OBJECTIVE：To identify Panax notoginseng and its processed products . METHODS ：The fingerprint was established by HPLC. Using ginsenoside Rb 1 as reference ，HPLC fingerprints of 15 batches of P. notoginseng and its processed products were drawn and the similarity evaluation was conducted by using the Similarity Evaluation System for TCM Chromatographic Fingerprints（2012 edition）. The common peaks were confirmed by comparing with substance control. SPSS 21.0 and SIMCA 14.1 software were used to perform cluster analysis ，principal component analysis and orthogonal partial least squares-discriminant analysis；taking the variable importance projection （VIP）value greater than 1 as the standard ，the differential marker components causing the quality difference between P. notoginseng and its processed products were screened. IR fingerprints of P. notoginseng and its processed products were established by OMNIC 8.2.0 software，and the spectral similarity was evaluated ；double index sequence analysis was used to analyze absorption peaks of IR fingerprints of 15 batches of P. notoginseng and its processed products. RESULTS ：There were 16 common peaks in the fingerprints of 15 batches of P. notoginseng ， and the similarities were 0.911-1.000；there were 25 common peaks in the fingerprints of processed products ，and the similaritieswere 0.862-1.000. They had 12 identical common peaks ，and wang668@sina.com three of them were ident ified as sanchinoside R 1，ginsenoside Rg1 and ginsenoside Rb 1. Results of cluster analysi s showed that when the distance was 10，15 batches of P. notoginseng could be clustered into two categories ，SW1-SW5 into one category ，SH1-SH5 and SQ 1-SQ5 into one category ，ZW1-ZW5，ZH1-ZH5 and ZQ1-ZQ5 of 15 batches of processed products could be clustered into one category. When the distance was 5，15 batches of P. notoginseng could be clustered into three categories ，SW1-SW5 into one category ，SH2-SH5 and SQ 2 into one category ，SQ1， SQ3-SQ5 and SH 1 into one category. Fifteen batches of processed products could be clustered into two categories ，ZW1-ZW5 into one category ，ZH1-ZH5 and ZQ 1-ZQ5 into one category. The results of principal component analysis showed that the cumulative variance contribution rate of the first two principal components was 80.104％ . The results of orthogonal partial least squares-discriminant analysis showed that the VIP values of the five peaks were greater than 1，which were peak H ，peak G ，peak J，peak F （ginsenoside Rg 1）and peak I. The similarity of IR fingerprints of 15 batches of P. notoginseng and its processed products were 0.889 7-1.000 0 and 0.972 8-1.000 0；the common peak rates were 80％-100％，and the variation peak rates were 0-17.65％ and 0-18.75％，respectively. By comparing the wave numbers of absorption peaks ，it was found that there were differences between P. notoginseng at 3 440 and 1 450 cm－1 and processed products at 1 530 and 575 cm－1. CONCLUSIONS ：Established HPLC fingerprint and IR fingerprint have good similarity ，and could effectively distinguish P. notoginseng and its processed products. P. notoginseng and its processed products from different habitats have high common peak rate and low variation rate ，and their chemical components are different ；peak H ，peak G ，peak J ，ginsenoside Rg 1 and peak I are differential marker components causing the quality difference between P. notoginseng and processed products.

