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OBJECTIVES@#The plateau environment is characterized by low oxygen partial pressure, leading to the reduction of oxygen carrying capacity in alveoli and the reduction of available oxygen in tissues, and thus causing tissue damage. Cilostazol is a phosphodiesterase III inhibitor that has been reported to increase the oxygen release of hemoglobin (Hb) in tissues. This study aims to explore the anti-hypoxic activity of cilostazol and its anti-hypoxic effect.@*METHODS@#A total of 40 male BALB/C mice were randomly divided into a low-dose cilostazol (6.5 mg/kg) group, a medium-dose (13 mg/kg) group, a high-dose (26 mg/kg) group, and a control group. The atmospheric airtight hypoxia experiment was used to investigate the anti-hypoxic activity of cilostazol and to screen the optimal dosage. Twenty-four male Wistar rats were randomly divided into a normoxia control group, a hypoxia model group, an acetazolamide (22.33 mg/kg) group, and a cilostazol (9 mg/kg) group. After 3 days of hypoxia in the 4 010 m high altitude, blood from the abdominal aorta was collected to determine blood gas indicators, the levels of IL-6 and TNF-α in plasma were determined by enzyme-linked immunosorbent assay, and the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutataione (GSH) were measured. The degree of pathological damage for rat tissues was observed with HE staining.@*RESULTS@#Compared with the control group, the survival time of mice in the low, medium, and high dose group of cilostazol was significantly prolonged, and the survival time of mice in the medium dose group was the longest, with an extension rate at 29.34%, so the medium dose was the best dose. Compared with the hypoxia model group, the P50 (oxygen partial pressure at Hb oxygen saturation of 50%) value of rats in the cilostazol group was significantly increased by 1.03%; Hb and Hct were significantly reduced by 8.46% and 8.43%, and the levels of IL-6 and TNF-α in plasma were reduced by 50.65% and 30.77%. The MDA contents in heart, brain, lung, liver, and kidney tissues were reduced by 37.12%, 29.55%, 25.00%, 39.34%, and 21.47%, respectively. The SOD activities were increased by 94.93%, 9.14%, 9.42%, 13.29%, and 20.80%, respectively. The GSH contents were increased by 95.24%, 28.62%, 28.57%, 20.80%, and 44.00%, respectively. The results of HE staining showed that compared with the hypoxia model group, cilostazol significantly improved the damage of heart, lung, and kidney tissues in rats after hypoxia.@*CONCLUSIONS@#Cilostazol can significantly improve the oxidative stress and inflammatory reaction caused by rapid altitude hypoxia, and it has a significant protective effect on tissue damage caused by hypoxia, suggesting that it has obvious anti-hypoxic activity.
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Animals , Male , Mice , Rats , Altitude Sickness , Cilostazol/therapeutic use , Hypoxia/drug therapy , Interleukin-6/pharmacology , Mice, Inbred BALB C , Oxidative Stress , Oxygen , Rats, Wistar , Superoxide Dismutase/metabolism , Tumor Necrosis Factor-alpha/pharmacologyABSTRACT
Transsynaptic retrograde degeneration of optic neuropathy (TRDON) refers to the degeneration and/or apoptosis of presynaptic neurons (retinal ganglion cells) caused by damage to the lateral geniculate body and post-geniculate visual pathway. At present, the pathogenesis of TRDON is secondary apoptosis of P β-type retinal ganglion cells, resulting in the atrophy of optic tract, thinning of the retinal nerve fiber layer and retinal ganglion cell layer thickness and declining of retinal microvascular density, which are consistent with the visual field defect attributed to the primary disease. Of which, the thinning of the retinal ganglion cell layer thickness is considered as the characteristic of TRDON. Now, there is little understanding and related research on TRDON in China. Clinicians should pay attention to the characteristics and severity, occurrence time and location of the above structural changes in these patients through optical coherence tomography, and monitor the activity and progress of the lesions, so as to determine the cut-off point for drug intervention and the drug targets for developing new treatment methods, and bring benefits for patients in partial visual function recovery and disability reduction.
