1.Effect of electroacupuncture preconditioning on microglia polarization after cerebral ischemia reperfusion injury in rats
Xiangxiang ZHANG ; Qianyun TAO ; Haofei LIU ; Yang YUAN ; Mingshan WANG ; Gaofeng ZHANG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(2):207-211
Objective To investigate the effect of electroacupuncture preconditioning on microglia polarization in rats after cerebral ischemia reperfusion(IR)injury and explore the role of tyrosine kinase 2(J AK2)/signal transducer and activator of transcription 3(STAT3)pathway in the process.Methods Forty-five clean-grade healthy male Sprague-Dawley rats were randomly and equally divided into sham operation group,IR group and electroacupuncture preconditioning group.Rat model of IR injury was induced with thread occlusion of the internal carotid artery.Before modeling,electroacupuncture preconditioning was applied to Baihui acupoint for 5 consec-utive days in the preconditioning group,and exposure of the cervical blood vessels were inflicted in the sham-operation group.At 24 h after reperfusion,the severity of neurological deficit was observed by modified neurological deficit score(mNSS),and the cerebral infarct volume was observed by TTC staining.Western blotting was used to detect the protein levels of classical acti-vated type(M1)marker inducible nitric oxide synthase(iNOS),alternative activated type(M2)marker arginase 1(Arg-1),JAK2 and p-JAK2,and STAT3 and p-STAT3,and q-PCR was applied to detect the mRNA expression of iNOS and Arg-1.The expression of TNF-α and IL-10 was measured by ELISA.Results Compared with the sham operation group,the mNSS,infarct vol-ume,protein levels of p-JAK2/JAK2,p-STAT3/STAT3,protein and mRNA levels of iNOS and Arg-1,and expression of TNF-α and IL-10 were significantly increased in the IR and electroacu-puncture preconditioning groups(P<0.01).The preconditioning group had obviously lower mNSS,smaller infarct volume,decreased protein levels of p-JAK2/JAK2,p-STAT3/STAT3,re-duced protein and mRNA levels of iNOS,and declined TNF-α expression,but elevated expression of Arg-1 at protein(2.0±0.2 vs 1.5±0.1)and mRNA(4.2±0.8 vs 3.1±0.3)levels and increased IL-10 expression(49.1±7.1 pg/mg vs 27.9±5.9 pg/mg)when compared with the IR group(P<0.01).Conclusion Electroacupuncture preconditioning can promote the polarization of microglia to M2 and inhibit the polarization of microglia to M1 after cerebral IR injury,which may be relat-ed to the inhibition of JAK2/STAT3 pathway.
2.Retrospective analysis of childcare center disinfection in some regions of Anhui Province during 2019-2022
CHEN Fang, XU Peiru, CHENG Wenjun, YANG Kang, LIN Haofei,WU Lei, HUANG Fayuan, XU Qinghua
Chinese Journal of School Health 2023;44(11):1743-1746
Objective:
To understand the status of childcare center disinfection around the COVID-19 pandemic, the needs of professional technical support, so as to give advice for improvement measures.
Methods:
Using multi stage stratified sampling method, one was selected from each area of northern and southern Anhui Province, with 3 counties/districts selected from each city. A total of 54, 58, 60 childcare institutions were selected. A questionnaire survey, as well as on site visits and data check were administered in these childcare centers in Anhui Province were implemented. Information regarding the three stage disinfection work from 2019 to 2022 and technical support needs were collected.
Results:
A total of 54, 58, 60 childcare centers were investigated in 2019, 2020 and 2021-2022. Most of the childcare centers recorded disinfection work (96.3%, 96.6%, 98.3%), while few of them ( 26.4% , 26.3%, 58.3%) monitored disinfection factor intensity. The implementing rate of disinfection effect evaluation was 68.3% at the stage of normal prevention and control, the highest demand rate for professional technical support was guidance and training ( 95.0% ), and the highest demand rate for training content was disinfectant preparation method (81.7%). There were significant differences in the rate of disinfection tableware room allocation (A: 93.3%, B: 70.0%), and the rate of disinfection effect evaluation among different cities (A: 53.3%, B: 83.3%)( χ 2=6.24, 5.46, P <0.05).
