1.Screening key genes of PANoptosis in hepatic ischemia-reperfusion injury based on bioinformatics
Lirong ZHU ; Qian GUO ; Jie YANG ; Qiuwen ZHANG ; Guining HE ; Yanqing YU ; Ning WEN ; Jianhui DONG ; Haibin LI ; Xuyong SUN
Organ Transplantation 2025;16(1):106-113
Objective To explore the relationship between PANoptosis and hepatic ischemia-reperfusion injury (HIRI), and to screen the key genes of PANoptosis in HIRI. Methods PANoptosis-related differentially expressed genes (PDG) were obtained through the Gene Expression Omnibus database and GeneCards database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to explore the biological pathways related to PDG. A protein-protein interaction network was constructed. Key genes were selected, and their diagnostic value was assessed and validated in the HIRI mice. Immune cell infiltration analysis was performed based on the cell-type identification by estimating relative subsets of RNA transcripts. Results A total of 16 PDG were identified. GO analysis showed that PDG were closely related to cellular metabolism. KEGG analysis indicated that PDG were mainly enriched in cellular death pathways such as apoptosis and immune-related signaling pathways such as the tumor necrosis factor signaling pathway. GSEA results showed that key genes were mainly enriched in immune-related signaling pathways such as the mitogen-activated protein kinase (MAPK) signaling pathway. Two key genes, DFFB and TNFSF10, were identified with high accuracy in diagnosing HIRI, with areas under the curve of 0.964 and 1.000, respectively. Immune infiltration analysis showed that the control group had more infiltration of resting natural killer cells, M2 macrophages, etc., while the HIRI group had more infiltration of M0 macrophages, neutrophils, and naive B cells. Real-time quantitative polymerase chain reaction results showed that compared with the Sham group, the relative expression of DFFB messenger RNA in liver tissue of HIRI group mice increased, and the relative expression of TNFSF10 messenger RNA decreased. Cibersort analysis showed that the infiltration abundance of naive B cells was positively correlated with DFFB expression (r=0.70, P=0.035), and the infiltration abundance of M2 macrophages was positively correlated with TNFSF10 expression (r=0.68, P=0.045). Conclusions PANoptosis-related genes DFFB and TNFSF10 may be potential biomarkers and therapeutic targets for HIRI.
2.Safety analysis of Yttrium-90 resin microsphere selective internal radiation therapy on malignant liver tumors
Jia CAI ; Shiwei TANG ; Rongli LI ; Mingxin KONG ; Hongyan DING ; Xiaofeng YUAN ; Yuying HU ; Ruimei LIU ; Xiaoyan ZHU ; Wenjun LI ; Haibin ZHANG ; Guanwu WANG
Chinese Journal of Clinical Medicine 2025;32(1):24-29
Objective To explore the safety of Yttrium-90 resin microsphere selective internal radiation therapy (90Y-SIRT) on malignant liver tumors. Methods A retrospective analysis was conducted on 64 patients with malignant liver tumors who underwent 90Y-SIRT from February 2023 to November 2024 at Weifang People’s Hospital. The clinical characteristics of the patients and the occurrence of adverse reactions after treatment were analyzed to assess the safety of 90Y-SIRT. Results Among the 64 patients, there were 52 males (81.25%) and 12 females (18.75%); the average age was (56.29±11.08) years. Seven patients (10.94%) had tumors with maximum diameter of less than 5 cm, 38 patients (59.38%) had tumors with maximum diameter of 5-10 cm, and 19 patients (29.68%) had tumors with maximum diameter of greater than 10 cm. There were 47 cases (73.44%) of solitary lesions and 17 cases (26.56%) of multiple lesions; 53 cases (82.81%) were primary liver cancers and 11 cases (17.19%) were metastatic liver cancers. Of the 64 patients, 63 successfully completed the Technetium-99m macroaggregated albumin (99mTc-MAA) perfusion test and received the 90Y-SIRT; one patient received 90Y-SIRT after the second 99mTc-MAA perfusion test due to a work error. The most common adverse reactions included grade 1 alanine aminotransferase (ALT) elevation in 26 cases (40.62%) and grade 2 in 2 cases (9.37%), grade 1 aspartate aminotransferase (AST) elevation in 27 cases (42.18%) and grade 2 in 7 cases (10.93%); grade 1 nausea in 17 cases (26.56%) and grade 2 in 6 cases (9.37%); grade 1 abdominal pain in 12 cases (18.75%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%); grade 1 vomiting in 11 cases (17.18%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%). Conclusion The adverse reactions of 90Y-SIRT for treating malignant liver tumors are mild, indicating good safety.
