1.Prediction of postoperative pulmonary complications in video-assisted thoracic surgery for lung cancer based on cardiopulmonary exercise testing and machine learning
Lei GUO ; Fusong LIU ; Zhilong OU ; Lan GUO ; Tiantian LI ; Chongfeng ZHOU ; Kun LUAN ; Xiaoman CHEN ; Yucheng WEI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(01):44-52
Objective To develop a predictive model for postoperative pulmonary complications (PPC) following video-assisted thoracic surgery (VATS) in lung cancer patients by integrating cardiopulmonary exercise testing (CPET) parameters and machine learning techniques. Methods A retrospective analysis was conducted on patients with early-stage non-small cell lung cancer who underwent CPET and VATS at Guangdong Provincial People’s Hospital between October 2021 and July 2023. Patients were divided into a PPC group and a non-PPC group. The least absolute shrinkage and selection operator (LASSO) regression was used to select important features associated with PPC. Six machine learning algorithms were utilized to construct prediction models, including logistic regression, support vector machine, k-nearest neighbors, random forest, gradient boosting machine, and extreme gradient boosting. The optimal model was interpreted using SHapley Additive exPlanations (SHAP). Results A total of 325 patients were included, with an average age of 60.36 years, and 55.1% were male. Significant differences were observed between the PPC and non-PPC groups in age, diabetes, coronary heart disease, surgical approach, forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FVC% predicted, peak oxygen uptake (peak VO2), anaerobic threshold (AT), and ventilatory equivalent for carbon dioxide slope (VE/VCO2 slope) (P<0.05). In the predictive model constructed by selecting 7 key features using LASSO regression, the random forest model demonstrated the best overall performance across various metrics, with an area under the receiver operating curve of 0.930, an F1 score of 0.836, and a Brier score of 0.133 in the training set. It also exhibited good predictive ability and calibration in the test set. SHAP analysis ranked feature importance as follows: peak VO2, VE/VCO2 slope, age, FEV1, smoking history, diabetes, and surgical approach. Conclusion Integrating CPET parameters, the random forest model can effectively identify high-risk patients for PPC and has the potential for clinical application.
2.Huanglian Jiedutang Improves Cognitive Impairment after Schemic Stroke by Regulating Neuron via NF-κB Signaling Pathway
Mengying SUN ; Lizhen WANG ; Tong LI ; Leilei WANG ; Shiyan JIA ; Tingting WANG ; Yanwen YANG ; Kaiqiang SI ; Youxiang CUI ; Zhilong LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):68-76
ObjectiveTo investigate the effects of Huanglian Jiedutang (HLJDT) on cognitive function in mice with ischemic stroke (IS) and to elucidate whether its neuroprotective effects are mediated by inhibition of the nuclear factor-κB (NF-κB) signaling pathway and subsequent suppression of NF-κB-regulated neuronal apoptosis. MethodsAn IS model was established using middle cerebral artery occlusion (MCAO). Sixty C57BL/6J mice were randomly assigned to five groups (n =12 per group), i.e., sham operation, model, HLJDT low-dose (3.9 g·kg-1·d-1), HLJDT high-dose (7.8 g·kg-1·d-1), and Ginkgo biloba extract (GBE, 31.2 mg·kg-1·d-1). Post-operatively, neurological deficit scores (Longa score), cerebral infarct volume assessed by 2,3,5-triphenyltetrazolium chloride (TTC) staining, and brain water content were evaluated. Learning and memory were assessed using new object recognition (NOR) and fear conditioning (FC) tests. Hippocampal pathology was examined via hematoxylin and eosin (HE) staining. Immunofluorescence detected expression of glial fibrillary acidic protein (GFAP, astrocyte marker), cellular oncogene Fos (c-Fos, neuronal activation marker), and glutamate decarboxylase 65 (GAD65). Western blot measured nuclear factor-κB inhibitor protein α (IκBα), phosphorylated IκBα (p-IκBα), NF-κB p65, phosphorylated NF-κB p65 (p-NF-κB p65), ionic calcium binding adapter molecule 1 (Iba-1), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and apoptosis-related proteins, such as cleaved cysteinyl aspartate-specific protease 3 (Caspase-3), B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X protein (Bax). Real-time quantitative PCR (Real-time PCR) was used to assess mRNA levels of Iba-1, TNF-α, IL-1β, NF-κB p65, cleaved Caspase-3, Bax, and Bcl-2. ResultsCompared with the sham group, the model group exhibited significantly increased neurological deficit scores, brain water content, and cerebral infarct volume (P<0.01). Hippocampal CA1 neurons were disorganized, showing nuclear pyknosis and karyolysis. NOR exploration time and FC freezing time were significantly reduced (P<0.01). GFAP and c-Fos expression were increased, while GAD65 expression was decreased (P<0.01). Cleaved Caspase-3 and Bax were upregulated, Bcl-2 was downregulated, and the Bax/Bcl-2 ratio was elevated (P<0.01). Expression levels of p-IκBα, p-NF-κB p65, IL-1β, TNF-α, and Iba-1 were significantly increased (P<0.01). Compared with the model group, HLJDT high-dose, low-dose, and GBE groups showed significant improvements in all parameters (P<0.01). Among them, the HLJDT high-dose group showed the most pronounced neuronal structural recovery and superior performance in NOR and FC tests (P<0.01). In this group, GFAP and c-Fos decreased, GAD65 increased (P<0.01), apoptosis-related protein expression was reversed, and NF-κB signaling and related inflammatory factor expression were suppressed (P<0.01). ConclusionHLJDT ameliorates cognitive dysfunction in mice after IS, potentially by inhibiting the NF-κB signaling pathway, thereby reducing neuroinflammation and hippocampal neuronal apoptosis.
