1.Mechanism of human umbilical cord mesenchymal stem cell-derived exosomes against mouse renal ischemia/reperfusion injury
Lingyu LI ; Huafeng WEI ; Hao LUO ; Hao WANG ; Jiahui HE ; Yawei YAO ; Xinghua LYU
Chinese Journal of Tissue Engineering Research 2025;29(13):2706-2712
BACKGROUND:Human umbilical cord mesenchymal stem cell-derived exosomes are involved in multiple injury repair processes,and the effects and the specific mechanisms of renal ischemia/reperfusion injury have not been fully elucidated.OBJECTIVE:To investigate the molecular mechanism of human umbilical cord mesenchymal stem cell-derived exosomes in the treatment of renal ischemia/reperfusion injury.METHODS:(1) Human umbilical cord mesenchymal stem cells were cultured and exosomes were obtained and identified using an exosome extraction kit.(2) The distribution of exosomes in the kidney of mice with renal ischemia/reperfusion injury was examined by intravital fluorescence imaging.(3) Thirty C57/BL6 male mice were divided into five groups according to the random number table method:sham operation group,renal ischemia/reperfusion group,sham operation group+Compound C group,renal ischemia/reperfusion+exosome group (exosome group),and renal ischemia/reperfusion+exosome+Compound C group (exosome+Compound C group),with 6 mice in each group.Except the sham operation group,bilateral renal pedicles were clamped for 45 minutes and a mouse model of renal ischemia/reperfusion injury was established after 24 hours of reperfusion.In sham operation+Compound C group and exosome+Compound C group,AMPK inhibitor Compound C was intraperitoneally injected 30 minutes before model establishment.In the exosome group and exosome+Copmpound C group,exosomes were injected through the tail vein 15 minutes before renal pedicle clipping.The levels of serum creatinine and urea nitrogen,interleukin 6,and tumor necrosis factor α in renal tissue,and the expression of apoptosis-related factors in renal tissue were detected after 24 hours of reperfusion in each group.RESULTS AND CONCLUSION:(1) Human umbilical cord mesenchymal stem cell exosomes had the typical tea tray morphology,with the diameter distribution in the range of 40-160 nm,and expressed the specific marker membrane protein of exosome surface.(2) Murine kidneys after renal ischemia/reperfusion injury were more likely to gather human umbilical cord mesenchymal stem cell exosomes compared with the sham operation group.(3) Exosome pretreatment reduced renal injury and the level of renal cell apoptosis in mice treated with renal ischemia/reperfusion injury.Moreover,this protective effect could be reversed by AMPK inhibitors.These findings verify that human umbilical cord mesenchymal stem cell-derived exosomes exerting a protective effect on renal ischemia/reperfusion injury may be related to the activation of the AMPK/YAP1 pathway to antiapoptosis.
2.Trend of incidence of postoperative pneumonia in a tertiary first-class cancer hospital in Fujian Province:an analysis based on Joinpoint regre-ssion model
Lingyu LAI ; Shilun LI ; Cuiyun ZHOU ; Jinchan YAO ; Haiyan LIN ; Jianzhong XIE
Chinese Journal of Infection Control 2025;24(11):1619-1626
Objective To analyze the temporal changing trend of postoperative pneumonia(POP)monitoring data in a tertiary first-class cancer hospital in Fujian Province from 2018 to 2023,and provide reference for the effective-ness of implementation of healthcare-associated infection(HAI)prevention and control measures.Methods The temporal changing trend of POP monitoring data of cancer patients in this hospital from 2018 to 2023 was analyzed by Joinpoint regression model,and the average annual percentage change(AAPC)was calculated.Results From 2018 to 2023,the POP incidences of all cancer patients and patients with different tumors in this hospital were as follows:3.46%in all cancer patients,4.77%,18.16%,11.50%,4.66%,0.85%,3.74%,and 0.46%in pa-tients with lung cancer,esophageal cancer,gastric cancer,intestinal cancer,gynecological tumors,hepatobiliary-pancreatic tumor,as well as head and neck tumors,respectively.From 2018 to 2023,the POP incidence of all can-cer patients in the hospital decreased from 5.47%to 1.73%,and POP incidences of patients with lung