1.Development and multicenter validation of machine learning models for predicting postoperative pulmonary complications after neurosurgery.
Ming XU ; Wenhao ZHU ; Siyu HOU ; Hongzhi XU ; Jingwen XIA ; Liyu LIN ; Hao FU ; Mingyu YOU ; Jiafeng WANG ; Zhi XIE ; Xiaohong WEN ; Yingwei WANG
Chinese Medical Journal 2025;138(17):2170-2179
BACKGROUND:
Postoperative pulmonary complications (PPCs) are major adverse events in neurosurgical patients. This study aimed to develop and validate machine learning models predicting PPCs after neurosurgery.
METHODS:
PPCs were defined according to the European Perioperative Clinical Outcome standards as occurring within 7 postoperative days. Data of cases meeting inclusion/exclusion criteria were extracted from the anesthesia information management system to create three datasets: The development (data of Huashan Hospital, Fudan University from 2018 to 2020), temporal validation (data of Huashan Hospital, Fudan University in 2021) and external validation (data of other three hospitals in 2023) datasets. Machine learning models of six algorithms were trained using either 35 retrievable and plausible features or the 11 features selected by Lasso regression. Temporal validation was conducted for all models and the 11-feature models were also externally validated. Independent risk factors were identified and feature importance in top models was analyzed.
RESULTS:
PPCs occurred in 712 of 7533 (9.5%), 258 of 2824 (9.1%), and 207 of 2300 (9.0%) patients in the development, temporal validation and external validation datasets, respectively. During cross-validation training, all models except Bayes demonstrated good discrimination with an area under the receiver operating characteristic curve (AUC) of 0.840. In temporal validation of full-feature models, deep neural network (DNN) performed the best with an AUC of 0.835 (95% confidence interval [CI]: 0.805-0.858) and a Brier score of 0.069, followed by Logistic regression (LR), random forest and XGBoost. The 11-feature models performed comparable to full-feature models with very close but statistically significantly lower AUCs, with the top models of DNN and LR in temporal and external validations. An 11-feature nomogram was drawn based on the LR algorithm and it outperformed the minimally modified Assess respiratory RIsk in Surgical patients in CATalonia (ARISCAT) and Laparoscopic Surgery Video Educational Guidelines (LAS VEGAS) scores with a higher AUC (LR: 0.824, ARISCAT: 0.672, LAS: 0.663). Independent risk factors based on multivariate LR mostly overlapped with Lasso-selected features, but lacked consistency with the important features using the Shapley additive explanation (SHAP) method of the LR model.
CONCLUSIONS:
The developed models, especially the DNN model and the nomogram, had good discrimination and calibration, and could be used for predicting PPCs in neurosurgical patients. The establishment of machine learning models and the ascertainment of risk factors might assist clinical decision support for improving surgical outcomes.
TRIAL REGISTRATION
ChiCTR 2100047474; https://www.chictr.org.cn/showproj.html?proj=128279 .
Adult
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Aged
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Female
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Humans
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Male
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Middle Aged
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Algorithms
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Lung Diseases/etiology*
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Machine Learning
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Neurosurgical Procedures/adverse effects*
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Postoperative Complications/diagnosis*
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Risk Factors
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ROC Curve
2.Cerium single-atom catalysts-armed Lactobacillus reuteri for multipronged anti-inflammatory/anti-fibrotic therapy of inflammatory bowel disease.
Yinying PU ; Shaorong HUANG ; Shuang GAO ; Yangying DUAN ; Wenhao LI ; Qiyue LI ; Han LIN ; Kun ZHANG ; Min ZHOU ; Wencheng WU
Acta Pharmaceutica Sinica B 2025;15(10):5400-5415
Simultaneous management of intestinal mucosal barrier dysfunction and gut microbiota dysregulation represents a significant challenge in the treatment of inflammatory bowel disease (IBD). Herein, we report a novel system that integrates multi-enzyme mimicking cerium single-atom nanocatalysts (CeSACs) with Lactobacillus reuteri probiotics (LR@CeSACs) for multipronged management of IBD. In this system, CeSACs demonstrate robust multi-enzyme activities across a broad pH range, effectively scavenging elevated reactive oxygen species, downregulating pro-inflammatory cytokines, and suppressing the expression of fibrosis-related genes. Moreover, probiotics promote the targeting and retention of the CeSACs for sustained catalytic antioxidant therapy. In turn, the inflammation relief enabled by CeSACs promotes bacterial viability, allowing for the rapid reshaping of intestinal barrier function and the restoration of gut microbiota. Therefore, LR@CeSACs exhibit excellent catalytic anti-inflammatory and anti-fibrotic therapeutic effects, as well as a certain prophylactic effect, as demonstrated in several murine models.
