1.Mechanism of Taishan Panshisan in Inhibiting Oxidative Stress Injury of Trophoblast Cells by Regulating KEAP1/Nrf2/FoxO3 Signaling Pathway
Yangyang DUAN ; Xianglun JI ; Jiahong CHEN ; Jinghang YANG ; Xinyu XIAO ; Shutao CHEN ; Chaorui LIN ; Fan LIN ; Shu JIANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):12-22
ObjectiveTo explore the effect and mechanism of Taishan Panshi powder (TSPSP) on inhibiting oxidative stress injury in human chorionic trophoblast cells (HTR-8/SVneo), and to uelucidate the underlying mechanism of TSPSP in the treatment of spontaneous abortion (SA). MethodsGene differential analysis of SA was performed using the Gene Expression Omnibus (GEO) database and correlated with oxidative stress. Network pharmacology was employed to screen the active components of TSPSP, and a "Chinese medicine-component-target-disease" network was constructed to predict the mechanism of action of TSPSP. For in vitro validation experiments, HTR-8/SVneo cells were divided into blank group, model group, TSPSP-containing serum 2.5%, 5%, 10% groups, and nuclear factor E2-related factor 2 (Nrf2) inhibitor group (ML385, 30 μmol·L-1). Except for the blank group, other groups were stimulated with 150 μmol·L-1 H2O2 for 3 h to establish a cell oxidative stress injury model. After successful modeling, the blank group and model group were given 10% blank serum, each TSPSP-containing serum group was treated with the corresponding concentration of drug-containing serum, and the Nrf2 inhibitor group was additionally given 30 μmol·L-1 ML385 on the basis of 10% TSPSP-containing serum. All groups of cells were continuously cultured under the above conditions for 24 h, and then samples were collected for subsequent detection. Cell viability in each group was detected by CCK-8 assay. Cell migration rate was detected by scratch test. The contents of malondialdehyde (MDA), Fe2+, and Glutathione (GSH) were detected by enzyme-linked immunosorbent assay (ELISA). Intracellular reactive oxygen species (ROS) level was detected by a fluorescent probe (DCF-DA). The protein and mRNA expression levels of Kelch-like ECH-associated protein 1 (KEAP1), Nrf2, and forkhead box protein O3 (FoxO3) in cells were detected by immunofluorescence (IF) and real-time quantitative polymerase chain reaction (Real-time PCR). The protein expression levels of KEAP1, Nrf2, FoxO3, Glutathione peroxidase 4 (GPX4), and superoxide dismutase (SOD) in cells were detected by Western blot. ResultsThe GSE76862 and GSE22490 datasets were obtained from the GEO database. Differential gene analyses showed that the KEAP1, Nrf2, and FoxO3 genes were all associated with the disease. After matching with the oxidative stress pathway, nine significantly differential pathways were identified (P<0.05), among which three contained the target genes Nrf2 and FoxO3. A total of 246 active ingredient targets of TSPSP and 2 804 SA-related targets were obtained through network pharmacology, and 154 potential action targets were obtained after taking the intersection. Topological analysis showed that targets such as KEAP1 and Nrf2 exhibited high degree values. GO and KEGG enrichment analyses indicated that the intersection targets were mainly involved in oxidative stress response, FOXO and MAPK signaling pathways, etc. In in vitro experiments, compared with the blank group, the cell viability in the model group was significantly decreased (P<0.01). Compared with the model group, the cell viability in each TSPSP-containing serum group was significantly increased (P<0.01). Compared with the 10% TSPSP-containing serum group, the cell viability in the ML385 group decreased to approximately 70% (P<0.01). Compared with the blank group, the model group showed significantly increased contents of MDA, Fe2+, and ROS, decreased GSH expression (P<0.01), significantly reduced cell migration rate (P<0.01), and increased protein and mRNA expression levels of KEAP1 and FoxO3 (P<0.01), while decreased protein and mRNA expression levels of Nrf2, GPX4, and SOD (P<0.01). Compared with the model group, each TSPSP-containing serum group showed significantly decreased contents of MDA, Fe²⁺, and ROS, increased GSH expression (P<0.01), significantly increased migration rate (P<0.01), significantly decreased protein and mRNA expression levels of KEAP1 and FoxO3 (P<0.05, P<0.01), and significantly increased protein and mRNA expression levels of Nrf2, GPX4, and SOD (P<0.05, P<0.01). Compared with the 10% TSPSP-containing serum group, the ML385 group showed reversed trends in all indicators (P<0.05, P<0.01). ConclusionTSPSP can inhibit H2O2-induced oxidative stress injury of trophoblast cells, and its mechanism of action may be related to the drug activating the KEAP1/Nrf2/FoxO3 signaling pathway.
