OBJECTIVE To explore whether diterpenoid 12-deoxyphorbol-13-palmitate （DP） from Euphorbia fischeriana can exert anti-leukemia effects through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signal pathway， and to provide experimental evidence for developing it into a new anti-leukemia drug. METHODS Using LY294002 （PI3K specific inhibitor） as tool drug， the effects of 24 h DP treatment on the proliferation and apoptosis of human myeloid leukemia HL60 cells were detected by MTT method， Annexin Ⅴ-FITC/PI staining and AO-EB staining. ELISA method was used to detect lactic dehydrogenase （LDH） release and the activities of cysteinyl aspartate specific proteinase 3 （caspase-3） and caspase-9. The transcriptional level of caspase-3， caspase-9， forkhead box O3a （FoxO3a） and B cell lymphoma 2 interacting mediator of cell death （Bim） mRNA were detected by real-time quantitative polymerase chain reaction （qRT-PCR）. The protein expression of phosphorylated FoxO3a （p- FoxO3a） and phosphorylated Akt （p-Akt） were detected by Western blot method. The nuclear translocation of FoxO3a protein was detected by immunostaining combined with laser confocal microscopy. RESULTS 10 μmol/L DP and 10 μmol/L DP+LY294002 could inhibit the proliferation and induce the apoptosis of HL60 cells （P＜0.01）. After treatment of 5， 10， 20 μmol/L DP， HL60 cells showed typical morphological characteristics of apoptosis； DP could significantly increase the levels of LDH release and the activities of caspase-3 and caspase-9 （P＜0.05 or P＜0.01）， in dose-dependent manner. After treatment of 10 μmol/L DP and 10 μmol/L DP+LY294002， the transcriptional levels of caspase-3， caspase-9 and Bim mRNA were increased significantly （P＜0.05 or P＜0.01）， and transcriptional level of FoxO3a mRNA and protein expressions of p-FoxO3a and p-Akt were decreased significantly （P＜0.05 or P＜0.01）. Nuclear translocation changes were observed in FoxO3a protein in 10 μmol/L DP+LY294002 group， and the change was more significant than that of LY294002 group. CONCLUSIONS DP can inhibit the proliferation and induce the apoptosis of HL60 cells via inhibiting PI3K/Akt signaling pathway.

Natural medicinal chemistry is one of the important courses for students in pharmacy majors. Its experimental teaching focuses on fostering comprehensive experimental skills and innovative abilities of undergraduates. Liaoning University has explored ways to promote the experimental teaching of natural drug chemistry based on the graduate employment and practical teaching experience in the past decade. These explorations include three aspects, such as synchronizing experimental teaching with theoretical teaching, fostering students' awareness of experimental safety, and improving experimental teaching methods in natural drug chemistry experiments. The practices showed that the reform has achieved a good effect. A teaching system that can achieve the three expected aspects has been established, which improved the teaching effect and quality of natural medicinal chemistry experimental courses for undergraduates. Furthermore, these explorations may facilitate fostering pharmacy specialists who can meet the opportunities of developing Chinese medicine and natural drug research and meet the requirements of employment.
