Objective To analyze the protective effects of heat-shock response on the retinae of the rats after retinal ischemic reperfusion injury.Method Twenty Wistar rats (20 eyes) were divided into 4 groups: intracameral perfusion group (group P), intracameral perfusion after quercetin injection group (group P+Q), intracameral perfusion after heat shock group (group P+H), and in tracameral perfusion after quercetin injection and heat shock group (group P+Q+H ). According to the standard program established by International Society for Clinical Visual Electrophysiology, we recorded the results of the dark-adapted electroretinogram (D-ERG ),oscillatory potentials (OPs),and light-adapted ERG (L-ERG) of the rats with intraocular hypertension after induced by heat shock response. The expressions of HSP 70 of the rats in all groups were observed by Western blotting.Results The expression of HSP 70 of the rats in group P+H was the highest in all groups, but the expressions of HSP70 in group P+Q and P+Q+H were inhibited significantly. The amplitudes of a and b wave of ERG and O2 wave of OPs decreased, and the delitescence of them were delayed significantly in rats after intracameral perfusion. The amplitude of b wave of D-ERG and O2 wave of OPs in group P+H were higher than which in group P. Zero hour after perfusion, the amplitudes of all waves in group P+H increased significantly (Plt;0.05). Twenty-four hours after perfusion, the retinal functional resumption of the rats in group P+H was better than which in group P. In group P+Q and P+Q+H, the delitescences of all waves of ERG and O2 wave of OPs were the longest and the amplitudes were the lowest, and some waves even disappeared.Conclusions The heat-shock response may improve the recovery ability of the retinal cells after injury of ischemic reperfusion.(Chin J Ocul Fundus Dis，2003，19：117-120)
ObjectiveTo evaluate the effect of different doses of dexmedetomidine on hemodynamics during endotracheal extubation of laparoscopic cholecystectomy in patients with hypertension. MethodsA total of 120 hypertension patients ready to undergo laparoscopic cholecystectomy under general anesthesia between December 2013 and December 2014 were chosen to be our study subjects. They were randomly divided into 4 groups with 30 patients in each:saline control group (group C), low-dose dexmedetomidine hydrochloride injection group (group D1), moderate-dose dexmedetomidine hydrochloride injection group (group D2), and high-dose dexmedetomidine hydrochloride injection group (group D3). The anesthesia methods and drugs were kept the same in each group, and 20 mL of saline, 0.25, 0.50, 1.00 μg/kg dexmedetomidine (diluted to 20 mL with saline) were given to group C, D1, D2, and D3 respectively 15 minutes before the end of surgery. Time of drug administration was set to 15 minutes. We observed and recorded each patient's mean arterial pressure (MAP) and heart rate (HR) in 5 particular moments:the time point before administration (T1), immediately after administration (T2), extubation after administration (T3), one minute after extubation (T4), and 5 minutes after extubation (T5). Surgery time, recovery time, extubation time and the number of adverse reactions were also detected. ResultsCompared at with, MAP and HR increased significantly at the times points of T3, T4, T5 compared with T1 and T2 in Group C and group D1 (P<0.05), while the correspondent difference was not statistically significant in group D2 and D3 (P>0.05). Compared with group C, MAP and HR decrease were not significantly at the time points of T3, T4, T5 in group D1 (P>0.05). However, MAP and HR decrease at times points of T3, T4, T5 in group D2 and D3 were significantly different from group C and D1 (P<0.05). After extubation, there were two cases of dysphoria in group C and two cases of somnolence in group D3, but there were no cases of dysphoria, nausea or shiver in group D1, D2, D3. ConclusionIntravenously injecting moderate dose of dexmedetomidine 15 minutes before the end of surgery can effectively reduce patients' cardiovascular stress response during laparoscopic cholecystectomy extubation for patients with hypertension, and we suggest a dose of 0.5 μg/kg of dexmedetomidine.
Although great progress has been achieved in the techniques and materials of cardiopulmonary bypass (CPB), cardiac surgery under CPB is still one of the surgeries with the highest complication rate. The systemic inflammatory response is an important cause of complications, mainly characterized by activation of innate immune cells and platelets, and up-regulation of inflammatory cytokines. After activation, a variety of molecules on the membrane surface are up-regulated or down-regulated, which can amplify tissue inflammatory damage by releasing cytoplasmic protease and reactive oxygen species, and activate multiple inflammatory signaling pathways in the cell, ultimately leading to organ dysfunction. Therefore, the expression of these cell membrane activation markers is not only a marker of cell activation, but also plays an important role in the process of vital organ injury after surgery. Identification of these specific activation markers is of great significance to elucidate the mechanisms related to organ injury and to find new prevention and treatment methods. This article will review the relationship between these activated biomarkers in the innate immune cells and vital organ injuries under CPB.