Conclusions
From 2019 to 2022, childcare center disinfection has significantly improved, however, disinfection factor intensity monitoring and disinfection effect evaluation are neglected during the stage of normal prevention and control. The demand for professional technical institutions to provide disinfectant preparation method guidance and training is high.It is suggested to strengthen the monitoring and evaluation of disinfection and related technical guidance.
3.Role of GSTM1 expression in mild hypothermia-induced mitigation of cerebral ischemia-reperfusion injury: relationship with microglial polarization
Huijie ZHU ; Cuimei LI ; Huailong CHEN ; Xiangxiang ZHANG ; Haofei LIU ; Yang YUAN ; Gaofeng ZHANG ; Fei SHI ; Mingshan WANG ; Rui DONG
Chinese Journal of Anesthesiology 2023;43(10):1226-1231
Objective:To evaluate the role of glutathione S-transferase μ1 (GSTM1) expression in mild hypothermia-induced mitigation of cerebral ischemia-reperfusion (I/R) injury and the relationship with microglial polarization.Methods:Eighty clean-grade healthy male Sprague-Dawley rats, aged 8 weeks, weighing 260-280 g, were divided into 4 groups ( n=20 each) using a random number table method: sham operation group (S group), cerebral I/R group (I/R group), mild hypothermia group (H group), and GSTM1 inhibitor + mild hypothermia group (IH group). The rat model of cerebral I/R injury was prepared using the filament occlusion method. The filament was removed to restore blood flow after the left middle cerebral artery was blocked for 2 h, and the rats′ brain and rectal temperature were maintained at 36-37 ℃ during the period. The vessels were only isolated and ligated without occlusion in S group. In H group, the entire body was wiped with 75% ethanol immediately after removing the filament, and the brain and rectal temperatures were maintained at 32-33 ℃ for 3 h, and the other procedures were the same as those previously described in I/R group. In IH group, GSTM1 inhibitor itaconic acid 8.6 mg/kg was intraperitoneally injected at 24 and 1 h before developing the model, and the other procedures were the same as those previously described in H group. Neurological deficits were evaluated using a modified neurological severity score (mNSS) at 24 h of reperfusion, and then the animals were sacrificed and the brains were removed for observation of cerebral infarction (by TTC staining) and for determination of the expression of GSTM1, M1-type microglial marker inducible nitric oxide synthase (iNOS), and M2-type microglial marker arginase-1 (Arg-1) (by Western blot), expression of GSTM1, iNOS and Arg-1 mRNA (quantitative real-time polymerase chain reaction) and contents of interleukin-6 (IL-6), IL-10, tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) (by enzyme-linked immunosorbent assay). Results:Compared with S group, the mNSS and percentage of cerebral infarct size were significantly increased, and the expression of iNOS and Arg-1 protein and mRNA was up-regulated, the expression of GSTM1 and mRNA was down-regulated, and the contents of IL-6, TNF-α, IL-10 and TGF-β were increased in the other three groups ( P<0.05). Compared with I/R group and IH group, the mNSS and percentage of cerebral infarct size were significantly decreased, and the expression of iNOS protein and mRNA was down-regulated, the expression of Arg-1 protein and mRNA and GSTM1 was up-regulated, the contents of TNF-α and IL-6 were decreased, and the contents of TGF-β and IL-10 were increased in H group ( P<0.05). Conclusions:Up-regulated expression of GSTM1 is involved in mild hypothermia-induced mitigation of cerebral I/R injury, which is associated with inhibition of microglial polarization toward the M1 phenotype and promotion of polarization toward the M2 phenotype.