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Objective By participating in the process of drug treatment and pharmaceutical monitoring for a patient with cancer pain, clinical pharmacists participated in formulating drug treatment plans and proposed rational medication recommendations. At the same time, patients were given health education to reduce or avoid adverse drug reactions. Methods Pharmacists participate in the process of pharmacy monitoring of patients by participating in the review of prescriptions, discovering problems, intervening in time for improper prescriptions, communicating with doctors, changing medication plans, and providing health education to patients. Results Physicians accepted the suggestions of pharmacists and modified the medication regimen. The patient's condition improved. Conclusion The pharmacist participated in the intervention of an improperly prescribed medication for a patient with metastatic breast cancer postoperative cancer pain, and gave the patient a full range of pharmaceutical care, which reflects the importance of the pharmacist in pharmaceutical care.
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When this paper was first published the following ethical statement was omitted in error: Animal experiments were conducted in accordance with the guidelines of Laboratory Animal Ethics Committee of Tianjin University of Traditional Chinese Medicine (TCM-LAEC2019071). The authors would like to apologise for any inconvenience caused. DOI of original article: https://doi.org/10.1016/j.chmed.2018.10.002
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Objective To summarize the factors and the corresponding treatments for patients with coronary heart disease (CHD) complicated by thrombocytopenia, and provide medical advises for clinical treatment. Methods Literatures and case reports were analyzed and summarized. Results Thrombocytopenia in patient with CHD could be mainly divided into two types, one group was induced by the antithrombotic therapies for CHD, and the other group was caused by some concurrent diseases or combined non-antithrombotic medications. There were different medical decisions and prognoses according to the causes in different groups. Conclusion The treatment strategies of CHD will be considered in the CHD patients with thrombocytopenia. Identifying thrombocytopenia by monitoring the platelet counts in early stage, finding out the causes quickly and providing proper treatments are the key for the prognosis of the patients.
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Objective@#To explore the clinical value of low molecular weight heparin(LMWH) plus low dose aspirin(LDA) in preventing twin pregnancy with preeclampsia high risk factors.@*Methods@#From January 2013 to December 2017, the twin pregnancy cases with preeclampsia high risk factors who were diagnosed in Shanxi Rongjun Hospital were randomly divided into two groups according to the order of the treatment.The observation group(n=53) used LMWH plus LDA to prevent preeclampsia, while the control group(n=53) used LDA alone.The incidence of preeclampsia and pregnancy outcome were compared between the two groups.@*Results@#The incidence of severe preeclampsia in the observation group(5.7%) was lower than that in the control group(18.9%)(χ2=4.296, P<0.05), and there was statistically significant difference in the delivery time between the two groups(χ2=7.993, P<0.05). While the incidence of preeclampsia, placental abruption, postpartum hemorrhage and FGR between the two groups had no statistically significant differences (all P>0.05). The proportion of NICU transferred fetus in the observation group(18.3%) was lower than that in the control group(30.7%)(χ2=4.289, P<0.05). There were no statistically significant differences in perinatal mortality and neonatal asphyxia(all P>0.05).@*Conclusion@#Compared with using the LDA alone, LMWH plus LDA prevention can effectively reduce the incidence of severe preeclampsia in twin pregnancies; at the same time, it also can delay the delivery time and reduce the rate of NICU transferred.
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Objective To introduce the improvements of multi-mode outpatient pharmacy services based on the new medical reform policy. Methods The pharmacist’s roles, responsibilities, working procedures and the achievements were discussed. Results and conclusion On-site pharmacy counseling services and online WeChat pharmacy consulting services were established to include collaborative drug therapy management of pharmacists and physicians (Alzheimer's disease and anticoagulation clinic), the outpatient pharmacy services by pharmacists (chemo medication counseling). The multi-mode pharmacy services in our hospital have optimized patient's medication regime, safeguarded patient's medication therapy, improved patient's compliance and reduced medication cost. The individualized medication therapy reduced adverse reactions significantly. The multi-mode outpatient pharmacy services established by our hospital were successful and could serve as a model for other pharmacies in our country.