Objective To investigate the percentage of CD4+CD25+ Treg in peripheral blood of patients with severe multiple trauma and systemic inflammatory response syndrome（SIRS） and its effects on cellular immunity and secondary infection.Metheds Peripheral blood of 23 patients with severe multiple trauma was collected in 24 h after SIRS was diagnosed，and flow cytometry was used to determine the percentage of CD4+CD25+ Treg and CD4/CD8 ratio.Simultaneously，in order to explore the cell proliferation，silver staining was used to determine Ag-NORs of leukomonocyte in peripheral blood represented by IS%.In order to investigate the infection in patients，sputum and secretion sample were collected for bacteriological examination on 1 and 5 day after SIRS was established.Forty healthy volunteers were enrolled as control.Results Compared with the control，the percentage of CD4+CD25+ Treg was significant higher[（14.21±3.43）% vs（9.53±3.22），Plt;0.01] and the ratio of CD4/CD8 and IS% were significant lower in patients with severe multiple trauma[（5.94±0.66）% vs（6.74±0.95）%，（1.22±0.25）% vs（1.72±0.36）%，respectively，both Plt;0.01].In those patients（n=14） who developed secondary infection，Treg% was significant higher [（18.69±4.21）% vs（12.58±2.49）%，Plt;0.01]，while IS% and CD4/CD8 were significant lower [（5.79±0.68）% vs（6.15±0.57）%，（1.15±0.25）% vs（1.39±0.25）%，both Plt;0.01].compared to the patients without secondary infection Conlusion CD4+CD25+ Treg is valuable to estimate the cellular immunity and predict secondary infection in patients with severe multiple trauma.
Nuclear factor-erythroid 2-related factor 2 (Nrf2) is an important factor for cells to resist oxidative stress and electrophilic attack. It is involved in the formation and control of oxidative stress defense pathways. It is associated with oxidative stress-related diseases, including cancer, neurodegenerative diseases, cardiovascular diseases and aging, and is a potential pharmacological target for the treatment of chronic diseases. This article will review the important role of Nrf2 in the regulation of cell proliferation, including direct regulation of cell proliferation, regulation of reactive oxygen species, intracellular metabolism, regulation of mitochondrial function, cell lifespan and inflammatory response. The aim is to provide a theoretical basis for further research on how to use Nrf2 to regulate cell proliferation.
Dose-response meta-analysis, as a subset of meta-analysis, plays an important role in dealing with the relationship between exposure level and risk of diseases. Traditional models limited in linear regression between the independent variables and the dependent variable. With the development of methodology and functional model, Nonlinear regression method was applied to dose-response meta-analysis, such as restricted cubic spline regression, quadratic B-spline regression. However, in these methods, the term and order of the independent variables have been assigned that may not suit for any trend distribution and it may lead to over fitting. Flexible fraction polynomial regression is a good method to solve this problem, which modelling a flexible fraction polynomial and choosing the best fitting model by using the likelihood-ratio test for a more accurate evaluation. In this article, we will discuss how to conduct a dose-response meta-analysis by flexible fraction polynomial.
ObjectiveTo explore the influence of norepinephrine on the prediction of fluid responsiveness by passive leg raising (PLR) during septic shock. MethodsForty-six septic shock patients in intensive care unit of Nanjing Drum Tower Hospital were prospectively observed from September to November 2012. Among which 36 septic shock patients were enrolled with a positive PLR test (defined by an increase in stroke volume index ≥10%). A PLR test was performed at baseline (PLR1). A second PLR test (PLR2) was performed at returning to supine position for 10 min and the dose of norepinephrine was increased to maintain MAP ≥65 mmHg for 20 min. The changes of heart rate(HR),mean arterial pressure(MAP),central venous pressure(CVP),cardiac index(CI),stroke volume index(SVI),index of systemic vascular resistance(SVRI),global end-diastolic volume index(GEDVI),and cardiac function index(CFI) were monitored by transpulmonary thermodilution technique (PiCCO). ResultsPLR1 significantly increased SVI by (20.54±9.63)%,CI by (20.57±9.89)%,MAP by (7.64±5.77)%,and CVP by (25.83±23.39)%. As the dose of norepinephrine increased,SVI was increased by (16.97±9.06)%,CI by (16.78±8.39)%,GEDVI by (9.08±4.47)%,MAP by (28.07±12.48)%,and CVP by (7.86±8.52)%. PLR2 increased SVI by (13.74±8.79)%,CI by (13.79±9.08)%,MAP by (2.93±5.06)%,and CVP by (13.36±14.74)%. The PLR2 and the dose increase of norepinephrine augmented SVI to a significantly lesser extent than the PLR1 performed at baseline (both P<0.05). However,SVI increased by <10% in 6 patients while the baseline PLR was positive in these patients. ConclusionIn septic patients with a positive PLR at baseline,norepinephrine increases cardiac preload and cardiac output and influences the fluid responsiveness.
