1.Development of a postoperative recurrence prediction model for stage Ⅰ non-small cell lung cancer patients using multimodal data based on machine learning
Di ZHANG ; Yi WU ; Yu XU ; Shuai WANG ; Yue HU ; Huawei CHEN ; Nana HU ; Rong HE ; Xueling TONG ; Mengxia LI
Journal of Army Medical University 2025;47(14):1602-1611
Objective To develop a machine learning model integrating preoperative chest CT radiomic features with clinical data for predicting 5-year postoperative recurrence risk in stage Ⅰ non-small cell lung cancer(NSCLC)patients undergoing surgical resection.Methods A total of 217 patients with pathologically confirmed stage Ⅰ NSCLC(selected from 778 initially screened cases based on our inclusion and exclusion criteria)treated in Army Medical Center of PLA between January 2014 and December 2019 were retrospectively enrolled,including 53 recurrence cases and 164 non-recurrence cases within 5-year follow-up.They were randomly divided into a training set(n=173)and a validation set(n=44)in a ratio of 8:2.Radiomic models were established based on extracted features from tumor-dominant regions of interest(ROI)on CT images,while clinical models were developed using demographic characteristics and preoperative laboratory examinations.A combined model was further constructed by integrating both feature sets,and model performance was compared to identify the optimal predictive model.Results This study screened the features from non-contrast CT images and ultimately selected 7 radiomic features for constructing radiomic model.Among 6 machine learning algorithms,the adaptive boosting(Adaboost)model demonstrated the best overall predictive performance,with an area under the curve(AUC)of 0.866(95%CI:0.808~0.923;accuracy:0.832,specificity:0.884)in the training set and of 0.806(95%CI:0.630~0.983;accuracy:0.795,specificity:0.971)in the validation set.Univariate and multivariate logistic regression analyses identified 4 clinical features for clinical model construction.The clinical model achieved an AUC value of 0.874(95%CI:0.821~0.928;accuracy:0.827,specificity:0.891)in the training set and 0.813(95%CI:0.677~0.948;accuracy:0.636,specificity:0.600)in the validation set.By integrating the 7 radiomic features and 4 clinical features using a feature-level fusion strategy,the combined model exhibited further improved predictive performance,with an AUC value of 0.953(95%CI:0.924~0.983;accuracy:0.884,specificity:0.860)and 0.852(95%CI:0.729~0.976;accuracy:0.682,specificity:0.629),respectively in the training set and the validation set.Conclusion The combined model integrating preoperative CT radiomic features with clinical risk factors may provide an evidence-based framework for evaluating 5-year postoperative recurrence risk in stage Ⅰ NSCLC patients.
2.Evolution-guided design of mini-protein for high-contrast in vivo imaging.
Nongyu HUANG ; Yang CAO ; Guangjun XIONG ; Suwen CHEN ; Juan CHENG ; Yifan ZHOU ; Chengxin ZHANG ; Xiaoqiong WEI ; Wenling WU ; Yawen HU ; Pei ZHOU ; Guolin LI ; Fulei ZHAO ; Fanlian ZENG ; Xiaoyan WANG ; Jiadong YU ; Chengcheng YUE ; Xinai CUI ; Kaijun CUI ; Huawei CAI ; Yuquan WEI ; Yang ZHANG ; Jiong LI
Acta Pharmaceutica Sinica B 2025;15(10):5327-5345
Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with 99mTc, 68Ga, and 18F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.
