1.Identification of high-risk preoperative blood indicators and baseline characteristics for multiple postoperative complications in rheumatoid arthritis patients undergoing total knee arthroplasty: a multi-machine learning feature contribution analysis.
Kejia ZHU ; Zhiyang HUANG ; Biao WANG ; Hang LI ; Yuangang WU ; Bin SHEN ; Yong NIE
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(12):1532-1542
OBJECTIVE:
To explore, identify, and develop novel blood-based indicators using machine learning algorithms for accurate preoperative assessment and effective prediction of postoperative complication risks in patients with rheumatoid arthritis (RA) undergoing total knee arthroplasty (TKA).
METHODS:
A retrospective cohort study was conducted including RA patients who underwent unilateral TKA between January 2019 and December 2024. Inpatient and 30-day postoperative outpatient follow-up data were collected. Six machine learning algorithms, including decision tree, random forest, logistic regression, support vector machine, extreme gradient boosting, and light gradient boosting machine, were used to construct predictive models. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), F1-score, accuracy, precision, and recall. SHapley Additive exPlanations (SHAP) values were employed to interpret and rank the importance of individual variables.
RESULTS:
According to the inclusion criteria, a total of 1 548 patients were enrolled. Ultimately, 18 preoperative indicators were identified as effective predictive features, and 8 postoperative complications were defined as prediction labels for inclusion in the study. Within 30 days after surgery, 453 patients (29.2%) developed one or more complications. Considering overall accuracy, precision, recall, and F1-score, the random forest model [AUC=0.930, 95% CI (0.910, 0.950)] and the extreme gradient boosting model [AUC=0.909, 95% CI (0.880, 0.938)] demonstrated the best predictive performance. SHAP analysis revealed that anti-cyclic citrullinated peptide antibody, C-reactive protein, rheumatoid factor, interleukin-6, body mass index, age, and smoking status made significant contributions to the overall prediction of postoperative complications.
CONCLUSION
Machine learning-based models enable accurate prediction of postoperative complication risks among RA patients undergoing TKA. Inflammatory and immune-related blood biomarkers, such as anti-cyclic citrullinated peptide antibody, C-reactive protein, and rheumatoid factor, interleukin-6, play key predictive roles, highlighting their potential value in perioperative risk stratification and individualized management.
Humans
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Arthroplasty, Replacement, Knee/adverse effects*
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Arthritis, Rheumatoid/blood*
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Machine Learning
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Postoperative Complications/blood*
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Female
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Male
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Retrospective Studies
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Middle Aged
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Aged
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Risk Factors
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Preoperative Period
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C-Reactive Protein/analysis*
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Risk Assessment
2.The role and mechanism of quercetin in promoting diabetic wound healing by regulating the PI3K/Akt/GSK-3β signaling pathway and NLRP3 activation
Ding ZHU ; Yijing LIN ; Xinying LI ; Chunhua MA ; Yuangang LU
Immunological Journal 2024;40(10):752-760
Objective To investigate the promoting effect of quercetin(QR)on diabetic wound repair and its possible mechanism.Methods HUVEC cell injury model was induced by 33.36 mmol/L high glucose.The cells were divided into normal control group(NG group),mannitol group(MA group),high glucose group(HG group),low dose quercetin+high glucose group(QR 5 μmol/L+HG group),high dose quercetin+high glucose group(QR 20 μmol/L+HG group).Treatment for 24 hours;CCK-8 and Edu were used to measure cell viability.Cell scratch test and Transwell migration assay were used to detect cell migration ability.Matrigel tube formation assay was used to measure the angiogenesis ability.The levels of IL-1β,IL-18 and TNF-α were detected by ELISA.Network pharmacology was used to screen the potential targets of QR on diabetic wounds.Western blot was used to detect the expression of NLRP3 inflammasome,PI3K/Akt/GSK-3β pathway and its phosphorylation.The diabetic wound model of C57 mice was established and divided into STZ group and QR+STZ group.The wound healing rate within 14 days was calculated and analyzed,and the wound tissue was stained with HE and Masson on the 14th day.Results CCK-8 and Edu results showed that a high dose of QR could improve the viability of huvecs induced by high glucose.Scratch test and Transwell migration test showed that high dose of QR could enhance the migration ability of HUVEC cells induced by high glucose.Matrigel tube formation assay showed that high dose of QR could enhance the angiogenesis ability of HUVEC cells induced by high glucose.ELISA results showed that high dose of QR could inhibit the secretion of IL-1β,IL-18 and TNF-α induced by high glucose.Network pharmacology screening results showed that PI3K/Akt/GSK-3β pathway was significantly enriched.Western blot showed that 20 μmol/L QR could increase the phosphorylation level of PI3K/Akt/GSK-3β pathway and inhibit the expression of NLRP3 inflammasome,which could be reversed by the addition of PI3K phosphorylation inhibitor LY294002.Animal experiments have shown that QR can promote diabetic wound healing by enhancing granulation tissue growth,epithelial regeneration,and collagen deposition.Conclusion QR can improve HUVEC injury induced by high glucose and promote wound healing in diabetic mice,and its mechanism may be related to inhibiting NLRP3 expression through PI3K/Akt/GSK-3β pathway.
