1.An Ethical Reflection on Informed Consent in the Research and Application of Assisted Reproduction Technique
Yuanhua HUANG ; Wen XV ; Weiying LU
Chinese Medical Ethics 1995;0(02):-
With the transformation of marketization of economy and legislation of society in recent 20 years in China,the traditional mechanism in which medical therapy is decided by patients' relatives and doctors has not been able to offer sufficient protection for the legal rights of patients.So the rights of informed consent and decision making have been transferred passively to the patients' side.But in the field of assisted reproduction technique(ART),informed consent has to face some specific and unique problems.Firstly,being fully informed is sharply against the privacy of his(her) spouse as reproduction involved both the couple and their families.Secondly,it is a question that whether a wife can make her freewill choice when she accepts an ART program,because of the pressures coming from her family,the society,and her low social status well.And thirdly,The ART has the characteristics of both clinical therapy and scientific research as it is imperfect and its protocols still need to be improved.Ethicists should focus on thiese challenges.In the aspect of ethics,the regulations established by government and occupational association are the safeguard of the commonweal of society and general rights and benefits,and the ethics review and informed consent offered the final protection for the patients.
2.The influence of positive end-expiratory pressure on cerebral blood flow and cerebrovascular autoregulation in patients with acute respiratory distress syndrome
Chunli YANG ; Zhi CHEN ; Yuanhua LU ; Huiwei HE ; Weihua ZENG
Chinese Critical Care Medicine 2014;26(5):335-338
Objective To explore the influence of different positive end-expiratory pressure (PEEP) levels on cerebral blood flow (CBF) and cerebrovascular autoregulation in patients with acute respiratory distress syndrome (ARDS).Methods A prospective study was conducted.Moderate or severe ARDS patients admitted to Department of Critical Care Medicine of Jiangxi Provincial People's Hospital from January 1st,2013 to October 1st,2013 were enrolled.The changes in hemodynamics,respiratory mechanics and gas exchange under different levels of PEEP were observed.CBF velocity of middle cerebral artery (MCA) was measured using transcranial Doppler (TCD),and breath-holding index (BHI) was also calculated.Results 35 patients with ARDS were included.The oxygenation index (OI),peak inspiratory pressure (PIP),plat pressure (Pplat) and central venous pressure (CVP) were markedly elevated [OI (mmHg,1 mmHg=0.133 kPa):324.7± 117.2 vs.173.4± 95.8,t=5.913,P=0.000; PIP (cmH2O):34.7 ± 9.1 vs.26.1 ± 7.9,t=4.222,P=0.000; Pplat (cmH2O):30.5 ± 8.4 vs.22.2 ± 7.1,t=4.465,P=0.000; CVP (mmHg):12.1 ± 3.5 vs.8.8 ± 2.2,t=4.723,P=0.000] when PEEP was increased from (6.4 ± 1.0) cmH2O to (14.5-± 2.0) cmH2O (1 cmH2O=0.098 kPa).But no significant difference in the heart rate (beats/min:85.5 ± 19.1 vs.82.7 ± 17.3,t=0.643,P=0.523),mean arterial pressure (mmHg:73.5 ± 12.4 vs.76.4 ± 15.1,t=0.878,P=0.383) and CBF velocity of MCA [peak systohc flow velocity (Vmax,cm/s):91.26 ± 17.57 vs.96.64 ± 18.71,t=1.240,P=0.219; diastolic flow velocity (Vmin,cm/s) 31.54 ±7.71 vs.33.87 ±8.53,t=1.199,P=0.235; mean velocity (Vmean,cm/s) 51.19 ± 12.05 vs.54.27 ± 13.36,t=1.013,P=0.315] was found.18 patients with BHI<0.1 at baseline demonstrated that cerebral vasomotor reactivity was poor.BHI was slightly decreased with increase in PEEP (0.78 ± 0.16 vs.0.86 ± 0.19,t=1.905,P=0.061).Conclusions Some of moderate or severe ARDS patients without central nervous system disease have independent of preexisting cerebral autoregulation impairment.However,independent of preexisting cerebral autoregulation may not further be impaired when a high PEEP was chosen.