3.Study on the Detection of MMP-2,-7,-9,and-12 Enzymatic Activity Using CEACAM1-Derived Fluorescent Peptide Substrate Site 84
Wen WAN ; Yujia YE ; Xiaona YANG ; Lihong YANG ; Huawei WANG ; Ling DONG ; Lixing CHEN ; Zhaohui MENG
Journal of Kunming Medical University 2025;46(2):9-16
Objective To explore the the detection of MMP-2,-7,-9,and-12 enzymatic activity using the CEACAM1-derived fluorescent peptide substrate Site 84,investigating the application of substrate Site 84 to distinguishing between MMP-2 and MMP-9 in the gelatinase spectrum of MMPs.Methods The fluorescent enzymatic method was employed to observe the detection of MMP-2,-7,-9,and-12 enzymatic activity using substrate Site 84;further observations were made on the sensitivity and specificity of substrate Site 84 to enzymatic activity of MMP-2 and MMP-9 within the gelatinase spectrum;the kinetic parameters(Km and Kcat)of the enzymatic reaction between substrate Site 84 and MMP-2 were obtained.Results Using Site 84 as a substrate,enzymic kinetics curves for MMP-12,-7,-2 were obtained,but no enzymatic activity curve for MMP-9 was observed.Furthermore,Site 84 specifically detected the enzymatic activity of MMP-2 within the gelatinase spectrum,capable of detecting low concentration(0.6 μM)of MMP-2 enzymatic activity,but no obvious enzymatic reaction was observed for high concentration(6 μM)of MMP-9;the kinetics parameters for the enzymatic reaction between Site 84 and MMP-2 were Km=315 μM,Kcat/Km=2 565/MS.Conclusion The CEACAM1-derived substrate Site 84 serves as a novel fluorescent peptide substrate,enabling the acquisition of enzymatic activity curves for MMP-12,-7 and-2,and specifically detecting the enzymatic activity of MMP-2 within the MMP gelatinase spectrum.
4.Predictive Value and Model Construction of C-reactive Protein/D-dimer Ratio and Fibrinogen/Albumin Ratio for the Occurrence of MACE after PCI in Patients with Coronary Artery Disease
Shumei QIU ; Haiyan ZHANG ; Huawei WANG
Journal of Kunming Medical University 2025;46(7):92-100
Objective To comprehensively assess the predictive value of C-reactive protein(CRP)/D-dimer(D-D)and albumin/fibrinogen(FAR)in predicting major adverse cardiovascular events(MACE)after percutaneous coronary intervention(PCI)in patients with coronary heart disease(CHD)and to construct a nomogram model for predicting post-procedural MACE in CHD patients.Methods A retrospective study was conducted on 201 CHD patients who underwent PCI at the First Affiliated Hospital of Kunming Medical University between June 2022 and March 2025.These patients were divided into MACE group(n=77)and non-MACE group(n=124)based on whether MACE occurred or not.84 CHD patients from another medical center were also collected as the validation set.The expression levels of CRP/D-D and FAR were compared between the two groups;independent predictors of postoperative MACE in CHD patients were screened by univariate and multivariate logistic regression analyses;the predictive value of CRP/D-D and FAR for the occurrence of postoperative MACE in CHD patients was assessed using ROC curves;A nomogram model was established integrating indicators such as CRP/D-D and FAR,and internal and external validations of the nomogram model were conducted using ROC curves,calibration curves,and decision curve analysis(DCA)curves.Results Compared with CHD patients in the non-MACE group,CRP/D-D and FAR levels were significantly higher in the MACE group(P<0.05).Multivariate analysis showed that age,NTproBNP,WBC,CRP/D-D,and FAR were independent risk factors for postoperative MACE in CHD patients(P<0.05).ROC curve analysis indicated that the AUC predicted by CRP/D-D combined with FAR was higher than that of CRP/D-D alone(Z=3.473,P<0.001),and FAR alone(Z=2.812,P<0.05).The Nomogram model constructed based on the aforementioned factors was validated internally and externally,and the results showed that the Nomogram model had good calibration,excellent discriminative ability,and reliable clinical utility,accurately predicting the risk of postoperative MACE.Conclusion The CRP/D-D ratio and FAR,as emerging composite biomarkers,showed significant predictive ability in predicting the risk of MACE after PCI in patients with CHD,providing a new reliable tool for clinical risk stratification.