cancer,gas-tric cancer,and intestinal cancer decreased from 12.23%,14.93%,and 4.40%to 2.60%,3.73%,and 2.09%,respectively.Joinpoint regression model analysis showed that from 2018 to 2023,the AAPC of POP incidence of all cancer patients in the hospital was-19.78%,and the AAPCs of patients with lung cancer,gastric cancer,and in-testinal cancer were-23.69%,-27.30%,and-19.40%,respectively.The incidences of POP in all cancer pa-tients,as well as patients with lung cancer,gastric cancer,and intestinal cancer all showed downward trends,and the differences were all statistically significant(all P<0.05).According to age,the AAPCs of the ≤60 and>60 year old groups were-22.02%and-20.48%,respectively,both groups showed statistically significant difference in trends(both P<0.05).In terms of gender,the AAPCs of the male and female groups were-16.56%and-28.35%,respectively,both groups showed statistically significant difference in trends(both P<0.05).From 2018 to 2023,Klebsiella pneumoniae showed a significant upward trend in the constituent of POP pathogens in cancer patients,with an AAPC of 6.92%,and the difference was statistically significant(P<0.05).Conclusion The incidences of POP in some cancer patients in the hospital present significant downward trends,indicating that HAI infection prevention and control measures are effective,but it is still necessary to strengthen the meticulous management of the whole perioperative process.
3.Trend of incidence of postoperative pneumonia in a tertiary first-class cancer hospital in Fujian Province:an analysis based on Joinpoint regre-ssion model
Lingyu LAI ; Shilun LI ; Cuiyun ZHOU ; Jinchan YAO ; Haiyan LIN ; Jianzhong XIE
Chinese Journal of Infection Control 2025;24(11):1619-1626
Objective To analyze the temporal changing trend of postoperative pneumonia(POP)monitoring data in a tertiary first-class cancer hospital in Fujian Province from 2018 to 2023,and provide reference for the effective-ness of implementation of healthcare-associated infection(HAI)prevention and control measures.Methods The temporal changing trend of POP monitoring data of cancer patients in this hospital from 2018 to 2023 was analyzed by Joinpoint regression model,and the average annual percentage change(AAPC)was calculated.Results From 2018 to 2023,the POP incidences of all cancer patients and patients with different tumors in this hospital were as follows:3.46%in all cancer patients,4.77%,18.16%,11.50%,4.66%,0.85%,3.74%,and 0.46%in pa-tients with lung cancer,esophageal cancer,gastric cancer,intestinal cancer,gynecological tumors,hepatobiliary-pancreatic tumor,as well as head and neck tumors,respectively.From 2018 to 2023,the POP incidence of all can-cer patients in the hospital decreased from 5.47%to 1.73%,and POP incidences of patients with lung cancer,gas-tric cancer,and intestinal cancer decreased from 12.23%,14.93%,and 4.40%to 2.60%,3.73%,and 2.09%,respectively.Joinpoint regression model analysis showed that from 2018 to 2023,the AAPC of POP incidence of all cancer patients in the hospital was-19.78%,and the AAPCs of patients with lung cancer,gastric cancer,and in-testinal cancer were-23.69%,-27.30%,and-19.40%,respectively.The incidences of POP in all cancer pa-tients,as well as patients with lung cancer,gastric cancer,and intestinal cancer all showed downward trends,and the differences were all statistically significant(all P<0.05).According to age,the AAPCs of the ≤60 and>60 year old groups were-22.02%and-20.48%,respectively,both groups showed statistically significant difference in trends(both P<0.05).In terms of gender,the AAPCs of the male and female groups were-16.56%and-28.35%,respectively,both groups showed statistically significant difference in trends(both P<0.05).From 2018 to 2023,Klebsiella pneumoniae showed a significant upward trend in the constituent of POP pathogens in cancer patients,with an AAPC of 6.92%,and the difference was statistically significant(P<0.05).Conclusion The incidences of POP in some cancer patients in the hospital present significant downward trends,indicating that HAI infection prevention and control measures are effective,but it is still necessary to strengthen the meticulous management of the whole perioperative process.