4.Effects of mild hypothermia on microglia polarization and JAK2/STAT3 signaling pathway during cerebral ischemia-reperfusion in rats
Xiangxiang ZHANG ; Huailong CHEN ; Mingshan WANG ; Jiawen ZHANG ; Huijie ZHU ; Haofei LIU ; Yang YUAN ; Fei SHI ; Gaofeng ZHANG
Chinese Journal of Anesthesiology 2023;43(4):468-472
Objective:To investigate the effects of mild hypothermia on microglia polarization and janus kinase 2/signal transduction and transcriptional activation factor 3 (JAK2/STAT3) signaling pathway during cerebral ischemia-reperfusion (I/R) in rats.Methods:Forty-five clean-grade healthy male Sprague-Dawley rats, aged 8 weeks, weighing 260-280 g, were divided into 3 groups ( n=15 each) by the random number table method: sham operation group (S group), cerebral I/R group (I/R) and mild hypothermia group (H group). In I/R group and H group, cerebral I/R was induced by middle cerebral artery occlusion using a nylon thread in anesthetized animals, the nylon thread was removed to restore the perfusion after 2 h of occlusion, and the rectal temperature was maintained at 36-37 ℃ during the period. Group H was wiped with 75% alcohol for 3 h starting from the time point immediately after reperfusion, and the rectal temperature was maintained at 32-33℃. Modified neurological severity score (mNSS) was evaluated at 24 h of reperfusion. Animals were then sacrificed for determination of the cerebral infarct size (using TTC staining), expression of M1 marker inducible nitric oxide synthase (iNOS), M2 marker arginase 1(Arg-1), phosphorylated JAK2(p-JAK2)and phosphorylated STAT3(p-STAT3)(by Western blot), expression of iNOS mRNA and Arg-1 mRNA (by quantitative polymerase chain reaction), and contents of interleukin-6 (IL-6) and IL-10 (by enzyme-linked immunosorbent assay). Results:Compared with group S, mNSS and cerebral infarct size were significantly increased, the expression of iNOS, Arg-1 protein and mRNA in cerebral ischemic penumbral zone was up-regulated, and the p-JAK2/JAK2 ratio, p-STAT3/STAT3 ratio, and contents of IL-6 and IL-10 were increased in the other two groups ( P<0.05). Compared with I/R group, mNSS and cerebral infarct size were significantly decreased, the expression of iNOS protein and mRNA in cerebral ischemic penumbral zone was down-regulated, the expression of Arg-1 and mRNA was up-regulated, and the p-JAK2/JAK2 ratio, p-STAT3/STAT3 ratio and IL-6 content were decreased, and the IL-10 content was increased in group H ( P<0.05). Conclusions:Mild hypothermia can promote the polarization shift of microglia from M1 to M2 phenotype during cerebral I/R and inhibit the central inflammatory responses, and the mechanism may be related to inhibition of JAK2/STAT3 signaling pathway in rats.
5.Effect of selective cerebral mild hypothermia on SUMO2/3 modification of Drp1 in a rat model of cerebral ischemia-reperfusion
Haofei LIU ; Yang LIU ; Xiangxiang ZHANG ; Ruijiao NIU ; Mingshan WANG ; Fei SHI ; Yang YUAN ; Gaofeng ZHANG ; Rui DONG
Chinese Journal of Anesthesiology 2023;43(5):591-596
Objective:To evaluate the effect of selective cerebral mild hypothermia on small ubiquitin-like modifier 2/3 (SUMO2/3) modification of dynamin-related protein 1 (Drp1) in a rat model of cerebral ischemia-reperfusion (I/R).Methods:Sixty clean-grade healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 240-260 g, were divided into 4 groups ( n=15 each) using a random number table method: sham operation group (S group), cerebral I/R group (I/R group), selective cerebral mild hypothermia group (HT group) and normal temperature group (NT group). The operation was performed under the monitoring of cerebral temperature and rectal temperature.Only the cervical blood vessels were exposed in S group, while focal cerebral I/R was induced by 2 h middle cerebral artery occlusion (MCAO) followed by 24 h reperfusion in anesthetized animals in the other three groups.In HT group and NT group, 4 and 37 ℃ normal saline was perfused through the left internal carotid artery at a rate of 80 ml·kg -1·h -1 for 15 min, respectively. Modified neurological severity score (mNSS) was assessed at 24 h of reperfusion. Then the rats were sacrificed under deep anesthesia, brains were removed, brain tissues were obtained for determination of the percentage of cerebral infarct size (by TTC staining), and the ischemic penumbra tissues in the cerebral cortex were removed for examination of