Objective:To systematically evaluate correlation between the risk of malignancy and dapagliflozin in type 2 diabetes mellitus.Methods:The databases such as PubMed, the Cochrane Library, American Clinical Trial Registry, Embase, JAMA, Wiley-Blackwell, Springer Link, Elsevier, Ovid, Taylor & Francis Online, CNKI, Wanfang, and VIP (up to March 2021) were searched. The randomized controlled trials (RCTs) on dapagliflozin with outcome indicators including malignancy occurrence were collected. Data extraction and quality analysis were performed for the enrolled literature, and meta-analysis was conducted using RevMan 5.3 software.Results:A total of 22 studies were enrolled in the analysis, all of which were multicenter RCTs, and the quality evaluation results were all grade A. Thirty-one thousand four hundred and fifty-one patients were involved in the 22 studies, of which 16 267 were in the experimental group (dapagliflozin 5 or 10 mg daily) and 15 184 in the control group (placebo or other hypoglycemic drugs). The course of treatment in the 22 studies ranged from 24 weeks to 5.2 years and it was 24 weeks in 15 studies (68.2%). A total of 1 302 patients developed malignancy during the trials, including 661 in the experimental group and 641 in the control group. The results of the meta-analysis showed that, regardless in the overall study of different dapagliflozin doses or in studies of dapagliflozin 5 or 10 mg/d, the differences in the risk of malignancy between the experimental group and the control group were not statistically significant [overall study: 4.2% (661/15 911) vs. 4.1% (648/15 884), RR=1.02, 95 %CI: 0.92-1.13, P=0.72; dapagliflozin 5 mg/d: 0.8% (10/1 181) vs. 0.6% (7/1 172), RR=1.35, 95 %CI: 0.57-3.17, P=0.49; dapagliflozin 10 mg/d: 4.4% (651/14 730) vs. 4.4% (641/14 712), RR=1.01, 95 %CI: 0.91-1.13, P=0.78]; the differences in the risk of breast cancer were not statistically significant [overall study: 0.2% (25/12 216) vs. 0.2% (25/12 215), RR=1.00, 95 %CI: 0.59-1.69, P=1.00; dapagliflozin 5 mg/d: 0.6% (2/348) vs. 0 (0/347), RR=3.00, 95 %CI: 0.31-28.65, P=0.34; dapagliflozin 10 mg/d: 0.2% (23/11 868) vs. 0.2% (25/11 868), RR=0.93, 95 %CI: 0.54-1.59, P=0.78]; the differences in the risk of bladder cancer were not significantly significant [overall study: 0.1% (16/12 021) vs. 0.2% (28/12 019), RR=0.59, 95 %CI: 0.33-1.07), P=0.08; dapagliflozin 5 mg/d: 0.7% (1/137) vs. 0 (0/137), RR=3.00, 95 %CI: 0.12-73.00, P=0.50; dapagliflozin 10 mg/d: 0.1% (15/11 884) vs. 0.2% (28/11 882), RR=0.55, 95 %CI: 0.30-1.02, P=0.06]. Conclusion:Dapagliflozin may not increase the risk of malignancy in patients with type 2 diabetes mellitus, but its long-term safety needs further study.

Objective:To systematically evaluate correlation between the risk of malignancy and dapagliflozin in type 2 diabetes mellitus.Methods:The databases such as PubMed, the Cochrane Library, American Clinical Trial Registry, Embase, JAMA, Wiley-Blackwell, Springer Link, Elsevier, Ovid, Taylor & Francis Online, CNKI, Wanfang, and VIP (up to March 2021) were searched. The randomized controlled trials (RCTs) on dapagliflozin with outcome indicators including malignancy occurrence were collected. Data extraction and quality analysis were performed for the enrolled literature, and meta-analysis was conducted using RevMan 5.3 software.Results:A total of 22 studies were enrolled in the analysis, all of which were multicenter RCTs, and the quality evaluation results were all grade A. Thirty-one thousand four hundred and fifty-one patients were involved in the 22 studies, of which 16 267 were in the experimental group (dapagliflozin 5 or 10 mg daily) and 15 184 in the control group (placebo or other hypoglycemic drugs). The course of treatment in the 22 studies ranged from 24 weeks to 5.2 years and it was 24 weeks in 15 studies (68.2%). A total of 1 302 patients developed malignancy during the trials, including 661 in the experimental group and 641 in the control group. The results of the meta-analysis showed that, regardless in the overall study of different dapagliflozin doses or in studies of dapagliflozin 5 or 10 mg/d, the differences in the risk of malignancy between the experimental group and the control group were not statistically significant [overall study: 4.2% (661/15 911) vs. 4.1% (648/15 884), RR=1.02, 95 %CI: 0.92-1.13, P=0.72; dapagliflozin 5 mg/d: 0.8% (10/1 181) vs. 0.6% (7/1 172), RR=1.35, 95 %CI: 0.57-3.17, P=0.49; dapagliflozin 10 mg/d: 4.4% (651/14 730) vs. 4.4% (641/14 712), RR=1.01, 95 %CI: 0.91-1.13, P=0.78]; the differences in the risk of breast cancer were not statistically significant [overall study: 0.2% (25/12 216) vs. 0.2% (25/12 215), RR=1.00, 95 %CI: 0.59-1.69, P=1.00; dapagliflozin 5 mg/d: 0.6% (2/348) vs. 0 (0/347), RR=3.00, 95 %CI: 0.31-28.65, P=0.34; dapagliflozin 10 mg/d: 0.2% (23/11 868) vs. 0.2% (25/11 868), RR=0.93, 95 %CI: 0.54-1.59, P=0.78]; the differences in the risk of bladder cancer were not significantly significant [overall study: 0.1% (16/12 021) vs. 0.2% (28/12 019), RR=0.59, 95 %CI: 0.33-1.07), P=0.08; dapagliflozin 5 mg/d: 0.7% (1/137) vs. 0 (0/137), RR=3.00, 95 %CI: 0.12-73.00, P=0.50; dapagliflozin 10 mg/d: 0.1% (15/11 884) vs. 0.2% (28/11 882), RR=0.55, 95 %CI: 0.30-1.02, P=0.06]. Conclusion:Dapagliflozin may not increase the risk of malignancy in patients with type 2 diabetes mellitus, but its long-term safety needs further study.