5.Construction and application of the "Huaxi Hongyi" large medical model
Rui SHI ; Bing ZHENG ; Xun YAO ; Hao YANG ; Xuchen YANG ; Siyuan ZHANG ; Zhenwu WANG ; Dongfeng LIU ; Jing DONG ; Jiaxi XIE ; Hu MA ; Zhiyang HE ; Cheng JIANG ; Feng QIAO ; Fengming LUO ; Jin HUANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(05):587-593
Objective To construct large medical model named by "Huaxi HongYi"and explore its application effectiveness in assisting medical record generation. Methods By the way of a full-chain medical large model construction paradigm of "data annotation - model training - scenario incubation", through strategies such as multimodal data fusion, domain adaptation training, and localization of hardware adaptation, "Huaxi HongYi" with 72 billion parameters was constructed. Combined with technologies such as speech recognition, knowledge graphs, and reinforcement learning, an application system for assisting in the generation of medical records was developed. Results Taking the assisted generation of discharge records as an example, in the pilot department, after using the application system, the average completion times of writing a medical records shortened (21 min vs. 5 min) with efficiency increased by 3.2 time, the accuracy rate of the model output reached 92.4%. Conclusion It is feasible for medical institutions to build independently controllable medical large models and incubate various applications based on these models, providing a reference pathway for artificial intelligence development in similar institutions.
6.Exploration of the comprehensive management practice pathway for long-term prescription medications in psychiatry
Mengxi NIU ; Pengfei LI ; Xue WANG ; Shanshan LIU ; Yanxiang CAO ; Hongyan ZHUANG ; Hu WANG ; Li BAI ; Huawei LI ; Fei PAN ; Sha SHA ; Qing’e ZHANG
China Pharmacy 2025;36(19):2366-2371
OBJECTIVE To explore comprehensive management and potential issues associated with long-term prescriptions medications of psychiatry, in order to provide a reference for the comprehensive management of long-term prescriptions of psychiatry in psychiatric hospitals and other medical institutions’ pharmacies. METHODS Starting from the applicable principles for long-term prescriptions of psychiatry, this study introduced the standardized assessment and precautions before issuing long-term prescriptions, the formulation and adjustment of the drug list, as well as the rational management of the long-term prescriptions. It also analyzed potential issues that may arise in the comprehensive management of long-term prescription medications and proposed corresponding countermeasures and suggestions. RESULTS & CONCLUSIONS Prior to initiating long-term prescriptions, a standardized assessment should be conducted on patients from the aspects of their psychiatric condition and long-term potential risk factors, pharmacological treatment plans and other non-pharmacological therapies, physical illnesses. Additionally, healthcare providers should fulfill their obligation to inform patients or their family members. The comprehensive management of long-term prescription medications should be jointly established and improved by multiple departments, and the formulation of drug catalogs should avoid including drugs with potential social harm or medication risks while complying with policy requirements. Furthermore, measures such as adding special identifiers to long-term prescriptions, providing patients with reminders about (No.YGLX202537) prescription expiration, or offering online consultations can also effectively enhance the rationality of medication use under long-term prescriptions. Currently, the implementation of long-term prescriptions in psychiatry remains challenged by inconsistencies in prescription duration, incomplete coverage of diagnostic categories, poor patient adherence, and the risk of deviation in clinical assessments. In this regard, measures such as collaborating with multiple departments to strengthen long-term prescription information management, providing matching pharmaceutical services, ensuring the quality and rationality of long-term prescription implementation, and using modern methods to screen high-risk patients can be taken to improve patient medication compliance and safety.