3.Mechanisms of aryl hydrocarbon receptor in liver diseases
Jing QIN ; Zhilong HE ; Yu LIU ; Kai HU
Journal of Clinical Hepatology 2025;41(9):1943-1948
Aryl hydrocarbon receptor (AhR) plays an important role in the development and progression of liver diseases. This article elaborates on the structure of AhR and its function in liver development and provides a detailed analysis of its molecular mechanisms in diseases such as metabolic associated fatty liver disease, alcoholic liver disease, viral hepatitis, drug-induced liver injury, autoimmune hepatitis, liver cirrhosis, and liver cancer. This article also reviews the research advances in AhR agonists and antagonists and analyzes their potential application prospects in disease treatment. At the same time, it points out that although AhR is a promising therapeutic target, there are still various challenges in its clinical application. It is suggested that future research should focus on developing AhR modulators with high specificity and low toxicity and further explore its mechanism of action in different liver diseases.
4.Impact of capsaicin on the gut microbiota and antimicrobial peptides expression of Anopheles stephensi
ZHENG Dan ; LIU Zhilong ; WANG Jing
China Tropical Medicine 2025;25(1):15-
Objective To investigate the effects of capsaicin on gut microbiota and antimicrobial peptide expression of Anopheles stephensi, providing experimental references for the application of capsaicin in mosquito-borne disease prevention and control. Methods Anopheles stephensi were continuously fed with sugary water containing capsaicin or DMSO for the capsaicin-treated group and the control, respectively. The DNA of the female mosquito's midguts and gut bacteria was extracted. Bacterial 16S rDNA high-throughput sequencing and real-time fluorescence quantitative PCR were used to analyze and compare the bacteria diversity, gut flora composition, relative abundance, and total bacterial load in female mosquitoes’ midgut between the control and capsaicin treatment groups. Total RNA was extracted from the midguts of the two groups of Anopheles mosquitoes, and the transcriptional levels of important antimicrobial peptides were detected and compared by reverse transcription and real-time fluorescence quantitative PCR. Results A total of 10 phyla, 11 classes, 28 orders, 43 families, and 62 genera were identified in the two groups. The capsaicin-treated group had fewer taxa, with significantly reduced bacterial diversity, and different community composition and relative abundance of the flora compared to the control group. At the phylum level, Bacteroidota, Proteobacteria, and Firmicutes predominated in both two groups. At the order level, Flavobacteriales, Acetobacterales, Pseudomonadales, and Lactobacillales were the dominant bacteria, with reduced relative abundance of Pseudomonadales and Acetobacterales and increased relative abundance of Flavobacteriales and Lactobacillales in the capsaicin-treated group. At the genus level, Elizabethkingia was predominantly abundant in both samples, with higher relative abundance of Elizabethkingia, Leuconostoc, and Gluconobacter in the capsaicin-treated group, while Asaia and Acinetobacter had significantly lower relative abundance compared to the control group. In addition to these changes, the total bacterial load was increased and the transcriptional levels of attacin C, cecropin A, and defensin were significantly decreased by capsaicin treatment. Conclusions Capsaicin treatment significantly affects the composition of the gut flora in Anopheles stephensi and increases the total bacterial load while inhibiting the expression of antimicrobial peptides. Based on the analysis, it indicates that capsaicin might affect the fecundity and vector competence of Anopheles by changing the energy metabolism and immune-related bacteria.