4.Mechanism of human umbilical cord mesenchymal stem cell-derived exosomes against mouse renal ischemia/reperfusion injury
Lingyu LI ; Huafeng WEI ; Hao LUO ; Hao WANG ; Jiahui HE ; Yawei YAO ; Xinghua LYU
Chinese Journal of Tissue Engineering Research 2025;29(13):2706-2712
BACKGROUND:Human umbilical cord mesenchymal stem cell-derived exosomes are involved in multiple injury repair processes,and the effects and the specific mechanisms of renal ischemia/reperfusion injury have not been fully elucidated.OBJECTIVE:To investigate the molecular mechanism of human umbilical cord mesenchymal stem cell-derived exosomes in the treatment of renal ischemia/reperfusion injury.METHODS:(1) Human umbilical cord mesenchymal stem cells were cultured and exosomes were obtained and identified using an exosome extraction kit.(2) The distribution of exosomes in the kidney of mice with renal ischemia/reperfusion injury was examined by intravital fluorescence imaging.(3) Thirty C57/BL6 male mice were divided into five groups according to the random number table method:sham operation group,renal ischemia/reperfusion group,sham operation group+Compound C group,renal ischemia/reperfusion+exosome group (exosome group),and renal ischemia/reperfusion+exosome+Compound C group (exosome+Compound C group),with 6 mice in each group.Except the sham operation group,bilateral renal pedicles were clamped for 45 minutes and a mouse model of renal ischemia/reperfusion injury was established after 24 hours of reperfusion.In sham operation+Compound C group and exosome+Compound C group,AMPK inhibitor Compound C was intraperitoneally injected 30 minutes before model establishment.In the exosome group and exosome+Copmpound C group,exosomes were injected through the tail vein 15 minutes before renal pedicle clipping.The levels of serum creatinine and urea nitrogen,interleukin 6,and tumor necrosis factor α in renal tissue,and the expression of apoptosis-related factors in renal tissue were detected after 24 hours of reperfusion in each group.RESULTS AND CONCLUSION:(1) Human umbilical cord mesenchymal stem cell exosomes had the typical tea tray morphology,with the diameter distribution in the range of 40-160 nm,and expressed the specific marker membrane protein of exosome surface.(2) Murine kidneys after renal ischemia/reperfusion injury were more likely to gather human umbilical cord mesenchymal stem cell exosomes compared with the sham operation group.(3) Exosome pretreatment reduced renal injury and the level of renal cell apoptosis in mice treated with renal ischemia/reperfusion injury.Moreover,this protective effect could be reversed by AMPK inhibitors.These findings verify that human umbilical cord mesenchymal stem cell-derived exosomes exerting a protective effect on renal ischemia/reperfusion injury may be related to the activation of the AMPK/YAP1 pathway to antiapoptosis.
5.Role of Nrf2/HO-1 signaling pathway in human umbilical cord mesenchymal stem cells-derived exosomes-induced reduction of renal ischemia-reperfusion injury in mice
Huafeng WEI ; Lingyu LI ; Hao LUO ; Hao WANG ; Jiahui HE ; Yawei YAO ; Xinghua LYU
Chinese Journal of Anesthesiology 2024;44(1):97-103
Objective:To evaluate the role of nuclear factor E2-related factor 2 (Nrf2)/heme oxidase-1 (HO-1) in reduction of renal ischemia-reperfusion (I/R) injury by the human umbilical cord mesenchymal stem cells (hucMSCs)-derived exosomes (hucMSCs-exo) in mice.Methods:The hucMSCs were cultured, and exosomes were extracted and identified by transmission electron microscopy, nanoparticle tracking analysis and Western blot. Thirty-six male SPF-grade C57BL/6 mice, weighing 20-25 g, were used. Thirty mice were selected and divided into 5 groups ( n=6 each) by a random number table method: sham operation group (Sham group), sham operation + Nrf2 inhibitor ML385 group (Sham + ML385 group), renal I/R group (I/R group), renal I/R + exosome group (I/R+ EXO group), and renal I/R + exosome + Nrf2 inhibitor ML385 group (I/R+ EXO+ ML385 group). A model of renal I/R injury was prepared by clamping the bilateral renal pedicles for 45 min followed by perfusion in anesthetized animals. ML385 30 mg/kg was intraperitoneally injected at 45 min before preparing the model in Sham+ ML385 group and I/R+ EXO+ ML385 group, and hucMSCs-exo 100 μg was injected via the tail vein at 15 min before reperfusion in I/R+ EXO group and I/R+ EXO+ ML385 group. Serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations were detected at 24 h of reperfusion. The