3.Comparison of effect of norepinephrine and terlipressin on patients with ARDS combined with septic shock: a prospective single-blind randomized controlled trial
Zhi CHEN ; Ping ZHOU ; Yuanhua LU ; Chunli YANG
Chinese Critical Care Medicine 2017;29(2):111-116
Objective To approach the effect of different vasopressor on hemodynamics, volume responsiveness, fluid volume balance, renal function and prognosis in patients with acute respiratory distress syndrome (ARDS) complicated with septic shock.Methods A prospective single-blind randomized controlled trial was conducted. ARDS patients with septic shock admitted to the Department of Critical Care Medicine of Jiangxi Provincial People's Hospital from January 1st, 2015 to May 1st, 2016 were enrolled. The patients satisfied ARDS Berlin diagnostic criteria, over 15 years old, needing vasopressor after fluid resuscitation were enrolled. The patients were divided into norepinephrine group (NE group) and terlipressin group (TP group) by randomise number table derived by computer. Patients in TP group were given terlipressin (0.01-0.04 U/min) with an intravenous pump, while those of NE group were given norepinephrine (> 1μg/min) with an intravenous pump, and the target mean arterial pressure (MAP) was maintained at 65-75 mmHg (1 mmHg = 0.133 kPa). Hemodynamics and extravascular lung water index (EVLWI) were monitored by pulse indicator continuous cardiac output (PiCCO). The volume responsiveness of patient was evaluated by passive leg raising (PLR) test, and cardiac index (CI) change (ΔCI ≥ 10%) served as positive volume responsiveness. The differences in hemodynamics, EVLWI, oxygenation index (OI), lactate clearance rate (LCR), rate of positive volume responsiveness, urinary output, fluid volume balance, renal function, and prognostic indicators were compared between the two groups.Results Fifty-seven patients with ARDS complicated with septic shock were enrolled, with 26 patients in NE group, and 31 patients in TP group, thebaseline data in both groups was balanced with comparability. Compare with NE group, 48-hour and 72-hour heart rate (HR) in TP group was significantly slowed (bpm: 82.1±6.8 vs. 87.6±7.4, 81.3±6.1 vs. 85.6±8.3, bothP < 0.05), 72-hour central venous pressure (CVP) was significantly decreased (mmHg: 9.4±2.6 vs. 10.9±3.0,P < 0.05), but no significant difference was found in HR, MAP, CVP, CI, EVLWI, OI and LCR at other time points between the two groups. 48-hour and 72-hour positive volume responsiveness rate in TP group were significantly increased as compared with those of NE group (74.2% vs. 46.2%, 64.5% vs. 38.5%, both P < 0.05), urinary output on the 2nd day (mL/24 h: 2342.8±704.1 vs. 1944.6±684.3) and fluid volume balance (mL: -319.7±54.8 vs. -169.6±27.2) were significantly decreased (bothP < 0.05). There was no significant difference in positive volume responsiveness rate, urine output, fluid volume balance, and the level of serum creatinine at other time points between the two groups. There was no statistically significant difference in the following features between TP group and NE group: duration of mechanical ventilation (days: 8.41±2.97 vs. 9.67±3.56), length of intensive care unit (ICU) stay (days: 12.84±4.47 vs. 14.77±5.01), total length of hospital stay (days: 19.34±7.37 vs. 21.07±8.41), and 28-day mortality (29.0% vs. 30.8%, allP > 0.05).Conclusions Compared with norepinephrine, terlipressin for ARDS patients with septic shock is more conducive to restrict fluid load, improve the renal perfusion and increase urine output. However, in both groups therewas no significant difference in the efficiency of stabilizing hemodynamics, shortening the duration of mechanical ventilation, reducing ICU or hospital days and decreasing 28-day mortality.