Objective:To observe the effect of different oxygen partial pressure on the survival of adrenal medullary pheochromocytoma (PC12) cells in rats and explore the possible mechanism.Methods:When carpeting 70%-80% of the entire flask bottom, the PC12 cells were randomly divided into 0.1 MPa group, 0.2 MPa group, and 0.4 MPa group. Then each group was placed in the experiment chamber respectively. The 0.1 MPa group was given pure oxygen under normal pressure in which oxygen partial was 0.1 MPa; while the other two groups was given 0.2 MPa and 0.4 MPa partial pure oxygen respectively with 0.03 MPa/min compresing and decompressing. Pure oxygen was given for 1 h under the corresponding stable pressure. Cell viability and the level of L-lactate dehydrogenase (LDH) in cultrue solution were determined by 3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyl tetrazolium bromide (MTT) colorimetric assay, intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were detected by flow cytometry.Results:(1) The cell viability in the 0.2 MPa group (118.35±5.42)% was significantly higher than that in the 0.1 MPa group (100.38±5.08)% ( P<0.01), while the cell viability in the 0.4 MPa group (83.50±7.11)% was lower than those in the 0.1 MPa group and the 0.2 MPa group ( P<0.01). (2) The level of LDH in the 0.4 MPa group (1 071.67±35.36) was significantly increased, which was significantly different from those in the 0.1 MPa group (959.19±34.06) and the 0.2 MPa group (966.66±31.38) ( P<0.01). (3) The level of ROS rised as the oxygen partial pressure increased. The differences of ROS level between the groups, i. e. the 0.1 MPa group (97.48±6.08) and the 0.2 MPa group (112.48±3.14), the 0.1 MPa group and the 0.4 MPa group (148.62±4.79), and the 0.2 MPa group and the 0.4 MPa group, were all statistically significant ( P<0.01). (4) The fluorescence intensity of Rh123 in each group were (797.63±60.05), (798.20±58.54), and (1 362.32±40.68) respectively, which were negatively correlated with MMP. There was no significant difference in MMP between the 0.1 MPa group and the 0.2 MPa group ( P=0.79), but the MMP in the 0.4 MPa group was lower than those in 0.1 group and the 0.2 MPa group with statistical significance ( P<0.01). Conclusion:The appropriate oxygen partial pressure could increase the viability of PC12 cells while a high oxygen partial pressure may be toxic, produce excessive ROS, and then induce the decrease of MMP, which is one of the possible mechanisms.