2.Mechanism of Taishan Panshisan in Inhibiting Oxidative Stress Injury of Trophoblast Cells by Regulating KEAP1/Nrf2/FoxO3 Signaling Pathway
Yangyang DUAN ; Xianglun JI ; Jiahong CHEN ; Jinghang YANG ; Xinyu XIAO ; Shutao CHEN ; Chaorui LIN ; Fan LIN ; Shu JIANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):12-22
ObjectiveTo explore the effect and mechanism of Taishan Panshi powder (TSPSP) on inhibiting oxidative stress injury in human chorionic trophoblast cells (HTR-8/SVneo), and to uelucidate the underlying mechanism of TSPSP in the treatment of spontaneous abortion (SA). MethodsGene differential analysis of SA was performed using the Gene Expression Omnibus (GEO) database and correlated with oxidative stress. Network pharmacology was employed to screen the active components of TSPSP, and a "Chinese medicine-component-target-disease" network was constructed to predict the mechanism of action of TSPSP. For in vitro validation experiments, HTR-8/SVneo cells were divided into blank group, model group, TSPSP-containing serum 2.5%, 5%, 10% groups, and nuclear factor E2-related factor 2 (Nrf2) inhibitor group (ML385, 30 μmol·L-1). Except for the blank group, other groups were stimulated with 150 μmol·L-1 H2O2 for 3 h to establish a cell oxidative stress injury model. After successful modeling, the blank group and model group were given 10% blank serum, each TSPSP-containing serum group was treated with the corresponding concentration of drug-containing serum, and the Nrf2 inhibitor group was additionally given 30 μmol·L-1 ML385 on the basis of 10% TSPSP-containing serum. All groups of cells were continuously cultured under the above conditions for 24 h, and then samples were collected for subsequent detection. Cell viability in each group was detected by CCK-8 assay. Cell migration rate was detected by scratch test. The contents of malondialdehyde (MDA), Fe2+, and Glutathione (GSH) were detected by enzyme-linked immunosorbent assay (ELISA). Intracellular reactive oxygen species (ROS) level was detected by a fluorescent probe (DCF-DA). The protein and mRNA expression levels of Kelch-like ECH-associated protein 1 (KEAP1), Nrf2, and forkhead box protein O3 (FoxO3) in cells were detected by immunofluorescence (IF) and real-time quantitative polymerase chain reaction (Real-time PCR). The protein expression levels of KEAP1, Nrf2, FoxO3, Glutathione peroxidase 4 (GPX4), and superoxide dismutase (SOD) in cells were detected by Western blot. ResultsThe GSE76862 and GSE22490 datasets were obtained from the GEO database. Differential gene analyses showed that the KEAP1, Nrf2, and FoxO3 genes were all associated with the disease. After matching with the oxidative stress pathway, nine significantly differential pathways were identified (P<0.05), among which three contained the target genes Nrf2 and FoxO3. A total of 246 active ingredient targets of TSPSP and 2 804 SA-related targets were obtained through network pharmacology, and 154 potential action targets were obtained after taking the intersection. Topological analysis showed that targets such as KEAP1 and Nrf2 exhibited high degree values. GO and KEGG enrichment analyses indicated that the intersection targets were mainly involved in oxidative stress response, FOXO and MAPK signaling pathways, etc. In in vitro experiments, compared with the blank group, the cell viability in the model group was significantly decreased (P<0.01). Compared with the model group, the cell viability in each TSPSP-containing serum group was significantly increased (P<0.01). Compared with the 10% TSPSP-containing serum group, the cell viability in the ML385 group decreased to approximately 70% (P<0.01). Compared with the blank group, the model group showed significantly increased contents of MDA, Fe2+, and ROS, decreased GSH expression (P<0.01), significantly reduced cell migration rate (P<0.01), and increased protein and mRNA expression levels of KEAP1 and FoxO3 (P<0.01), while decreased protein and mRNA expression levels of Nrf2, GPX4, and SOD (P<0.01). Compared with the model group, each TSPSP-containing serum group showed significantly decreased contents of MDA, Fe²⁺, and ROS, increased GSH expression (P<0.01), significantly increased migration rate (P<0.01), significantly decreased protein and mRNA expression levels of KEAP1 and FoxO3 (P<0.05, P<0.01), and significantly increased protein and mRNA expression levels of Nrf2, GPX4, and SOD (P<0.05, P<0.01). Compared with the 10% TSPSP-containing serum group, the ML385 group showed reversed trends in all indicators (P<0.05, P<0.01). ConclusionTSPSP can inhibit H2O2-induced oxidative stress injury of trophoblast cells, and its mechanism of action may be related to the drug activating the KEAP1/Nrf2/FoxO3 signaling pathway.