4.Growth of human embryonic stem cells in three different feeder layers
Bin LI ; Qiuping PENG ; Weiying LU ; Wen XU ; Yingxia JIN ; Yuanhua HUANG
Chinese Journal of Tissue Engineering Research 2008;12(8):1586-1590
BACKGROUND: Key point for subculture of human embryonic stem cells (hESCs) is to inhibit spontaneous differentiation and make sure totipotency of cells. Although mouse embryonic fibroblasts (MEF) or human foreskin fibroblasts (HFF) used as the feeder layer can maintain undifferentiated state of embryonic stem cells, cell clone is still imperfect and parallel arranged. OBJECTIVE: To establish mixed feeder layer of mouse embryonic fibroblasts plus human foreskin fibroblasts and to observe the hESCs growth.DESIGN: Multi-sample observation and comparison.SETTING: Medical Center of Reproduction, the Affiliated Hospital of Hainan Medical College. MATERIALS: This study was performed at the Medical Center of Reproduction, the Affiliated Hospital of Hainan Medical College from April 2006 to July 2007. Foreskin was derived from the children who underwent circumcision and came from Urinary Surgery, the Affiliated Hospital of Haihan Medical College. The children's family members provided the informed consent, and the experiment received confirmed consent from the local ethic committee. hESCs line HN-1 was separated from human blastula. Eleven 12.5-14.5-day-old fetal mice of clean grade were selected in this study. The experimental animals were disposed according to ethical criteria. METHODS: Heads, four extremities, and viscera were removed from fetal mice under anesthesia. Subsequently, cell suspension was prepared using routine trypsinase digestion and inoculated. When cells were cultured in confluent monolayer, some primary cells were frozen, processed with mitocin-C for 2.0-3.0 hours, and inoculated based on the density of 1×108 L-1 in gelatin-coated dish, I.e., MEF feeder layer. The HFF separation and culture and the preparation of HFF feeder layer were the same as above-mentioned processing. In addition, the two fibroblasts were respectively counted and mixed together according to the ratios of 1∶0, 3∶1, 1∶1, 1∶3, and 0:1. And then, the mixture was inoculated based on the density of 1×108 L-1 in gelatin-coated dish, I.e., mixed feeder layer. The growth of subcultured hESCs in vitro was observed in three different feeder layers, and hESCs in the mixed feeder layer underwent alkaline phosphatase test, OCT-4 expression immunohistochemical measurement, and OCT-4 and telomerase mRNA expression RT-PCR detection. Finally, differentiation in vitro of hESCs was observed after removing the feeder layer.MAIN OUTCOME MEASURES: ① Growth of hESCs in the three different feeder layers; ② Growth of hESCs in the mixed feeder layer based on different mixed ratios; ③ undifferentiated state of hESCs in the mixed feeder layer; ④ differentiation in vitro.RESULTS: ① hESCs clone in the MEF and HFF feeder layers was thin and flat and imperfect, but hESCs clone in the mixed feeder layer was perfect and thick and solid. Apparently, the clone form in the mixed feeder layer was superior to MEF and HFF feeder layers. ② When MEF and HFF was mixed together according to the ratio of 1∶1, hESCs grew in apparent accumulation; clone border was clear; eminentia was apparent and perfect. However, there were no changes according to the ratio of 1∶3. The ratio of 1∶1 was superior to the ratios of 1∶0, 3∶1, and 0∶1. ③ Alkaline phosphatase staining and OCT-4 antigen expression were strongly positive. Specific straps of OCT-4 and telomerase mRNA expression were observed at 200-300 bp and 300-400 bp, respectively. ④ Embryoid bodies were formed. hESCs could differentiate into multi-morphological cells after attachment.CONCLUSION: ① The mixed feeder layer may well support in vitro subculture of hESCs to acquire excellent clone form compared to MEF or HFF feeder layer. ② The mixture of MEF and HFF has excellent effect according to the ratio of 1∶1.