renal tissues were obtained for examination of the pathological changes and for determination of contents of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and malondialdehyde (MDA), superoxide dismutase (SOD) activity and reactive oxygen species (ROS) levels and expression of Nrf2 and HO-1 protein and mRNA (by Western blot and quantitative real-time polymerase chain reaction). The left 6 mice were allocated to sham operation group (Sham-IM group, n=3) and renal I/R group (I/R-IM group, n=3) by a random number table method for VISQUE in living imaging observation. Results:The exosomes showed a typical cup-shaped morphology with a transmission electron microscope, the nanoparticles tracked and analyzed the average diameter of the exosome, with an average diameter of 96.7 nm, and the positive expression of surface markers CD9, CD63 and TSG101 was detected using Western blot. The renal fluorescence intensity value was significantly increased in I/R-IM group as compared with Sham-IM group ( P<0.05). Compared with Sham group, the serum BUN and Cr concentrations were significantly increased, the contents of IL-6, TNF-α and MDA and ROS levels were increased, the activity of SOD was decreased, the expression of Nrf2 and HO-1 protein and mRNA was down-regulated ( P<0.05), and the pathological changes of renal tissues were aggravated in I/R group, and no significant change was found in serum BUN and Cr concentrations in Sham+ ML385 group ( P>0.05). Compared with I/R group, the serum BUN and Cr concentrations were significantly decreased, the contents of IL-6, TNF-α and MDA and ROS levels were decreased, the activity of SOD was increased, the expression of Nrf2 and HO-1 protein and mRNA was up-regulated ( P<0.05), and the pathological changes of renal tissues were significantly attenuated in I/R+ EXO group. Compared with I/R+ EXO group, the serum BUN and Cr concentrations were significantly increased, the contents of IL-6, TNF-α and MDA and ROS levels were increased, the activity of SOD was decreased, the expression of Nrf2 and HO-1 protein and mRNA was down-regulated ( P<0.05), and the pathological changes of renal tissues were aggravated in I/R+ EXO+ ML385 group. Conclusions:The mechanism by which hucMSCs-exo reduces renal I/R injury may be related to activation of the Nrf2/HO-1 signaling pathway in mice.
6.Predictive efficacy of low grip strength and grip asymmetry on postoperative outcomes in elderly patients with colorectal cancer
Lingyu DING ; Jieman HU ; Yueming SUN ; Cui YAO
Journal of Clinical Medicine in Practice 2024;28(12):77-81
Objective To observe the efficacy of low grip strength and grip asymmetry in predicting multiple postoperative outcomes in elderly patients with colorectal cancer. Methods A total of 257 elderly colorectal cancer patients were selected as study objects. Data on general information, grip strength indicators and adverse postoperative outcomes were collected from all patients. Associations of low grip strength, grip asymmetry with adverse postoperative outcomes were explored by Logistic regression. Receiver operating characteristic curves were plotted to further analyze the efficacy of low grip strength and grip asymmetry alone and their combination in predicting adverse outcomes of patients. Results Grip strength, grip strength ratio, and the combination of grip strength and grip strength ratio could effectively predict the occurrence of complications. The areas under the curve (AUCs) and 95% confidence interval (95%CI) were 0.649 (0.587 to 0.707), 0.627 (0.565 to 0.686), and 0.672 (0.611 to 0.729) respectively. Grip strength ratio and the combination of grip strength and grip strength ratio could effectively predict prolonged hospital stays, with AUC(95%CI) of 0.671 (0.610 to 0.728) and 0.577 (0.514 to 0.638), respectively. Grip strength and the combination of grip strength and grip strength ratio could effectively predict the occurrence of frailty, with AUC (95%CI) of 0.585 (0.522 to 0.646) and 0.586 (0.523 to 0.647), respectively. Conclusion This study innovatively reveals the predictive efficacy of multiple grip strength indicators for postoperative outcomes in colorectal cancer patients. Low grip strength and grip asymmetry are effective in predicting the occurrence of complications in patients, grip asymmetry is effective in predicting the occurrence of prolonged hospitalization, and low grip strength is effective in predicting the occurrence of frailty in elderly patients with colorectal cancer.