Chemistry, Pharmaceutical/education* ; Humans ; Students ; Universities

Objective:To investigate the clinical efficacy of hemoperfusion in the treatment of severe organophosphorus poisoning and its effect on diaphragm function.Methods:Eighty-five patients with severe organophosphorus poisoning who received treatment in Affiliated Huxi Hospital of Jining Medical University (Shanxian Central Hospital), China between January 2018 and January 2020 were included in this study. They were randomly divided into treatment ( n = 43)and control ( n = 42) groups. The control group was given conventional treatment including gastric lavage, catharsis, and application of reactivators and anticholinergic drugs. The treatment group was subjected to three times of hemoperfusion, with an interval of 24 hours between two hemoperfusion interventions based on the conventional treatment used in the control group. Before and after three times of hemoperfusion, serum levels of cholinesterase (CHE), interleukin-6 (IL-6), arterial partial pressure of oxygen (PaO 2), and arterial partial pressure of carbon dioxide (PaCO 2) were measured. The Acute Physiology and Chronic Health Evaluation (APACHE) II score and oxygenation index (OI) in each group were calculated. Right diaphragmatic activity, diaphragmatic thickness at the end of inspiration (DTei) and diaphragmatic thickness at the end of expiration were measured by bedside ultrasound. The diaphragmatic thickening rate (DTF) and diaphragmatic rapid shallow breathing index (D-RSBI) were calculated. Serum CHE and IL-6 levels, OI, diaphragmatic activity, DTF and D-RSBI were compared between the treatment and control groups. The incidence of intermediate syndrome, tracheal intubation rate, 28-day mortality rate, and hospital stay were compared between the two groups. Results:Before hemoperfusion, there were no significant differences in serum levels of CHE and IL-6, OI, right diaphragmatic activity, DTF, and D-RSBI between the treatment and control groups (all P > 0.05). After three times of hemoperfusion, serum IL-6 level and D-RSBI in the treatment group were (37.9 ± 6.2) ng/L and (0.77 ± 0.20) times /min/mm, which were significantly lower than those in the control group [(45.9 ± 5.3) ng/L, (0.90 ± 0.16) times/min/mm ( t = -6.295, -3.382, P < 0.001, P = 0.001)]. Serum CHE level, OI, DE and DTF in the treatment group were (2.29 ± 0.52) kU/L, (264.5 ± 24.3) mmHg, (16.5 ± 1.9) mm, (27.2 ± 4.7) %, respectively, which were significantly higher than those in the control group [(1.96 ± 0.39) kU/L, (252.6 ± 27.2) mmHg, (14.3 ± 1.6) mm, (23.5 ± 4.1) %, t = 3.258, 2.141, 5.598, 3.877, all P < 0.05]. The incidence of intermediate syndrome, tracheal intubation rate, hospital stay in the treatment group were [4.7% (2/43)], [2.3% (1/43)] and [(11.8 ± 1.8) days], respectively, which were significantly lower than those in the control group [23.8% (10/42), 19.0% (8/42) and (12.9 ± 1.8) days, χ2 = 6.432, P = 0.011; χ2 = 6.276, P = 0.012; t = -2.932, P = 0.004]. There was no significant difference in 28-day mortality rate between the two groups ( P > 0.05). Conclusion:Hemoperfusion can improve diaphragmatic function, reduce inflammatory reaction and shorten hospital stay in patients with severe organophosphorus poisoning.

Objective To explore the clinical value of transnasal high volume oxygen therapy in the treatment of patients with acute heart failure.Methods From January 2016 to January 2018,61 cases with acute heart failure in Huxi Hospital Affiliated to Jining Medical College were selected.The patients were randomly divided into control group and treatment group according to the digital table,31 cases in the control group and 30 cases in the treatment group.The two groups were routinely given control of fluid volume,analgesia,strong heart,diuresis,vasodilator,anti-platelet aggregation,camp support and so on.The control group was given conventional oxygen therapy,and the treatment group was treated with high flow oxygen through nose.Before treatment and 12h,24h,48h,72h after treatment,the left ventricular ejection fraction (LVEF),oxygen index (PaO2/FiO2),serum lactic acid (Lac),B type sodium and titanium (BNP) in serum,and the application rate of non-invasive mechanical ventilation and invasive mechanical ventilation in 7d were observed in the two groups.Results Compared with the control group,the LVEF of the treatment group in each time point increased [(35.58 ± 3.64) ％ vs.