5.Effect of EGDT on tissue perfusion in patients with septic shock
Yuanhua LU ; Ling LIU ; Xiaohua QIU ; Qin YU ; Yi YANG ; Haibo QIU
Chinese Journal of Emergency Medicine 2013;22(4):346-351
Objective To observe the effect of early goal directed therapy (EGDT) on tissue perfusion,microcirculation and tissue oxygenation in patients with septic shock.Methods A prospective observational study was carried out in 20 patients with early septic shock admitted to ICU within 24 hours after onset.Patients with one of following conditions,including stroke,brain injury,other types of shock,severe heart failure,acute myocardium infarction,ages below 18,pregnancy,terminal stage of disease,cardiac arrest,extensive bums,mouth bleeding,oromandiblular dyetonia (difficult to open the mouth),and the time elapsed over 24 hours after onset of septic shock,were excluded.The eligible patients were treated with the standard procedure of EGDT.The partial pressure of transcutaneous oxygen and carbon dioxide (PtcO2,PtcCO2) was monitored and hemodynamic data were recorded.Sidestream dark field imaging device was applied to detect the sublingual microcirculation.Hemodynamics,tissue oxygen,and sublingual microcirculation were compared before treatment and after EGDT.When the variables met the normal distribution,t test was applied.Otherwise,Wilcoxon test was used.Correlation between variables was analyzed with Pearson Correlation Analysis.Results Of 20 patients,19 met all 4 elements in criteria of EGDT after treatment and were eligible for study.PtcO2 and PtcCO2 were monitored in 19 patients.Sublingual microcirculation was obtained in four of them.(1) After the criteria of EGDT were entirely met,PtcO2 increased from (62.7 ± 24.0) mm Hg to (78.0 ± 30.9) mm Hg (P < 0.05) ; tissue oxygenation index (PtcO2/FiO2) was (110.7 ± 60.4) mm Hg before treatment and (141.6 ± 78.2) mm Hg after EGDT (P < 0.05).PtcCO2 and PaCO2 gap (difference between PtcCO2 and PaCO2) decreased significantly after EGDT (P < 0.05).(2) Both proportion of small vessels with perfusion (PVP) and microcirculatory flow index of small vessels (MFI) showed a trend of increase after EGDT,but there were no significant differences between pre-and post-EGDT (P was 0.051 and 0.074 respectively).(3) PtcO2,PtcO2/FiO2,and PtcCO2 were not linearly related to central venous saturation,lactate,oxygen delivery,and oxygen consumption (All P > 0.05).Conclusions Peripheral perfusion improved after EGDT in patients with septic shock but those hemodynamic variables might not exactly reflect the authenticity of global perfusion.
6.Influence of total progressively motile sperm count after treatment on outcomes of intrauterine insemination with husband′s sperm
Juan ZHU ; Yuanhua HUANG ; Weiying LU ; Yi ZHANG ; Wei HUANG ; Jilong MAO ; Yanlin MA ; Zaijia YANG
Chongqing Medicine 2017;46(20):2758-2760
Objective To investigate the influence of total progressively motile sperm count(TPMSC) after treatment on clinical outcomes of intrauterine insemination(IUI) with the husband′s sperm in ovulation-promoting cycles.Methods The clinical data in 4179 cases undergoing IUI with the husband′s sperm in ovulation-promoting cycles were retrospectively analyzed.The correlation between clinical pregnancy rate and TPMSC was analyzed.Results Among all the clinical data,TPMSC was to 100×106 in occasional live sperm.TPMSC<0.15×106 was in 15 cases,1 case had pregnancy (live sperm was occasionally seen on IUI day after sperm processing).Ten cases of TPMSC >60×106 had no pregnancy.A total of 4 154 cases of TPMSC (0.15-60.00)×106 were analyzed.The female age,duration of infertility,number of follicles and endometrial thickness(EDM) had no statistical differences among various groups.The clinical pregnancy rate was 13.5%(576/4 154),the group with the highest clinical pregnancy rate was (5.00-<10.00)×106.But there was no statistically significant difference in clinical pregnancy rate among groups(P=0.133).Conclusion Performing IUI in PMSC (0.15-60.00)×106 after processing can get preferable pregnancy rates.
