1.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.
2.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.
3.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.
4.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.
5.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.
6.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.
7.Screening for congenital adrenal hyperplasia in infertile women with high androgenemia during childbearing age
Jing WANG ; Lingyu ZHANG ; Yao QIN ; Xiang MA ; Mei ZHANG
Chinese Journal of Endocrinology and Metabolism 2020;36(3):240-245
Objective:The causes of infertility are complex and diverse, and congenital adrenal hyperplasia (CAH) is often overlooked in screening for infertility. In this study, CAH was diagnosed in women with high androgenemia who were infertile during childbearing age, and the diagnosis and treatment of CAH in pregnant women was investigated.Methods:This study included 20 women with high androgenemia and infertility in the childbearing age who were referred to the Endocrinology Department after visiting the Reproductive Medicine Center of the First Affiliated Hospital of Nanjing Medical University from December 2016 to April 2019. All patients were tested for blood hormone levels, glucose, and lipid metabolism, underwent ACTH stimulation test, uterus and bilateral ovarian B-ultrasound, adrenal computed cosmography (CT), etc. Full-length sequencing of the CYP21A2 gene was performed as necessary.Results:Among the 20 women with hyperandrogenism who were infertile, there were 7 cases of CAH (35.0%), including 6 cases of 21-hydroxylase deficiency (21-OHD) confirmed by gene sequencing; 10 cases of polycystic ovary syndrome (PCOS); 3 cases of idiopathic hyperandrogenemia (IHA). Sex hormone results showed that testosterone in CAH group was significantly higher than that in PCOS group and IHA group [(4.4±2.0 vs 2.9±0.4, 2.8±0.8) nmol/L, P<0.05]; ACTH stimulation test showed that the 17-hydroxyprogesterone (17-OHP) in CAH group was significantly higher than that in PCOS group [(101.0±100.8 vs 1.4±0.8) ng/ml, P<0.05]. There was no significant difference between CAH group and IHA group [(101.0±100.8 vs 3.0±1.8)ng/ml, P>0.05]. However, the 17-OHP (60 min) in CAH group was significantly higher than that in PCOS group and IHA group [(200.1±80.8 vs 3.1±1.2, 3.4±0.2) ng/ml, P<0.05]. Glucocorticoid therapy was given to patients with CAH, and 4 patients had successful pregnancy. No clinical symptoms of CAH and external genital malformations were found in the offspring of patients who had been delivered. Conclusions:The ACTH stimulation test is of great significance in the differential diagnosis of CAH, especially 21-OHD. Genetic testing helps to identify the type of mutation in CAH patients. On the one hand, glucocorticoid therapy may improve the pregnancy rate of CAH patients, on the other hand, it can help to reduce the status of maternal high androgen and avoid masculine manifestation of female offspring.
8.2DGSTIforassessmentofleftventricularlongitudinalshrinkagefunctioninpatients withdifferentChildGPughgradeofcirrhosis
Lingyu MENG ; Xiufen YAO ; Peilu WANG
Journal of Practical Radiology 2019;35(3):459-463,487
Objective ToMeasureofleftventricularregionalsystolicfunctioninpatientswithcirrhosisby2DGSTItechnology.To exploretheclinicalvalueofleftventricularsystolicfunctionindifferentChildGPughgradedlivercirrhosispatientsanditscorrelation withthedegreeoflivercirrhosis.Methods Toselecting60casesoflivercirrhosispatientsincirrhosisgroup.AccordingtotheChildGPugh classification,thepatientsinA,BandCgradesweredividedintoA,BandCgroups.Toselecting30outpatientswithphysicalexaminations, whoseageandgendermatchedwithcirrhosispatientsatthesameperiodasnormal/controlgroup.Measuredtheconventionalindexes, andanalysedtwoGdimensionaldynamicimagesoftwoGchamber,threeGchamber,fourGchamberviewofapical.Thedifferencesinstrain indexandrelatedparametersbetweenthecirrhosisgroupsandthenormalcontrolgroupwerecompared.Results (1)Betweenliver cirrhosisgroupandcontrolgroup,therewerestatisticaldifferencesinheartrate,interventricularseptumthicknessandleftventricular enddiastolicvolume(P<0.05).leftventricularejectionfraction wassignificantlylowerintheChildCgroupthanintheChild A groupandtheChildBgroup(P<0.05),andwassignificantlyhigherintheChildBgroupthanthecontrolgroup(P<0.05).Withthe increaseofChildGPughscoreinlivercirrhosisgroup,interventricularseptumthickness,leftatrialanteroposteriordiameter,leftventricular enddiastolicdiameterandleftventricularenddiastolicvolumeweregraduallyincreasing.Therewerestatisticallysignificantdifferences betweensomegroups(P<0.05);(2)Longitudinalsystolicpeakstrainofeachsegmentofleftventricularwallwasgenerallylowerin thelivercirrhosisgroupthanthecontrolgroup,andthestrainin bothgroupsshowedincreasingtrendfromthebasaltotheapical segments.There werestatisticallysignificantdifferences between partialsegment(P<0.05);(3)WiththeincreaseofChildGPugh scoreincirrhosisgroup,longitudinalsystolicpeakstrainofthe leftventricularwallgraduallydecreased.ChildCgroupcomparedwithothergroups,theleftventricularlongitudinalstrainaverage valuedifferencewasstatisticallysignificant(P<0.05).Therewerestatisticallysignificantdifferencesinpartialsegmentbetweenthe othergroups(P<0.05).Conclusion (1)2DGSTItechnologycanbesensitiveandreliabletodetectsubGclinicalmyocardialregional systolicdysfunctioninpatientswithcirrhosis;(2)LeftventricularsystolicfunctionisnegativelycorrelatedwithChildGPughgradein patientswithlivercirrhosis.
