Ming QIU ; Peng YUAN ; Jing-Yi LIU ; Jiu-Mei HUANG ; Yu ZHOU
Chinese Pharmacological Bulletin 2024;40(12):2288-2294
Aim To observe the effect of Astragalus membranaceus and Angelica sinensis on the apoptosis of chondrocytes,and to investigate the effect of Astrag-alus membranaceus and Angelica sinensis on the sur-vival of fresh ostecartilage allograft.Methods Forty-eight 4-month-old New Zealand white rabbits,half male and half female,were randomly divided into sham operation group,model group,positive group and As-tragalus and Angelica 5∶1 group.In addition to the sham operation group,the other groups were both male and female donors and recipients for knee joint osteo-cartilage cross transplantation modeling.After 8 weeks of drug intervention,samples were taken for general observation,HE staining,saffrane-O staining,immu-nohistochemical staining,qPCR and Western blot de-tection.Results Compared with model group,As-tragalus and Angelica 5∶1 group and positive group,the repair site healed better,the morphology of osteo-chondrocytes tended to be normal,and the division and proliferation were obvious.Proteoglycan deposition in-creased and type Ⅱ collagen content was higher,the differences were statistically significant(P<0.05).qPCR and Western blot results showed that compared with model group,the mRNA and protein expressions of Bax,caspase-3 and caspase-9 in other groups were significantly decreased(P<0.05).Conclusion As-tragalus and Angelica can promote the survival of fresh osteochondral allograft,and its mechanism may be re-lated to promoting collagen production,promoting chondrocyte proliferation and inhibiting chondrocyte apoptosis.
3.Analysis of the therapeutic effect of trochanteric flip osteotomy combined with Kocher-Langenbeck approach for high acetabular posterior wall fracture
Xiao-Pan WANG ; Xiao-Tian CHEN ; Ren-Jie LI ; Le-Yu LIU ; Xiu-Song DAI ; Jian-Zhong GUAN ; Min WU ; Xiao-Dong CHEN
China Journal of Orthopaedics and Traumatology 2024;37(7):706-712
Objective Evaluation of the clinical efficacy of f trochanteric flip osteotomy combined with Kocher-Langen-beck approach for high acetabular posterior wall fracture.Methods Between January 2020 and December 2022,20 patients with high acetabular posterior wall fractures were retrospectively analyzed,including 12 males and 8 females,aged 18 to 75 years old.They were divided into two groups according to the different surgical methods.Ten patients were treated with greater trochanteric osteotomy combined with Kocher-Langenbeck approach as the observation group,including 5 males and 5 fe-males,aged from 18 to 75 years old.Ten patients were treated with Kocher-Langenbeck approach alone as the control group,including 7 males and 3 females,aged from 18 to 71 years old.Matta reduction criteria were used to evaluate the reduction quality of the two groups,and Harris score was used to compare the hip function of the two groups at the latest follow-up.The operation time,blood loss and postoperative complications of the two groups were analyzed.Results All patients were followed up for 10 to 24 months.According to the Matta fracture reduction quality evaluation criteria,the observation group achieved anatomical reduction in 6 cases,satisfactory reduction in 3 cases,and unsatisfactory reduction in 1 case,while the control group only achieved anatomical reduction in 3 cases,satisfactory reduction in 3 cases,and unsatisfactory reduction in 4 cases.At the final follow-up,the Harris hip score ranged from 71.4 to 96.6 in the observation group and 65.3 to 94.5 in the control group.According to the results of Harris score.The hip joint function of the observation group was excellent in 6 cases,good in 3 cases,and fair in 1 case.The hip joint function of the control group was excellent in 2 cases,good in 3 cases,fair in 3 cases,and poor in 2 cases.In the observation group,the intraoperative blood loss ranged from 300 to 700 ml,and the operation dura-tion ranged from 120 to 180 min;in the control group,the intraoperative blood loss ranged from 300 to 650 ml,and the opera-tion duration ranged from 100 to 180 min.Complications in the observation group included 1 case of traumatic arthritis and 1 case of heterotopic ossification,while complications in the control group included 3 cases of traumatic arthritis,3 cases of het-erotopic ossification and 1 case of hip abduction weakness.Conclusions Trochanteric flip osteotomy combined with the Kocher-Langenbeck approach significantly improved anatomical fracture reduction rates,enhanced excellent and good hip joint function outcomes,and reduced surgical complication incidence compared to the Kocher-Langenbeck approach alone.Clinical application of this combined approach is promising,although larger studies are needed for further validation.