3.The role and mechanism of quercetin in promoting diabetic wound healing by regulating the PI3K/Akt/GSK-3β signaling pathway and NLRP3 activation
Ding ZHU ; Yijing LIN ; Xinying LI ; Chunhua MA ; Yuangang LU
Immunological Journal 2024;40(10):752-760
Objective To investigate the promoting effect of quercetin(QR)on diabetic wound repair and its possible mechanism.Methods HUVEC cell injury model was induced by 33.36 mmol/L high glucose.The cells were divided into normal control group(NG group),mannitol group(MA group),high glucose group(HG group),low dose quercetin+high glucose group(QR 5 μmol/L+HG group),high dose quercetin+high glucose group(QR 20 μmol/L+HG group).Treatment for 24 hours;CCK-8 and Edu were used to measure cell viability.Cell scratch test and Transwell migration assay were used to detect cell migration ability.Matrigel tube formation assay was used to measure the angiogenesis ability.The levels of IL-1β,IL-18 and TNF-α were detected by ELISA.Network pharmacology was used to screen the potential targets of QR on diabetic wounds.Western blot was used to detect the expression of NLRP3 inflammasome,PI3K/Akt/GSK-3β pathway and its phosphorylation.The diabetic wound model of C57 mice was established and divided into STZ group and QR+STZ group.The wound healing rate within 14 days was calculated and analyzed,and the wound tissue was stained with HE and Masson on the 14th day.Results CCK-8 and Edu results showed that a high dose of QR could improve the viability of huvecs induced by high glucose.Scratch test and Transwell migration test showed that high dose of QR could enhance the migration ability of HUVEC cells induced by high glucose.Matrigel tube formation assay showed that high dose of QR could enhance the angiogenesis ability of HUVEC cells induced by high glucose.ELISA results showed that high dose of QR could inhibit the secretion of IL-1β,IL-18 and TNF-α induced by high glucose.Network pharmacology screening results showed that PI3K/Akt/GSK-3β pathway was significantly enriched.Western blot showed that 20 μmol/L QR could increase the phosphorylation level of PI3K/Akt/GSK-3β pathway and inhibit the expression of NLRP3 inflammasome,which could be reversed by the addition of PI3K phosphorylation inhibitor LY294002.Animal experiments have shown that QR can promote diabetic wound healing by enhancing granulation tissue growth,epithelial regeneration,and collagen deposition.Conclusion QR can improve HUVEC injury induced by high glucose and promote wound healing in diabetic mice,and its mechanism may be related to inhibiting NLRP3 expression through PI3K/Akt/GSK-3β pathway.