(37.77 ± 3.76) ％,(37.87 ± 3.58) ％ vs.(40.07 ±3.36)％,(44.94 ±3.19)％ vs.(46.83 ±3.21)％,(47.55 ±3.45％)％ vs.(40.07 ±3.36％)％,t =-2.308,-2.466,-2.316,-2.487,all P ＜ 0.05].The PaO2/FiO2 of the treatment group increased significantly at each time point after treatment [(177.39 ± 10.62) mmHg vs.(184.17 ± 10.49) mmHg,(188.00 ± 11.72) mmHg vs.(198.57 ± 18.47) mmHg,(204.06 ± 17.69) mmHg vs.(221.40 ± 23.80) mmHg,(265.23 ± 34.51) mmHg vs.(290.37 ± 26.72) mmHg,t =-2.507,-2.678,-3.236,-3.174,all P ＜ 0.05].The BNP level of the treatment group decreased significantly at each time point after treatment [(2 462.90 ± 288.00) ng/mL vs.(2 264.53 ± 366.44) ng/mL,(1 646.61 ± 377.19) ng/mL vs.(1 474.07 ± 214.03) ng/mL,(991.94 ± 242.95) ng/mL vs.(811.90 ±258.67) ng/mL,(653.77 ± 147.671) ng/mL vs.(526.47 ± 127.87) ng/mL,t =2.355,2.187,2.803,3.594,all P ＜ 0.05].The Lac level of the treatment group decreased significantly at 12h and 24h after treatment [(5.05 ± 0.69) mmol/L vs.(4.55 ± 0.80) mmol/L,(3.68 ± 0.89) mmol/L vs.(3.13 ± 0.77) mmol/L,t =2.610,2.601,all P ＜ 0.05],but there were no statistically significant differences between the two groups at 48h and 72h after treatment [(1.62 ± 0.65) mmol/L vs.(1.53 ± 0.65) mmol/L,(1.36 ± 0.64) mmol/L vs.(1.26 ± 0.46) mmol/L,all P ＞ 0.05].In the control group and the treatment group,the incidence rates of non-invasive mechanical ventilation in 7d were 35.48％ (11/31),13.33％ (4/30),respetively,the difference was statistically significant (x2 =4.034,P ＜ 0.05).In the control group and the treatment group,the incidence rates of invasive mechanical ventilation in 7d were 12.90％ (4/31),3.33％ (1/30),respetively,the difference was statistically significant (x2 =4.957,P ＜ 0.05).Conclusion Nasal high flow oxygen therapy has better clinical effect on patients with acute heart failure.It is a more active treatment measure,and is worthy of clinical application.

Objective To investigate the effect of early activities on risk factors of acute gastrointestinal injury (AGI) in patients with chronic obstructive pulmonary disease (COPD) induced by mechanical ventilation.Methods A total of 118 mechanically ventilated non-diabetic patients with chronic obstructive pulmonary disease who were admitted to our hospital from August 2017 to April 2018 were enrolled in the study.The patients were divided into AGI group (71 cases) and non-AGI group (47 cases) according to the presence or absence of AGI.The examined data were collected in the patients prospectively such as preprocalcitonin (PCT),D-lactic acid,serum albumin (ALB),fasting plasma glucose (FPG),fasting insulin (FINS),and Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) scores were calculated.The homeostasis model insulin resistance index was used (HOMA-IR) to assess the subjects' insulin resistance.Logistics regression analysis screened for risk factors that affected patients' AGI.The AGI patients were divided into treatment group (36 cases) and control group (35 cases) according to the random number table method.On the basis of the same conventional treatment,the treatment group were received early mobilization.The differences of PCT,D-lactate,FPG,HOMA-IR,APACHE Ⅱ scores,and AGI grades before and after treatment for 3 days were observed for both groups of patients.Results The PCT,D-lactate,FPG,HOMA-IR,and APACHE Ⅱ scores were higher in the AGI group than in the non-AGI group [(2.72 ±0.54)ng/ml vs (1.81 ±0.62)ng/ml;(17.43 ±2.63)mg/ml vs (13.61 ± 1.6)mg/ml;(10.1 ±l.0)mmol/L vs (8.4 ±0.9) mmol/L;(2.4 ±0.5) vs (1.7 ±0.4);(23.8 ±2.9) point vs (21.7 ±4.3)point],and the ALB were lower than non-AGl group [(29.1 ±2.2)g/L vs (30.6 ±3.2)g/L],with statistically significant difference (P ＜ 0.05).Multivariate logistic regression analysis showed that PCT,D-lactic acid,FPG,HOMA-IR,and APACHE Ⅱ scores were risk factors for AGI in mechanically ventilated non-diabetic patients with COPD (regression coefficients were 4.337,1.226,5.106,4.469,0.584 respectively,P ＜0.05).There were no significant difference in PCT,D-lactate,FPG,HOMA-IR,APACHE Ⅱ scores between the treatment group and the control group before treatment (P ＞ 0.05).The PCT,D-lactic acid,FPG,HOMA-IR,and APACHE Ⅱ scores in the treatment group were significantly lower than those in the control group after early treatment [(2.00 ± 0.49) ng/ml vs (2.34 ± 0.34) ng/ml;(15.38 ± 1.71)mg/ml vs (17.38 ±2.88)mg/ml;(8.9 ±0.9)mmol/L vs (9.6 ±0.7)mmol/L;(1.9 ± 0.4) vs (2.2 ± 0.4);(21.0 ± 1.8) point vs (22.2 ± 2.7) point],and AGI severity was reduced (There were 8,18,6,3 and 1 cases of 0,Ⅰ,Ⅱ,Ⅲ,and Ⅳ in the treatment group,and4,12,9,7 and 3 in the control group respectively),with statistically significant differences (P ＜ O.05).Conclusions PCT,Dlactic acid,FPG,HOMA-IR,and APACHE Ⅱ scores were risk factors for AGI in mechanically ventilated non-diabetic patients with COPD.Early mobilization could reduce the level of these risk factors and the severity of AGI.

Objective To investigate the effect of early mobilization on diaphragmatic function in patients with mechanical ventilation (MV). Methods Sixty chronic obstructive pulmonary disease with acute exacerbation (AECOPD) patients with respiratory failure (RF) and underwent MV admitted to intensive care unit (ICU) of Huxi Affiliated Hospital of Jining Medical College from January 2016 to January 2017 were enrolled. The patients were divided into treatment group (n = 30) and control group (n = 30) by randomly number table method. The two groups were given analgesia, sedation, MV, antibiotics, nutritional support and other treatments. An implementation plan was developed based on the clinical practice of pain, irritability and delirium in adult patients (PAD) with ICU, while the treatment group was given early mobilization (such as joint activity, stand to the bed, 3 times a day). The diaphragmatic thickness at the end of expiration (DTee), diaphragmatic thickness at the end of inspiration (DTei) and diaphragmatic thickening fraction (DTF) were measured by bedside ultrasonography before and 24 hours, 48 hours, 3 days and 5 days after treatment respectively. Results There were no significant differences in the parameters of the diaphragm before treatment between the two groups. In the control group, DTee was gradually decreased at 5 days after treatment and was significantly lower than that before treatment (cm: 0.26±0.06 vs. 0.28±0.08, t = 3.045, 1 = 0.005). While there was no significant change in DTee in the treatment group. There was no significant difference in DTee between the two groups at different time points after treatment. DTei and DTF were significantly increased in the two groups after treatment, and reached the peak value at 48 hours; with the prolonged of MV time, DTei and DTF in the control group at 3 days and 5 days were significantly lower than those at 48 hours [DTei (cm): 0.35±0.07, 0.34±0.07 vs. 0.36±0.08; DTF: (29.29±11.01)%, (28.62±11.97)% vs. (32.48±15.63)%, all 1 < 0.01]; there were no significant changes in the treatment group. DTF in the treatment group at 3 days and 5 days was significantly higher than that in the control groups [(38.53±11.39)% vs. (29.29±11.01)%, (37.27±11.26)% vs. (28.62±11.97)%, both 1 < 0.01]. Conclusion MV can lead to diaphragmatic dysfunction, while early mobilization can delay diaphragmatic atrophy and systolic dysfunction in MV patients.