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Objective To explore the clinical value of low molecular weight heparin(LMWH) plus low dose aspirin(LDA) in preventing twin pregnancy with preeclampsia high risk factors.Methods From January 2013 to December 2017,the twin pregnancy cases with preeclampsia high risk factors who were diagnosed in Shanxi Rongjun Hospital were randomly divided into two groups according to the order of the treatment .The observation group(n=53) used LMWH plus LDA to prevent preeclampsia ,while the control group ( n=53) used LDA alone.The incidence of preeclampsia and pregnancy outcome were compared between the two groups .Results The incidence of severe preeclampsia in the observation group(5.7％) was lower than that in the control group (18.9％)(χ2 =4.296,P<0.05),and there was statistically significant difference in the delivery time between the two groups (χ2 =7.993,P<0.05).While the incidence of preeclampsia ,placental abruption,postpartum hemorrhage and FGR between the two groups had no statistically significant differences (all P >0.05).The proportion of NICU transferred fetus in the observation group(18.3％) was lower than that in the control group (30.7％)(χ2 =4.289,P<0.05).There were no statistically significant differences in perinatal mortality and neonatal asphyxia ( all P >0.05 ).Conclusion Compared with using the LDA alone , LMWH plus LDA prevention can effectively reduce the incidence of severe preeclampsia in twin pregnancies;at the same time,it also can delay the delivery time and reduce the rate of NICU transferred.
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Objective To establish a LC-MS method of cisatracurium assay in human plasma for clinical therapeutic drug monitoring. Method Propafenone Hydrochloride was used as the internal standard. The plasma samples were treated with 2% formic acid aqueous solution and acetonitrile containing the internal standard to precipitate protein. Agilent SB-C18 column was used for gradient elution with the mobile phase of 0.1% formic acid-water and 0.1% formic acid-acetonitrile solution at 35 ℃ and 0.3 ml/min flow rate. The degradation products of cisatracurium m/z 464.6-358.4 and propafenone hydrochloride m/z 342.2-116.2 were identified by ESI positive-ion detection. Results There was a linear rage of cisatracurium in 2-500 ng/ml (r=0.996 5) with a detection limit of 2 ng/ml. The intra-day coefficients of variation (CVs) were less than 16.00%, and the inter-day CVs were less than 6.00%. The mean recoveries were in the range of 97.63%-111.93%. The plasma samples were stable for 4 hours at room temperature, 14 days at -80 ℃ and 24 hours after pretreated. Conclusion This method was simple, accurate, fast and repeatable for the cisatracurium assay in human plasma.
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The diagnosis and treatment of spontaneous rupture and massive hemorrhage of tuberous sclerosis-related renal hamartoma in a woman in the third trimester are reported. The patient was admitted at 39 weeks of gestation, with threatened labor and a history of bilateral renal hamartoma, which had been hidden. Placental abruption was considered due to persistent lumbago, abdominal pain, abdominal muscle tension, uterine tension and fetal heart rate dropping to 90 bpm, and an emergency cesarean section was performed at 39 +1 weeks. About 200 ml of bloody ascites was found in the peritoneal cavity. A live boy was delivered and no blood clot was seen in the maternal face of the placenta. After the uterine incision was closed, a huge bluish purple mass was detected on the right-side retroperitoneum and the renal angiography showed rupture and hemorrhage of a right renal hamartoma. A selective right renal artery embolization was performed. The patient recovered after the operation and was discharged seven days later required by the family. The patient was in good condition except for hematuria during a 30-day postpartum follow-up, and oral everolimus treatment and regular follow-up were continued. The newborn with a birth weight of 2 355 g was transferred to the neonatology department after birth due to severe asphyxia, and postnatal echocardiography suspected heart rhabdomyoma. The baby had one seizure but was otherwise well, and was discharged after eight days. The seizure did not recur to the neonate after discharge. Clinicians should pay attention to pregnant women with renal hamartoma. If abnormal abdominal distension, hematuria or lumbago occur during pregnancy, rupture of renal hamartoma and possible massive hemorrhage should be considered.