7.Effect of Stemona tuberosa Alkaloids on Apoptosis and PI3K/Akt and JNK/MAPK Signaling Pathways of Human Lung Cancer A549 Cells
Si LIN ; Huizhen QIN ; Zeyu LI ; Liba XU ; Lingyu DENG ; Jing LUO ; Fengfeng XIE ; Miao ZHANG ; Hua ZHU ; Xiaoxun WANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(4):69-76
ObjectiveTo investigate the effect of Stemona tuberosa alkaloids (STA) on apoptosis and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) and c-Jun N-terminal kinase/p38 mitogen-activated protein kinase (JNK/p38 MAPK) signaling pathways in human lung cancer A549 cells. MethodA549 cells were classified into blank group and STA groups (100, 150, 200, 250, 300 mg⋅L-1). Thiazole blue (MTT) assay and colony formation assay were used to evaluate the proliferation of A549 cells. Apoptosis was observed based on Hoechst 33258 staining, flow cytometry, and Annexin V-FITC/PI staining. Western blot was employed to detect the expression of apoptosis-related proteins cysteine-aspartic acid protease-3 (Caspase-3), B-cell lymphoma-2 (Bcl-2)-associated X protein (Bax), and Bcl-2, and the expression of PI3K, phosphorylated (p)-PI3K, Akt, p-Akt, JNK, p-JNK, p38 MAPK, and p-p38 MAPK. ResultCompared with the blank group, STA groups (150, 200, 250, 300 mg⋅L-1) demonstrated the increase in inhibition rate of cell proliferation (P<0.01) and cell clone inhibition rate, and decrease in cell clone formation rate (P<0.01). In comparison with the blank group, STA groups showed typical characteristics of apoptosis, such as chromatin condensation and enhanced fluorescence reaction. The apoptosis rate of STA groups was significantly higher than that of the blank group (P<0.01). Compared with the blank group, STA (150, 200, 250, 300 mg⋅L-1) significantly up-regulated the protein expression of Caspase-3 and Bax (P<0.05, P<0.01) and down-regulated the expression of Bcl-2 protein (P<0.01). Compared with the blank group, STA had no significant influence on the total protein expression of PI3K, Akt, JNK, and p38 MAPK. However, STA (150, 200, 250, 300 mg⋅L-1) significantly decreased the levels of p-PI3K and p-Akt (P<0.05, P<0.01) and increased the level of p-p38 MAPK (P<0.05, P<0.01). Compared with the blank group, STA (200, 250, 300 mg⋅L-1) significantly raised the level of p-JNK (P<0.05, P<0.01). ConclusionSTA can inhibit the proliferation and induce the apoptosis of A549 cells by inhibiting PI3K/Akt signaling pathway and activating JNK/p38 MAPK signaling pathway.
8.Research progress of pharmacological action and mechanism of piperine
Si LIN ; Huizhen QIN ; Lingyu DENG ; Miao ZHANG ; Fengfeng XIE ; Zeyu LI ; Hua ZHU
China Pharmacy 2022;33(13):1653-1659
Piperine is a kind of amide alkaloids presenting in Piper nigrum L.,which has the pharmacological action such as protecting cardiovascular system ,regulating glucose and lipid metabolism ,anti-tumor,improving nervous system diseases , anti-inflammation and so on. This paper summarized the pharmacological action and mechanisms of piperine in recent years and found that piperine ,as the main active ingredient of P. nigrum ,could protect the cardiovascular system by reducing inflammation and oxidative stress ;improve mitochondrial function through anti-inflammatory and antioxidant effects ,thereby regulate glucose and lipid metabolism ;play an anti-tumor role by mediating the signaling pathways of Wnt/β-catenin,NF-κB/Nrf-2/KeAP-1/HO-1, PI3K/Akt,TGF-β1/Smad2/ERK1/2;improve neurological diseases by inhibiting autophagy ,relieving inflammation ,improving antioxidant,inhibiting neuronal apoptosis and regulating the expression of related proteins in neurons ;play an anti-inflammatory effect by inhibiting the activity of NF-κB and other signaling pathways and reducing the expression of inflammation-related proteins. However,the mechanism of action of piperine is not perfect ,and most of the studies have been confined to the pharmacological level or a certain signaling pathway and a certain target ,without being able to elucidate the interconnection between the relevant signaling pathway and the specific target from a holistic perspective. In the follow-up ,the specific targets of piperine can be identified and clinical trials can be carried out to provide support for the clinical application of piperine.