3.Engineered Escherichia coli Nissle 1917 targeted delivery of extracellular PD-L1-mFc fragment for treating inflammatory bowel disease.
Yuhong WANG ; Lin HU ; Lei WANG ; Chonghai ZHANG ; Wenhao SHEN ; Hongli YANG ; Min LI ; Xin ZHANG ; Mengmeng XU ; Muxing ZHANG ; Kai YANG ; Xiaopeng TIAN
Acta Pharmaceutica Sinica B 2025;15(11):6019-6033
Inflammatory bowel disease (IBD) is an autoimmune disorder involving complex immune regulation, where balancing localized and systemic immunosuppression is a key challenge. This study aimed to enhance the therapeutic efficacy by engineering the probiotic Escherichia coli Nissle 1917 (EcN). We removed endogenous plasmids pMUT1 and pMUT2 from wild-type EcN and expressed the mPD-L1 (19‒238 aa)-mFc fusion protein on the bacterial surface using a cytolysin A (ClyA) fragment. This modification stabilized mPD-L1 (19‒238 aa) protein expression and promoted its recruitment to outer membrane vesicles (OMVs). The engineered strain, EcNΔpMUT1/2-ClyA-mPD-L1-mFc (EcN-ePD-L1-mFc), features conditional ePD-L1-mFc expression under the araBAD promoter, enhancing gut-targeted release and reducing systemic side effects. This strain improved treatment targeting and efficiency by enabling direct ePD-L1-mFc interaction with immune cells at inflammation sites. OMVs from this strain induced Treg proliferation, inhibited effector T cell proliferation in vitro, and significantly improved intestinal inflammation and colonic epithelial barrier repair in vivo. Additionally, the bacterium restored intestinal microbiota balance, increasing Lactobacillaceae and reducing Bacteroides. This study highlights the engineered bacterium's potential for targeted intestinal immune modulation and offers a novel local IBD treatment approach with promising clinical prospects.
4.Zebrafish as a vertebrate model for high-throughput drug toxicity screening: Mechanisms, novel techniques, and future perspectives.
Wenhao WANG ; Xuan GAO ; Lin LIU ; Sheng GUO ; Jin-Ao DUAN ; Ping XIAO
Journal of Pharmaceutical Analysis 2025;15(9):101195-101195
Drug toxicity is closely related to both clinical drug safety and new drug development. Therefore, it is vital to understand the mechanisms of drug toxicity fully and to use appropriate research models with advanced technologies. Zebrafish has become an important vertebrate animal model for high-throughput drug screening and toxicity assessment. At the same time, zebrafish has an intact biological complexity, reflecting the whole organism's toxicity, which gives it an advantage over other high-throughput models in toxicity studies. Despite the gradual increase in toxicity studies utilizing zebrafish, a comprehensive and systematic review of the underlying mechanisms and new techniques is still lacking. This review aims to analyze common toxicity mechanisms in zebrafish models, such as oxidative stress, endoplasmic reticulum stress, inflammation, and apoptosis, and macroscopic changes in biological processes like lipid metabolism disorders and neurotransmitter expression abnormalities. It also introduces new technologies applied in toxicity assessment, such as gene editing, novel fluorescence imaging technology, 3D imaging technology, and novel automated technology for high-throughput screening, such as fish capsules. In addition, it also summarizes the advantages and disadvantages of the model. By doing so, it will provide new suggestions for the development and improvement of the model, make it better serve the toxicity study of clinical drugs and provide a more comprehensive perspective for drug toxicity study, thus promoting the development of the field of drug toxicity study.