the ultra-structural changes of mitochondria (with a transmission electron microscope) and for determination of the SUMO2/3 modification of Drp1 (by CO-IP), expression of total Drp1 (T-Drp1) and total cytochrome c (T-Cytc) (by Western blot), and expression of mitochondrial outer membrane Drp1 (M-Drp1) and cytoplasmic Cytc (C-Cytc) (by Western blot) after isolation of mitochondria and cytoplasm. Results:Compared with S group, the mNSS and percentage of cerebral infarct size were significantly increased, the expression of M-Drp1, T-Drp1, C-Cytc and T-Cytc was up-regulated, and SUMO2/3 modification of Drp1 in ischemic penumbra area was increased ( P<0.05), the fragmentation of mitochondria was aggravated, and cristae rupture and vacuolation were obvious in the other three groups. Compared with I/R group, the mNSS and percentage of cerebral infarct size were significantly decreased, the expression of M-Drp1, T-Drp1, C-Cytc and T-Cytc was down-regulated, SUMO2/3 modification of Drp1 was increased ( P<0.05), the fragmentation of mitochondria was significantly attenuated, and cristae rupture and vacuolation were weakened in HT group. There were no significant differences in these detection parameters between NT group and I/R group ( P>0.05). Conclusions:The mechanism by which selective cerebral mild hypothermia alleviates the cerebral I/R injury is related to increased SUMO2/3 modification of Drp1, decreased binding of Drp1 to mitochondrial outer membrane, and reduced mitochondrial excessive fission in rats.
6.Effect of sodium bicarbonate Ringer′s solution on acute kidney injury following laparoscopic hepatectomy in elderly patients
Hui YU ; Xi LIU ; Gaofeng ZHANG ; Xiangxiang ZHANG ; Haofei LIU ; Mingshan WANG ; Fei SHI ; Yang YUAN
Chinese Journal of Anesthesiology 2023;43(6):714-719
Objective:To evaluate the effect of sodium bicarbonate Ringer′s solution on acute kidney injury(AKI) following laparoscopic hepatectomy in elderly patients.Methods:A total of 362 American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ elderly patients, aged 65-79 yr, with body mass index of 18-28 kg/m 2, scheduled for elective laparoscopic hepatectomy, were divided into 2 groups( n=181 each) using a random number table method: bicarbonate Ringer′s solution group(BR group) and lactated Ringer′s solution group(LR group). Bicarbonate Ringer′s solution and lactated Ringer′s solution were intravenously infused in BR group and LR group, respectively. All operations were performed under general anesthesia combined with abdominal fascia block, and the methods of controlled low central venous pressure and intermittent hepatic inflow occlusion were applied to reduce intraoperative bleeding. Radial artery blood samples were collected for blood gas analysis at 5 min before anesthesia induction(T 0), 20 min after occluding liver hilus(T 1), 10 min after hepatectomy and hemostasis(T 2), at the end of surgery(T 3) and at postanesthesia care unit discharge(T 4), and lactate value(Lac) was recorded. Blood samples from cubital vein were collected on admission to hospital(T A) and at 24(T 24) and 48 h after operation(T 48) for determination of serum creatinine(Cr) concentrations. Doppler-based renal resistive index(RRI) was measured at T A, T 4, T 24 and T 48. The incidence of AKI was calculated within 48 h after operation according to the Kidney Disease: Improving Global Outcomes criteria in 2012 for Cr concentration. Adverse reactions(such as nausea and vomiting) and complications(such as incision infection) within 48 h after operation were recorded. Results:Compared with the baseline at T 0, Lac concentrations were significantly increased at T 1-4 in both groups( P<0.01). Cr concentrations were significantly increased at T 24 and T 48, and RRI was increased at T 4, T 24 and T 48 than at T A in both groups( P<0.01). Compared with group LR, the incidence of AKI within 48 h after operation, Lac concentrations at T 3, 4, Cr concentrations at T 24 and T 48, and RRI at T 4, T 24 and T 48 were significantly decreased in group BR( P<0.05 or 0.01). There was no significant difference in the incidence of nausea, vomiting, incision infection, delirium, bile leakage and pulmonary infection within 48 h after operation among the two groups( P>0.05). Conclusions:Sodium bicarbonate Ringer′s solution can decrease the development of AKI following laparoscopic hepatectomy in elderly patients.