3.Genetic disease diagnosis and treatment in Shanghai: Survey and countermeasures for clinical genetics specialist training.
Xiaoju HUANG ; Lin HAN ; Li CAO ; Taosheng HUANG ; Duan MA ; Jian WANG ; Wenjuan QIU ; Fanyi ZENG ; Luming SUN ; Chenming XU ; Songchang CHEN ; Xinyu KUANG ; Hong TIAN
Chinese Journal of Medical Genetics 2026;43(4):241-247
OBJECTIVE:
To investigate the current status of clinical genetics specialization development and the diagnostic and therapeutic capabilities for hereditary diseases across medical institutions in Shanghai, and to assess the necessity and feasibility of establishing training bases for clinical genetics specialists.
METHODS:
By employing a cross-sectional survey design, the Clinical Genetics Committee of Shanghai Medical Association has conducted questionnaire surveys from March to April 2025 across 54 healthcare institutions in Shanghai (including 33 tertiary hospitals and 21 secondary hospitals). The survey involved administrative departments and medical personnel from 15 clinical specialties. The survey has covered current genetic disease diagnosis and treatment practices, relevant and specialised disease types, genetic department establishment, testing capabilities, personnel teams, and training requirements.
RESULTS:
The results revealed that 78.0% of clinical departments surveyed had treated patients with hereditary disorders. Shanghai possesses diagnostic and therapeutic expertise for over 95% of hereditary diseases listed in its rare disease catalogue, reflecting both the practical clinical demand for such conditions and the city's overall diagnostic and therapeutic strengths in this field. Nevertheless, significant disparities exist in the development of genetics departments across different tiers of healthcare institutions. Resources for genetic testing capabilities (including molecular, cellular, and biochemical testing) are also unevenly distributed across different tiers of hospitals. The survey further revealed that only 26.0% of departments believe that their current physician structure fully meets the diagnostic and treatment demands. Over 90% of departments consider standard training for clinical genetic specialists necessary, with 74.0% expressing willingness to participate in establishing training bases. Based on above findings and thorough deliberation, the Clinical Genetics Committee of the Shanghai Medical Association proposes advancing specialist training and discipline development through establishing a standard training system. The committee has drafted a three-year training protocol featuring a "joint training"-centered model, recommending a pilot-first, dynamically optimized strategy for steadily advancing training base development.
CONCLUSION
Shanghai faces substantial demand for genetic disease diagnosis and treatment, yet exhibits shortcomings in clinical genetics specialization development, resource allocation, and talent pipeline cultivation. To establish a standard training system holds significant practical importance and is underpinned by a broad demand.
Humans
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China
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Surveys and Questionnaires
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Genetic Diseases, Inborn/genetics*
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Cross-Sectional Studies
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Genetics, Medical/education*
;
Genetic Testing
4.Progress of Anti-osteoporosis Research of Traditional Chinese Medicine Based on Zebrafish Model
Henghong WANG ; Xinyu FAN ; Yihan GAO ; Zhilue LUO ; Peng DUAN ; Yunfeng ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):323-330
Osteoporosis (OP) is a systemic metabolic disease with a strong correlation with age. The prevalence of osteoporosis is rising annually as a consequence of the growing issue of population ageing. The current treatments for OP have numerous shortcomings. In contrast, traditional Chinese medicine has a long history and a rich species diversity. Furthermore, recent years have seen an increase in the number of studies examining the anti-OP properties of traditional Chinese medicine. This may provide a safe and effective alternative strategy for the treatment of OP. The zebrafish, due to its favourable optical transparency and high homology with human genes, has been extensively employed as an animal research model in the investigation of human skeletal-related disease mechanisms and drug screening. This paper presents a review of anti-osteoporosis studies of traditional Chinese medicine using zebrafish as a model for osteoporosis. It also provides a summary of the experimental evaluation methods involved in such studies, an analysis of the current status of traditional Chinese medicine in the treatment of osteoporosis using zebrafish as a model, and a summary of the mechanism of action and the signalling pathways involved in traditional Chinese medicine in the anti-osteoporosis treatment of zebrafish. The current research status of Chinese medicine in the treatment of OP was analysed, as well as the mechanism of action of Chinese medicine against OP and the signalling pathways involved. Furthermore, the advantages and disadvantages of various zebrafish modelling methods of OP were compared with those of traditional animal models. The objective of this study is to provide a reference for the evaluation method of the zebrafish model in the study of bone-related diseases, as well as for the study of the mechanism of action of traditional Chinese medicine against OP and for the reference of the research and development of new drugs.