4.Reversal Roles and Its Mechanism of Asiatic Acid on Multidrug Resistance in K562/ADR Cells Through the Wnt/β-catenin Pathway
Ting ZHANG ; Yong-Jiao LIU ; Lei ZHANG ; Xin-Yu ZHOU ; Xiu-Hong JIA
Journal of Experimental Hematology 2024;32(6):1696-1703
Objective:To investigate the reversal effect and mechanism of asiatic acid (AA)on multidrug resistance in human adriamycin (ADR)chronic myeloid leukemia K562/ADR cells.Methods:CCK-8 assay was used to detect the resistance of K562 cells and K562/ADR cells to ADR.CCK-8 assay was used to detect the effect of AA on K562/ADR cell viability and adriamycin sensitization.After K562/ADR cells were treated with non-toxic doses of AA(10,20μmol/L),the average fluorescence intensity of ADR was detected by flow cytometry.Real-time quantitative PCR was used to detect the expression levels of MRP1,P-gp,β-catenin,C-myc and cyclinD1 mRNA.Western blot was used to detect the expression levels of MRP1,P-gp,β-catenin,C-myc and cyclinD1 proteins.Western blot assay was used to detect the expression levels of MRP1,P-gp,β-catenin,C-myc and cyclinD1 proteins in K562/ADR cells treated with 20μmol/L AA and Wnt/β-catenin pathway agonist WAY-262611 (5 μmol/L).Results:The CCK-8 assay showed that the drug resistance of K562/ADR cells was 56.57 times that of K562 cells,showing stable drug resistance,and the difference was statistically significant (P<0.05 ).AA inhibited the proliferative activity of K562/ADR cells in a concentration-dependent manner(r=0.9666).Compared with 0 μmol/L AA group,the 10 and 20 μmol/L AA groups could significantly enhance the average fluorescence intensity of intracellular ADR (P<0.05 ),and reverse the cell resistance to ADR (P<0.05).The mRNA and protein expressions of MRP1,P-gp,β-catenin,C-myc and cyclinD1 in cells were down-regulated (P<0.05).Compared with 20μmol/L AA group,the expression levels of MRP1,P-gp,β-catenin,C-myc and cyclinD1 protein in 20 μmol/L AA+WAY group were significantly increased (P<0.05 ). Conclusion:AA inhibits K562/ADR cell proliferation in a concentration-dependent manner and reverse their resistance to ADR,the reversal mechanism may be related to the down-regulation of MRP1 and P-gp expression after inhibiting Wnt/β-catenin signaling pathway.
5.Factors influencing decision-to-delivery interval in emergency cesarean section in Guangzhou and its impact on maternal-infant outcomes
Huixiang LIU ; Huiyun XIAO ; Lifang ZHANG ; Yingfang WU ; Jia YU ; Songying SHEN ; Xiu QIU
Chinese Journal of Perinatal Medicine 2024;27(5):353-361
Objective:To investigate the factors influencing the decision to delivery interval (DDI) in emergency cesarean section in Guangzhou and the impact of DDI on maternal-infant outcomes.Methods:A retrospective study was conducted on clinical data of pregnant women who underwent emergency cesarean section at municipal and district maternal and child health hospitals in Guangzhou city in 2021. Per the classification method of emergency cesarean section and recommendations for DDI provided by National Institute for Health and Clinical Excellence guidelines, these subjects were classified into Category Ⅰ and Category Ⅱ cesarean sections. Each category was further divided into two subgroups based on DDI: the Category Ⅰ group into >30 min and ≤30 min subgroups, and the Category Ⅱ group into >75 min and ≤75 min subgroups. Chi-square test or Fisher's exact test, two independent samples t-test, Mann-Whitney U test, and logistic regression were used to analyze the potential factors influencing DDI and the impact of DDI on maternal-infant outcomes. Results:(1) Totally 502 women underwent urgent cesarean section, including 304 (60.6%) Category Ⅰ and 198 (39.4%) Category Ⅱ, were analyzed. Among the Category Ⅰ group, 30.3% (92/304) achieved a DDI of ≤30 min, while 37.4% (74/198) of Category Ⅱ cases had a DDI of ≤75 min. (2) For the Category Ⅰ cases, multivariate logistic regression showed that more patients under intravertebral anesthesia, than those under general anesthesia, had a DDI >30 min ( OR=14.04, 95% CI: 6.14-32.10) as well as more with ward-based emergencies than those with delivery room emergencies ( OR=3.21, 95% CI: 1.72-6.00, both P=0.001). Among the Category Ⅱ cases, logistic regression revealed that cesarean section during routine working hours was more likely to achieve DDI >75 min than that during resting hours ( OR=3.93, 95% CI: 2.03-7.63, P=0.001). The risk of DDI >75 min was higher in tertiary maternal and child health hospitals compared with secondary maternal and child