4.Application value of dual-layer spectral detector CT in precise radiotherapy for central lung cancer with atelectasis
Mingxin FAN ; Tianye LIU ; Lijuan WEN ; Jian ZHU ; Yuangang QI ; Qing ZHANG
Chinese Journal of Radiology 2023;57(8):849-854
Objective:To evaluate the value of dual-layer spectral detector CT (DLSDCT) in precise radiotherapy for central lung cancer (CLC) complicated with atelectasis.Methods:Clinical and imaging data (including DLSDCT, PET-CT, and radiotherapy simulation CT images) of 26 patients with pathologically confirmed CLC accompanied by atelectasis from the Third Affiliated Hospital of Shandong First Medical University and Shandong Cancer Hospital were analyzed retrospectively. There were 21 males and 5 females, aged 36-82 years. Two physicians assessed CLC identifiability on DLSDCT, PET-CT, and simulation localization CT images, respectively, and outlined the gross tumor volume (GTV) and measured GTV values (GTV DLSDCT, GTV PET-CT, GTV CT). Paired-sample Friedman test was used to compare the differences in GTV of the three images, and the SNK test with Bonferroni correction was used for a two-way comparison. The intra-class correlation coefficient (ICC) was used to compare the agreement of measured GTV between 2 physicians. Results:The differentiation rates on PET-CT, DLSDCT, and simulation CT images were 100% (26/26), 80.77% (21/26), and 11.54% (3/26), respectively. The differentiation rate of CLC on DLSDCT images was significantly higher than that on simulation CT images (χ 2=16.06, P<0.001). GTV CT, GTV PET-CT, and GTV DLSDCT measured on simulation localization CT images, PET-CT images, and DLSDCT images were 58.75 (22.57, 86.17) cm 3, 47.34 (18.13, 69.25) cm 3, and 51.40 (18.87, 71.31) cm 3, respectively, with statistically significant differences (χ 2=44.99, P<0.001). Both GTV DLSDCT and GTV PET-CT were significantly smaller than GTV CT (χ 2=4.23, 6.59, Bonferroni corrected P<0.001), and there was no significant difference between GTV DLSDCT and GTV PET-CT (χ 2=2.36, Bonferroni corrected P=0.055). The agreement between the two physicians was good for GTV values measured on both DLSDCT and PET-CT (ICC=0.86, 0.89). Conclusions:On DLSDCT images, most CLC and atelectasis can be identified. Compared to simulation localization CT, the tumor target areas outlined on DLSDCT are closer to PET-CT, and the tumor volumes outlined by different physicians are more consistent.
5.Clinical application and effect of pick-stab skill in eyebrow embroidery
Fengjun ZHU ; Yanying SONG ; Yadong YANG ; Yuanyuan WANG ; Hailin WANG ; Xingcun ZHANG ; Xiuhua HU ; Ling LI ; Yuangang LU
Chinese Journal of Medical Aesthetics and Cosmetology 2017;23(6):409-411
Objective To investigate the clinical application and effect of pick-stab skill in eyebrow embroidery.Methods From July 2015 to January 2016,36 cases were selected to receive eyebrow embroidery with pick-stab skill in our department,including 1 male and 35 females.The cosmetic outcomes,complications and satisfaction rate were observed in these cases.Results In these 36 cases,14 cases were colored in one time,19 cases were colored twice,and 3 cases were more than 3 times.All patients were followed up for 6 months.The color of the eyebrow was natural,and the blue color was not existed.Conclusions The pick-stab skill in eyebrow embroidery is worthy in clinic with better cosmetic effect,higher success rate and safety.