5.Preliminary study on the role of TM9SF2 knockdown in promoting the activity of the type I interferon signaling pathway to inhibit vesicular stomatitis virus replication.
Kang LI ; Xinyu WANG ; Ran YE ; Lingyun GUO ; Linxu WANG ; Nuo XU ; Tong ZHANG ; Xiaotao DUAN
Chinese Journal of Cellular and Molecular Immunology 2025;41(6):481-487
Objective To explore the effect of the knockdown of transmembrane 9 superfamily protein member 2 (TM9SF2) on the replication of vesicular stomatitis virus (VSV), and investigate its role in the mechanism of antiviral innate immunity. Methods Small interfering RNA (siRNA) was used to knock down the TM9SF2 gene in human non-small cell lung cancer A549 cells. The CCK-8 method was used to assess cell proliferation. A VSV-green fluorescent protein (VSV-GFP) infected cell model was established. The plaque assay was used to measure the viral titer in the supernatant. RT-qPCR and Western blotting were employed to quantify the mRNA and protein levels of VSV genome replication in A549 cells following VSV infection, as well as the expression of interferon β (IFN-β) mRNA and interferon regulatory factor 3 (IRF3) protein phosphorylation following polyinosinic-polycytidylic acid (poly(I:C)) stimulation. Results Compared to the negative control, the knockdown of TM9SF2 exhibited a significant effect, with no observed impact on A549 cell proliferation. The VSV-GFP infected A549 cell model was successfully established. After viral stimulation, fluorescence intensity was reduced following TM9SF2 knockdown, and the mRNA and protein levels of VSV were significantly downregulated. The viral titer of VSV was decreased. After poly(I:C) stimulation, TM9SF2 knockdown significantly upregulated the mRNA level of IFN-β and the phosphorylation level of IRF3 protein. Conclusion The knockdown of TM9SF2 inhibits the replication of vesicular stomatitis virus, and positively regulates the type I interferon signaling pathway, thus enhancing the host's antiviral innate immune response.
Humans
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Virus Replication/genetics*
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Signal Transduction
;
Membrane Proteins/metabolism*
;
A549 Cells
;
Vesiculovirus/physiology*
;
Interferon-beta/metabolism*
;
Interferon Regulatory Factor-3/genetics*
;
Interferon Type I/metabolism*
;
Vesicular Stomatitis/immunology*
;
Gene Knockdown Techniques
;
Vesicular stomatitis Indiana virus/physiology*
;
RNA, Small Interfering/genetics*
6.Progress and challenges of functionalized bacterial encapsulation: A novel biotechnology for next-generation biotherapeutics.
Ying ZHANG ; Yuwei WU ; Xinyu ZHAO ; Qinghua YE ; Lulu CAO ; Ming LIU ; Bao GAO ; Qinya NIU ; Nuo CHEN ; Zixuan DUAN ; Yu DING ; Juan WANG ; Moutong CHEN ; Ying LI ; Qingping WU
Acta Pharmaceutica Sinica B 2025;15(10):5167-5191
The disturbance of the human microbiota influences the occurrence and progression of many diseases. Live therapeutic bacteria, with their genetic manipulability, anaerobic tendencies, and immunomodulatory properties, are emerging as promising therapeutic agents. However, their clinical applications face challenges in maintaining activity and achieving precise spatiotemporal release, particularly in the harsh gastrointestinal environment. This review highlights the innovative bacterial functionalized encapsulation strategies developed through advances in physicochemical and biological techniques. We comprehensively review how bacterial encapsulation strategies can be used to provide physical barriers and enhanced adhesion properties to live microorganisms, while introducing superior material properties to live bacteria. In addition, this review outlines how bacterial surface coating can facilitate targeted delivery and precise spatiotemporal release of live bacteria. Furthermore, it elucidates their potential applications for treating different diseases, along with critical perspectives on challenges in clinical translation. This review comprehensively analyzes the connection between functionalized bacterial encapsulation and innovative biomedical applications, providing a theoretical reference for the development of next-generation bacterial therapies.
