1.Mitochondrial Transfer Promotes Immune Escape in Osteosarcoma Cells: Mechanisms and Research Advances
Qishun QIN ; Xingsheng WANG ; Kai LI ; Pei PENG ; Shihong XU
Medical Journal of Peking Union Medical College Hospital 2025;16(5):1250-1259
Osteosarcoma is a highly aggressive malignant bone tumor whose immuno evasion mechanisms play a pivotal role in tumor progression and therapeutic resistance. Recent studies have identified mitochondrial transfer as a novel mode of intercellular communication that significantly influences metabolic reprogramming and immune evasion in osteosarcoma cells. This mechanism operates through three principal pathways: (1) enhancing energy metabolic efficiency in tumor cells; (2) mitigating intracellular oxidative stress; and (3) modulating immune checkpoint molecule expression. Collectively, these alterations impair host immune surveillance while promoting tumor proliferation, invasion, and distant metastasis through metabolic remodeling, immune tolerance induction, and tumor microenvironment reconstruction. This review systematically elucidates the molecular mechanisms by which mitochondrial transfer regulates immune evasion in osteosarcoma and its dynamic impact on the tumor microenvironment. Furthermore, we discuss the translational potential of targeting this pathway for precision therapy and outline future research directions in this emerging field.
2.Research progress on median nerve electrical stimulation for awakening comatose patients with brain injury
Le AN ; Rui SHAO ; Xingsheng WANG ; Ziren TANG
Chinese Critical Care Medicine 2024;36(9):997-1000
With the development of medicine, the survival rate of patients with traumatic brain injury has gradually increased, and more lives have been successfully saved. However, the number of comatose patients has also risen, leading to prolonged medical care that increases economic burdens on families and society. The awakening of comatose patients is of great significance. As a non-invasive brain stimulation technique, median nerve electrical stimulation (MNS) has been widely used in clinical awakening therapy, and multiple clinical studies have confirmed the effectiveness of this technology. This article summarizes the research progress of this technology from the aspects of coma mechanism, median nerve pathway, awakening mechanism of MNS, clinical application of MNS, parameter setting of electrical stimulation, and neurological function evaluation.
3.Mechanism of Notch signaling pathway regulated by YAP in NASH liver fibrosis mice and the intervention effect of Cigu Xiaozhi prescription
Li WANG ; Xingsheng WANG ; Xiuping ZHAO ; Aidi WANG ; Hongmei QU ; Yanhua MA
Journal of China Medical University 2024;53(5):392-400
Objective To investigate the regulatory mechanism of Notch signaling pathway by YAP in non-alcoholic steatohep-atitis(NASH)liver fibrosis,and assess the intervention effect of Cigu Xiaozhi prescription in detoxification and phlegm treatment.Methods C57BL/6J mice were randomly divided into different groups,including a normal group,NASH liver fibrosis model group,verteporfin(VP)intervention group,VP+Chinese medicine(Cigu Xiaozhi prescription)low-dose group,VP+Chinese medicine high-dose group,and dimethyl sulfoxide control group.The methionine/choline-deficient diet combined with low-dose CCl4 was used to construct the NASH liver fibrosis model.The degree of liver fibrosis was evaluated using hematoxylin and eosin(HE)and Masson staining.Four protein factors associated with liver fibrosis were detected using enzyme-linked immunosorbent assay,and hydroxyproline levels in the mouse liver was determined using the alkaline water method.The localization of α-SMA,ColⅠ,YAP,and Notch1 proteins in the liver was determined using immunohistochemistry.Additionally,the mRNA and protein expression levels of the Notch signaling pathway molecules,namely Notch1/2,J agged1,and DLL4,were assessed using real-time quantitative PCR and Western blotting analyses,respectively.Results The HE and Masson staining results revealed that the liver cells of NASH liver fibrosis mice were swollen and the cytoplasm was transparent.Additionally,evident fibrosis was observed in the hepatic lobule,portal area,and sinus;it was accompanied by heightened levels of inflam-matory cell infiltration,a large number of fat droplets,and instances of local hepatocyte necrosis,dissolution,and cirrhosis.The four factors associated with liver fibrosis showed a substantial increase(P<0.01).α-SMA,ColⅠ,YAP,and Notch1 were localized in the cytoplasm of hepatocytes.YAP,Notch1/2,and Jagged1 were highly expressed in the liver(P<0.01)but were downregulated after intervention with VP and VP+high and low doses of Cigu Xiaozhi prescription(P<0.05).Meanwhile,DLL4 factor was upregulated in the VP+high-dose of Cigu Xiaozhi prescription group(P<0.05).Conclusion YAP may inhibit activation of the Notch pathway by downregulating Notch1/2 and Jagged1 and upregulating DLL4,thereby interfering with the occurrence of liver fibrosis in NASH.Treatment with Cigu Xiaozhi pre-scription may inhibit Notch signaling pathway activation by downregulating YAP,Notch1/2,and Jagged1 and upregulating DLL4 through its multi-components and multi-targets properties,ultimately slow the progression of liver fibrosis in NASH.