6.Inhibitory effect of recombinant human endostatin on angiogenesis in atherosclerotic plaque of rats by regulating Dll4/Notch pathway
Hongwen CAI ; Min ZHU ; Xinbin ZHOU ; Jing MIAO ; Yuangang QIU ; Wei MAO
Chinese Journal of Pathophysiology 2016;32(9):1700-1703
AIM: To observe the inhibitory effect of recombinant human endostatin (rhES) on plaque angio-genesis, and to explore the regulatory mechanism of Dll4 /Notch pathway in the anti-angiogenic effect of rhES.METH-ODS: Male Wistar rats were randomized into 3 groups: normal control group (N group), atherosclerotic model group (AS group), and rhES treated group (AS +rhES group).The rats in N group were fed a normal diet, while the remaining 2 groups were established to atherosclerotic rat model via high-cholesterol diet, intraperitoneal injection of vitamin D3 and aor-tic balloon injury.The rats in AS +rhES group received intraperitoneal injection of rhES.The blood total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), C-reactive protein (CRP), interleukin-1 (IL-1) and troponin I (TnI) were measured.The atherosclerotic abdominal aortas were taken for pathological observation.Immu-nohistochemical staining was used to measure the density of neovessels in the plaques, which were marked by CD31.The protein levels of Dll4 and Notch1 in the aortas were analyzed by Western blot.RESULTS: The levels of blood TC, TG, LDL-C, CRP and IL-1 in AS group and AS +rhES group were much higher than those in N group (P <0.05), and no sta-tistical difference between AS group and AS +rhES group was observed.The expression of CD31 in AS group was the high-est among all groups.Compared with AS group, the density of neovessels in the plaques of AS +rhES group decreased sig-nificantly (P <0.05).The protein expression of Dll4 and Notch1 in AS group was lower than that in N group (P <0.05). Compared with AS group, the protein expression of Dll4 and Notch1 increased significantly (P <0.05).CONCLUSION:rhES has the ability to inhibit plaque angiogenesis in rats.The activation of Dll4 /Notch pathway may be the mechanism of rhES in inhibiting plaque angiogenesis.
7.ULK1 and JNK are involved in mitophagy incurred by LRRK2 G2019S expression.
Yuangang ZHU ; Chunyan WANG ; Mei YU ; Jie CUI ; Liang LIU ; Zhiheng XU
Protein & Cell 2013;4(9):711-721
Mutations in LR RK2 (Leucine rich repeat kinase 2) are a major cause of Parkinson's disease (PD). We and others reported recently that expression of the pathogenic gainof-function mutant form of LRRK2, LRRK2 G2019S, induces mitochondrial fission in neurons through DLP1. Here we provide evidence that expression of LRRK2 G2019S stimulates mitochondria loss or mitophagy. We have characterized several LRRK2 interacting proteins and found that LRRK2 interacts with ULK1 which plays an essential role in autophagy. Knockdown of either ULK1 or DLP1 expression with shRNAs suppresses LRRK2 G2019S expression-induced mitochondrial clearance, suggesting that LRRK2 G2019S expression induces mitochondrial fission through DLP1 followed by mitophagy via an ULK1 dependent pathway. In addition to ULK1, we found that LRRK2 interacts with the endogenous MKK4/7, JIP3 and coordinates with them in the activation of JNK signaling. Interestingly, LRRK2 G2019S-induced loss of mitochondria can also be suppressed by 3 different JNK inhibitors, implying the involvement of the JNK pathway in the pathogenic mechanism of mutated LRRK2. Thus our findings may provide an insight into the complicated pathogenesis of PD as well as some clues to the development of novel therapeutic strategies.