3.Mediating effect of sleep quality between somatic symptoms and severity of depression in patients with depression
Xiaotong LI ; Zexin ZHAO ; Ye LIU ; Haibin LI ; Xiao HUANG
Chinese Journal of Clinical Medicine 2025;32(3):465-471
Objective To explore the mediating effect of sleep quality between somatic symptoms and severity of depression in patients with depression. Methods A total of 384 drug-naive patients diagnosed with depression were recruited from the Department of Psychological Medicine of Zhongshan Hospital, Fudan University, during the period from February to August 2024. The severity of depression, somatic symptoms, and sleep quality were assessed using Patient Health Qusetionaire (PHQ)-9, PHQ-15, and Pittsburgh sleep quality index (PSQI), respectively. Based on the PHQ-15 scores, all participants were stratified into two groups: a mild somatic symptoms group(<10 points, n=136)and a moderate-to-severe somatic symptoms group(≥10 points, n=248). Comparisons of sleep quality between the two groups were conducted, and partial correlation analysis was performed to examine the correlation between sleep quality and somatic symptoms. Additionally, linear regression and mediation analyses were conducted to investigate the mediating effect of sleep quality between somatic symptoms and severity of depression. Results The PSQI scores in moderate-to-severe somatic symptoms group were significantly higher than those in mild somatic symptoms group (P<0.001). Partial correlation analysis indicated that, after controlling for depression severity, the positive correlation between PSQI and PHQ-15 scores remained significant in both groups (P<0.01). Regression analysis identified both sleep quality and somatic symptoms as predictors of severity of depression (P<0.001). Additionally, mediation analysis demonstrated that sleep quality partially mediated the relationship between somatic symptoms and severity of depression, accounting for 26.63% (0.090/0.338) of the total effect. Conclusions In patients with depression, sleep quality is associated with somatic symptoms, and both contribute to an increased risk of the severity of depression. Moreover, sleep quality plays a partial mediating effect between somatic symptoms and severity of depression, highlighting the importance of addressing sleep-related issues in the management of depression.
4.Clinical study on risk factors and characteristics of Traditional Chinese Medicine syndrome of advanced adenomatous large intestine polyps
Shuni CHEN ; Haibin HE ; Feng LI ; Dan HONG ; Kaimin GU
International Journal of Traditional Chinese Medicine 2024;46(4):434-438
Objective:To investigate the risk factors of adenomatous colorectal polyps in advanced stage.Methods:Retrospective cross-sectional study. A total of 400 hospitalized patients with colorectal polypectomy and pathological diagnosis of adenomatous polyps (Aps) were selected from December 2020 to December 2022 in Shenzhen Hospital of Beijing University of Chinese Medicine (Longgang), of which 107 patients with progressive adenomas and 293 patients with common adenomas were selected. General information of patients (name, gender, age, BMI), history of smoking, alcohol consumption, history of hypertension, history of diabetes mellitus, and results of 13C urea breath test were collected to analyze the risk factors for the development of adenomas in patients with progressive adenomas and their syndromic characteristics. Results:The distribution of male patients with advanced