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Objective To study the serum levels of oxidative stress markers in the new type 2 diabetes mellitus (T2DM) patients with nonalcoholic fatty liver disease (NAFLD),and the effect of o-lipoic acid (A-LA) on oxidative stress markers.Methods From August 2016 to August 2017,80 new T2DM patients complicated with NAFLD (T2DM + NAFLD group) and 80 new T2DM patients without NAFLD (T2DM group) admitted to Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University were selected.The serum levels of Fasting blood glucose (FPG),body mass index (BMI),triglyceride (TG),total cholesterol (TC),high density lipoprotein cholesterol (HDL-C),low density lipoprotein cholesterol (LDL-C),insulin resistance index (HOMA-IR),serum superoxide dismutase (SOD),serum malondialdehyde (MDA),glutathione peroxidase (GSH-PX) were detected and compared between the two groups.And then,the T2DM patients with NAFLD were treated by A-LA for two weeks.The SOD,MDA,GSH-PX levels were compared before and after treatment.Results The FPG,BMI,TG,HOMA-IR of the T2DM + NAFLD group were (10.71 ± 3.63) mmol/L,(27.08 ± 3.87) kg/m2,(3.40 ± 1.85) mmol/L,(5.40 ± 2.98),respectively,which were significantly higher than those of the T2DM group[(9.50 ± 3.78)mmol/L,(23.58 ± 2.75) kg/m2,(1.79 ± 1.44) mmol/L,(2.41 ± 1.18)] (t =2.022,6.603,2.829,4.157,all P ＜ 0.05).The age and levels of HbA1c,TC,HDL-C,LDL-C between the two groups had no statistically significant differences (all P ＞ 0.05).The level of MDA in the T2DM + NAFLD group was (5.11 ± 0.25) μmol/L,which was significantly higher than (4.56 ±0.28) μmol/L in the T2DM group(t =2.106,P ＜0.05).The levels of SOD,GSH-PX,SOD/MDA in the T2DM + NAFLD group were (77.42 ± 10.31) U/mL,(69.62 ± 9.24) U,(15.39 ± 2.23),respectively,which were significantly lower than those in the T2DM group [(93.26 ± 11.21) U/mL,(87.54 ± 9.58) U,(20.33 ± 2.93)] (t =2.455,2.653,3.148,all P ＜ 0.05).After treatment with A-LA,the MDA level of the T2DM + NAFLD group was (4.81 ±0.26) μmol/L,which was significantly lower than that before treatment[(5.11 ±0.25) μmol/L,t=2.117,P ＜0.05],the levels of SOD,GSH-PX,SOD/MDA of the T2DM + NAFLD group were (87.15 ± 10.88) U/mL,(78.73 ± 9.57) U,(18.05 ± 2.51),respectively,which were significantly higher than those before treatment (t =2.117,2.207,2.228,3.148,all P ＜ 0.05).Conclusion A-LA might prove usefully in the treatment of patients with T2DM and NAFLD by change the oxidative stress.
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Objective To investigate the predict value of interleukin-18 (IL-18) combine with kidney injury molecule-1 (KIM-1) on 28-day mortality in patients with acute kidney injury (AKI) undergoing continuous renal replacement therapy (CRRT) in intensive care unit (ICU), and to look for the start time of CRRT. Methods A prospective observational study was conducted. The consecutive AKI critical patients who underwent CRRT from June 2017 to February 2018 admitted to ICU of the Fourth Hospital of Hebei Medical University were enrolled. Patients were divided into AKI 2 stage and AKI 3 stage groups according to the guidelines for Kidney Disease: Improving Global Outcomes (KDIGO). Basic vital signs were recorded for all enrolled patients, and ventilator parameters were recorded for patients on ventilation. Urine specimens were collected before CRRT, and IL-18 and KIM-1 levels were measured by enzyme-linked immunosorbent assay (ELISA). The patients were followed up for 28 days. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of urinary IL-18 and KIM-1 for prognosis. Results During the study period, 38 patients were treated. The patients with ICU stayed for less than 3 days, chronic obstructive kidney disease, intra-abdominal hypertension (IAH), diuretics usage within 4 hours or renal replacement therapy before urine collection were excluded. Finally, 30 patients were enrolled, including 12 patients with AKI phase 2 and 18 patients with AKI phase 3. There was no significant difference in basic medical characteristics such as gender, age, height, weight, basic vital signs, basic renal function, or severity of disease between AKI 2 stage and AKI 3 stage groups. Compared with the AKI 2 stage group, the level of urine KIM-1 in the AKI 3 stage group was significantly increased [ng/L: 6 195.6 (5 892.6, 7 935.4) vs. 5 487.5 (4 769.8, 6 353.4), P < 0.01], but urine IL-18 level was not statistically significant [ng/L: 52.1 (48.1, 62.6) vs. 53.9 (52.0, 57.2), P > 0.05]. All patients were followed up for