4.Adjuvant chemotherapy versus adjuvant concurrent chemoradiotherapy after radical surgery for early-stage cervical cancer: a randomized, non-inferiority, multicenter trial.
Danhui WENG ; Huihua XIONG ; Changkun ZHU ; Xiaoyun WAN ; Yaxia CHEN ; Xinyu WANG ; Youzhong ZHANG ; Jie JIANG ; Xi ZHANG ; Qinglei GAO ; Gang CHEN ; Hui XING ; Changyu WANG ; Kezhen LI ; Yaheng CHEN ; Yuyan MAO ; Dongxiao HU ; Zimin PAN ; Qingqin CHEN ; Baoxia CUI ; Kun SONG ; Cunjian YI ; Guangcai PENG ; Xiaobing HAN ; Ruifang AN ; Liangsheng FAN ; Wei WANG ; Tingchuan XIONG ; Yile CHEN ; Zhenzi TANG ; Lin LI ; Xingsheng YANG ; Xiaodong CHENG ; Weiguo LU ; Hui WANG ; Beihua KONG ; Xing XIE ; Ding MA
Frontiers of Medicine 2023;17(1):93-104
We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415-1.757; P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.
Female
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Humans
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Uterine Cervical Neoplasms/drug therapy*
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Prospective Studies
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Quality of Life
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Neoplasm Staging
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Chemoradiotherapy
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Chemotherapy, Adjuvant/adverse effects*
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Adjuvants, Immunologic
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Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
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Retrospective Studies
5.An immunochromatographic method for SARS-CoV-2 based on the assistance of internal reference protein
Ziyi WANG ; Xiaodan CHENG ; Xingsheng YANG ; Zhen RONG ; Shengqi WANG
Military Medical Sciences 2023;47(12):913-918
Objective To monitor the validity of the sample process flow and to improve the detection accuracy of a SARS-CoV-2 antigen by introducing internal reference into SARS-CoV-2 fluorescent lateral flow assay.Methods Silica-core double-layer quantum dots(SiO2-DQD)microspheres were prepared using a polyethyleneimine(PEI)-mediated self-assembly method before being separately conjugated with an internal reference detection antibody and SARS-CoV-2 antibody.Their capture antibodies were plotted on two test lines of the nitrocellulose membrane.Based on double-antibody sandwich detection principles,an internal reference-assisted fluorescent lateral flow assay for SARS-CoV-2 antigen was established.Results According to the readout fluorescent signals,the detection limit of the method for the SARS-CoV-2 antigen reached 0.01 ng/ml with a validated sample process,suggesting its good specificity and stability.Conclusion In this study,a rapid internal reference-integrated fluorescent lateral flow assay for SARS-CoV-2 has been established,which provides control reference for the analysis workflow so that the false-negative rate of the test results can be reduced.
6.Role of Nrf2/HO-1 Signaling Pathway in Osteoporosis and Chinese Medicine Intervention: A Review
Jirong ZHAO ; Peng JIANG ; Wen CHEN ; Xiaping XIAO ; Xingsheng WANG ; Qianwen CHEN ; Junfei MA ; Zhenghan YANG
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(20):241-249
Osteoporosis is a chronic skeletal disease characterized by low bone mass, destruction of bone tissue microarchitecture, and imbalance of bone homeostasis, leading to increased bone fragility and increased risk of fractures. Oxidative stress caused by the disruption of the balance between excess reactive oxygen species (ROS) and the anti-oxidative system is an important factor in the occurrence and progression of osteoporosis. Nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) is an important anti-oxidative stress pathway. Nrf2 is a primary factor in regulating cellular oxidative stress. Activating Nrf2 can stimulate the expression of HO-1. HO-1 is a key enzyme whose metabolites are bile green Oxygen, carbon monoxide, and free iron. The metabolites can scavenge ROS, thereby exerting an antioxidant effect in cells. At present, domestic and foreign scholars have reported that the Nrf2/HO-1 signaling pathway is closely related to the occurrence and development of osteoporosis and the mechanism of drugs. Chinese medicine can effectively solve the insufficiency of western medicine with multi-target, multi-channel, and multi-level advantages. Chinese medicine can resist oxidative stress, inflammatory response, and apoptosis by regulating the Nrf2/HO-1 signaling pathway, thus treating osteoporosis. This article reviewed the relationship between Nrf2/HO-1 signaling pathway and its key target protein factors and osteoporosis, to clarify the important role of the Nrf2/HO-1 signaling pathway in osteoporosis. At the same time, a systematic summary of Chinese medicines targeting and regulating the Nrf2/HO-1 signaling pathway for the treatment of osteoporosis was conducted, to provide a theoretical basis for further precise treatment of osteoporosis.