health hospitals ( OR=2.45, 95% CI: 1.06-5.70, P=0.037). (3) Among the Category Ⅰ cases, compared with the DDI ≤30 min group, the DDI >30 min group had a lower risk of neonatal Apgar score ≤7 at 1 min ( OR=0.31, 95% CI: 0.14-0.69, P=0.004), but there was no significant difference in the risk of neonatal Apgar score ≤7 at 5 min ( OR=0.21, 95% CI: 0.04-1.17) or neonatal asphyxia ( OR=0.32, 95% CI: 0.07-1.44) between the two subgroups. In cases of Category Ⅱ cesarean sections, there was no significant difference in any maternal-infant outcomes between DDI ≤75 min and DDI >75 min subgroups. Conclusions:The location of emergency and types of anesthesia are the influencing factors of DDI for Category Ⅰ cesarean sections, while the operation time and level of maternal and child health hospital are the influencing factors of DDI for Category Ⅱ cesarean sections. We did not find any impact of DDI on maternal or infant outcome.
6.Design and application of portable intelligent cleaner for medical lumen instruments
Mei-Hua YU ; Chen-Yang ZHAN ; Li-Yun HE ; Cai-Hong LIU ; Bao-Xiu HUANG ; Yan-Min YAN ; Xiang-Dong HUANG
Chinese Medical Equipment Journal 2024;45(10):114-117
Objective To design a portable intelligent cleaner for medical lumen instruments to enhance cleaning efficiency.Methods The portable intelligent cleaner had a box-body shape and a shell made of 304 stainless steel,which was composed of a circuit control board,a micro pump,lithium batteries,a charging interface,a rinse tube and connectors.The circuit control board used a STM32G030C8T6 integraged circuit,which was equipped with a countdown digital tube to display the time left for cleaning;the micro pump and lithium batteries were placed at the inner wall of the box bottom,the charging interface and water inlet/outlet inteface were put on the outside of the front wall of the box bottom,the water inlet/outlet interface was connected with a silicon rinse tube linked to an adapter at its distal end,and the adapters with different calibers were compatible with sizes of medical lumen instruments.Totally 9 672 pieces of lumen instruments received by some hospital's disinfection supply center from May to October 2021 were divided into 2 groups with the convenience sampling method,with 4 836 pieces in each group.The odd-numbered instruments were enrolled into a control group and cleaned with an ultrasonic cleaner and a lumen brush,and the even-numbered instruments were included into an experimental group and cleaned conventionally after pretreatment by the intelligent cleaner.The two groups were compared in terms of eaning efficiency and satisfaction.Results Testing by visual inspection,magnifying glass with light source and white stripe method showed that the experimental group behaved better than the control group in the cleaning qualification rate,whose satisfaction rate(100%)was also higher than that of the control group(86.53%),with all the differences being statistically significant(P<0.05).Conclusion The portable cleaner with easy operation enhances the cleaning quality and efficiency for medical lumen instruments.[Chinese Medical Equipment Journal,2024,45(10):114-117]
7.A multicenter study of neonatal stroke in Shenzhen,China
Li-Xiu SHI ; Jin-Xing FENG ; Yan-Fang WEI ; Xin-Ru LU ; Yu-Xi ZHANG ; Lin-Ying YANG ; Sheng-Nan HE ; Pei-Juan CHEN ; Jing HAN ; Cheng CHEN ; Hui-Ying TU ; Zhang-Bin YU ; Jin-Jie HUANG ; Shu-Juan ZENG ; Wan-Ling CHEN ; Ying LIU ; Yan-Ping GUO ; Jiao-Yu MAO ; Xiao-Dong LI ; Qian-Shen ZHANG ; Zhi-Li XIE ; Mei-Ying HUANG ; Kun-Shan YAN ; Er-Ya YING ; Jun CHEN ; Yan-Rong WANG ; Ya-Ping LIU ; Bo SONG ; Hua-Yan LIU ; Xiao-Dong XIAO ; Hong TANG ; Yu-Na WANG ; Yin-Sha CAI ; Qi LONG ; Han-Qiang XU ; Hui-Zhan WANG ; Qian SUN ; Fang HAN ; Rui-Biao ZHANG ; Chuan-Zhong YANG ; Lei DOU ; Hui-Ju SHI ; Rui WANG ; Ping JIANG ; Shenzhen Neonatal Data Network
Chinese Journal of Contemporary Pediatrics 2024;26(5):450-455
Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75%(27/36);boys accounted for 64%(23/36).Among the 36 neonates,31(86%)had disease onset within 3 days after birth,and 19(53%)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61%)had left cerebral infarction and 13(36%)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75%)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72%)and seizures in 10 neonates(34%).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33%,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44%(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.
