1.Applications of Lactoferrin and Its Nanoparticles in Cancer Therapy
Wen-Tian YUE ; Shu-Rong HE ; Qin AN ; Yun-Xia ZOU ; Wen-Wen DONG ; Qing-Yong MENG ; Ya-Li ZHANG
Progress in Biochemistry and Biophysics 2026;53(2):342-355
Cancer remains a leading cause of global mortality, necessitating the development of advanced therapeutic strategies with enhanced efficacy and reduced systemic toxicity. Among promising bioactive agents, lactoferrin (LF)—a multifunctional iron-binding glycoprotein abundantly found in mammalian milk and exocrine secretions—has garnered significant interest for its potent and multifaceted anti-cancer properties. This review provides a comprehensive analysis of the current understanding of LF’s role in oncology, encompassing its structural biology, diverse mechanisms of action, and groundbreaking advancements in its application through nano-engineering. LF exerts anti-tumor effects through multiple pathways, including extracellular action, intracellular action, and immune regulation. It demonstrates a remarkable affinity for cancer cell membranes, binding to overexpressed anionic components such as glycosaminoglycans and sialic acids, as well as to specific receptors including the low-density lipoprotein receptor-related protein-1 (LRP-1). This selective binding facilitates targeted uptake. Upon internalization, LF orchestrates a direct assault by inducing cell-cycle arrest in phases such as G0/G1 or S phase through the modulation of key regulators including cyclins, CDKs, and p53. Furthermore, it promotes programmed cell death via apoptotic pathways, involving caspase activation and downregulation of anti-apoptotic proteins such as survivin. A more recently elucidated mechanism is the induction of ferroptosis, an iron-dependent form of cell death characterized by overwhelming lipid peroxidation. Beyond direct cytotoxicity, LF acts as a potent immunomodulator. It enhances natural killer (NK) cell activity, modulates T-lymphocyte populations, and crucially reprograms tumor-associated macrophages (TAMs) from a pro-tumor M2 state to an anti-tumor M1 state, thereby reversing the immunosuppressive tumor microenvironment (TME). The translation of LF’s potential has been significantly accelerated by nanotechnology. The inherent biocompatibility and natural tumor-targeting capabilities of LF make it an ideal platform for sophisticated drug-delivery systems. This review details various fabrication strategies for LF-based nanoparticles (NPs), including self-assembly, sol-in-oil emulsion, and electrostatic nanocomplexes, among others. Research demonstrates that nano-formulations not only protect LF from degradation but also enhance its bioactivity and anti-cancer potency. More importantly, LF NPs serve as versatile carriers for a wide array of therapeutic agents, including conventional chemotherapeutics, natural compounds, and imaging agents. These engineered systems enable synergistic therapy and facilitate site-specific delivery. Notably, the ability of LF to bind to receptors on the blood-brain barrier (BBB) has been leveraged to develop nano-systems for glioblastoma treatment. Other innovative designs utilize LF to modulate the TME—for instance, by alleviating tumor hypoxia to sensitize cells to radiotherapy and chemotherapy. Despite compelling pre-clinical evidence, the clinical translation of LF and its nano-formulations remains nascent. While early-phase trials have established a favorable safety profile for recombinant human LF, larger Phase III studies have yielded mixed results, underscoring the complexity of its action in humans. Key challenges include enhancing drug targeting, optimizing loading efficiency, ensuring batch-to-batch reproducibility, and achieving deep tumor penetration. Future research must focus on the rational design of next-generation LF-NPs. This entails developing standardized manufacturing protocols, engineering “smart” stimuli-responsive systems for targeted drug release in the TME, and constructing multi-targeting platforms. A concerted interdisciplinary effort is paramount to bridge the gap between bench and bedside. In conclusion, LF, particularly in its nano-engineered forms, represents a highly promising and versatile agent in the oncological arsenal, holding immense potential for precise and effective cancer therapy.