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This study investigated the effect of angiotensin II (Ang II) on apoptosis and thioredoxin-interacting protein (TXNIP) expression in INS-1 islet cells and the underlying mechanism. INS-1 cells cultured in vitro were treated with different concentration of Ang II for different time, and the viability was measured using cell counting kit-8 (CCK-8). After treatment with 1 × 10 mol/L Ang II for 24 h, flow cytometry and Western blot were used to measure the cell apoptosis, and Western blot was used to analyze the protein expression of TXNIP, carbohydrate response element-binding protein (ChREBP) and angiotensin II type 1 receptor (AT1R). Real-time PCR was used to detect TXNIP and ChREBP mRNA expression. IF/ICC was used to observe the TXNIP, ChREBP and AT1R expression. The results showed that Ang II reduced cell viability and induced the expression of TXNIP in a dose- and time-dependent manner (P < 0.05, n = 6) compared with the control group. Ang II induced apoptosis and up-regulated the expression of ChREBP and AT1R (P < 0.05, n = 6). AT1R inhibitor, telmisartan (TM), blocked Ang II-induced TXNIP and ChREBP overexpression (P < 0.05, n = 6) and inhibited Ang II-induced apoptosis. Taken together, Ang II increased ChREBP activation through AT1R, which subsequently increased TXNIP expression and promoted cell apoptosis. These findings suggest a therapeutic potential of targeting TXNIP in preventing Ang II-induced INS-1 cell apoptosis in diabetes.
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Diabetes can cause a significant increase in the expression of thioredoxin (Trx)-interacting protein (TXNIP), which binds to Trx and inhibits its activity. The present study was aimed to investigate the effect of TXNIP on proliferation of rat INS-1 islet β cells and the underlying mechanism. TXNIP overexpressing adenovirus vectors (Ad-TXNIP-GFP and Ad-TXNIPc247s-GFP) were constructed and used to infect INS-1 cells. Ad-TXNIPc247s-GFP vector carries a mutant C247S TXNIP gene, and its expression product (TXNIPc247s) cannot attach and inhibit Trx activity. The expression of TXNIP was detected by real-time PCR and Western blot. EdU and Ki67 methods were used to detect cell proliferation. Protein phosphorylation levels of ERK and AKT were detected by Western blot. The results showed that both TXNIP and TXNIPc247s protein overexpressions inhibited the proliferation of INS-1 cells, and the former's inhibitory effect was greater. Moreover, both of the two kinds of overexpressions inhibited the phosphorylation of ERK and AKT. These results suggest that TXNIP overexpression may inhibit the proliferation of INS-1 cells through Trx-dependent and non-Trx-dependent pathways, and the mechanism involves the inhibition of ERK and AKT phosphorylation.
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OBJECTIVE@#MicroRNA-155 (miR-155) is significantly highly expressed in breast cancer, lung cancer, liver cancer and other malignant tumors. This study was to design and construct a radiolabeled probe targeting miR-155 for in vivo imaging in breast cancer.@*METHODS@#Anti-miR-155 oligonucleotide (AMO-155) was chemically synthesized with 2' OMe modification. Its 5' end was linked with acetyl amine group. After chelated with a bifunctional chelator NHS-MAG3, AMO-155 was radiolabeled with 99mTc using stannous chloride. The serum stability was evaluated at cellular level. In vivo imaging was performed in MCF-7 tumor bearing mice after the administration of 99mTc radiolabeled AMO-155 and scramble control probes, respectively. Furthermore, the blocked imaging of tumor bearing mice was obtained after the injection of unlabeled AMO-155 2 hours ahead. MCF-7 and MDA-MB-231 tumor bearing mice with different expression level of miR-155 were imaged, respectively. Quantitative real-time PCR (qRT-PCR) was used to identify the expression level of miR-155 in the bearing tumors.@*RESULTS@#99mTc-AMO-155 was prepared with high radiolabeled efficiency (97%), radiochemical purity (greater than 98%), and radioactive specific activity (3.75 GBq/μg). 99mTc-AMO-155 was stable in fresh human serum for 12 hours. After the administration via tail vein, 99mTc-AMO-155 displayed significant accumulation in MCF-7 bearing tumors with high expression level of miR-155, whereas 99mTc-control showed little accumulation. After blocked with unlabeled AMO-155, the tumor could not be visualized clearly after the administration of 99mTc-AMO-155. Furthermore, 99mTc-AMO-155 could show the differential expression of miR-155 in vivo. MCF-7 tumor was shown with significantly higher radioactive accumulation than MDA-MB-231, based on its higher expression level of miR-155, which was verified by qRT-PCR.@*CONCLUSION@#99mTc-labeled AMO-155 with chemical modification showed good serum stability and in vivo tumor targeting ability. This study provides a potential probe for in vivo imaging of breast cancer.