Objective:To observe the effect of different oxygen partial pressure on the survival of adrenal medullary pheochromocytoma (PC12) cells in rats and explore the possible mechanism.Methods:When carpeting 70%-80% of the entire flask bottom, the PC12 cells were randomly divided into 0.1 MPa group, 0.2 MPa group, and 0.4 MPa group. Then each group was placed in the experiment chamber respectively. The 0.1 MPa group was given pure oxygen under normal pressure in which oxygen partial was 0.1 MPa; while the other two groups was given 0.2 MPa and 0.4 MPa partial pure oxygen respectively with 0.03 MPa/min compresing and decompressing. Pure oxygen was given for 1 h under the corresponding stable pressure. Cell viability and the level of L-lactate dehydrogenase (LDH) in cultrue solution were determined by 3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyl tetrazolium bromide (MTT) colorimetric assay, intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were detected by flow cytometry.Results:(1) The cell viability in the 0.2 MPa group (118.35±5.42)% was significantly higher than that in the 0.1 MPa group (100.38±5.08)% ( P<0.01), while the cell viability in the 0.4 MPa group (83.50±7.11)% was lower than those in the 0.1 MPa group and the 0.2 MPa group ( P<0.01). (2) The level of LDH in the 0.4 MPa group (1 071.67±35.36) was significantly increased, which was significantly different from those in the 0.1 MPa group (959.19±34.06) and the 0.2 MPa group (966.66±31.38) ( P<0.01). (3) The level of ROS rised as the oxygen partial pressure increased. The differences of ROS level between the groups, i. e. the 0.1 MPa group (97.48±6.08) and the 0.2 MPa group (112.48±3.14), the 0.1 MPa group and the 0.4 MPa group (148.62±4.79), and the 0.2 MPa group and the 0.4 MPa group, were all statistically significant ( P<0.01). (4) The fluorescence intensity of Rh123 in each group were (797.63±60.05), (798.20±58.54), and (1 362.32±40.68) respectively, which were negatively correlated with MMP. There was no significant difference in MMP between the 0.1 MPa group and the 0.2 MPa group ( P=0.79), but the MMP in the 0.4 MPa group was lower than those in 0.1 group and the 0.2 MPa group with statistical significance ( P<0.01). Conclusion:The appropriate oxygen partial pressure could increase the viability of PC12 cells while a high oxygen partial pressure may be toxic, produce excessive ROS, and then induce the decrease of MMP, which is one of the possible mechanisms.

Objective To observe the effect of hyperbaric oxygenation (HBO) on apoptosis-inducing factor (AIF) and Caspase-3 levels in rats with permanent middle cerebral artery occlusion (MCAO),and to elucidate the apoptosis pathways.Methods Sixty Sprague-Dawley rats were subjected to permanent MCAO and then randomly divided into a control group and an HBO group,each of 30.Three hours later the rats of the HBO group were put into a hyperbaric cabin held at a pressure of 0.2 MPa for 9 hours.They inhaled supplementary oxygen at the 1st,3rd,5th,7th and 9th hour while the rats in the control group inhaled air at normal pressure.The neurological outcome was measured at the 3rd,13th and 72nd hour after the MCAO using Garcia scores.Apoptosis in the tissue of the ischemic penumbra,nuclear and mitochondrial AIF and Caspase-3 levels were measured at the 13th and 72nd hours after the modeling.Results The scores were significantly higher at the 13th hour than after the 3rd hour in both groups,and then even higher at the 72nd hour.Apoptosis was evident in the ischemic penumbra at the 13th and 72nd hours in both groups,but the number of cells was less at the 72nd hour than at the 13th hour in the control group.There was significantly less apoptosis in the HBO group than in the control group at the 13th hour.The average AIF level had significantly decreased in the nuclei and increased in the mitochondria by the 72nd hour compared with the 13th hour in both groups.The average levels of nuclear AIF at the 13th hour and the 72nd hour were lower than those in the mitochondria.But they were significantly higher in the HBO group than in the control group at the same time points.The levels of Caspase-3,normally zero,had increased by the 13th hour in both groups.The average level of Caspase-3 was significantly lower in both groups at the 72nd hour than at the 13th hour.Conclusions HBO can improve neurological function,inhibit the transfer of AIF from the mitochondria to the nucleus and reduce Caspase-3 levels.The mechanism may involve reducing apoptosis through caspase-dependent and caspase-independent pathways in the mitochondria.

Objective To observe the effect of single intensive hyperbaric oxygenation (HBO) on cytochrome C and caspase-3 in rats af-ter permanent middle cerebral artery occlusion (MCAO) very early. Methods Forty-eight male Sprague-Dawley rats were subjected to per-manent MCAO model using the intraluminal suture method, and were divided into control group (n=24) and HBO group (n=24). The HBO group stayed in the hyperbaric cabin with a pressure of 0.2 MPa for 9 hours 3 hours after MCAO. They were measured with Garcia scores 3 hours, 13 hours and 24 hours after MCAO. Apoptosis cells of ischemic penumbra tissue were investigated with TUNEL 13 hours and 24 hours after MCAO, while the level of cytochrome C and caspase-3 were measured with ELISA. Results The Garcia scores increased 13 hours and 24 hours after MCAO in both groups, but there was no significant difference between groups (t<2.07, P>0.05). The apoptosis cells were found in both groups 13 hours and 24 hours after MCAO, and less in the HBO group than in the control group (t>6.57, P<0.01). The levels of cytochrome C and caspase-3 were less in the HBO group than in the control group 24 hours after MCAO (t>2.41, P<0.05). Conclusion A single intensive HBO in very early stage may improve neurological function after cerebral ischemia in rats, which may associ-ate with the inhibition of cytochrome C and caspase-3 to reduce cell apoptosis.