5.Effects of acupuncture on podocyte autophagy and the LncRNA SOX2OT/mTORC1/ULK1 pathway in rats with diabetic kidney disease.
Xu WANG ; Yue ZHANG ; Hongwei LI ; Handong LIU ; Jie LI ; Ying FAN ; Zhilong ZHANG
Chinese Acupuncture & Moxibustion 2025;45(10):1450-1458
OBJECTIVE:
To observe the effects of acupuncture on podocyte autophagy and long non-coding RNA SOX2 overlapping transcript (LncRNA SOX2OT)/mammalian target of rapamycin C1 (mTORC1)/Unc-51-like kinase 1 (ULK1) pathway in rats with diabetic kidney disease (DKD), and to explore the mechanism by which acupuncture reduces urinary protein.
METHODS:
A total of 40 SPF-grade male Sprague-Dawley rats were randomly divided into a control group (n=10) and a modeling group (n=30). The DKD model was established by feeding a high-fat, high-sugar diet combined with intraperitoneal injection of streptozotocin (STZ) in the modeling group. Twenty rats with successful DKD model were randomly divided into a model group (n=10) and an acupuncture group (n=10). The acupuncture group received "spleen and stomach-regulating" acupuncture at bilateral "Zusanli" (ST36), "Fenglong" (ST40), "Yinlingquan" (SP9), and "Zhongwan" (CV12), 30 min per session, once daily, five times per week, for four weeks. The general condition, fasting blood glucose (FBG), 2-hour postprandial glucose (2hPG), serum creatinine (SCr), blood urea nitrogen (BUN), 24-hour urinary protein quantification, and urine albumin-to-creatinine ratio (UACR) were compared before and after the intervention. After intervention, urinary podocyte injury marker SPON2 was measured by ELISA. Podocyte autophagosomes and glomerular basement membrane ultrastructure in renal tissue were observed via transmission electron microscopy. Podocyte apoptosis was assessed by TUNEL staining. The protein expression of microtubule-associated protein 1 light chain 3Ⅱ (LC3-Ⅱ), mTORC1, ULK1, Beclin-1, and p62 in renal tissue was detected by Western blot. LncRNA SOX2OT expression in renal tissue was measured by real-time PCR.
RESULTS:
After the intervention, compared with the control group, the model group exhibited increased food and water intake, increased urine output, weight loss, and loose stools; compared with the model group, the food and water intake, urine volume, and loose stools were improved in the acupuncture group. Compared with the control group, FBG, 2hPG, SCr, BUN, 24-hour urinary protein quantification, UACR, and urinary SPON2 were all higher in the model group (P<0.01); compared with the model group, the FBG, 2hPG, SCr, BUN, 24-hour urinary protein quantification, UACR, and urinary SPON2 were all lower in the acupuncture group (P<0.01). Compared with the control group, the model group showed reduced podocyte autophagosomes and thickened glomerular basement membrane; compared with the model group, the acupuncture group had increased podocyte autophagosomes and less thickened basement membrane. Compared with the control group, the podocyte apoptosis index (AI) was higher in the model group (P<0.01); compared with the model group, the AI was lower in the acupuncture group (P<0.01). Compared with the control group, the expression of ULK1, Beclin-1, and LC3-Ⅱ proteins was lower, and the expression of mTORC1 and p62 proteins was higher in the model group (P<0.01). Compared with the model group, the expression of ULK1, Beclin-1, and LC3-Ⅱ proteins was higher, and the expression of mTORC1 and p62 proteins was lower in the acupuncture group (P<0.01). Compared with the control group, the LncRNA SOX2OT expression was lower in the model group (P<0.01). Compared with the model group, LncRNA SOX2OT expression was higher in the acupuncture group (P<0.01).
CONCLUSION
The "spleen and stomach-regulating" acupuncture method could improve renal function in DKD rats, reduce blood glucose and urinary protein excretion, alleviate podocyte injury, and enhance podocyte autophagy. The mechanism may be related to modulation of the renal LncRNA SOX2OT/mTORC1/ULK1 pathway.