7.Establishment of a diagnostic model for glomerular micro thrombosis in patients with lupus nephritis based on machine learning
Haofei HU ; Ricong XU ; Yang LIU ; Jianyu CHEN ; Zheyi CHANG ; Qijun WAN
Chinese Journal of Rheumatology 2022;26(11):721-729,C11-1
Objective:To establish a diagnostic model for glomerular micro thrombosis (GMT) in lupus nephritis through clinical indicators.Methods:A continuous collection of patients diagnosed with lupus nephritis (LN) by renal biopsy in the Department of Nephrology, Shenzhen Second People's Hospital, from January 2010 to March 2021. All patients were admitted and discharged through the inclusion and exclusion criteria. Demographic data, clinical characteristics, biochemical indicators, and immune indicators were collected. A GMT diagnosis model was established from the most important variables among the abovementioned variables through machine learning and Logistic stepwise regression analysis. The model was presented through a nomogram. The receiver operating characteristic curve (ROC), the clinical decision curve and the calibration curve were used to evaluate the model discrimination, clinical use and accuracy, respectively. The internal verification of the model was carried out by repeated sampling 500 times by the Bootstrap method.Results:There were a total of 129 patients with lupus nephritis including the study, including 117 females (90.7%); the average age was (34±11) years. There were 39 patients with GMT (30.2%). Using machine learning to screen out the top 10 important variables from 47 candidate variables, then through logistic stepwise regression analysis, five variables were further screened to establish the diagnostic model of GMT, namely hemoglobin [ OR(95% CI)=0.966(0.943, 0.990), P=0.005], serum C3 [ OR(95% CI)=0.133(0.022, 0.819), P=0.030], systolic blood pressure [ OR(95% CI)=1.027(1.005, 1.049), P=0.017], lymphocyte count [ OR(95% CI)=0.462(0.213, 0.999), P=0.049], and TT [ OR(95% CI)=1.260(0.993, 1.597), P=0.057]. Draw up the equation of the GMT diagnosis model of lupus nephritis and establish a nomogram to present the model. The area under curve (AUC) of the diagnostic model was 0.823, 95% CI(0.753, 0.893), indicating that the model had a reasonable degree of discrimin-ation. The Hosmer-Lemeshow test showed a perfect fit between the predicted GMT risk and the observed GMT risk ( χ2= 14.62, P=0.067). The clinical decision curve and clinical impact curve reflect that the model had a good clinical application value, especially when the threshold probability is between 0.4 and 0.6, the application value is more significant. In addition, after 500 repeated samplings by the Bootstrap method, the average AUC was 0.825, 95% CI(0.753, 0.893), which is basically the same as the AUC obtained by the original model. Conclusion:We established a diagnostic model of GMT inLN based on clinical indicators through machine learning and logistic stepwise regression analysis. It is used for early diagnosis of the risk of GMT before the renal biopsy.
8.Is oral microbiome of children able to maintain resistance and functional stability in response to short-term interference of ingesta?