7.VEGF165 transfected endothelial progenitor cells mediated by lentivirus alleviated ALI in rats
Zhaohui HE ; Huiwei HE ; Yuanhua LU ; Zhi CHEN ; Fanghua XU ; Rongsheng WANG ; Chunli YANG
Chinese Critical Care Medicine 2017;29(11):1015-1020
Objective To investigate the protective effects of vascular endothelial growth factor-165 (VEGF165) transfected the endothelial progenitor cells (EPCs) mediated by lentivirus on acute lung injury (ALI) in rats. Methods The mononuclear cells from the male Sprague-Dawley (SD) rats were isolated and cultured to get the EPCs for study. The lentivirus vector carrying the human VEGF165 gene was constructed. According to the random number table method, 90 male SD rats were divided into ALI model group, phosphate buffer solution (PBS) group, EPCs treatment group, none transfected EPCs treatment group and VEGF165 transfected EPCs treatment group, and the rats in each group were subdivided into 4, 12 and 48 hours subgroups, with 6 rats in each subgroup. The rat model of ALI was reproduced by intravenous injection of oleic acid (0.15 μL/g). Then each treatment group was given PBS, EPCs, none transfected EPCs and VEGF165 transfected EPCs respectively with the same volume of 0.2 mL. For the groups with cells, about 1×106cells were contained. Abdominal aortic blood and lung tissue were harvested at 4, 12 and 48 hours. Arterial blood gas analysis was performed. The lung wet/dry weight ratio (W/D) was calculated. The expressions of induced nitric oxide synthase (iNOS), endothelin-1 (ET-1) and VEGF165 were determined by enzyme-linked immunosorbent assay (ELISA). After dyed with hematoxylin-eosin (HE), the lung tissue pathology was observed and the lung injury score was performed. Results Compared with the ALI model group, the arterial partial pressure of oxygen (PaO2) in EPCs, none transfected EPCs and VEGF165 transfected EPCs treatment groups was significantly increased from 4 hours, and lung W/D, expressions of iNOS and ET-1 were significantly decreased, and VEGF165 expression was significantly increased. Compared with the EPCs treatment group, the increase in PaO2, the decrease in lung W/D and expressions of iNOS and ET-1, and the increase in VEGF165 expression in VEGF165 transfected EPCs treatment group were more significant [4 hours: PaO2(mmHg, 1 mmHg = 0.133 kPa) was 82.84±10.69 vs. 72.34±9.36, lung W/D ratio was 4.83±0.23 vs. 5.55±0.37, iNOS (ng/mg) was 8.77±1.10 vs. 14.84±1.34, ET-1 (ng/mg) was 103.41±5.66 vs. 153.08±5.12, VEGF165 (ng/mg) was 130.56±12.16 vs. 83.03±5.95; 12 hours: PaO2(mmHg) was 91.67±6.81 vs. 78.5±8.81, lung W/D ratio was 4.44±0.35 vs. 5.32±0.25, iNOS (ng/mg) was 7.23±0.24 vs. 14.04±1.18, ET-1 (ng/mg) was 91.98±3.52 vs. 125.99±7.55, VEGF165 (ng/mg) was 164.49±5.71 vs. 96.61±6.12]; individual parameters reached valley value or peak value at 48 hours [lung W/D ratio was 4.26±0.30 vs. 4.89±0.15, iNOS (ng/mg) was 5.79±0.85 vs. 12.72±1.10, ET-1 (ng/mg) was 74.53±7.10 vs. 108.33±5.84, VEGF165 (ng/mg) was 237.43±10.79 vs. 134.24±11.99, all P < 0.05]. Over time, lung tissue injury in each group was gradually increased, and the lung injury score was gradually increased. The lung injury score at 48 hours in the EPCs, none transfected EPCs and VEGF165 transfected EPCs treatment groups were lower than that in the ALI model group. Compared with the EPCs treatment group, the VEGF165 transfected EPCs treatment group had a lower score at 48 hours (8.50±1.05 vs. 10.50±1.05, P < 0.05). Conclusion The transplantation of EPCs which were transfected with VEGF165 mediated by lentivirus could obviously improve the oxygen pressure, reduce the lung water seepage, decrease the iNOS and ET-1 expressions in lung tissue, and had obvious protective effects on ALI.