2.Applications of Lactoferrin and Its Nanoparticles in Cancer Therapy
Wen-Tian YUE ; Shu-Rong HE ; Qin AN ; Yun-Xia ZOU ; Wen-Wen DONG ; Qing-Yong MENG ; Ya-Li ZHANG
Progress in Biochemistry and Biophysics 2026;53(2):342-355
Cancer remains a leading cause of global mortality, necessitating the development of advanced therapeutic strategies with enhanced efficacy and reduced systemic toxicity. Among promising bioactive agents, lactoferrin (LF)—a multifunctional iron-binding glycoprotein abundantly found in mammalian milk and exocrine secretions—has garnered significant interest for its potent and multifaceted anti-cancer properties. This review provides a comprehensive analysis of the current understanding of LF’s role in oncology, encompassing its structural biology, diverse mechanisms of action, and groundbreaking advancements in its application through nano-engineering. LF exerts anti-tumor effects through multiple pathways, including extracellular action, intracellular action, and immune regulation. It demonstrates a remarkable affinity for cancer cell membranes, binding to overexpressed anionic components such as glycosaminoglycans and sialic acids, as well as to specific receptors including the low-density lipoprotein receptor-related protein-1 (LRP-1). This selective binding facilitates targeted uptake. Upon internalization, LF orchestrates a direct assault by inducing cell-cycle arrest in phases such as G0/G1 or S phase through the modulation of key regulators including cyclins, CDKs, and p53. Furthermore, it promotes programmed cell death via apoptotic pathways, involving caspase activation and downregulation of anti-apoptotic proteins such as survivin. A more recently elucidated mechanism is the induction of ferroptosis, an iron-dependent form of cell death characterized by overwhelming lipid peroxidation. Beyond direct cytotoxicity, LF acts as a potent immunomodulator. It enhances natural killer (NK) cell activity, modulates T-lymphocyte populations, and crucially reprograms tumor-associated macrophages (TAMs) from a pro-tumor M2 state to an anti-tumor M1 state, thereby reversing the immunosuppressive tumor microenvironment (TME). The translation of LF’s potential has been significantly accelerated by nanotechnology. The inherent biocompatibility and natural tumor-targeting capabilities of LF make it an ideal platform for sophisticated drug-delivery systems. This review details various fabrication strategies for LF-based nanoparticles (NPs), including self-assembly, sol-in-oil emulsion, and electrostatic nanocomplexes, among others. Research demonstrates that nano-formulations not only protect LF from degradation but also enhance its bioactivity and anti-cancer potency. More importantly, LF NPs serve as versatile carriers for a wide array of therapeutic agents, including conventional chemotherapeutics, natural compounds, and imaging agents. These engineered systems enable synergistic therapy and facilitate site-specific delivery. Notably, the ability of LF to bind to receptors on the blood-brain barrier (BBB) has been leveraged to develop nano-systems for glioblastoma treatment. Other innovative designs utilize LF to modulate the TME—for instance, by alleviating tumor hypoxia to sensitize cells to radiotherapy and chemotherapy. Despite compelling pre-clinical evidence, the clinical translation of LF and its nano-formulations remains nascent. While early-phase trials have established a favorable safety profile for recombinant human LF, larger Phase III studies have yielded mixed results, underscoring the complexity of its action in humans. Key challenges include enhancing drug targeting, optimizing loading efficiency, ensuring batch-to-batch reproducibility, and achieving deep tumor penetration. Future research must focus on the rational design of next-generation LF-NPs. This entails developing standardized manufacturing protocols, engineering “smart” stimuli-responsive systems for targeted drug release in the TME, and constructing multi-targeting platforms. A concerted interdisciplinary effort is paramount to bridge the gap between bench and bedside. In conclusion, LF, particularly in its nano-engineered forms, represents a highly promising and versatile agent in the oncological arsenal, holding immense potential for precise and effective cancer therapy.