8.Study on the feasibility of low-dose chest CT combined with deep learning reconstruction algorithm in the diagnosis of pediatric mycoplasma pneumonia
Xiu CHENG ; Guihua LIU ; Sirun YU ; Dehong WU ; Wen CHEN ; Guan WANG ; Chao LIU
China Medical Equipment 2024;21(6):12-17
Objective:To explore the feasibility of 60 kV low-dose scanning technique on chest combined with ClearInfinity deep learning reconstruction algorithm in the diagnosis of pediatric mycoplasma pneumonia.Methods:A total of 132 pediatric patients,who admitted to Taihe Hospital Affiliated to Hubei Medical College and were diagnosed as mycoplasma pneumonia,were selected,and all of them underwent computed tomography(CT)scans on chest.They were randomly divided into routine dose group(66 cases),low dose ClearView and ClearInfinity group(66 cases).In the routine dose group,the tube voltage of CT scan on chest was 100 kV,and 50%ClearView iterative algorithm was adopted in this group.The tube voltage of CT scan on chest was 60kV in low dose ClearView and ClearInfinity group,and 50%ClearView iterative algorithm and 50%ClearInfinity deep learning reconstruction algorithm were used respectively to conduct reconstruction.The difference of radiation dose among the three groups was compared.The CT values and standard deviation(SD)values,signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of the region of interest(ROI)of the images of 3 groups were measured and calculated.The images were subjectively evaluated by two diagnostic attending physicians with 10 years of work experience,and the Kappa test was adopted to analyze the consistency of the score results.Results:Compared with the routine dose group,the volume CT dose index(CTDIvol)values,dose-length product(DLP)values and effective radiation dose(ED)values of the low dose ClearView group and ClearInfinity group reduced respectively by 87.58%,87.24%and 88.00%,and the differences were statistically significant(t=4 584.07,63.73,61.27,P<0.01).The noise values of left and right lung of the routine dose group were significantly lower than those of the low dose ClearView group,while were significantly higher than those of ClearInfinity group,and the differences were significant(Z=-9.912,-7.013,P<0.01),and the difference of them between low dose ClearView group and ClearInfinity group was significant(Z=-9.912,P<0.01).The SNR and CNR of left and right lung of low dose ClearView group were significantly lower than those of the routine dose group,with statistically significant(t=-34.810,5.522,P<0.01),while these of the low dose ClearInfinity group were significant higher than them of the routine dose group(t=3.544,-8.674,P<0.05),respectively.The two attending physicians had favorable consistency in the subjective evaluation for images(Kappa>0.75,P<0.01).The subjective score of the routine dose group was not significantly different with that of the low dose ClearInfinity group(P>0.05),but was significantly better than that of the low dose ClearView group(Z=-6.425,P<0.01).Conclusion:For pediatric patients with mycoplasma pneumonia,the 60 kV low dose CT on chest combined with ClearInfinity deep learning reconstruction algorithm can ensure image quality on the premise of reducing radiation,which can ensure the diagnostic effect.