8.The effect of c-Myc on regulating the immune-related ligands in Y subtype small cell lung cancer through histone deacetylase 1
Peiyan ZHAO ; Xiaodan SUN ; Hui LI ; Lin TIAN ; Yuanhua LU ; Ying CHENG
Chinese Journal of Oncology 2024;46(11):1009-1018
Objective:To explore the effect and mechanism of c-Myc on regulating the expression of immune-related ligands in Y subtype small-cell lung cancer (SCLC) characterized by high expression of immune-related molecules.Methods:The Y subtype SCLC cell line H196 was randomly divided into the control group, c-Myc inhibitor 10058-F4 group, histone deacetylase 1 (HDAC1) inhibitor pyroxamide group, and 10058-F4 plus pyroxamide group. The co-culture system with NK-92MI cells was used to determine the effect of H196 cells on the function of natural killer (NK) cells. Western Blotting and co-immunoprecipitation assays were used to detect the effect of c-Myc on class Ⅰ HDAC, and flow cytometry was used to detect the regulatory effect of c-Mycon CD47, programmed cell death ligand 1 (PD-L1), and CD155, which are highly expressed immune checkpoints in Y subtype SCLC, and major histocompatibility complex classⅠ-related chains A and (MICA/B), which is a poorly expressed immune-activating ligand in SCLC, and the role of HDAC. Chromatin immunoprecipitation (ChIP) assay and real-time quantitative polymerase chain reaction (RT-qPCR) were used to determine the regulatory mechanism of c-Myc-HDAC1 on MICA/B expression.Results:Inhibition of c-Myc decreased the mortality of H196 cells in the co-culture system and down-regulated the expression of MICA/B. Compared with the NK+H196 group [(42.54±2.47)%], the proportion of cells killed by NK-92MI cells in the NK+H196+10058-F4 group was lower [(28.48±3.38)%, P<0.001]. The mean fluorescence intensity (MFI) of MICA/B on the cells in the 10058-F4 group (36.40±0.82) was lower than that in the control group (91.23±8.60, P<0.001). And c-Myc could bind to HDAC1, whose protein level was up-regulated by 10058-F4 while the mRNA level was not. Compared with the cells in the control group (90.10±4.91), the MFI of MICA/B on the cells in the pyroxamide group was significantly increased (145.70±5.86, P<0.001), and the MFI of MICA/B on the cells in the 10058-F4+pyroxamide group (54.60±2.88) was significantly increased compared with the cells in the 10058-F4 group (35.97±1.60, P<0.001). The percentage of MICA promoter gene fragments in the c-Myc antibody precipitation group (0.125±0.037) was significantly higher than that in the IgG group (0.000 8±0.000 3, P=0.004). MICB had a similar trend, suggesting that the c-Myc-HDAC1 complex could bind to the promoter region of MICA/B. The MFI of CD47 on the cells in the 10058-F4 group (60.07±0.21) was significantly lower than cells in the control group (70.27±1.37, P<0.001), but the MFIs of PD-L1 (13.50±0.61) and CD155 (829.70±41.19) were significantly higher than those on the cells in the control group (9.23±0.94, P<0.01; 496.00±4.36, P<0.001, respectively). Conclusions:c-Myc may promote the expression of MICA/B and CD47 in Y subtype SCLC cells by binding and inhibiting HDAC1, while it may also be involved in inhibiting the expression of PD-L1 and CD155 in SCLC cells.