3.Effectiveness of generative large language model MedGo in nursing decision-making for elderly patients with multimorbidity
Qiaoyun YAN ; Min LI ; Yawen YAN ; Yaqing NI ; Yun GU ; Jiawen QIN ; Haiping YU ; Haitao ZHANG ; Liming ZHAO
Chinese Journal of Clinical Medicine 2026;33(1):16-23
Objective To explore the effectiveness of the generative large language model MedGo in nursing decision-making for elderly patients with multimorbidity. Methods A quasi-randomized controlled trial study was conducted involving 6 junior nurses, 6 senior nurses and the MedGo model from January 1, 2025 to March 31, 2025 at the Emergency Internal Medicine Ward of Shanghai East Hospital Affiliated to Tongji University. Clinical data of 120 elderly patients with multimorbidity were analyzed to compare the performance of the three groups in four tasks (nursing diagnosis assessment, nursing intervention formulation, complication identification, and complication prevention) from three evaluation dimensions: decision-making time consumption, decision accuracy, and decision-making quality. Results In terms of decision-making time, the senior nurse group completed all four tasks faster than the junior nurse group (P<0.01), and the MedGo group completed all four tasks faster than the junior nurse group (P<0.001) and the senior nurse group (P<0.001). In terms of decision-making accuracy, senior nurse group scored higher than junior nurse group in all four tasks (P<0.001), while the MedGo group outperformed the senior nurse group only in complication identification (P<0.001). In terms of decision-making quality, the MedGo group scored higher than junior nurse group (P<0.001) and senior nurse group (P<0.001) in all four tasks. Conclusions The MedGo model demonstrates advantages of high efficiency, accuracy, and quality in nursing decision-making for elderly patients with multimorbidity; senior nurses outperform junior nurses in decision-making, providing diverse references for clinical nursing decision-making.
4.Effects of shaving or segmental bowel resection on intestinal function in patients with bowel endometriosis:a 10-year follow-up study
Qi TIAN ; Yun CHEN ; Xin-xiang LI ; Wei-qi LU ; Jiang-feng YE ; Ke-qin HUA ; Xiao-fang YI
Fudan University Journal of Medical Sciences 2025;52(3):349-357
Objective To investigate the clinical characteristics of preoperative intestinal symptoms in patients with bowel endometriosis and to compare the effects of shaving versus segmental bowel resection on postoperative intestinal function.Methods A total of 105 patients diagnosed with bowel endometriosis and treated by the same surgical team at the Obstetrics and Gynecology Hospital,Fudan University between Aug 1,2013 and Dec 30,2017 were prospectively enrolled in this study.Clinical data were collected via outpatient visits and telephone follow-ups at four time points:preoperative(T0)and postoperative(T1:Nov 2018;T2:Nov 2020;T3:Apr 2024).The primary outcome was bowel symptoms and gastrointestinal function scores;secondary outcome was pain scores.A generalized estimating equation(GEE)model was used to analyze the interaction effect of surgical approach and follow-up time on outcomes.Results Ultimately,a total of 89 patients were included(15.24%loss to follow-up),among whom 79 patients(88.76%)underwent shaving excision.Preoperatively,46 patients(51.68%)presented with bowel symptoms,primarily anus bulge(21 cases,46.65%)and diarrhea(15 cases,32.61%)during menstruation.Postoperatively,there was a significant increase in constipation rates(T1:71.43%;T2:50.00%;T3:72.00%).Both surgical groups exhibited significant improvements in dysmenorrhea,gastrointestinal discomfort scores as well as gastrointestinal quality of life index(P<0.000 5).However,the segmental resection group had significantly higher scores for low anterior resection syndrome,constipation compared with the shaving excision group(P=0.02 and P=0.05).Conclusion Approximately half of the patients with bowel endometriosis exhibit typical bowel symptoms preoperatively,such as anus bulge and diarrhea.Both shaving excision and segmental resection effectively alleviate pain;however,shaving excision demonstrates an advantage regarding preservation of bowel function,whereas segmental resection may elevate risks associated with postoperative constipation or altered defecation patterns due to structural changes.The selection of surgical approach should carefully balance lesion removal and functional preservation,moreover,be sure that potential risks are thoroughly informed to patients prior to surgery.
