OBJECTIVES: To explore the effects of hypoxic and hypobaric conditions on blood gas and erythrocyte-related indicators in rats. METHODS: SD male rats were exposed to low-pressure hypoxic conditions simulating an altitude of 6500 m in a small or a large experimental cabin. Abdominal aortic blood samples were collected and blood gas indicators, red blood cells (RBCs) count, and hemoglobin (Hb) content were measured. The effects of exposure to different hypoxia times, different hypoxia modes, normal oxygen recovery after hypoxia, and re-hypoxia after hypoxia preconditioning on blood gas indicators, RBCs count and Hb content were investigated. RESULTS: The effect of blood gas indicators was correlated with the length of exposure time of hypoxia and the reoxygenation after leaving the cabin. Hypoxia caused acid-base imbalance and its severity was associated with the duration of hypoxia; hypoxia also led to an increase in RBCs count and Hb content, and the increase was also related to the time exposed to hypoxia. The effects of reoxygenation on acid-base imbalance in rats caged in a small animal cabin were more severe that those in a large experimental cabin. Acetazolamide alleviated the effects of reoxygenation after leaving the cabin. Different hypoxia modes and administration of acetazolamide had little effect on RBCs count and Hb content. Normal oxygen recovery can alleviate the reoxygenation and acid-base imbalance of hypoxic rats after leaving the cabin and improve the increase in red blood cell and hemoglobin content caused by hypoxia. The improvement of hypoxia preconditioning on post hypoxia reoxygenation is not significant, but it can alleviate the acid-base imbalance caused by hypoxia in rats and to some extent improve the increase in red blood cell and hemoglobin content caused by hypoxia. CONCLUSIONS Due to excessive ventilation and elevated RBCs count and Hb content after hypoxia reoxygenation, oxygen partial pressure and other oxygenation indicators in hypoxic rats are prone to become abnormal, while blood gas acid-base balance indicators are relatively stable, which are more suitable for evaluating the degree of hypoxia injury and related pharmacological effects in rats.
Rats ; Animals ; Male ; Acetazolamide ; Hypoxia ; Oxygen ; Erythrocytes ; Hemoglobins ; Acid-Base Imbalance

Objective To study the superiority of severe multiple trauma treatment model based on damage control strategy. Methods In the intergrated injury first-aid mode, the intensive care unit-guided damage control strategy was used to treat severe multiple trauma. Results A total of 789 severe multiple damage patients were treated with damage control strategies in our hospital from December 2018 to December 2018. Sixty-nine patients died and the survival rate was 91.25％. Conclusions The intensive care unit-guided trauma control strategy has a satisfactory clinical effect in the treatment of patients with severe multiple trauma.

Objective To investigate the related factors and prognosis of pulmonary hypertension (PAH) in hemodialysis (HD) patients for early diagnosis and intervention of PAH.Methods A retrospective cohort study was conducted in 183 long-term hemodialysis patients with complete follow-up data from January 1,2010 to December 30,2015 from the blood purification center of the Third Affiliated Hospital of Sun Yat-sen University.The follow-up deadline was December 30,2017,and the endpoints were death and cardiovascular events.The clinical data,laboratory examinations,cardiac color Doppler ultrasound parameters and prognosis of patients with and without PAH were compared.Multivariate logistic regression was used to analyze the risk factors for PAH in HD patients.The survival rates were calculated by Kaplan-Meier method,and the survival curves were compared by Log-rank test between the two groups.A multivariate Cox proportional hazard regression model was used to examine the association between PAH and all-cause mortality in HD patients.Results Of the 183 hemodialysis patients,79(43.2％) were female,104(56.8％) were male,and the age was (56.1±16.9) years,of which 72(39.3％) were complicated with PAH.Compared with the non-PAH group,patients in the PAH group was older and had a longer duration of dialysis (both P ＜ 0.05).The left atrial diameter (P=0.002) and the proportion of valvular calcification (P=0.004) were significantly higher in the PAH group than that in the non-PAH group.Logistic regression analysis showed increased age (OR=1.027,95％ CI 1.001-1.053,P=0.041) and increased duration of dialysis (OR=1.129,95％ CI 1.004-1.269,P=0.042) were risk factors for PAH in HD patients.After a median follow-up of 27.8 months,Kaplan-Meier survival analysis showed that all-cause mortality was higher in the PAH group than that in the non-PAH group ~x2=5.636,P=0.018).The main cause of death in two groups was cardiovascular event.Afteradjusting for age,diabetes mellitus,duration of dialysis,valvular calcification,and hypertension,Cox regression showed that PAH increased the risk of all-cause mortality in HD patients (HR=1.894,95％ CI 1.083-3.313,P=0.025).Conclusions HD patients complicated with PAH are more common and the prognosis is poor.Increased age and increased duration of dialysis may be risk factors for PAH in HD patients.Regular color Doppler echocardiography is helpful for early detection and diagnosis of PAH.