9.The effect of c-Myc on regulating the immune-related ligands in Y subtype small cell lung cancer through histone deacetylase 1
Peiyan ZHAO ; Xiaodan SUN ; Hui LI ; Lin TIAN ; Yuanhua LU ; Ying CHENG
Chinese Journal of Oncology 2024;46(11):1009-1018
Objective:To explore the effect and mechanism of c-Myc on regulating the expression of immune-related ligands in Y subtype small-cell lung cancer (SCLC) characterized by high expression of immune-related molecules.Methods:The Y subtype SCLC cell line H196 was randomly divided into the control group, c-Myc inhibitor 10058-F4 group, histone deacetylase 1 (HDAC1) inhibitor pyroxamide group, and 10058-F4 plus pyroxamide group. The co-culture system with NK-92MI cells was used to determine the effect of H196 cells on the function of natural killer (NK) cells. Western Blotting and co-immunoprecipitation assays were used to detect the effect of c-Myc on class Ⅰ HDAC, and flow cytometry was used to detect the regulatory effect of c-Mycon CD47, programmed cell death ligand 1 (PD-L1), and CD155, which are highly expressed immune checkpoints in Y subtype SCLC, and major histocompatibility complex classⅠ-related chains A and (MICA/B), which is a poorly expressed immune-activating ligand in SCLC, and the role of HDAC. Chromatin immunoprecipitation (ChIP) assay and real-time quantitative polymerase chain reaction (RT-qPCR) were used to determine the regulatory mechanism of c-Myc-HDAC1 on MICA/B expression.Results:Inhibition of c-Myc decreased the mortality of H196 cells in the co-culture system and down-regulated the expression of MICA/B. Compared with the NK+H196 group [(42.54±2.47)%], the proportion of cells killed by NK-92MI cells in the NK+H196+10058-F4 group was lower [(28.48±3.38)%, P<0.001]. The mean fluorescence intensity (MFI) of MICA/B on the cells in the 10058-F4 group (36.40±0.82) was lower than that in the control group (91.23±8.60, P<0.001). And c-Myc could bind to HDAC1, whose protein level was up-regulated by 10058-F4 while the mRNA level was not. Compared with the cells in the control group (90.10±4.91), the MFI of MICA/B on the cells in the pyroxamide group was significantly increased (145.70±5.86, P<0.001), and the MFI of MICA/B on the cells in the 10058-F4+pyroxamide group (54.60±2.88) was significantly increased compared with the cells in the 10058-F4 group (35.97±1.60, P<0.001). The percentage of MICA promoter gene fragments in the c-Myc antibody precipitation group (0.125±0.037) was significantly higher than that in the IgG group (0.000 8±0.000 3, P=0.004). MICB had a similar trend, suggesting that the c-Myc-HDAC1 complex could bind to the promoter region of MICA/B. The MFI of CD47 on the cells in the 10058-F4 group (60.07±0.21) was significantly lower than cells in the control group (70.27±1.37, P<0.001), but the MFIs of PD-L1 (13.50±0.61) and CD155 (829.70±41.19) were significantly higher than those on the cells in the control group (9.23±0.94, P<0.01; 496.00±4.36, P<0.001, respectively). Conclusions:c-Myc may promote the expression of MICA/B and CD47 in Y subtype SCLC cells by binding and inhibiting HDAC1, while it may also be involved in inhibiting the expression of PD-L1 and CD155 in SCLC cells.
10.Association between blood glucose-to-lymphocyte ratio and prognosis of patients with sepsis-associated acute kidney injury.