Objective To investigate the functions of Monocyte chemotactic protein-induced protein 1 (MCPIP1) in human breast cancer cell line MDA-MB-231.Methods MDA-MB-231 cells were transfected with GFP-tagged MCPIP1 by Tet-on inducing expression system.Endogenous MCPIP1 was knocked down by stable expressing shRNA.MTT assay was performed to measure the growth of MDA-MB-231 cells after overexpression or knockdown of MCPIP1.FACS method was used to analyze cell cycle in MDA-MB-231 cells.Real-time PCR was used to test the expression of cell cycle-related mRNAs expression and their half-lives.RNA-IP experiment was conducted to detect the mRNA directly enriched by MCPIP1.Luciferase assay was performed to determine whether the mRNA decay was mediated through 3′UTR.Results MCPIP1 overexpression significantly inhibited cell proliferation(P<0.05), while knockdown MCPIP1 promoted cell proliferation with statistical significances (P<0.05).MCPIP1 induced cell cycle arrest in MDA-MB-231 with statistical significance (P<0.01).MCPIP1 overexpression reduced the half-lives of cell cycle mRNAs (CDK2,CDK6,cyclin D1,cyclin E1,respectively) with significance (P<0.01).In addition, cell cycle-related mRNAs were able to be pulled down by GFP-MCPIP1 but not isotype IgG(P<0.05).Compared with control vector, MCPIP1 significant suppressed luciferase activities of all four 3′UTR reporters (P<0.05).Conclusions MCPIP1 functions as a tumor suppressor in human breast cancer cell line MDA-MB-231 through inducing G1 cell cycle arrest.

Objective To evaluate the effect of comprehensive schistosomiasis control measures based on infection source control in plateau mountain areas of Yunnan Province. Methods From 2006 to 2004,four administrative villages were selected as test areas from plateau canyon and plateau basin endemic areas in Jindun Town,Heqing County,two villages each type,and the comprehensive control measures were implemented,including the examination and treatment of schistosomiasis,Oncomela?nia hupensis snail survey and control,health education,improving drinking water and lavatories,banning grazing,constructing sanitary pen of livestock,replacing cattle with machine,etc. The schistosome infection state and snail status in 2006 were treat?ed as the baseline information,and the effect of the comprehensive measures were evaluated. Results The infection rate of hu?man in plateau canyon areas decreased from 4.94%in 2006 to 0.06%in 2014,and that of livestock decreased from 1.11%to 0. In plateau basin areas,there was only 1 case of schistosomiasis found in Xiaolian Village in 2007,and no any other cases found in the other years,the infection rates of livestock dropped from 7.38%to 0. Compared with 2006,the snail areas in the two type areas decreased by 74.89%and 75.30%,respectively,meanwhile,the percentage of snail area,the occurrence rate of frames with snails,as well as the average density of living snails also decreased,and no infected snails were found since 2008. Xidian and Xinzhuang villages in plateau canyon area reached the criteria of schistosomiasis transmission controlled in 2009,and Xiao?lian and Kangfu villages in plateau basin reached the criteria of transmission interrupted in 2014. Conclusions The comprehen?sive schistosomiasis control measures based on infection source control can effectively control the endemic situation of schistoso? miasis in plateau areas of Yunnan Province. In the future,we should pay an equal attention to the infection sources control and snail control to consolidate and amplify the achievement of schistosomiasis control.