Objective To realize the research progress of regulating the endoplasmic reticulum stress response to inhibit autophagy in tumor cells. Method The literatures about regulating the endoplasmic reticulum stress response to inhibit autophagy in tumor cells were reviewed. Result In the endoplasmic reticulum stress response induced by the release of calcium and accumulation of unfolded proteins, autophagy can be activated by several pathways, and to regulate physiological and pathological processes. Conclusion Further research about the endoplasmic reticulum stress response in tumor cells need to be done to regulate the response factors to inhibit autophagy.
Objective To systematically evaluate the efficacy and safety of dose-dense neoadjuvant chemotherapy (ddNACT) and conventional neoadjuvant chemotherapy (cNACT) for locally advanced breast cancer (LABC). Methods PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP databases were searched for randomized controlled trials (RCT) comparing ddNACT regimen with cNACT regimen for breast cancer. The time limit for retrieval was from establishment to March 1st, 2021. Two reviewers independently screened literatures, extracted data and assessed risk bias of included studies; then, meta-analysis was performed by using Stata 15.0 software. Results A total of 13 RCTs were included, including 3 258 patients, of which 1 625 patients received ddNACT and 1 633 patients received cNACT. The results of meta-analysis showed that the ddNACT regimen could improve the pathological complete response rate (pCR, P<0.001), objective response rate (ORR, P<0.001), and disease free survival (DFS, P=0.037) as compared with the cNACT regimen, there was no significant difference in the overall survival (OS) between the two groups (P=0.098). The incidences of grade 3 or 4 oral stomatitis (P=0.005) and neurotoxicity (P<0.001) were higher and the incidence of grade 3 or 4 neutropenia was lower (P=0.025) in the patients with ddNACT regimen, there were no significant differences in grade 3 or 4 thrombocytopenia (P=0.152), grade 3 or 4 anemia (P=0.123), chemotherapy completion rate (P=0.161) and breast conservative surgery rate (P=0.186) between the two groups. Patients with hormone receptor (HR) negative (HR–) were more likely to get pCR after neoadjuvant chemotherapy (P<0.001). ConclusionsCurrent evidence shows that the use of anthracycline/taxane-based ddNACT regimen in LABC patients can improve the pCR, ORR, and DFS as compared with cNACT regimen. The pCR after neoadjuvant chemotherapy in the patients with HR– is higher than that with HR+. Prophylactic use of granulocyte-colony stimulating factor could significantly reduce the incidence of neutropenia, and most patients are tolerant to ddNACT regimen, 2 regimens have similar chemotherapy completion rates.
ObjectiveTo investigate the influence of endoplasmic reticulum stress (ERS) on smoking-induced nucleus pulposus cells apoptosis and inflammatory response.MethodsBetween October 2016 and October 2018, 25 patients with cervical disc herniation receiving discectomy were collected and divided into smoking group (14 cases) and non-smoking group (11 cases). The baseline data of age, gender, herniated segment, and Pfirrmann grading showed no significant difference between the two groups (P>0.05). The obtained nucelus pulposus tissues were harvested to observe the cell apoptosis via detecting the apoptosis-related proteins (Caspase-3 and PRAP) by TUNEL staining and Western blot test. The nucleus pulposus cells were isolated and cultured with enzyme digestion, of which the third generation cells were used in follow-up experiments. Then, the expressions of inflammatory factors [interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α)] were detected by ELISA; the nuclear translocation of P65 was monitored by cell immunofluorescence staining. Furthermore, ERS-related proteins (GRP78 and CHOP) were detected by Western blot; and endoplasmic reticulum ultrastructure was observed under transmission electron microscope. To verify the regulatory effect of ERS, cells were pretreated by ERS specific inhibitor (4-PBA), then cell apoptosis and inflammatory response were tested.ResultsThe nucleus pulposus tissue observation showed that the cell apoptotic rate and the expressions of apoptosis-related proteins (Caspase-3 and PARP) were obviously higher in smoking group than in non-smoking group (P<0.05). The nucleus pulposus cells observation indicated that the expressions of the inflammatory factors (IL-1β and TNF-α) and the ERS-related proteins (GRP78 and CHOP) were also higher in smoking group than in non-smoking group (P<0.05). The results of cell immunofluorescence staining further confirmed that smoking stimulated nuclear translocation of P65 in nucleus pulposus cells. The ERS injury was much more serious in smoking group than in non-smoking group. Furthermore, after 4-PBA inhibiting ERS, the expressions of GRP78, CHOP, IL-1β, TNF-α, and P65 were significantly decreased (P<0.05), and flow cytometry results showed that cell apoptotic rate in smoking group was decreased, showing significant difference compared with the non-smoking group (P<0.05).ConclusionSomking can stimulate cell apoptosis and inflammatory response in nucleus pulposus cells via ESR pathway. Suppressing ESR may be a novel target to suspend smoking-induced intervertebral disc degeneration.