Objective: To analyze the relationship between serum uric acid (SUA) level and clinical indicators in maintenance hemodialysis (MHD) patients, and explore its influence on all-cause mortality and cardiovascular mortality. Methods: This study was a retrospective cohort study. Patients who received MHD from the blood purification center of the Third Affiliated Hospital of Sun Yat-sen University from January 1, 2011 to December 30, 2015 were enrolled in the queue. They were divided into 3 groups according to the first and third quantile of the SUA level quartiles, and the baseline data of clinical and laboratory examinations were compared. The correlation between SUA level and clinical indicators was analyzed by Pearson correlation coefficient. Kaplan-Meier method and Cox proportional hazard regression model were used to examine the association between SUA and all-cause mortality and cardiovascular mortality in MHD patients. Results: A total of 201 patients were enrolled in the study. The age of the patients was (56.9±16.7) years and the baseline SUA level was (531.1±137.9) μmol/L. Patients were divided into 3 groups with the first quantile (442 μmol/L) and the third quantile (620 μmol/L) of the SUA quartiles as the boundary points: group 1 (SUA<442 μmol/L, n=52), group 2 (SUA 442-620 μmol/L, n=101) and group 3 (SUA>620 μmol/L, n=48). The results showed that the patients in group 1 were older and had more proportion of patients with diabetes mellitus and cardiovascular diseases than those in group 3 (all P<0.05). Compared to group 3, the serum albumin, serum phosphorus and serum creatinine were lower in group 1, while the hypersensitive C-reactive protein was higher (all P<0.05). Pearson correlation analysis showed that SUA level was positively correlated with albumin (r=0.135, P=0.047), blood phosphorus (r=0.269, P<0.001) and serum creatinine (r=0.333, P<0.001), and negatively correlated with hypersensitive C-reactive protein (r=-0.216, P=0.002). After a median follow-up of 49.8 months, 66(32.8%) all-cause deaths and 32(15.9%) cardiovascular deaths were recorded. Kaplan-Meier method showed that with the decrease of SUA, all-cause mortality (Log-rank χ²=18.27, P<0.001) and cardiovascular mortality (Log-rank χ²=15.04, P=0.001) increased. After adjusting for age, gender, comorbidity and other factors using the Cox proportional hazards model, the all-cause mortality and cardiovascular mortality decreased by 20.1% (HR=0.799, 95% CI 0.651-0.980, P=0.031) and 29.6% (HR=0.704, 95% CI 0.524-0.946, P=0.020) for each 100 μmol/L increase in baseline SUA. Compared to group 1, all-cause mortality (HR=0.332, 95%CI 0.142-0.774, P=0.011) and cardiovascular mortality (HR=0.140, 95%CI 0.030-0.657, P=0.013) were lower in the group 3. Conclusion Low SUA level increases the risk of all-cause mortality and cardiovascular mortality in MHD patients.