Lihua ZHANG ; Fen LIU ; Qi LI ; Yang LI ; Qiang SHAO ; Wenqiang TAO ; Ping HU ; Kejian QIAN ; Yuanhua LU
Chinese Critical Care Medicine 2023;35(12):1262-1267
OBJECTIVE:
To investigate the association between the glucose-to-lymphocyte ratio (GLR) and prognosis of patients with sepsis-associated acute kidney injury (SA-AKI).
METHODS:
Based on the Medical Information Mart for Intensive Care-IV (MIMIC-IV), SA-AKI patients aged ≥ 18 years were selected. According to the tertiles of GLR, the patients were divided into GLR1 group (GLR ≤ 4.97×10-9 mmol), GLR2 group (4.97×10-9 mmol < GLR < 9.75×10-9 mmol) and GLR3 group (GLR ≥ 9.75×10-9 mmol). Patients with SA-AKI were divided into survival group and death group according to whether they survived 28 days after admission. The patient's gender, age, vital signs, laboratory test results, comorbidities, sequential organ failure assessment (SOFA), acute physiology score III (APS III) score and treatment measures were extracted from the database. Kaplan-Meier survival analysis was used to make the survival curves of patients with SA-AKI at 28 days, 90 days, 180 days and 1 year. Multivariate Logistic regression analysis model was used to explore the independent risk factors of 28-day mortality in patients with SA-AKI. Receiver operator characteristic curve (ROC curve) was used to analyze the predictive efficacy of GLR for the prognosis of patients with SA-AKI.
RESULTS:
A total of 1 524 patients with SA-AKI were included, with a median age of 68.28 (58.96, 77.24) years old, including 612 females (40.16%) and 912 males (59.84%). There were 507 patients in the GLR1 group, 509 patients in the GLR2 group and 508 patients in the GLR3 group. There were 1 181 patients in the 28-day survival group and 343 patients in the death group. Grouping according to GLR tertiles showed that with the increase of GLR, the 28-day, 90-day, 180-day and 1-year mortality of SA-AKI patients gradually increased (28-day mortality were 11.64%, 22.00%, 33.86%, respectively; 90-day mortality were 15.98%, 26.72%, 40.55%, respectively; 180-day mortality were 17.16%, 28.29% and 41.73%, and the 1-year mortality were 17.95%, 29.27% and 42.72%, respectively, all P < 0.01). According to 28-day survival status, the GLR of the death group was significantly higher than that of the survival group [×10-9 mmol: 9.81 (5.75, 20.01) vs. 6.44 (3.64, 10.78), P < 0.01]. Multivariate Logistic regression analysis showed that GLR was an independent risk factor for 28-day mortality in patients with SA-AKI [when GLR was used as a continuous variable: odds ratio (OR) = 1.065, 95% confidence interval (95%CI) was 1.045-1.085, P < 0.001; when GLR was used as a categorical variable, compared with GLR1 group: GLR2 group OR = 1.782, 95%CI was 1.200-2.647, P = 0.004; GLR3 group OR = 2.727, 95%CI was 1.857-4.005, P < 0.001]. ROC curve analysis showed that the area under the ROC curve (AUC) of GLR for predicting 28-day mortality in patients with SA-AKI was 0.674, when the optimal cut-off value was 8.769×10-9 mmol, the sensitivity was 57.1% and the specificity was 67.1%. The predictive performance was improved when GLR was combined with APS III score and SOFA score, and the AUC was 0.806, the sensitivity was 74.6% and the specificity was 71.4%.
CONCLUSIONS
GLR is an independent risk factor of 28-day mortality in patients with SA-AKI, and high GLR is associated with poor prognosis in patients with SA-AKI.
Male
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Humans
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Blood Glucose
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Glucose
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ROC Curve
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Prognosis
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Sepsis/diagnosis*
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Acute Kidney Injury
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Retrospective Studies
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Intensive Care Units