5.Expert consensus on holistic integrative management of oropharyngeal squamous cell carcinoma
Moyi SUN ; Zongxuan HE ; Qianwei NI ; Xiaoying LI ; Lin KONG ; Qing XI ; Wei GUO ; Zhangui TANG ; Guoxin REN ; Zhijun SUN ; Jian MENG ; Jie ZHANG ; Jichen LI ; Yue HE ; Chunjie LI ; Lizheng QIN ; Kai YANG ; Bing HAN ; Yan SUN ; Haijun LU ; Xiaohong ZHAN ; Dapeng HAO ; Kai SONG ; Haoyue XU ; Lingxue BU ; Jieying LI ; Man HU ; Mingjin XU ; Yun LI ; Wei SHANG
Journal of Practical Stomatology 2025;41(3):293-304
Oropharyngeal squamous cell carcinoma(OPSCC)is a malignant tumor originating from the squamous epithelium of the oro-pharyngeal mucosa,accounting for more than 90%of oropharyngeal malignancies.In recent years,human papillomavirus(HPV)infec-tion has become one of the primary etiological factors of oropharyngeal squamous carcinoma.The incidence of HPV-associated oropharyn-geal squamous carcinoma has been rising annually,with a noticeable trend toward younger populations,posing a significant threat to hu-man health.Due to the distinct biological behavior and clinical characteristics of HPV-associated oropharyngeal squamous carcinoma com-pared to its non-HPV-related counterpart,the diagnostic and treatment strategies for oropharyngeal squamous carcinoma have undergone substantial changes.Prevention and screening for oropharyngeal squamous carcinoma are of critical importance.The diagnostic and treat-ment process involves multi-disciplinary collaboration,including oral and maxillofacial surgery,otolaryngology,head and neck surgery,oncology,radiology and pathology.Based on evidence from clinical practice,a comprehensive,integrated diagnostic and therapeutic ap-proach has been established,centered around the concept of"prevention,screening,diagnosis,treatment,and rehabilitation",covering the entire patient lifecycle and providing a valuable reference for clinical practice.
6.Investigation on Risk Stratification of Atherosclerotic Cardiovascular Disease and Target Achievement of Lipid and Blood Pressure in Community-Based Hypertensive Patients
Yun-li PENG ; Lu-qiang YIN ; Jie-tao LU ; Qin XIAO ; Xiu-lan ZHU
Progress in Modern Biomedicine 2025;25(14):2315-2321
Objective:This study aimed to investigate the atherosclerotic cardiovascular disease(ASCVD)risk stratification and target achievement of lipid and blood pressure control among community-based hypertensive patients,with the goal of optimizing integrated management strategies.Methods:A total of 2832 hypertensive patients registered in 2021 at the Bicheng Community Health Service Center in Bishan District of Chongqing,were included.Baseline data were collected through retrospective analysis of health records.Non-high-density lipoprotein cholesterol(non-HDL-C)levels and estimated glomerular filtration rate(eGFR)were calculated.ASCVD risk stratification was performed,and target achievement for lipid and blood pressure control were analyzed,including comparisons among patients with different comorbidities.Results:Based on ASCVD risk stratification,patients were categorized as follows:ultra-high risk(22 cases,0.78%),very high risk(111 cases,3.92%),high risk(1324 cases,46.75%),moderate risk(997 cases,35.20%),and low risk(378 cases,13.35%).The LDL-C target achievement rate was 4.55%(1/22)in the ultra-high risk group and 15.32%(17/111)in the very high risk group,with blood pressure target achievement rate of 18.18%(4/22)and 11.71%(13/111),respectively.In the high-risk group,LDL-C and blood pressure target achievement rate were only 4.76%(63/1324)and 8.08%(107/1324),while moderate-risk groups showed 25.68%(256/997)and 26.18%(261/997),respectively.The low-risk group achieved 99.74%(377/378)LDL-C target achievement and 30.69%(116/378)blood pressure target achievement.Patients with ischemic stroke had a significantly higher lipid target achievement rate(13.73%,7/51)compared to non-ischemic stroke patients(6.40%,178/2781)(P<0.05).Similarly,those with coronary heart disease(12.65%,13/87)exhibited higher lipid target achievement than non-coronary heart disease patients(6.27%,172/2745)(P<0.05).However,no significant difference was observed between hypertensive patients with diabetes(8.04%,52/647)and non-diabetic patients(6.09%,133/2185)(P>0.05),or between those with chronic kidney disease(CKD)stages 3/4(6.72%,16/238)and non-CKD 3/4 patients(6.52%,169/2594)(P>0.05).Conclusion:Over half of the community-based hypertensive patients were classified as high-risk or above in ASCVD stratification,yet their lipid and blood pressure target achievement rates were markedly suboptimal.Hypertension patients with comorbidities,particularly diabetes or CKD stages 3/4,showed poor lipid target achievement.These findings underscore the necessity of incorporating ASCVD risk stratification into community management assessments for hypertensive patients,enhancing personalized management for high-risk populations,and prioritizing lipid target achievement in those with diabetes or CKD stages 3/4.