7.The study of contributors and obstacles to the evidence transformation of airway humidification manage-ment for hospitalized patients who receive laryngectomy and tracheostomy without mechanical ventilation
Mingyue LUO ; Ting ZHENG ; Le PAN ; Yajie LI ; Shumeng ZHANG ; Xinyu DUAN ; Yongxia DING
Chinese Journal of Nursing 2025;60(13):1603-1609
Objective To explore the potential contributors and obstacles of evidence translation for airway hu-midification management in hospitalized patients with laryngectomy tracheostomy and non-mechanical ventilation,so as to provide references for clinical evidence-based practice.Methods An interview outline and questionnaire were developed according to the consolidated framework for implementation research(CFIR).Using purposive sampling,12 healthcare professionals from Department of Otorhinolaryngology,Head and Neck Surgery of a tertiary hospital in Shanxi Province were recruited for semi-structured interviews,and thematic analysis was applied to extract main themes.The interview themes were transformed into survey items,and a survey was conducted among 42 healthcare professionals in the same department.Results Totally 16 contributors and 20 obstacles were identified across 4 domains:the credibility of the evidence and research team,the external support environment for evidence-based practice,the internal conditions for evidence-based practice,and the role recognition of implementers.Contributors include efficient internal collaboration and communication,and rigorous processes for evidence acquisition.Obstacles include insufficient educational resources,low patient knowledge acceptance capacity,lack of professional value a-mong healthcare staff.Conclusion Evidence translation of the humidification management for patients with non-mechanical ventilation after laryngectomy and tracheostomy was influenced by various factors.Future efforts should focus on constructing targeted airway humidification education content and an evaluation index system,and enhanc-ing the professional value and practical leadership of nursing staff.
8.Clinical features and prognosis of patients with primary sclerosing cholangitis:An analysis of 107 cases
Tongtong MENG ; Weijia DUAN ; Xinyu LI ; Junqi NIU ; Huiguo DING ; Ying HAN ; Wen XIE ; Lu ZHOU ; Bangmao WANG ; Liping GUO ; Jie LI ; Bei JIA ; Lingyi ZHANG ; Liang WANG ; Xiaoqian XU ; Yu WANG ; Xiaojuan OU ; Xinyan ZHAO ; Hong YOU ; Jidong JIA ; Yuanyuan KONG
Journal of Clinical Hepatology 2025;41(7):1337-1343
Objective To describe the clinical features of patients with primary sclerosing cholangitis(PSC)in China based on a nationwide multicenter patient cohort,and to investigate the risk factors for prognosis.Methods A retrospective cohort study was conducted among the patients with a confirmed diagnosis of PSC based on the electronic medical record system of seven grade A tertiary hospitals across the country,and related data were extracted.The Mann-Whitney U test was used for comparison of continuous data between groups,and the chi-square test was used for comparison of categorical data between groups.The Kaplan-Meier method was used to estimate liver transplant-free survival,and the log-rank test was used for comparison of survival rate between PSC patients with different features.The Cox regression model was used to identify independent risk factors for the prognosis of PSC patients and the interactions between key factors.Results A total of 107 patients were enrolled,among whom 55.6%(55/99)had large-duct PSC and 29.0%(31/107)had comorbidity with inflammatory bowel disease(IBD).The positivity rate of anti-neutrophil cytoplasmic antibody(ANCA)was 32.9%(24/73),and 50.0%(40/80)of the patients had an increase in IgG/IgM.The median symptom-to-diagnosis interval was 1 year(<1-4.0),and 38.3%(41/107)of the patients had progressed to decompensated cirrhosis at the time of diagnosis.The median liver transplant-free survival time was 114 months(95%confidence interval[CI]:62-166),with a 5-year survival rate of 65.7%.The multivariate analysis showed that an increase in total bile acid(TBA)(hazard ratio[HR]=1.006,95%CI:1.002-1.010,P=0.001)and a prolonged symptom-to-diagnosis interval(HR=1.252,95%CI:1.059-1.480,P=0.009)were independent risk factors for prognosis.The interaction analysis showed that compared with the female patients with TBA<50 μmol/L,both male and female patients with TBA≥50 μmol/L had a significant increase in the risk of liver transplantation or death(male:HR=16.563,95%CI:2.103-130.449,P<0.001;female:HR=17.009,95%CI:2.113-136.934,P<0.001),and compared with the patients