7.Analysis of the relationship between serum Melatonin,MIP-1α,NLRP3 inflammasome and prognosis in children with acute respiratory distress syndrome
Juan YU ; Jian WANG ; Huawei DU ; Xueqin YANG ; Jie YANG
International Journal of Laboratory Medicine 2024;45(11):1331-1337
Objective To study the relationship between serum Melatonin,macrophage inflammatory pro-tein-1α(MIP-1α)and nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflamma-some and prognosis in children with acute respiratory distress syndrome(ARDS).Methods A total of 140 children with ARDS who were admitted to the hospital from January 2021 to January 2023 were enrolled as the ARDS group,and 100 healthy children who underwent physical examination during the same period were enrolled as the control group.According to the clinical outcome on 28 d after admission,the children with ARDS were divided into a death group(29 cases)and a survival group(111 cases).Enzyme-linked immu-nosorbent assay was used to detect the serum levels of Melatonin,MIP-1α,interleukin(IL)-1β,and IL-18.Re-al-time fluorescent quantitative PCR was used to detect the mRNA levels of NLRP3 and Caspase-1.Pearson correlation was used to analyze the correlation between serum levels of Melatonin and MIP-1α and NLRP3 in-flammasome related indicators(NLRP3 mRNA,Caspase-1 mRNA,IL-1β,IL-18)in children with ARDS.Mul-tivariate Cox regression analysis was used to analyze the factors affecting the prognosis of children with ARDS.According to the mean levels of serum Melatonin and MIP-1α,the children with ARDS were divided in-to a high/low Melatonin group and MIP-1α group.The Kaplan-Meier method was used to draw the survival curves of ARDS children with high/low levels of serum Melatonin and MIP-1α.The receiver operating charac-teristic(ROC)curve was used to analyze the predictive value of serum Melatonin and MIP-1α for death in children with ARDS.Results Compared with the control group,the ARDS group had a significantly decreased serum Melatonin level and significantly increased serum MIP-1α,IL-1β,IL-18 and NLRP3 mRNA and Caspase-1 mRNA levels in peripheral blood mononuclear cells(P<0.05).Pearson correlation analysis showed that the serum Melatonin level of ARDS children was negatively correlated with NLRP3 mRNA,Caspase-1 mRNA,IL-1β and IL-18(P<0.05),the level of MIP-1α was positively correlated with NLRP3 mR-NA,Caspase-1 mRNA,IL-1β and IL-18(P<0.05).Multivariate Cox regression analysis showed that acute physiology and chronic health evaluation Ⅱ score,NLRP3 mRNA,Caspase-1 mRNA,IL-1β,IL-18 and MIP-1αwere independent risk factors affecting the prognosis of children with ARDS.Melatonin was an independent protective factor(P<0.05).Kaplan-Meier survival curve analysis showed that the 28 d survival rate in high Melatonin group was higher than that in low Melatonin group(P<0.05),and the 28 d survival rate in high MIP-1α group was lower than that in low MIP-1α group(P<0.05).ROC curve analysis showed that the area under the curve of Melatonin and MIP-1α combined to predict the death of ARDS children was 0.881(95%CI 0.816-0.930).It was higher than 0.785(95%CI 0.708-0.850)and 0.778(95%CI 0.700-0.844)predic-ted by Melatonin or MIP-1α alone.Conclusion The serum Melatonin level is decreased and MIP-1α level is in-creased in children with ARDS,which is closely related to NLRP3 inflammasome and prognosis.Combined de-tection of serum Melatonin and MIP-1α levels has a high predictive value for the prognosis of children with ARDS.