7.Study on influencing factors and needs of medical personnel in scientific research of a tertiary hospital in Jieyang
Qiongmiao WU ; Xingsheng CAI ; Kaisheng LIN ; Xian WANG ; Chudong LIN ; Peifeng FANG ; Yichun CHEN
Chinese Journal of Medical Science Research Management 2022;35(2):136-140
Objective:To understand the needs, problems and challenges of medical personnel in the hospital for scientific research, propose tailored management measurements and suggestions for the hospital.Methods:The questionnaire was prepared by " Questionnaire Star" , the convenience sampling method was used, and information was collected by WeChat online chat group. Factor analysis and multi-dimensional preference analysis were adopted to analyze information collected.Results:Four main factors that affect the scientific research of medical personnel were identified. The most significant impact is the lack of information platform, followed by the lack of environmental atmosphere, lack of personal capacity and lack of personal interest. The research needs of medical personnel are divided into two categories: one is the more basic skill needs, which are mainly targeted at female, nurses, undergraduates, 5~10 years′ working experiences, medium-grade professional title, and people with no knowledge and experience in research. The other one is the needs of skill improvement, which are mainly targeted at younger, physicians, early career, lower professional titles, and had certain research knowledge.Conclusions:So far, there is a lot of space for improvement. It is recommended to promote the capacity building by training, strengthen the research team building and construct of research communication platform, at the same time, update the scientific research management system.
8.Glasgow coma score combined with optic nerve sheath diameter in predicting the risk of death from cerebrocardiac syndrome
Xincai WANG ; Xingsheng LIN ; Jing LU ; Yuhang ZHOU ; Long HUANG
Chinese Journal of Emergency Medicine 2022;31(12):1628-1634
Objective:To explore the value of Glasgow coma score (GCS) combined with optic nerve sheath diameter (ONSD) in predicting the death risk of patients with cerebrocardiac syndrome (CCS).Methods:From January 2021 to September 2021, 83 patients with CCS secondary to severe traumatic brain injury (sTBI) in our hospital were collected and divided into a survival group ( n = 37) and death group ( n = 46) according to CCS-related death. The clinical data including age, sex, underlying diseases, head CT imaging manifestations, electrolytes, blood glucose, C-reactive protein (CRP), neuron-specific enolase (NSE), lactate dehydrogenase (LDH), creatine kinase (CK), creatine phosphokinase isoenzyme (CKMB), intracranial pressure (ICP), ONSD, cardiac color ultrasound, acute physiology and chronic health evaluationII (APACHEⅡ ) and GCS were analyzed and compared between the two groups. The proportion and dosage of vasoactive drugs used at admission, daily fluid balance volume during hospitalization, total amount of sedative and analgesic drugs, and average daily dose were analyzed and compared between the two groups. The independent risk factors for CCS-related death were analyzed using multivariate logistic regression. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of the independent risk factors in CCS-related death. Results:In this study, 55.4% of the patients died of CCS. The ONSD, ICP change rate, right ventricular Tei index and NSE in the death group were higher than those in the survival group, with statistically significant differences ( P < 0.05), while the GCS in the death group was significantly lower than that in the survival group, with a statistically significant difference ( P < 0.01). ONSD ( OR = 23.890, 95% CI: 5.526-103.286, P < 0.001), GCS ( OR = 17.066, 95% CI: 1.476-197.370, P = 0.023) and ICP change rate ( OR = 0.060, 95% CI: 0.007-0.477, P = 0.008) were the independent risk factors for CCS-related death. The area under the ROC curve (AUC = 0.897) of ONSD combined with GCS in evaluating CCS-related death was larger than that of ONSD, ICP change rate alone and the corresponding AUC of 1/GCS (0.876, 0.785, 0.800, respectively), with the advantages of non-invasive, dynamic monitoring and low inspection costs. Conclusions:The mortality rate of CCS is high. ONSD, GCS and ICP change rates are independently correlated with the death of CCS patients. ONSD combined with GCS is an ideal indicator for clinical prediction of CCS-related death.
9.Microorganisms in the typical anaerobic digestion system of organic solid wastes: a review.