9.The efficacy and safety of injection-related risk management based on WeChat platform in type 2 diabetic patients with the first insulin self-injection
Lingyu ZHENG ; Chunxia XU ; Jiaqi YAO ; Jing ZHAN ; Jia LYU ; Yun RUAN ; Jing WANG ; Qingying TAN
Chinese Journal of General Practitioners 2021;20(3):339-343
Objective:To assess the implementation of injection-related risk management based on WeChat platform for type 2 diabetic patients with the insulin self-injection.Methods:A total of 124 diabetic patients, who would receive insulin therapy by self-injection at home after discharge from the PLA 903 hospital during April 2017 to July 2018, were divided into the control group( n=62)and the study group( n=62). All patients were given routine education on insulin injection during the hospitalization,while the study group( n=62)received additional video and text education based on WeChat platform after discharge. The skill of self-injection and the status of blood glucose control were evaluated in both groups 4 weeks and 8 weeks after discharge, respectively. Results:The insulin injection skill, including skin disinfection [36(58%) vs. 11(18%),χ 2=21.42, P<0.01], exhaust before injection [62(100%) vs. 51(82%),χ 2=12.07, P<0.01], stay 10s after injection [60 (97%) vs. 47(76%),χ 2=11.52, P<0.01], disposal of used needle[49(79%) vs. 18(29%),χ 2=31.20, P<0.01], rotation of injection site [48(77%) vs. 35(56%),χ 2=6.16, P=0.01], insulin storage [62(100%) vs. 57(92%),χ 2=5.21, P=0.02], and the ability of correctly dealing with hypoglycemia [52(84%) vs. 38(61%),χ 2=7.94, P=0.01] in the study group were significantly better than those in the control group after 4 weeks of injection-related risk management. The fasting plasma glucose [(6.41±0.76) vs.(7.19±0.81)mmol/L, t=5.61, P<0.01], glycosylated hemoglobin A1c [(6.71±0.64)% vs. (7.37±0.78)%, t=5.18, P<0.01], incidence of hypoglycemia [6(10%) vs. 15(24%),χ 2=4.64, P=0.03] in the study group were significantly lower than those in the control group after 12 weeks of the management. Conclusion:The risk management based on WeChat platform can improve insulin self-injection skill and the ability of dealing with hypoglycemia,also promote effective blood glucose control for diabetes patients.
10.Correlation between posttraumatic growth and fear of cancer recurrence in patients with breast cancer during chemotherapy
Lingyu YAO ; Baoying ZHANG ; Na LIU ; Aihua ZHANG
Chinese Journal of Practical Nursing 2020;36(15):1133-1139
Objective:To investigate the relationship between posttraumatic growth and fear of cancer recurrence in patients with breast cancer during chemotherapy.Methods:The Posttraumatic Growth Inventory-C (PTGI-C) and the Fear of Cancer Recurrence Inventory-Chinese Version (FCRI-CV) were used in the Tai'an Central Hospital of Shandong Province and the Second Affiliated Medicine of Shandong First Medical University. A cross-sectional survey was conducted in 208 patients with breast cancer during chemotherapy.Results:The total score of posttraumatic growth of breast cancer patients during chemotherapy period was 65.80±12.36, which was at the middle level. The total score of fear of cancer recurrence was 79.52 ±18.15, which was at the low-medium level. The total score of posttraumatic growth of breast cancer patients during chemotherapy was negatively correlated with the total score of fear of cancer recurrence ( r=-0.449, P<0.01). Conclusion:Posttraumatic growth of breast cancer patients during chemotherapy is closely related to fear of cancer recurrence. The higher the level of posttraumatic growth, the lower the fear of cancer recurrence. This suggests that the fear of cancer recurrence can be reduced by improving the growth level of patients after trauma.


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