adenoma was significantly higher than that of common adenoma patients [70.09% (75/107) vs. 57.34% (168/293), P=0.021], and the ages were [(52.25±9.81) years vs. (48.41±10.23) years, P=0.001], BMI [(24.37±3.19) kg/m 2vs. (23.38±3.25) kg/m 2, P=0.007] significantly higher than those of ordinary adenoma patients. Intestinal damp-heat syndrome was the common witness type in both advanced and common adenomas, and the distribution of intestinal damp-heat syndrome in advanced adenomas was significantly higher than that in common adenomas [43.0% (46/107) vs. 32.1% (94/293); χ2=4.10, P=0.043]. The distribution of patients with alcohol drinking history in advanced adenomas was significantly higher than that in common adenomas [61.7% (66/107) vs. 39.3% (115/293); χ2=15.92, P<0.001]. The distribution of diabetic patients with advanced adenoma was significantly higher than that of common adenoma patients [29.9% (32/107) vs. 14.7% (43/293); χ2=19.94, P<0.001]. The infection rate of Hp in advanced adenoma patients was significantly higher than that in common adenoma patients [66.4% (71/107) vs. 44.7% (131/293); χ2=14.69, P<0.001]. Logistic regression analysis showed that age, BMI, male, intestinal damp-heat syndrome, drinking history, diabetes history and Hp infection were risk factors for the development of patients with progressive adenomas ( P<0.05 or P<0.01). Conclusion:Intestinal damp-heat syndrome is the key syndrome in patients with progressive adenoma, and age, BMI, male, history of alcohol consumption, history of diabetes mellitus and Hp infection are the risk factors for its development.
5.Histological characteristics of elastase-induced mouse abdominal aortic aneurysm in regression stage
Meng LI ; Haole LIU ; Panpan WEI ; Kexin LI ; Haibin WU ; Haiwen HOU ; Enqi LIU ; Yankui LI ; Sihai ZHAO
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(1):119-125
Objective To determine the time point when porcine pancreatic elastase(PPE)induced abdominal aortic aneurysm(AAA)reaches the regression phase in mice and observe the histological characteristics of AAA in regression phase.Methods AAAs were induced by transient intraluminal infusion of PPE in C57BL/6J mice.The diameters of the mouse abdominal aortas were measured before PPE infusion and sacrifice time,day 14 for AAA progression phase or day 56 for regression phase after PPE infusion,respectively.The histological characteristics of the aneurysm lesion site on day 14 and day 56 after surgery were compared and analyzed.Results The diameters of the abdominal aortas were significantly increased in both day 14 and day 56 after PPE infusion groups(diameter growth rate 147%and 155%,respectively)as compared to the baseline diameters.In the day 14 group,the infused aortas showed typical AAA characteristics,such as elastin break/degradation,medial smooth muscle cells depletion,and inflammatory cell diffused infiltration.In the day 56 group after PPE infusion,although the artery diameter did not change significantly as compared to the day 14 group,histology showed that elastin was partially repaired,new smooth muscle cells were added to the damaged aorta media,the infiltrated inflammatory cells were significantly subsided,and the adventitia neovascularization was reduced,showing a significant feature of the disease regression phase.Conclusion In the PPE-induced mouse AAA model,day 56 after surgery is an appropriate time point for observing aneurysm regression,and the histological characteristics of the regression are obvious.