Animals
;
Podocytes/cytology*
;
Diabetic Nephropathies/physiopathology*
;
Rats, Sprague-Dawley
;
Male
;
Rats
;
Mechanistic Target of Rapamycin Complex 1/genetics*
;
Autophagy
;
Acupuncture Therapy
;
Autophagy-Related Protein-1 Homolog/genetics*
;
RNA, Long Noncoding/metabolism*
;
Humans
;
Signal Transduction
6.Regulation of Ferroptosis by Traditional Chinese Medicine for Colorectal Cancer Intervention: A Review
Xiangchen LIU ; Weihan ZHAO ; Feixue FENG ; Xiaodong YANG ; Zhilong ZHAO ; Dezhen YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):276-286
Colorectal cancer (CRC) is a common malignant tumor of the digestive tract with high morbidity and mortality. Although existing treatments can prolong the survival of patients, problems such as low quality of life, obvious side effects, and unsatisfactory clinical efficacy still exist, which cannot fully satisfy the overall needs of patients. For this reason, it is crucial to explore the mechanism underlying the development of CRC and to identify new treatment strategies. In recent years, with the deepening of research, ferroptosis has been gradually proven to effectively inhibit the proliferation and metastasis of CRC cells, overcome tumor drug resistance, enhance anti-tumor efficacy, and prevent tumor progression and recurrence. Therefore, regulating ferroptosis is expected to become a new strategy for the treatment of CRC. Traditional Chinese medicine (TCM) has been widely used in CRC treatment due to its advantages of multiple components, multiple targets, low drug resistance, and few side effects, and has gradually become a current research hotspot. Extensive studies have shown that TCM active ingredients and compound formulae can regulate ferroptosis-related pathways, such as iron metabolism, lipid metabolism, the cystine/glutamate antiporter system Xc- (System Xc-)/glutathione (GSH)/glutathione peroxidase 4 (GPX4), ferroptosis suppressor protein 1 (FSP1)/coenzyme Q10 (CoQ10)/nicotinamide adenine dinucleotide phosphate [NAD(P)H], tumor protein 53 (p53), nuclear factor erythroid-2-related factor 2 (Nrf2), and non-coding RNA pathways to inhibit the growth and proliferation of CRC, thereby exerting anti-tumor effects. This review systematically summarized the mechanisms of ferroptosis related to CRC, therapeutic targets and prognosis-related markers associated with ferroptosis in CRC, and research progress on TCM targeting and regulating ferroptosis for CRC intervention, aiming to provide new perspectives and a theoretical basis for the prevention and treatment of CRC with TCM.
7.Regulation of Ferroptosis by Traditional Chinese Medicine for Colorectal Cancer Intervention: A Review
Xiangchen LIU ; Weihan ZHAO ; Feixue FENG ; Xiaodong YANG ; Zhilong ZHAO ; Dezhen YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):276-286
Colorectal cancer (CRC) is a common malignant tumor of the digestive tract with high morbidity and mortality. Although existing treatments can prolong the survival of patients, problems such as low quality of life, obvious side effects, and unsatisfactory clinical efficacy still exist, which cannot fully satisfy the overall needs of patients. For this reason, it is crucial to explore the mechanism underlying the development of CRC and to identify new treatment strategies. In recent years, with the deepening of research, ferroptosis has been gradually proven to effectively inhibit the proliferation and metastasis of CRC cells, overcome tumor drug resistance, enhance anti-tumor efficacy, and prevent tumor progression and recurrence. Therefore, regulating ferroptosis is expected to become a new strategy for the treatment of CRC. Traditional Chinese medicine (TCM) has been widely used in CRC treatment due to its advantages of multiple components, multiple targets, low drug resistance, and few side effects, and has gradually become a current research hotspot. Extensive studies have shown that TCM active ingredients and compound formulae can regulate ferroptosis-related pathways, such as iron metabolism, lipid metabolism, the cystine/glutamate antiporter system Xc- (System Xc-)/glutathione (GSH)/glutathione peroxidase 4 (GPX4), ferroptosis suppressor protein 1 (FSP1)/coenzyme Q10 (CoQ10)/nicotinamide adenine dinucleotide phosphate [NAD(P)H], tumor protein 53 (p53), nuclear factor erythroid-2-related factor 2 (Nrf2), and non-coding RNA pathways to inhibit the growth and proliferation of CRC, thereby exerting anti-tumor effects. This review systematically summarized the mechanisms of ferroptosis related to CRC, therapeutic targets and prognosis-related markers associated with ferroptosis in CRC, and research progress on TCM targeting and regulating ferroptosis for CRC intervention, aiming to provide new perspectives and a theoretical basis for the prevention and treatment of CRC with TCM.