Objective To cxplore the optimal levels of serum calcium,phosphorus and intact parathyroid hormone (iPTH) in peritoneal dialysis (PD) patients.Methods This study is a single center,retrospective cohort study.The associations between serum calcium,phosphorus and iPTH and all-cause mortality in 217 PD patients were analyzed.All patients started PD between January 1,2008 and April 30,2016 were enrolled and followed up to December 31,2016.At baseline and every 3 months,biochemical and therapeutic information was collected.Cox proportional hazard regression models and cubic splines analysis were employed to assess the lowest mortality risk ranges in serum markers of bone metabolism.Results There was no significantly difference between patients within target ranges based on KDOQI or KDIGO guideline and those outside the target ranges by Kaplan-Meier survival analysis.The lowest mortality risk ranges were 2.17-2.40 mmol/L for serum calcium,1.20-1.67 mmol/L for serum phosphorus and 180-350 ng/L for serum iPTH by using Cox models and cubic splines analysis.Moreover,cumulate survival had significant difference between patients within the descriptive ranges and those out of the descriptive ranges at time-averaged values but not at baseline values.Conclusions The optimal time-averaged ranges of PD patients are 2.17-2.40mmol/L for serum calcium,1.20-1.67 mmol/L for serum phosphorus and 180-350 ng/L for serum iPTH.These ranges need further validation by large population studies to further conform.

OBJECTIVE To study the cardiotoxicity of ophiopogonin D′(OPD′) for rat H9c2 cardio? myocytes. METHODS H9c2 cells were exposed to OPD′ 0.1, 1, 5, 10, 20, 25 and 50 μmol·L-1 for 24 h. Cell viability was examined by MTS assay, and the morphological changes in H9c2 cells were quanti? fied. The cell nucleus injury was examined by high content immune fluorescence screening and the morphological changes were observed under a fluorescence microscope. After treatment with OPD′ 0.1, 1, 5 and 10 μmol·L- 1 for 24 h, the effect on reactive oxygen species (ROS), mitochondrial mem? brane potential(MMP) and apoptosis was detected by flow cytometry. RESULTS The viability was sig? nificantly reduced following exposure to OPD′ 0.1, 1, 5, 10, 20, 25 and 50 μmol·L- 1 (P<0.05,P<0.01). The IC50 value was 9.9 μmol ·L- 1 and cell shrinkage and apoptosis occurred. The levels of ROS and apoptosis rate of H9c2 cells were significantly increased after exposure to OPD′ 0.1, 1, 5 and 10 μmol·L-1 for 24 h (P<0.05,P<0.01) and MMP markedly declined (P<0.05,P<0.01). CONCLUSION OPD′ has significent cytotoxicity on H9c2 cells. It may be related to inducing apopotsis pathways.

Objective To investigate the potential mechanism that melatonin at higher concentrations inhibits the proliferation of human MG-63 osteosarcoma cells,so as to provide a certain experimental basis for the better application of melatonin in the treatment of diseases in Department of Orthopedics. Methods MG-63 cells cultured in vitro were treated with melatonin at a concentration of 4 mmol/L . Western blotting and real-time PCR method were used to analyze the effect of melatonin on the expression of cyclins and CDKs at protein and mRNA levels ,respectively. Results Western blotting and real-time PCR analyses showed that melatonin's inhibitory effect was possibly through the downregulation of cyclin D1 and CDK4 that related to the G1 phase,and downregulation of cyclin B1 and CDK1 that related to the G2/M phase. However,there was no obvious dif-ference of cyclin E,CDK2,and cyclin A,which were related to G1/S transition and S phase. Conclusion Melatonin may significantly inhibit hu-man osteosarcoma cell proliferation by inducing cell cycle arrest in a time-dependent manner,which is related to the downregulation of cyclin D1, CDK4,cyclin B1 and CDK1.