7.Research on ST-T change recognition algorithm based on lead attention network
Liang WEI ; Yun-chi LI ; Jun XIE ; Tong XU ; Feng ZUO ; Yong-qin LI ; Bi-hua CHEN ; Mi HE ; Yu-shun GONG
Chinese Medical Equipment Journal 2025;46(7):1-11
Objective To propose a lead attention network-based ST-T change recognition algorithm to detect ECG ST-T changes accurately.Methods Firstly,heartbeat signals were extracted through R-wave localization,and a 12-lead heartbeat matrix was generated by correlation-based screening and merging to realize data augmentation.Secondly,a lead attention module was constructed by combining depthwise convolution(DWConv)with the channel attention squeeze-and-excitation block(SE-block)structure to perceive the differences in ST-T status among electrocardiogram leads.Thirdly,the mapping output by two independent attention modules was fused and splicing with the original signal residual was carried out,so that attention information extraction and original information transfer were enhanced effectively.Finally,SE-ResNet was used as the backbone network to extract signal features to complete the classification and identification of ST-T changes.To validate the recognition performance of the proposed algorithm for ST-T changes in ECG,the 12-lead ECG data of 97 472 patients containing different ECG rhythms were collected for ablation and comparison experiments at the First Affiliated Hospital of Army Medical University.Results The proposed algorithm achieved an AUC of 0.965 with a sensitivity of 90.51%,specificity of 90.23%,positive predictive value of 89.24%and overall accuracy of 90.36%on an independent test set.Comparative analysis demonstrated superior performance to four benchmark architectures,including VGG16,ResNet18,MobileNetV3-Small and ShuffleNet,in terms of both classification accuracy and computational efficiency.Conclusion The algorithm designed can accurately detect ST-T changes and can be used for wearable ECG automatic analysis to assist in the early warning of cardiovascular diseases in both acute and chronic patients and highland residents.[Chinese Medical Equipment Journal,2025,46(7):1-11]
8.Research on the cognition,preference and willingness to pay of Traditional Chinese Medicine intelligent diagnosis device of Beijing residents based on Discrete Choice Experiment
Rui-xi QIN ; Rui-feng LI ; Hong-yun WANG ; Han XUE ; Liang-ru ZHOU
Chinese Journal of Health Policy 2025;18(8):46-52
Objective:This paper investigates residents'awareness and preference for Traditional Chinese Medicine intelligent diagnostic device(hereinafter referred to as the device),and provides basis and suggestions for further promoting the integrated development of artificial intelligence and traditional Chinese medicine clinical diagnosis.Method:A random sampling survey was conducted,and a Discrete Choice Experiment was designed to conduct an offline survey in Beijing.Use chi square test,count analysis,and conditional Logit model for data analysis.Result:A total of 480 valid questionnaires were collected and surveyed.Most respondents have heard of it(58.96%),a few have used it(31.67%),and most would recommend the device(71.25%).Knowing and using experience will increase the probability of recommendation.Residents attach the highest importance to annual average expenses;More inclined to use devices in the community that can see family data,connect data and hospitals,monitor electrocardiogram,provide comprehensive health reports,and have low annual costs;Willing to pay an additional 572 yuan per year for the comprehensive health report device.Conclusion:There should be more collaboration with hospitals in usage scenarios and cloud data.In addition,manufacturers should enrich output information and service methods of the e.