8.The Development and Equivalence Analysis of Mandarin Tracking of Noise Tolerance Test Materials
Yuqing ZHENG ; Jiamin GONG ; Pengfei GUAN ; Jialing FENG ; Yongtao XIAO ; Ting FAN ; Aqiang DAI ; Roujia ZHOU ; Huawei LI ; Yunfeng WANG
Journal of Audiology and Speech Pathology 2024;32(4):302-307
Objective To develop and evaluate the equivalence of the Mandarin test material for tracking of noise tolerance(TNT)test.Methods Six different speech materials were developed(themes including daily life,entertainment,family,festivals,outdoors,and school).Four-minute TNT tests were measured in 21 normal hear-ing subjects using six different test materials.For each session,the tolerable noise level(TNL)and TNT scores were acquired and calculated for 3 time windows(31~240 s,31~120 s,151~240 s).Results Statistic analysis showed significant differences in the TNL(F=43.611,P<0.05)among the normal hearing listeners.There were statistically significant differences in standardize z-scored TNT scores of the six different materials in the three time windows(P<0.05).Post-hoc comparisons revealed that all significant differences involved the family and daily life themes.Conclusion Entertainment,festival,outdoors and school themed test materials can serve as the materials of Mandarin tracking of noise tolerance test and can be appied in research and clinical testing.
9.Effectiveness of bone plate reduction combined with resorbable plate fixation in the treatment of large mandibu-lar cysts
Yifan HU ; Qingyan SUN ; Chenyi WANG ; Xiaoting ZHAI ; Hua JIANG ; Huawei LIU
West China Journal of Stomatology 2024;42(4):470-475
Objective This study aims to observe the clinical effect of bone plate reduction in combination with a re-sorbable plate on large mandibular cysts.Methods Between October 2017 and September 2022,patients with large mandibular cysts in the presence of labial and buccal cortical bone were involved in the study.Intraoral approach was performed for bone plate reduction.Cone beam computed tomography(CBCT)scan was reviewed at 3,6,and 9 months postoperatively to observe postoperative complications.Osteogenic results were assessed at these times to determine the clinical outcomes of this procedure.Results Eleven cases with large mandibular cysts in the presence of cortical bone were evaluated.The average thickness of the cortical bone on the labial and buccal sides was measured to be about(1.98±0.37)mm before surgery,with a mean value of(0.73±0.17)mm at the thinnest part of the plate and up to 0.51 mm at the thinnest part of the plate.The cystic cavities were well re-vealed during the surgeries,which were completed suc-cessfully.Postoperatively,the wounds healed in one stage without infection.The percentages of cyst shrinkage were 20.01%,41.76%,and 73.41%at 3,6,and 9 months after surgery,respectively.Quantitative measurement of bone mineral density in the jaws by CBCT with MIMICS software.The bone mineral densities of the adult bone were 313.78,555.85,and 657.45 HU at the 3,6,and 9 month time intervals,respectively.No significant change in the patient's maxillofacial appearance were observed from the preoperative period as assessed by the patient's and observer's visual analog scale.Conclusion Bone plate reduction is an effective treatment for large mandibular cysts of the oral and maxillofacial re-gion with the presence of cortical bone.
10.A Case Report and Literature Review of A Child with Refractory Anti-N-methyl-D-aspartate Receptor Encephalitis Treated with Tocilizumab
Weiqin ZHANG ; Huawei ZHAO ; Zhenzhen WANG ; Feng GAO ; Zhefeng YUAN
Chinese Journal of Modern Applied Pharmacy 2024;41(6):834-838
OBJECTIVE
To explore the safety and efficacy of tocilizumab in the treatment of refractory anti-N-methyl-D-aspartate receptor encephalitis in children, and to provide reference for the treatment of this disease.
METHODS
The clinical manifestations, diagnosis and treatment, safety and efficacy of tocilizumab in a case of refractory anti-NMDAR encephalitis in Children’s Hospital, Zhejiang University School of Medicine were analyzed retrospectively, and the relevant literature was reviewed.
RESULTS
The clinical symptoms of the patient were not improved after 2 doses of methylprednisolone, immunoglobulin and 6 doses of rituximab. After 6 doses of tocilizumab, the modified Rankin scale(mRS) score was improved without adverse reactions.
CONCLUSION
Tocilizumab, as a escalation second-line immunotherapy, is effective and well tolerated in the treatment of refractory anti-NMDAR encephalitis. It is one of the potential therapeutic means.


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