5.Preventive and therapeutic effects of berberine on liver diseases and its mechanism
Huili WANG ; Wenhao QIN ; Dangdang YANG ; Yaqian NING ; Shan LIN ; Songlin DAI ; Bing HU
Journal of Clinical Hepatology 2024;40(11):2326-2331
Berberine is an antipyretic and detoxicating drug commonly used in clinical practice,and it is currently used for the routine treatment of gastrointestinal diseases such as bacterial gastroenteritis and diarrhea.However,several recent studies have shown that berberine can exert a therapeutic effect on the diseases such as autoimmune hepatitis,viral hepatitis,nonalcoholic fatty liver disease,and liver cancer by regulating the AMPK and TGF-β pathways and altering the composition of intestinal flora.This provides new drugs for the treatment of these diseases,expands the potential indications of berberine,and provides clues for the follow-up research and development of similar drugs.This article summarizes the therapeutic effect and mechanism of berberine on various liver diseases,in order to provide a reference for effective clinical application.
6.Advancements in the development and technological fabrication of wound healing biomaterials
Diandian LI ; Muran ZHOU ; Yang ZHAO ; Wenhao WU ; Keyi LIN ; Aimei ZHONG
Chinese Journal of Plastic Surgery 2024;40(3):355-361
Promoting wound healing is a common clinical challenge faced by surgeons, with a variety of repair method and materials currently available for clinical use. In recent years, with the continuous development of disciplines such as tissue engineering, regenerative medicine, and materials science, research on wound repair materials has progressed rapidly. This article will organize the classification, advantages and disadvantages, and the latest advancements in the preparation processes of wound repair materials. It will also discuss the current challenges faced by wound repair materials and future research directions, with the aim of providing a reference for related studies in wound repair.
7.Advancements in the development and technological fabrication of wound healing biomaterials
Diandian LI ; Muran ZHOU ; Yang ZHAO ; Wenhao WU ; Keyi LIN ; Aimei ZHONG
Chinese Journal of Plastic Surgery 2024;40(3):355-361
Promoting wound healing is a common clinical challenge faced by surgeons, with a variety of repair method and materials currently available for clinical use. In recent years, with the continuous development of disciplines such as tissue engineering, regenerative medicine, and materials science, research on wound repair materials has progressed rapidly. This article will organize the classification, advantages and disadvantages, and the latest advancements in the preparation processes of wound repair materials. It will also discuss the current challenges faced by wound repair materials and future research directions, with the aim of providing a reference for related studies in wound repair.
8.A review of research advances in virtual reality-based interventions for children with autism
Yu FANG ; Wenhao LIN ; Xiaohua SUN ; Yuan ZHAO ; Liying DONG ; Haidong SONG
Chinese Mental Health Journal 2024;38(5):394-399
This paper analyzes the literature on virtual reality(VR)technology interventions for autistic children published from 2014 to 2022.It shows that different VR systems in these studies have improved different symptoms of autism,and points out the feasibility of VR technology interventions for autistic children.