with an age of<45 years and a TBA level of<50 μmol/L,the patients with an age of≥45 years and a TBA level of≥50 μmol/L had a significant increase in the risk of liver transplantation or death(HR=10.729,95%CI:1.325-86.859,P=0.026).Compared with the female patients with an symptom-to-diagnosis interval of≤2 years,the male patients with a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.825,95%CI:1.725-13.644,P=0.003),and compared with the patients with an age of<45 years and a symptom-to-diagnosis interval of≤2 years,the patients with an age of<45 years and a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.983,95%CI:1.366-18.173,P=0.015).Conclusion Compared with the reports from Western countries,large-duct PSC is also the main type of PSC in China,but with a relatively low proportion,and there is also a relatively low proportion of patients with IBD or positive ANCA.An increase in TBA and a prolonged symptom-to-diagnosis interval are independent risk factors for prognosis,with significant interactions with age and sex.This suggests that early screening and intervention should be enhanced to improve prognosis.
9.Risk factors analysis of non-small cell lung cancer immune checkpoint inhibitor-related pneumonia and the construction and validation of nomogram prediction model
Xinyu MA ; Kaituo ZHANG ; Xin SONG ; Qiaona SU ; Jianfeng ZHANG ; Haifeng ZHAO ; Jinfang ZHAI ; Jianchun DUAN ; Jianxin ZHANG
Cancer Research and Clinic 2025;37(8):584-590
Objective:To analyze risk factors for immune checkpoint inhibitor-related pneumonitis (CIP) in non-small cell lung cancer (NSCLC) patients based on clinical and radiological characteristics, and to develop and validate a nomogram model for predicting the risk of CIP.Methods:A retrospective case-controlled study was conducted. The clinical data of 159 patients diagnosed with NSCLC in Shanxi Province Cancer Hospital between January 2020 and December 2023 who received immune checkpoint inhibitor (ICI) therapy were retrospectively analyzed. Based on the development of CIP after immunotherapy, the patients were divided into the CIP group (30 cases) and the control group (129 cases). The clinical data of NSCLC patients, hematological indicators and the data of imaging characteristics before their first ICI treatment were collected. Quantitative assessments were performed on pretreatment chest CT images, including lung total tumor volume, number of involved lung segments, and pulmonary infection index. Logistic regression analysis was used to screen out the factors influencing the development of CIP. R 4.3.0 statistical software was used to construct a nomogram model for predicting CIP based on the statistically significant risk factors identified in the multivariate logistic regression analysis. The predictive performance of the model was evaluated by using receiver operating characteristic (ROC) curves and the area under the curve (AUC). Calibration curves and decision curve analysis (DCA) were employed to assess the model's consistency and clinical benefit.Results:There were statistically significant differences in the proportions of patients with a history of chest radiotherapy and those receiving different immunotherapy regimens between the control group and the CIP group (both P < 0.001). The difference in the lactate dehydrogenase (LDH) [ M ( IQR)] between the both groups was statistically significant [211.00 U/L (57.00 U/L) vs. 276.00 U/L (136.00 U/L), Z = -3.41, P < 0.001]; additionally, the difference in lung status score between the 2 groups was statistically significant ( P < 0.001). Multivariate logistic regression analysis revealed that a history of chest radiotherapy (with vs. without: OR = 4.200, 95% CI: 1.466-12.036), the combination of immunotherapy (monotherapy vs. the combined therapy: OR = 0.106, 95% CI: 0.022-0.509), LDH ≥ 255.5 U/L (< 255.5 U/L vs. ≥ 255.5 U/L: OR = 0.988, 95% CI: 0.981-0.995), and severe lung status score(mild vs. moderate vs. severe: OR = 0.187, 95% CI: 0.059-0.593) were independent risk factors for CIP development in NSCLC patients after immunotherapy (all P < 0.05). A nomogram model for predicting CIP occurrence was constructed based on chest radiotherapy history, immunotherapy regimen, LDH, and lung status score. ROC curve analysis showed the AUC was 0.878 (95% CI: 0.813-0.942). The calibration curve demonstrated the good consistency between the predicted risk probability of CIP and the observed outcomes; DCA indicated that the model had favorable clinical benefits. Conclusions:The constructed nomogram prediction model shows a good predictive performance.