9.Application of formatted text message in follow-up improves treatment compliance of patients with hyperthyroidism
Lingyu ZHENG ; Jingyan QIN ; Jing WANG ; Yun RUAN ; Xiujing WANG ; Jiaqi YAO ; Qingying TAN
Chinese Journal of General Practitioners 2019;18(3):261-264
Eighty patients with hyperthyroidism treated in PLA 903 Hospital from February 2016 to May 2017 were randomly divided into two groups with 40 cases in each group.Patients in control group received routine outpatient education and those in study group received regular formatted mobile short message during follow-up in addition to routine education.The knowledge of disease,the compliance and satisfaction of treatment were assessed.After 12 weeks of follow-up,the TSH level was higher [0.430(0.050,2.806) vs.0.210(0.003,1.098) mU/L,Z=-8.07,P<0.01],FT3 [(3.24± 1.18) vs.(4.18±2.07)ng/L,t=-2.49,P< 0.05] and FT4 levels [(12.43±6.82) vs.(19.58±19.06) ng/L,t=-2.26,P<0.05] were lower in study group than those in control group.The scores of disease knowledge (6.12± 1.77 vs.5.25±1.79,t=4.67,P<0.05),the Morisky scores of medication compliance (3.77±0.47 vs.3.37±0.73,t=8.22,P<0.01),the rates of compliance for returning (85% vs.65%,x2=4.27,P<0.05) and the satisfaction rates with treatments (93% vs.75%,x2=3.30,P<0.05) in the study group were significantly higher than those in the control group.The score of disease knowledge in study group increased from 4.32± 1.55 before treatment to 6.12± 1.77 after 12 weeks of follow-up (t=22.65,P<0.01).The results indicate that the health education plus regular formatted text message during follow-up can effectively improve the disease knowledge score,the compliance and satisfaction with treatment in patients with hyperthyroidism.
10.Assessment of the left ventricular function in patients with post - hepatitis b cirrhosis using Tei index
The Journal of Practical Medicine 2018;34(10):1649-1651
Objective To investigate the clinical value of assessment of the left ventricular function in pa-tients with post-hepatitis b cirrhosis using Tei index and its related parameters measured by Tissue Dopple Imaging. Methods Ninety-seven subjects were enrolled,with 43 ones in the normal control group,and 54 ones in the post-hepatitis b cirrhosis group. According to the Child-Pugh grading standard,patients in the post-hepatitis b cirrhosis group were divided into grade Child A(24 cases),grade Child B(15 cases)and grade Child c(15 cases). Color ul-trasonograph was used to detect the left ventricle Tei indexes of patients in each group,and comparison was made in the differences of the parameters among all groups. Results (1)The Tei index,IRT/ET and ICT/ET of left ven-tricular in the liver cirrhosis group were higher than those in the normal/control group,with significant differences between the two groups(P < 0.05). The Tei index,IRT/ET and ICT/ET of the left ventricular increased gradually in patients of grade Child A,B,and C,and significant differences were observed in Tei index,IRT/ET(P < 0.05), but no significant diference in ICT/ET was found.(2)There were no significant difference in LVEF and Ea/Aa be-tween the cirrhosis group and the normal control group. LVEF and Ea/Aa in grade Child C were significantly lower than those in the normal control group(P < 0.05). Conclusion Tei index is superior to conventional echocardiog-raphy on assessment of the left ventricular function in patients with liver cirrhosis. Patients with higher the Child-Pugh score may be suffered from the worse the left ventricular function,especially the diastolic dysfunction.


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