9.Role of exosomes in propofol-induced elimination of cardioprotective effect of remote ischemic preconditioning in rats
Shuai QIN ; Aoxue LI ; Min WANG ; Xinzhe WU ; Yun WU
Chinese Journal of Anesthesiology 2025;45(8):959-965
Objective:To evaluate the role of exosomes in propofol-induced elimination of cardioprotective effect of remote ischemic preconditioning (RIPC) in rats.Methods:This experiment was performed in 2 parts. In vivo experiment Forty-eight healthy SPF male Sprague-Dawley rats, aged 8-10 weeks, weighing 250-300 g, were divided into 5 groups using the random number table method: sham operation group (Sham group, n=12), ischemia-reperfusion (I/R) group ( n=12), RIPC group ( n=8), RIPC+ propofol group (RIPC+ P group, n=8), and propofol+ I/R group (P+ I/R group, n=8). The model of myocardial I/R injury was developed by ligating the left anterior descending branch of coronary artery for 30 min followed by 120 min reperfusion in anesthetized animals. Four cycles of 5-min ischemia induced by occlusion of the bilateral hind limbs with a tourniquet/5-min reperfusion served as the RIPC stimulus. Propofol was intravenously infused at a rate of 12 mg·kg -1·h -1 in RIPC+ P group (during RIPC) and in P+ I/R group (for 40 min). Exosomes from RIPC-treated and RIPC+ propofol-treated rats were extracted (RIPC-EXO and RIPC+ P-EXO respectively) for determination of the expression of surface markers of exosomes CD9 and HSP70. Another 24 rats were randomly selected, and the aforementioned exosomes were injected at 15 min before myocardial ischemia, resulting in RIPC-EXO+ I/R group ( n=12) and RIPC+ P-EXO+ I/R group ( n=12). At the end of reperfusion, the area of myocardial infarction was determined, the concentration of serum cardiac troponin I (cTnI) was measured by the enzyme-linked immunosorbent assay, and the expression of B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) in myocardial tissues was detected by Western blot. Cell experiment H9c2 cells were cultured in vitro and divided into 4 groups ( n=6 each) using a random number table method: control group (C group), hypoxia-reoxygenation group (H/R group), RIPC-EXOc group and RIPC+ P-EXOc group. The cells were exposed to hypoxia for 4 h followed by reoxygenation for 16 h in H/R group. RIPC-EXO and RIPC+ P-EXO were added at a final concentration of 300 μg/ml before hypoxia in RIPC-EXOc group and RIPC+ P-EXOc group, respectively. The cell viability was determined using a cell counting kit-8 assay and the expression of Bax and Bcl-2 expression was detected by Western blot. Results:In vivo experiment Compared with RIPC-EXO group, the expression of CD9 and HSP70 was significantly down-regulated in RIPC+ P-EXO group ( P<0.05). Compared with Sham group, the percentage of the area of myocardial infarction was significantly increased, and the serum cTnI concentration and Bax/Bcl-2 ratio in myocardial tissues were increased in I/R group ( P<0.05). Compared with I/R group, the percentage of the area of myocardial infarction was significantly decreased in RIPC group and RIPC-EXO+ I/R group, the serum cTnI concentration and Bax/Bcl-2 ratio in myocardial tissues were significantly decreased in RIPC-EXO+ I/R group ( P<0.05), and no significant change was found in the percentage of the area of myocardial infarction in RIPC+ P group ( P>0.05). The percentage of the area of myocardial infarction was significantly larger in RIPC+ P group than in RIPC group ( P<0.05). Compared with RIPC-EXO+ I/R group, the percentage of the area of myocardial infarction was significantly increased, and the serum cTnI concentration and Bax/Bcl-2 ratio were increased in RIPC+ P-EXO+ I/R group ( P<0.05). Cell experiment Compared with C group, the cell viability was significantly decreased, and the Bax/Bcl-2 ratio was increased in H/R group ( P<0.05). Compared with H/R group, the cell viability was significantly increased, and the Bax/Bcl-2 ratio was decreased in RIPC-EXOc group ( P<0.05). Compared with RIPC+ EXOc group, the cell viability was significantly decreased, and the Bax/Bcl-2 ratio was increased in RIPC+ P-EXOc group ( P<0.05). Conclusions:Propofol may abolish the myocardial protective effect of RIPC by decreasing the production and release of serum exosomes in rats.