Xingsheng YANG ; Shang WANG ; Qing HE ; Zhujun WANG ; Zhaojing ZHANG ; Chengying JIANG ; Liping MA ; Xianwei LIU ; Baolan HU ; Yongmei LI ; Ye DENG
Chinese Journal of Biotechnology 2021;37(10):3425-3438
The facultative anaerobic and strict anaerobic microorganisms enriched and acclimated during the anaerobic digestion process are crucial for the efficiency of the anaerobic digestion system. Most of the problems encountered during running anaerobic digestion processes could be effectively improved via stimulation of microbial metabolic activity. Benefited from the rapid development of microbiome techniques, deeper insights into the microbial diversity in anaerobic digestion systems, e.g. the microbe-microbe interactions and microbe-environment interactions, have been gained. A complex and intricate metabolic network exists in the anaerobic digestion system of solid organic wastes. However, little is known about these interactions and the underlying mechanisms. This review briefly summarized the representative interactions between microbial communities during anaerobic digestion process discovered to date. In addition, typical issues encountered during the anaerobic digestion of solid organic wastes and how microbes can tackle and alleviate these issues were discussed. Finally, future priorities on microbiome research were proposed based on present contribution of microbiome analysis in anaerobic digestion system.
Anaerobiosis
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Bioreactors
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Methane
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Microbial Interactions
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Microbiota
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Solid Waste
10.Effects of metformin on prognosis of type Ⅰ endometrial carcinoma patients complicated with type 2 diabetes mellitus
Xue WANG ; Guoxin JI ; Chao JI ; Xingsheng YANG
Journal of International Oncology 2020;47(7):404-408
Objective:To explore the effects of metformin on the prognosis of type Ⅰ endometrial carcinoma (EC) patients complicated with type 2 diabetes mellitus (T2DM).Methods:The clinical data of 45 type Ⅰ EC patients complicated with T2DM (T2DM group) and 147 type Ⅰ EC patients without diabetes mellitus (non-diabetes group) admitted to Qilu Hospital of Shandong University from January 2010 to December 2014 were retrospectively analyzed. The type Ⅰ EC patients with T2DM were divided into two groups, metformin group ( n=23, taking metformin to control blood glucose in normal range) and non-metformin group ( n=22, taking other hypoglycemic drugs or using insulin to control blood glucose in normal range). The clinicopathological characteristics of T2DM group and non-diabetes group were compared, and the effects of metformin on the prognosis of type Ⅰ EC patients with T2DM were analyzed. Results:Compared with non-diabetes group, the type Ⅰ EC patients in T2DM group have the older onset age ( t=4.331, P<0.001), more complicated with hypertension ( χ2=19.252, P<0.001), later surgical pathological stage ( χ2=4.588, P=0.032), higher histological grade ( χ2=6.069, P=0.048), deeper myometrial infiltration ( χ2=7.743, P=0.005) and higher incidence of lymph node metastasis ( χ2=4.885, P=0.027). The median progression-free survival (PFS) (47.0 months vs. 38.0 months) and median overall survival (OS) (52.0 months vs. 41.0 months) in metformin group were significantly longer than those in non-metformin group ( χ2=10.899, P=0.001; χ2=10.090, P=0.001). There was no significant difference in median PFS (47.0 months vs. 46.0 months) and median OS (52.0 months vs. 46.0 months) between metformin group and non-diabetes group ( χ2=0.791, P=0.374; χ2=0.836, P=0.360). Cox multivariate analysis showed that the risk factors of PFS and OS in type ⅠEC patients were old onset age( OR=2.128, 95% CI: 1.361-3.328, P=0.001; OR=4.502, 95% CI: 1.696-11.954, P=0.003), late surgical pathological stage( OR=2.231, 95% CI: 1.437-3.462, P=0.001; OR=4.005, 95% CI: 1.480-10.836, P=0.006), high histological grade( P=0.001; P=0.017; G2 vs.G1: OR=5.660, 95% CI: 3.424-9.357, P=0.001; OR=5.763, 95% CI: 1.666-19.938, P=0.006), deep myometrial invasion( OR=1.531, 95% CI: 1.049-2.235, P=0.027; OR=3.759, 95% CI: 1.890-7.476, P=0.001), positive lymph node metastasis ( OR=11.277, 95% CI: 2.774-45.838, P=0.001; OR=8.451, 95% CI: 1.138-62.767, P=0.037)and T2DM ( OR=1.897, 95% CI: 1.096-3.281, P=0.008; OR=1.813, 95% CI: 1.043-3.151, P=0.012). Metformin was the protective factor of PFS ( OR=0.412, 95% CI: 0.207-0.818, P=0.002) and OS ( OR=0.455, 95% CI: 0.228-0.905, P=0.008) in type Ⅰ EC patients with T2DM. Conclusion:Complication with T2DM is the negative factor on the prognosis of type Ⅰ EC patients. Intake of metformin can significantly improve the PFS and OS of type Ⅰ EC patients complicated with T2DM and improve the prognosis.

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