10.Changes and therapeutic effects of Ginkgo biloba extract,Donepezil and combination therapy on gray matter volume and cortical morphology in patients with cognitive dysfunction
Xinyu DU ; Lihui DUAN ; Peng YAN
Journal of Clinical Neurology 2025;38(4):268-275
Objective To investigate the changes and therapeutic effects of Ginkgo biloba extract(GBE),Donepezil and combination therapy on gray matter volume and cortical morphology in patients with cognitive dysfunction.Methods According to different treatment methods,59 patients with mild cognitive impairment and Alzheimer's disease were divided into GBE group(n=20),Donepezil group(n=20)and combined treatment group(n=19).Before and after treatment,the patients were evaluated by MMSE,Alzheimer's disease assessment scale-cognitive subscale(ADAS-cog),instrumental activities of daily living scale(IADL),geriatric depression scale(GDS),neuropsychiatric inventory(NPI),and quality of life-Alzheimer's disease scale(QOL-AD).Before and after treatment,T1-weighted structural sequence images were acquired using cranial MRI,and voxel-based morphometry(VBM)and cortical morphological analyses were performed.Results There was no significant difference in the scores of MMSE,ADAS-cog,GDS,NPI,IADL and QOL-AD among the GBE group,Donepezil group and combined treatment group before and after treatment(all P>0.05).Compared with those before treatment,there were significant differences in MMSE and ADAS-cog scores in the GBE group,MMSE,ADAS-cog,IADL and NPI scores in Donepezil group,and MMSE,ADAS-cog and IADL scores in combined treatment group after treatment(P<0.05-0.01).The volume of gray matter in the cerebellar region of GBE group was significantly increased(voxel P<0.005,cluster P<0.05,GRF corrected,one-tailed test).In the left putamen region,the difference of gray matter volume in the combined treatment group was significantly higher than that in the GBE group and Donepezil group(all P<0.01).In the right putamen area,there was no significant difference among the three groups(all P>0.05).In the right hippocampus,the difference in gray matter volume between combined treatment group and GBE group was significantly higher than that in Donepezil group(all P<0.05).In the left hippocampus,the difference in gray matter volume between GBE group and combined treatment group was significantly higher than that in Donepezil group(all P<0.001).Correlation analysis showed that the volume of left and right hippocampal gray matter was positively correlated with MMSE before treatment(r=0.352,P=0.008;r=0.424,P=0.001),and negatively correlated with ADAS-cog(r=-0.336,P=0.012;r=-0.362,P=0.007)and IADL scores(r=-0.345,P=0.01;r=-0.312,P=0.02);after treatment,the gray matter volume of the left and right hippocampus was strong positively correlated with MMSE(r=0.582,P<0.001;r=0.560,P<0.001),strong negatively correlated with ADAS-cog(r=-0.512,P<0.001;r=-0.567,P<0.001)and IADL(r=-0.454,P<0.001;r=-0.435,P<0.001).The difference of gray matter volume in the right hippocampus before and after treatment was only weakly negatively correlated with GDS score(r=-0.269,P=0.047),the gray matter volume of right hippocampus was positively correlated with GDS score before treatment(r=0.451,P<0.001),and this correlation disappeared after intervention(r=0.131,P=0.340).There was no correlation between the difference of gray matter volume before and after treatment in the left hippocampus and the neuropsychological test scores(all P>0.05).The cortex of the superior parietal lobule and inferior parietal lobe in the combined treatment group was significantly thickened(all P<0.05,FWE corrected).Conclusions GBE,Donepezil and the combined therapy have significant effects on the reduction of cognitive function,and the changes of brain gray matter and cortical morphology are different.GBE improve the volume of the posterior superior cerebellum and other regions,and the combined therapy improve the cortical thickness of the superior parietal lobule and the inferior parietal lobule.

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