10.Role of exosomes in reduction of myocardial ischaemia-reperfusion injury by remote preconditioning of trauma in rats
Aoxue LI ; Shuai QIN ; Xinzhe WU ; Min WANG ; Yun WU
Chinese Journal of Anesthesiology 2025;45(9):1135-1141
Objective:To evaluate the role of exosomes in reduction of myocardial ischemia-reperfusion (I/R) injury (MIRI) by remote preconditioning of trauma (RPCT) in rats.Methods:This experiment was performed in 2 parts. In vivo experiment Adult male Sprague-Dawley rats, aged 8 weeks, weighing 250-300 g, were used. Six rats were selected and randomly divided into 2 groups ( n=3 each): control group and RPCT group. Rats in control group underwent thoracotomy only, while rats in RPCT group were subjected to an additional 4 cm transverse skin incision along the abdominal midline after thoracotomy. Blood samples were collected, and serum exosomes were isolated from blood samples and labeled as control exosomes and RPCT exosomes. The expression of exosomal surface marker proteins CD9 and heat shock protein 70 (HSP70) was determined by Western blot, and the serum exosome concentration was measured. Another 30 rats were selected and randomly assigned to 5 groups ( n=6 each): sham operation group (Sham group), I/R group, I/R+ RPCT group, I/R+ control exosomes group (I/R+ EXO-CON group), and I/R+ RPCT exosomes group (I/R+ EXO-RPCT group). The MIRI model was established by ligating the left anterior descending coronary artery for 30 min followed by 120 min of reperfusion in anesthetized animals. In I/R+ RPCT group, the MIRI model was prepared at 15 min after the end of RPCT. In I/R+ EXO-CON and I/R+ EXO-RPCT groups, control exosomes and RPCT exosomes 100 μg were administered via the jugular vein at 15 min before ischemia respectively. At the end of reperfusion, the myocardial infarct size was measured, serum concentrations of cardiac troponin T (cTnT) and lactate dehydrogenase (LDH) were determined, and the contents of malondialdehyde (MDA) and superoxide dismutase (SOD) in myocardial tissues were measured. The expression of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3 and cleaved caspase-3 was detected. In vitro experiment H9c2 cells were cultured in vitro and randomly divided into 4 groups ( n=6 each): control group (Con group), hypoxia/reoxygenation (H/R) group, H/R+ control exosomes group (H/R+ EXO-CON group), and H/R+ RPCT exosomes group (H/R+ EXO-RPCT group). The rats were subjected to 4 h of hypoxia followed by 16 h of reoxygenation to establish the H/R injury model. In H/R+ EXO-CON and H/R+ EXO-RPCT groups, control exosomes and RPCT exosomes 4 μg were added at 15 min before hypoxia respectively. The cell survival rate and concentration of lactate dehydrogenase (LDH) in the supernatant were measured, and the expression of Bax, Bcl-2, cleaved caspase-3 and caspase-3 was detected. Results:In vivo experiment Compared with control group, the expression of serum CD9 and HSP70 was significantly up-regulated, and the exosome concentration was increased in RPCT group ( P<0.05). Compared with Sham group, the serum concentrations of cTnT and LDH, percentage of myocardial infarct size, content of MDA in myocardial tissues, Bax/Bcl-2 ratio, and cleaved caspase-3/caspase-3 ratio were significantly increased, and the activity of SOD was decreased in I/R group ( P<0.05). Compared with I/R group, the serum cTnT and LDH concentrations, percentage of myocardial infarct size, content of MDA in myocardial tissues, Bax/Bcl-2 ratio and cleaved caspase-3/caspase-3 ratio were significantly decreased, and the activity of SOD was increased in I/R+ RPCT group ( P<0.05), and no significant changes were observed in the aforementioned parameters in I/R+ EXO-CON group ( P>0.05). There were no significant differences in the aforementioned parameters between I/R+ RPCT group and I/R+ EXO-RPCT group ( P>0.05). In vitro experiment Compared with Con group, the cell survival rate was significantly decreased, and the LDH concentration in the supernatant and Bax/Bcl-2 and cleaved caspase-3/caspase-3 ratios were increased in H/R group ( P<0.05). Compared with H/R group, the cell survival rate was significantly increased, the LDH concentration in the supernatant, and Bax/Bcl-2 and cleaved caspase-3/caspase-3 ratios were decreased in H/R+ EXO-CON group ( P<0.05), and no significant changes were found in the aforementioned parameters in H/R+ EXO-RPCT group ( P>0.05). Conclusions:The mechanism by which RPCT reduces MIRI may be related to the increased release of serum exosomes in rats.

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