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Animals , Female , Humans , Mice , Breast Neoplasms/diagnostic imaging , Cell Line, Tumor , MicroRNAs/analysis , Oligonucleotides, Antisense , Oligopeptides , Radiopharmaceuticals , Succinimides , Technetium , Tissue DistributionABSTRACT
Objective To evaluate the accuracy of color Doppler in predicting acute kidney injury ( AKI) . Methods Patients of both sexes with AKI risk factors not diagnosed with AKI, aged ≥18 yr, were enrolled in this study. Within 1 h after inclusion, the renal blood flow ( RBF) grade was monitored u-sing color Doppler, and renal resistive index ( RRI) value of renal interlobar artery was monitored at the level of renal interlobar or arcuate arteries, and corrected RRI value was calculated. The development of AKI was recorded within 24 h through measuring serum creatinine and urine volume, and the receiver oper-ating characteristic curve was plotted. Results Thirty-eight patients were included in non-AKI group and 40 ones in AKI group. Compared with non-AKI group, RBF grade was significantly decreased, RRI value was increased ( P<0. 05) , and no significant change was found in the corrected RRI value in AKI group ( P>0. 05) . The area under the curve of RBF grade and RRI value in predicting AKI occurred within 24 h and 95％ confidence interval were 0. 659 ( 0. 561-0. 747) and 0. 669 ( 0. 572-0. 756) , respectively. Con-clusion Color Doppler has a certain value in predicting AKI within 24 h.
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Objective To evaluate the ocular pharmacokinetics of a novel antibody, MIL60, tar-geting vascular endothelial growth factor ( VEGF) after subconjunctival injection. Methods After subcon-junctival injection of MIL60 in rabbits, aqueous humour, vitreous from both eyes and peripheral blood were collected of each rabbit to analyze the concentration of MIL60 with ELISA. Results After subconjunctival administration, MIL60 could penetrate into the injected eye′s anterior chamber and vitreous, and maintained at an effective concentration in the aqueous or vitreous for about 10. 7 or 6. 8 days. Moreover, MIL60 could be found in the uninjected eye. Conclusion After subconjunctival injection, MIL60 could maintain at a therapeutic concentration in injected eyes. The pharmacokinetics analysis of MIL60 might provide some basis and guidance for its application in humans in the near future.
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Objective To investigate the quality control indexes of intensive care units in Hebei province.Methods Statistical analysis was made on the quality control indexes of 48 hospitals in Hebei, which were registered in the critical medical quality management and control website of Hebei province. Results The physician-bed ratio of ICUs was (0.699 ± 0.231):1, with the beds accounting for (1.5 ± 0.5)% of the total beds in the hospital; nurse-bed ratio was (1.956 ± 0.544):1. The patients with APACHE II score greater than 15 accounted for (57.6 ± 23.2)%. In the course of treatment for septic shock patient,their 3h/6h bundle treatment completion rate was (57.0 ± 39.1)% and (57.0 ± 37.8)% respectively. Actual mortality of Hebei ICUs was(21.2 ± 16.5)%,and their unplanned tracheal intubation rate was (7.9 ± 7.7)%. Conclusions Given the overall capacity of ICUs in Hebei, there exist such shortcomings as insufficient beds and irrational staffing, which calls for better intensive care education and greater manpower for healthy development of critical care medicine.