9.Retrospective study on the impact of penile corpus cavernosum injection test on pe-nile vascular function
Yan CHEN ; Kuangmeng LI ; Kai HONG ; Shudong ZHANG ; Jianxing CHENG ; Zhongjie ZHENG ; Wenhao TANG ; Lianming ZHAO ; Haitao ZHANG ; Hui JIANG ; Haocheng LIN
Journal of Peking University(Health Sciences) 2024;56(4):680-686
Objective:To investigate the impact of age,various hormonal levels,and biochemical markers on penile cavernous body vascular function in patients with erectile dysfunction(ED).Me-thods:A retrospective analysis of clinical data from male patients with ED who underwent color duplex Doppler ultrasonography(CDDU)and intracavernosal injection test(ICI)at the Reproductive Medicine Center of Peking University Third Hospital from January 2020 to August 2023.Data were managed and processed using SPSS 29.0,and a multivariable Logistic regression analysis was conducted.Results:A total of 700 ED patients were included,with 380 showing negative ICI results and 320 positive.In the study,84 patients had a peak systolic velocity(PSV)<25 cm/s,while 616 had PSV ≥ 25 cm/s;202 patients had end-diastolic velocity(EDV)>5 cm/s,and 498 had EDV ≤5 cm/s.264 patients had ab-normal PSV and/or EDV results,and 436 had normal results for both.Patients with vascular ED had sig-nificantly lower estrogen levels(t=-3.546,P<0.001),lower testosterone levels(t=-2.089,P=0.037),and a higher rate of hyperglycemia(x2=12.772,P=0.002)compared with those with non-vascular ED.The patients with arterial ED were older(t=3.953,P<0.001),had a higher rate of hyperglycemia(x2=9.518,P=0.009),and a higher estrogen/testosterone ratio(t=2.330,P=0.020)compared with those with non-arterial ED.The patients with mixed arteriovenous ED had higher age(t=3.567,P<0.001),lower testosterone levels(t=-2.288,P=0.022),a higher rate of hyperglycemia(x2=12.877,P=0.002),and a larger estrogen/testosterone ratio(t=2.096,P=0.037)compared with those with normal findings.Multifactorial Logistic regression analysis indicated that higher levels of estrogen were a protective factor for vascular ED(OR=1.009,95%CI:1.004-1.014),and glucose 7.0 mmol/L was a risk factor(OR=0.381,95%CI:0.219-0.661).Older age was a risk factor for arte-rial ED(OR=0.960,95%CI:0.938-0.982).Additionally,older age(OR=0.976,95%CI:0.958-0.993)and glucose levels of 5.6-6.9 mmol/L(OR=0.591,95%CI:0.399-0.876)were also risk fac-tors for mixed arterio-venous ED.Conclusion:Hyperglycemia and aging may impair penile cavernous body vascular function,while higher levels of estrogen may have a protective effect on it.
10.Nomogram for predicting the risk of post hepatectomy liver failure was established based on preoperative routine test indexes
Guoping DONG ; Chen CHEN ; Xudong LU ; Jiali WU ; Wenhao ZHENG ; Lin TONG
Chinese Journal of Laboratory Medicine 2024;47(8):895-901
Objective:To establish a risk prediction model of liver failure after liver resection for hepatocellular carcinoma.Method:A retrospective case-control study was designed. Clinical data and laboratory results, including gender, age, and preoperative 18 laboratory indicators, were collected from 320 patients with hepatocellular carcinoma undergoing liver resection in Eastern Hepatobiliary Surgery Hospital Affiliated to Naval Medical University from January 1, 2013 to December 31, 2023. According to the surgical time, 252 cases in the training cohort were divided into 62 and 190 cases with and without postoperative liver failure, respectively. Of the 68 cases in validation cohort, 34 developed postoperative liver failure and 34 did not. Binary Logistic regression analysis was used to conduct univariate analysis of gender, age, and 18 preoperative laboratory indicators, and multivariate analysis was carried out for significant results to determine the influencing factors of liver failure after liver resection for hepatocellular carcinoma, and Logistic regression model was established.Result:In the training cohort, indicators significantly associated with liver failure after liver resection for hepatocellular carcinoma included age ( P=0.016), platelets ( P=0.005), prealbumin ( P<0.001), and alkaline phosphatase ( P<0.001). Logistic regression was used to construct a nomogram model and draw a calibration curve by combining these four indicators. In the training cohort, the nomogram model showed good discriminability in predicting the risk of liver failure after hepatectomy for hepatocellular carcinoma. The area under the curve of was 0.82 (95% CI 0.76-0.88), and the sensitivity was 73% and specificity was 80% when the optimal cut-off value was 0.2646. In the validation cohort, the predictive performance of the nomogram model was comparable to that of the training cohort, with an area under the curve of 0.81 (95% CI 0.71-0.92), sensitivity of 82%, and specificity of 77%. Conclusion:Preoperative platelet and prealbumin decreases, alkaline phosphatase increases, and elderly patients are prone to liver failure after liver resection. The nomogram model constructed with preoperative test data has shows good discriminatory ability and accuracy in predicting liver failure after liver resection for hepatocellular carcinoma.

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