6.An insight into the mechanism of iron overload in knee osteoarthritis under the theory of blood stasis
Jiaxu ZENG ; Qi HE ; Bohao CHEN ; Miao LI ; Shaocong LI ; Junzheng YANG ; Zhaofeng PAN ; Haibin WANG
Chinese Journal of Tissue Engineering Research 2024;28(11):1743-1748
BACKGROUND:Knee osteoarthritis is a common disease in middle-aged and elderly people.It is a kind of disease that seriously affects the quality of life of patients and even has the risk of disability.Therefore,the pathogenesis and treatment of knee osteoarthritis have become the focus of research.In Chinese medicine,knee osteoarthritis is often treated as"biness,"which is closely related to"biness"caused by blood stasis and blood vessels blocking collaterals in the theory of"blood stasis"in traditional Chinese medicine.Iron overload is a kind of pathological state caused by iron metabolism disorder,which highly coincides with the pathogenic characteristics and clinical manifestations of the"blood stasis"theory of traditional Chinese medicine,and is a risk factor that promotes the development of knee osteoarthritis. OBJECTIVE:Based on the"blood stasis"theory,to summarize the effects of iron overload on cartilage metabolism and subchondral bone reconstruction,to lay a new theoretical foundation for the treatment of knee osteoarthritis with traditional Chinese medicine,and to explore the therapeutic effect of traditional Chinese medicine for promoting blood circulation after interfering with bone tissue. METHODS:CNKI,WanFang database,PubMed and Web of Science databases were searched for relevant literature.The Chinese search terms were"ferroptosis,iron,iron overload,osteoarthritis,blood stasis"and the English search terms were"ferroptosis,iron,iron overload,osteoarthritis,TCM."In the end,76 articles were included for further review. RESULTS AND CONCLUSION:First of all,we explored the potential of the"blood stasis"theory in treating knee osteoarthritis,and found that"blood stasis"is a crucial part in the progress of knee osteoarthritis,indicating that the"blood stasis"theory is the key to the treatment of knee osteoarthritis in traditional Chinese medicine.Secondly,"blood stasis"and iron overload have a high degree of similarity in pathogenic factors,clinical manifestations,and pathogenic characteristics,suggesting the possibility of"blood stasis"theory in treating iron overload.This finding reminds us that iron overload may be an important mechanistic basis for the"blood stasis"theory in the treatment of knee osteoarthritis.The extracts of blood-activating drugs can relieve iron overload and treat knee osteoarthritis,but the specific mechanism is still unclear.Therefore,we believe that the relationship between"blood stasis"theory and iron overload and related mechanisms are important research directions for knee osteoarthritis in the future.The related mechanism of"blood stasis"theory to alleviate iron overload and then treat knee osteoarthritis also provides a theoretical basis for the modernization of traditional Chinese medicine,such as the development of new drugs and innovative usage,and has certain guiding significance for clinical practice.
7.Regulation of chondrocyte autophagy by acupotomy to promote chondrocyte homeostasis in osteoarthritis
Xiaofei JIA ; Li RAN ; Xiaoshuang MA ; Xiaoyan HEI ; Jiani LIU ; Nan YANG ; Haibin MA ; Jingpeng CHANG
Chinese Journal of Tissue Engineering Research 2024;28(34):5452-5457
BACKGROUND:Acupotomy is an effective method for the clinical treatment of osteoarthritis,with affirmed clinical outcomes,but the specific mechanisms remain unclear OBJECTIVE:To investigate the role of acupotomy in modulating chondrocyte autophagy to promote chondrocyte homeostasis in osteoarthritis. METHODS:Twenty-eight New Zealand rabbits were randomly divided into control group,osteoarthritis group,acupotomy group,and hyaluronic acid group,with seven rabbits in each group.The knee osteoarthritis rabbit model was prepared using the Videman method in the latter three groups.After modeling,the control group and osteoarthritis group received no interventions.The acupotomy group received acupotomy treatment 15 minutes per time,once a week,while the hyaluronic acid group received intra-articular injection of hyaluronic acid once a week,with a continuous treatment duration of 5 weeks.The day after the final intervention,knee joint macrostructure was observed using DR imaging,chondrocyte ultrastructure was examined through transmission electron microscopy,apoptosis of chondrocytes was assessed using Tunel staining,and western blot analysis was used to detect the expression of proteins related to the PI3K/Akt/mTOR pathway. RESULTS AND CONCLUSION:The DR imaging results revealed that the osteoarthritis group exhibited narrowed knee joint spaces and the formation of periarticular osteophytes,while the hyaluronic acid group and acupotomy group showed widened knee joint spaces with a reduction in periarticular osteophytes.Transmission electron microscopy results demonstrated a decreased number of autophagosomes in chondrocytes in the osteoarthritis group,along with nuclear shrinkage,nuclear membrane rupture,incomplete organelle morphology,and a clear tendency towards cell death.In contrast,both the hyaluronic acid group and acupotomy group exhibited a significant increase in autophagosomes,intact nuclear membranes,and a well-preserved cellular state.Tunel staining results indicated a considerable decrease in the number of apoptotic cells in the hyaluronic acid group and acupotomy group compared with the osteoarthritis group.Western blot results revealed that,compared with the control group,the expression levels of Beclin1,Cath D,and LC3II/LC3I were significantly decreased in the osteoarthritis group(P<0.05),while the expression levels of p-Akt/Akt and p-mTOR/mTOR were significantly increased(P<0.05);compared with the osteoarthritis group,the expression levels of Beclin1,Cath D,and LC3II/LC3I were significantly increased in both the hyaluronic acid group and acupotomy group(P<0.05),while the expression levels of p-Akt/Akt and p-mTOR/mTOR were significantly decreased(P<0.05).To conclude,acupotomy intervention can modulate the PI3K/Akt/mTOR signaling pathway to enhance the autophagic level in chondrocytes,thereby maintaining chondrocyte homeostasis.This ultimately leads to a slowdown in cartilage degeneration.