Objective To investigate the effects of sequential blood purification on cardiac function in patients with acute organophosphorus pesticide poisoning (AOPP),and to analyze its application value.Methods Forty-five patients with severe AOPP and toxic myocarditis were researched and randomly divided into two groups.Sequential blood purification included hemoperfusion(HP) and continuous veno-venous hemofiltration (CVVH).In treatment group,23 patients were treated with HP + CVVH on the basis of the conventional therapy.Twenty-two patients of control group received the conventional therapy with HP.The differences of two groups on left ventricular ejection fraction (LVEF) and B-type natriuretic peptide (BNP) were compared before treatment and at 24,48 and 72 h after treatment.Results Before treatment,the levels of LVEF and BNP in treatment group were (47.7 ± 9.8)％ and (511.3 ± 285.3) ng/L,in control group were (47.3 ± 10.2)％ and (535.4 ± 303.9) ng/L,and there were no significant differences (P ＞ 0.05).The levels of LVEF at each time point after treatment in treatment group were significantly higher than those of control group:(52.7 ± 7.3) ％ vs.(47.8 ± 8.4)％,(55.2 ± 5.2)％ vs.(50.6 ± 7.1)％,(60.7 ± 6.3)％ vs.(53.3 ± 5.2)％,and the levels of BNP in treatment group were significantly lower than those of control group:(320.7 ± 181.8) ng/L vs.(496.7 ±268.9) ng/L,(252.7 ±113.8) ng/L vs.(384.3 ±167.5) ng/L,(122.4 ±66.7) ng/L vs.(294.8 ± 121.8) ng/L,there were significant differences between two groups (P＜ 0.05 or ＜ 0.01).In treatment group,the levels of LVEF at 24,48 and 72 h after treatment were significantly increased:(52.7 ± 7.3)％,(55.2 ± 5.2)％,(60.7 ± 6.3)％ vs.(47.7 ± 9.8)％,and the levels of BNP were significantly decreased:(320.7 ± 181.8),(252.7 ± 113.8),(122.4 ±66.7) ng/L vs.(511.3 ±285.3) ng/L,there were significant differences (P ＜ 0.01).In control group,the levels of LVEF and BNP at 24 h after treatment were (47.8 ± 8.4)％ and (496.7 ± 268.9) ng/L,before treatment were (47.3 ± 10.2)％ and (535.4 ± 303.9) ng/L,and there were no significant differences (P ＞ 0.05);the levels of LVEF at 48 and 72 h after treatment were significantly increased:(50.6 ± 7.1)％,(53.3 ± 5.2)％ vs.(47.3 ± 10.2)％,the levels of BNP were significantly decreased:(384.3 ± 167.5),(294.8 ± 121.8) ng/L vs.(535.4 ± 303.9) ng/L,and there were significantl differences (P ＜ 0.05 or ＜ 0.01).Conclusion Sequential blood purification treatment of AOPP can reduce myocardial injury and improve the cardiac function.

Objective To observe the effects of Fuyanshu Capsule on phenol mucilage-induced endometritis rats and the possible anti-inflammation mechanism of the therapeutic effects.Methods Chronic endometritis in rats was induced by injection of phenol mucilage suspension into the uterus.Sixty female SD rats were randomly divided into 6 groups,namely,sham-operation group (distilled water,10mL/kg),model group,Jinji capsule group (0.65 g/kg),and Fuyanshu Capsule groups (1.8 g/kg,0.9 g/kg and 0.45 g/kg).After the rats were treated 28 days with corresponding medicine by intragastric administration,the pathology of the endometrium and changes of tumor necrosis factor α(TNF-α)and interleukin-2 (IL-2)levels were detected to evaluate the effects of Fuyanshu Capsule. Results Fuyanshu Capsule (1.8 g/kg and 0.9 g/kg)ameliorated the body weight reduction caused by endometritis in rats.Fuyanshu Capsule (1.8 g/kg,0.9 g/kg and 0.45 g/kg)reduced the ratio of the swelling uterus and ovaries to body weight of the rats.It ameliorated obviously the hyperplasia,necrosis and degeneration of endometrial epithelia and infiltration of inflammatory cells.The capsule (1.8 g/kg)decreased the serum IL-2 level in the rats with phenol mucilage-induced endometritis. Conclusion The anti-inflammatory effect of Fuyanshu Capsule on chronic endometritis induced by phenol mucilage in rats may be related to the decrease of IL-2 level.