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Objective To observe and explore the effects of different tidal volume (VT) ventilation on right ventricular (RV) function in patients with critical respiratory failure.Methods Consecutive respiratory failure patients who were treated with invasive ventilator over 24 h in the Department of Critical Care Medicine at the Fourth Hospital of Hebei Medical University from June to December in 2015 were enrolled in this study.Clinical data including patients′ vital signs, ventilator parameters and RV echocardiography were collected within 6 h (D0), day1(D1), day2 (D2) and day3 (D3) after ventilation started.According to the VT, patients with acute respiratory distress syndrome (ARDS) were assigned to low VT group [S6, ≤6 ml/kg predicted body weight (PBW)] and high VT group (L6, >6 ml/kg PBW), while non-ARDS patients were also assigned to low VT group (S8, ≤8 ml/kg PBW) and high VT group (L8, >8 ml/kg PBW).Results A total of 84 patients were enrolled in this study.44.2% ARDS patients and 58.5% non-ARDS patients were in low VT groups.After ventilation, tricuspid annulus plane systolic excursion(TAPSE)decreased progressively in S6 [from 18.30(16.70,20.70) mm to 17.55(15.70,19.50) mm, P=0.001], L6 [from 19.50(17.00,21.00) mm to 16.30(15.00,18.00) mm P=0.001], S8[from 18.00(16.00,21.00) mm to 16.50(15.50,18.00) mm, P=0.001] and L8 [from 19.00(17.50,21.50) mm to 16.35(15.15,17.00) mm, P=0.001] groups.However, TAPSE decreased less in small VT groups (S6 and S8) than those of in large VT groups (S8 and L8) without significant differences.There were not statistical differences between different VT groups in terms of ventilation days, including right ventricle area/left ventricle area (RVarea/LVarea),TAPSE,peak mitral flow velocity of the early rapid filling wave (E),peak mitral flow velocity of the late rapid filling wave (A),early diastolic velocity of the tricuspid annulus (e′),pulmonary artery systolic pressure,inferior vena cava diameter (all P>0.05).Compared to L6 group, low VT (S6 group) resulted in decreased mortality at 28 days [1/19 vs 37.5%(9/24), P=0.014].There were not statistical differences between different VT groups in terms of ventilation days, length of intensive care unit stay, length of hospital stay (all P>0.05).Logistic regression analysis showed that VT could be the independent factor of TAPSE (OR=1.104,95%CI 0.100-1.003,P=0.049).Conclusions Positive pressure mechanical ventilation resulted in RV systolic dysfunction.Lower VT may have the protective effect on RV function.Trial registration Chinese Clinical Trial Registry,ChiCTR-POC-15007563.
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Objective To explore the inhibitory effect of harmine on melanoma A375 cells and its mechanism thereof.Methods (1) Melanoma A375 cells were treated with harmine at 0,0.5,1,2,5,10,20,50 and 100 mg/L for 48 h in vitro.CCK-8 method was used to detect the cell viability and confirm the experimental concentrations.(2) After the cells were treated with 0,1,2 mg/L harmine,the scratch and transwell assays were used to detect the cell migration and invasion ability.Western blot assay was used to detect the expression levels of epithelial mesenchymal transition (EMT)-related protein E-cadherin,N-cadherin,Snail and p53.(3) Three groups of ceils were set up.The control group was transfected with empty vector ordy.The empty vector group was transfected with empty vector after treated with 2 mg/L harmine for 24 h.The Snail transfection group was transfected with Snail cDNA after treated with 2 mg/L harmine for 24 h.The cell migration and invasion ability were detected after the transfection.Results (1) When the concentration of harmine was above 2 mg/L,the survival rate of A375 cells was significantly lower than that of the control group with the increase of harmine concentrations (P ＜ 0.05).Then,the concentrations of 0,1 and 2 mg/L of harmine were used in the following experiments.(2) With the increase of the harmine concentrations,the number of cells in the scratched area and the number of trans-membrane cells in each group were significantly decreased.The migration and invasion ability of the ceils were decreased gradually.The expression levels of E-cadherin and p53 were increased,while the expression levels of N-cadherin and Snail were decreased.(3) Cell transfection experiments showed that the migration and invasion ability of the cells were increased compared with those of empty vector group after transfection with Snail.Conclusion Harmine can inhibit the proliferation of A375 cells and decrease the abilities of metastasis and invasion,which may be achieved by decreasing the expression of Snail after activating the p53,thereby increasing E-cadherin and down-regulating N-cadherin to inhibit the EMT process.