8.Effect of zirconia personalized gingival penetration on peri-implant soft and hard tissue of thin gingival biotypes in the anterior region: a retrospective study
Yarong WANG ; Mu ZHANG ; Pei CHEN ; Shaobing LI ; Haibin LU ; Mianyan ZENG ; Yan ZENG ; Mingdeng RONG
Chinese Journal of Stomatology 2024;59(7):690-695
Objective:To investigate the effect of zirconia personalized gingival structure on peri-implant soft and hard tissue stability after single-tooth implant restorations in patients with thin gingival biotypes in the anterior region, with a view to provide a clinical guideline.Methods:This retrospective study included 20 patients with thin gingival biotype and implant restorations in the anterior region. These patients included 9 males and 11 females, and the age was (35.2± 10.3) years. The patients were from the Department of Periodontal Implantology, Stomatology Hospital, Southern Medical University from January 2018 to December 2022. Computer-aided design/computer-aided manufacturing (CAD/CAM) techniques were used to fabricate a titanium base zirconia personalized gingival structure to maintain the soft-tissue perforated gingival contour of the anterior esthetic zone. This structure consists of two modalities: titanium base + zirconia outer crown or titanium base personalized zirconia abutment + zirconia outer crown. Clinical outcomes were recorded immediately and after delivery of the final restorations. Implant retention was recorded, esthetic scoring was performed using the pink esthetic index, the amount of bone resorption at the implant margins was measured based on digitized apical radiographs, and periodontal health was evaluated using the modified plaque index and the modified bleeding index.Results:The survival rate of the 20 implants was 100% after 3 years of wearing the final restorations, with a pink aesthetic score of 9.3±0.9. Bone resorption at the proximal and distal mesial margins of the implants was 0.09 (-0.21, 0.20) mm, 0.17 (-0.12, 0.27) mm after 3 years, respectively, and the difference was not statistically significant when compared to bone resorption immediately after placement of the final restoration [0(0, 0) mm] ( Z=-1.03, P=0.394; Z=-2.05, P=0.065). Conclusions:Zirconia personalized gingival structure maintains the stability of peri-implant hard and soft tissues of thin gingival biotypes in the anterior region.