Amino Acid Substitution
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Autophagosomes
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metabolism
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pathology
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Autophagy-Related Protein-1 Homolog
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chemistry
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genetics
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metabolism
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GTP Phosphohydrolases
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antagonists & inhibitors
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genetics
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metabolism
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Gene Knockdown Techniques
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HeLa Cells
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Humans
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Intracellular Signaling Peptides and Proteins
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chemistry
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genetics
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metabolism
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Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
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chemistry
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genetics
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metabolism
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MAP Kinase Signaling System
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Microtubule-Associated Proteins
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antagonists & inhibitors
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genetics
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metabolism
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Mitochondrial Degradation
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genetics
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physiology
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Mitochondrial Proteins
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antagonists & inhibitors
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genetics
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metabolism
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Mutant Proteins
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chemistry
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genetics
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metabolism
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Mutation
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Parkinson Disease
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genetics
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metabolism
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pathology
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Protein Interaction Domains and Motifs
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Recombinant Proteins
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chemistry
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genetics
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metabolism
8.Effect of hepatocyte growth factor on the migration and apoptosis of,as well as p-Akt expression in cultured human eccrine sweat gland epithelial cells
Xia LEI ; Bo LIU ; Jinjin WU ; Yuangang LU ; Tangyou ZHU ; Yadong YANG
Chinese Journal of Dermatology 2010;43(6):411-414
Objective To investigate the effect of hepatocyte growth factor (HGF) on migration and apoptosis of,as well as phosphorylated-Akt (p-Akt) expression in cultured human eccrine sweat gland epithehal cells (hESGc).Methods The first generation of hESGc were cultured in keratinocyte serum free medium (KSFM) and treated with various concentrations (2,20,40μg/L) of HGF for different durations.Then,cell scratch test was performed to detect cell migration,a double staining flow cytometry assay using annexin VFITC/propidium iodide to detect cell apoptosis.and Western blot to measure the expression of p-Akt.Results HGF of 2μg/L had no effect on the migration of hESGc,while that of 20 μg/L and 40μg/L could promote the migration of hESGc by 33.2% and 228.2%.respectively.The average number of cells migrating into the scrach zone was significantly lower in untreated cell group than that in 20 and 40μg/L HGF-treated cell group (17.3±5.5 vs 23.0±6.3 and 56.7±7.9,t=2.653, 15.858,P<0.05,0.01, respectively).The apoptosis rate was 14.76% in untreated cells,14.16%,13.5% and 8.87% in cells treated with HGF of 2,20 and 40μ/L, respectively;there was a significant difference between untreated cells and 40μg/L HGF-treated cells (t=7.852,P<0.01).HGF could activate the phosphorylation of Akt protein and increase the expression of p-Akt.Conclusion HGF could promote the migration of,inhibit the apoptosis of,and stimulate the p-Akt expression in.hESGc.
9.Surgical excision combined with recombinant interferon alpha-2b in the treatment of 15 cases of acral malignant melanoma
Yuangang LU ; Yadong YANG ; Tangyou ZHU ; Hongzhen YANG ; Jinjin WU ; Tao YANG
Chinese Journal of Dermatology 2008;41(9):591-593
Objective To investigate the clinical outcomes of surgical excision combined with recom binant interferon aipha-2b in the treatment of acral malignant melanoma (MM). Methods Fifteen patients with acral MM admitted to the department since 2004 were recruited into this study. The tumors varied from 1.8 mm to 3.9 mm in invasion depth. Thin tumors with an invasion depth of 1.8 - 2.0 mm were excised with a margin of lcm beyond the tumors, and those with an invasion depth of 2.0 - 3.9 mm were excised with a margin of 2 cm beyond the tumors. After excision, 4 cases of minor excision were sutured directly, 10 cases of large excision were repaired with adjacent skin grafts and flaps, 1 patient with the involvement of the first metatarsophalangeal joint underwent toe amputation followed by the repair of planta wound surface with the remaining skin on the dorsa of toes. Patients received intramuscular recombinant interferon alpha-2b for 3 months (3 million units daily for the first 3 days and 6 million units for the remaining days) following operation. Results There were 6 cases of MM in situ and 9 cases of invasive MM in this study. All the skin grafts and flaps survived. Within the 3-year follow up, relapse was observed only in 1 patient with invasive MM. Recovery was achieved in the functions of feet in all patients. Conclusion The excision of tumors with a margin determined by tumor thickness plus intramuscular interferon alpha-2h may improve the survival of patients with cutaneous MM in planta pedis with avoidance of amputation.
10.Review on Rapamycin as a potential therapeutic agent against neurodegenerative disease
Guang YANG ; Yuangang ZHU ; Hui YANG
Basic & Clinical Medicine 2006;0(12):-
Autophagy contributes to the pathology of various neurodegenerative conditions.Rapamycin,an agent against Candida albicans or immunosuppressive,was found to be effective against tumor.Furthermore,it also induces autophagy by inactivating the protein mammalian target of rapamycin(mTOR),FKBP and VMP1,thus could offer a tractable therapeutic agent for neurodegenerative diseases.

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