Fangqiao WEI ; Xiangyu SUN ; Yufeng GAO ; Haoyu DOU ; Yang LIU ; Lili SU ; Haofei LUO ; Ce ZHU ; Qian ZHANG ; Peiyuan TONG ; Wen REN ; Zhe XUN ; Ruochun GUO ; Yuanlin GUAN ; Shenghui LI ; Yijun QI ; Junjie QIN ; Feng CHEN ; Shuguo ZHENG
Protein & Cell 2021;12(6):502-510
9.Stress Analysis of Aortic Vessels under Stent Graft
Shuaixing YANG ; Ming ZHANG ; Xiangchen DAI ; Yuguo XUE ; Haofei LIU
Journal of Medical Biomechanics 2021;36(1):E014-E021
Objective To simulate the interaction between the stent graft (SG) and the aortic wall with finite element (FE) analysis by considering the influence of residual stress field, so as to study the stent influence on stress distributions of the aortic wall. Methods The three-dimensional (3D) residual stress field was generated in an idealized bi-layered thick-wall aortic model via a stress-driven anisotropic growth model by reducing the transmural stress gradient. Upon virtually deploying the SG, the stress on the aortic wall was calculated. Results The 3D residual stress field, corresponding to an opening angle of 117.5°, was shown to reduce the transmural stress gradient in both the circumferential and axial directions. The maximum stress was found at the contact area between aortic wall and wave peak of the stent. At 20% oversize ratio of the stent, the maximum stresses on the aortic wall in circumferential and axial direction were 412 and 132 kPa, respectively, while the in-plane shear stresses σrθ and σrz were both 78 kPa. Under residual stress, the maximum radial, circumferential and axial stresses were decreased by 14.9%, 40.5% and 33.8%, respectively, while the maximum shear stresses σrθ ,σrz,σθz were reduced by 2.5%, 7.1% and 27%, respectively. With the increase of oversize ratio from 10% to 20%, the maximum radial, circumferential and axial stresses were increased by 316%, 129% and 41%, respectively, while the maximum shear stresses σrθ ,σrz,σθz were increased by 661%, 450% and 466%, respectively. Conclusions The residual stress can effectively reduce the transmural stress gradient. Both the residual stress and the oversize ratio of the stent play an important role in modulating the wall stress distribution and the maximum stress.
10.Correlation between hemoglobin and progression of renal function in patients with proliferative lupus nephritis
Yang LIU ; Haofei HU ; Jianyu CHEN ; Tao CAO ; Qijun WAN
Chinese Journal of Nephrology 2021;37(11):889-895
Objective:To explore the correlation between hemoglobin (Hb) and progression of renal function in patients with proliferative lupus nephritis (PLN).Methods:Data of biopsy-proven PLN patients from January 2010 to February 2019 in Department of Nephrology, the First Affiliated Hospital of Shenzhen University were retrospectively analyzed. The patients were divided into stable renal function group and renal function progression group according to changes of renal function including serum creatinine doubling/end-stage renal disease (ESRD) and the demographic, clinical, and pathological characteristics were compared between the two groups. Cox regression and smooth curve fitting of generalized additive model analysis were used to explore the correlation between Hb and progression of renal function.Results:A total of 87 patients were included in this study. The age was (34.97±11.95) years old and 79 cases (90.80%) were females. During follow-up of 19.0(6.5, 43.5) months, renal function of 15 patients (17.24%) progressed. Compared with stable renal function group, Hb level of patients in renal function progression group were lower ( t=3.887, P<0.001), and serum creatinine ( Z=-2.466, P=0.003) and uric acid ( t=-2.154, P=0.034) were higher. As to the pathological characteristics, the proportion of class lupus nephritis-IV, renal tubular atrophy and interstitial fibrosis in renal function progression group were higher than those in stable renal function group, but there was no statistical difference between the two groups (all P>0.05). Multivariate Cox regression analysis indicated that high Hb was an independent protective factor of renal function progression in PLN patients ( HR=0.893, 95% CI 0.836-0.954, P=0.001). The risk of progression to serum creatinine doubling/ESRD would decrease by 10.7% when Hb increased by 1 unit (g/L). Smooth curve fitting of generalized additive model analysis showed that Hb was linearly correlated with the risk of renal function progression ( P=0.100). Receiver operating characteristic curve indicated that the risk of doubling serum creatinine/ESRD in PLN patients would be relatively low when Hb level was above 77 g/L (area under the curve 0.788, best threshold 77 g/L, sensitivity 0.600, specificity 0.903). Conclusions:Hb is closely related to progression of renal function in patients with PLN. More attention and management of Hb levels in patients with PLN can play an important role in improving renal prognosis.


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