9.Oral submucosal fibrosis induced by active components in areca nut:a network pharmacology-based analysis and validation of the mechanism
Ruibo LI ; Ge GAO ; Xi XIE ; Haibin LUO
Journal of Southern Medical University 2024;44(5):930-940
Objective To explore the pharmacologically active components in areca nut that induce oral submucosal fibrosis(OSF)and the possible mechanism.Methods The chemical components in areca nut were analyzed using Thermo QE plus liquid chromatography tandem high-resolution mass spectrometer and Compound discover 3.2 data processing software.The chemical activity of the top 20 compounds was analyzed based on Chinese Pharmacopoeia(2015),PubChem,Chemical book,and SciFinder databases.The potential active components,core targets,biological functions and signaling pathways affecting OSF were analyzed by network pharmacology.The targets of OSF were obtained by integrating Genecards and KEGG databases.The compounds acting on the targets were selected from the Systematic Pharmacology Technology Platform of Traditional Chinese Medicine(TCMSP),and the target-compound,compound-TCM,target-compound-TCM network was constructed.Molecular docking was used to analyze the component-target binding.Immunohistochemistry was used to examine the expressions of key proteins in the PI3K-Akt and MAPK pathways in clinical samples of OSF.Results The core intersection target genes between the top 10 active ingredients in areca nut extract and OSF involved mainly the PI3K-Akt and MAPK pathways.In the clinical samples,the expressions of PI3K protein decreased and the expressions p-PI3K,AKT1 and P-Akt all increased significantly in OSF tissue,where increased JNK protein expression and enhanced activity of c-Jun and c-Fos transcriptional factors were also detected.The OSF patients had significantly elevated plasma levels of IL-6 and IL-8 compared with healthy individuals.Conclusion The main active ingredients including arecoline,arecaine,and guvacine are capable of activating the PI3K-Akt and MAPK pathways to promote the expressions of inflammatory mediators IL-6 and IL-8 and induce collagen hyperplasia,thus leading to the occurrence of oral submucosal fibrosis.
10.Molecular markers of postoperative recurrence and malignant transformation in low-grade gliomas and their predictive value
Xuzhao LI ; Shiqi ZHOU ; Haibin LENG ; Dakuan GAO ; Lixin XU
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(2):284-291
【Objective】 To identify the risk factors for recurrence and malignant transformation (MT) in patients with low-grade glioma (LGG) after surgery. 【Methods】 The data of 163 patients who underwent LGG resection and subsequent follow-up from March 2009 to April 2019 were retrospectively collected. Patients who did not experience recurrence or MT after surgery were included in the control group (85 cases), those who experienced recurrence after surgery were included in the observation 1 group (44 cases), and those who experienced MT after surgery were included in the observation 2 group (34 cases). Based on the clinical data of the three groups of patients, their clinical characteristics were analyzed, and the risk factors and predictive value for recurrence and MT were explored using Logistic regression model and receiver operating characteristic (ROC) curve. 【Results】 There were significant differences between the control group and the observation 1 group in preoperative seizure, preoperative Karnofsky performance status (KPS) score, and surgical approach (P<0.05). There were significant differences between the control group and the observation 2 group in gender, preoperative KPS score, tumor size, and surgical approach (P<0.05). There were significant differences between the control group and the observation 1 group in isocitrate dehydrogenase (IDH) mutation, proliferating cell nuclear antigen (PCNA), matrix metalloproteinase-9 (MMP-9), cancer-testis antigen OY-TES-1, OY-TES-1 mRNA protein, tumor suppressor protein p53, mouse double minute 2 (MDM2), vascular endothelial growth factor (VEGF), or epidermal growth factor receptor (EGFR) (P<0.05). There were significant differences between the control group and the observation 2 group in PCNA, MMP-9, cancer-testis antigen OY-TES-1, OY-TES-1 mRNA protein, or VEGF (P<0.05). Logistic regression analysis showed that IDH mutation, MMP-9, and PCNA were independent risk factors for LGG recurrence (P<0.05), while VEGF, MMP-9, and PCNA were independent risk factors for LGG MT (P<0.05). The area under curve (AUC) of PCNA, MMP-9 and IDH mutation for predicting LGG MT after surgery was 0.744, 0.790, and 0.799, respectively. The AUC of PCNA, MMP-9, and VEGF for predicting LGG recurrence after surgery was 0.729, 0.750, and 0.900, respectively. 【Conclusion】 This study found that IDH mutation, MMP-9 and PCNA were independent risk factors for LGG recurrence, while VEGF, MMP-9 and PCNA were independent risk factors for LGG MT by retrospectively analyzing the clinical data and protein expression of 163 patients with LGG after surgery. These proteins have high accuracy in predicting LGG recurrence and MT after surgery. Therefore, the proteins may play an important role in the biological behavior and treatment effect of LGG, and can be used as reference indicators for prognosis evaluation and individualized treatment of LGG patients after surgery.

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