8.Establishment and validation of urine AD7c-NTP reference intervals for healthy adults in Mianyang area using the indirect method
Yurong ZHANG ; Yifei HE ; Ping YANG ; Zixi XU ; Zhilong CAI ; Yang LIU ; Dan WANG ; Liang HUANG ; Bing HOU ; Jia YANG ; Xuemei JIANG ; Kun FANG
Chinese Journal of Clinical Laboratory Science 2025;43(5):378-381
Objective To establish the reference interval of urine Alzheimer-associated neuronal thread protein(AD7c-NTP)for healthy adults in Mianyang area using the indirect method.Methods The detection results of urine AD7c-NTP from 5 093 healthy in-dividuals were collected from the information management database of Medical Laboratory Department of Sichuan Science City Hospital from March 2017 to March 2022.Skewness-kurtosis and Kolmogorov-Smirnov tests were used to determine whether the data followed a normal distribution.After removing outliers using the Box Plots method,the enrolled subjects were grouped by gender and age.The Mann-Whitney U or Kruska-Wallis H tests were used to analyze the between-group differences of urine AD7c-NTP in healthy individu-als with different genders and ages.The adjacent age groups without statistically significant difference(P>0.05)were combined,and the indirect method(non-parametric test method)was used to calculate the reference intervals for different gender and age groups.Results Skewness-kurtosis and Kolmogorov-Smirnov tests showed that the data followed a non-normal distribution.After removing 293 outliers using the Box Plots method,a total of 4 800 subjects,including 3 199 males and 1 601 females,were enrolled.The enrolled subjects were grouped by gender and age,and the non-parametric test method were used to establish the reference intervals of urine AD7c-NTP in healthy populations with different genders.The Mann-Whitney U test confirmed that urine AD7c-NTP levels existed gen-der differences(Z=14.09,P<0.01),and the reference intervals for males and females were≤1.10 ng/mL and≤1.40 ng/mL,re-spectively.There were also statistical differences in urine AD7c-NTP levels among different age groups of the same gender.After combi-ning adjacent age groups without statistically significant difference(P>0.05),the reference intervals of urine AD7c-NTP in healthy populations with different genders and ages were established by the non-parametric test method,which were≤1.00 ng/mL for male 20-39 years old group,≤1.10 ng/mL for male 40-79 years old group,≤1.60 ng/mL for male≥80 years old group,≤1.30 ng/mL for female 20-69 years old group,and≤1.60 ng/mL for female≥70 years old group,respectively.The established reference intervals of urine AD7c-NTP were further verified by healthy individuals,and the results met the standards.Conclusion The reference intervals of urine AD7c-NTP in healthy populations with different genders and ages in Mianyang area are established successfully using the indi-rect method,which may help to predict the risk of Alzheimer's disease in clinical practice and provide support for the diagnosis and treatment of the disease.
9.Research progress of B lymphocytes in the tumor microenvironment of thyroid cancer
Zhilong ZHANG ; Chao FENG ; Fangshu LI ; Wei ZHANG ; Chaomei LIU
Immunological Journal 2025;41(7):512-518
The incidence of thyroid cancer has significantly increased in the past decade or so.The tumor tissues,stromal cells and immune cells that exist in thyroid cancer itself constitute the dynamic and changing tumor microenvironment of thyroid cancer.The tumor microenvironment plays a decisive role in the occurrence,development and treatment of thyroid cancer,among which B lymphocytes have received increasing attention.This review systematically summarizes the latest research progress of B lymphocytes in the tumor microenvironment of thyroid cancer,to better explore the characteristics of the tumor microenvironment of thyroid cancer.
10.Research progress of B lymphocytes in the tumor microenvironment of thyroid cancer
Zhilong ZHANG ; Chao FENG ; Fangshu LI ; Wei ZHANG ; Chaomei LIU
Immunological Journal 2025;41(7):512-518
The incidence of thyroid cancer has significantly increased in the past decade or so.The tumor tissues,stromal cells and immune cells that exist in thyroid cancer itself constitute the dynamic and changing tumor microenvironment of thyroid cancer.The tumor microenvironment plays a decisive role in the occurrence,development and treatment of thyroid cancer,among which B lymphocytes have received increasing attention.This review systematically summarizes the latest research progress of B lymphocytes in the tumor microenvironment of thyroid cancer,to better explore the characteristics of the tumor microenvironment of thyroid cancer.

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