Objective To investigate effect of hyperbaric oxygen therapy (HBOT) on delayed encephalopathy after carbon monoxide poisoning (DEACMP).Methods This was a prospective random study of 60 patients with DEACMP admitted to Beijing Tiantan Hospital.Among them,32 constituted the HBOT group and 28 were controls.All of the patients in both groups were given drugs to improve microcirculation and rehabilitation treatment.Additionally,the patients in the HBOT group were given hyperbaric oxygen therapy.The Mini-Mental State Examination (MMSE),the Barthel index and an index of age-related white matter changes (ARWMC) were used assess the patients' cognition,motor function and cerebral white matter lesions on the day of enrollment and on the 35th and 70th day after treatment.Results Before treatment there was no significant difference in average MMSE,Barthel index or ARWMC scores between the groups.In the HBOT group the average MMSE and Barthel index scores on the 35th and 70th day after enrollment were significantly higher than on the day of enrollment and the average ARWMC score on the 70th day was significantly lower than at enrollment.On the 35th day the average MMSE and Barthel index scores of the HBOT group were significantly higher than those of the control group,but there was no significant difference in the groups' average ARWMC scores.On the 70th day after enrollment the HBOT group's average MMSE and Barthel index scores were still significantly higher than those of the control group,but its average ARWMC score was significantly lower.Conclusion HBOT can help improve cognitive and notor function and also alleviate cerebral white matter lesions of DEACMP patients.

OBJECTIVE:To study the pharmacokinetics effects of naloxone combination on Shenmai injection in rats in vivo. METHODS:12 rats were randomly divided into monotherapy group (Shenmai injection 9.00 ml/kg,iv) and combination group (Shenmai injection 9.00 ml/kg+naloxone 1.80 ml/kg,iv). The blood samples were collected before administration and 0.083,0.25, 0.5,0.75,1,1.5,2,3,6,12,24,48,96 and 144 h after administration. HPLC was adopted to determine the plasma concentra-tions of ginsenosides Rg1,Re and Rb1,and DAS 2.0 software was used to calculate the pharmacokinetic parameters. RESULTS:Compared with monotherapy group,the plasma concentration of ginsenosides Rg1 in combination group was increased,CL was de-creased,t1/2 and MRT were prolonged,and AUC0-144 h was increased;the plasma concentration of ginsenosides Re was increased,Ke was decreased,t1/2 was prolonged,MRT was shortened,and AUC0-144 h was increased;the plasma concentration of ginsenosides Rb1 was decreased,Ke was increased,t1/2 and MRT were shortened,and AUC0-144 h was decreased,with significant differences(P<0.01 or P<0.05). CONCLUSIONS:Shenmai injection combined with naloxone can slow down the removing of ginsenosides Rg1 and Re in vivo,and obviously the plasma concentration of Shenmai injection is higher than monotherapy group;speed up the removing of ginsenosides Rb1,and the plasma concentration of Shenmai injection is lower than monotherapy group obviously.

Objective To explore the effect of oxygen inhalation on auditory sensory gating P50 in healthy human brain. Methods 28 healthy male academician right-handed were included. They were divided into control group (n=12) and experiment group (n=16) according to the random numerical table, and blinded about groups. The subjects inhaled pure oxygen in the experiment group, and air in the control group through a mask for 60 min. The electroencephalograph was recorded while an auditory paired-click sensory gating test was conducted during 4 study periods: before inhalation (pre0), inhale for 20 min (Oxy20) and 50 min (Oxy50), and 30 min after inhalation (post30). The latency and amplitude (S1-S2) of auditory sensory gating P50 were calculated. Results The latencies of P50 from S1 were stable in each group (P>0.7), and the latency of Oxy50 was shorter in the experiment group than in the control group (P<0.05). The latencies from S2 were stable in each group (P>0.30), and there was no significant difference between groups in all the time points (P>0.05). The amplitudes of (S1-S2) of P50 were stable in the control group (P=0.70), and was higher on Oxy20 (P=0.04) and Oxy50 (P=0.02) than post30 in the experiment group. There was no difference between the groups in all the time points (P>0.05). Conclusion Oxygen inhalation may be helpful to shorten the active time to stimulate, and trend to enhancing the amplitude of P50.