OBJECTIVE To investigate the hepatotoxicity mechanisms of ethanol extract of Radix Polygoni Multiflori (RPM) and Radix Polygoni Multiflori Praeparata (RPMP) by high-content screen assay.METHODS HepG2 cells were treated with RPM (10,25,50,100,200 and 300 mg·L-1) and RPMP (10,50,100,300,600 and 1200 mg· L-1) for 3-24 h,respectively.The cell viability was detected by a CellTiter-GloTM luminescent cell viability assay kit.Cell count,reactive oxygen species (ROS),mitochondrial membrane potential (MMP),glutathione (GSH),superoxide dismutase 2 (SOD2),activating transcription factor 4 (ATF4),apoptosis,and cell cycles were investigated by high-content screen assay.Besides,SOD2 and ATF4 levels were confirmed by Western blotting.RESULTS RPM 300 mg· L-1 showed nearly 48 ％ reduction in cell viability compared with cell control (P＜0.01),while RPMP had no significant effect at the same concentration.Both RPM and RPMP decreased the level of MMP (P＜0.05) but incresed levels of GSH,ROS,SOD2 and ATF4 significantly (P＜0.05).Besides,RPM 200 mg· L-1 significantly increased the expression of SOD2 (P＜0.05) at 3 h by high-content screen assay,and the enhanced expression of ATF4 was shown at 6 h (P＜0.05).RPMP 300 mg· L-1 markedly increased the expression of ATF4 at 6 h (P＜0.05),while the expression of SOD2 significantly increased at 24 h (P＜0.05).CONCLUSION Both RPM and RPMP have some cytotoxicity,and the cytotoxicity of RPM is stronger than that of RPMP.The hepatotoxicity mechanisms of RPM and RPMP may be related to cell apoptosis caused by long-term oxidative stress and endoplasmic reticulum stress.

Aim To investigate the induction effect of ginsenoside Rc, Re, Rf and Rg1 on CYP1A1, and further validate the role of aryl hydrocarbon receptor in CYP1A1 expression. Methods Dual luciferase re-porter gene system was performed. Four kinds of gin-senoside were screened for aryl hydrocarbon receptor activation by reporter assays, and TCDD as the positive control. Further with different concentrations of ginsen-oside Rc, Re, Rf and Rg1 treated on LS174T cells, RNA and total protein were extracted to detect the reg-ulating effect of ginsenosides on CYP1 A1 mRNA and protein expression with Real-time PCR and Western blot technology respectively. Results Reporter gene screening showed that the ginsenoside Rc, Re, Rf and Rg1 could activate AhR and had potential effects on the induction of CYP1A1 enzyme. Meanwhile, dose-de-pendent induction of the gene expression were observed in response to ginsenoside Rc, Re, Rf and Rg1 and the levels of CYP1 A1 protein expression were increased by ginsenoside Rc, Re, Rf and Rg1 in varying de-grees. Conclusion Ginsenoside Rc, Re, Rf and Rg1 can up-regulate the gene and protein expression of CYP1 A1 possibly via the AhR-mediated CYP1 A1 path-way.

Aim With metabolomics method, to study Shen-Mai decoction’ s function on protecting the myo-cardial injured rats caused by doxorubicin for probing into the functioning mechanism of Shen-Mai decoction’ s medical effect. Methods By means of UPLC-TOF-MS, the metabolites of urine of the rats treated by Shen-Mai decoction were analyzed. Then, the differ-ences between each group of the metabolites were sought with PLS-DA ( the partial least square discrimi-nant analysis ) and OPLS-DA ( the orthogonal partial least squares discriminant analysis ) . VIP ( variable importance in projection ) and t test were used to screen out potential biomarkers. Results Fourteen endogenous metabolites such as succinyladenosine, a-denosine 2′, 3′-cyclic phosphate, S-( 3-methylbu-tanoyl )-dihydrolipoamide-E, cis-4-hydroxycyclohexy-lacetic acid, phenylbutyrylglutamine, 3-butyn-1-al, 3-hydroxytetradecanedioic acid, dihydrolipoamide and pyruvic acid, etc. were characterized. Conclusions The results indicate that Shen-Mai decoction can pro-tect the body from myocardial injury by regulating pu-rine metabolism, some acid metabolism, fat metabo-lism and energy metabolism, etc. The study expounds the functioning mechanism for Shen-Mai decoction ’ s medical effect in the body and provides theoretical grounds for the rationality of the two medical herbs ’ compatibility and their combination in clinical treat-ment of diseases.