9.Compliance and Influencing Factors of Endoscopic Screening in High-Risk Population of Upper Gastroin-testinal Cancer in Chongqing
Jia DU ; Zhikai YU ; Yan ZHANG ; Qing GUO ; Shenglin ZHAO ; Xiu LIU ; Hong ZHOU ; Mei HE
China Cancer 2024;33(12):1019-1026
[Purpose]To analyze the compliance and influencing factors of endoscopic screening in high-risk population of upper gastrointestinal cancer(UGC)in Chongqing Municipality.[Methods]Risk assessment of UGC was conducted among residents aged 40~74 years old in the areas covered by the Chongqing Urban Cancer Early Diagnosis and Treatment Program from 2012 to 2019.The residents with high risk of UGC were advised to receive free endoscopic screening in designated hospitals.The compliance and influencing factors of endoscopic screening among high-risk sub-jects were analyzed.[Results]There were 266 611 residents who completed the questionnaires and UGC risk assessment,among whom 48 000(18.00%)were assessed as high risk.A total of 9 162 high-risk individuals received the following endoscopic screening with a compliance rate of 19.09%.Multivariate Logistic regression analysis showed that residents aged 45~64 years old,with high school or above education,divorced or widowed status,occupational exposure to haza-rdous substances,hot food preference,high fat diet,frequent consumption of pickled and dried food,exposure to kitchen fume,psychic trauma or depression,upper gastrointestinal disease his-tory and family history of UGC were likely to accept endoscopic screening;while those aged 70 years old and above,current smokers,and having regular physical exercise were likely to have low compliance.[Conclusion]Among high-risk residents of UGC in Chongqing,the compliance to endoscopic screening needs be improved,health education and management should be targeted to those likely to have low compliance.
10.Efficacy and safety of whole-brain low-dose radiotherapy combined with ICI and intrathecal chemotherapy for leptomeningeal metastases from lung cancer
Xiang LISHA ; Zhang XUANWEI ; Yu MIN ; Xiu WEIGANG ; Zou BINGWEN ; Xu YONG ; Liu YONGMEI ; Zhou LIN ; Xue JIANXIN ; Lu YOU
Chinese Journal of Clinical Oncology 2024;51(18):943-949
Objective:To explore the efficacy and safety of whole-brain low-dose radiotherapy(LDRT)combined with PD-1 inhibitor sin-tilimab and intrathecal pemetrexed(IP)for the treatment of refractory non-small cell lung cancer(NSCLC)with leptomeningeal metastases(LM).Methods:Retrospective analysies were was performed on eight NSCLC patients with LM at the West China Hospital of Sichuan Uni-versity from December 2022 to May 2024.Among the eight patients,there were four were males and four were females,with a median age of 49 years(rangeing,between 34 to 58 years).All patients were treated with whole-brain LDRT combined with immune checkpoint inhibit-or(ICI)and intrathecal chemotherapy regimens,and the therapeutic efficacy was evaluated according to the Response Assessment in Neuro-Oncology(RANO)criteria and the Karnofsky physical status(KPS)score.Adverse reactions were assessed according to the Common Criteria for the Evaluation of Adverse Events(CTCAE version 5.0).Survival analysis was performed using the Kaplan-Meier method.The classification proportion of cerebrospinal fluid subsets before and after treatment was analyzed using by single-cell sequencing,and the differential ana-lysis of gene expression in parallel cells was performed.Results:The best clinical treatment effects in eight patients were were evaluated us-ing the RANO criteria:five patients(62.5%)were evaluated as improved and three(37.5%)as stable.The median KPS score of the eight pa-tients was 30(20-50)before treatment,which was significantly improved to 60(40-90)after treatment(P=0.000 9).The remission rate of neurological symptoms was 100%(8/8)in eight patients.The median neurological progression-free survival(NPFS)was 12 months.The res-ults of single-cell sequencing in CSF of patientss(P1)showed that the proportion of T cells in the patient samples after whole-brain LDRT treatment was significantly higher than that before treatment(6.08%vs.68.87%),and the proportion of tumor cells was significantly lower(12.92%vs.0.6%).The differential analysis of gene expression showed that CCL5 and CXCL13 were significantly upregulated in T cells of CSF after WB-LDRT treatment.Conclusions:The combination of whole-brain LDRT with ICI and IP in the treatment of NSCLC with LM can signific-antly alleviate neurological symptoms,improve quality of life and prolong the NPFS of patients,which is a safe and effective treatment.

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